Zobrazení zdroje stránky Briggssolomon2612

© The Author(s) 2020. Published by Oxford University Press on behalf of the Society of Pediatric Psychology. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.BACKGROUND Increased pericardial adipose tissue is associated with higher risk of cardiovascular disease. We aimed to determine if HIV status was independently associated with larger pericardial adipose tissue volume and to explore possible HIV-specific risk factors. METHODS Persons with HIV (PWH) were recruited from the Copenhagen Comorbidity in HIV Infection (COCOMO) Study and matched 11 on age and sex to uninfected controls. Pericardial adipose tissue volume was measured using cardiac CT. RESULTS A total of 587 PWH and 587 controls were included. Median age was 52 years, 88% were male. HIV status was independently associated with 17 mL (95% confidence interval [10, 23]), p less then .001 larger pericardial adipose tissue volume. Larger pericardial adipose tissue volume was associated with low CD4+ nadir and prior use of stavudine, didanosine and indinavir. Among PWH without thymidine analogue or didanosine exposure, time since initiating cART (per 5-year use) was associated with l6 mL [-6, -25] lower pericardial adipose tissue volume, p=.002. CONCLUSION HIV status was independently associated with larger pericardial adipose tissue volume. Severe immunodeficiency, stavudine, didanosine and indinavir were associated with larger pericardial adipose tissue volume. PWH with prior exposure to these drugs may constitute a distinct cardiovascular risk population. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Pikas are widely distributed in the Northern Hemisphere and are highly adapted to cold and alpine environments. They are one of the most complex and problematic groups in mammalian systematics, and the origin and evolutionary history of extant pikas remain controversial. In this study, we sequenced the whole coding sequences of 105 pika samples (29 named species, 1 putative new species) and obtained DNA data for more than 10000 genes. Our phylogenomic analyses recognized four subgenera of extant pikas Alienauroa, Conothoa, Ochotona and Pika. The interrelationships between the four subgenera were strongly resolved as (Conothoa, (Alienauroa, (Ochotona, Pika))), with the mountain group Conothoa being the sister group of all other pikas. Our divergence time and phylogeographic analyses indicated that the last common ancestor of extant pikas first occurred on in the middle Miocene, approximately 14 million years ago. The emergence of opportunities related to the climate, food supply and spreading paths in concert promoted the dispersal of pikas from the Qinghai-Tibetan Plateau (QTP) to other parts of Eurasia and North America. [https://www.selleckchem.com/products/5-n-ethylcarboxamidoadenosine.html 5'-N-Ethylcarboxamidoadenosine clinical trial] We found that the genes that were positively selected in the early evolution of pikas were most concentrated in functional categories related to cold tolerance. These results suggest that the QTP may have served as a training ground for cold tolerance in early pikas, which gives pikas a great advantage when the climate continued to cool after the middle Miocene. Our study highlights the importance of the QTP as a center of origin for many cold-adapted animals. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.Our capacity to study individual cells has enabled a new level of resolution for understanding complex biological systems like multicellular organisms or microbial communities. Not surprisingly, several methods have been developed in recent years with a formidable potential to investigate the somatic evolution of single cells in both healthy and pathological tissues. However, single-cell genomic data can be quite noisy due to different technical biases, so inferences resulting from these new methods need to be carefully contrasted. Here I introduce CellCoal, a software tool for the coalescent simulation of single-cell genotypes. CellCoal simulates the history of single-cell samples obtained from somatic cell populations with different demographic histories and produces single-nucleotide variants under a variety of mutation models, sequencing read counts and genotype likelihoods, considering allelic imbalance, allelic dropout, amplification and sequencing errors, typical of this type of data. CellCoal is a flexible tool that can be used to understand the implications of different somatic evolutionary processes at the single-cell level, and to benchmark dedicated bioinformatic tools for the analysis of single-cell genotypes. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.Bacterial plasmids substantially contribute to the rapid spread of antibiotic resistance, which is a crisis in healthcare today. Coevolution of plasmids and their hosts promotes this spread of resistance by ameliorating the cost of plasmid carriage. However, our knowledge of plasmid-bacteria coevolution is solely based on studies done in well-mixed liquid cultures, even though biofilms represent the main way of bacterial life on Earth and are responsible for most infections. The spatial structure and heterogeneity provided by biofilms is known to lead to increased genetic diversity as compared to well-mixed liquids. Therefore we expect that growth in this complex environment could affect the evolutionary trajectories of plasmid-host dyads. We experimentally evolved Shewanella oneidensis MR-1 with plasmid pBP136Gm in biofilms and chemostats and sequenced the genomes of clones and populations. Biofilm populations not only maintained a higher diversity of mutations than chemostat populations, but contained a few clones with markedly more persistent plasmids that evolved via multiple distinct trajectories. These included the acquisition of a putative toxin-antitoxin transposon by the plasmid and chromosomal mutations. Some of these genetic changes resulted in loss of plasmid transferability or decrease in plasmid cost. Growth in chemostats led to a higher proportion of variants with decreased plasmid persistence, a phenomenon not detected in biofilms. We suggest that the presence of more stable plasmid-host dyads in biofilms reflects higher genetic diversity and possibly unknown selection pressures. Overall this study underscores the importance of the mode of growth in the evolution of antibiotic resistant bacteria. © The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.