59 research outputs found
Al-26 and the formation of the Solar System from a molecular cloud contaminated by Wolf-Rayet winds
In agreement with previous work, we show that the presence of the short-lived
radionuclide Al-26 in the early Solar System was unlikely (<2% a priori
probability) to be the result of direct introduction of supernova ejecta into
the gaseous disk during the Class II stage of protosolar evolution. We also
show that any Bondi-Hoyle accretion of contaminated residual gas from the natal
star cluster made a negligible contribution to the primordial Al-26 inventory
of the Solar System. These results are consistent with the absence of the
oxygen isotopic signature expected with any late introduction of supernova
ejecta into the protoplanetary disk. Instead, the presence of Al-26 in the
oldest Solar System solids (calcium-aluminum-rich inclusions or CAIs) and its
apparent uniform distribution with the inferred canonical Al-26/Al-27 ratio of
(4.5-5)E-5 support the inheritance of Al-26 from the parent giant molecular
cloud. We propose that this radionuclide originated in a prior generation of
massive stars that formed in the same host molecular cloud as the Sun and
contaminated that cloud by Wolf-Rayet winds. We calculated the Galactic
distribution of Al-26/Al-27 ratios that arise from such contamination using the
established embedded cluster mass and stellar initial mass functions, published
nucleosynthetic yields from the winds of massive stars, and by assuming rapid
and uniform mixing into the cloud. Although our model predicts that the
majority of stellar systems contain no Al-26 from massive stars, and that the a
priori probability that the Al-26/Al-27 ratio will reach or exceed the
canonical Solar System value is only ~6%, the maximum in the distribution of
non-zero values is close to the canonical ratio.Comment: accepted to the Astrophysical Journa
Designing a course model for distance-based online bioinformatics training in Africa: the H3ABioNet experience
Africa is not unique in its need for basic bioinformatics training for individuals from a diverse
range of academic backgrounds. However, particular logistical challenges in Africa, most
notably access to bioinformatics expertise and internet stability, must be addressed in order
to meet this need on the continent. H3ABioNet (www.h3abionet.org), the Pan African Bioinformatics
Network for H3Africa, has therefore developed an innovative, free-of-charge
"Introduction to Bioinformatics" course, taking these challenges into account as part of its
educational efforts to provide on-site training and develop local expertise inside its network.
A multiple-delivery±mode learning model was selected for this 3-month course in order to
increase access to (mostly) African, expert bioinformatics trainers. The content of the
course was developed to include a range of fundamental bioinformatics topics at the introductory
level. For the first iteration of the course (2016), classrooms with a total of 364
enrolled participants were hosted at 20 institutions across 10 African countries. To ensure
that classroom success did not depend on stable internet, trainers pre-recorded their lectures,
and classrooms downloaded and watched these locally during biweekly contact sessions.
The trainers were available via video conferencing to take questions during contact sessions, as well as via online "question and discussion" forums outside of contact session time. This learning model, developed for a resource-limited setting, could easily be adapted
to other settings.IS
Intestinal epithelial cell endoplasmic reticulum stress promotes MULT1 up-regulation and NKG2D-mediated inflammation.
Endoplasmic reticulum (ER) stress is commonly observed in intestinal epithelial cells (IECs) and can, if excessive, cause spontaneous intestinal inflammation as shown by mice with IEC-specific deletion of X-box-binding protein 1 (Xbp1), an unfolded protein response-related transcription factor. In this study, Xbp1 deletion in the epithelium (Xbp1ΔIEC ) is shown to cause increased expression of natural killer group 2 member D (NKG2D) ligand (NKG2DL) mouse UL16-binding protein (ULBP)-like transcript 1 and its human orthologue cytomegalovirus ULBP via ER stress-related transcription factor C/EBP homology protein. Increased NKG2DL expression on mouse IECs is associated with increased numbers of intraepithelial NKG2D-expressing group 1 innate lymphoid cells (ILCs; NK cells or ILC1). Blockade of NKG2D suppresses cytolysis against ER-stressed epithelial cells in vitro and spontaneous enteritis in vivo. Pharmacological depletion of NK1.1+ cells also significantly improved enteritis, whereas enteritis was not ameliorated in Recombinase activating gene 1-/-;Xbp1ΔIEC mice. These experiments reveal innate immune sensing of ER stress in IECs as an important mechanism of intestinal inflammation
The James Webb Space Telescope Mission
Twenty-six years ago a small committee report, building on earlier studies,
expounded a compelling and poetic vision for the future of astronomy, calling
for an infrared-optimized space telescope with an aperture of at least .
With the support of their governments in the US, Europe, and Canada, 20,000
people realized that vision as the James Webb Space Telescope. A
generation of astronomers will celebrate their accomplishments for the life of
the mission, potentially as long as 20 years, and beyond. This report and the
scientific discoveries that follow are extended thank-you notes to the 20,000
team members. The telescope is working perfectly, with much better image
quality than expected. In this and accompanying papers, we give a brief
history, describe the observatory, outline its objectives and current observing
program, and discuss the inventions and people who made it possible. We cite
detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space
Telescope Overview, 29 pages, 4 figure
Genomic basis for RNA alterations in cancer.
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
High-coverage whole-genome analysis of 1220 cancers reveals hundreds of genes deregulated by rearrangement-mediated cis-regulatory alterations.
The impact of somatic structural variants (SVs) on gene expression in cancer is largely unknown. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole-genome sequencing data and RNA sequencing from a common set of 1220 cancer cases, we report hundreds of genes for which the presence within 100 kb of an SV breakpoint associates with altered expression. For the majority of these genes, expression increases rather than decreases with corresponding breakpoint events. Up-regulated cancer-associated genes impacted by this phenomenon include TERT, MDM2, CDK4, ERBB2, CD274, PDCD1LG2, and IGF2. TERT-associated breakpoints involve ~3% of cases, most frequently in liver biliary, melanoma, sarcoma, stomach, and kidney cancers. SVs associated with up-regulation of PD1 and PDL1 genes involve ~1% of non-amplified cases. For many genes, SVs are significantly associated with increased numbers or greater proximity of enhancer regulatory elements near the gene. DNA methylation near the promoter is often increased with nearby SV breakpoint, which may involve inactivation of repressor elements
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts
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