Ease of registering land in selected countries (2017).
\r\n\tThe book aims to introduce the potential reader to the problems associated with aeronautics, ranging from academic research to actual application and precise work, and to be of interest to those who want to research and build their techniques in the related fields.
",isbn:"978-1-80355-301-6",printIsbn:"978-1-80355-300-9",pdfIsbn:"978-1-80355-302-3",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!1,isSalesforceBook:!1,isNomenclature:!1,hash:"a6b8e86015392b400a37551116fc0c13",bookSignature:"Associate Prof. Zain Anwar Anwar Ali",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11522.jpg",keywords:"Aeronautics, Aircraft, Control System, Surveillance, Guidance, Fixed-Wing, Rotorcraft, Jet Engine, Modern Drone, Path Planning, Adaptive Control, Hybrid Control",numberOfDownloads:18,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"February 9th 2022",dateEndSecondStepPublish:"April 12th 2022",dateEndThirdStepPublish:"June 11th 2022",dateEndFourthStepPublish:"August 30th 2022",dateEndFifthStepPublish:"October 29th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"3 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:4,editedByType:null,kuFlag:!1,biosketch:"Engr. Dr. Zain Anwar Ali is working as an Associate Prof. and Editor of Sir Syed University Research Journal of Engineering and Technology. He received research funding from Higher Education Commission (HEC), Pakistan, and has research collaborations with several universities in China, including Nanjing University of Aeronautics and Astronautics, Donghua University, Shanghai University, and South East University, under different research grants provided by the National Nature Science Foundation of China.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"415526",title:"Associate Prof.",name:"Zain",middleName:"Anwar",surname:"Anwar Ali",slug:"zain-anwar-ali",fullName:"Zain Anwar Ali",profilePictureURL:"https://mts.intechopen.com/storage/users/415526/images/system/415526.png",biography:"Engr. Dr. Zain Anwar Ali received his B.S. degree in Electronic Engineering from Sir Syed University of Engineering and Technology, Karachi, Pakistan, in 2009. In the same year, he joined Sir Syed UET as a Research Assistant in the Electronic Engineering department, and was soon promoted to a Junior Lecturer due to his hard work and research contributions. He completed his Master's in Industrial Control and Automation at the Hamdard University of Engineering in 2012, securing his second position and soon being promoted to a Lecturer. Later he joined Nanjing University of Aeronautics and Astronautics (NUAA) as a Ph.D. research scholar and the Nanjing Strong Flight Electronics and Machinery LTD to complete his Ph.D. experimental work there. In 2017, he completed his Ph.D. in the field of Control Theory and Control Engineering NUAA. He then rejoined Sir Syed UET as an Assistant Professor in the Electronics Engineering department. In the same year, he was selected as a highly talented foreign expert by the Ministry of China, Beijing, at Liaocheng. After seeing his research background, the vice-chancellor of SSUET gave him the extra responsibility of an Associate Editor of Sir Syed UET research journal which is indexed at various indexing agencies and published in two issues annually. In 2018-2019, he received research funding from Higher Education Commission (HEC), Pakistan, and started some different research collaborations with several universities in China, including Nanjing University of Aeronautics and Astronautics (NUAA-Nanjing), Donghua University (DU-Shanghai), Shanghai University (SU-Shanghai), and South East University (SEU-Nanjing), under different research grants provided by the National Nature Science Foundation of China (NSFC). Currently, Dr. Ali is working as an Associate Professor at the Electronic Engineering Department, Sir Syed University of Engineering and Technology, Karachi, Pakistan, and as the Editor of Sir Syed University Research Journal of Engineering and Technology.",institutionString:"Sir Syed University of Engineering and Technology",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Sir Syed University of Engineering and Technology",institutionURL:null,country:{name:"Pakistan"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"11",title:"Engineering",slug:"engineering"}],chapters:[{id:"82261",title:"Military Aircraft Flight Control",slug:"military-aircraft-flight-control",totalDownloads:14,totalCrossrefCites:0,authors:[null]},{id:"82328",title:"The Impact of the Pandemic Effect on the Aviation in the Environmental Quality of the Air Transport and Travelers",slug:"the-impact-of-the-pandemic-effect-on-the-aviation-in-the-environmental-quality-of-the-air-transport-",totalDownloads:4,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"347258",firstName:"Marica",lastName:"Novakovic",middleName:null,title:"Ms.",imageUrl:"//cdnintech.com/web/frontend/www/assets/author.svg",email:"marica@intechopen.com",biography:null}},relatedBooks:[{type:"book",id:"10198",title:"Response Surface Methodology in Engineering Science",subtitle:null,isOpenForSubmission:!1,hash:"1942bec30d40572f519327ca7a6d7aae",slug:"response-surface-methodology-in-engineering-science",bookSignature:"Palanikumar Kayaroganam",coverURL:"https://cdn.intechopen.com/books/images_new/10198.jpg",editedByType:"Edited by",editors:[{id:"321730",title:"Prof.",name:"Palanikumar",surname:"Kayaroganam",slug:"palanikumar-kayaroganam",fullName:"Palanikumar Kayaroganam"}],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:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],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:"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:"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"}},{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:"314",title:"Regenerative Medicine and Tissue Engineering",subtitle:"Cells and Biomaterials",isOpenForSubmission:!1,hash:"bb67e80e480c86bb8315458012d65686",slug:"regenerative-medicine-and-tissue-engineering-cells-and-biomaterials",bookSignature:"Daniel Eberli",coverURL:"https://cdn.intechopen.com/books/images_new/314.jpg",editedByType:"Edited by",editors:[{id:"6495",title:"Dr.",name:"Daniel",surname:"Eberli",slug:"daniel-eberli",fullName:"Daniel Eberli"}],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:"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:"2270",title:"Fourier Transform",subtitle:"Materials Analysis",isOpenForSubmission:!1,hash:"5e094b066da527193e878e160b4772af",slug:"fourier-transform-materials-analysis",bookSignature:"Salih Mohammed Salih",coverURL:"https://cdn.intechopen.com/books/images_new/2270.jpg",editedByType:"Edited by",editors:[{id:"111691",title:"Dr.Ing.",name:"Salih",surname:"Salih",slug:"salih-salih",fullName:"Salih Salih"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},chapter:{item:{type:"chapter",id:"63289",title:"Land Acquisition and Use in Nigeria: Implications for Sustainable Food and Livelihood Security",doi:"10.5772/intechopen.79997",slug:"land-acquisition-and-use-in-nigeria-implications-for-sustainable-food-and-livelihood-security",body:'\nLand acquisitions are broadly defined to include not only the purchase of ownership rights but also the acquisition of user rights, for instance through leases or concessions, whether short or long term [1]. Land tenure system can be defined as the rights and institution that governs access to and use of land [2]. Tenure system of land involves a system of rights, duties and responsibilities concerning the use, transfer, alienation and ownership security of land and its resources. From the ongoing, it is clear that land acquisition and use cannot be discussed extensively without incorporating land tenure system. This chapter therefore presents a comprehensive review of literature on the land acquisition and use in Nigeria and the implications for sustainable food and livelihood security in the country.
\nLand is a veritable ingredient of development especially in the agricultural and tourism sector of any economy. Nigeria has a total land mass of 924,768 sq.km with a population of 198 million and annual population growth rate of 2.8% [3]. Nigeria comprises over 250 ethnic groups located within the 36 states and the Federal Capital Territory [4]. Land is an asset and factor of production for households in Nigeria [5]. However, the level of access and title ownership is determined by the state [6]. Therefore, the land system is characterised by several actors including government, community leaders, families, lawyers, middle men and estate agents among others. All activities of the different actors are regulated by the government through policies and programmes. Generally, land systems thrive on clearly stated property rights. Two types of proprietary rights have been defined in literature-absolute or nonderivative interests and derivative interests [6]. The absolute or nonderivative interest is a nonrestrictive access and use of land conferred on the holder. The absolute interest on land has also been explained as inclusive of highest scope of proprietary decisions on the use and management of land. Derivative interest derives from a larger estates or superior estates. The derivative rights cover leaseholds, life interests, mortgage, rents and pledges among others. The two types of property rights (absolute or nonderivative interest and derivative interest) exist in Nigeria.
\nThe Nigerian land system has evolved over the years as classified into precolonial, colonial and postcolonial periods in literature [7]. The three periods are explained below:
Precolonial land ownership structure: Prior to the colonial era, lands were solely owned by families and communities. The land was owned by the community and family heads who then allocate based on the needs of their subordinates [8]. The legal estate or authority existed at the community or family level. Thus, the leadership of communities and families had absolute interests, while constituents had derivative interests.
Ownership structure during colonial rule: The ownership of land was regulated by the colonial authorities before independence. The legislations included Treaty of Cession (1861), Land Proclamation Ordinance (1900), Land and Native Rights Act (1916), Public Lands Acquisition (1917), State Land Acts (1918) and Town and Country Planning Act (1947). The colonial legislations were meant to take property rights out of the reach community leaders. For instance, in 1900, the Land Proclamation Ordinance created by Lord Lugard regarded the principles of native law and custom and stipulated that the title of land can only be acquired through the high commissioner [6].
Postcolonial ownership structure: As depicted earlier, the land ownership structure in Nigeria has evolved over the years. Two key legislations have been enacted since independence: Land Tenure Law of Northern Nigeria of 1962 and Land Use Act of 1978. The land tenure law of Northern Nigeria of 1962 stipulated that the minister responsible for land matter controls, holds and allocates land (unoccupied or occupied native lands) to natives of Northern Nigeria. This implies that non-natives except for the approval of the minister could not land titles. The law granted the natives of Northern Nigeria the right to own land for a limited number of years. The individual/native may sell, mortgage or transfer the land subject to the minister’s approval. The Land Tenure Law of 1962 was repealed, and land use decree of 1978 was implemented.
Land tenure issues are important components of developmental discourse [9]. This is because unplanned or weak regulatory undermines development as informal settlements grow thereby stressing already inadequate urban infrastructure [5]. Therefore, poor land management affects security and growth as it induces, slums and suboptimal living conditions [10, 11]. The Nigerian land use decree of 1978 stipulates that all land belong to the government holding same in trust for the public [12]. This implies that the government allocates land to individuals and corporate entities based on the objectives of interested parties [13].
\nObjectives of Land Use Act 1978
Make land accessible to all Nigerians
Prevent speculative purchases of communal land
Streamline and simplify the management and ownership of land
Land available to governments at all levels for development
Provide a system of government administration of rights towards improving tenure security
The aftermath was political considerations in the allocation of land, corruption and rise in lobbyist tendencies. The land use act avails the opportunities to own lands without recourse to families and communal land holdings. The process of obtaining certificates of occupancy is characterised by bureaucratic bottlenecks, high registration fees and perpetual payment of levies and taxes [10]. Till date, land tenure is governed by customary laws, especially in rural Nigeria. Therefore, tenure security is low as the transactions in the land market are largely informal.
\nNigeria trails other African countries in the ease of registering land indices (see Table 1) [14]. Nigeria ranks 179th in the ease of registering land compared to Botswana (81st position), Morocco (86th position), South Africa (107th position) and Ghana (119th position). In terms of the number of procedures required to complete land title registration, there are 11 procedures in Nigeria compared to Botswana, Morocco, South Africa and Ghana with four procedures, six procedures, seven procedures and six procedures, respectively. This depicts low level of innovation and inefficiency in the land registration process in Nigeria. As expected from a country with one of the highest number of procedures for land title registration, it takes more days to register land title in Nigeria than elsewhere (see Table 1).
\nS/N | \nCountry | \nRegistering of property (DTF) | \nRegistering property index | \nProcedures (number) | \nTime (days) | \nCost (% of property value) | \nQuality of land administration index (0–30) | \n
---|---|---|---|---|---|---|---|
1 | \nNew Zealand | \n94.97 | \n1 | \n2 | \n1 | \n0.1 | \n26 | \n
2 | \nUnited States | \n76.80 | \n37 | \n4.4 | \n15.2 | \n2.5 | \n17.6 | \n
3 | \nChina | \n76.15 | \n41 | \n4 | \n19.5 | \n3.4 | \n18.3 | \n
4 | \nUnited Kingdom | \n74.51 | \n47 | \n6 | \n21.5 | \n4.8 | \n24.5 | \n
5 | \nBotswana | \n65.45 | \n81 | \n4 | \n27 | \n5.1 | \n10 | \n
6 | \nMorocco | \n64.35 | \n86 | \n6 | \n22 | \n6.4 | \n15.5 | \n
7 | \nSouth Africa | \n58.43 | \n107 | \n7 | \n23 | \n7.6 | \n13.5 | \n
8 | \nCote d’Ivoire | \n57.56 | \n113 | \n6 | \n30 | \n7.4 | \n10.5 | \n
9 | \nGhana | \n55.5 | \n119 | \n6 | \n52 | \n6.7 | \n8.0 | \n
10 | \nBurkina Faso | \n50.44 | \n140 | \n4 | \n67 | \n12 | \n11.5 | \n
11 | \nAlgeria | \n43.83 | \n163 | \n10 | \n5.5 | \n7.1 | \n7 | \n
12 | \nNigeria | \n34.08 | \n179 | \n11.3 | \n68.9 | \n10.5 | \n7.4 | \n
Generally, lands are small and fragmented which imparts significantly on the mechanisation potentials of farming households. Similarly, fragmented nature of land systems inhibits the creation of an effective land market, which consequently hinders the emergence and development of an overall equitable distribution of wealth [15]. Land markets should be accessible to all categories of people including women and minority groups.
\nAccording to Dale et al. [15], land markets should possess the following features:
Guaranteed security of land rights
Low transaction cost for all users
Access to credit
Transparency, openness and ease of access to all
Protection of minorities
Support for social, economic and environmental sustainability
Public/private partnerships to provide value-for-money services
Small-scale farmers dominate rural landholdings with average farm size ranging from 0.5 ha in the South to 4 ha in the North. About 50% of the Nigerian farms are less than 1 ha, while 15% are less than 5 ha [16]. There are three types of land markets in Nigeria. The types of markets are:
Formal markets where certificates of occupancy from the government are allocated.
Combination of formal and informal markets where transfer of land rights are certificate of occupancy.
Informal market where the bulk of the transactions are not documented as title owners do not obtain certificate of occupancy [16].
The land can be used for different purposes including agricultural production, industrial production, buildings for households and establishment of parks among others [5]. There are location, gender, income-class considerations in the allocation and ownership of land in Nigeria [17]. In terms of ownership structure, men typically own more land compared to women in Nigeria (see Table 2). Majority of the land owners inherited it from their family, while only 7 and 2.2% of male and female, respectively, reported purchase of land (National Bureau of Statistics; World Bank and Federal Ministry of Agriculture and Rural Development, [18]).
\nOutright purchase | \nRented | \nUsed free of charge | \nAllocated by community | \nFamily inheritance | \n|||||
---|---|---|---|---|---|---|---|---|---|
Male (%) | \nFemale (%) | \nMale (%) | \nFemale (%) | \nMale (%) | \nFemale (%) | \nMale (%) | \nFemale (%) | \nMale (%) | \nFemale (%) | \n
7.0 | \n2.2 | \n6.8 | \n11.8 | \n7.9 | \n11.8 | \n7.1 | \n5.9 | \n71.2 | \n68.4 | \n
In the study conducted by Eze et al. [19], they examined land tenure systems, farm sizes, agricultural productivity and innovation by looking at the socio-economic characteristics of farmers and identified the factors that affected agricultural productivity in the Imo State. Five communities were chosen randomly, and from each of these communities, twenty farmers were randomly chosen. Data were collected, collated and analysed using relevant techniques such as means, percentages, frequency distribution and multiple regression analysis. The results showed that 85% of the respondents practiced individual land tenure system alone. It was also revealed that the laws of inheritance and increase in population led to the subdivision and fragmentation of existing farmland in such a manner that the sizes of farm holdings discouraged agricultural commercialization. Also, the study revealed that fragmentation widened the distance between plots that led to increased waste of man-hour and energy. It was also shown that mechanisation of agriculture was impracticable under land fragmentation and adoption of modern innovation was reduced since just 35.0% of the respondents claimed to have adopted other forms of innovation. From the analysis, it was found that lands were severally fragmented during the acquisition and sharing of either family or community lands, and this went a long way in discouraging adoption of laudable innovation like mechanised farming as a result of reduced farm size of land. Also farmers were not at liberty to sell a portion of land acquired through communal ownership and thus majority of them could not acquire extensive land for considerable agricultural productivity. The econometric result revealed those socioeconomic factors that significantly affected the farmers’ productivity in the area to include planting materials, household size, farming experience, tenure system and labour cost.
\nAlarima et al. [12] examined the land rights and rental systems followed by sawah rice farmers in Nigeria. The study was conducted in six states in Nigeria that use sawah rice technology: Kwara, Ondo, Niger, Ebonyi, Kaduna and Abuja. A total of 124 sawah farmers were selected for participation based on their involvement in sawah-based rice production. Data used in this study were collected from October 2009 to January 2011 in all the sawah sites in Nigeria. T-test was used to determine significant differences in the yields and farm sizes of landlord and tenant farmers. The land tenure system practiced in the lowlands is governed primarily by inheritance (71.8%), with temporary arrangements made through rentals (37.1%). Tenants pay ₦12,000 ha−1 year−1 in land-for-cash agreements and 5% of the total yield of rice in land-for-paddy agreements. Generally, agreements between landlords and tenants were verbal, binding and honoured by both parties. Land conflicts occurred when either party breaches the agreement and always result in the landlords taking over the land. Significant differences in the farm sizes and yields of landlord and tenant farmers were found. The findings of the study indicate the importance of secured land tenure, which affects the practice of sawah and the productivity of rice farming. Sustaining and improving sawah rice production in the study area would require addressing the land tenure issues of both landlords and tenants. Access to land for tenants will enhance their participation in sawah and increase their chances of increasing their income and emerging from poverty. Investment in more durable inputs such as power tillers, dykes and irrigation canals will decrease if the land is not secured. Therefore, tenants and landless people need more secure access to land to provide them with opportunities to manage their sawah plots so that they will have higher yields. Farmers whose land security was not guaranteed would be more inclined towards short-term investments in land, and the sustainability of sawah would not be expected to be their priority.
\nAlso, the study by Ojo [20] examined the effects of land acquisition for large-scale farming on the performance, productivity and technical efficiency of small-scale farming in Nigeria. The farmers were grouped into two groups: farmers whose families donated land for large-scale oil palm project (A) and those who did not (B). Data collected were analysed using descriptive statistics, gross margin and stochastic frontier production function analyses. The study revealed that acquisition of land for large-scale farming in the study area had adverse effects on small-scale farming. This could further worsen the food security crisis in Nigeria because about 80% of farmers in Nigeria practice small-scale farming [21] that constitutes over 90% of food and agricultural production in the country [22]. It was revealed that group B farms were more productive in the allocation of resources and overall production as measured by the decreasing positive elasticity of production of most of the variables involved in the production function analysis. The group B farms were also more technically efficient than the group A farms.
\nThe study therefore recommended that government in its drive to encourage large-scale agricultural production should not acquire land near the towns and people’s settlements; rather, land on the highways/expressways should be opened up and allocated to prospective large-scale farmers.
\nAgain, Twene [23] investigated the effects of the large-scale agricultural land grabbed for the Bui Dam project on the livelihoods of the affected people. Both quantitative and qualitative data were collected through the use of interviewer questionnaire administration, interview guide, focus group discussions and observations. A total of 142 household heads were interviewed, although some key informants such as chiefs and community development officers of the district assemblies were also interviewed. The descriptive statistical tools and the t-test were employed to analyse the quantitative data whilst content analysis was applied to qualitative data with the result presented in the form of direct quotations. The study revealed through the result of the t-test for difference in output within 2005/2006 and 2013/2014 production seasons that local food crop production and the quantity of fish catch have declined after the land grabs.
\nEqually, it was found that annual income levels of the local people had fallen after the Bui Dam project due to reduction in their productivity of both crop production and the quantity of fish caught. Thus, farming and fishing were the most affected occupations in the study area. These were attributed to loss of farmland and low level of experience for fishing in the newly created lake as well as the problem of proximity between the resettled communities and the river.
\nIn addition, it was found that the land grabbing situation resulted in conflict between some communities and the Bui Power Authority. The study showed that the local people initially reacted by engaging in conflict with officials of the Bui Power Authority, particularly in Dokokyina. Equally, it was found that the land-grabbing incident in the study area was not accompanied by adequate compensation packages as promised which were the bases for the conflict because assets lost were not in commensurate measure with compensation packages received.
\nHowever, it was also revealed that the acquisition of the land for the Bui Dam project and its associated relocation of the affected people have adversely affected the natural capital base of the people (land, forest and water bodies). Thus, generally, the study discovered that the local people’s access to the natural capital had worsened, while access to the physical capital had improved.
\nFinally, with regard to interventions and coping strategies, the study revealed that the main coping strategies adopted by both men and women in the study communities after the land was taken for the Bui Dam project are casual work (by-day) and petty trading, respectively. The growing interest in petty trading was attributed to the view that the construction of the dam has caused influx of people into the study area, thereby providing market for consumable goods. Other coping strategies included farming, premixed fuel business, wood gathering and pito brewing. The local people in the study communities were unaware of any alternative livelihood interventions provided by the Bui Power Authority and the district assemblies to ensure the sustainability of their livelihoods.
\nThe study therefore recommended the introduction of a comprehensive livelihood enhancement programme such as skill training for the youth and the landless group of people in the study communities by the Bui Power Authority and the district assemblies. This would enable them to promote their livelihood sustainability.
\nRural Nigeria is agricultural as 85% of the residents depend on agriculture for their livelihood. However, access to land is limited as families and community heads still manage to control land thereby determining access to land. Given the position of Land Use Act 1978, it implies that the beneficiaries of the communal land allocation system are not formally recognised as the legal holders of right to the land. Again, family and community heads rely on memory and reference to natural and artificial features to define plots of land that is prone to uncertainty regarding the location of boundaries [23]. This is because most communal land allocations are not documented [23].
\nAvailability of land determines food and livelihood security given the level of agricultural development in Nigeria [17]. This is because farming operations will remain at subsistence level due to inadequate access to land. In fact, an estimated 95% of agricultural lands in Nigeria are not titled [24]. This undermines the capacity of farmers to present lands as collateral to access formal loans from financial institutions [24]. Again, the lack of absolute or nonderivative property interest constrains the ability of farming households to plant cash crops consequently limiting their income generation potentials [17]. Therefore, food security is difficult as the population continues to grow and agricultural land becomes scarce [25]. The challenges of agricultural production and food security including inadequate access to land, finance and technology, inconsistent policy regime, infrastructure deficit and adverse climate change impacts have been documented in literature [26, 27].
\nMoreover, Onoja and Achike [28] reviewed cases of land grabbing by foreign investors in West Africa, identified the possible drivers of large-scale land acquisition by foreign investors in the region and discussed the implications of the findings for agricultural and land policy reforms in West Africa. Prior to the study, reports indicating that large portions of land (estimated 50–80 m ha) have been bought by international investors in middle- and low-income countries, with roughly two-thirds of those purchases occurring in sub-Saharan Africa, called for a cursory appraisal of the implications of the trend of land grabbing for West African food security (Sahel West Africa Countries, SWAC/OECD, [29]). Land transactions involving foreign investors had increased in the area over the years. Over 100,000 ha have been documented in Nigeria. Ghana and Mali have many significant transactions on land by foreign investors. Several investors have more than 100,000 ha. Burkina Faso has one significant land transaction (200,000 ha), while Niger and Senegal have relatively small land transactions. Most lands grabbed in West Africa were profit driven (by biofuel investors) and were made under the guise of using the lands acquired for agricultural investments. Land tenure and investment in land have far-reaching economic and social implications and are therefore key issues for small family–operated farms and their relations with agribusiness (Sahel West Africa Countries, SWAC/OECD, [29]). According to the Food and Agriculture Organisation [30], many problems that are now being recognised in natural and agricultural land systems have arisen out of the use of inadequate technologies for assessing and monitoring land resources, preventing land pollution and rehabilitating contaminated lands. According to Cotula, Vermeulen, Leonard, and Keeley, transactions labelled as “large-scale” involved between 1000 and 500,000 ha [31, 32]. Increasing evidence is emerging to affirm that the problem of large-scale land acquisition by foreign investors in Africa is following a dangerous trend, which needs to be monitored.
\nGlobal Development [33] reported that research findings have indicated that a million Chinese farmers have joined the rush to Africa and that some of the world’s richest countries are buying or leasing land in some of the world’s poorest to satisfy their insatiable appetites for food and fuel. In the new scramble for Africa, the report added, 2.5 m ha (6.2 m acres) of farmland in five sub-Saharan countries have been bought or rented in the past 5 years at a total cost of $920 m (£563 m). Recent high-profile land purchases encompassing thousands of hectares of prime agricultural land have raised concerns over equitable land access [30]. Sub-Saharan Africa, especially Nigeria and other West African countries, is not exempt from this development (see Cotula, Vermeulen, Leonard, and Keeley, [31, 32]). Such a trend is more disturbing when considered alongside the future of food production from SSA land, where FAO [34] put the estimated share of arable land in total agricultural land at only 15.6% as of 2000. Response indicators showed that the value of agricultural production per hectare of agricultural land is highest in South Asia, at I$ 720.6, while Sub-Saharan Africa trailed behind, globally ranking lowest with a value of I$ 71.8. Under this scenario, worrying over the growing trend of large-scale land acquisition by foreign investors‑who are, at best, interested in growing crops that can only contribute to food security and economic growth of countries outside SSA‑while the limited land available for African farmers is diminishing in the face of lingering hunger and poverty is justified.
\nFood security is a current issue in Nigeria, as it is across Africa. According to the review, it was noted that there are 307 million hungry people in Africa, most of whom live in Sub-Saharan Africa (265 million). A FAO statistic indicated that at least 9.4 million Nigerians were undernourished and that out of Nigeria’s 147.7 million citizens, 6% were highly undernourished (2011). Instead of dealing with food supply or food security problems at such a critical time, the country is selling off arable lands to foreign investors prospecting in biofuels production to the extent of losing greater than 136,000 ha of land from only eight deals that could have been used in producing food crops. The implication of this is that the drive for food security will still be a far-fetched dream as long as attraction of foreign investment in agriculture only aims to produce biofuels for profit. The auctioning of fertile farmlands for this purpose also portends danger of losing job opportunities, increasing poverty in the country, and helping the growth of foreign companies to the disadvantage of poor land owners in Nigeria. The overall implication of these trends is to increase poverty, unfavourable terms of trade against Nigeria, desertification, increased global warming and the adverse consequences of climate change and the disempowerment of indigenous citizens, who will now be left with few pieces of land that may not reach even 1 ha. The study therefore recommended that a regional approach should be applied by African countries, implementing land reforms that will involve the local communities who own the land, stopping long-term leasing beyond 50 years, building capacity and creating awareness about land transactions of large magnitudes.
\nFurthermore, a report by Economic Commission for Africa [35] to show the linkages between land tenure and food security in Africa confirms that land plays an important role in the livelihoods of the majority of Africans. This asserts that food security and poverty reduction cannot be achieved unless issues of access to land, security of tenure and the capacity to use land productively and in a sustainable manner are addressed. This chapter suggests that land is central in promoting rural livelihoods in Africa because access to land and security of tenure are the main means through which food security and sustainable development can be realised because the livelihoods of over 70% of the population in Africa are mainly linked to land and natural resources exploitation.
\nThis chapter studied the land policy generic model developed by Moyo [36], based upon Shivji et al. [37], derived from five analytical constructs of land management, namely, land distribution, land utilisation, land tenure security, land administration and land adjudication. It posits land tenure as one of the central factors determining food security and sustainable development.
\nIn terms of land distribution, the major problem relates to unequal access to land according to race, gender, class and ethnic distinctions. The second analytical construct relates to land utilisation and how this has been economically and socially constructed. There is a tendency to view small farms as inefficient and large farms as highly efficient in terms of yields per unit of land [38], especially in settler countries. But such a perception has long since been debunked [39, 40] and multinational organisations (IMF and World Bank) have come to accept the efficiency of smallholder land use. The main question of analysis is how the regulation of land-use is consensual or coercive and whether it is free of discrimination. The third conceptual issue is how land tenure has been constructed and qualified in most African countries. The main question relates to how secure the tenure systems are and whether there is equity or not. It was argued that access to more productive land and control of natural resources by the poor offers the most stable form of security for poor households. In this case, livelihood security cannot be achieved without some form of redistribution of land held by wealthy classes (constituted of individuals and multinational companies). The assumption tends to be that enhancing access to land, security of tenure or sustainability of land resource use will ultimately enhance welfare, including food security.
\nThe fourth conceptual issue relates to how land is administered. The management regimes of land and natural resources differ due to the nature of the historical experiences. The main issues relate to the accessibility, transparency and accountability of the administrative systems. There has been a tendency towards too much administration, due to the different layers of the state, local and indigenous authority, particularly within customary tenure systems. The fifth analytical construct relates to systems of adjudicating land disputes. There are key questions with regard to how to resolve current and past land problems in situations where multiple tenure regimes exist. In most countries, the legal framework has been biased towards the market and the state.
\nThe study also reviewed the model by Maxwell and Weibe [41] that illustrates a causal flow relationship between resources, production, income, consumption and nutritional status.
\nBelow is an example of a conventional conceptual nexus between land and food: Resources → Production → Income → Consumption → Nutritional status (Source: Adopted from Maxwell and Wiebe [41].
\nBut it was suggested that a simple linear model does not adequately capture the inter-relationships between consumption and investment decisions, household endowments, production and exchange decisions, and household entitlements. A more comprehensive model illustrates a circular relationship between these four factors, which are further impacted upon by tenure institutions and asset markets and have outputs in terms of environmental impact, generation and redistribution of wealth. The most apparent qualitative link that was suggested was that increased security of tenure in productive resources enables more efficient and profitable agricultural production and hence greater access to food via both own production and trade.
\nAlso, a report was given by the European Union on Development in 2011 that was driven mainly by concerns about the scarcity of food, energy and arable land and linked to these expectations of rising land values with issues relating to:
How the land deals come about, the quality of the contracts, and who will benefit and who will lose (i.e., governance and accountability issues with respect to decision-making on transactions and terms of the contracts).
Whether there is recognition of all local rights (including informal and secondary rights) and adequate compensation.
Whether the contracts override customary rights, resulting in smallholders, pastoralists and forest dwellers being driven from the land.
The implications for food security/sovereignty, rural development and the future of smallholder farming.
Risks related to water availability, environmental degradation and loss of ecosystem services.
The report explained that it was not only transnational investors but also migrants who use their remittances to buy land in their country of origin [42] that were acquiring large areas of farmland. Although not a new phenomenon, studies indicated that this form of land acquisition is accelerating [43].
\nAlso, LSLAs (large-scale land acquisitions) were also taking place for purposes other than food and biofuel or agricultural production [44, 45] that included nature conservation, parks and new initiatives under the United Nations Collaborative Programme on Reducing Emissions from Deforestation and Forest Degradation in Developing Countries (UN-REDD).
\nAccording to the report, the debate on global food security continues to stimulate the interest in large-scale farming, which is perceived as more productive and efficient. The argument runs as follows: given that by 2050, some 9 billion people will need to be fed and there is a need for a significant increase in production and productivity, which can be achieved only by replacing smallholder farming with industrial-type farming. Others contend, however, that smallholder farming can be just as efficient (e.g., [46]).
\nMoreso, the direct contribution of LSLAs to national food sovereignty depends on the type of crop grown and whether it is locally marketed at affordable prices. In Ethiopia, these large farms sell grain to WFP (World Food Programme), which uses them to feed those who left the famine areas and are now in camps. It is important to look at local as well as national food security. As mentioned, the first effect of these large-scale farms is often that local smallholders lose access to land and natural resources, which undermines their livelihoods, food security and ability to accumulate resources. These losses may be partly compensated for if new jobs are created that allow these people to earn sufficient to feed themselves and their families to a comparable level in terms of quantity and quality and also to pay for other services.
\nFombe et al. [47] studied security of land ownership by women in Anglophone Cameroon. In most parts of Africa, land ownership is affected by traditional values, inheritance rights and government influence. This study illustrates that land acquisition and development by women constitute a problem because of traditional pressures and the law guiding the process of land certification. Aluko and Amidu (2006) however argue that the complexity of land tenure in Nigeria is the result of the co-existence of several systems; none of which is completely dominant. This legal pluralism causes a degree of uncertainty about land rights, particularly for vulnerable groups, like women. In most of Anglophone Cameroon, there are basically two ways in which women can acquire land either through family bond (users’ rights) or through transactions (purchase, lease and rent). In the current context of land scarcity, population mobility, urbanisation and land reforms, the competitive demand for land has not only generated a diversity of struggles over land but has further complicated the prospects of women accessing land in a predominantly patriarchal setting (Lotsmart et al., 2010). In Anglophone Cameroon, the majority of women do not own land or have the right to inherit land and other property where statutory laws and customary practices co-exist.
\nThe study’s major aim was to ascertain the effectiveness of government’s legal instrument (the Land Consultative Board) that regulates the purchase and ownership of land; random interviews were conducted with traditional and local administrative authorities as well as men and women landowners in five of six divisions in the North West and four of five in the South West Region. These two English-speaking regions were considered as Anglophone Cameroon because they were administered by British Cameroon during the colonial period.
\nA random but stratified survey method was adopted with 20% of the sampled population comprised males based on their traditional and societal roles, while 80% was addressed to rural and urban women in eight divisions.
\nWomen’s land rights can contribute to their empowerment and constitute a key to reducing poverty and developing a community. With secured land rights, crop production will increase; women will have better access to credit, develop self-esteem and will be able to develop their own skills (Mantobang, 2011). According to Sengupta (2000), empowerment is inextricably linked to rights language, whereby it constitutes the ability or opportunity of the poor to claim and exercise their rights.
\nSustainable development should be inextricably linked to tenure rights. This concept is not mentioned in the Declaration of the Right to Development adopted by the UN General Assembly in 1986 (Marks, 2008). In as much as women have a right to development, so do they have a right to sustainable development, though this latter concept hinges more on rights and obligations of humans towards nature. Taking an ethical perspective on the concept of sustainable development, Marks (2008) looks at it as fairness at three levels; “intragenerational”, “intergenerational” and “between humans and the environment”, by enhancing people’s moral consciousness and environmental protection, altering traditional ideologies and behaviours and promoting sustainable survival.
\nWomen’s lack of ownership and access to land results from some traditional practices that violate sustainable development. This is exemplified by those who uphold the values on the one hand and the environment on the other, with the victims (women) being at the centre. It follows therefore that depriving a woman of the right to inherit land for the simple fact that she is a woman puts her in a disadvantaged socio-economic and political position vis-à-vis the men. This only accentuates the feminization of poverty.
\nIt was noted that there is need to exhume the barriers of government’s legal instrument (the Land Consultative Board) that regulates the ownership of land and to revisit some traditional practices as regards land ownership that impact negatively on women in a changing and globalising world. A compromise approach was advocated for land acquisition that can transcend traditional barriers as well as render the process of land registration more realistic especially for women.
\nIn the same vein, Odoemelam et al. [48] evaluated women access and rights to land and its implication on rural household food security in Abia State, Nigeria. The study established that it was not just the shortage of land that affects the output of agriculture but the structure of the land tenure, lack of proper land ownership and rights.
\nMultistage sampling procedure was used in the selection of the sample size with a total of 180 respondents. Data were generated through the use of Focus Group Discussion and participatory observation. Data generated were analysed through the use of simple descriptive statistics like frequency distribution and means.
\nResults showed that most of the women were in the economically active age and majority were married with a very high percentage having only up to primary school level of education. The level of income indicated that majority of the respondents 34% earned between (N160–180,000), while 16% earned between (N200–220,000) per annum. Methods of land inheritance showed that women acquired land for cultivation through majorly matrilineal ties and purchases, while other forms of acquisition such as renting, borrowing and through inheritance were minimal. In terms of access and use rights on lands, the study found about 30% of the respondents were allowed to cultivate only annual crops, 15% perennial crops, 11% were not allowed to harvest production from the trees, 13% were not allowed to retain land after long fallow and 8% complained about limited access to inputs.
\nOn effect of access and land use rights on food security, the 25% respondents stated that due to the lack of access to land use right, their expertise on farming activities are underutilised leading to food insecurity, 15% said they lack commitment, 26% complained about their inability to get credit facilities from bank because they can not use their cultivating land to get collateral, unfertile plots 13% leading to low yield and nonmechanised farms, 24% due to scattered plots. The study concluded that ownership rights are critical to securing a sustainable livelihood and income, and the lack of rights is one of the main sources of economic insecurity. When men and women have equal access to land use rights, they have effective decision-making power in the household and food production will be enhanced to its full capacity to support the welfare of all family members and to promote food security in the society.
\nDe Zoysa [1] examined the implications of large-scale land acquisition on small landholder’s food security. This chapter analysed the implications of LSLA (large-scale land acquisition) on local population’s food security and livelihoods using Ethiopia as a case study to measure the progression of vulnerability created by land reform policies that encourages such investments. Using the analytical framework of the Pressure and Release (PAR) model, this chapter argued that Ethiopia’s land reform has systematically weakened small landholder’s access to food and livelihood. The Pressure and Release (PAR) model was selected because the model allows one to understand that food insecurity as defined as the availability, access and utilisation of food does not occur due to a drought but more so a systematic breakdown of coping mechanisms and the lack of consideration paid to rectify root causes of food insecurity. It was recognised that all frameworks have limitations in analysing complex situations including the PAR, and it was treated with caution to ensure there is no oversimplifications.
\nThe PAR originally developed by Blaikie et al. in 1994 demonstrates that disasters were not simply a random natural phenomenon but a result of development regression [49]. The PAR identified three factors that exacerbate vulnerabilities that include: (1) root causes; (2) dynamic pressures; (3) unsafe conditions.
\nThe study was based on secondary data through the forms of both academic and grey literature.
\nIn order to capture the impact of LSLA on affected populations, the case study needs to narrow the scope into a region of the country that faces the highest amount of LSLA such as the Gambela Region of Ethiopia.
\nStructures: Political and economic structures reproduce domination against the marginalised in order to maintain the control of power. In the case of the Gambela Region, the lack of secure land tenure was a structure that reinforced the deeper issue of an ethnic minority who had a lack of political power.
The major lessons learned from the Ethiopian case study was that the ‘new phenomenon’ of land acquisitions in the Gambela Region was actually a process that had historical roots dating to Ethiopia’s imperial colonialism making it ‘an old wine in a new bottle.’ The local conditions of suppressing press freedoms and NGOs’ operational space ensured that such oppressive actions continued in the future without critical review. Another lesson from the case study is that disasters are never a one-off event but manifests from embedded vulnerabilities. This chapter does not argue with the fact that a high level of investment is needed in Ethiopia, but the concern is that without rectifying the root causes of disasters that have plagued Ethiopia, large-scale land acquisition only exacerbates the progression of vulnerability.
\nThis study examined the issues around land acquisition and the implications on livelihood and food security. It was found that the land acquisition is bound by the Land Use Act 1978, which stipulates that all lands belong to the government. However, the bulk of the land transactions are carried out in informal markets under customary laws with poor or lack of documentation, especially in rural Nigeria. The land market in Nigeria has evolved over the years from the pre-colonial era when land titles were in custody of family and community heads through colonial era and post-colonial era. The current framework undermines food security as farmers typically lack the access to land and as such cannot scale their subsistence farming or even present land as collateral for formal loans. This study identified bureaucratic bottlenecks, high cost of registration of land title, weak land markets and policy inconsistency as the challenges of land acquisition and use in Nigeria. Based on the findings of the study, the following are recommended:
Government should reduce and make the processes to be completed easier in registering lands in Nigeria.
The Land Use Act 1978 should be amended to capture prevailing realities around customary laws and informal markets.
Government should reduce the cost of land registration in Nigeria.
Multilateral organisations and government should co-create and co-finance innovative interventions to improve activities in the land market.
Water molecules, which reside on the surfaces of proteins or lipid bilayers or in tissues and cells, exhibit properties that are significantly different from those found in pure or bulk water as water molecules in such biological systems face additional interactions [1, 2, 3, 4, 5, 6, 7]. Unique properties of such water molecules, which are confined in microenvironments of biological surfaces or interfaces are popularly termed as ‘biological water’. This water drives many biological processes, in which it plays wide varieties of roles at different levels of complexity making its participation increasingly evident as an active agent and not simply as the spectator solvent [8, 9, 10, 11, 12]. Biological water differs from bulk water in a number of ways. First, clustering of the water molecules at the surface of a protein increases the local density by as much as 25% compared to that in bulk water [13, 14]. MD simulation by Smith et al. has revealed that about half of this density increase arises from the shortening of the average water – water distances and the other half from an increase in the coordination number [15]. Second, replacement of the water–water hydrogen bonds by the water–protein hydrogen bonds in the protein hydration layer lowers the freezing point of the hydration water (i.e. prevents formation of ice). The hydration layer of many proteins does not freeze even at sub-zero temperatures and thus life may sustain even at low temperatures [16, 17, 18]. Third, in bulk water, mutual polarization of the hydrogen bonded water molecules increases the dipole moment and dielectric constant. Such polarization is absent for water molecules in hydration layers of biological molecules, i.e. biological water is less polar than bulk water [19]. Further, measurements of water dynamics suggest that around 10–25% of water molecules in cells have slower reorientation dynamics, by around an order of magnitude, than those in the bulk [2, 20]. Centrality of liquid water to life can be easily understood from the fact that condition for the search for the possibility of life elsewhere is the presence of trace of water [21]. In spite of this status, role of water in sustaining life is still not understood perfectly [12]. It is now, however, clear that water plays an active role in the life of the cell over many scales of time and distance and exhibits diverse structural and dynamical roles in molecular cell biology [3, 22].
In liquid (or bulk) water, the molecules form a tetrahedrally coordinated motif, which is the building block of ephemeral six-membered (ice-like) or five-membered (clathrate-like) ring structure, consisting of fluctuating network of hydrogen bonds, but each bond has an average lifetime of about a picosecond [23]. Thermodynamics of hydration in water are generally governed by a balance between the enthalpic and entropic consequences, namely the enthalpies of water–water and water–solute interactions (hydrogen bonding, electrostatic, and van der Waals) and the entropies of disrupting the relatively ordered hydrogen-bonded networks of bulk water and forming new hydrogen bonds to suit the geometric factors of the biological interfaces [15, 24, 25].
Similarities in water dynamics in hydration shells of various proteins [26] suggest that the dynamics are determined by rather general features of surface chemistry and topology, which induce excluded volume effects and hinder the approach of new hydrogen bond acceptors within the hydration network. There is now universal recognition that the dynamical behavior of biological macromolecules cannot be decoupled from that of water and the dynamical behavior of the hydration shell largely controls the chemical function of the biological molecules [27, 28].
Since the development of this understanding that biomolecules are surrounded by a sheath of hydration water, which takes active part in all of their normal activities, extensive efforts have been made to perceive the detailed structure and dynamics of the hydration layer using a variety of spectroscopic methods, such as X-ray and neutron scattering [14, 29, 30], NMR [31, 32, 33], second harmonic generation [34, 35] and ultrafast fluorescence and IR spectroscopies [1, 2, 22, 26, 36, 37], assisted by ab initio and molecular dynamics simulations [24, 25, 38, 39]. However, these measurements could provide information about the dynamics of water and the biomolecules at a low-hydration level corresponding to the first layer of hydration water only. Since fluctuations of protein and solvent dynamics take place over a wide range of length scales (in the range of a few nm) and timescales (from milliseconds to picoseconds) influencing several aspects of protein function, no single technique can span so many spatial and temporal orders of magnitude. Therefore, there has obviously been a debate about how to reconcile the results of different experimental methods that explore dynamics [1, 2, 22, 40, 41].
Recent realization that low-frequency and large-amplitude modes of water molecules in the hydration shell are particularly important in controlling the conformational changes that dominate protein function, has led to using the terahertz (THz) spectroscopy to observe water dynamics around biological molecules [42, 43]. THz radiation (1 THz = 1012 Hz = 33.33 cm−1) excites the low frequency vibrations of the solvated protein and directly probes the collective hydrogen bond dynamics of the coupled protein-water system in (sub-) ps time domain. Librational, translational and intermolecular, collective motions of hydration water, as well as large amplitude motions of biomolecules, also occur in similar time scale (see Figure 1). In frequency domain, this corresponds to low-frequency modes in the 1–10 THz frequency region. In spite of the fact that water molecules strongly attenuate the THz radiation in this frequency region, laser or accelerator-based THz sources (vide Section 2) are now powerful enough to penetrate water layers. Modern THz spectroscopic techniques can provide valuable information about water dynamics in the frequency region of the electromagnetic spectrum (0.3–20 THz or 10 to 600 cm−1, the so-called “terahertz gap” between the dielectric and the infrared regimes). This has offered a unique view of the hydration water in fully solvated biomolecules.
The hierarchy of time scales for motions of proteins and their hydration environment. (Adopted with permission from ref. [
Two kinds of THz spectroscopy techniques, namely THz transmission and THz time-domain spectroscopy (THz-TDS), have extensively been used to record the THz absorption spectra of biological materials. THz transmission spectroscopy is a simple single or dual beam steady state spectrometer using THz radiation beam to estimate the THz absorption coefficient. THz transmission or absorption spectroscopy of fully solvated biomolecules in water yields direct information on the global dynamical correlations among solvent (water) molecules. However, application of THz spectroscopy to study solvated biomolecules was not possible because of huge absorption of water in the THz frequency range. This problem was solved by the development of the p-Ge laser, which was a strong the THz emitter [44, 45, 46, 47]. Prior to this development, weak radiation power of standard sources like a globar or an arc lamp in the far IR and THz region was the cause for poor signal to noise ratio and the measurements were limited to powders or hydrated films of biomolecules, but not in their native aqueous environment. Free-electron lasers [48, 49] and synchrotrons [50], which are also sources of high power far-IR and THz pulses, have also been reported to be used for spectroscopy studies of biomolecules but are not easily accessible. THz transmission spectroscopy of water in biological systems received a momentum after the discovery of the p-Ge laser. This laser is a powerful table-top THz source (up to about 400 W) and has the tunability in the 80–100 cm−1 (2.4-3.3 THz) frequency region. Development of a table top dual beam (reference and sample arms) THz transmission spectrometer ensured accurate measurements of absorption of water of thickness as large as 100 μm [51].
Accelerators delivering ultrashort pulses of relativistic electrons have been widely used as a source of high intensity THz radiation. Free electron lasers and synchrotrons are actually seeded by short duration electron pulses. An easier method of generating high intensity and tuneable THz radiation using an ultrafast electron accelerator is the coherent transition radiation (CTR). CTR occurs when a charged particle passes through an interface between media with different dielectric constants [52, 53, 54, 55]. Sudden change in the dielectric constants along the electron’s path causes a discontinuity in the electric field at the interface and this discontinuity readjusts itself as radiation spreading out from the point where the electron passes through the discontinuity. The angular spectral energy density of the CTR depends on the dielectric constants of the two media [56, 57]. Since the dielectric constants of aluminum and gold are much more than that of vacuum in far-IR region, these two metals are frequently used as perfect conductors. Direction of propagation and the intensity distribution of the CTR with respect to the angle of incidence of the electron pulse on the target has been discussed in detail in Ref. [53].
At wavelengths shorter than the bunch length, the emitted radiation field is incoherent and total intensity is proportional to the number of electrons (N). But at wavelengths longer than the electron bunch length, the radiation emitted from the bunch is coherent. With a typical number of electrons per bunch on the order of 108–109, the coherent radiation intensity greatly exceeds that of incoherent radiation. Especially, at long wavelengths compared to the bunch length, the radiation intensity is proportional to the square of the number of electrons in the bunch. Therefore, it is possible to generate coherent radiation in the far-IR or THz spectral range from short electron bunches with bunch lengths of hundred micron or less. Moreover, the shorter the bunch length, the broader is the radiation spectrum that can be generated. With larger number of electrons in the bunch, the total intensity (both coherent and incoherent components) of the CTR at frequency ω is given by,
In this equation, contribution of the coherent component, Icoherent(ω), is given by,
Here,
and Ie(ω) is the radiation intensity generated from one electron in the bunch and Eqs. (1) and (2) have been derived assuming that all electrons in the bunch have the same energy.
In THz transmission measurements at AIST, Tsukuba, Japan, a femtosecond linear accelerator system, which delivered electron pulses of about 300 fs duration, and electron energy of 42 MeV and ∼ 100 pC charge (∼108 electrons per one macro-pulse) [58], was used. Electron beam was directed to hit a thin gold foil (thickness is about 500 μm) at an incidence angle of 45°. CTR, which contained the component of THz radiation, was collected in the direction perpendicular to the electron beam using a gold coated parabolic mirror and the intensity of the THz radiation was measured using a Schottky diode detector [54]. Intensity of the THz pulse generated by this method was of high intensity (about 100 nJ/micropulse and covered a wide frequency range (0.3–2.5 THz), which was practically determined by the frequency response of the Schottky diode detector. Band pass filters (Tydex, Russia) were used to select a band of THz frequencies for estimation of absorption of protein solutions. Absorbance of the solutions of different path lengths were measured. Samples were taken in Bruker liquid sample cells, path lengths of which were varied using Teflon spacers of required thicknesses. Fused silica windows having thickness of 1.5 mm were used in the Bruker sample cell. Thicknesses of the Teflon spacers used were in the range of 20 to 150 μm. Absorption coefficient value (in cm−1) of the solution was estimated from the slope of the linear plot of absorbance vs. path length of the cell (Eq. (4)) [59]. Experimental arrangement used here corresponded to that of a single beam absorption spectrometer.
Here, I0 and Id represent the beam intensities in the absence (i.e. using the blank cell) and presence of the sample solution, respectively. αsol represents the absorption coefficient of the sample solution, d is the path length or thickness of the sample.
The absorption coefficient of the sample, α, is defined by,
The real part
Presently, the THz-TDS in the 0.1–10 THz (3.33 cm−1– 333 cm−1) region is the most popular technique, which has been extensively applied in the fields of research in chemistry, materials science, physics, engineering, medicine as well as in industry [60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74]. THz -TDS has also been proved to be a valuable technique for investigation of low frequency dielectric relaxation and vibrational spectroscopy of hydrogen bonded liquids, such as water, alcohols, and others [75, 76, 77]. While various configurations of the THz time-domain spectrometer have been used depending on the kind of applications, we will describe here the general principle of the technique and the spectrometer configuration used for investigation of biomolecules.
The core principle of the THz-TDS technique, which uses a short duration (say a few tens of femtosecond) pulses of THz radiation, is measurement of the transient electric field associated with the THz pulse rather than variation of intensity of the frequency components of the THz pulse. However, since the response or the rise times of the electronic components and detectors are slower than a few ps, it is the normal practice to use the pump-and-probe kind of optical configurations in ultrafast spectrometers in order to overcome the slow response of the detectors. To achieve sub-picosecond time resolution in THz-TDS, the ultrashort NIR optical pulse (typically shorter than 100 fs) is beam-split along two paths to generate pump and probe pulses and to detect the time dependent THz field using a time-delay stage. Schematic diagram presented in Figure 2 represents the principle of a THz- time-domain spectrometer.
(a): Schematic diagram of a typical THz - time-domain spectrometer. (b): Temporal variation of electric field of the THz pulse and its Fourier transform in air and in presence of water.
The pump pulse, which contains the major amount of energy (more than 70% of the total energy of the laser beam), is used for generating broadband pulses of THz radiation using a photoconductive antenna consisting of a low temperature grown GaAs or InGaAs film covered with metallic contacts for application of bias voltage, or by optical rectification in ZnTe(110) crystal. The pulsed beam of THz radiation is collimated and focused onto the sample using gold coated parabolic mirrors. After transmission through the sample, the THz beam is recollimated and refocused on another photoconductive antenna or ZnTe(110) crystal, which works as the THz detector. Recently, ZnTe (110) crystal are being used extensively both as THz emitter as well as in detection because of possibility of its application in much wider THz frequency region as compared to that has been possible using photoconductive antenna.
The probe beam is used to gate the detector and measure the instantaneous THz electric field using the method of electro-optic sampling. A high precision linear motion stage is used to delay the probe pulses to arrive at detector crystal with respect to the pump pulses. The THz pulse and the gate (NIR) pulse are propagated collinearly through the ZnTe crystal. The THz pulse induces a birefringence in ZnTe crystal, which is read out by a linearly polarized gate pulse. When both the gate pulse and the THz pulse are present in the crystal at the same time, the polarization of the gate pulse will be rotated by the THz pulse depending on the strength of the electric field of the THz pulse. Using a λ/4 waveplate and a beam splitting polarizer together with a set of balanced photodiodes, the THz pulse amplitude is mapped by monitoring the gate pulse polarization rotation after the ZnTe crystal at various delay times with respect to the THz pulse (Figure 2(a)). A Fourier transform is then used to convert this time domain electrical signal to a frequency domain spectrum (Figure 2(b)). The optical path from THz generation to THz detection is purged with dry nitrogen gas to avoid the effect of the humidity.
Dielectric relaxation measurement is a sound method to investigate intermolecular interactions and is capable of monitoring cooperative processes at the molecular level [78, 79, 80]. This method is appropriate to monitor molecular motions in widely varied time scales and has been used extensively to study the structure, dynamics, and macroscopic behavior of complex systems [81]. A brief discussion (more details may be found elsewhere [81]) on the basic principle of dielectric polarization is presented below.
(a) Polarization of dielectric. (b) Polarization vector.
If a static electric field of strength,
where ε0 is the dielectric permittivity of the vacuum. Applying the macroscopic Maxwell theory, the electric displacement (electric induction) vector,
Now, in the linear regime, the relative dielectric permittivity (or
There are different types of polarization mechanisms by an applied electric field in different frequency regions: i)
Therefore,
For
The orientation polarization is given by the dipole density due to the dipoles
where
where
where
where
Eq. (17) gives equivalent information on dielectric relaxation properties of the sample both in frequency domain and time domain measurements. Therefore, the dielectric response might be measured experimentally as a function of either frequency or time, providing data in the form of a dielectric spectrum ε*(ω) or the macroscopic relaxation function
Where, τm indicates the relaxation time. Eqs. (17) and (19) give rise to the following relation,
i.e,
This is known as the Debye model for frequency dependent dielectric permittivity. According to the Debye model, the complex frequency dependent dielectric response [
where,
The dynamics of water around small as well as complex molecules changes owing to their specific interaction with the solute surface; the specific nature of the interaction could mostly be electrostatic or hydrogen bonding. Such interaction expectedly ruptures/modifies the tetrahedral water network structure as well as its dynamics, a clear imprint of that gets reflected in the THz frequency window. Measurement of optical parameters α(ν) and n(ν) enables one to determine the change in water dynamics at the vicinity of (bio)surface and consequently one can infer on the changes of the corresponding solute also.
Metal ions are perhaps the simplest solutes that can induce perturbation in water dynamics, the interaction being mostly electrostatic in nature. A systematic investigation using alkali monovalent cations [85] and alkaline earth bivalent cations [86] in aqueous solutions have been put forward by the group of Martina Havenith using far-IR and THz FTIR measurements coupled with classical MD simulation studies. Their study concluded that ion rattling motions can account for the observed changes in the THz absorption. They have shown that the spectrum of the salt solutions can be approximated by a linear superposition of concentration weighted neat water and ion contributions. Ab initio MD simulation study by Marx et al. [87] has successfully reproduced the spectral responses of the solvation shell around the ions in infrared and THz frequency range. Their study has shown that the solute-solvent dipolar couplings and the dipole–dipole correlations are the important factors that govern the absorption features in this frequency regions. The group of Martina Havenith has subsequently put forward a series of studies on the hydration dynamics of heavy metal ions, e.g. lithium [88], manganese [89], iron [90] and ytterbium [91]. An elaborate description of the process involved has recently been put forward by this group [92]. The overall THz effect of the ions could be apprehended in terms of the contributions from various modes as depicted in Figure 4.
Schematic representation of ion hydration. (a): Bulk-like water (blue), water around ions (yellow and green), and hydration water (lighter shades of yellow and green). The total absorption of the solution (αsol) has contribution from all. (b): Concentration-weighted bulk-water values are subtracted from αsol. (c): This yields the effective absorption of the solvated ion or ion pair (αeffion).
In a systematic study using THz-TDS in the frequency region (0.3–2.1 THz; 10–70 cm−1), experimental evidences for the ultrafast collective hydrogen bond dynamics of water in the extended hydration layers of alkali metal chlorides have been obtained [93]. The real and imaginary part of the permittivity (ε), as obtained from the THz-TDS measurements was fitted using a triple Debye relaxation model. The time scales obtained for bulk water are of the order of ∼8–9 ps (τ1), 200 fs (τ2) and 80 fs (τ3). The ∼9 ps and ∼ 200 fs timescales are due to the well-known cooperative rearrangement of the H-bonded network structure and the small angular rotational modes of individual polar water molecules, respectively. It has been reported that (τ1) decreases with increasing salt concentration, which identifies an acceleration of the cooperative hydrogen bond dynamics affirming a positive support towards the most debated notion of these ions to act as water structure breakers (see Figure 5(a)). The extent of this effect has been found to be mostly ion specific, K+ being the most effective ion and a simple consideration of ionic charge density is insufficient to account for the observed changes. Very recently, Havenith and Marx [94] have put forward a combined experimental and simulation investigation to provide a detailed mechanistic analyses based on cross-correlation analysis (CCA) technique to understand the minute details of water-solute interactions.
(a) Cooperative relaxation dynamics (τ1) and relaxation strength (S1) of aqueous solutions of different alkaline metal cations. (b) Relaxation dynamics (as defined by the timescales τ1 and τ2 of aqueous urea solution as a function of urea concentration. A sharp change in the τ1 is observed at ∼4 M urea. (c) Cooperative hydrogen bond relaxation time constant (τ2) of aqueous solutions of amino acids as a function of their concentration. The dotted line is the time constant for the buffer solution. The inset shows the change in τ2 (measured at maximum amino acid concentration) as a function of the SASA of amino acid. (d) Relaxation time scale τ3 corresponding to the jump orientation of water (obtained by Debye fitting of THz data) of different amino acids solutions. The dotted line is the time constant for that of the buffer. The inset shows the change in the timescale (Δτ3 = τsolution-τbuffer) at the maximum concentration of the amino acids.
While the interaction of metal ions with water is more straight-forward, complexity arises when an ion is associated with a hydrophobic moiety. Such molecules are often of biological importance and therefore their interaction with water is essential to establish. There have been several reports on the THz studies of sucrose and saccharides [95, 96, 97, 98, 99]. In a pioneering work Heyden et al. [100] have described the nature of hydration around small carbohydrate molecules and a detailed simulation study has revealed that the extent of the hydration shell and their absorption co-efficient change with the solute specificity. One such molecule is urea, which is well known to be a protein denaturant, however, the exact molecular mechanism of the processes involved still remains a strongly debatable issue, specially the argument of whether the interaction is water mediated (the water structure breakers notion of urea) or a direct interaction of urea with protein surface.
An elaborate attempt has been made to understand the effect of urea (and its derivatives) on the ultrafast solvation dynamics of water using a Debye type dielectric relaxation model in the 0.3–2.0 THz frequency region using THz-TDS technique [101]. The relaxation dynamics shows considerable acceleration beyond a threshold concentration. Such acceleration is possibly associated with a disruption of the tetrahedral water network structure. It seems also intriguing that the observed collapse occurs at a certain urea concentration (see Figure 5(b)), which strikingly coincides with the denaturation concentration of urea for many proteins. Another molecule of such biological interest is guanidinium chloride (GdmCl), which offers remarkable protein denaturation ability beyond a certain threshold concentration (∼2–3 M) [102, 103]. Like in the case of urea, protein denaturation mechanism of GdmCl has also been debatable concerning a direct or indirect interaction. We have investigated the collective hydrogen bond dynamics around GdmCl in aqueous solutions as well as in the presence of a model globular protein human serum albumin (HSA) using the THz-TDS technique. It is found that the relaxation dynamics gets faster which renders support to the previously speculated notion that GdmCl acts as a water structure breaker. A similar but more prominent trend is observed in case of NaCl, which, however, does not interact with proteins.
The change in hydration dynamics in presence of HSA has been found to be in complete contrast in these two salts unambiguously pointing out towards a possibility of the collective hydration dynamics to share a pivotal contribution in the protein unfolding phenomenon. These studies seem to conjecture that ions with complex hydrophobic moiety acts as water structure breaker, and this very nature of such molecules makes them protein denaturant. To investigate the validity of such conjecture we investigated the ultrafast (sub-ps to ps) collective hydrogen bond dynamics of water in the extended hydration layers in a series of alkylammonium chloride salts using THz -TDS technique [104]. We found these salts to transform from being a water ‘structure breaker’ to ‘structure maker’ with increasing carbon content. For example, the THz-TDS measurements reveal that ammonium chloride (AC) acts as a water network structure breaker while tri-ethyl ammonium chloride (EAC) and higher carbon containing salts are distinct water structure makers. The change in protein hydration is also found to trace its secondary structure rupture and the exposure of hydrophobic moieties accordingly changes the protein hydration. Our study strongly concludes that it is the hydrophobic effect, at least in the case of this type of salts, that plays the decisive role in determining their interaction with biomolecules.
Amino acids, which are the building blocks of proteins, often act as intermediates in metabolism as well as osmolytes that can stabilize proteins. Depending upon the ‘side group’, the amino acids are classified as hydrophilic or hydrophobic. Hydrophobicity of amino acids is believed to be a key parameter that regulates phenomena like protein folding - unfolding, aggregation, activity, protein-ligand binding and protein hydration in aqueous environments. While to analyze the solvation of hydrophobic and hydrophilic parts of a protein separately, one needs to take into consideration that the environment of amino acid residues is heterogeneous in nature as they are often composed of hydrophobic alkyl chains and hydrophilic groups. It is therefore essential to study the hydration of amino acids of various side chains in the exposure to solvents. Niehues et al. [105] have studied the hydration of a series of amino acids in ∼2.4 THz window and observed that the THz absorption coefficient, α(νTHz), of hydrated amino acids can be correlated with the hydrophobicity and the fraction of polar volume of amino acids. They have shown that glycine has the largest positive THz slope followed by serine, whereas for the other amino acids, the slope becomes gradually negative with increasing hydrophobicity. In another study [106], the same group, by analyzing the corresponding THz spectrum in terms of the correlated dynamics of solute and solvent molecules, demonstrates the line shape of the low-frequency vibrational response of glycine in water. Recently, they [107] have shown that hydrophilic solvation of the zwitterionic groups in valine and glycine leads to similar THz responses, which are fully decoupled from the side chain. This result concludes that the hydrophilic groups and their solvation shells dominate the THz absorption difference, while on the same intensity scale, the influence of hydrophobic water can be neglected. Shiraga et al. [108] concludes a correlation between the extent of H-bonding and the hydrophobicity of the solute. Glycine (Gly) and the L- isomers of five different amino acids: serine (Ser), aspartic acid (Asp), lysine (Lys), arginine (Arg) and tryptophan (Trp) of varying hydrophobicity and solvent accessible surface area (SASA) have been used by Samanta et al. [109] to study the dielectric relaxation up to their maximum water solubility in the frequency window of GHz-THz at neutral pH. The various rotational dynamics of the solutes and water are obtained by fitting the dielectric data in a multiple Debye relaxation model. From GHz study, we observed that the molecular rotation of amino acids correlates their respective molecular volume. Also, it was concluded that the amino acids do not usually aggregate even at high concentrations. From THz study, the authors found that Gly is a water structure breaker while the other amino acids are structure makers. Consequently, Gly accelerates cooperative hydration, while the others retard (see Figure 5(c) and (d)). It has been established that hydration in amino acids depends both on its hydrophobic as well as its hydrophilic nature of side chains. Born et al. [110] have studied the hydration dynamics of some small model peptides using THz spectroscopy. They observed that the cooperative hydration dynamics changes as the extent of hydration of such molecules change.
Addition of otherwise indifferent organic solvents can influence marked changes in aqueous environments as well as they can induce misfunction in biologically important molecules e.g. protein, DNA, etc. Water - dimethyl sulfoxide (DMSO) binary mixture has been found to be of potential interest as it plays a significant role in the field of chemistry, physics, biology and pharmacology. Das Mahanta et al. have investigated the change in the collective hydration dynamics in presence of DMSO at different concentrations using THz-TDS. We found that α(ν) of the mixed solvents shows a non-linear change with XDMSO [111]. This change has been correlated with the water-DMSO structural heterogeneity in the mixed solvents. Luong et al. have also studied the evolution of water hydrogen bonded collective network dynamics in water −1,4-dioxane (Dx) mixtures as the mole fraction of water (Xw) increases from 0.005 to 0.54 [112]. The inter- and intra-molecular vibrations of water be observed using THz-TDS in the frequency range 0.4–1.4 THz (13–47 cm−1) and Fourier transform infrared (FTIR) spectroscopy in the far-infrared (30–650 cm−1) regions. From the absorption coefficient measurements, they infer that the mixtures are not ideal in nature, which suggests a significant change in the network by the addition of the solute. The authors found an increase in the collective hydrogen bond network as evidenced from dielectric relaxation studies in which τ1 has been found to be small at low Xw (where Xw is the mole fraction of water in the mixture), but at Xw > 0.1, it increases rapidly to reach a value identical to that in bulk water. It has been concluded that hetero-molecular (water - Dx) hydrogen bond dominates in the water diluted region in water-Dx mixtures, and with progressive addition of water, bulk-like intermolecular three-dimensional hydrogen bonded water network dynamics evolves beyond Xw = 0.1. In a separate study [113], a combined experimental (mid- and far-infrared FTIR spectroscopy, THz-TDS (0.3–1.6 THz)) and molecular dynamics (MD) simulation technique has been carried out to understand the evolution of the structure and dynamics of water in its binary mixture with 1,2-dimethoxy ethane (DME) over the entire concentration range. Debye relaxation data reveals a non-monotonous behavior in which the collective dynamics is much faster in the low Xw region, whereas in the Xw ∼ 0.8 region, the dynamics gets slower than that of pure water. The concentration dependence of the reorientation times of water, estimated from the MD simulations, also captures this non-monotonous character. Bohm et al. [114] have demonstrated that the THz response of alcohols can be decomposed into the spectrum of bulk water, tetrahedral hydration water, and more disordered (or interstitial) hydration water. They also concluded that it is not the tetrahedrally ordered component, rather it is the interstitial hydration water which is responsible for the temperature-dependent change in ΔCp and ΔG in such mixtures.
The surface of proteins is extremely heterogeneous owing to the presence of amino acids of varying types of charges. The pioneering studies by the group of Havenith et al. have shown that protein molecules are hydrated and the cooperative dynamics of water changes accordingly. An earlier study using a small protein ubiquitin [115] shows how the measurement of α(νTHz) reveals a change in the protein hydration dynamics as the authors termed it as the “THz dance”. In a subsequent ever important simulation paper, the same group has established different THz absorption of the hydrophobic and hydrophilic residues of a protein as they interact differently with water [116]. In the later years, this group has put forward substantial contribution on the hydration dynamics of proteins using THz measurements [117, 118] as well as simulation studies [42, 119]. Their studies have unambiguously suggested that fast protein motion and solvent dynamics are correlated with enzymatic reactions [120]. In a recent study this group has established the pivotal role of collective motion of water during an electron transfer reaction between flavoenzyme ferredoxin - NADP+ − reductase and ferredoxin-1 [121]. In a seminal paper, Marklez et al. [122] have used THz-TDS measurements to show that the protein (hen egg white lysozyme) dynamical transition (the rapid increase in protein dynamics occurring at ∼200 K) needs neither tertiary nor secondary structure. Their results revealed that the temperature dependency essentially arises from the protein side-chain interaction with the solvent. He et al. [123] have investigated the presence of structural collective motions on a picosecond timescale for the heme protein, cytochrome C, as a function of oxidation and hydration, using THz-TDS and molecular dynamics simulations. Marklez group has developed a novel measurement technique (anisotropy THz microscopy) [124] wherein they were able to detect the long range protein vibration modes in chicken egg white lysozyme single crystals. They found the underdamped modes to exist for frequencies >10 cm−1. Such underdamped vibrational modes have also been identified using optical Kerr effect measurements in the THz frequency window [125]. In a recent study, Niessen et al. [126] have used anisotropy THz microscopy, which is found to be sensitive to inhibitor binding and unique vibrational spectra for several proteins and an RNA G-quadruplex. There have been other reports from several experimental groups: Sun et al. [127] have reported the application of a new machine learning methods for quantitative characterization of bovine serum albumin (BSA) deposited thin-films detected by THz-TDS. The group of Emma Pickwell-MacPherson [128] have used THz spectroscopy to study the hydration shell formation around H9 subtype influenza A virus’s HA protein (H9 HA). They have also detected antigen binding of H9 HA with the broadly neutralizing monoclonal antibody. They observed a remarkable concentration dependent nonlinear response of the H9 HA, which reveals the formation process of the hydration shell around H9 HA molecules. The same group has also reported the dielectric properties of two different antibodies in water-glycerol mixtures using THz-TDS measurements [129]. Sun et al. [130] used THZ-TDS to investigate the molecular processes involved above and below the transition temperature (TD) for GP2 peptide.
While much research has been focused on proteins, relatively less attention has been paid on the other biologically important molecule, DNA. There had been a few preliminary studies to understand the vibronic bands in the THz frequency region using single and double stranded DNAs and RNAs [131, 132, 133]. Arora et al. [134] have presented a label free quantitative detection method for DNA samples amplified by polymerase chain reaction (PCR) in aqueous medium using THz-TDS in the frequency range from 0.3 to 1.2 THz. Tang et al. [135] have recently investigated the feasibility of THz spectroscopy combined with microstructures for marker-free detection of DNA and oligonucleotides. Polley et al. have investigated the collective dynamics of two DNA molecules extracted from salmon sperm and calf thymus and observed that the dynamics did not differ much at the concentration range of the experiments [136].
There have been only limited studies on the THz studies on lipid membranes and/or vesicles. One of the preliminary results was due to Tielrooij et al. [137] who had studied the dielectric relaxation in mixed system of hydrated DOPC lipid bilayers in the THz frequency domain. They could identify three distinct water types: fast, bulk and irrotational. The relative content of those change with the extent of hydration. Later, Yamamoto et al. [138] have studied the temperature and hydration dependent low frequency spectra of lipid bilayers of 1,2-dimyristoyl-sn-glycero-3-phosphoryl-3′- rac-glycerol (DMPG) and 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) using THz-TDS. They found that the THz absorption patterns reflect the lipid packing pattern in the bilayers. They subsequently extended their investigations towards purple membrane (PM, a complex of lipids and a membrane protein, bacteriorhodopsin) [139] and lipid bilayer of DMPC [140]. Pal et al. have recently studied the microstructure and collective dynamics of the membrane interfacial hydration shell in zwitterionic and negatively charged phospholipid membrane bilayers using THz-TDS [141]. They observed a dependence of the critical lipid concentration corresponding to the inflection point on the charge of the lipid head-group, thereby implicating membrane electrostatics as a major factor in the microstructure and dynamics of water at the membrane interface.
Hydration dynamics of biomolecules is significantly influenced upon changing its physical conditions as well as in the presence of additional chemical agents, like alcohols, glycols, etc. Protein molecules undergo various physical and chemical changes, which could induce conformational modifications in their secondary as well as tertiary structures. It can be noted here that as protein structures get disrupted (during unfolding or denaturation) the hydrophobic moieties (amino acid residues), which are otherwise buried inside in the native structure, get exposed, and this produces a definite alteration in THz absorption coefficient, α(νTHz). It therefore suggests that estimation of α(νTHz) provides a direct evidence of the structural perturbation in proteins.
Several experimental techniques are available to determine the structural evolution of proteins during unfolding, while THz provides with the estimation of the associated hydration changes. In a pioneering experimental work, in which a stopped-flow techniques was synchronized with THz-TDS, which the authors termed as Kinetic terahertz absorption (KITA) spectroscopy, Kim et al. [142] have shown that the pH induced unfolding-refolding kinetics (in real time) of Ub* could easily be traced by the associated α(νTHz) measurements. The THz results very well reconcile with the results obtained from circular dichroism (CD) and fluorescence measurements.
Another important physical environment that induces protein unfolding is temperature. In a study using HSA as a model protein, Mitra and Havenith [143] have shown that water dynamics associated with the protein during its reversible unfolding pathway up to 55°C as well as its irreversible denaturation pathway up to 70°C traces the protein’s structural rupture pathway. The THz measurements do support the conventional CD and fluorescence measurements. Sudden increase in the environment (like temperature or pressure) for a very short period of time (often termed as T-jump experiments) leads protein molecules to be structurally ruptured but upon removal of the intense pulse, the protein refolds. T-jump experiments have previously been characterized using conventional CD and fluorescence measurements. However, THz measurements was demanded to obtain explicit information of water dynamics. The first report of such experiment was from the group of Havenith [144], wherein the authors put forward a coupled KITA setup with a T-jump attachment. The authors monitored changes in the THz absorption λ∗6 − 85protein with a time resolution of >50 μs. They reported that the spectral changes are correlated with the hydrophobic collapse of the protein. In a subsequent study from the same group, Wirtz et al. [145] used an even better time resolution of about 500 ns to reveal the coupled ubiquitin−solvent dynamics in the initial phase of hydrophobic collapse (temperature induced unfolding). They propose that, in the case of ubiquitin, a rapid (∼500 ns) initial phase of the hydrophobic collapse from the elongated protein to a molten globule structure precedes secondary structure formation. Recently there have been a few reports of using THz spectroscopy technique to underline thermal denaturation of BSA [146], temperature- and pH-dependent protein conformational changes in pepsin A [147]. In a very recent study Cao et al. [148] have successfully employed THz-TDS to track the hydrolysis of BSA protein by pepsin. The results indicate that protein hydrolysis can be easily monitored over time by focusing on the variation of the absorption coefficient from a macroscopic perspective. The authors explored the use of the Debye model to analyze the dielectric properties of the solution during protein hydrolysis. The results of the Debye analysis prove that it is possible to investigate in detail the microscopic dynamics of bio-macromolecule solutions at the molecular level by THz-TDS.
Samanta et al. have been involved in determining the changes in protein hydration in various distressed environments using the THz-TDS measurements. They have investigated the hydration dynamics around HSA in presence of short chain polyethylene glycols of different chain lengths (PEG 200, PEG 400, and PEG 10000) at different concentrations [149]. FIR-FTIR studies conclude that the protein hydration is affected in a distinct way below and above the critical PEG concentration of 30% (v/v). THz-TDS study unambiguously confirmed a retardation of the solvation dynamics by PEGs. This study clearly shows an independent behavior of protein hydration at low PEG concentrations and a noticeable interaction between protein and PEG hydration beyond a critical PEG concentration. In another study, Das et al. have made an attempt to understand whether the DMSO induced conformation changes in lysozyme conformation perturbs its hydration dynamics [150]. CD study establishes a marked change in the protein tertiary structure in presence of DMSO. The relative change in the THz absorption coefficient (Δα/α0) shows a negative minimum at XDMSO = 0.05 and a positive value at XDMSO = 0.15. The observed minimum is found to be due to the increased size of the protein while the positive value is attributed to the increased SASA and consequent increased hydration of the protein surface. In a recent report, Das et al. put forward an experimental observation of nonmonotonic changes in the collective hydration of BSA in the presence of alcohols of varying carbon-chain lengths, that is, ethanol, 2-propanol, and tert-butyl alcohol (TBA), by using THz – TDS [151]. They observe an anomalous hydration behavior of the protein hydration with the alcohol concentration, which correlates the alcohol-induced α-helix to random coil transition of the protein secondary structure, as revealed by CD spectroscopy measurements. Recently, Das Mahanta have investigated the effect of alkyl-ammonium chloride salts on BSA and found a systematic trend towards disrupting the protein secondary structure [104]. The associated changes in the protein hydration in the presence of these salts have also been investigated using THz-TDS. The change in protein hydration is also found to trace its secondary structure rupture, and the exposure of hydrophobic moieties accordingly change the protein hydration. The THz-TDS measurements strongly conclude that it is the hydrophobic effect, at least in the case of this type of salts, that plays the decisive role in determining their interaction with biomolecules.
Aggregated protein is toxic to functioning of living systems and many of human diseases are associated with misfolded protein disorders [152, 153, 154, 155, 156]. This is why understanding of mechanisms of interactions between protein molecules in solutions have been the subject of extensive investigations during the last two decades [157, 158, 159, 160, 161]. Additionally, understanding the protein aggregation propensity may offer novel design principles for producing aggregation-resistant proteins for biotherapeutics.
Globular proteins, e.g. HSA and BSA, in their native states are present in living cells at concentrations as high as about 200 mg mL−1 and bimolecular interactions are significant. We explained earlier that stability of the three - dimensional structure of a monomeric protein molecule in physiological environments is the result of an intricate interplay between electrostatic, hydrophobic, hydrogen bonding and other interactions and any variation of temperature, pH of the medium or any other physiochemical conditions including concentration of protein in the cell may result in imbalance of the stabilization forces leading to misfolding [162, 163], thus triggering aggregation [164, 165, 166, 167, 168].
A native and structurally stable protein molecule is strongly hydrated with a well-defined hydration layer of thickness of about a few tens of Å (20–40 Å) around it [50, 59, 169]. The role of water molecules in the hydration shell could be crucial for the intermolecular interactions and the overall protein hydrophobicity, which may be defined by its hydration free energy, which may play an important role in protein aggregation in aqueous solution [162, 163, 166]. However, the role of hydration water in protein aggregation has largely been unexplored owing to the perception that protein – protein interaction is the major factor and the surrounding water is just a spectator playing no role in aggregation of protein, ignoring water as an active constituent of biological systems. In fact, whether a protein remains soluble or forms aggregation should intrinsically rely on its state of hydration in the monomeric state.
We have described in the earlier sections of this article that how the properties of water molecules in the hydration layer on an average are different from those in the bulk, which determines the stability of a monomer protein in aqueous environment. Protein aggregation proceeds through a multistep process initiated by conformational transitions, called protein misfolding, of monomer species towards aggregation-prone structures. Chong and Ham applied the fluctuating thermodynamic analysis method to understand the variations of the thermodynamic functions, which occur during the course of misfolding and dimerization of the Amylase-β protein. They suggest that the time variation of the solvent-averaged effective energy, F = Eu + Gsolv, describes the protein dynamics on the free energy landscape [170]. Here, the protein potential energy (Eu), comprises both intra and intermonomer contributions and the solvation free energy (Gsolv), represents the interaction of the protein with surrounding water, which plays a critical role in protein aggregation. The free energy, F, decreases as the dimerization proceeds, but the decrease in F has different origins in the approach and structural adjustment regimes. The thermodynamic force driving the approach of two monomers is the decrease in Gsolv and hence, the misfolded monomers acquire a large hydrophobicity, which leads to conformational changes in monomers. This drives two monomers to approach each other to a contact distance. In absence of this thermodynamic driving forces, two negatively charged protein monomers (the total charge of Amylase-β and BSA monomer proteins at neutral pH are −3, and − 16, respectively [170, 171]) would never approach each other by overcoming the electrostatic repulsion. On the other hand, decrease of the protein potential energy Eu, due to direct protein–protein interactions, such as intermonomer van der Waals contacts and hydrogen bonds, drives the structural rearrangement required for formation of compact dimer structure leading to energetic stabilization. Interestingly, structural rearrangements are also associated with an increase in the solvation free energy, which originates from the dehydration of the protein surface and of the interfacial region. On contrast to other spectroscopic techniques, THz spectroscopy probes directly the collective intermolecular vibrations of the hydrogen bond network, and is thus able to detect sensitively solute induced changes in the solvation dynamics. Extensive works on THz absorption of protein solutions have demonstrated that the absorption coefficient of the protein solutions (αsol) are dependent on the concentration of protein [50, 59, 169, 170, 171]. For example, at the low concentration regime (e.g. in the case of HSA, <0.5 x 10−3 mol dm−3) αsol value increases linearly and this has been explained by increasing concentration of hydrated monomer protein molecules since water in the hydration shell has larger αsol value as compared to that of bulk water. However, on further increase of the protein concentration, αsol value starts decreasing.
To delineate this issue in more detail, Manna et al. made a detailed investigation on the concentration dependence of THz absorption of the aqueous buffered solutions of HSA protein (up to 2.6 mM of protein concentration) at three THz frequencies, namely, 0.1, 1.5 and 2 THz [59]. Similar results were obtained from these three measurements. αsol value was expected to change linearly to follow Eqs. (23) and (24), which could be derived assuming that the protein solution is a two-component system.
Here, αpr is the absorption coefficient of the protein, αbw is the absorption coefficient of bulk water,
Therefore, the plots of
(a): Plots of
To understand the reasons for significant decrease of THz absorption coefficient of the protein solutions with increasing concentration beyond 6 x 10−4 mol dm−3, the possibility of aggregation of proteins at higher concentration regime was explored. To delineate this aspect, dynamic light scattering (DLS) measurements (Figure 6) were carried out using concentrations of proteins covering the entire range of THz absorption measurements. The DLS data recorded for the solution containing protein concentration of 0.4 x 10−3 mol dm−3 revealed the existence of only monomeric protein molecules with the most probable diameter of about 6–8 nm in the solution. This is quite in good agreement with the diameter of the hydrated monomer protein molecules. However, at higher concentrations (say, >1 x10−3 mol dm−3 of protein), the DLS data revealed two important features. Firstly, the size distribution of the monomer band became wider indicating the presence of particles of diameter in the range 12–15 nm, possibly suggesting formation of dimers or trimers of HSA, in addition to the monomeric species. Secondly, at higher concentrations of the protein, DLS data also revealed the presence of large size aggregates of the most probable diameter of about 700 nm. However, a quantitative estimation of the relative percentages of monomer, dimer and aggregates was not possible from the DLS data because the intensity distribution of the scattered radiation was not directly proportional to the number of the particles. However, this experiment confirmed the presence of protein aggregates in solutions with higher concentrations of protein and the formation of aggregates may possibly be held responsible for nonlinear dependence of THz.
On the other hand, CD measurements confirmed that the tertiary structure of HSA remained unchanged through the entire range of HSA concentrations used for THz measurements. This suggested that the native structure of HSA molecules remained unaltered through the entire range of concentrations of HSA. Therefore, hydration states of proteins, even in the aggregated state, remain unchanged and hence possibly justifies the assumption made in the earlier works regarding overlapping of hydration shells at higher concentrations of proteins.
Patro and Przybycien have simulated the structures of reversible protein aggregates as a function of protein surface characteristics, protein–protein interaction energies and assessed the aggregate properties [174]. Results of their simulation reveals that aggregate particles have the kind of organization of the hydrophobic and hydrophilic domains as they are present in HSA protein monomer molecules and aggregation of protein molecules causes the loss in the total solvent accessible surface area (SAS) is about 67% and the mean solvent content for these aggregates vary in the range of 0.37–0.55 volume fraction depending on the conformation of the monomer protein [175]. Therefore, at higher concentrations of protein, volume fraction of hydration water decreases due to formation of aggregates. In addition, proteins are THz transparent and as we increase the protein concentration, protein aggregates replace the water molecules and leads to lowering of total THz absorbance of the solution.
A method of analysis was adopted to analytically fit the data in the regime of higher concentrations of the protein to predict the relative concentrations of the monomer and aggregated particles. In this analysis, the value of αhl, which was estimated from the linear regime of the plot of
Here, x is the concentration of monomer in the unit of 1 × 10−3 mol dm−3 and
Manna et al. estimated the percentage of the number of HSA molecules, which exist as monomer (or dimer or trimer) in solution without being associated with aggregate formation, for each of the HSA concentrations used for THz absorption measurements [59]. We find that for the protein solution with its concentration of 8 x 10−4 mol dm−3, about 40% of the protein molecules exists as monomer (or dimer or trimer) in solution and 60% protein molecules are part of aggregates. The monomer (or dimer or trimer) concentration becomes <1% at the protein concentration of 2.6 x 10−3 mol dm−3, i.e. nearly all the protein molecules are associated with aggregate formation. These calculations suggest that formation of aggregates at higher concentrations of protein may be the responsible factor for the turnover of the THZ absorbance of the protein solution at ∼6 x 10−4 mol dm−3 concentration.
The absorption coefficient of a complex system is the weighted sum of the absorption of its components. However, determination of the complex dielectric function of proteins in solution using THZ-TDS spectroscopy allowed detailed analysis beyond what was possible from simple absorption measurements. Following this approach, Novelli et al. determined both the phase and amplitude of the induced dipole in the volume containing the protein and hydration water [170]. This result revealed that not only the amplitude of the induced dipole varied with the concentration of protein, but also its phase changed above a concentration threshold (Figure 7). They proposed a phenomenological model, which explained that the phase of the induced dipole in the protein-solvent interaction region began to vary when there was significant overlap between hydration layers of the neighboring protein. This result suggested that indirect electromagnetic protein–protein interactions could take place if mediated by the extended hydration layers surrounding each protein.
(a) Cartoon of a human lysozyme protein (red sphere) in water. Water molecules tightly-bound to the protein surface (white), extended hydration layers (blue) and unperturbed bulk water (light blue). (b) Sketch of the evolution of the modulus and the phase of the induced dipole in a unit volume of solution versus protein concentration. The effect of phase gain at larger concentrations is represented by darker colors on the bottom right panel (adopted with permission from Ref. [
THz spectroscopy, from its very inception, has mostly been used by scientists studying cosmology, condensed matter physics and materials. The huge absorption of water in this frequency range used to be treated as a drawback of this technique; however, for chemists and biologists this point serves as an advantage since all the biological function is somehow or other related to water dynamics. Due to its inherent sensitivity to water hydrogen bonding dynamics, THz spectroscopy has become an indispensable tool for direct observation of fast and coupled biomolecule-water network. The initial studies by the groups of E. W. Heilweil, P.U. Jepsen, A. Marklez, C. Schmuttenmaer and M. Havenith in the late 1990s and early 2000s have established THz spectroscopy at a concrete platform to be recognized as a potential tool to label free detection of water dynamics in the vicinity of biomolecules, the effect being extended to several layers and remains practically undetected using conventional spectroscopic methods. The last decade has witnessed a huge leap towards exploiting this frequency window in biophysical studies, a few of such results have been depicted in this article. Now that the phenomenon has been established beyond any doubt, new sort of experimental studies, where the role of hydration in ultrafast processes (like electron transfer or proton transfer) could explicitly be determined, is the new challenge to the researchers.
IntechOpen - where academia and industry create content with global impact
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\n\nDr Alex Lazinica
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Various environmental attributes in these seven KPIs in the workplace affect not only health but also performance and engagement of employees via their physical, mental, and social interactions within the environment. For instance, ergonomics, acoustics, lighting, thermal comfort, and olfactory comfort address the overall physical comfort while biophilic components contribute to employee cognitive functions as well as their capacity to cope with mental stress and fatigue. These seven KPIs of workplace health ultimately contribute to five positive organizational outcomes, including healthy organizational culture, higher productivity, improved individual health and safety, financial savings, and enhanced reputation of the organization. This chapter discusses critical health factors in the workplace and their contributions to the capacity of human capital at the individual as well as organizational levels.",book:{id:"8529",slug:"indoor-environment-and-health",title:"Indoor Environment and Health",fullTitle:"Indoor Environment and Health"},signatures:"Young Lee",authors:null},{id:"67890",title:"Air Quality and Airflow Characteristic Studies for Passenger Aircraft Cabins",slug:"air-quality-and-airflow-characteristic-studies-for-passenger-aircraft-cabins",totalDownloads:1217,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"This chapter summarizes the work done at the Airliner Cabin Environment Research Lab (ACERL) related to air quality, airflow characteristics, and human thermal comfort inside aircraft cabins. The laboratory is part of the Institute for Environmental Research (IER) at Kansas State University. It has a Boing 767 mockup cabin, bleed air simulator, and a Boeing 737 actual aircraft section that were all utilized to conduct experimental studies to understand air quality inside aircraft cabins. The studies summarized in this chapter include particle image velocimetry (PIV) investigations, particle dispersion, computational fluid dynamics (CFD) simulations, tracer gas and smoke visualization studies, and bleed air investigations. The chapter also summarizes other related studies including virus dispersion, air quality monitoring devices, and related developed air quality standards. The scope of this chapter is to summarize the setup and results of each of the above categories. This summary along with the cited references provides results for full size aircraft cabin environments, helps validate data for CFD simulations, and provides comparison data for other similar studies. This helps improve the design of future aircraft cabins and their ventilation systems and recommends changes to maintenance practices done that can improve the health and safety of humans inside these enclosed compartments.",book:{id:"8529",slug:"indoor-environment-and-health",title:"Indoor Environment and Health",fullTitle:"Indoor Environment and Health"},signatures:"Maher Shehadi",authors:null},{id:"67373",title:"Noise Calculation Charts and Indoor Environmental Quality for Evaluating Industrial Indoor Environment and Health",slug:"noise-calculation-charts-and-indoor-environmental-quality-for-evaluating-industrial-indoor-environme",totalDownloads:1157,totalCrossrefCites:1,totalDimensionsCites:2,abstract:"Noise, defined as “a sensation of unwanted intensity of a wave,” is perception of a pollutant and a type of environmental stressor. An environmental stressor such as noise may have detrimental effects on various aspects of health. The unwanted intensity of a wave is a propagation of noise due to transmission of waves (viz. physical agents) such as sun, light, sound, heat, electricity, fluid, and fire. The effects of these physical agents on human health as noise-intruding elements in an industrial indoor environment are discussed. Noise characterization is discussed from indoor air quality and health perspective. The noise calculation charts are detailed for interference of noise waves based on a benchmark solution. These charts calculate positive and negative magnitudes of noise based on noise characterization of waves due to power difference of two intensities. The noise interference is calculated from newly devised noise measurement equations and their units. The grades and flag colors are notated to the noise calculation charts. Furthermore, illustrated examples of noise characterization calculations for indoor environment are presented using devised noise measurement equations. Indoor environmental quality and noise instrumentation are discussed. Adverse effects of pollutants on human health are summarized. Ventilation systems for dispersion of pollutants from industrial indoor environment are also elaborated.",book:{id:"8529",slug:"indoor-environment-and-health",title:"Indoor Environment and Health",fullTitle:"Indoor Environment and Health"},signatures:"Himanshu Dehra",authors:[{id:"12304",title:"Mr.",name:"Himanshu",middleName:null,surname:"Dehra",slug:"himanshu-dehra",fullName:"Himanshu Dehra"}]},{id:"19157",title:"Interaction of Urban Vegetation Cover to Sequester Air Pollutants from Ambient Air Environment",slug:"interaction-of-urban-vegetation-cover-to-sequester-air-pollutants-from-ambient-air-environment",totalDownloads:3906,totalCrossrefCites:4,totalDimensionsCites:5,abstract:null,book:{id:"488",slug:"air-pollution-new-developments",title:"Air Pollution",fullTitle:"Air Pollution - New Developments"},signatures:"Sharda Dhadse, D. G. Gajghate, P.R. 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Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. 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Biochemistry examines macromolecules - proteins, nucleic acids, carbohydrates, and lipids – and their building blocks, structures, functions, and interactions. Much of biochemistry is devoted to enzymes, proteins that catalyze chemical reactions, enzyme structures, mechanisms of action and their roles within cells. Biochemistry also studies small signaling molecules, coenzymes, inhibitors, vitamins, and hormones, which play roles in life processes. Biochemical experimentation, besides coopting classical chemistry methods, e.g., chromatography, adopted new techniques, e.g., X-ray diffraction, electron microscopy, NMR, radioisotopes, and developed sophisticated microbial genetic tools, e.g., auxotroph mutants and their revertants, fermentation, etc. More recently, biochemistry embraced the ‘big data’ omics systems. Initial biochemical studies have been exclusively analytic: dissecting, purifying, and examining individual components of a biological system; in the apt words of Efraim Racker (1913 –1991), “Don’t waste clean thinking on dirty enzymes.” Today, however, biochemistry is becoming more agglomerative and comprehensive, setting out to integrate and describe entirely particular biological systems. The ‘big data’ metabolomics can define the complement of small molecules, e.g., in a soil or biofilm sample; proteomics can distinguish all the comprising proteins, e.g., serum; metagenomics can identify all the genes in a complex environment, e.g., the bovine rumen. 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Dr. Blumenberg’s research is focused on the epidermis, expression of keratin genes, transcription profiling, keratinocyte differentiation, inflammatory diseases and cancers, and most recently the effects of the microbiome on the skin. 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In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. 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Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. 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Thus proteomics, an area of research that detects all protein forms expressed in an organism, including splice isoforms and post-translational modifications, is more suitable than genomics for a comprehensive understanding of the biochemical processes that govern life. The most common proteomics applications are currently in the clinical field for the identification, in a variety of biological matrices, of biomarkers for diagnosis and therapeutic intervention of disorders. From the comparison of proteomic profiles of control and disease or different physiological states, which may emerge, changes in protein expression can provide new insights into the roles played by some proteins in human pathologies. Understanding how proteins function and interact with each other is another goal of proteomics that makes this approach even more intriguing. Specialized technology and expertise are required to assess the proteome of any biological sample. Currently, proteomics relies mainly on mass spectrometry (MS) combined with electrophoretic (1 or 2-DE-MS) and/or chromatographic techniques (LC-MS/MS). MS is an excellent tool that has gained popularity in proteomics because of its ability to gather a complex body of information such as cataloging protein expression, identifying protein modification sites, and defining protein interactions. 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