Cerebellar abnormalities in mouse models of ASD.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\\n"}]',published:!0,mainMedia:{caption:"Highly Cited",originalUrl:"/media/original/117"}},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 191 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 261 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
Note: Edited in March 2021
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{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"}]},book:{item:{type:"book",id:"5810",leadTitle:null,fullTitle:"Socialization - A Multidimensional Perspective",title:"Socialization",subtitle:"A Multidimensional Perspective",reviewType:"peer-reviewed",abstract:"This is the first book that highlights how socialization is experienced as being a complex concept in everyday life in various countries of the world. The book represents the first attempt to provide an original and multidimensional definition of socialization that takes into account the contribution of different disciplines, such as philosophy, psychology, sociology, education, and even architecture, to underline its importance as a key aspect of human experience. Therefore, it represents an extraordinary opportunity to outline new horizons in the field.",isbn:"978-1-78923-309-4",printIsbn:"978-1-78923-308-7",pdfIsbn:"978-1-83881-245-4",doi:"10.5772/65537",price:119,priceEur:129,priceUsd:155,slug:"socialization-a-multidimensional-perspective",numberOfPages:202,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"bfac2e9c0ec2963193e9d15d617c6a01",bookSignature:"Rosalba Morese, Sara Palermo and Juri Nervo",publishedDate:"June 20th 2018",coverURL:"https://cdn.intechopen.com/books/images_new/5810.jpg",numberOfDownloads:10952,numberOfWosCitations:9,numberOfCrossrefCitations:12,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:18,numberOfDimensionsCitationsByBook:2,hasAltmetrics:1,numberOfTotalCitations:39,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 3rd 2016",dateEndSecondStepPublish:"October 24th 2016",dateEndThirdStepPublish:"July 29th 2017",dateEndFourthStepPublish:"August 29th 2017",dateEndFifthStepPublish:"October 29th 2017",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"214435",title:"Dr.",name:"Rosalba",middleName:null,surname:"Morese",slug:"rosalba-morese",fullName:"Rosalba Morese",profilePictureURL:"https://mts.intechopen.com/storage/users/214435/images/system/214435.jpg",biography:"Rosalba Morese, born in Italy, holds a bachelor\\'s degree in psychology at the University of Parma and a Ph.D. in neuroscience at the University of Turin. She aims to develop new techniques and approaches in cognitive science and social neuroscience. She is an expert in experimental neuroscience, neuroeconomics, psychophysiology, and cognitive and social neuroscience. She performs neuroimaging studies in social contexts in order to investigate neural correlates involved during social interactions, such as, social exclusion, social support, empathy, communicative intention, social decision-making, in-group and out-group settings, etc. She currently works at Università della Svizzera italiana, Lugano, Switzerland.\n\nFor more information: http://usi.to/xuj",institutionString:"Faculty of Biomedical Sciences",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"8",totalChapterViews:"0",totalEditedBooks:"4",institution:{name:"Universita della Svizzera Italiana",institutionURL:null,country:{name:"Switzerland"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"233998",title:"Ph.D.",name:"Sara",middleName:null,surname:"Palermo",slug:"sara-palermo",fullName:"Sara Palermo",profilePictureURL:"https://mts.intechopen.com/storage/users/233998/images/system/233998.png",biography:"Sara Palermo has an MSc in clinical psychology and a PhD in experimental neuroscience. She is specialty chief editor of Frontiers in Psychology, Neuropsychology, and scientific director of the Italian National Institute of Philanthropy, Filantropolis. She is a member of the Italian Society of Neuropsychology, the Italian Association of Psychogeriatrics, the Italian Society of Neurology for Dementia, and the Society for Interdisciplinary Placebo Studies. She was a member of the European Innovation Partnership on Active and Healthy Ageing (EIP AHA), for which she was involved in Action Group A3: Action for Prevention of Functional Decline and Frailty. Dr Palermo works as a researcher at the Department of Psychology - University of Turin (Italy) and as Scientific Consultant at the Fondazione IRCCS, Istituto Neurologico Carlo Besta (FINCB), Milan, Italy.",institutionString:"University of Turin, Italy & The Foundation of the Carlo Besta Neurological Institute IRCCS",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"6",totalChapterViews:"0",totalEditedBooks:"5",institution:{name:"University of Turin",institutionURL:null,country:{name:"Italy"}}},coeditorTwo:{id:"218983",title:"BSc.",name:"Juri",middleName:null,surname:"Nervo",slug:"juri-nervo",fullName:"Juri Nervo",profilePictureURL:"https://mts.intechopen.com/storage/users/218983/images/system/218983.jpg",biography:"Juri Nervo is an expert Social Project Manager, studying Professional Counseling at the Adler Institute of Turin, Italy. He has worked as a teacher in primary schools, then as Director of Fondazione Agape dello Spirito Santo Onlus. He began working at Ferrante Aporti, a prison for minors in Turin, improving educational projects (sports and work project with young inmates). Currently, he is the President of EssereUmani Onlus, Italy. He has coordinated different formative and informative campaigns about justice, legality, bullying and conflict management that involve kids, especially from schools, but also adult groups for primary and secondary prevention by different “human instruments” like empathy, listening, silence and mediation. He has dedicated himself to studying bullying dynamics, with an important project called “Mediamente Bullo.”",institutionString:"Alder Institute of Turin",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"2",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"281",title:"Sociology",slug:"sociology"}],chapters:[{id:"59476",title:"Socialization from the Point of View of Postnonclassical (Universum) Sociological Theory of Rationality",doi:"10.5772/intechopen.74130",slug:"socialization-from-the-point-of-view-of-postnonclassical-universum-sociological-theory-of-rationalit",totalDownloads:981,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The chapter is focused on the theoretical perspective of analyzing the process of socialization from the standpoint of the postnonclassical (universum) rationality theory. Rationality is defined as the cognitive self-reference of a society, a recursive layer of social reality, reflecting its existence and development via the means of consciousness and thinking. Socialization is considered as a process of mastering culture, the former having rational and irrational sides. The rational side is connected with the individual’s acquisition of the ability to reflect reality discretely, normatively, symbolically, and reflexively. These abilities are necessary conditions to enter the world of human society culture. The irrational side is expressed in the process of the needs’ socialization, during which the individual’s extra-subjective needs in emotional satisfaction are transformed into orientations toward experiencing certain emotional states associated with the possibilities of satisfying needs in a particular society and culture. An important result of the socialization process is the formation of a system of the individual’s value orientations. The rational level of this system consists of orientations that have become the subject of the individual’s conscious choice. The irrational level consists of orientations to value experiences; these are the individual’s emotional experiences of his/her relationships with reality.",signatures:"Dmitry O. Trufanov",downloadPdfUrl:"/chapter/pdf-download/59476",previewPdfUrl:"/chapter/pdf-preview/59476",authors:[{id:"213869",title:"Dr.",name:"Dmitry",surname:"Trufanov",slug:"dmitry-trufanov",fullName:"Dmitry Trufanov"}],corrections:null},{id:"59448",title:"Socialization in Modern Transitive World",doi:"10.5772/intechopen.74237",slug:"socialization-in-modern-transitive-world",totalDownloads:979,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The peculiarity of socialization in transitivity world is examined. Social and personal aspects of socialization in transitivity are revealed. It was stated that different aspects of transitivity are associated with various problems—the uncertainty with a destruction of identity and multiplicity—with difficulties with directions of socialization. Challenges-consequences of socio-psychological transitivity are shown. The analysis of obtained material showed the decrease of positive socialization in transitive space because it appears for youth as difficult situation which includes multicultural, uncertain and changing aspects of surrounding world. The results of two empirical studies are presented. The leading trends of transitivity in adolescence are the “weakening” of the criteria for self-assessing and value orientations. It leads to the increasing of conformism and positive attitudes towards schoolmates and decreasing orientation toward interaction with them. It is also decrease dominance, activity and responsibility. It was shown that reflection of the situation as a transitivity crisis situation has a particularly negative impact on socialization in a multicultural space. The ethnic identification is carried out on the basis of native, rather than the most commonly used language. Majority of teenagers and youth have an unambiguously positive, idealized attitude towards their ethnos, which leads to ethnocentrism and a negative attitude towards alien nations.",signatures:"Tatiana Martsinkovskaya, Ekaterina Kiseleva, Oksana Gavrichenko\nand Darja Tkachenko",downloadPdfUrl:"/chapter/pdf-download/59448",previewPdfUrl:"/chapter/pdf-preview/59448",authors:[{id:"214496",title:"Prof.",name:"Tatiana",surname:"Martsinkovskaya",slug:"tatiana-martsinkovskaya",fullName:"Tatiana Martsinkovskaya"}],corrections:null},{id:"60254",title:"Improving Social Skills through Collaborative Artwork and Group Activity",doi:"10.5772/intechopen.74789",slug:"improving-social-skills-through-collaborative-artwork-and-group-activity",totalDownloads:948,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"In this chapter, we introduce the framework and practice of collaborative artwork and group activity. In particular, we focus on the collaborative block creation method and show its psychological evidence. The first section introduces the theoretical background underlying collaborative work and overviews recent studies concerning social skills, especially from psychological perspective. The second section introduces this study, in which we demonstrated the effectiveness of collaborative LEGO® block creation work as a medium of communication in group therapy and investigated the effects of fostering communication, especially for developing social skills and trust. The third section focuses on interpersonal relations. We examined the psychological effect of collaborative block creation from the perspective of Ibasho, a Japanese term for one’s whereabouts or a place of our own. Next, we show a case study of collaborative LEGO block creation for Japanese adolescents with autism spectrum disorder (ASD). Finally, we introduce a new type of group approach in the area of student counseling.",signatures:"Daiki Kato",downloadPdfUrl:"/chapter/pdf-download/60254",previewPdfUrl:"/chapter/pdf-preview/60254",authors:[{id:"198255",title:"Ph.D.",name:"Daiki",surname:"Kato",slug:"daiki-kato",fullName:"Daiki Kato"}],corrections:null},{id:"59668",title:"A Review of Research on Gamification Approach in Education",doi:"10.5772/intechopen.74131",slug:"a-review-of-research-on-gamification-approach-in-education",totalDownloads:1805,totalCrossrefCites:6,totalDimensionsCites:10,hasAltmetrics:1,abstract:"Gamification has become the most popular topic of the last few years. Studies in gamification area are examined based on certain different criteria in this study and content analysis method was used in order to identify trends in this area. Web of Science were scanned through using gamification as keyword without year restriction. A total number of 313 studies were regarded as appropriate for the aim of the study and examined. It is seen that research in this area have begun in 2011 and increased every year. It is also seen that motivational theories are mostly preferred in the studies conducted in gamification area. It was determined that goal-duty, reward and progression sticks are the mostly used components as game components. It is seen that gamification applications are frequently preferred in virtual environment, simulation and augmented reality learning environments after mobile environments and in parallel with these, they are also preferred in learning areas such as public, service, food and health. Therefore, identifying different activities which could affect success in online environments, integrating these into education environment and provide these activities with theories appropriate for students’ ages for them not to lose their motivation are essential.",signatures:"Senay Kocakoyun and Fezile Ozdamli",downloadPdfUrl:"/chapter/pdf-download/59668",previewPdfUrl:"/chapter/pdf-preview/59668",authors:[{id:"198755",title:"Associate Prof.",name:"Fezile",surname:"Ozdamli",slug:"fezile-ozdamli",fullName:"Fezile Ozdamli"},{id:"199223",title:"MSc.",name:"Senay",surname:"Kocakoyun",slug:"senay-kocakoyun",fullName:"Senay Kocakoyun"}],corrections:null},{id:"59680",title:"Socialization Processes toward Children and Adolescents for Developing Empathy, Sympathy and Prosocial Behaviors",doi:"10.5772/intechopen.74132",slug:"socialization-processes-toward-children-and-adolescents-for-developing-empathy-sympathy-and-prosocia",totalDownloads:1137,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter addresses the socialization processes for the development of empathy, sympathy and prosocial behaviors in children and adolescents. Democratic or authoritative socialization practices contribute to prosocial development. Parental support, warmth and sensitivity, parental induction and inductive reasoning, parental demandingness and control have been associated with empathy, sympathy and behavior in children and adolescents. Parental warmth/responsiveness can develop a secure attachment between the parent and the child. Securely attached children tend to be responsive to parental controls and more eager learners and prosocial during the socialization process. Parents may foster behavior in children by modeling and concerning for the needs of others. Parents may induce perspective-taking, empathy and sympathy in their children and adolescents by pointing out the beneficial or harmful consequences of their actions through inductive reasoning and explanations. Parental inductive reasoning and explanations can lead to empathy-based guilt in them by highlighting consequences of the deviating behavior in the children and adolescents for the victim. Children and adolescents can attend to and care about parental messages, internalize prosocial values of their parents, socialize to acquire prosocial behavior when parents behave warmly, responsively and supportively and use inductive reasoning and explanations for their children and adolescents in socialization practices.",signatures:"Turhan Şengönül",downloadPdfUrl:"/chapter/pdf-download/59680",previewPdfUrl:"/chapter/pdf-preview/59680",authors:[{id:"213860",title:"Associate Prof.",name:"Turhan",surname:"Şengönül",slug:"turhan-sengonul",fullName:"Turhan Şengönül"}],corrections:null},{id:"61316",title:"I Teach You to Quarrel - Empathy and Mediation: Tools for Preventing Bullying",doi:"10.5772/intechopen.76882",slug:"i-teach-you-to-quarrel-empathy-and-mediation-tools-for-preventing-bullying",totalDownloads:1025,totalCrossrefCites:4,totalDimensionsCites:5,hasAltmetrics:0,abstract:"Bullying is a very common, complex and important public health problem among school students. Dovigo describes the school as a place where the conflict can emerge among relational dynamics and involve students, teachers and families. Through the description of an Italian pilot project “Mediamente Bullo,” this chapter examines two tools for preventing bullying: empathy, the ability to share and understand emotional states of others, and mediation, useful to cope interpersonal conflicts. Using the mediation tool, students can learn that many forms of conflicts, including violence, can be solved by identifying the causes, discussing them and practicing nonviolent methods and behaviors. This process helps students to become more aware of positive aspects during the conflict and the power that they have in making important and positive choices. In addition, using the empathy tool, they can better understand the experience of social exclusion. In fact, several studies show that children with higher levels of empathy show less aggressive and more prosocial behaviors and they are more able to regulate their emotions. The goal of this chapter is to provide a contribution about integrated application of two important tools, mediation and empathy, in bullying among school-aged youth for future directions and intervention efforts.",signatures:"Rosalba Morese, Matteo Defedele and Juri Nervo",downloadPdfUrl:"/chapter/pdf-download/61316",previewPdfUrl:"/chapter/pdf-preview/61316",authors:[{id:"214435",title:"Dr.",name:"Rosalba",surname:"Morese",slug:"rosalba-morese",fullName:"Rosalba Morese"},{id:"218983",title:"BSc.",name:"Juri",surname:"Nervo",slug:"juri-nervo",fullName:"Juri Nervo"},{id:"218984",title:"MSc.",name:"Matteo",surname:"Defedele",slug:"matteo-defedele",fullName:"Matteo Defedele"}],corrections:null},{id:"60857",title:"Socialization, Poverty and Love: Contributions from the Sociology of the Body/Emotion",doi:"10.5772/intechopen.74391",slug:"socialization-poverty-and-love-contributions-from-the-sociology-of-the-body-emotion",totalDownloads:1111,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"This chapter aims to describe the central features of some conditions that enable the socialization of children and adolescents in Argentina as a possible example of them in the Global South, from the perspective of a sociology of the body/emotion. To achieve this goal, we propose the following argumentative strategy: (1) first, we will present a general approach to a sociology of bodies/emotions that allows us to access the phenomenon of socialization in an “oblique” way; (2) we will present general data related to the transformation of the educational institution as processes associated to the conditions of possibility/obstacle to the connection education-socialization; (3) we present and analyze data on the status of child poverty in order to render some central features of the processes that condition the possibilities from which children and adolescents “become part” of society; (4) the same is done regarding the nutritional deficit in Argentina; (5) to conclude, the re-constructed scenario is completed by identifying and describing interstitial forms from which maternal “love” is constituted as a platform for the possibility of certain axes of socialization in spaces of socio-segregation and expropriation.",signatures:"Adrián Scribano, Angélica De Sena and Pedro Lisdero",downloadPdfUrl:"/chapter/pdf-download/60857",previewPdfUrl:"/chapter/pdf-preview/60857",authors:[{id:"214973",title:"Dr.",name:"Adrian",surname:"Scribano",slug:"adrian-scribano",fullName:"Adrian Scribano"},{id:"214974",title:"Dr.",name:"Angelica",surname:"De Sena",slug:"angelica-de-sena",fullName:"Angelica De Sena"},{id:"214976",title:"Dr.",name:"Pedro",surname:"Lisdero",slug:"pedro-lisdero",fullName:"Pedro Lisdero"}],corrections:null},{id:"59697",title:"Entrepreneurship and Interdisciplinary School Projects of Vulnerable Students in Santiago de Chile: Experiences from the “123 Emprender” Program",doi:"10.5772/intechopen.74088",slug:"entrepreneurship-and-interdisciplinary-school-projects-of-vulnerable-students-in-santiago-de-chile-e",totalDownloads:845,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Currently, to learn entrepreneurial skills, economic and financial literacy is relevant to understand the globalized world. In this way, around the world various programs are being developed to support the learning process of relevant knowledge and skills. Therefore, financial and entrepreneurial education is being added to different curricular programs from elementary schools to universities, aimed at developing basic skills to survive in this increasingly complex world. From the Center of Excellence in Economic Psychology and Consumption (CEPEC), economic literacy and entrepreneurship have been taught to schoolchildren through the methodology of interdisciplinary classroom projects, where multidisciplinary pedagogical interests and school interests are articulated through a central axis. The second version of the program, “Teaching to Teach: Economics and Entrepreneurship,” for students between 11 and 14 years old, was created in 2016 in conjunction with Juega+, and sought to promote financial knowledge as well as entrepreneurial skills in children, which are developed through a social entrepreneurship project. To evaluate the experience of this program descriptive-type qualitative research has been carried out through six focus groups, one for each participating school, whose general objective was to describe the experience of the participants of the “123 emprender” program, the results obtained show acceptance, enthusiasm and enjoyment to this new form of learning. In addition, students show an incorporation of economic and financial concepts; they give relevance to the collaborative work, among other skills.",signatures:"Marianela Denegri-Coria, Pamela Salazar-Valenzuela, Pamela\nCanales-Poo and Alejandra Gallo-Poblete",downloadPdfUrl:"/chapter/pdf-download/59697",previewPdfUrl:"/chapter/pdf-preview/59697",authors:[{id:"214321",title:"Dr.",name:"Marianela",surname:"Denegri-Coria",slug:"marianela-denegri-coria",fullName:"Marianela Denegri-Coria"}],corrections:null},{id:"59833",title:"The Hijab as Gift: Mechanisms of Community Socialisation in the Muslim Diaspora",doi:"10.5772/intechopen.74649",slug:"the-hijab-as-gift-mechanisms-of-community-socialisation-in-the-muslim-diaspora",totalDownloads:968,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:1,abstract:"In the worldwide Islamic diaspora today, how does the socialisation of women into Islamic belief and observance operate? This chapter considers such matters in the contemporary Finnish context. It deals with issues of bodily comportment and types of garments intended to be expressive of Islamic piety, and made available by the globalised Islamic fashion industry. The focus is on the means whereby sartorial objects are used to encourage females to adopt certain kinds of practices, thought to be expressive of the religious norms of particular diasporic communities. Attention is directed to what happens when one woman gives another woman an Islamic garment as a gift. The gift brings with it a set of obligations on the part of the receiver, which functions as often potent means of ensuring acceptance of group norms as to acceptable and unacceptable visual appearance and behaviour. We discuss this with reference to Marcel Mauss’s classical anthropological work on the institution of gift-giving. It is found that Mauss’s original insights continue to be valuable for understanding socialisation processes in globalised, diaspora contexts today.",signatures:"Anna-Mari Almila and David Inglis",downloadPdfUrl:"/chapter/pdf-download/59833",previewPdfUrl:"/chapter/pdf-preview/59833",authors:[{id:"202010",title:"Prof.",name:"David",surname:"Inglis",slug:"david-inglis",fullName:"David Inglis"},{id:"202118",title:"Dr.",name:"Anna-Mari",surname:"Almila",slug:"anna-mari-almila",fullName:"Anna-Mari Almila"}],corrections:null},{id:"59406",title:"How Do Social Values and Norms Affect Architecture of the Turkish House?",doi:"10.5772/intechopen.74166",slug:"how-do-social-values-and-norms-affect-architecture-of-the-turkish-house-",totalDownloads:1155,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"This chapter investigates the relationship between social, cultural and religious traditions and the architecture of vernacular housing. It also represents a search for answers as to how the Turkish cultural traditions of the traditional Turkish family, beliefs, values and rituals influence housing architecture. The relationship between the house form and sociocultural factors can be explained through a model. Therefore, in this chapter, a model that consists of four parts and is flexible is used. It shows the linkages between architectural artifacts selected or devised by a culture, architectural values, social norms and social values. We illustrate the model through a study of the traditional Turkish house, focusing on how social values such as religious beliefs or the relationship between the male and the female figure, family structure, statue of the family in the society, privacy of the family, neighborhood, hospitality and social values in Turkish-Islamic tradition relate, in order to build form in Anatolia.",signatures:"Nevnihal Erdoğan",downloadPdfUrl:"/chapter/pdf-download/59406",previewPdfUrl:"/chapter/pdf-preview/59406",authors:[{id:"197524",title:"Prof.",name:"Nevnihal",surname:"Erdoğan",slug:"nevnihal-erdogan",fullName:"Nevnihal Erdoğan"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8262",title:"The New Forms of Social Exclusion",subtitle:null,isOpenForSubmission:!1,hash:"29bf235aa7659d3651183fe9ea49dc0d",slug:"the-new-forms-of-social-exclusion",bookSignature:"Rosalba Morese and Sara Palermo",coverURL:"https://cdn.intechopen.com/books/images_new/8262.jpg",editedByType:"Edited by",editors:[{id:"214435",title:"Dr.",name:"Rosalba",surname:"Morese",slug:"rosalba-morese",fullName:"Rosalba Morese"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10450",title:"Evolutionary Psychology Meets Social Neuroscience",subtitle:null,isOpenForSubmission:!1,hash:"bd4df54e3fb185306ec3899db7044efb",slug:"evolutionary-psychology-meets-social-neuroscience",bookSignature:"Rosalba Morese, Vincenzo Auriemma and Sara Palermo",coverURL:"https://cdn.intechopen.com/books/images_new/10450.jpg",editedByType:"Edited by",editors:[{id:"214435",title:"Dr.",name:"Rosalba",surname:"Morese",slug:"rosalba-morese",fullName:"Rosalba Morese"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"7818",title:"Social Isolation",subtitle:"An Interdisciplinary View",isOpenForSubmission:!1,hash:"db3b513d7d35476f333a0d4a3147935b",slug:"social-isolation-an-interdisciplinary-view",bookSignature:"Rosalba Morese, Sara Palermo and Raffaella Fiorella",coverURL:"https://cdn.intechopen.com/books/images_new/7818.jpg",editedByType:"Edited by",editors:[{id:"214435",title:"Dr.",name:"Rosalba",surname:"Morese",slug:"rosalba-morese",fullName:"Rosalba Morese"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10656",title:"Intellectual Property",subtitle:null,isOpenForSubmission:!1,hash:"135df9b403b125a6458eba971faab3f6",slug:"intellectual-property",bookSignature:"Sakthivel Lakshmana Prabu and Timmakkondu Narasimman Kuppusami Suriyaprakash",coverURL:"https://cdn.intechopen.com/books/images_new/10656.jpg",editedByType:"Edited by",editors:[{id:"91590",title:"Dr.",name:"Sakthivel",surname:"Lakshmana Prabu",slug:"sakthivel-lakshmana-prabu",fullName:"Sakthivel Lakshmana Prabu"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10227",title:"Rural Development",subtitle:"Education, Sustainability, Multifunctionality",isOpenForSubmission:!1,hash:"091e1f8266ec9fc776113a71c002cf7f",slug:"rural-development-education-sustainability-multifunctionality",bookSignature:"Paola de Salvo and Manuel Vaquero Piñeiro",coverURL:"https://cdn.intechopen.com/books/images_new/10227.jpg",editedByType:"Edited by",editors:[{id:"289820",title:"Prof.",name:"Paola",surname:"de Salvo",slug:"paola-de-salvo",fullName:"Paola de Salvo"}],equalEditorOne:{id:"289817",title:"Prof.",name:"Manuel",middleName:null,surname:"Vaquero Pineiro",slug:"manuel-vaquero-pineiro",fullName:"Manuel Vaquero Pineiro",profilePictureURL:"https://mts.intechopen.com/storage/users/289817/images/system/289817.png",biography:"Manuel Vaquero Piñeiro was awarded a Ph.D. in Modern and Contemporary History by the University of Cantabria (Spain); since 2006, he is a professor of economic history at the University of Perugia, Italy (manuel.vaqueropineiro@unipg.it). 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The disease is chronic, multisystem, and immune-mediated in terms of nature while it can be life-threatening in occasional patients. A wide range of symptoms, signs, and laboratory findings may be found in patients with lupus while long-term prognosis depends upon the disease severity and type of organ involvement. Yet, establishing the diagnosis of SLE may be challenging, and the approach to the diagnosis and differential diagnosis are occasionally crucial. Due to the variable disease course, effective management of SLE requires regular clinical and laboratory monitoring to assess disease activity; guide therapy to alleviate symptoms and reduce progressive organ damage; prevent and treat relapses; assess side effects related to drug therapy; encourage adherence with medications; and coordinate care with the patient's other providers.
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\r\n\tRecent advances regarding pathogenesis, cardiovascular risk assessment, prediction of damage, and recent advances in treatment, including tolerogenic and biological agents, are welcome to be included in this book. Relevant contributions regarding standard therapies and their optimal use, as well as the role of new therapeutic options, either in combination with previous agents or alone are of interest.
Autism spectrum disorder (ASD) represents a group of heterogeneous neurodevelopmental conditions characterized by deficits in social cognition, together with the presence of restricted and/or repetitive patterns of behaviors, activities, or interests [1]. Social cognition refers to those cognitive processes that allow individuals to successfully navigate the challenges of living in a social group. Thus, a functional social cognitive system involves the integration of several domains of behavior including attention, memory, emotion, and motivation to be able to understand identity, potential actions, social hierarchy, and emotional status of a conspecific and therefore guide the appropriate behavioral response [2]. In autism, deficits in social cognition processes are found at multiple levels, such as failure to initiate or respond to social interactions, lack of interest in social situations, abnormal social approach, difficulties expressing and understanding verbal and nonverbal communication (i.e., body language and facial expressions), and problems adjusting behavior to different social situations, among others [1]. Autism affects roughly 1 in 59 children, becoming one of the primary mental health issues worldwide [3]. In addition to the main symptoms, ASD is usually associated with other behavioral and/or neurological problems, such as hyperactivity, epilepsy, aggression, irritability, sleep problems, gastrointestinal symptoms, and sensory processing abnormalities [4].
Although currently accepted to be highly genetic (over 90% of the risk of developing ASD is due to genetic variation) [5], the etiology of ASD is complex, and its genetic architecture is diverse. Common allelic variation with small effect sizes is responsible for most cases, while rare but highly penetrant mutations that usually lead to other syndromes associated with autism are observed in about 20% of the cases [6]. In addition to genetic factors, exposition to some environmental factors during prenatal periods has also been associated with autism. Some of the most replicated are the intake of valproic acid, a drug used to treat epilepsy, during pregnancy and maternal infections. In all, the combination of interactions between genetic predisposition and environmental factors will determine the development of the disorder [7]. Given the clinical and etiological heterogeneity of ASD, the investigation of its pathophysiology has been challenging. From a research point of view, the study of “single gene” causes of autism, although rare in the population, has been proven to be useful to understand its pathophysiology and develop targeted treatments. In addition, animal models of monogenic causes of autism are easily generated and constitute a critical component of research. Research from both human and animal studies converge in a series of key brain structures and circuits involved in social cognition and their dysfunction in autism. Within these circuits, the cerebellum, traditionally associated with movement control, is becoming an important player in the social brain network. In this chapter, we will first start by describing the social brain circuitry traditionally thought to be affected in autism; we will then present evidence for the role of the cerebellum as a new player in the social circuitry and its role in the pathophysiology of ASD; finally, we will present data from animal models of monogenic causes of ASD in which a cerebellar pathology has been described such as Fragile X syndrome
In humans, brain regions implicated in social cognition have been identified mainly by lesion studies or by functional magnetic resonance imaging (fMRI) detecting differential activation in response to social versus nonsocial cues. Accordingly, a network of key brain structures involved in the perception, integration, and coding of social cues have been identified, receiving the denomination of “the social brain.” These structures comprise brain areas traditionally involved in
The cerebellum, conventionally associated with motor functions, is lately being considered a key structure within the social circuitry [18]. In fact, cerebellar neuroanatomical alterations, including the reduced size and number of Purkinje cells, are among the most replicated findings in postmortem brain samples of individuals with autism [19]. In addition, cerebellar defects have been proposed to affect the functioning of distal brain areas to which the cerebellum projects [20]. For example, the PFC long-range connection deficits observed in ASD mentioned above include the cerebellum [13]. The
Although human neuroanatomical and functional studies have been very useful in the identification of the brain regions involved in social cognition, animal studies are critical to understand how information is processed at the circuit and molecular level, from the perception of the stimulus to the expression of a behavioral response. The mouse (
Brain circuits linked to social cognition in mice. Olfactory signals from a social stimulus are perceived through the olfactory bulb and transferred to the amygdala (AMYG) and probably other structures to be processed. This social cue will modulate the activity of several structures. One of such, the ventral tegmental area (VTA), mainly composed of dopaminergic neurons, projects to the PFC (executive function) and NAcc (reward system). Of note, the cerebellum modulates VTA activity implying a role in social behavior and reward. Adapted from [
The cerebellum (Latin,
Structurally, the cerebellum is constituted of ten lobules: lobules I through V (which form the anterior lobe), lobules VI through IX (posterior lobe), and lobule X (flocculonodular lobe). Lobules VII and VIII are further subdivided (VIIA and VIIB and VIIIA and VIIIB); besides, the hemispheric extension of lobe VIIA is expanded and forms two major lobules, Crus I and Crus II. Dividing the cerebellum ventrally into two hemispheres, there is a central midline called the vermis (Figure 2) [20]. Within this anatomical division, a functional division according to the connection of each lobe can be found, establishing a topographic organization (see Subsection 3.2).
Structural anatomy of the human cerebellum. Representation of the cerebellar lobules: anterior, posterior, and flocculonodular and their subdivisions. Lobules VII and VIII are further subdivided into lobules A and B. Crus I/Crus II constitutes further subdivisions of lobule VIIA. The vermis represents a midline separating the cerebellum in two hemispheres. Modified from [
At the cellular level, the cerebellum is composed of an outer cortex constituted of gray matter, the cerebellar cortex, and an inner core formed mainly by white matter which encloses the deep cerebellar nuclei, the sole output channel of the cerebellum (see below). The cerebellar cortex is structured in three different cell layers: (1)
Neurons in the deep cerebellar nuclei represent virtually all the output from the cerebellum. They receive inhibitory information from the PC and excitatory inputs from outside the cerebellum through the mossy and climbing fibers. The
Main cerebellar circuits. The mossy and climbing fibers carry the input information toward the cerebellum. The PC transmit the information to the deep cerebellar nuclei, which are the cerebellar output. The interactions between the cells are represented with (+) in case of excitatory connections and (−) when connections are inhibitory. Modified from [
The cerebellum has a unique topographic organization such as each region is attributed with a separate function based on their specific connectivity. Thus, the anterior lobe and lobule VIII contain the representation of the sensorimotor cerebellum; lobules VI and VII (including Crus I/Crus II and lobule VIIB) of the posterior lobe comprise the cognitive cerebellum; and the posterior vermis encompasses the limbic cerebellum. Dysfunction in the connection of these cerebellar areas with the spinal cord or cerebral regions will result in alterations in movement or cognitive functions, respectively [30, 31]. More specifically, the cerebellum has been proposed to have an important role in language by means of its connections with cortical areas implicated in this process. Studies using viral tracing in nonhuman primates report the existence of strong connections between right Crus I/Crus II and different cortical regions implicated in language, such as Brodmann’s area BA46 in the PFC [32]. In fact, dysfunction in cerebellar-prefrontal loops might underlie poorer performance on measures of language-related executive function in human patients with cerebellar abnormalities [33]. The cerebellum also seems to play a role in several social and affective processes. For example, imitation is a critical skill for implicit learning of social rules, and fMRI studies in humans show that during a task that involves observation and imitation of an action performed by a human model, activation of the Crus I/Crus II regions in the posterior cerebellum is increased [34]. Also, during a passive viewing paradigm, a stronger activation in the posterior cerebellum (lobules VI, VII, and X) has been found when comparing social versus nonsocial stimuli [35]. In fact, a recent meta-analysis of over 350 fMRI studies exploring the role of the cerebellum in social cognition supports that it plays a crucial role in several social paradigms such as mirroring (i.e., observation of human motion) and mentalizing (i.e., interpreting other people’s thoughts and intentions) [36, 37].
In the recent years, there has been increasing evidence showing a crucial role for the cerebellum in the etiology of ASD [38, 39, 40]. Although the field of cerebellar research in disorders of social cognition such as autism is still in its early stages, below we will describe the main structural and functional cerebellar abnormalities that have been described to date in autism, which provide strong evidence to grant further research.
The cerebellum is actually one of the most consistent sites of neural abnormalities found in autism [41]. Specifically, the reduced size and number of PCs are among the most replicated findings in postmortem brain tissue of individuals with autism [19]. This reduction in PC in autism patients has been found to be more pronounced in the Crus I/Crus II region of lobule VIIA [42]. Accordingly, a reduction in gray matter volume, smaller ratio of gray to white matter, and smaller vermis lobules VI–VII have been found in children with autism compared to controls [43, 44]. Further, in ASD patients, the degree of reduction in gray matter of Crus I/Crus II has been repeatedly found to correlate with the severity of symptoms in the social interaction and communication behavioral domains of ASD [39, 45]. Of note, some reports using adult brains indicate the presence of gliosis as an accompanying factor to the reduction of PC [46]. Other observed cerebellar cellular abnormalities are the presence of neuro-inflammatory processes [47].
Besides structural and cellular alterations, molecular abnormalities have also been reported in the cerebellum of ASD individuals. Alterations in the distribution of the mRNA levels of glutamic acid decarboxylase 67 (GAD67), an enzyme involved in the synthesis of the inhibitory neurotransmitter GABA, have been found. Thus, decreased GAD67 mRNA has been reported in PC [48], while increased GAD67 mRNA has been reported in cerebellar interneurons [49]. These cerebellar imbalances could account for the proposed E/I disequilibrium in ASD, as they could affect cerebro-cerebellar circuits [50].
Studies in humans using resting-state functional connectivity (rsFC) techniques have reported connectivity alterations between cerebellar and cortical areas in autism compared to typically developing individuals. Overall, a general cerebro-cerebellar over-connectivity has been found in the ASD group. However, both hyper-connectivity and hypo-connectivity have been reported depending on the regions analyzed. For example, cerebellar-sensorimotor FC (premotor and primary motor cortices, somatosensory temporal cortex, and occipital lobe) has been found to be atypically increased in ASD, while cerebellar-supramodal FC (prefrontal cortex, posterior parietal cortex, and inferior and middle temporal gyri) has been found to be decreased [51]. Analysis of cerebellar FC with language-related areas revealed a significantly reduced FC in ASD between the cerebellum and Broca’s area and Wernicke’s area [52], suggesting that the cerebellum plays a role in language functioning. Studies aiming at assessing the developmental pattern of cerebello-cerebral FC also report developmental alterations in ASD. FC between the cerebellum and subcortical regions was found to decrease in neurotypical individuals, while it increased in ASD [53]. It must be noted that no specific correlation between FC patterns and autism behavior has been detected, although reduced connectivity seems to be accompanied by an increase in the severity of the disorder [52], as assessed by the Social Communication Questionnaire, an ASD screening measure consisting of a brief (40-item) parent report that focuses on ASD symptomatology likely to be observed by a primary caregiver.
Few studies have investigated to date the FC between the cerebellum and cortical areas during task performance in ASD. During a sequential finger-tapping task, activations in motor circuits were found in both cases and controls. However, children with typical development showed activation of cerebellar structures that were silent in autistic children (lobules IV/V and anterior cerebellum). In addition, a reduced FC between premotor areas and the cerebellum was observed in autistic children, suggesting alterations in long-range cerebro-cerebellar connections [54]. In a task that requires perception and imitation of human actions, fMRI detected an engagement between the posterior superior temporal sulcus (pSTS) and the cerebellar region Crus I [55]. Interestingly, the degree of functional coactivation of pSTS and Crus I could predict social deficits in ASD in the “mentalizing skills” questionnaire, a parent report for specific social cognition skills based on imaginative mental activity that allows an understanding of the behavior of other people (intentions, needs, desires, or goals). Thus, stronger Crus I-pSTS interactions were associated with better mentalizing ability [55]. On a similar note, during a task that involves decoding the interactions between animated figures, aimed at examining the “theory of mind” network, that is, the ability to attribute mental states to others, a reduced cerebellar activation, particularly in Crus I, in participants with ASD was found [56]. Although many more studies are needed, overall the above-presented data indicate a role for cerebellar connections with key cortical social brain sites and, specifically for region Crus I/Crus II, in the pathogenesis of ASD.
The clinical and genetic heterogeneity present in ASD has made the study of the pathophysiology of the disease challenging. The study of genetically defined autism, as in the case of monogenic forms of ASD, which show a relatively homogeneous and well-characterized clinical manifestation, allows us to understand cellular and molecular mechanisms relevant to the disease. Although monogenic causes of ASD are often syndromic and not all patients with the syndrome show autistic features, by studying patients with and without ASD, we can start deciphering the pathomechanisms that lead to the disorder. As shown below, human postmortem and brain imaging studies of syndromic forms of ASD support the role of the cerebellum in the pathophysiology of the disease. Animal models of monogenic autism are easily generated and provide opportunities for direct manipulation of these brain regions and circuits to test their precise functions in social behavior paradigms. We will describe below the main syndromes with reported cerebellar dysfunction and supporting data from animal models (Table 1). In all, human and animal data point out a role for the cerebellum in social deficits in ASD.
Mouse model | Structural abnormalities | Functional abnormalities | Refs. |
---|---|---|---|
Fmr1 KO |
|
| [57, 58, 59, 60] |
Fmr1-PC cKO |
|
| [60] |
TSC1-PC cKO +/− |
|
| [61, 62] |
TSC1-PC cKO −/− |
|
| [61, 62] |
TSC2-PC cKO+/− |
| N/A | [63] |
SHANK2 KO | N/A |
| [64] |
SHANK3 ΔC |
|
| [62] |
Cerebellar abnormalities in mouse models of ASD.
Fragile X syndrome (FXS) is the most common form of inherited intellectual disability, and ~30% of FXS patients are also diagnosed with ASD. FXS is considered also as the most common genetic cause of ASD, representing around 3% of ASD individuals. FXS arises from loss of function mutations in the X-linked FMR1 gene, which result in either total absence or functional inactivation of the encoded protein (FMRP), an mRNA-binding protein involved in translational regulation [65]. Although FXS affects many brain regions, cerebellar PC loss and cell displacement, as seen in idiopathic autism, have been reported in human postmortem studies of FXS [66]. Interestingly, imaging studies have identified specific abnormalities in the posterior cerebellar vermis (lobules VI–VII) in FXS patients with ASD that are not seen in FXS patients without comorbid ASD diagnosis. Further, these lobules are also abnormal in non-syndromic ASD [57]. Moreover, positive correlations between the size of the posterior vermis and several subscales of the autism behavior checklist, a list of nonadaptive behaviors that represent an individual’s challenges to respond appropriately to daily life situations, in persons with FXS, have been reported [58]. On a different note, recent postmortem work has shown reductions in FMRP in cerebella and frontal cortices of subjects with autism who do not carry a mutation for FXS [59].
The Fmr1 knockout (KO) mouse is a validated and widely studied animal model of ASD. By means of high-resolution MRI imaging to study brain structure, the cerebellum in Fmr1 KO mice was found to show significant volume alterations comparing with wild-type controls. Specifically, the deep cerebellar nuclei, which transfer the output of the cerebellar cortex to the thalamus and cerebral cortex, were smaller in Fmr1 mice. Moreover, this reduced volume was accompanied by loss of neurons and increase in astrocytes, as measured by immunohistochemical techniques [60]. Later, the same authors also identified a volume reduction in the cerebellar cortex in these mice [67]. Further, a detailed study by diffusion tensor imaging of postnatal development in the Fmr1 KO mouse showed reduced cerebellar volume in the first few weeks after birth [68]. In addition to the full KO, a conditional Fmr1 KO mouse (Fmr1 cKO) has also been generated. Deletion of Fmr1 specifically in PC leads to several structural and functional abnormalities in the cerebellum also seen in the full Fmr1 KO, such as a reduction of cerebellar volume, cellular loss in the cerebellar nuclei, and longer spines in PC. Functionally, an enhanced LTD induction at the parallel fiber synapses that innervate these spines is seen [63]. In addition, both Fmr1 KO and PC-Fmr1 cKO mice present alterations in classical delay eyeblink conditioning, a Pavlovian associative learning where subjects learn to execute an appropriately timed eyeblink in response to a previously neutral conditioning stimulus in which the cerebellum plays a key role. Specifically, the percentage of conditioned responses and their peak amplitude and peak velocity were reduced. [63]. Interestingly, FXS patients were found to display the same cerebellar deficits in eyeblink conditioning as mutant mice [63]. Together these results suggest that the deficits in eyeblink conditioning are likely due to the loss of FMRP in PC.
Tuberous sclerosis (TS) is another rare syndromic disorder associated with ASD. TS is characterized by the development of non-cancerous tumors in the brain and other organs leading to neurological symptoms such as developmental delay, epilepsy, and ASD. It is an autosomal dominant condition caused by mutations in either the TSC1 or TSC2 genes, which form a tumor suppressor complex involved in the regulation of the mTOR signaling pathway. Approximately 40% of TS patients are co-diagnosed with ASD, and, interestingly, those with cerebellar lesions have been found to have a more severe ASD diagnosis [61]. Further, PC loss has been found in postmortem cerebellum samples from TSC patients [62].
Several lines of mutant TSC mice have been generated and studied in detail. A mutant mouse in which the Tsc2 gene was selectively deleted from PCs starting at postnatal day 6 was generated to mimic patients with one nonfunctioning TSC2 allele [62]. The haploinsufficiency of TSC2 caused a progressive increase in PC cell size and subsequent death from apoptosis. TSC2-null PCs showed increased endoplasmic reticulum and oxidative stress, which were rescued by treatment with the mTOR inhibitor rapamycin. In a subsequent study, the authors reported that PC-TSC2-haploinsufficient mice showed social deficits and repetitive behaviors [64]. These observations indicate that selective loss of TSC2 in PCs in a TSC2-haploinsufficient background is enough to lead to autistic-like behavioral deficits. A conditional PC-TSC1 KO mouse has also been generated. Both heterozygous and homozygous losses of TSC1 in mouse cerebellar PCs result in autistic-like behaviors, including abnormal social interaction and repetitive behavior and vocalizations, in addition to decreased PC excitability. Similar to TSC2 mutants, treatment of TSC1 mutant mice with the mTOR inhibitor, rapamycin, prevented the pathological and behavioral deficits. Strikingly, PC-TSC1 homozygous mice, but not PC-TSC1 heterozygous mice, showed PC loss at 2 months of age. The fact that PC-TSC1 heterozygous mice showed autistic symptoms and PC excitability alterations in the absence of PC loss suggests that the decrease in PC excitability is likely driving the phenotype [69]. Further, this model has also been reported to show deficits in eyeblink conditioning; they specifically show lower percentage of conditioned response in this test [70]. These findings demonstrate new roles for TSC1/TSC2 in PC function and define a molecular basis for a cerebellar contribution to cognitive disorders such as autism.
Phelan-McDermid syndrome (PMS) is due to heterozygous chromosome 22q13 deletions and is often co-diagnosed with ASD. The clinical manifestations of PMS include global developmental delay/intellectual disability and absent or delayed speech [71]. Although the deletion encompasses numerous genes, a good candidate that could account for ASD symptoms is SHANK3, a gene within which mutations have independently been associated with non-syndromic ASD. ASD patients with SHANK3 deletions are also known to have severe core symptoms and mental disabilities [72]. Although to our knowledge there is no data addressing the effect of SHANK3 mutations on cerebellar anatomy and function, recent research suggests that mutations in
Multiple mouse lines with SHANK3 mutations exist, and several display behaviors analogous to the core symptoms of autism, including isoform-specific SHANK3B KO [76], SHANK3 (∆exons4–9) deleting major isoforms of the gene [77], and SHANK3 (∆C), deleting the C-terminal region of the gene [78]. SHANK3 (∆C) mice present a decreased density of PC compared to controls [70], and they show deficits in the eyeblink conditioning task, showing lower percentage of conditioning response and a delay in the response latency [70].
Interestingly, mutations in other proteins from the SHANK family, such as SHANK2, have been also linked to ASD. A KO mouse for SHANK2 shows alterations in social and repetitive behaviors and presents changes in PC electrophysiological characteristics, such as decreased intrinsic PC plasticity, synaptic strength at the PC-parallel fiber synapse, and enhanced inhibitory input into PC. Further PC-specific SHANK2 KO replicated these findings, arguing for a cerebellar role in autistic-like behaviors [79].
The cerebellum has been recently indicated as a key structure not only for sensorimotor control but also for language, social cognition, and emotion, via its extensive connections with cortical areas. In the present work, we aimed to provide an up-to-date overview of current findings on cerebellar involvement in the pathophysiology of ASD. Anatomical studies report cerebellar abnormalities in postmortem brain tissue from autistic individuals, neuroimaging studies indicate abnormal cerebellar activation when performing social paradigms, and animal models of monogenic forms of autism converge on the cerebellum as one of the common sites of abnormalities. The cerebellum represents an emerging field of interest for ASD research, based on the hypothesis that ASD is a connectivity disorder and cerebellar dysfunction could impact other brain areas within the social network, leading to the core ASD symptoms. Although the literature in this new field is at a very early stage, based on the presented data, future studies should not exclude the cerebellum in analyses of structural and functional differences in ASD.
This work was supported by the following grants: Spanish Ministry of Economy and Competitiveness/European Regional Development Fund (MINECO/FEDER grant SAF2015-64163-R). OP is a Ramon y Cajal Fellow (RYC-2013-12558), MF is supported by a predoctoral fellowship from the Spanish Ministry of Economy and Competitiveness MINECO (BES-2016-078420), and TS-A is supported by a predoctoral fellowship from the Basque Government.
Plants have developed a wide variety of highly sophisticated and efficient mechanisms to sense, respond, and acclimatize to a wide range of environmental changes. They have responded by activating tolerance mechanisms at multiple levels of organization (molecular, tissue, anatomical, and morphological), through the adjustment of membrane systems and cell wall architecture. This includes altering the cell cycle and rate of cell division and also by metabolic tuning [1]. Many molecular genes are induced and repressed by abiotic stresses at molecular level involving a precise regulation of extensive stress-gene networks [2, 3], and their products may function in stress response and tolerance at cellular level. Proteins involved in multiple protein functions, such as biosynthesis of osmo-protectant compounds, detoxification enzyme systems, proteases, transporters and chaperones, act as a first line of direct protection from stress. Moreover, regulatory proteins, for instance, transcription factors, protein phosphatases and kinases, and signaling molecules activation are essential in regulation of signal transduction and stress-responsive gene expression [4, 5].
Generally, observed tolerance responses toward abiotic stress in plants are composed of stress-specific response mechanisms and adaptive responses that confer strategic advantages in adverse conditions. In energy maintenance, general response mechanisms related to central pathway are involved, including calcium signal cascades [6], reactive oxygen species (ROS) signaling elements [7, 8], and energy deprivation signaling (energy sensor protein kinase, SnRK1) [9]; and induction of these central pathways is observed during plant acclimation toward different stress. Protein kinase SnRK1, despite being central metabolic regulator of the expression of genes related to energy-depleting conditions, also get activates when plants face different sorts of abiotic stresses such as drought, salt, flooding, or nutrient depravation [10, 11]. SnRk1 kinases alter over 1000 stress-responsive genes expression allowing the re-establishment of homeostasis by repressing energy consuming processes, thus promoting stress tolerance [10, 12]. Optimization of cellular energy resources during stress for plant acclimation has been found to be imperative; and partially arrested energetically expensive process, such as reproductive activities, translation, and some biosynthetic pathways [13]. For instance, in maize, during salt stress and potassium deficiency stress, nitrogen and carbon assimilations are impaired; also, the synthesis of free amino acids, chlorophyll, and protein is also affected [14, 15]. After cessation of energy-expensive process, energy resources can be redirected to activate protective mechanisms [16].
Plants are sessile organisms, which are continuously being confronted with several detrimental factors rising from ever-changing environment, and to cope with these problems, they have developed sophisticated and delicate defense mechanisms. In fact, diverse defense signal including the production of reactive oxygen species (ROS), change in redox potential or cellular level of Ca2+ ion, disruption of ion homeostasis, and membrane fluidity adjustments are activated [17, 18]. Once external stress is sensed via specific receptors, foreign signal is induced into intracellular downstream signaling pathways including the activation of protein kinase or phosphatase, stimulation of downstream target proteins, and biosynthesis of phytohormones for the control of plant growth/development [19, 20].
Gene expression can be adversely affected by salinity, drought, and temperature stress, and many genes coding for enzymes involved in cellular metabolism are differentially expressed upon stress, thus modeling some stress-related transcription factors to induce changes in stress-associated metabolite levels [4].
For the synthesis of secondary metabolites and signaling molecules, several amino acids can act as precursors, for instance, polyamines are derived from Arg [21], Met synthesized the plant hormone ethylene [22], and conversion of Lys to N-hydroxy pipecoline is necessary for immune signaling [17, 23]. Moreover, several aromatic amino acids, such as Phe, Tyr, and Trp, or intermediates of their synthesis pathways produce a broad spectrum of secondary metabolites possessing multiple biological functions and health-promoting properties [24]. Usually, plants exposed to different abiotic stresses tend to accumulate free amino acids [25, 26], as exemplified to this response, [27] reported extensive accumulation of amino acid in response to drought stress in maize, cotton, tomato, and the resurrection plant. Also, recent studies conducted by [26, 28, 29, 30] suggest increment in free amino acids as a result of autophagy and abscisic acid. Similarly, plants surviving in stressed environment can use amino acids as an alternative for mitochondrial respiration substrates during inadequate carbohydrate supply due to a decrease in photosynthesis rates [29, 31]. Although ambiguity still remains for the specific role of catabolic pathways, the degradation pathways for Lys and the branched-chain amino acids Val, Leu, and Ile have already been identified as crucial factors for dehydration tolerance for
Members of the AP2/EREBP (Apetala2/ethylene-responsive element binding protein) family of transcription factors, CBF/DREB1 proteins (C-repeat binding factor or dehydration responsive element binding proteins), such as CBF1/DREB1B, CBF2/DREB1C, and CBF3/DREB1A play an important role in the transcriptional response to osmotic stress [33, 34, 35, 36, 37] and stated improved tolerance of
The biological research of abiotic stress in plants can be studied in broad range of transcriptomic and proteomic-based, provides the comprehensive information, during and following stress condition, on alteration of gene expression and proteome profile, the study about 30 min to 1 day after induction, and time lapse between transcriptomic and proteomic suggest more than 50% of genes responsive to flood, heat, and other stress were found to encode transcription regulators [41].
Prolonged water deficit in the soil causes drought, which vastly affects the metabolism and physiological function in growing plant especially roots and responsive for water supply from soils to leaves and photosynthesis, respectively. Most of the proteomic evidence has been noticed due to drought condition, six steps prominently occur in the responsive drought stress. Signaling and sensing receptor, yet not specially but drought-responsive photoreceptor, phytochrome C1, found in maize, phytochrome gene (i.e.,
Phytohormones play important role in signal transduction pathways such as drought-increased ethylene-responsive transcription factor (ERF) in
Gene expression plays important role in the transcriptional regulatory networks, requires chromatin structure modification, i.e., histone, major protein of chromatin, and regulates the expression and high mobility group protein (HMG), involved in cell cycle progression. Among several histones, histone H1 was decreased in a drought-sensitive
Several RNA processing-related proteins changed over the stress condition, represent the critical for plants to cope with. Five glycine-rich RNA-binding proteins (GR-RBPs) increased with drought and three GR-RBPs decreased with drought, which bind to RNA molecules for transcriptional gene regulation and suspected to function in the regulation of specific gene expression. For instances, transgenic rice consists of GR-RBPs gene showing higher yield and drought recovery rate as compared with wild rice [56], besides overexpressed in
Most fundamental metabolic process to cope with drought stress, a plant can attribute to protein synthesis and turnover. Several proteins are involved in protein biosynthesis, such as ribosomal protein (RP), elongation factor (EF), translation initiation factor (TIF), tRNA synthase (TRS), and ribosome recycling factor (RRF), beneficial to protein synthesis, besides protein folding and processing varies cultivars and species. Instances, peptidyl-prolyl
Protein degradation, process of removing the abnormal, damaged protein, and maintenance of certain level of regulatory proteins during drought, includes the components such as ubiquitin/26S proteasomes, small ubiquitin-like modifier (E3 SUMO) ligase, and proteases/peptidases (ATP-dependent Clp proteas, cysteine proteinase, zinc metalloprotease, aspartic proteinase, serine carboxypeptidase, and aminopeptidases (APs)). These components show positive response in
Due to drought condition, it interrupts the normal cellular mechanism, results to produce the ROS. Plants evolve diverse mechanism to keep ROS homeostasis in cells, including antioxidative enzymes, e.g., SOD (first defense mechanism by converting O2 into H2O2) and CAT (convert H2O2 into H2O and O2) and chemical antioxidant (e.g., glutathione and ascorbate). Diverse abundance of SODs in cystolic, peroxisomeas as well as in chloroplast helps in the drought tolerance and avoidance. For instance, increment of cystolic Cu-Zn SODs drought avoidance CT9993 and drought tolerance IR62266), while e chloroplast Cu-Zn SODs were increased in CT9993, but decreased in IR62266 [57], additionally in cultivar of
There will be occurrence of pathogen when left plant for water deficit condition, but some pathogenesis-related protein, namely chitinase, disease resistance protein (DRP), polyphenol oxidase (PPO), oryzacystain, pathogen defense-related protein 10 (PR10), and disease resistance gene analog PIC15 increased in the response of drought condition. These proteins act as the pathogen by acting on insect exoskeleton and fungi cell walls, catalyzing the oxygen-dependent oxidation of phenols to quinines’ during plant defense, acting as cysteine proteinase inhibitor in the phytocystatin family of proteinase inhibitors. For example, overexpression of oryzacystain gene in Tobacco displayed an increase of drought tolerance by improving total SOD and guaiacol POD activities.
Osmotic regulation will be hindered due to exposed to water deficit, but important osmotic homeostasis-related protein, namely embryogenesis abundant (LEA) protein, dehydrin (DHN), and betaine aldehyde dehydrogenase (BADH), which function as cellular protectants to stabilize cellular components, protein structure through detergents and chaperone like properties, act as calcium buffer. LEA proteins were also increased in
Cell division and cell wall formation decreased due to decrease of phosphorylation of several protein (cell division cycle protein, division protein ftsZ1, and cyclin A2) when exposed to drought, which implies the suppression of cell growth. Cytoskeleton and cell wall component require for cell division, morphogenesis, and signal transduction, while cytoskeleton protein, namely actin, kinesin motor protein, tubulin, profilin, actin depolymerizing factor, and fibrillin to check the cell growth during stress. Additionally, the translationally controlled tumor protein homolog (TCTP) is a Ca2+-binding protein, which protect against stress and apotosis, cell growth, and microtubule organization, which was significantly drought increased in
Cell wall extensibility was directly affected by water loss, while cell wall polysaccharide synthesis/hydrolysis, lignin biosynthesis, and cell wall loosening in leaves were drought-responsive enzymes. Two enzymes, glycosylated polypeptide and pectinacetylesterase, involved for polysaccharides synthesis, another two enzymes xylanase inhibitor and polygalacturonase inhibitor, involved in polysaccharide hydrolysis inhibition. Three lignin biosynthesis-related proteins, phenylalanine ammonia-lyase (PAL), caffeic acid 3-
Membrane trafficking localized in mitochondrion, plasma, and vacuole. Two mitochondrion protein carriers (dicarboxylate/tricarboxylate carrier (DTC) and 2-oxoglutarate/malate carrier protein (OMC)), catalyze the transport of various metabolites (e.g., dicarboxylates, tricarboxylates, amino acids, and keto acids), play important role in gluconeogenesis, nitrogen metabolism, as well as biotic stress [68]. Another, Remorin, aquaporin and PEG, plant-specific plasma membrane protein have importance in plant-microbe interaction and signal transduction [69]. In addition, vacuolar H+-pyrophosphatase (V-PPase), vacuolar-ATPase (V-ATPase), and ABC transporter ATPase, important for or translocating H+ into the vacuoles to generate a gradient of H+, which provide a driving force for the accumulation of ions and other solutes in the vacuole and function for abiotic stress.
Photosynthesis inhibition is the primary detrimental effect due to drought stress, and related protein decrease. To cope with this situation, drought increased protein involved in the photoreaction and Calvin cycle in leaves. Light-harvesting chlorophyll a/b-binding proteins (LHCB), involved in ABA signaling partially by modulating ROS homeostasis, besides, abundance of sedoheptulose-1,7-bisphosphatase (SBPase) and carbonic anhydrase (CA), catalyzes the reversible hydration of CO2, and influence in internal conductance and abundance of protein involved in photorespiration, significantly increases and decreases glycolate oxidase, glycine dehydrogenase, serine glyoxylate aminotransferase, and serine transhydroxymethyl transferase, aminomethyl transferase (AMT), and glycine dehydrogenase to adapt the drought stress. The mechanism in photorespiration can protect the photosynthesis from photoinhibition and prevent ROS accumulation in green tissues.
Involvement in carbohydrate and energy metabolism is important step to cope with drought condition. Phosphoglucomutases (PGluMs), fructose-bisphosphate aldolase (FBPA) in glycolysis and aconitate hydratases in TCA cycle increased in drought condition, which inhibit the accumulation of sugars as osmolyte or energy source for recovery, while the increase of glycolysis and TCA may act as a strategy for providing energy during the activation of stress defenses, especially when the photosynthesis was inhibited. The change in mitochondrial electron transport chain and ATP synthesis related protein implies ability to enhance energy production to maintain physiological activity and inhibit stress damage.
Due to the drought condition, nitrogen assimilation decreased in the reduction of NR, GS, and GOGAT, which was main reason for yield reduction. Similarly, the decline of aspartate aminotransferase (AST) and alanine aminotransferase (ALAT) indicates that drought stress inhibits the amino-acid metabolism and synthesis of other metabolites. At the same time,
Acetyl-coenzyme A carboxylase carboxyl transferase, acyl carrier protein, enoyl-acyl carrier protein reductase, and lipoxygenase 6 involved in fatty acid biosynthesis, and enzymes thiolase I, thiolase II, and acyl-CoA dehydrogenase used for fatty acid degradation. Greater composition of unsaturated fatty acid in membrane lipids contribute to superior leaf dehydration tolerance and maintain membrane integrity and preserve cell compartmentation under water stress, in addition, two flavonoid biosynthesis related proteins (i.e., chalcone isomerase (CHI) and dihydroflavonol-4-reductase) involved in secondary metabolism were also changed in response to drought.
Deprivation of the soil oxygen due to consequence of flooding and forced the plant to shift from aerobic to anerobic respiration [70], which regenerate NAD+, through ethanol fermentation by selectively synthesizing flooding-inducible proteins involved in sucrose breakdown, glycolysis, and fermentation [13]. Several glycolysis-related proteins, including fructose-bisphosphate aldolase, phosphoglycerate kinase [64], glyceraldehyde-3-phosphate dehydrogenase [71], enolase [72], sugar isomerase, phosphofructo-kinase [73], and pyruvate kinase [72] are increased in soybean under flooding stress, indicate the glycolysis and fermentation pathways activation, initiating for plants protecting plant from flooding induced damage, whereas decrease of fructose-1,6-bisphosphate aldolase and sucrose-fructan 6-fructosyl transferase in wheat show response to flooding stress. Othersides, fermentation under anaerobic condition, influence the accumulation of fermented related proteins such as alcohol dehydrogenase (ADH) and pyruvate carboxylase, and indicates that activation of the alcohol fermentation pathways, to cope the hypoxic condition. The conversion of acetaldehyde to ethanol by ADH with concurrent reoxidation of NAD+ for the continuation of glycolysis. The fermentation related enzyme pyruvate decarboxylase, and aldehyde dehydrogenase increase to accelerate the energy production via nonoxidative pathways, even growth is suppressed.
In other sides, flooding stress induces impairment of the electron transport chain in plants. Protein related to complexes II, IV, and V of the electron transport chain decreased in abundance and while, succinate-semialdehyde dehydrogenase, 2-oxoglutarate dehydrogenase, and gamma-amino butyrate are significantly increased, which are required for energy production via non-oxidative pathways [72]. Oxaloacetate produced in TCA cycle stimulates phosphoenol pyruvate synthesis and provides the indirect simulation for the continuation of glycolysis. Reduction of energy metabolism-related proteins, including citrate synthase, glutamate dehydrogenase, and adenosine kinase, in wheat roots under waterlogging stress [74]. In addition, energy-related proteins such as beta-amylase, malate dehydrogenase, fructose-1,6-bisphosphatase, and phosphoenol pyruvate carboxykinase are decreased in response to flooding stress, indicating that gluconeogenesis is suppressed in wheat under these conditions [10]. RuBisCo sub unit binding protein alpha sub unit and RuBisCO activate degraded and senescence in high ROS condition and decreased the chlorophyll content, results to decrease in net energy production.
ROS recognized as toxic byproduct of aerobic metabolism and controlled by anti-oxidants and anti-oxidative enzymes. The plant development of well-organized scavenging mechanism to overcome ROS toxicity likely to led to the use of reactive molecules as signal transducers in plant cells. ROS production in cellular organelles, such as plastids, mitochondria, and peroxisomes, involved in signaling cascades controlled by production and scavenging of ROS intermediates [27]. ROS scavengers, such as peroxidase, APX, cytosolic APX, and superoxide dismutase (SOD), linked to bio photon emissions and decreased photosynthesis and beneficial for normal metabolism and cell signaling.
Cell wall modification related proteins, namely polygalactouronase inhibitor-like and expansion-like B1-like proteins and cell wall synthesis related protein such as cinnamyl-alcohol dehydrogenase and cellulose synthase-interactive protein-like protein abundance response under water logged condition. Flooding stress induces the assimilation of methionine and promotes cell wall hydrolysis, thereby restricting growth so, under the waterlogged stress, cell wall synthesis related proteins decrease, cell wall loosening related protein increase and cell wall lignification is suppressed.
Proteolysis, protein folding and storage plays important role in the removing the flooding damage induced non-active proteins [40]. Heat shock proteins act as molecular chaperones in preventing protein aggregation, translocation of nascent chains across membranes, assembly or disassembly of multimeric protein complexes, and targeting proteins for lysosomal or proteasomal degradation [40]. The ubiquitin/proteasome-mediated proteolysis of enzymes involved in glycolysis and fermentation pathways may be negatively controlled under the hypoxic condition caused by flooding stress [40].
Post recovery protein metabolism is less studied but studied by [75] Gro-EL-like chaperone ATPase, 26 S proteasome regulatory subunit 7, 26 S regulatory subunit S 10B, and cyclophilin were decreased in seedlings recovering from flooding stress, whereas globulin-like protein, Kunitz trypsin protease inhibitor, and peptidyl-prolyl cis-trans isomerase 1 were increased, and soybean root recovers from flooding by altering cell structure, strengthening cell wall lignification, and scavenging toxic ROS.
One of the major abiotic stresses is cold or low temperatures (LTs) that severely affect plant growth and survival. Chilling or freezing with temperatures <20°C and < 0°C respectively can induce ice formation in plant tissues which causes cellular dehydration [39]. To be able to withstand in this adverse condition, plants adopt several strategies, such as production of more energy via activation of primary metabolisms, leveling up of antioxidants content and chaperones, and maintenance of osmotic balance by altering membrane structure [76].
Several articles and reviews deals with the metabolic responses of plants at low temperature, where some attempted correlating metabolic and biochemical responses with cold tolerance. Solaw [77] noted correlative studies of biochemical changes does not enable understanding of cold acclimation (CA) leading to increased freezing tolerance and till date no any new approaches in molecular biology and genetics have been extensively enlisted on study of cold-tolerance and injury mechanisms. However, few studies of CA started focusing on some of the more rapid plant physiological and molecular responses subjected to LTs, which revealed that within the hours of LT exposure, plant and algal cells can rapidly initiate to alter membrane lipid composition [78], RNA [79], and protein content. These findings of rapid biochemical alterations in response to L T convince the rapid induction of freezing tolerance at inductive temperatures and by desiccation and ABA at non inductive temperatures [80] and ABA [10]. This suggests a possible molecular basis, at minimum, for the adjustment of metabolism to low nonfreezing temperature, and perhaps for freezing tolerance. Also, upon exposure to LT, it consists of repeated observations that a number of enzymes show shifts in isozymic composition, whereas both quantitative and qualitative differences in the protein content is shown by numerous electrophoretic studies between non-acclimated and cold acclimated tissues.
Compared with plants maintained at warm temperature, [20] reported changes in activity, freeze stability, and isozymic variation in plants subjected to LTs. He mentioned increased peroxidase activity in hardened stems of four widely unrelated woody species when electrophoretic techniques to separate enzymes from non-hardened and hardened tissues. Here, peroxidase isozymes present in hardened tissues were not found in other three non-hardened tissues. Similarly, during deacclimation, no change in peroxidases, glucose-6-phosphate, 6-phosphogluconate, and malate dehydrogenases was observed in willow stem [81], however, differences were observed in lactate dehydrogenase where the activity increased during deacclimation. Similarity as above findings was illustrated by [82] in which invertase enzyme in wheat leaves undergoes a shift from a lower-molecular weight form to a higher-molecular-weight form at LT. Different kinetic properties is exhibited in larger form functionally replacing small form in cold-hardened plants [83]. Also, Krasnuk and colleagues [6, 84] observed increased activity of a number of dehydrogenases associated with respiratory pathways, including glucose-6-phosphate dehydrogenase, lactate, and isocitrate dehydrogenase [6] during a comprehensive studies with alfalfa. Thus [85] suggests higher amounts of enzyme may increase in activity and soluble protein content indicating increased soluble protein content and enzyme activity could be part of the adjustment of metabolism to the kinetic constraints imposed by LTs.
A more recent study of glutathione reductase from spinach carried out by [26] demonstrated not only additional isozymic forms in cold-acclimated tissue but also increased activity, freezing stability, and altered kinetic behavior and the activity of this particular enzyme was decreased by freezing/thawing both in vitro and in vivo. However, the enzyme found in cold-acclimated plants was less sensitive than its counterpart from non-acclimated plants to freezing from nonacclimated plants. In contrary, kinetic parameters and freeze/thaw inactivation was observed identical in ferredoxin NADP reductase from nonacclimated and cold-acclimated wheat [86], whereas activity was increased during CA. Therefore, [85] illustrated the potential for alterations in enzymes in response to low temperature exposure and the apparent selective basis where such changes can occur.
Ribulose bisphosphate or oxygenase from winter rye is the best-characterized enzyme relative to non-acclimated and cold-acclimated plants. Early in vitro studies studied by [87] noted purified enzyme from both non- and cold-acclimated plants demonstrated an increased stability of catalytic activity to denaturants and storage at −25°C of the enzyme from cold-acclimated plants. Moreover, [87] presented evidence of a stability in vivo conformational change during low-temperature adaptation that was not altered by purification of the enzyme. Also, osmotic concentration of the purified enzyme caused a greater degree of aggregation through intermolecular disulfide bond formation of the large subunit from non-acclimated plants [4] also claimed, similar to rye, the enzyme purified from freezing sensitive and -tolerant potato species demonstrated structural differences that paralleled variation in freezing tolerance much in the same way. However, the study still remains in ambiguity for the stable change in conformation, kinetic properties, and differential cryostabilities of this enzyme from cold-acclimated leaves or cold tolerant potato species. Given that a single chloroplastic gene encodes for large subunit and not possess even a minute chance for the synthesis of an alternative cryostable large subunit from another gene. Also, in many plants, always, a small gene family codes the small subunit, a change in the small subunit may possess subtle effect on the cryostability and other properties of the holoenzyme. Equally possibility occurs in LT -specific posttranslational processing, although there is no evidence to support this concept. In addition to isozymic and conformational differences of enzymes in response to L T exposure, Griffith, stated supramolecular interactions can also be affected.
According to [88], accumulation of soluble protein in cold-acclimated cortical bark cells of black locust trees was first correlated with freezing tolerance about 40 years ago. These study may not be explained as simply as stated in past, [88] suggests there are many reasons why some plants might accumulate soluble proteins during CA; but with the exception of a protoplasmic augmentation hypothesis without clear mechanistic rationale for conferring greater freezing tolerance for this hardening response. In temperate deciduous perennials like black locust could provide the nitrogen source for the accumulation of proteins in the cortical cells of the living bark, in expense of nitrogenous materials during senescence. Parsell and Lindquist [89] supports a possible functional role of the increased soluble protein in cold tolerance was the fact that an evergreen, red pine, also accumulated soluble proteins during the winter, similarly, cortical bark cells need not to act as vegetative storage in evergreens nevertheless, it cannot be refused that one or more minor components of the total protein content could function in freezing-tolerance mechanisms.
Most of the studies have confirmed the presence of new protein species in cold-acclimated and freezing-tolerant plants. When these plants are compared to non-acclimated plants, subtle shift in protein content in cold-acclimated tissues involving mostly the appearance and disappearance of minor bands in gel can be observed [85]. Existing evidence at present includes several studies of purified plasma membranes from non-acclimated and cold-acclimated tissue. Tzin and Galili [90] emphasized on declination of more than 20 proteins in cold-acclimated leaf plasma membranes, whereas 11 had increased their concentration, while 26 proteins were new and unique to membranes from hardened tissue, yet increased levels of high-molecular-weight glycoproteins were other alterations included during CA.
Some defense mechanisms can be triggered in response to several stresses, such as expression of obvious genes which were not expressed under normal situations, resulting increased synthesis of protein groups [60]. These groups in cases of heat are called as Heat Shock Proteins (HSPs), “Stress-induced proteins” or “Stress proteins” [49].
According to [14] declination in normal protein synthesis occurs when exposed to high temperatures, thereby increasing selective translation of mRNAs for characteristic sets of HSPs. Heat responding phenomena in plants generally observed with concomitant reduction in protein synthesis of new or constitutive HSPs. Jin et al. [35] observed reduction in total protein synthesis at of 40°C and above in soybean. The HSPs, in plants, consists an abundant group of low mo1 wt polypeptides with higher molecular weight families [91], where some of them found to function as chaperones minimizing high-temperature stress damage partially denaturing proteins and preventing breakdown or aggregation. Response toward heat includes increase in binding of ubiquitin to conglomerated high molecular weight protein [11] which both increase and decrease ubiquitin transcripts expression [17].
Levitt et al. [92] reported formation and folding patterns of any protein in three dimensional structure determines their function and [93] favored above statement and confronted with the findings illustrating 50% of principle amino acids sequence is necessary for formation of three dimensional structure which signifies the importance of HSPs in folding of other proteins. As plants were induced in heat stress, HSPs protects cells from injury and facilitates their recovery and survival to normal growth conditions [49]. Also, [94] specified the role of HSps as molecular chaperones during heat stressed condition, apart from ensuring maintenance of correct protein structure, which is basically different than in non-thermal stress where proteins unfolding is not the primary effect and protection could occur in any ways.
Seo et al. [95] also focused the general role of HSPs as molecular chaperones, regulating folding and accumulation of proteins as well as localization and degradation in all plant and animal species, thus preventing the irreversible aggregation of other proteins and participate in refolding proteins during heat stress conditions [96].
Different HSPs with their unique role are described below:
These contains a common alpha-crystallin domain containing 80–100 amino acid residues contained in the C-terminal region [97]. The characteristics features of this proteins is degradation of protein having unsuitable folding [11]. Another attributes that make it indifferent from other class is independency of its activity from ATP [98]. A recent review from [99] concluded the presence of some indications that sHSPs play crucial role in membrane quality control, thereby potentially contributing the maintenance of membrane integrity under stress conditions.
This class, called as chaperonins, is known to be important in assisting plastid proteins such as Rubisco [100]. Some studies like [101] pointed out that they might participate in folding and aggregation of proteins that were transported to chloroplasts and mitochondria. These proteins are different from other proteins, after transcription and before folding, to prevent their aggregation [42].
These HSP70 functions as chaperones, in almost all organisms, for newly formed proteins to check their accumulations as aggregates and folds in a proper way during their transfer to final location [102]. Furthermore, cooperation in the activity of HSp70 and sHSPs primarily function as molecular chaperone and play an important role in protecting plant cell from detrimental effects of heat stress [83] stressed on crucial role played by HSp70 and sHSP17.6 in the development of cross adaptation to temperature stress in grape vines induced by heat acclimation (HA) and cold acclimation (CA).
The protein from HSP90 class shares the role in many chaperone complexes and has important role in signaling protein function and trafficking [89]. Furthermore, other important attributes retained by these class includes regulation of cellular signals, such as the regulation of glucocorticoid receptor (GR) activity [103].
What makes it unique from other class is the reactivation of aggregated proteins [42] by re-solubilizing nonfunctional protein aggregates and also by degrading irreversibly damaged polypeptides [104, 105]. Members of this class are not restricted only to acclimation to high temperatures but also housekeeping functions necessary in chloroplast development are also provided by specific member (Figures 1 and 2) [106].
Plant stress tolerance and resistance [
Transcription [
Abiotic stresses are major limiting factors for plant growth and yields and with various acclimation responses at morphological, physiological, metabolic, and molecular level coordinated by complicated regulatory networks comprising genes, phytohormones, ROS, and other signaling components. The abundance of ion channels protein and trans-membrane water found indicated the change in ions/osmotic balances, but the phenomenon was not observed in flooding conditions. In addition, the preventive measure against the oxidative damage caused due to ROS levels under abiotic stress, higher abundance of ROS scavengers plays a great role in this matter, whereas the abundance of ROS scavengers was low in the flooding condition. On the other hand, protein folding due to molecular chaperone and disease, defense-related proteins such as proteolytic enzymes and proteosomal factors under stress, indicating the refolding of denatured proteins and proteolytic elimination of damaged proteins. This review paper showed the different protein metabolism occurs during the metabolic stages, and secondary metabolism-associated proteins escape and tolerate mechanism under different abiotic stress.
At the recovery stages, increased lignin biosynthesis results in enhanced mechanical strength by hardening of cell wall. Changes in abundance for cyto-skeletons associated proteins can be overlooked upon compensation against the reduced cell size as well as repairing injuries caused by drought and flood stress. Moreover, the levels of proteins related to
Only after proteomic studies could make us aware about the mechanism involved in abiotic stress condition. Analyzing of the plant response and abundance of protein and stress tolerant crops will lead to better understanding of the mechanism of plant to overcome the stress and recover. Moreover, some proteins showed the dynamic changes depending on plant species and stress intensity, which gives a clear interpretation of the mechanism in stress response. The integration of those finding from physiological, gene expression, and other large scale “omics” will help us to establish molecular networks of stress response and tolerance.
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\\n"}]'},components:[{type:"htmlEditorComponent",content:'Copyright is the term used to describe the rights related to the publication and distribution of original Works. Most importantly from a publisher's perspective, copyright governs how Authors, publishers and the general public can use, publish, and distribute publications.
\n\nIntechOpen only publishes manuscripts for which it has publishing rights. This is governed by a publication agreement between the Author and IntechOpen. This agreement is accepted by the Author when the manuscript is submitted and deals with both the rights of the publisher and Author, as well as any obligations concerning a particular manuscript. However, in accepting this agreement, Authors continue to retain significant rights to use and share their publications.
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\n\nWork - a Chapter, including Conference Papers, a Scientific Article and any and all text, graphics, images and/or other materials forming part of or accompanying the Chapter/Conference Paper.
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\n\nIntechOpen - Registered publisher with office at 5 Princes Gate Court, London, SW7 2QJ - UNITED KINGDOM
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On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. His research interests include pattern recognition, bioinformatics, and biometric systems (fingerprint classification and recognition, signature verification, face recognition).",institutionString:null,institution:null},{id:"496",title:"Dr.",name:"Carlos",middleName:null,surname:"Leon",slug:"carlos-leon",fullName:"Carlos Leon",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Seville",country:{name:"Spain"}}},{id:"512",title:"Dr.",name:"Dayang",middleName:null,surname:"Jawawi",slug:"dayang-jawawi",fullName:"Dayang Jawawi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Technology Malaysia",country:{name:"Malaysia"}}},{id:"528",title:"Dr.",name:"Kresimir",middleName:null,surname:"Delac",slug:"kresimir-delac",fullName:"Kresimir Delac",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/528/images/system/528.jpg",biography:"K. 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From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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He is also a faculty member in the Molecular Oncology Program. He obtained his MSc and Ph.D. at Oregon State University and Texas Tech University, respectively. He pursued his postdoctoral studies at Rutgers University Medical School and the National Institutes of Health (NIH/NIDDK), USA. His research focuses on biochemistry, biophysics, genetics, molecular biology, and molecular medicine with specialization in the fields of drug design, protein structure-function, protein folding, prions, microRNA, pseudogenes, molecular cancer, epigenetics, metabolites, proteomics, genomics, protein expression, and characterization by spectroscopic and calorimetric methods.",institutionString:"University of Health Sciences",institution:null},{id:"180528",title:"Dr.",name:"Hiroyuki",middleName:null,surname:"Kagechika",slug:"hiroyuki-kagechika",fullName:"Hiroyuki Kagechika",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180528/images/system/180528.jpg",biography:"Hiroyuki Kagechika received his bachelor’s degree and Ph.D. in Pharmaceutical Sciences from the University of Tokyo, Japan, where he served as an associate professor until 2004. He is currently a professor at the Institute of Biomaterials and Bioengineering (IBB), Tokyo Medical and Dental University (TMDU). From 2010 to 2012, he was the dean of the Graduate School of Biomedical Science. Since 2012, he has served as the vice dean of the Graduate School of Medical and Dental Sciences. He has been the director of the IBB since 2020. Dr. Kagechika’s major research interests are the medicinal chemistry of retinoids, vitamins D/K, and nuclear receptors. He has developed various compounds including a drug for acute promyelocytic leukemia.",institutionString:"Tokyo Medical and Dental University",institution:{name:"Tokyo Medical and Dental University",country:{name:"Japan"}}},{id:"268659",title:"Ms.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/268659/images/8143_n.jpg",biography:"Dr. Zhan received his undergraduate and graduate training in the fields of preventive medicine and epidemiology and statistics at the West China University of Medical Sciences in China during 1989 to 1999. He received his post-doctoral training in oncology and cancer proteomics for two years at the Cancer Research Institute of Human Medical University in China. In 2001, he went to the University of Tennessee Health Science Center (UTHSC) in USA, where he was a post-doctoral researcher and focused on mass spectrometry and cancer proteomics. Then, he was appointed as an Assistant Professor of Neurology, UTHSC in 2005. He moved to the Cleveland Clinic in USA as a Project Scientist/Staff in 2006 where he focused on the studies of eye disease proteomics and biomarkers. He returned to UTHSC as an Assistant Professor of Neurology in the end of 2007, engaging in proteomics and biomarker studies of lung diseases and brain tumors, and initiating the studies of predictive, preventive, and personalized medicine (PPPM) in cancer. In 2010, he was promoted to Associate Professor of Neurology, UTHSC. Currently, he is a Professor at Xiangya Hospital of Central South University in China, Fellow of Royal Society of Medicine (FRSM), the European EPMA National Representative in China, Regular Member of American Association for the Advancement of Science (AAAS), European Cooperation of Science and Technology (e-COST) grant evaluator, Associate Editors of BMC Genomics, BMC Medical Genomics, EPMA Journal, and Frontiers in Endocrinology, Executive Editor-in-Chief of Med One. He has\npublished 116 peer-reviewed research articles, 16 book chapters, 2 books, and 2 US patents. His current main research interest focuses on the studies of cancer proteomics and biomarkers, and the use of modern omics techniques and systems biology for PPPM in cancer, and on the development and use of 2DE-LC/MS for the large-scale study of human proteoforms.",institutionString:null,institution:{name:"Xiangya Hospital Central South University",country:{name:"China"}}},{id:"40482",title:null,name:"Rizwan",middleName:null,surname:"Ahmad",slug:"rizwan-ahmad",fullName:"Rizwan Ahmad",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/40482/images/system/40482.jpeg",biography:"Dr. Rizwan Ahmad is a University Professor and Coordinator, Quality and Development, College of Medicine, Imam Abdulrahman bin Faisal University, Saudi Arabia. Previously, he was Associate Professor of Human Function, Oman Medical College, Oman, and SBS University, Dehradun. Dr. Ahmad completed his education at Aligarh Muslim University, Aligarh. He has published several articles in peer-reviewed journals, chapters, and edited books. His area of specialization is free radical biochemistry and autoimmune diseases.",institutionString:"Imam Abdulrahman Bin Faisal University",institution:{name:"Imam Abdulrahman Bin Faisal University",country:{name:"Saudi Arabia"}}},{id:"41865",title:"Prof.",name:"Farid A.",middleName:null,surname:"Badria",slug:"farid-a.-badria",fullName:"Farid A. Badria",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/41865/images/system/41865.jpg",biography:"Farid A. Badria, Ph.D., is the recipient of several awards, including The World Academy of Sciences (TWAS) Prize for Public Understanding of Science; the World Intellectual Property Organization (WIPO) Gold Medal for best invention; Outstanding Arab Scholar, Kuwait; and the Khwarizmi International Award, Iran. He has 250 publications, 12 books, 20 patents, and several marketed pharmaceutical products to his credit. He continues to lead research projects on developing new therapies for liver, skin disorders, and cancer. Dr. Badria was listed among the world’s top 2% of scientists in medicinal and biomolecular chemistry in 2019 and 2020. He is a member of the Arab Development Fund, Kuwait; International Cell Research Organization–United Nations Educational, Scientific and Cultural Organization (ICRO–UNESCO), Chile; and UNESCO Biotechnology France",institutionString:"Mansoura University",institution:{name:"Mansoura University",country:{name:"Egypt"}}},{id:"329385",title:"Dr.",name:"Rajesh K.",middleName:"Kumar",surname:"Singh",slug:"rajesh-k.-singh",fullName:"Rajesh K. Singh",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329385/images/system/329385.png",biography:"Dr. Singh received a BPharm (2003) and MPharm (2005) from Panjab University, Chandigarh, India, and a Ph.D. (2013) from Punjab Technical University (PTU), Jalandhar, India. He has more than sixteen years of teaching experience and has supervised numerous postgraduate and Ph.D. students. He has to his credit more than seventy papers in SCI- and SCOPUS-indexed journals, fifty-five conference proceedings, four books, six Best Paper Awards, and five projects from different government agencies. He is currently an editorial board member of eight international journals and a reviewer for more than fifty scientific journals. He received Top Reviewer and Excellent Peer Reviewer Awards from Publons in 2016 and 2017, respectively. He is also on the panel of The International Reviewer for reviewing research proposals for grants from the Royal Society. He also serves as a Publons Academy mentor and Bentham brand ambassador.",institutionString:"Punjab Technical University",institution:{name:"Punjab Technical University",country:{name:"India"}}},{id:"142388",title:"Dr.",name:"Thiago",middleName:"Gomes",surname:"Gomes Heck",slug:"thiago-gomes-heck",fullName:"Thiago Gomes Heck",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/142388/images/7259_n.jpg",biography:null,institutionString:null,institution:{name:"Universidade Regional do Noroeste do Estado do Rio Grande do Sul",country:{name:"Brazil"}}},{id:"336273",title:"Assistant Prof.",name:"Janja",middleName:null,surname:"Zupan",slug:"janja-zupan",fullName:"Janja Zupan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/336273/images/14853_n.jpeg",biography:"Janja Zupan graduated in 2005 at the Department of Clinical Biochemistry (superviser prof. dr. Janja Marc) in the field of genetics of osteoporosis. Since November 2009 she is working as a Teaching Assistant at the Faculty of Pharmacy, Department of Clinical Biochemistry. In 2011 she completed part of her research and PhD work at Institute of Genetics and Molecular Medicine, University of Edinburgh. She finished her PhD entitled The influence of the proinflammatory cytokines on the RANK/RANKL/OPG in bone tissue of osteoporotic and osteoarthritic patients in 2012. From 2014-2016 she worked at the Institute of Biomedical Sciences, University of Aberdeen as a postdoctoral research fellow on UK Arthritis research project where she gained knowledge in mesenchymal stem cells and regenerative medicine. She returned back to University of Ljubljana, Faculty of Pharmacy in 2016. She is currently leading project entitled Mesenchymal stem cells-the keepers of tissue endogenous regenerative capacity facing up to aging of the musculoskeletal system funded by Slovenian Research Agency.",institutionString:null,institution:{name:"University of Ljubljana",country:{name:"Slovenia"}}},{id:"357453",title:"Dr.",name:"Radheshyam",middleName:null,surname:"Maurya",slug:"radheshyam-maurya",fullName:"Radheshyam Maurya",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/357453/images/16535_n.jpg",biography:null,institutionString:null,institution:{name:"University of Hyderabad",country:{name:"India"}}},{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",institution:null},{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. With 16+ years of trans-disciplinary research experience in Drug Design, development, and pre-clinical validation; 20+ research article publications in journals of repute, 9+ years of teaching experience, trained with cross-disciplinary education, Dr. Basu is a life-long learner and always thrives for new challenges.\r\nHer research area is the design and synthesis of small molecule partial agonists of PPAR-γ in lung cancer. She is also using artificial intelligence and deep learning methods to understand the exosomal miRNA’s role in cancer metastasis. Dr. Basu is the recipient of many awards including the Early Career Research Award from the Department of Science and Technology, Govt. of India. She is a reviewer of many journals like Molecular Biology Reports, Frontiers in Oncology, RSC Advances, PLOS ONE, Journal of Biomolecular Structure & Dynamics, Journal of Molecular Graphics and Modelling, etc. She has edited and authored/co-authored 21 journal papers, 3 book chapters, and 15 abstracts. She is a Board of Studies member at her university. She is a life member of 'The Cytometry Society”-in India and 'All India Cell Biology Society”- in India.",institutionString:"Dr. D.Y. Patil Vidyapeeth, Pune",institution:{name:"Dr. D.Y. Patil Vidyapeeth, Pune",country:{name:"India"}}},{id:"354817",title:"Dr.",name:"Anubhab",middleName:null,surname:"Mukherjee",slug:"anubhab-mukherjee",fullName:"Anubhab Mukherjee",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y0000365PbRQAU/ProfilePicture%202022-04-15%2005%3A11%3A18.480",biography:"A former member of Laboratory of Nanomedicine, Brigham and Women’s Hospital, Harvard University, Boston, USA, Dr. Anubhab Mukherjee is an ardent votary of science who strives to make an impact in the lives of those afflicted with cancer and other chronic/acute ailments. He completed his Ph.D. from CSIR-Indian Institute of Chemical Technology, Hyderabad, India, having been skilled with RNAi, liposomal drug delivery, preclinical cell and animal studies. He pursued post-doctoral research at College of Pharmacy, Health Science Center, Texas A & M University and was involved in another postdoctoral research at Department of Translational Neurosciences and Neurotherapeutics, John Wayne Cancer Institute, Santa Monica, California. In 2015, he worked in Harvard-MIT Health Sciences & Technology as a visiting scientist. He has substantial experience in nanotechnology-based formulation development and successfully served various Indian organizations to develop pharmaceuticals and nutraceutical products. He is an inventor in many US patents and an author in many peer-reviewed articles, book chapters and books published in various media of international repute. Dr. Mukherjee is currently serving as Principal Scientist, R&D at Esperer Onco Nutrition (EON) Pvt. Ltd. and heads the Hyderabad R&D center of the organization.",institutionString:"Esperer Onco Nutrition Pvt Ltd.",institution:null},{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",institution:{name:"University of California Los Angeles",country:{name:"United States of America"}}},{id:"311457",title:"Dr.",name:"Júlia",middleName:null,surname:"Scherer Santos",slug:"julia-scherer-santos",fullName:"Júlia Scherer Santos",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/311457/images/system/311457.jpg",biography:"Dr. Júlia Scherer Santos works in the areas of cosmetology, nanotechnology, pharmaceutical technology, beauty, and aesthetics. Dr. Santos also has experience as a professor of graduate courses. Graduated in Pharmacy, specialization in Cosmetology and Cosmeceuticals applied to aesthetics, specialization in Aesthetic and Cosmetic Health, and a doctorate in Pharmaceutical Nanotechnology. Teaching experience in Pharmacy and Aesthetics and Cosmetics courses. She works mainly on the following subjects: nanotechnology, cosmetology, pharmaceutical technology, aesthetics.",institutionString:"Universidade Federal de Juiz de Fora",institution:{name:"Universidade Federal de Juiz de Fora",country:{name:"Brazil"}}},{id:"219081",title:"Dr.",name:"Abdulsamed",middleName:null,surname:"Kükürt",slug:"abdulsamed-kukurt",fullName:"Abdulsamed Kükürt",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/219081/images/system/219081.png",biography:"Dr. Kükürt graduated from Uludağ University in Turkey. He started his academic career as a Research Assistant in the Department of Biochemistry at Kafkas University. In 2019, he completed his Ph.D. program in the Department of Biochemistry at the Institute of Health Sciences. He is currently working at the Department of Biochemistry, Kafkas University. He has 27 published research articles in academic journals, 11 book chapters, and 37 papers. He took part in 10 academic projects. He served as a reviewer for many articles. He still serves as a member of the review board in many academic journals.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"178366",title:"Associate Prof.",name:"Volkan",middleName:null,surname:"Gelen",slug:"volkan-gelen",fullName:"Volkan Gelen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/178366/images/system/178366.jpg",biography:"Volkan Gelen is a Physiology specialist who received his veterinary degree from Kafkas University in 2011. Between 2011-2015, he worked as an assistant at Atatürk University, Faculty of Veterinary Medicine, Department of Physiology. In 2016, he joined Kafkas University, Faculty of Veterinary Medicine, Department of Physiology as an assistant professor. Dr. Gelen has been engaged in various academic activities at Kafkas University since 2016. There he completed 5 projects and has 3 ongoing projects. He has 60 articles published in scientific journals and 20 poster presentations in scientific congresses. His research interests include physiology, endocrine system, cancer, diabetes, cardiovascular system diseases, and isolated organ bath system studies.",institutionString:"Kafkas University",institution:{name:"Kafkas University",country:{name:"Turkey"}}},{id:"418963",title:"Dr.",name:"Augustine Ododo",middleName:"Augustine",surname:"Osagie",slug:"augustine-ododo-osagie",fullName:"Augustine Ododo Osagie",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/418963/images/16900_n.jpg",biography:"Born into the family of Osagie, a prince of the Benin Kingdom. I am currently an academic in the Department of Medical Biochemistry, University of Benin. Part of the duties are to teach undergraduate students and conduct academic research.",institutionString:null,institution:{name:"University of Benin",country:{name:"Nigeria"}}},{id:"192992",title:"Prof.",name:"Shagufta",middleName:null,surname:"Perveen",slug:"shagufta-perveen",fullName:"Shagufta Perveen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/192992/images/system/192992.png",biography:"Prof. Shagufta Perveen is a Distinguish Professor in the Department of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. Dr. Perveen has acted as the principal investigator of major research projects funded by the research unit of King Saud University. She has more than ninety original research papers in peer-reviewed journals of international repute to her credit. She is a fellow member of the Royal Society of Chemistry UK and the American Chemical Society of the United States.",institutionString:"King Saud University",institution:{name:"King Saud University",country:{name:"Saudi Arabia"}}},{id:"49848",title:"Dr.",name:"Wen-Long",middleName:null,surname:"Hu",slug:"wen-long-hu",fullName:"Wen-Long Hu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49848/images/system/49848.jpg",biography:"Wen-Long Hu is Chief of the Division of Acupuncture, Department of Chinese Medicine at Kaohsiung Chang Gung Memorial Hospital, as well as an adjunct associate professor at Fooyin University and Kaohsiung Medical University. Wen-Long is President of Taiwan Traditional Chinese Medicine Medical Association. He has 28 years of experience in clinical practice in laser acupuncture therapy and 34 years in acupuncture. He is an invited speaker for lectures and workshops in laser acupuncture at many symposiums held by medical associations. He owns the patent for herbal preparation and producing, and for the supercritical fluid-treated needle. Dr. Hu has published three books, 12 book chapters, and more than 30 papers in reputed journals, besides serving as an editorial board member of repute.",institutionString:"Kaohsiung Chang Gung Memorial Hospital",institution:{name:"Kaohsiung Chang Gung Memorial Hospital",country:{name:"Taiwan"}}},{id:"298472",title:"Prof.",name:"Andrey V.",middleName:null,surname:"Grechko",slug:"andrey-v.-grechko",fullName:"Andrey V. Grechko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/298472/images/system/298472.png",biography:"Andrey Vyacheslavovich Grechko, Ph.D., Professor, is a Corresponding Member of the Russian Academy of Sciences. He graduated from the Semashko Moscow Medical Institute (Semashko National Research Institute of Public Health) with a degree in Medicine (1998), the Clinical Department of Dermatovenerology (2000), and received a second higher education in Psychology (2009). Professor A.V. Grechko held the position of Сhief Physician of the Central Clinical Hospital in Moscow. He worked as a professor at the faculty and was engaged in scientific research at the Medical University. Starting in 2013, he has been the initiator of the creation of the Federal Scientific and Clinical Center for Intensive Care and Rehabilitology, Moscow, Russian Federation, where he also serves as Director since 2015. He has many years of experience in research and teaching in various fields of medicine, is an author/co-author of more than 200 scientific publications, 13 patents, 15 medical books/chapters, including Chapter in Book «Metabolomics», IntechOpen, 2020 «Metabolomic Discovery of Microbiota Dysfunction as the Cause of Pathology».",institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"199461",title:"Prof.",name:"Natalia V.",middleName:null,surname:"Beloborodova",slug:"natalia-v.-beloborodova",fullName:"Natalia V. Beloborodova",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/199461/images/system/199461.jpg",biography:'Natalia Vladimirovna Beloborodova was educated at the Pirogov Russian National Research Medical University, with a degree in pediatrics in 1980, a Ph.D. in 1987, and a specialization in Clinical Microbiology from First Moscow State Medical University in 2004. She has been a Professor since 1996. Currently, she is the Head of the Laboratory of Metabolism, a division of the Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology, Moscow, Russian Federation. N.V. Beloborodova has many years of clinical experience in the field of intensive care and surgery. She studies infectious complications and sepsis. She initiated a series of interdisciplinary clinical and experimental studies based on the concept of integrating human metabolism and its microbiota. Her scientific achievements are widely known: she is the recipient of the Marie E. Coates Award \\"Best lecturer-scientist\\" Gustafsson Fund, Karolinska Institutes, Stockholm, Sweden, and the International Sepsis Forum Award, Pasteur Institute, Paris, France (2014), etc. Professor N.V. Beloborodova wrote 210 papers, five books, 10 chapters and has edited four books.',institutionString:"Federal Research and Clinical Center of Intensive Care Medicine and Rehabilitology",institution:null},{id:"354260",title:"Ph.D.",name:"Tércio Elyan",middleName:"Azevedo",surname:"Azevedo Martins",slug:"tercio-elyan-azevedo-martins",fullName:"Tércio Elyan Azevedo Martins",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/354260/images/16241_n.jpg",biography:"Graduated in Pharmacy from the Federal University of Ceará with the modality in Industrial Pharmacy, Specialist in Production and Control of Medicines from the University of São Paulo (USP), Master in Pharmaceuticals and Medicines from the University of São Paulo (USP) and Doctor of Science in the program of Pharmaceuticals and Medicines by the University of São Paulo. Professor at Universidade Paulista (UNIP) in the areas of chemistry, cosmetology and trichology. Assistant Coordinator of the Higher Course in Aesthetic and Cosmetic Technology at Universidade Paulista Campus Chácara Santo Antônio. Experience in the Pharmacy area, with emphasis on Pharmacotechnics, Pharmaceutical Technology, Research and Development of Cosmetics, acting mainly on topics such as cosmetology, antioxidant activity, aesthetics, photoprotection, cyclodextrin and thermal analysis.",institutionString:null,institution:{name:"University of Sao Paulo",country:{name:"Brazil"}}},{id:"334285",title:"Ph.D. Student",name:"Sameer",middleName:"Kumar",surname:"Jagirdar",slug:"sameer-jagirdar",fullName:"Sameer Jagirdar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334285/images/14691_n.jpg",biography:"I\\'m a graduate student at the center for biosystems science and engineering at the Indian Institute of Science, Bangalore, India. I am interested in studying host-pathogen interactions at the biomaterial interface.",institutionString:null,institution:{name:"Indian Institute of Science Bangalore",country:{name:"India"}}},{id:"329248",title:"Dr.",name:"Md. Faheem",middleName:null,surname:"Haider",slug:"md.-faheem-haider",fullName:"Md. Faheem Haider",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329248/images/system/329248.jpg",biography:"Dr. Md. Faheem Haider completed his BPharm in 2012 at Integral University, Lucknow, India. In 2014, he completed his MPharm with specialization in Pharmaceutics at Babasaheb Bhimrao Ambedkar University, Lucknow, India. He received his Ph.D. degree from Jamia Hamdard University, New Delhi, India, in 2018. He was selected for the GPAT six times and his best All India Rank was 34. Currently, he is an assistant professor at Integral University. Previously he was an assistant professor at IIMT University, Meerut, India. He has experience teaching DPharm, Pharm.D, BPharm, and MPharm students. He has more than five publications in reputed journals to his credit. Dr. Faheem’s research area is the development and characterization of nanoformulation for the delivery of drugs to various organs.",institutionString:"Integral University",institution:{name:"Integral University",country:{name:"India"}}},{id:"329795",title:"Dr.",name:"Mohd Aftab",middleName:"Aftab",surname:"Siddiqui",slug:"mohd-aftab-siddiqui",fullName:"Mohd Aftab Siddiqui",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/329795/images/15648_n.jpg",biography:"Dr. Mohd Aftab Siddiqui is currently working as Assistant Professor in the Faculty of Pharmacy, Integral University, Lucknow for the last 6 years. He has completed his Doctor in Philosophy (Pharmacology) in 2020 from Integral University, Lucknow. He completed his Bachelor in Pharmacy in 2013 and Master in Pharmacy (Pharmacology) in 2015 from Integral University, Lucknow. He is the gold medalist in Bachelor and Master degree. He qualified GPAT -2013, GPAT -2014, and GPAT 2015. His area of research is Pharmacological screening of herbal drugs/ natural products in liver and cardiac diseases. He has guided many M. Pharm. research projects. He has many national and international publications.",institutionString:"Integral University",institution:null},{id:"333824",title:"Dr.",name:"Ahmad Farouk",middleName:null,surname:"Musa",slug:"ahmad-farouk-musa",fullName:"Ahmad Farouk Musa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/333824/images/22684_n.jpg",biography:"Dato’ Dr Ahmad Farouk Musa\nMD, MMED (Surgery) (Mal), Fellowship in Cardiothoracic Surgery (Monash Health, Aust), Graduate Certificate in Higher Education (Aust), Academy of Medicine (Mal)\n\n\n\nDato’ Dr Ahmad Farouk Musa obtained his Doctor of Medicine from USM in 1992. He then obtained his Master of Medicine in Surgery from the same university in the year 2000 before subspecialising in Cardiothoracic Surgery at Institut Jantung Negara (IJN), Kuala Lumpur from 2002 until 2005. He then completed his Fellowship in Cardiothoracic Surgery at Monash Health, Melbourne, Australia in 2008. He has served in the Malaysian army as a Medical Officer with the rank of Captain upon completing his Internship before joining USM as a trainee lecturer. He is now serving as an academic and researcher at Monash University Malaysia. He is a life-member of the Malaysian Association of Thoracic & Cardiovascular Surgery (MATCVS) and a committee member of the MATCVS Database. He is also a life-member of the College of Surgeons, Academy of Medicine of Malaysia; a life-member of Malaysian Medical Association (MMA), and a life-member of Islamic Medical Association of Malaysia (IMAM). Recently he was appointed as an Interim Chairperson of Examination & Assessment Subcommittee of the UiTM-IJN Cardiothoracic Surgery Postgraduate Program. As an academic, he has published numerous research papers and book chapters. He has also been appointed to review many scientific manuscripts by established journals such as the British Medical Journal (BMJ). He has presented his research works at numerous local and international conferences such as the European Association for Cardiothoracic Surgery (EACTS) and the European Society of Cardiovascular Surgery (ESCVS), to name a few. He has also won many awards for his research presentations at meetings and conferences like the prestigious International Invention, Innovation & Technology Exhibition (ITEX); Design, Research and Innovation Exhibition, the National Conference on Medical Sciences and the Annual Scientific Meetings of the Malaysian Association for Thoracic and Cardiovascular Surgery. He was awarded the Darjah Setia Pangkuan Negeri (DSPN) by the Governor of Penang in July, 2015.",institutionString:null,institution:{name:"Monash University Malaysia",country:{name:"Malaysia"}}},{id:"30568",title:"Prof.",name:"Madhu",middleName:null,surname:"Khullar",slug:"madhu-khullar",fullName:"Madhu Khullar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/30568/images/system/30568.jpg",biography:"Dr. Madhu Khullar is a Professor of Experimental Medicine and Biotechnology at the Post Graduate Institute of Medical Education and Research, Chandigarh, India. She completed her Post Doctorate in hypertension research at the Henry Ford Hospital, Detroit, USA in 1985. She is an editor and reviewer of several international journals, and a fellow and member of several cardiovascular research societies. Dr. Khullar has a keen research interest in genetics of hypertension, and is currently studying pharmacogenetics of hypertension.",institutionString:"Post Graduate Institute of Medical Education and Research",institution:{name:"Post Graduate Institute of Medical Education and Research",country:{name:"India"}}},{id:"223233",title:"Prof.",name:"Xianquan",middleName:null,surname:"Zhan",slug:"xianquan-zhan",fullName:"Xianquan Zhan",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/223233/images/system/223233.png",biography:"Xianquan Zhan received his MD and Ph.D. in Preventive Medicine at West China University of Medical Sciences. He received his post-doctoral training in oncology and cancer proteomics at the Central South University, China, and the University of Tennessee Health Science Center (UTHSC), USA. He worked at UTHSC and the Cleveland Clinic in 2001–2012 and achieved the rank of associate professor at UTHSC. Currently, he is a full professor at Central South University and Shandong First Medical University, and an advisor to MS/PhD students and postdoctoral fellows. He is also a fellow of the Royal Society of Medicine and European Association for Predictive Preventive Personalized Medicine (EPMA), a national representative of EPMA, and a member of the American Society of Clinical Oncology (ASCO) and the American Association for the Advancement of Sciences (AAAS). He is also the editor in chief of International Journal of Chronic Diseases & Therapy, an associate editor of EPMA Journal, Frontiers in Endocrinology, and BMC Medical Genomics, and a guest editor of Mass Spectrometry Reviews, Frontiers in Endocrinology, EPMA Journal, and Oxidative Medicine and Cellular Longevity. He has published more than 148 articles, 28 book chapters, 6 books, and 2 US patents in the field of clinical proteomics and biomarkers.",institutionString:"Shandong First Medical University",institution:{name:"Affiliated Hospital of Shandong Academy of Medical Sciences",country:{name:"China"}}},{id:"297507",title:"Dr.",name:"Charles",middleName:"Elias",surname:"Assmann",slug:"charles-assmann",fullName:"Charles Assmann",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/297507/images/system/297507.jpg",biography:"Charles Elias Assmann is a biologist from Federal University of Santa Maria (UFSM, Brazil), who spent some time abroad at the Ludwig-Maximilians-Universität München (LMU, Germany). He has Masters Degree in Biochemistry (UFSM), and is currently a PhD student at Biochemistry at the Department of Biochemistry and Molecular Biology of the UFSM. His areas of expertise include: Biochemistry, Molecular Biology, Enzymology, Genetics and Toxicology. He is currently working on the following subjects: Aluminium toxicity, Neuroinflammation, Oxidative stress and Purinergic system. Since 2011 he has presented more than 80 abstracts in scientific proceedings of national and international meetings. Since 2014, he has published more than 20 peer reviewed papers (including 4 reviews, 3 in Portuguese) and 2 book chapters. He has also been a reviewer of international journals and ad hoc reviewer of scientific committees from Brazilian Universities.",institutionString:"Universidade Federal de Santa Maria",institution:{name:"Universidade Federal de Santa Maria",country:{name:"Brazil"}}},{id:"217850",title:"Dr.",name:"Margarete Dulce",middleName:null,surname:"Bagatini",slug:"margarete-dulce-bagatini",fullName:"Margarete Dulce Bagatini",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/217850/images/system/217850.jpeg",biography:"Dr. Margarete Dulce Bagatini is an associate professor at the Federal University of Fronteira Sul/Brazil. She has a degree in Pharmacy and a PhD in Biological Sciences: Toxicological Biochemistry. She is a member of the UFFS Research Advisory Committee\nand a member of the Biovitta Research Institute. She is currently:\nthe leader of the research group: Biological and Clinical Studies\nin Human Pathologies, professor of postgraduate program in\nBiochemistry at UFSC and postgraduate program in Science and Food Technology at\nUFFS. She has experience in the area of pharmacy and clinical analysis, acting mainly\non the following topics: oxidative stress, the purinergic system and human pathologies, being a reviewer of several international journals and books.",institutionString:"Universidade Federal da Fronteira Sul",institution:{name:"Universidade Federal da Fronteira Sul",country:{name:"Brazil"}}}]}},subseries:{item:{id:"6",type:"subseries",title:"Viral Infectious Diseases",keywords:"Novel Viruses, Virus Transmission, Virus Evolution, Molecular Virology, Control and Prevention, Virus-host Interaction",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. This series will focus on various crucial factors related to emerging viral infectious diseases, including epidemiology, pathogenesis, host immune response, clinical manifestations, diagnosis, treatment, and clinical recommendations for managing viral infectious diseases, highlighting the recent issues with future directions for effective therapeutic strategies.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/6.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11402,editor:{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",biography:"Professor Dr. Shailendra K. Saxena is a vice dean and professor at King George's Medical University, Lucknow, India. His research interests involve understanding the molecular mechanisms of host defense during human viral infections and developing new predictive, preventive, and therapeutic strategies for them using Japanese encephalitis virus (JEV), HIV, and emerging viruses as a model via stem cell and cell culture technologies. His research work has been published in various high-impact factor journals (Science, PNAS, Nature Medicine) with a high number of citations. He has received many awards and honors in India and abroad including various Young Scientist Awards, BBSRC India Partnering Award, and Dr. JC Bose National Award of Department of Biotechnology, Min. of Science and Technology, Govt. of India. Dr. Saxena is a fellow of various international societies/academies including the Royal College of Pathologists, United Kingdom; Royal Society of Medicine, London; Royal Society of Biology, United Kingdom; Royal Society of Chemistry, London; and Academy of Translational Medicine Professionals, Austria. He was named a Global Leader in Science by The Scientist. 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