Coronary Atherosclerosis in Indigenous South American Tsimane: A Cross-Sectional Cohort Study

Background—Conventional coronary artery disease risk factors might potentially explain at least 90% of the attributable risk of coronary artery disease. To better understand the association between the pre-industrial lifestyle and low prevalence of coronary artery disease risk factors, we examined the Tsimane, a Bolivian population living a subsistence lifestyle of hunting, gathering, fishing, and farming with few cardiovascular risk factors, but high infectious inflammatory burden. Methods—We did a cross-sectional cohort study including all individuals who self-identified as Tsimane and who were aged 40 years or older. Coronary atherosclerosis was assessed by coronary artery calcium (CAC) scoring done with non-contrast CT in Tsimane adults. We assessed the difference between the Tsimane and 6814 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). CAC scores higher than 100 were considered representative of significant atherosclerotic disease. Tsimane blood lipid and inflammatory biomarkers were obtained at the time of scanning, and in some patients, longitudinally. Findings—Between July 2, 2014, and Sept 10, 2015, 705 individuals, who had data available for analysis, were included in this study. 596 (85%) of 705 Tsimane had no CAC, 89 (13%) had CAC scores of 1–100, and 20 (3%) had CAC scores higher than 100. For individuals older than age 75 years, 31 (65%) Tsimane presented with a CAC score of 0, and only four (8%) had CAC scores of 100 or more, a five-fold lower prevalence than industrialised populations (p≤0-0001 for all age categories of MESA). Mean LDL and HDL cholesterol concentrations were 2.35 mmol/L (91 mg/dL) and 1.0 mmol/L (39.5 mg/dL), respectively; obesity, hypertension, high blood sugar, and regular cigarette smoking were rare. High- sensitivity C-reactive protein was elevated beyond the clinical cutoff of 3.0 mg/dL in 360 (51%) Tsimane participants. Interpretation—Despite a high infectious inflammatory burden, the Tsimane, a forager-horticulturalist population of the Bolivian Amazon with few coronary artery disease risk factors, have the lowest reported levels of coronary artery disease of any population recorded to date. These findings suggest that coronary atherosclerosis can be avoided in most people by achieving a lifetime with very low LDL, low blood pressure, low glucose, normal body-mass index, no smoking, and plenty of physical activity. The relative contributions of each are still to be determined

Microbiomes of Velloziaceae from phosphorus-impoverished soils of the campos rupestres, a biodiversity hotspot

The rocky, seasonally-dry and nutrient-impoverished soils of the Brazilian campos rupestres impose severe growth-limiting conditions on plants. Species of a dominant plant family, Velloziaceae, are highly specialized to low-nutrient conditions and seasonal water availability of this environment, where phosphorus (P) is the key limiting nutrient. Despite plant-microbe associations playing critical roles in stressful ecosystems, the contribution of these interactions in the campos rupestres remains poorly studied. Here we present the first microbiome data of Velloziaceae spp. thriving in contrasting substrates of campos rupestres. We assessed the microbiomes of Vellozia epidendroides, which occupies shallow patches of soil, and Barbacenia macrantha, growing on exposed rocks. The prokaryotic and fungal profiles were assessed by rRNA barcode sequencing of epiphytic and endophytic compartments of roots, stems, leaves and surrounding soil/rocks. We also generated root and substrate (rock/soil)-associated metagenomes of each plant species. We foresee that these data will contribute to decipher how the microbiome contributes to plant functioning in the campos rupestres, and to unravel new strategies for improved crop productivity in stressful environments6COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP88881.068071/2014-012016/23218-0Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2016/23218-0]; U.S. Department of Energy Joint Genome Institute (DOE-JGI)United States Department of Energy (DOE) [CSP 503222]; Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CAPES [88881.068071/2014-01]; FAPESPFundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2018/04240-0]; CAPESCAPES; Office of Science of the U.S. Department of EnergyUnited States Department of Energy (DOE) [DE-AC02-05CH11231

Membrane curvature during peroxisome fission requires Pex11

Pex11p is required for peroxisome proliferation. This study demonstrates that the N-terminus of Pex11p forms an amphipathic helix that generates membrane curvature required for peroxisome fission

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Optimising CO2 storage in geological formations; a case study ofshore Scotland - CO2 MultiStore project

Carbon capture, transport and storage (CCS) is considered a key technology to provide a secure, low-carbon energy supply and reduce the greenhouse gas emissions (DECC, 2014) that contribute to the adverse effects of climatic change (IPCC, 2014). Commercialisation projects for the permanent storage of carbon dioxide (CO2) captured at power plants are currently in the design stage for the Peterhead, White Rose, Caledonia Clean Energy (DECC, 2013, 2015) and Don Valley projects. Storage of the CO2 captured by these projects is planned in strata deep beneath the North Sea in depleted hydrocarbon fields or regionally extensive sandstones containing brine (saline aquifer sandstones). The vast majority of the UK and Scotland's potential storage resource, which is of European significance (SCCS, 2009), is within brine-saturated sandstone formations. The sandstone formations are each hundreds to thousands of square kilometres in extent and underlie all sectors of the North Sea. The immense potential to store CO2 in these rocks can only be fully achieved by the operation of more than one injection site within each formation. Government, university and research institutes, industry, and stakeholder organisations have anticipated the need to inform a second phase of CCS developments following on from a commercialisation project in Scotland. The CO2MultiStore study, led by Scottish Carbon Capture and Storage (SCCS), investigates the operation of more than one injection site within a storage formation using a North Sea case study. The Captain Sandstone, within the mature oil and gas province offshore Scotland, contains the Goldeneye Field, which is the planned storage site for the Peterhead CCS project. Previous research (SCCS, 2011) was augmented by data from offshore hydrocarbon exploration and detailed investigation of the Goldeneye Field for CO2 storage (Shell, 2011a-i). The research was targeted to increase understanding and confidence in the operation of two or more sites within the Captain Sandstone. Methods were implemented to reduce the effort and resources needed to characterise the sandstone, and increase understanding of its stability and performance during operation of more than one injection site. Generic learning was captured throughout the CO2MultiStore project relevant to the characterisation of the extensive storage sandstones, management of the planned injection operations and monitoring of CO2 injection at two (or more) sites within any sandstone formation. The storage of CO2 can be optimised by the operation of more than one injection site in a geological formation by taking a regional-scale approach to site assessment. The study concludes that at least 360 million tonnes of CO2 captured over the coming 35 years could be permanently stored using two injection sites in the Captain Sandstone. Confidence in the planned operation of two or more injection sites in a storage formation is greatly increased by the use of existing information, knowledge and data acquired during hydrocarbon exploitation. Widespread pressure changes should be expected by the injection of CO2 at more than one site. Assessment, management and monitoring of pressure changes on a regional scale will optimise the storage capacity, ensure security of storage and prevent adverse effects to existing storage and hydrocarbon operations. The vast offshore potential across all sectors of the North Sea could be made accessible and practical for storage of CO2 captured from European sources by the operation of two or more sites in a storage formation by following the approach taken in CO2MultiStore.Carbon capture, transport and storage (CCS) is considered a key technology to provide a secure, low-carbon energy supply and reduce the greenhouse gas emissions (DECC, 2014) that contribute to the adverse effects of climatic change (IPCC, 2014). Commercialisation projects for the permanent storage of carbon dioxide (CO2) captured at power plants are currently in the design stage for the Peterhead, White Rose, Caledonia Clean Energy (DECC, 2013, 2015) and Don Valley projects. Storage of the CO2 captured by these projects is planned in strata deep beneath the North Sea in depleted hydrocarbon fields or regionally extensive sandstones containing brine (saline aquifer sandstones). The vast majority of the UK and Scotland's potential storage resource, which is of European significance (SCCS, 2009), is within brine-saturated sandstone formations. The sandstone formations are each hundreds to thousands of square kilometres in extent and underlie all sectors of the North Sea. The immense potential to store CO2 in these rocks can only be fully achieved by the operation of more than one injection site within each formation. Government, university and research institutes, industry, and stakeholder organisations have anticipated the need to inform a second phase of CCS developments following on from a commercialisation project in Scotland. The CO2MultiStore study, led by Scottish Carbon Capture and Storage (SCCS), investigates the operation of more than one injection site within a storage formation using a North Sea case study. The Captain Sandstone, within the mature oil and gas province offshore Scotland, contains the Goldeneye Field, which is the planned storage site for the Peterhead CCS project. Previous research (SCCS, 2011) was augmented by data from offshore hydrocarbon exploration and detailed investigation of the Goldeneye Field for CO2 storage (Shell, 2011a-i). The research was targeted to increase understanding and confidence in the operation of two or more sites within the Captain Sandstone. Methods were implemented to reduce the effort and resources needed to characterise the sandstone, and increase understanding of its stability and performance during operation of more than one injection site. Generic learning was captured throughout the CO2MultiStore project relevant to the characterisation of the extensive storage sandstones, management of the planned injection operations and monitoring of CO2 injection at two (or more) sites within any sandstone formation. The storage of CO2 can be optimised by the operation of more than one injection site in a geological formation by taking a regional-scale approach to site assessment. The study concludes that at least 360 million tonnes of CO2 captured over the coming 35 years could be permanently stored using two injection sites in the Captain Sandstone. Confidence in the planned operation of two or more injection sites in a storage formation is greatly increased by the use of existing information, knowledge and data acquired during hydrocarbon exploitation. Widespread pressure changes should be expected by the injection of CO2 at more than one site. Assessment, management and monitoring of pressure changes on a regional scale will optimise the storage capacity, ensure security of storage and prevent adverse effects to existing storage and hydrocarbon operations. The vast offshore potential across all sectors of the North Sea could be made accessible and practical for storage of CO2 captured from European sources by the operation of two or more sites in a storage formation by following the approach taken in CO2MultiStore