ACE2 and TMPRSS2 are key players on SARS-CoV-2 entry into host cells. However, it is still unclear whether expression levels of these factors could reflect disease severity. Here, a case–control study was conducted with 213 SARS-CoV-2 positive individuals where cases were defined as COVID-19 patients with respiratory distress requiring oxygen support (N = 38) and controls were those with mild to moderate symptoms of the disease who did not need oxygen therapy along the entire clinical course (N = 175). ACE2 and TMPRSS2 mRNA levels were evaluated in nasopharyngeal swab samples by RT-qPCR and logistic regression analyzes were applied to estimate associations with respiratory outcomes. ACE2 and TMPRSS2 levels positively correlated with age, which was also strongly associated with respiratory distress. Increased nasopharyngeal ACE2 levels showed a protective effect against this outcome (adjOR = 0.30; 95% CI 0.09–0.91), while TMPRSS2/ACE2 ratio was associated with risk (adjOR = 4.28; 95% CI 1.36–13.48). On stepwise regression, TMPRSS2/ACE2 ratio outperformed ACE2 to model COVID-19 severity. When nasopharyngeal swabs were compared to bronchoalveolar lavages in an independent cohort of COVID-19 patients under mechanical ventilation, similar expression levels of these genes were observed. These data suggest nasopharyngeal TMPRSS2/ACE2 as a promising candidate for further prediction models on COVID-19.
The evolution of sex chromosomes and their differentiation from autosomes is a major event during genome evolution that happened many times in several lineages.The repeated evolution and lability of sex-determination mechanisms in fishes makes this a well-suited system to test for general patterns in evolution. According to current theory, differentiation is triggered by the suppression of recombination following the evolution of a new master sex-determining gene. However, the molecular mechanisms that establish recombination suppression are known from few examples, owing to the intrinsic difficulties of assembling sex-determining regions (SDRs). The development of forward-genetics and long-read sequencing have generated a wealth of data questioning central aspects of the current theory. Here, we demonstrate that sex in Midas cichlids is determined by an XY system, and identify and assemble the SDR by combining forward-genetics, long-read sequencing and optical mapping. We show how long-reads aid in the detection of artefacts in genotype-phenotype mapping that arise from incomplete genome assemblies. The male-specific region is restricted to a 100-kb segment on chromosome 4 that harbours transposable elements and a Y-specific duplicate of the anti-Mullerian receptor 2 gene, which has evolved master | 1399 NACIF et Al.
Trinomys, one of the most species-rich spiny rat genera in Brazil, is widely distributed in Caatinga, Cerrado and Atlantic Forest biomes, and currently includes ten recognized species, three of which are polytypic. Although some studies employing molecular data have been conducted to better characterize phylogenetic relationships among species, 19 nominal taxa have been suggested, implying considerable incongruence regarding species boundaries. We addressed this incongruence by intensively sampling all species across the geographic distribution of the genus. In addition to publicly available data, we generated 182 mt-Cytb gene sequences, and employed phylogenetic and computational species delimitation methods to obtain a clearer picture of the genus diversity. Moreover, we evaluated populational diversity within each accepted species, considering their geographical distribution and a timescale for the evolution of the genus. Beyond confirming the general patterns described for the evolution of the group, this new analysis suggests that Trinomys is comprised of at least 16 evolutionary lineages, 13 of them recognized as species or subspecies, and three never before characterized. This study highlights the importance of increased sample sizes and computational species delimitation methods in uncovering hidden diversity in Trinomys.
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