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https://www.readbyqxmd.com/read/29332246/an-historical-perspective-of-the-discovery-of-titin-filaments-part-2
#1
REVIEW
Cristobal G Dos Remedios
In 2017, a Special Issue of Biophysical Reviews was devoted to "Titin and Its Binding Partners. The issue contained a review: "An historical perspective of the discovery of titin filaments" by dos Remedios and Gilmour that was intended to be a history of the discovery of the giant protein titin, previously named connectin. The review took readers back to the earliest discovery of the so-called third filament component of skeletal and cardiac muscle sarcomeres and ended in 1969. Recently, my colleague Shin'ichi Ishiwata gently reminded me of two papers published in 1990 and 1993 that were unwittingly omitted from the original historical perspective...
January 13, 2018: Biophysical Reviews
https://www.readbyqxmd.com/read/29331839/functional-characterization-of-a-novel-herg-variant-in-a-family-with-recurrent-sudden-infant-death-syndrome-retracting-a-genetic-diagnosis
#2
Valentine Sergeev, Frances Perry, Thomas M Roston, Shubhayan Sanatani, Glen F Tibbits, Thomas W Claydon
Long QT syndrome (LQTS) is the most common cardiac ion channelopathy and has been found to be responsible for approximately 10% of sudden infant death syndrome (SIDS) cases. Despite increasing use of broad panels and now whole exome sequencing (WES) in the investigation of SIDS, the probability of identifying a pathogenic mutation in a SIDS victim is low. We report a family-based study who are afflicted by recurrent SIDS in which several members harbor a variant, p.Pro963Thr, in the C-terminal region of the human-ether-a-go-go (hERG) gene, published to be responsible for cases of LQTS type 2...
December 20, 2017: Forensic Science International
https://www.readbyqxmd.com/read/29331721/understanding-protein-drug-interactions-using-ion-mobility-mass-spectrometry
#3
REVIEW
Claire E Eyers, Matthias Vonderach, Samantha Ferries, Kiani Jeacock, Patrick A Eyers
Ion mobility-mass spectrometry (IM-MS) is an important addition to the analytical toolbox for the structural evaluation of proteins, and is enhancing many areas of biophysical analysis. Disease-associated proteins, including enzymes such as protein kinases, transcription factors exemplified by p53, and intrinsically disordered proteins, including those prone to aggregation, are all amenable to structural analysis by IM-MS. In this review we discuss how this powerful technique can be used to understand protein conformational dynamics and aggregation pathways, and in particular, the effect that small molecules, including clinically-relevant drugs, play in these processes...
January 10, 2018: Current Opinion in Chemical Biology
https://www.readbyqxmd.com/read/29331641/enzymes-from-piezophiles
#4
REVIEW
Toshiko Ichiye
The discovery of microbial communities in extreme conditions that would seem hostile to life leads to the question of how the molecules making up these microbes can maintain their structure and function. While microbes that live under extremes of temperature have been heavily studied, those that live under extremes of pressure, or "piezophiles", are now increasingly being studied because of advances in sample collection and high-pressure cells for biochemical and biophysical measurements. Here, adaptations of enzymes in piezophiles against the effects of pressure are discussed in light of recent experimental and computational studies...
January 10, 2018: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/29331509/selenolanthionine-is-the-major-water-soluble-selenium-compound-in-the-selenium-tolerant-plant-cardamine-violifolia
#5
Eszter Borbála Both, Shuxun Shao, Jiqian Xiang, Zsuzsa Jókai, Hongqing Yin, Yafeng Liu, Anna Magyar, Mihály Dernovics
BACKGROUND: Selenium hyperaccumulation in plants often involves the synthesis of non-proteinaceous methylated selenoamino acids serving for the elimination of excess selenium from plant metabolism to protect plant homeostasis. METHODS: Our study aimed at the identification of the main selenium species of the selenium hyperaccumulator plant Cardamine violifolia (Brassicaceae) that grows in the wild in the seleniferous region of Enshi, China. A sample of this plant (3...
January 10, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29331449/quantifying-axonal-responses-in-patient-specific-models-of-subthalamic-deep-brain-stimulation
#6
Kabilar Gunalan, Bryan Howell, Cameron C McIntyre
Medical imaging has played a major role in defining the general anatomical targets for deep brain stimulation (DBS) therapies. However, specifics on the underlying brain circuitry that is directly modulated by DBS electric fields remain relatively undefined. Detailed biophysical modeling of DBS provides an approach to quantify the theoretical responses to stimulation at the cellular level, and has established a key role for axonal activation in the therapeutic mechanisms of DBS. Estimates of DBS-induced axonal activation can then be coupled with advances in defining the structural connectome of the human brain to provide insight into the modulated brain circuitry and possible correlations with clinical outcomes...
January 10, 2018: NeuroImage
https://www.readbyqxmd.com/read/29331233/a-biophysical-modelling-platform-of-the-cochlear-nucleus-and-other-auditory-circuits-from-channels-to-networks
#7
Paul B Manis, Luke Campagnola
Models of the auditory brainstem have been an invaluable tool for testing hypotheses about auditory information processing and for highlighting the most important gaps in the experimental literature. Due to the complexity of the auditory brainstem, and indeed most brain circuits, the dynamic behavior of the system may be difficult to predict without a detailed, biologically realistic computational model. Despite the sensitivity of models to their exact construction and parameters, most prior models of the cochlear nucleus have incorporated only a small subset of the known biological properties...
December 28, 2017: Hearing Research
https://www.readbyqxmd.com/read/29331201/impact-of-polymer-geometry-on-the-interactions-of-protein-peg-conjugates
#8
Jonathan Zarzar, Whitney Shatz, Nikhil Peer, Rosalynn Taing, Brian McGarry, Yun Liu, Daniel G Greene, Isidro E Zarraga
The conjugation of high molecular weight polyethylene glycol (PEG) to an active pharmaceutical ingredient (API) is an attractive strategy for the modification of biophysical and biodistribution properties of the API. Indeed, several therapeutic proteins conjugated to PEG have been safely administered in the clinic. While there have been studies on the configuration of these conjugates in solution, investigations on the impact of PEG geometry on protein-PEG conjugate interactions is limited. In this study, we use dynamic light scattering (DLS), rheology, and small-angle neutron scattering (SANS) to investigate the biophysical solution and interaction behavior of a 50kDa Fab protein attached to either a linear or tetrameric (branched) 40kDa PEG molecule...
November 8, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/29330458/architecture-of-a-mammalian-glomerular-domain-revealed-by-novel-volume-electroporation-using-nanoengineered-microelectrodes
#9
D Schwarz, M Kollo, C Bosch, C Feinauer, I Whiteley, T W Margrie, T Cutforth, A T Schaefer
Dense microcircuit reconstruction techniques have begun to provide ultrafine insight into the architecture of small-scale networks. However, identifying the totality of cells belonging to such neuronal modules, the "inputs" and "outputs," remains a major challenge. Here, we present the development of nanoengineered electroporation microelectrodes (NEMs) for comprehensive manipulation of a substantial volume of neuronal tissue. Combining finite element modeling and focused ion beam milling, NEMs permit substantially higher stimulation intensities compared to conventional glass capillaries, allowing for larger volumes configurable to the geometry of the target circuit...
January 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29329756/phospholipid-composition-of-the-outer-membrane-of-escherichia-coli-influences-its-susceptibility-against-antimicrobial-peptide-apidaecin-1b
#10
Rico Schmidt, Ding Yonghong, Ralf Hoffmann
Proline-rich antimicrobial peptides (PrAMPs) kill bacteria in a multimodal mechanism by inhibiting the 70S ribosome (i.e., protein translation) as dominant lethal mechanism besides inhibition of several other proteins, such as chaperone DnaK. PrAMPs pass the outer membrane of Gram-negative bacteria, probably by a self-promoted uptake followed by a transporter-mediated uptake from the periplasm. Mutation of transporter protein SbmA is a well-studied resistance mechanism observed in vitro by resistance induction with PrAMPs...
November 21, 2017: Diagnostic Microbiology and Infectious Disease
https://www.readbyqxmd.com/read/29329385/reassessing-the-evidence-for-capacity-limits-in-neural-signals-related-to-working-memory
#11
Paul M Bays
In 2004, two landmark studies described the discovery of brain imaging (functional magnetic resonance imaging and electroencephalography) signals that increase with the number of items held in visual working memory (WM). These studies claimed that the signals leveled off (plateaued) once the number of memoranda reached the capacity of WM, as estimated by the prevailing model of the time. However, alternative models were not considered, and changing concepts of WM in the more than a decade since these studies were published necessitate a re-evaluation of their findings; newer models that provide the most accurate account of behavioral data do not incorporate a fixed limit on the number of items stored...
January 10, 2018: Cerebral Cortex
https://www.readbyqxmd.com/read/29328778/engineering-approaches-to-study-cellular-decision-making
#12
Pamela K Kreeger, Laura E Strong, Kristyn S Masters
In their native environment, cells are immersed in a complex milieu of biochemical and biophysical cues. These cues may include growth factors, the extracellular matrix, cell-cell contacts, stiffness, and topography, and they are responsible for regulating cellular behaviors such as adhesion, proliferation, migration, apoptosis, and differentiation. The decision-making process used to convert these extracellular inputs into actions is highly complex and sensitive to changes both in the type of individual cue (e...
January 12, 2018: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/29328338/binding-affinity-prediction-of-nanobody-protein-complexes-by-scoring-of-molecular-dynamics-trajectories
#13
Miguel A Soler, Sara Fortuna, Ario de Marco, Alessandro Laio
Nanobodies offer a viable alternative to antibodies for engineering high affinity binders. Their small size has an additional advantage: it allows exploiting computational protocols for optimizing their biophysical features, such as the binding affinity. The efficient prediction of this quantity is still considered a daunting task especially for modelled complexes. We show how molecular dynamics can successfully assist in the binding affinity prediction of modelled nanobody-protein complexes. The approximate initial configurations obtained by in silico design must undergo large rearrangements before achieving a stable conformation, in which the binding affinity can be meaningfully estimated...
January 12, 2018: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/29327314/computational-modeling-for-cardiac-resynchronization-therapy
#14
Angela W C Lee, Caroline Mendonca Costa, Marina Strocchi, Christopher A Rinaldi, Steven A Niederer
Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure (HF) patients with an electrical substrate pathology causing ventricular dyssynchrony. However 40-50% of patients do not respond to treatment. Cardiac modeling of the electrophysiology, electromechanics, and hemodynamics of the heart has been used to study mechanisms behind HF pathology and CRT response. Recently, multi-scale dyssynchronous HF models have been used to study optimal device settings and optimal lead locations, investigate the underlying cardiac pathophysiology, as well as investigate emerging technologies proposed to treat cardiac dyssynchrony...
January 11, 2018: Journal of Cardiovascular Translational Research
https://www.readbyqxmd.com/read/29326166/a-skeletal-muscle-l-type-ca2-channel-with-a-mutation-in-the-selectivity-filter-cav1-1-e1014k-conducts-k
#15
Donald Beqollari, Karen Dockstader, Roger A Bannister
A glutamate to lysine substitution at position 1014 within the selectivity filter of the skeletal muscle L-type Ca2+ channel (CaV1.1) abolishes Ca2+ flux through the channel pore. Mice engineered to exclusively express the mutant channel display accelerated muscle fatigue, changes in muscle composition and altered metabolism relative to wild-type littermates. By contrast, mice expressing another mutant CaV1.1 channel that is impermeable to Ca2+ (CaV1.1 N617D) have shown no detectable phenotypic differences from wild-type mice to date...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29326068/slime-mould-the-fundamental-mechanisms-of-biological-cognition
#16
Jordi Vallverdú, Oscar Castro, Richard Mayne, Max Talanov, Michael Levin, Frantisek Baluška, Yukio Gunji, Audrey Dussutour, Hector Zenil, Andrew Adamatzky
The slime mould Physarum polycephalum has been used in developing unconventional computing devices for in which the slime mould played a role of a sensing, actuating, and computing device. These devices treated the slime mould rather as an active living substrate yet the slime mould is a self-consistent living creature which evolved for millions of years and occupied most part of the world, but in any case, that living entity did not own true cognition, just automated biochemical mechanisms. To "rehabilitate" the slime mould from the rank of a purely living electronics element to a "creature of thoughts" we are analyzing the cognitive potential of P...
January 8, 2018: Bio Systems
https://www.readbyqxmd.com/read/29325925/microfluidic-approaches-for-the-characterization-of-therapeutic-proteins
#17
REVIEW
Marie R G Kopp, Paolo Arosio
In the last decades the pharmaceutical market has experienced an increase in the number of therapeutic proteins. The high activity and selectivity of these macromolecules is often achieved at the expense of complex structures, which exhibit several biophysical properties that must be carefully controlled and optimized for the successful development of these drugs as well as for guaranteeing their quality and safety. This need has motivated the application of a variety of biophysical techniques to analyze properties of therapeutic proteins and protein solutions including interactions, aggregation, solubility, viscosity and thermal stability...
January 8, 2018: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/29324815/biophysical-insights-from-a-single-chain-camelid-antibody-directed-against-the-disrupted-in-schizophrenia-1-protein
#18
Antony S K Yerabham, Andreas Müller-Schiffmann, Tamar Ziehm, Andreas Stadler, Sabrina Köber, Xela Indurkhya, Rita Marreiros, Svenja V Trossbach, Nicholas J Bradshaw, Ingrid Prikulis, Dieter Willbold, Oliver H Weiergräber, Carsten Korth
Accumulating evidence suggests an important role for the Disrupted-in-Schizophrenia 1 (DISC1) protein in neurodevelopment and chronic mental illness. In particular, the C-terminal 300 amino acids of DISC1 have been found to mediate important protein-protein interactions and to harbor functionally important phosphorylation sites and disease-associated polymorphisms. However, long disordered regions and oligomer-forming subdomains have so far impeded structural analysis. VHH domains derived from camelid heavy chain only antibodies are minimal antigen binding modules with appreciable solubility and stability, which makes them well suited for the stabilizing proteins prior to structural investigation...
2018: PloS One
https://www.readbyqxmd.com/read/29324757/genome-downsizing-physiological-novelty-and-the-global-dominance-of-flowering-plants
#19
Kevin A Simonin, Adam B Roddy
The abrupt origin and rapid diversification of the flowering plants during the Cretaceous has long been considered an "abominable mystery." While the cause of their high diversity has been attributed largely to coevolution with pollinators and herbivores, their ability to outcompete the previously dominant ferns and gymnosperms has been the subject of many hypotheses. Common among these is that the angiosperms alone developed leaves with smaller, more numerous stomata and more highly branching venation networks that enable higher rates of transpiration, photosynthesis, and growth...
January 2018: PLoS Biology
https://www.readbyqxmd.com/read/29324422/assimilation-of-biophysical-neuronal-dynamics-in-neuromorphic-vlsi
#20
Jun Wang, Daniel Breen, Abraham Akinin, Frederic Broccard, Henry D I Abarbanel, Gert Cauwenberghs
Representing the biophysics of neuronal dynamics and behavior offers a principled analysis-by-synthesis approach toward understanding mechanisms of nervous system functions. We report on a set of procedures assimilating and emulating neurobiological data on a neuromorphic very large scale integrated (VLSI) circuit. The analog VLSI chip, NeuroDyn, features 384 digitally programmable parameters specifying for 4 generalized Hodgkin-Huxley neurons coupled through 12 conductance-based chemical synapses. The parameters also describe reversal potentials, maximal conductances, and spline regressed kinetic functions for ion channel gating variables...
December 2017: IEEE Transactions on Biomedical Circuits and Systems
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