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Author: James Hyun-Woo Park Publisher: ISBN: 9781369594829 Category : Brain Languages : en Pages : 379
Book Description
Single-cell transcriptional heterogeneity pervades the fully differentiated brain. This heterogeneity is particularly prevalent in brain nuclei involved in the autonomic regulation of physiological functions such as cardiovascular homeostasis. Because neuronal function largely depends on its transcriptome, such heterogeneity confounds our understanding of how heterogeneous neurons contribute to their broader phenotypic function. In addition to the transcriptome, functional connectivity and in vivo anatomical environment are additional factors central to defining a neuron’s functional state. Given their importance, these factors may provide the added context necessary to understand how a distribution of heterogeneous neurons contributes to phenotypic function. Consequently, the overall goal of this work is to establish an organizational framework that characterizes single-neuron heterogeneity within a brain nucleus and elucidates its functional relevance. ☐ Towards this goal, we have taken a combined experimental and computational approach to determine the organizing principles driving complex interaction networks within and among transcriptionally diverse neurons within a brain nucleus. First, we generated a large-scale gene expression dataset from several hundred neurons, selected on the basis of their synaptic input types, taken from the nucleus tractus solitarius (NTS), a brainstem nucleus involved in the central regulation of blood pressure. Our analysis of these neurons revealed an organizational structure in which transcriptional variability aligns with synaptic input type along a continuum of graded gene expression. This continuum is populated by distinct neuronal subtypes characterized by gene groups exhibiting correlated expression. ☐ In order to identify the molecular mechanisms driving this correlated behavior, we next developed a fuzzy logic modeling-based methodology to model quantitatively causal gene interaction networks from single-cell transcriptomic data. Our modeling results suggest that distinct input stimuli operating on distinct network structures corresponding to these subtypes can drive neurons through various transcriptional states. These results suggest that transcriptional heterogeneity represents a neuron’s adaptive response to various inputs. Based on these results, we propose that neuronal adaptation may be a mechanism through which the NTS robustly regulates blood pressure and cardiovascular homeostasis. ☐ To test this proposal, we examined what impact adaptation to neuronal subtypes in the NTS and brainstem would have on the short-term autonomic regulation of cardiovascular homeostasis under the simulated disease state of systolic heart failure via mathematical modeling. We developed a closed-loop control model characterizing neuronal regulation of the cardiovascular system by integrating previous quantitative models that simulated various aspects of the cardiovascular system. Because the goal of this study was to investigate the effects of neuronal subtype adaptation, we incorporated brainstem neuronal subtypes, such as those identified in our analysis of the NTS. Modeling simulation results suggest that adaptation of these neuronal components can compensate for an impaired cardiovascular state due to systolic heart failure by decreasing neuronal inhibition (i.e. parasympathetic tone) of cardiac contractility. ☐ Finally, we tested the utility of a single-cell analysis approach to interpret single-cell heterogeneity throughout the brain by identifying a cellular network organization in a distinct brain nucleus – the suprachiasmatic nucleus (SCN), which regulates circadian rhythms in mammals. Similar to our analysis of the NTS, we generated and analyzed a high-dimensional gene expression dataset consisting of hundreds of transcriptionally heterogeneous SCN neurons. Our multivariate analysis of these neurons revealed both known and previously undescribed SCN neuron-types, which organize into a neuronal interaction network via known paracrine signaling mechanisms underlying the synchronizing functions of the SCN. ☐ Based on the analysis of heterogeneous single neurons, we have identified an organizational framework with which we can now interpret single-cell heterogeneity; a heterogeneous neuronal population comprises a mixture of distinct neuronal subtypes whose adaptive response to inputs is driven by distinct regulatory networks. Such adaptation provides a mechanism in which the brain is able to regulate robustly physiological functions by providing compensatory effects under perturbed or challenged states.
Author: James Hyun-Woo Park Publisher: ISBN: 9781369594829 Category : Brain Languages : en Pages : 379
Book Description
Single-cell transcriptional heterogeneity pervades the fully differentiated brain. This heterogeneity is particularly prevalent in brain nuclei involved in the autonomic regulation of physiological functions such as cardiovascular homeostasis. Because neuronal function largely depends on its transcriptome, such heterogeneity confounds our understanding of how heterogeneous neurons contribute to their broader phenotypic function. In addition to the transcriptome, functional connectivity and in vivo anatomical environment are additional factors central to defining a neuron’s functional state. Given their importance, these factors may provide the added context necessary to understand how a distribution of heterogeneous neurons contributes to phenotypic function. Consequently, the overall goal of this work is to establish an organizational framework that characterizes single-neuron heterogeneity within a brain nucleus and elucidates its functional relevance. ☐ Towards this goal, we have taken a combined experimental and computational approach to determine the organizing principles driving complex interaction networks within and among transcriptionally diverse neurons within a brain nucleus. First, we generated a large-scale gene expression dataset from several hundred neurons, selected on the basis of their synaptic input types, taken from the nucleus tractus solitarius (NTS), a brainstem nucleus involved in the central regulation of blood pressure. Our analysis of these neurons revealed an organizational structure in which transcriptional variability aligns with synaptic input type along a continuum of graded gene expression. This continuum is populated by distinct neuronal subtypes characterized by gene groups exhibiting correlated expression. ☐ In order to identify the molecular mechanisms driving this correlated behavior, we next developed a fuzzy logic modeling-based methodology to model quantitatively causal gene interaction networks from single-cell transcriptomic data. Our modeling results suggest that distinct input stimuli operating on distinct network structures corresponding to these subtypes can drive neurons through various transcriptional states. These results suggest that transcriptional heterogeneity represents a neuron’s adaptive response to various inputs. Based on these results, we propose that neuronal adaptation may be a mechanism through which the NTS robustly regulates blood pressure and cardiovascular homeostasis. ☐ To test this proposal, we examined what impact adaptation to neuronal subtypes in the NTS and brainstem would have on the short-term autonomic regulation of cardiovascular homeostasis under the simulated disease state of systolic heart failure via mathematical modeling. We developed a closed-loop control model characterizing neuronal regulation of the cardiovascular system by integrating previous quantitative models that simulated various aspects of the cardiovascular system. Because the goal of this study was to investigate the effects of neuronal subtype adaptation, we incorporated brainstem neuronal subtypes, such as those identified in our analysis of the NTS. Modeling simulation results suggest that adaptation of these neuronal components can compensate for an impaired cardiovascular state due to systolic heart failure by decreasing neuronal inhibition (i.e. parasympathetic tone) of cardiac contractility. ☐ Finally, we tested the utility of a single-cell analysis approach to interpret single-cell heterogeneity throughout the brain by identifying a cellular network organization in a distinct brain nucleus – the suprachiasmatic nucleus (SCN), which regulates circadian rhythms in mammals. Similar to our analysis of the NTS, we generated and analyzed a high-dimensional gene expression dataset consisting of hundreds of transcriptionally heterogeneous SCN neurons. Our multivariate analysis of these neurons revealed both known and previously undescribed SCN neuron-types, which organize into a neuronal interaction network via known paracrine signaling mechanisms underlying the synchronizing functions of the SCN. ☐ Based on the analysis of heterogeneous single neurons, we have identified an organizational framework with which we can now interpret single-cell heterogeneity; a heterogeneous neuronal population comprises a mixture of distinct neuronal subtypes whose adaptive response to inputs is driven by distinct regulatory networks. Such adaptation provides a mechanism in which the brain is able to regulate robustly physiological functions by providing compensatory effects under perturbed or challenged states.
Author: Charles Watson Publisher: Academic Press ISBN: 0123694973 Category : Science Languages : en Pages : 815
Book Description
The Mouse Nervous System provides a comprehensive account of the central nervous system of the mouse. The book is aimed at molecular biologists who need a book that introduces them to the anatomy of the mouse brain and spinal cord, but also takes them into the relevant details of development and organization of the area they have chosen to study. The Mouse Nervous System offers a wealth of new information for experienced anatomists who work on mice. The book serves as a valuable resource for researchers and graduate students in neuroscience. Systematic consideration of the anatomy and connections of all regions of the brain and spinal cord by the authors of the most cited rodent brain atlases A major section (12 chapters) on functional systems related to motor control, sensation, and behavioral and emotional states A detailed analysis of gene expression during development of the forebrain by Luis Puelles, the leading researcher in this area Full coverage of the role of gene expression during development and the new field of genetic neuroanatomy using site-specific recombinases Examples of the use of mouse models in the study of neurological illness
Author: Anna Abraham Publisher: Cambridge University Press ISBN: 1107176468 Category : Psychology Languages : en Pages : 391
Book Description
Discover how the creative brain works across musical, literary, visual artistic, kinesthetic and scientific spheres, and how to study it.
Author: Xiangdong Wang Publisher: Springer ISBN: 9401797536 Category : Medical Languages : en Pages : 184
Book Description
The volume focuses on the genomics, proteomics, metabolomics, and bioinformatics of a single cell, especially lymphocytes and on understanding the molecular mechanisms of systems immunology. Based on the author’s personal experience, it provides revealing insights into the potential applications, significance, workflow, comparison, future perspectives and challenges of single-cell sequencing for identifying and developing disease-specific biomarkers in order to understand the biological function, activation and dysfunction of single cells and lymphocytes and to explore their functional roles and responses to therapies. It also provides detailed information on individual subgroups of lymphocytes, including cell characters, function, surface markers, receptor function, intracellular signals and pathways, production of inflammatory mediators, nuclear receptors and factors, omics, sequencing, disease-specific biomarkers, bioinformatics, networks and dynamic networks, their role in disease and future prospects. Dr. Xiangdong Wang is a Professor of Medicine, Director of Shanghai Institute of Clinical Bioinformatics, Director of Fudan University Center for Clinical Bioinformatics, Director of the Biomedical Research Center of Zhongshan Hospital, Deputy Director of Shanghai Respiratory Research Institute, Shanghai, China.
Author: George Comninel Publisher: Routledge ISBN: 1317487966 Category : Political Science Languages : en Pages : 311
Book Description
The International Workingmen’s Association was the prototype of all organizations of the Labour movement and the 150th anniversary of its birth (1864-2014) offers an important opportunity to rediscover its history and learn from its legacy. The International helped workers to grasp that the emancipation of labour could not be won in a single country but was a global objective. It also spread an awareness in their ranks that they had to achieve the goal themselves, through their own capacity for organization, rather than by delegating it to some other force; and that it was essential to overcome the capitalist system itself, since improvements within it, though necessary to pursue, would not eliminate exploitation and social injustice. This book reconsider the main issues broached or advanced by the International – such as labor rights, critiques of capitalism and the search for international solidarity – in light of present-day concerns. With the recent crisis of capitalism, that has sharpened more than before the division between capital and labour, the political legacy of the organization founded in London in 1864 has regained profound relevance, and its lessons are today more timely than ever. This book was published as a special issue of Socialism and Democracy.
Author: Xinghua Pan Publisher: Frontiers Media SA ISBN: 2889459209 Category : Languages : en Pages : 129
Book Description
Single-cell omics is a progressing frontier that stems from the sequencing of the human genome and the development of omics technologies, particularly genomics, transcriptomics, epigenomics and proteomics, but the sensitivity is now improved to single-cell level. The new generation of methodologies, especially the next generation sequencing (NGS) technology, plays a leading role in genomics related fields; however, the conventional techniques of omics require number of cells to be large, usually on the order of millions of cells, which is hardly accessible in some cases. More importantly, harnessing the power of omics technologies and applying those at the single-cell level are crucial since every cell is specific and unique, and almost every cell population in every systems, derived in either vivo or in vitro, is heterogeneous. Deciphering the heterogeneity of the cell population hence becomes critical for recognizing the mechanism and significance of the system. However, without an extensive examination of individual cells, a massive analysis of cell population would only give an average output of the cells, but neglect the differences among cells. Single-cell omics seeks to study a number of individual cells in parallel for their different dimensions of molecular profile on genome-wide scale, providing unprecedented resolution for the interpretation of both the structure and function of an organ, tissue or other system, as well as the interaction (and communication) and dynamics of single cells or subpopulations of cells and their lineages. Importantly single-cell omics enables the identification of a minor subpopulation of cells that may play a critical role in biological process over a dominant subpolulation such as a cancer and a developing organ. It provides an ultra-sensitive tool for us to clarify specific molecular mechanisms and pathways and reveal the nature of cell heterogeneity. Besides, it also empowers the clinical investigation of patients when facing a very low quantity of cell available for analysis, such as noninvasive cancer screening with circulating tumor cells (CTC), noninvasive prenatal diagnostics (NIPD) and preimplantation genetic test (PGT) for in vitro fertilization. Single-cell omics greatly promotes the understanding of life at a more fundamental level, bring vast applications in medicine. Accordingly, single-cell omics is also called as single-cell analysis or single-cell biology. Within only a couple of years, single-cell omics, especially transcriptomic sequencing (scRNA-seq), whole genome and exome sequencing (scWGS, scWES), has become robust and broadly accessible. Besides the existing technologies, recently, multiplexing barcode design and combinatorial indexing technology, in combination with microfluidic platform exampled by Drop-seq, or even being independent of microfluidic platform but using a regular PCR-plate, enable us a greater capacity of single cell analysis, switching from one single cell to thousands of single cells in a single test. The unique molecular identifiers (UMIs) allow the amplification bias among the original molecules to be corrected faithfully, resulting in a reliable quantitative measurement of omics in single cells. Of late, a variety of single-cell epigenomics analyses are becoming sophisticated, particularly single cell chromatin accessibility (scATAC-seq) and CpG methylation profiling (scBS-seq, scRRBS-seq). High resolution single molecular Fluorescence in situ hybridization (smFISH) and its revolutionary versions (ex. seqFISH, MERFISH, and so on), in addition to the spatial transcriptome sequencing, make the native relationship of the individual cells of a tissue to be in 3D or 4D format visually and quantitatively clarified. On the other hand, CRISPR/cas9 editing-based In vivo lineage tracing methods enable dynamic profile of a whole developmental process to be accurately displayed. Multi-omics analysis facilitates the study of multi-dimensional regulation and relationship of different elements of the central dogma in a single cell, as well as permitting a clear dissection of the complicated omics heterogeneity of a system. Last but not the least, the technology, biological noise, sequence dropout, and batch effect bring a huge challenge to the bioinformatics of single cell omics. While significant progress in the data analysis has been made since then, revolutionary theory and algorithm logics for single cell omics are expected. Indeed, single-cell analysis exert considerable impacts on the fields of biological studies, particularly cancers, neuron and neural system, stem cells, embryo development and immune system; other than that, it also tremendously motivates pharmaceutic RD, clinical diagnosis and monitoring, as well as precision medicine. This book hereby summarizes the recent developments and general considerations of single-cell analysis, with a detailed presentation on selected technologies and applications. Starting with the experimental design on single-cell omics, the book then emphasizes the consideration on heterogeneity of cancer and other systems. It also gives an introduction of the basic methods and key facts for bioinformatics analysis. Secondary, this book provides a summary of two types of popular technologies, the fundamental tools on single-cell isolation, and the developments of single cell multi-omics, followed by descriptions of FISH technologies, though other popular technologies are not covered here due to the fact that they are intensively described here and there recently. Finally, the book illustrates an elastomer-based integrated fluidic circuit that allows a connection between single cell functional studies combining stimulation, response, imaging and measurement, and corresponding single cell sequencing. This is a model system for single cell functional genomics. In addition, it reports a pipeline for single-cell proteomics with an analysis of the early development of Xenopus embryo, a single-cell qRT-PCR application that defined the subpopulations related to cell cycling, and a new method for synergistic assembly of single cell genome with sequencing of amplification product by phi29 DNA polymerase. Due to the tremendous progresses of single-cell omics in recent years, the topics covered here are incomplete, but each individual topic is excellently addressed, significantly interesting and beneficial to scientists working in or affiliated with this field.
Author: Gerald M. Edelman Publisher: ISBN: Category : Medical Languages : en Pages : 414
Book Description
One of the nation's leading neuroscientists presents a radically new view of the function of the brain and the nervous system. Its central idea is that the nervous system in each individual operates as a selective system resembling natural selection in evolution, but operating by different mechanisms. This far-ranging theory of brain functions is bound to stimulate renewed discussion of such philosophical issues as the mind-body problem, the origins of knowledge and the perceptual bases of language. Notes and Index.
Author: Adriana Galván Publisher: Cambridge University Press ISBN: 1107089921 Category : Medical Languages : en Pages : 341
Book Description
Written by an award-winning developmental neuroscientist, this is a comprehensive and cutting-edge account of the latest research on the adolescent brain.
Author: James Hyun-Woo Park
Author: James Hyun-Woo Park
Author: Charles Watson
Author: 
Author: Anna Abraham
Author: Xiangdong Wang
Author: George Comninel
Author: Enrica Boda
Author: Xinghua Pan
Author: Gerald M. Edelman
Author: Adriana Galván