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Author: Simarjeet K. Negi
Publisher:
ISBN:
Category :
Languages : en
Pages : 120
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Book Description
The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed a gene expression model that accurately defines the consistent blueprint of the brain transcriptome; thereby, identifying the core brain specific transcriptional processes conserved across individuals. Functionally characterizing this model would provide profound insights into the transcriptional landscape, biological pathways and the expression distribution of neurotransmitter systems. Here, in this dissertation we developed an expression model by capturing the similarly expressed gene patterns across congruently annotated brain structures in six individual brains by using data from the Allen Brain Atlas (ABA). We found that 84% of genes are expressed in at least one of the 190 brain structures. By employing hierarchical clustering we were able to show that distinct structures of a bigger brain region can cluster together while still retaining their expression identity. Further, weighted correlation network analysis identified 19 robust modules of coexpressing genes in the brain that demonstrated a wide range of functional associations. Since signatures of local phenomena can be masked by larger signatures, we performed local analysis on each distinct brain structure. Pathway and gene ontology enrichment analysis on these structures showed, striking enrichment for brain region specific processes. Besides, we also mapped the structural distribution of the gene expression profiles of genes associated with major neurotransmission systems in the human. We also postulated the utility of healthy brain tissue gene expression to predict potential genes involved in a neurological disorder, in the absence of data from diseased tissues. To this end, we developed a supervised classification model, which achieved an accuracy of 84% and an AUC (Area Under the Curve) of 0.81 from ROC plots, for predicting autism-implicated genes using the healthy expression model as the baseline. This study represents the first use of healthy brain gene expression to predict the scope of genes in autism implication and this generic methodology can be applied to predict genes involved in other neurological disorders.
Author: Simarjeet K. Negi
Publisher:
ISBN:
Category :
Languages : en
Pages : 120
Get Book Here
Book Description
The human brain is the most complex structure known to mankind and one of the greatest challenges in modern biology is to understand how it is built and organized. The power of the brain arises from its variety of cells and structures, and ultimately where and when different genes are switched on and off throughout the brain tissue. In other words, brain function depends on the precise regulation of gene expression in its sub-anatomical structures. But, our understanding of the complexity and dynamics of the transcriptome of the human brain is still incomplete. To fill in the need, we designed a gene expression model that accurately defines the consistent blueprint of the brain transcriptome; thereby, identifying the core brain specific transcriptional processes conserved across individuals. Functionally characterizing this model would provide profound insights into the transcriptional landscape, biological pathways and the expression distribution of neurotransmitter systems. Here, in this dissertation we developed an expression model by capturing the similarly expressed gene patterns across congruently annotated brain structures in six individual brains by using data from the Allen Brain Atlas (ABA). We found that 84% of genes are expressed in at least one of the 190 brain structures. By employing hierarchical clustering we were able to show that distinct structures of a bigger brain region can cluster together while still retaining their expression identity. Further, weighted correlation network analysis identified 19 robust modules of coexpressing genes in the brain that demonstrated a wide range of functional associations. Since signatures of local phenomena can be masked by larger signatures, we performed local analysis on each distinct brain structure. Pathway and gene ontology enrichment analysis on these structures showed, striking enrichment for brain region specific processes. Besides, we also mapped the structural distribution of the gene expression profiles of genes associated with major neurotransmission systems in the human. We also postulated the utility of healthy brain tissue gene expression to predict potential genes involved in a neurological disorder, in the absence of data from diseased tissues. To this end, we developed a supervised classification model, which achieved an accuracy of 84% and an AUC (Area Under the Curve) of 0.81 from ROC plots, for predicting autism-implicated genes using the healthy expression model as the baseline. This study represents the first use of healthy brain gene expression to predict the scope of genes in autism implication and this generic methodology can be applied to predict genes involved in other neurological disorders.
Author: Christopher Hartl
Publisher:
ISBN:
Category :
Languages : en
Pages : 172
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Book Description
Neuropsychiatric disorders are behavioral conditions marked by intellectual, social, or emotional deficits that can be linked to diseases of the nervous system. Autism spectrum disorder (ASD), schizophrenia (SCZ), bipolar disorder (BP), major depressive disorder (MDD), and attention deficit and hyperactivity disorder (ADHD) are common, heritable diseases each with a prevalence exceeding 1% of the population, none of which can be characterized by discernable anatomical or neurological pathologies. Genetic association studies have identified mutations in hundreds of genes that contribute to risk for at least one of these disorders, and have shown that a substantial fraction of the genetic liability is shared between many of these neuropsychiatric diseases. It has long been hoped that with enough genetic evidence we will identify the biological pathways, developmental time points, and brain regions that, when disrupted, give rise to neuropsychiatric disorders. However, the cellular and functional complexity of the human brain, as well as the genetic complexity of neuropsychiatric disease, make it difficult to search for such convergence. In this thesis, I investigate global and local transcriptional regulation within and across 12 regions of the human brain in order to investigate the regional specificity of neuropsychiatric disorders. I develop novel bioinformatics methods - ranging from data processing to network construction - to identify whether the transcriptional regulation of a set of genes is shared or specific. I hypothesize that local, region-specific transcriptional regulation corresponds directly to cell types and processes that are specific to, or far more prevalent in, a given region; that cross-regional transcriptional regulation corresponds to cell types that show little heterogeneity across brain regions; and that genetic disruption of region-specific transcriptional programs results in regional susceptibility. I use a systems-biology approach to summarize transcriptional regulation into reproducibly co-expressed gene sets ("co-expression modules"), which can be analyzed statistically to identify common functions, pathways, and cell types. I then integrate data from genetic association studies to ascertain gene sets conferring outsized risk for neuropsychiatric disorders, thereby implicating the corresponding pathways for further investigation in disease etiology. Finally, I use the network structure itself to investigate the genetic architecture of ASD and SCZ in terms of omnigenics and network polygenics. Chapter 1 presents the biological background for the studies and summarizes some of the major studies of neuropsychiatric disorders along with their principal methods and conclusions. In chapter 2, utilizing my multi-regional co-expression approach, I identify 12 brain-wide, 114 region-specific, and 50 cross-regional co-expression modules. Nearly 40% of expressed genes fall into brain-wide modules and correspond to major cell classes and conserved biological processes, while region-specific modules comprise 25% of expressed genes and correspond to region-specific cell types. The detailed study in chapter 3 demonstrates that neuropsychiatric risk concentrates in both brain wide and multi-regional modules, implicating major core cell types in disease etiology but not region-specific susceptibility. Chapter 4 presents a new and more general framework for defining genetic networks. Using this framework, I show that the network pattern of ASD-associated rare loss-of-function mutations, as well as the large number of significant targets for trans master regulators in BP and SCZ, support a classical polygenic architecture with thousands of directly causal genes. These results suggest that a nontrivial component of risk for neuropsychiatric disease comes from the global polygenic disruption of neuronal function and neuronal maturation.
Author: Yannis Karamanos
Publisher: Humana Press
ISBN: 9781617794476
Category : Medical
Languages : en
Pages : 0
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Book Description
Transcriptomics and proteomics, studying the profile of the expression of nucleic acids and proteins respectively, are increasingly applied to gain a mechanistic insight into a wide spectrum of investigation, and the use of expression profiling studies for the central nervous system and brain function aids in the understanding of neurodegenerative disorders and tumor development mechanisms. In Expression Profiling in Neuroscience, expert researchers provide a survey of the most commonly used approaches in the field and scan the different ways of studying the central nervous system/brain environment through expression profiling. The first part addresses the gene expression profiling of the brain at a large scale or to a specific cell type such as blood-brain barrier endothelium. Then, the second part describes the protein expression studies and the different technologies applied. Written for the popular Neuromethods series, chapters include corresponding background information, tested laboratory protocols, and step-by-step methods for reproducible laboratory experiments. Detailed and authoritative, Expression Profiling in Neuroscience presents the state-of-the-art techniques necessary to expand research further into this vital area of study.
Author:
Publisher: Elsevier
ISBN: 0444636420
Category : Medical
Languages : en
Pages : 448
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Book Description
Brain Banking, Volume 150, serves as the only book on the market offering comprehensive coverage of the functional realities of brain banking. It focuses on brain donor recruitment strategies, brain bank networks, ethical issues, brain dissection/tissue processing/tissue dissemination, neuropathological diagnosis, brain donor data, and techniques in brain tissue analysis. In accordance with massive initiatives, such as BRAIN and the EU Human Brain Project, abnormalities and potential therapeutic targets of neurological and psychiatric disorders need to be validated in human brain tissue, thus requiring substantial numbers of well characterized human brains of high tissue quality with neurological and psychiatric diseases. Offers comprehensive coverage of the functional realities of brain banking, with a focus on brain donor recruitment strategies, brain bank networks, ethical issues, and more Serves as a valuable resource for staff in existing brain banks by highlighting best practices Enhances the sharing of expertise between existing banks and highlights a range of techniques applicable to banked tissue for neuroscience researchers Authored by leaders from brain banks around the globe – the broadest, most expert coverage available
Author: Yulia Kovas
Publisher: Springer Nature
ISBN: 1349960489
Category : Psychology
Languages : en
Pages : 241
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Book Description
This book explores the answers to fundamental questions about the human mind and human behaviour with the help of two ancient texts. The first is Oedipus Rex (Oedipus Tyrannus) by Sophocles, written in the 5th century BCE. The second is human DNA, with its origins around 4 billion years ago, and continuously revised by chance and evolution. With Sophocles as a guide, the authors take a journey into the Genomic era, an age marked by ever-expanding insights into the human genome. Over the course of this journey, the book explores themes of free will, fate, and chance; prediction, misinterpretation, and the burden that comes with knowledge of the future; self-fulfilling and self-defeating prophecies; the forces that contribute to similarities and differences among people; roots and lineage; and the judgement of oneself and others. Using Oedipus Rex as its lens, this novel work provides an engaging overview of behavioural genetics that demonstrates its relevance across the humanities and the social and life sciences. It will appeal in particular to students and scholars of genetics, education, psychology, sociology, and law.
Author: Institute of Medicine
Publisher: National Academies Press
ISBN: 0309120926
Category : Science
Languages : en
Pages : 90
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Book Description
Neuroscience has made phenomenal advances over the past 50 years and the pace of discovery continues to accelerate. On June 25, 2008, the Institute of Medicine (IOM) Forum on Neuroscience and Nervous System Disorders hosted more than 70 of the leading neuroscientists in the world, for a workshop titled "From Molecules to Minds: Challenges for the 21st Century." The objective of the workshop was to explore a set of common goals or "Grand Challenges" posed by participants that could inspire and rally both the scientific community and the public to consider the possibilities for neuroscience in the 21st century. The progress of the past in combination with new tools and techniques, such as neuroimaging and molecular biology, has positioned neuroscience on the cusp of even greater transformational progress in our understanding of the brain and how its inner workings result in mental activity. This workshop summary highlights the important issues and challenges facing the field of neuroscience as presented to those in attendance at the workshop, as well as the subsequent discussion that resulted. As a result, three overarching Grand Challenges emerged: How does the brain work and produce mental activity? How does physical activity in the brain give rise to thought, emotion, and behavior? How does the interplay of biology and experience shape our brains and make us who we are today? How do we keep our brains healthy? How do we protect, restore, or enhance the functioning of our brains as we age?
Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309493412
Category : Medical
Languages : en
Pages : 621
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Book Description
Children are the foundation of the United States, and supporting them is a key component of building a successful future. However, millions of children face health inequities that compromise their development, well-being, and long-term outcomes, despite substantial scientific evidence about how those adversities contribute to poor health. Advancements in neurobiological and socio-behavioral science show that critical biological systems develop in the prenatal through early childhood periods, and neurobiological development is extremely responsive to environmental influences during these stages. Consequently, social, economic, cultural, and environmental factors significantly affect a child's health ecosystem and ability to thrive throughout adulthood. Vibrant and Healthy Kids: Aligning Science, Practice, and Policy to Advance Health Equity builds upon and updates research from Communities in Action: Pathways to Health Equity (2017) and From Neurons to Neighborhoods: The Science of Early Childhood Development (2000). This report provides a brief overview of stressors that affect childhood development and health, a framework for applying current brain and development science to the real world, a roadmap for implementing tailored interventions, and recommendations about improving systems to better align with our understanding of the significant impact of health equity.
Author:
Publisher: Elsevier
ISBN: 0444634266
Category : Science
Languages : en
Pages : 312
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Book Description
Progress in Brain Research is the most acclaimed and accomplished series in neuroscience, firmly established as an extensive documentation of the advances in contemporary brain research. The volumes, some of which are derived from important international symposia, contain authoritative reviews and original articles by invited specialists. The rigorous editing of the volumes assures that they will appeal to all laboratory and clinical brain research workers in the various disciplines: neuroanatomy, neurophysiology, neuropharmacology, neuroendocrinology, neuropathology, basic neurology, biological psychiatry, and the behavioral sciences. This volume, The Cerebellum and Memory Formation: Structure, Computation and Function, covers topics including feedback control of cerebellar learning; cortico-cerebellar organization and skill acquisition; cerebellar plasticity and learning in the oculomotor system, and more. Leading authors review the state-of-the-art in their field of investigation, and provide their views and perspectives for future research The volume reflects current thinking about the ways in which the cerebellum can engage in learning, and the contributors come from a variety of research fields The chapters express perspectives from different levels of analysis that range from molecular and cellular mechanisms through to long-range systems that allow the cerebellum to communicate with other brain areas
Author: Greg Stuart
Publisher: Frontiers Media SA
ISBN: 2889660699
Category : Medical
Languages : en
Pages : 131
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Book Description
This eBook is a collection of articles from a Frontiers Research Topic. Frontiers Research Topics are very popular trademarks of the Frontiers Journals Series: they are collections of at least ten articles, all centered on a particular subject. With their unique mix of varied contributions from Original Research to Review Articles, Frontiers Research Topics unify the most influential researchers, the latest key findings and historical advances in a hot research area! Find out more on how to host your own Frontiers Research Topic or contribute to one as an author by contacting the Frontiers Editorial Office: frontiersin.org/about/contact.
Author: Wolfgang Grisold
Publisher: Springer Nature
ISBN: 3031430816
Category : Medical
Languages : en
Pages : 291
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Book Description
This book presents a complete summary about the 12 pairs of cranial nerves (CN). They control much of the motor and sensory functions of the head and neck such as smell, sight, eye movement, and feeling in the face. The CN also control balance, hearing, and swallowing. The examination of the CN is an important part of the clinical neurological examination. Additionally, to the anatomy, extensive knowledge about further diagnostic tools are necessary such as neuroimaging, and electrophysiology. The book is divided into three parts: a general part with anatomy and imaging, a systematic part grouping the 12 pairs of cranial nerves, and a part describing cranial nerve functions in specific conditions and diseases.
