\r\n\tBoth diagnosis and clinical manipulation of the patient with vasospasm is a unique and challenging situation. Multi-clinical approach is extremely mandatory. The patient must be treated in a center, which requires a experienced team with both neurological surgeons, interventional radiologists, neurologists and neuroanesthesiologists. Moreover, a well-equiped, isolated neurointensive care is needed for all patients suffering form subarachnoid hemorraghe. \r\n\tIn their daily practice, both neurological surgeons, interventional radiologists, neurologists, neuroanesthesiologists, and even intensive care providers have to deal and challenge of vasospasm. Numerous studies relevant to pathophysiological mechanisms underlying vasospasm had been published, but we still know little about the exact mechanisms causing vasospasm. In the last decades of modern medical era, despite the technological developments concerning the neurological care of the patients with vasospasm, we still have no effective treatment and preventive care of this devastating entity. \r\n\tThe aim of this book project is to provide in detailed knowledge to both physicians and scientists dealing with cerebral vasospasm. This book will attract interest of both students, residents, specialists and academics of neurological sciences.
",isbn:null,printIsbn:"979-953-307-X-X",pdfIsbn:null,doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,hash:"1a824e678bcab74178b208a6bb6f6bb5",bookSignature:"Dr. Bora Gürer",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/9448.jpg",keywords:"vasospasm, cellular responses, vascular tone, blood breakdown products, biogenic amins, electrolytes, transcranial doppler, digital subtraction angiography, cerebral blood flow studies, nitrovasodilators, free radical scavengers, calcium channel blockers, endothelin based approaches, balloon angioplasty, medical angioplasty, microneurosurgery, intraoperative manipulations",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"August 19th 2019",dateEndSecondStepPublish:"September 9th 2019",dateEndThirdStepPublish:"November 8th 2019",dateEndFourthStepPublish:"January 27th 2020",dateEndFifthStepPublish:"March 27th 2020",remainingDaysToSecondStep:"a year",secondStepPassed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:null,coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"95341",title:"Dr.",name:"Bora",middleName:null,surname:"Gürer",slug:"bora-gurer",fullName:"Bora Gürer",profilePictureURL:"https://mts.intechopen.com/storage/users/95341/images/system/95341.jpg",biography:"Bora Gurer is currently affiliated to Department of Neurosurgery, University of Health Sciences, Fatih Sultan Mehmet Education and Research Hospital, Istanbul, Turkey. He graduated from Dokuz Eylul University, Faculty of Medicine. Besides being the youngest associate professor of neurosurgery in this country, he has a keen interest in complex neurovascular, neurooncological and skull base surgeries. He has authored numerous papers in peer-reviewed national and international journals.",institutionString:"Fatih Sultan Mehmet Education and Research Hospital",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"2",institution:null}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"304289",firstName:"Rebekah",lastName:"Pribetic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/304289/images/13255_n.png",email:"rebekah@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"8204",title:"Vascular Malformations of the Central Nervous System",subtitle:null,isOpenForSubmission:!1,hash:"2b6a8a26a78af3ac73731663a494fbad",slug:"vascular-malformations-of-the-central-nervous-system",bookSignature:"Bora Gürer and Pinar Kuru Bektaşoğlu",coverURL:"https://cdn.intechopen.com/books/images_new/8204.jpg",editedByType:"Edited by",editors:[{id:"95341",title:"Dr.",name:"Bora",surname:"Gürer",slug:"bora-gurer",fullName:"Bora Gürer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6374",title:"Hydrocephalus",subtitle:"Water on the Brain",isOpenForSubmission:!1,hash:"b431d113b9d7fca7e67c463f0970ed04",slug:"hydrocephalus-water-on-the-brain",bookSignature:"Bora Gürer",coverURL:"https://cdn.intechopen.com/books/images_new/6374.jpg",editedByType:"Edited by",editors:[{id:"95341",title:"Dr.",name:"Bora",surname:"Gürer",slug:"bora-gurer",fullName:"Bora Gürer"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"René Mauricio",surname:"Barría",slug:"rene-mauricio-barria",fullName:"René Mauricio Barría"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophanides",surname:"Theophile",slug:"theophanides-theophile",fullName:"Theophanides Theophile"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3092",title:"Anopheles mosquitoes",subtitle:"New insights into malaria vectors",isOpenForSubmission:!1,hash:"c9e622485316d5e296288bf24d2b0d64",slug:"anopheles-mosquitoes-new-insights-into-malaria-vectors",bookSignature:"Sylvie Manguin",coverURL:"https://cdn.intechopen.com/books/images_new/3092.jpg",editedByType:"Edited by",editors:[{id:"50017",title:"Prof.",name:"Sylvie",surname:"Manguin",slug:"sylvie-manguin",fullName:"Sylvie Manguin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"72",title:"Ionic Liquids",subtitle:"Theory, Properties, New Approaches",isOpenForSubmission:!1,hash:"d94ffa3cfa10505e3b1d676d46fcd3f5",slug:"ionic-liquids-theory-properties-new-approaches",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/72.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1373",title:"Ionic Liquids",subtitle:"Applications and Perspectives",isOpenForSubmission:!1,hash:"5e9ae5ae9167cde4b344e499a792c41c",slug:"ionic-liquids-applications-and-perspectives",bookSignature:"Alexander Kokorin",coverURL:"https://cdn.intechopen.com/books/images_new/1373.jpg",editedByType:"Edited by",editors:[{id:"19816",title:"Prof.",name:"Alexander",surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"57",title:"Physics and Applications of Graphene",subtitle:"Experiments",isOpenForSubmission:!1,hash:"0e6622a71cf4f02f45bfdd5691e1189a",slug:"physics-and-applications-of-graphene-experiments",bookSignature:"Sergey Mikhailov",coverURL:"https://cdn.intechopen.com/books/images_new/57.jpg",editedByType:"Edited by",editors:[{id:"16042",title:"Dr.",name:"Sergey",surname:"Mikhailov",slug:"sergey-mikhailov",fullName:"Sergey Mikhailov"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. Venkateswarlu",coverURL:"https://cdn.intechopen.com/books/images_new/371.jpg",editedByType:"Edited by",editors:[{id:"58592",title:"Dr.",name:"Arun",surname:"Shanker",slug:"arun-shanker",fullName:"Arun Shanker"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"41620",title:"Climatic Conditions and Production of Soybean in Northeastern Brazil",doi:"10.5772/52184",slug:"climatic-conditions-and-production-of-soybean-in-northeastern-brazil",body:'\n\t\t
\n\t\t\t
1. Introduction
\n\t\t\t
Brazil has become the second largest soybean producer after the USA. Projections to the year 2020 indicate the country’s soybean production will increase to 105 million tons, largely due to Brazil’s large expanse of potential arable land. This expansion of soybean production will occur mainly in the North and Northeast parts of the country that includes the states of Maranhão, Piauí, Tocantins and Bahia, a region collectively referred to as the MAPITOBA. Within this region, the Cerrados, an area of stable climate, consistent rainfall, and flat topography, is especially suited for soybean production [17].
\n\t\t\t
Soybean was introduced into Brazil in the late nineteenth century. However,widespreadproduction did not occur until about 60 years ago in the southern part of the country. Cultivation then spread from the southern to the middle and northern sections of the country. In recent years, production has spread into the Cerrado Region, an area in the middle and northern parts of Brazil’s interior containing 204 million hectares of land. The northern states of Piaui and Maranhao contain about 21 million hectares of land [6]. The savannas of this region are characterized by having acid soils of low fertility, high average temperatures (25-26 ° C) and average rainfall of 1,200 mm from October to April. However, they are subject to occurrences of dry spells [18].
\n\t\t\t
The expansion of soybean into the low latitudes of northeast Brazil has been facilitated by cultivar development for adaptation to the soils and climate of this region. This process has allowed for a large expansion of soybean production into the Cerrado region of Brazil [1].
\n\t\t\t
Cultivar Tropical was first released in 1980 for production in the low latitude regions of Brazil. This created a continual demand for more adapted cultivars [4]. Other cultivars released for northeastern Brazil between 1982 and 1998 are: Timbira; BR 10 (Teresina) and BR 11 (Carajás); BR-27 (Cariri) and BR-28 (Seridó); BR- 32 (Nova Tropical); BR/ EMGOPA 312 (Potiguar) and BR 35 (Rio Balsas); Embrapa 9 (Bays); Embrapa 30 (Vale do Rio Doce), Embrapa 31 (Mina), Embrapa 33 (Cariri RC) and the Embrapa 34 (Teresina RC); Embrapa 63 (Mirador); MA/BR 64 (Parnaíba) and MA/BR 65 (Sambaíba) and MA/BRS-164 (Patí) and MA/BRS-165 (Seridó RCH).
\n\t\t\t
Characteristics that have been selected for production in low latitude areas are: suitable maturity, adequate plant height, height to first pod of more than 12 cm ,a non-woody stem, erect plant stature, lodging resistance, pest resistance, good seed quality and high oil content and protein content, high yield, yield stability (robustness), uniform ripening, indehiscent pods, high capacity for N2 fixation, tolerance to aluminum and manganese toxicity, a long juvenile phase and photoperiod insensitivity. Across planting dates and environments, the growing season can vary from 75 to 200 days. Thus a wide range of cultivars have had to be developed for adaptation to many environmental conditions [22, 43]. The average height of the plant can range from 20 to 150 cm or more, according to the cultivar and environment, and the height to first pod may be characteristic of the cultivar. Environmental factors or cultural practices may also affect height to first pod [35], which prevents mechanical harvesting and can cause harvest loss.
\n\t\t
\n\t\t
\n\t\t\t
2. Production of soybeans in Northeast Brazil
\n\t\t\t
The Northeast region of Brazil is situated between latitudes 1°20\'00\'\' and 19º00\'00\'\' S. Maturity groups adapted to this region range from maturity group 7 to 9.Examples of cultivars developed for this region are BRS 326 (maturity group 8.7) and BRSMA Seridó RCH (9.7). Both cultivars have the long-juvenile trait which reduces the photoperiod sensitivity to the short days of this region; thus allowing soybean to have an adequate developmental period for optimal yield. Much of the success of soybean expansion into Northeast Brazil is due to the development of cultivars having the long-juvenile trait [3]. Development of these cultivars was done through breeding programs using the following cultivars and genotypes: PI 240664, PI 159925, Santa Maria, PR Paranagoiana 77-10001 [24, 20]. Experimental studies in the past century, especially in the United States, led to the classification of soybeans into maturity groups based on their photoperiod response. The maturity groups were: classify groups of soybean according to the response to photoperiod, a total of 13 classes of maturation, which are 000, 00, 0, I, II, III, IV, V, VI, VII, VIII, IX and X [27, 35].
\n\t\t\t
Besides the issue of photoperiodism, soybean expansion into Northeast Brazil is also limited by drought, waterlogging, the harsh environment of the Amazon region, infrastructure, marketing, and the availability of manual labor [11]. Cultivar development was initiated in Piaui state in 1972 and resulted in the release of cultivar Tropical in 1980.This was followed by the development and release of more cultivars for production in Northeast Brazil [3]. Examples are the cultivars DM-Soberana and DM-Nobre released in the central region of Brazil in the states of Bahia and Maranhão. These cultivars were well adapted to the tropical conditions of this region, demonstrated greater yield than check cultivars, had good yield stability across environments, proper maturity for the growing season, and were adapted for mechanical harvest [39]. In the states of Maranhão, Piauí and Tocantins, a new cultivar, BRSMA-Babacu, was developed for commercial production. Across seven environments in the late 1990’s, it demonstrated an average yield of 2,952 kg/ha which was 4% higher than the local cultivar Doko Millionario. It is a late-maturing cultivarwith a maturity of 130 days from emergence to maturity, a plant height of 99 cm, moderately resistant to lodging, purple flower color, brown pod and pod pubescence, yellow seed coat, brown hilum, good resistance theto pod dehiscence, average seed quality and average seed weight of 15.8 g/100 seeds [23]. In these states, the time of planting depends on the rainy season, which occurs in summer (Table 1).
Number of days to flowering (NDF), number of days to fruit set (NDFT), reproductive period (RP), plant height at maturity (ALTM), number of nodes / plant (NPP) Observed in different cultivars of soybean-green. Sand-PB, UFPB, 2004.
In each column, the same letter not differ at 5% probability by Tukey test.
\n\t\t\t
Research conducted in the Brazilian states located in Northeast Brazil have shown promising results regarding the adaptation of cultivars to cultivation. Research conducted at the Federal University of Paraiba, Center for Agrarian Sciences, resulted in the development of cultivar Pirarara. This cultivar was adapted to the Entisol soils of the region, as well as the sort days, warm and humid climate, rainfall, and acid soils. It had a plant height of about 63 cm and developed about 12 main stem nodes. Days from emergence to maturity was about 75. Data for the cultivar is shown in Table 2 [40]. Further research with this cultivar demonstrated that when intercropped with corn, it had a vegetative period (days from planting to first flower) of about 55 days. This was a sufficient period to allow for enough dry matter accumulation to optimize yield. Other developed cultivars had shorter vegetative periods, such as Pati (50 days) and JLM 004 (39 days).The significant factor is to allow enough time for node production, since nodes are plant structures from which pods, seeds, and yield are made. This has been demonstrated in research conducted by [19] in which yield was shown to be related to the number of nodes formed. Cultivar Black Alliance had the most at 33, while Kanro had the fewest at 8.
\n\t\t\t\n\t\t\t\n\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
Cultivars
\n\t\t\t\t\t\t
Mean (kg ha-1)
\n\t\t\t\t\t\t
ᵦli
\n\t\t\t\t\t\t
ᵟij
\n\t\t\t\t\t\t
R2\n\t\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS TRACAJÁ
\n\t\t\t\t\t\t
1882,87
\n\t\t\t\t\t\t
0,52**
\n\t\t\t\t\t\t
792,69**
\n\t\t\t\t\t\t
99,25
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BR JUÇARA
\n\t\t\t\t\t\t
1555,41
\n\t\t\t\t\t\t
1,84**
\n\t\t\t\t\t\t
145934,72**
\n\t\t\t\t\t\t
90,12
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS MA 165 SERIDÓ
\n\t\t\t\t\t\t
1511,10
\n\t\t\t\t\t\t
1,04ns
\n\t\t\t\t\t\t
21982,14**
\n\t\t\t\t\t\t
95,07
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRR 219 BOA VISTA
\n\t\t\t\t\t\t
1585,36
\n\t\t\t\t\t\t
1,14ns
\n\t\t\t\t\t\t
30844,36**
\n\t\t\t\t\t\t
94,35
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS SAMBAÍBA
\n\t\t\t\t\t\t
1893,58
\n\t\t\t\t\t\t
0,94ns
\n\t\t\t\t\t\t
145903,06**
\n\t\t\t\t\t\t
70,40
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS CANDEIA
\n\t\t\t\t\t\t
1552,88
\n\t\t\t\t\t\t
0,91ns
\n\t\t\t\t\t\t
10589,73**
\n\t\t\t\t\t\t
75,27
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
MA BR 971665
\n\t\t\t\t\t\t
1725,72
\n\t\t\t\t\t\t
0,61**
\n\t\t\t\t\t\t
14432,72**
\n\t\t\t\t\t\t
91,06
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
CV (%)
\n\t\t\t\t\t\t
22,52
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
General mean (kg ha-1)
\n\t\t\t\t\t\t
1672,42
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t
Table 3.
Average linear regression coefficient (ᵦ li), misuse of linear regression (ᵟ ij) and coefficient of determination (R2) According to the methodology of Eberhart and Russell (1996) for grain production of soybean genotypes in Ceará.
ns not significant; * Significant at 5% probability level; ** Significant to 1% probability by the F test
\n\t\t\t
Although production of soybean is still restricted in some areas for the northeastern states of Bahia, Maranhão and Piauí, it has shown potential for expansion for other states in the region such as Ceará. Near the city of Pentecost (3o 47’ S Latitude), cultivar trials during 2005 and 2005 have identified genotypes BRS TRACAJÁ, and BRS Sambaíba MA BR 97 1665as having potential to be grown in Ceará (Table 3). Certain soybean cultivars, when intercropped with corn, were capable of producing large biomass relative to other cultivars [42].
\n\t\t\t\n\t\t\t
Preliminary testing of three soybean cultivars is being conducted by [9] in the coastal plains in the state of Alagoas, near the city of Rio Largo, at a latitude of 9°29\'45\'\'. Cultivars used in the study were MG / BR - 46 (Conquista), and BRS Tracajá MA/BRS-165 (Seridó RCH). Agronomic data for plant height is shown in Table 4 and data for yield and seed weight is in Table 5.Although plant height was somewhat lower than that which is usually required for mechanical harvesting, [9] demonstrated that yield production was good for all cultivars ranging from 2,620 to 3,600 kg ha-1 (Table 5), being equal to or superior to the traditional regions of production soybean.
\n\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
Cultivars
\n\t\t\t\t\t\t
Plant height (cm)
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
Plant height stage R2
\n\t\t\t\t\t\t
Plant height stage R9
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
MG/BR – 46 (conquista)
\n\t\t\t\t\t\t
37.13 a
\n\t\t\t\t\t\t
51.08 a
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS Tracajá
\n\t\t\t\t\t\t
41.95 a
\n\t\t\t\t\t\t
63.88 a
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
MA/BRS – 165 (Seriado RCH)
\n\t\t\t\t\t\t
35. 35 a
\n\t\t\t\t\t\t
59.98 a
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
CV (%)
\n\t\t\t\t\t\t
13.7
\n\t\t\t\t\t\t
12.2
\n\t\t\t\t\t
\n\t\t\t\t
Table 4.
Height of plant growth stages R2 and R9 of three soybean varieties grown in the Coastal Plain region of the state of Alagoas.
Means Followed by the same letter not differ at the 5% level of probability by the Tukey test.
\n\t\t\t
In research conducted by [5], agronomic performance of several soybean cultivars in the rugged areas of the states of Bahia and Sergipe (latitude 10°14\'S and 10°55\' S). There were two series of screening studies conducted, the first having 14 genotypes and the second having 24. The tests were conducted during the growing seasons of 2006 and 2007 in several cities in remote rural areas of Sergipe and Bahia. Among the many cultivars tested, the ones performing the best were BRS SAMBAÍBA and EMGOPA, followed by BRS TRACAJÁ, BRS CONQUISTA, BRS BELA VISTA, BRS CORISCO and BRS BARREIRAS. All cultivars demonstrated a yield range of 2,285-3,373 kg/ha.
\n\t\t\t
Studies with 18 soybean cultivars, performed by [28] in the state of Piauí, (Lat05°02\'40 "S), were planted on 28 February 2010. Based on differences in days to first flower, the cultivars were separated into four groups (Table 6): early (45 to 47.7 days), medium (48-57), late (>57 days), and average.
\n\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
GENOTYPES* \n\t\t\t\t\t\t
\n\t\t\t\t\t\t
Cycle (days)
\n\t\t\t\t\t\t
Classificationcycle
\n\t\t\t\t\t\t
Reproductive period
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
NDF days
\n\t\t\t\t\t\t
NDM days
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
(PR) days
\n\t\t\t\t\t\t
(% PR) \n\t\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS SAMBAÍBA
\n\t\t\t\t\t\t
49.00 C
\n\t\t\t\t\t\t
114.00 F
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
55.25 C
\n\t\t\t\t\t\t
47.12 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS CANDEIA
\n\t\t\t\t\t\t
48.25 C
\n\t\t\t\t\t\t
117.00 E
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
66.50 A
\n\t\t\t\t\t\t
55.64 A
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS 219 BOA VISTA
\n\t\t\t\t\t\t
46.25 D
\n\t\t\t\t\t\t
101.25 I
\n\t\t\t\t\t\t
Early
\n\t\t\t\t\t\t
56.00 C
\n\t\t\t\t\t\t
47.14 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS 271RR
\n\t\t\t\t\t\t
45.75 D
\n\t\t\t\t\t\t
104.50 H
\n\t\t\t\t\t\t
Early
\n\t\t\t\t\t\t
60.00 B
\n\t\t\t\t\t\t
48.62 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
114 BCR336F8
\n\t\t\t\t\t\t
50.50 C
\n\t\t\t\t\t\t
134.00 A
\n\t\t\t\t\t\t
Late
\n\t\t\t\t\t\t
59.25 B
\n\t\t\t\t\t\t
43.40 D
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
142 SOY94F5G
\n\t\t\t\t\t\t
53.75 B
\n\t\t\t\t\t\t
130.50 B
\n\t\t\t\t\t\t
Late
\n\t\t\t\t\t\t
65.00 A
\n\t\t\t\t\t\t
49.34 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
164 SOY94F5G
\n\t\t\t\t\t\t
51.00 C
\n\t\t\t\t\t\t
114.50 F
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
55.50 C
\n\t\t\t\t\t\t
45.63 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
168 BCR1069X7RG
\n\t\t\t\t\t\t
53.25 B
\n\t\t\t\t\t\t
120.75 D
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
55.50 C
\n\t\t\t\t\t\t
45.30 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
169 BCR1069X7RG
\n\t\t\t\t\t\t
45.00 D
\n\t\t\t\t\t\t
121.25 D
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
55.50 C
\n\t\t\t\t\t\t
45.31 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
170 BCR1069X7RG
\n\t\t\t\t\t\t
48.50 C
\n\t\t\t\t\t\t
123.00 D
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
50.00 D
\n\t\t\t\t\t\t
39.52 E
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
171 BCR1069X7RG
\n\t\t\t\t\t\t
50.25 C
\n\t\t\t\t\t\t
120.25 D
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
65.25 A
\n\t\t\t\t\t\t
53.59 A
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
172 BCR1069X7RG
\n\t\t\t\t\t\t
50.50 C
\n\t\t\t\t\t\t
126.00 C
\n\t\t\t\t\t\t
Late
\n\t\t\t\t\t\t
62.50 B
\n\t\t\t\t\t\t
48.54 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
173 BCR1069X7RG
\n\t\t\t\t\t\t
51.00 C
\n\t\t\t\t\t\t
121.25 D
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
56.75 C
\n\t\t\t\t\t\t
46.32 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
174 BCR1069X7RG
\n\t\t\t\t\t\t
47.75 D
\n\t\t\t\t\t\t
122.75 D
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
55.00 C
\n\t\t\t\t\t\t
45.17 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
175 BCR1069X7RG
\n\t\t\t\t\t\t
49.00 C
\n\t\t\t\t\t\t
128.00 C
\n\t\t\t\t\t\t
Late
\n\t\t\t\t\t\t
62.00 B
\n\t\t\t\t\t\t
48.06 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
176 BCR1069X7RG
\n\t\t\t\t\t\t
57.25 A
\n\t\t\t\t\t\t
117.50 E
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
63.00 B
\n\t\t\t\t\t\t
48.64 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
177 BCR1069X7RG
\n\t\t\t\t\t\t
58.00 A
\n\t\t\t\t\t\t
114.00 F
\n\t\t\t\t\t\t
Medium
\n\t\t\t\t\t\t
56.25 C
\n\t\t\t\t\t\t
45.93 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
179 SOY24F5G
\n\t\t\t\t\t\t
50.25 C
\n\t\t\t\t\t\t
107.50 G
\n\t\t\t\t\t\t
Early
\n\t\t\t\t\t\t
61.25 B
\n\t\t\t\t\t\t
48.62 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
C.V. (%)
\n\t\t\t\t\t\t
4.62
\n\t\t\t\t\t\t
1.55
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
5.16
\n\t\t\t\t\t\t
4.85
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
General mean
\n\t\t\t\t\t\t
50.29
\n\t\t\t\t\t\t
118.77
\n\t\t\t\t\t\t
\n\t\t\t\t\t\t
58.91
\n\t\t\t\t\t\t
47.33
\n\t\t\t\t\t
\n\t\t\t\t
Table 6.
Mean values for the number of days to flowering (NDF), number of days to maturity (NDM), reproductive period in days (PR) and percentage (RP%) of different soybean genotypes Evaluated in low latitude, in Teresina - PI.
* Means Followed by the same letter not differ by Scott-Knott test (P ≤ 0.05).
\n\t\t\t
[28] reported excellent yields with genotypes 171BCR1069X7RG and 174 BCR1069X7RG. They both produced yields of about 4000 kg ha-1. These were much better than other genotypes, the lowest of which yielded below 2000 kg ha-1 (Table 7).
\n\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
GENOTYPES*
\n\t\t\t\t\t\t
PRODUCTIVITY (kg ha-1)
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
171 BCR1069X7RG
\n\t\t\t\t\t\t
4,188.53 A
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
174 BCR1069X7RG
\n\t\t\t\t\t\t
3,838.66 A
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
170 BCR1069X7RG
\n\t\t\t\t\t\t
3,464.27 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
177 BCR1069X7RG
\n\t\t\t\t\t\t
3,248.29 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
169 BCR1069X7RG
\n\t\t\t\t\t\t
3,084.99 B
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
175 BCR1069X7RG
\n\t\t\t\t\t\t
2,802.35 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
176 BCR1069X7RG
\n\t\t\t\t\t\t
2,766.36 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS 219 (BOA VISTA)
\n\t\t\t\t\t\t
2,736.91 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
172 BCR1069X7RG
\n\t\t\t\t\t\t
2,673.71 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
164 SOY94F5G
\n\t\t\t\t\t\t
2,630.52 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
179 SOY24F5G
\n\t\t\t\t\t\t
2,529.99 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
173 BCR1069X7RG
\n\t\t\t\t\t\t
2,446.89 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
142 SOY94F5G
\n\t\t\t\t\t\t
2,403.11 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
168 BCR1069X7RG
\n\t\t\t\t\t\t
2,353.72 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS SAMBAÍBA
\n\t\t\t\t\t\t
2,352.66 C
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
114 BCR336F8
\n\t\t\t\t\t\t
1,857.68 D
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS CANDEIA
\n\t\t\t\t\t\t
1,813.55 D
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS 271RR
\n\t\t\t\t\t\t
1,735.16 D
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
C.V %
\n\t\t\t\t\t\t
13.21
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
General mean
\n\t\t\t\t\t\t
2,718.19
\n\t\t\t\t\t
\n\t\t\t\t
Table 7.
Mean values of grain yield in different soybean genotypes evaluated in low latitude, Teresina - PI.
* Means followed by same letter do not differ by Scott-Knott test (P ≤ 0.05)
\n\t\t\t
Research conducted in western Bahia, near the city of São Desidério (Lat 12o45’S). Growth and yield of soybean at different planting dates are shown in Table 8. Although there were some planting dates at which all cultivars showed good yields, only cultivar M-SOY 8411 yielded well at all four planting dates [9].
\n\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
Cultivars
\n\t\t\t\t\t\t
Productivity (kg/ha)
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
Ep1
\n\t\t\t\t\t\t
Ep2
\n\t\t\t\t\t\t
Ep3
\n\t\t\t\t\t\t
Ep4
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
M-SOY 8411
\n\t\t\t\t\t\t
3,924 aA
\n\t\t\t\t\t\t
3,518 aA
\n\t\t\t\t\t\t
2,460 aB
\n\t\t\t\t\t\t
938 aC
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS Corisco
\n\t\t\t\t\t\t
4,142 aA
\n\t\t\t\t\t\t
2,768 bB
\n\t\t\t\t\t\t
1,745 bC
\n\t\t\t\t\t\t
585 aD
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS 263
\n\t\t\t\t\t\t
3,956 aA
\n\t\t\t\t\t\t
2,518 bcB
\n\t\t\t\t\t\t
1,163 bcC
\n\t\t\t\t\t\t
659 aC
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
BRS Barreiras
\n\t\t\t\t\t\t
3,930 aA
\n\t\t\t\t\t\t
1,956 cB
\n\t\t\t\t\t\t
715 cC
\n\t\t\t\t\t\t
642 aC
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
M-SOY 9350
\n\t\t\t\t\t\t
4,006 aA
\n\t\t\t\t\t\t
2,635 bB
\n\t\t\t\t\t\t
1,029 cC
\n\t\t\t\t\t\t
851 aC
\n\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t\t\t
D.M.S = 238,38
\n\t\t\t\t\t\t
C.V. (%)= 14.35
\n\t\t\t\t\t\t
\n\t\t\t\t\t
\n\t\t\t\t
Table 8.
Average grain yield (kg / ha) from five soybean sown in times Ep1 (29/11/2006), Ep2 (12/14/2006) Ep3 (28/12/2006) and ep4 (01/12/2007), in western Bahia.
Data for Value for Cultivation and Use (VCU) of soybean BRS 278RR for the state of São Paulo indicated that it belongs to a medium maturity group (maturity group 9.4), with the number of days to maturity ranging from 115 to 127 days [26]. According to these authors, the average yield of soybean tested in 24 environments of evaluation was 2,973 kg/ha, and 5.2% more productive than the standard transgenic BRS 271RR, and 5% less productive than the conventional BRS tracajá (Table 9).
Average grain yield (kg / ha) and relative yield (%) of BRS 278RR, BRS and BRS 271RR turtle in the agricultural years 2004/05 to 2006/07 of the southern regions of the Maranhão, Piauí southwestern and northern Tocantins.
Because of these pioneering studies to develop cultivars adapted to different regions of northern Brazil, soybean production has expanded rapidly throughout the region. For all the soybean growing regions of Brazil, the greatest expansion has occurred in the North and Northeast regions of the country [8]. Across the region, between the 2008/2009 growing season to the 2009/2010 season, the area of production increased by 8.9% from 2,105,600 to 2,292,600 hectares. A more recent survey by [7] highlights the states of Bahia, Piauí and Maranhão. In the state of Piaui area there was a 16.6% increase in soybean acreage between 2011 and 2012, with the entire state having a production area of 447,300 hectares for soybean. In the state of Bahia, the largest producer of oilseeds in the Northeast, the area planted to soybean increased by 6.6%, from 1,040,000 to 1,110,000 hectares across the same period. The same type of expansion occurred in Maranhao where the growing area increased 12.2%, from 518,200 to 581,400 hectares.
\n\t\t\t
Development of adapted cultivars for Northeast Brazil has greatly aided this expansion into tropical regions. This has made a significant contribution to strengthening the regional agricultural economy. Soybeans provides oil for the food industry and livestock meal for meat production, enhances agricultural development in undeveloped areas, and helps to add a protein-rich source of human food to ameliorate the widespread protein deficiencies common to Northeast Brazil [3].
\n\t\t
\n\t\t
\n\t\t\t
3. Edaphoclimatic Factors
\n\t\t\t
Expansion of soybean into tropical areas of Brazil has been made possible by development of genotypes having the long juvenile or late flowering trait in short-day photoperiods. This was required to allow soybean to have a sufficiently long developmental period to achieve enough size for optimal yield [37]. Soybean cultivars are affected by photoperiod, humidity, temperature, planting date, altitude, latitude, level of soil fertility and other factors [35]. According to [44], these are the main elements responsible for the variability and difficulties for growing the crop in Brazil. Environmental factors interact with soybean’s developmental periods in affecting the growth and yield production of the crop.
\n\t\t\t
Although soybean originated in the temperate world, it has a wide range of adaptability and can be grown well in tropical and subtropical locations. Average temperatures optimal for the best soybean development are between 20 and 35oC. At temperatures outside this range there can be physiological disorders with flowering and rhizobial inoculation, as well as poor growth. [35] claimed that at temperatures below 24oC flowering is retarded by two to three days for each decrease of 0.5°C. Such conditions can happen in the Northeast at altitudes greater than 500 m in the rainy winter period. Such cases occur in Areia-Paraíba, Garanhuns-Pernambuco and Triumfo-Pernambuco, among other cities.
\n\t\t\t
Temperature has a strong influence on the rates of all the metabolic and physiological processes occur during development. This has a direct effect on growth rate and yield. Temperature also has a significant effect on the duration ofthe different developmental periods that make up soybean’s crop cycle. In particular, the periods from emergence to flowering and flowering to maturity are affected by it [16]. It is recommended that the planting of soybeans should not be done when the soil temperature is below 20 oC so that germination and plant emergence are not compromised. Once temperatures reach this level, the germination rate increases exponentially with increasing temperature [21]. Thus, the number of days from sowing to the state of emergency (LV) can vary from about 5-15 days, depending on temperature [35]. Also according to the authors, temperature is the main factor influencing plant development, where low temperatures delay and high temperaturesaccelerate seedling emergence and leaf development.
\n\t\t\t
The time course of the vegetative activity of plants is adjusted to local conditions during the growing season. In the dry tropics and subtropics, the growing season is limited by the intensification of water stress when the dry season begins [21]. Under the conditions of northeastern Brazil, the predominant climate is hot and dry. According to some authors [14, 35], for soybean temperatures above 40 oC have an adverse effect on the rate of growth, the rate of formation of the nodes and internode growth and floral initiation. This causes problems with flowering, pod formation and retention, and results in lower yield. These problems are accentuated with the occurrence of water deficits.
\n\t\t\t
Differences in flowering date between yearsby a cultivar sown in the same season are due to temperature variations. Thus, high temperatures can cause soybean to flower too early, which may cause a decrease in plant height,and accelerate the maturity of the crop [14]. The nodulation and nitrogen fixation in soybean are greatly affected by soil temperature and the growth of Bradyrhizobiumjaponicum is limited by temperatures above 33 oC [35]. When facing environmental stress, there is always a genotype x environmental interaction which must be considered during the breeding program for cultivar development [32].Solar radiation is a critical environmental factor because it directly affects the crop growth rate and the ability to obtain enough dry matter for optimal yield potential. Water availability is also very important, because it affects leaf expansion, photosynthetic rate, crop growth rate, and nitrogen fixation [30].
\n\t\t\t
Not only is the level of light important, but length of day, or photoperiod, is also important. Photoperiod affects many developmental processes such as flowering, seed germination, growth of stems and leaves, formation of storage organs and assimilate partitioning [38]. It also affects leaf expansion, photosynthesis, senescence, dormancy of buds, and other processes [16]. Photoperiodism is a term describing all these plant responses to day length or photoperiod. Photoperiod will be determined by the latitude of where the crop is grown and the planting date.For soybean, the effective photoperiod includes the time from sunrise to sunset and some of civil twilight. Three types of photoperiodic response are recognized: short-day response in which flowering is induced and/or accelerated at a certain critical day length or less; long-day response in which flowering is induced and/or accelerated at a certain critical daylength or longer; and day neutral in which flowering time is unaffected by day length. Soybean is a short-day plant.
\n\t\t\t
Since vegetative growth in soybean occurs between emergence and the start of seed filling, it is important that soybean be planted at a latitude and planting date where day lengths will be long enough to allow enough time to the start of seed filling so that dry matter accumulation is large enough for optimal yield potential. The major problem with the expansion of soybean into northern Brazil is in these low latitudes, day length is seldom longer than 12 hours per day. Ideally, it is best to plant in October or November to take advantage of the lengthening days that occur at this time and continue until the summer solstice in late December. Since the critical short-day period to hasten flowering occurs when the photoperiod is shorter than 13.5 to 14.5 hours (the length varies with maturity group and cultivars within maturity groups), the typical soybean planted in this region will have too short a time to flowering and the start of seed filling to achieve enough size for optimal yield. For this reason, much research in Brazil has concentrated on incorporating the “long-juvenile” trait into soybean cultivars. The juvenile period is the initial period in the plant’s growth when it’s developmental rate does not accelerate in response to short days. Thus, cultivars having this trait will have a longer time to flowering and the start of seed filling compared to those that do not. Incorporation of this trait into Brazilian cultivars has greatly facilitated soybean expansion into northern Brazil. [25, 15, 14] .
\n\t\t\t
The physiology of the mode of action of the long juvenile period is still unknown. The trait is either caused by a delayed ability of the plant to respond to short days or a requirement for more short day cycles to induce and promote flowering relative to other soybeans [14].The problem of short-day induced premature flowering in northern Brazil was approached by selecting genotypes with insensitivity to photoperiod and/or having a long juvenile period [27]. Several breeding programs have contributed to the development of high-yielding cultivars adapted to different agro-climatic conditions of Brazil. For expansion into central and northern Brazil, breeding programs have followed a strategy of developing genotypes adapted to low latitudes, through the incorporation of the long juvenile trait. Research conducted by [33] concluded that the germplasm bank of soybeans genetic variability has remained relatively constant over the last 30 years.
\n\t\t\t
The availability of water is another important environmental stress for soybean culture in northern Brazil. The first critical period is seed germination and seedling development. Soybean seeds need to absorb enough water to achieve 50% moisture content to ensure good germination. Soil water content needs to be between 50-85% of total available water. According to [25], an annual rainfall 700-1200 mm that is well distributed during the soybean cycle (500 to 700 mm) will meet the crops water needs. Soybean’s water requirement increases with plant development, reaching a maximum during the flowering and grain filling periods (7-8 mm / day), and decreasing thereafter [12].
\n\t\t\t
The growing season in northern Brazil is largely determined by occurrence of the rainy and dry seasons of the region. The dry season occurs between May to September and any agriculture during this time requires irrigation [16]. Drought is usually the main factor responsible for crop losses. The two most critical periods for drought stress in soybean are during seed emergence to seedling establishment and the grain filling period. During germination, both excess and lack of water are harmful to crop establishment. Soils having a low water storage in general are unfit for soybean production for most cultivars and planting dates [13].
\n\t\t\t
The soybean plant requires more water as growth and development proceed. Peak demand is during flowering and early pod formation and remains high until physiological maturity. The most critical period is during flowering and early pod formation. Drought stress at this time will cause abortion of flowers and pods, resulting in lower seed production and reduced yield [27]. Rainfall data from the state of Bahia indicates that there is a 80% chance for receiving sufficient rainfall to avoid drought stress during the critical periods [36]. The most important variable to be considered when dealing with drought stress is water retention in the soil during the growing season [27]. In summary, obtaining optimal yield in a given environment, depends upon maximizing the genetic potential of a given cultivar [31]. This involves having a long enough time for vegetative growth so that the prevailing photoperiod does not reduce yield, and the avoidance of drought stress [34]. Experimental trials in Brazil have shown there is a genetic yield potential of more than 5,000 kg/ha grain [2]. Genetic potential for most cultivated crops has increased greatly over the last 100 years. However, realizing this potential will depend on coping with environmental stress [27]. Soybean is recognized as having wide genetic diversity and with proper genetic and breeding research it can be adapted to a wide range of environmental conditions. Efforts in Brazil over the last 40 years to deal with problems presented by photoperiodic adaptation and coping with other environmental stresses have shown how this can happen through cooperative research efforts involving breeders, physiologists, geneticists, and agronomists.
\n\t\t
\n\t\t
\n\t\t\t
4. Conclusion
\n\t\t\t
Brazil has become the second largest producer of soybeans in the world. This has occurred largely because of our success at developing soybean cultivation in the low latitude regions (1°20\'00\'\' and 19º00\'00\'\' S) in central and northern Brazil. Much of the area opened to soybean production lies in the Cerrado region which is Brazil’s agricultural frontier.
\n\t\t\t
Northeast Brazil is also an area for agricultural development. It has a wide variety of environmental zones and is suitable for mechanized agriculture on small- or medium-sized farms. It has potential for production of many crops ranging from pastures for dairy cattle to bio-energy crops like sugar cane (ethanol) and biodiesel (soybean). Our progress in the agricultural development of this region is due to concentrated investment of financial and human resources in genetic improvement of cultivars and their adaptation to different climates in this region. The largest effort has been the development of cultivars with the long-juvenile trait which has overcome the problem of the short photoperiods common to this tropical region. Thus, short-day induced premature flowering is no longer a problem, and soybean can be grown in northern Brazil that achieve a size suitable for optimal yield. The greatest expanse of soybean production in northern Brazil has occurred in the states of “Bahia, Maranhão and Piauí”. It is in these states that the public and private research efforts have been focused. Similar efforts have now been started in other northern states such as “Ceará, Sergipe, Paraiba, Pernambuco, Alagoas and Rio Grande do Norte”. University and state research efforts are now being conducted to develop adapted soybean cultivars for the small and medium-sized farms of this region. Much effort will also have to be invested into marketing and transport. We firmly believe that with continued research efforts, soybean production in northern Brazil will expand into the future and that Brazil will become the largest soybean producer in the world within the next 20 years.
\n\t\t
\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/41620.pdf",chapterXML:"https://mts.intechopen.com/source/xml/41620.xml",downloadPdfUrl:"/chapter/pdf-download/41620",previewPdfUrl:"/chapter/pdf-preview/41620",totalDownloads:2089,totalViews:588,totalCrossrefCites:0,totalDimensionsCites:2,hasAltmetrics:0,dateSubmitted:"April 16th 2012",dateReviewed:"August 8th 2012",datePrePublished:null,datePublished:"January 2nd 2013",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/41620",risUrl:"/chapter/ris/41620",book:{slug:"a-comprehensive-survey-of-international-soybean-research-genetics-physiology-agronomy-and-nitrogen-relationships"},signatures:"Jeandson Silva Viana, Edilma Pereira Gonçalves, Abraão Cicero Silva and Valderez Pontes Matos",authors:[{id:"155340",title:"Dr.",name:"Jeandson",middleName:"Silva",surname:"Viana",fullName:"Jeandson Viana",slug:"jeandson-viana",email:"jeandson@cnpq.br",position:null,institution:{name:"Federal Rural University of Pernambuco",institutionURL:null,country:{name:"Brazil"}}},{id:"155341",title:"Ph.D.",name:"Edilma",middleName:"Pereira",surname:"Gonçalves",fullName:"Edilma Gonçalves",slug:"edilma-goncalves",email:"edilma@uag.ufrpe.br",position:null,institution:null},{id:"155343",title:"M.Sc.",name:"Abraão",middleName:"Cícero Da",surname:"Silva",fullName:"Abraão Silva",slug:"abraao-silva",email:"abraaocicero@yahoo.com.br",position:null,institution:{name:"Federal Rural University of Pernambuco",institutionURL:null,country:{name:"Brazil"}}},{id:"167355",title:"Dr.",name:"Valderez",middleName:null,surname:"Matos",fullName:"Valderez Matos",slug:"valderez-matos",email:"vpmatos@ig.com.br",position:null,institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Production of soybeans in Northeast Brazil",level:"1"},{id:"sec_3",title:"3. Edaphoclimatic Factors",level:"1"},{id:"sec_4",title:"4. Conclusion ",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKiihl\n\t\t\t\t\t\t\tR. A. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiranda\n\t\t\t\t\t\t\tM. A. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCampelo\n\t\t\t\t\t\t\tG. J. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tSoybean breeding for low latitude regions.\n\t\t\t\t\tQUEIRÓZ, M. A. de; GOEDERT, C.O.; RAMOS, S.R.R. (Ed.). Genetic Resources and Plant Breeding for the Brazilian Northeast. (on line). Versão 1.0. Petrolina-PE: Embrapa Semi-Árido/Brasília-DF: Embrapa Recursos Genéticos e Biotecnologia\n\t\t\t\t\tnov\n\t\t\t\t\tDisponível via Word Wide Web\n\t\t\t\t\thttp://www.cpatsa.embrapa.br\n\t\t\t\t\n\t\t\t'},{id:"B2",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonato\n\t\t\t\t\t\t\tE. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000\n\t\t\t\t\tStress in soybean.\n\t\t\t\t\tPasso Fundo: EMBRAPA Trigo\n\t\t\t\t\t254\n\t\t\t\t\n\t\t\t'},{id:"B3",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCampelo\n\t\t\t\t\t\t\tG. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKiihl\n\t\t\t\t\t\t\tR. A. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998\n\t\t\t\t\tSoybean: development for low latitude regions.\n\t\t\t\t\tTeresina: Embrapa Meio-Norte\n\t\t\t\t\t36\n\t\t\t\t\t(Embrapa Meio-Norte. Documentos, 37)\n\t\t\t\t\n\t\t\t'},{id:"B4",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCampelo\n\t\t\t\t\t\t\tG. J. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKiihl\n\t\t\t\t\t\t\tR. A. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tMorphological and agronomic characteristics of soybean cultivars developed for the low latitude regions.\n\t\t\t\t\tQUEIRÓZ, M. A. de; GOEDERT, C.O.; RAMOS, S.R.R. (Ed.). Genetic Resources and Plant Breeding for the Brazilian Northeast. (on line). Versão 1.0. Petrolina-PE: Embrapa Semi-Árido/Brasília-DF: Embrapa Recursos Genéticos e Biotecnologia\n\t\t\t\t\tnov\n\t\t\t\t\t Disponível via Word Wide Web\n\t\t\t\t\thttp://www.cpatsa.embrapa.br\n\t\t\t\t\n\t\t\t'},{id:"B5",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarvalho\n\t\t\t\t\t\t\tH. W. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOliveira\n\t\t\t\t\t\t\tI. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarcia\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFeitosa\n\t\t\t\t\t\t\tL. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRodrigues\n\t\t\t\t\t\t\tC. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMenezes\n\t\t\t\t\t\t\tA. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelo\n\t\t\t\t\t\t\tK. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009\n\t\t\t\t\tEvaluation of the agronomic performance of soybean cultivars in the rugged area of the states of Bahia and Sergipe.\n\t\t\t\t\tAracajú. Comunicado técnico.\n\t\t\t\t\thttp://www.cpatc.embrapa.br/publicacoes_2010/cot_91.pdf\n\t\t\t\t\taccessed: 01 de may de 2012\n\t\t\t\t\n\t\t\t'},{id:"B6",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCastro\n\t\t\t\t\t\t\tA. A. J. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997\n\t\t\t\t\tCharacteristics of the vegetation of the Mid-North.\n\t\t\t\t\tCERRADOS SYMPOSIUM ON THE MID-NORTH, 1997. Teresina. Anais... Teresina: Embrapa/Meio-Norte\n\t\t\t\t\t45\n\t\t\t\t\t56\n\t\t\t\t\n\t\t\t'},{id:"B7",body:'\n\t\t\t\t\n\t\t\t\t\tCompanhia Nacional de Abastecimento.\n\t\t\t\t\t2012\n\t\t\t\t\tCONAB:Raising production and productivity in Brazil.\n\t\t\t\t\thttp://www.conab.gov.br/OlalaCMS/uploads/arquivos/12_04_11_15_04_18_boletimabril_2012.pdf\n\t\t\t\t\taccessed: june\n\t\t\t\t\n\t\t\t'},{id:"B8",body:'\n\t\t\t\t\n\t\t\t\t\tCompanhia Nacional de Abastecimento- CONAB.\n\t\t\t\t\t2010\n\t\t\t\t\tMonitoring of the Brazilian harvest: grains, the sixth survey\n\t\t\t\t\tMarch 2010/ Brasília\n\t\t\t\t\t42\n\t\t\t\t\n\t\t\t'},{id:"B9",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCruz\n\t\t\t\t\t\t\tT. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeixoto\n\t\t\t\t\t\t\tC. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartins\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010\n\t\t\t\t\tGrowth and yield of soybean at different planting dates in western Bahia.\n\t\t\t\t\t Scientia Agraria, Curitiba\n\t\t\t\t\t11\n\t\t\t\t\t1\n\t\t\t\t\t033\n\t\t\t\t\t042\n\t\t\t\t\tJan./Feb\n\t\t\t\t\n\t\t\t'},{id:"B10",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDias\n\t\t\t\t\t\t\tF. T. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPitombeira\n\t\t\t\t\t\t\tJ. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTeofilo\n\t\t\t\t\t\t\tE. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarbosa\n\t\t\t\t\t\t\tF. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009\n\t\t\t\t\tAdaptability and phenotypic stability for the character grain yield in soybean cultivars for the State of Ceará.\n\t\t\t\t\tRevista Ciência Agronômica, Fortaleza, 40\n\t\t\t\t\t1\n\t\t\t\t\t129\n\t\t\t\t\t134\n\t\t\t\t\tjan-mar\n\t\t\t\t\n\t\t\t'},{id:"B11",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDossa\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tContini\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tÁvila\n\t\t\t\t\t\t\tA. F. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1986\n\t\t\t\t\tThe allocation of resources and profitability of the National Center for Soybean Research.\n\t\t\t\t\t Londrina, EMBRAPA, CNPS, (EMBRAPA-CNPS. Documentos, 26)\n\t\t\t\t\t35\n\t\t\t\t\n\t\t\t'},{id:"B12",body:'\n\t\t\t\t\n\t\t\t\t\tEMBRAPA, Empresa Brasileira de Pesquisa Agropecuária.\n\t\t\t\t\t2010\n\t\t\t\t\tSoybean production technologies central Brazil in 2011.\n\t\t\t\t\tLondrina, PR: Embrapa Soja: Embrapa Cerrados: Embrapa Agropecuária Oeste\n\t\t\t\t\t255\n\t\t\t\t\n\t\t\t'},{id:"B13",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tJ. R. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAssad\n\t\t\t\t\t\t\tE. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tI. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvangelista\n\t\t\t\t\t\t\tB. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLazzarotto\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeumaier\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNepomuceno\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001\n\t\t\t\t\tCharacterization of risk of drought in the soybean growing regions in Brazil.\n\t\t\t\t\tRevista Brasileira de Agrometeorologia, Passo Fundo\n\t\t\t\t\t9\n\t\t\t\t\t3\n\t\t\t\t\t(N#Special: Agricultural Zoning)\n\t\t\t\t\t415\n\t\t\t\t\t421\n\t\t\t\t\n\t\t\t'},{id:"B14",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFarias\n\t\t\t\t\t\t\tJ. R. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNepomuceno\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeumaier\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007\n\t\t\t\t\tEcophysiology soybean.\n\t\t\t\t\tEMBRAPA/Soja, Londrina\n\t\t\t\t\t9\n\t\t\t\t\t(Circular Técnica, 48)\n\t\t\t\t\n\t\t\t'},{id:"B15",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFieltz\n\t\t\t\t\t\t\tM. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRangel\n\t\t\t\t\t\t\tM. A. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004\n\t\t\t\t\tEffect of water stress and photoperiod on the yield of soybean planted in Dourados, MS.\n\t\t\t\t\tDourados: Embrapa Agropecuária Oeste\n\t\t\t\t\t5\n\t\t\t\t\t(Embrapa Agropecuária Oeste. Comunicado Técnico, 89)\n\t\t\t\t\n\t\t\t'},{id:"B16",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFloss\n\t\t\t\t\t\t\tE. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004\n\t\t\t\t\tPhysiology of crop plants: a study that is behind what you see.\n\t\t\t\t\t Passo Fundo: UPF\n\t\t\t\t\t536\n\t\t\t\t\n\t\t\t'},{id:"B17",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFreitas\n\t\t\t\t\t\t\tM. C. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011\n\t\t\t\t\tThe soybean crop in Brazil: the growth of Brazilian production and the emergence of a new agricultural frontier.\n\t\t\t\t\t EnciclopédiaBiosfera, Goiânia\n\t\t\t\t\t7\n\t\t\t\t\t12\n\t\t\t\t\n\t\t\t'},{id:"B18",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrota\n\t\t\t\t\t\t\tA. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCampelo\n\t\t\t\t\t\t\tG. J. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tEvolution and prospects of soybean production in the Middle-North region of Brazil.\n\t\t\t\t\tQUEIRÓZ, M. A. de; GOEDERT, C.O.; RAMOS, S.R.R. (Ed.). Genetic Resources and Plant Breeding for the Brazilian Northeast. (on line). Versão 1.0. Petrolina-PE: Embrapa Semi-Árido/Brasília-DF: Embrapa Recursos Genéticos e Biotecnologia\n\t\t\t\t\tnov\n\t\t\t\t\t Disponível via Word Wide Web\n\t\t\t\t\thttp://www.cpatsa.embrapa.br.\n\t\t\t\t\n\t\t\t'},{id:"B19",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuerra\n\t\t\t\t\t\t\tE. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDestro\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiranda\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMontalvan\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tPerformance of foodtype genotypes and their possibility for adaptation to Brazilian latitudes.\n\t\t\t\t\tPesquisa Agropecuária Brasileira, Brasília, 34\n\t\t\t\t\t4\n\t\t\t\t\t575\n\t\t\t\t\t583\n\t\t\t\t\n\t\t\t'},{id:"B20",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHartwig\n\t\t\t\t\t\t\tE. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKliihl\n\t\t\t\t\t\t\tR. A. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1979\n\t\t\t\t\tIdentification and utilization of a delayed flowering character in soybean for short-day conditions.\n\t\t\t\t\tField Crop Research.\n\t\t\t\t\t2\n\t\t\t\t\t145\n\t\t\t\t\t51\n\t\t\t\t\n\t\t\t'},{id:"B21",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLarcher\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004\n\t\t\t\t\tEnvironmental influences on growth and on development.\n\t\t\t\t\tLARCHER, W. Plant ecophysiology. São Carlos: RiMa\n\t\t\t\t\t531\n\t\t\t\t\n\t\t\t'},{id:"B22",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMarchiori\n\t\t\t\t\t\t\tL. F. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCamara\n\t\t\t\t\t\t\tG. M. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeixoto\n\t\t\t\t\t\t\tC. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartins\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tVegetative performance of soybean cultivars in normal times and off-season.\n\t\t\t\t\tScientia Agricola, Piracicaba\n\t\t\t\t\t56\n\t\t\t\t\t2\n\t\t\t\t\t383\n\t\t\t\t\t390\n\t\t\t\t\n\t\t\t'},{id:"B23",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiranda\n\t\t\t\t\t\t\tM. A. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKiihl\n\t\t\t\t\t\t\tR. A. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCampello\n\t\t\t\t\t\t\tG. J. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlepker\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tCultivar BRSMA BABAÇU.\n\t\t\t\t\tSOYBEAN RESEARCH MEETING OF THE CENTRAL REGION OF BRAZIL, 2. Dourados, MS. Abstract... Dourados: Embrapa Agropecuária Oeste, Londrina: Embrapa Soja, 1999\n\t\t\t\t\t (Embrapa Agropecuária Oeste. Documentos, 7, Embrapa Soja. Documentos, 134)\n\t\t\t\t\t202\n\t\t\t\t\t247\n\t\t\t\t\n\t\t\t'},{id:"B24",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiyasaka\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuimaraes\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKiihl\n\t\t\t\t\t\t\tR. S. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLovadini\n\t\t\t\t\t\t\tL. A. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDematte\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1970\n\t\t\t\t\tSoybean varieties indifferent to photoperiodism and tolerant to low temperatures.\n\t\t\t\t\tBragantia, Campinas\n\t\t\t\t\t29\n\t\t\t\t\n\t\t\t'},{id:"B25",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMondine\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVieira\n\t\t\t\t\t\t\tC. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCambraia\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001\n\t\t\t\t\tSeeding time: an important factor affecting the productivity of soybean.\n\t\t\t\t\tDourados: Embrapa Agropecuária Oeste\n\t\t\t\t\t16\n\t\t\t\t\t(Embrapa Agropecuária Oeste. Documentos, 34)\n\t\t\t\t\n\t\t\t'},{id:"B26",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoreira\n\t\t\t\t\t\t\tJ. U. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLambert\n\t\t\t\t\t\t\tE. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPereira\n\t\t\t\t\t\t\tM. J. Z.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeyer\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlepker\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMontalvan\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPipolo\n\t\t\t\t\t\t\tA. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToledo\n\t\t\t\t\t\t\tJ. F. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaster\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArias\n\t\t\t\t\t\t\tC. A. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarneiro\n\t\t\t\t\t\t\tG. E. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOliveira\n\t\t\t\t\t\t\tM. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSoares\n\t\t\t\t\t\t\tR. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlmeida\n\t\t\t\t\t\t\tA. M. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDias\n\t\t\t\t\t\t\tW. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarrao-Panizzi\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAbdelnoor\n\t\t\t\t\t\t\tR. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrogin\n\t\t\t\t\t\t\tR. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tArantes\n\t\t\t\t\t\t\tN. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMello\n\t\t\t\t\t\t\tFilho. O. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEl -Husny\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGianluppi\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008\n\t\t\t\t\tCultivar BRS 278RR: indication for cultivation in the south of Maranhão, Piauí southwestern and northern Tocantins.\n\t\t\t\t\tXXX Soybean Research Meeting of the Central Region of Brazil.- Londrina: EmbrapaSoja\n\t\t\t\t\t173\n\t\t\t\t\t174\n\t\t\t\t\n\t\t\t'},{id:"B27",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMundstock\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005\n\t\t\t\t\tSoybeans: factors affecting growth and yield.\n\t\t\t\t\t Department of crop plants, Federal University of Rio Grande doSul: EVANGRAF\n\t\t\t\t\t31\n\t\t\t\t\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNeves\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011\n\t\t\t\t\tAgronomic performance of soybean under low latitude in Teresina-PI.\n\t\t\t\t\tDissertação. Teresina\n\t\t\t\t\t94\n\t\t\t\t\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPereira\n\t\t\t\t\t\t\tM. J. Z.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlepker\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoreira\n\t\t\t\t\t\t\tJ. U. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011\n\t\t\t\t\tSoybean varieties, northern and northeastern Brazil.\n\t\t\t\t\tEmbrapa soja, Londrina\n\t\t\t\t\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPortugal\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPeixoto\n\t\t\t\t\t\t\tC. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCosta\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCristina\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000\n\t\t\t\t\tLight intensity and water regime in dry matter accumulation of soybean plants potted [Glycine max (L.) Merril].\n\t\t\t\t\tAnais... Brazilian Meeting on management and conservation of soil and water. Ilhéus, CD-Room\n\t\t\t\t\n\t\t\t'},{id:"B31",body:'\n\t\t\t\t\n\t\t\t\t\tPotafos, Brazilian Association for Research and Potash Phosphate.\n\t\t\t\t\t1997\n\t\t\t\t\tAs the soybean plant develops.\n\t\t\t\t\tPiracicaba\n\t\t\t\t\t20\n\t\t\t\t\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPrado\n\t\t\t\t\t\t\tE. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHiromoto\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodinho\n\t\t\t\t\t\t\tV. P. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tUtumi\n\t\t\t\t\t\t\tM. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRamalho\n\t\t\t\t\t\t\tA. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001\n\t\t\t\t\tAdaptability and stability of soybean cultivars in five planting seasons in Rondônia cerrado.\n\t\t\t\t\tPesquisa Agropecuária Brasileira, Brasília\n\t\t\t\t\t36\n\t\t\t\t\t4\n\t\t\t\t\t625\n\t\t\t\t\t635\n\t\t\t\t\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPriolli\n\t\t\t\t\t\t\tR. H. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMendes-Junior\n\t\t\t\t\t\t\tC. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSousa\n\t\t\t\t\t\t\tS. M. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSousa\n\t\t\t\t\t\t\tN. E. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tContel\n\t\t\t\t\t\t\tE. P. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004\n\t\t\t\t\tGenetic diversity of soybean in time and among breeding programs in Brazil.\n\t\t\t\t\tPesquisa Agropecuária Brasileira, Brasília\n\t\t\t\t\t39\n\t\t\t\t\t10\n\t\t\t\t\t967\n\t\t\t\t\t975\n\t\t\t\t\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRodrigues\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDidonet\n\t\t\t\t\t\t\tA. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLhamby\n\t\t\t\t\t\t\tJ. C. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBertagnolli\n\t\t\t\t\t\t\tP. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuz\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001\n\t\t\t\t\tQuantitative response of soybean flowering to temperature and photoperiod.\n\t\t\t\t\tPesquisa Agropecuária Brasileira, Brasília\n\t\t\t\t\t36\n\t\t\t\t\t3\n\t\t\t\t\t431\n\t\t\t\t\t437\n\t\t\t\t\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSediyama\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009\n\t\t\t\t\tTechnology of production and use of soy.\n\t\t\t\t\tLondrina, Mecenas\n\t\t\t\t\t314\n\t\t\t\t\n\t\t\t'},{id:"B36",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDa Silva\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAssad\n\t\t\t\t\t\t\tE. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001\n\t\t\t\t\tClimatic risks zoning for upland rice in the states of Goias, Mato Grosso, Mato Grosso do Sul, Minas Gerais, Tocantins and Bahia.\n\t\t\t\t\tRevista Brasileira de Agrometeorologia, Passo Fundo\n\t\t\t\t\t9\n\t\t\t\t\t3\n\t\t\t\t\t(n#Special: Agricultural Zoning)\n\t\t\t\t\t536\n\t\t\t\t\t543\n\t\t\t\t\n\t\t\t'},{id:"B37",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpehar\n\t\t\t\t\t\t\tC. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tBreeding soybeans to the latitudes of Brazilian cerrados (savannahs)\n\t\t\t\t\tPesquisa Agropecuária Brasileira, Brasília\n\t\t\t\t\t29\n\t\t\t\t\t8\n\t\t\t\t\t1167\n\t\t\t\t\t1180\n\t\t\t\t\n\t\t\t'},{id:"B38",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaiz\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZeiger\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004\n\t\t\t\t\tplant physiology.\n\t\t\t\t\t 3.ed. Porto Alegre: Artmed\n\t\t\t\t\t613\n\t\t\t\t\n\t\t\t'},{id:"B39",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVehrmann\n\t\t\t\t\t\t\tV. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999\n\t\t\t\t\tLaunch of the soybean cultivar’DM-Sovereign "in Bahia.\n\t\t\t\t\t SOYBEAN RESEARCH MEETING OF THE CENTRAL REGION OF BRAZIL, 2. Dourados, MS. RESUMOS... Dourados: Embrapa Agropecuária Oeste, Londrina: Embrapa Soja, 1999. p247\n\t\t\t\t\t(Embrapa Agropecuária Oeste. Documentos, 7, Embrapa Soja. Documentos, 134)\n\t\t\t\t\t91\n\t\t\t\t\n\t\t\t'},{id:"B40",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tViana\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007\n\t\t\t\t\tCultivars and soybean cropping systems in green Areia-PB.\n\t\t\t\t\t(Doctorate in Agronomy) by the Centre for Agrarian Sciences, Federal University of Paraíba. Areia- PB\n\t\t\t\t\t139\n\t\t\t\t\n\t\t\t'},{id:"B41",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tViana\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBruno\n\t\t\t\t\t\t\tR. L. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMendonca\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoncalves\n\t\t\t\t\t\t\tE. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlves\n\t\t\t\t\t\t\tE. U.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBraga Jr\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009a\n\t\t\t\t\tPrecocity of soybean in cropping systems with maize in sand, State of Paraiba.\n\t\t\t\t\tActa Scientiarum Agronomy\n\t\t\t\t\t31\n\t\t\t\t\t3\n\t\t\t\t\t481\n\t\t\t\t\t488\n\t\t\t\t\n\t\t\t'},{id:"B42",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tViana\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBruno\n\t\t\t\t\t\t\tR. L. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSantos\n\t\t\t\t\t\t\tH. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSilva\n\t\t\t\t\t\t\tI. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOliveira\n\t\t\t\t\t\t\tA. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBraga Jr\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009b\n\t\t\t\t\tDry weight of green soybean cropping systems with corn.\n\t\t\t\t\t Scientia Agraria, Curitiba\n\t\t\t\t\t10\n\t\t\t\t\t5\n\t\t\t\t\t413\n\t\t\t\t\t418\n\t\t\t\t\n\t\t\t'},{id:"B43",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYokomizo\n\t\t\t\t\t\t\tG. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDuarte\n\t\t\t\t\t\t\tJ. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVello\n\t\t\t\t\t\t\tN. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000\n\t\t\t\t\tCorrelations between grain size and other characters in topcrosses soybean type food with grain type.\n\t\t\t\t\tPesquisa Agropecuária Brasileira, Brasília\n\t\t\t\t\t35\n\t\t\t\t\t11\n\t\t\t\t\t2235\n\t\t\t\t\t2241\n\t\t\t\t\n\t\t\t'},{id:"B44",body:'\n\t\t\t\tMoraes, AVC, Camargo, MBP, Mascarenhas, HAA, Miranda, MAC & Perera, JCVNA (1998). Testing and analysis of agrometeorological models to estimate yield for the soybean crop in the region of Ribeirão Preto. Bragantia, Campinas, 57 (2), 393-406.\n\t\t\t\t\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Jeandson Silva Viana",address:"jeandson@uag.ufrpe.br, edilma@uag.ufrpe.br, abraaocicero@yahoo.com.br, vpmatos@ig.com.br",affiliation:'
Unidade Acadêmica de Garanhuns, Universidade Federal Rural de \nPernambuco, Brazil
Departamento de Fitotecnia, Universidade Federal Rural de \nPernambuco, Brazil
'}],corrections:null},book:{id:"3245",title:"A Comprehensive Survey of International Soybean Research",subtitle:"Genetics, Physiology, Agronomy and Nitrogen Relationships",fullTitle:"A Comprehensive Survey of International Soybean Research - Genetics, Physiology, Agronomy and Nitrogen Relationships",slug:"a-comprehensive-survey-of-international-soybean-research-genetics-physiology-agronomy-and-nitrogen-relationships",publishedDate:"January 2nd 2013",bookSignature:"James E. Board",coverURL:"https://cdn.intechopen.com/books/images_new/3245.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"28828",title:"Prof.",name:"James",middleName:null,surname:"Board",slug:"james-board",fullName:"James Board"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"41170",title:"A Proteomics Approach to Study Soybean and Its Symbiont Bradyrhizobium japonicum –A Review",slug:"a-proteomics-approach-to-study-soybean-and-its-symbiont-bradyrhizobium-japonicum-a-review",totalDownloads:2402,totalCrossrefCites:4,signatures:"Sowmyalakshmi Subramanian and Donald L. Smith",authors:[{id:"153862",title:"Dr",name:"Donald",middleName:null,surname:"Smith",fullName:"Donald Smith",slug:"donald-smith"},{id:"153863",title:"Dr.",name:"Sowmya",middleName:null,surname:"Subramanian",fullName:"Sowmya Subramanian",slug:"sowmya-subramanian"}]},{id:"41171",title:"The Development and Regulation of Soybean Nodules",slug:"the-development-and-regulation-of-soybean-nodules",totalDownloads:2597,totalCrossrefCites:1,signatures:"Brett James Ferguson",authors:[{id:"153283",title:"Dr.",name:"Brett",middleName:null,surname:"Ferguson",fullName:"Brett Ferguson",slug:"brett-ferguson"}]},{id:"37899",title:"Soybean as a Nitrogen Supplier",slug:"soybean-as-a-nitrogen-supplier",totalDownloads:2137,totalCrossrefCites:1,signatures:"Matsumiya Yoshiki, Horii Sachie, Matsuno Toshihide and Kubo Motoki",authors:[{id:"33767",title:"Prof.",name:"Motoki",middleName:null,surname:"Kubo",fullName:"Motoki Kubo",slug:"motoki-kubo"}]},{id:"38695",title:"How to Increase the Productivity of the Soybean-Rhizobial Symbiosis",slug:"how-to-increase-the-productivity-of-the-soybean-rhizobial-symbiosis",totalDownloads:1695,totalCrossrefCites:1,signatures:"Denis M. Sytnikov",authors:[{id:"32488",title:"Dr.",name:"Denis",middleName:"M.",surname:"Sytnikov",fullName:"Denis Sytnikov",slug:"denis-sytnikov"}]},{id:"41724",title:"Inoculation Methods of Bradyrhizobium japonicum on Soybean in South-West Area of Japan",slug:"inoculation-methods-of-bradyrhizobium-japonicum-on-soybean-in-south-west-area-of-japan",totalDownloads:2009,totalCrossrefCites:2,signatures:"Takeo Yamakawa and Yuichi Saeki",authors:[{id:"153004",title:"Dr.",name:"Takeo",middleName:null,surname:"Yamakawa",fullName:"Takeo Yamakawa",slug:"takeo-yamakawa"}]},{id:"40085",title:"Soybean Seed Production and Nitrogen Nutrition",slug:"soybean-seed-production-and-nitrogen-nutrition",totalDownloads:3162,totalCrossrefCites:13,signatures:"Takuji Ohyama, Ritsuko Minagawa, Shinji Ishikawa, Misaki Yamamoto, Nguyen Van Phi Hung, Norikuni Ohtake, Kuni Sueyoshi, Takashi Sato, Yoshifumi Nagumo and Yoshihiko Takahashi",authors:[{id:"30061",title:"Prof.",name:"Takuji",middleName:null,surname:"Ohyama",fullName:"Takuji Ohyama",slug:"takuji-ohyama"}]},{id:"37937",title:"The Comparative Advantage of Soybean Production in Vietnam: A Policy Analysis Matrix Approach",slug:"the-comparative-advantage-of-soybean-production-in-vietnam-a-policy-analysis-matrix-approach",totalDownloads:2111,totalCrossrefCites:0,signatures:"Huynh Viet Khai and Mitsuyasu Yabe",authors:[{id:"152248",title:"Dr.",name:"Huynh",middleName:null,surname:"Viet Khai",fullName:"Huynh Viet Khai",slug:"huynh-viet-khai"}]},{id:"40089",title:"Molecular Design of Soybean Lipoxygenase Inhibitors Based on Natural Products",slug:"molecular-design-of-soybean-lipoxygenase-inhibitors-based-on-natural-products",totalDownloads:1917,totalCrossrefCites:0,signatures:"Isao Kubo, Tae Joung Ha and Kuniyoshi Shimizu",authors:[{id:"153359",title:"Prof.",name:"Isao",middleName:null,surname:"Kubo",fullName:"Isao Kubo",slug:"isao-kubo"},{id:"166028",title:"Dr.",name:"Kuniyoshi",middleName:null,surname:"Shimizu",fullName:"Kuniyoshi Shimizu",slug:"kuniyoshi-shimizu"}]},{id:"40088",title:"Challenges to Increased Soybean Production in Brazil",slug:"challenges-to-increased-soybean-production-in-brazil",totalDownloads:1566,totalCrossrefCites:0,signatures:"Hilton S. Pinto, Ana Maria H. de Avila and Andrea O. Cardoso",authors:[{id:"137898",title:"Dr.",name:"Hilton",middleName:null,surname:"Silveira Pinto",fullName:"Hilton Silveira Pinto",slug:"hilton-silveira-pinto"}]},{id:"40090",title:"Drought Stress and Tolerance in Soybean",slug:"drought-stress-and-tolerance-in-soybean",totalDownloads:5347,totalCrossrefCites:14,signatures:"Yee-Shan Ku, Wan-Kin Au-Yeung, Yuk-Lin Yung, Man-Wah Li, Chao-Qing Wen, Xueyi Liu and Hon-Ming Lam",authors:[{id:"18448",title:"Prof.",name:"Hon-Ming",middleName:null,surname:"Lam",fullName:"Hon-Ming Lam",slug:"hon-ming-lam"},{id:"21943",title:"Mr.",name:"Man-Wah",middleName:null,surname:"Li",fullName:"Man-Wah Li",slug:"man-wah-li"},{id:"154164",title:"Ms.",name:"Yee Shan",middleName:null,surname:"Ku",fullName:"Yee Shan Ku",slug:"yee-shan-ku"},{id:"154165",title:"Ms.",name:"Yuk Lin",middleName:null,surname:"Yung",fullName:"Yuk Lin Yung",slug:"yuk-lin-yung"},{id:"154166",title:"Ms.",name:"Chao Qing",middleName:null,surname:"Wen",fullName:"Chao Qing Wen",slug:"chao-qing-wen"},{id:"154167",title:"Prof.",name:"Xueyi",middleName:null,surname:"Liu",fullName:"Xueyi Liu",slug:"xueyi-liu"},{id:"164136",title:"Dr.",name:"Wan-Kin",middleName:null,surname:"Au-Yeung",fullName:"Wan-Kin Au-Yeung",slug:"wan-kin-au-yeung"},{id:"164755",title:"Mr.",name:"Wan-Kin",middleName:null,surname:"Au-Yeung",fullName:"Wan-Kin Au-Yeung",slug:"wan-kin-au-yeung"}]},{id:"40086",title:"Biologically Active Constituents of Soybean",slug:"biologically-active-constituents-of-soybean",totalDownloads:1954,totalCrossrefCites:0,signatures:"Tzi Bun Ng, Randy Chi Fai Cheung and Jack Ho Wong",authors:[{id:"21099",title:"Prof.",name:"Tzi-Bun",middleName:null,surname:"Ng",fullName:"Tzi-Bun Ng",slug:"tzi-bun-ng"},{id:"166185",title:"Dr.",name:"Jack Ho",middleName:null,surname:"Wong",fullName:"Jack Ho Wong",slug:"jack-ho-wong"}]},{id:"40082",title:"Cell Death Signaling From the Endoplasmic Reticulum in Soybean",slug:"cell-death-signaling-from-the-endoplasmic-reticulum-in-soybean",totalDownloads:1366,totalCrossrefCites:0,signatures:"Pedro A.B. Reis and Elizabeth P. B. Fontes",authors:[{id:"21426",title:"Prof.",name:"Elizabeth",middleName:null,surname:"Fontes",fullName:"Elizabeth Fontes",slug:"elizabeth-fontes"},{id:"152998",title:"M.Sc.",name:"Pedro",middleName:null,surname:"Reis",fullName:"Pedro Reis",slug:"pedro-reis"}]},{id:"40862",title:"Soybean Under Water Deficit: Physiological and Yield Responses",slug:"soybean-under-water-deficit-physiological-and-yield-responses",totalDownloads:3335,totalCrossrefCites:3,signatures:"Gustavo M. Souza, Tiago A. Catuchi, Suzana C. Bertolli and Rogerio P. Soratto",authors:[{id:"152492",title:"Dr.",name:"Gustavo",middleName:null,surname:"Souza",fullName:"Gustavo Souza",slug:"gustavo-souza"},{id:"164331",title:"MSc.",name:"Suzana",middleName:null,surname:"Bertolli",fullName:"Suzana Bertolli",slug:"suzana-bertolli"},{id:"164333",title:"MSc.",name:"Tiago",middleName:null,surname:"Catuchi",fullName:"Tiago Catuchi",slug:"tiago-catuchi"},{id:"164334",title:"Dr.",name:"Rogerio",middleName:null,surname:"Soratto",fullName:"Rogerio Soratto",slug:"rogerio-soratto"}]},{id:"37907",title:"Interaction of Photosynthetic Source-Sink Balance and Activities of Membrane H+ Pumps in Soybean",slug:"interaction-of-photosynthetic-source-sink-balance-and-activities-of-membrane-h-pumps-in-soybean",totalDownloads:1886,totalCrossrefCites:0,signatures:"Minobu Kasai and Wataru Takahashi",authors:[{id:"29226",title:"Dr.",name:"Minobu",middleName:null,surname:"Kasai",fullName:"Minobu Kasai",slug:"minobu-kasai"}]},{id:"41626",title:"Soybean Urease: Over a Hundred Years of Knowledge",slug:"soybean-urease-over-a-hundred-years-of-knowledge",totalDownloads:2286,totalCrossrefCites:1,signatures:"Rafael Real-Guerra, Fernanda Stanisçuaski and Célia Regina Carlini",authors:[{id:"153183",title:"Prof.",name:"Celia R.",middleName:null,surname:"Carlini",fullName:"Celia R. Carlini",slug:"celia-r.-carlini"},{id:"153186",title:"Dr.",name:"Rafael",middleName:null,surname:"Real-Guerra",fullName:"Rafael Real-Guerra",slug:"rafael-real-guerra"},{id:"163380",title:"Dr.",name:"Fernanda",middleName:null,surname:"Stanisçuaski",fullName:"Fernanda Stanisçuaski",slug:"fernanda-staniscuaski"}]},{id:"38718",title:"Explanations for the Rise of Soybean in Brazil",slug:"explanations-for-the-rise-of-soybean-in-brazil",totalDownloads:2298,totalCrossrefCites:1,signatures:"Eduardo Antonio Gavioli",authors:[{id:"33036",title:"Dr.",name:"Eduardo Antonio",middleName:null,surname:"Gavioli",fullName:"Eduardo Antonio Gavioli",slug:"eduardo-antonio-gavioli"}]},{id:"41451",title:"Climatic Restrictions for Maximizing Soybean Yields",slug:"climatic-restrictions-for-maximizing-soybean-yields",totalDownloads:1540,totalCrossrefCites:1,signatures:"Ana Maria Heuminski de Avila, José Renato Bouças Farias, Hilton Silveira Pinto and Felipe Gustavo Pilau",authors:[{id:"137897",title:"PhD.",name:"Ana Maria",middleName:null,surname:"Heuminski De Avila",fullName:"Ana Maria Heuminski De Avila",slug:"ana-maria-heuminski-de-avila"}]},{id:"41620",title:"Climatic Conditions and Production of Soybean in Northeastern Brazil",slug:"climatic-conditions-and-production-of-soybean-in-northeastern-brazil",totalDownloads:2089,totalCrossrefCites:0,signatures:"Jeandson Silva Viana, Edilma Pereira Gonçalves, Abraão Cicero Silva and Valderez Pontes Matos",authors:[{id:"155340",title:"Dr.",name:"Jeandson",middleName:"Silva",surname:"Viana",fullName:"Jeandson Viana",slug:"jeandson-viana"},{id:"155341",title:"Ph.D.",name:"Edilma",middleName:"Pereira",surname:"Gonçalves",fullName:"Edilma Gonçalves",slug:"edilma-goncalves"},{id:"155343",title:"M.Sc.",name:"Abraão",middleName:"Cícero Da",surname:"Silva",fullName:"Abraão Silva",slug:"abraao-silva"},{id:"167355",title:"Dr.",name:"Valderez",middleName:null,surname:"Matos",fullName:"Valderez Matos",slug:"valderez-matos"}]},{id:"39382",title:"Soybean Proteomics: Applications and Challenges",slug:"soybean-proteomics-applications-and-challenges",totalDownloads:1576,totalCrossrefCites:0,signatures:"Alka Dwevedi and Arvind M Kayastha",authors:[{id:"18216",title:"Prof.",name:"Arvind",middleName:"M.",surname:"Kayastha",fullName:"Arvind Kayastha",slug:"arvind-kayastha"},{id:"21064",title:"Dr.",name:"Alka",middleName:null,surname:"Dwevedi",fullName:"Alka Dwevedi",slug:"alka-dwevedi"}]},{id:"41172",title:"In vitro Regeneration and Genetic Transformation of Soybean: Current Status and Future Prospects",slug:"in-vitro-regeneration-and-genetic-transformation-of-soybean-current-status-and-future-prospects",totalDownloads:2272,totalCrossrefCites:1,signatures:"Thankaraj Salammal Mariashibu, Vasudevan Ramesh Anbazhagan, Shu-Ye Jiang, Andy Ganapathi and Srinivasan Ramachandran",authors:[{id:"153343",title:"Dr.",name:"Srinivasan",middleName:null,surname:"Ramachandran",fullName:"Srinivasan Ramachandran",slug:"srinivasan-ramachandran"}]},{id:"41173",title:"Advancements in Transgenic Soy: From Field to Bedside",slug:"advancements-in-transgenic-soy-from-field-to-bedside",totalDownloads:2227,totalCrossrefCites:2,signatures:"Laura C. Hudson, Kevin C. Lambirth, Kenneth L. Bost and Kenneth J. Piller",authors:[{id:"19743",title:"Dr.",name:"Kenneth J.",middleName:null,surname:"Piller",fullName:"Kenneth J. Piller",slug:"kenneth-j.-piller"},{id:"20579",title:"Dr.",name:"Kenneth L.",middleName:null,surname:"Bost",fullName:"Kenneth L. Bost",slug:"kenneth-l.-bost"},{id:"22101",title:"Dr.",name:"Laura C.",middleName:null,surname:"Hudson",fullName:"Laura C. Hudson",slug:"laura-c.-hudson"},{id:"153481",title:"Mr.",name:"Kevin C.",middleName:null,surname:"Lambirth",fullName:"Kevin C. Lambirth",slug:"kevin-c.-lambirth"}]},{id:"37748",title:"Functional Diversity of Early Responsive to Dehydration (ERD) Genes in Soybean",slug:"functional-diversity-of-early-responsive-to-dehydration-erd-genes-in-soybean",totalDownloads:1976,totalCrossrefCites:1,signatures:"Murilo Siqueira Alves and Luciano Gomes Fietto",authors:[{id:"152493",title:"PhD.",name:"Luciano",middleName:null,surname:"Fietto",fullName:"Luciano Fietto",slug:"luciano-fietto"},{id:"153430",title:"MSc.",name:"Murilo",middleName:null,surname:"Alves",fullName:"Murilo Alves",slug:"murilo-alves"}]},{id:"37722",title:"An Overview of Genetic Transformation of Soybean",slug:"an-overview-of-genetic-transformation-of-soybean",totalDownloads:3343,totalCrossrefCites:4,signatures:"Hyeyoung Lee, So-Yon Park and Zhanyuan J. Zhang",authors:[{id:"152319",title:"Dr.",name:"Zhanyuan",middleName:null,surname:"Zhang",fullName:"Zhanyuan Zhang",slug:"zhanyuan-zhang"}]},{id:"38261",title:"Gene Duplication and RNA Silencing in Soybean",slug:"gene-duplication-and-rna-silencing-in-soybean",totalDownloads:2210,totalCrossrefCites:1,signatures:"Megumi Kasai, Mayumi Tsuchiya and Akira Kanazawa",authors:[{id:"153402",title:"Dr.",name:"Akira",middleName:null,surname:"Kanazawa",fullName:"Akira Kanazawa",slug:"akira-kanazawa"}]},{id:"38177",title:"Proteomics and Its Use in Obtaining Superior Soybean Genotypes",slug:"proteomics-and-its-use-in-obtaining-superior-soybean-genotypes",totalDownloads:1955,totalCrossrefCites:0,signatures:"Cristiane Fortes Gris and Alexana Baldoni",authors:[{id:"29582",title:"Prof.",name:"Cristiane",middleName:"Fortes",surname:"Gris",fullName:"Cristiane Gris",slug:"cristiane-gris"},{id:"153438",title:"Ph.D.",name:"Alexana",middleName:null,surname:"Baldoni",fullName:"Alexana Baldoni",slug:"alexana-baldoni"}]},{id:"41318",title:"Use of Organelle Markers to Study Genetic Diversity in Soybean",slug:"use-of-organelle-markers-to-study-genetic-diversity-in-soybean",totalDownloads:2171,totalCrossrefCites:5,signatures:"Lidia Skuza, Ewa Filip and Izabela Szućko",authors:[{id:"153658",title:"Ph.D.",name:"Lidia",middleName:null,surname:"Skuza",fullName:"Lidia Skuza",slug:"lidia-skuza"},{id:"153919",title:"Ph.D.",name:"Ewa",middleName:null,surname:"Filip",fullName:"Ewa Filip",slug:"ewa-filip"},{id:"153920",title:"MSc.",name:"Izabela",middleName:null,surname:"Szućko",fullName:"Izabela Szućko",slug:"izabela-szucko"}]},{id:"40087",title:"Comparative Studies Involving Transgenic and Non-Transgenic Soybean: What is Going On?",slug:"comparative-studies-involving-transgenic-and-non-transgenic-soybean-what-is-going-on-",totalDownloads:1665,totalCrossrefCites:0,signatures:"Marco Aurélio Zezzi Arruda, Ricardo Antunes Azevedo, Herbert de Sousa Barbosa, Lidiane Raquel Verola Mataveli, Silvana Ruella Oliveira, Sandra Cristina Capaldi Arruda and Priscila Lupino Gratão",authors:[{id:"153353",title:"Prof.",name:"Marco",middleName:null,surname:"Arruda",fullName:"Marco Arruda",slug:"marco-arruda"},{id:"153741",title:"Dr.",name:"Herbert",middleName:null,surname:"Barbosa",fullName:"Herbert Barbosa",slug:"herbert-barbosa"},{id:"153743",title:"MSc.",name:"Lidiane",middleName:null,surname:"Mataveli",fullName:"Lidiane Mataveli",slug:"lidiane-mataveli"},{id:"153744",title:"Dr.",name:"Silvana",middleName:"Ruella",surname:"Oliveira",fullName:"Silvana Oliveira",slug:"silvana-oliveira"},{id:"153746",title:"Dr.",name:"Sandra",middleName:null,surname:"Arruda",fullName:"Sandra Arruda",slug:"sandra-arruda"},{id:"153749",title:"Prof.",name:"Ricardo",middleName:null,surname:"Azevedo",fullName:"Ricardo Azevedo",slug:"ricardo-azevedo"},{id:"164014",title:"Dr.",name:"Priscila",middleName:null,surname:"Gratão",fullName:"Priscila Gratão",slug:"priscila-gratao"}]}]},relatedBooks:[{type:"book",id:"3568",title:"Recent Advances in Plant in vitro Culture",subtitle:null,isOpenForSubmission:!1,hash:"830bbb601742c85a3fb0eeafe1454c43",slug:"recent-advances-in-plant-in-vitro-culture",bookSignature:"Annarita Leva and Laura M. R. Rinaldi",coverURL:"https://cdn.intechopen.com/books/images_new/3568.jpg",editedByType:"Edited by",editors:[{id:"142145",title:"Dr.",name:"Annarita",surname:"Leva",slug:"annarita-leva",fullName:"Annarita Leva"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"},chapters:[{id:"40180",title:"Plant Tissue Culture: Current Status and Opportunities",slug:"plant-tissue-culture-current-status-and-opportunities",signatures:"Altaf Hussain, Iqbal Ahmed Qarshi, Hummera Nazir and Ikram Ullah",authors:[{id:"147617",title:"Dr.",name:"Altaf",middleName:null,surname:"Hussain",fullName:"Altaf Hussain",slug:"altaf-hussain"}]},{id:"40181",title:"Plant Tissue Culture Media",slug:"plant-tissue-culture-media",signatures:"Abobkar I.M. Saad and Ahmed M. Elshahed",authors:[{id:"144204",title:"Prof.",name:"Abobkar",middleName:null,surname:"Mohamed",fullName:"Abobkar Mohamed",slug:"abobkar-mohamed"}]},{id:"40186",title:"The Science of Plant Tissue Culture as a Catalyst for Agricultural and Industrial Development in an Emerging Economy",slug:"the-science-of-plant-tissue-culture-as-a-catalyst-for-agricultural-and-industrial-development-in-an-",signatures:"S.E. Aladele, A.U. Okere, E. Jamaldinne , P.T. Lyam, O. Fajimi, A. Adegeye and C.M. Zayas",authors:[{id:"144798",title:"Dr.",name:"Sunday",middleName:null,surname:"Aladele",fullName:"Sunday Aladele",slug:"sunday-aladele"}]},{id:"40187",title:"The Prerequisite of the Success in Plant Tissue Culture: High Frequency Shoot Regeneration",slug:"the-prerequisite-of-the-success-in-plant-tissue-culture-high-frequency-shoot-regeneration",signatures:"Mustafa Yildiz",authors:[{id:"141637",title:"Prof.",name:"Mustafa",middleName:null,surname:"Yildiz",fullName:"Mustafa Yildiz",slug:"mustafa-yildiz"}]},{id:"40182",title:"In vitro Tissue Culture, a Tool for the Study and Breeding of Plants Subjected to Abiotic Stress Conditions",slug:"in-vitro-tissue-culture-a-tool-for-the-study-and-breeding-of-plants-subjected-to-abiotic-stress-cond",signatures:"Rosa Ma Pérez-Clemente and Aurelio Gómez-Cadenas",authors:[{id:"141481",title:"Dr.",name:"Rosa Maria",middleName:null,surname:"Pérez-Clemente",fullName:"Rosa Maria Pérez-Clemente",slug:"rosa-maria-perez-clemente"}]},{id:"40183",title:"Flow Cytometry Applied in Tissue Culture",slug:"flow-cytometry-applied-in-tissue-culture",signatures:"Moacir Pasqual, Leila Aparecida Salles Pio, Ana Catarina Lima Oliveira and Joyce Dória Rodrigues Soares",authors:[{id:"148433",title:"Dr.",name:"Moacir",middleName:null,surname:"Pasqual",fullName:"Moacir Pasqual",slug:"moacir-pasqual"}]},{id:"40179",title:"Somaclonal Variation in Tissue Culture: A Case Study with Olive",slug:"somaclonal-variation-in-tissue-culture-a-case-study-with-olive",signatures:"A.R. Leva, R. Petruccelli and L.M.R. Rinaldi",authors:[{id:"142145",title:"Dr.",name:"Annarita",middleName:null,surname:"Leva",fullName:"Annarita Leva",slug:"annarita-leva"}]},{id:"40196",title:"Tissue Culture Techniques for Native Amazonian Fruit Trees",slug:"tissue-culture-techniques-for-native-amazonian-fruit-trees",signatures:"Moacir Pasqual, Edvan Alves Chagas, Joyce Dória Rodrigues Soares and Filipe Almendagna Rodrigues",authors:[{id:"148433",title:"Dr.",name:"Moacir",middleName:null,surname:"Pasqual",fullName:"Moacir Pasqual",slug:"moacir-pasqual"}]},{id:"40184",title:"Polyamines, Gelling Agents in Tissue Culture, Micropropagation of Medicinal Plants and Bioreactors",slug:"polyamines-gelling-agents-in-tissue-culture-micropropagation-of-medicinal-plants-and-bioreactors",signatures:"Giuseppina Pace Pereira Lima, Renê Arnoux da Silva Campos, Lilia Gomes Willadino, Terezinha J.R. Câmara and Fabio Vianello",authors:[{id:"146379",title:"Prof.",name:"Giuseppina",middleName:null,surname:"Lima",fullName:"Giuseppina Lima",slug:"giuseppina-lima"},{id:"149761",title:"Prof.",name:"Fabio",middleName:null,surname:"Vianello",fullName:"Fabio Vianello",slug:"fabio-vianello"},{id:"149762",title:"MSc.",name:"René",middleName:null,surname:"Campos",fullName:"René Campos",slug:"rene-campos"},{id:"149767",title:"Prof.",name:"Lilia",middleName:null,surname:"Willadino",fullName:"Lilia Willadino",slug:"lilia-willadino"},{id:"149768",title:"Prof.",name:"Terezinha",middleName:null,surname:"Camara",fullName:"Terezinha Camara",slug:"terezinha-camara"}]},{id:"40185",title:"Effect of Additives on Micropropagation of an Endangered Medicinal Tree Oroxylum indicum L. Vent",slug:"effect-of-additives-on-micropropagation-of-an-endangered-medicinal-tree-oroxylum-indicum-l-vent",signatures:"Y.K. Bansal and Mamta Gokhale",authors:[{id:"149283",title:"Prof.",name:"Yogendra",middleName:null,surname:"Bansal",fullName:"Yogendra Bansal",slug:"yogendra-bansal"},{id:"152962",title:"Dr.",name:"Mamta",middleName:null,surname:"Gokhale",fullName:"Mamta Gokhale",slug:"mamta-gokhale"}]},{id:"40188",title:"Production of Useful Secondary Metabolites Through Regulation of Biosynthetic Pathway in Cell and Tissue Suspension Culture of Medicinal Plants",slug:"production-of-useful-secondary-metabolites-through-regulation-of-biosynthetic-pathway-in-cell-and-ti",signatures:"Hu Gaosheng and Jia Jingming",authors:[{id:"145206",title:"Prof.",name:"Jingming",middleName:null,surname:"Jia",fullName:"Jingming Jia",slug:"jingming-jia"}]}]}]},onlineFirst:{chapter:{type:"chapter",id:"72563",title:"Contribution of Gut Microbiome to Human Health and the Metabolism or Toxicity of Drugs and Natural Products",doi:"10.5772/intechopen.92840",slug:"contribution-of-gut-microbiome-to-human-health-and-the-metabolism-or-toxicity-of-drugs-and-natural-p",body:'
1. Introduction
The human gastrointestinal tract has various microorganisms, and “gut microbiota” has received attentions recently because the microbe population living in human intestine has significant effects to human health. Gut microbiota plays important roles in human, involving in many activities in a host body, for example, metabolism of xenobiotic compounds, immune system, nutrition, inflammation, and behavior. The delivery of prebiotics and probiotics to the human gastrointestinal tract, via dietary products or supplements, is one of the tools for management of microbiota in order to improve host health [1]. Moreover, gut microbiome has interactions with drugs and natural products, producing metabolites, which give effects on efficacy, metabolism, and toxicity of drugs. Gut microbiota plays a role in the metabolism of drugs and natural products, as well as nutrients in diet or food. The conversion of a dietary soybean isoflavone, daidzein (1) or genistein (2), to a bioactive compound, S-equol (3) (Figure 1) [2, 3], is a good example for the role of gut bacteria in the production of pharmacologically active agent in human because S-equol (3) is a potent ligand for estrogen receptor β [4]. Daidzein (1) is also derived from its corresponding isoflavone glycoside, daidzin (4), by Bifidobacterium, a representative of major bacterial species of human origin; this bacterium could transform daidzin (4) to daidzein (1) by cell-associated β-glucosidases (Figure 1) [5]. Moreover, O-desmethylangolensin (5) is also found as an intestinal bacterial metabolite of daidzein (1) [6, 7].
Figure 1.
Bioconversion of soybean isoflavones, daidzein (1), genistein (2), and daidzin (4), to S-equol (3) and O-desmethylangolensin (5) by intestinal bacteria.
The transformation of achiral molecule daidzein (1) to a chiral molecule equol, which has one chiral center in its molecule, should provide two possible enantiomers of S-equol (3) and R-equol (3R) (Figure 2). However, gut bacteria selectively gives only S-equol (3), not R-equol (3R); this is interesting because only S-equol (3) has a high affinity to bind with estrogen receptor β, while R-equol (3R) has much less activity [4]. Therefore, S-equol (3), but not R-equol (3R), has high affinity for estrogen receptor β in human, and S-equol (3) has more potent estrogenic activity than estradiol [4]. In animal model, although a mixture of the two enantiomers of equol have the ability to inhibit bone loss in ovariectomized mice [8], S-equol (3) has better inhibitory effects on bone fragility than the racemic mixture containing both S-equol (3) and R-equol (3R) [9].
Figure 2.
Structures of two enantiomers of S-equol (3) and R-equol (3R) and the bioconversion of daidzein (1) to S-equol (3) by the bacterium Lactococcus sp. through the metabolites (R)-dihydrodaidzein (6), (S)-dihydrodaidzein (7), and trans-tetrahydrodaidzein (8).
The ability of gut bacteria to selectively produce the correct bioactive isomer of S-equol (3) needed for human is intriguing. Shimada and co-workers identified enzymes involved in the bioconversion of daidzein (1) to S-equol (3) by the bacterium Lactococcus sp. strain 20–92, which was isolated from feces of healthy human [10]. The enzyme daidzein reductase catalyzes the transformation of daidzein (1) to (R)-dihydrodaidzein (6), which is in turn converted to (S)-dihydrodaidzein (7) by the enzyme dihydrodaidzein racemase (Figure 2). The enzyme dihydrodaidzein reductase catalyzes the conversion of (S)-dihydrodaidzein (7) to trans-tetrahydrodaidzein (8), which is converted to S-equol (3) by the enzyme tetrahydrodaidzein reductase [10]. The bioconversion of daidzein (1) selectively to S-equol (3), not R-equol (3R), by gut bacteria provides human the correct enantiomer for binding with estrogen receptor β; this may be host-bacterial mutualism in human intestine. An isoflavone daidzein (1) is found in leguminous plants such as soybeans and other legumes, which have been used as food for human since ancient times. Therefore, it is possible that gut bacteria have experienced with daidzein (1) long time ago, and their enzymatic evolutions lead to the selective bioconversion of daidzein (1) to S-equol (3), which has biological activity for human. Interestingly, many studies revealed that there is the intestinal microbiota-to-host relationship, i.e., a cross talk, between gut microbiota and human host and interactions between gene products from the microbiome with metabolic systems of human diseases such as obesity and diabetes [11].
The conversion of a dietary soybean isoflavone, daidzein (1) or genistein (2), to S-equol (3), by gut bacteria has been known for many years; however, scientists might not be aware of the importance of gut microorganisms in the past. Recently, a number of studies have revealed many essential roles of gut microbiota in human health and diseases. Gut microbiome can transform nutrients and dietary fibers to produce bioactive metabolites, for example, short-chain fatty acids (SCFAs) and nicotinamide, which have a significant impact on human health and diseases. There have been reports on interactions of gut microbiome and compounds, e.g., drugs and natural products, after humans take these compounds as drugs for the treatment of diseases. The metabolites obtained from the metabolism of drugs/natural products by the activities of gut microbiome have either positive or negative effects on therapeutic efficiency. This chapter provides the information of recent studies on the influence of the metabolites produced by gut microbiome on human health and diseases and on the interactions of microbiome and drugs/natural products.
2. Contributions of metabolites produced by gut microbiome to human health and diseases
The human gastrointestinal tract has trillions of microorganisms with a complex and diverse community. Gut microbiome is recognized as an “organ” because gut microorganisms have metabolic activities similar to an organ and have several essential functions to human health [12]. It is estimated that microbial cells in the human body are 10 times more than human cells and that gut microbiome has 150 times more genes than human genome [13]. Perturbation of gut microbial communities leads to the imbalance of gut microorganisms, by either reducing or increasing particular microbial species or altering the relative abundance of certain microorganisms; this is collectively known as “dysbiosis.” Microbial dysbiosis can cause certain diseases such as irritable bowel syndrome, diabetes, cancer, inflammatory bowel diseases, and obesity [14, 15, 16]. Gut microorganisms are able to produce many metabolites, which give substantial contributions to human health because they are involved in various physiological processes, i.e., host immunity, cell-to-cell communication, and energy metabolism [17, 18]. The metabolites produced by gut microbiome are linked with human diseases, for example, colorectal cancer [19], depression [20], inflammation and cancer [21], and cardiovascular and metabolic diseases [22, 23]. Among the metabolites produced by gut microbiome, SCFAs considerably play critical roles in human health. Gut microbiome produces acetate (9), propionate (10), and butyrate (11) (Figure 3), the respective conjugate bases of acetic acid, propionic acid, and butyric acid; these SCFAs are from saccharolytic fermentation of dietary fibers by gut microorganisms [24]. Butyrate (11) from the metabolism of gut microbiome could induce differentiation of colonic regulatory T cells in mice, suggesting that gut microorganisms are substantially involved in immunological homeostasis in the gastrointestinal tract of human [25]. SCFAs produced by gut microbiota are significantly linked with hypertension and kidney diseases [26]. SCFAs are vital fuels for intestinal epithelial cells and can maintain intestinal homeostasis; they are involved in the regulation of gut epithelial cells and immunity that is relevant to inflammatory bowel diseases [27, 28]. SCFAs are able to activate G-protein-coupled receptor, for example, GPR43, which has a role in intestinal inflammatory diseases, i.e., inflammatory bowel diseases [29]. Moreover, SCFAs produced by gut microbiome are energy source for colonocytes and can inhibit histone deacetylases, the enzymes catalyzing the removal of acetyl groups from the lysine residue of histone [30]. Recent study revealed that butyrate (11) from the metabolism of gut microbiome could promote histone crotonylation in colon epithelial cells and that the reduction of the gut microbiota leads to many changes in histone crotonylation in the colon [31].
Figure 3.
Structures of SCFAs including acetate (9), propionate (10), and butyrate (11).
Recent study revealed that SCFAs produced by gut microbiome had relationships with metabolic diseases [32]. The level increase of butyrate (11) (Figure 3) by gut microbiome can improve insulin response after an oral glucose tolerance test; moreover, the defects in the production or absorption of propionate (10) led to an increased risk of type 2 diabetes [32]. Previous study also demonstrated that type 2 diabetes is linked with changes in the composition of gut microbiome because the profile of gut microorganisms in human with type 2 diabetes is different from that without type 2 diabetes (a control group) [33]. SCFAs are known to have a significant impact on the energy homeostasis, i.e., controlling the energy metabolism; therefore, modulation of SCFAs could be a nutritional target to prevent diseases associated with metabolism disorders, for example, type 2 diabetes and obesity [34]. Gut microbiome is also linked with food allergy in human, and changes in the population and composition of gut microbiota might cause food allergy [35], and the use of gut microbiome is a potential innovative strategy to prevent food allergy in human [36]. In an animal model, certain gut bacteria, e.g., Clostridia species, might be useful for prevention or therapy of food allergy [37]. Recent investigation led by Nagler showed that butyrate (11) (Figure 3) produced by the gut bacterium, Anaerostipes caccae, could contribute to the prevention of milk allergy in children [38]. Germ-free mice colonized with bacteria in feces of healthy infants can protect mice against milk allergy, while those colonized with bacteria in feces of milk allergic infants could not protect mice from milk allergy; this result indicates that gut microbiotas are involved in milk allergy. Detailed analysis revealed that compositions of gut bacteria in healthy infants were different from milk allergic infants, and the gut bacterium, A. caccae, was the key agent to protect against an allergic response to food [38]. A. caccae is a saccharolytic intestinal bacterium producing butyrate (11) [39]. It is known that butyrate (11) is a key energy source for colonic epithelial cells, regulating energy metabolism and autophagy in the mammalian colon [40]. Therefore, butyrate (11) is likely to be the key metabolite responsible for the protection of milk allergy [38]. An independent study revealed that a dietary supplemented with the bacterium Lactobacillus rhamnosus could promote tolerance in infants with cow’s milk allergy by enrichment of butyrate-producing bacterial strains [41]. The increased levels of butyrate (11) in feces of infants who received the supplement with L. rhamnosus were observed in the most tolerant infants against milk allergy [41].
Nicotinamide (12) is an amide derivative of vitamin B3 or niacin or nicotinic acid (13) (Figure 4) and is a substrate for nicotinamide adenine dinucleotide (NAD), a coenzyme in many important enzymatic oxidation–reduction reactions, for example, electron transport chain, citric acid cycle, and glycolysis. Nicotinamide (12) is known to have a role in neuronal systems in the central nervous system, thus implicating in neuronal death and neuroprotection [42]. Recent study led by Elinav revealed that nicotinamide (12) produced by the gut bacterium, Akkermansia muciniphila, significantly protected the progression of the neurodegenerative disease, amyotrophic lateral sclerosis (ALS) [43]. The experiment demonstrated that removal of gut microorganisms by treating mice with antibiotics could promote the ALS symptoms in mice, indicating that gut microbiome modulated the progress of ALS disease [43]. The study showed that the species of gut bacteria in healthy human were different from that in ALS patients; A. muciniphila was abundant in healthy people, while Ruminococcus torques and Parabacteroides distasonis were relatively abundant in ALS patients. Remarkably, transplantation of gut bacteria from human gut to germ-free mice revealed that the gut bacterium A. muciniphila improved the ALS symptoms, while the gut bacteria R. torques and P. distasonis worsened the ALS symptoms [43]. Detailed analysis found that the gut bacterium A. muciniphila provided nicotinamide (12) as a bioactive metabolite that improves the ALS symptoms. Indeed, a direct injection of nicotinamide (12) into mice with ALS could improve a motor-neuron function. The study in 37 patients with ALS revealed that the levels of nicotinamide (12) in cerebrospinal fluid of ALS patients were lower than that in people without ALS. Moreover, analysis of microbial genes involved in nicotinamide synthesis in feces of ALS patients revealed that people with ALS had less number of the genes for nicotinamide synthesis; these genes were mainly from the gut bacterium A. muciniphila. Therefore, it is likely that ALS patients might have less abundance of A. muciniphila in their gastrointestinal tract [43]. This work suggests that gut microbiome has a significant link with human disease pathophysiology and that there is an opportunity to use microbial therapeutic targets for certain diseases. Indeed, a clinical trial on human using the gut bacterium, A. muciniphila, in overweight and obese insulin-resistant volunteers demonstrated that the gut bacterium could reduce insulin resistance indices and could lower the levels of circulating insulin and blood cholesterol, thus improving the profile of blood lipid and insulin sensitivity [44]. This microbial therapeutic approach is safe and may be applied for the treatment of overweight or obese insulin-resistant people.
Figure 4.
Structures of nicotinamide (12) and niacin or nicotinic acid (13).
It is known that gut microbiota is significantly associated with autism spectrum disorder, a form of mental disorder with difficulties in social communication and interaction [45]. Intriguingly, a recent study led by Sharon and Mazmanian revealed that gut microbiota could produce neuroactive metabolites which contribute to the pathophysiology of autism spectrum disorder, thus regulating behaviors in mice [46]. The experiment showed that germ-free mice receiving gut microbiota from human donors with autism spectrum disorder could induce autistic behaviors in mice. The metabolites produced by gut bacteria, 5-aminovaleric acid (14) and taurine (15) (Figure 5), were found to modulate behaviors related to autism spectrum disorder. Both 5-aminovaleric acid (14) and taurine (15) are GABAA receptor agonists [47, 48]. Levels of 5-aminovaleric acid (14) in mice with autism spectrum disorder were significantly lower than that in the control mice, while levels of taurine (15) in mice with autism spectrum disorder were ca. 50% less than the control group [46]. Administration of 5-aminovaleric acid (14) and taurine (15) to mice with autism spectrum disorder could improve repetitive and social behaviors, i.e., modulating neuronal excitability in mice brain and improving behavioral abnormalities [46]. This finding suggests that autism spectrum disorder is also related to the influence of gut microbiota; therefore microbiome interventions using fecal microbiota transplantation, as well as supplementation with metabolites produced by gut microorganisms or with probiotics, may improve the quality of life for people with autism spectrum disorder.
Figure 5.
Structures of 5-aminovaleric acid or 5-aminopentanoic acid (14) and taurine or 2-aminoethanesulfonic acid (15).
Gut microbiome substantially contributes to human health and diseases, and the metabolites produced by gut microbiome mentioned earlier underscore the importance of gut microorganisms in health and certain diseases in human. Health and diseases of individuals partly rely on the conditions of gut microbiome whether they have healthy gut microbiota or unhealthy ones. Gut microbiota is therefore considered as a “hidden” or “forgotten” human organ [12], involving in pathology of Alzheimer’s disease [49], endocrine organ involving metabolic diseases [50], and chronic gastrointestinal disease [51]. Moreover, gut microbiota is also considered as an “invisible” organ that controls and manipulates the function of drugs [52]. The imbalance of gut microbiota, or known as dysbiosis, leads to unhealthy conditions for human or even causes certain diseases. Therefore, the use of gut microbiota as a therapeutic target for treatments of human diseases is an emerging approach for many diseases, for example, Parkinson’s disease [53], cardiovascular disease [54], metabolic disorders [55], hepatocellular carcinoma [56], nonalcoholic fatty liver disease [57], food allergy [58], and heart failure [59]. Supplementation with probiotics or with health-promoting bacteria is a possible therapeutic method and may widely be used in the near future. Fecal microbiota transplantation or supplementation with metabolites from gut microorganism needs more clinical studies; the two approaches will be a challenging research on gut microbiota in the near future.
3. Interactions of gut microbiome and drugs and/or natural products
It is estimated that a total mass of bacteria in the human body is around 0.2 kg (for people with a weight of 70 kg) and that the densities of commensal microorganisms in the human gastrointestinal tract ranged from 108 to 1011 bacterial cells/g [60]. Oral administration of drugs delivers drugs to the gastrointestinal tract that contains high densities of gut microorganisms, which could encode 150-fold more genes than those of the human genome [61]; therefore, gut microbes are able to encode many enzymes with drug-metabolizing potential [62]. Gut microbiota is recognized as an “invisible organ” responsible for controlling drug functions and modulation of drug metabolism processes [52]. Normally, antibiotic drugs give direct effects toward microorganisms in the human gastrointestinal tract, providing either negative or positive (beneficial) effects to the composition of gut microbiota [63]. However, intestinal microbiota have many important roles in maintenance of human health; therefore, perturbation of gut microbiome by antibiotics could give negative impact to human, for example, loss of colonization resistance that can prevent invading microorganisms colonizing in the human gastrointestinal tract [64]. In addition to antibiotic drugs, a recent study led by Typas demonstrated that nonantibiotic drugs also gave extensive impact on human gut bacteria because around 24% of 1197 drugs showed antibacterial activity toward at least one strain of gut bacteria [65]. This is considered as “antibiotic-like side effects” of nonantibiotic drugs, which could potentially promote antibiotic resistance that is one of the major public health problems worldwide. This finding provides essential information for drug discovery research, i.e., addressing a potential new side effect of drugs and repurposing of nonantibiotic drugs as antibacterial agents.
The next sections will highlight the interactions of gut microbiome, especially the chemistry of the drug metabolites produced by gut microorganisms, toward certain drugs and natural products. The metabolism of drugs or natural products by gut microbiome could lead to the production of bioactive metabolites, which have either beneficial effects or negative properties (i.e., reducing efficacy of drugs or natural products). The study on the interactions of gut microbiota and drugs or natural products as part of drug development process is discussed in the next sections.
3.1 Interactions of gut microbiome and commonly used drugs
Once drugs enter the human gastrointestinal tract, they encounter trillions of microorganisms, which are able to encode 150-fold more genes than human genome [61]. A number of enzymes encoded by gut microbial genes catalyze the biotransformation of drugs, producing bioactive metabolites, which have effects on human health [60]. Advances in liquid chromatography-mass spectrometry (LC–MS) technology allow the identification of the metabolites produced by gut microbiome, as well as detailed study of pharmacokinetics of drugs and their metabolites, while genome sequencing substantially assists the identification of genes encoding enzymes in gut microorganisms. Zimmermann and co-workers investigated the drug metabolism of an antiviral nucleoside drug, brivudine (16), which is used for the treatment of herpes zoster virus; the study was performed using mice inoculated with mutant microbiota [66]. It was found that the bioconversion of brivudine (16) to bromovinyluracil (18) (or 5-(E)-(2-bromovinyl)uracil) was achieved by enzymes from both mammalian cells and gut microbial communities isolated from mice, suggesting that both host and microbiota are capable of such biotransformation (Figure 6). Previously, intestinal anaerobic bacteria were found to convert another antiviral drug, sorivudine (17), to bromovinyluracil (18) (Figure 6) [67].
Figure 6.
Biotransformation of antiviral drugs brivudine (16) and sorivudine (17) to bromovinyluracil (18) by gut bacteria.
Gut bacteria, Bacteroides thetaiotaomicron and B. ovatus, were the major species having the highest metabolic activity to convert brivudine (16) to bromovinyluracil (18) [66]. Comparison of serum kinetics of brivudine (16) and bromovinyluracil (18) in conventional (a control with bacteria) and germ-free mice after feeding with the drug brivudine (16) suggested that intestinal bacteria contributed to the amount of bromovinyluracil (18) in serum because the level of bromovinyluracil (18) in conventional mice serum was five times higher than that of germ-free mice [66]. The gene, bt4554, encoding the enzyme purine nucleoside phosphorylase necessary for the metabolism of brivudine (16) is present in B. ovatus and conserved in the bacterial phylum Bacteroidetes; the expression of the gene bt4554 is a rate-limiting step [66]. The gut bacterium, B. thetaiotaomicron, was found to completely metabolize the drug brivudine (16) to bromovinyluracil (18), which is absorbed from both the cecum and colon. This study was also able to predict the levels in serum and sources of the metabolite bromovinyluracil (18) derived from a drug sorivudine (17) (Figure 6) [66].
Zimmermann and co-workers also used clonazepam (19) (Figure 7), an anticonvulsant and antianxiety drug, as a model [66]; the metabolism of this drug in rats gave metabolic products through nitroreduction, oxidation, glucuronidation, and enterohepatic cycling [68]. After an oral administration of a drug clonazepam (19) to mice, 7-NH2-clonazepam (20) and 7-NH2-3-OH-clonazepam (21) were found as major metabolites in serum of the conventional mice (Figure 7). The host-microbiome pharmacokinetic model revealed that 7-NH2-clonazepam (20) in serum was substantially from a microbial contribution. Experiments also revealed that intestinal microbes could convert glucuronyl-3-OH-clonazepam (23) to 3-OH-clonazepam (22), which in turn transformed to 7-NH2-3-OH-clonazepam (21) by microbial reduction (Figure 7) [66]. The study established a pharmacokinetic model that can predict microbiome or host (human) contributions to drug metabolism, e.g., the ability to distinguish drug-metabolizing activity by human or gut bacteria [66]. This research model is particularly useful for the study on drug metabolism in an animal model.
Figure 7.
Biotransformation of clonazepam (19) to the metabolites 20–23 by human intestinal microbes.
Gut microbiome has potential ability to metabolite many drugs, thus affecting the therapeutic efficacy due to lower concentrations of drugs. The study on the drug metabolism of 271 commonly used drugs by gut bacteria revealed that, after incubation of drugs with gut bacteria, the levels of 176 drugs (accounting for two thirds of 271 drugs) were significantly reduced, indicating that these drugs were metabolized by gut bacteria [62]. Intriguingly, each bacterial strain (from 76 human gut bacterial strains) could metabolize up to 11–95 drugs [62]. This result suggests that, when designing the drug molecules, the drug metabolism by gut microbes should be seriously considered, particularly the drugs delivered by an oral administration. Therefore, the action of gut microbiome toward individual drug candidates should also be evaluated during the drug development process. Untargeted metabolomics analysis is used to identify products derived from drug metabolism by gut bacteria, and it could properly identify the metabolites from microbial metabolism of drugs [62]. Some drugs, for example, paliperidone, sulfasalazine, and pantoprazole, were previously investigated for their metabolism by gut microbes [69]. Detailed analysis by high-resolution mass spectrometry (HRMS) revealed that drugs with an acetyl ester or an alkene functional group, such as norethisterone acetate (24), drospirenone (25), and roxatidine acetate (26), were metabolized through either deacetylation (removing C2H2O) or hydrogenation (adding H2) by gut bacteria (Figure 8) [62]. Gut bacteria metabolized drugs with aliphatic hydroxyl or amine functional group such as dasatinib (27), fluphenazine (28), and primaquine (29) through propionylation (adding C3H4O), giving their corresponding O- or N-propionyl products 30, 31, and 32, respectively (Figure 8). The HRMS data clearly indicated the mass difference of 56.026 unit of a propionyl group between the drug and its corresponding derivative [62].
Figure 8.
Structures of the drugs, norethisterone acetate (24), drospirenone (25), and roxatidine acetate (26) and biotransformation of dasatinib (27), fluphenazine (28), and primaquine (29) to their corresponding products 30, 31, and 32, respectively, by gut bacteria.
Zimmermann and co-workers investigated the metabolism of drug in mice model and in human gut microbial communities using a corticosteroid drug, dexamethasone (33), as a model (Figure 9) [62]. It is known that this class of drug is metabolized by the bacterium Clostridium scindens through the side-chain cleavage, known as the desmolytic activity, to produce the active androgen form of the drug, dexamethasone-desmo (34) (Figure 9) [70, 71]. Levels of dexamethasone-desmo (34) were measured after an oral administration of dexamethasone (33) to germ-free mice and to mice that have only one bacterial species of C. scindens, technically known as gnotobiotic mice (GNC. scindens). Although dexamethasone (33) was found in the cecum of germ-free mice and gnotobiotic mice, the levels of the drug were significantly reduced in gnotobiotic mice, suggesting that the bacterium C. scindens associated in these mice is involved in the drug metabolism. Accordingly, levels of the androgen form of the drug, dexamethasone-desmo (34), which are derived from the metabolism of dexamethasone (33), were higher in both serum and cecum of gnotobiotic mice than that of germ-free mice [62]. Moreover, similar corticosteroid drugs, i.e., prednisone (35), prednisolone (36), cortisone (37), and cortisol (38), were also metabolized by the intestinal bacterium C. scindens through the desmolytic activity, giving the metabolite products of prednisone-desmo (39), prednisolone-desmo (40), cortisone-desmo (41), and cortisol-desmo (42), respectively (Figure 9). However, when incubating the drug dexamethasone (33) with gut bacterial community isolated from 28 healthy human participants under anaerobic condition, the drug-metabolizing activity had considerable interpersonal variation as suggested by level variations of the drug metabolite, dexamethasone-desmo (34) [62]. This result implies that dexamethasone (33) is also metabolized by other gut bacterial species, not only C. scindens.
Figure 9.
Gut bacterial metabolism of corticosteroid drugs, dexamethasone (33), prednisone (35), prednisolone (36), cortisone (37), and cortisol (38), to their respective products 34, 39, 40, 41, and 42 via the desmolytic activity.
Systematic identification of drug-metabolizing genes encoded by gut bacteria provides the mechanistic insights into drug metabolism in human [62]. Genes of the gut bacterium Bacteroides thetaiotaomicron were cloned into Escherichia coli, leading to the identification of new 16 gene products, which were able to metabolite 18 drugs to 41 different metabolites [62]. Certain gene products have specificity and cross-activity, and gene deletion and complementation techniques revealed the mechanisms of individual gene products. For instance, the bt2068 gene encodes the enzyme that could reduce (adding H2) norethisterone acetate (24) (Figure 8), as well as other similar steroid drugs such as levonorgestrel and progesterone, while the bt2367 gene encodes acyltransferase that converts the drug pericyazine (43) to both acetyl- and propionyl-pericyazine products, e.g., acetyl-O-pericyazine (44) and propionyl-O-pericyazine (45), respectively (Figure 10) [62]. It is known that the metabolism products of a drug diltiazem (46) are N-desmethyldiltiazem (47), N,N-didesmethyldiltiazem (48), O-desmethyldiltiazem (49), N,O-didesmethyldiltiazem (50), desacetyldiltiazem (51), desacetyl-N-desmethyldiltiazem (52), desacetyl-N,N-didesmethyldiltiazem (53), desacetyl-O-desmethyldiltiazem (54), and desacetyl-N,O-didesmethyldiltiazem (55) (Figure 10) [72]. The gene bt4096 in gut bacteria is responsible for the deacetylation of diltiazem (46) and its metabolites 47–50 to give their corresponding deacetylated products 51–55, respectively (Figure 10) [62]. This study suggests that gut bacteria substantially contribute to drug metabolism in the human gastrointestinal tract, and the metabolism of drug candidates by gut microbiome should be studied as a part of the drug development processes.
Figure 10.
Metabolism of pericyazine (43) to acetyl-O-pericyazine (44) and propionyl-O-pericyazine (45) and metabolism of diltiazem (46) to the metabolite products 47–55 by gut bacteria.
The drug metabolism by gut microbiome can give negative effects to drug efficacy, thus leading to the decrease in efficiency and potency of certain drugs. L-dopa or levodopa (56) (Figure 11) is the first-line drug for the treatment of Parkinson’s disease; the metabolism of this drug by gut microbiome provides negative effects for Parkinson’s patients. The drug L-dopa (56) can cross the blood–brain barrier, entering the central nervous system and then transforming to a neurotransmitter, dopamine (57), by the enzyme pyridoxal phosphate l-amino acid decarboxylase (Figure 11). It is known that intestinal microflora (gut microbiome) can metabolite L-dopa (56) [73] and that the formation of m-tyramine (58) from L-dopa (56) is a side effect of this drug for parkinsonism (Figure 11) [74]. A neurotransmitter, dopamine (57), is the only active agent needed for the treatment of parkinsonism, and it should be formed from L-dopa (56) at the central nervous system after L-dopa (56) crossing the blood–brain barrier. However, the generation of dopamine (57) from the drug L-dopa (56) can occur at the human gastrointestinal tract (known as peripheral metabolism), not at the central nervous system, thus giving undesirable side effects. To prevent this peripheral metabolism, an inhibitor of pyridoxal phosphate l-amino acid decarboxylase, carbidopa (59) (Figure 11), is coadministered with the drug L-dopa (56). It is known for many years that microorganisms can decarboxylate L-dopa (56) to dopamine (57), which in turn undergoes the dehydroxylation reaction to give m-tyramine (58) [75]. The treatment of L-dopa (56) is improved when patients receive broad-spectrum antibiotics, which suppress the growth of gut bacteria, indicating that gut bacteria are involved in the decrease of therapeutic efficiency of L-dopa (56) [76]. Therefore, gut microbiome can potentially reduce the drug efficacy of L-dopa (56) through their metabolic activities toward the drug.
Figure 11.
Bioconversion of L-dopa (56) to dopamine (57) and m-tyramine (58) by gut bacteria and structures of inhibitors of amino acid decarboxylases, carbidopa (59), (S)-α-fluoromethyltyrosine (60), benserazide (61), and methyldopa (62).
Recent study led by Prof. Balskus revealed that the gut bacterium Enterococcus faecalis has the tyrDC gene encoding the enzyme tyrosine decarboxylase that is able to decarboxylate both L-dopa (56) and an amino acid, tyrosine [77]. Moreover, the gut bacterium Eggerthella lenta has the dadh gene encoding a molybdenum cofactor-dependent dopamine dehydroxylase, which is the enzyme responsible for the dehydroxylation of dopamine (57) to m-tyramine (58) (Figure 11). The metabolism of L-dopa (56) and dopamine (57) in complex gut microbiotas of Parkinson’s patients is dependent on the tyrDC and dadh genes [77]. The study demonstrated that carbidopa (59), an inhibitor of pyridoxal phosphate l-amino acid decarboxylase, failed to prevent L-dopa (56) metabolism in complex gut microbiotas of Parkinson’s patients [77]. However, another inhibitor, (S)-α-fluoromethyltyrosine (60) (Figure 11), could prevent the decarboxylation of L-dopa (56) that is from the metabolic activities of both the bacterium E. faecalis and complex gut microbiotas of Parkinson’s patients [77]. In a mouse model, levels of the drug L-dopa (56) increased in serum when coadministered (S)-α-fluoromethyltyrosine (60) with L-dopa (56) to mice colonized with the gut bacterium E. faecalis [77]. An independent study led by Prof. Aidy also identified the tdc gene responsible for tyrosine decarboxylases in the gut bacterium E. faecium; bacterial tyrosine decarboxylases efficiently convert the drug L-dopa (56) to dopamine (57) [78]. Aidy and co-workers also found that carbidopa (59) in L-dopa (56) combination therapy did not inhibit the activities of decarboxylase enzymes in gut bacteria, E. faecalis and E. faecium [78]. Moreover, other decarboxylase inhibitors, benserazide (61) and methyldopa (62) (Figure 11), also failed to inhibit the decarboxylase activity of gut bacteria toward the drug L-dopa (56). These studies demonstrated gut microbiota significantly reduced the levels of the drug L-dopa (56) in a body, thus contributing to the higher dosages required for the Parkinson’s patients that have gut microbiome with high metabolism toward the drug L-dopa (56). Variations in gut microbiota among Parkinson’s patients might contribute to the different responses, i.e., harmful side effects and decreased efficacy, to the drug L-dopa (56). Therefore, gut microbiota plays a critical role in the drug metabolism and considerably contributes to treatment outcomes of this drug.
Gut microbiota can improve therapeutic efficiency of certain drugs for particular treatments. Cancer immunotherapy is relatively new for cancer treatment using human immune system to control and eradicate cancer cells, and it is more precise and personalized, thus providing more effectiveness with fewer side effects than other cancer treatments. Gut microbiota was found to play a role in cancer immunotherapy targeting CTLA-4, a protein receptor downregulating the immune system, because anticancer effects of CTLA-4 blockade were found to depend on gut bacteria of Bacteroides species, e.g., Bacteroides thetaiotaomicron or B. fragilis [79]. The study demonstrated that germ-free mice did not show the response to CTLA blockade, thus defecting an anticancer property of the drug. Indeed, this drug deficiency could be improved by gavage with the gut bacterium B. fragilis through immunization with the bacterium polysaccharides or by adoptive transfer of B. fragilis-specific T cells. Therefore, this research study demonstrates that the gut bacterium could help patients treated with a monoclonal antibody drug for the treatment of cancer targeting CTLA-4 [79].
Gut microbiome also improves therapeutic effect of a cancer immunotherapy targeting immune checkpoint inhibitor via the PD-1/PD-L1 pathway [59]. Antibiotics are found to give negative effects for patients treated with cancer immunotherapies as they inhibit the efficacy of immune checkpoint inhibitor drug that targets the programmed cell death receptor of the PD-1/PD-L1 pathway [59]. Moreover, suppression of growth of gut bacteria by antibiotic drugs leads to the decrease of drug efficacy, suggesting that gut microorganisms are important for this cancer therapy. The study demonstrated that gut microbiota provided significant effects on cancer immunotherapies targeting the PD-1/PD-L1 interaction because there was substantial association between commensal microorganisms and therapeutic response of anticancer drug that inhibits the activity of PD-1 and PD-L1 immune checkpoint proteins [80]. Gut bacteria including Collinsella aerofaciens, Enterococcus faecium, and Bifidobacterium longum were found to be associated with the improvement of this cancer immunotherapy. Intriguingly, reconstitution of germ-free mice with fecal samples from patients with good drug response could help to control tumor, leading to better efficacy of anti-PD-L1 cancer therapy [80]. An independent study revealed that the gut bacterium Akkermansia muciniphila assists cancer immunotherapy targeting the PD-1/PD-L1 interaction toward epithelial tumors [81]. The study on fecal microbiota transplantation demonstrated that germ-free or antibiotic-treated mice receiving gut bacteria from patients with good response to cancer immunotherapy have significant therapeutic improvement, while those receiving the samples from nonresponding patients do not have such improvement for cancer immunotherapy [81]. Restoration of the drug efficacy in germ-free mice receiving the samples from nonresponding patients was simply achieved by oral supplementation with the gut bacterium A. muciniphila, indicating the benefit of gut microbiota for this cancer immunotherapy. Another independent research also found similar benefits of gut microbiota on anti-PD-1 immunotherapy in melanoma patients; this study investigated microbiome samples from 112 patients with metastatic melanoma and found that there were substantial differences in the composition and diversity of gut microbiome obtained from patients with good drug response and from nonresponding patients [82]. Patients with good response to immunotherapeutic PD-1 blockade have abundance of gut bacteria of the family Ruminococcaceae and Faecalibacterium, while patients with poor response to immunotherapeutic PD-1 blockade tend to have relative abundance of Bacteroidales. It is possible that patients with a favorable gut microbiome, e.g., Ruminococcaceae and Faecalibacterium, toward the immunotherapeutic PD-1 blockade therapy have improved systemic and immune responses mediated by certain factors such as improvement of effector T cell function in the periphery, increase of antigen production, and improvement of the tumor microenvironment [82].
Gut microbiota also has an important role in chemotherapy for cancer treatment because they can modulate drug efficacy, for example, eliminating the anticancer properties of the drug or mediating toxicity [83]. Cyclophosphamide (63) (Figure 12) is a drug used in cancer chemotherapy for many types of cancers, as well as for autoimmune diseases, and its mechanism is through the stimulation of anticancer immune responses. In a mouse model, the composition of gut microbiota is changed after administration of cyclophosphamide (63), and this drug induces the translocation of certain Gram-positive bacteria into secondary lymphoid organs. Gut bacteria could stimulate certain immune responses beneficial to cancer therapy. Germ-free mice carrying tumor treated with antibiotics to kill Gram-positive bacteria had less therapeutic response, and their tumors exhibited resistance to the drug cyclophosphamide (63), suggesting that gut microbiota improves anticancer immune response [84]. Gut bacteria, Enterococcus hirae and Barnesiella intestinihominis, were found to help cyclophosphamide-induced therapeutic immunomodulatory response, thus improving the efficacy of this alkylating immunomodulatory drug [85].
Figure 12.
Structure of an anticancer drug, cyclophosphamide (63).
The research studies mentioned earlier demonstrate the interactions of drugs and gut microbiome that provide beneficial effects on cancer therapy. However, interactions of gut microbiome and drugs can also give negative influence in cancer treatment, for example, the treatment of an anticancer drug, gemcitabine (64) or 2′,2′-difluorodeoxycytidine (Figure 13), which is a derivative of cytidine nucleoside base. A research led by Straussman showed that the bacterium Mycoplasma hyorhinis was found to be the cause of gemcitabine (64) resistance in colon carcinoma models [86]. In a colon cancer mouse model, M. hyorhinis could metabolize gemcitabine (64) to the corresponding deaminated derivative, 2′,2′-difluorodeoxyuridine (65), that does not have anticancer activity (Figure 13). The conversion of gemcitabine (64) to 2′,2′-difluorodeoxyuridine (65) was previously reported [87], and the nucleoside-catabolizing enzymes, i.e., cytidine deaminase, in the bacterium, M. hyorhinis, were also identified [88]. Straussman and co-workers analyzed genes and genomes of 2674 bacterial species and found that most of the Gammaproteobacteria class had the gene coding for the enzyme cytidine deaminase, thus potentially mediating gemcitabine resistance [86]. In a mouse model of colon carcinoma, mice receiving an antibiotic, ciprofloxacin, showed a good response to the anticancer drug gemcitabine (64), indicating that suppression of the growth of certain bacteria led to the improvement of the drug efficacy. Investigation of human pancreatic ductal adenocarcinoma collected from pancreatic cancer surgery revealed that there were intratumor bacteria, mainly belonging to the class Gammaproteobacteria such as Enterobacteriaceae and Pseudomonadaceae families in these samples; the intratumor bacteria can mediate resistance to chemotherapy of the drug gemcitabine (64) [86]. Therefore, the metabolism of the drug gemcitabine (64) to 2′,2′-difluorodeoxyuridine (65) by gut microbiota provides the negative effects for cancer treatment. This study underscores the importance of the research on drug metabolism by gut microbiome, which should be investigated for the new drug candidates during the drug development processes.
Figure 13.
Biotransformation of gemcitabine (64) to its metabolite 2′,2′-difluorodeoxyuridine (65); structures of anticancer drugs, oxaliplatin (66) and fluorouracil or 5-FU (67), and autophagy lysosomal inhibitor, chloroquine (68).
Additional example for the negative effects of gut microbiota for cancer chemotherapy is the treatment of colorectal cancer with the drugs, oxaliplatin (66) and fluorouracil or 5-FU (67) (Figure 13); the gut bacterium Fusobacterium nucleatum was found to promote resistance to chemotherapy for colorectal cancer [89]. Analysis of colorectal cancer tissues collected from patients with recurrence or without recurrence of cancer revealed that the bacterium F. nucleatum is associated with the recurrence of colorectal cancer, which is derived from chemoresistance toward the drugs [89]. Cultivation of colorectal cancer cells co-cultured with F. nucleatum revealed that the bacterium potentially activated an autophagy pathway in colorectal cancer cells. An addition of a known autophagy lysosomal inhibitor, chloroquine (68) (Figure 13), could inhibit autophagic flux in the F. nucleatum-cultured cells, confirming the autophagy activation induced by the gut bacterium F. nucleatum [89]. Moreover, this bacterium reduced cell apoptosis of colorectal cancer cells, indicating that it specifically induced resistance toward the drugs oxaliplatin (66) and fluorouracil (67). Co-cultured cancer cells with the bacterium F. nucleatum and treated cancer cells with the drugs oxaliplatin (66) and fluorouracil (67) in the presence of autophagy lysosomal inhibitor, chloroquine (68), could eradicate chemoresistant effect, strongly confirming that the bacterium F. nucleatum induced chemoresistance through the autophagy pathway [89]. Detailed mechanistic study revealed that the bacterium F. nucleatum mediated chemoresistance through the TLR4 and MYD88 signaling pathway [89]. An independent study showed that the gut bacterium F. nucleatum is a diagnostic marker of colorectal cancer because patients with this cancer generally have high density of this bacterium in tumor cells [90]. Several studies have shown the prevalence of the bacterium F. nucleatum in colorectal tissues and fecal samples of patients, and those with high density of this bacterium tend to have lower rate of survival [91]. Therefore, manipulation of the bacterial population of F. nucleatum might be useful for the treatment of colorectal cancer, and this bacterium is potentially a diagnostic and/or prognostic marker for colorectal cancer.
In addition to drug metabolism, gut microbiota is also involved in drug–drug interactions when patients take two drugs at the same time, particularly when using antibiotics together with other drugs. Several studies have demonstrated the effects of antibiotic drugs on the metabolic activities of gut microbiota toward drugs and phytochemicals [92]. An example of a drug–drug interaction is the contribution of an antibiotic drug, amoxicillin (69), to a nonsteroidal anti-inflammatory drug aspirin (70) (Figure 14) [93]. It is worth mentioning that aspirin (70) is used not only for a pain reliever but also for primary prevention of cardiovascular disease [94] and cancer chemoprevention [95]. Recent study showed that amoxicillin (69) potentially affected the composition of gut microbiota by reducing number and species of intestinal bacteria in rats; the abundance of the gut bacteria, Prevotella copri and Helicobacter pylori, was reduced significantly after rats receiving amoxicillin (69) [93]. Gut microorganisms in rats could metabolite aspirin (70) to salicylate or salicylic acid (71) (Figure 14). Salicylate is a conjugate base of salicylic acid (71). It is known that the drug aspirin (70) is not responsible for a pain relief, but its metabolite, salicylic acid (71), is the active metabolite responsible for a pain relief with anti-inflammatory effect [96]. Therefore, gut microbiota plays an important role in the biotransformation of the drug aspirin (70) into the active metabolite, salicylic acid (71). After an oral administration of an antibiotic drug amoxicillin (69) to rats, the reduction of the metabolism of aspirin (70) into salicylic acid (71) was observed, suggesting the decrease of gut microbiota by amoxicillin (69) led to the reduction of the biotransformation of aspirin (70) into salicylic acid (71). Further study on the pharmacokinetics of aspirin (70) in rats revealed that amoxicillin (69) significantly affected the pharmacokinetic properties of aspirin (70) [93]. This study indicates that changes of the composition of gut microbiome by antibiotic drugs could substantially disturb the therapeutic effect of other drugs.
Figure 14.
Structures of amoxicillin (69), aspirin (70) and its metabolite, salicylate or salicylic acid (71), and nifedipine (72).
Previous study also showed that antibiotics substantially reduced the metabolic activity of gut microbiota toward aspirin (70), leading to the reduction of an antithrombotic effect of aspirin (70) [97]. Moreover, environmental changes, e.g., high-altitude hypoxia, also give effects on the pharmacokinetics and pharmacodynamics of aspirin (70) because of the changes in gut microbiota [98]. In an animal model, the plateau hypoxic environment affected the composition of gut microbiome because it increased the bacterial species of Bacteroides in rat feces but reduced numbers of the bacteria of the genus Prevotella, Coprococcus, and Corynebacterium. Changes in gut microbiome affected the metabolism of aspirin (70), thus altering the bioavailability of aspirin (70) in patients [98]. Plateau hypoxic environment also has the effects on the drug nifedipine (72), which could be metabolized by gut microorganisms (Figure 14) [99]. Nifedipine (72) is a drug for the treatment of hypertension, precordial angina, and certain vascular diseases. Plateau hypoxic environment was found to alter the composition of gut microbiota in an animal model, thus affecting the bioavailability of nifedipine (72) [99].
Recent study led by Kittakoop revealed that valproic acid or valproate (73) (Figure 15), an anticonvulsive drug used for treatments of epilepsy and bipolar disorder, had effects on the biosynthesis of fatty acids in microorganisms including representative gut microbiome [100]. Valproic acid (73) is also an epigenetic modulator, acting as an inhibitor of histone deacetylase [101]. Initially, Kittakoop and co-workers employed “One strain many compound” (OSMAC) approach using the marine fungus Trichoderma reesei treated with an epigenetic modulator, valproic acid (73), aiming to modulate the fungus T. reesei to produce new natural products, which are secondary metabolites. However, valproic acid (73) was found to have the effects on the biosynthesis of fatty acids, which are primary metabolites, instead of natural products that are secondary metabolites [100]. The study revealed that valproic acid (73) at a concentration of 100 μM could either inhibit or induce the biosynthesis of certain fatty acids in fungi, yeast, and bacteria. Valproic acid (73) inhibited the biosynthesis of palmitoleic acid (C16:1), α-linolenic acid (C18:3), arachidic acid (C20:0), and lignoceric acid (C24:0) in the fungus Fusarium oxysporum, while it induced the production of α-linolenic acid (C18:3) in the fungus Aspergillus aculeatus [100]. The bacterium of the genus Pediococcus is commonly found as gut microbiome in humans and animals [102]; valproic acid (73) was found to inhibit the production of lignoceric acid (C24:0) in the bacterium, Pediococcus acidilactici [100]. The yeast Candida utilis was found as gut microbiome in pediatric patients with inflammatory bowel disease [103]; valproic acid (73) inhibited the biosynthesis of palmitoleic acid (C16:1) and α-linolenic acid (C18:3) in C. utilis [100]. The yeast Saccharomyces cerevisiae was previously found as a prevalent gut microbiome in human [104], and the drug valproic acid (73) was found to inhibit the production of α-linolenic acid (C18:3) in the yeast S. cerevisiae [100]. Interestingly, valproic acid (73) could induce the biosynthesis of trans-9-elaidic acid (74) (Figure 15) in the yeast Saccharomyces ludwigii [100]. In human, trans-9-elaidic acid (74) could increase intracellular Zn2+ in macrophages and inhibit β-oxidation in peripheral blood macrophages [105, 106]; this suggests that the production of trans-9-elaidic acid (74) in gut microorganisms induced by the drug valproic acid (73) may indirectly give the effects to human. Valproic acid (73) also had effects on the biosynthesis of polyketides because it substantially reduced the production of austdiol (75) (90% reduction) and quadricinctone A (76) (50% reduction) (Figure 15), which are the polyketides of the fungus Dothideomycetes sp. [100]. The biosynthesis of fatty acids is considerably similar to that of polyketides, i.e., sharing the same catalytic roles and biosynthetic precursors [107]. Therefore, the drug valproic acid (73) possibly gives effects on the biosynthetic pathways of both fatty acids and polyketides because of their biosynthetic similarities. Gut microbes have biosynthetic gene clusters involving in the biosynthesis of many bioactive natural products including polyketides [108]; some natural products produced by gut microbiome have biological activities. This study suggests that commonly used drugs could potentially give the effects on the biosynthesis of secondary metabolites (natural products) of gut microbiome.
Figure 15.
Structures of valproic acid or valproate (73), trans-9-elaidic acid (74), austdiol (75), and quadricinctone A (76).
3.2 Interactions of gut microbiome and natural products
Traditional medicine and natural products have significant interactions with gut microbiome. Many studies revealed that dietary natural products modulating gut microbiota are useful for prevention and management of diabetes mellitus [109]. Recent study revealed that a traditional Chinese herbal formula and an antidiabetic drug, metformin (77) (Figure 16), could improve the treatment of type 2 diabetes with hyperlipidemia by enriching certain beneficial species of gut bacteria, for example, Faecalibacterium sp. and Blautia [110]. The study was carried out in 450 patients with type 2 diabetes and hyperlipidemia, and the profiles of gut microbiota were analyzed using fecal samples in patients treated with metformin and a traditional Chinese herbal formula. An antidiabetic drug metformin (77) and herbal medicine significantly changed the gut microbiota profile that led to the enhancement of therapeutic effects of the drugs [110]. The traditional Chinese herbal formula used in the study contains the plants including Coptis chinensis, Momordica charantia, Rhizoma anemarrhenae, and Aloe vera, as well as red yeast rice from the fermentation; this herbal recipe is practically used in clinical application [110]. Among the plants used in this formula, Coptis chinensis contains an alkaloid berberine (78) (Figure 16). An independent study revealed that berberine (78) could significantly change the composition of gut microbiota in high-fat diet-fed rats [111]. An alkaloid berberine (78) was able to enrich selectively short-chain fatty acid-producing bacteria such as the genus Blautia and Allobaculum [111]. Another independent study also revealed that both metformin (77) and berberine (78) could change profiles of gut microbiota in high-fat diet-induced obesity in rats [112]. Substantial reduction of the diversity of gut microbiota was observed by both metformin (77) and berberine (78) because 60 out of the 134 operational taxonomic units were decreased after treatment with both drugs. However, there were considerable increases in short-chain fatty acid-producing bacteria, e.g., the genus Butyricicoccus, Blautia, Allobaculum, Phascolarctobacterium, and Bacteroides, after treatment with both metformin (77) and berberine (78) [112]. Therefore, in addition to the direct benefit toward the treatment of diabetes and obesity, the drugs, metformin (77) and berberine (78), could also improve gut microbiota profile by increasing short-chain fatty acid-producing bacteria and thus mediating their useful effects on the host [112]. As mentioned earlier in Section 2, gut microbiomes that produce short-chain fatty acids provide many beneficial effects on human health [24, 25].
Figure 16.
Structures of metformin (77), berberine (78), and theobromine (79).
Recent study revealed that berberine (78) could prevent ulcerative colitis by modifying gut microbiota and regulating T regulatory cell and T helper 17 cell in a dextran sulfate sodium-induced ulcerative colitis mouse model [113]. The diversity of gut microbiota was reduced by berberine (78), which markedly interfered the abundance of certain bacterial genus such as Bacteroides, Desulfovibrio, and Eubacterium. Therefore, the mechanisms of berberine (78) for the prevention of ulcerative colitis are by regulating the balance of T regulatory cell and T helper 17 cell, as well as by modifying gut microbiota [113]. Theobromine (79) (Figure 16) is a xanthine alkaloid of cocoa beans and found in chocolate, and its structure is closely related to caffeine. A cocoa-enriched diet containing theobromine (79) could decrease the intestinal immunoglobulin A secretion and immunoglobulin A-coating bacteria, i.e., the genus of Bacteroides, Staphylococcus, and Clostridium [114]. A cocoa-enriched diet had effects on a differential toll-like receptor pattern, which led to changes in the intestinal immune system [114]. Moreover, further experiments in rats revealed that a diet containing 10% cocoa and a diet supplemented with 0.25% theobromine (79) could reduce the gut bacterium Escherichia coli, while a diet with 0.25% theobromine (79) reduced the gut bacterial community of Clostridium histolyticum, C. perfringens, Streptococcus sp., and Bifidobacterium sp. [115]. The amounts of short-chain fatty acids increased after feeding rats with a diet containing 10% cocoa and that supplemented with 0.25% theobromine (79), while both diets decreased the abundance of immunoglobulin A (IgA)-coated bacteria. It is worth mentioning that gut IgA-coated bacteria could potentially cause intestinal disease such as inflammatory bowel disease, and eradication of these bacteria may prevent or reduce intestinal disease development [116]. Therefore, the active natural product theobromine (79) in cocoa able to reduce the amounts of immunoglobulin A-coated bacteria, and to modify the profile of gut microbiota, provides beneficial effects on human health [115].
It is known that berberine (78) has poor solubility; however, it can show effectiveness for the treatment of certain diseases; therefore, there might be a specific mechanism to deliver berberine (78) to an organ system. In an animal model, berberine (78) was found to convert to dihydroberberine (80) in an intestinal ecosystem of rats (Figure 17); the metabolite dihydroberberine (80) exhibited much better absorption rate than its parent drug, berberine (78) [117]. Incubation of berberine (78) with human gut bacteria isolated from gastrointestinal human specimens also produced dihydroberberine (80), and the amounts of dihydroberberine (80) obtained from the biotransformation of gut bacteria were higher than that obtained from other bacteria, which were not gut bacteria and used as the control. This experiment confirmed that gut microbiota could convert berberine (78) into its absorbable form, dihydroberberine (80); therefore intestinal microbiota is considered to be a “tissue” or an “organ” that is able to transform berberine (78) into an absorbable form, dihydroberberine (80) [117]. Mechanistic study revealed that gut microbiome uses the enzyme nitroreductases to catalyze the conversion of berberine (78) to dihydroberberine (80) (Figure 17). Dihydroberberine (80) was found to be absorbed in intestinal epithelia, but it was reverted to the active form berberine (78) soon after entering tissues of the intestinal wall. Detailed analysis showed that the conversion of dihydroberberine (80) back to berberine (78) was by a nonenzymatic oxidation through multi-faceted factors, for example, superoxide anion and metal ions, which occurred in intestinal epithelial tissues (Figure 17) [117]. Previous report demonstrated that dihydroberberine (80) in its sulfate form, e.g., dihydroberberine sulfate, also showed better absorption in the intestine than its parent drug, berberine (78) [118]. Recent independent studies revealed that dihydroberberine (80) has interesting biological activities, for example, anti-inflammatory activity through dual modulation of NF-κB and MAPK signaling pathways [119], synergistic effects with an anticancer drug sunitinib on human non-small cell lung cancer cell lines by inflammatory mediators and repressing MAP kinase pathways [120], and inhibition of ether-a-go-go-related gene (hERG) channels expressed in human embryonic kidney 293 (HEK293) cells [121]. It is worth mentioning that the metabolite products from gut biomicrobiota, i.e., dihydroberberine (80), have different biological activity from its parent drug, berberine (78). Therefore, the drug development process should include a research study on the metabolism of natural products (as drug candidates) by gut microbiota.
Figure 17.
Bioconversion of berberine (78) into an absorbable form, dihydroberberine (80), by gut bacteria; absorption of dihydroberberine (80) into the intestine wall and nonenzymatic conversion of dihydroberberine (80) to the active form berberine (78).
Demethyleneberberine (81), berberrubine (82), jatrorrhizine (83), and thalifendine (84) were found as major metabolites in rats after an oral administration of berberine (78) (Figure 18) [122]. Comparison of the levels of these metabolites in conventional rats (a control group) and pseudo germ-free rats revealed that liver and intestinal bacteria were involved in the metabolism and disposition of berberine (78) in vivo. It is worth mentioning that some metabolites from this biotransformation exert important biological activities. For example, demethyleneberberine (81) inhibits oxidative stress, steatosis, and mitochondrial dysfunction in a mouse model, which is a potential therapy for alcoholic liver disease [123]. Berberrubine (82) was found to reduce inflammation and mucosal lesions in dextran sodium sulfate-induced colitis in mice, which might be useful for the treatment of ulcerative colitis [124]. Jatrorrhizine (83) could reduce the uptake of 5-hydroxytryptamine and norepinephrine by the inhibition of uptake-2 transporters, thus exerting antidepressant-like action in mice [125]. Therefore, the biotransformation of berberine (78) by gut bacteria leads to the production of bioactive metabolites, which have interesting pharmacological properties; this underscores the impact of gut microbiota in the drug development process for natural products.
Figure 18.
Biotransformation of berberine (78) to demethyleneberberine (81), berberrubine (82), jatrorrhizine (83), and thalifendine (84) by gut bacteria.
Since there are interactions between gut microbiota and natural products, efforts have been made to use natural compounds for the treatment of gut microbiota dysbiosis, which is the imbalance of microorganisms in the human gastrointestinal tract. Dysbiosis of gut microbiota is strongly associated with some diseases such as type 2 diabetes, inflammatory bowel disease, obesity, and nonalcoholic fatty liver disease [16, 126]. Alkaloids of a medicinal plant, Corydalis saxicola, were used to prevent gut microbiota dysbiosis in an animal model [127]. Major alkaloids in Corydalis saxicola are berberine (78), jatrorrhizine (83), dehydrocavidine (85), palmatine (86), and chelerythrine (87) (Figures 18 and 19). Among these alkaloids, berberine (78), palmatine (86), and chelerythrine (87) are the main active principles for the treatment of antibiotic-induced gut microbiota dysbiosis through the key enzyme, CYP27A1, which is involved in the biosynthesis of bile acid [127]. This study provides insights for the discovery of natural products for the treatment of gut microbiota dysbiosis.
Figure 19.
Structures of dehydrocavidine (85), palmatine (86), and chelerythrine (87).
Xanthohumol (88) is a prenylflavonoid in hops (Humulus lupulus), which is responsible bitter flavor in beer (Figure 20). Xanthohumol (88) has interesting pharmacological properties, for example, improving cognitive flexibility in young mice [128] and having beneficial effects toward metabolic syndrome-related diseases such as type 2 diabetes and obesity [129]. The comparative study on germ-free and human microbiota-associated rats toward the metabolism of xanthohumol (88) revealed that gut bacteria could transform xanthohumol (88) to isoxanthohumol (89) and 8-prenylnaringenin (90), respectively (Figure 20) [130]. The metabolism of xanthohumol (88) was further studied using human intestinal bacteria, Eubacterium ramulus and E. limosum. It is worth mentioning that an independent study revealed that the bacteria of the genus Eubacterium are normally abundant in the human gastrointestinal tract; their densities in human gut are up to 1010 colony-forming units/g of intestinal content [131]. Xanthohumol (88) is spontaneously converted to isoxanthohumol (89), which is in turn bioconverted to 8-prenylnaringenin (90) by the gut bacterium, E. limosum (Figure 20) [132]. 8-Prenylnaringenin (90) is biotransformed to O-desmethylxanthohumol (91) by the bacterium E. ramulus; this bacterium could also convert O-desmethylxanthohumol (91) to desmethyl-α,β-dihydroxanthohumol (92). Moreover, the bacterium E. ramulus was able to transform xanthohumol (88) to α,β-dihydroxanthohumol (93) (Figure 20) [132]. An independent study in healthy women volunteers revealed that isoxanthohumol (89) could be bioconverted to 8-prenylnaringenin (90) in human intestine and that the bacterial microbiota isolated from fecal samples of female volunteers could also biotransform isoxanthohumol (89) to 8-prenylnaringenin (90) [133]. Another study demonstrated that 8-prenylnaringenin (90) has potent estrogenic property, and it could relieve climacteric symptoms, i.e., vasomotoric complaints and osteoporosis, and may be useful for the treatment of menopausal complaints [134]. These studies conclusively show that the metabolites produced by gut microbiome, i.e., 8-prenylnaringenin (90), are actually bioactive compounds, not the parent natural products, and they have different pharmacological activities from their parent natural products. Gut microbiome is therefore important for in vivo biotransformation of natural products, providing bioactive metabolites responsible for therapeutic effects.
Figure 20.
Bioconversion of xanthohumol (88) to isoxanthohumol (89), 8-prenylnaringenin (90), O-desmethylxanthohumol (91), desmethyl-α,β-dihydroxanthohumol (92), and α,β-dihydroxanthohumol (93) by human gut bacteria.
Gut microbiome can biotransform natural products to bioactive metabolite essentially for therapeutic effects, for example, the biotransformation of isoxanthohumol (89) to bioactive 8-prenylnaringenin (90) [133]. However, gut microbiome can also produce toxic metabolites from the biotransformation of natural products, thus giving negative side effects. Camptothecin (CPT) is a natural alkaloid of a plant, Camptotheca acuminata, and has anticancer property with topoisomerase inhibitory activity [135]. Irinotecan or CPT-11 (94) is an alkaloid derivative of camptothecin and used as anticancer drug (Figure 21). Irinotecan (94) is a prodrug, which is transformed in vivo through hydrolysis by carboxylesterase enzymes, giving an active metabolite, SN-38 (95) (Figure 21) [136]. Uridine diphosphate-glucuronosyltransferase enzymes catalyze the conversion of SN-38 (95) to a glucuronidated derivative, SN-38G (96) (Figure 21). The metabolite SN-38G (96) is inactive for cancer cells and is excreted into the gastrointestinal tract [137], where the gut bacteria use β-glucuronidase enzymes to convert SN-38G (96) to SN-38 (95) that causes severe diarrhea in patients (Figure 21) [138]. This side effect reflects the significant negative effects of gut bacteria in the drug metabolism. However, the use of antibiotics, e.g., levofloxacin, to reduce the population of gut bacteria in the gastrointestinal tract is not recommended for patients because it has many consequent problems [139]. Gut microbiotas are important for a healthy gastrointestinal tract, and they play many essential roles in dietary metabolisms [140, 141]; the treatment of cancer should not give any effects to gut microorganisms. Therefore, the use of antibiotic drugs, which affect gut microbiota, is not recommended. To reduce the diarrhea side effect without affecting gut microorganisms, a research led by Redinbo employed appropriate inhibitors of gut bacterial β-glucuronidase enzymes, in order to prevent the formation of SN-38 (95), a causative agent of severe diarrhea in patients [142]. Certain inhibitors exhibited β-glucuronidase inhibitory activity in living bacterial cells without disturbing the growth of gut bacteria or giving any damaging effects toward mammalian cells. Indeed, in a mouse model, mice treated with both irinotecan (94) and a β-glucuronidase inhibitor had less diarrhea and bloody diarrhea than the group receiving only the drug irinotecan (94). Therefore, the inhibition of microbial β-glucuronidases could prevent the production of toxic metabolite, SN-38 (95), during the treatment of anticancer drug, irinotecan (94) [142]. This is an example of a toxic drug metabolite produced by the activity of gut microbiome, and the manipulation of the enzyme activity of gut bacteria could be done by using another drug (an inhibitor of bacterial enzyme).
Figure 21.
Structures of irinotecan or CPT-11 (94) and its metabolites, SN-38 (95) and SN-38G (96), and the bioconversion of SN-38G (96) to SN-38 (95) by gut bacterial β-glucuronidase.
Some natural products can alter the composition of gut microbiome, and changes in gut microbiome lead to the drug-induced negative side effects on certain treatments. Paclitaxel or Taxol (97) is an anticancer drug for the treatment of many types of cancers (Figure 22), and it is a natural product isolated from a Pacific yew tree, Taxus brevifolia. In a mouse model, paclitaxel (97) chemotherapy could change the composition of gut bacterial community and induce negative effects such as sickness behaviors, i.e., fatigue and anorexia, increased central and peripheral inflammation, and impaired cognitive performance [143]. These negative effects might be associated with changes in gut bacteria because paclitaxel (97) therapy decreased the abundance of gut bacteria including Lachnospiraceae bacteria and butyrate-producing bacteria, which are necessary for human gut health [143]. Therefore, the negative effects of cancer chemotherapy may be attenuated by improving the composition of gut microbiota, for example, the use of prebiotic or probiotic supplements, which has become one of the emerging approaches to change the microbiota composition, thus improving therapeutic outcome for patients treated with anticancer drugs [144].
Figure 22.
Structure of an anticancer drug paclitaxel or Taxol (97).
Antibiotic drugs have significant effects on the metabolism of drugs and phytochemicals because they could suppress enzymatic activities of gut microbiome [92]. Therefore, if patients are treated with an antibiotic drug together with another drug, there are possible drug–drug interactions due to changes of gut microbiota caused by antibiotic drugs. Lovastatin (98) (Figure 23), a natural polyketide isolated from the fungus Aspergillus terreus [145], is a cholesterol-lowering drug, which is a member of the statin family. Lovastatin (98) has the interactions with antibiotics through the mediation of gut microbiome [146]. Incubation of lovastatin (98) with human and rat fecalase revealed the biotransformation of this drug by gut microbiota, giving four major metabolites including demethylbutyryl-lovastatin (99), hydroxylated-lovastatin (100), hydroxy acid-lovastatin (101), and OH-hydroxy acid-lovastatin (102) (Figure 23) [146]. These four metabolites were also found in rat plasma, and they might be from gut microbiota-mediated metabolism of the drug lovastatin (98). Among the drug metabolites, hydroxy acid-lovastatin (101) is the active form, which could effectively inhibit 3-hydroxy-3-methylglutaryl coenzyme-A reductase, the target enzyme of this cholesterol-lowering drug [147].
Figure 23.
Structures of major metabolites of lovastatin (98) including demethylbutyryl-lovastatin (99), hydroxylated-lovastatin (100), hydroxy acid-lovastatin (101), and OH-hydroxy acid-lovastatin (102).
In an animal model, rats with an oral administration of lovastatin (98) were compared with those treated with lovastatin (98) and antibiotics; the pharmacokinetic study revealed that the levels of the active metabolite hydroxy acid-lovastatin (101) in antibiotic-treated rats were lower than that without antibiotics. This result indicates that antibiotic drugs reduce the biotransformation of the drug lovastatin (98) to its active form, hydroxy acid-lovastatin (101), because antibiotics affect gut microbiome. The in vivo metabolism of lovastatin (98) to its active form, hydroxy acid-lovastatin (101), is important for the therapeutic efficacy of this drug; therefore antibiotic intake of patients treated with lovastatin (98) would lead to the decrease of the active form, hydroxy acid-lovastatin (101), thus decreasing its therapeutic effects [146]. This study clearly demonstrates the drug–drug interaction mediated by changes of gut microbiome.
4. Conclusions
Intriguingly, gut microbiome is very important for human health and diseases, and it is therefore recognized as an “organ” or a “tissue” in the human body. Gut microorganisms have much more genes encoding enzymes than those of human genome; therefore, enzymes of these microbes are involved in many biochemical processes, i.e., metabolism of xenobiotics (compounds not produced in human host, e.g., drugs and pollutants) and dietary sources. Metabolites produced by gut microbiome play significant roles in human health and diseases; these metabolites include short-chain fatty acids such as butyrate (11), as well as other metabolites, e.g., nicotinamide (12), 5-aminovaleric acid (14), and taurine (15) (see Section 2). Since gut microbiome and its metabolites substantially contribute to human health and diseases, a therapy by intervention strategies using gut microbiota can potentially be useful for some diseases, for example, metabolic disorders, cardiovascular disease, food allergy, and neurological disorders. Supplementation with probiotics or certain gut bacteria, as well as their metabolites, may be a new therapeutic method in the future. Fecal microbiota transplantation, e.g., transferring gut bacteria from healthy individuals into patients, is a challenging research study in the near future.
Gut microbiome can metabolite commonly used drugs and natural products. Drug metabolism by gut microorganisms decreases the levels of drugs in serum, thus disturbing the drug pharmacokinetics, which can lead to alteration of therapeutic efficiency. Moreover, metabolites produced by the drug metabolism of gut microbiome contribute considerably to the drug efficacy. For example, the levels of the drug L-dopa (56) are substantially reduced by the metabolic activity of gut microbiome, and this results in the requirement of higher doses for the Parkinson’s patients with gut microbiome that has high metabolic activity toward the drug L-dopa (56) (see Section 3.1). This example well demonstrates the role of gut microorganisms on treatment outcomes of the commonly used drugs. Gut microbiome could improve many drug therapies, for example, cancer immunotherapy targeting CTLA-4 blockade and immune checkpoint inhibitor via the PD-1/PD-L1 pathway. Moreover, the metabolism of gut microbiome improves drug efficacy because it assists the bioconversion of some drugs into their active forms, for example, a biotransformation of lovastatin (98) to its active form, hydroxy acid-lovastatin (101), and a bioconversion of aspirin (70) to salicylic acid (71) that actively reduces pain. Interestingly, gut microbiome involves in a biotransformation of an alkaloid natural product berberine (78) to an absorbable form, dihydroberberine (80), which is absorbed at the intestine system (see Section 3.2). This result demonstrates that gut microbiome facilitates drug delivery of berberine (78) that has poor solubility by a biotransformation to an absorbable form, dihydroberberine (80), which is in turn converted to its active form berberine (78) in the human body. Since gut microbiome plays many important roles in drugs and natural products, the metabolism of natural products and drug candidates by gut microbiome should therefore be studied, and it should be a part of the drug development process. Gut microbiome can potentially play a crucial role for the improvement of drug safety and efficacy.
Acknowledgments
The author thanks the Center of Excellence on Environmental Health and Toxicology, Science & Technology Postgraduate Education and Research Development Office (PERDO), Ministry of Education, for the support of research that leads to this book chapter.
Conflict of interest
The author declares no competing interests or no conflict of interest.
\n',keywords:"gut microbiota, gut microbiome, drug-microbiome interactions, drug-microbiota interactions, natural products-microbiome interactions, drug metabolism, drug toxicity, biotransformation, bioconversion",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72563.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72563.xml",downloadPdfUrl:"/chapter/pdf-download/72563",previewPdfUrl:"/chapter/pdf-preview/72563",totalDownloads:71,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 26th 2020",dateReviewed:"May 15th 2020",datePrePublished:"June 19th 2020",datePublished:null,dateFinished:null,readingETA:"0",abstract:"Trillions of microorganisms with a complex and diverse community are in the human gastrointestinal tract. Gut microbial genomes have much more genes than human genome, thus having a variety of enzymes for many metabolic activities; therefore, gut microbiota is recognized as an “organ” that has essential functions to human health. There are interactions between host and gut microbiome, and there are correlations between gut microbiome in the healthy state and in certain disease states, such as cancer, liver diseases, diabetes, and obesity. Gut microbiota can produce metabolites from nutrients of dietary sources and from drug metabolisms; these metabolites, for example, short-chain fatty acids (SCFAs), have substantial effects on human health. Drug-microbiome interactions play a crucial role in therapeutic efficiency. Some drugs are able to change compositions of gut microbiota, which can lead to either enhance or reduce therapeutic efficiency. This chapter provides an overview of roles of gut microbiota in human health and diseases and recent research studies on the metabolism or toxicity of drugs and natural products. Since gut bacteria considerably contribute to drug metabolism, research on the influence of gut microbiome on drug candidates (or natural products) should be part of the drug development processes.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72563",risUrl:"/chapter/ris/72563",signatures:"Prasat Kittakoop",book:{id:"9403",title:"Human Microbiome",subtitle:null,fullTitle:"Human Microbiome",slug:null,publishedDate:null,bookSignature:"Prof. Natalia Beloborodova and Prof. A.V. Grechko",coverURL:"https://cdn.intechopen.com/books/images_new/9403.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"199461",title:"Prof.",name:"Natalia",middleName:null,surname:"Beloborodova",slug:"natalia-beloborodova",fullName:"Natalia Beloborodova"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Contributions of metabolites produced by gut microbiome to human health and diseases",level:"1"},{id:"sec_3",title:"3. Interactions of gut microbiome and drugs and/or natural products",level:"1"},{id:"sec_3_2",title:"3.1 Interactions of gut microbiome and commonly used drugs",level:"2"},{id:"sec_4_2",title:"3.2 Interactions of gut microbiome and natural products",level:"2"},{id:"sec_6",title:"4. Conclusions",level:"1"},{id:"sec_7",title:"Acknowledgments",level:"1"},{id:"sec_10",title:"Conflict of interest",level:"1"}],chapterReferences:[{id:"B1",body:'Sanders ME, Merenstein DJ, Reid G, Gibson GR, Rastall RA. Probiotics and prebiotics in intestinal health and disease: From biology to the clinic. Nature Reviews. Gastroenterology & Hepatology. 2019;16(10):605-616. DOI: 10.1038/s41575-019-0173-3'},{id:"B2",body:'Matthies A, Loh G, Blaut M, Braune A. Daidzein and genistein are converted to equol and 5-hydroxy-equol by human intestinal Slackia isoflavoniconvertens in gnotobiotic rats. The Journal of Nutrition. 2012;142(1):40-46. DOI: 10.3945/jn.111.148247'},{id:"B3",body:'Matthies A, Clavel T, Gutschow M, Engst W, Haller D, Blaut M, et al. Conversion of daidzein and genistein by an anaerobic bacterium newly isolated from the mouse intestine. Applied and Environmental Microbiology. 2008;74(15):4847-4852. DOI: 10.1128/AEM.00555-08'},{id:"B4",body:'Setchell KD, Clerici C, Lephart ED, Cole SJ, Heenan C, Castellani D, et al. S-equol, a potent ligand for estrogen receptor beta, is the exclusive enantiomeric form of the soy isoflavone metabolite produced by human intestinal bacterial flora. The American Journal of Clinical Nutrition. 2005;81(5):1072-1079. DOI: 10.1093/ajcn/81.5.1072'},{id:"B5",body:'Raimondi S, Roncaglia L, De Lucia M, Amaretti A, Leonardi A, Pagnoni UM, et al. Bioconversion of soy isoflavones daidzin and daidzein by Bifidobacterium strains. Applied Microbiology and Biotechnology. 2009;81(5):943-950. DOI: 10.1007/s00253-008-1719-4'},{id:"B6",body:'Frankenfeld CL. O-Desmethylangolensin: The importance of equol’s lesser known cousin to human health. Advances in Nutrition. 2011;2(4):317-324. DOI: 10.3945/an.111.000539'},{id:"B7",body:'Rowland I, Wiseman H, Sanders T, Adlercreutz H, Bowey E. Metabolism of oestrogens and phytoestrogens: Role of the gut microflora. Biochemical Society Transactions. 1999;27(2):304-308. DOI: 10.1042/bst0270304'},{id:"B8",body:'Fujioka M, Uehara M, Wu J, Adlercreutz H, Suzuki K, Kanazawa K, et al. Equol, a metabolite of daidzein, inhibits bone loss in ovariectomized mice. The Journal of Nutrition. 2004;134(10):2623-2627. DOI: 10.1093/jn/134.10.2623'},{id:"B9",body:'Kimira Y, Katsumata S, Suzuki K, Ishimi Y, Ueno T, Uchiyama S, et al. Comparative activities of the S-enantiomer and racemic forms of equol on bone fragility in ovariectomized mice. Bioscience, Biotechnology, and Biochemistry. 2012;76(5):1018-1021. DOI: 10.1271/bbb.110973'},{id:"B10",body:'Shimada Y, Takahashi M, Miyazawa N, Abiru Y, Uchiyama S, Hishigaki H. Identification of a novel dihydrodaidzein racemase essential for biosynthesis of equol from daidzein in Lactococcus sp. strain 20-92. Applied and Environmental Microbiology. 2012;78(14):4902-4907. DOI: 10.1128/AEM.00410-12'},{id:"B11",body:'Burcelin R. Regulation of metabolism: A cross talk between gut microbiota and its human host. Physiology. 2012;27(5):300-307. DOI: 10.1152/physiol.00023.2012'},{id:"B12",body:'O’Hara AM, Shanahan F. The gut flora as a forgotten organ. EMBO Reports. 2006;7(7):688-693. DOI: 10.1038/sj.embor.7400731'},{id:"B13",body:'Zhu B, Wang X, Li L. Human gut microbiome: The second genome of human body. Protein & Cell. 2010;1(8):718-725. DOI: 10.1007/s13238-010-0093-z'},{id:"B14",body:'Iacob S, Iacob DG. Infectious threats, the intestinal barrier, and its Trojan horse: Dysbiosis. Frontiers in Microbiology. 2019;10:1676. DOI: 10.3389/fmicb.2019.01676'},{id:"B15",body:'Hills RD Jr, Pontefract BA, Mishcon HR, Black CA, Sutton SC, Theberge CR. Gut microbiome: Profound implications for diet and disease. Nutrients. 2019;11(7):1613. DOI: 10.3390/nu11071613'},{id:"B16",body:'Carding S, Verbeke K, Vipond DT, Corfe BM, Owen LJ. Dysbiosis of the gut microbiota in disease. Microbial Ecology in Health and Disease. 2015;26:26191. DOI: 10.3402/mehd.v26.26191'},{id:"B17",body:'Rooks MG, Garrett WS. Gut microbiota, metabolites and host immunity. Nature Reviews. Immunology. 2016;16(6):341-352. DOI: 10.1038/nri.2016.42'},{id:"B18",body:'Li Z, Quan G, Jiang X, Yang Y, Ding X, Zhang D, et al. Effects of metabolites derived from gut microbiota and hosts on pathogens. Frontiers in Cellular and Infection Microbiology. 2018;8:314. DOI: 10.3389/fcimb.2018.00314'},{id:"B19",body:'Louis P, Hold GL, Flint HJ. The gut microbiota, bacterial metabolites and colorectal cancer. Nature Reviews. Microbiology. 2014;12(10):661-672. DOI: 10.1038/nrmicro3344'},{id:"B20",body:'Caspani G, Kennedy S, Foster JA, Swann J. Gut microbial metabolites in depression: Understanding the biochemical mechanisms. Microbial Cell. 2019;6(10):454-481. DOI: 10.15698/mic2019.10.693'},{id:"B21",body:'Zeng H, Umar S, Rust B, Lazarova D, Bordonaro M. Secondary bile acids and short chain fatty acids in the colon: A focus on colonic microbiome, cell proliferation, inflammation, and cancer. International Journal of Molecular Sciences. 2019;20(5):1214. DOI: 10.3390/ijms20051214'},{id:"B22",body:'Brial F, Le Lay A, Dumas ME, Gauguier D. Implication of gut microbiota metabolites in cardiovascular and metabolic diseases. Cellular and Molecular Life Sciences. 2018;75(21):3977-3990. DOI: 10.1007/s00018-018-2901-1'},{id:"B23",body:'Wang Z, Zhao Y. Gut microbiota derived metabolites in cardiovascular health and disease. Protein & Cell. 2018;9(5):416-431. DOI: 10.1007/s13238-018-0549-0'},{id:"B24",body:'den Besten G, van Eunen K, Groen AK, Venema K, Reijngoud DJ, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. Journal of Lipid Research. 2013;54(9):2325-2340. DOI: 10.1194/jlr.R036012'},{id:"B25",body:'Furusawa Y, Obata Y, Fukuda S, Endo TA, Nakato G, Takahashi D, et al. Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature. 2013;504(7480):446-450. DOI: 10.1038/nature12721'},{id:"B26",body:'Felizardo RJF, Watanabe IKM, Dardi P, Rossoni LV, Camara NOS. The interplay among gut microbiota, hypertension and kidney diseases: The role of short-chain fatty acids. Pharmacological Research. 2019;141:366-377. DOI: 10.1016/j.phrs.2019.01.019'},{id:"B27",body:'Parada Venegas D, De la Fuente MK, Landskron G, Gonzalez MJ, Quera R, Dijkstra G, et al. Short chain fatty acids (SCFAs)-mediated gut epithelial and immune regulation and its relevance for inflammatory bowel diseases. Frontiers in Immunology. 2019;10:277. DOI: 10.3389/fimmu.2019.00277'},{id:"B28",body:'Zhuang X, Li T, Li M, Huang S, Qiu Y, Feng R, et al. Systematic review and meta-analysis: Short-chain fatty acid characterization in patients with inflammatory bowel disease. Inflammatory Bowel Diseases. 2019;25(11):1751-1763. DOI: 10.1093/ibd/izz188'},{id:"B29",body:'Yang G, Chen S, Deng B, Tan C, Deng J, Zhu G, et al. Implication of G protein-coupled receptor 43 in intestinal inflammation: A mini-review. Frontiers in Immunology. 2018;9:1434. DOI: 10.3389/fimmu.2018.01434'},{id:"B30",body:'Koh A, De Vadder F, Kovatcheva-Datchary P, Backhed F. From dietary fiber to host physiology: Short-chain fatty acids as key bacterial metabolites. Cell. 2016;165(6):1332-1345. DOI: 10.1016/j.cell.2016.05.041'},{id:"B31",body:'Fellows R, Denizot J, Stellato C, Cuomo A, Jain P, Stoyanova E, et al. Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases. Nature Communications. 2018;9(1):105. DOI: 10.1038/s41467-017-02651-5'},{id:"B32",body:'Sanna S, van Zuydam NR, Mahajan A, Kurilshikov A, Vich Vila A, Vosa U, et al. Causal relationships among the gut microbiome, short-chain fatty acids and metabolic diseases. Nature Genetics. 2019;51(4):600-605. DOI: 10.1038/s41588-019-0350-x'},{id:"B33",body:'Larsen N, Vogensen FK, van den Berg FW, Nielsen DS, Andreasen AS, Pedersen BK, et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS One. 2010;5(2):e9085. DOI: 10.1371/journal.pone.0009085'},{id:"B34",body:'Hu J, Lin S, Zheng B, Cheung PCK. Short-chain fatty acids in control of energy metabolism. Critical Reviews in Food Science and Nutrition. 2018;58(8):1243-1249. DOI: 10.1080/10408398.2016.1245650'},{id:"B35",body:'Zhao W, Ho HE, Bunyavanich S. The gut microbiome in food allergy. Annals of Allergy, Asthma & Immunology. 2019;122(3):276-282. DOI: 10.1016/j.anai.2018.12.012'},{id:"B36",body:'Berni Canani R, Paparo L, Nocerino R, Di Scala C, Della Gatta G, Maddalena Y, et al. Gut microbiome as target for innovative strategies against food allergy. Frontiers in Immunology. 2019;10:191. DOI: 10.3389/fimmu.2019.00191'},{id:"B37",body:'Rachid R, Chatila TA. The role of the gut microbiota in food allergy. Current Opinion in Pediatrics. 2016;28(6):748-753. DOI: 10.1097/MOP.0000000000000427'},{id:"B38",body:'Feehley T, Plunkett CH, Bao R, Choi Hong SM, Culleen E, Belda-Ferre P, et al. Healthy infants harbor intestinal bacteria that protect against food allergy. Nature Medicine. 2019;25(3):448-453. DOI: 10.1038/s41591-018-0324-z'},{id:"B39",body:'Schwiertz A, Hold GL, Duncan SH, Gruhl B, Collins MD, Lawson PA, et al. Anaerostipes caccae gen. nov., sp. nov., a new saccharolytic, acetate-utilising, butyrate-producing bacterium from human faeces. Systematic and Applied Microbiology. 2002;25(1):46-51. DOI: 10.1078/0723-2020-00096'},{id:"B40",body:'Donohoe DR, Garge N, Zhang X, Sun W, O’Connell TM, Bunger MK, et al. The microbiome and butyrate regulate energy metabolism and autophagy in the mammalian colon. Cell Metabolism. 2011;13(5):517-526. DOI: 10.1016/j.cmet.2011.02.018'},{id:"B41",body:'Berni Canani R, Sangwan N, Stefka AT, Nocerino R, Paparo L, Aitoro R, et al. Lactobacillus rhamnosus GG-supplemented formula expands butyrate-producing bacterial strains in food allergic infants. The ISME Journal. 2016;10(3):742-750. DOI: 10.1038/ismej.2015.151'},{id:"B42",body:'Fricker RA, Green EL, Jenkins SI, Griffin SM. The influence of nicotinamide on health and disease in the central nervous system. International Journal of Tryptophan Research. 2018;11:1-11. DOI: 10.1177/1178646918776658'},{id:"B43",body:'Blacher E, Bashiardes S, Shapiro H, Rothschild D, Mor U, Dori-Bachash M, et al. Potential roles of gut microbiome and metabolites in modulating ALS in mice. Nature. 2019;572(7770):474-480. DOI: 10.1038/s41586-019-1443-5'},{id:"B44",body:'Depommier C, Everard A, Druart C, Plovier H, Van Hul M, Vieira-Silva S, et al. Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: A proof-of-concept exploratory study. Nature Medicine. 2019;25(7):1096-1103. DOI: 10.1038/s41591-019-0495-2'},{id:"B45",body:'Xu M, Xu X, Li J, Li F. Association between gut microbiota and autism spectrum disorder: A systematic review and meta-analysis. Frontiers in Psychiatry. 2019;10:473. DOI: 10.3389/fpsyt.2019.00473'},{id:"B46",body:'Sharon G, Cruz NJ, Kang DW, Gandal MJ, Wang B, Kim YM, et al. Human gut microbiota from autism spectrum disorder promote behavioral symptoms in mice. Cell. 2019;177(6):1600-1618.e17. DOI: 10.1016/j.cell.2019.05.004'},{id:"B47",body:'Callery PS, Geelhaar LA. 1-Piperideine as an in vivo precursor of the gamma-aminobutyric acid homologue 5-aminopentanoic acid. Journal of Neurochemistry. 1985;45(3):946-968. DOI: 10.1111/j.1471-4159.1985.tb04085.x'},{id:"B48",body:'Park E, Cohen I, Gonzalez M, Castellano MR, Flory M, Jenkins EC, et al. Is taurine a biomarker in autistic spectrum disorder? Advances in Experimental Medicine and Biology. 2017;975(Pt 1):3-16. DOI: 10.1007/978-94-024-1079-2_1'},{id:"B49",body:'Seo DO, Holtzman DM. Gut microbiota: From the forgotten organ to a potential key player in the pathology of Alzheimer disease. The Journals of Gerontology: Series A. 2019:glz262. DOI: 10.1093/gerona/glz262'},{id:"B50",body:'Clarke G, Stilling RM, Kennedy PJ, Stanton C, Cryan JF, Dinan TG. Minireview: Gut microbiota: The neglected endocrine organ. Molecular Endocrinology. 2014;28(8):1221-1238. DOI: 10.1210/me.2014-1108'},{id:"B51",body:'Guinane CM, Cotter PD. Role of the gut microbiota in health and chronic gastrointestinal disease: Understanding a hidden metabolic organ. Therapeutic Advances in Gastroenterology. 2013;6(4):295-308. DOI: 10.1177/1756283X13482996'},{id:"B52",body:'Li X, Liu L, Cao Z, Li W, Li H, Lu C, et al. Gut microbiota as an “invisible organ” that modulates the function of drugs. Biomedicine & Pharmacotherapy. 2020;121:109653. DOI: 10.1016/j.biopha.2019.109653'},{id:"B53",body:'Lubomski M, Davis RL, Sue CM. The gut microbiota: A novel therapeutic target in Parkinson’s disease? Parkinsonism & Related Disorders. 2019;66:265-266. DOI: 10.1016/j.parkreldis.2019.08.010'},{id:"B54",body:'Yang S, Li X, Yang F, Zhao R, Pan X, Liang J, et al. Gut microbiota-dependent marker TMAO in promoting cardiovascular disease: Inflammation mechanism, clinical prognostic, and potential as a therapeutic target. Frontiers in Pharmacology. 2019;10:1360. DOI: 10.3389/fphar.2019.01360'},{id:"B55",body:'Okubo H, Nakatsu Y, Kushiyama A, Yamamotoya T, Matsunaga Y, Inoue MK, et al. Gut microbiota as a therapeutic target for metabolic disorders. Current Medicinal Chemistry. 2018;25(9):984-1001. DOI: 10.2174/0929867324666171009121702'},{id:"B56",body:'Amedei A. Potential therapeutic strategies to target gut microbiota in hepatocellular carcinoma. Hepatobiliary Surgery and Nutrition. 2019;8(5):527-529. DOI: 10.21037/hbsn.2019.09.04'},{id:"B57",body:'Suk KT, Kim DJ. Gut microbiota: Novel therapeutic target for nonalcoholic fatty liver disease. Expert Review of Gastroenterology & Hepatology. 2019;13(3):193-204. DOI: 10.1080/17474124.2019.1569513'},{id:"B58",body:'Aitoro R, Paparo L, Amoroso A, Di Costanzo M, Cosenza L, Granata V, et al. Gut microbiota as a target for preventive and therapeutic intervention against food allergy. Nutrients. 2017;9(7):672. DOI: 10.3390/nu9070672'},{id:"B59",body:'Zhao S, Gao G, Li W, Li X, Zhao C, Jiang T, et al. Antibiotics are associated with attenuated efficacy of anti-PD-1/PD-L1 therapies in Chinese patients with advanced non-small cell lung cancer. Lung Cancer. 2019;130:10-17. DOI: 10.1016/j.lungcan.2019.01.017'},{id:"B60",body:'Sender R, Fuchs S, Milo R. Revised estimates for the number of human and bacteria cells in the body. PLoS Biology. 2016;14(8):e1002533. DOI: 10.1371/journal.pbio.1002533'},{id:"B61",body:'Qin J, Li R, Raes J, Arumugam M, Burgdorf KS, Manichanh C, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature. 2010;464(7285):59-65. DOI: 10.1038/nature08821'},{id:"B62",body:'Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Mapping human microbiome drug metabolism by gut bacteria and their genes. Nature. 2019;570(7762):462-467. DOI: 10.1038/s41586-019-1291-3'},{id:"B63",body:'Ianiro G, Tilg H, Gasbarrini A. Antibiotics as deep modulators of gut microbiota: Between good and evil. Gut. 2016;65(11):1906-1915. DOI: 10.1136/gutjnl-2016-312297'},{id:"B64",body:'Kim S, Covington A, Pamer EG. The intestinal microbiota: Antibiotics, colonization resistance, and enteric pathogens. Immunological Reviews. 2017;279(1):90-105. DOI: 10.1111/imr.12563'},{id:"B65",body:'Maier L, Pruteanu M, Kuhn M, Zeller G, Telzerow A, Anderson EE, et al. Extensive impact of non-antibiotic drugs on human gut bacteria. Nature. 2018;555(7698):623-628. DOI: 10.1038/nature25979'},{id:"B66",body:'Zimmermann M, Zimmermann-Kogadeeva M, Wegmann R, Goodman AL. Separating host and microbiome contributions to drug pharmacokinetics and toxicity. Science. 2019;363(6427):eaat9931. DOI: 10.1126/science.aat9931'},{id:"B67",body:'Nakayama H, Kinouchi T, Kataoka K, Akimoto S, Matsuda Y, Ohnishi Y. Intestinal anaerobic bacteria hydrolyse sorivudine, producing the high blood concentration of 5-(E)-(2-bromovinyl)uracil that increases the level and toxicity of 5-fluorouracil. Pharmacogenetics. 1997;7(1):35-43. DOI: 10.1097/00008571-199702000-00005'},{id:"B68",body:'Elmer GW, Remmel RP. Role of the intestinal microflora in clonazepam metabolism in the rat. Xenobiotica. 1984;14(11):829-840. DOI: 10.3109/00498258409151481'},{id:"B69",body:'Wilson ID, Nicholson JK. Gut microbiome interactions with drug metabolism, efficacy, and toxicity. Translational Research. 2017;179:204-222. DOI: 10.1016/j.trsl.2016.08.002'},{id:"B70",body:'Winter J, Morris GN, O’Rourke-Locascio S, Bokkenheuser VD, Mosbach EH, Cohen BI, et al. Mode of action of steroid desmolase and reductases synthesized by Clostridium “scindens” (formerly Clostridium strain 19). Journal of Lipid Research. 1984;25(10):1124-1131. Available from: https://www.jlr.org/content/25/10/1124.long'},{id:"B71",body:'Morris GN, Winter J, Cato EP, Ritchie AE, Bokkenheuser VD. Clostridium scindens sp. nov., a human intestinal bacterium with desmolytic activity on corticoids. International Journal of Systematic and Evolutionary Microbiology. 1985;35(4):478-481. DOI: 10.1099/00207713-35-4-478'},{id:"B72",body:'Yeung PK, Prescott C, Haddad C, Montague TJ, McGregor C, Quilliam MA, et al. Pharmacokinetics and metabolism of diltiazem in healthy males and females following a single oral dose. European Journal of Drug Metabolism and Pharmacokinetics. 1993;18(2):199-206. DOI: 10.1007/BF03188796'},{id:"B73",body:'Goldin BR, Peppercorn MA, Goldman P. Contributions of host and intestinal microflora in the metabolism of L-dopa by the rat. The Journal of Pharmacology and Experimental Therapeutics. 1973;186(1):160-166. Available from: http://jpet.aspetjournals.org/content/186/1/160.long'},{id:"B74",body:'Sandler M, Goodwin BL, Ruthven CR. Therapeutic implications in Parkinsonism of m-tyramine formation from L-dopa in man. Nature. 1971;229(5284):414-415. DOI: 10.1038/229414a0'},{id:"B75",body:'Goldman P, Peppercorn MA, Goldin BR. Metabolism of drugs by microorganisms in the intestine. The American Journal of Clinical Nutrition. 1974;27(11):1348-1355. DOI: 10.1093/ajcn/27.11.1348'},{id:"B76",body:'Fasano A, Bove F, Gabrielli M, Petracca M, Zocco MA, Ragazzoni E, et al. The role of small intestinal bacterial overgrowth in Parkinson’s disease. Movement Disorders. 2013;28(9):1241-1249. DOI: 10.1002/mds.25522'},{id:"B77",body:'Maini Rekdal V, Bess EN, Bisanz JE, Turnbaugh PJ, Balskus EP. Discovery and inhibition of an interspecies gut bacterial pathway for Levodopa metabolism. Science. 2019;364(6445):eaau6323. DOI: 10.1126/science.aau6323'},{id:"B78",body:'van Kessel SP, Frye AK, El-Gendy AO, Castejon M, Keshavarzian A, van Dijk G, et al. Gut bacterial tyrosine decarboxylases restrict levels of levodopa in the treatment of Parkinson’s disease. Nature Communications. 2019;10(1):310. DOI: 10.1038/s41467-019-08294-y'},{id:"B79",body:'Vetizou M, Pitt JM, Daillere R, Lepage P, Waldschmitt N, Flament C, et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science. 2015;350(6264):1079-1084. DOI: 10.1126/science.aad1329'},{id:"B80",body:'Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre M-L, et al. The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science. 2018;359(6371):104-108. DOI: 10.1126/science.aao3290'},{id:"B81",body:'Routy B, Le Chatelier E, Derosa L, Duong CPM, Alou MT, Daillère R, et al. Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors. Science. 2018;359(6371):91-97. DOI: 10.1126/science.aan3706'},{id:"B82",body:'Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, et al. Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science. 2018;359(6371):97-103. DOI: 10.1126/science.aan4236'},{id:"B83",body:'Ma W, Mao Q , Xia W, Dong G, Yu C, Jiang F. Gut microbiota shapes the efficiency of cancer therapy. Frontiers in Microbiology. 2019;10:1050. DOI: 10.3389/fmicb.2019.01050'},{id:"B84",body:'Viaud S, Saccheri F, Mignot G, Yamazaki T, Daillere R, Hannani D, et al. The intestinal microbiota modulates the anticancer immune effects of cyclophosphamide. Science. 2013;342(6161):971-976. DOI: 10.1126/science.1240537'},{id:"B85",body:'Daillere R, Vetizou M, Waldschmitt N, Yamazaki T, Isnard C, Poirier-Colame V, et al. Enterococcus hirae and Barnesiella intestinihominis facilitate cyclophosphamide-induced therapeutic immunomodulatory effects. Immunity. 2016;45(4):931-943. DOI: 10.1016/j.immuni.2016.09.009'},{id:"B86",body:'Geller LT, Barzily-Rokni M, Danino T, Jonas OH, Shental N, Nejman D, et al. Potential role of intratumor bacteria in mediating tumor resistance to the chemotherapeutic drug gemcitabine. Science. 2017;357(6356):1156-1160. DOI: 10.1126/science.aah5043'},{id:"B87",body:'Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine: Metabolism, mechanisms of action, and self-potentiation. Seminars in Oncology. 1995;22(4 Suppl 11):3-10. Available from: https://scinapse.io/papers/2284799106'},{id:"B88",body:'Vande Voorde J, Sabuncuoglu S, Noppen S, Hofer A, Ranjbarian F, Fieuws S, et al. Nucleoside-catabolizing enzymes in mycoplasma-infected tumor cell cultures compromise the cytostatic activity of the anticancer drug gemcitabine. The Journal of Biological Chemistry. 2014;289(19):13054-13065. DOI: 10.1074/jbc.M114.558924'},{id:"B89",body:'Yu T, Guo F, Yu Y, Sun T, Ma D, Han J, et al. Fusobacterium nucleatum promotes chemoresistance to colorectal cancer by modulating autophagy. Cell. 2017;170(3):548-563.e16. DOI: 10.1016/j.cell.2017.07.008'},{id:"B90",body:'Ganesan K, Guo S, Fayyaz S, Zhang G, Xu B. Targeting programmed Fusobacterium nucleatum Fap2 for colorectal cancer therapy. Cancers. 2019;11(10):1592. DOI: 10.3390/cancers11101592'},{id:"B91",body:'Gethings-Behncke C, Coleman HG, Jordao HWT, Longley DB, Crawford N, Murray LJ, et al. Fusobacterium nucleatum in the colorectum and its association with cancer risk and survival: A systematic review and meta-analysis. Cancer Epidemiology, Biomarkers & Prevention. 2020;29(3):539-548. DOI: 10.1158/1055-9965.EPI-18-1295'},{id:"B92",body:'Kim D-H. Gut microbiota-mediated drug-antibiotic interactions. Drug Metabolism and Disposition. 2015;43(10):1581-1589. DOI: 10.1124/dmd.115.063867'},{id:"B93",body:'Zhang J, Sun Y, Wang R, Zhang J. Gut microbiota-mediated drug-drug interaction between amoxicillin and aspirin. Scientific Reports. 2019;9(1):16194. DOI: 10.1038/s41598-019-52632-5'},{id:"B94",body:'Patrono C, Baigent C. Role of aspirin in primary prevention of cardiovascular disease. Nature Reviews. Cardiology. 2019;16(11):675-686. DOI: 10.1038/s41569-019-0225-y'},{id:"B95",body:'Zhang X, Feng Y, Liu X, Ma J, Li Y, Wang T, et al. Beyond a chemopreventive reagent, aspirin is a master regulator of the hallmarks of cancer. Journal of Cancer Research and Clinical Oncology. 2019;145(6):1387-1403. DOI: 10.1007/s00432-019-02902-6'},{id:"B96",body:'Choi HW, Tian M, Song F, Venereau E, Preti A, Park S-W, et al. Aspirin’s active metabolite salicylic acid targets high mobility group box 1 to modulate inflammatory responses. Molecular Medicine. 2015;21(1):526-535. DOI: 10.2119/molmed.2015.00148'},{id:"B97",body:'Kim IS, Yoo DH, Jung IH, Lim S, Jeong JJ, Kim KA, et al. Reduced metabolic activity of gut microbiota by antibiotics can potentiate the antithrombotic effect of aspirin. Biochemical Pharmacology. 2016;122:72-79. DOI: 10.1016/j.bcp.2016.09.023'},{id:"B98",body:'Sun Y, Zhang J, Zhao A, Li W, Feng Q , Wang R. Effects of intestinal flora on the pharmacokinetics and pharmacodynamics of aspirin in high-altitude hypoxia. PLoS One. 2020;15(3):e0230197. DOI: 10.1371/journal.pone.0230197'},{id:"B99",body:'Zhang J, Chen Y, Sun Y, Wang R, Zhang J, Jia Z. Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine. Drug Delivery. 2018;25(1):1175-1181. DOI: 10.1080/10717544.2018.1469687'},{id:"B100",body:'Poolchanuan P, Unagul P, Thongnest S, Wiyakrutta S, Ngamrojanavanich N, Mahidol C, et al. An anticonvulsive drug, valproic acid (valproate), has effects on the biosynthesis of fatty acids and polyketides in microorganisms. Scientific Reports. 2020;10:9300. DOI: 10.1038/s41598-020-66251-y'},{id:"B101",body:'Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS. Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. The Journal of Biological Chemistry. 2001;276(39):36734-36741. DOI: 10.1074/jbc.M101287200'},{id:"B102",body:'Vaughan EE, Heilig HG, Ben-Amor K, de Vos WM. Diversity, vitality and activities of intestinal lactic acid bacteria and bifidobacteria assessed by molecular approaches. FEMS Microbiology Reviews. 2005;29(3):477-490. DOI: 10.1016/j.femsre.2005.04.009'},{id:"B103",body:'Chehoud C, Albenberg LG, Judge C, Hoffmann C, Grunberg S, Bittinger K, et al. Fungal signature in the gut microbiota of pediatric patients with inflammatory bowel disease. Inflammatory Bowel Diseases. 2015;21(8):1948-1956. DOI: 10.1097/MIB.0000000000000454'},{id:"B104",body:'Nash AK, Auchtung TA, Wong MC, Smith DP, Gesell JR, Ross MC, et al. The gut mycobiome of the human microbiome project healthy cohort. Microbiome. 2017;5(1):153. DOI: 10.1186/s40168-017-0373-4'},{id:"B105",body:'Zacherl JR, Mihalik SJ, Chace DH, Christensen TC, Robinson LJ, Blair HC. Elaidate, an 18-carbon trans-monoenoic fatty acid, inhibits beta-oxidation in human peripheral blood macrophages. Journal of Cellular Biochemistry. 2014;115(1):62-70. DOI: 10.1002/jcb.24633'},{id:"B106",body:'Zacherl JR, Tourkova I, St Croix CM, Robinson LJ, Peck Palmer OM, Mihalik SJ, et al. Elaidate, an 18-carbon trans-monoenoic fatty acid, but not physiological fatty acids increases intracellular Zn(2+) in human macrophages. Journal of Cellular Biochemistry. 2015;116(4):524-532. DOI: 10.1002/jcb.25002'},{id:"B107",body:'Smith S, Tsai SC. The type I fatty acid and polyketide synthases: A tale of two megasynthases. Natural Product Reports. 2007;24(5):1041-1072. DOI: 10.1039/b603600g'},{id:"B108",body:'Wang L, Ravichandran V, Yin Y, Yin J, Zhang Y. Natural products from mammalian gut microbiota. Trends in Biotechnology. 2019;37(5):492-504. DOI: 10.1016/j.tibtech.2018.10.003'},{id:"B109",body:'Li BY, Xu XY, Gan RY, Sun QC, Meng JM, Shang A, et al. Targeting gut microbiota for the prevention and management of diabetes mellitus by dietary natural products. Food. 2019;8(10):440. DOI: 10.3390/foods8100440'},{id:"B110",body:'Tong X, Xu J, Lian F, Yu X, Zhao Y, Xu L, et al. Structural alteration of gut microbiota during the amelioration of human type 2 diabetes with hyperlipidemia by metformin and a traditional Chinese herbal formula: a multicenter, randomized, open label clinical trial. mBio. 2018;9(3):e02392-e02317. DOI: 10.1128/mBio.02392-17'},{id:"B111",body:'Zhang X, Zhao Y, Zhang M, Pang X, Xu J, Kang C, et al. Structural changes of gut microbiota during berberine-mediated prevention of obesity and insulin resistance in high-fat diet-fed rats. PLoS One. 2012;7(8):e42529. DOI: 10.1371/journal.pone.0042529'},{id:"B112",body:'Zhang X, Zhao Y, Xu J, Xue Z, Zhang M, Pang X, et al. Modulation of gut microbiota by berberine and metformin during the treatment of high-fat diet-induced obesity in rats. Scientific Reports. 2015;5(1):14405. DOI: 10.1038/srep14405'},{id:"B113",body:'Cui H, Cai Y, Wang L, Jia B, Li J, Zhao S, et al. Berberine regulates Treg/Th17 balance to treat ulcerative colitis through modulating the gut microbiota in the colon. Frontiers in Pharmacology. 2018;9:571. DOI: 10.3389/fphar.2018.00571'},{id:"B114",body:'Massot-Cladera M, Perez-Berezo T, Franch A, Castell M, Perez-Cano FJ. Cocoa modulatory effect on rat faecal microbiota and colonic crosstalk. Archives of Biochemistry and Biophysics. 2012;527(2):105-112. DOI: 10.1016/j.abb.2012.05.015'},{id:"B115",body:'Martin-Pelaez S, Camps-Bossacoma M, Massot-Cladera M, Rigo-Adrover M, Franch A, Perez-Cano FJ, et al. Effect of cocoa’s theobromine on intestinal microbiota of rats. Molecular Nutrition & Food Research. 2017;61(10):1700238. DOI: 10.1002/mnfr.201700238'},{id:"B116",body:'Palm NW, de Zoete MR, Cullen TW, Barry NA, Stefanowski J, Hao L, et al. Immunoglobulin A coating identifies colitogenic bacteria in inflammatory bowel disease. Cell. 2014;158(5):1000-1010. DOI: 10.1016/j.cell.2014.08.006'},{id:"B117",body:'Feng R, Shou J-W, Zhao Z-X, He C-Y, Ma C, Huang M, et al. Transforming berberine into its intestine-absorbable form by the gut microbiota. Scientific Reports. 2015;5(1):12155. DOI: 10.1038/srep12155'},{id:"B118",body:'Turner N, Li JY, Gosby A, To SWC, Cheng Z, Miyoshi H, et al. Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: A mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. Diabetes. 2008;57(5):1414-1418. DOI: 10.2337/db07-1552'},{id:"B119",body:'Tan L, Wang Y, Ai G, Luo C, Chen H, Li C, et al. Dihydroberberine, a hydrogenated derivative of berberine firstly identified in Phellodendri Chinese Cortex, exerts anti-inflammatory effect via dual modulation of NF-kappaB and MAPK signaling pathways. International Immunopharmacology. 2019;75:105802. DOI: 10.1016/j.intimp.2019.105802'},{id:"B120",body:'Dai B, Ma Y, Wang W, Zhan Y, Zhang D, Liu R, et al. Dihydroberberine exhibits synergistic effects with sunitinib on NSCLC NCI-H460 cells by repressing MAP kinase pathways and inflammatory mediators. Journal of Cellular and Molecular Medicine. 2017;21(10):2573-2585. DOI: 10.1111/jcmm.13178'},{id:"B121",body:'Yu D, Lv L, Fang L, Zhang B, Wang J, Zhan G, et al. Inhibitory effects and mechanism of dihydroberberine on hERG channels expressed in HEK293 cells. PLoS One. 2017;12(8):e0181823. DOI: 10.1371/journal.pone.0181823'},{id:"B122",body:'Zuo F, Nakamura N, Akao T, Hattori M. Pharmacokinetics of berberine and its main metabolites in conventional and pseudo germ-free rats determined by liquid chromatography/ion trap mass spectrometry. Drug Metabolism and Disposition. 2006;34(12):2064-2072. DOI: 10.1124/dmd.106.011361'},{id:"B123",body:'Zhang P, Qiang X, Zhang M, Ma D, Zhao Z, Zhou C, et al. Demethyleneberberine, a natural mitochondria-targeted antioxidant, inhibits mitochondrial dysfunction, oxidative stress, and steatosis in alcoholic liver disease mouse model. The Journal of Pharmacology and Experimental Therapeutics. 2015;352(1):139-147. DOI: 10.1124/jpet.114.219832'},{id:"B124",body:'Yu XT, Xu YF, Huang YF, Qu C, Xu LQ , Su ZR, et al. Berberrubine attenuates mucosal lesions and inflammation in dextran sodium sulfate-induced colitis in mice. PLoS One. 2018;13(3):e0194069. DOI: 10.1371/journal.pone.0194069'},{id:"B125",body:'Sun S, Zhou S, Lei S, Zhu S, Wang K, Jiang H, et al. Jatrorrhizine reduces 5-HT and NE uptake via inhibition of uptake-2 transporters and produces antidepressant-like action in mice. Xenobiotica. 2019;49(10):1237-1243. DOI: 10.1080/00498254.2018.1542188'},{id:"B126",body:'Mahana D, Trent CM, Kurtz ZD, Bokulich NA, Battaglia T, Chung J, et al. Antibiotic perturbation of the murine gut microbiome enhances the adiposity, insulin resistance, and liver disease associated with high-fat diet. Genome Medicine. 2016;8(1):48. DOI: 10.1186/s13073-016-0297-9'},{id:"B127",body:'Liu X, Zheng H, Lu R, Huang H, Zhu H, Yin C, et al. Intervening effects of total alkaloids of Corydalis saxicola bunting on rats with antibiotic-induced gut microbiota dysbiosis based on 16S rRNA gene sequencing and untargeted metabolomics analyses. Frontiers in Microbiology. 2019;10:1151. DOI: 10.3389/fmicb.2019.01151'},{id:"B128",body:'Zamzow DR, Elias V, Legette LL, Choi J, Stevens JF, Magnusson KR. Xanthohumol improved cognitive flexibility in young mice. Behavioural Brain Research. 2014;275:1-10. DOI: 10.1016/j.bbr.2014.08.045'},{id:"B129",body:'Legette LL, Luna AY, Reed RL, Miranda CL, Bobe G, Proteau RR, et al. Xanthohumol lowers body weight and fasting plasma glucose in obese male Zucker fa/fa rats. Phytochemistry. 2013;91:236-241. DOI: 10.1016/j.phytochem.2012.04.018'},{id:"B130",body:'Hanske L, Loh G, Sczesny S, Blaut M, Braune A. Recovery and metabolism of xanthohumol in germ-free and human microbiota-associated rats. Molecular Nutrition & Food Research. 2010;54(10):1405-1413. DOI: 10.1002/mnfr.200900517'},{id:"B131",body:'Rajilic-Stojanovic M, de Vos WM. The first 1000 cultured species of the human gastrointestinal microbiota. FEMS Microbiology Reviews. 2014;38(5):996-1047. DOI: 10.1111/1574-6976.12075'},{id:"B132",body:'Paraiso IL, Plagmann LS, Yang L, Zielke R, Gombart AF, Maier CS, et al. Reductive metabolism of xanthohumol and 8-prenylnaringenin by the intestinal bacterium Eubacterium ramulus. Molecular Nutrition & Food Research. 2019;63(2):e1800923. DOI: 10.1002/mnfr.201800923'},{id:"B133",body:'Possemiers S, Bolca S, Grootaert C, Heyerick A, Decroos K, Dhooge W, et al. The prenylflavonoid isoxanthohumol from hops (Humulus lupulus L.) is activated into the potent phytoestrogen 8-prenylnaringenin in vitro and in the human intestine. The Journal of Nutrition. 2006;136(7):1862-1867. DOI: 10.1093/jn/136.7.1862'},{id:"B134",body:'Keiler AM, Zierau O, Kretzschmar G. Hop extracts and hop substances in treatment of menopausal complaints. Planta Medica. 2013;79(7):576-579. DOI: 10.1055/s-0032-1328330'},{id:"B135",body:'Martino E, Della Volpe S, Terribile E, Benetti E, Sakaj M, Centamore A, et al. The long story of camptothecin: From traditional medicine to drugs. Bioorganic & Medicinal Chemistry Letters. 2017;27(4):701-707. DOI: 10.1016/j.bmcl.2016.12.085'},{id:"B136",body:'Ramesh M, Ahlawat P, Srinivas NR. Irinotecan and its active metabolite, SN-38: Review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomedical Chromatography. 2010;24(1):104-123. DOI: 10.1002/bmc.1345'},{id:"B137",body:'Nagar S, Blanchard RL. Pharmacogenetics of uridine diphosphoglucuronosyltransferase (UGT) 1A family members and its role in patient response to irinotecan. Drug Metabolism Reviews. 2006;38(3):393-409. DOI: 10.1080/03602530600739835'},{id:"B138",body:'Tobin PJ, Dodds HM, Clarke S, Schnitzler M, Rivory LP. The relative contributions of carboxylesterase and β-glucuronidase in the formation of SN-38 in human colorectal tumours. Oncology Reports. 2003;10(6):1977-1979. DOI: 10.3892/or.10.6.1977'},{id:"B139",body:'Flieger D, Klassert C, Hainke S, Keller R, Kleinschmidt R, Fischbach W. Phase II clinical trial for prevention of delayed diarrhea with cholestyramine/levofloxacin in the second-line treatment with irinotecan biweekly in patients with metastatic colorectal carcinoma. Oncology. 2007;72(1-2):10-16. DOI: 10.1159/000111083'},{id:"B140",body:'Wang X-Q, Zhang A-H, Miao J-H, Sun H, Yan G-L, Wu F-F, et al. Gut microbiota as important modulator of metabolism in health and disease. RSC Advances. 2018;8(74):42380-42389. DOI: 10.1039/C8RA08094A'},{id:"B141",body:'Rowland I, Gibson G, Heinken A, Scott K, Swann J, Thiele I, et al. Gut microbiota functions: Metabolism of nutrients and other food components. European Journal of Nutrition. 2018;57(1):1-24. DOI: 10.1007/s00394-017-1445-8'},{id:"B142",body:'Wallace BD, Wang H, Lane KT, Scott JE, Orans J, Koo JS, et al. Alleviating cancer drug toxicity by inhibiting a bacterial enzyme. Science. 2010;330(6005):831-835. DOI: 10.1126/science.1191175'},{id:"B143",body:'Loman BR, Jordan KR, Haynes B, Bailey MT, Pyter LM. Chemotherapy-induced neuroinflammation is associated with disrupted colonic and bacterial homeostasis in female mice. Scientific Reports. 2019;9(1):16490. DOI: 10.1038/s41598-019-52893-0'},{id:"B144",body:'Panebianco C, Andriulli A, Pazienza V. Pharmacomicrobiomics: Exploiting the drug-microbiota interactions in anticancer therapies. Microbiome. 2018;6(1):92. DOI: 10.1186/s40168-018-0483-7'},{id:"B145",body:'Subhan M, Faryal R, Macreadie I. Exploitation of Aspergillus terreus for the production of natural statins. Jounal of Fungi. 2016;2(2):13. DOI: 10.3390/jof2020013'},{id:"B146",body:'Yoo D-H, Kim IS, Van Le TK, Jung I-H, Yoo HH, Kim D-H. Gut microbiota-mediated drug interactions between lovastatin and antibiotics. Drug Metabolism and Disposition. 2014;42(9):1508-1513. DOI: 10.1124/dmd.114.058354'},{id:"B147",body:'Vyas KP, Kari PH, Prakash SR, Duggan DE. Biotransformation of lovastatin. II. In vitro metabolism by rat and mouse liver microsomes and involvement of cytochrome P-450 in dehydrogenation of lovastatin. Drug Metabolism and Disposition. 1990;18(2):218-222. Available from: http://dmd.aspetjournals.org/content/18/2/218.long'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Prasat Kittakoop",address:"prasat@cri.or.th",affiliation:'
Chulabhorn Graduate Institute, Program in Chemical Sciences, Chulabhorn Royal Academy, Thailand
Chulabhorn Research Institute, Thailand
Center of Excellence on Environmental Health and Toxicology (EHT), CHE, Ministry of Education, Thailand
'}],corrections:null},book:{id:"9403",title:"Human Microbiome",subtitle:null,fullTitle:"Human Microbiome",slug:null,publishedDate:null,bookSignature:"Prof. Natalia Beloborodova and Prof. A.V. Grechko",coverURL:"https://cdn.intechopen.com/books/images_new/9403.jpg",licenceType:"CC BY 3.0",editedByType:null,editors:[{id:"199461",title:"Prof.",name:"Natalia",middleName:null,surname:"Beloborodova",slug:"natalia-beloborodova",fullName:"Natalia Beloborodova"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}}},profile:{item:{id:"152249",title:"Mr.",name:"Alexander",middleName:null,surname:"Suslyakov",email:"susl@thermo.isp.nsc.ru",fullName:"Alexander Suslyakov",slug:"alexander-suslyakov",position:null,biography:null,institutionString:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",totalCites:0,totalChapterViews:"0",outsideEditionCount:0,totalAuthoredChapters:"1",totalEditedBooks:"0",personalWebsiteURL:null,twitterURL:null,linkedinURL:null,institution:null},booksEdited:[],chaptersAuthored:[{title:"LWIR Photodiodes and Focal Plane Arrays Based on Novel HgCdTe/CdZnTe/GaAs Heterostructures Grown by MBE Technique",slug:"lwir-photodiodes-and-focal-plane-arrays-based-on-novel-hgcdte-cdznte-gaas-heterostructures-grown-by-",abstract:null,signatures:"V. V. Vasiliev, V. S. Varavin, S. A. Dvoretsky, I. M. Marchishin, N. N. Mikhailov, A. V. Predein, I. V. Sabinina, Yu. G. Sidorov, A. O. Suslyakov and A. L. Aseev",authors:[{id:"96743",title:"Dr.",name:"Vasily",surname:"Varavin",fullName:"Vasily Varavin",slug:"vasily-varavin",email:"varavin@isp.nsc.ru"},{id:"96745",title:"Dr.",name:"Vladimir",surname:"Vasilyev",fullName:"Vladimir Vasilyev",slug:"vladimir-vasilyev",email:"vas@thermo.isp.nsc.ru"},{id:"96746",title:"Dr.",name:"Sergey",surname:"Dvoretsky",fullName:"Sergey Dvoretsky",slug:"sergey-dvoretsky",email:"dvor@isp.nsc.ru"},{id:"96747",title:"Dr.",name:"Irina",surname:"Sabinina",fullName:"Irina Sabinina",slug:"irina-sabinina",email:"sabinina@isp.nsc.ru"},{id:"96749",title:"Dr.",name:"Yuri",surname:"Sidorov",fullName:"Yuri Sidorov",slug:"yuri-sidorov",email:"sidorov@isp.nsc.ru"},{id:"96753",title:"Dr.",name:"Aleksandr",surname:"Aseev",fullName:"Aleksandr Aseev",slug:"aleksandr-aseev",email:"aseev@isp.nsc.ru"},{id:"152245",title:"Mr.",name:"Igor",surname:"Marchishin",fullName:"Igor Marchishin",slug:"igor-marchishin",email:"march@thermo.isp.nsc.ru"},{id:"152246",title:"Dr.",name:"Nikolai",surname:"Mikhailov",fullName:"Nikolai Mikhailov",slug:"nikolai-mikhailov",email:"mikhailov@isp.nsc.ru"},{id:"152247",title:"Mr.",name:"Alexander",surname:"Predein",fullName:"Alexander Predein",slug:"alexander-predein",email:"alpred@thermo.isp.nsc.ru"},{id:"152249",title:"Mr.",name:"Alexander",surname:"Suslyakov",fullName:"Alexander Suslyakov",slug:"alexander-suslyakov",email:"susl@thermo.isp.nsc.ru"}],book:{title:"Photodiodes",slug:"photodiodes-from-fundamentals-to-applications",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"16260",title:"Prof.",name:"Yong-Gang",surname:"Zhang",slug:"yong-gang-zhang",fullName:"Yong-Gang Zhang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"16262",title:"Prof.",name:"Yi",surname:"Gu",slug:"yi-gu",fullName:"Yi Gu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"96743",title:"Dr.",name:"Vasily",surname:"Varavin",slug:"vasily-varavin",fullName:"Vasily Varavin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"96745",title:"Dr.",name:"Vladimir",surname:"Vasilyev",slug:"vladimir-vasilyev",fullName:"Vladimir Vasilyev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"96746",title:"Dr.",name:"Sergey",surname:"Dvoretsky",slug:"sergey-dvoretsky",fullName:"Sergey Dvoretsky",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"96747",title:"Dr.",name:"Irina",surname:"Sabinina",slug:"irina-sabinina",fullName:"Irina Sabinina",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"96749",title:"Dr.",name:"Yuri",surname:"Sidorov",slug:"yuri-sidorov",fullName:"Yuri Sidorov",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"96753",title:"Dr.",name:"Aleksandr",surname:"Aseev",slug:"aleksandr-aseev",fullName:"Aleksandr Aseev",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"151202",title:"Prof.",name:"Toshiaki",surname:"Kagawa",slug:"toshiaki-kagawa",fullName:"Toshiaki Kagawa",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"151925",title:"Prof.",name:"Lung-Chien",surname:"Chen",slug:"lung-chien-chen",fullName:"Lung-Chien Chen",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"open-access-funding-funders-list",title:"List of Funders by Country",intro:"
If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).
\n\n
IMPORTANT: You must be a member or grantee of the listed funders in order to apply for their Open Access publication funds. Do not attempt to contact the funders if this is not the case.
",metaTitle:"List of Funders by Country",metaDescription:"If your research is financed through any of the below-mentioned funders, please consult their Open Access policies or grant ‘terms and conditions’ to explore ways to cover your publication costs (also accessible by clicking on the link in their title).",metaKeywords:null,canonicalURL:"/page/open-access-funding-funders-list",contentRaw:'[{"type":"htmlEditorComponent","content":"
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
UK Research and Innovation (former Research Councils UK (RCUK) - including AHRC, BBSRC, ESRC, EPSRC, MRC, NERC, STFC.) Processing charges for books/book chapters can be covered through RCUK block grants which are allocated to most universities in the UK, which then handle the OA publication funding requests. It is at the discretion of the university whether it will approve the request.)
Wellcome Trust (Funding available only to Wellcome-funded researchers/grantees)
\n
\n'}]},successStories:{items:[]},authorsAndEditors:{filterParams:{sort:"featured,name"},profiles:[{id:"6700",title:"Dr.",name:"Abbass A.",middleName:null,surname:"Hashim",slug:"abbass-a.-hashim",fullName:"Abbass A. Hashim",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/6700/images/1864_n.jpg",biography:"Currently I am carrying out research in several areas of interest, mainly covering work on chemical and bio-sensors, semiconductor thin film device fabrication and characterisation.\nAt the moment I have very strong interest in radiation environmental pollution and bacteriology treatment. The teams of researchers are working very hard to bring novel results in this field. I am also a member of the team in charge for the supervision of Ph.D. students in the fields of development of silicon based planar waveguide sensor devices, study of inelastic electron tunnelling in planar tunnelling nanostructures for sensing applications and development of organotellurium(IV) compounds for semiconductor applications. I am a specialist in data analysis techniques and nanosurface structure. I have served as the editor for many books, been a member of the editorial board in science journals, have published many papers and hold many patents.",institutionString:null,institution:{name:"Sheffield Hallam University",country:{name:"United Kingdom"}}},{id:"54525",title:"Prof.",name:"Abdul Latif",middleName:null,surname:"Ahmad",slug:"abdul-latif-ahmad",fullName:"Abdul Latif Ahmad",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"20567",title:"Prof.",name:"Ado",middleName:null,surname:"Jorio",slug:"ado-jorio",fullName:"Ado Jorio",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Universidade Federal de Minas Gerais",country:{name:"Brazil"}}},{id:"47940",title:"Dr.",name:"Alberto",middleName:null,surname:"Mantovani",slug:"alberto-mantovani",fullName:"Alberto Mantovani",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"12392",title:"Mr.",name:"Alex",middleName:null,surname:"Lazinica",slug:"alex-lazinica",fullName:"Alex Lazinica",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/12392/images/7282_n.png",biography:"Alex Lazinica is the founder and CEO of IntechOpen. After obtaining a Master's degree in Mechanical Engineering, he continued his PhD studies in Robotics at the Vienna University of Technology. Here he worked as a robotic researcher with the university's Intelligent Manufacturing Systems Group as well as a guest researcher at various European universities, including the Swiss Federal Institute of Technology Lausanne (EPFL). During this time he published more than 20 scientific papers, gave presentations, served as a reviewer for major robotic journals and conferences and most importantly he co-founded and built the International Journal of Advanced Robotic Systems- world's first Open Access journal in the field of robotics. Starting this journal was a pivotal point in his career, since it was a pathway to founding IntechOpen - Open Access publisher focused on addressing academic researchers needs. Alex is a personification of IntechOpen key values being trusted, open and entrepreneurial. Today his focus is on defining the growth and development strategy for the company.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"19816",title:"Prof.",name:"Alexander",middleName:null,surname:"Kokorin",slug:"alexander-kokorin",fullName:"Alexander Kokorin",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/19816/images/1607_n.jpg",biography:"Alexander I. Kokorin: born: 1947, Moscow; DSc., PhD; Principal Research Fellow (Research Professor) of Department of Kinetics and Catalysis, N. Semenov Institute of Chemical Physics, Russian Academy of Sciences, Moscow.\r\nArea of research interests: physical chemistry of complex-organized molecular and nanosized systems, including polymer-metal complexes; the surface of doped oxide semiconductors. He is an expert in structural, absorptive, catalytic and photocatalytic properties, in structural organization and dynamic features of ionic liquids, in magnetic interactions between paramagnetic centers. The author or co-author of 3 books, over 200 articles and reviews in scientific journals and books. He is an actual member of the International EPR/ESR Society, European Society on Quantum Solar Energy Conversion, Moscow House of Scientists, of the Board of Moscow Physical Society.",institutionString:null,institution:{name:"Semenov Institute of Chemical Physics",country:{name:"Russia"}}},{id:"62389",title:"PhD.",name:"Ali Demir",middleName:null,surname:"Sezer",slug:"ali-demir-sezer",fullName:"Ali Demir Sezer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62389/images/3413_n.jpg",biography:"Dr. Ali Demir Sezer has a Ph.D. from Pharmaceutical Biotechnology at the Faculty of Pharmacy, University of Marmara (Turkey). He is the member of many Pharmaceutical Associations and acts as a reviewer of scientific journals and European projects under different research areas such as: drug delivery systems, nanotechnology and pharmaceutical biotechnology. Dr. Sezer is the author of many scientific publications in peer-reviewed journals and poster communications. Focus of his research activity is drug delivery, physico-chemical characterization and biological evaluation of biopolymers micro and nanoparticles as modified drug delivery system, and colloidal drug carriers (liposomes, nanoparticles etc.).",institutionString:null,institution:{name:"Marmara University",country:{name:"Turkey"}}},{id:"61051",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"100762",title:"Prof.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"St David's Medical Center",country:{name:"United States of America"}}},{id:"107416",title:"Dr.",name:"Andrea",middleName:null,surname:"Natale",slug:"andrea-natale",fullName:"Andrea Natale",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Texas Cardiac Arrhythmia",country:{name:"United States of America"}}},{id:"64434",title:"Dr.",name:"Angkoon",middleName:null,surname:"Phinyomark",slug:"angkoon-phinyomark",fullName:"Angkoon Phinyomark",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/64434/images/2619_n.jpg",biography:"My name is Angkoon Phinyomark. I received a B.Eng. degree in Computer Engineering with First Class Honors in 2008 from Prince of Songkla University, Songkhla, Thailand, where I received a Ph.D. degree in Electrical Engineering. My research interests are primarily in the area of biomedical signal processing and classification notably EMG (electromyography signal), EOG (electrooculography signal), and EEG (electroencephalography signal), image analysis notably breast cancer analysis and optical coherence tomography, and rehabilitation engineering. I became a student member of IEEE in 2008. During October 2011-March 2012, I had worked at School of Computer Science and Electronic Engineering, University of Essex, Colchester, Essex, United Kingdom. In addition, during a B.Eng. I had been a visiting research student at Faculty of Computer Science, University of Murcia, Murcia, Spain for three months.\n\nI have published over 40 papers during 5 years in refereed journals, books, and conference proceedings in the areas of electro-physiological signals processing and classification, notably EMG and EOG signals, fractal analysis, wavelet analysis, texture analysis, feature extraction and machine learning algorithms, and assistive and rehabilitative devices. I have several computer programming language certificates, i.e. Sun Certified Programmer for the Java 2 Platform 1.4 (SCJP), Microsoft Certified Professional Developer, Web Developer (MCPD), Microsoft Certified Technology Specialist, .NET Framework 2.0 Web (MCTS). I am a Reviewer for several refereed journals and international conferences, such as IEEE Transactions on Biomedical Engineering, IEEE Transactions on Industrial Electronics, Optic Letters, Measurement Science Review, and also a member of the International Advisory Committee for 2012 IEEE Business Engineering and Industrial Applications and 2012 IEEE Symposium on Business, Engineering and Industrial Applications.",institutionString:null,institution:{name:"Joseph Fourier University",country:{name:"France"}}},{id:"55578",title:"Dr.",name:"Antonio",middleName:null,surname:"Jurado-Navas",slug:"antonio-jurado-navas",fullName:"Antonio Jurado-Navas",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/55578/images/4574_n.png",biography:"Antonio Jurado-Navas received the M.S. degree (2002) and the Ph.D. degree (2009) in Telecommunication Engineering, both from the University of Málaga (Spain). He first worked as a consultant at Vodafone-Spain. From 2004 to 2011, he was a Research Assistant with the Communications Engineering Department at the University of Málaga. In 2011, he became an Assistant Professor in the same department. From 2012 to 2015, he was with Ericsson Spain, where he was working on geo-location\ntools for third generation mobile networks. Since 2015, he is a Marie-Curie fellow at the Denmark Technical University. His current research interests include the areas of mobile communication systems and channel modeling in addition to atmospheric optical communications, adaptive optics and statistics",institutionString:null,institution:{name:"University of Malaga",country:{name:"Spain"}}}],filtersByRegion:[{group:"region",caption:"North America",value:1,count:5681},{group:"region",caption:"Middle and South America",value:2,count:5161},{group:"region",caption:"Africa",value:3,count:1683},{group:"region",caption:"Asia",value:4,count:10200},{group:"region",caption:"Australia and Oceania",value:5,count:886},{group:"region",caption:"Europe",value:6,count:15610}],offset:12,limit:12,total:117095},chapterEmbeded:{data:{}},editorApplication:{success:null,errors:{}},ofsBooks:{filterParams:{sort:"dateendthirdsteppublish"},books:[],filtersByTopic:[{group:"topic",caption:"Agricultural and Biological Sciences",value:5,count:9},{group:"topic",caption:"Biochemistry, Genetics and Molecular Biology",value:6,count:17},{group:"topic",caption:"Business, Management and Economics",value:7,count:2},{group:"topic",caption:"Chemistry",value:8,count:7},{group:"topic",caption:"Computer and Information Science",value:9,count:10},{group:"topic",caption:"Earth and Planetary Sciences",value:10,count:5},{group:"topic",caption:"Engineering",value:11,count:14},{group:"topic",caption:"Environmental Sciences",value:12,count:2},{group:"topic",caption:"Immunology and Microbiology",value:13,count:5},{group:"topic",caption:"Materials Science",value:14,count:4},{group:"topic",caption:"Mathematics",value:15,count:1},{group:"topic",caption:"Medicine",value:16,count:60},{group:"topic",caption:"Nanotechnology and Nanomaterials",value:17,count:1},{group:"topic",caption:"Neuroscience",value:18,count:1},{group:"topic",caption:"Pharmacology, Toxicology and Pharmaceutical Science",value:19,count:6},{group:"topic",caption:"Physics",value:20,count:2},{group:"topic",caption:"Psychology",value:21,count:3},{group:"topic",caption:"Robotics",value:22,count:1},{group:"topic",caption:"Social Sciences",value:23,count:3},{group:"topic",caption:"Technology",value:24,count:1},{group:"topic",caption:"Veterinary Medicine and Science",value:25,count:2}],offset:0,limit:12,total:null},popularBooks:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9279",title:"Concepts, Applications and Emerging Opportunities in Industrial Engineering",subtitle:null,isOpenForSubmission:!1,hash:"9bfa87f9b627a5468b7c1e30b0eea07a",slug:"concepts-applications-and-emerging-opportunities-in-industrial-engineering",bookSignature:"Gary Moynihan",coverURL:"https://cdn.intechopen.com/books/images_new/9279.jpg",editors:[{id:"16974",title:"Dr.",name:"Gary",middleName:null,surname:"Moynihan",slug:"gary-moynihan",fullName:"Gary Moynihan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7807",title:"A Closer Look at Organizational Culture in Action",subtitle:null,isOpenForSubmission:!1,hash:"05c608b9271cc2bc711f4b28748b247b",slug:"a-closer-look-at-organizational-culture-in-action",bookSignature:"Süleyman Davut Göker",coverURL:"https://cdn.intechopen.com/books/images_new/7807.jpg",editors:[{id:"190035",title:"Associate Prof.",name:"Süleyman Davut",middleName:null,surname:"Göker",slug:"suleyman-davut-goker",fullName:"Süleyman Davut Göker"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:12,limit:12,total:5126},hotBookTopics:{hotBooks:[],offset:0,limit:12,total:null},publish:{},publishingProposal:{success:null,errors:{}},books:{featuredBooks:[{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8697",title:"Virtual Reality and Its Application in Education",subtitle:null,isOpenForSubmission:!1,hash:"ee01b5e387ba0062c6b0d1e9227bda05",slug:"virtual-reality-and-its-application-in-education",bookSignature:"Dragan Cvetković",coverURL:"https://cdn.intechopen.com/books/images_new/8697.jpg",editors:[{id:"101330",title:"Dr.",name:"Dragan",middleName:"Mladen",surname:"Cvetković",slug:"dragan-cvetkovic",fullName:"Dragan Cvetković"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9343",title:"Trace Metals in the Environment",subtitle:"New Approaches and Recent Advances",isOpenForSubmission:!1,hash:"ae07e345bc2ce1ebbda9f70c5cd12141",slug:"trace-metals-in-the-environment-new-approaches-and-recent-advances",bookSignature:"Mario Alfonso Murillo-Tovar, Hugo Saldarriaga-Noreña and Agnieszka Saeid",coverURL:"https://cdn.intechopen.com/books/images_new/9343.jpg",editors:[{id:"255959",title:"Dr.",name:"Mario Alfonso",middleName:null,surname:"Murillo-Tovar",slug:"mario-alfonso-murillo-tovar",fullName:"Mario Alfonso Murillo-Tovar"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7831",title:"Sustainability in Urban Planning and Design",subtitle:null,isOpenForSubmission:!1,hash:"c924420492c8c2c9751e178d025f4066",slug:"sustainability-in-urban-planning-and-design",bookSignature:"Amjad Almusaed, Asaad Almssad and Linh Truong - Hong",coverURL:"https://cdn.intechopen.com/books/images_new/7831.jpg",editors:[{id:"110471",title:"Dr.",name:"Amjad",middleName:"Zaki",surname:"Almusaed",slug:"amjad-almusaed",fullName:"Amjad Almusaed"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"9376",title:"Contemporary Developments and Perspectives in International Health Security",subtitle:"Volume 1",isOpenForSubmission:!1,hash:"b9a00b84cd04aae458fb1d6c65795601",slug:"contemporary-developments-and-perspectives-in-international-health-security-volume-1",bookSignature:"Stanislaw P. Stawicki, Michael S. Firstenberg, Sagar C. Galwankar, Ricardo Izurieta and Thomas Papadimos",coverURL:"https://cdn.intechopen.com/books/images_new/9376.jpg",editors:[{id:"181694",title:"Dr.",name:"Stanislaw P.",middleName:null,surname:"Stawicki",slug:"stanislaw-p.-stawicki",fullName:"Stanislaw P. Stawicki"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}},{type:"book",id:"7769",title:"Medical Isotopes",subtitle:null,isOpenForSubmission:!1,hash:"f8d3c5a6c9a42398e56b4e82264753f7",slug:"medical-isotopes",bookSignature:"Syed Ali Raza Naqvi and Muhammad Babar Imrani",coverURL:"https://cdn.intechopen.com/books/images_new/7769.jpg",editors:[{id:"259190",title:"Dr.",name:"Syed Ali Raza",middleName:null,surname:"Naqvi",slug:"syed-ali-raza-naqvi",fullName:"Syed Ali Raza Naqvi"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],latestBooks:[{type:"book",id:"8468",title:"Sheep Farming",subtitle:"An Approach to Feed, Growth and Sanity",isOpenForSubmission:!1,hash:"838f08594850bc04aa14ec873ed1b96f",slug:"sheep-farming-an-approach-to-feed-growth-and-sanity",bookSignature:"António Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/8468.jpg",editedByType:"Edited by",editors:[{id:"190314",title:"Prof.",name:"António",middleName:"Cardoso",surname:"Monteiro",slug:"antonio-monteiro",fullName:"António Monteiro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9523",title:"Oral and Maxillofacial Surgery",subtitle:null,isOpenForSubmission:!1,hash:"5eb6ec2db961a6c8965d11180a58d5c1",slug:"oral-and-maxillofacial-surgery",bookSignature:"Gokul Sridharan",coverURL:"https://cdn.intechopen.com/books/images_new/9523.jpg",editedByType:"Edited by",editors:[{id:"82453",title:"Dr.",name:"Gokul",middleName:null,surname:"Sridharan",slug:"gokul-sridharan",fullName:"Gokul Sridharan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9785",title:"Endometriosis",subtitle:null,isOpenForSubmission:!1,hash:"f457ca61f29cf7e8bc191732c50bb0ce",slug:"endometriosis",bookSignature:"Courtney Marsh",coverURL:"https://cdn.intechopen.com/books/images_new/9785.jpg",editedByType:"Edited by",editors:[{id:"255491",title:"Dr.",name:"Courtney",middleName:null,surname:"Marsh",slug:"courtney-marsh",fullName:"Courtney Marsh"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8816",title:"Financial Crises",subtitle:"A Selection of Readings",isOpenForSubmission:!1,hash:"6f2f49fb903656e4e54280c79fabd10c",slug:"financial-crises-a-selection-of-readings",bookSignature:"Stelios Markoulis",coverURL:"https://cdn.intechopen.com/books/images_new/8816.jpg",editedByType:"Edited by",editors:[{id:"237863",title:"Dr.",name:"Stelios",middleName:null,surname:"Markoulis",slug:"stelios-markoulis",fullName:"Stelios Markoulis"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9585",title:"Advances in Complex Valvular Disease",subtitle:null,isOpenForSubmission:!1,hash:"ef64f11e211621ecfe69c46e60e7ca3d",slug:"advances-in-complex-valvular-disease",bookSignature:"Michael S. Firstenberg and Imran Khan",coverURL:"https://cdn.intechopen.com/books/images_new/9585.jpg",editedByType:"Edited by",editors:[{id:"64343",title:null,name:"Michael S.",middleName:"S",surname:"Firstenberg",slug:"michael-s.-firstenberg",fullName:"Michael S. Firstenberg"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10150",title:"Smart Manufacturing",subtitle:"When Artificial Intelligence Meets the Internet of Things",isOpenForSubmission:!1,hash:"87004a19de13702d042f8ff96d454698",slug:"smart-manufacturing-when-artificial-intelligence-meets-the-internet-of-things",bookSignature:"Tan Yen Kheng",coverURL:"https://cdn.intechopen.com/books/images_new/10150.jpg",editedByType:"Edited by",editors:[{id:"78857",title:"Dr.",name:"Tan Yen",middleName:null,surname:"Kheng",slug:"tan-yen-kheng",fullName:"Tan Yen Kheng"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9386",title:"Direct Numerical Simulations",subtitle:"An Introduction and Applications",isOpenForSubmission:!1,hash:"158a3a0fdba295d21ff23326f5a072d5",slug:"direct-numerical-simulations-an-introduction-and-applications",bookSignature:"Srinivasa Rao",coverURL:"https://cdn.intechopen.com/books/images_new/9386.jpg",editedByType:"Edited by",editors:[{id:"6897",title:"Dr.",name:"Srinivasa",middleName:"P",surname:"Rao",slug:"srinivasa-rao",fullName:"Srinivasa Rao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9139",title:"Topics in Primary Care Medicine",subtitle:null,isOpenForSubmission:!1,hash:"ea774a4d4c1179da92a782e0ae9cde92",slug:"topics-in-primary-care-medicine",bookSignature:"Thomas F. Heston",coverURL:"https://cdn.intechopen.com/books/images_new/9139.jpg",editedByType:"Edited by",editors:[{id:"217926",title:"Dr.",name:"Thomas F.",middleName:null,surname:"Heston",slug:"thomas-f.-heston",fullName:"Thomas F. Heston"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"9208",title:"Welding",subtitle:"Modern Topics",isOpenForSubmission:!1,hash:"7d6be076ccf3a3f8bd2ca52d86d4506b",slug:"welding-modern-topics",bookSignature:"Sadek Crisóstomo Absi Alfaro, Wojciech Borek and Błażej Tomiczek",coverURL:"https://cdn.intechopen.com/books/images_new/9208.jpg",editedByType:"Edited by",editors:[{id:"65292",title:"Prof.",name:"Sadek Crisostomo Absi",middleName:"C. Absi",surname:"Alfaro",slug:"sadek-crisostomo-absi-alfaro",fullName:"Sadek Crisostomo Absi Alfaro"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},subject:{topic:{id:"125",title:"Earth Science",slug:"earth-science",parent:{title:"Environmental Sciences",slug:"environmental-sciences"},numberOfBooks:33,numberOfAuthorsAndEditors:825,numberOfWosCitations:768,numberOfCrossrefCitations:495,numberOfDimensionsCitations:1346,videoUrl:null,fallbackUrl:null,description:null},booksByTopicFilter:{topicSlug:"earth-science",sort:"-publishedDate",limit:12,offset:0},booksByTopicCollection:[{type:"book",id:"8974",title:"Current Topics in Tropical Cyclone Research",subtitle:null,isOpenForSubmission:!1,hash:"3bf6428d456edbadac595a8417045865",slug:"current-topics-in-tropical-cyclone-research",bookSignature:"Anthony Lupo",coverURL:"https://cdn.intechopen.com/books/images_new/8974.jpg",editedByType:"Edited by",editors:[{id:"18289",title:"Prof.",name:"Anthony",middleName:"Rocco",surname:"Lupo",slug:"anthony-lupo",fullName:"Anthony Lupo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8007",title:"Estuaries and Coastal Zones",subtitle:"Dynamics and Response to Environmental Changes",isOpenForSubmission:!1,hash:"ec140486c42d62e69ef428e6cf71b6d7",slug:"estuaries-and-coastal-zones-dynamics-and-response-to-environmental-changes",bookSignature:"Jiayi Pan and Adam Devlin",coverURL:"https://cdn.intechopen.com/books/images_new/8007.jpg",editedByType:"Edited by",editors:[{id:"179303",title:"Prof.",name:"Jiayi",middleName:null,surname:"Pan",slug:"jiayi-pan",fullName:"Jiayi Pan"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7606",title:"Coastal and Marine Environments",subtitle:"Physical Processes and Numerical Modelling",isOpenForSubmission:!1,hash:"dd1227726856d58b88116129b0de8384",slug:"coastal-and-marine-environments-physical-processes-and-numerical-modelling",bookSignature:"José Simão Antunes Do Carmo",coverURL:"https://cdn.intechopen.com/books/images_new/7606.jpg",editedByType:"Edited by",editors:[{id:"67904",title:"Prof.",name:"José Simão",middleName:null,surname:"Antunes Do Carmo",slug:"jose-simao-antunes-do-carmo",fullName:"José Simão Antunes Do Carmo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"8476",title:"Earth Crust",subtitle:null,isOpenForSubmission:!1,hash:"ebef9911d87b6db8cb55dad47250a6be",slug:"earth-crust",bookSignature:"Muhammad Nawaz, Farha Sattar and Sandeep Narayan Kundu",coverURL:"https://cdn.intechopen.com/books/images_new/8476.jpg",editedByType:"Edited by",editors:[{id:"269790",title:"Dr.",name:"Muhammad",middleName:null,surname:"Nawaz",slug:"muhammad-nawaz",fullName:"Muhammad Nawaz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7767",title:"Rainfall",subtitle:"Extremes, Distribution and Properties",isOpenForSubmission:!1,hash:"9f9b3b7d86cb46e2ce3653587805475d",slug:"rainfall-extremes-distribution-and-properties",bookSignature:"John Abbot and Andrew Hammond",coverURL:"https://cdn.intechopen.com/books/images_new/7767.jpg",editedByType:"Edited by",editors:[{id:"225780",title:"Dr.",name:"John",middleName:null,surname:"Abbot",slug:"john-abbot",fullName:"John Abbot"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6982",title:"Arctic Studies",subtitle:"A Proxy for Climate Change",isOpenForSubmission:!1,hash:"6545831965fb2dcef181c46d18fed1ba",slug:"arctic-studies-a-proxy-for-climate-change",bookSignature:"Masaki Kanao, Yoshihiro Kakinami and Genti Toyokuni",coverURL:"https://cdn.intechopen.com/books/images_new/6982.jpg",editedByType:"Edited by",editors:[{id:"51959",title:"Dr.",name:"Masaki",middleName:null,surname:"Kanao",slug:"masaki-kanao",fullName:"Masaki Kanao"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7484",title:"Topics in Hydrometerology",subtitle:null,isOpenForSubmission:!1,hash:"8d7e790445c691226a5778a32abd15cf",slug:"topics-in-hydrometerology",bookSignature:"Theodore V Hromadka II and Prasada Rao",coverURL:"https://cdn.intechopen.com/books/images_new/7484.jpg",editedByType:"Edited by",editors:[{id:"181008",title:"Dr.",name:"Theodore",middleName:null,surname:"Hromadka",slug:"theodore-hromadka",fullName:"Theodore Hromadka"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6836",title:"Groundwater",subtitle:"Resource Characterisation and Management Aspects",isOpenForSubmission:!1,hash:"7cad088c49e61c898abc7d7511de42f6",slug:"groundwater-resource-characterisation-and-management-aspects",bookSignature:"Modreck Gomo",coverURL:"https://cdn.intechopen.com/books/images_new/6836.jpg",editedByType:"Edited by",editors:[{id:"185450",title:"Dr.",name:"Modreck",middleName:null,surname:"Gomo",slug:"modreck-gomo",fullName:"Modreck Gomo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6973",title:"Advanced Evapotranspiration Methods and Applications",subtitle:null,isOpenForSubmission:!1,hash:"7c54751778dc2ff4a19cd84f1bf0c706",slug:"advanced-evapotranspiration-methods-and-applications",bookSignature:"Daniel Bucur",coverURL:"https://cdn.intechopen.com/books/images_new/6973.jpg",editedByType:"Edited by",editors:[{id:"50794",title:"Prof.",name:"Daniel",middleName:"G",surname:"Bucur",slug:"daniel-bucur",fullName:"Daniel Bucur"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6012",title:"Morphodynamic Model for Predicting Beach Changes Based on Bagnold's Concept and Its Applications",subtitle:null,isOpenForSubmission:!1,hash:"79ce8dc1cde58947a61fe4aea725d437",slug:"morphodynamic-model-for-predicting-beach-changes-based-on-bagnold-s-concept-and-its-applications",bookSignature:"Takaaki Uda, Masumi Serizawa and Shiho Miyahara",coverURL:"https://cdn.intechopen.com/books/images_new/6012.jpg",editedByType:"Authored by",editors:[{id:"13491",title:"Dr.",name:"Takaaki",middleName:null,surname:"Uda",slug:"takaaki-uda",fullName:"Takaaki Uda"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored by"}},{type:"book",id:"8669",title:"Coastal Environment, Disaster, and Infrastructure",subtitle:"A Case Study of China's Coastline",isOpenForSubmission:!1,hash:"52abc534177a147ffd3154db2f4f4ba1",slug:"coastal-environment-disaster-and-infrastructure-a-case-study-of-china-s-coastline",bookSignature:"X. San Liang and Yuanzhi Zhang",coverURL:"https://cdn.intechopen.com/books/images_new/8669.jpg",editedByType:"Edited by",editors:[{id:"210315",title:"Prof.",name:"X. San",middleName:null,surname:"Liang",slug:"x.-san-liang",fullName:"X. San Liang"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"3",chapterContentType:"chapter",authoredCaption:"Authored by"}},{type:"book",id:"6732",title:"Desalination and Water Treatment",subtitle:null,isOpenForSubmission:!1,hash:"eee2f03e0328f289e68fde28738c333f",slug:"desalination-and-water-treatment",bookSignature:"Murat Eyvaz and Ebubekir Yüksel",coverURL:"https://cdn.intechopen.com/books/images_new/6732.jpg",editedByType:"Edited by",editors:[{id:"170083",title:"Associate Prof.",name:"Murat",middleName:null,surname:"Eyvaz",slug:"murat-eyvaz",fullName:"Murat Eyvaz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],booksByTopicTotal:33,mostCitedChapters:[{id:"27305",doi:"10.5772/39363",title:"Water Stress in Plants: Causes, Effects and Responses",slug:"water-stress-in-plants-causes-effects-and-responses",totalDownloads:27651,totalCrossrefCites:38,totalDimensionsCites:112,book:{slug:"water-stress",title:"Water Stress",fullTitle:"Water Stress"},signatures:"Seyed Y. S. Lisar, Rouhollah Motafakkerazad, Mosharraf M. Hossain and Ismail M. M. Rahman",authors:[{id:"110740",title:"Dr.",name:"Ismail M. M.",middleName:null,surname:"Rahman",slug:"ismail-m.-m.-rahman",fullName:"Ismail M. M. Rahman"}]},{id:"53211",doi:"10.5772/66416",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:14914,totalCrossrefCites:30,totalDimensionsCites:70,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Maurício Gustavo Coelho Emerenciano, Luis Rafael Martínez-\nCórdova, Marcel Martínez-Porchas and Anselmo Miranda-Baeza",authors:[{id:"146126",title:"Dr.",name:"Maurício Gustavo Coelho",middleName:null,surname:"Emerenciano",slug:"mauricio-gustavo-coelho-emerenciano",fullName:"Maurício Gustavo Coelho Emerenciano"},{id:"186970",title:"Prof.",name:"Marcel",middleName:null,surname:"Martínez-Porchas",slug:"marcel-martinez-porchas",fullName:"Marcel Martínez-Porchas"},{id:"186971",title:"Prof.",name:"Anselmo",middleName:null,surname:"Miranda-Baeza",slug:"anselmo-miranda-baeza",fullName:"Anselmo Miranda-Baeza"},{id:"195101",title:"Dr.",name:"Luis Rafael",middleName:null,surname:"Martínez-Córdoba",slug:"luis-rafael-martinez-cordoba",fullName:"Luis Rafael Martínez-Córdoba"}]},{id:"26970",doi:"10.5772/29578",title:"Plant Water-Stress Response Mechanisms",slug:"plant-water-stress-response-mechanisms",totalDownloads:20267,totalCrossrefCites:6,totalDimensionsCites:39,book:{slug:"water-stress",title:"Water Stress",fullTitle:"Water Stress"},signatures:"Şener Akıncı and Dorothy M. Lösel",authors:[{id:"78435",title:"Associate Prof.",name:"Sener",middleName:null,surname:"Akinci",slug:"sener-akinci",fullName:"Sener Akinci"},{id:"126728",title:"Dr.",name:"Dorothy M.",middleName:null,surname:"Lösel",slug:"dorothy-m.-losel",fullName:"Dorothy M. Lösel"}]}],mostDownloadedChaptersLast30Days:[{id:"53211",title:"Biofloc Technology (BFT): A Tool for Water Quality Management in Aquaculture",slug:"biofloc-technology-bft-a-tool-for-water-quality-management-in-aquaculture",totalDownloads:14914,totalCrossrefCites:30,totalDimensionsCites:70,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Maurício Gustavo Coelho Emerenciano, Luis Rafael Martínez-\nCórdova, Marcel Martínez-Porchas and Anselmo Miranda-Baeza",authors:[{id:"146126",title:"Dr.",name:"Maurício Gustavo Coelho",middleName:null,surname:"Emerenciano",slug:"mauricio-gustavo-coelho-emerenciano",fullName:"Maurício Gustavo Coelho Emerenciano"},{id:"186970",title:"Prof.",name:"Marcel",middleName:null,surname:"Martínez-Porchas",slug:"marcel-martinez-porchas",fullName:"Marcel Martínez-Porchas"},{id:"186971",title:"Prof.",name:"Anselmo",middleName:null,surname:"Miranda-Baeza",slug:"anselmo-miranda-baeza",fullName:"Anselmo Miranda-Baeza"},{id:"195101",title:"Dr.",name:"Luis Rafael",middleName:null,surname:"Martínez-Córdoba",slug:"luis-rafael-martinez-cordoba",fullName:"Luis Rafael Martínez-Córdoba"}]},{id:"58138",title:"Water Pollution: Effects, Prevention, and Climatic Impact",slug:"water-pollution-effects-prevention-and-climatic-impact",totalDownloads:18980,totalCrossrefCites:7,totalDimensionsCites:14,book:{slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Inyinbor Adejumoke A., Adebesin Babatunde O., Oluyori Abimbola\nP., Adelani-Akande Tabitha A., Dada Adewumi O. and Oreofe Toyin\nA.",authors:[{id:"101570",title:"MSc.",name:"Babatunde Olufemi",middleName:null,surname:"Adebesin",slug:"babatunde-olufemi-adebesin",fullName:"Babatunde Olufemi Adebesin"},{id:"187738",title:"Dr.",name:"Adejumoke",middleName:"Abosede",surname:"Inyinbor",slug:"adejumoke-inyinbor",fullName:"Adejumoke Inyinbor"},{id:"188818",title:"Dr.",name:"Abimbola",middleName:null,surname:"Oluyori",slug:"abimbola-oluyori",fullName:"Abimbola Oluyori"},{id:"188819",title:"Mrs.",name:"Tabitha",middleName:null,surname:"Adelani-Akande",slug:"tabitha-adelani-akande",fullName:"Tabitha Adelani-Akande"},{id:"208501",title:"Dr.",name:"Adewumi",middleName:null,surname:"Dada",slug:"adewumi-dada",fullName:"Adewumi Dada"},{id:"208502",title:"Ms.",name:"Toyin",middleName:null,surname:"Oreofe",slug:"toyin-oreofe",fullName:"Toyin Oreofe"}]},{id:"63043",title:"Desalination of Water",slug:"desalination-of-water",totalDownloads:2063,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"desalination-and-water-treatment",title:"Desalination and Water Treatment",fullTitle:"Desalination and Water Treatment"},signatures:"Manish Thimmaraju, Divya Sreepada, Gummadi Sridhar Babu,\nBharath Kumar Dasari, Sai Kiran Velpula and Nagaraju Vallepu",authors:[{id:"249016",title:"Dr.",name:"Manish Kumar",middleName:null,surname:"Thimmaraju",slug:"manish-kumar-thimmaraju",fullName:"Manish Kumar Thimmaraju"},{id:"256566",title:"Mrs.",name:"Sreepada",middleName:null,surname:"Divya",slug:"sreepada-divya",fullName:"Sreepada Divya"}]},{id:"52622",title:"Review of the Impact on Water Quality and Treatment Options of Cyanide Used in Gold Ore Processing",slug:"review-of-the-impact-on-water-quality-and-treatment-options-of-cyanide-used-in-gold-ore-processing",totalDownloads:2216,totalCrossrefCites:1,totalDimensionsCites:3,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Benias C. Nyamunda",authors:[{id:"186506",title:"Dr.",name:"Benias",middleName:null,surname:"Nyamunda",slug:"benias-nyamunda",fullName:"Benias Nyamunda"}]},{id:"53194",title:"Impact of Wastewater on Surface Water Quality in Developing Countries: A Case Study of South Africa",slug:"impact-of-wastewater-on-surface-water-quality-in-developing-countries-a-case-study-of-south-africa",totalDownloads:5751,totalCrossrefCites:15,totalDimensionsCites:32,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Joshua N. Edokpayi, John O. Odiyo and Olatunde S. Durowoju",authors:[{id:"187867",title:"Dr.",name:"Joshua",middleName:null,surname:"Edokpayi",slug:"joshua-edokpayi",fullName:"Joshua Edokpayi"},{id:"189690",title:"Prof.",name:"John",middleName:null,surname:"Odiyo",slug:"john-odiyo",fullName:"John Odiyo"},{id:"194678",title:"Dr.",name:"Olatunde",middleName:"Samod",surname:"Durowoju",slug:"olatunde-durowoju",fullName:"Olatunde Durowoju"}]},{id:"57345",title:"Safe Drinking Water: Concepts, Benefits, Principles and Standards",slug:"safe-drinking-water-concepts-benefits-principles-and-standards",totalDownloads:4153,totalCrossrefCites:3,totalDimensionsCites:6,book:{slug:"water-challenges-of-an-urbanizing-world",title:"Water Challenges of an Urbanizing World",fullTitle:"Water Challenges of an Urbanizing World"},signatures:"Megersa Olumana Dinka",authors:[{id:"206964",title:"Dr.",name:"Megersa Olumana",middleName:null,surname:"Dinka",slug:"megersa-olumana-dinka",fullName:"Megersa Olumana Dinka"}]},{id:"68134",title:"Introductory Chapter: Earth Crust - Origin, Structure, Composition and Evolution",slug:"introductory-chapter-earth-crust-origin-structure-composition-and-evolution",totalDownloads:782,totalCrossrefCites:0,totalDimensionsCites:1,book:{slug:"earth-crust",title:"Earth Crust",fullTitle:"Earth Crust"},signatures:"Muhammad Nawaz",authors:[{id:"269790",title:"Dr.",name:"Muhammad",middleName:null,surname:"Nawaz",slug:"muhammad-nawaz",fullName:"Muhammad Nawaz"}]},{id:"61215",title:"Solar Desalination",slug:"solar-desalination",totalDownloads:1657,totalCrossrefCites:1,totalDimensionsCites:2,book:{slug:"desalination-and-water-treatment",title:"Desalination and Water Treatment",fullTitle:"Desalination and Water Treatment"},signatures:"Fadi Alnaimat, James Klausner and Bobby Mathew",authors:[{id:"151722",title:"Dr.",name:"Fadi",middleName:null,surname:"Alnaimat",slug:"fadi-alnaimat",fullName:"Fadi Alnaimat"},{id:"245337",title:"Prof.",name:"James",middleName:null,surname:"Klausner",slug:"james-klausner",fullName:"James Klausner"},{id:"245338",title:"Dr.",name:"Bobby",middleName:null,surname:"Mathew",slug:"bobby-mathew",fullName:"Bobby Mathew"}]},{id:"66437",title:"Detection of Underground Water by Using GPR",slug:"detection-of-underground-water-by-using-gpr",totalDownloads:1497,totalCrossrefCites:0,totalDimensionsCites:0,book:{slug:"groundwater-resource-characterisation-and-management-aspects",title:"Groundwater",fullTitle:"Groundwater - Resource Characterisation and Management Aspects"},signatures:"Dalia N. Elsheakh and Esmat A. Abdallah",authors:[{id:"111813",title:"Dr.",name:"Dalia",middleName:null,surname:"Elsheakh",slug:"dalia-elsheakh",fullName:"Dalia Elsheakh"},{id:"111867",title:"Prof.",name:"Esmat",middleName:null,surname:"Abdallah",slug:"esmat-abdallah",fullName:"Esmat Abdallah"}]},{id:"52639",title:"Metals Toxic Effects in Aquatic Ecosystems: Modulators of Water Quality",slug:"metals-toxic-effects-in-aquatic-ecosystems-modulators-of-water-quality",totalDownloads:3153,totalCrossrefCites:11,totalDimensionsCites:20,book:{slug:"water-quality",title:"Water Quality",fullTitle:"Water Quality"},signatures:"Stefania Gheorghe, Catalina Stoica, Gabriela Geanina Vasile, Mihai\nNita-Lazar, Elena Stanescu and Irina Eugenia Lucaciu",authors:[{id:"186964",title:"Dr.",name:"Stefania",middleName:null,surname:"Gheorghe",slug:"stefania-gheorghe",fullName:"Stefania Gheorghe"},{id:"194072",title:"Dr.",name:"Catalina",middleName:null,surname:"Stoica",slug:"catalina-stoica",fullName:"Catalina Stoica"}]}],onlineFirstChaptersFilter:{topicSlug:"earth-science",limit:3,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[{type:"book",id:"10176",title:"Microgrids and Local Energy Systems",subtitle:null,isOpenForSubmission:!0,hash:"c32b4a5351a88f263074b0d0ca813a9c",slug:null,bookSignature:"Prof. Nick Jenkins",coverURL:"https://cdn.intechopen.com/books/images_new/10176.jpg",editedByType:null,editors:[{id:"55219",title:"Prof.",name:"Nick",middleName:null,surname:"Jenkins",slug:"nick-jenkins",fullName:"Nick Jenkins"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter"}}],offset:8,limit:8,total:1},route:{name:"profile.detail",path:"/profiles/152249/alexander-suslyakov",hash:"",query:{},params:{id:"152249",slug:"alexander-suslyakov"},fullPath:"/profiles/152249/alexander-suslyakov",meta:{},from:{name:null,path:"/",hash:"",query:{},params:{},fullPath:"/",meta:{}}}},function(){var t;(t=document.currentScript||document.scripts[document.scripts.length-1]).parentNode.removeChild(t)}()