Chandyhr7004

RESULTS Mechanical force increased the expression of integrin alpha₅ß₁, FAK (p-FAK), and COL-1 in HGFs, and induced the formation of stress fibers. Blocking integrin alpha₅ß₁ reduced the expression of FAK (p-FAK), while the expression of COL-1 was not fully inhibited. CONCLUSIONS The integrin alpha₅ß₁/FAK signaling pathway and actin cytoskeleton appear to be involved in the mechanotransduction of HGFs. There could be other mechanisms involved in the promotion effect of mechanical force on collagen synthesis in addition to the integrin alpha₅ß₁ pathway.New technologies of induced pluripotent stem cells (iPSCs) and genome editing have emerged, allowing for the development of autologous transfusion therapies. We previously demonstrated definitive β-globin production from human embryonic stem cell (hESC)-derived erythroid cell generation via hemangioblast-like ES-sacs. In this study, we demonstrated normal β-globin protein production from biallelic corrected sickle cell disease (SCD) iPSCs. We optimized our ES/iPS-sac method for feeder cell-free hESC maintenance followed by serum-free ES-sac generation, which is preferred for electroporation-based genome editing. Surprisingly, the optimized protocol improved yields of ES-sacs (25.9-fold), hematopoietic-like spherical cells (14.8-fold), and erythroid cells (5.8-fold), compared with our standard ES-sac generation. We performed viral vector-free gene correction in SCD iPSCs, resulting in one clone with monoallelic and one clone with biallelic correction, and using this serum-free iPS-sac culture, corrected iPSC-generated erythroid cells with normal β-globin, confirmed at DNA and protein levels. Our serum-free ES/iPS-sac protocol with gene correction will be useful to develop regenerative transfusion therapies for SCD. © 2020 The Authors. This article is a U.S. Government work and is in the public domain in the USA.Identification of the novel HLA-A*31177 allele that differs from HLA-A*31010204 in exon 5. © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.OBJECTIVE Previous studies have revealed decreased mitochondrial respiration in adipocytes of obese mice. This study aimed to identify the molecular underpinnings of altered mitochondrial metabolism in adipocytes. METHODS Untargeted proteomics of mitochondria isolated from adipocytes and metabolite profiling of adipose tissues were conducted in diet-induced obese (DIO) and lean mice. Subcutaneous and intra-abdominal adipose tissues were studied to depict depot-specific alterations. RESULTS In subcutaneous adipocytes of DIO mice, changes in proteins related to mitochondrial structure and function were observed. Mitochondrial proteins of the inner and outer membrane were strongly reduced, whereas proteins of key matrix metabolic pathways were increased in the obese versus lean state, as further substantiated by metabolite profiling. A pronounced decrease in the oxidative phosphorylation (OXPHOS) enzymatic equipment and cristae density of the inner membrane was identified. In intra-abdominal adipocytes, similar systematic downregulation of the OXPHOS machinery in obesity occurred, but there was no regulation of outer membrane or matrix proteins. CONCLUSIONS Protein components of the OXPHOS machinery are systematically downregulated in adipose tissues of DIO mice compared with lean mice. Loss of the mitochondrial OXPHOS capacity in adipocytes may aggravate the development of metabolic disease. © 2020 The Authors. Obesity published by Wiley Periodicals, Inc. on behalf of The Obesity Society (TOS).DKMS is a leading stem cell donor registry with more than 9 million donors. Donor registry activities share many touch points with topics from immunogenetics or population genetics. In this two-part review article, we deal with these aspects of donor registry work by using the example of DKMS. In the second part of the review, we focus on donor typing of non-HLA genes, the impact of donor age, gender and CMV serostatus on donation probabilities, the identification of novel HLA, KIR and MIC alleles by high-throughput donor typing, the activities of the Collaborative Biobank and pharmacogenetics in the donor registry context. © 2020 The Authors. International Journal of Immunogenetics . Published by John Wiley & Sons Ltd.Aortopathies encompass a variety of inherited and acquired pathologies that increase risk of life-threatening dissection or rupture. Identifying individuals with hereditary thoracic aortic aneurysm and dissection (HTAAD) for longitudinal monitoring, medical therapy, or elective and preventative repair is paramount to reduce risk of cardiovascular-related mortality and complications from dissection and rupture. Over the past couple of decades, pathogenic variants in numerous genes have been identified in relation to HTAAD. The genetic diagnosis can help stratify patient risk and provide guidance on medical treatment, timing of prophylactic surgical repair, as well as longitudinal surveillance and imaging. Implicated genes and their associated proteins have been found to act on a diverse variety of pathways, cells and structural components linked to transforming growth factor beta (TGF-β) signaling pathways, disruption of the vascular smooth muscle cell contractile apparatus, and primary disruption of extracellular matrix homeostasis. This review describes relevant genetic variants that may help identify and guide the management of hereditary thoracic aortic aneurysms and dissections. © 2020 Wiley Periodicals, Inc.The purpose of this study was to investigate the relationship between fatigue-induced reductions in isometric torque and isotonic power and to quantify the extent to which the decreases in angular velocity and dynamic torque can explain the power loss immediately following an isotonic fatiguing task and throughout recovery in seven young males and six young females. All measurements were performed with both legs. For dorsiflexion, fatigue-related time-course changes in isometric maximal voluntary contraction (MVC) torque, angular velocity, dynamic torque, and power production following repeated maximal isotonic contractions (load 20% MVC) were investigated before, immediately after, and 1, 2, 5 and 10 min after a fatiguing task. There were no relationships between the fatigue-related reductions in isometric MVC torque and peak power at any timepoint, suggesting that fatigue-induced reductions in isometric MVC torque does not entirely reflect fatigue-induced changes in dynamic performance. The relative contribution of fatigue-related reduction in dynamic torque on power loss was greater immediately following the task, and lower throughout recovery than the corresponding decrease in angular velocity. Thus, power loss immediately following the task was more strongly related to the decline in dynamic torque; however, this relationship shifted throughout recovery to a greater dependence on slowing of angular velocity for power loss. © 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.Hantavirus pulmonary syndrome is an emerging infectious disease caused by viruses of the genus Orthohantavirus. The rodent Oligoryzomys flavescens is distributed along four countries of South America. In Argentina, O. flavescens acts as a reservoir of three genotypes of ANDV orthohantavirus. Cobimetinib MEK inhibitor The aims of this work were to estimate home range size and movements-with spool-and-line and radiotelemetry-of infected and non-infected O. flavescens in order to understand the spread and transmission of the virus. O. flavescens use a wide area to satisfice its requirements, reaching a home range of 1.82 ha during spring. Orthohantavirus infection did not change the behaviour of individuals. We observed a great overlapping in the home range of infected and non-infected individuals resulting in a high probability of virus dispersion on rodent population. These results show that human health risks could be high on island environments and knowledge about the movement ecology of O. flavescens provides useful information on prevention. © 2020 Blackwell Verlag GmbH.The role of wildlife in the dissemination of antimicrobial-resistant bacteria and antimicrobial resistance genes (ARGs) in the environment is of increasing concern. We investigated the occurrence, richness and transmissibility potential of ARGs detected in the faeces of three mesocarnivore species the coyote (Canis latrans), raccoon (Procyon lotor) and Virginia opossum (Didelphis virginiana), and of stray and owned dogs in suburban Chicago, IL, USA. Rectal swabs were collected from live-captured coyotes (n = 32), raccoons (n = 31) and Virginia opossums (n = 22). Fresh faecal samples were collected from locally owned (n = 13) and stray dogs (n = 18) and from the live-captured mesocarnivores, when available. Faecal samples and rectal swabs were enriched to select for Enterobacteriaceae and pooled by mesocarnivore species and dog type (owned or stray). Pooled enriched samples were then analysed for the presence of ARGs using shotgun sequencing. The three mesocarnivore and stray dog samples had twice as many unique ARGs compared to the owned dog sample, which was partly driven by a greater richness of beta-lactamase genes (genes conferring resistance to penicillins and cephalosporins). Raccoon and stray dog samples had the most ARGs in common, suggesting possible exposure to similar environmental sources of ARGs. In addition to identifying clinically relevant ARGs (e.g. blaCMY and qnrB), some ARGs were linked to the class 1 integrase gene, intI1, which may indicate anthropogenic origin. Findings from this pilot investigation suggest that the microbial communities of suburban mesocarnivores and stray dogs can host ARGs that can confer resistance to several antimicrobials used in human and veterinary medicine. © 2020 Blackwell Verlag GmbH.The highly polarized, typically very long, and nonmitotic nature of neurons present them with unique challenges in the maintenance of their homeostasis. This architectural complexity serves a rich and tightly controlled set of functions that enables their fast communication with neighboring cells and endows them with exquisite plasticity. The submembrane neuronal cytoskeleton occupies a pivotal position in orchestrating the structural patterning that determines local and long-range subcellular specialization, membrane dynamics, and a wide range of signaling events. At its center is the partnership between ankyrins and spectrins, which self-assemble with both remarkable long-range regularity and micro- and nanoscale specificity to precisely position and stabilize cell adhesion molecules, membrane transporters, ion channels, and other cytoskeletal proteins. To accomplish these generally conserved, but often functionally divergent and spatially diverse, roles these partners use a combinatorial program of a couple of dozens interacting family members, whose code is not fully unraveled. In a departure from their scaffolding roles, ankyrins and spectrins also enable the delivery of material to the plasma membrane by facilitating intracellular transport. Thus, it is unsurprising that deficits in ankyrins and spectrins underlie several neurodevelopmental, neurodegenerative, and psychiatric disorders. Here, I summarize key aspects of the biology of spectrins and ankyrins in the mammalian neuron and provide a snapshot of the latest advances in decoding their roles in the nervous system. © 2020 Wiley Periodicals, Inc.