Notes

Multiview Data Constrained Boltzmann Models.
MIFlowCyt-EV provides a structure for sharing EV-FC results, but it does not prescribe specific protocols, as there will continue to be rapid evolution of instruments and methods for the foreseeable future. MIFlowCyt-EV accommodates this evolution, while providing information needed to evaluate and compare different approaches. Because MIFlowCyt-EV will ensure consistency in the manner of reporting of EV-FC studies, over time we expect that adoption of MIFlowCyt-EV as a standard for reporting EV- FC studies will improve the ability to quantitatively compare results from different laboratories and to support the development of new instruments and assays for improved measurement of EVs. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles.The forces actively generated by motile cells must be transmitted to their environment in a spatiotemporally regulated manner, in order to produce directional cellular motion. This task is accomplished through integrin-based adhesions, large macromolecular complexes that link the actin-cytoskelton inside the cell to its external environment. Despite their relatively large size, adhesions exhibit rapid dynamics, switching between assembly and disassembly in response to chemical and mechanical cues exerted by cytoplasmic biochemical signals, and intracellular/extracellular forces, respectively. While in material science, force typically disrupts adhesive contact, in this biological system, force has a more nuanced effect, capable of causing assembly or disassembly. This initially puzzled experimentalists and theorists alike, but investigation into the mechanisms regulating adhesion dynamics have progressively elucidated the origin of these phenomena. This review provides an overview of recent studies focused on the theoretical understanding of adhesion assembly and disassembly as well as the experimental studies that motivated them. We first concentrate on the kinetics of integrin receptors, which exhibit a complex response to force, and then investigate how this response manifests itself in macromolecular adhesion complexes. We then turn our attention to studies of adhesion plaque dynamics that link integrins to the actin-cytoskeleton, and explain how force can influence the assembly/disassembly of these macromolecular structure. Subsequently, we analyze the effect of force on integrins populations across lengthscales larger than single adhesions. Finally, we cover some theoretical studies that have considered both integrins and the adhesion plaque and discuss some potential future avenues of research. © 2020 The Authors.Pulmonary atresia (PA) is a rare congenital heart defect (CHD) with complex manifestations and a high mortality rate. Since the genetic determinants in the pathogenesis of PA remain elusive, a thorough identification of the genetic factors through whole exome sequencing (WES) will provide novel insights into underlying mechanisms of PA. Docetaxel We performed WES data from PA/VSD (n = 60), PA/IVS (n = 20), TOF/PA (n = 20) and 100 healthy controls. Rare variants and novel genes were identified using variant-based association and gene-based burden analysis. Then we explored the expression pattern of our candidate genes in endothelium cell lines, pulmonary artery tissues, and embryonic hearts. 56 rare damage variants of 7 novel candidate genes (DNAH10, DST, FAT1, HMCN1, HNRNPC, TEP1, and TYK2) were certified to have function in PA pathogenesis for the first time. In our research, the genetic pattern among PA/VSD, PA/IVS and TOF/PA were different to some degree. Taken together, our findings contribute new insights into the molecular basis of this rare congenital birth defect. © 2020 The Authors.Patient-derived organoids (PDO) and patient-derived xenografts (PDX) continue to emerge as important preclinical platforms for investigations into the molecular landscape of cancer. While the advantages and disadvantage of these models have been described in detail, this review focuses in particular on the bioinformatics and state-of-the art techniques that accompany preclinical model development. We discuss the strength and limitations of currently used technologies, particularly 'omics profiling and bioinformatics analyses, in addressing the 'efficacy' of preclinical models, both for tumour characterization as well as their use in identifying potential therapeutics. We select pancreatic ductal adenocarcinoma (PDAC) as a case study to highlight the state of the art of the field, and address new avenues for improved bioinformatics characterization of preclinical models. © 2020 The Author.Embryonic stem cells (ESCs) can differentiate into diverse cell types and have the ability of self-renewal. Therefore, the study of cell fate decisions on embryonic stem cells has far-reaching significance for regenerative medicine and other biomedical fields. Mathematical models have been used to study emryonic stem cell differentiation. However, the underlying mechanisms of cell differentiation and lineage reprogramming remain to be elucidated. Especially, how to integrate the computational models with quantitative experimental data is still challenging. In this work, we developed a data-constrained modelling approach, and established a model of mouse embryonic stem cells. We used the truncated moment equations (TME) method to quantify the potential landscape of the ESC network. We identified two attractors on the landscape, which represent the embryonic stem cell (ESC) state and differentiated cell (DC) state, respectively, and quantified high dimensional biological paths for differentiation and reprogramming process. Through identifying the optimal combinations of gene targets based on a landscape control strategy, we offered some predictions about the key regulatory factors that govern the differentiation and reprogramming in ESCs. © 2020 The Authors.The prevalence of congenital coronary artery anomalies is approximately 1% in the general population. They are a common cause of sudden death in younger persons. The origination of the posterior descending artery (PDA) from left anterior descending (LAD) artery is an extremely rare anomaly. We present a case of a 54-year-old female who presented with diabetic ketoacidosis with co-existing non-ST elevation myocardial infarction, therefore, had an invasive angiogram that identified the anomalous origin of PDA from LAD. It is vital to define coronary anatomy as anomalies dictate which cardiac intervention should be attempted in cases of ischemia. © 2020 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of Greater Baltimore Medical Center.
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