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Hydrothermal pretreatment (HTP) conditions were optimized for continuous mesophilic (MAD) and thermophilic (TAD) anaerobic digestion of high-solid sludge (10-11% total solids). COD solubilization increased with prolonged HTP durations, and became not significant after 210 min. According to the methane production rate and energy consumption, the optimal HTP temperature was determined at 160 °C. Regarding continuous operation without HTP, TAD achieved higher methane yield and volatile solids (VS) reduction, at 0.12 L/g VSadded and 23.9%, respectively. After HTP, methane yield and VS reduction in MAD and TAD were increased by 400% and 191% (MAD), 67% and 72% (TAD), respectively. TAD was limited due to the inhibition from about 2800 mg/L of NH4+-N concentration. The methanogenic activity of MAD was enhanced, whereas TAD displayed a reduced value owing to ammonia inhibition. Ultimately, MAD with HTP and TAD without HTP achieved the higher energy balance, 5.25 and 3.27 kJ/g VS, respectively.The complex glycans comprising 'dietary fiber' evade the limited repertoire of human digestive enzymes and hence feed the vast community of microbes in the lower gastrointestinal tract. As such, complex glycans drive the composition of the human gut microbiota and, in turn, influence diverse facets of our nutrition and health. To access these otherwise recalcitrant carbohydrates, gut bacteria produce coordinated, substrate-specific arsenals of carbohydrate-active enzymes, glycan-binding proteins, oligosaccharide transporters, and transcriptional regulators. A recent explosion of biochemical and enzymological studies of these systems has led to the discovery of manifold new carbohydrate-active enzyme (CAZyme) families. Crucially underpinned by structural biology, these studies have also provided unprecedented molecular insight into the exquisite specificity of glycan recognition in the diverse CAZymes and non-catalytic proteins from the HGM. DOX inhibitor chemical structure The revelation of a multitude of new three-dimensional structures and substrate complexes constitutes a 'gold rush' in the structural biology of the human gut microbiota.The United States currently has one of the highest numbers of cumulative COVID-19 cases globally, and Latino and Black communities have been disproportionately affected. Understanding the community-level factors that contribute to disparities in COVID-19 case and death rates is critical to developing public health and policy strategies. We performed a cross-sectional analysis of U.S. counties and found that a 10% point increase in the Black population was associated with 324.7 additional COVID-19 cases per 100,000 population and 14.5 additional COVID-19 deaths per 100,000. In addition, we found that a 10% point increase in the Latino population was associated with 293.5 additional COVID-19 cases per 100,000 and 7.6 additional COVID-19 deaths per 100,000. Independent predictors of higher COVID-19 case rates included average household size, the share of individuals with less than a high school diploma, and the percentage of foreign-born non-citizens. In addition, average household size, the share of individuals with less than a high school diploma, and the proportion of workers that commute using public transportation independently predicted higher COVID-19 death rates within a community. After adjustment for these variables, the association between the Latino population and COVID-19 cases and deaths was attenuated while the association between the Black population and COVID-19 cases and deaths largely persisted. Policy efforts must seek to address the drivers identified in this study in order to mitigate disparities in COVID-19 cases and deaths across minority communities.

Antimicrobial resistance (AMR) poses a major threat to human health. Whole-genome sequencing holds great potential for AMR identification; however, there remain major gaps in accurately and comprehensively detecting AMR across the spectrum of AMR-conferring determinants and pathogens.

Using 16 wild-type Burkholderia pseudomallei and 25 with acquired AMR, we first assessed the performance of existing AMR software (ARIBA, CARD, ResFinder, and AMRFinderPlus) for detecting clinically relevant AMR in this pathogen. B. pseudomallei was chosen due to limited treatment options, high fatality rate, and AMR caused exclusively by chromosomal mutation (i.e. single-nucleotide polymorphisms [SNPs], insertions-deletions [indels], copy-number variations [CNVs], inversions, and functional gene loss). Due to poor performance with existing tools, we developed ARDaP (Antimicrobial Resistance Detection and Prediction) to identify the spectrum of AMR-conferring determinants in B. pseudomallei.

CARD, ResFinder, and AMRFinderPes can be constructed for any microbial species of interest for comprehensive AMR detection.

National Health and Medical Research Council (BJC, EPP, DSS); Australian Government (DEM, ES); Advance Queensland (EPP, DSS).

National Health and Medical Research Council (BJC, EPP, DSS); Australian Government (DEM, ES); Advance Queensland (EPP, DSS).In this review we describe the application of CRISPR tools for functional genomics screens in bacteria, with a focus on the use of interference (CRISPRi) approaches. We review recent developments in CRISPRi titration, which has enabled essential gene functional screens, and genome-scale pooled CRISPRi screens. We summarize progress toward enabling CRISPRi screens in non-model and pathogenic bacteria, including the development of new dCas9 variants. Taking into account the current state of the field, we provide a forward-looking analysis of CRISPRi strategies for determining gene function in bacteria.

Placental passage of drugs in twins is poorly understood, and is unknown regarding antiretrovirals (ARVs). In the event of large differences in the exposure of 2 twins to the same maternal therapy, this could have a clinical impact in terms of prevention of perinatal HIV transmission or adverse effects.

To describe the frequency of differential transplacental passage of antiretrovirals between twins.

The study was performed retrospectively, on data from women included in a multicenter perinatal HIV cohort study. All twin pairs for which the mother received antiretroviral therapy and for which drug concentrations in both of the umbilical cords after cord clamping at delivery were studied. We considered that a difference in concentrations of more than 50 % between twins was a substantial difference (ratios below 0.67 or above 1.50).

We analyzed 29 twin pairs, 27 dichorionic and 2 monochorionic diamniotic. Cord blood concentrations differed between the 2 twins by more than 50 % for at least one ARV in 9 twin pairs, 8 dichorionic and 1 monochorionic.

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