For use in prevention and treatment, HIV-1 broadly neutralizing antibodies (bnAbs) have to overcome Env conformational heterogeneity of viral quasispecies and neutralize with constant high potency. Comparative analysis of neutralization data from the CATNAP database revealed a nuanced relationship between bnAb activity and Env conformational flexibility, with substantial epitope-specific variation of bnAb potency ranging from increased to decreased activity against open, neutralization-sensitive Env. To systematically investigate the impact of variability in Env conformation on bnAb potency we screened 126 JR-CSF point mutants for generalized neutralization sensitivity to weakly neutralizing antibodies (weak-nAbs) depending on trimer opening and plasma from people with chronic HIV-1 infection.
View Article and Find Full Text PDFLife cycle assessment (LCA) was used, next to green chemistry concepts, to compare the full environmental impacts of the epoxidation of a bio-based monomer, which can be used for the synthesis of vitrimers. On a laboratory scale, the synthesis of the monomer can either be done via a petrochemical route or via an enzymatic reaction pathway. Both reaction pathways were initially optimized to minimize the impact of suboptimal routes on the sustainability evaluation.
View Article and Find Full Text PDFNutrient-dependent mTORC1 regulation upon amino acid deprivation is mediated by the KICSTOR complex, comprising SZT2, KPTN, ITFG2, and KICS2, recruiting GATOR1 to lysosomes. Previously, pathogenic SZT2 and KPTN variants have been associated with autosomal recessive intellectual disability and epileptic encephalopathy. We identified bi-allelic KICS2 variants in eleven affected individuals presenting with intellectual disability and epilepsy.
View Article and Find Full Text PDFIn the age of big data and open science, what processes are needed to follow open science protocols while upholding Indigenous Peoples' rights? The Earth Data Relations Working Group (EDRWG), convened to address this question and envision a research landscape that acknowledges the legacy of extractive practices and embraces new norms across Earth science institutions and open science research. Using the National Ecological Observatory Network (NEON) as an example, the EDRWG recommends actions, applicable across all phases of the data lifecycle, that recognize the sovereign rights of Indigenous Peoples and support better research across all Earth Sciences.
View Article and Find Full Text PDFThe purpose of this study was to investigate the evolution of digit health (DH) on Swiss dairy farms participating in a nationwide DH program and to identify risk factors associated with poor DH. Specially trained claw trimmers recorded disorders of the digits (DOD) electronically during routine trimmings between January 2020 and June 2023. The first part of the study was a non-randomized controlled implementation study, comparing the evolution of DH in 75 herds that received professional on-farm risk assessments as well as veterinary advice with 49 herds that did not.
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