Age Appropriate Wisdom? Ethnobiological Knowledge Ontogeny in Pastoralist Mexican Choyeros

We investigate whether age profiles of ethnobiological knowledge development are consistent with predictions derived from life history theory about the timing of productivity and reproduction. Life history models predict complementary knowledge profiles developing across the lifespan for women and men as they experience changes in embodied capital and the needs of dependent offspring. We evaluate these predictions using an ethnobiological knowledge assessment tool developed for an off-grid pastoralist population, known as Choyeros, from Baja California Sur, Mexico. Our results indicate that while individuals acquire knowledge of most dangerous items and edible resources by early adulthood, knowledge of plants and animals relevant to the age and sex divided labor domains and ecologies (e.g., women’s house gardens, men’s herding activities in the wilderness) continues to develop into middle adulthood but to different degrees and at different rates for men and women. As the demands of offspring accumulate for parents with age, reproductive aged adults continue to develop their knowledge to meet their children’s needs. After controlling for vision, post-reproductive adults’ show the greatest ethnobiological knowledge. These findings extend our understanding of the evolved human life history by illustrating how changes in embodied capital and the needs of dependent offspring predict the development of men’s and women’s ethnobiological knowledge across the lifespan

The Sextet Arcs: a Strongly Lensed Lyman Break Galaxy in the ACS Spectroscopic Galaxy Survey towards Abell 1689

We present results of the HST Advanced Camera for Surveys spectroscopic ground-based redshift survey in the field of A1689. We measure 98 redshifts, increasing the number of spectroscopically confirmed objects by sixfold. We present two spectra from this catalog of the Sextet Arcs, images which arise from a strongly-lensed Lyman Break Galaxy (LBG) at a redshift of z=3.038. Gravitational lensing by the cluster magnifies its flux by a factor of ~16 and produces six separate images with a total r-band magnitude of r_625=21.7. The two spectra, each of which represents emission from different regions of the LBG, show H I and interstellar metal absorption lines at the systemic redshift. Significant variations are seen in Ly-alpha profile across a single galaxy, ranging from strong absorption to a combination of emission plus absorption. A spectrum of a third image close to the brightest arc shows Ly-alpha emission at the same redshift as the LBG, arising from either another spatially distinct region of the galaxy, or from a companion galaxy close to the LBG. Taken as a group, the Ly-alpha equivalent width in these three spectra decreases with increasing equivalent width of the strongest interstellar absorption lines. We discuss how these variations can be used to understand the physical conditions in the LBG. Intrinsically, this LBG is faint, ~0.1L*, and forming stars at a modest rate, ~4 solar masses per year. We also detect absorption line systems toward the Sextet Arcs at z=2.873 and z=2.534. The latter system is seen across two of our spectra.Comment: Accepted for publication in Ap

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

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

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies

Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies