COMMUNITY ECOLOGY -ORIGINAL PAPER Coexistence in streams: do source-sink dynamics allow salamanders to persist with fish predators?

Abstract Theory suggests that source-sink dynamics can allow coexistence of intraguild predators and prey, but empirical evidence for this coexistence mechanism is limited. We used capture-mark-recapture, genetic methods, and stable isotopes to test whether source-sink dynamics promote coexistence between stream fishes, the intraguild predator, and stream salamanders (Dicamptodon aterrimus), the intraguild prey. Salamander populations from upstream reaches without fish were predicted to maintain or supplement sink populations in downstream reaches with fish. We found instead that downstream reaches with fish were not sinks even though fish consumed salamander larvae-apparent survival, recruitment, and population growth rate did not differ between upstream and downstream reaches. There was also no difference between upstream and downstream reaches in net emigration. We did find that D. aterrimus moved frequently along streams, but believe that this is a response to seasonal habitat changes rather than intraguild predation. Our study provides empirical evidence that local-scale mechanisms are more important than dispersal dynamics to coexistence of streams salamanders and fish. More broadly, it shows the value of empirical data on dispersal and gene flow for distinguishing between local and spatial mechanisms of coexistence

Exploration of the 2016 Yellowstone River fish kill and proliferative kidney disease in wild fish populations

Proliferative kidney disease (PKD) is an emerging disease that recently resulted in a large mortality event of salmonids in the Yellowstone River (Montana, USA). Total PKD fish mortalities in the Yellowstone River were estimated in the tens of thousands, which resulted in a multi-week river closure and an estimated economic loss of US$500,000. This event shocked scientists, managers, and the public, as this was the first occurrence of the disease in the Yellowstone River, the only reported occurrence of the disease in Montana in the past 25 yr, and arguably the largest wild PKD fish kill in the world. To understand why the Yellowstone River fish kill occurred, we used molecular and historical data to evaluate evidence for several hypotheses: Was the causative parasite Tetracapsuloides bryosalmonae a novel invader, was the fish kill associated with a unique parasite strain, and/or was the outbreak caused by unprecedented environmental conditions? We found that T. bryosalmonae is widely distributed in Montana and have documented occurrence of this parasite in archived fish collected in the Yellowstone River prior to the fish kill. T. bryosalmonae had minimal phylogeographic population structure, as the DNA of parasites sampled from the Yellowstone River and distant water bodies were very similar. These results suggest that T. bryosalmonae could be endemic in Montana. Due to data limitations, we could not reject the hypothesis that the fish kill was caused by a novel and more virulent genetic strain of the parasite. Finally, we found that single-year environmental conditions are insufficient to explain the cause of the 2016 Yellowstone River PKD outbreak. Other regional rivers where we documented T. bryosalmonae had similar or even more extreme conditions than the Yellowstone River and similar or more extreme conditions have occurred in the Yellowstone River in the recent past, yet mass PKD mortalities have not been documented in either instance. We conclude by placing these results and unresolved hypotheses into the broader context of international research on T. bryosalmonae and PKD, which strongly suggests that a better understanding of bryozoans, the primary host of T. bryosalmonae, is required for better ecosystem understanding

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

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

A Prospective Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Cardiovascular Disease Risk

Vitamin D (VitD) supplementation has been advocated for cardiovascular risk reduction; however, supporting data are sparse. The objective of this study was to determine whether VitD supplementation reduces cardiovascular risk. Subjects in this prospective, randomized, double-blind, placebo-controlled trial of post-menopausal women with serum 25-hydroxyvitamin D concentrations >10 and <60 ng/mL were randomized to Vitamin D3 2500 IU or placebo, daily for 4 months. Primary endpoints were changes in brachial artery flow-mediated vasodilation (FMD), carotid-femoral pulse wave velocity (PWV), and aortic augmentation index (AIx). The 114 subjects were mean (standard deviation) 63.9 (3.0) years old with a 25-hydroxyvitamin D level of 31.3 (10.6) ng/mL. Low VitD (<30 ng/mL) was present in 47% and was associated with higher body-mass index, systolic blood pressure, glucose, CRP, and lower FMD (all p<0.05). After 4 months, 25-hydroxyvitamin D levels increased by 15.7 (9.3) ng/mL on vitamin D3 vs. −0.2 (6.1) ng/mL on placebo (p<0.001). There were no significant differences between groups in changes in FMD (0.3 [3.4] vs. 0.3 [2.6] %, p = 0.77), PWV (0.00 [1.06] vs. 0.05 [0.92] m/s, p = 0.65), AIx (2.7 [6.3] vs. 0.9 [5.6] %, p = 0.10), or CRP (0.3 [1.9] vs. 0.3 [4.2] mg/L, p = 0.97). Multivariable models showed no significant interactions between treatment group and low VitD status (<30 ng/mL) for changes in FMD (p = 0.65), PWV (p = 0.93), AIx (p = 0.97), or CRP (p = 0.26).In conclusion, VitD supplementation did not improve endothelial function, arterial stiffness, or inflammation. These observations do not support use of VitD supplementation to reduce cardiovascular disease risk

Moving towards an enhanced community palliative support service (EnComPaSS): protocol for a mixed method study

BACKGROUND: The challenge of an ageing population and consequential increase of long term conditions means that the number of people requiring palliative care services is set to increase. One UK hospice is introducing new information and communication technologies to support the redesign of their community services; improve experiences of existing patients; and allow efficient and effective provision of their service to more people. Community Palliative Care Nurses employed by the hospice will be equipped with a mobile platform to improve communication, enable accurate and efficient collection of clinical data at the bedside, and provide access to clinical records at the point of care through an online digital nursing dashboard. It is believed that this will ensure safer clinical interventions, enable delegated specialist care deployment, support the clinical audit of patient care and improve patient safety and patient/carer experience. Despite current attempts to evaluate the implementation of such technology into end of life care pathways, there is still limited evidence supporting the notion that this can be sustained within services and implemented to scale. This study presents an opportunity to carry out a longitudinal evaluation of the implementation of innovative technology to provide evidence for designing more efficient and effective community palliative care services. METHODS: A mixed methods approach will be used to understand a wide range of organisational, economic, and patient-level factors. The first stage of the project will involve the development of an organisational model incorporating proposed changes resulting from the introduction of new novel mobile technologies. This model will guide stage two, which will consist of gathering and analysing primary evidence. Data will be collected using interviews, focus groups, observation, routinely collected data and documents. DISCUSSION: The implementation of this new approach to community-based palliative care delivery will require significant changes to established working patterns. This new service delivery model is being developed by the Hospice in collaboration with a team of international academic, industry, and clinical commissioning service improvement specialists. The findings from this initial evaluation will provide valuable baseline evidence regarding the delivery of palliative and end-of-life care services