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https://www.readbyqxmd.com/read/28736756/advancing-the-science-of-myocardial-recovery-with-mechanical-circulatory-support-a-working-group-of-the-national-heart-lung-and-blood-institute
#1
Stavros G Drakos, Francis D Pagani, Martha S Lundberg, J Timothy Baldwin
The medical burden of heart failure (HF) has spurred interest in clinicians and scientists to develop therapies to restore the function of a failing heart. To advance this agenda, the National Heart Lung Blood Institute (NHLBI) convened a Working Group of experts on June 2-3, 2016 in Bethesda Maryland to develop recommendations for the NHLBI aimed at advancing the science of cardiac recovery in the setting of mechanical circulatory support (MCS). MSC devices effectively reduce volume and pressure overload that drives the cycle of progressive myocardial dysfunction, thereby triggering structural and functional reverse remodeling...
June 2017: JACC. Basic to Translational Science
https://www.readbyqxmd.com/read/28732770/pharmacologic-modeling-of-primary-mitochondrial-respiratory-chain-dysfunction-in-zebrafish
#2
James Byrnes, Rebecca Ganetzky, Richard Lightfoot, Michael Tzeng, Eiko Nakamaru-Ogiso, Christoph Seiler, Marni J Falk
Mitochondrial respiratory chain (RC) disease is a heterogeneous and highly morbid group of energy deficiency disorders for which no proven effective therapies exist. Robust vertebrate animal models of primary RC dysfunction are needed to explore the effects of variation in RC disease subtypes, tissue-specific manifestations, and major pathogenic factors contributing to each disorder, as well as their pre-clinical response to therapeutic candidates. We have developed a series of zebrafish (Danio rerio) models that inhibit, to variable degrees, distinct aspects of RC function, and enable quantification of animal development, survival, behaviors, and organ-level treatment effects on function as well as mitochondrial biochemistry and physiology...
July 18, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28730481/label-free-phosphoproteomic-approach-for-kinase-signaling-analysis
#3
Edmund Wilkes, Pedro R Cutillas
Phosphoproteomics is a powerful platform for the unbiased profiling of kinase-driven signaling pathways. Quantitation of phosphorylation can be performed by means of either labeling or label-free mass spectrometry (MS) methods. Because of their simplicity and universality, label-free methodology is gaining acceptance and popularity in molecular biology research. Analytical workflows for label-free quantification of phosphorylation, however, need to overcome several hurdles for the technique to be accurate and precise...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28728997/sepsis-reconsidered-identifying-novel-metrics-for-behavioral-landscape-characterization-with-a-high-performance-computing-implementation-of-an-agent-based-model
#4
Chase Cockrell, Gary An
OBJECTIVES: Sepsis affects nearly 1 million people in the United States per year, has a mortality rate of 28-50% and requires more than $20 billion a year in hospital costs. Over a quarter century of research has not yielded a single reliable diagnostic test or a directed therapeutic agent for sepsis. Central to this insufficiency is the fact that sepsis remains a clinical/physiological diagnosis representing a multitude of molecularly heterogeneous pathological trajectories. Advances in computational capabilities offered by High Performance Computing (HPC) platforms call for an evolution in the investigation of sepsis to attempt to define the boundaries of traditional research (bench, clinical and computational) through the use of computational proxy models...
July 17, 2017: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/28719603/the-%C3%A2-100-lab-a-3d-printable-open-source-platform-for-fluorescence-microscopy-optogenetics-and-accurate-temperature-control-during-behaviour-of-zebrafish-drosophila-and-caenorhabditis-elegans
#5
Andre Maia Chagas, Lucia L Prieto-Godino, Aristides B Arrenberg, Tom Baden
Small, genetically tractable species such as larval zebrafish, Drosophila, or Caenorhabditis elegans have become key model organisms in modern neuroscience. In addition to their low maintenance costs and easy sharing of strains across labs, one key appeal is the possibility to monitor single or groups of animals in a behavioural arena while controlling the activity of select neurons using optogenetic or thermogenetic tools. However, the purchase of a commercial solution for these types of experiments, including an appropriate camera system as well as a controlled behavioural arena, can be costly...
July 2017: PLoS Biology
https://www.readbyqxmd.com/read/28719044/symmetry-breaking-in-development-and-stochastic-gene-expression
#6
REVIEW
Jonathan R Chubb
The prevailing emphasis in developmental biology since the expansion of the molecular biology age has been that developmental decisions are instructive. A cell differentiates to become a specific cell type because it receives a signal, whereas its neighbor that does not receive the signal adopts a different fate. This emphasis has been generally accepted, largely because of the success of this view in tractable invertebrate model organisms, and the widespread similarities in molecular regulation to the development of more complex species...
July 18, 2017: Wiley Interdisciplinary Reviews. Developmental Biology
https://www.readbyqxmd.com/read/28714473/prioritizing-multiple-therapeutic-targets-in-parallel-using-automated-dna-encoded-library-screening
#7
Carl A Machutta, Christopher S Kollmann, Kenneth E Lind, Xiaopeng Bai, Pan F Chan, Jianzhong Huang, Lluis Ballell, Svetlana Belyanskaya, Gurdyal S Besra, David Barros-Aguirre, Robert H Bates, Paolo A Centrella, Sandy S Chang, Jing Chai, Anthony E Choudhry, Aaron Coffin, Christopher P Davie, Hongfeng Deng, Jianghe Deng, Yun Ding, Jason W Dodson, David T Fosbenner, Enoch N Gao, Taylor L Graham, Todd L Graybill, Karen Ingraham, Walter P Johnson, Bryan W King, Christopher R Kwiatkowski, Joël Lelièvre, Yue Li, Xiaorong Liu, Quinn Lu, Ruth Lehr, Alfonso Mendoza-Losana, John Martin, Lynn McCloskey, Patti McCormick, Heather P O'Keefe, Thomas O'Keeffe, Christina Pao, Christopher B Phelps, Hongwei Qi, Keith Rafferty, Genaro S Scavello, Matt S Steiginga, Flora S Sundersingh, Sharon M Sweitzer, Lawrence M Szewczuk, Amy Taylor, May Fern Toh, Juan Wang, Minghui Wang, Devan J Wilkins, Bing Xia, Gang Yao, Jean Zhang, Jingye Zhou, Christine P Donahue, Jeffrey A Messer, David Holmes, Christopher C Arico-Muendel, Andrew J Pope, Jeffrey W Gross, Ghotas Evindar
The identification and prioritization of chemically tractable therapeutic targets is a significant challenge in the discovery of new medicines. We have developed a novel method that rapidly screens multiple proteins in parallel using DNA-encoded library technology (ELT). Initial efforts were focused on the efficient discovery of antibacterial leads against 119 targets from Acinetobacter baumannii and Staphylococcus aureus. The success of this effort led to the hypothesis that the relative number of ELT binders alone could be used to assess the ligandability of large sets of proteins...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28711317/invasion-fitness-for-gene-culture-co-evolution-in-family-structured-populations-and-an-application-to-cumulative-culture-under-vertical-transmission
#8
Charles Mullon, Laurent Lehmann
Human evolution depends on the co-evolution between genetically determined behaviors and socially transmitted information. Although vertical transmission of cultural information from parent to offspring is common in hominins, its effects on cumulative cultural evolution are not fully understood. Here, we investigate gene-culture co-evolution in a family-structured population by studying the invasion fitness of a mutant allele that influences a deterministic level of cultural information (e.g., amount of knowledge or skill) to which diploid carriers of the mutant are exposed in subsequent generations...
July 12, 2017: Theoretical Population Biology
https://www.readbyqxmd.com/read/28709986/comparison-of-different-strategies-for-using-fossil-calibrations-to-generate-the-time-prior-in-bayesian-molecular-clock-dating
#9
Jose Barba-Montoya, Mario Dos Reis, Ziheng Yang
Fossil calibrations are the utmost source of information for resolving the distances between molecular sequences into estimates of absolute times and absolute rates in molecular clock dating analysis. The quality of calibrations is thus expected to have a major impact on divergence time estimates even if a huge amount of molecular data is available. In Bayesian molecular clock dating, fossil calibration information is incorporated in the analysis through the prior on divergence times (the time prior). Here, we evaluate three strategies for converting fossil calibrations (in the form of minimum- and maximum-age bounds) into the prior on times, which differ according to whether they borrow information from the maximum age of ancestral nodes and minimum age of descendent nodes to form constraints for any given node on the phylogeny...
July 11, 2017: Molecular Phylogenetics and Evolution
https://www.readbyqxmd.com/read/28709262/coexisting-origins-of-subdiffusion-in-internal-dynamics-of-proteins
#10
Yasmine Meroz, Victor Ovchinnikov, Martin Karplus
Subdiffusion in conformational dynamics of proteins is observed both experimentally and in simulations. Although its origin has been attributed to multiple mechanisms, including trapping on a rugged energy landscape, fractional Brownian noise, or a fractal topology of the energy landscape, it is unclear which of these, if any, is most relevant. To obtain insights into the actual mechanism, we introduce an analytically tractable hierarchical trapping model and apply it to molecular dynamics simulation trajectories of three proteins in solution...
June 2017: Physical Review. E
https://www.readbyqxmd.com/read/28706963/crispr-cas9-editing-of-the-bacillus-subtilis-genome
#11
Peter E Burby, Lyle A Simmons
A fundamental procedure for most modern biologists is the genetic manipulation of the organism under study. Although many different methods for editing bacterial genomes have been used in laboratories for decades, the adaptation of CRISPR/Cas9 technology to bacterial genetics has allowed researchers to manipulate bacterial genomes with unparalleled facility. CRISPR/Cas9 has allowed for genome edits to be more precise, while also increasing the efficiency of transferring mutations into a variety of genetic backgrounds...
April 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/28706521/evolution-and-function-of-thioester-containing-proteins-and-the-complement-system-in-the-innate-immune-response
#12
REVIEW
Upasana Shokal, Ioannis Eleftherianos
The innate immune response is evolutionary conserved among organisms. The complement system forms an important and efficient immune defense mechanism. It consists of plasma proteins that participate in microbial detection, which ultimately results in the production of various molecules with antimicrobial activity. Thioester-containing proteins (TEPs) are a superfamily of secreted effector proteins. In vertebrates, certain TEPs act in the innate immune response by promoting recruitment of immune cells, phagocytosis, and direct lysis of microbial invaders...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28706460/pricing-timer-options-and-variance-derivatives-with-closed-form-partial-transform-under-the-3-2-model
#13
Wendong Zheng, Pingping Zeng
Most of the empirical studies on stochastic volatility dynamics favour the 3/2 specification over the square-root (CIR) process in the Heston model. In the context of option pricing, the 3/2 stochastic volatility model (SVM) is reported to be able to capture the volatility skew evolution better than the Heston model. In this article, we make a thorough investigation on the analytic tractability of the 3/2 SVM by proposing a closed-form formula for the partial transform of the triple joint transition density [Formula: see text] which stand for the log asset price, the quadratic variation (continuous realized variance) and the instantaneous variance, respectively...
September 2, 2016: Applied Mathematical Finance
https://www.readbyqxmd.com/read/28705643/gpcrs-and-egfr-cross-talk-of-membrane-receptors-in-cancer
#14
REVIEW
Meryem Köse
G protein-coupled receptors (GPCRs) and receptor-tyrosine kinases (RTKs) are two important classes of cell surface receptors proven to be highly tractable as drug targets. Both receptor classes are involved in various complex (patho-) physiological processes in the human body including cellular growth and differentiation. More recently, accumulating data suggest that GPCR-induced activation of EGFR, the prototyp of RTKs represents a major mechanism in various cancers. The present review will focus on this cross-talk with particular emphasis on intracellular scaffold proteins regulating EGFR transactivation...
July 3, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28699036/spatiotemporal-expression-of-a-twist-homolog-in-the-leech-helobdella-austinensis
#15
Jin-Se Kim, Brenda Irene Medina Jiménez, Hee-Jin Kwak, Soon Cheol Park, Ping Xiao, David A Weisblat, Sung-Jin Cho
Genes of the twist family encode bHLH transcription factors known to be involved in the regulation and differentiation of early mesoderm. Here, we report our characterization of Hau-twist, a twist homolog from the leech Helobdella austinensis, a tractable lophotrochozoan representative. Hau-twist was expressed in segmental founder cells of the mesodermal lineage, in subsets of cells within the mesodermal lineage of the germinal plate, in circumferential muscle fibers of a provisional integument during segmentation and organogenesis stages and on the ventral side of the developing proboscis...
July 11, 2017: Development Genes and Evolution
https://www.readbyqxmd.com/read/28696692/evaluating-force-field-performance-in-thermodynamic-calculations-of-cyclodextrin-host-guest-binding-water-models-partial-charges-and-host-force-field-parameters
#16
Niel M Henriksen, Michael K Gilson
Computational prediction of noncovalent binding free energies with methods based on molecular mechanical force fields has become increasingly routine in drug discovery projects, where they promise to speed the discovery of small molecule ligands to bind targeted proteins with high affinity. Because the reliability of free energy methods still has significant room for improvement, new force fields, or modifications of existing ones, are regularly introduced with the aim of improving the accuracy of molecular simulations...
July 11, 2017: Journal of Chemical Theory and Computation
https://www.readbyqxmd.com/read/28694436/expression-and-regulation-of-drug-transporters-in-vertebrate-neutrophils
#17
Matthew J Foulkes, Katherine M Henry, Julien Rougeot, Edward Hooper-Greenhill, Catherine A Loynes, Phil Jeffrey, Angeleen Fleming, Caroline O Savage, Annemarie H Meijer, Simon Jones, Stephen A Renshaw
There remains a need to identify novel pro-resolution drugs for treatment of inflammatory disease. To date, there are no neutrophil-specific anti-inflammatory treatments in clinical use, perhaps due to our lack of understanding of how drugs access this complex cell type. Here we present the first comprehensive description and expression of both major classes of drug transporters, SLC and ABC, in resting human blood neutrophils. Moreover, we have studied the expression of these carriers in the tractable model system, the zebrafish (Danio rerio), additionally examining the evolutionary relationship between drug transporters in zebrafish and humans...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28691355/ultrastrong-and-tough-supramolecular-hydrogels-from-multiurea-linkage-segmented-copolymers-with-tractable-processablity-and-recyclability
#18
Nannan Yang, Huili Yang, Zengwu Shao, Mingyu Guo
Strong and tough synthetic hydrogels have received ever-increasing interests due to their potential applications as load-bearing structural materials. However, strong, tough, and recyclable hydrogels in different forms that can be generated by different methods according to various practical applications still remain an intrinsic bottleneck. A simple one-pot synthesis of multiurea linkage segmented linear copolymers with easy recyclability, hybridization, and processability, including compression molding, solution casting, and spinning methods, to yield ultrastrong and tough hydrogel films or stretchable hydrogel fibers with diameters ranged from macro-, micro-, to nanoscale, is reported here...
July 10, 2017: Macromolecular Rapid Communications
https://www.readbyqxmd.com/read/28691013/identification-of-pharmacologically-tractable-protein-complexes-in-cancer-using-the-r-based-network-clustering-and-visualization-program-mcoder
#19
Sungjin Kwon, Hyosil Kim, Hyun Seok Kim
Current multiomics assay platforms facilitate systematic identification of functional entities that are mappable in a biological network, and computational methods that are better able to detect densely connected clusters of signals within a biological network are considered increasingly important. One of the most famous algorithms for detecting network subclusters is Molecular Complex Detection (MCODE). MCODE, however, is limited in simultaneous analyses of multiple, large-scale data sets, since it runs on the Cytoscape platform, which requires extensive computational resources and has limited coding flexibility...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28690439/grasshopper-dcmd-an-undergraduate-electrophysiology-lab-for-investigating-single-unit-responses-to-behaviorally-relevant-stimuli
#20
Dieu My T Nguyen, Mark Roper, Stanislav Mircic, Robert M Olberg, Gregory J Gage
Avoiding capture from a fast-approaching predator is an important survival skill shared by many animals. Investigating the neural circuits that give rise to this escape behavior can provide a tractable demonstration of systems-level neuroscience research for undergraduate laboratories. In this paper, we describe three related hands-on exercises using the grasshopper and affordable technology to bring neurophysiology, neuroethology, and neural computation to life and enhance student understanding and interest...
2017: Journal of Undergraduate Neuroscience Education: JUNE: a Publication of FUN, Faculty for Undergraduate Neuroscience
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