305 research outputs found
Repellent Surface Applications for Pest Birds
Common pest birds in the United States include the non-native European starling (Sturnus vulgaris), house sparrow (Passer domesticus), and the pigeon (Columba livia domestica), as well as native birds including Canada geese (Branta canadensis) and gull species (Laridae). Large concentrations of pest birds can create human health hazards and monetary losses due to consumption of crops, depredation, and fecal contamination and accumulation. Fecal contamination hazards include the potential spread of zoonotic diseases including antimicrobial-resistant zoonoses and human injury due to the accumulation of fecal material on walking surfaces. Additionally, fecal accumulation causes structural and aesthetic damage due to the accelerated deterioration of building materials and increased maintenance costs. Methods to alleviate hazards and damages from aggregations of pest birds are needed. In a series of 3 experiments conducted in Fort Collins, Colorado, USA, between 2016 and 2018, we evaluated 3 surface-application repellent formulations for the reduction of fecal accumulations due to European starlings: Airepel® HC with castor oil, an anthraquinone-based repellent; Airepel HC with castor oil without anthraquinone; and MS2, a novel inert formulation with a tacky, oily texture. We compared each formulation directly to an untreated control. All 3 formulations reduced fecal accumulations beneath treated aluminum perches as compared to fecal accumulations beneath untreated aluminum perches. Interestingly, both formulations that contained no anthraquinone worked equally well or better than Airepel HC with castor oil, the anthraquinone-based formulation. The benefits of an exclusively inert formulation include less risk to applicators and non-target species. Comprehensive experimental field testing of these surface-application repellent formulations is warranted
Vaccinia Virus Arrests and Shifts the Cell Cycle
Modulation of the host cell cycle is a common strategy used by viruses to create a proreplicative environment. To facilitate viral genome replication, vaccinia virus (VACV) has been reported to alter cell cycle regulation and trigger the host cell DNA damage response. However, the cellular factors and viral effectors that mediate these changes remain unknown. Here, we set out to investigate the effect of VACV infection on cell proliferation and host cell cycle progression. Using a subset of VACV mutants, we characterise the stage of infection required for inhibition of cell proliferation and define the viral effectors required to dysregulate the host cell cycle. Consistent with previous studies, we show that VACV inhibits and subsequently shifts the host cell cycle. We demonstrate that these two phenomena are independent of one another, with viral early genes being responsible for cell cycle inhibition, and post-replicative viral gene(s) responsible for the cell cycle shift. Extending previous findings, we show that the viral kinase F10 is required to activate the DNA damage checkpoint and that the viral B1 kinase and/or B12 pseudokinase mediate degradation of checkpoint effectors p53 and p21 during infection. We conclude that VACV modulates host cell proliferation and host cell cycle progression through temporal expression of multiple VACV effector proteins. (209/200.
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
Development of a core set of outcome measures for OAB treatment
© 2017, The Author(s). Introduction and hypothesis: Standardized measures enable the comparison of outcomes across providers and treatments giving valuable information for improving care quality and efficacy. The aim of this project was to define a minimum standard set of outcome measures and case-mix factors for evaluating the care of patients with overactive bladder (OAB). Methods: The International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group (WG) of leading clinicians and patients to engage in a structured method for developing a core outcome set. Consensus was determined by a modified Delphi process, and discussions were supported by both literature review and patient input. Results: The standard set measures outcomes of care for adults seeking treatment for OAB, excluding residents of long-term care facilities. The WG focused on treatment outcomes identified as most important key outcome domains to patients: symptom burden and bother, physical functioning, emotional health, impact of symptoms and treatment on quality of life, and success of treatment. Demographic information and case-mix factors that may affect these outcomes were also included. Conclusions: The standardized outcome set for evaluating clinical care is appropriate for use by all health providers caring for patients with OAB, regardless of specialty or geographic location, and provides key data for quality improvement activities and research
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
Low linkage disequilibrium in wild Anopheles gambiae s.l. populations
<p>Abstract</p> <p>Background</p> <p>In the malaria vector <it>Anopheles gambiae</it>, understanding diversity in natural populations and genetic components of important phenotypes such as resistance to malaria infection is crucial for developing new malaria transmission blocking strategies. The design and interpretation of many studies here depends critically on Linkage disequilibrium (LD). For example in association studies, LD determines the density of Single Nucleotide Polymorphisms (SNPs) to be genotyped to represent the majority of the genomic information. Here, we aim to determine LD in wild <it>An. gambiae s.l</it>. populations in 4 genes potentially involved in mosquito immune responses against pathogens (<it>Gambicin</it>, <it>NOS</it>, <it>REL2 </it>and <it>FBN9</it>) using previously published and newly generated sequences.</p> <p>Results</p> <p>The level of LD between SNP pairs in cloned sequences of each gene was determined for 7 species (or incipient species) of the <it>An. gambiae </it>complex. In all tested genes and species, LD between SNPs was low: even at short distances (< 200 bp), most SNP pairs gave an r<sup>2 </sup>< 0.3. Mean r<sup>2 </sup>ranged from 0.073 to 0.766. In most genes and species LD decayed very rapidly with increasing inter-marker distance.</p> <p>Conclusions</p> <p>These results are of great interest for the development of large scale polymorphism studies, as LD generally falls below any useful limit. It indicates that very fine scale SNP detection will be required to give an overall view of genome-wide polymorphism. Perhaps a more feasible approach to genome wide association studies is to use targeted approaches using candidate gene selection to detect association to phenotypes of interest.</p
A Hypothesis-Testing Framework for Studies Investigating Ontogenetic Niche Shifts Using Stable Isotope Ratios
Ontogenetic niche shifts occur across diverse taxonomic groups, and can have critical implications for population dynamics, community structure, and ecosystem function. In this study, we provide a hypothesis-testing framework combining univariate and multivariate analyses to examine ontogenetic niche shifts using stable isotope ratios. This framework is based on three distinct ontogenetic niche shift scenarios, i.e., (1) no niche shift, (2) niche expansion/reduction, and (3) discrete niche shift between size classes. We developed criteria for identifying each scenario, as based on three important resource use characteristics, i.e., niche width, niche position, and niche overlap. We provide an empirical example for each ontogenetic niche shift scenario, illustrating differences in resource use characteristics among different organisms. The present framework provides a foundation for future studies on ontogenetic niche shifts, and also can be applied to examine resource variability among other population sub-groupings (e.g., by sex or phenotype)
- …