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Exploring whole-genome duplicate gene retention with complex genetic interaction analysis

Whole-genome duplication has played a central role in the genome evolution of many organisms, including the human genome. Most duplicated genes are eliminated, and factors that influence the retention of persisting duplicates remain poorly understood. We describe a systematic complex genetic interaction analysis with yeast paralogs derived from the whole-genome duplication event. Mapping of digenic interactions for a deletion mutant of each paralog, and of trigenic interactions for the double mutant, provides insight into their roles and a quantitative measure of their functional redundancy. Trigenic interaction analysis distinguishes two classes of paralogs: a more functionally divergent subset and another that retained more functional overlap. Gene feature analysis and modeling suggest that evolutionary trajectories of duplicated genes are dictated by combined functional and structural entanglement factors.

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Erratum for the Report: "Estimating the burden of SARS-CoV-2 in France," by H. Salje, C. Tran Kiem, N. Lefrancq, N. Courtejoie, P. Bosetti, J. Paireau, A. Andronico, N. Hoze, J. Richet, C.-L. Dubost, Y. Le Strat, J. Lessler, D. Levy-Bruhl, A. Fontanet, L. Opatowski, P.-Y. Boelle, S. Cauchemez


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Erratum for the Report "Forest microclimate dynamics drive plant responses to warming" by F. Zellweger, P. De Frenne, J. Lenoir, P. Vangansbeke, K. Verheyen, M. Bernhardt-Römermann, L. Baeten, R. Hedl, I. Berki, J. Brunet, H. Van Calster, M. Chudomelova, G. Decocq, T. Dirnböck, T. Durak, T. Heinken, B. Jaroszewicz, M. Kopecky, F. Malis, M. Macek, M. Marek, T. Naaf, T. A. Nagel, A. Ortmann-Ajkai, P. Petrik, R. Pielech, K. Reczynska, W. Schmidt, T. Standovar, K. Swierkosz, B. Teleki, O. Vild, M. Wulf, D. Coomes


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Flexible recruitment of memory-based choice representations by the human medial frontal cortex

Decision-making in complex environments relies on flexibly using prior experience. This process depends on the medial frontal cortex (MFC) and the medial temporal lobe, but it remains unknown how these structures implement selective memory retrieval. We recorded single neurons in the MFC, amygdala, and hippocampus while human subjects switched between making recognition memory–based and categorization-based decisions. The MFC rapidly implemented changing task demands by using different subspaces of neural activity and by representing the currently relevant task goal. Choices requiring memory retrieval selectively engaged phase-locking of MFC neurons to amygdala and hippocampus field potentials, thereby enabling the routing of memories. These findings reveal a mechanism for flexibly and selectively engaging memory retrieval and show that memory-based choices are preferentially represented in the frontal cortex when required.

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Muscle and neuronal guidepost-like cells facilitate planarian visual system regeneration

Neuronal circuits damaged or lost after injury can be regenerated in some adult organisms, but the mechanisms enabling this process are largely unknown. We used the planarian Schmidtea mediterranea to study visual system regeneration after injury. We identify a rare population of muscle cells tightly associated with photoreceptor axons at stereotyped positions in both uninjured and regenerating animals. Together with a neuronal population, these cells promote de novo assembly of the visual system in diverse injury and eye transplantation contexts. These muscle guidepost-like cells are specified independently of eyes, and their position is defined by an extrinsic array of positional information cues. These findings provide a mechanism, involving adult formation of guidepost-like cells typically observed in embryos, for axon pattern restoration in regeneration.

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The pressure to assimilate


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Structural basis for inhibition of the RNA-dependent RNA polymerase from SARS-CoV-2 by remdesivir

The pandemic of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global crisis. Replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp) enzyme, a target of the antiviral drug remdesivir. Here we report the cryo–electron microscopy structure of the SARS-CoV-2 RdRp, both in the apo form at 2.8-angstrom resolution and in complex with a 50-base template-primer RNA and remdesivir at 2.5-angstrom resolution. The complex structure reveals that the partial double-stranded RNA template is inserted into the central channel of the RdRp, where remdesivir is covalently incorporated into the primer strand at the first replicated base pair, and terminates chain elongation. Our structures provide insights into the mechanism of viral RNA replication and a rational template for drug design to combat the viral infection.

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Arctic-adapted dogs emerged at the Pleistocene-Holocene transition

Although sled dogs are one of the most specialized groups of dogs, their origin and evolution has received much less attention than many other dog groups. We applied a genomic approach to investigate their spatiotemporal emergence by sequencing the genomes of 10 modern Greenland sled dogs, an ~9500-year-old Siberian dog associated with archaeological evidence for sled technology, and an ~33,000-year-old Siberian wolf. We found noteworthy genetic similarity between the ancient dog and modern sled dogs. We detected gene flow from Pleistocene Siberian wolves, but not modern American wolves, to present-day sled dogs. The results indicate that the major ancestry of modern sled dogs traces back to Siberia, where sled dog–specific haplotypes of genes that potentially relate to Arctic adaptation were established by 9500 years ago.

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Quieting a noisy antenna reproduces photosynthetic light-harvesting spectra

Photosynthesis achieves near unity light-harvesting quantum efficiency yet it remains unknown whether there exists a fundamental organizing principle giving rise to robust light harvesting in the presence of dynamic light conditions and noisy physiological environments. Here, we present a noise-canceling network model that relates noisy physiological conditions, power conversion efficiency, and the resulting absorption spectra of photosynthetic organisms. Using light conditions in full solar exposure, light filtered by oxygenic phototrophs, and light filtered under seawater, we derived optimal absorption characteristics for efficient solar power conversion. We show how light-harvesting antennae can be tuned to maximize power conversion efficiency by minimizing excitation noise, thus providing a unified theoretical basis for the observed wavelength dependence of absorption in green plants, purple bacteria, and green sulfur bacteria.

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Metalens-array-based high-dimensional and multiphoton quantum source

The development of two-dimensional metasurfaces has shown great potential in quantum-optical technologies because of the excellent flexibility in light-field manipulation. By integrating a metalens array with a nonlinear crystal, we demonstrate a 100-path spontaneous parametric down-conversion photon-pair source in a 10 x 10 array, which shows promise for high-dimensional entanglement and multiphoton-state generation. We demonstrate two-, three- and four-dimensional two-photon path entanglement with different phases encoded by metalenses with fidelities of 98.4, 96.6, and 95.0%, respectively. Furthermore, four-photon and six-photon generation is observed with high indistinguishability of photons generated from different metalenses. Our metalens-array–based quantum photon source is compact, stable, and controllable, indicating a new platform for integrated quantum devices.

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Changes in contact patterns shape the dynamics of the COVID-19 outbreak in China

Intense nonpharmaceutical interventions were put in place in China to stop transmission of the novel coronavirus disease 2019 (COVID-19). As transmission intensifies in other countries, the interplay between age, contact patterns, social distancing, susceptibility to infection, and COVID-19 dynamics remains unclear. To answer these questions, we analyze contact survey data for Wuhan and Shanghai before and during the outbreak and contact-tracing information from Hunan province. Daily contacts were reduced seven- to eightfold during the COVID-19 social distancing period, with most interactions restricted to the household. We find that children 0 to 14 years of age are less susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than adults 15 to 64 years of age (odds ratio 0.34, 95% confidence interval 0.24 to 0.49), whereas individuals more than 65 years of age are more susceptible to infection (odds ratio 1.47, 95% confidence interval 1.12 to 1.92). Based on these data, we built a transmission model to study the impact of social distancing and school closure on transmission. We find that social distancing alone, as implemented in China during the outbreak, is sufficient to control COVID-19. Although proactive school closures cannot interrupt transmission on their own, they can reduce peak incidence by 40 to 60% and delay the epidemic.

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A multiplanet system of super-Earths orbiting the brightest red dwarf star GJ 887

The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.

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Micelle-directed chiral seeded growth on anisotropic gold nanocrystals

Surfactant-assisted seeded growth of metal nanoparticles (NPs) can be engineered to produce anisotropic gold nanocrystals with high chiroptical activity through the templating effect of chiral micelles formed in the presence of dissymmetric cosurfactants. Mixed micelles adsorb on gold nanorods, forming quasihelical patterns that direct seeded growth into NPs with pronounced morphological and optical handedness. Sharp chiral wrinkles lead to chiral plasmon modes with high dissymmetry factors (~0.20). Through variation of the dimensions of chiral wrinkles, the chiroptical properties can be tuned within the visible and near-infrared electromagnetic spectrum. The micelle-directed mechanism allows extension to other systems, such as the seeded growth of chiral platinum shells on gold nanorods. This approach provides a reproducible, simple, and scalable method toward the fabrication of NPs with high chiral optical activity.

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Meridional flow in the Suns convection zone is a single cell in each hemisphere

The Sun’s magnetic field is generated by subsurface motions of the convecting plasma. The latitude at which the magnetic field emerges through the solar surface (as sunspots) drifts toward the equator over the course of the 11-year solar cycle. We use helioseismology to infer the meridional flow (in the latitudinal and radial directions) over two solar cycles covering 1996–2019. Two data sources are used, which agree during their overlap period of 2001–2011. The time-averaged meridional flow is shown to be a single cell in each hemisphere, carrying plasma toward the equator at the base of the convection zone with a speed of ~4 meters per second at 45° latitude. Our results support the flux-transport dynamo model, which explains the drift of sunspot-emergence latitudes through the meridional flow.

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Mass-resolved electronic circular dichroism ion spectroscopy

DNA and proteins are chiral: Their three-dimensional structures cannot be superimposed with their mirror images. Circular dichroism spectroscopy is widely used to characterize chiral compounds, but data interpretation is difficult in the case of mixtures. We recorded the electronic circular dichroism spectra of DNA helices separated in a mass spectrometer. We studied guanine-rich strands having various secondary structures, electrosprayed them as negative ions, irradiated them with an ultraviolet nanosecond optical parametric oscillator laser, and measured the difference in electron photodetachment efficiency between left and right circularly polarized light. The reconstructed circular dichroism ion spectra resembled those of their solution-phase counterparts, thereby allowing us to assign the DNA helical topology. The ability to measure circular dichroism directly on biomolecular ions expands the capabilities of mass spectrometry for structural analysis.

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Mechanisms of OCT4-SOX2 motif readout on nucleosomes

Transcription factors (TFs) regulate gene expression through chromatin where nucleosomes restrict DNA access. To study how TFs bind nucleosome-occupied motifs, we focused on the reprogramming factors OCT4 and SOX2 in mouse embryonic stem cells. We determined TF engagement throughout a nucleosome at base-pair resolution in vitro, enabling structure determination by cryo–electron microscopy at two preferred positions. Depending on motif location, OCT4 and SOX2 differentially distort nucleosomal DNA. At one position, OCT4-SOX2 removes DNA from histone H2A and histone H3; however, at an inverted motif, the TFs only induce local DNA distortions. OCT4 uses one of its two DNA-binding domains to engage DNA in both structures, reading out a partial motif. These findings explain site-specific nucleosome engagement by the pluripotency factors OCT4 and SOX2, and they reveal how TFs distort nucleosomes to access chromatinized motifs.

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Cryo-EM structure of the human cohesin-NIPBL-DNA complex

As a ring-shaped adenosine triphosphatase (ATPase) machine, cohesin organizes the eukaryotic genome by extruding DNA loops and mediates sister chromatid cohesion by topologically entrapping DNA. How cohesin executes these fundamental DNA transactions is not understood. Using cryo–electron microscopy (cryo-EM), we determined the structure of human cohesin bound to its loader NIPBL and DNA at medium resolution. Cohesin and NIPBL interact extensively and together form a central tunnel to entrap a 72–base pair DNA. NIPBL and DNA promote the engagement of cohesin’s ATPase head domains and ATP binding. The hinge domains of cohesin adopt an "open washer" conformation and dock onto the STAG1 subunit. Our structure explains the synergistic activation of cohesin by NIPBL and DNA and provides insight into DNA entrapment by cohesin.

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Single-molecule regulatory architectures captured by chromatin fiber sequencing

Gene regulation is chiefly determined at the level of individual linear chromatin molecules, yet our current understanding of cis-regulatory architectures derives from fragmented sampling of large numbers of disparate molecules. We developed an approach for precisely stenciling the structure of individual chromatin fibers onto their composite DNA templates using nonspecific DNA N6-adenine methyltransferases. Single-molecule long-read sequencing of chromatin stencils enabled nucleotide-resolution readout of the primary architecture of multikilobase chromatin fibers (Fiber-seq). Fiber-seq exposed widespread plasticity in the linear organization of individual chromatin fibers and illuminated principles guiding regulatory DNA actuation, the coordinated actuation of neighboring regulatory elements, single-molecule nucleosome positioning, and single-molecule transcription factor occupancy. Our approach and results open new vistas on the primary architecture of gene regulation.

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Charmed excitations


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The double punch of perchlorate


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Loss of shelf


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Avoiding multiphoton artifacts


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Not just for the trees


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Pol II kicks out histone variant


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Seeds of change


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Intuitive CD8+ T cells sense DNA


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Lighting a spark from the lysosome


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Sled dog arctic adaptations go far back


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Pairs of peaks stabilize output power


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A nearby multiplanet system


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DNA circular dichroism in gas phase


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A blueprint to understand cohesin


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Engaging the nucleosome


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The adaptive human frontal cortex


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Guiding regeneration


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The fate of genes after duplication


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Reducing airborne transmission


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Sex, age, and the macrophage


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A wrench in the works of COVID-19


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Who and what next?


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Metalens-array-based quantum source


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The flow of plasma inside the Sun


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Groovy chiral gold particles


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Primary architecture of chromatin fibers


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Easier polar plunge for penguins


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Screeners needed for journalism awards


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A view from my basement


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Afforestation falls short as a biodiversity strategy


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Misguided forest action in EU Biodiversity Strategy


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COVID-19's unsustainable waste management


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Humankind: A Hopeful History


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Like other species, we have always been on the move


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Confronting bias


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"Explaining" machine learning reveals policy challenges


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Multiple, quiet, and close by


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Microplastic in terrestrial ecosystems


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Guide cells help navigate axon regeneration


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The simplicity of robust light harvesting


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Action spectra of chiral secondary structure


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Evolution after genome duplication


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Reducing transmission of SARS-CoV-2


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Mars mission would put China among space leaders


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Martian chronicler


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Senate bill to curb foreign threats raises alarms


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Online GRE test heightens equity concerns


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Could a blood 'observatory stop pandemics?


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Charities that fund research face deep revenue declines


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Dawn of the chicken revealed in Southeast Asia


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Lawsuit alleges scientific misconduct at weapons lab


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Hope grows for targeting the brain with ultrasound


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News at a glance


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Persuasive words are not enough


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