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

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

True Religion and Hume's Practical Atheism

The argument and discussion in this paper begins from the premise that Hume was an atheist who denied the religious or theist hypothesis. However, even if it is agreed that that Hume was an atheist this does not tell us where he stood on the question concerning the value of religion. Some atheists, such as Spinoza, have argued that society needs to maintain and preserve a form of “true religion”, which is required for the support of our ethical life. Others, such as D’Holbach have argued that religion is not only false it is pernicious and it should be eradicated. This paper argues that Hume rejected both theseproposals, on the ground that they rest, in different ways, on excessively optimistic assumptions. The sensible, practical form of atheism that Hume defends has a more modest and realistic aim, which is simply to restrict and limit the most pernicious forms of religion. Understood this way, Hume’s practical atheism is very different from the forms of “old” atheism associated with Spinoza and D’Holbach, as well as from the “new atheism” of thinkers such as Dawkins and Dennett. Reprinted in Paul Russell, "Recasting Hume and Early Modern Philosophy: Selected Essays" (New York: Oxford University Press, 2021): 340-383

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

Evaluation of the bacterial diversity of Pressure ulcers using bTEFAP pyrosequencing

<p>Abstract</p> <p>Background</p> <p>Decubitus ulcers, also known as bedsores or pressure ulcers, affect millions of hospitalized patients each year. The microflora of chronic wounds such as ulcers most commonly exist in the biofilm phenotype and have been known to significantly impair normal healing trajectories.</p> <p>Methods</p> <p>Bacterial tag-encoded FLX amplicon pyrosequencing (bTEFAP), a universal bacterial identification method, was used to identify bacterial populations in 49 decubitus ulcers. Diversity estimators were utilized and wound community compositions analyzed in relation to metadata such as Age, race, gender, and comorbidities.</p> <p>Results</p> <p>Decubitus ulcers are shown to be polymicrobial in nature with no single bacterium exclusively colonizing the wounds. The microbial community among such ulcers is highly variable. While there are between 3 and 10 primary populations in each wound there can be hundreds of different species present many of which are in trace amounts. There is no clearly significant differences in the microbial ecology of decubitus ulcer in relation to metadata except when considering diabetes. The microbial populations and composition in the decubitus ulcers of diabetics may be significantly different from the communities in non-diabetics.</p> <p>Conclusions</p> <p>Based upon the continued elucidation of chronic wound bioburdens as polymicrobial infections, it is recommended that, in addition to traditional biofilm-based wound care strategies, an antimicrobial/antibiofilm treatment program can be tailored to each patient's respective wound microflora.</p

Connectivity within and among a Network of Temperate Marine Reserves

Networks of marine reserves are increasingly being promoted as a means of conserving marine biodiversity. One consideration in designing systems of marine reserves is the maintenance of connectivity to ensure the long-term persistence and resilience of populations. Knowledge of connectivity, however, is frequently lacking during marine reserve design and establishment. We characterise patterns of genetic connectivity of 3 key species of habitat-forming macroalgae across an established network of temperate marine reserves on the east coast of Australia and the implications for adaptive management and marine reserve design. Connectivity varied greatly among species. Connectivity was high for the subtidal macroalgae Ecklonia radiata and Phyllospora comosa and neither species showed any clear patterns of genetic structuring with geographic distance within or among marine parks. In contrast, connectivity was low for the intertidal, Hormosira banksii, and there was a strong pattern of isolation by distance. Coastal topography and latitude influenced small scale patterns of genetic structure. These results suggest that some species are well served by the current system of marine reserves in place along this temperate coast but it may be warranted to revisit protection of intertidal habitats to ensure the long-term persistence of important habitat-forming macroalgae. Adaptively managing marine reserve design to maintain connectivity may ensure the long-term persistence and resilience of marine habitats and the biodiversity they support

Parental breeding age effects on descendants' longevity interact over 2 generations in matrilines and patrilines

Individuals within populations vary enormously in mortality risk and longevity, but the causes of this variation remain poorly understood. A potentially important and phylogenetically widespread source of such variation is maternal age at breeding, which typically has negative effects on offspring longevity. Here, we show that paternal age can affect offspring longevity as strongly as maternal age does and that breeding age effects can interact over 2 generations in both matrilines and patrilines. We manipulated maternal and paternal ages at breeding over 2 generations in the neriid fly Telostylinus angusticollis. To determine whether breeding age effects can be modulated by the environment, we also manipulated larval diet and male competitive environment in the first generation. We found separate and interactive effects of parental and grand-parental ages at breeding on descendants' mortality rate and life span in both matrilines and patrilines. These breeding age effects were not modulated by grand-parental larval diet quality or competitive environment. Our findings suggest that variation in maternal and paternal ages at breeding could contribute substantially to intrapopulation variation in mortality and longevity