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A cell type-specific cortico-subcortical brain circuit for investigatory and novelty-seeking behavior

Exploring the physical and social environment is essential for understanding the surrounding world. We do not know how novelty-seeking motivation initiates the complex sequence of actions that make up investigatory behavior. We found in mice that inhibitory neurons in the medial zona incerta (ZIm), a subthalamic brain region, are essential for the decision to investigate an object or a conspecific. These neurons receive excitatory input from the prelimbic cortex to signal the initiation of exploration. This signal is modulated in the ZIm by the level of investigatory motivation. Increased activity in the ZIm instigates deep investigative action by inhibiting the periaqueductal gray region. A subpopulation of inhibitory ZIm neurons expressing tachykinin 1 (TAC1) modulates the investigatory behavior.

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A prometastatic splicing program regulated by SNRPA1 interactions with structured RNA elements

Aberrant alternative splicing is a hallmark of cancer, yet the underlying regulatory programs that control this process remain largely unknown. Here, we report a systematic effort to decipher the RNA structural code that shapes pathological splicing during breast cancer metastasis. We discovered a previously unknown structural splicing enhancer that is enriched near cassette exons with increased inclusion in highly metastatic cells. We show that the spliceosomal protein small nuclear ribonucleoprotein polypeptide A' (SNRPA1) interacts with these enhancers to promote cassette exon inclusion. This interaction enhances metastatic lung colonization and cancer cell invasion, in part through SNRPA1-mediated regulation of PLEC alternative splicing, which can be counteracted by splicing modulating morpholinos. Our findings establish a noncanonical regulatory role for SNRPA1 as a prometastatic splicing enhancer in breast cancer.

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Arene diversification through distal C(sp2)-H functionalization

Transition metal–catalyzed aryl C–H activation is a powerful synthetic tool as it offers step and atom-economical routes to site-selective functionalization. Compared with proximal ortho-C–H activation, distal (meta- and/or para-) C–H activation remains more challenging due to the inaccessibility of these sites in the formation of energetically favorable organometallic pretransition states. Directing the catalyst toward the distal C–H bonds requires judicious template engineering and catalyst design, as well as prudent choice of ligands. This review aims to summarize the recent elegant discoveries exploiting directing group assistance, transient mediators or traceless directors, noncovalent interactions, and catalyst and/or ligand selection to control distal C–H activation.

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SLFN2 protection of tRNAs from stress-induced cleavage is essential for T cell-mediated immunity

Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell–specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2R fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2’s mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

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Erratum for the Report "Electrophotocatalytic diamination of vicinal C-H bonds," by T. Shen and T. H. Lambert


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Radiation-related genomic profile of papillary thyroid carcinoma after the Chernobyl accident

The 1986 Chernobyl nuclear power plant accident increased papillary thyroid carcinoma (PTC) incidence in surrounding regions, particularly for radioactive iodine (131I)–exposed children. We analyzed genomic, transcriptomic, and epigenomic characteristics of 440 PTCs from Ukraine (from 359 individuals with estimated childhood 131I exposure and 81 unexposed children born after 1986). PTCs displayed radiation dose–dependent enrichment of fusion drivers, nearly all in the mitogen-activated protein kinase pathway, and increases in small deletions and simple/balanced structural variants that were clonal and bore hallmarks of nonhomologous end-joining repair. Radiation-related genomic alterations were more pronounced for individuals who were younger at exposure. Transcriptomic and epigenomic features were strongly associated with driver events but not radiation dose. Our results point to DNA double-strand breaks as early carcinogenic events that subsequently enable PTC growth after environmental radiation exposure.

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What's in a name?


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New Products


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Watersheds may not recover from drought

The Millennium Drought (southeastern Australia) provided a natural experiment to challenge the assumption that watershed streamflow always recovers from drought. Seven years after the drought, the runoff (as a fraction of precipitation) had not recovered in 37% of watersheds, and the number of recovered watersheds was not increasing. When recovery did occur, it was not explained by watershed wetness. For those watersheds not recovered, ~80% showed no evidence of recovering soon, suggesting persistence within a low-runoff state. The post-drought precipitation not going to runoff was found to be likely going to increased evapotranspiration per unit of precipitation. These findings show that watersheds can have a finite resilience to disturbances and suggest that hydrological droughts can persist indefinitely after meteorological droughts.

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60Fe and 244Pu deposited on Earth constrain the r-process yields of recent nearby supernovae

Half of the chemical elements heavier than iron are produced by the rapid neutron capture process (r-process). The sites and yields of this process are disputed, with candidates including some types of supernovae (SNe) and mergers of neutron stars. We search for two isotopic signatures in a sample of Pacific Ocean crust—iron-60 (60Fe) (half-life, 2.6 million years), which is predominantly produced in massive stars and ejected in supernova explosions, and plutonium-244 (244Pu) (half-life, 80.6 million years), which is produced solely in r-process events. We detect two distinct influxes of 60Fe to Earth in the last 10 million years and accompanying lower quantities of 244Pu. The 244Pu/60Fe influx ratios are similar for both events. The 244Pu influx is lower than expected if SNe dominate r-process nucleosynthesis, which implies some contribution from other sources.

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Shared B cell memory to coronaviruses and other pathogens varies in human age groups and tissues

Vaccination and infection promote the formation, tissue distribution, and clonal evolution of B cells, which encode humoral immune memory. We evaluated pediatric and adult blood and deceased adult organ donor tissues to determine convergent antigen-specific antibody genes of similar sequences shared between individuals. B cell memory varied for different pathogens. Polysaccharide antigen–specific clones were not exclusive to the spleen. Adults had higher clone frequencies and greater class switching in lymphoid tissues than blood, while pediatric blood had abundant class-switched convergent clones. Consistent with reported serology, prepandemic children had class-switched convergent clones to severe acute respiratory syndrome coronavirus 2 with weak cross-reactivity to other coronaviruses, while adult blood or tissues showed few such clones. These results highlight the prominence of early childhood B cell clonal expansions and cross-reactivity for future responses to novel pathogens.

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Macroevolutionary stability predicts interaction patterns of species in seed dispersal networks

Assessing deep-time mechanisms affecting the assembly of ecological networks is key to understanding biodiversity changes on broader time scales. We combined analyses of diversification rates with interaction network descriptors from 468 bird species belonging to 29 seed dispersal networks to show that bird species that contribute most to the network structure of plant–frugivore interactions belong to lineages that show higher macroevolutionary stability. This association is stronger in warmer, wetter, less seasonal environments. We infer that the macroevolutionary sorting mechanism acts through the regional pool of species by sorting species on the basis of the available relative differences in diversification rates, rather than absolute rates. Our results illustrate how the interplay between interaction patterns and diversification dynamics may shape the organization and long-term dynamics of ecological networks.

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The chain of chirality transfer in tellurium nanocrystals

Despite persistent and extensive observations of crystals with chiral shapes, the mechanisms underlying their formation are not well understood. Although past studies suggest that chiral shapes can form because of crystallization in the presence of chiral additives, or because of an intrinsic tendency that stems from the crystal structure, there are many cases in which these explanations are not suitable or have not been tested. Here, an investigation of model tellurium nanocrystals provides insights into the chain of chirality transfer between crystal structure and shape. We show that this transfer is mediated by screw dislocations, and shape chirality is not an outcome of the chiral crystal structure or ligands.

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Lack of transgenerational effects of ionizing radiation exposure from the Chernobyl accident

Effects of radiation exposure from the Chernobyl nuclear accident remain a topic of interest. We investigated germline de novo mutations (DNMs) in children born to parents employed as cleanup workers or exposed to occupational and environmental ionizing radiation after the accident. Whole-genome sequencing of 130 children (born 1987–2002) and their parents did not reveal an increase in the rates, distributions, or types of DNMs relative to the results of previous studies. We find no elevation in total DNMs, regardless of cumulative preconception gonadal paternal [mean = 365 milligrays (mGy), range = 0 to 4080 mGy] or maternal (mean = 19 mGy, range = 0 to 550 mGy) exposure to ionizing radiation. Thus, we conclude that, over this exposure range, evidence is lacking for a substantial effect on germline DNMs in humans, suggesting minimal impact from transgenerational genetic effects.

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Electric field control of superconductivity at the LaAlO3/KTaO3(111) interface

The oxide interface between LaAlO3 and KTaO3(111) can harbor a superconducting state. We report that by applying a gate voltage (VG) across KTaO3, the interface can be continuously tuned from superconducting into insulating states, yielding a dome-shaped Tc-VG dependence, where Tc is the transition temperature. The electric gating has only a minor effect on carrier density but a strong one on mobility. We interpret the tuning of mobility in terms of change in the spatial profile of the carriers in the interface and hence, effective disorder. As the temperature is decreased, the resistance saturates at the lowest temperature on both superconducting and insulating sides, suggesting the emergence of a quantum metallic state associated with a failed superconductor and/or fragile insulator.

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Cell-specific transcriptional control of mitochondrial metabolism by TIF1{gamma} drives erythropoiesis

Transcription and metabolism both influence cell function, but dedicated transcriptional control of metabolic pathways that regulate cell fate has rarely been defined. We discovered, using a chemical suppressor screen, that inhibition of the pyrimidine biosynthesis enzyme dihydroorotate dehydrogenase (DHODH) rescues erythroid differentiation in bloodless zebrafish moonshine (mon) mutant embryos defective for transcriptional intermediary factor 1 gamma (tif1). This rescue depends on the functional link of DHODH to mitochondrial respiration. The transcription elongation factor TIF1 directly controls coenzyme Q (CoQ) synthesis gene expression. Upon tif1 loss, CoQ levels are reduced, and a high succinate/α-ketoglutarate ratio leads to increased histone methylation. A CoQ analog rescues mon’s bloodless phenotype. These results demonstrate that mitochondrial metabolism is a key output of a lineage transcription factor that drives cell fate decisions in the early blood lineage.

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Extreme oxidant amounts produced by lightning in storm clouds

Lightning increases the atmosphere’s ability to cleanse itself by producing nitric oxide (NO), leading to atmospheric chemistry that forms ozone (O3) and the atmosphere’s primary oxidant, the hydroxyl radical (OH). Our analysis of a 2012 airborne study of deep convection and chemistry demonstrates that lightning also directly generates the oxidants OH and the hydroperoxyl radical (HO2). Extreme amounts of OH and HO2 were discovered and linked to visible flashes occurring in front of the aircraft and to subvisible discharges in electrified anvil regions. This enhanced OH and HO2 is orders of magnitude greater than any previous atmospheric observation. Lightning-generated OH in all storms happening at the same time globally can be responsible for a highly uncertain, but substantial, 2 to 16% of global atmospheric OH oxidation.

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Molecular insights into the complex mechanics of plant epidermal cell walls

Plants have evolved complex nanofibril-based cell walls to meet diverse biological and physical constraints. How strength and extensibility emerge from the nanoscale-to-mesoscale organization of growing cell walls has long been unresolved. We sought to clarify the mechanical roles of cellulose and matrix polysaccharides by developing a coarse-grained model based on polymer physics that recapitulates aspects of assembly and tensile mechanics of epidermal cell walls. Simple noncovalent binding interactions in the model generate bundled cellulose networks resembling that of primary cell walls and possessing stress-dependent elasticity, stiffening, and plasticity beyond a yield threshold. Plasticity originates from fibril-fibril sliding in aligned cellulose networks. This physical model provides quantitative insight into fundamental questions of plant mechanobiology and reveals design principles of biomaterials that combine stiffness with yielding and extensibility.

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A twist on the Ising model


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Population-level lupus


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Risk and replacement


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Building bridges in the brain


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A pre-eruptive fever


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Costs of moving stem cells


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Imaging cancer cell by cell


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RAFs not always required


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Staying dry


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The evolution of ecological networks


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What makes things twist?


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Genomics of radiation-induced damage


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A brain circuit that drives and gates curiosity


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A T cell sleeper agent against stress


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Characterizing a cancer spliceosome


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Targeting distal C-H bonds in arenes


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Progress in RSV prevention


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Controlling interfacial superconductivity


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Computational analysis of cell walls


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Building back colonic crypts


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Developing an immunotherapy for AD


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Kids armed with anti-coronavirus B cells


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Natural plutonium from supernovae


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Metabolic pathway regulates cell fate


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Cleaning in a flash


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Salmon aquaculture threatens Patagonia


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Ban veterinary use of diclofenac in Europe


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Investigate the origins of COVID-19


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Promoting a culture of climate care


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The hunt for habitable planets gets a new tool


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A paradigm shift to combat indoor respiratory infection


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Is chiral crystal shape inherited or acquired?


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Preventing respiratory syncytial virus (RSV) disease in children


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Neurobiology of novelty seeking


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De-stressing the T cells in need


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The footprint of evolution in seed dispersal interactions


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River basins on the edge of change


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When the levees break


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Do coronavirus genes slip into human chromosomes?


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As U.S. pandemic subsides, conferences explore 'hybrids


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Shipping rule cleans the air but dirties the water


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Ancient poop reveals extinction in gut bacteria


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Fission reactions are smoldering again at Chernobyl


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China's population still growing, census shows--but barely


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Arctic ice loss not a big culprit in harsh winters


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News at a glance


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Israel's COVID-19 endgame


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