scholarly journals Assembly and Maintenance of Sarcomere Thin Filaments and Associated Diseases

2020 ◽  
Vol 21 (2) ◽  
pp. 542 ◽  
Author(s):  
Kendal Prill ◽  
John F. Dawson
Keyword(s):  
Thin Filament ◽  
Reverse Genetics ◽  
Medical Intervention ◽  
Model Organisms ◽  
Skeletal Muscle Function ◽  
Thin Filaments ◽  
Physiological Processes ◽  
Open Research ◽  
Research Questions ◽  
Sarcomere Assembly

Sarcomere assembly and maintenance are essential physiological processes required for cardiac and skeletal muscle function and organism mobility. Over decades of research, components of the sarcomere and factors involved in the formation and maintenance of this contractile unit have been identified. Although we have a general understanding of sarcomere assembly and maintenance, much less is known about the development of the thin filaments and associated factors within the sarcomere. In the last decade, advancements in medical intervention and genome sequencing have uncovered patients with novel mutations in sarcomere thin filaments. Pairing this sequencing with reverse genetics and the ability to generate patient avatars in model organisms has begun to deepen our understanding of sarcomere thin filament development. In this review, we provide a summary of recent findings regarding sarcomere assembly, maintenance, and disease with respect to thin filaments, building on the previous knowledge in the field. We highlight debated and unknown areas within these processes to clearly define open research questions.

scholarly journals Muscle ankyrin repeat protein 1 (MARP1) locks titin to the sarcomeric thin filament and is a passive force regulator

2021 ◽  
Vol 153 (7) ◽  
Author(s):  
Robbert J. van der Pijl ◽  
Marloes van den Berg ◽  
Martijn van de Locht ◽  
Shengyi Shen ◽  
Sylvia J.P. Bogaards ◽  
...  
Keyword(s):  
Thin Filament ◽  
Mechanical Damage ◽  
Super Resolution ◽  
Ankyrin Repeat ◽  
Passive Force ◽  
Skeletal Muscle Function ◽  
Thin Filaments ◽  
Mechanically Ventilated ◽  
Repeat Protein ◽  
Ankyrin Repeat Protein

Muscle ankyrin repeat protein 1 (MARP1) is frequently up-regulated in stressed muscle, but its effect on skeletal muscle function is poorly understood. Here, we focused on its interaction with the titin–N2A element, found in titin’s molecular spring region. We show that MARP1 binds to F-actin, and that this interaction is stronger when MARP1 forms a complex with titin–N2A. Mechanics and super-resolution microscopy revealed that MARP1 “locks” titin–N2A to the sarcomeric thin filament, causing increased extension of titin’s elastic PEVK element and, importantly, increased passive force. In support of this mechanism, removal of thin filaments abolished the effect of MARP1 on passive force. The clinical relevance of this mechanism was established in diaphragm myofibers of mechanically ventilated rats and of critically ill patients. Thus, MARP1 regulates passive force by locking titin to the thin filament. We propose that in stressed muscle, this mechanism protects the sarcomere from mechanical damage.

scholarly journals Users roles identification on online crowdsourced Q&A platforms and encyclopedias: a survey

2021 ◽  
Author(s):  
Akrati Saxena ◽  
Harita Reddy
Keyword(s):  
Network Analysis ◽  
Knowledge Sharing ◽  
Informal Learning ◽  
Social Roles ◽  
Online Discussion ◽  
State Of The Art ◽  
Temporal Analysis ◽  
The State ◽  
Open Research ◽  
Research Questions

AbstractOnline informal learning and knowledge-sharing platforms, such as Stack Exchange, Reddit, and Wikipedia have been a great source of learning. Millions of people access these websites to ask questions, answer the questions, view answers, or check facts. However, one interesting question that has always attracted the researchers is if all the users share equally on these portals, and if not then how the contribution varies across users, and how it is distributed? Do different users focus on different kinds of activities and play specific roles? In this work, we present a survey of users’ social roles that have been identified on online discussion and Q&A platforms including Usenet newsgroups, Reddit, Stack Exchange, and MOOC forums, as well as on crowdsourced encyclopedias, such as Wikipedia, and Baidu Baike, where users interact with each other through talk pages. We discuss the state of the art on capturing the variety of users roles through different methods including the construction of user network, analysis of content posted by users, temporal analysis of user activity, posting frequency, and so on. We also discuss the available datasets and APIs to collect the data from these platforms for further research. The survey is concluded with open research questions.

Binding of adenylosuccinate synthetase to contractile proteins of muscle

1989 ◽  
Vol 257 (1) ◽  
pp. C29-C35 ◽  
Author(s):  
J. P. Manfredi ◽  
R. Marquetant ◽  
A. D. Magid ◽  
E. W. Holmes
Keyword(s):  
Ionic Strength ◽  
Dissociation Constant ◽  
Thin Filament ◽  
Contractile Proteins ◽  
Purine Nucleotide ◽  
Apparent Dissociation Constant ◽  
Thin Filaments ◽  
Adenylosuccinate Synthetase ◽  
Purine Nucleotide Cycle ◽  
Low Ionic Strength

The muscle isozyme of adenylosuccinate synthetase (AdSS), an enzyme of the purine nucleotide cycle, has previously been shown to bind to purified F-actin in buffers of low ionic strength and pH (Ogawa et al. Eur. J. Biochem. 85: 331-338, 1978). We have extended these observations by measuring the association of both crude and purified AdSS with the contractile proteins of muscle in buffers of physiological ionic strength and pH. Under these conditions, the enzyme binds to F-actin, actin-tropomyosin complexes, reconstructed thin filaments, and myofibrils but not to myosin. The apparent dissociation constant of 1.2 microM and binding maximum of 2.6 nmol enzyme/mg myofibrils indicate that binding of AdSS to myofibrils can be physiologically significant. The results suggest that AdSS in muscle may be associated with the thin filament of myofibrils.

scholarly journals The structure of the native cardiac thin filament at systolic Ca2+ levels

2021 ◽  
Vol 118 (13) ◽  
pp. e2024288118
Author(s):  
Cristina M. Risi ◽  
Ian Pepper ◽  
Betty Belknap ◽  
Maicon Landim-Vieira ◽  
Howard D. White ◽  
...  
Keyword(s):  
Cardiac Muscle ◽  
Binding Sites ◽  
Short Range ◽  
Bound States ◽  
Thin Filament ◽  
Narrow Range ◽  
The Other ◽  
Thin Filaments ◽  
Troponin Complex ◽  
Myosin Binding

Every heartbeat relies on cyclical interactions between myosin thick and actin thin filaments orchestrated by rising and falling Ca2+ levels. Thin filaments are comprised of two actin strands, each harboring equally separated troponin complexes, which bind Ca2+ to move tropomyosin cables away from the myosin binding sites and, thus, activate systolic contraction. Recently, structures of thin filaments obtained at low (pCa ∼9) or high (pCa ∼3) Ca2+ levels revealed the transition between the Ca2+-free and Ca2+-bound states. However, in working cardiac muscle, Ca2+ levels fluctuate at intermediate values between pCa ∼6 and pCa ∼7. The structure of the thin filament at physiological Ca2+ levels is unknown. We used cryoelectron microscopy and statistical analysis to reveal the structure of the cardiac thin filament at systolic pCa = 5.8. We show that the two strands of the thin filament consist of a mixture of regulatory units, which are composed of Ca2+-free, Ca2+-bound, or mixed (e.g., Ca2+ free on one side and Ca2+ bound on the other side) troponin complexes. We traced troponin complex conformations along and across individual thin filaments to directly determine the structural composition of the cardiac native thin filament at systolic Ca2+ levels. We demonstrate that the two thin filament strands are activated stochastically with short-range cooperativity evident only on one of the two strands. Our findings suggest a mechanism by which cardiac muscle is regulated by narrow range Ca2+ fluctuations.

scholarly journals Lessons Learnt, Open Research Questions and Recommendations

2016 ◽  
pp. 279-292
Author(s):  
Christine Bismuth ◽  
Bernd Hansjürgens ◽  
Timothy Moss ◽  
Sebastian Hoechstetter ◽  
Klement Tockner ◽  
...  
Keyword(s):  
Open Research ◽  
Lessons Learnt ◽  
Research Questions

scholarly journals A comprehensive review of plus-minus ratings for evaluating individual players in team sports

2019 ◽  
Vol 18 (1) ◽  
pp. 1-23 ◽  
Author(s):  
Lars Magnus Hvattum
Keyword(s):  
Decision Making ◽  
Team Sports ◽  
Sports Analytics ◽  
Comprehensive Review ◽  
Sports Events ◽  
Open Research ◽  
New Directions ◽  
Individual Player ◽  
Research Questions ◽  
The Many

AbstractThe increasing availability of data from sports events has led to many new directions of research, and sports analytics can play a role in making better decisions both within a club and at the level of an individual player. The ability to objectively evaluate individual players in team sports is one aspect that may enable better decision making, but such evaluations are not straightforward to obtain. One class of ratings for individual players in team sports, known as plus-minus ratings, attempt to distribute credit for the performance of a team onto the players of that team. Such ratings have a long history, going back at least to the 1950s, but in recent years research on advanced versions of plus-minus ratings has increased noticeably. This paper presents a comprehensive review of contributions to plus-minus ratings in later years, pointing out some key developments and showing the richness of the mathematical models developed. One conclusion is that the literature on plus-minus ratings is quite fragmented, but that awareness of past contributions to the field should allow researchers to focus on some of the many open research questions related to the evaluation of individual players in team sports.

scholarly journals Tropomodulin isoforms regulate thin filament pointed-end capping and skeletal muscle physiology

2010 ◽  
Vol 189 (1) ◽  
pp. 95-109 ◽  
Author(s):  
David S. Gokhin ◽  
Raymond A. Lewis ◽  
Caroline R. McKeown ◽  
Roberta B. Nowak ◽  
Nancy E. Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Thin Filament ◽  
Striated Muscle ◽  
Fiber Type ◽  
Actin Dynamics ◽  
Muscle Physiology ◽  
Skeletal Muscle Function ◽  
Capping Proteins ◽  
Locomotor Deficits ◽  
End Capping

During myofibril assembly, thin filament lengths are precisely specified to optimize skeletal muscle function. Tropomodulins (Tmods) are capping proteins that specify thin filament lengths by controlling actin dynamics at pointed ends. In this study, we use a genetic targeting approach to explore the effects of deleting Tmod1 from skeletal muscle. Myofibril assembly, skeletal muscle structure, and thin filament lengths are normal in the absence of Tmod1. Tmod4 localizes to thin filament pointed ends in Tmod1-null embryonic muscle, whereas both Tmod3 and -4 localize to pointed ends in Tmod1-null adult muscle. Substitution by Tmod3 and -4 occurs despite their weaker interactions with striated muscle tropomyosins. However, the absence of Tmod1 results in depressed isometric stress production during muscle contraction, systemic locomotor deficits, and a shift to a faster fiber type distribution. Thus, Tmod3 and -4 compensate for the absence of Tmod1 structurally but not functionally. We conclude that Tmod1 is a novel regulator of skeletal muscle physiology.

Positional Correlative Anatomy of Invertebrate Model Organisms Increases Efficiency of TEM Data Production

2014 ◽  
Vol 20 (5) ◽  
pp. 1392-1403 ◽  
Author(s):  
Irina Kolotuev
Keyword(s):  
Developmental Biology ◽  
Cell Biology ◽  
Sampling Rate ◽  
Unmet Need ◽  
Region Of Interest ◽  
Model Organisms ◽  
Data Generation ◽  
Step Method ◽  
Efficient Data ◽  
Research Questions

AbstractTransmission electron microscopy (TEM) is an important tool for studies in cell biology, and is essential to address research questions from bacteria to animals. Recent technological innovations have advanced the entire field of TEM, yet classical techniques still prevail for most present-day studies. Indeed, the majority of cell and developmental biology studies that use TEM do not require cutting-edge methodologies, but rather fast and efficient data generation. Although access to state-of-the-art equipment is frequently problematic, standard TEM microscopes are typically available, even in modest research facilities. However, a major unmet need in standard TEM is the ability to quickly prepare and orient a sample to identify a region of interest. Here, I provide a detailed step-by-step method for a positional correlative anatomy approach to flat-embedded samples. These modifications make the TEM preparation and analytic procedures faster and more straightforward, supporting a higher sampling rate. To illustrate the modified procedures, I provide numerous examples addressing research questions in Caenorhabditis elegans and Drosophila. This method can be equally applied to address questions of cell and developmental biology in other small multicellular model organisms.

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