USA wildfire-related fatalities per year 1929–2017 by grouping (National Interagency Fire Center 2019).
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"intechopen-supports-asapbio-s-new-initiative-publish-your-reviews-20220729",title:"IntechOpen Supports ASAPbio’s New Initiative Publish Your Reviews"},{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"}]},book:{item:{type:"book",id:"9815",leadTitle:null,fullTitle:"Cystic Fibrosis - Facts, Management and Advances",title:"Cystic Fibrosis",subtitle:"Facts, Management and Advances",reviewType:"peer-reviewed",abstract:"Cystic fibrosis, a genetic disorder in children and young adults, is a multisystemic disease that mainly affects the lungs. Advances and improvements in the diagnosis and management of this condition have led to increased overall and symptom-free survival in cystic fibrosis patients. This book examines recent advances in the field and presents an evidence-based approach to the management of cystic fibrosis.",isbn:"978-1-83881-074-0",printIsbn:"978-1-83881-073-3",pdfIsbn:"978-1-83881-075-7",doi:"10.5772/intechopen.87623",price:119,priceEur:129,priceUsd:155,slug:"cystic-fibrosis-facts-management-and-advances",numberOfPages:124,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"69745423f00df1a6b73be06d7ae13601",bookSignature:"Prashant Mohite, Anna Reed and André R. Simon",publishedDate:"June 9th 2021",coverURL:"https://cdn.intechopen.com/books/images_new/9815.jpg",numberOfDownloads:2152,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:1,numberOfDimensionsCitationsByBook:0,hasAltmetrics:1,numberOfTotalCitations:1,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"November 6th 2019",dateEndSecondStepPublish:"March 2nd 2020",dateEndThirdStepPublish:"May 1st 2020",dateEndFourthStepPublish:"July 20th 2020",dateEndFifthStepPublish:"September 18th 2020",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"286049",title:"Dr.",name:"Prashant",middleName:null,surname:"Mohite",slug:"prashant-mohite",fullName:"Prashant Mohite",profilePictureURL:"https://mts.intechopen.com/storage/users/286049/images/system/286049.png",biography:"Prashant Mohite is trained as a cardiac surgeon in India and works as a Locum Consultant in Cardiac Retrieval at Golden Jubilee National Hospital. He was involved in the development of several programs at Harefield Hospital, England, including Organ Care Systems for heart and lungs, ex vivo lung perfusion, awake extracorporeal life support (ECLS), ECLS as a bridge to lung transplant, and donation after cardiac death (DCD) heart transplantation. 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She graduated from Leeds University in 1998 and obtained a Ph.D. in Pulmonary Vascular Pharmacology from Imperial College London in 2011. She maintains an active research interest in areas such as surfactant flux in primary graft dysfunction, ECMO bridging to lung transplant, pharmacokinetic and pharmacodynamic alterations of commonly used anti-infectives on extracorporeal life support, Aspergillus disease and the immunological impact on the transplanted lung, and more. 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He has also contributed chapters to several textbooks. He has raised more than £2 million in funding for research into transplantation immunology, cardiac imaging, and ventricular assist devices. Dr. Simon is the founder and president of HeartHelp, a charitable non-government organization.",institutionString:"Royal Brompton and Harefield NHS Foundation Trust",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"Royal Brompton & Harefield NHS Foundation Trust",institutionURL:null,country:{name:"United Kingdom"}}},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1047",title:"Pulmonology",slug:"pulmonology"}],chapters:[{id:"76709",title:"Introductory Chapter: Basics of Cystic Fibrosis",doi:"10.5772/intechopen.97537",slug:"introductory-chapter-basics-of-cystic-fibrosis",totalDownloads:224,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Prashant N. Mohite and Vicky Gerovasili",downloadPdfUrl:"/chapter/pdf-download/76709",previewPdfUrl:"/chapter/pdf-preview/76709",authors:[{id:"286049",title:"Dr.",name:"Prashant",surname:"Mohite",slug:"prashant-mohite",fullName:"Prashant Mohite"},{id:"416266",title:"Dr.",name:"Vicky",surname:"Gerovasili",slug:"vicky-gerovasili",fullName:"Vicky Gerovasili"}],corrections:null},{id:"72407",title:"Cystic Fibrosis-Related Diabetes (CFRD)",doi:"10.5772/intechopen.92767",slug:"cystic-fibrosis-related-diabetes-cfrd-",totalDownloads:388,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cystic fibrosis-related diabetes (CFRD) is the most frequent comorbidity in CF. The prevalence is age-dependent and abnormalities in/of glucose homeostasis start early in life. As CFRD has an impact on pulmonary function and life expectancy, early diagnosis and treatment is mandatory. Screening is needed because initially, most patients with CFRD do not show any typical symptoms of diabetes. The question of which screening method gets the best results is still under discussion. For treatment insulin is recommended but a relevant percentage of patients do not use it, and even if insulin is used, there is no consensus on what the best insulin regime in the case of CFRD is. Recently, oral antidiabetic drugs were shown to be as effective and safe as insulin in the initial treatment of CFRD. This treatment might reduce the additional treatment burden for patients with CFRD. The best way to monitor CFRD is also under discussion (HbA1c and/or continuous glucose monitoring; CGM). The threshold of HbA1c might be lower than for other types of diabetes. As patients with CF become older, the duration of CFRD will also increase and typical diabetes complications will occur. So far, these are mainly microvascular complications. The new CFTR modulators might influence not only pulmonary function but potentially also glucose homeostasis.",signatures:"Manfred Ballmann",downloadPdfUrl:"/chapter/pdf-download/72407",previewPdfUrl:"/chapter/pdf-preview/72407",authors:[{id:"314947",title:"Prof.",name:"Manfred",surname:"Ballmann",slug:"manfred-ballmann",fullName:"Manfred Ballmann"}],corrections:null},{id:"72572",title:"Detection and Management of Early Glucose Abnormalities in Cystic Fibrosis",doi:"10.5772/intechopen.92847",slug:"detection-and-management-of-early-glucose-abnormalities-in-cystic-fibrosis",totalDownloads:504,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"With advances in technology, it is now possible to detect the emergence of glucose abnormalities in cystic fibrosis with improved sensitivity, and from a very early age. These abnormalities are increasingly recognized as predictors of clinical decline, raising the possibility that early intervention may slow or prevent this deterioration. In this chapter, we will review the available literature on methods of detecting glucose abnormalities in cystic fibrosis (random and fasting glucose, HbA1c, oral glucose tolerance testing, and continuous glucose monitoring), and detail their advantages and possible limitations in the interpretation of glycemic data. We will also discuss treatment outcomes of early intervention, prior to the diagnosis of diabetes as currently defined.",signatures:"Katerina Theocharous, Bernadette Prentice, Charles F. Verge, Adam Jaffé and Shihab Hameed",downloadPdfUrl:"/chapter/pdf-download/72572",previewPdfUrl:"/chapter/pdf-preview/72572",authors:[{id:"196333",title:"Dr.",name:"Bernadette",surname:"Prentice",slug:"bernadette-prentice",fullName:"Bernadette Prentice"},{id:"197023",title:"Dr.",name:"Shihab",surname:"Hameed",slug:"shihab-hameed",fullName:"Shihab Hameed"},{id:"197024",title:"Dr.",name:"Charles F.",surname:"Verge",slug:"charles-f.-verge",fullName:"Charles F. 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In the last century, the relationship between CF, respiratory microbiology, and inflammation has been understood with increased longevity and development of new treatments and laboratory techniques. In this chapter, we will illustrate causes of CF lung diseases and modern therapeutic strategies.",signatures:"Waleed Mohamed Abdulkhair and Mousa Abdullah Alghuthaymi",downloadPdfUrl:"/chapter/pdf-download/71325",previewPdfUrl:"/chapter/pdf-preview/71325",authors:[{id:"175713",title:"Dr.",name:"Waleed Mohamed Hussain",surname:"Abdulkhair",slug:"waleed-mohamed-hussain-abdulkhair",fullName:"Waleed Mohamed Hussain Abdulkhair"},{id:"315906",title:"Dr.",name:"Mousa",surname:"Alghuthaymi",slug:"mousa-alghuthaymi",fullName:"Mousa Alghuthaymi"}],corrections:null},{id:"74734",title:"Lung Transplantation in Patients with Cystic Fibrosis",doi:"10.5772/intechopen.94523",slug:"lung-transplantation-in-patients-with-cystic-fibrosis",totalDownloads:349,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cystic fibrosis (CF) is one of the most common indications for lung transplant (LTx) and nearly one-third of the LTx worldwide are performed in people with CF (PwCF). Due to vast developments in diagnostic modalities, antibiotic therapies, and management of associated comorbidities in dedicated and experienced centres, over the past few decades, more PwCF are reaching adulthood than ever before. This has increased the burden on transplant programs particularly in a universal donor shortage scenario. To improve the donor pool a diligent and proactive donor care management, acceptance of marginal organs and utilisation of ex-vivo lung perfusion systems for organ preservation, assessment, and improvement is being advocated widely. LTx is not a readily available therapy and the average waiting time is 18 months in the UK. Therefore, it is essential that PwCF are referred for LTx assessment when their disease is stable, before respiratory deterioration leads to overall deconditioning of the patients. Once listed for LTx, it is crucial to control waiting list mortality by prioritising rapidly deteriorating patients through schemes like the lung allocation score, national urgent and super-urgent waiting lists, and institutional highlighting of deteriorating patients that do not meet other urgent criteria. LTx in PwCF is challenging due to colonisation of the respiratory tract with multi-drug resistant organisms, associated comorbidities such as diabetes, liver disease, gastro-oesophageal reflux, and distal intestinal obstruction syndrome (DIOS) and CF-specific technical difficulties (adhesions due to prior pneumothoraces or pleurodesis, or bronchial collaterals that increase surgical time). Hilar lymphadenopathy and bronchial collaterals may increase surgical time, organ ischemia time, intra and post-operative bleeding, and blood transfusions. Advances in immunosuppression, prophylactic anti-viral and anti-fungal therapies, early ambulation and rigorous physiotherapy, and meticulous postoperative follow up with spirometry, x-rays, and bronchoscopies to detect rejection at the early stage followed by its efficient treatment have helped to improve post-LTx survival in the CF patients. Constant development in the surgical field with adoption of off-pump transplantation, sternal sparing bilateral thoracotomy approach, and utilisation of mechanical circulatory assist as a bridge to transplant and as a support for primary graft failure strives for better outcomes. However, chronic lung allograft dysfunction, chronic refractory infections, malignancies, and CF associated comorbidities remain major determinants of post-LTx long term survival. Despite this, CF patients are often good candidates for re-do LTx with improving survival outcomes. In this chapter, we are compiling the different aspects of LTx in PwCF emphasising the advances in bridge to transplantation, the surgical approach, management of primary graft failure, and immunosuppression as well as complications post-transplant.",signatures:"Prashant N. Mohite, Kavita Dave, Anna Reed and André R. 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Recently, novel gene therapy strategies have been developed, including mRNA delivery, genome editing, and mRNA repair; all these strategies are collectively named “genetic medicines.” The last quarter of the century showed a significant boost in the development of viral and nonviral vectors to deliver genetic treatment. This chapter will provide a brief overview of the CFTR gene and its different classes of mutations as well as a review of the different genetic therapeutic options that are under research. Later in this chapter, drugs that target different CFTR mutation classes and are currently approved to treat CF patients will be briefly presented.",signatures:"Salsabil Elboraie, Konstantinos N. Kafetzis, Rajeev Shrivastava and Aristides D. 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The book consists of several chapters. The first chapter seeks to familiarise readers with the diagnostic classification of Personality disorders, their aetiology and prevalence rooted in systematic research, but also offers a discussion on the limitations and challenges of the current diagnostic system.
\r\n\r\n\tThe following chapters will offer an overview of the most predominant presentations of Personality disorders in clinical practice, namely the Borderline, Narcissistic, Schizoid and Antisocial types. Case studies arising from clinical practice will be presented and the chapters will offer a comprehensive discussion of the processes and treatment outcomes of various psychotherapeutic models employed in treatment.
\r\n\r\n\tThe final chapter is dedicated to broader manifestations of Personality Disorders and their associated clinical presentations which may have not received sufficient clinical attention, arising challenges and treatment approaches.
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Academically she is based at London Metropolitan University where she holds a Senior Lecturer post in Counselling Psychology. Clinically, she is a Lead Psychologist in the NHS where she practices in the area of substance misuse and clinical neuropsychology. She has over 15 years of clinical experience in various clinical settings in the UK and she specializes in Psychodynamic, CBT and integrative models of practice. She has authored a number of papers in the fields of Counselling Psychology and psychotherapy, and she has also collaborated with other researchers on numerous projects.",institutionString:"London Metropolitan University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"London Metropolitan University",institutionURL:null,country:{name:"United Kingdom"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"16",title:"Medicine",slug:"medicine"}],chapters:null,productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"278926",firstName:"Ivana",lastName:"Barac",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/278926/images/8058_n.jpg",email:"ivana.b@intechopen.com",biography:"As an Author Service Manager my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review, to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"6550",title:"Cohort Studies in Health Sciences",subtitle:null,isOpenForSubmission:!1,hash:"01df5aba4fff1a84b37a2fdafa809660",slug:"cohort-studies-in-health-sciences",bookSignature:"R. Mauricio Barría",coverURL:"https://cdn.intechopen.com/books/images_new/6550.jpg",editedByType:"Edited by",editors:[{id:"88861",title:"Dr.",name:"R. Mauricio",surname:"Barría",slug:"r.-mauricio-barria",fullName:"R. 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Recently, an astonishing number of connections to human physiology and disease for autophagy have been made. Thus, autophagy plays a critical role during development and differentiation, in cancer, neurodegeneration, combating viral and microbial infections, and has been linked to life span extension and ageing. For these reasons, the ability to follow autophagy in living mammalian cells is of particular interest, both in terms of developing better understanding at a mechanistic level and in terms of possible future clinical applications.
In this chapter our intention is not to summarise the available autophagy assays, but to highlight the application of biosensors used to monitor autophagic processes in live cells. Firstly, we briefly outline current knowledge about the molecular mechanism and function of autophagy (Section 1.2). Then, we outline how autophagy can be measured in live cells in a non-invasive manner and indicate some of the advantages and disadvantages of the biosensor-based assays of autophagy currently in use (Section 2). In particular we focus here on the design and use of Rosella - a dual wavelength emission biosensor based on a fusion of fluorescent proteins whose use exploits alterations in pH during autophagy. The advantages of this approach will be highlighted (Section 2.3) and illustrated by applications to follow autophagy both in yeast, an important eukaryotic model organism (Section 2.3.1) and mammalian cells (Section 2.3.2). Finally, we address the future prospects for application of alternative approaches (Section 3) to the measurement of autophagy based on the use of novel probes.
The biological importance of autophagy is such that the molecular mechanism is the focus of intense research efforts (reviewed in Yang & Klionsky, 2010). Three distinct autophagic pathways have been shown to operate in eukaryotic cells namely, macroautophagy, microautophagy and chaperone-mediated autophagy-CMA (Orenstein & Cuervo, 2010). In order to understand the rationale of biosensor design and function it is necessary to have a basic understanding of the particular process to be monitored. The key aspects of each of the three different forms of autophagy are shown in Fig. 1.
The morphological hallmark of macroautophagy (hereafter referred as autophagy) is the formation of a double-membrane structure called an autophagosome, encapsulating the
Three main types of autophagy. Three morphologically and mechanistically distinct types of autophagy have been described in cells: macroautophagy, microautophagy and chaperone-mediated autophagy (CMA).Microautophagy is best described in yeast cells and CMA is restricted to mammalian cells. The degradative vacuole in yeast cells is large, whereas the lysosomes are much smaller and far more numerous. In this diagram the lysosome is not drawn to scale in order to illustrate the three processes that deliver material to it. Microautophagy can be considered a two-step process: lysosomal membrane invagination (I) followed by cargo breakdown (II). The individual steps of macroautophagy are numbered (see shaded box for key). Inset (LC3 processing) summarises the steps leading to the recruitment of LC3-II (green spheres) to the forming autophagosome. Completed autophagosomes fuse with lysosomes, after which LC3-II on the cytoplasmic face of autolysosomes is delipidated through the activity of Atg4 and recycled. LC3-II located on the internal surface of autophagosomes is degraded in the autolysosomes. The association of LC3-II with autophagosomes has been widely exploited as a marker for autophagy. LC3, microtubule-associated protein 1 light chain 3; PE, phosphatidylethanolamine.
material for degradation (reviewed in Xie & Klionsky, 2007). The pathway consists of a number of distinct steps and includes: (1) induction, (2) nucleation and phagophore formation, (3) phagophore expansion, (4) cargo selection and packaging, (5) autophagosome completion, (6) cargo delivery and fusion of the autophagosome with the lysosome/vacuole, (7) breakdown of the sequestered cargo and (8) efflux (reviewed in Lagakis & Klionsky, 2006) (Fig. 1). Upon autophagy induction, that is tightly regulated by Tor (target of rapamycin kinase), a double membrane structure termed the phagophore is initiated and expands to engulf the cargo. The sequential expansion of the phagophore allows the cell to adjust the size of the autophagosome to sequester cellular components over a wide size range and can include organelles such as a mitochondrion (reviewed in He & Klionsky 2009; Kanki & Klionsky, 2010). The ends of the phagophore membrane fuse to form the autophagosome, thereby, sequestering the cargo from the rest of the cell. The outer-membrane of the autophagosome then fuses with the membrane of the lysosome (mammalian cells) or the vacuole (yeast cells) to deliver the cargo into to the acidic lumen (~pH 4.5-6). Cargo is degraded through the action of resident hydrolases to basic polymer building blocks (e.g., nucleotides, amino acids, sugars) which are exported to the cytosol for recycling by the cell (reviewed in Yorimitsu & Klionsky, 2005).
Autophagy is regulated by the autophagy-related genes (
Nevertheless, details of how a number of individual gene products function in the process is emerging. Some of the gene products act sequentially in two ubiquitin-like conjugation systems (Atg8 and Atg12) that are involved in vesicle expansion and completion (Chen & Klionsky, 2011).
Autophagy plays a role in the degradation of a wide range of cellular components, including long-lived proteins, protein complexes and aggregates, macromolecules (ribosomes, lipids), organelles (the endoplasmic reticulum, peroxisomes, the nucleus and mitochondria) and even intracellular pathogens (bacteria and viruses) (reviewed in Klionsky et al., 2007a). Although starvation-induced autophagy is thought to act non-selectively in the degradation of bulk cytoplasm, it can be highly selective in cargo selection. Protein aggregates (Rubinsztein, 2006), nuclear components (Krick et al., 2008; Roberts et al., 2003) or superfluous, damaged/stressed or nutritionally-challenged organelles, such as mitochondria (Kanki et al., 2011; Youle & Narendra, 2011) may be targeted. Selective autophagy is best characterised in yeast (reviewed in Farré et al., 2009; van der Vaart et al., 2008) and includes other modes not described in mammalian cells such as the cytoplasm to vacuole targeting (Cvt) pathway (reviewed in Lynch-Day & Klionsky, 2010) and the vacuolar import and degradation (vid) pathway (Brown et al., 2010).
Cargo sequestration can take place through microautophagy, but the limiting/sequestering membrane in this case is the vacuolar/lysosomal membrane itself, which invaginates to form tubules or vesicles that pinch off into the lysosomal lumen (Fig. 1). Our current understanding of microautophagy mechanism and regulation is largely based on studies in yeast. Microautophagy remains poorly understood in mammals (Mijaljica et al., 2011; Shpilka & Elazar, 2011).
Delivery of cargo via CMA does not require formation of intermediate vesicle compartments or membrane fusion. Instead, the substrates, soluble proteins, are translocated from the cytosol into the lysosomal lumen directly across the membrane in a process mediated by a translocation protein complex that requires activity of chaperones, substrate unfolding and the presence of receptors on the lysosomal membrane (Fig. 1). CMA occurs only in mammalian cells (reviewed in Orenstein & Cuervo, 2010).
“Static measurements” of a particular biological process can be limiting in terms of the insights they provide. Autophagy is a complex, highly regulated and dynamic process involving membrane rearrangement events including formation of the autophagosome and fusion of intracellular membranes. Monitoring such dynamic events represents a challenge and biosensors specific for many of the selective forms of autophagy in particular are yet to be developed. The lack of suitable biosensors likely underlies many of the misconceptions in our understanding of the function of autophagy, mammalian autophagy in particular.
Nevertheless, new techniques have been developed both to monitor autophagy as a dynamic process and to modulate autophagy to facilitate probing its function in a given cellular process (reviewed in Klionsky et al., 2008; Mizushima, 2004; Mizushima et al., 2010; Mizushima & Yoshimori, 2007; Rubinsztein et al., 2009). Key components of the molecular mechanism have been identified, many of which have the potential to be exploited as useful reporters (Fig. 1).
As interest in selective modes of autophagy gains momentum, it is increasingly important to have access to probes able to follow events in a selective manner. Since it is likely that some cellular targets are present in only small quantities, biosensors that allow monitoring of autophagy at low levels are required. Such a biosensor is also likely to facilitate the detection of autophagy at early stages after induction. It is often important to follow biological processes in living cells, tissues or organisms requiring the application of non-invasive techniques. Such applications are based commonly on the use of light-based probes that rely on the chemical production of light, or are based on fluorescence emission. Autophagy is a temporally and spatially dynamic process; therefore, it is desirable that biosensor outputs do not persist or accumulate in a way that would prevent successive cycles of activity to be detected. A single ideal biosensor fulfilling each of these requirements has yet to be developed.
Biosensor-based approaches for monitoring autophagy can be considered to fall into either of two major categories (Fig. 2), examples of which have been reported in the literature (reviewed in Klionsky et al., 2007b; Klionsky et al., 2008; Mizushima et al., 2010). In the first category, autophagic activity can be assessed by monitoring the behaviour, modification or activity of key molecules involved in the molecular mechanism of autophagy (Section 2.2). Alternatively, the fate of the target material itself can be followed either by monitoring delivery to the lysosome/vacuole, or its degradation (Section 2.3). In order to follow the fate of the target material itself, it is crucial to be able to identify or selectively label the target. This can be achieved to a limited extent by visualising characteristic staining patterns of particular targets such as mitochondria or intracellular pathogens using electron microscopy (Klionsky et al., 2007b; Klionsky et al., 2008; Mizushima et al., 2010), or by labelling with dyes suitable for detection by fluorescence microscopy. The scope for labelling autophagic targets is greatly expanded if genetically encoded probes such as fluorescent proteins (FPs) are considered. Genetic fusions of target proteins with FPs can be readily expressed in cells allowing the delivery of targets to the lysosome or vacuole to be tracked using fluorescence microscopy in individual cells. FPs are remarkably stable molecules and persist as
Approaches for monitoring autophagy. The molecular mechanism of autophagy maybe exploited to monitor the process by tracking the modification or activity of key molecules in the pathway (Approach 1). For example, post-translational modification of LC3 or its recruitment to the autophagosome is commonly used. This approach does not provide information on the identity of the cargo, which must also be labelled if selective forms of autophagy are to be tracked. Alternatively, (Approach 2) labelling the target with a biosensor (e.g., Rosella) that continually senses and reports on the environment of the target material allows for monitoring of selective autophagy. However, this approach does not provide information on the mechanistic aspects of the particular process involved.
fluorescent forms in the degradative organelle long enough to detect their presence (Katayama et al., 2008). Furthermore, the fate of such genetic fusions can be followed in populations of cells using western blots to follow changes in sizes of the fusion produced by proteolytic degradation within the degradative organelle (Mizushima et al., 2010; Klionsky et al., 2008). In specific cases, enzymatic activities can also be used to follow delivery to the lysosome/vacuole (Ketteler et al., 2008; Ketteler & Seed, 2008; Kimura et al., 2007; Klionsky et al., 2007b; Klionsky et al., 2008; Mizushima et al., 2010). As new forms of selective autophagy are reported in the literature approaches that label and follow the target material for autophagy are becoming the focus of attention.
Monitoring autophagic activity or flux in cells, tissues or organs is of considerable interest to many researchers, and is a technology undergoing continual development. In recent years, methods for detection of autophagy suitable for
In the following section, we describe some of the available biosensors suitable for analysis of autophagy/autophagy-related pathways
LC3 (or Atg8 in yeast), fused at its N-terminus to one of a number of different colour FPs including GFP, CFP (Ravikumar et al., 2010) or mCherry (Axe et al., 2008; Klionsky et al., 2008; Mizushima et al., 2010), has been used with great success to monitor autophagy in a number of different model organisms including
When viewed using fluorescence microscopy, the diffuse cytosolic GFP-LC3-I is converted to GFP-LC3-II upon induction of autophagy, which subsequently associates with the phagophore membrane and appears as bright fluorescent puncta in the cytoplasm. The number of puncta in a cell has been used as a measure of autophagic activity (Kabeya et al., 2000; Klionsky et al., 2008; Mizushima et al., 2010). GFP-LC3 on the outer surface of the completed autophagosome is removed by action of an autophagin just prior to its fusion with the degradative organelle. Fluorescence due to GFP-LC3 residing on the internal membrane of the autophagosome can persist in the autolysosome until degraded, dependent on the identity of the FP and pKa of its chromophore (Section 2.3).
Image based assays can be time consuming, labour-intensive and require experience for accurate interpretation. Fluorescence activated cell sorting (FACS) allows the rapid acquisition of large datasets and has been used to monitor autophagy by following the time–dependent decrease in the cellular GFP-LC3 signal as it is consumed during autophagy in live cells (Shvets et al., 2008).
Fusing LC3 to a red fluorescent protein (mRFP) and a GFP (EGFP) in tandem to form tfLC3, represents an approach that allows the environment of the probe to be monitored (Kimura et al., 2007; Klionsky et al., 2008). The fluorescence emissions of these two FPs differ in their response to pH such that mRFP remains highly fluorescent in the acidic lumen of the lysosome, whereas EGFP emission is essentially quenched. tfLC3 enables simultaneous estimation of both the induction of autophagy and flux through autophagic compartments without the need to use inhibitors and inducers of autophagy or any other drug treatment (Kimura et al., 2007).
An approach has been developed that monitors the enzymatic activity of Atg4b using LC3 fused to luciferase as a substrate (Ketteler et al., 2008; Ketteler & Seed, 2008). The luciferase is expressed fused at its C-terminus to LC3 and in turn to (-actin. Anchored to actin, the modified
The growing interest in understanding the regulation and mechanism of selective forms of autophagy (reviewed in Farré et al., 2009; van der Vaart et al., 2008) demands the use of approaches that provide information on specific or individual cargos. However, each of the forgoing assays (Section 2.2) report on the activity of a component of the autophagic pathway, and require the use of additional probes in combination if individual autophagic cargo is to be followed. We have established an alternative approach that senses and reports delivery of the target material to the lysosome or vacuole (Fig.2). The assay is based upon a genetically encoded dual colour-emission biosensor, Rosella, the fusion of a relatively pH-stable fast-maturing variant of the red fluorescent protein, DsRed.T3 with a pH-sensitive variant of green fluorescent protein, pHluorin (Fig. 3A) (Devenish et al., 2008; Rosado et al., 2008). By virtue of it being targeted to specific cellular compartments or fused to an individual protein, the biosensor provides information about the identity of the cellular component being delivered to the lysosome or vacuole for degradation. Importantly, the pH-sensitive dual colour fluorescence emission provides information about the environment of the biosensor (Fig. 3B) (Devenish et al., 2008; Rosado et al., 2008).
We have already shown that the Rosella biosensor can be used to follow autophagic degradation of specific cargo (cytosol, mitochondria and the nucleus) in yeast cells (Devenish et al., 2008; Mijaljica et al., 2010; Nowikovsky et al., 2007; Rosado et al., 2008) by fluorescence microscopy and FACS analysis (Devenish et al., 2008; Mijaljica et al., 2010; Rosado et al., 2008). Here, we extend those findings and demonstrate the use of Rosella to study reorganisation of the nuclear membrane in mutant yeast strains. We also show that Rosella can be used for monitoring both non-selective autophagy (cytosol) and selective autophagy (mitochondria) in mammalian cells highlighting the benefits of use of this biosensor.
Rosella can be used to monitor autophagy of different cellular compartments in yeast and mammalian cells.(A) A schematic of Rosella. The components of Rosella are as follows: targeting sequence for subcellular localisation (cyan box) or other protein to which it is fused; red fluorescent protein (DsRed.T3); polypeptide linker (black bar) and a pH-sensitive GFP variant (pHluorin). A targeting sequence is not required for cytosolic Rosella. The wavelength of lasers suitable for excitation of each component fluorescent protein is indicated. The λmaxem (maximum emission wavelength) of each FP is indicated.(B) Appropriately targeted Rosella can be used to monitor delivery of cytosol, mitochondria or nucleus to the vacuole of yeast cells or cytosol and mitochondria to the lysosome of mammalian cells. When autophagy is induced, increased amounts of Rosella which fluoresces both red and green outside of the acidic vacuole or lysosome (indicated by red and green colour) accumulate in these compartments (indicated by red colour), whereby the green fluorescence emission is quenched. C, cytosol; L, lysosome; M, mitochondria; N, nucleus; V, vacuole.
Nucleophagy in the yeast
n-Rosella is a variant of Rosella targeted to the nucleus. Under growing conditions, wildtype yeast cells expressing n-Rosella exhibit fluorescent labelling of the entire nuclear lumen (nucleoplasm), which appears as a single red and green body (Fig. 4) (Devenish et al., 2008; Mijaljica et al., 2007; Mijaljica et al. 2010; Rosado et al., 2008). When incubated in nitrogen starvation medium for 24 h, cells show red and green fluorescence of the nucleus as well as markedly visible accumulation of red fluorescence in the vacuole indicative of autophagy (nucleophagy) (Fig. 4A).
n-Rosella labelling allows both the morphology of the nucleus to be readily visualized and its own accumulation inside the vacuole. The biosensor can also be used to monitor intermediate steps in the process, using yeast cells lacking expression of particular
Mutant yeast cells lacking specific vacuolar enzyme activities required for efficient disassembly of membranes delivered by autophagy (e.g.,
The yeast vacuole is a relatively large and readily recognisable organelle, often accounting for much of the cell volume (Fig. 4). Monitoring delivery of fluorescent cargo to the vacuole therefore is relatively simple. In contrast, the internal membrane structure of the mammalian cell is considerably more intricate and constitutes a profusion of vesicular compartments of various sizes. The mammalian lysosome is a much smaller organelle compared to the vacuole, usually present in large numbers that are distributed throughout the cytosol. The task of visualising delivery of cellular material to the lysosome is accordingly more complex and often requires specific labelling of the acidic organelle with proprietary dyes such asLysotracker or Lysosensor (Klionsky et al., 2007b). The pH–sensing capability of Rosella allows the delivery of labelled material to be followed without the use
n-Rosella in yeast: (A) Wild type cells expressing n-Rosella were imaged using fluorescence microscopy under growing and nitrogen starvation conditions. Accumulation of diffused red fluorescence in the vacuole after 24 h of commencement of nitrogen starvation indicates nucleophagy. (B) The absence of expression a particular gene product essential for nucleophagy influences nuclear morphology and abrogates correct delivery of n-Rosella to the vacuole. Nuclear blebs remain red and green indicating high pH environment. (C) The absence of the
of additional probes to highlight the location of the lysosome. We next demonstrate in mammalian cells that Rosella can be used to monitor delivery of the cytosol or mitochondrion to the lysosome.
HeLa cells maintained in a replete growth medium and transfected with an expression vector encoding c-Rosella (Rosella without any additional targeting sequence) (Fig. 3B) when imaged using fluorescence microscopy showed both strong red and green fluorescence distributed throughout the cytosol. Rosella appears to have restricted access to the nuclear compartment (less intense staining) and is completely excluded from other compartments (Fig. 5). Importantly, only 1-2 red and weakly green puncta/cell were observed (Fig. 5A, white arrows) suggesting that Rosella has accumulated in a relatively acidic compartment such as a lysosome. These puncta correspond to autophagolysosomes, and represent fusion of an autophagosome carrying the Rosella cargo and a lysosome. Low numbers of puncta observed under growth conditions are consistent with basal autophagic activity and the homeostatic role of autophagy under these conditions.
Rapamaycin, an inhibitor of mTor (mammalian Tor), has been used in numerous studies to induce autophagy in HeLa cells (Ravikumar, et al., 2006). Following 4 h incubation in the presence of rapamycin (0.2μg/ml) a ~10-fold increase in the number of strongly red fluorescent puncta that were only weakly green fluorescent and corresponding to autophagolysosomes was observed (Fig. 5A, white arrows).
The lysosome can be independently labelled using acidotropic dyes that accumulate in the lumen of the organelle (Klionsky et al., 2007b). The blue fluorescence emission of LysoTrackerBlue-White (LTBW) in the lysosome can be imaged together with the red and green emission of Rosella. In a separate experiment, prior to treatment with rapamycin to induce autophagy, lysosomes in Rosella-transfected HeLa cells were labelled with LTBW
Rosella can monitor autophagy in HeLa cells.(A) HeLa cells expressing c-Rosella were imaged 24 h post-transfection for red and green fluorescence (left panel). 1-2 red puncta (white arrows) lacking green fluorescence and corresponding to uptake of cytosolic Rosella are visible in each cell. The number of red puncta lacking green fluorescence increased after incubation in the presence of rapamycin (0.2μg/ml) for 4 h (right panel). (B) In a separate experiment cells were incubated with LysoTrackerBlue-White (LTBW) to label lysosomal compartments. The scale bar is 20 μm.
(Fig. 5B). The puncta were both red and blue fluorescent, but not green fluorescent suggesting that these vesicles represent lysosomal derived compartments.
We next investigated whether Rosella was suitable for monitoring mitophagy in HeLa cells. For these experiments mt-Rosella (a variant of Rosellafused at its N-terminus to the mitochondrial targeting sequence of subunit VIII of cytochrome
Rosella can be used to monitor mitophagy in mammalian cells.(A) DIC and fluorescence images are shown for HeLa cells transfected with an expression vector encoding m-Rosella. Cells were labelled after transfection with a far-red fluorescent mitochondrial probe, MitoTracker Deep Red (MTDR), whose emission is distinct from those of Rosella. (B) HeLa cells were co-transfected with expression vectors encoding m-Rosella and mCer-LC3, and subsequently incubated for 12 h in growth medium containing 0.2μg/ml rapamycin (+ Rapamycin) to induce autophagy. Control cells were not treated with the inducer (-Rapamycin). The white outlined inset region is shown enlarged. Yellow circles highlight red vesicles that co-localise with mCer-LC3, but contain little or no green fluorescence emission. The scale bar is 20 μm.
To confirm efficient targeting of mt-Rosella to the mitochondrion, transfected cells were incubated with the far-red fluorescent mitochondrial probe MitoTracker Deep Red (MTDR) (Fig. 6A) (Hallap et al., 2005). The far-red fluorescence emission of MTDR was observed to co-localise with the red and green fluorescence of mt-Rosella. Collectively, these results show that Rosella is efficiently imported into mitochondria, and subsequently becomes both red and green fluorescent.
Next, HeLa cells were co-transfected with expression vectors encoding mt-Rosella or a cyan FP (mCer) fused to the N-terminus of LC3. mCer-LC3 labels the autophagosome for reasons indicated in Figure 1. Transfected cells were cultured for 12 h without (control) or with the addition of rapamycin (0.2μg/ml) and imaged by fluorescence microscopy (Fig. 6B). In control cells not stimulated with rapamycin, the presence of 1-2 cyan puncta per cell indicates autophagy occurring at a low homeostatic level. Since LC3-II will label autophagosomes resulting from both non-selective and selective autophagy, both of which will be induced by rapamycin, it is not expected that the puncta would exhibit the red fluorescence of mt-Rosella. Images of cells stimulated with rapamycin showed the presence of numerous cyan puncta indicating the recruitment of the LC3-II to the autophagosome (Fig. 6B). Selected regions of the image (inset) are enlarged to highlight several autophagosomes that co-localise with bright red fluorescence, and therefore contain mitochondrial material labelled with Rosella. Green fluorescence emission is very weak or non-existent indicating that the pH inside the vesicles is relatively low and suggests that these autophagosomes have fused with lysosomes to form autophagolysosomes. Collectively, these data indicate that mt-Rosella can be used to monitor the delivery of mitochondrial contents to the lysosome.
A better understanding of the molecular mechanism of autophagy in living cells and tissues is essential for the development of new therapeutic strategies to treat disease (Fleming et al., 2011). Accordingly, there is a need for the validation of reliable, meaningful and quantitative assays to monitor autophagy in live cells (Klionsky et al., 2007b; Klionsky et al., 2008; Mizushima et al., 2010).
Increased interest in selective forms of autophagy highlights the need to develop biosensors suitable for monitoring autophagy of specific targets. Exploiting components of the molecular mechanism such as LC3 to follow autophagy have proven to be particularly useful strategy, and LC3 tagged with a fluorescent protein remains the most commonly used marker of the autophagosome. However, such approaches involve additional labelling to identify target material. Labelling the target with Rosella allows delivery of the material to the acidic vacuole/lysosome to be followed by exploiting the unique pH-sensitive dual emission properties. Nevertheless, scope remains to improve development of new selective probes.
Biosensors suitable for high throughput, high content applications such as large scale drug or genetic screens are required. Although in some experimental regimes (e.g., yeast nucleophagy) the dual emission output Rosella can be analysed using conventional FACS analysis, sensitivity is somewhat reduced as the spatial information is lost and the assay relies on integrating the total red and green fluorescence emission from each cell (Rosado et al., 2008). New instrument technology such as imaging flow cytometry, an example of which is manufactured by the Amnis Corporation (https://www.amnis.com/autophagy.html),would provide access to both spatial and colour information in cell populations (Lee et al., 2007). Our preliminary experiments in yeast cells suggest that this approach has potential but requires further validation and improvements under both physiological and autophagy-induced conditions (Rosado et al., 2008).
The development of biosensors with considerably improved signal-to-noise ratio may be possible using alternative probe technologies based on fragment complementation. Fragment complementation for a variety of different fluorescent proteins is now available (Kerpolla, 2006). The technology might be implemented to measure autophagy in one of several ways. For example, yeast cells in which one FP fragment is targeted to the mitochondrion and the complementing fragment targeted to the vacuole might be expected to have strongly fluorescent vacuoles
Given the interest in autophagy, it is likely in the near future that some of these ideas will result in the development of new sensitive and selective probes for this process.
This work was supported in-part by Australian Research Council Grant (DP0986937) awarded to R. J. Devenish.
Fire is a dynamic process, predictable but uncertain, that varies over time and landscape space. It has shaped plant communities for as long as vegetation and lightning have existed on earth [1, 2]. Wildland fire covers a spectrum from low-severity, localized prescribed fires, to landscape-level high-severity wildfires. Earth is a fire planet whose terrestrial ecosystems have been modified and impacted by fire since the Carboniferous Period, some 300–350 million years before the present time. In the Holocene Epoch of the past 10,000 years, humans have played a major role in fire spread across the planet. In the present Anthropocene Epoch (11,700 years before the present to the current date) of the twenty-first century, climate change, as well as the burgeoning human population, is now poised to increase the ecosystem hazards of wildland, rangeland, and cropland fire [3, 4].
Fire plays an important function in ecosystem processes [5]. Recycling of carbon (C) and nutrients depends on biological decomposition and fire. In regions where decay is constrained either by dry or cold climates or by saturated soil conditions, fire has a dominant role in recycling organic matter and maintaining some vegetation types [3]. In warmer, moist climates, decay plays the dominant role in organic matter recycling [6], except in soils that are predominantly water saturated such as hydric soils. Periodic wildfire has an important function in wildland ecosystems. However, the wildfire trend in the past several decades has raised the risk of short- and long-term damage to natural resources, infrastructure, and human health and safety.
The worldwide threat to humans and natural resources from catastrophic wildfire is greater now than at any other time in human history (Figure 1). Changes brought on by global warming, land management, and population expansion have resulted in much larger, more destructive wildfire events [7]. This has given rise to greater loss of life and property as well as the occurrence of postfire hazards including flooding, erosion, desertification, and environmental degradation [5, 8]. This chapter will look at the physical hazards and effects of wildfire both during and after conflagrations in wildland ecosystems.
High-severity wildfire, Mt. Carmel Fire, Haifa, Israel, 2017 (photo courtesy of Naama Tessler, University of Haifa).
The hazards produced by wildfires affect both the biotic and abiotic components of ecosystems. They occur during active fire as well as afterwards. While the destruction produced by combustion is spectacular, the effects after burning has ceased can be subtle or dramatic and often long lasting [3, 5]. Hazards and deleterious effects produced by wildfires during the active combustion phase include vegetation combustion, loss of human and animal life, air quality deterioration, human health deterioration, destruction of personal property, loss of commercial property, and infrastructure damage and destruction. After a wildfire is extinguished, hazards and risks arise from potential flooding, erosion, debris flows, and infrastructure damage. Water supplies and infrastructure, if not damaged during the active fire period, can be at risk during subsequent postfire flood events. Economic losses accrue from declines in tourism, loss of timber and wood fiber resources, and declines in property values. Ecological impacts not assessed by traditional economic valuations include vegetation type conversion, aquatic species loss, decreased water quality, increased stream temperatures, and reduced soil quality. All of these changes are hazards in that they reduce the values and services of ecosystems or threaten human health and safety.
The trend of a growing occurrence of fire around the world brings with it many of the consequences both direct and indirect [9]. This analysis indicated that the future for potential wildfire increases significantly in fire-prone regions of North America, South America, central Asia, southern Europe, southern Africa, and Australia [9]. Fire potential is projected to increase in these regions, from currently low to future moderate potential or from moderate to high potential. The increased fire risk is driven by climate warming in North and South America and Australia, and by the combination of temperature increases and desertification in the other regions. The analysis in Ref. [9] indicates that future increases in wildfire trends will require substantial investment of financial resources and management actions for wildfire disaster prevention and recovery.
In a discussion to the contrary [10], the argument is made that there is evidence of reduced fire worldwide today than centuries ago. Regarding fire severity, limited data are available. They indicate evidence of little change in the western USA and declines in the area of high-severity fire compared to eighteenth and nineteenth century conditions. The authors argue that direct fatalities from fire and economic losses also show no clear trends over the past 30 years [10]. Trends in indirect impacts are insufficiently quantified to be examined in any significant degree.
On the other hand, an analysis of large wildfire trends in the western USA reported a significant increase in fire numbers and area burned [11]. This was particularly true in southern mountain regions with drought. The reported increase of wildland fires in these areas has amounted to 355 km2 yr.−1. An analysis of wildfire in Russia demonstrated an acceleration of wildfire in the twenty-first century as a result of climate change [12]. Trends in wildfire on US Forest Service lands from 1970 to 2002 were examined in a 2005 paper in the Journal of Forestry [13]. Authors reported that the number of large fires has more than doubled over this period and the area burned has increased fourfold. The number of fires and area burned by wildfires in eastern Spain from 1941 to 1994 documented increasing fire activity in southern Europe [14]. They reported that even during this time period the areas and numbers of fires were increasing significantly and were associated with high fire hazard indices.
Wildfire appears to be on the increase globally but not uniformly. Drought and elevated temperatures are major factors contributing to wildfires and the hazards they pose to natural ecosystems and humans. Wildfire sizes and severity thus have the potential to present significant hazards to human health and safety and infrastructure in the twenty-first century [5].
The immediate and most obvious hazard of wildfire is the effect on vegetation. Impacts of wildfire on vegetation vary greatly, not only by vegetation type but also by the severity of the fire. Grassland vegetation in general is thought to be fire resilient, burning often and regrowing quickly after a fire event [15]. Some mixed conifer stands on the other hand have historically burned very infrequently and can take centuries to return to a climax state after a severe wildfire event [3]. The overall trend however is that areas that have been prone to burn in the past are now burning more frequently and at higher severity due to climate change [16]. Areas thought to rarely burn such as tropical systems or be incapable of burning such as permafrost are now undergoing changes that result in more frequent occurrences of fire [17, 18].
The general character of fire that occurs within a particular vegetation type or ecosystem across long successional time frames, typically centuries, is defined as the characteristic fire regime [3]. The fire regime describes the typical fire severity that occurs and the hazard it presents to humans and wildlife. But it is recognized that, on occasion, fires of greater or lesser severity also occur within a vegetation type. For example, a stand-replacing crown fire is usually seen in long fire-return-interval forests (Figure 2). The fire regime concept is useful for comparing the relative role of fire between ecosystems, describing the degree of departure from historical conditions, and assessing the relative hazards of wildfires [19]. The development of fire regime classifications has been based on fire characteristics, effects, and combinations of factors including fire frequency, periodicity, intensity, size, pattern, season, depth of burn, and severity [15, 20]. There are four main fire regimes: understory, stand replacement, mixed, and nonfire. The understory and nonfire regimes are normally not important for understanding fire hazard.
Stand replacement wildfire, 2002 Rodeo-Chediski Fire, Apache-Sitgreaves National Forest, USA (photo courtesy of Dr. Peter Ffolliott, University of Arizona).
The stand replacement regime fires are lethal to most of the dominant aboveground vegetation. Approximately 80% or more of the aboveground dominant vegetation is either consumed or dies as a result of fire, substantially changing the aboveground vegetative structure and creating substantial hazards. This regime applies to fire-susceptible forests and woodlands, shrublands, and grasslands.
The mixed regime severity of fires varies between nonlethal understory and lethal stand replacement fires with the variation occurring in space or time. First, spatial variability occurs when fire severity varies, producing a spectrum from understory burning to stand replacement within an individual fire. This results from small-scale changes in the fire environment (fuels, terrain, or weather) and random changes in plume dynamics. Within a single fire, stand replacement can occur with the peak intensity at the head of the fire, while a nonlethal fire occurs on the flanks. These changes create gaps in the canopy and small- to medium-sized openings. The result is a fine pattern of young, older, and multiple-aged vegetation patches. This type of fire regime commonly occurs in some ecosystems because of fluctuations in the fire environment [3, 21]. For example, complex terrain favors mixed-severity fires because fuel moisture and wind vary on small spatial scales. Secondly, temporal variation in fire severity occurs when individual fires alternate over time between low-intensity surface fires and high-severity stand replacement fires, resulting in a variable fire regime [15, 21]. Temporal variability also occurs when periodic cool-moist climate cycles are followed by warm-dry periods leading to cyclic (in other words, multiple decade-level) changes in the role of fire in ecosystem dynamics and human hazards. For example, in an upland forest, reduced fire occurrence during the cool-moist cycle leads to increased stand density and fuel buildup. Fires that occur during the transition between cool-moist and warm-dry periods can be expected to be more severe and have long-lasting effects on vegetation dynamics [22].
The commonly accepted term for describing the ecological, hydrological, and geological effects of a specific fire is fire severity. This term describes the magnitude of the disturbance and, therefore, reflects the degree of change in ecosystem components. Fire affects both the aboveground and belowground components of ecosystems due to energy pulses aboveground and heat pulse transferred downward into the soil. It reflects the amount of energy (heat) that is released by a fire that ultimately affects natural resources and their functions, and human infrastructure. It reflects the amount of energy (heat) that is released by a fire that ultimately affects resource responses. Fire severity is largely dependent upon the nature of the fuels available for burning, and the characteristics of combustion that occur when these fuels are burned [3, 7].
Although the literature historically contains confusion between the terms fire intensity and fire severity, a fairly consistent distinction between the two terms has been emerging in recent years. Fire managers trained in fire behavior prediction systems use the term fire intensity in a strict thermodynamic sense to describe the rate of energy released [23]. Fire intensity is concerned mainly with the rate of aboveground fuel consumption and, therefore, the energy release rate [24]. The faster a given quantity of fuel burns, the greater the intensity, the higher the severity, the greater the energy release, and the shorter the duration [25]. Fire intensity is not necessarily related to the total amount of energy produced during the burning process. Most energy released by flaming combustion of aboveground fuels is not transmitted downward. For example, Ref. [26] found that only about 5% of the heat released by a surface fire was transmitted into the ground during Australian bushfires. Therefore, fire intensity is not necessarily a good measure of the amount of energy transmitted downward into the soil, or the associated changes that occur in physical, chemical, and biological properties of the soil. For example, it is possible that a high-intensity and fast-moving crown fire will consume little of the surface litter because only a small amount of the energy released during the combustion of fuels is transferred downward to the litter surface [27]. In this case, the surface litter is blackened (charred) but not consumed. In the extreme, examples have been reported in Australia, Alaska, and North Carolina where fast-spreading crown fires did not even scorch all of the surface fuels [7]. However, if the fire also consumes substantial surface and ground fuels, the residence time on a site is greater, and more energy is transmitted into the soil. In such cases, a “white ash” or “red ash” layer is often the only postfire material left on the soil surface [27] (Figure 3). Because one can rarely measure the actual energy release of a fire, the term fire intensity can have limited practical application when evaluating ecosystem responses to fire. Increasingly, the term fire severity is used to describe the effects of fire on the different ecosystem components and human resources [3].
Red and white ash deposits on high-severity burn areas after the 2006 Brins Fire, Coconino National Forest, Arizona (photo by Daniel G. Neary, Rocky Mountain Research Station, USDA Forest Service).
Fires have been major hazards for humans for many centuries. With the development of large cities, fire became a significant risk to infrastructure and human life. The lack of organized and trained fire-fighting resources was a big factor in some of the more notorious urban fires. Rome burned in A.D. 64 during windy conditions from a fire that escaped from the Circus Maximus [28]. Of the city’s 14 districts, only 4 escaped fire damage. Deaths numbered in the thousands. An urban fire in Tokyo in 1657 destroyed 70% of the city and killed 100,000 inhabitants. Moscow burned during the French invasion in 1812 killing 55,000.
Wildfire in forests became a hazard factor in urban fires in the nineteenth century. The Miramichi Fire in Canada in 1825 burned 2 million ha of land and resulted in the death of 160–300 people. It was fueled by drought and spread at a rate of 1.6 km min−1. The real toll was unknown and could be much higher (3000) due to inaccurate accounts of persons in the rural area [29]. Seven towns were severely damaged or destroyed. The Peshtigo Fire of 1871 burned over 250,000 ha of Wisconsin and Michigan [28]. Sixteen communities were destroyed with a loss of 1150 lives.
Although human mortality rates associated with wildfires have declined in the twentieth century, wildfires continue to exact a toll on human lives because of the increase in area burned and the numbers of large fires [13]. Wildfire fatalities from 1910 to 2017 resulted in a cumulative toll of 1128 deaths for the USA [30]. Most fire years had human losses of less than 10 per year (Table 1). Of the yearly fatalities over 20 per year, 67% have occurred since 1990. Most wildfire-related deaths are caused by vehicle accidents, airplane crashes, and medical incidents. The exceptions involved fatalities in fire crews (1910, 1933, 1994, 2003, and 2013). Risks and incidents from wildfires that have spread into urban areas have been on the increase in the twenty-first century due to population expansion into wildland-urban interface areas, increased wildfire area coverage, greater numbers and size of wildfires, and higher fire severity [5]. Consequently, urban fatalities from wildfire incursions into urban areas have increased since 2017.
Fatality grouping | Number per grouping | Percentage |
---|---|---|
0 | 3 | 1.3 |
1–4 | 13 | 16.7 |
5–9 | 18 | 23.1 |
10–14 | 20 | 25.7 |
15–19 | 11 | 14.1 |
20–24 | 7 | 11.5 |
>25 | 6 | 7.6 |
USA wildfire-related fatalities per year 1929–2017 by grouping (National Interagency Fire Center 2019).
Australia suffered high human fatalities from the Black Saturday Kilmore East Fire in Victoria in 2009 [31]. Over 450,000 ha of forest and native bush burned in February of 2009 due to drought conditions and gale force winds. Speeds of 46–68 km hr.−1 with gusts to 91 km hr.−1 from hot air originating in the deserts of central Australia drove fire spreads of 68–153 m min−1. Spot fires developed 5–33 km ahead of the main fire front. The 173 human fatalities occurred mainly among the local rural population due to the rapid fire spread and insufficient time to evacuate the wildfire-threatened areas. At one point, the fires consumed 100,000 ha in <12 hours. Wildfires of this size and severity are extremely hazardous and almost impossible to comprehend.
In 2017, Portugal experienced its most deadly fire season on record losing at least 66 people to catastrophic summer wildfires. The following year, wildfires in Greece damaged over 2000 homes and killed at least 100 people. Although nationally deaths due to wildfires are on the decline, record-breaking wildfires in northern California in 2017–2018 produced substantial increases in deaths, mostly civilians [32]. A total of 8527 fires burned an area of 766,439 ha and resulted in 102 firefighter and civilian deaths.
In the summer of 2018, the Camp Fire in Northern California burned 62,053 ha and destroyed 18,804 structures including the entire town of Paradise, California. In total, the fire caused $16.5 billion in damages with over a quarter of those damages uninsured [33]. It was the costliest single natural disaster in the world to that point and caused the bankruptcy of a major utility provider, the Pacific Gas and Electric Company, which was held responsible for starting the fire due to faulty equipment.
Unfortunately, it is part of a trend in California, driven mostly by climate change, of increasing destruction and cost of seasonal wildfires. Just the previous year (2017), in December, the Thomas Fire destroyed at least 1063 structures at a cost of $2.2 billion in damages [34] and was preceded by only a couple of months by a complex of fires in the northern part of the state, which destroyed at least 8900 structures and cost in excess of $14.5 billion in damages [35].
Similar trends are being seen around the world. In 2017, Portugal experienced its most deadly and expensive fire season on record due to catastrophic summer wildfires. The 2018 wildfires in Greece suffered through what was considered to be one of the worst fire events in Europe in over a century. Canada set successive records in area burned with 1,216,053 ha 2017 and 1,298,450 ha 2018, losing at least 305 and 50 structures in those respective years [36].
Common factors in these events include months of below-average precipitation followed by untimely ignitions, both natural and anthropogenic and wind events that caused fires to spread in a dramatic fashion. The speed and ferocity with which these fires burned were commonly described as “unheard of” in the past and in many cases completely uncontrollable. The only choice of fire managers at the time was to stand-down and wait for conditions to improve. Unfortunately, this predicament appears to be a hazard becoming more common worldwide.
Fire events, particularly in California, USA, where dense population areas border highly fire-prone wildland areas have seen staggering losses as described above. A study conducted by the U.S. Department of the Interior in 2016 estimated that total “costs,” which includes preparedness, mitigation, and suppression, as well as “losses,” which includes both direct (e.g., deaths, structure loss, timber loss, etc.) and indirect (e.g., property devaluation, supply chain disruption, evacuation costs, etc.) of wildfire within the USA range from $71.1 to $347.8 billion annually [32]. Estimates like these continue the long debate of who should pay for natural disaster losses in an era of global warming as they become more expensive and what should the future costs be to insure assets in fire-prone areas? These are difficult and complex questions to answer and are made even more urgent in an era where losses seem to be compounded every year.
Another immediate effect of fire is the release of gases and particulate pollutants by the combustion of biomass and soil organic matter. Air quality in large-scale airsheds can be degraded during and following fires [37]. Among the pollutants emitted, the release of fine particulate matter and ozone (O3) can have particularly deleterious effects on human health, which can be exacerbated when smoke from wildfires affect large population centers. Unfortunately, our understanding of the hazard that large-scale wildfires have on air quality is lacking and current estimates of emissions and impacts may be significantly underestimated [38].
Wildfires can cause both short- and long-term air quality impacts that are usually viewed as negative effects on environmental quality (Figure 4). Scientific information about air pollution from wildfires is motivated by government policies to restore the role of fire in ecosystems, to improve air quality, to protect human health, and to minimize emissions of greenhouse gases that are driving climate change [37]. Managing both fire and air quality to the standards set by national and regional governments requires sophisticated scientific knowledge of fire-related air pollution, a delicate management balancing act, and comprehensive educational outreach to both the public and government officials. The three main components of wildland fire and air quality are air resource, scale of impact, and fire management. Air resource includes such factors as smoke source, ambient air quality, and effects on receptors. Scales at which air quality is affected by wildland fires range from site and event to regional and global. Since wildland fire is a pervasive global, regional, and local phenomenon (Figure 5), air quality issues and interactions are inter-regional, transnational, and global. Fire management factors that are involved in air quality include planning, operations, and monitoring [39].
Smoke plume from the Schultz fire, June 2002, Coconino National Forest, Arizona (photo courtesy of USDA Forest Service, Peaks Ranger District, Coconino National Forest).
Regional air quality impacts from smoke generated by the Wallow Fire, 2011, Arizona, USA (image courtesy of MODIS web, U.S. National Aeronautics and Space Administration).
National and international air quality standards are set by legislative acts or agency regulations to protect the human population of negative health effects of fire-derived air pollutants [40, 41]. For most of the twentieth century, smoke emissions from prescribed fires were treated as human-caused, while wildfires were considered to be natural [37]. Policy debates have blurred the distinct separation between the two types of fires since some lightening starts are managed as prescribed natural fires for ecosystem restoration and fuel reduction purposes, and some wildfires have human ignition sources and burn in fuel loads made unnaturally high by human activity or the lack of management.
Some of the key pollutants targeted in air quality regulations include PM10 (particulate matter <10 μm in diameter), PM2.5 (particulate matter <2.5 μm in diameter) total suspended particulates, sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), ozone (O3), and lead and other heavy metals. The amounts and types of pollutants released by fires are affected by area burned, fuel characteristics prior to combustions, fire behavior, combustion stages, level of fuel consumption, and source strength [37]. Wildfires occur as episodic events that can threaten public health, cause smoke damage to buildings, and disrupt public activities [42]. Particulate concentrations rarely affect large city’s air quality, but they can rise to harmful levels (e.g., 600 μg m−3) in smaller communities located in forested regions. In some regions, wildfire smoke is the main cause of visibility reductions.
Although the public can be exposed to and become affected by wildland smoke and its constituents, the main concern is for firefighters and fire managers. Anyone who has been involved in wildfire suppression or prescribed fire management understands this. Unlike structural firefighters who utilize PBAs (personal breathing apparatus), wildland fire fighters at best have dust masks that reduce exposure to dust and large particulates but not small particulates and gases. Many data gaps exist in the understanding of human health hazards of wildland fire suppression and management [43].
The individuals whose health is most at risk include those with cardiopulmonary diseases and the elderly. However, normally healthy individuals, such as firefighters, are at increased risk of developing cardiopulmonary disease over the long term. Effects of PM10 and PM2.5 particulates, dust-borne silica, aldehydes, carbon monoxide, polyaromatic hydrocarbons, ozone, and heavy metals are poorly understood. The temporary nature of wildland fire personnel assignments make compilation of long-term health data difficult or impossible to achieve. Permanent fire personnel can be adequately assessed and monitored, but the bulk of wildland fire personnel cannot be properly evaluated.
In many cases, the greatest hazard posed by wildfires occurs in the postfire period when flooding events, made worse by the loss of vegetation, create debris flows (Figure 6). These catastrophic events often result in property and infrastructure destruction and in some cases loss of life [3, 7]. Debris flows typically occur in areas with steep topography after being subjected to wetting rains, which mobilize soil, rock, and other debris into a concrete-like torrent that moves downslope toward low-lying areas. These flows tend to have immense force due to the speed in which they move and can cause total destruction of objects in their path and contribute to human mortality. For example, it has been estimated based on insurance claims following the Thomas Fire southern California in 2017 that postfire damage assessments were mostly related to massive debris flows that originated in the burned area. The economic cost of these debris flows exceeded $1.8 billion [34].
Flood flows in an urbanized area below the 2010 Schultz Fire in Arizona, USA (photo by Daniel G. Neary, Rocky Mountain Research Station, USDA Forest Service).
While these events can be highly destructive and very costly, they can also be somewhat mitigated through prefire planning and zoning regulations as well as adequate infrastructure. The problem is that often the size of flooding events following wildfire can fall into a once in a century or even a millennia event making the cost justification for accommodating such an event beforehand challenging. However, as these events begin to become more common and costs begin to escalate, the argument for increased preparation must be considered.
Take for example the Schultz Fire, which occurred just outside of Flagstaff, Arizona, USA, in 2010. The fire burned on steep slopes within the Coconino National Forest immediately adjacent to subdivisions located in the valley below. Summer rainfall events following the fire initiated massive flooding and debris flows into the area. Fortunately, there was only one flood-related mortality. While estimates of the costs related directly to the fire suppression were around $9,460,909, the cost of the response to the flood was nearly twice that at $16,470,682. However, both these costs were outdone by the nearly $33,172,803 that was invested in infrastructure over the following 4 years needed to mitigate future flood risk. The financial analysis published on this event [44] in 2013 also pointed out that the cost estimates were only for official expenditures by government agencies and local utilities. The loss in property devaluation, infrastructure damage, increased insurance premiums, and other associated costs totaled more than $60 million in additional losses, making the argument for increased spending on hazard mitigation valid. The economic hazards of the fire were 10 times the funds expended to suppress the Schultz Fire. And this accounting did not include the value of lost or damaged natural resources.
Landscape scale fire events can have profound influence on elements of water quality including increasing turbidity, temperature, and contaminants sometimes for many years following the fire [45, 46, 47, 48, 49]. One study near Denver, Colorado, found that average spring and summer water temperatures increased by 5–6°C and that nitrate concentrations increased over 100 times greater than typical stream concentrations following the Hayman Fire in 2002. In addition, summer storms continued to mobilize sediment and create surface runoff corresponding to spikes in nutrient concentration and turbidity for years following the fire event [50].
Ecologically, flooding events following a wildfire can be catastrophic on aquatic communities. This is due primarily to the depletion of oxygen and the increase in turbidity in ash-laden debris flows (Figure 7). The two biggest factors affecting long-term recovery and health of aquatic habitats impacted by fire are physical channel stability and water temperature [51]. Loss of streamside vegetation due to fire and instability or changes in physical habitat due to flooding can diminish aquatic habitats for decades. The timing and severity of flooding events are directly related to preceding fire incident. Typically, low order or headwater streams are more susceptible to vegetation changes and flooding than higher order streams; however, depending on the magnitude of input, even larger rivers and reservoirs can be subjected to diminished water quality and loss of aquatic species due to ash-laden flow inputs.
Post-fire runoff with high concentrations of sediment, ash, and charcoal, Rodeo-Chediski Fire, Apache-Sitgreaves National Forest, Arizona, 2002 (photo by Daniel G. Neary, Rocky Mountain Research Station, USDA Forest Service).
The increase in scope and scale of wildfire worldwide tends to have a more intrinsic effect on ecosystem function, affecting qualities that are not always measureable in economic terms. Degradation of soil [8] and water resources [3, 5] along with landscape scale changes in vegetation [51] has the ability to shape ecosystems for decades if not centuries [52]. These cascading effects are becoming selective for plant and animal species, which are pioneer species at first and later are disturbance oriented as these systems begin the slow process of recovery, often punctuated by reoccurring disturbance events such as flooding or even subsequent fire events. At relatively small scales, the input of fire, even high-severity fire, can introduce heterogeneity into a landscape that can be beneficial to the ecosystem as a whole, creating niches and freeing up resources for new species to establish in an area. However, there is a size threshold that once crossed starts to become an impediment to recovery and results in long-term loss of habitat suitability for specific species. For example, the loss of seed sources both in the soil bank and from mature plants for obligate seed species can have a limiting effect on the recolonization and distribution of many long-lived conifer species [53]. Similarly, the impact from flooding events on fragmented streams due to anthropogenic or natural barriers may make the recolonization of some aquatic species impossible and result in permanent extirpation [54]. In these cases, wildfire begins to act on a genetic level to influence the long-term stability and ecosystem function of an area. This poses a serious environmental hazard due to the permanent loss of important species in an ecosystem and increasing the risk of desertification [8].
Humans live in or adjacent to wildland ecosystems that burn periodically and are part of nearly all ecosystems that are in the pyrosphere. There are many hazards posed by wildfire and certain consequences of living in these ecosystems. Most are associated with wildfire but the increased use of prescribed fire is an issue because of associated risks with human attempts to manage ecological goals. The economic and social consequences of wildfire have been discussed by a number of authors [3, 5, 7, 42]. These consequences involve cultural and economic loss, social disruption, infrastructure damage, human injury and mortality, damage to natural resources, and deterioration in air quality. The economic and human health and safety costs are on the rise due to increasing wildland-urban interface problems and extreme wildfire behavior brought on by climate change. In the past, urban fires have been the greatest threat to human health and safety killing over 100,000 people.
With modern fire control organizations in cities, the greatest hazard has shifted to wildlands. The Miramichi Fire in Canada’s eastern woodlands in 1825 may have killed 3000. In the USA, the most devastating wildland wildfire known was the Peshtigo Fire of 1871 that killed over 1150 people. Recent wildfires in Australia in 2009 and California in 2017 and 2018 claimed up to 270 lives in a single fire event in each country. The increasing development of the wildland-urban interface in the USA and other countries is raising the risks that a similar fatal event could occur in the future. Large fatalities due to wildfire hazards may be a thing of the past, but frequent deaths such as those in Australia in 2009 may tally up to greater numbers. In addition, the economic hazards of wildfires are growing. The large amounts of funds needed to suppress large wildfires are a small fraction of the total economic damage. Nationally, in the USA, fire suppression, collateral infrastructure damage, urban destruction, and other wildfire mitigation efforts exceed the total management budgets of the state and federal agencies.
World ecosystems have been modified extensively by fire. We live on a “fire planet” [1, 2, 42]. With larger human populations and a changing, drying climate, the impact of fire on humans and the hazards faced by our natural and developed world will continue to increase. The increase in wildfire hazards in the twenty-first century will require higher levels of training, increased investments in wildfire personnel and infrastructure, greater wildfire awareness, and improved planning to reduce fire impacts.
The authors would like to thank the Rocky Mountain Research Station, Air-Water-Aquatic Environments Research Program, and the Program Manager, Frank McCormick, for support of this effort.
There are no “Conflicts of Interest” associated with this paper. It was produced by US Forest Service employees during normal work hours and on appropriated funding.
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Many of these genes contribute to immunity. Particularly, MHC‐encoded class I and class II molecules, which are typically highly polymorphic and polygenic, are central in defining the specificity of the adaptive immune response. Among the diversity of genes associated with disease resistance, MHC genes are particularly interesting as they are associated with resistance and susceptibility to a wide range of diseases, some of which produce important economic losses in livestock. Enzootic bovine leukosis is an infectious disease caused by the retrovirus bovine leukemia virus (BLV), with an important economic impact, mainly in dairy herds. In this chapter, MHC‐associated genetic resistance to BLV is revised. Certain alleles of the bovine MHC (BoLA) class II locus have been found strongly associated with resistance to viral dissemination. Genetic selection of resistant animals emerges as a natural strategy for the control of infectious diseases, especially when there is no other alternative of control or prevention, as vaccines. Founded on this knowledge, a BLV control program based on selection of genetically resistant cattle was designed. The proof of concept indicates that this strategy is feasible to implement in dairy herds.",book:{id:"5405",slug:"trends-and-advances-in-veterinary-genetics",title:"Trends and Advances in Veterinary Genetics",fullTitle:"Trends and Advances in Veterinary Genetics"},signatures:"Silvina Elena Gutiérrez, Eduardo Néstor Esteban, Claudia María\nLützelschwab and Marcela Alicia Juliarena",authors:[{id:"188776",title:"Dr.",name:"Silvina Elena",middleName:null,surname:"Gutiérrez",slug:"silvina-elena-gutierrez",fullName:"Silvina Elena Gutiérrez"},{id:"189290",title:"Dr.",name:"Marcela Alicia",middleName:null,surname:"Juliarena",slug:"marcela-alicia-juliarena",fullName:"Marcela Alicia Juliarena"},{id:"189291",title:"Dr.",name:"Eduardo Néstor",middleName:null,surname:"Esteban",slug:"eduardo-nestor-esteban",fullName:"Eduardo Néstor Esteban"},{id:"189293",title:"Dr.",name:"Claudia María",middleName:null,surname:"Lützelschwab",slug:"claudia-maria-lutzelschwab",fullName:"Claudia María Lützelschwab"}]},{id:"52940",doi:"10.5772/65848",title:"Beyond Fifty Shades: The Genetics of Horse Colors",slug:"beyond-fifty-shades-the-genetics-of-horse-colors",totalDownloads:3239,totalCrossrefCites:3,totalDimensionsCites:5,abstract:"Since the dawn of horse domestication, coat colors have always fascinated humankind. In the last century, knowledge of genetics and development of scientific tools have become powerful enough so that the effects of many DNA mutations could be critically studied. Coat color nomenclature varies according to countries and breed associations; in addition, many factors can modify the color of the coat, such as sun exposure, age, sex, and nutritional status of the animal. Nevertheless, horses are capable of producing only two pigments. Several genes have been indicated as putative to coat color modification, altering the basic color by dilution, redistribution, or lacking of pigments.",book:{id:"5405",slug:"trends-and-advances-in-veterinary-genetics",title:"Trends and Advances in Veterinary Genetics",fullTitle:"Trends and Advances in Veterinary Genetics"},signatures:"Adriana Pires Neves, Eduardo Brum Schwengber, Fabiola Freire\nAlbrecht, José Victor Isola and Liana de Salles van der Linden",authors:[{id:"188768",title:"Associate Prof.",name:"Adriana",middleName:null,surname:"Pires Neves",slug:"adriana-pires-neves",fullName:"Adriana Pires Neves"},{id:"188993",title:"Dr.",name:"Eduardo",middleName:null,surname:"Brun Schwengber",slug:"eduardo-brun-schwengber",fullName:"Eduardo Brun Schwengber"},{id:"188994",title:"Mrs.",name:"Fabiola",middleName:null,surname:"Freire Albrecht",slug:"fabiola-freire-albrecht",fullName:"Fabiola Freire Albrecht"},{id:"188996",title:"Ph.D. Student",name:"Liana",middleName:null,surname:"de Salles van der Linden",slug:"liana-de-salles-van-der-linden",fullName:"Liana de Salles van der Linden"},{id:"188997",title:"Mr.",name:"José Victor",middleName:null,surname:"Vieira Isola",slug:"jose-victor-vieira-isola",fullName:"José Victor Vieira Isola"}]},{id:"59305",doi:"10.5772/intechopen.74008",title:"Avian Coccidiosis, New Strategies of Treatment",slug:"avian-coccidiosis-new-strategies-of-treatment",totalDownloads:3735,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The control of avian coccidiosis since the 1940s has been associated with the use of ionophores and chemical drugs. Recently, a significant interest in natural sources has developed due to the pressure to poultry industry to produce drug-free birds. Consequently, the search of products derived from plants and other natural sources has increased in the last years. Today, many commercial products containing essential oils, extracts, and other compounds are available. The use of these compounds of natural origin is related to an increased immune response, a body weight gain, destruction of oocyst, among other benefits. The main inconvenience of these products is the act on some species of Eimeria, but not all. This genetic variability found in the parasite makes the use of products difficult to control and treat coccidiosis. In this chapter, several proposals of treatment are presented based on the use of natural products, considering the new strategies of treatment with minimal consequences to birds.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Rosa Estela Quiroz-Castañeda",authors:[{id:"187735",title:"Dr.",name:"Rosa Estela",middleName:null,surname:"Quiroz Castañeda",slug:"rosa-estela-quiroz-castaneda",fullName:"Rosa Estela Quiroz Castañeda"}]},{id:"58461",doi:"10.5772/intechopen.72638",title:"Natural Compounds as an Alternative to Control Farm Diseases: Avian Coccidiosis",slug:"natural-compounds-as-an-alternative-to-control-farm-diseases-avian-coccidiosis",totalDownloads:2093,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Coccidiosis is one of the most aggressive and expensive parasite diseases in poultry industry worldwide. Currently, the most used control techniques are chemoprophylaxis and anticoccidial feed additives. Although there is a great variety of commercial anticoccidial drugs and vaccines in the market, there is also a significant resistance to use them in animals with human as final consumer. To date, none available product offers effective protection toward coccidiosis; however, the search for novel strategies to control this disease continues, and natural products have arisen as a potential way to cope with avian coccidiosis. In this chapter, we highlight recent advances in natural compounds, their anticoccidial properties, and mechanisms.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Mayra E. Cobaxin-Cárdenas",authors:[{id:"223051",title:"Dr.",name:"Mayra E.",middleName:null,surname:"Cobaxin-Cárdenas",slug:"mayra-e.-cobaxin-cardenas",fullName:"Mayra E. Cobaxin-Cárdenas"}]},{id:"58679",doi:"10.5772/intechopen.72636",title:"Genome-Based Vaccinology Applied to Bovine Babesiosis",slug:"genome-based-vaccinology-applied-to-bovine-babesiosis",totalDownloads:1185,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Genomics approaches in veterinary research have been a very useful tool to identify candidates with potential to be used in prevention of animal diseases. In Babesia, genome information analysis has elucidated a wide variety of protein families and some members are described in this chapter. Here, we present some of the most recent studies about B. bovis and B. bigemina genomes where some proteins have been identified with potential to prevent infections by these parasites.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Juan Mosqueda, Diego Josimar Hernández-Silva and Mario\nHidalgo-Ruiz",authors:[{id:"220191",title:"Dr.",name:"Juan",middleName:null,surname:"Mosqueda",slug:"juan-mosqueda",fullName:"Juan Mosqueda"}]}],mostDownloadedChaptersLast30Days:[{id:"59305",title:"Avian Coccidiosis, New Strategies of Treatment",slug:"avian-coccidiosis-new-strategies-of-treatment",totalDownloads:3733,totalCrossrefCites:2,totalDimensionsCites:4,abstract:"The control of avian coccidiosis since the 1940s has been associated with the use of ionophores and chemical drugs. Recently, a significant interest in natural sources has developed due to the pressure to poultry industry to produce drug-free birds. Consequently, the search of products derived from plants and other natural sources has increased in the last years. Today, many commercial products containing essential oils, extracts, and other compounds are available. The use of these compounds of natural origin is related to an increased immune response, a body weight gain, destruction of oocyst, among other benefits. The main inconvenience of these products is the act on some species of Eimeria, but not all. This genetic variability found in the parasite makes the use of products difficult to control and treat coccidiosis. In this chapter, several proposals of treatment are presented based on the use of natural products, considering the new strategies of treatment with minimal consequences to birds.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Rosa Estela Quiroz-Castañeda",authors:[{id:"187735",title:"Dr.",name:"Rosa Estela",middleName:null,surname:"Quiroz Castañeda",slug:"rosa-estela-quiroz-castaneda",fullName:"Rosa Estela Quiroz Castañeda"}]},{id:"58604",title:"Genomics of Apicomplexa",slug:"genomics-of-apicomplexa",totalDownloads:1193,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Apicomplexa is a eukaryotic phylum of intracellular parasites with more than 6000 species. Some of these single-celled parasites are important pathogens of livestock. At present, 128 genomes of phylum Apicomplexa have been reported in the GenBank database, of which 17 genomes belong to five genera that are pathogens of farm animals: Babesia, Theileria, Eimeria, Neospora and Sarcocystis. These 17 genomes are Babesia bigemina (five chromosomes), Babesia divergens (514 contigs) and Babesia bovis (four chromosomes and one apicoplast); Theileria parva (four chromosomes and one apicoplast), Theileria annulata (four chromosomes), Theileria orientalis (four chromosomes and one apicoplast) and Theileria equi (four chromosomes and one apicoplast); Eimeria brunetti (24,647 contigs), Eimeria necatrix (4667 contigs), Eimeria tenella (12,727 contigs), Eimeria acervulina (4947 contigs), Eimeria maxima (4570 contigs), Eimeria mitis (65,610 contigs) and Eimeria praecox (53,359 contigs); Neospora caninum (14 chromosomes); and Sarcocystis neurona strains SN1 (2862 contigs) and SN3 (3191 contigs). The study of these genomes allows us to understand their mechanisms of pathogenicity and identify genes that encode proteins as a possible vaccine antigen.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Fernando Martínez-Ocampo",authors:[{id:"195818",title:"Dr.",name:"Fernando",middleName:null,surname:"Martinez",slug:"fernando-martinez",fullName:"Fernando Martinez"}]},{id:"59436",title:"Pathogenomics and Molecular Advances in Pathogen Identification",slug:"pathogenomics-and-molecular-advances-in-pathogen-identification",totalDownloads:1657,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Today exists a spread spectrum of tools to be used in pathogen identification. Traditional staining and microscopic methods as well as modern molecular methods are presented in this chapter. Pathogen identification is only the beginning to obtain information related to pathogenicity of the microorganism in the near future. Once the pathogen is identified, genome-sequencing methods will provide a significant amount of information that can be elucidated only through bioinformatics methods. In this point, pathogenomics is a powerful tool to identify potential virulence factors, pathogenicity islands, and many other genes that could be used as therapeutic targets or in vaccine development. In this chapter, we present an update of the molecular advances used to identify pathogens and to obtain information of their diversity. We also review the most recent studies on pathogenomics with a special attention on pathogens of veterinary importance.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Rosa Estela Quiroz-Castañeda",authors:[{id:"187735",title:"Dr.",name:"Rosa Estela",middleName:null,surname:"Quiroz Castañeda",slug:"rosa-estela-quiroz-castaneda",fullName:"Rosa Estela Quiroz Castañeda"}]},{id:"58730",title:"Metagenomics and Diagnosis of Zoonotic Diseases",slug:"metagenomics-and-diagnosis-of-zoonotic-diseases",totalDownloads:1827,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Zoonotic diseases represent a public health problem worldwide, since approximately 60% of human pathogens have a zoonotic origin. A variety of methodologies have been developed to diagnose zoonosis, including culture-dependent and immunological-based methods, which allow the identification of a huge range of pathogens. However, some of them are not detected easily with these approaches. Additionally, molecular tests have been developed, and they are designed to identify a single pathogen or mixtures of them. In this context, metagenomics comes as an alternative to get genome sequences of different microorganisms, which comprise a microbial community. Metagenomics have been used to characterize microbiomes and viromes, which are not cultivable under laboratory conditions. This methodology could be a powerful tool in the diagnosis of zoonotic diseases because it allows not only identification of genus and species, but also detection of some proteins in specific conditions on specific tissues, through structural and functional metagenomics, respectively.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Laura Inés Cuervo-Soto, Silvio Alejandro López-Pazos and Ramón\nAlberto Batista-García",authors:[{id:"201362",title:"Dr.",name:"Ramón Alberto",middleName:null,surname:"Batista-García",slug:"ramon-alberto-batista-garcia",fullName:"Ramón Alberto Batista-García"}]},{id:"58461",title:"Natural Compounds as an Alternative to Control Farm Diseases: Avian Coccidiosis",slug:"natural-compounds-as-an-alternative-to-control-farm-diseases-avian-coccidiosis",totalDownloads:2093,totalCrossrefCites:1,totalDimensionsCites:3,abstract:"Coccidiosis is one of the most aggressive and expensive parasite diseases in poultry industry worldwide. Currently, the most used control techniques are chemoprophylaxis and anticoccidial feed additives. Although there is a great variety of commercial anticoccidial drugs and vaccines in the market, there is also a significant resistance to use them in animals with human as final consumer. To date, none available product offers effective protection toward coccidiosis; however, the search for novel strategies to control this disease continues, and natural products have arisen as a potential way to cope with avian coccidiosis. In this chapter, we highlight recent advances in natural compounds, their anticoccidial properties, and mechanisms.",book:{id:"5543",slug:"farm-animals-diseases-recent-omic-trends-and-new-strategies-of-treatment",title:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment",fullTitle:"Farm Animals Diseases, Recent Omic Trends and New Strategies of Treatment"},signatures:"Mayra E. 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