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Postnatal connectomic development of inhibition in mouse barrel cortex

Brain circuits in the neocortex develop from diverse types of neurons that migrate and form synapses. Here we quantify the circuit patterns of synaptogenesis for inhibitory interneurons in the developing mouse somatosensory cortex. We studied synaptic innervation of cell bodies, apical dendrites and axon initial segments using 3D electron microscopy...

COVID-19 vaccine trial ethics once we have efficacious vaccines

Some placebo-controlled trials can continue ethically after a candidate vaccine is found to be safe and efficacious

Quantum computational advantage using photons

Quantum computers promises to perform certain tasks that are believed to be intractable to classical computers. Boson sampling is such a task and is considered as a strong candidate to demonstrate the quantum computational advantage. We perform Gaussian boson sampling by sending 50 indistinguishable single-mode squeezed states into a 100-mode ultralow-loss...

A ubiquitous tire rubber-derived chemical induces acute mortality in coho salmon

In U.S. Pacific Northwest coho salmon (Oncorhynchus kisutch), stormwater exposure annually causes unexplained acute mortality when adult salmon migrate to urban creeks to reproduce. By investigating this phenomenon, we identified a highly toxic quinone transformation product of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine) (6PPD), a globally ubiquitous...

Noncanonical transnitrosylation network contributes to synapse loss in Alzheimers disease

We describe mechanistically-distinct enzymes, i.e., a kinase, a guanosine triphosphatase and a ubiquitin protein hydrolase, which function in disparate biochemical pathways, that can also act in concert to mediate a series of redox reactions. Each enzyme manifests a second, noncanonical function – transnitrosylation – triggering a pathological biochemical...

Mechanism of spliceosome remodeling by the ATPase/helicase Prp2 and its coactivator Spp2

Spliceosome remodeling, executed by conserved ATPase/helicases including Prp2, enables pre-mRNA splicing. However, the structural basis for the function of the ATPase/helicases remains poorly understood. Here, we report atomic structures of Prp2 in isolation, Prp2 complexed with its coactivator Spp2, and Prp2-loaded activated spliceosome, and results...

Human NLRP1 is a sensor for double-stranded RNA

Inflammasomes function as intracellular sensors of pathogen infection or cellular perturbation and thereby play a central role in numerous diseases. Given the high abundance of NLRP1 in epithelial barrier tissues, we screened a diverse panel of viruses for inflammasome activation in keratinocytes. We identified Semliki Forest virus (SFV), a positive-strand...

Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation

Spliceosome activation involves extensive protein and RNA rearrangements that lead to formation of a catalytically-active U2/U6 RNA structure. At present, little is known about the assembly pathway of the latter and the mechanism whereby proteins aid its proper folding. Here we report the cryo-electron microscopy structures of two human pre-Bact complexes...

Steps toward translocation-independent RNA polymerase inactivation by terminator ATPase {rho}

Factor-dependent transcription termination mechanisms are poorly understood. We determined a series of cryo-electron microscopy structures portraying the hexameric ATPase on path to terminating NusA/NusG-modified elongation complexes. An open ring contacts NusA, NusG, and multiple regions of RNA polymerase, trapping and locally unwinding proximal...

Transmission heterogeneities, kinetics, and controllability of SARS-CoV-2

A long-standing question in infectious disease dynamics concerns the role of transmission heterogeneities, driven by demography, behavior and interventions. Based on detailed patient and contact tracing data in Hunan, China we find 80% of secondary infections traced back to 15% of SARS-CoV-2 primary infections, indicating substantial transmission heterogeneities....

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