Broadly Neutralizing Antibodies for HIV Prevention

In the last decade, over a dozen potent broadly neutralizing antibodies (bnAbs) to several HIV envelope protein epitopes have been identified, and their in vitro neutralization profiles have been defined. Many have demonstrated prevention efficacy in preclinical trials and favorable safety and pharmacokinetic profiles in early human clinical trials. The first human prevention efficacy trials using 10 sequential, every-two-month administrations…
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The authors used single cell transcriptomic techniques to compare retinal organoids to normal fetal development. At least for the first few months of development, the stem cell-derived organoids were pretty close to the normal retina, but as time went on, they diverged in several ways. They made a new type of organ culture, called retinospheres that much more like the normal fetal cells, even after long periods of time in culture dishes.
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Stimulator of interferon genes (STING) plays a central role in sensing intracellular DNA in mammalian cells. By studying the ability of adenoviral oncoprotein E1A to repress DNA sensing in human cells, Burleigh et al. have found a STING-independent intracellular DNA sensing pathway that relies on DNA-dependent protein kinase (DNA-PK). They report that DNA-PK–dependent DNA sensing pathway is not activated by cyclic guanosine…
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The human gene catalogue is essentially complete, but we lack an equivalently vetted inventory of bona fide human enhancers. Hundreds of thousands of candidate enhancers have been nominated via biochemical annotations; however, only a handful of these have been validated and confidently linked to their target genes. Here we review emerging technologies for discovering, characterizing and validating human enhancers at…
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Most infants with cystic fibrosis (CF) have pancreatic exocrine insufficiency that results in nutrient malabsorption and requires oral pancreatic enzyme replacement. Newborn screening for CF has enabled earlier diagnosis, nutritional intervention and enzyme replacement for these infants, allowing most infants with CF to achieve their weight goals by 12 months of age1. Nevertheless, most infants with CF continue to have…
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Patients with cystic fibrosis (CF) have altered fecal microbiomes compared to those of healthy controls. The magnitude of this dysbiosis correlates with measures of CF gastrointestinal (GI) disease, including GI inflammation and nutrient malabsorption. However, whether this dysbiosis is caused by mutations in the CFTR gene, the underlying defect in CF, or whether CF-associated dysbiosis augments GI disease was not…
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It is known that capillaries in vivo are often blocked or obstructed in these diseases, which block blood flow to cause organ damage. There is no good understanding or effective treatment. The authors modeled the interactions of red blood cells with capillaries that mimicked in vivo structures, and demonstrated the sequential role of biochemical and biophysical factors of infected RBCs in their sequestration and microvascular occlusion in the capillaries.
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Metabolic syndrome, including obesity and insulin resistance, compromises energy metabolism, mitochondrial function and heart performance. The authors found that lipid overload decreased NAD+ levels and increased the acetylation of a fission protein Drp1 at K642. This mechanism promoted Drp1 activation, mitochondrial translocation, VDAC1 binding, and eventually mitochondrial fission and heart cell dysfunction.
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Deletions within genes coding for subunits of the transcription coactivator SAGA caused strong genome-wide defects in transcription and SAGA-mediated chromatin modifications. In contrast, rapid SAGA depletion produced only modest transcription defects at 13% of protein-coding genes – genes that are generally more sensitive to rapid TFIID depletion. However, transcription of these ‘coactivator-redundant’ genes is strongly affected by rapid depletion of…
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Chimeric antigen receptor (CAR) T-cell therapy has produced remarkable anti-tumor responses in patients with B-cell malignancies. However, clonal kinetics and transcriptional programs that regulate the fate of CAR-T cells after infusion remain poorly understood. Here we perform TCRB sequencing, integration site analysis, and single-cell RNA sequencing (scRNA-seq) to profile CD8+ CAR-T cells from infusion products (IPs) and blood of patients undergoing…
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