Granting Agency Criteria for Awarding Graduate Research Scholarships

Eleven Canadian research granting agencies were surveyed concerning the weights that they apply to various criteria when reviewing applications for graduate student awards. Nine agencies responded, seven providing useful data. The undergraduate academic grades of applicants for research training awards were found to carry high weight in selection decisions, especially in competitions that were either large or were open to students at the master's level. However, the literature on early career indicators suggests that the undergraduate academic achievement of graduate students is not an effective predictor of their future research productivity. Strategies through which agencies might improve the use of more predictive criteria, such as applicant characteristics and quality of the graduate training environment, are discussed.Onze organisations subventionnaires canadiennes ont fait l'objet d'une enquête concernant le poids qu'elles attribuent à divers critères dans leur évaluation de demandes de bourses. Neuf questionnaires ont été retournés; sept d'entre eux ont pu être utilisés. Les notes de premier cycle obtenues par les candidats de bourses de recherche revêtaient une grande importance dans les décisions, surtout dans les concours ouverts aux étudiants de deuxième cycle. Cependant, la littérature sur les indicateurs précoces d'une carrière scientifique suggère que les notes de premier cycle obtenues par les étudiants gradués ne sont pas un bon indicateur de leur productivité future en recherche. Les stratégies susceptibles d'augmenter l'utilisation des critères plus fiables, comme les caractéristiques des candidats et la qualité de leur environnement de recherche, sont discutées dans cet article

Sensibilité à la récompense et à la punition chez les individus à risque de dépendance aux drogues et à l’alcool

Affiche présentée dans le cadre du colloque de l'ARC «Favoriser l’accès et le partage par la création d’un observatoire» lors du 86e Congrès de l'Acfas à l' Université du Québec à Chicoutimi (UQAC), les 7 et 8 mai 2018.Une minorité de consommateurs de drogues et d’alcool développe un trouble d’utilisation de substances (TUS). Les jeunes dont le niveau de comportements externalisés (EXT) est supérieur sont à risque plus élevé de TUS. Cette étude examine si les individus aux traits EXT élevés (eEXT), comparés à des EXT faibles (fEXT), ont une sensibilité altérée aux récompenses et punitions – par exemple, des évaluations sociales positives. Un total de 72 jeunes adultes (18-20 ans) suivis depuis la naissance ont été catégorisés comme fEXT (n=37) ou eEXT (n=35) selon leurs données (11-16 ans). Ils ont rempli l’Alcohol Use Disorders Identification Test (AUDIT), le Baratt Impulsiveness Scale, Sensitivity to Punishment & Reward Questionnaire, et la Substance Use Risk Profile Scale (SURPS). Des tests t pour échantillons indépendants et des corrélations de Pearson ont été utilisés pour examiner les différences entre les groupes et le lien entre les mesures comportementales. On constate chez les eEXT une sensibilité accrue aux récompenses et punitions, une impulsivité plus élevée et une consommation significativement supérieure de cannabis. Au total, la sensibilité aux récompenses corrèle avec l’AUDIT et la consommation de cannabis. Les individus avec eEXT sont plus sensibles aux récompenses, ce qui peut contribuer à leur développement de TUS. Ces résultats fournissent des informations importantes pour le développement de stratégies d’intervention précoces, la prévention et le traitement des TUS

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

Serotonergic Contribution to Boys' Behavioral Regulation

Animal and human adult studies reveal a contribution of serotonin to behavior regulation. Whether these findings apply to children is unclear. The present study investigated serotonergic functioning in boys with a history of behavior regulation difficulties through a double-blind, acute tryptophan supplementation procedure.Participants were 23 boys (age 10 years) with a history of elevated physical aggression, recruited from a community sample. Eleven were given a chocolate milkshake supplemented with 500 mg tryptophan, and 12 received a chocolate milkshake without tryptophan. Boys engaged in a competitive reaction time game against a fictitious opponent, which assessed response to provocation, impulsivity, perspective taking, and sharing. Impulsivity was further assessed through a Go/No-Go paradigm. A computerized emotion recognition task and a staged instrumental help incident were also administered.Boys, regardless of group, responded similarly to high provocation by the fictitious opponent. However, boys in the tryptophan group adjusted their level of responding optimally as a function of the level of provocation, whereas boys in the control group significantly decreased their level of responding towards the end of the competition. Boys in the tryptophan group tended to show greater perspective taking, tended to better distinguish facial expressions of fear and happiness, and tended to provide greater instrumental help to the experimenter.The present study provides initial evidence for the feasibility of acute tryptophan supplementation in children and some effect of tryptophan supplementation on children's behaviors. Further studies are warranted to explore the potential impact of increased serotonergic functioning on boys' dominant and affiliative behaviors

The Dopamine Augmenter L-DOPA Does Not Affect Positive Mood in Healthy Human Volunteers

Dopamine neurotransmission influences approach toward rewards and reward-related cues. The best cited interpretation of this effect proposes that dopamine mediates the pleasure that commonly accompanies reward. This hypothesis has received support in some animal models and a few studies in humans. However, direct assessments of the effect of transiently increasing dopamine neurotransmission have been largely limited to the use of psychostimulant drugs, which elevate brain levels of multiple neurotransmitters in addition to dopamine. In the present study we tested the effect of more selectively elevating dopamine neurotransmission, as produced by administration of the immediate dopamine precursor, L-DOPA (0, 100/25, 200/50 mg, Sinemet), in healthy human volunteers. Neither dose altered positive mood. The results suggest that dopamine neurotransmission does not directly influence positive mood in humans

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