We have performed two-photon ultraviolet direct frequency comb spectroscopy on the 1S-3S transition in atomic hydrogen to illuminate the so-called proton radius puzzle and to demonstrate the potential of this method. The proton radius puzzle is a significant discrepancy between data obtained with muonic hydrogen and regular atomic hydrogen that could not be explained within the framework of quantum electrodynamics. By combining our result [f1S-3S = 2,922,743,278,665.79(72) kilohertz] with a previous measurement of the 1S-2S transition frequency, we obtained new values for the Rydberg constant [R∞ = 10,973,731.568226(38) per meter] and the proton charge radius [rp = 0.8482(38) femtometers]. This result favors the muonic value over the world-average data as presented by the most recent published CODATA 2014 adjustment.Bertrand et al question our interpretation about warming effects on the thermophilization in forest plant communities and propose an alternative way to analyze climatic debt. We show that microclimate warming is a better predictor than macroclimate warming for studying forest plant community responses to warming. Their additional analyses do not affect or change our interpretations and conclusions.The number of disease risk genes and loci identified through human genetic studies far outstrips the capacity to systematically study their functions. We applied a scalable genetic screening approach, in vivo Perturb-Seq, to functionally evaluate 35 autism spectrum disorder/neurodevelopmental delay (ASD/ND) de novo loss-of-function risk genes. Using CRISPR-Cas9, we introduced frameshift mutations in these risk genes in pools, within the developing mouse brain in utero, followed by single-cell RNA-sequencing of perturbed cells in the postnatal brain.  https://www.selleckchem.com/products/cc-930.html  We identified cell type-specific and evolutionarily conserved gene modules from both neuronal and glial cell classes. Recurrent gene modules and cell types are affected across this cohort of perturbations, representing key cellular effects across sets of ASD/ND risk genes. In vivo Perturb-Seq allows us to investigate how diverse mutations affect cell types and states in the developing organism.The 14-subunit metazoan-specific Integrator contains an endonuclease that cleaves nascent RNA transcripts. Here, we identified a complex containing Integrator and protein phosphatase 2A core enzyme (PP2A-AC), termed INTAC. The 3.5-angstrom-resolution structure reveals that nine human Integrator subunits and PP2A-AC assemble into a cruciform-shaped central scaffold formed by the backbone and shoulder modules, with the phosphatase and endonuclease modules flanking the opposite sides. As a noncanonical PP2A holoenzyme, the INTAC complex dephosphorylates the carboxy-terminal repeat domain of RNA polymerase II at serine-2, -5, and -7 and thus regulates transcription. Our study extends the function of PP2A to transcriptional regulation and reveals how dual enzymatic activities-RNA cleavage and RNA polymerase II dephosphorylation-are structurally and functionally integrated into the INTAC complex.Epithelial structure is generated by the dynamic reorganization of cells in response to mechanical forces. Adherens junctions transmit forces between cells, but how cells sense and respond to these forces in vivo is not well understood. We identify a mechanotransduction pathway involving the Abl tyrosine kinase and Canoe/Afadin that stabilizes cell adhesion under tension at tricellular junctions in the Drosophila embryo. Canoe is recruited to tricellular junctions in response to actomyosin contractility, and this mechanosensitivity requires Abl-dependent phosphorylation of a conserved tyrosine in the Canoe actin-binding domain. Preventing Canoe tyrosine phosphorylation destabilizes tricellular adhesion, and anchoring Canoe at tricellular junctions independently of mechanical inputs aberrantly stabilizes adhesion, arresting cell rearrangement. These results identify a force-responsive mechanism that stabilizes tricellular adhesion under tension during epithelial remodeling.Zellweger et al (Reports, 15 May 2020, p. 772) claimed that forest plant communities' response to global warming is primarily controlled by microclimate dynamics. We show that community thermophilization is poorly explained by the underlying components of microclimate, and that global warming primarily controls the climatic lag of plant communities. Deconstructing the underlying components of microclimate provides insights for managers.Every protein has a story-how it folds, what it binds, its biological actions, and how it misbehaves in aging or disease. Stories are often inferred from a protein's shape (i.e., its structure). But increasingly, stories are told using computational molecular physics (CMP). CMP is rooted in the principled physics of driving forces and reveals granular detail of conformational populations in space and time. Recent advances are accessing longer time scales, larger actions, and blind testing, enabling more of biology's stories to be told in the language of atomistic physics.
  Technological advances and high throughput biological assays can facilitate discovery science in biobanks from population cohorts, including pregnant women. Biological pathways associated with health outcomes differ depending on geography, and high-income country data may not generalise to low-resource settings. We conducted a systematic review to identify prospective pregnancy cohorts in sub-Saharan Africa (SSA) that include biobanked samples with potential to enhance discovery science opportunity.
 
  Inclusion criteria were prospective data collection during pregnancy, with associated biobanking in SSA. Data sources included scientific databases (with comprehensive search terms), grey literature, hand searching applicable reference lists and expert input. Results were screened in a three-stage process based on title, abstract and full text by two independent reviewers. The review is registered on PROSPERO (CRD42019147483).
 
  Fourteen SSA studies met the inclusion criteria from database searches (n=8), refeing of the high regional risks of maternal, fetal and neonatal morbidity and mortality. Future studies should align protocols and consider their added value and distinct contributions.