Showing papers by "University of California, Santa Cruz published in 2020"

The ATLAS Experiment at the CERN Large Hadron Collider

Abstract: The ATLAS detector as installed in its experimental cavern at point 1 at CERN is described in this paper. A brief overview of the expected performance of the detector when the Large Hadron Collider begins operation is also presented.

The IntCal20 Northern Hemisphere Radiocarbon Age Calibration Curve (0-55 cal kBP)

Abstract: Radiocarbon (14C) ages cannot provide absolutely dated chronologies for archaeological or paleoenvironmental studies directly but must be converted to calendar age equivalents using a calibration curve compensating for fluctuations in atmospheric 14C concentration. Although calibration curves are constructed from independently dated archives, they invariably require revision as new data become available and our understanding of the Earth system improves. In this volume the international 14C calibration curves for both the Northern and Southern Hemispheres, as well as for the ocean surface layer, have been updated to include a wealth of new data and extended to 55,000 cal BP. Based on tree rings, IntCal20 now extends as a fully atmospheric record to ca. 13,900 cal BP. For the older part of the timescale, IntCal20 comprises statistically integrated evidence from floating tree-ring chronologies, lacustrine and marine sediments, speleothems, and corals. We utilized improved evaluation of the timescales and location variable 14C offsets from the atmosphere (reservoir age, dead carbon fraction) for each dataset. New statistical methods have refined the structure of the calibration curves while maintaining a robust treatment of uncertainties in the 14C ages, the calendar ages and other corrections. The inclusion of modeled marine reservoir ages derived from a three-dimensional ocean circulation model has allowed us to apply more appropriate reservoir corrections to the marine 14C data rather than the previous use of constant regional offsets from the atmosphere. Here we provide an overview of the new and revised datasets and the associated methods used for the construction of the IntCal20 curve and explore potential regional offsets for tree-ring data. We discuss the main differences with respect to the previous calibration curve, IntCal13, and some of the implications for archaeology and geosciences ranging from the recent past to the time of the extinction of the Neanderthals.

Visualizing and interpreting cancer genomics data via the Xena platform.

Abstract: To the Editor — There is a great need for easy-to-use cancer genomics visualization tools for both large public data resources such as TCGA (The Cancer Genome Atlas)1 and the GDC (Genomic Data Commons)2, as well as smaller-scale datasets generated by individual labs. Commonly used interactive visualization tools are either web-based portals or desktop applications. Data portals have a dedicated back end and are a powerful means of viewing centrally hosted resource datasets (for example, Xena’s predecessor, the University of California, Santa Cruz (UCSC) Cancer Browser (currently retired3), cBioPortal4, ICGC (International Cancer Genomics Consortium) Data Portal5, GDC Data Portal2). However, researchers wishing to use a data portal to explore their own data have to either redeploy the entire platform, a difficult task even for bioinformaticians, or upload private data to a server outside the user’s control, a non-starter for protected patient data, such as germline variants (for example, MAGI (Mutation Annotation and Genome Interpretation6), WebMeV7 or Ordino8). Desktop tools can view a user’s own data securely (for example, Integrated Genomics Viewer (IGV)9, Gitools10), but lack well-maintained, prebuilt files for the ever-evolving and expanding public data resources. This dichotomy between data portals and desktop tools highlights the challenge of using a single platform for both large public data and smaller-scale datasets generated by individual labs. Complicating this dichotomy is the expanding amount, and complexity, of cancer genomics data resulting from numerous technological advances, including lower-cost high-throughput sequencing and single-cell-based technologies. Cancer genomics datasets are now being generated using new assays, such as whole-genome sequencing11, DNA methylation whole-genome bisulfite sequencing12 and ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing13). Visualizing and exploring these diverse data modalities is important but challenging, especially as many tools have traditionally specialized in only one or perhaps a few data types. And although these complex datasets generate insights individually, integration with other omics datasets is crucial to help researchers discover and validate findings. UCSC Xena was developed as a high-performance visualization and analysis tool for both large public repositories and private datasets. It was built to scale with the current and future data growth and complexity. Xena’s privacy-aware architecture enables cancer researchers of all computational backgrounds to explore large, diverse datasets. Researchers use the same system to securely explore their own data, together or separately from the public data, all the while keeping private data secure. The system easily supports many tens of thousands of samples and has been tested with up to a million cells. The simple and flexible architecture supports a variety of common and uncommon data types. Xena’s Visual Spreadsheet visualization integrates gene-centric and genomic-coordinate-centric views across multiple data modalities, providing a deep, comprehensive view of genomic events within a cohort of tumors. UCSC Xena (http://xena.ucsc.edu) has two components: the front end Xena Browser and the back end Xena Hubs (Fig. 1). The web-based Xena Browser empowers biologists to explore data across multiple Xena Hubs with a variety of visualizations and analyses. The back end Xena Hubs host genomics data from laptops, public servers, behind a firewall, or in the cloud, and can be public or private (Supplementary Fig. 1). The Xena Browser receives data simultaneously from multiple Xena Hubs and integrates them into a single coherent visualization within the browser. A private Xena Hub is a hub installed on a user’s own computer (Supplementary Fig. 2). It is configured to only respond to requests from the computer’s localhost network interface (that is, http://127.0.0.1). This ensures that the hub only communicates with the computer on which the hub is installed. A public hub is configured to respond to requests from external computers. There are two types of public Xena Hubs (Supplementary Fig. 2). The first type is an open-public hub, which is a public hub accessible by everyone. While we host several open-public hubs (Supplementary Table 1), users can also set up their own as a way to share data. An example of one is the Treehouse Hub set up by the Childhood Cancer Initiative to share pediatric cancer RNA-seq gene expression data (Supplementary Note). The second type W eb s er ve r

Pan-cancer analysis of whole genomes

Abstract: Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10,11,12,13,14,15,16,17,18.

TRY plant trait database : Enhanced coverage and open access

Abstract: Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.

The 16th Data Release of the Sloan Digital Sky Surveys: First Release from the APOGEE-2 Southern Survey and Full Release of eBOSS Spectra

Abstract: This paper documents the sixteenth data release (DR16) from the Sloan Digital Sky Surveys; the fourth and penultimate from the fourth phase (SDSS-IV). This is the first release of data from the southern hemisphere survey of the Apache Point Observatory Galactic Evolution Experiment 2 (APOGEE-2); new data from APOGEE-2 North are also included. DR16 is also notable as the final data release for the main cosmological program of the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), and all raw and reduced spectra from that project are released here. DR16 also includes all the data from the Time Domain Spectroscopic Survey (TDSS) and new data from the SPectroscopic IDentification of ERosita Survey (SPIDERS) programs, both of which were co-observed on eBOSS plates. DR16 has no new data from the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey (or the MaNGA Stellar Library "MaStar"). We also preview future SDSS-V operations (due to start in 2020), and summarize plans for the final SDSS-IV data release (DR17).

An astronomically dated record of Earth's climate and its predictability over the last 66 million years.

Abstract: Much of our understanding of Earth's past climate comes from the measurement of oxygen and carbon isotope variations in deep-sea benthic foraminifera. Yet, long intervals in existing records lack the temporal resolution and age control needed to thoroughly categorize climate states of the Cenozoic era and to study their dynamics. Here, we present a new, highly resolved, astronomically dated, continuous composite of benthic foraminifer isotope records developed in our laboratories. Four climate states-Hothouse, Warmhouse, Coolhouse, Icehouse-are identified on the basis of their distinctive response to astronomical forcing depending on greenhouse gas concentrations and polar ice sheet volume. Statistical analysis of the nonlinear behavior encoded in our record reveals the key role that polar ice volume plays in the predictability of Cenozoic climate dynamics.

Towards complete and error-free genome assemblies of all vertebrate species

Abstract: High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are only available for a few non-microbial species. To address this issue, the international Genome 10K (G10K) consortium has worked over a five-year period to evaluate and develop cost-effective methods for assembling the most accurate and complete reference genomes to date. Here we summarize these developments, introduce a set of quality standards, and present lessons learned from sequencing and assembling 16 species representing major vertebrate lineages (mammals, birds, reptiles, amphibians, teleost fishes and cartilaginous fishes). We confirm that long-read sequencing technologies are essential for maximizing genome quality and that unresolved complex repeats and haplotype heterozygosity are major sources of error in assemblies. Our new assemblies identify and correct substantial errors in some of the best historical reference genomes. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an effort to generate high-quality, complete reference genomes for all ~70,000 extant vertebrate species and help enable a new era of discovery across the life sciences.

The evolutionary history of 2,658 cancers

Abstract: Cancer develops through a process of somatic evolution1,2. Sequencing data from a single biopsy represent a snapshot of this process that can reveal the timing of specific genomic aberrations and the changing influence of mutational processes3. Here, by whole-genome sequencing analysis of 2,658 cancers as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)4, we reconstruct the life history and evolution of mutational processes and driver mutation sequences of 38 types of cancer. Early oncogenesis is characterized by mutations in a constrained set of driver genes, and specific copy number gains, such as trisomy 7 in glioblastoma and isochromosome 17q in medulloblastoma. The mutational spectrum changes significantly throughout tumour evolution in 40% of samples. A nearly fourfold diversification of driver genes and increased genomic instability are features of later stages. Copy number alterations often occur in mitotic crises, and lead to simultaneous gains of chromosomal segments. Timing analyses suggest that driver mutations often precede diagnosis by many years, if not decades. Together, these results determine the evolutionary trajectories of cancer, and highlight opportunities for early cancer detection.

Telomere-to-telomere assembly of a complete human X chromosome

Abstract: After two decades of improvements, the current human reference genome (GRCh38) is the most accurate and complete vertebrate genome ever produced. However, no single chromosome has been finished end to end, and hundreds of unresolved gaps persist1,2. Here we present a human genome assembly that surpasses the continuity of GRCh382, along with a gapless, telomere-to-telomere assembly of a human chromosome. This was enabled by high-coverage, ultra-long-read nanopore sequencing of the complete hydatidiform mole CHM13 genome, combined with complementary technologies for quality improvement and validation. Focusing our efforts on the human X chromosome3, we reconstructed the centromeric satellite DNA array (approximately 3.1 Mb) and closed the 29 remaining gaps in the current reference, including new sequences from the human pseudoautosomal regions and from cancer-testis ampliconic gene families (CT-X and GAGE). These sequences will be integrated into future human reference genome releases. In addition, the complete chromosome X, combined with the ultra-long nanopore data, allowed us to map methylation patterns across complex tandem repeats and satellite arrays. Our results demonstrate that finishing the entire human genome is now within reach, and the data presented here will facilitate ongoing efforts to complete the other human chromosomes. High-coverage, ultra-long-read nanopore sequencing is used to create a new human genome assembly that improves on the coverage and accuracy of the current reference (GRCh38) and includes the gap-free, telomere-to-telomere sequence of the X chromosome.

Advanced Electrocatalysts with Single-Metal-Atom Active Sites.

Abstract: Electrocatalysts with single metal atoms as active sites have received increasing attention owing to their high atomic utilization efficiency and exotic catalytic activity and selectivity. This review aims to provide a comprehensive summary on the recent development of such single-atom electrocatalysts (SAECs) for various energy-conversion reactions. The discussion starts with an introduction of the different types of SAECs, followed by an overview of the synthetic methodologies to control the atomic dispersion of metal sites and atomically resolved characterization using state-of-the-art microscopic and spectroscopic techniques. In recognition of the extensive applications of SAECs, the electrocatalytic studies are dissected in terms of various important electrochemical reactions, including hydrogen evolution reaction (HER), oxygen evolution reaction (OER), oxygen reduction reaction (ORR), carbon dioxide reduction reaction (CO2RR), and nitrogen reduction reaction (NRR). Examples of SAECs are deliberated in each case in terms of their catalytic performance, structure-property relationships, and catalytic enhancement mechanisms. A perspective is provided at the end of each section about remaining challenges and opportunities for the development of SAECs for the targeted reaction.

Macromolecular modeling and design in Rosetta: recent methods and frameworks

Abstract: The Rosetta software for macromolecular modeling, docking and design is extensively used in laboratories worldwide. During two decades of development by a community of laboratories at more than 60 institutions, Rosetta has been continuously refactored and extended. Its advantages are its performance and interoperability between broad modeling capabilities. Here we review tools developed in the last 5 years, including over 80 methods. We discuss improvements to the score function, user interfaces and usability. Rosetta is available at http://www.rosettacommons.org.

HiCanu: accurate assembly of segmental duplications, satellites, and allelic variants from high-fidelity long reads

Abstract: Complete and accurate genome assemblies form the basis of most downstream genomic analyses and are of critical importance. Recent genome assembly projects have relied on a combination of noisy long-read sequencing and accurate short-read sequencing, with the former offering greater assembly continuity and the latter providing higher consensus accuracy. The recently introduced Pacific Biosciences (PacBio) HiFi sequencing technology bridges this divide by delivering long reads (>10 kbp) with high per-base accuracy (>99.9%). Here we present HiCanu, a modification of the Canu assembler designed to leverage the full potential of HiFi reads via homopolymer compression, overlap-based error correction, and aggressive false overlap filtering. We benchmark HiCanu with a focus on the recovery of haplotype diversity, major histocompatibility complex (MHC) variants, satellite DNAs, and segmental duplications. For diploid human genomes sequenced to 30× HiFi coverage, HiCanu achieved superior accuracy and allele recovery compared to the current state of the art. On the effectively haploid CHM13 human cell line, HiCanu achieved an NG50 contig size of 77 Mbp with a per-base consensus accuracy of 99.999% (QV50), surpassing recent assemblies of high-coverage, ultralong Oxford Nanopore Technologies (ONT) reads in terms of both accuracy and continuity. This HiCanu assembly correctly resolves 337 out of 341 validation BACs sampled from known segmental duplications and provides the first preliminary assemblies of nine complete human centromeric regions. Although gaps and errors still remain within the most challenging regions of the genome, these results represent a significant advance toward the complete assembly of human genomes.

Cell stress in cortical organoids impairs molecular subtype specification

Abstract: Cortical organoids are self-organizing three-dimensional cultures that model features of the developing human cerebral cortex1,2. However, the fidelity of organoid models remains unclear3-5. Here we analyse the transcriptomes of individual primary human cortical cells from different developmental periods and cortical areas. We find that cortical development is characterized by progenitor maturation trajectories, the emergence of diverse cell subtypes and areal specification of newborn neurons. By contrast, organoids contain broad cell classes, but do not recapitulate distinct cellular subtype identities and appropriate progenitor maturation. Although the molecular signatures of cortical areas emerge in organoid neurons, they are not spatially segregated. Organoids also ectopically activate cellular stress pathways, which impairs cell-type specification. However, organoid stress and subtype defects are alleviated by transplantation into the mouse cortex. Together, these datasets and analytical tools provide a framework for evaluating and improving the accuracy of cortical organoids as models of human brain development.

Nanopore sequencing and the Shasta toolkit enable efficient de novo assembly of eleven human genomes.

Abstract: De novo assembly of a human genome using nanopore long-read sequences has been reported, but it used more than 150,000 CPU hours and weeks of wall-clock time. To enable rapid human genome assembly, we present Shasta, a de novo long-read assembler, and polishing algorithms named MarginPolish and HELEN. Using a single PromethION nanopore sequencer and our toolkit, we assembled 11 highly contiguous human genomes de novo in 9 d. We achieved roughly 63× coverage, 42-kb read N50 values and 6.5× coverage in reads >100 kb using three flow cells per sample. Shasta produced a complete haploid human genome assembly in under 6 h on a single commercial compute node. MarginPolish and HELEN polished haploid assemblies to more than 99.9% identity (Phred quality score QV = 30) with nanopore reads alone. Addition of proximity-ligation sequencing enabled near chromosome-level scaffolds for all 11 genomes. We compare our assembly performance to existing methods for diploid, haploid and trio-binned human samples and report superior accuracy and speed. High contiguity human genomes can be assembled de novo in 6 h using nanopore long-read sequences and the Shasta toolkit.

A census of baryons in the Universe from localized fast radio bursts.

Abstract: More than three-quarters of the baryonic content of the Universe resides in a highly diffuse state that is difficult to detect, with only a small fraction directly observed in galaxies and galaxy clusters1,2. Censuses of the nearby Universe have used absorption line spectroscopy3,4 to observe the ‘invisible’ baryons, but these measurements rely on large and uncertain corrections and are insensitive to most of the Universe’s volume and probably most of its mass. In particular, quasar spectroscopy is sensitive either to the very small amounts of hydrogen that exist in the atomic state, or to highly ionized and enriched gas4–6 in denser regions near galaxies7. Other techniques to observe these invisible baryons also have limitations; Sunyaev–Zel’dovich analyses8,9 can provide evidence from gas within filamentary structures, and studies of X-ray emission are most sensitive to gas near galaxy clusters9,10. Here we report a measurement of the baryon content of the Universe using the dispersion of a sample of localized fast radio bursts; this technique determines the electron column density along each line of sight and accounts for every ionized baryon11–13. We augment the sample of reported arcsecond-localized14–18 fast radio bursts with four new localizations in host galaxies that have measured redshifts of 0.291, 0.118, 0.378 and 0.522. This completes a sample sufficiently large to account for dispersion variations along the lines of sight and in the host-galaxy environments11, and we derive a cosmic baryon density of $${\varOmega }_{{\rm{b}}}={0.051}_{-0.025}^{+0.021}{h}_{70}^{-1}$$ (95 per cent confidence; h70 = H0/(70 km s−1 Mpc−1) and H0 is Hubble’s constant). This independent measurement is consistent with values derived from the cosmic microwave background and from Big Bang nucleosynthesis19,20. The baryon density determined along the lines of sight to localized fast radio bursts is consistent with that determined from the cosmic microwave background and required by Big Bang nucleosynthesis.

Initial results from the InSight mission on Mars

Abstract: NASA’s InSight (Interior exploration using Seismic Investigations, Geodesy and Heat Transport) mission landed in Elysium Planitia on Mars on 26 November 2018. It aims to determine the interior structure, composition and thermal state of Mars, as well as constrain present-day seismicity and impact cratering rates. Such information is key to understanding the differentiation and subsequent thermal evolution of Mars, and thus the forces that shape the planet’s surface geology and volatile processes. Here we report an overview of the first ten months of geophysical observations by InSight. As of 30 September 2019, 174 seismic events have been recorded by the lander’s seismometer, including over 20 events of moment magnitude Mw = 3–4. The detections thus far are consistent with tectonic origins, with no impact-induced seismicity yet observed, and indicate a seismically active planet. An assessment of these detections suggests that the frequency of global seismic events below approximately Mw = 3 is similar to that of terrestrial intraplate seismic activity, but there are fewer larger quakes; no quakes exceeding Mw = 4 have been observed. The lander’s other instruments—two cameras, atmospheric pressure, temperature and wind sensors, a magnetometer and a radiometer—have yielded much more than the intended supporting data for seismometer noise characterization: magnetic field measurements indicate a local magnetic field that is ten-times stronger than orbital estimates and meteorological measurements reveal a more dynamic atmosphere than expected, hosting baroclinic and gravity waves and convective vortices. With the mission due to last for an entire Martian year or longer, these results will be built on by further measurements by the InSight lander. Geophysical and meteorological measurements by NASA’s InSight lander on Mars reveal a planet that is seismically active and provide information about the interior, surface and atmospheric workings of Mars.

Evolutionary roads leading to low effective spins, high black hole masses, and O1/O2 rates for LIGO/Virgo binary black holes

Abstract: All ten LIGO/Virgo binary black hole (BH-BH) coalescences reported following the O1/O2 runs have near-zero effective spins. There are only three potential explanations for this. If the BH spin magnitudes are large, then: (i) either both BH spin vectors must be nearly in the orbital plane or (ii) the spin angular momenta of the BHs must be oppositely directed and similar in magnitude. Then there is also the possibility that (iii) the BH spin magnitudes are small. We consider the third hypothesis within the framework of the classical isolated binary evolution scenario of the BH-BH merger formation. We test three models of angular momentum transport in massive stars: A mildly efficient transport by meridional currents (as employed in the Geneva code), an efficient transport by the Tayler-Spruit magnetic dynamo (as implemented in the MESA code), and a very-efficient transport (as proposed by Fuller et al.) to calculate natal BH spins. We allow for binary evolution to increase the BH spins through accretion and account for the potential spin-up of stars through tidal interactions. Additionally, we update the calculations of the stellar-origin BH masses, including revisions to the history of star formation and to the chemical evolution across cosmic time. We find that we can simultaneously match the observed BH-BH merger rate density and BH masses and BH-BH effective spins. Models with efficient angular momentum transport are favored. The updated stellar-mass weighted gas-phase metallicity evolution now used in our models appears to be key for obtaining an improved reproduction of the LIGO/Virgo merger rate estimate. Mass losses during the pair-instability pulsation supernova phase are likely to be overestimated if the merger GW170729 hosts a BH more massive than 50âMâS. We also estimate rates of black hole-neutron star (BH-NS) mergers from recent LIGO/Virgo observations. If, in fact. angular momentum transport in massive stars is efficient, then any (electromagnetic or gravitational wave) observation of a rapidly spinning BH would indicate either a very effective tidal spin up of the progenitor star (homogeneous evolution, high-mass X-ray binary formation through case A mass transfer, or a spin-up of a Wolf-Rayet star in a close binary by a close companion), significant mass accretion by the hole, or a BH formation through the merger of two or more BHs (in a dense stellar cluster). (Less)

A review of the major threats and challenges to global bat conservation

Abstract: Bats are an ecologically and taxonomically diverse group accounting for roughly a fifth of mammalian diversity worldwide. Many of the threats bats face (e.g., habitat loss, bushmeat hunting, and climate change) reflect the conservation challenges of our era. However, compared to other mammals and birds, we know significantly less about the population status of most bat species, which makes prioritizing and planning conservation actions challenging. Over a third of bat species assessed by the International Union for Conservation of Nature (IUCN) are considered threatened or data deficient, and well over half of the species have unknown or decreasing population trends. That equals 988 species, or 80% of bats assessed by IUCN, needing conservation or research attention. Delivering conservation to bat species will require sustained efforts to assess population status and trends and address data deficiencies. Successful bat conservation must integrate research and conservation to identify stressors and their solutions and to test the efficacy of actions to stabilize or increase populations. Global and regional networks that connect researchers, conservation practitioners, and local stakeholders to share knowledge, build capacity, and prioritize and coordinate research and conservation efforts, are vital to ensuring sustainable bat populations worldwide.

Genomic basis for RNA alterations in cancer

Abstract: Transcript alterations often result from somatic changes in cancer genomes1. Various forms of RNA alterations have been described in cancer, including overexpression2, altered splicing3 and gene fusions4; however, it is difficult to attribute these to underlying genomic changes owing to heterogeneity among patients and tumour types, and the relatively small cohorts of patients for whom samples have been analysed by both transcriptome and whole-genome sequencing. Here we present, to our knowledge, the most comprehensive catalogue of cancer-associated gene alterations to date, obtained by characterizing tumour transcriptomes from 1,188 donors of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA)5. Using matched whole-genome sequencing data, we associated several categories of RNA alterations with germline and somatic DNA alterations, and identified probable genetic mechanisms. Somatic copy-number alterations were the major drivers of variations in total gene and allele-specific expression. We identified 649 associations of somatic single-nucleotide variants with gene expression in cis, of which 68.4% involved associations with flanking non-coding regions of the gene. We found 1,900 splicing alterations associated with somatic mutations, including the formation of exons within introns in proximity to Alu elements. In addition, 82% of gene fusions were associated with structural variants, including 75 of a new class, termed 'bridged' fusions, in which a third genomic location bridges two genes. We observed transcriptomic alteration signatures that differ between cancer types and have associations with variations in DNA mutational signatures. This compendium of RNA alterations in the genomic context provides a rich resource for identifying genes and mechanisms that are functionally implicated in cancer.

The impact of COVID-19 on small business owners: Evidence from the first 3 months after widespread social-distancing restrictions.

Abstract: Social-distancing restrictions and health- and economic-driven demand shifts from COVID-19 are expected to shutter many small businesses and entrepreneurial ventures, but there is very little early evidence on impacts. This paper provides the first analysis of impacts of the pandemic on the number of active small businesses in the United States using nationally representative data from the April 2020 Current Population Survey-the first month fully capturing early effects. The number of active business owners in the United States plummeted by 3.3 million or 22% over the crucial 2-month window from February to April 2020. The drop in active business owners was the largest on record, and losses to business activity were felt across nearly all industries. African-American businesses were hit especially hard experiencing a 41% drop in business activity. Latinx business owner activity fell by 32%, and Asian business owner activity dropped by 26%. Simulations indicate that industry compositions partly placed these groups at a higher risk of business activity losses. Immigrant business owners experienced substantial losses in business activity of 36%. Female business owners were also disproportionately affected (25% drop in business activity). Continuing the analysis in May and June, the number of active business owners remained low-down by 15% and 8%, respectively. The continued losses in May and June, and partial rebounds from April were felt across all demographic groups and most industries. These findings of early-stage losses to small business activity have important implications for policy, income losses, and future economic inequality.

Full-length transcript characterization of SF3B1 mutation in chronic lymphocytic leukemia reveals downregulation of retained introns

Abstract: While splicing changes caused by somatic mutations in SF3B1 are known, identifying full-length isoform changes may better elucidate the functional consequences of these mutations. We report nanopore sequencing of full-length cDNA from CLL samples with and without SF3B1 mutation, as well as normal B cell samples, giving a total of 149 million pass reads. We present FLAIR (Full-Length Alternative Isoform analysis of RNA), a computational workflow to identify high-confidence transcripts, perform differential splicing event analysis, and differential isoform analysis. Using nanopore reads, we demonstrate differential 3' splice site changes associated with SF3B1 mutation, agreeing with previous studies. We also observe a strong downregulation of intron retention events associated with SF3B1 mutation. Full-length transcript analysis links multiple alternative splicing events together and allows for better estimates of the abundance of productive versus unproductive isoforms. Our work demonstrates the potential utility of nanopore sequencing for cancer and splicing research.

The COVID-19 Pandemic, Small-Scale Fisheries and Coastal Fishing Communities

Abstract: The COVID-19 pandemic has rapidly spread around the world with extensive social and economic effects. This editorial focuses specifically on the implications of the pandemic for small-scale fishers, including marketing and processing aspects of the sector, and coastal fishing communities, drawing from news and reports from around the world. Negative consequences to date have included complete shut-downs of some fisheries, knock-on economic effects from market disruptions, increased health risks for fishers, processors and communities, additional implications for marginalized groups, exacerbated vulnerabilities to other social and environmental stressors, and increased Illegal, Unreported and Unregulated fishing. Though much of the news is dire, there have been some positive outcomes such as food sharing, the revival of local food networks, increases in local sales through direct marketing and deliveries, collective actions to safeguard rights, collaborations between communities and governments, and reduced fishing pressure in some places. While the crisis is still unfolding, there is an urgent need to coordinate, plan and implement effective short- and long-term responses. Thus, we urge governments, development organizations, NGOs, donors, the private sector, and researchers to rapidly mobilize in support of small-scale fishers, coastal fishing communities, and associated civil society organizations, and suggest actions that can be taken by each to help these groups respond to the COVID-19 pandemic.

Electrocatalysis of Single-Atom Sites: Impacts of Atomic Coordination

Abstract: Single metal atoms embedded within select supporting matrices have shown great potential in the development of high-efficiency, low-cost electrocatalysts because of maximal atom utilization and mas...

The Impacts of Ocean Acidification on Marine Ecosystems and Reliant Human Communities

Abstract: Rising atmospheric carbon dioxide (CO2) levels, from fossil fuel combustion and deforestation, along with agriculture and land-use practices are causing wholesale increases in seawater CO2 and inor

Constraints on the shallow elastic and anelastic structure of Mars from InSight seismic data

Abstract: Mars’s seismic activity and noise have been monitored since January 2019 by the seismometer of the InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) lander. At night, Mars is extremely quiet; seismic noise is about 500 times lower than Earth’s microseismic noise at periods between 4 s and 30 s. The recorded seismic noise increases during the day due to ground deformations induced by convective atmospheric vortices and ground-transferred wind-generated lander noise. Here we constrain properties of the crust beneath InSight, using signals from atmospheric vortices and from the hammering of InSight’s Heat Flow and Physical Properties (HP3) instrument, as well as the three largest Marsquakes detected as of September 2019. From receiver function analysis, we infer that the uppermost 8–11 km of the crust is highly altered and/or fractured. We measure the crustal diffusivity and intrinsic attenuation using multiscattering analysis and find that seismic attenuation is about three times larger than on the Moon, which suggests that the crust contains small amounts of volatiles. The crust beneath the InSight lander on Mars is altered or fractured to 8–11 km depth and may bear volatiles, according to an analysis of seismic noise and wave scattering recorded by InSight’s seismometer.

Mapping carbon accumulation potential from global natural forest regrowth

Abstract: To constrain global warming, we must strongly curtail greenhouse gas emissions and capture excess atmospheric carbon dioxide1,2. Regrowing natural forests is a prominent strategy for capturing additional carbon3, but accurate assessments of its potential are limited by uncertainty and variability in carbon accumulation rates2,3. To assess why and where rates differ, here we compile 13,112 georeferenced measurements of carbon accumulation. Climatic factors explain variation in rates better than land-use history, so we combine the field measurements with 66 environmental covariate layers to create a global, one-kilometre-resolution map of potential aboveground carbon accumulation rates for the first 30 years of natural forest regrowth. This map shows over 100-fold variation in rates across the globe, and indicates that default rates from the Intergovernmental Panel on Climate Change (IPCC)4,5 may underestimate aboveground carbon accumulation rates by 32 per cent on average and do not capture eight-fold variation within ecozones. Conversely, we conclude that maximum climate mitigation potential from natural forest regrowth is 11 per cent lower than previously reported3 owing to the use of overly high rates for the location of potential new forest. Although our data compilation includes more studies and sites than previous efforts, our results depend on data availability, which is concentrated in ten countries, and data quality, which varies across studies. However, the plots cover most of the environmental conditions across the areas for which we predicted carbon accumulation rates (except for northern Africa and northeast Asia). We therefore provide a robust and globally consistent tool for assessing natural forest regrowth as a climate mitigation strategy. A one-kilometre-resolution map of aboveground carbon accumulation rates of forest regrowth shows 100-fold variation across the globe, with rates 32% higher on average than IPCC estimates.

Searching for long-lived particles beyond the Standard Model at the Large Hadron Collider

Abstract: Particles beyond the Standard Model (SM) can generically have lifetimes that are long compared to SM particles at the weak scale. When produced at experiments such as the Large Hadron Collider (LHC) at CERN, these long-lived particles (LLPs) can decay far from the interaction vertex of the primary proton–proton collision. Such LLP signatures are distinct from those of promptly decaying particles that are targeted by the majority of searches for new physics at the LHC, often requiring customized techniques to identify, for example, significantly displaced decay vertices, tracks with atypical properties, and short track segments. Given their non-standard nature, a comprehensive overview of LLP signatures at the LHC is beneficial to ensure that possible avenues of the discovery of new physics are not overlooked. Here we report on the joint work of a community of theorists and experimentalists with the ATLAS, CMS, and LHCb experiments—as well as those working on dedicated experiments such as MoEDAL, milliQan, MATHUSLA, CODEX-b, and FASER—to survey the current state of LLP searches at the LHC, and to chart a path for the development of LLP searches into the future, both in the upcoming Run 3 and at the high-luminosity LHC. The work is organized around the current and future potential capabilities of LHC experiments to generally discover new LLPs, and takes a signature-based approach to surveying classes of models that give rise to LLPs rather than emphasizing any particular theory motivation. We develop a set of simplified models; assess the coverage of current searches; document known, often unexpected backgrounds; explore the capabilities of proposed detector upgrades; provide recommendations for the presentation of search results; and look towards the newest frontiers, namely high-multiplicity 'dark showers', highlighting opportunities for expanding the LHC reach for these signals.