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Drug-induced phospholipidosis confounds drug repurposing for SARS-CoV-2

Repurposing drugs as treatments for COVID-19 has drawn much attention. Beginning with sigma receptor ligands, and expanding to other drugs from screening in the field, we became concerned that phospholipidosis was a shared mechanism underlying the antiviral activity of many repurposed drugs. For all of the 23 cationic amphiphilic drugs tested, including...

Chimeric spike mRNA vaccines protect against Sarbecovirus challenge in mice

The emergence of SARS-CoV in 2003 and SARS-CoV-2 in 2019 highlights the need to develop universal vaccination strategies against the broader Sarbecovirus subgenus. Using chimeric spike designs, we demonstrate protection against challenge from SARS-CoV, SARS-CoV-2, SARS-CoV-2 B.1.351, bat CoV (Bt-CoV) RsSHC014, and a heterologous Bt-CoV WIV-1 in vulnerable...

ARPA-H: Accelerating biomedical breakthroughs

A DARPA-like culture at NIH can drive biomedical and health advances

Plant "helper" immune receptors are Ca2+-permeable nonselective cation channels

Plant nucleotide-binding leucine-rich repeat receptors (NLRs) regulate immunity and cell death. In Arabidopsis, a subfamily of "helper" NLRs are required by many "sensor" NLRs. Active NRG1.1 oligomerized, was enriched in plasma membrane puncta and conferred cytoplasmic Ca2+ influx in plant and human cells. NRG1.1-dependent Ca2+ influx and cell death...

Interfacial ferroelectricity by van der Waals sliding

Despite their partial ionic nature, many layered diatomic crystals avoid internal electric polarization by forming a centrosymmetric lattice at their optimal van-der-Waals stacking. Here, we report a stable ferroelectric order emerging at the interface between two naturally-grown flakes of hexagonal-boron-nitride, which are stacked together in a metastable...

Glaciohydrology of the Himalaya-Karakoram

Understanding the response of Himalayan-Karakoram (HK) rivers to climate change is crucial for ~1 billion people who partly depend on these water resources. Policymakers tasked with the sustainable water resources management for agriculture, hydropower, drinking, sanitation, and hazards require an assessment of rivers’ current status and potential future...

A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya

On 7 Feb 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. Over 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos...

Senolytics reduce coronavirus-related mortality in old mice

The COVID-19 pandemic has revealed the pronounced vulnerability of the elderly and chronically-ill to SARS-CoV-2-induced morbidity and mortality. Cellular senescence contributes to inflammation, multiple chronic diseases, and age-related dysfunction, but effects on responses to viral infection are unclear. Here, we demonstrate that senescent cells (SnC)...

Estimating epidemiologic dynamics from cross-sectional viral load distributions

Estimating an epidemic’s trajectory is crucial for developing public health responses to infectious diseases, but case data used for such estimation are confounded by variable testing practices. We show that the population distribution of viral loads observed under random or symptom-based surveillance, in the form of cycle threshold (Ct) values obtained...

Heterogeneity of meningeal B cells reveals a lymphopoietic niche at the CNS borders

The meninges contain adaptive immune cells that provide immunosurveillance of the CNS. These cells are thought to derive from the systemic circulation. Through single-cell analyses, confocal imaging, bone marrow chimeras, and parabiosis experiments, we show that meningeal B cells derive locally from the calvaria, which harbors a bone marrow niche for...

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