Myofibrillogenesis
Myofibrillogenesis

Author: Dipak K. Dube

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 281

ISBN-13: 1461201993

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Myofibrillogenesis has been studied extensively over the last 100 years. Until recently, we have not had a comprehensive understanding of this fundamental process. The emergence of new technologies in molecular and cellular biology, combined with classical embryology, have started to unravel some of the complexities of myofibril assembly in striated muscles. In striated muscles, the contractile proteins are arranged in a highly ordered three dimensional lattice known as the sarcomere. The assembly of a myofibril involves the precise ordering of several proteins into a linear array of sarcomeres. Multiple isoforms in many of these proteins further complicate the process, making it difficult to define the precise role of each component. This volume has been compiled as a comprehensive reference on myofibrillogenesis. In addition, the book includes reviews on myofibrillar disarray under various pathological conditions, such as familial hypertrophic cardiomyopathy (FHC), and incorporates a section on the conduction system in the heart. Much of the information in this volume has not been described elsewhere. Presented in a manner to be of value to students and teachers alike, "Myofibrillogenesis" will be an invaluable reference source for all in the fields of muscle biology and heart development.

Science of Flexibility
Science of Flexibility

Author: Michael J. Alter

Publisher: Human Kinetics

Published: 2004

Total Pages: 382

ISBN-13: 9780736048989

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Based on the latest research, this revised & updated edition includes detailed illustrations throughout & an expanded section of scholarly & professional references.

Elastic Filaments of the Cell
Elastic Filaments of the Cell

Author: H.L. Granzier

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 427

ISBN-13: 1461542677

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Elastic filaments refer mainly to titin, the largest of all known proteins. Titin was discovered initially in muscle cells, where it interconnects the thick filament with the Z-line. Titin forms a molecular spring that is responsible for maintaining the structural integrity of contracting muscle, ensuring efficient muscle contraction. More recently, it has become clear that titin is not restricted to muscle cells alone. For example, titin is found in chromosomes of neurons and also in blood platelets. This topic is fast becoming a focal point for research in understanding viscoelastic properties at the molecular, cellular, and tissue levels. In titin may lie a generic basis for biological viscoelasticity. It has become clear that titin may hold the key to certain clinical anomalies. For example, it is clear that titin-based ventricular stiffness is modulated by calcium and that titin is responsible for the altered stiffness in cardiomyopathies. It is also clear from evidence from a group of Finnish families that titin mutations may underlie some muscular dystrophies and that with other mutations chromatids fail to separate during mitosis. Thus, it is clear that this protein will have important clinical implications stemming from its biomechanical role. One aspect of this field is the bringing together of bioengineers with clinical researchers and biologists. Genetic and biochemical aspects of titin-related proteins are being studied together with front-line engineering approaches designed to measure the mechanics of titin either in small aggregates or in single molecules.

Zebrafish at the Interface of Development and Disease Research
Zebrafish at the Interface of Development and Disease Research

Author:

Publisher: Academic Press

Published: 2017-03-21

Total Pages: 386

ISBN-13: 0128033436

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Zebrafish at the Interface of Development and Disease Research presents the latest on the shared pathways that govern development and contribute to disease. Zebrafish have traditionally been used to study vertebrate development, providing interesting data on the developmental processes and genes that are implicated in disease. This new release in the series contains informative discussions on congenital heart defects in zebrafish, the use of zebrafish in studying kidney development and disease, and muscle development, homeostasis and disease in zebrafish. Each chapter interweaves the study of zebrafish development and its application to the immune system, the kidney, liver, heart and others. The subject matter is unique - no single volume has pulled together the theme of development and disease with zebrafish as a centerpiece Leading experts in the field - all of them running zebrafish focused labs for each chapter

Ca2+ Dependent Changes in the Myocyte Proteome During Myofibrillogenesis
Ca2+ Dependent Changes in the Myocyte Proteome During Myofibrillogenesis

Author: Jeffery D. Eskew

Publisher:

Published: 2009

Total Pages: 368

ISBN-13:

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Striated muscle is a conserved contractile tissue in both vertebrates and invertebrates. At its most fundamental level, striated muscle is composed of individual contractile cables, called myofibrils, which are composed of tandem, repeating units called sarcomeres. The nearly solid complexity of sarcomeres, reminiscent of crystal packing, is a direct result of millions of years of evolution that has "fine-tuned" its ability to convert chemical into mechanical energy in the form of contraction. The process of sarcomere assembly is called myofibrillogenesis and it has been studied for decades. However, there are many important questions still unanswered including how discrete oscillatory Ca2+ signals (Ca2+ transients) function in the initiation and progression of assembly. Utilizing cutting edge proteomics approaches, I have shown that only a few protein differences can be detected in Xenopus embryos when Ca2+ transients are blocked. One of the most prominent differences involved the myosin regulatory light chain (RLC), which can be phosphorylated on at least two residues. Prior work suggested that phosphorylation is required for myofibrillogenesis, but the evidence was indirect. I have utilized an experimental approach to knockdown the endogenous expression of two classes of RLCs that combined morpholino antisense oligonucleotides together with site-directed mutational analysis to specifically and directly test the necessity of RLC phosphorylation during sarcomere assembly. I have shown that not only is the fast skeletal RLC isoform required for normal myosin assembly, but also that phosphorylation of RLC is a required regulatory step. There is evidence of a functional link between the phosphorylation sites of RLCs and the Ca2+ binding domain. Therefore, I also examined two RLC point mutations that disrupt Ca2+ binding and are associated with familial hypertrophic cardiac myopathy. These results show that the Ca2+ binding domain plays a significant role during the assembly of myosin arrays. Overall, my data show that phosphorylation of the fast skeletal RLC is an active process governed by spontaneous Ca2+ transients and furthermore that this post-translational modification is a required step for myofibrillogenesis. This dissertation thus includes not only original results with potential biomedical relevance, but also important methodological advances of high utility for the study of myofibrillogenesis.

Clarifying the Molecular Events of Early Myofibrillogenesis in Zebrafish
Clarifying the Molecular Events of Early Myofibrillogenesis in Zebrafish

Author: Layne Myhre

Publisher:

Published: 2013

Total Pages: 200

ISBN-13:

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Sarcomeres are highly-structured protein arrays, consisting of precisely-aligned thick and thin filaments. The contractile mechanisms of sarcomeres are generally well understood, but how their patterning is initiated during early striated muscle development remains uncertain. Two of the most widely-accepted hypotheses for this process include the "molecular ruler" model, in which the massive protein titin provides a scaffold along which the myosin thick filament is assembled, and t he "pre-myofibril" model, which proposes that thick filament formation rather involves "pre-myofibril" templates, modified stress fibers consisting of non-muscle myosin (NMM) and cytoskeletal actin. These models have proven difficult to test in vivo, but zebrafish motility mutants with developmental defects in sarcomere patterning are useful for the elucidation of such mechanisms. One such mutant, steif, lacks Unc45b, a molecular chaperone that mediates the folding of thick-filament myosin during sarcomere formation. However, Unc45b may also mediate specific functions of NMMs, and unc45b mutants display myocyte detachment, indicative of dysfunctional adhesion complex formation. Given the necessity for non-muscle myosin function in the formation of adhesion complexes and pre-myofibril templates, we tested the hypothesis that the unc45b mutant phenotype is not mediated solely by interaction with muscle myosin. Our results demonstrate co-expression and co-localization of Unc45b and NMM in myogenic tissue several hours before any muscle myosin is expressed. We also noted deficiencies in the localization of adhesion complex components and NMM in unc45b mutants, that areconsistent with a NMM-mediated role for Unc45b during early myogenesis. Further, we report the analysis of the previously uncharacterized herzschlag mutant, which has similar striated muscle deficits. The herzschlag mutant produces a truncated titin protein, lacking the C-terminal rod domain that is proposed to act as a thick filament scaffold, yet muscle patterning was still initiated, with grossly normal thick and thin filament assembly. Only after embryonic muscle contraction begins is breakdown of sarcomeric myosin patterning observed, consistent with a role for titin in maintaining the contractile integrity of mature sarcomeres. These results support the pre-myofibril model, and conflict with the molecular ruler model of early sarcomere patterning, while demonstrating a novel role for Unc45b in early myogenesis.

The Actin Cytoskeleton
The Actin Cytoskeleton

Author: Brigitte M. Jockusch

Publisher: Springer

Published: 2017-01-03

Total Pages: 356

ISBN-13: 3319463713

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Actin is one of the most abundant proteins and ubiquitously expressed in all eukaryotes. In recent years, the analysis of structure and function of such complexes has shed new light on actin's role in cellular and tissue morphogenesis, locomotion and various forms of intracellular motility, but also on its role in nuclear processes like chromatin architecture and transcription. Progress in understanding these different physiological phenomena, but also in unravelling the basis of actin-based pathophysiological processes has been made by combining video microscopy, molecular biology, genetics and biochemistry. Thus, the current research on actin, as ongoing in many international laboratories, is a "hot spot" in basic and translational research in life sciences. In this book on "The Actin Cytoskeleton", twelve internationally renowned authors present specific chapters that cover their recent work concerned with the various roles of actin mentioned above. This comprehensive volume is therefore an attractive handbook for teachers and students in many fields of medicine and pharmacology.

Epilepsy in Children and Adolescents
Epilepsy in Children and Adolescents

Author: James W. Wheless

Publisher: John Wiley & Sons

Published: 2012-10-22

Total Pages: 362

ISBN-13: 1118388518

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Epilepsy in childhood presents a profound challenge Epilepsy is an unsettling, complex condition. There is no ‘one size fits all’ option. For effective treatment a full understanding of each patient’s situation and clinical history is needed. Recent remarkable improvements in our ability to image brain structures, to define physiological patterns and in treatment options has made the task of care of the child with epilepsy potentially more effective. Epilepsy in Children and Adolescents provides the contemporary, caring guidance you need to diagnose and manage seizures in a young patient. Beginning with an overview of the classification of epilepsy syndromes, the experienced authors cover: Diagnostic evaluation of childhood epilepsies Principles of treatment Generalized seizures and generalized epilepsy syndromes Partial onset seizures and localization-related epilepsy syndromes Epilepsies relative to age, etiology or duration The full range of treatment options: medical, dietary, surgical Epilepsy in Children and Adolescents takes a practical approach to a common but complex clinical challenge.