Ubiquitin conjugation determines the intracellular fate of a substrate protein.
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Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{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"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"},{slug:"intechopen-identified-as-one-of-the-most-significant-contributor-to-oa-book-growth-in-doab-20210809",title:"IntechOpen Identified as One of the Most Significant Contributors to OA Book Growth in DOAB"}]},book:{item:{type:"book",id:"10766",leadTitle:null,fullTitle:"Landscape Architecture Framed from an Environmental and Ecological Perspective",title:"Landscape Architecture Framed from an Environmental and Ecological Perspective",subtitle:null,reviewType:"peer-reviewed",abstract:"Landscape architecture involves designing, planning, and managing natural and built environments. Its goal is to balance natural spaces with the human element. As such, new methods and analysis techniques are necessary for creating healthy and user-friendly spaces in both urban developments and natural environments. This book discusses these approaches to planning and designing natural spaces with a focus on sustainability.",isbn:"978-1-83969-699-2",printIsbn:"978-1-83969-698-5",pdfIsbn:"978-1-83969-700-5",doi:"10.5772/intechopen.94789",price:119,priceEur:129,priceUsd:155,slug:"landscape-architecture-framed-from-an-environmental-and-ecological-perspective",numberOfPages:116,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"bf47534a17fef030dc256b541482553c",bookSignature:"Mustafa Ergen and Yaşar Bahri Ergen",publishedDate:"April 28th 2022",coverURL:"https://cdn.intechopen.com/books/images_new/10766.jpg",numberOfDownloads:660,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:0,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"March 15th 2021",dateEndSecondStepPublish:"April 12th 2021",dateEndThirdStepPublish:"June 11th 2021",dateEndFourthStepPublish:"August 30th 2021",dateEndFifthStepPublish:"October 29th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"166961",title:"Dr.Ing.",name:"Mustafa",middleName:null,surname:"Ergen",slug:"mustafa-ergen",fullName:"Mustafa Ergen",profilePictureURL:"https://mts.intechopen.com/storage/users/166961/images/system/166961.png",biography:"Mustafa Ergen graduated from the Department of Landscape Architecture, Abant İzzet Baysal University, Turkey, in 2000. In 2005, he completed his first master’s degree in Urban and Regional Planning at the Gebze Institute of Technology, Turkey. He completed his second master’s degree in Landscape Architecture at Anhalt University of Applied Sciences, Germany, in 2006. During 2007–2008, he studied Geographic Information Systems and Remote Sensing at the Mediterranean Agronomic Institute of Chania, Greece, and was granted a specialization diploma in Environmental Management. He also received a Dr.Eng from the Technical University of Dortmund, Germany. Currently, he works in the Department of Landscape Architecture, Faculty of Agriculture, Sakarya University of Applied Sciences, Turkey.",institutionString:"Sakarya University of Applied Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"4",totalChapterViews:"0",totalEditedBooks:"3",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"167276",title:"Associate Prof.",name:"Yasar",middleName:"Bahri",surname:"Ergen",slug:"yasar-ergen",fullName:"Yasar Ergen",profilePictureURL:"https://mts.intechopen.com/storage/users/167276/images/system/167276.png",biography:"Yasar Bahri Ergen graduated from Istanbul State Academy of Engineering and Architecture, Department of Architecture, in 1973. In 1976 he completed his master’s degree in Urban Planning at the Istanbul State Academy of Engineering and Architecture. From 1983 to 1984 he lived in the USA to conduct research in his field of expertise. He received a doctorate degree from Gazi University in 1987. His academic life started in 1982 and took a turn from the USA to Gazi University. In 1995 he established the Department of Urban and Regional Planning at Bozok University and in 2009 he established the Department of Urban and Regional Planning at Amasya University. In 2017 he established the Faculty of Fine Arts and Design at Siirt University In 2018 he received the title of associate professor. After that, he started to work at Aksaray University in 2021 and still works at Aksaray University.",institutionString:"Aksaray University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"132",title:"Environmental Planning",slug:"environmental-planning"}],chapters:[{id:"80638",title:"Introductory Chapter: Understanding the Ataturk Forest Farm from an Ecological Perspective",doi:"10.5772/intechopen.102880",slug:"introductory-chapter-understanding-the-ataturk-forest-farm-from-an-ecological-perspective",totalDownloads:15,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:null,signatures:"Mustafa Ergen, Bayram Cemil Bilgili and Yaşar Bahri Ergen",downloadPdfUrl:"/chapter/pdf-download/80638",previewPdfUrl:"/chapter/pdf-preview/80638",authors:[{id:"166961",title:"Dr.Ing.",name:"Mustafa",surname:"Ergen",slug:"mustafa-ergen",fullName:"Mustafa Ergen"}],corrections:null},{id:"78138",title:"Erosion Quantification and Management: Southeastern Nigeria Case Study",doi:"10.5772/intechopen.99551",slug:"erosion-quantification-and-management-southeastern-nigeria-case-study",totalDownloads:153,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Soil erosion in Southeastern Nigeria is assuming an unusual dimension despite efforts by successive governments to control the phenomenon. Agronomic activities on eroding surfaces can give rise to landscapes much different from the original. Research activities in erosion quantification, the findings and how their applications have contributed to soil erosion management are highlighted. A key factor is the community efforts which have been relegated to a top-down approach occasioned by land use, land tenure and technological changes. The system is often a preventive management approach which achieves ecological and economic benefits. This chapter also discusses the indigenous methods of soil conservation and proposes their inclusions for sustainable management. To manage soil erosion in the region, emphasis must be placed on preventive management rather than crisis-management. Such approach will ensure that fewer resources are expended and land is appropriately conserved. To this end, soil can play its many environmental roles adequately.",signatures:"Frank Chibuzor Okenmuo",downloadPdfUrl:"/chapter/pdf-download/78138",previewPdfUrl:"/chapter/pdf-preview/78138",authors:[{id:"355142",title:"Dr.",name:"Frank",surname:"Chibuzor Okenmuo",slug:"frank-chibuzor-okenmuo",fullName:"Frank Chibuzor Okenmuo"}],corrections:null},{id:"78209",title:"Therapeutic Landscapes: A Natural Weaving of Culture, Health and Land",doi:"10.5772/intechopen.99272",slug:"therapeutic-landscapes-a-natural-weaving-of-culture-health-and-land",totalDownloads:153,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:1,abstract:"Current concepts of therapeutic landscape combine landscape with principles of holistic health and the interaction of social, affective and material factors. As social tensions widen the gap between the places of emotional retreat and healing from those of everyday sociability, concepts of therapeutic landscape are evolving to reflect society’s current values. This chapter examines how cultural place-based values affect and maintain physical, emotional, mental and spiritual health and well-being in the context of a therapeutic landscape. Five case studies from Australasia, Africa, Middle East and Latin America are analysed to understand better the interrelationships between land, culture and health that make an environment therapeutic. The case studies were selected based on their engagement with the cultural traditions of landscape architecture and how the boundaries of these cultural traditions are negotiated within a modern context. The chapter contributes to the knowledge base of landscape architects and academics interested in the role of culture in producing and maintaining therapeutic landscapes by presenting a cross-cultural analysis to illustrate a range of strategies for incorporating cultural traditions and customs into modern landscape architectural contexts to promote health and well-being.",signatures:"Bruno Marques, Jacqueline McIntosh and Hayley Webber",downloadPdfUrl:"/chapter/pdf-download/78209",previewPdfUrl:"/chapter/pdf-preview/78209",authors:[{id:"162973",title:"Dr.",name:"Jacqueline",surname:"McIntosh",slug:"jacqueline-mcintosh",fullName:"Jacqueline McIntosh"},{id:"355200",title:"Dr.",name:"Bruno",surname:"Marques",slug:"bruno-marques",fullName:"Bruno Marques"},{id:"355394",title:"Ms.",name:"Hayley",surname:"Webber",slug:"hayley-webber",fullName:"Hayley Webber"}],corrections:null},{id:"78330",title:"Community Attachment and Environmental Stewardship: A Peri-Urban Perspective",doi:"10.5772/intechopen.99495",slug:"community-attachment-and-environmental-stewardship-a-peri-urban-perspective",totalDownloads:100,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This Chapter questions the negligence of attachment scholarship in the context of environmental stewardship with a specific focus in peri-urban areas. This Chapter has illuminated the imperatives of considering place attachement as an important factor in realizing environment stewardship in peri-urban areas. Three selected hamlets (Nzasa, Kisarawe and Pugu-Kibaoni) constitute the study area. A standard closed-ended questionnaire for assessing the extent of attachment of the community was deployed. Literature review on the other hand was used to map baseline information of the study area including the historical significance of the Pugu and Kazimzumbwi forest reserves. Three attachment attributes were explored;, community knowlegiability levels of the area; level of thoughts and feelings of the area; and the extent of community connection to natural resources in the area. It was revealed that the extent of community connection to the forest reserves are relatively strong. The study revealed considerable contrast on forest knowledgiability levels among men and women in the Pugu and Kazimzumbwi forest reserves. Males are generally revealed to be more knowledgiable of the Pugu and Kazimzumbwi forest reserves as compared to their female counterparts. The study revealed that there was substantial relationship between residence status and the level of thoughts and feelings on the forest reserves. The study has shown that natives have more thoughts and feelings of the present and the future of the forest reserves as compared to those who migrated from other parts of the country. The findings suggest that community attachment is of considerable importance in influencing environmental behavior either positively or negatively. Whilist the empirical evidence are drawn from the peri-urban areas of Pugu and Kazimzumbwi forest reserves of Dar es Salaam city, the message thereoff is representing a broad reality in the peri-urban areas of the Global South. The inclusion of community attachment perspective in negotiating environmental stewardship is advocated for as it might contribute in addressing the growing degradation of natural resources in peri-urban areas which has been increasingly declining.",signatures:"Lazaro Eliyah Mngumi and Yonggui Chen",downloadPdfUrl:"/chapter/pdf-download/78330",previewPdfUrl:"/chapter/pdf-preview/78330",authors:[{id:"355836",title:"Ph.D. Student",name:"Lazaro",surname:"Eliyah Mngumi",slug:"lazaro-eliyah-mngumi",fullName:"Lazaro Eliyah Mngumi"},{id:"423866",title:"Dr.",name:"Yonggui",surname:"Chen",slug:"yonggui-chen",fullName:"Yonggui Chen"}],corrections:null},{id:"78391",title:"Contributing to Healthy Landscapes by Sustainable Land Use Planning: A Vision for Restoring the Degraded Landscape of the Centre Region of Portugal",doi:"10.5772/intechopen.99666",slug:"contributing-to-healthy-landscapes-by-sustainable-land-use-planning-a-vision-for-restoring-the-degra",totalDownloads:120,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The ecological-based methodologies are determinant to develop complete strategies in restoring the ecosystems at a landscape scale. Those methodologies start with comprehending ecological processes by mapping fundamental structures of the territory (water, soil, biodiversity), also called green infrastructures. The adequate land use planning and its forthcoming implementation will guarantee a multifunctional landscape, better ecosystem services provision, and a possibility of developing new economies. The intervention of Landscape Architecture at the landscape scale will also provide information about the place and the type of restoration actions to be implemented. The Centre Region was the most affected by rural fires from 2017, representing 15% of the total region area (416 thousand hectares). These events reflect the high importance of rethinking the territory with more suitable land uses, considering the concepts of sustainability, resilience, and ecological integrity. This work proposes a Landscape Transformation Plan for the Centre Region of Portugal, applying the FIRELAN model. The results show that about 35% of the Centre Region should have restoration action towards a more sustainable landscape.",signatures:"Selma B. Pena, Maria Luísa Franco and Manuela R. 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In this study, the latent nature of the landscape architecture discipline was revealed by constructing a principal component citation analysis representation (the landscape architecture research universe) concerning several decades of literature (1982–2017) in Landscape Journal, a preeminent American journal addressing landscape architecture research. In addition, an ordination was developed describing the curriculum relationships between fifteen top American universities teaching landscape architecture as identified by ‘DesignIntelligence,’ preparing students for practicing in the profession of landscape architecture. The results revealed that in the discipline, the research activity is highly diverse along many dimensions, constantly evolving as new topics are explored. The pattern in landscape architecture research is broad, as the discipline integrates knowledge and ideas in many fields. In contrast, landscape architecture curriculums, teaching the fundamentals of the profession, are fairly closely clustered together and quite similar, with small differences reflecting emphasis in either landscape history or the visual arts, and mathematics or course electives. This dual identity is both a source of conflict and a unique opportunity.",signatures:"Chunqing Liu, Xiaowen Jin, Zhi Yue, Zhen Wu and Jon Bryan Burley",downloadPdfUrl:"/chapter/pdf-download/79007",previewPdfUrl:"/chapter/pdf-preview/79007",authors:[{id:"95281",title:"Dr.",name:"Jon",surname:"Bryan Burley",slug:"jon-bryan-burley",fullName:"Jon Bryan Burley"},{id:"425830",title:"Dr.",name:"Chunqing",surname:"Liu",slug:"chunqing-liu",fullName:"Chunqing Liu"},{id:"425831",title:"Dr.",name:"Xiaowen",surname:"Jin",slug:"xiaowen-jin",fullName:"Xiaowen Jin"},{id:"425832",title:"Dr.",name:"Zhi",surname:"Yue",slug:"zhi-yue",fullName:"Zhi Yue"},{id:"425833",title:"Dr.",name:"Zhen",surname:"Wu",slug:"zhen-wu",fullName:"Zhen Wu"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"5235",title:"Sustainable Urbanization",subtitle:null,isOpenForSubmission:!1,hash:"76200e89c8c93b3c0b22062aa09a84ff",slug:"sustainable-urbanization",bookSignature:"Mustafa Ergen",coverURL:"https://cdn.intechopen.com/books/images_new/5235.jpg",editedByType:"Edited by",editors:[{id:"166961",title:"Dr.Ing.",name:"Mustafa",surname:"Ergen",slug:"mustafa-ergen",fullName:"Mustafa Ergen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"6396",title:"Urban Agglomeration",subtitle:null,isOpenForSubmission:!1,hash:"da1643c7ce5482ec846a188d34ce2839",slug:"urban-agglomeration",bookSignature:"Mustafa Ergen",coverURL:"https://cdn.intechopen.com/books/images_new/6396.jpg",editedByType:"Edited by",editors:[{id:"166961",title:"Dr.Ing.",name:"Mustafa",surname:"Ergen",slug:"mustafa-ergen",fullName:"Mustafa Ergen"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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Ubiquitylation is an essential post-translational modification that regulates numerous intracellular processes including protein localization and trafficking, DNA damage response, immune system and viral response, apoptosis and proteolysis [1, 2]. E3 ubiquitin ligases play an important role in recognizing, binding, and covalently attaching ubiquitin to their various substrates to elicit a specific cellular response [3]. The homologous to E6AP C-terminus (HECT) E3 ubiquitin ligases are a unique subfamily that use a multistep pathway to selectively target substrate proteins for ubiquitylation [4]. HECT-dependent ubiquitylation requires the recruitment of an E2 ubiquitin conjugating enzyme charged with ubiquitin to the N-terminal lobe of the HECT domain on the E3 ligase [5, 6]. The ubiquitin cargo is then transferred from the E2 enzyme to the conserved catalytic cysteine within the C-terminal lobe of the HECT domain
The destiny of a ubiquitin-tagged protein is dependent on (i) the site(s) of ubiquitin attachment on the substrate, (ii) the number of ubiquitin moieties attached to the substrate (i.e. mono-, multi-mono-, or polyubiquitin), and (iii) the specific type(s) of linkages between the different ubiquitin molecules in a polyubiquitin chain (i.e. K48, K63, branched, etc.) [1, 2, 7]. Potential fates of a ubiquitin-tagged substrate include changes in cellular localization/trafficking, enhanced/inhibited protein activity, changes in protein–protein affinity/interactions, and proteolysis [1, 2, 6, 7, 8].
\nDifferences in ubiquitin lysine linkage specificity determine the destination and/or fate of the targeted protein in the cell (Table 1). For example, the well-established K48-polyubiquitylation chain, heterotypic K11/K48-polyubiquitin, K29/K48-polyubiquitin monoubiquitin tagged peptides and multiple monoubiquitin tagged proteins have also been found to signal for 26S proteasomal degradation [7, 8]. K63-polyubiquitin chains signal for protein degradation through the initiation of K48/K63 polyubiquitin branch formation [5] but cannot be recognized by the 26S proteosome [26]. To date, many different varieties of ubiquitin chain types have been identified, but their distinct biological functions remain unclear.
\nChain types | \nLinker | \nProposed function | \n
---|---|---|
Monoubiquitylation | \n||
Monoubiquitylation/multi-monoubiquitylation | \n\n | Endocytosis [9] DNA damage repair [10, 11, 12, 13, 14, 15] Histone regulation [10, 11, 12, 13, 14, 15] Mitophagy [10, 11, 12, 13, 14, 15] Protein localization [10, 11, 12, 13, 14, 15] Protein interactions [10, 11, 12, 13, 14, 15] Protein transportation [10, 11, 12, 13, 14, 15] Transcription activation [10, 11, 12, 13, 14, 15] | \n
Polyubiquitylation | \n||
Chain (homotypic) | \nM1 | \nInnate immunity [2, 9, 16] Linear chain formation [9] NF-κB activation [9, 16] Signaling cascades [9, 16] | \n
K6 | \nDNA damage response [14] NF-κB regulation [14] Mitophagy [14] | \n|
K11 | \nCell cycle regulation [17] DNA damage response [18] Mitophagy [17] NF-κB activation [16] Protein degradation [17] | \n|
K27 | \nDNA damage response [18] Kinase activation [19] Protein degradation [20] Protein scaffolding [21] Protein trafficking [22] | \n|
K29 | \nDNA damage response [18] Kinase activation [19] Protein degradation [9] | \n|
K33 | \nDNA damage response [10, 11, 12, 13, 14, 15, 18] Kinase activation [23] Post-golgi trafficking [24] T-cell signaling [23] | \n|
K48 | \nProtein degradation [1, 2, 25] | \n|
K63 | \nDNA damage response [9, 18] NF-κB activation [9, 16] Protein trafficking [9] | \n|
Chain (heterotypic; branched) | \nM1/K63 | \nNF-κB activation [16] | \n
K11/K48 | \nProtein degradation [26, 27] | \n|
K29/K48 | \nProtein degradation [26] | \n|
K48/K63 | \nProtein degradation [26] | \n|
K11/K63 | \nEndocytosis [28] | \n
Ubiquitin conjugation determines the intracellular fate of a substrate protein.
Monoubiquitylation can occur at one site or at multiple sites (multi-monoubiquitylation) on a substrate. Polyubiquitylation can build off of a mono-ubiquitin attachment site with a specific lysine linkage (homotypic) or have multiple chains with different lysine linkages (branch) at the end of a growing ubiquitin chain (heterotypic). These modifications can also influence signaling pathways, whether it is through enhancing or inhibiting participating proteins and processes.
\nThe HECT E3 ubiquitin ligases can be categorized into three subfamilies –NEDD4, HERC, and “other” – based on their sequence/structure similarity and domain architecture [4, 5]. Of the 28 HECT E3 ubiquitin ligases identified in humans, there are 12 “other” HECT E3 ubiquitin ligases that do not fall under the well-studied NEDD4 or HERC subfamilies. Each member of the “other” HECTs have variable N-terminal domains that are thought to be involved in protein–protein interactions and/or intracellular localization [4, 5]. Having prominent responsibilities in cellular homeostasis would leave the impression there is ample research on the HECT E3 ubiquitin ligase family as a whole, however, there remain many unanswered questions about the biological functions and mechanisms of this important E3 ligase family, particularly for members of the more mysterious “other” subfamily. With new research and discoveries becoming available, there is mounting evidence that the lesser known HECT E3 ubiquitin ligases play critical roles in regulating intracellular processes and their dysfunction have been suggested to contribute to the onset of many diseases and disorders [4, 29, 30, 31, 32]. Here we discuss the latest discoveries on these lesser known members of the HECT E3 ubiquitin ligases and on their emerging roles in developmental and neurological abnormalities, cancers, and embryogenesis.
\nApoptosis resistant E3 ubiquitin protein ligase 1(AREL1; 823 residues) is a cytosolic enzyme responsible for regulating apoptosis through the inhibition of proapoptotic proteins
AREL1 domain architecture. AREL1 contains a putative immunoglobulin fold domain (IGF, residues 52-158) and the canonical HECT domain (436-823) as annotated on UniProt and InterPro. Representative crystal structures of an IGF fold (human IGF FAB in yellow/orange; PDB 7FAB [
Apoptosis (aka programmed cell death) is an important and highly regulated biological process that occurs during early embryonic development and the immune response [38, 39]. Once apoptosis is initiated the cell is committed to die, which is mediated by a caspase cascade [40]. Intrinsic apoptosis is turned on by the release of intermembrane mitochondrial proteins when cells are under oxidative stress [38, 39, 41]. In contrast, the extrinsic apoptotic pathway is activated by extracellular signaling at the cell membrane leading to the formation of the death-inducing signaling complex (DISC) [42, 43, 44].
\nAREL1 was first identified in 2013 and was immediately recognized as an oncogenic target due to its inhibitory role in apoptosis [33]. Identified substrates for AREL1 include second mitochondrial activator of caspase (SMAC), HtrA serine peptidase 2 (HtrA2) and septin 4 (ARTS), which are known antagonists of inhibitor of apoptosis proteins (IAPs) [45]. Studies have shown that AREL1 can build K48 and K63 polyubiquitin chains to target substrates for proteolysis, as well as atypical K33 polyubiquitin chains whose biological function is still being clarified [35, 46]. Various IAPs, including SMAC, HtrA1, and ARTS, are released from the mitochondrial intermembrane into the cytosol when the cell is triggered or stressed. AREL1 inhibits apoptosis by ubiquitylating these IAP antagonists with K48-linked polyubiquitin chains targeting the IAPs for proteasomal degradation [33].
\nThe induction of apoptosis is thought to require the release of numerous IAPs in the cytosol to allow different signaling pathways to initiate apoptosis depending on the cell’s specific stress. For example, the release of SMAC into the cytosol allows it to bind cellular inhibitor of apoptosis protein 1/2 (cIAP1/2), which then targets cIAP1/2 for proteasomal degradation to initiate apoptosis. However, when AREL1 is present, SMAC is ubiquitylated by AREL1 and degraded, thus blocking SMAC-cIAP1/2 complex formation enabling cell survival [33]. Many cancer therapies are interested in specifically turning on apoptosis through IAPs in cancer cells [47, 48, 49], thus AREL1 could prove to be a novel enzyme in drug development. Continued studies on AREL1’s mechanisms in controlling cell death are warranted.
\nFirst identified in 2004, HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 (HACE1; 909 residues) has been shown to take part in various cellular processes. For example, HACE1 is best known as a tumor suppressor as altered HACE1 expression levels have been observed in various cancers including colorectal, breast, liver, kidney, osteosarcoma, lymphoma and gastric cancer [50, 51, 52, 53, 54]. HACE1 contains six ankyrin repeats near its N-terminus that likely take part in HACE1-substrate recognition and protein–protein interactions (Figure 2). While it is not yet fully understood how the ankyrin repeats support HACE1 function, ankyrin repeats in other proteins have been shown to instigate the development of a wide array of diseases including cancer [56]. HACE1 also supports Golgi membrane biogenesis during cell division by ubiquitylating members of the Ras-related superfamily of small G proteins [57].
\nPredicted domain architecture of HACE1. HACE1 contains six putative ankyrin-repeats (ANK; residues 64-258) and a HECT domain (574-909) as annotated on UniProt and InterPro. Representative crystal structures of an ANK repeat fold (in shades of pink, PDB 4O60 [
Studies have shown that HACE1 expression levels are altered when comparing normal and cancerous tissue. Specifically, in the Wilms’ tumor cell line, HACE1 expression was essentially nonexistent, whereas in other cancer cell lines expression levels were lower than average [50]. This study concluded that HACE1 was essential in repressing cancer development as the lowered expression levels of HACE1 were not mutation dependent. Low expression levels of HACE1 have also been observed in other cancer cell lines. For instance, it was found that the methylation of the HACE1 promoter resulted in decreased HACE1 expression in liver cancer cells, which in turn decreased HACE1’s ability to ubiquitylate its identified substrates optineurin (OPTN) and microtubule-associated proteins 1A/1B light chain 3B protein [53]. Many different substrates of HACE1 have been identified to date (summarized in [4]), including β2-adrenergic receptor (ß2AR) [58], OPTN [59], retinoic acid receptor beta (RAR-β) [57], tumor necrosis factor receptor-2 (TNFR2) [60], and various Ras-related proteins [57, 58, 61, 62, 63, 64, 65]. Expanded studies on how HACE1 binds and recognizes its substrates are needed to further clarify the role of HACE1 in cancer development.
\nHACE1 also plays an essential role in neurodevelopment as it was recently shown to be involved in the spastic paraplegia and psychomotor retardation with or without seizures (SPPRS) phenotype [66]. HACE1 also has cardiac protection function during hemodynamic stress when it was shown in mice with
HECT domain containing E3 ubiquitin protein ligase 1 (HECTD1; 2610 residues) was discovered in 2007 as a novel and important regulator of neurodevelopment [68]. HECTD1 has similar domain architecture to HACE1 with four ankyrin repeats near its N-terminus and a C-terminal HECT domain (Figure 3). HECTD1 plays an important role in pulmonary fibrosis during endothelial-mesenchymal transition (EndMT) with reports of increased circular RNA HECTD1 (circHECTD1) transcription, which causes decreased HECTD1 protein expression in lung tissue [72, 73]. Elevated circHECTD1 gene expression has also been found in patients with acute ischemic stroke (AIS) [74]. HECTD1 also contains a Smad4 activation SAD1/UNC (SUN) domain and a mind bomb (MIB) domain, with each having unique roles in intracellular signaling due to Smad-DNA complex formation and cellular interactions through the Notch pathway, respectively [75, 76].
\nHECTD1 domain architecture. HECTD1 contains putative protein-protein interaction domains including two armadillo-repeat containing domains (ARM1, residues 8-254; ARM2 residues 892-925 in purple; PDB 4DB8 [
HECTD1 supports fetal growth and proper placenta development. Specifically, HECTD1 aids in the development of the labyrinthine and junctional zones of the placenta, regions where the fetus acquires nutrients and disposes of waste, as well as a bilayer between the labyrinthine and decidual cells, respectively [77, 78]. HECTD1 ensures the proper size development of the labyrinthine, yet the mechanisms to ensure this are still not fully understood. Mutations within HECTD1 lead to the onset of irregular labyrinthine development, which in turn depletes nutrients for the fetus. Fetal fatality can occur without proper maintenance of these placental regions, suggesting that HECTD1 expression is essential for the proper development and survival of fetuses
HECT domain containing E3 ubiquitin protein ligase 4 (HECTD4; 3996 residues) was recently discovered in 2014. A pleiotropic gene screen showed that there were links between metabolic syndromes and inflammation, specifically with single nucleotide polymorphisms (SNPs) in the
Being one of the larger enzymes within the “other” HECT E3 ubiquitin ligase subfamily, it is intriguing that there have been no putative domains annotated for HECTD4 except the C-terminal HECT domain (residues 3627–3996). There are likely different domains located in the N-terminal region of the HECTD4 protein that need to be identified and functionally examined.
\nGenetic screening has identified various mutations in
Already having various genetic links to cancers and cardiovascular disease, HECTD4 deserves more attention by the research community to further clarify its biological and functional roles in the cell. Currently very little is known about HECTD4, therefore it will be imperative to first identify potential similarities in protein sequence and/or domain architecture. To better clarify HECTD4’s role in ubiquitin biology, it will also be important to discover HECTD4 substrates and annotate the sites of HECTD4-dependent ubiquitylation to answer how this mysterious HECT E3 ubiquitin ligase contributes to disease development.
\nG2/M-phase specific E3 ubiquitin protein ligase (G2E3; 706 residues) was first identified in 2006 and named for its role during the G2/M phase of cell division and for having a conserved C-terminal HECT domain [85]. Knockout studies of G2E3 in mice demonstrated that this enzyme is essential in preventing apoptotic cell death during early embryonic development [86]. Expression levels in G2E3 were also observed to increase during early embryogenesis, specifically during central nervous system development. This enzyme is also implicated in cell cycle progression and DNA damage response [85, 87, 88].
\nG2E3 contains three plant homeodomain (PHD)-type zinc finger repeats, a domain typically known to bind to modified histones and act as epigenetic readers [89], making it the only known HECT E3 ubiquitin ligase to possess “RING”-like characteristics (Figure 4). G2E3 is primarily found within the nucleus due to its N-terminal nucleolar localization signal sequence, while the PHD domains have been suggested to cause the translocation of G2E3 to the cytoplasm [85, 86]. Previous biochemical studies showed that the ubiquitin ligase activity of G2E3 was exclusively found in two of the putative N-terminal PHD domains while the C-terminal HECT domain of G2E3 had apparently lost its ubiquitylation activity [86]. Since the PHD domains of G2E3 appear to be capable of recruiting E2 enzymes to build K48-linked polyubiquitin chains [86], this suggests that the HECT domain of G2E3 may have become vestigial through evolutionary pressure. Intriguingly, G2E3 has aspects of the RING and HECT E3 ubiquitin ligase families, analogous to members of the RING-between-RING (aka RING-BRcat-Rcat) E3 ubiquitin ligases that includes parkin and HOIL-interacting protein (HOIP) of the LUBAC complex [91, 92].
\nDomain architecture of G2E3. G2E3 contains three putative plant homeodomain (PHD)-type domains (residues 78-128) and a unique HECT-like domain (371-678) as annotated on UniProt and InterPro. Representative crystal structures of a PHD domain (human PHD finger protein 13 in cyan with Zn-coordinating residues in yellow; PDB 3O70 [
G2E3 was recently identified as a potential drug target to increase the efficacy of chemotherapy drugs, specifically with Cisplatin [88]. Since Cisplatin is the most common chemotherapy drug, much research has been dedicated to increasing Cisplatin’s ability to specifically trigger the DNA damage response in cancer cells to initiate apoptosis while limiting its exposure time and prescribed duration for patients [93]. Clearly, G2E3 is an important nuclear protein whose mechanism is currently unresolved. Further studies are needed to clarify how this divergent HECT-domain containing E3 ubiquitin ligase works in the cell.
\nThyroid hormone receptor interactor 12 (TRIP12; 2040 residues), was first identified in 2001 for containing a unique tryptophan-tryptophan-glutamate (WWE) domain that is predicted to be involved in ubiquitylation and ADP-ribosylation [94] (Figure 5). It also contains two N-terminal ARM domains, similar to HECTD1, and a conserved HECT domain at its C-terminus. TRIP12 is a novel HECT E3 ubiquitin ligase that has been shown to take part in various cellular pathways and processes including embryogenesis, DNA damage response and the neddylation pathway [95, 96, 97]. It has been reported that TRIP12 preferentially builds mono- as well as K48 and K63 polyubiquitin chains to tag its substrates for degradation and for DNA damage site recruitment, respectively [96].
\nTRIP12 domain architecture. TRIP12 contains two putative armadillo-repeat containing domains (ARM1, residues 437-713; ARM2, residues 826-938), a tryptophan-tryptophan-glutamate (WWE)-domain (residues 749-836) and a conserved HECT domain (1885-1992) as annotated on UniProt and InterPro. Representative crystal structures of an ARM domain (in purple; PDB 4DB8 [
TRIP12 has been shown to be directly and/or indirectly involved in cancer progression. For example, TRIP12 may serve as an oncogenic drug target for patients with acute myeloid leukemia (AML) by blocking a TRIP12 alternative splicing event, specifically excising exon3 from the mature TRIP12 mRNA [98]. TRIP12 also targets pancreas transcription factor 1a (PTF1a) for proteasomal degradation, a protein essential for pancreatic cancer development [99]. TRIP12 forms a ternary complex with deubiquitylase ubiquitin-specific protease 7 (USP7) that aids in hepatocellular carcinoma (HCC) proliferation; when USP7 expression levels are heightened, TRIP12 cannot tag ARF tumor suppressor (p14ARF) for ubiquitylation [100]. Furthermore, TRIP12 is associated with human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) due to its mediation of p16-related radiation efficacy [101].
\nMembers of the HECT E3 ubiquitin ligase family play important roles in neurodevelopment and their malfunction may be causative in different neurological diseases and disorders (reviewed in [4]). Recent genetic screens have been looking to identify genetic markers for autism spectrum disorder (ASD) and intellectual disability (ID). Interestingly, a
Although much research has and continues to be performed for E6AP and members of the NEDD4 family, greater attention on the mysterious “other” HECT E3 ubiquitin ligases is warranted due to their emerging involvement in various diseases and neurological disorders. Combining genetic, cell biology, biochemical, and biophysical approaches to study these unique HECT E3 ubiquitin ligases will help to decipher their specific roles and/or functions in the cell as well as potentially aid in novel therapy development to treat rare conditions caused by the dysfunction of these lesser known members of the HECT E3 ubiquitin ligase family.
\nThis work was supported by the National Institutes of Health (R15GM126432 to D.E.S.) and start-up funds from Clark University (to D.E.S.).
\nThe authors declare that there is no conflict of interest regarding the publication of this chapter.
AIS | acute ischemic stroke |
AML | acute myeloid leukemia |
ANK | ankyrin repeat |
AREL1 | apoptosis resistant E3 ubiquitin protein ligase 1 |
ARM | armadillo-repeat domain |
ARTS | septin 4 |
ASD | autism spectrum disorder |
β2AR | adrenergic receptor β2AR |
cIAP1/2 | cellular inhibitor of apoptosis protein 1/2 |
circHECTD1 | circular RNA HECTD1 |
CIT | citron rho-interacting kinase |
EndMT | endothelial-mesenchymal transition |
FBN3 | fibrillin-3 precursor |
G2E3 | G2/M-phase specific E3 ubiquitin protein ligase |
H | helix-bundle domain |
HACE1 | HECT domain and ankyrin repeat containing E3 ubiquitin protein ligase 1 |
HCC | hepatocellular carcinoma |
HECT | hmologous to E6AP C-terminus |
HECTD1 | HECT domain containing E3 ubiquitin protein ligase 1 |
HECTD4 | HECT domain containing E3 ubiquitin protein ligase 4 |
HERC | HECT and RLD domain-containing |
HNSCC | head and neck squamous cell carcinoma |
HOIP | HOIL-interacting protein |
HPV | human papillomavirus |
Hsp90 | heat shock protein 90 |
HtrA2 | HtrA serine peptidase 2 |
ID | intellectual disability |
IGF | immunoglobulin-like fold |
MIB | mind bomb domain |
NEDD4 | neuronal precursor cell-expressed developmentally down-regulated 4 |
SMAC | second mitochondrial activator of caspase |
OEM | ovarian endometriosis |
OPTN | optineurin |
p14ARF | ARF tumor suppressor |
PHD | plant homeodomain-type zinc finger |
PTF1a | pancreas transcription factor 1a |
RAR-β | retinoic acid receptor beta |
RING | really interesting new gene |
TNFR2 | tumor necrosis factor receptor-2 |
SNPs | single nucleotide polymorphisms |
SPPRS | spastic paraplegia and psychomotor retardation with or without seizures |
SUN | Smad4 activation SAD1/UNC domain |
TRIP12 | thyroid hormone receptor interactor 12 |
UCB | urothelial carcinoma in the bladder |
USP7 | deubiquitylase ubiquitin-specific protease 7 |
WWE | tryptophan-tryptophan-glutamate domain |
The
As defined in the Guide to Banking Supervision, the European Central Bank (ECB) has identified three objectives to be achieved by the
The safety and soundness of the European banking system.
Integration and stability of the financial sector.
The increased consistency of banking supervision across the Euro area.
The Single Supervisory Mechanism (SSM) has no legal personality and its purpose is the prudential supervision of banking activities. It consists of the ECB, which also plays the lead role, and the national competent authorities (NCAs) of the participating countries. Although the ECB has the ultimate responsibility for decision-making, it carries out its supervisory tasks under the MVU in close cooperation with the NCAs. Working with the NCAs, the ECB performs direct supervision of institutions defined as Significant (SIs). On the other hand, the supervision of Less Significant institutions (LSIs) is carried out directly by the NCAs in a unified supervisory approach guided by the general guidelines and instructions given by the ECB. In addition, all supervisory tasks that are not conferred within the MVU, such as consumer protection or anti-money laundering, remain with the NCAs. The criteria for determining whether banks can be considered significant – and therefore subject to direct ECB supervision – are defined in the MVU Regulation.
\nTo qualify as significant, banks must meet at least one of these criteria4:
The total value of assets exceeds €30 billion or, unless the total value of assets is less than €5 billion, exceeds 20% of national GDP.
Be one of the three most significant credit institutions in a Member State.
Receive direct assistance from the European Stability Mechanism.
The total value of assets exceeds €5 billion and the ratio of cross-border assets in more than one other participating Member State to total assets exceeds 20%, or the ratio of cross-border liabilities in more than one other participating Member State to total liabilities exceeds 20%.
The ECB may decide at any time to classify a bank as significant to ensure that high supervisory standards are applied consistently, and conducts periodic reviews of all licenced banks within the SSM. The classification of banks may be changed due to the normal operations of credit institutions or as a result of extraordinary events such as mergers or acquisitions. In such cases, the ECB and the national supervisory authorities involved coordinate the transfer of supervisory responsibilities. The purpose of balancing the regulatory requirements for institutions of different sizes is to promote the stability of the financial system and to ensure a level playing field within the financial system and an appropriate comparison of risk, capital and liquidity profiles between intermediaries of different sizes and operational complexity.
\nFor significant institutions, the ECB carries out its supervision through a specific methodology, the periodic assessment of their economic and financial situations, the verification of compliance with prudential rules, the adoption of any necessary supervisory measures, and the performance of stress tests. All of this is done by the Joint Supervisory Teams (JST) composed of staff from the ECB and the NCAs of the significant institutions’ countries of establishment. The JST is responsible for drafting and organising the supervisory review programme, as well as for performing day-to-day supervision at consolidated, sub-consolidated and individual levels (assessments of the institutions’ risk profiles, business models and strategies, risk management and control systems and internal governance). JST members may also participate in on-site inspections and investigations of internal models.
\nIn our country, the supervision of less significant banks and banking groups is instead exercised directly by the Bank of Italy with a view to unitary supervision under the guidelines and general instructions given by the ECB. Among the less significant banks are the so-called “High Priority” banks for which the exchange of information between the BoI and the ECB is more intense. (These are the first banks “below the threshold” of €30bn in assets.) However, the BoI retains full and autonomous competence in the areas of consumer protection, combating money laundering and terrorist financing, supervision of payment services and markets for financial instruments, and supervision of non-banks and branches of non-EU banks.
\nAs regards SIMs and OICR managers, the Consolidated Law on Finance (TUF) assigns to the Bank of Italy supervisory tasks for risk containment, stability and sound and prudent management, and to Consob those for the transparency and propriety of the conduct of these intermediaries in offering investment products.
\nThe First Pillar of the MUV (SSM) is based on the so-called Basel framework, or rather on the following regulatory sources:
CRR (
CRD IV (
Starting from 2021, the two regulatory packages will be gradually replaced by the new CRR II and CRD V, whose regulatory changes define the final structure of the new “
CRR II and CRD V.6\n
Basel III: Finalising post-crisis reforms.
EU Regulation 2017/2401–2402 (
The prudential supervisory framework for risk and capital (Basel IV) has always been ideally divided into three pillars:
\n
\n
\n
In general terms, the MUV is based on the European single rulebook, which therefore consists – in addition to the Regulation and the Directives (Directive 2013/36/EU-CRD IV, EU Regulation no. 575/2013 - CRR, Directive 2014/49/EU -
The entire structure of the Single Supervisory Mechanism is based on a principle of proportionality aimed at achieving a uniform application of the rules while respecting the diversity of banks’ business models, identities, size and operational complexity. However, the operational implementation of this principle does not always seem to have been able to fully achieve these objectives, which is why the application of this principle continues to be a priority on the agenda of European authorities.
\nHowever, the approach of European supervision has historically been oriented towards the definition of a set of rules equal for all, in order to ensure homogeneity of treatment for different banks: the principle of “one size fits all”. However, this approach, while further tightened in the immediate post-crisis years, has been revisited from a proportional perspective (at least in theory) with the introduction of the current CRR and CRD IV and the future entry into the scene of the new CRR II and CRD V.
\nThe application of the principle of proportionality within the Single European Supervisory Mechanism is therefore substantiated by the application of the same rules to all banking intermediaries, but with a “depth” and an articulation proportionate to the significance and/or operational complexity. The significance of an intermediary is relevant to the identification of the competent Supervision Authority, even though, in this regard, an intense collaboration between the European Central Bank and the NCAs is foreseen to guarantee the harmonised application of the Community rules. Specifically, the SSM provides that, with regard to the supervision of the
Priority classes | \nIntermediary | \n
---|---|
Very High | \nAny LSIs identified as O-SIIs | \n
High | \nHigh priority LSI | \n
Medium | \nMedium priority LSI | \n
Low | \nLow priority LSI | \n
Classification of LSIs into priority classes.
Source: Bank of Italy.
Based on this classification, the NCAs establish the intensity of Pillar II assessments, supervisory expectations and information requirements at the data collection stage, calibrated according to the classes.10 Supervisory activities for less significant institutions consist of regular assessments conducted jointly by the ECB and the NCAs of the Member States, with the aim of making the best use of the information available to the national authorities. Moreover, for high priority LSIs, the ECB examines the supervisory procedures and relevant draft decisions established by the NCAs themselves11.
\nThe subject of the proportionality of the rules of supervision and surveillance in the European banking system is of strategic importance, also due to the fact that the LSIs represent a pillar of the European real and financial economy, even though 80% of these institutions are concentrated in nine countries (primarily Austria, Germany and Italy, but also Croatia, Denmark, Luxembourg, Poland, Slovakia and Slovenia).12 It is interesting, in this context, to observe how the principle of proportionality is implemented overseas.
\nIn fact, US banking regulations basically implement the Basel standards for large banks, while the provisions of the reform known as the “Wall Street Reform” or also the “Dodd-Frank Act”13 establish a series of rules tailored to the size of small and medium-sized banks, which make up about 95% of US credit institutions. From the outset, the main objective of the definition of new common rules was to guarantee greater stability to the US financial apparatus and above all to avoid the spread of systemic risk. Although this objective was perfectly consistent with that of European legislators, the approach used on the other side of the Atlantic was more oriented towards defining more stringent rules for large banks (identified as those with total assets of over $50 billion), and therefore by definition carrying systemic risk, while a set of new, less onerous rules proportionate to their operations was envisaged for community banks. In addition, in 2018, the Dodd-Frank Act was revised and amended with a view to further calibrating it towards a more pervasive application of the proportionality principle. For example, while initially the more stringent rules on stress testing, MREL requirements and the weakening of the role of advanced internal models were only applicable to institutions with assets in excess of $50 billion, from 2019 they would be limited to institutions with assets in excess of $250 billion. In the case of smaller banks, the legislature instead focused its attention on the need to hold high capital requirements, which – especially initially – resulted in the closure of smaller, underperforming banks [1].
\nWith regard to Community banks, however, the principle of proportionality does not take the form of applying the same regulatory requirements with a different degree of depth, but rather provides for total exemption from certain supervisory standards (this is the case for banks with assets of less than $10 billion, which are not subject to the macroprudential stress tests that are mandatory for all larger institutions, including those with assets of between $10 and $50 billion). The application in the United States of the regulatory standards envisaged by Basel III applies, with due differentiation, to two categories of credit intermediaries:
\n\nTable 2\n summarises the regulatory capital and liquidity requirements for different types of banks operating in the US system.
\nApplicable Regulations | \nCurrent Tailoring of Rules | \n||||
---|---|---|---|---|---|
G-SIB | \nInt’l Active ($250b+) | \nRegional ($50-250b) | \nMid-size ($10-50b) | \nSmall (<$10b) | \n|
\n | \n|||||
Global market shock for trading | \nYes (6/8) | \nNo | \nNo | \nNo | \nNo | \n
Counterparty default scenario | \nYes (8/8) | \nNo | \nNo | \nNo | \nNo | \n
Qualitative Fed-run process review | \nYes | \nYes | \nNo | \nNo | \nNo | \n
Quantitative Fed-run stress tests | \nYes | \nYes | \nYes | \nNo | \nNo | \n
Fed ability to object to capital plans through CCAR | \nYes | \nYes | \nYes | \nNo | \nNo | \n
\n | \n|||||
Quantitative Fed-run stress tests | \nYes | \nYes | \nYes | \nNo | \nNo | \n
Company-run stress tests | \nYes | \nYes | \nYes | \nYes | \nNo | \n
Annual stress test | \nYes | \nYes | \nYes | \nYes | \nNo | \n
Mid-year stress test | \nYes | \nYes | \nYes | \nNo | \nNo | \n
\n | \n|||||
Risk-based | \n\n | \n | \n | \n | \n |
G-SIB capital buffers | \nYes | \nNo | \nNo | \nNo | \nNo | \n
Countercyclical capital buffer | \nYes | \nYes | \nNo | \nNo | \nNo | \n
Including AOCI changes in capital | \nYes | \nYes | \nNo | \nNo | \nNo | \n
Risk-based (i.e., Base III) | \nYes | \nYes | \nYes | \nYes | \nYes | \n
Leverage ratio | \n\n | \n | \n | \n | \n |
Enhanced Supplementary leverage ratio (eSLR) | \nYes | \nNo | \nNo | \nNo | \nNo | \n
Supplementary leverage ratio (SLR) of 3% | \nYes | \nYes | \nNo | \nNo | \nNo | \n
U.S. leverage ratio | \nYes | \nYes | \nYes | \nYes | \nYes | \n
TLAC and long-term debt requirement | \nYes | \nNo | \nNo | \nNo | \nNo | \n
\n | \n|||||
Liquidity coverage ratio (LCR) | \nYes | \nYes | \nNo | \nNo | \nNo | \n
Modified LCR | \nNo | \nNo | \nYes | \nNo | \nNo | \n
Net stable funding ratio (NSFR), proposed rule | \nYes | \nYes | \nNo | \nNo | \nNo | \n
Modified NSFR, proposed rule | \nNo | \nNo | \nYes | \nNo | \nNo | \n
Breakdown of the main regulatory obligations in the US system.
Source: U.S. Treasury (A Financial System That Creates Economic Opportunities - Banks and Credit Unions. Pag.41. www.treasury.gov).
A comparison of the regulatory indicators in the US and European systems reveals some differences in the proportionate application of supervisory rules with respect to bank size. First, while US regulation provides for a full exemption from stress testing for community banks, in Europe this exemption does not apply to LSIs. With respect to capital requirements, however, the main difference is that while the EU framework allows NCAs to require even smaller institutions to hold an additional countercyclical capital buffer in good times, this only applies to banks with assets greater than $250 billion in the US. Ultimately, evidence of different application of the proportionality principle can also be found with respect to liquidity requirements. Specifically, while in the US full compliance with the LCR (Liquidity Coverage Ratio14 [2]) and NSFR (Net Stable funding Ratio)15 [2] is only required for banks with assets greater than $250 billion, and less stringent application is demanded of institutions with assets between $50 billion and $250 billion, in Europe compliance with an LCR of at least 100% is mandatory for all intermediaries. In addition, as of 2021, compliance with an NSFR of at least 100% will also be mandatory for all intermediaries, although a simplified version will be available for small and less complex institutions. \nTable 3\n below summarises the differences just discussed.
\nSupervisory obligations | \n\n | \n\n | \n
---|---|---|
\n
| \nNO | \nYES | \n
\n
| \nNO | \nYES | \n
\n
| \nNO | \nYES | \n
\n
| \nNO | \nYES | \n
Differences between the US and the EU in the application of the principle of proportionality.
Source: Author elaboration.
Finally, the application of the principle of proportionality in the US banking system manifests its effects also in the phase of resolution of banks in crisis, contrary to what actually happens in the European Banking Union. In Europe, in fact, as highlighted by Masera [3], while the SSM provides for the assignment of the tasks of supervision on the LSIs to the NCAs, the performance of this activity is effectively limited only to the banks in ordinary administration, and as highlighted in paragraph 3.2, in the cases in which a Less Significant bank shows signs of vulnerability, the ECB has the right to take over the supervision of the institution, making the principle of subsidiarity prevail over that of proportionality. In the US, on the other hand, resolution interventions are led by the Orderly Liquidity Authority for banks subject to
In this context, it should be noted that the definition of the identification threshold for banks to which size-related measures are to be applied is not straightforward and can hardly be standardised. The difficulty lies primarily in defining criteria that are adaptable to the financial systems of different jurisdictions, which are different from each other. Policymakers and the literature have provided much food for thought [3, 4, 5] on the effective application of a two-tiered approach to less complex institutions identified through parameters such as:
\nArticle 97 of the CRDIV (Directive 2013/36) requires supervisors to review the organisation, strategies, processes and methodologies that banks put in place to address the range of risks they face.
\nThe Supervisory Review and Evaluation Process (SREP) is conducted annually by the supervisory Authorities to verify that each bank has implemented strategies, processes, capital and liquidity appropriate to the risks to which it is or might be exposed and that they have appropriate capital and organisational safeguards in place to address the risks they face, ensuring overall balance of operations and market resilience.
\nThe SREP process is not new, as it has always been carried out before the SSM by national supervisors with different and non-homogeneous methodologies and practices. For this reason, the European regulation intended to standardise the SREP methodologies and practices used by the different Authorities at the level of the Banking Union.
\nSREP entered into force in 2016 for IS and only from 2018 became mandatory first for high priority LSIs and then for other LSIs. Following the harmonisation of the SREP process for LSIs, national authorities have been given full flexibility regarding the definition of Pillar 2 guidelines (P2G) [6]. Finally, one of the focal points of the MUV is the possibility for the ECB to take over the supervision of LSIs that are more vulnerable, for example due to a change in materiality profile or due to a choice by the Central Bank as a result of new assessments of the impact the institution might have on the financial system. Supervision of less significant institutions takes the form of periodic assessments conducted jointly by the ECB and the national supervisory authorities of the Member States, with the aim of making best use of the information available to the national authorities. Moreover, for high priority LSIs, the ECB examines the supervisory procedures and relevant draft decisions established by the NCAs themselves [6].
\nThe SREP is a process by which the European Central Bank and the NCA specifically:
Review and assess the ICAAP (Internal Capital Adequacy Process).
Review and evaluate the ILAAP (Internal Liquidity Adequacy Process).
Carry out Business Model Analysis (BMA).
Analyse the bank’s risk individually and in the aggregate, including under stressed conditions, and its contribution to systemic risk.
Evaluate the corporate governance system, the organisational structure and the system of internal controls.
Monitor compliance with all prudential rules.
Make an overall assessment of the bank and initiate corrective action where appropriate.
At the end of the process, the supervisory Authorities send the banks a letter (called a “SREP decision”) specifying the objectives and areas to be addressed and corrected within a defined time frame16.
\nThe SREP is an articulated process that develops through a continuous dialogue and confrontation between supervisor and supervised in order to make an overall assessment, from an integrated perspective, of the stability and resilience of the latter. The inspectors’ findings and the on- and off-site supervision feed the subsequent SREP cycle. In this perspective, the SREP is not a control and assessment activity carried out by the Supervisor once a year, but rather a process of second-pillar prudential control, which unfolds continuously and starts from the identification of the category17 to which the bank belongs (with respect to which to calibrate the intensity of the supervisory activity) against which the intensity of the SREP assessment is established, the supervisory expectations and the information required during the data collection phase, calibrated according to the classes [7] to finally arrive at the so-called SREP decision. The classification is calibrated according to the systemic impact of the intermediary, based on: size, structure, internal organisation, type, purpose and complexity.
\nThe classification of institutions is followed by monitoring of indicators for changes in financial conditions and risk with the objective of updating the assessment of SREP elements. If monitoring reveals a deterioration in the institution’s risk, the Supervisor investigates the causes and may revise the assessments of the SREP elements. Vigilance develops different sets of ratios based on the different specificities of banks, including: ratios for all risks subject to SREP. All ratios used for regulatory requirements (see EU Regulation 575/2013 and Directive 2013/36/EU), minimum requirements on own funds and eligible liabilities under Directive 2014/59/EU (bank recovery), market indicators (equity price, CDS spread, etc.), recovery indicators. The frequency of assessment of all items of the SREP process is calibrated according to the category that the financial intermediary belongs to.
\nThe four central blocks covered by the SREP assessment are: business model analysis, the governance and risk management framework, the capital adequacy framework (ICAAP) and the liquidity management framework (ILAAP).
\nFor each of the four main blocks covered by the SREP, banks are assessed by the Supervisory Authorities on a scale of 1 to 4.18 The outcome of the assessment constitutes the basis for the overall assessment of the SREP: the SREP decision, which is the basis for supervisory measures. The SREP decision is the final summary of the entire Pillar 2 supervisory review process, which reports the bank’s overall score (compared to the assessment of the four main blocks) and, if anomalies are found, any corrective measures of an organisational, capital or liquidity risk containment nature or
Early intervention measures may be triggered by events that could have a significant prudential impact19 on the institution’s financial condition. They should be considered if the institution’s overall or individual SREP score is 4 and even if the SREP score inclusive was 3, but individual elements for governance and internal control, business model strategy, capital adequacy or liquidity score were instead 4. However, the early intervention measures are the result of ongoing monitoring of compliance with the requirements of the CRR and CRDIV with respect to the anomalous situations foreseen by the BRRD in the supervisory activity.
\nIn the SREP decision the Authorities also define the so-called Pillar 2 Requirement (P2R), which
By its very nature, the entire process of Pillar 2 prudential supervision gives shape and content to the fundamental moments of intermediaries’ strategic planning, business choices, capital and liquidity allocation, funding plan, governance and organisational structure. The SREP is certainly a holistic approach to supervision that calls for an equally integrated approach by individual intermediaries to business choices, risk, capital and liquidity management both in normal and stressed conditions (Crisis and Recovery Risk Management), governance and the overall Risk Management framework. In this perspective, the SREP certainly represents a regulatory “stimulus” to a significant qualitative leap in the functions that deal with risks, capital and liquidity in the bank, recognising them as having a primary role in the strategic planning of the bank, as well as a flexible and proactive integration of the corporate control functions (\nTable 4\n).
\n\n | \nDegree of feasibility (within the year) and sustainability (over a three-year horizon) of the business model declared by the bank. Identification of the key elements of the Business Model and assessment of the main areas of vulnerability. | \n
\n | \nAdequacy of the governance model including the main control functions (risk management, internal audit and compliance). Adequacy of the Risk Management system/infrastructure and degree of establishment of a “risk culture”. | \n
\n | \nAdequacy of capital to cover specific risk categories (e.g. credit, market, operational and interest rate risk in the banking book). Overall assessment of ICAAP (documentation, data quality, risk measurement processes, capital planning, ...). | \n
\n | \nAdequacy of overall liquidity management processes/governance; Funding capacity. | \n
SREP process::Building blocks.
Within the SREP process, one of the main moments of assessment is represented by the analysis of the business model of financial intermediaries and the related operational and strategic risks (Business Model Analysis) aimed at establishing the economic (viability) and strategic sustainability of the business model20 of the institution based on its ability to generate acceptable profits over the next 12 months and over a three-year horizon. With the BMA, legislators attempt to investigate in detail the profitability of the current and prospective business model, but also to assess its resilience and weaknesses, which could jeopardise the future survival of the bank and which may not be highlighted by other elements of the SREP. The business model is not to be confused with the concept of “intermediation model”. On closer inspection, the former refers to a broader concept that encompasses both the issue of the intermediation model and other aspects such as the use of technology, the creation of value for the set of stakeholders and the management and operation of the most relevant processes (Maurizio [8]). The business model describes the logic with which an organisation creates, distributes and captures value [9]. However, there is no unambiguous definition of the business model in the literature, nor have European legislators ventured to define it in relation to the financial intermediation sector (Di [10]).
\nFrom this perspective, it is clear that the introduction of the BMA within the SREP process is a clear sign of the importance that European lawmakers assign to strategic planning and therefore to the choice of the intermediary’s business model, which, as is well known, has a large impact on the levels of profit produced. The latter is an issue of strategic importance given the negative trend in profitability in the context of the low profitability of Italian and European banks caused by the international financial crisis and the strong tightening of prudential supervisory obligations on risk, capital and liquidity, which require a thorough review of the intermediary’s strategic choices along possible lines of development of intermediation margins (Artificial Intelligence, attention to sustainable or rather ESG-oriented finance, etc.). The possibility for a bank to exploit resources with a high technological content, albeit following significant initial investments, allows it to achieve cost-reduction objectives, especially with regard to traditional credit activities, but in general for all activities whose costs (e.g. personnel costs) are not adequately remunerated by the revenues generated [11].
\nWhile it is true that business model choices have an impact on the profitability of individual banks, they also have important implications for the stability of the entire financial system (through funding structure,21 revenue composition, cost composition, ownership structure), which is why the BMA has been given an important role in the overall Pillar 2 prudential control process.
\nThe BMA starts with a preliminary assessment of the environment the bank operates in, with particular reference to its core activities. In this initial step, the supervisor is required to assess a number of parameters (total revenues/costs, market position, etc.) and monitor their evolution over time in order to have a clear picture of the condition of the institution and to establish the relevance of its business areas in the context of reference. Competent authorities should use this preliminary assessment to establish the materiality of business lines/areas (i.e. determine which geographic areas, subsidiaries/branches, business lines and product lines are the most relevant based on profit contribution, risk and/or organisational/regulatory priorities -specific requirements for public sector banks to offer certain products- identify the peer group based on competing product/business lines that target the same source of profits/customers, support the application of the proportionality principle.
\nAfter the preliminary macroeconomic assessment, the competent authority should focus on the current business model, on the business lines that are most important in terms of viability or future sustainability of the current business model and/or that are most likely to increase the institution’s exposure to existing or new vulnerabilities, whereby they should assess the relevance of the business lines, previous SREP findings, findings and observations of internal and external audit reports, the importance of strategic plans identifying any business lines to be substantially increased or decreased, results of topical supervisory reviews, observed changes in the business model and peer comparisons (i.e. whether a business line has performed atypically compared to peers). As outlined in the EBA guidelines on the SREP process, the areas for which authorities are tasked with conducting analysis should include, at a minimum, an assessment of the trend in profits and losses in recent years, looking at the most significant indicators of banking activity such as net interest income, net banking income, cost-to-income ratio and loan impairment rate; the composition of the balance sheet in recent years, with particular attention to the composition of liabilities; the concentration of assets by customer, sector or geographic area; an assessment of the intermediary’s risk appetite, taking into account the formal definition of the current limits and the real tendency to respect them in practice; and finally an assessment that takes into account both internal and external factors capable of impacting on the functioning of the business model.
\nIt should be made clear that the BMA has as its ultimate goal:
The feasibility/viability of the current business model over a 12-month horizon.
The sustainability of strategic plans over a three-year horizon.
In other words, the supervisors’ “ultimate” objective is to assess whether the financial intermediary, with its business model and strategy, is credibly capable of generating acceptable returns over a short (12-month) and long-term (three-year) time horizon.
\nThe BMA does not aim to give a rating to the possible business models since the choice of these remains the responsibility of the management body, but to assess viability and sustainability, therefore verifying the bank’s ability to generate “acceptable returns” in the time horizons considered (12 months and 36 months). With regard to viability, having carried out the preliminary analysis, the Supervisor considers:
\n
\n
\n
After the preliminary assessment, that of the entrepreneurial context, the detailed analysis of the current business model for the purposes of assessing the viability thereof, the Authority must
The
The impact of supervisors’ estimates on the business environment (if different from that assumed by the bank).
The level of
The most obvious problem that arises in the assessment phase of the financial intermediary’s business model concerns the existence of documents capable of providing comprehensive information to the supervisory authority on the subject in question. Indeed, in many cases it is difficult to find the documentation relating to the detailed description of the business model adopted or, again, a definition of the responsibilities of the corporate functions involved in the implementation of the activities aimed at complying with the regulatory obligations on the subject. After the process described above and at the end of the BMA process, the authority will have the task of formulating an overall opinion on the business model adopted by the intermediary, highlighting any critical points identified.
\nThe second assessment of the SREP process is devoted to the following areas: Internal governance framework; Risk management framework and risk culture; Risk infrastructure and data and reporting.
\nAt this stage of the assessment, the main objective of the supervisory authority is to evaluate whether the bank’s governance system and risk management process are adequate and consistent with the adopted business model and with what is planned in the risk appetite framework. More specifically, the suitability of the governance is assessed and whether the governance is adequately informed about the risks assumed by the bank, the risk management policies, the impact of the risk management policies on the banking activity as well as the level of capitalisation and whether this level is in balance with the risks assumed. It also assesses whether the bank has remuneration policies that comply with applicable regulations and whether the bank has an adequate system of internal controls (focusing on the risk management and compliance function), and in particular whether: (a) risk management policies have been properly defined and documented; (b) whether operational limits to the risk that can be taken are properly defined for the various business units and the bank’s risk appetite; (c) whether these limits are complied with; (d) whether the risk management function is able to measure, control and manage the risks the bank is exposed to; and (e) whether the bank in its operations complies with the rules affecting its business and internal regulations. Finally, in order for the analysis to be complete, the authority examines the technological infrastructure supporting the risk management process, as well as the quality of the data and the data collection mechanism. In fact, it is easy to see how scarce or irrelevant information can compromise the proper operation of the banking business, especially in terms of risk management and control. In summary, the areas impacted by this analysis are:
Overall internal governance framework.
Corporate and risk culture.
Organisation and operation of the management body.
Remuneration policies and practices.
Risk management framework, including ICAAP and ILAAP.
Internal control framework, including the internal audit function.
Information systems and business continuity.
Recovery planning arrangements.
Particular attention is paid to the assessment of the Risk management framework and the diffusion of an adequate risk culture at all organisational levels of the bank. The attention paid by supervisors to the three corporate control functions and in particular to the Risk Management function highlights the strategic role assumed by this function in recent years: there is no possibility of planning the opening of new branches, offering new products, changing the funding plan without taking into account the impact of these choices on the governance of risks, capital and liquidity. Given the strategic role that this function plays in the overall governance of the bank, it is clear that it must be staffed with adequate professionalism to oversee the various tasks and responsibilities that regulation has greatly articulated in recent years. In carrying out its activities, the Risk Management then has the moral obligation to spread the culture of risk at every organisational level; it is the culture of risk that is the real engine of change to guide the bank in the current hyper-regulated, volatile and complex market context. As pointed out by FSB [12]22 “
An appropriate risk–return combination, consistent with the financial institution’s risk appetite.
An effective system of controls, commensurate with the size and complexity of the financial institution.
The quality of risk models, the accuracy of data, the ability to measure risks accurately, using appropriate tools.
Limit possible violations of the policies followed.
A sound and widespread risk culture is the
For this reason, the culture of risk, being the humus of the sound and prudent management of a bank, cannot remain the exclusive property of the relative Risk Management function, but must become part of the common language and cultural baggage of the other actors involved in the governance of the company at any organisational level. In this perspective, it seems useful to clarify the skills and professionalism required by the corporate control functions, and therefore also by the Risk Management.
\nOn 26 September 2017, EBA and ESMA [13] issued guidelines pursuant to article 9(1) of Directive 2014/65/EU (MiFID II) and article 91(12) of Directive 2013/36/EU (CRD IV). The Guidelines explicitly identify
In compliance with the guidelines, banking and financial institutions must ensure and assess that KFH have an appropriate level of reputation, honesty, integrity, knowledge, skills and experience:
When applying for the authorisation;
When appointing a new KFH (within one month of appointment);
When necessary to ensure “ongoing” monitoring, in particular when “events” occur that make it appropriate to reassess the fitness of KFH (changes in the organisational structure, occurrence of episodes with reputational impact, changes in the business model).
In this regard, banks and financial institutions should establish their own fitness policy, including an appropriate induction plan (for new appointments) and ongoing training to ensure that they are familiar with the required areas and have the necessary skills. The Guidelines outline a perimeter of competencies for the fitness assessment of KFHs that includes not only their previous experience but also technical competencies23 (banking and financial markets, legal requirements, regulatory framework, strategic planning, etc.) and a very articulated set of soft skills including: independence of mind, decision-making ability, authenticity (consistency with stated values), communication and judgement skills (examines, recognises and understands the essential elements of issues with respect to which he/she is able to weigh different courses of action and project himself/herself beyond his/her area of responsibility), customer and quality orientation (of products, services, relationships), leadership, loyalty (identifies with the company, its value system defends the interests of the company and operates objectively and critically with a sense of involvement), stress resistance, negotiation skills, awareness of the external context (he/she is well informed about financial, economic, social and other relevant developments at a national and international level that may affect the company), ability to work in a team, persuasiveness, strategic acumen (he/she is able to develop a realistic vision of future developments by translating it into long-term objectives, e.g. by applying scenario analysis), ability to chair meetings efficiently and effectively creating an open atmosphere that encourages everyone to participate.
\nIndependence of mind should not be confused with the independence required of members of the management body. In the latter case, reference is made to the fact that a member of the body in question must not have had any present or recent relationship or connection of any kind with the intermediary that could influence the latter’s ability to take balanced and independent decisions in the performance of his/her functions. For example, the fact that a member of the board of directors is considered to be “independent” does not mean that the member simultaneously has independence of mind [14]. The latter is in fact a set of necessary behavioural skills, including courage, conviction and strength to effectively evaluate and challenge the proposed decisions of other board members, the ability to ask questions of board members and to resist group-think.
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The combination of electronics and computer science with biology and medicine has improved patient diagnosis, reduced rehabilitation time, and helped to facilitate a better quality of life. Nowadays, all medical imaging devices, medical instruments, or new laboratory techniques result from the cooperation of specialists in various fields. The series of Biomedical Engineering books covers such areas of knowledge as chemistry, physics, electronics, medicine, and biology. 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Dr. Koprowski has authored more than a hundred research papers with dozens in impact factor (IF) journals and has authored or co-authored six books. Additionally, he is the author of several national and international patents in the field of biomedical devices and imaging. Since 2011, he has been a reviewer of grants and projects (including EU projects) in biomedical engineering.",institutionString:null,institution:{name:"University of Silesia",institutionURL:null,country:{name:"Poland"}}},subseries:[{id:"7",title:"Bioinformatics and Medical Informatics",keywords:"Biomedical Data, Drug Discovery, Clinical Diagnostics, Decoding Human Genome, AI in Personalized Medicine, Disease-prevention Strategies, Big Data Analysis in Medicine",scope:"Bioinformatics aims to help understand the functioning of the mechanisms of living organisms through the construction and use of quantitative tools. The applications of this research cover many related fields, such as biotechnology and medicine, where, for example, Bioinformatics contributes to faster drug design, DNA analysis in forensics, and DNA sequence analysis in the field of personalized medicine. Personalized medicine is a type of medical care in which treatment is customized individually for each patient. Personalized medicine enables more effective therapy, reduces the costs of therapy and clinical trials, and also minimizes the risk of side effects. Nevertheless, advances in personalized medicine would not have been possible without bioinformatics, which can analyze the human genome and other vast amounts of biomedical data, especially in genetics. The rapid growth of information technology enabled the development of new tools to decode human genomes, large-scale studies of genetic variations and medical informatics. The considerable development of technology, including the computing power of computers, is also conducive to the development of bioinformatics, including personalized medicine. In an era of rapidly growing data volumes and ever lower costs of generating, storing and computing data, personalized medicine holds great promises. Modern computational methods used as bioinformatics tools can integrate multi-scale, multi-modal and longitudinal patient data to create even more effective and safer therapy and disease prevention methods. Main aspects of the topic are: Applying bioinformatics in drug discovery and development; Bioinformatics in clinical diagnostics (genetic variants that act as markers for a condition or a disease); Blockchain and Artificial Intelligence/Machine Learning in personalized medicine; Customize disease-prevention strategies in personalized medicine; Big data analysis in personalized medicine; Translating stratification algorithms into clinical practice of personalized medicine.",annualVolume:11403,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/7.jpg",editor:{id:"351533",title:"Dr.",name:"Slawomir",middleName:null,surname:"Wilczynski",fullName:"Slawomir Wilczynski",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035U1loQAC/Profile_Picture_1630074514792",institutionString:null,institution:{name:"Medical University of Silesia",institutionURL:null,country:{name:"Poland"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"5886",title:"Dr.",name:"Alexandros",middleName:"T.",surname:"Tzallas",fullName:"Alexandros Tzallas",profilePictureURL:"https://mts.intechopen.com/storage/users/5886/images/system/5886.png",institutionString:"University of Ioannina, Greece & Imperial College London",institution:{name:"University of Ioannina",institutionURL:null,country:{name:"Greece"}}},{id:"257388",title:"Distinguished Prof.",name:"Lulu",middleName:null,surname:"Wang",fullName:"Lulu Wang",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRX6kQAG/Profile_Picture_1630329584194",institutionString:null,institution:{name:"Shenzhen Technology University",institutionURL:null,country:{name:"China"}}},{id:"225387",title:"Prof.",name:"Reda",middleName:"R.",surname:"Gharieb",fullName:"Reda Gharieb",profilePictureURL:"https://mts.intechopen.com/storage/users/225387/images/system/225387.jpg",institutionString:"Assiut University",institution:{name:"Assiut University",institutionURL:null,country:{name:"Egypt"}}}]},{id:"8",title:"Bioinspired Technology and Biomechanics",keywords:"Bioinspired Systems, Biomechanics, Assistive Technology, Rehabilitation",scope:'Bioinspired technologies take advantage of understanding the actual biological system to provide solutions to problems in several areas. Recently, bioinspired systems have been successfully employing biomechanics to develop and improve assistive technology and rehabilitation devices. The research topic "Bioinspired Technology and Biomechanics" welcomes studies reporting recent advances in bioinspired technologies that contribute to individuals\' health, inclusion, and rehabilitation. Possible contributions can address (but are not limited to) the following research topics: Bioinspired design and control of exoskeletons, orthoses, and prostheses; Experimental evaluation of the effect of assistive devices (e.g., influence on gait, balance, and neuromuscular system); Bioinspired technologies for rehabilitation, including clinical studies reporting evaluations; Application of neuromuscular and biomechanical models to the development of bioinspired technology.',annualVolume:11404,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/8.jpg",editor:{id:"144937",title:"Prof.",name:"Adriano",middleName:"De Oliveira",surname:"Andrade",fullName:"Adriano Andrade",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRC8QQAW/Profile_Picture_1625219101815",institutionString:null,institution:{name:"Federal University of Uberlândia",institutionURL:null,country:{name:"Brazil"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"49517",title:"Prof.",name:"Hitoshi",middleName:null,surname:"Tsunashima",fullName:"Hitoshi Tsunashima",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYTP4QAO/Profile_Picture_1625819726528",institutionString:null,institution:{name:"Nihon University",institutionURL:null,country:{name:"Japan"}}},{id:"425354",title:"Dr.",name:"Marcus",middleName:"Fraga",surname:"Vieira",fullName:"Marcus Vieira",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003BJSgIQAX/Profile_Picture_1627904687309",institutionString:null,institution:{name:"Universidade Federal de Goiás",institutionURL:null,country:{name:"Brazil"}}},{id:"196746",title:"Dr.",name:"Ramana",middleName:null,surname:"Vinjamuri",fullName:"Ramana Vinjamuri",profilePictureURL:"https://mts.intechopen.com/storage/users/196746/images/system/196746.jpeg",institutionString:"University of Maryland, Baltimore County",institution:{name:"University of Maryland, Baltimore County",institutionURL:null,country:{name:"United States of America"}}}]},{id:"9",title:"Biotechnology - Biosensors, Biomaterials and Tissue Engineering",keywords:"Biotechnology, Biosensors, Biomaterials, Tissue Engineering",scope:"The Biotechnology - Biosensors, Biomaterials and Tissue Engineering topic within the Biomedical Engineering Series aims to rapidly publish contributions on all aspects of biotechnology, biosensors, biomaterial and tissue engineering. We encourage the submission of manuscripts that provide novel and mechanistic insights that report significant advances in the fields. Topics can include but are not limited to: Biotechnology such as biotechnological products and process engineering; Biotechnologically relevant enzymes and proteins; Bioenergy and biofuels; Applied genetics and molecular biotechnology; Genomics, transcriptomics, proteomics; Applied microbial and cell physiology; Environmental biotechnology; Methods and protocols. Moreover, topics in biosensor technology, like sensors that incorporate enzymes, antibodies, nucleic acids, whole cells, tissues and organelles, and other biological or biologically inspired components will be considered, and topics exploring transducers, including those based on electrochemical and optical piezoelectric, thermal, magnetic, and micromechanical elements. Chapters exploring biomaterial approaches such as polymer synthesis and characterization, drug and gene vector design, biocompatibility, immunology and toxicology, and self-assembly at the nanoscale, are welcome. Finally, the tissue engineering subcategory will support topics such as the fundamentals of stem cells and progenitor cells and their proliferation, differentiation, bioreactors for three-dimensional culture and studies of phenotypic changes, stem and progenitor cells, both short and long term, ex vivo and in vivo implantation both in preclinical models and also in clinical trials.",annualVolume:11405,isOpenForSubmission:!0,coverUrl:"https://cdn.intechopen.com/series_topics/covers/9.jpg",editor:{id:"126286",title:"Dr.",name:"Luis",middleName:"Jesús",surname:"Villarreal-Gómez",fullName:"Luis Villarreal-Gómez",profilePictureURL:"https://mts.intechopen.com/storage/users/126286/images/system/126286.jpg",institutionString:null,institution:{name:"Autonomous University of Baja California",institutionURL:null,country:{name:"Mexico"}}},editorTwo:null,editorThree:null,editorialBoard:[{id:"35539",title:"Dr.",name:"Cecilia",middleName:null,surname:"Cristea",fullName:"Cecilia Cristea",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYQ65QAG/Profile_Picture_1621007741527",institutionString:null,institution:{name:"Iuliu Hațieganu University of Medicine and Pharmacy",institutionURL:null,country:{name:"Romania"}}},{id:"40735",title:"Dr.",name:"Gil",middleName:"Alberto Batista",surname:"Gonçalves",fullName:"Gil Gonçalves",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYRLGQA4/Profile_Picture_1628492612759",institutionString:null,institution:{name:"University of Aveiro",institutionURL:null,country:{name:"Portugal"}}},{id:"211725",title:"Associate Prof.",name:"Johann F.",middleName:null,surname:"Osma",fullName:"Johann F. 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