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Author: Min Wang Publisher: ISBN: 9780494776711 Category : Languages : en Pages : 406
Book Description
Many pathological processes are associated with excessive neurotransmitter release that leads to the over-stimulation of post-synaptic neurotransmitter receptors. Examples include excessive activation of glutamate receptors in ischemic stroke and hyper-dopaminergic state in schizophrenia and drug addiction. Thus, it would seem that simply antagonizing the involved receptors should be able to correct the pathological condition. In some instances, this strategy has been somewhat effective, such as with the use of dopamine D2 receptor antagonists as antipsychotics in the treatment of positive symptoms of schizophrenia despite severe side effect. However, clinical application of drugs antagonizing glutamate receptor in the treatment of stoke, although attracting intensive research effort, has been restricted by serious side effects caused by suppressing postsynaptic responses that are needed for normal brain function. As a consequence, it is important to develop novel therapeutics aiming at specific targets with minimized side effects. Numerous studies have suggested that the pathophysiology of neuropsychiatric disorders, drug addictions and stroke involves multiple neurotransmitter receptor systems such as the dopamine and glutamate systems. The activation or inhibition of one receptor can have cross-functional effect that will be better understood by investigating the functional and structural relationship between receptor systems. Thus, the present study has focused on characterizing receptor-receptor interactions associated with dopamine receptors and glutamate receptors, and to elucidate the physiological and pathological consequence of altered receptor interactions in schizophrenia, depression and ischemic stroke.
Author: Min Wang Publisher: ISBN: 9780494776711 Category : Languages : en Pages : 406
Book Description
Many pathological processes are associated with excessive neurotransmitter release that leads to the over-stimulation of post-synaptic neurotransmitter receptors. Examples include excessive activation of glutamate receptors in ischemic stroke and hyper-dopaminergic state in schizophrenia and drug addiction. Thus, it would seem that simply antagonizing the involved receptors should be able to correct the pathological condition. In some instances, this strategy has been somewhat effective, such as with the use of dopamine D2 receptor antagonists as antipsychotics in the treatment of positive symptoms of schizophrenia despite severe side effect. However, clinical application of drugs antagonizing glutamate receptor in the treatment of stoke, although attracting intensive research effort, has been restricted by serious side effects caused by suppressing postsynaptic responses that are needed for normal brain function. As a consequence, it is important to develop novel therapeutics aiming at specific targets with minimized side effects. Numerous studies have suggested that the pathophysiology of neuropsychiatric disorders, drug addictions and stroke involves multiple neurotransmitter receptor systems such as the dopamine and glutamate systems. The activation or inhibition of one receptor can have cross-functional effect that will be better understood by investigating the functional and structural relationship between receptor systems. Thus, the present study has focused on characterizing receptor-receptor interactions associated with dopamine receptors and glutamate receptors, and to elucidate the physiological and pathological consequence of altered receptor interactions in schizophrenia, depression and ischemic stroke.
Author: Amy Davenport Migliori Publisher: ISBN: 9781303687983 Category : Languages : en Pages : 139
Book Description
Often, proteins are studied using bulk techniques, in which the average properties of large ensembles of molecules are studied. Although this has led to substantial new knowledge, the use of single-molecule biophysics and computational techniques to understand individual molecular actions and dynamics and the role of each residue allows for a more complete picture of activity in some cases. We present two applications of such techniques, first to determine the relationship between structure and function of the DNA translocation motor gp17 in Bacteriophage T4, and second to study looping of DNA mediated by the tumor suppressor protein p53. Specifically, we studied the role of an interface between the N- and C-terminal subdomains in generation of the high packaging forces and translocation velocities using a dual-beam optical trap. Mutation of charged amino acids located within this interface region confirmed that electrostatic forces play a role in force and velocity generation, with mutants showing a reduction in forward velocity, average velocity, and percentage of time spent packaging at different applied forces. To explain these experimental results, we generated a two-state computational model to calculate the free energy of the translocation step in gp17. We found excellent correlation between experimental data and calculated free energy change of translocation. Decomposition of the free energy change allowed for the identification of key residues involved in gp17-mediated packaging, and the role of each was explained. These results reveal that the power stroke of the motor requires substantial contributions from charged residues, hydrophobic residues, and polar residues instead of charged residues alone. Finally, we propose that several of these key residues may be hot spot residues, contributing a significant portion of the free energy used to package DNA. p53-mediated loop formation in DNA was studied using direct measurement with a dual optical tweezer setup. Looping of DNA by p53 has previously been demonstrated qualitatively using cryo-electron microscopy as well as transcription assays. we demonstrated formation of loops in purified human Col18A promoter containing five p53 binding sites. This looping may be directly related to p53 activity at transcriptional start sites.
Author: Paul Marangos Publisher: Elsevier ISBN: 0323151566 Category : Nature Languages : en Pages : 411
Book Description
Neuronal and Glial Proteins: Structure, Function, and Clinical Application focuses on the basic and clinical information relating to a number of proteins that are either enriched in or unique to nervous tissue. This book discusses the structural and functional characteristics of cell-specific proteins, which provide a better understanding of the molecular mechanisms involved in processes that are specific to glia or neurons. Organized into three sections encompassing 15 chapters, this book starts with an overview of the fundamental principles and strategies involved in studying the anatomical, structural, functional, and immunological aspects of brain protein. This text then discusses the techniques, including the preparation of brain tissues as well as the preparation of neural and glial cells in purified form. Other chapters review the two-dimensional gel electrophoresis, which is recognized as a significant technique for discovering brain molecules. The final chapter deals with the membrane-associated nervous system proteins. Neurochemists and clinical researchers will find this book useful.
Author: Soma Mondal Publisher: Library and Archives Canada = Bibliothèque et Archives Canada ISBN: 9780494028148 Category : Languages : en Pages : 300
Book Description
Astrocytes are glial cells of the central nervous system (CNS) that have a number of key functions including structural support of CNS cells and providing guidance for neuronal axon migration during development. This study describes the isolation and characterization of protein-protein interactions that are important in contributing to glial cell fates in the developing Drosophila embryo and those that maintain astrocyte cytoskeletal stability. The master glial fate determinant in Drosophila melanogaster is the transcription factor, glial cells missing (gcm). In flies, Gcm instructs progenitor cells to adopt glial fates. In the absence of gcm, progenitor cells assume a neuronal cell fate and a lack of glial cells results in mutant gcm embryos. We show that Gcm binds related forkhead-domain containing proteins, sloppy paired (Slp) 1 and S1p2. Slp1 binding to Gcm represses its transcriptional activation capacity. In a Drosophila model, we demonstrate that ectopic Slp1/2 expression in embryos leads to a severe reduction in gcm and glial cell numbers. In addition, we find a concomitant increase in neurons and further demonstrate that axonogenesis is disrupted. In contrast, mutant slp1/2 null embryos display a marked increase in gcm expression and glial cell number. These results demonstrate a novel mechanism of gcm regulation by Slp1 and Slp2. The second protein-protein interaction characterized relates to astrocyte cytoskeletal stability. Glial fibrillary acidic protein (GFAP) is an astrocyte-specific intermediate filament protein. One of its functions is to maintain cytoskeletal cell integrity within the astrocyte. A novel interaction between the GFAP and the actin-bundling protein, fascin is demonstrated. We show that GFAP and fascin colocalize in glial cell lines and normal astrocytes. Because fascin also binds to actin we propose that fascin links the actin cytoskeleton to GFAP, and that this interaction provides structural integrity to the astrocyte. Taken together, the studies presented offer insight into glial cell commitment during embryogenesis and structure.
Author: IConcept Press Staff Publisher: CreateSpace ISBN: 9781477555057 Category : Languages : en Pages : 326
Book Description
Chapter 1 is a review of the bioinformatics literature on protein-protein interactions (PPIs). A protein-protein interaction network (PPIN) is a collection of PPIs, often deposited in online databases. PPINs may complement other datasets, such as protein structural information. Chapter 2 describes the usability and advantages of the micro-patterning technique to study protein-protein interactions in a live cell context. It summarizes results achieved so far, discusses latest technical developments and describes potential future applications. Chapter 3 describes a strategy for identification of protein peptides cross-linked to radiolabeled RNA derivatives in specific complexes of proteins or ribonucleoproteins with these derivatives. This strategy is alternative to the identification based on mass-spectrometry and can be used for determination of protein sites involved in interactions with specific RNAs when mass-spectrometry is not applicable. Chapter 4 describes biochemical methods for assessing interaction between distinct ligand-gated channels. This chapter proposes also methods to examine functional impact of these receptor-receptor interactions in the nervous system. Chapter 5 proposes a statistical approach based on Structural Equation Modeling, in combination with step-wise factor analysis, to infer protein-DNA interactions for gene transcriptional control in the absence of protein information. Such approach only uses gene expression profiles. Chapter 6 describes procedures for the biochemical analysis of amyloid proteins in transgenic Drosophila, specifically the prion protein. The authors show that protocols from the mammalian literature can be easily adapted and scaled to these small flies and by ensuring robust expression of the prion protein and proper handling of these delicate samples. Chapter 7 discusses DEAD-box proteins. DEAD-box protein family members participate in many aspects of RNA metabolism, particularly in the ATP-driven disruption of secondary structures of RNA. Genes coding for these types of proteins are recognised in all free living bacteria. Chapter 8 provides an experimental model of restriction-modification enzyme fusion and proposes a molecular mechanism for appearance of type IIC restriction-modification and M.SsoII-related enzymes, as well as other multifunctional proteins. Chapter 9 describes the role of branched chain amino acids, leucine, isoleucine and valine, in exercise with respect to performance, muscle kinetics, fatigue and immunity. It also discusses the existing evidence on any superior benefits of branched chain amino acid supplements to exercising individuals and athletes. Chapter 10 provides an overview of the protein-peptide based research in dermatology and the recent emergence of many new dermatologic therapeutic modalities. Chapter 11 summarizes the adverse health effects of prenatal or early postnatal exposure to environmental pollutants (lead, arsenic and dioxins are the best known), pharmaceuticals, some food additives, and other chemicals through the mechanism of cell deprogramming or imprinting. Chapter 12 put forward 2D-PAGE as an important tool, especially for clinical laboratories involved in the determination of protein expression levels and disease biomarker discovery. Chapter 13 shows how to investigate and characterize an open reading frame, from exploiting the similarity in amino acid sequence, until the cloning, expression, purification and activity of the protein and its biological partners. Chapter 14 focuses on the cloning, heterologous expression and physicochemical characterization of Als5, one of the GPI-anchored adhesins from Candida albicans.
Author: Reesha Raja Publisher: ISBN: Category : Languages : en Pages :
Book Description
"The functional assembly of the nervous system requires the organization of billions of neurons growing axons to connect to one another in remarkably precise patterns. These connections are formed by the orchestration of many developmental processes, from neurogenesis, to neurite outgrowth, axon guidance, target selection and synaptogenesis. Each of these individual processes are mediated by thousands of molecules expressed in precise locations and developmental time points, accuracy of which is crucial for proper nervous system functionality. One family of molecules involved in these processes are the leucine-rich repeat (LRR) containing proteins. The LRR domains are known to mediate homophilic or heterophilic protein interactions, providing the proteins with the ability to serve in diverse functions such as cell-cell interaction or adhesion. Importantly, several neurological disorders have been linked by genetic studies to mutations in the genes encoding LRR family members. Herein, we use both in vitro and in vivo methods to provide evidence for roles of two LRR proteins in multiple developmental processes crucial for proper nervous system development. First, we identify a role for Slitrk1 in excitatory synapse formation and characterize roles for its LRR domains in mediating protein interactions. Second, we show differential requirement for the LRR and Ig domain-containing Amigo1 in mouse nervous system development. While Amigo1 is dispensable for the targeting of olfactory sensory axons to their targets, it is crucial for proper targeting of hippocampal mossy fibers in fasciculated tracts. In addition to identifying a function for Amigo1 in axonal fasciculation, our in vivo analyses revealed potential off-target effects associated with the insertion of an antibiotic resistance selection gene in the mouse genome, thereby serving as a cautionary tale for the interpretation of phenotypes in genetically-targeted mouse models. Taken together, our results show that Slirtk1 and Amigo1 both contribute in spatially and temporally specific ways in nervous system development"--
Author: Stefan Canzar Publisher: Humana ISBN: 9781493998722 Category : Science Languages : en Pages : 0
Book Description
This volume explores techniques that study interactions between proteins in different species, and combines them with context-specific data, analysis of omics datasets, and assembles individual interactions into higher-order semantic units, i.e., protein complexes and functional modules. The chapters in this book cover computational methods that solve diverse tasks such as the prediction of functional protein-protein interactions; the alignment-based comparison of interaction networks by SANA; using the RaptorX-ComplexContact webserver to predict inter-protein residue-residue contacts; the docking of alternative confirmations of proteins participating in binary interactions and the visually-guided selection of a docking model using COZOID; the detection of novel functional units by KeyPathwayMiner and how PathClass can use such de novo pathways to classify breast cancer subtypes. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary hardware- and software, step-by-step, readily reproducible computational protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Protein-Protein Interaction Networks: Methods and Protocols is a valuable resource for both novice and expert researchers who are interested in learning more about this evolving field.
Author: Min Wang
Author: Min Wang
Author: Amy Davenport Migliori
Author: Paul Marangos![Characterization of Molecular Interactions Regulating Glial Development and Cytoskeletal Structure [microform] PDF](https://books.google.com/books/content/images/frontcover/xs-StgAACAAJ?fife=w80-h100)
Author: Soma Mondal
Author: IConcept Press Staff
Author: Reesha Raja
Author: M. Kameron Brown
Author: Stefan Canzar
Author: Kai Ying Lai
Author: Bruce Alberts