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Environmental robustness of the global yeast genetic interaction network

Phenotypes associated with genetic variants can be altered by interactions with other genetic variants (GxG), with the environment (GxE), or both (GxGxE). Yeast genetic interactions have been mapped on a global scale, but the environmental influence on the plasticity of genetic networks has not been examined systematically. To assess environmental rewiring of genetic networks, we examined 14 diverse conditions and scored 30,000 functionally representative yeast gene pairs for dynamic, differential interactions. Different conditions revealed novel differential interactions, which often uncovered functional connections between distantly related gene pairs. However, the majority of observed genetic interactions remained unchanged in different conditions, suggesting that the global yeast genetic interaction network is robust to environmental perturbation and captures the fundamental functional architecture of a eukaryotic cell.

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The coding and long noncoding single-cell atlas of the developing human fetal striatum

Deciphering how the human striatum develops is necessary for understanding the diseases that affect this region. To decode the transcriptional modules that regulate this structure during development, we compiled a catalog of 1116 long intergenic noncoding RNAs (lincRNAs) identified de novo and then profiled 96,789 single cells from the early human fetal striatum. We found that D1 and D2 medium spiny neurons (D1- and D2-MSNs) arise from a common progenitor and that lineage commitment is established during the postmitotic transition, across a pre-MSN phase that exhibits a continuous spectrum of fate determinants. We then uncovered cell type–specific gene regulatory networks that we validated through in silico perturbation. Finally, we identified human-specific lincRNAs that contribute to the phylogenetic divergence of this structure in humans. This work delineates the cellular hierarchies governing MSN lineage commitment.

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Fossil apes and human evolution

Humans diverged from apes (chimpanzees, specifically) toward the end of the Miocene ~9.3 million to 6.5 million years ago. Understanding the origins of the human lineage (hominins) requires reconstructing the morphology, behavior, and environment of the chimpanzee-human last common ancestor. Modern hominoids (that is, humans and apes) share multiple features (for example, an orthograde body plan facilitating upright positional behaviors). However, the fossil record indicates that living hominoids constitute narrow representatives of an ancient radiation of more widely distributed, diverse species, none of which exhibit the entire suite of locomotor adaptations present in the extant relatives. Hence, some modern ape similarities might have evolved in parallel in response to similar selection pressures. Current evidence suggests that hominins originated in Africa from Miocene ape ancestors unlike any living species.

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Unearthing Neanderthal population history using nuclear and mitochondrial DNA from cave sediments

Bones and teeth are important sources of Pleistocene hominin DNA, but are rarely recovered at archaeological sites. Mitochondrial DNA (mtDNA) has been retrieved from cave sediments but provides limited value for studying population relationships. We therefore developed methods for the enrichment and analysis of nuclear DNA from sediments and applied them to cave deposits in western Europe and southern Siberia dated to between 200,000 and 50,000 years ago. We detected a population replacement in northern Spain about 100,000 years ago, which was accompanied by a turnover of mtDNA. We also identified two radiation events in Neanderthal history during the early part of the Late Pleistocene. Our work lays the ground for studying the population history of ancient hominins from trace amounts of nuclear DNA in sediments.

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From professor to patient X


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New Products


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Extreme altitudes during diurnal flights in a nocturnal songbird migrant

Billions of nocturnally migrating songbirds fly across oceans and deserts on their annual journeys. Using multisensor data loggers, we show that great reed warblers (Acrocephalus arundinaceus) regularly prolong their otherwise strictly nocturnal flights into daytime when crossing the Mediterranean Sea and the Sahara Desert. Unexpectedly, when prolonging their flights, they climbed steeply at dawn, from a mean of 2394 meters above sea level to reach extreme cruising altitudes (mean 5367 and maximum 6267 meters above sea level) during daytime flights. This previously unknown behavior of using exceedingly high flight altitudes when migrating during daytime could be caused by diel variation in ambient temperature, winds, predation, vision range, and solar radiation. Our finding of this notable behavior provides new perspectives on constraints in bird flight and might help to explain the evolution of nocturnal migration.

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X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput x-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied x-ray fragment screening experiments with molecules of low complexity, our screen tested already-approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six nonpeptidic compounds showed antiviral activity at nontoxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.

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The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia

Slovakia conducted multiple rounds of population-wide rapid antigen testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% confidence interval: 57 to 58%) within 1 week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1 to 6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared with a scenario of unmitigated growth was 70% (67 to 73%). Modeling indicated that this decrease could not be explained solely by infection control measures but required the addition of the isolation and quarantine of household members of those testing positive.

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Reversible oxygen migration and phase transitions in hafnia-based ferroelectric devices

Unconventional ferroelectricity exhibited by hafnia-based thin films—robust at nanoscale sizes—presents tremendous opportunities in nanoelectronics. However, the exact nature of polarization switching remains controversial. We investigated a La0.67Sr0.33MnO3/Hf0.5Zr0.5O2 capacitor interfaced with various top electrodes while performing in situ electrical biasing using atomic-resolution microscopy with direct oxygen imaging as well as with synchrotron nanobeam diffraction. When the top electrode is oxygen reactive, we observe reversible oxygen vacancy migration with electrodes as the source and sink of oxygen and the dielectric layer acting as a fast conduit at millisecond time scales. With nonreactive top electrodes and at longer time scales (seconds), the dielectric layer also acts as an oxygen source and sink. Our results show that ferroelectricity in hafnia-based thin films is unmistakably intertwined with oxygen voltammetry.

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Quantum mechanics-free subsystem with mechanical oscillators

Quantum mechanics sets a limit for the precision of continuous measurement of the position of an oscillator. We show how it is possible to measure an oscillator without quantum back-action of the measurement by constructing one effective oscillator from two physical oscillators. We realize such a quantum mechanics–free subsystem using two micromechanical oscillators, and show the measurements of two collective quadratures while evading the quantum back-action by 8 decibels on both of them, obtaining a total noise within a factor of 2 of the full quantum limit. This facilitates the detection of weak forces and the generation and measurement of nonclassical motional states of the oscillators. Moreover, we directly verify the quantum entanglement of the two oscillators by measuring the Duan quantity 1.4 decibels below the separability bound.

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Direct observation of deterministic macroscopic entanglement

Quantum entanglement of mechanical systems emerges when distinct objects move with such a high degree of correlation that they can no longer be described separately. Although quantum mechanics presumably applies to objects of all sizes, directly observing entanglement becomes challenging as masses increase, requiring measurement and control with a vanishingly small error. Here, using pulsed electromechanics, we deterministically entangle two mechanical drumheads with masses of 70 picograms. Through nearly quantum-limited measurements of the position and momentum quadratures of both drums, we perform quantum state tomography and thereby directly observe entanglement. Such entangled macroscopic systems are poised to serve in fundamental tests of quantum mechanics, enable sensing beyond the standard quantum limit, and function as long-lived nodes of future quantum networks.

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Interfacial toughening with self-assembled monolayers enhances perovskite solar cell reliability

Iodine-terminated self-assembled monolayer (I-SAM) was used in perovskite solar cells (PSCs) to achieve a 50% increase of adhesion toughness at the interface between the electron transport layer (ETL) and the halide perovskite thin film to enhance mechanical reliability. Treatment with I-SAM also increased the power conversion efficiency from 20.2% to 21.4%, reduced hysteresis, and improved operational stability with a projected T80 (time to 80% initial efficiency retained) increasing from ~700 hours to 4000 hours under 1-sun illumination and with continuous maximum power point tracking. Operational stability–tested PSC without SAMs revealed extensive irreversible morphological degradation at the ETL/perovskite interface, including voids formation and delamination, whereas PSCs with I-SAM exhibited minimal damage accumulation. This difference was attributed to a combination of a decrease in hydroxyl groups at the interface and the higher interfacial toughness.

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Reversible fusion and fission of graphene oxide-based fibers

Stimuli-responsive fusion and fission are widely observed in both bio-organizations and artificial molecular assemblies. However, the design of a system with structure and property persistence during repeated fusion and fission remains challenging. We show reversible fusion and fission of wet-spun graphene oxide (GO) fibers, in which a number of macroscopic fibers can fuse into a thicker one and can also separate into original individual fibers under stimulation of solvents. The dynamic geometrical deformation of GO fiber shells, caused by solvent evaporation and infiltration, is the key to the reversible fusion-fission cycles. This principle is extended to implement flexible transitions between complex fiber assemblies and the inclusion or expulsion of guest compounds.

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Evolution of vision and hearing modalities in theropod dinosaurs

Owls and nightbirds are nocturnal hunters of active prey that combine visual and hearing adaptations to overcome limits on sensory performance in low light. Such sensory innovations are unknown in nonavialan theropod dinosaurs and are poorly characterized on the line that leads to birds. We investigate morphofunctional proxies of vision and hearing in living and extinct theropods and demonstrate deep evolutionary divergences of sensory modalities. Nocturnal predation evolved early in the nonavialan lineage Alvarezsauroidea, signaled by extreme low-light vision and increases in hearing sensitivity. The Late Cretaceous alvarezsauroid Shuvuuia deserti had even further specialized hearing acuity, rivaling that of today’s barn owl. This combination of sensory adaptations evolved independently in dinosaurs long before the modern bird radiation and provides a notable example of convergence between dinosaurs and mammals.

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The early origin of a birdlike inner ear and the evolution of dinosaurian movement and vocalization

Reptiles, including birds, exhibit a range of behaviorally relevant adaptations that are reflected in changes to the structure of the inner ear. These adaptations include the capacity for flight and sensitivity to high-frequency sound. We used three-dimensional morphometric analyses of a large sample of extant and extinct reptiles to investigate inner ear correlates of locomotor ability and hearing acuity. Statistical analyses revealed three vestibular morphotypes, best explained by three locomotor categories—quadrupeds, bipeds and simple fliers (including bipedal nonavialan dinosaurs), and high-maneuverability fliers. Troodontids fall with Archaeopteryx among the extant low-maneuverability fliers. Analyses of cochlear shape revealed a single instance of elongation, on the stem of Archosauria. We suggest that this transformation coincided with the origin of both high-pitched juvenile location, alarm, and hatching-synchronization calls and adult responses to them.

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Sex chromosome transformation and the origin of a male-specific X chromosome in the creeping vole

The mammalian sex chromosome system (XX female/XY male) is ancient and highly conserved. The sex chromosome karyotype of the creeping vole (Microtus oregoni) represents a long-standing anomaly, with an X chromosome that is unpaired in females (X0) and exclusively maternally transmitted. We produced a highly contiguous male genome assembly, together with short-read genomes and transcriptomes for both sexes. We show that M. oregoni has lost an independently segregating Y chromosome and that the male-specific sex chromosome is a second X chromosome that is largely homologous to the maternally transmitted X. Both maternally inherited and male-specific sex chromosomes carry fragments of the ancestral Y chromosome. Consequences of this recently transformed sex chromosome system include Y-like degeneration and gene amplification on the male-specific X, expression of ancestral Y-linked genes in females, and X inactivation of the male-specific chromosome in male somatic cells. The genome of M. oregoni elucidates the processes that shape the gene content and dosage of mammalian sex chromosomes and exemplifies a rare case of plasticity in an ancient sex chromosome system.

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Extending the reach of LIDAR


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Plastic dust in the wind


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Policy changing culture


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Signals of stress


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Fragile queen mole rats


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Pollinator-focused solar arrays


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Fill-up for the forest


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Stabilized by protein interactions


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DUBbing new inflammasome inhibitors


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The Slovakian test case


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Reversible fiber fusion and fission


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A role for vacancies


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Mystery solved?


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Development of the human striatum revealed


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The value of dirty DNA


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Environmental impacts on gene networks


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Reconstructing ancestral bacteria


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A distinctive ancestor


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Rethinking insulin in obesity


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Human impact on landscapes in early Africa


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Through a shrimp eye brightly


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Revealing behavioral secrets in extinct species


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A large-scale screen to target SARS-CoV-2


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Quantum entanglement goes large


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Tougher solar cell interfaces


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High fliers


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Integrate US science and diplomacy


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Inclusion through part-time science


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Biosecurity for humanitarian aid


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The people at the dawn of civilization


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More than the message


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Carbohydrates, insulin, and obesity


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Making sense of dinosaurs and birds


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Illuminating the first bacteria


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Reversible fusion-fission fibers


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Rapid antigen testing in COVID-19 responses


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Macroscale entanglement and measurement


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Mapping out a future for ungulate migrations


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Sea of doubts


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USDA now only partially inspects some animal labs


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'Campfires may drive heating of solar atmosphere


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Fatal attraction to light at night pummels insects


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NASA set to announce Earth system observatory


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Brazil and Russia face off over vaccine contamination charge


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Is India's coronavirus death 'paradox vanishing?


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News at a glance


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The frontier is not endless for all


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Opening the path to biotech


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A rooted phylogeny resolves early bacterial evolution

A rooted bacterial tree is necessary to understand early evolution, but the position of the root is contested. Here, we model the evolution of 11,272 gene families to identify the root, extent of horizontal gene transfer (HGT), and the nature of the last bacterial common ancestor (LBCA). Our analyses root the tree between the major clades Terrabacteria and Gracilicutes and suggest that LBCA was a free-living flagellated, rod-shaped double-membraned organism. Contrary to recent proposals, our analyses reject a basal placement of the Candidate Phyla Radiation, which instead branches sister to Chloroflexota within Terrabacteria. While most gene families (92%) have evidence of HGT, overall, two-thirds of gene transmissions have been vertical, suggesting that a rooted tree provides a meaningful frame of reference for interpreting bacterial evolution.

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