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Covington Lehman
Covington Lehman

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Overall, repair did not occur in adults. These results identify an exciting cellular mechanism of neonatal AF regeneration that is predominantly driven by Scx-lineage annulocytes.Currently, there are no markers to identify patients with liver-only or liver-dominant metastases that would benefit from hepatic surgery. Here we characterized histopathological growth patterns (HGPs) of liver metastases in a consecutive series of 36 breast cancer patients who underwent hepatic surgery. Survival analyses showed that the presence of a desmoplastic HGP in the liver metastases (a rim of fibrous tissue separating cancer cells from the liver parenchyma, present in 20 (56%) patients) is independently associated with favorable progression-free and overall survival when compared with the replacement HGP (cancer cells growing into the liver parenchyma, present in 16 (44%) patients).RNA synthesis is central to life, and RNA polymerase (RNAP) depends on accessory factors for recovery from stalled states and adaptation to environmental changes. Here, we investigated the mechanism by which a helicase-like factor HelD recycles RNAP. We report a cryo-EM structure of a complex between the Mycobacterium smegmatis RNAP and HelD. The crescent-shaped HelD simultaneously penetrates deep into two RNAP channels that are responsible for nucleic acids binding and substrate delivery to the active site, thereby locking RNAP in an inactive state. We show that HelD prevents non-specific interactions between RNAP and DNA and dissociates stalled transcription elongation complexes. The liberated RNAP can either stay dormant, sequestered by HelD, or upon HelD release, restart transcription. Our results provide insights into the architecture and regulation of the highly medically-relevant mycobacterial transcription machinery and define HelD as a clearing factor that releases RNAP from nonfunctional complexes with nucleic acids.We present a method that measures the accuracy of NMR protein structures. It compares random coil index [RCI] against local rigidity predicted by mathematical rigidity theory, calculated from NMR structures [FIRST], using a correlation score (which assesses secondary structure), and an RMSD score (which measures overall rigidity). We test its performance using structures refined in explicit solvent, which are much better than unrefined structures; decoy structures generated for 89 NMR structures; and conventional predictors of accuracy such as number of restraints per residue, restraint violations, energy of structure, ensemble RMSD, Ramachandran distribution, and clashscore. Restraint violations and RMSD are poor measures of accuracy. Comparisons of NMR to crystal structures show that secondary structure is equally accurate, but crystal structures are typically too rigid in loops, whereas NMR structures are typically too floppy overall. We show that the method is a useful addition to existing measures of accuracy.The majority of the area contaminated by the Fukushima Daiichi Nuclear Power Plant accident is covered with forests. We developed a dataset for radiocaesium (137Cs) in trees, soil, and mushrooms measured at numerous forest sites. The 137Cs activity concentration and inventory data reported in scientific journal papers written in English and Japanese, governmental reports, and governmental monitoring data on the web were collated. The ancillary information describing the forest stands were also collated, and further environmental information (e.g. climate) was derived from the other databases using longitude and latitude coordinates of the sampling locations. The database contains 8593, 4105, and 3189 entries of activity concentration data for trees, soil, and mushrooms, and 471 and 3521 entries of inventory data for trees and soil, respectively, which were collected from 2011 to 2017, and covers the entire Fukushima prefecture. The data can be used to document and understand the spatio-temporal dynamics of radiocaesium in the affected region and to aid the development and validation of models of radiocaesium dynamics in contaminated forests.In bacteria, transcription complexes stalled on DNA represent a major source of roadblocks for the DNA replication machinery that must be removed in order to prevent damaging collisions. Gram-positive bacteria contain a transcription factor HelD that is able to remove and recycle stalled complexes, but it was not known how it performed this function. Here, using single particle cryo-electron microscopy, we have determined the structures of Bacillus subtilis RNA polymerase (RNAP) elongation and HelD complexes, enabling analysis of the conformational changes that occur in RNAP driven by HelD interaction. HelD has a 2-armed structure which penetrates deep into the primary and secondary channels of RNA polymerase. One arm removes nucleic acids from the active site, and the other induces a large conformational change in the primary channel leading to removal and recycling of the stalled polymerase, representing a novel mechanism for recycling transcription complexes in bacteria.Sexual reproduction is almost ubiquitous among extant eukaryotes. As most asexual lineages are short-lived, abandoning sex is commonly regarded as an evolutionary dead end. Still, putative anciently asexual lineages challenge this view. One of the most striking examples are bdelloid rotifers, microscopic freshwater invertebrates believed to have completely abandoned sexual reproduction tens of Myr ago. Here, we compare whole genomes of 11 wild-caught individuals of the bdelloid rotifer Adineta vaga and present evidence that some patterns in its genetic variation are incompatible with strict clonality and lack of genetic exchange. These patterns include genotype proportions close to Hardy-Weinberg expectations within loci, lack of linkage disequilibrium between distant loci, incongruent haplotype phylogenies across the genome, and evidence for hybridization between divergent lineages. Analysis of triallelic sites independently corroborates these findings. Our results provide evidence for interindividual genetic exchange and recombination in A. vaga, a species previously thought to be anciently asexual.Pharmaceutical drugs targeting dyslipidemia and cardiovascular disease (CVD) may increase the risk of fatty liver disease and other metabolic disorders. To identify potential novel CVD drug targets without these adverse effects, we perform genome-wide analyses of participants in the HUNT Study in Norway (n = 69,479) to search for protein-altering variants with beneficial impact on quantitative blood traits related to cardiovascular disease, but without detrimental impact on liver function. We identify 76 (11 previously unreported) presumed causal protein-altering variants associated with one or more CVD- or liver-related blood traits. Nine of the variants are predicted to result in loss-of-function of the protein. This includes ZNF529p.K405X, which is associated with decreased low-density-lipoprotein (LDL) cholesterol (P = 1.3 × 10-8) without being associated with liver enzymes or non-fasting blood glucose. Silencing of ZNF529 in human hepatoma cells results in upregulation of LDL receptor and increased LDL uptake in the cells. This suggests that inhibition of ZNF529 or its gene product should be prioritized as a novel candidate drug target for treating dyslipidemia and associated CVD.Over 250 million people suffer from schistosomiasis, a tropical disease caused by parasitic flatworms known as schistosomes. Humans become infected by free-swimming, water-borne larvae, which penetrate the skin. The earliest intra-mammalian stage, called the schistosomulum, undergoes a series of developmental transitions. These changes are critical for the parasite to adapt to its new environment as it navigates through host tissues to reach its niche, where it will grow to reproductive maturity. Unravelling the mechanisms that drive intra-mammalian development requires knowledge of the spatial organisation and transcriptional dynamics of different cell types that comprise the schistomulum body. To fill these important knowledge gaps, we perform single-cell RNA sequencing on two-day old schistosomula of Schistosoma mansoni. We identify likely gene expression profiles for muscle, nervous system, tegument, oesophageal gland, parenchymal/primordial gut cells, and stem cells. In addition, we validate cell markers for all these clusters by in situ hybridisation in schistosomula and adult parasites. Taken together, this study provides a comprehensive cell-type atlas for the early intra-mammalian stage of this devastating metazoan parasite.BACKGROUND Up to 47% of pregnant women with COVID-19 have preterm deliveries. A severe, symptomatic COVID-19 infection in close-to-term pregnancies can have a poor prognosis. Early identification of COVID-19 in pregnant women can prevent the progression of the disease. Currently, there is very little guidance on treating pregnant close-to-term women with COVID-19; this case report suggests changes to current management to maximize positive maternal and fetal outcomes. CASE REPORT A pregnant woman (37 weeks of gestation) presented to the Emergency Department with a chief complaint of fever with an associated cough for 2 days. She was diagnosed with COVID-19 in the Emergency Department, and discharged in a stable condition. She returned 5 days later in preterm labor with severe respiratory distress. After an emergency cesarean section, she remained intubated in the Surgical Intensive Care Unit; she was persistently hypotensive and hypoxic despite maximal ventilator and medical treatment. She died after a cardiac arrest and unsuccessful resuscitation, 15 days after the delivery. selleckchem We discuss the possible benefit of a planned C-section for close-to-term pregnancies prior to the onset of COVID-19 symptoms. The patient's next of kin gave informed consent for this case report. Approval from the Institutional Review Board or Ethics Review Board was not required as this is a case report. CONCLUSIONS Currently, asymptomatic pregnant women are not tested for COVID-19 infection until hospitalization for delivery. It could be beneficial to have a protocol in place to screen asymptomatic pregnant women so they can be identified early and monitored, as COVID-19 symptoms can escalate quickly.BACKGROUND Emerging studies noted that liver injury in coronavirus disease 2019 (COVID-19) patients may be induced by virus-mediated inflammation, which was confirmed by liver pathology. The aim of this study was to observe clinical characteristics and explore risk factors in COVID-19 patients with liver injury. MATERIAL AND METHODS In this retrospective study, 40 confirmed COVID-19 patients with normal alanine transaminase (ALT) on admission were divided into a group of normal ALT patients whose ALT was always less than 40 U/l during hospitalization and a group of elevated ALT patients whose ALT was at least once more than 40 U/l after admission. Clinical data, especially virus-induced inflammatory parameters, were analyzed for risk factors and predictive value. The Mann-Whitney U test and t test for comparing means and logistic regression were performed for analysis of risk factors. Area under the ROC curve was used for predictive values. RESULTS Sixteen of 40 (40.0%) patients developed elevated ALT, many of them with more severe COVID-19.selleckchem

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