Signal transduction comprises the intracellular biochemical signals which induce the appropriate cell response to an external stimulus.
Author: Joana Vieira Silva
Publisher: Springer Nature
Signal transduction comprises the intracellular biochemical signals which induce the appropriate cell response to an external stimulus. The players in signal transduction are diverse, from small molecules as first messengers, to proteins, receptors, transcription factors, among many others. The different signaling pathways and the crosstalk between them originates the unique signaling profile of every cell type in the human body. The cell signaling specificity depends on several aspects including protein composition, subcellular localization and complexes and gene promoters. This textbook provides a comprehensive overview of the specific signaling pathways on a variety of human tissues. This information can be of great value for health science researchers, professionals and students to understand key pathways for tissue-specific functions in the plethora of signals, signals receptors, transducers and effectors. Chapter 3 and 15 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
CLE (CLV3/ESR-like) genes share a putative N-terminal signal peptide and a conserved C-terminal 14-amino-acid CLE motif, from which, recent studies suggest, a new family of 12-amino-acid plant peptide hormones is derived.
Author: Ling Meng
CLE (CLV3/ESR-like) genes share a putative N-terminal signal peptide and a conserved C-terminal 14-amino-acid CLE motif, from which, recent studies suggest, a new family of 12-amino-acid plant peptide hormones is derived. Using computational approaches, for the first time, the 3D structures of 12-amino-acid CLV3 peptide and CLV1 and CLV2 receptors, and their interacting models were predicted in this study. The putative interacting partners for some CLE peptides were also inferred using statistic machine learning methods. The results from over-expression of some CLE genes suggest that CLE proteins function in a tissue-specific manner. This leads to the question of which region(s) of the CLE sequence determine its functional tissue specificities in planta. Using domain swapping and deletion my results suggest that the CLE motif likely determines much of the functional tissue-specificity of the proteins. However, the results also support a view that sequences outside the CLE motif contribute to CLE function, and show that the CLE signal peptides are required for the entrance of CLE proteins into the secretory pathway and for their functionalities in vivo. But what role, if any, does the variable domain play? Due to probable proteolytic separation, use of a gene-tag system such as GFP may only indicate the sub-cellular localizations of CLE proproteins. Nevertheless, the cleaved tags may indicate where the processing of CLE peptides takes place. Using GFP-tagged and domain swapping, my results show that neither the CLE motif nor the CLE signal peptide controls the localization of the GFP signals of the CLE proteins. Rather, the results show that the variable region determines the localization, implying that the variable region influences where the CLE-GFP is processed. These results further imply that the CLE motif itself may determine its functional tissue-specificity by dictating the direct interaction of each CLE peptide with its optimal receptor(s), whereas the receptor(s) may be available in a tissue-specific manner. On the other hand, the sequences outside the CLE motif may influence CLE function by affecting the processing of CLE peptides, resulting in a change in the availability of CLE peptides in specific tissues and/or cells. Subsequently, my studies on the CLE family focused on CLE14 and CLE20, because over-expression of CLE14/CLE20 caused strong short-root phenotypes. Using CLE promoter and GFP translational fusions, CLE14 and CLE20 were found to be expressed in highly specific domains. Both CLE14 and CLE20 peptides inhibit irreversibly root growth by reducing cell division rates in the RAM. Intriguingly, it was found that exogenous application of cytokinin, but not auxin was able to partially rescue the short-root phenotype induced by over-expression of CLE14/CLE20 in planta, but there was no rescue by in vitro application of the synthesized CLE peptide, suggesting a requirement for a condition provided only by the living plants. The results imply that cytokinin may influence the CLE functions by affecting the processing of CLE peptides in vivo, resulting in a change in the availability and/or abundance of CLE peptides. Gain-of-function analysis provides important insights into understanding the function of different CLE sequence regions. However, the gain-of-function analysis cannot truly reveal the in vivo function of the CLE peptides, as the activity of a given CLE member depends on its availability, which is tightly restricted in a spatial and temporal manner. To explore the in vivo functional nature of CLE14 and CLE20, efforts were made to isolate loss-of-function mutants for CLE14/CLE20. Unfortunately, this effort by screening the T-DNA insertion lines, and using the RNAi silencing approach did not result in the identification of any loss-of-function mutants for CLE14 and CLE20. This result may be explained by the fact that CLE genes have a small coding region with a low expression level, and thus may be less likely to be the targets for T-DNA insertion or for the RNAi silencing mechanism. To date, except for CLV1, CLV2, and the recently identified CORYNE receptor kinase, no other signal receptor has been associated with any other CLE peptide ligands. Furthermore, except for the signal perception mediated by CLV1-3 complex at the cell surface, other cellular components involved in CLAVATA-CLE signaling transduction pathways remain largely unknown. Thus identification of novel corresponding receptors for the distinct CLE peptide ligands, and/or other interacting partners or downstream components will significantly advance our understanding of CLE signal transduction and stem cell homeostasis in plants. To identify such components I screened for the suppressors of the short-root phenotype caused by over-expressing CLE14/CLE20 using EMS mutagenesis and attempted to isolate the corresponding gene(s) using the Illumina sequencing approach. Seven such suppressor lines showing resistance to the application of the CLE peptides were isolated, and 35 candidate loci were obtained from Illumina sequencing of one suppressor (M-59). Further identification and confirmation of the mutation loci are underway. In addition, I identified in Arabidopsis a CLE-like putative peptide family, which shares an overall similar domain structure with the CLE family, e.g., a N-terminal putative signal peptide, a variable region in the middle, and a conserved 13-amino-acid C-terminal CLE-like motif. Exogenous application of a synthetic 12-/13-amino-acid peptide derived from the CLE-like motif of this family caused wavy roots. Similar phenotypes were observed when the full-length sequences of two CLE-like genes are over-expressed individually in the Arabidopsis plants. The finding of a CLE-like family in Arabidopsis opens a new avenue for studies of cell signaling, root growth and development. Finally, I isolated a loss-of-function phenotype for a membrane-associated thioredoxin (Trx h9) characterized by dwarf plants with shortened root meristems and small yellowish leaves. Trx h9 was found to be able to move from cell to cell. Mutagenesis analysis demonstrated that glycine at position 2 (Gly2) was required for its membrane binding, possibly via myristoylation. Both Gly2 and a cysteine in position 4 (Cys4) were needed for the movement, the latter seemingly for protein structure and palmitoylation. These results extend the known boundaries of thioredoxin and suggest a role in cell-to-cell communication in plant growth and specifically in root meristem development. The results from this study provide new evidences and insights towards understanding the molecular basis of the cell signaling in plant meristem activity and development in Arabidopsis.
Author: Elizabeth Kristine StroebelePublish On: 2016
Cell signaling pathways are frequently used in multiple tissue and stage-specific contexts during multicellular development.
Author: Elizabeth Kristine Stroebele
Cell signaling pathways are frequently used in multiple tissue and stage-specific contexts during multicellular development. The integration of these signaling pathways by transcriptional enhancers controls the tissue specific gene expression necessary for proper development. Enhancers are segments of DNA that interpret developmental signals to produce patterns of gene expression. A set of operational rules defines how different enhancers targeted by the same signals interpret and act on these signals. Using the Drosophila model system, my thesis work focuses on determining the operational rules used by developmental enhancers that integrate the Notch signaling pathway with other pathways. During development, the Notch signaling pathway in used to pattern cell territories involved in cell fate determination, and plays a role in differentiation. I first used a computational approach to identify a set of candidate Notch-target enhancers. From this set I carefully studied one specific enhancer from the nab gene that integrates the Notch and Bone Morphogenetic Protein (BMP) signaling pathways in the developing wing. This nab enhancer is a part of a cluster of enhancers that work together to drive the global nab expression pattern during development. Each of these enhancers drives the expected expression patterns as well as atypical expression patterns, which are silenced by adjacent enhancers. These results suggest that Notch targeted enhancers are involved in both tissue specific gene activation and gene silencing.
This timely volume explores tissue-derived stem cells, summarizing and evaluating the current body of knowledge.
Author: Kursad Turksen
This timely volume explores tissue-derived stem cells, summarizing and evaluating the current body of knowledge. Sixteen chapters cover hematopoietic, osteoblast, skeletal, cardiac, pancreatic, epithelial, corneal, hepatic, renal, testicular, ovarian, fingernail, hair follicle and other stem cells- discussing their individual development, functions and pathologies, as well as the commonalities and interdependence between niches. This installment of the popular Stem Cell Biology and Regenerative Medicine series delivers authoritative, international perspectives on this rapidly growing field. Tissue-Specific Stem Cell Niche is an ideal complementary volume to Biology of Stem Cell Niche and Adult Stem Cells, Second Edition and will be invaluable to clinicians and researchers working with stem cells as well as to postgraduate trainees who are studying them.
Author: Alexandra Christin RacanelliPublish On: 2009
A targeted approach to the development of antifolate therapies has been sought for many years.
Author: Alexandra Christin Racanelli
A targeted approach to the development of antifolate therapies has been sought for many years. Central to the success of such development is an understanding of the molecular mechanisms dictating the sensitivity of cells to antifolates and the fundamental differences of these processes between normal and neoplastic phenotypes. This dissertation addressed transcriptional mechanisms and cell-signaling events responsible for the efficacy of antifolate therapies. Transcriptional processes and cell signaling pathways are often aberrant in neoplastic tissues, providing a potential point of distinction between a normal and neoplastic cellular state. Folylpolyglutamate synthetase (FPGS) catalyzes the formation of poly-?-glutamate derivatives of folates and antifolates, which permits intracellular retention and accumulation of these compounds. The mouse fpgs gene uses two distant promoters to produce functionally distinct isozymes in a tissue-specific pattern. We questioned how the two promoters were differentially controlled. An analysis of DNA methylation and histone post-translational modifications across the length of the mouse fpgs gene showed that epigenetic mechanisms contributed to the tissue-specific control of the upstream (P1), but not the downstream (P2) fpgs promoter. RNAPII complexes and general transcription factors were present over P1 only when P1 was transcribed, but these components were present over P2 in most tissues, and promoter-proximal pausing was evident in brain. Clear promoter occlusion was found over P2 in liver. These studies concluded that tissue-specific coordination of dual promoters required multiple interacting controls. The mammalian target of rapamycin (mTOR) controls protein translation initiation, and is central to a cell-signaling pathway rich in tumor suppressor and oncogenic proteins. mTOR dysregulation is a common feature of several human cancers and inhibition of this protein has been sought as an ideal cancer drug target. We have determined that antifolates inhibiting the two folate-dependent steps of purine synthesis (GART or AICART) activate AMP-dependent protein kinase (AMPK) and inhibit mTOR. The mechanism of AMPK stimulation appears to be mediated by either nucleotide depletion (GART inhibitors), or ZMP accumulation (AICART inhibitors). These studies discovered a new mechanism for antifolates that surprisingly defines them as molecularly targeted therapeutics.
A collection of readily reproducible experimental methods for studying the subversion of normal cell signaling that leads to cancer.
Author: David M. Terrian
Publisher: Springer Science & Business Media
A collection of readily reproducible experimental methods for studying the subversion of normal cell signaling that leads to cancer. Presented in step-by-step detail to ensure successful results, the methods include proven techniques for the investigation of apoptosis and cell death, complementary protocols for manipulating and/or monitoring oncogenic signals in cancer cells, and techniques for studying protein-protein interactions. Analyze multigene families with readily reproducible techniques Employ laser capture microdissection techniques to target cell populations.
"Cell signaling, which is also often referred to as signal transduction or, in more specialized cases, transmembrane signaling, is the process by which cells communicate with their environment and respond temporally to external cues that ...
Author: Edward A. Dennis
Publisher: Academic Press
"Cell signaling, which is also often referred to as signal transduction or, in more specialized cases, transmembrane signaling, is the process by which cells communicate with their environment and respond temporally to external cues that they sense there. All cells have the capacity to achieve this to some degree, albeit with a wide variation in purpose, mechanism, and response. At the same time, there is a remarkable degree of similarity over quite a range of species, particularly in the eukaryotic kingdom, and comparative physiology has been a useful tool in the development of this field. The central importance of this general phenomenon (sensing of external stimuli by cells) has been appreciated for a long time, but it has truly become a dominant part of cell and molecular biology research in the past three decades, in part because a description of the dynamic responses of cells to external stimuli is, in essence, a description of the life process itself. This approach lies at the core of the developing fields of proteomics and metabolomics, and its importance to human and animal health is already plainly evident"--Provided by publisher.
We further discuss the potential of using synthetic biology approaches to decipher signaling networks. All of this is discussed in light of complementary quantitative mathematical modeling approaches.
Author: Christina Kiel
Publisher: Elsevier Inc. Chapters
This chapter brings mammalian signal transduction to the center of quantitative and integrative sciences. Historically imbedded within human physiology, thanks to proteomics, interactomics, and molecular biology approaches, signaling is now far beyond the “black box” principle. However, despite the large amount of data available, we still have only limited insight into general design principles, and we lack knowledge on how cell type-specific signaling is achieved. Here, we summarize recent efforts in elucidating cell type-specific signaling, and in particular the role of protein abundances, signaling complexes and modules. We further discuss the potential of using synthetic biology approaches to decipher signaling networks. All of this is discussed in light of complementary quantitative mathematical modeling approaches. Signaling, more than any other discipline, needs computational biology to capture the dynamic systems behavior, and to reach its final goal: to be truly predictive for both the physiological and disease perturbed cellular conditions.
Another pathway recently implicated in vitamin Dmediated apoptosis involves ... the tissue specific molecular targets of the vitamin D signaling pathway ...
Author: Janos Zempleni
Publisher: CRC Press
Cell signaling is at the core of most biological processes from the simplest to the most complex. In addition to unicellular organisms possessing the essential ability to receive inputs with regard to nutrient availability and noxious stimuli, the cells in multicellular organisms require signaling from adjacent, as well as distant cells to maintain normal internal function, including growth, differentiation, and homeostasis. Conversely, the etiology of many disease processes, such as those involving immune system dysfunction and tumor development, have been traced to aberrant cell signaling. Nutrients and Cell Signaling, in presenting contributions from a wide array of experts in the field, fully delineates the role of nutrients in cell signaling. The text emphasizes broad concepts and covers all major groups of nutrients. Contributors discuss the role of carbohydrates, amino acids, lipids, vitamins, minerals, and trace elements in essential processes such as cell proliferation, immune function, and DNA repair. The editors have organized the work to provide select examples organized under these contemporary research areas: Nuclear receptors, transcription factors, and signaling cascades Amino acids, lipids, and glycation Insulin release, signaling, and insulin resistance Calcium-dependent signaling Feeding and nutrient homeostasis Nutrients and Cell Signaling answers the need in the post-genomic era, for an authoritative resource that provides an in-depth understanding of how these complex and dynamic biomolecular networks control cell function. Those professionals and students in molecular biology, nutrition, biochemistry, as well as any branch involved with cell signaling and function will find this book to be an invaluable tool in promoting both understanding and further inquiry.
DHR39 is also expressed in the primordia of female reproductive tissues and ... cellular processes upon nuclear receptor activity in individual cell types ...
Author: Ralph A. Bradshaw
Publisher: Academic Press
Handbook of Cell Signaling, Three-Volume Set, 2e, is a comprehensive work covering all aspects of intracellular signal processing, including extra/intracellular membrane receptors, signal transduction, gene expression/translation, and cellular/organotypic signal responses. The second edition is an up-to-date, expanded reference with each section edited by a recognized expert in the field. Tabular and well illustrated, the Handbook will serve as an in-depth reference for this complex and evolving field. Handbook of Cell Signaling, 2/e will appeal to a broad, cross-disciplinary audience interested in the structure, biochemistry, molecular biology and pathology of cellular effectors. Contains over 350 chapters of comprehensive coverage on cell signaling Includes discussion on topics from ligand/receptor interactions to organ/organism responses Provides user-friendly, well-illustrated, reputable content by experts in the field
Even though there is still much to learn, this volume explores this fascinating system with compelling information.
Author: John D. Haley
Publisher: Springer Science & Business Media
The epidermal gro wth factor (EGF ) receptor and its downstream signal transduction networks have been implicated in the ontology and maintenance of tumor tissues, which has motivated the discovery and development of molecularly targeted anti-EGF receptor therapies. Over decades of study, the EGF receptor structure, its ligand binding domains, the physical biochemistry underlying its intrinsic tyrosine kinase catalytic function and the modular interactions with SH2, PTB, and SH3 domain containing signaling adaptor p- teins required for signal transduction, have been extensively dissected. Not only is the EGF receptor the nexus of many streams of information, but it also forms one part of a calcul- ing device by forming dimers and oligomers with the other three receptors in its family in response to at least eleven ligands (some of which are expressed in multiple forms with overlapping or quite distinct functions). This phenomenon, while recruiting to the inner surface of the cell membrane and activating multiple second messenger proteins, also allows the possibility of cross talk between these systems, permitting a further layer of information to be exchanged. Less well described are the cross re gulation of the EGF receptor and other anti-apoptotic, mitogenic and metabolic signaling systems. The study of these systems has yielded new surprises. One hurdle in these efforts has been that signal transduction pathways have frequently been defined in the generic absence of their tissue-specific or cell-interaction specific context.
vitro, cellular transformation in vitro seemed to require additional ... a tissue-specific promoter, have supported the view that deregulated c-Myc, ...
Author: Rakesh Srivastava
Publisher: Springer Science & Business Media
These volumes present a concise synthesis of recent developments in the understanding of both cell survival and apoptotic pathways. Particular attention is given to apoptosis in human diseases, such as different forms of cancer and neurodegenerative diseases. These comprehensive volumes integrate the most innovative and current findings from several related disciplines of scientific research, including pathology, genetics, virology, cell biology, immunology, and molecular biology.
Redox status is thus dependent on the degree to which tissue-specific cell components are in the oxidized state. In general, the reducing environments ...
Author: Zigang Dong
Publisher: CRC Press
A consequence of rapid progress in the science of nutrigenomics and nutrigenetics is the substantial accumulation of data covering nutrienal modulation of gene expression at the cellular and subcellular levels. Current research is increasingly focused on the role of nutrition and diet in modifying oxidative damage in the progression of disease. Dietary Modulation of Cell Signaling Pathways reviews some of these findings, focusing on nutrient-gene interactions with particular emphasis on the intracellular signaling network. Explore a Pivotal Function for Maintaining Homeostasis The book addresses the dietary modulation of particular gene expression systems and highlights the underlying molecular and cellular mechanisms that involve upstream signaling molecules, such as kinases and transcription factors in the context of their therapeutic potential. It describes nutrients’ actions on the activation of an antioxidant and inflammatory transcription factor and the induction of their target gene expression. Provides a Mechanistic Understanding of the Action of Dietary Components Comprehensively covering dietary modulation of cell signaling, leading experts provide information on state-of-the-art research in their own specialty. For those working in the fields of dietary components, molecular mechanisms, and health benefits, this book presents a useful tool for mechanistic understanding of the action of dietary components.
This book gives insights on basic processes that occur (or may occur) in the human body as a result of the application of mechanical stimulus. It is ideal for both biomedical engineers and biologists, and is an ideal resource for teaching.
Author: Paul A. Sundaram
Publisher: Academic Press
Category: Technology & Engineering
Mechanotransduction: Cell Signaling to Cell Response covers the cell machinery responsible for the process of mechanotransduction and the manner in which cells respond to an external mechanical stimulus. The effect of mechanical stimulus on individual cells and entire tissues is discussed, with an emphasis on the practical results of this physiological process. Mechanotransduction of stem cells and cancerous cells are also covered, along with future directions in this yet nascent field. This book gives insights on basic processes that occur (or may occur) in the human body as a result of the application of mechanical stimulus. It is ideal for both biomedical engineers and biologists, and is an ideal resource for teaching. It provides a current state of conceptual and practical aspects of the field and will enable students and professionals to venture further into this incipient area which is of fundamental importance to biomedical engineering and biology fields. Covers fundamental concepts of signaling in cells as a result of mechanical stimulus Includes the physiological results of mechanical stimulus on the human body Explores the advantages of mechanical loads on the human body
These studies also validate isotype-specific pharmacology as an attractive ... families within cell signaling pathways in both normal and diseased settings.
Author: Cy A. Stein
This book helps investigators understand the basic concepts and practical concerns associated with the use of antisense oligonucleotides to modify gene expression. It provides a balanced overview of the field from a very practical standpoint and describes this cutting-edge technology that has been embraced because of its potential therapeutic uses in clinical conditions ranging from cancers to infectious diseases.
Tissue-specific transcription factors cooperate with signaling pathways to promote specification, in part by co-regulating transcription.
Author: Nfsonsam Landry Ewongkem
Category: Drosophila melanogaster
Tissue-specific transcription factors cooperate with signaling pathways to promote specification, in part by co-regulating transcription. The Drosophila melanogaster Pax6 homolog Eyeless forms a complex, incompletely understood regulatory network with signaling pathways to control eye-specific gene expression. I employed mRNAseq and microarray approaches to identify targets co-regulated by Eyeless and Hedgehog, Decapentaplegic or Notch signals, to further understand the Drosophila eye network. The gene encoding the neprilysin family peptidase 'Abnormally blistered and morphologically misshapen eyes', Abams and the Drosophila class II 'Myosin heavy chain' protein, Mhc, were expressed at higher levels in the eye tissues versus wing tissues, and were highly expressed in eye tissues in response to Ey+N. Thus, both abams and Mhc were predicted to have roles in eye development. Whereas wild type eyes have a regular array of ommatidia interspersed with regularly occurring sensory bristles, using RNA interference (RNAi), I showed that reduction of abams function resulted in smaller eyes that consisted of patches of individual ommatidia surrounded by numerous bristles. Photoreceptor development was disrupted when abams function was reduced in eye precursors. Loss of function analyses and RNAi of Mhc revealed disruptions in the eye lattice and the mispositioning of photoreceptor nuclei within the eye precursor epithelium. My results suggest that Abams is involved in cell-cell signaling while Mhc regulates cell morphology and/or cell-cell adhesion during eye development. Transcription factor binding site (BS) analyses using computational modeling revealed [greater than or equal to] 94 other candidate genes as potential direct targets of Ey or Ey+Hh, Dpp or N. These included genes with already known roles in Drosophila eye development, as well as genes with unknown function, thus providing potential new directions to pursue to further understand the mechanism of interaction between Ey and Hh, Dpp or Notch during Drosophila eye development. Given the similarity between D. melanogaster and vertibrate eye development, further study of Abams and Mhc in Drosophila eye development will provide novel insights into our understanding of eye development in D. melanogaster and humans.
The book is divided into six parts, arranged according to major developmental phenomena demonstrated in illustrative systems derived from amphibian, avian, mammalian, and piscine sources.
Author: E.J. Robertson
Publisher: Academic Press
Cell-Cell Signaling in Vertebrate Development provides a comprehensive discussion of cell-cell interactions in vertebrate development and the molecular signals that mediate them. The book is divided into six parts, arranged according to major developmental phenomena demonstrated in illustrative systems derived from amphibian, avian, mammalian, and piscine sources. Part I introduces the mechanisms of gene activation in the context of early vertebrate development. Part II is concerned with cellular contacts and the induction process. Cell-cell interactions are illustrated through analyses of neurogenesis in the mouse; embryonic induction is considered in the frog and in the chick. Part III deals with cell migration and differentiation. It examines cell lineages in the frog eyebud; migration phenomena in connection with axon guidance in the embryonic rat spinal cord and mouse visual system; pathfinding by primary motoneurons; and the formation of terminal arbors in zebrafish embryos. Part IV discusses developmental processes that depend on diffusible signals and signal gradients. Part V illustrates pattern formation as exemplified in the developing chick hindbrain and in urodele limb regeneration. Part VI highlights gene expression and its regulation by transcription factors or growth factors in rodent development.
Author: Kristen Leigh MittelsteadtPublish On: 2020
Foxp3+ regulatory T cells (TR) are a population of CD4+ T cells with a well-recognized ability to restrain inappropriate or overreactive immune responses against both self- and foreign-antigens.
Author: Kristen Leigh Mittelsteadt
Foxp3+ regulatory T cells (TR) are a population of CD4+ T cells with a well-recognized ability to restrain inappropriate or overreactive immune responses against both self- and foreign-antigens. T[subscript[R are vitally important in maintaining immune tolerance and act at different tissue sites to prevent the development of autoimmunity, lymphoproliferative disease, and pathological tissue damage. Our lab and others have demonstrated considerable phenotypic and functional heterogeneity among T[subscript]R localized in lymphoid versus nonlymphoid tissues. Broadly, central T[subscript]R (cT[subscript]R) found in lymphoid tissues rely on paracrine IL-2 signals for their maintenance and prevent priming of autoreactive T cells, whereas effector T[subscript]R (eT[subscript]R) residing in nonlymphoid organs are dependent on T cell receptor (TCR)/costimulatory ICOS signals and modulate ongoing inflammatory responses. Adding another layer to this complexity, there is growing evidence that T[subscript]R found across nonlymphoid tissues are distinct from one another and respond to unique cues within their respective microenvironments. Although they display hallmarks of eT[subscript]R, tissue-specific T[subscript]R exhibit unique transcriptional and epigenetic profiles, express distinct chemokine receptors and TCR repertoires, and exert functions that go beyond classical modulation of immune responses, including tissue repair and maintaining organismal metabolic homeostasis. The costimulatory molecule ICOS is highly expressed on eT[subscript]R that migrate to nonlymphoid tissues and contributes to their maintenance and function in models of autoimmunity. In this dissertation, we report an unexpected cell-intrinsic role for ICOS expression and downstream PI3K signaling in limiting the maintenance, phenotype, and function of T[subscript]R specifically in visceral adipose tissue (VAT). Icos[superscript]-/- mice and mice expressing a knock-in form of ICOS with the inability to activate PI3K demonstrated increased VAT-T[subscript]R abundance and expression of canonical VAT-T[subscript]R markers. Loss of ICOS signaling facilitated enhanced accumulation of TR to VAT associated with increased CCR3 expression and resulted in reduced adipose inflammation and retained insulin sensitivity in the context of high-fat diet. In contrast, preliminary studies utilizing models of autoimmune central nervous system (CNS) inflammation indicated a requirement for ICOS signaling in disease resolution mediated by CNS-T[subscript]R. Collectively, these findings suggest that eT[subscript]R residing within different tissues and immune environments differentially rely on ICOS signaling, highlighting new and surprising mechanisms that regulate eT[subscript]R development, accumulation, and function.
investigate the cell signal transduction, which is a complex phenomenon and ... signaling systems that are active in specific cells and/or tissues (i.e., ...
Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics combines elements of computer science, information technology, mathematics, statistics and biotechnology, providing the methodology and in silico solutions to mine biological data and processes. The book covers Theory, Topics and Applications, with a special focus on Integrative –omics and Systems Biology. The theoretical, methodological underpinnings of BCB, including phylogeny are covered, as are more current areas of focus, such as translational bioinformatics, cheminformatics, and environmental informatics. Finally, Applications provide guidance for commonly asked questions. This major reference work spans basic and cutting-edge methodologies authored by leaders in the field, providing an invaluable resource for students, scientists, professionals in research institutes, and a broad swath of researchers in biotechnology and the biomedical and pharmaceutical industries. Brings together information from computer science, information technology, mathematics, statistics and biotechnology Written and reviewed by leading experts in the field, providing a unique and authoritative resource Focuses on the main theoretical and methodological concepts before expanding on specific topics and applications Includes interactive images, multimedia tools and crosslinking to further resources and databases