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The organization of genomic DNA into defined nucleosomes has long been viewed as a hallmark of eukaryotes. This paradigm has been challenged by the identification of "minimalist" histones in archaea and more recently by the discovery of genes that encode fused remote homologs of the four eukaryotic histones in Marseilleviridae, a subfamily of giant viruses that infect amoebae. We demonstrate that viral doublet histones are essential for viral infectivity, localize to cytoplasmic viral factories after virus infection, and ultimately are found in the mature virions. Cryogenic electron microscopy (cryo-EM) structures of viral nucleosome-like particles show strong similarities to eukaryotic nucleosomes despite the limited sequence identify. The unique connectors that link the histone chains contribute to the observed instability of viral nucleosomes, and some histone tails assume structural roles. Our results further expand the range of "organisms" that require nucleosomes and suggest a specialized function of histones in the biology of these unusual viruses.
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Vírus de DNA/metabolismo , Histonas/metabolismo , Nucleossomos/metabolismo , Amoeba/virologia , Corantes Fluorescentes/metabolismo , Histonas/química , Modelos Moleculares , Proteômica , Vírion/metabolismoRESUMO
The dichotomous model of "drivers" and "passengers" in cancer posits that only a few mutations in a tumor strongly affect its progression, with the remaining ones being inconsequential. Here, we leveraged the comprehensive variant dataset from the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) project to demonstrate that-in addition to the dichotomy of high- and low-impact variants-there is a third group of medium-impact putative passengers. Moreover, we also found that molecular impact correlates with subclonal architecture (i.e., early versus late mutations), and different signatures encode for mutations with divergent impact. Furthermore, we adapted an additive-effects model from complex-trait studies to show that the aggregated effect of putative passengers, including undetected weak drivers, provides significant additional power (â¼12% additive variance) for predicting cancerous phenotypes, beyond PCAWG-identified driver mutations. Finally, this framework allowed us to estimate the frequency of potential weak-driver mutations in PCAWG samples lacking any well-characterized driver alterations.
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Genoma Humano/genética , Genômica/métodos , Mutação/genética , Neoplasias/genética , Análise Mutacional de DNA/métodos , Progressão da Doença , Humanos , Neoplasias/patologia , Sequenciamento Completo do GenomaRESUMO
Antibiotic resistance genes predate the therapeutic uses of antibiotics. However, the current antimicrobial resistance crisis stems from our extensive use of antibiotics and the generation of environmental stressors that impose new selective pressure on microbes and drive the evolution of resistant pathogens that now threaten human health. Similar to climate change, this global threat results from human activities that change habitats and natural microbiomes, which in turn interact with human-associated ecosystems and lead to adverse impacts on human health. Human activities that alter our planet at global scales exacerbate the current resistance crisis and exemplify our central role in large-scale changes in which we are both protagonists and architects of our success but also casualties of unanticipated collateral outcomes. As cognizant participants in this ongoing planetary experiment, we are driven to understand and find strategies to curb the ongoing crises of resistance and climate change.
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Farmacorresistência Bacteriana , Microbiota , Humanos , Farmacorresistência Bacteriana/genética , Antibacterianos/farmacologia , Microbiota/genéticaRESUMO
When making contact with an undercooled target, a drop freezes. The colder the target is, the more rapid the freezing is supposed to be. In this research, we explore the impact of droplets on cold granular material. As the undercooling degree increases, the bulk freezing of the droplet is delayed by at least an order of magnitude. The postponement of the overall solidification is accompanied by substantial changes in dynamics, including the spreading-retraction process, satellite drop generation, and cratering in the target. The solidification of the wetted pores in the granular target primarily causes these effects. The freezing process over the pore dimension occurs rapidly enough to match the characteristic timescales of impact dynamics at moderate undercooling degrees. As a result, the hydrophilic impact appears "hydrophobic," and the dimension of the solidified droplet shrinks. A monolayer of cold grains on a surface can reproduce these consequences. Our research presents a potential approach to regulate solidified morphology for subfreezing drop impacts. It additionally sheds light on the impact scenario of strong coupling between the dynamics and solidification.
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Certain fox species plunge-dive into snow to catch prey (e.g., rodents), a hunting mechanism called mousing. Red and arctic foxes can dive into snow at speeds ranging between 2 and 4 m/s. Such mousing behavior is facilitated by a slim, narrow facial structure. Here, we investigate how foxes dive into snow efficiently by studying the role of skull morphology on impact forces it experiences. In this study, we reproduce the mousing behavior in the lab using three-dimensional (3D) printed fox skulls dropped into fresh snow to quantify the dynamic force of impact. Impact force into snow is modeled using hydrodynamic added mass during the initial impact phase. This approach is based on two key facts: the added mass effect in granular media at high Reynolds numbers and the characteristics of snow as a granular medium. Our results show that the curvature of the snout plays a critical role in determining the impact force, with an inverse relationship. A sharper skull leads to a lower average impact force, which allows foxes to dive head-first into the snow with minimal tissue damage.
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Raposas , Crânio , Neve , Animais , Raposas/anatomia & histologia , Raposas/fisiologia , Crânio/anatomia & histologia , Mergulho/fisiologia , Comportamento Predatório/fisiologiaRESUMO
What explains human consequences of weather-related disaster? Here, we explore how core socioeconomic, political, and security conditions shape flood-induced displacement worldwide since 2000. In-sample regression analysis shows that extreme displacement levels are more likely in contexts marked by low national income levels, nondemocratic political systems, high local economic activity, and prevalence of armed conflict. The analysis also reveals large residual differences across continents, where flood-induced displacement in the Global South often is much more widespread than direct human exposure measures would suggest. However, these factors have limited influence on our ability to accurately predict flood displacement on new data, pointing to important, hard-to-operationalize heterogeneity in flood impacts across contexts and critical data limitations. Although results are consistent with an interpretation that the sustainable development agenda is beneficial for disaster risk reduction, better data on societal consequences of natural hazards are critically needed to support evidence-based decision-making.
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Water striders are abundant in areas with high humidity and rainfall. Raindrops can weigh more than 40 times the adult water strider and some pelagic species spend their entire lives at sea, never contacting ground. Until now, researchers have not systematically investigated the survival of water striders when impacted by raindrops. In this experimental study, we use high-speed videography to film drop impacts on water striders. Drops force the insects subsurface upon direct contact. As the ensuing crater rebounds upward, the water strider is propelled airborne by a Worthington jet, herein called the first jet. We show the water strider's locomotive responses, low density, resistance to wetting when briefly submerged, and ability to regain a super-surface rest state, rendering it impervious to the initial impact. When pulled subsurface during a second crater formation caused by the collapsing first jet, water striders face the possibility of ejection above the surface or submersion below the surface, a fate determined by their position in the second crater. We identify a critical crater collapse acceleration threshold â¼ 5.7 gravities for the collapsing second crater which determines the ejection and submersion of passive water striders. Entrapment by submersion makes the water strider poised to penetrate the air-water interface from below, which appears impossible without the aid of a plastron and proper locomotive techniques. Our study is likely the first to consider second crater dynamics and our results translate to the submersion dynamics of other passively floating particles such as millimetric microplastics atop the world's oceans.
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Ultralight architected materials enabled by advanced manufacturing processes have achieved density-normalized strength and stiffness properties that are inaccessible to bulk materials. However, the majority of this work has focused on static loading and elastic-wave propagation. Fundamental understanding of the mechanical behavior of architected materials under large-deformation dynamic conditions remains limited, due to the complexity of mechanical responses and shortcomings of characterization methods. Here, we present a microscale suspended-plate impact testing framework for three-dimensional micro-architected materials, where supersonic microparticles to velocities of up to 850 m/s are accelerated against a substrate-decoupled architected material to quantify its energy dissipation characteristics. Using ultra-high-speed imaging, we perform in situ quantification of the impact energetics on two types of architected materials as well as their constituent nonarchitected monolithic polymer, indicating a 47% or greater increase in mass-normalized energy dissipation under a given impact condition through use of architecture. Post-mortem characterization, supported by a series of quasi-static experiments and high-fidelity simulations, shed light on two coupled mechanisms of energy dissipation: material compaction and particle-induced fracture. Together, experiments and simulations indicate that architecture-specific resistance to compaction and fracture can explain a difference in dynamic impact response across architectures. We complement our experimental and numerical efforts with dimensional analysis which provides a predictive framework for kinetic-energy absorption as a function of material parameters and impact conditions. We envision that enhanced understanding of energy dissipation mechanisms in architected materials will serve to define design considerations toward the creation of lightweight impact-mitigating materials for protective applications.
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Soil organic carbon (SOC) is vital for terrestrial ecosystems, affecting biogeochemical processes, and soil health. It is known that soil salinity impacts SOC content, yet the specific direction and magnitude of SOC variability in relation to soil salinity remain poorly understood. Analyzing 43,459 mineral soil samples (SOC < 150 g kg-1) collected across different land covers since 1992, we approximate a soil salinity increase from 1 to 5 dS m-1 in croplands would be associated with a decline in mineral soils SOC from 0.14 g kg-1 above the mean predicted SOC ([Formula: see text] = 18.47 g kg-1) to 0.46 g kg-1 below [Formula: see text] (~-430%), while for noncroplands, such decline is sharper, from 0.96 above [Formula: see text] = 35.96 g kg-1 to 4.99 below [Formula: see text] (~-620%). Although salinity's significance in explaining SOC variability is minor (<6%), we estimate a one SD increase in salinity of topsoil samples (0 to 7 cm) correlates with respective [Formula: see text] declines of ~4.4% and ~9.26%, relative to [Formula: see text] and [Formula: see text]. The [Formula: see text] decline in croplands is greatest in vegetation/cropland mosaics while lands covered with evergreen needle-leaved trees are estimated with the highest [Formula: see text] decline in noncroplands. We identify soil nitrogen, land cover, and precipitation Seasonality Index as the most significant parameters in explaining the SOC's variability. The findings provide insights into SOC dynamics under increased soil salinity, improving understanding of SOC stock responses to land degradation and climate warming.
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It is common for social scientists to discuss the implications of our research for policy. However, what actions can we take to inform policy in more immediate and impactful ways, regardless of our existing institutional affiliations or personal connections? Focusing on federal policy, I suggest that the answer requires understanding a basic coordination problem. On the government side, the Foundations of Evidence-based Policymaking Act (2018) requires that large federal agencies pose, communicate, and answer research questions related to their effects on people and communities. This advancement has opened the black box of federal agency policy priorities, but it has not addressed capacity challenges: These agencies often do not have the financial resources or staff to answer the research questions they pose. On the higher education side, we have more than 150,000 academic social scientists who are knowledge producers and educators by training and vocation. However, especially among those in disciplinary departments, or those without existing institutional or personal connections to federal agencies, we often feel locked out of federal policymaking processes. In this article, I define the coordination problem and offer concrete actions that the academic and federal government communities can take to address it. I also offer leading examples of how academics and universities are making public policy impact possible in multiple governmental spheres. I conclude by arguing that both higher education institutions and all levels of government can do more to help academic social scientists put our knowledge to work in service of the public good.
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Formulação de Políticas , Política Pública , Humanos , Órgãos Governamentais , Governo FederalRESUMO
Genomic studies of human disorders are often performed by distinct research communities (i.e., focused on rare diseases, common diseases, or cancer). Despite underlying differences in the mechanistic origin of different disease categories, these studies share the goal of identifying causal genomic events that are critical for the clinical manifestation of the disease phenotype. Moreover, these studies face common challenges, including understanding the complex genetic architecture of the disease, deciphering the impact of variants on multiple scales, and interpreting noncoding mutations. Here, we highlight these challenges in depth and argue that properly addressing them will require a more unified vocabulary and approach across disease communities. Toward this goal, we present a unified perspective on relating variant impact to various genomic disorders.
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Genoma , Genômica , Humanos , Mutação , FenótipoRESUMO
Sediments in southern Laos and eastern Thailand confirm that the Australasian tektite strewn field came from an extraterrestrial impact crater on the Bolaven Plateau of southern Laos. The principal evidence is the Bolaven diamicton, a pebbly to bouldery breccia that is thickest and coarsest on the plateau. Tektites, the melted target material strewn widely by the forces of the impact 789.0 ± 1.8 ka ago, lie either within the uppermost part of the diamicton or atop it. On the flanks of the plateau, the basal diamicton often contains clasts from preimpact lavas and gravels and sometimes mantles broken Mesozoic bedrock. Locally, its upper portions contain unweathered boulders of basalt or sandstone. Its sharp upper contact with a thick sandy silt implies that the two beds formed in rapid succession. These characteristics of the Bolaven diamicton show that it resulted primarily from the excavation, comminution, and launch of sandstone and weathered basaltic lavas from a crater on the Bolaven Plateau, and entrained other materials while in transit.
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The impact of a scientific publication is often measured by the number of citations it receives from the scientific community. However, citation count is susceptible to well-documented variations in citation practices across time and discipline, limiting our ability to compare different scientific achievements. Previous efforts to account for citation variations often rely on a priori discipline labels of papers, assuming that all papers in a discipline are identical in their subject matter. Here, we propose a network-based methodology to quantify the impact of an article by comparing it with locally comparable research, thereby eliminating the discipline label requirement. We show that the developed measure is not susceptible to discipline bias and follows a universal distribution for all articles published in different years, offering an unbiased indicator for impact across time and discipline. We then use the indicator to identify science-wide high impact research in the past half century and quantify its temporal production dynamics across disciplines, helping us identifying breakthroughs from diverse, smaller disciplines, such as geosciences, radiology, and optics, as opposed to citation-rich biomedical sciences. Our work provides insights into the evolution of science and paves a way for fair comparisons of the impact of diverse contributions across many fields.
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Bibliometria , Fator de Impacto de Revistas , Viés , LogroRESUMO
Astrobiology studies are a top priority in answering one of the most fundamental questions in planetary science: Is there life beyond Earth? Saturn's icy moon Enceladus is a prime target in the search for life in our solar system, identified by NASA as the second-highest priority site for a flagship mission in the next decade. The orbital sampling technique of impact ionization mass spectrometry indicated the presence of complex organics in the small icy plume particles ejected by Enceladus encountered previously by Cassini. However, high interaction velocities caused ambiguity as to the origin and identity of the organics. Laboratory validation of this technique is needed to show that biosignature molecules can survive an impact at hypervelocity speeds for detection. Here, we present results on the hypervelocity impact of organic-laden submicron ice grains for in situ mass spectrometric characterization with the first technique to accurately replicate this plume sampling scenario: the Hypervelocity Ice Grain Impact Mass Spectrometer. Our results show good agreement with Cassini data at comparable compositions. We show that amino acids entrained in ice grains can be detected intact after impact at speeds up to 4.2 km/s and that salt reduces their detectability, validating the predictions from other model systems. Our results provide a benchmark for this orbital sampling method to successfully detect signs of life and for the interpretation of past and future data. This work has implications not only for a potential Enceladus mission but also for the forthcoming Europa Clipper mission.
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How difficult is it for an early career academic to climb the ranks of their discipline? We tackle this question with a comprehensive bibliometric analysis of 57 disciplines, examining the publications of more than 5 million authors whose careers started between 1986 and 2008. We calibrate a simple random walk model over historical data of ranking mobility, which we use to 1) identify which strata of academic impact rankings are the most/least mobile and 2) study the temporal evolution of mobility. By focusing our analysis on cohorts of authors starting their careers in the same year, we find that ranking mobility is remarkably low for the top- and bottom-ranked authors and that this excess of stability persists throughout the entire period of our analysis. We further observe that mobility of impact rankings has increased over time, and that such rise has been accompanied by a decline of impact inequality, which is consistent with the negative correlation that we observe between such two quantities. These findings provide clarity on the opportunities of new scholars entering the academic community, with implications for academic policymaking.
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With a sample of 228 psychology papers that failed to replicate, we tested whether the trajectory of citation patterns changes following the publication of a failure to replicate. Across models, we found consistent evidence that failing to replicate predicted lower future citations and that the size of this reduction increased over time. In a 14-y postpublication period, we estimated that the publication of a failed replication was associated with an average citation decline of 14% for original papers. These findings suggest that the publication of failed replications may contribute to a self-correcting science by decreasing scholars' reliance on unreplicable original findings.
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Payments for ecosystem services (PES) are increasingly being implemented worldwide as conservation instruments that provide conditional economic incentives to landowners for a prespecified duration. However, in the psychological and economic literature, critics have raised concerns that PES can undermine the recipient's intrinsic motivation to engage in pro-environmental behavior. Such "crowding out" may reduce the effectiveness of PES and may even worsen conservation outcomes once programs are terminated. In this study, we harnessed a randomized controlled trial that provided PES to land users in Western Uganda and evaluated whether these incentives had a persistent effect on pro-environmental behavior and its underlying behavioral drivers 6 y after the last payments were made. We elicited pro-environmental behavior with an incentivized, experimental measure that consisted of a choice for respondents between more and less environmentally friendly tree seedlings. In addition to this main outcome, survey-based measures for underlying behavioral drivers captured self-efficacy beliefs, intrinsic motivation, and perceived forest benefits. Overall, we found no indications that PES led to the crowding out of pro-environmental behavior. That is, respondents from the treatment villages were as likely as respondents from the control villages to choose environmentally friendly tree seedlings. We also found no systematic differences between these two groups in their underlying behavioral drivers, and nor did we find evidence for crowding effects when focusing on self-reported tree planting behavior as an alternative outcome measure.
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Conservação dos Recursos Naturais , Ecossistema , Humanos , Uganda , Florestas , Árvores , MotivaçãoRESUMO
Subconcussive head impacts are associated with the development of acute and chronic cognitive deficits. We recently reported that high-frequency head impact (HFHI) causes chronic cognitive deficits in mice through synaptic changes. To better understand the mechanisms underlying HFHI-induced memory decline, we used TRAP2/Ai32 transgenic mice to enable visualization and manipulation of memory engrams. We labeled the fear memory engram in male and female mice exposed to an aversive experience and subjected them to sham or HFHI. Upon subsequent exposure to natural memory recall cues, sham, but not HFHI, mice successfully retrieved fearful memories. In sham mice the hippocampal engram neurons exhibited synaptic plasticity, evident in amplified AMPA:NMDA ratio, enhanced AMPA-weighted tau, and increased dendritic spine volume compared with nonengram neurons. In contrast, although HFHI mice retained a comparable number of hippocampal engram neurons, these neurons did not undergo synaptic plasticity. This lack of plasticity coincided with impaired activation of the engram network, leading to retrograde amnesia in HFHI mice. We validated that the memory deficits induced by HFHI stem from synaptic plasticity impairments by artificially activating the engram using optogenetics and found that stimulated memory recall was identical in both sham and HFHI mice. Our work shows that chronic cognitive impairment after HFHI is a result of deficiencies in synaptic plasticity instead of a loss in neuronal infrastructure, and we can reinstate a forgotten memory in the amnestic brain by stimulating the memory engram. Targeting synaptic plasticity may have therapeutic potential for treating memory impairments caused by repeated head impacts.
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Amnésia , Memória , Masculino , Camundongos , Feminino , Animais , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico , Memória/fisiologia , Plasticidade Neuronal/fisiologia , Hipocampo/fisiologia , Camundongos TransgênicosRESUMO
The glacial cycles of the Quaternary heavily impacted species through successions of population contractions and expansions. Similarly, populations have been intensely shaped by human pressures such as unregulated hunting and land use changes. White-tailed and mule deer survived in different refugia through the Last Glacial Maximum, and their populations were severely reduced after the European colonization. Here, we analyzed 73 resequenced deer genomes from across their North American range to understand the consequences of climatic and anthropogenic pressures on deer demographic and adaptive history. We found strong signals of climate-induced vicariance and demographic decline; notably, multiple sequentially Markovian coalescent recovers a severe decline in mainland white-tailed deer effective population size (Ne) at the end of the Last Glacial Maximum. We found robust evidence for colonial overharvest in the form of a recent and dramatic drop in Ne in all analyzed populations. Historical census size and restocking data show a clear parallel to historical Ne estimates, and temporal Ne/Nc ratio shows patterns of conservation concern for mule deer. Signatures of selection highlight genes related to temperature, including a cold receptor previously highlighted in woolly mammoth. We also detected immune genes that we surmise reflect the changing land use patterns in North America. Our study provides a detailed picture of anthropogenic and climatic-induced decline in deer diversity and clues to understanding the conservation concerns of mule deer and the successful demographic recovery of white-tailed deer.
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Cervos , Genética Populacional , Humanos , Animais , Cervos/genética , Genômica , Demografia , EquidaeRESUMO
Disrupted protein phosphorylation due to genetic variation is a widespread phenomenon that triggers oncogenic transformation of healthy cells. However, few relevant phosphorylation disruption events have been verified due to limited biological experimental methods. Because of the lack of reliable benchmark datasets, current bioinformatics methods primarily use sequence-based traits to study variant impact on phosphorylation (VIP). Here, we increased the number of experimentally supported VIP events from less than 30 to 740 by manually curating and reanalyzing multi-omics data from 916 patients provided by the Clinical Proteomic Tumor Analysis Consortium. To predict VIP events in cancer cells, we developed VIPpred, a machine learning method characterized by multidimensional features that exhibits robust performance across different cancer types. Our method provided a pan-cancer landscape of VIP events, which are enriched in cancer-related pathways and cancer driver genes. We found that variant-induced increases in phosphorylation events tend to inhibit the protein degradation of oncogenes and promote tumor suppressor protein degradation. Our work provides new insights into phosphorylation-related cancer biology as well as novel avenues for precision therapy.