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A double-blind randomized trial of hyperbaric oxygen for persistent symptoms after brain injury

Broadly neutralizing antibodies isolated from HEV convalescents confer protective effects in human liver-chimeric mice

Abstract Hepatitis E virus (HEV) causes 3.3 million symptomatic cases and 44,000 deaths per year. Chronic infections can arise in immunocompromised individuals, and pregnant women may suffer from fulminant disease as a consequence of HEV infection. Despite these important implications for public health, no specific antiviral treatment has been approved to date. Here, we report combined functional, biochemical, and X-ray crystallographic studies that characterize the human antibody response in convalescent HEV patients. We identified a class of potent and broadly neutralizing human antibodies (bnAbs), targeting a quaternary epitope located at the tip of the HEV capsid protein pORF2 that contains an N-glycosylation motif and is conserved across members of the Hepeviridae. These glycan-sensitive bnAbs specifically recognize the non-glycosylated pORF2 present in infectious particles but not the secreted glycosylated form acting as antibody decoy. Our most potent bnAb protects human liver-chimeric mice from intraperitoneal HEV challenge and co-housing exposure. These results provide insights into the bnAb response to this important emerging pathogen and support the development of glycan-sensitive antibodies to combat HEV infection.

Modified raw cellulose filaments material as polyol substitute in rigid insulating polyurethane foam

ETVs dictate hPSC differentiation by tuning biophysical properties

Abstract Stem cells maintain a dynamic dialog with their niche, integrating biochemical and biophysical cues to modulate cellular behavior. Yet, the transcriptional networks that regulate cellular biophysical properties remain poorly defined. Here, we leverage human pluripotent stem cells (hPSCs) and two morphogenesis models – gastruloids and pancreatic differentiation – to establish ETV transcription factors as critical regulators of biophysical parameters and lineage commitment. Genetic ablation of ETV1 or ETV1/ETV4/ETV5 in hPSCs enhances cell-cell and cell-ECM adhesion, leading to aberrant multilineage differentiation including disrupted germ-layer organization, ectoderm loss, and extraembryonic cell overgrowth in gastruloids. Furthermore, ETV1 loss abolishes pancreatic progenitor formation. Single-cell RNA sequencing and follow-up assays reveal dysregulated mechanotransduction via the PI3K/AKT signaling. Our findings highlight the importance of transcriptional control over cell biophysical properties and suggest that manipulating these properties may improve in vitro cell and tissue engineering strategies.

Fusion of circulant singular spectrum analysis and multiscale local ternary patterns for effective spectral-spatial feature extraction and small sample hyperspectral image classification

Reversible ubiquitination conferred by domain shuffling controls paired NLR immune receptor complex homeostasis in plant immunity

Berberine inhibits the tarO gene to impact MRSA cell wall synthesis

PBRM1 directs PBAF to pericentromeres and protects centromere integrity

Abstract The specialised structure of the centromere is critical for effective chromosome segregation, but its repetitive nature makes it vulnerable to rearrangements. Centromere fragility can drive tumorigenesis, but protective mechanisms preventing fragility are still not fully understood. The PBAF chromatin remodelling complex is frequently misregulated in cancer, but its role in cancer is incompletely characterized. Here, we identify PBAF as a protector of centromere and pericentromere structure with profound consequences for genome stability. A conserved feature of isogenic cell lines lacking PBRM1, a subunit of PBAF, is compromised centromere and pericentromere integrity. PBAF is present at these regions, and binding patterns of PBAF and H3K9 methylation change when PBRM1 is absent. PBRM1 loss creates a dependence on the spindle assembly checkpoint, which represents a therapeutic vulnerability. Importantly, we find that even in the absence of any perturbations, PBRM1 loss leads to centromere fragility, thus identifying a key player in centromere protection.

Dietary protein intake and stomach cancer, insights from a case-control study

Unveiling the neglected role of oxygen doping in nitrogen-doped carbon for enhanced capacitive deionization performance

Enhanced water transport when a tropical storm meets an atmospheric cold front

The Drosophila epidermal growth factor receptor pathway regulates Hedgehog signalling and cytoneme behaviour

Factors associated with reduction in quality of life after SARS-CoV-2 infection

Abstract Long-term changes in health-related quality of life (HrQoL) after SARS-CoV-2 infection are common, but their causes and consequences are poorly understood. This prospective, population-based study examined associations between HrQoL and 49 demographic and clinical variables. HrQoL was assessed using the European Quality-of-Life-5-Dimensions-5-Level-Version in 3,475 participants (56% female; aged 18–88 years) approximately 9 months (baseline) and 26 months (follow-up) after their initial infection. Results were compared with the demographic and clinical variables using recursive feature elimination and random forest regression analyses. A statistically significant improvement in HrQoL was observed during the observation period. At baseline, 39% of the variance in HrQoL was explained by fatigue, muscle pain, number of remaining symptoms (RS), perceived stress, and age. At follow-up, fatigue, RS, perceived stress, muscle and joint pain, and age explained 54% of the variance in HrQoL. Changes in HrQoL were associated with changes in fatigue, RS, and perceived stress, meaning that if these decreased from baseline to follow-up, then HrQoL was improved. However, it was not possible to predict whether an individual’s HrQoL would improve or worsen 1 year later based on baseline variable scores. The aforementioned symptoms are specifically associated with impairment in the population’s usual activities.

Precise placement of thioester bonds into sequence-controlled polymers containing ABAC-type units

Relationship between glucose to lymphocyte ratio and the first peritonitis episode in patients treated with peritoneal dialysis

Back to chromite as a mineralogical strategy for long-term chromium pollution control

Urinary prostaglandin D2 and E2 metabolites are elevated with disease severity in patients with Fukuyama congenital muscular dystrophy

Size control and oscillations of active droplets in synthetic cells

Abstract Oscillations in the formation and dissolution of molecular assemblies inside living cells are pivotal in orchestrating various cellular functions and processes. However, designing such rhythmic patterns in synthetic cells remains a challenge. Here, we demonstrate the spontaneous emergence of spatio-temporal oscillations in the number of droplets, size, and their spatial distribution within a synthetic cell. The coacervate-based droplets in these synthetic cells sediment and fuse at the cell’s bottom. Through a size control mechanism, the sedimented, large droplets shrink by expelling droplet material. The expelled molecules nucleate new droplets at the top of the synthetic cell, which grow and sediment again. These oscillations are sustained by converting chemical fuel into waste and can continue for hundreds of periods without evidence of fatigue. Strikingly, the period of the oscillation is in the minute’s regime and tunable. The design of oscillating artificial organelles in synthetic cells brings us closer to creating more life-like materials and de novo life.

Rates of female mouse ultrasonic vocalizations are low and are not modulated by estrous state during interactions with muted males

Structures of TGF-β with betaglycan and signaling receptors reveal mechanisms of complex assembly and signaling

Abstract Betaglycan (BG) is a transmembrane co-receptor of the transforming growth factor-β (TGF-β) family of signaling ligands. It is essential for embryonic development, tissue homeostasis and fertility in adults. It functions by enabling binding of the three TGF-β isoforms to their signaling receptors and is additionally required for inhibin A (InhA) activity. Despite its requirement for the functions of TGF-βs and InhA in vivo, structural information explaining BG ligand selectivity and its mechanism of action is lacking. Here, we determine the structure of TGF-β bound both to BG and the signaling receptors, TGFBR1 and TGFBR2. We identify key regions responsible for ligand engagement, which has revealed binding interfaces that differ from those described for the closely related co-receptor of the TGF-β family, endoglin, thus demonstrating remarkable evolutionary adaptation to enable ligand selectivity. Finally, we provide a structural explanation for the hand-off mechanism underlying TGF-β signal potentiation.