Scalar Implicature in Chitonga-Speaking Children

Research on the acquisition of scalar implicature (SI) has provided evidence that young children interpret SI differently from adults. However, results have varied, and there is now mounting evidence that around six years of age, children are able to derive the pragmatic inferences associated with SI (Foppolo, Guasti, and Chierchia, 2012). Variability in results across studies could be due to factors such as data collection methods and language-specific differences. In order to add to the growing body of literature in a meaningful way, this research investigated the interpretation of sentences that include SI by Chitonga-speaking children (7-15 years old) in rural Southern Province, Zambia, who were notably beyond the key age of six. The results of this study provide valuable insight into the interpretation of SI in a Bantu language and suggest that the acquisition of pragmatic felicity with words on a scale follows the order of acquisition identified in previous research, but may emerge at a later age in this linguistic context

Does comorbidity increase the risk of mortality among children under 3 years of age?

Objectives Diarrhoea and pneumonia remain leading causes of morbidity and mortality in children under 5 years of age. Little data is available to quantify the burden of comorbidity and the relationship between comorbid diarrhoea and pneumonia infections and mortality. We sought to quantify the relationship between comorbidity and risk of mortality among young children in two community-based studies conducted among South Asian children. Design Secondary data analysis of two cohort studies. Participants We identified two cohort studies of children under 3 years of age with prospective morbidity at least once every 2 weeks and ongoing mortality surveillance. Outcome measures We calculated the mortality risk for diarrhoea and acute lower respiratory infection (ALRI) episodes and further quantified the risk of mortality when both diseases occur at the same time using a semiparametric additive model. Results Among Nepali children, the estimated additional risk of mortality for comorbid diarrhoea and ALRI was 0.0014 (−0.0033, 0.0060). Among South Indian children, the estimated additional risk of mortality for comorbid diarrhoea and ALRI was 0.0032 (−0.0098, 0.0162). This risk is in addition to the single infection risk of mortality observed among these children. Conclusions We observed an additional risk of mortality in children who experienced simultaneous diarrhoea and ALRI episodes though the CI was wide indicating low statistical support. Additional studies with adequate power to detect the increased risk of comorbidity on mortality are needed to improve confidence around the effect size estimate

A database and tool, IM Browser, for exploring and integrating emerging gene and protein interaction data for Drosophila

BACKGROUND: Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins or genes as nodes linked by interactions. Several programs have been developed for graphical representation and analysis of interaction data, yet there remains a need for alternative programs that can provide casual users with rapid easy access to many existing and emerging data sets. DESCRIPTION: Here we describe a comprehensive database of Drosophila gene and protein interactions collected from a variety of sources, including low and high throughput screens, genetic interactions, and computational predictions. We also present a program for exploring multiple interaction data sets and for combining data from different sources. The program, referred to as the Interaction Map (IM) Browser, is a web-based application for searching and visualizing interaction data stored in a relational database system. Use of the application requires no downloads and minimal user configuration or training, thereby enabling rapid initial access to interaction data. IM Browser was designed to readily accommodate and integrate new types of interaction data as it becomes available. Moreover, all information associated with interaction measurements or predictions and the genes or proteins involved are accessible to the user. This allows combined searches and analyses based on either common or technique-specific attributes. The data can be visualized as an editable graph and all or part of the data can be downloaded for further analysis with other tools for specific applications. The database is available at CONCLUSION: The Drosophila Interactions Database described here places a variety of disparate data into one easily accessible location. The database has a simple structure that maintains all relevant information about how each interaction was determined. The IM Browser provides easy, complete access to this database and could readily be used to publish other sets of interaction data. By providing access to all of the available information from a variety of data types, the program will also facilitate advanced computational analyses

Conservation and diversity in expression of candidate genes regulating socially-induced female-male sex change in wrasses

International audienc

Up-regulation of transporters and enzymes by the vitamin D receptor ligands

ABSTRACT The effects of 1␣,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] on gene expression and function were studied in Caco-2 cells. Microarray analyses, real-time quantitative polymerase chain reactions, and Western blotting were used to determine the mRNA and protein expression of transporters and enzymes after 1,25(OH) 2 D 3 or vehicle (0.1% ethanol) treatment for 1, 3, 6, and 10 days. The mRNA and protein expressions of the apical sodium-dependent bile acid transporter, oligopeptide transporter 1, multidrug resistance-associated protein (MRP) 3, and sulfotransferase 1E1 remained unchanged with 1,25(OH) 2 D 3 treatment, whereas those for CYP3A4, multidrug resistance protein 1, and MRP2 were significantly increased (P Ͻ 0.05). 1,25(OH) 2 D 3 treatment significantly enhanced MRP4 protein expression by increasing protein stability without affecting mRNA expression, as confirmed in cycloheximide experiments. Marked increase in 6␤-hydroxylation of testosterone by CYP3A4 was also observed in the 6-day 1,25(OH) 2 D 3 -treated (100 nM) cell lysate. The transport of [ 3 H]digoxin, the P-glycoprotein (P-gp) substrate, after treatment with 100 nM 1,25(OH) 2 D 3 for 3 days revealed a higher apparent permeability (P app ) value in the basal (B)-to-apical (A) direction over that of vehicle treatment (15.1 Ϯ 0.53 ϫ 10 Ϫ6 versus 11.8 Ϯ 0.58 ϫ 10 Ϫ6 cm/s; P Ͻ 0.05), whereas the P app in the A-to-B direction was unchanged; the efflux ratio was increased (from 5.8 to 8.0). Reduced cellular retention of 5-(and-6)-carboxy-2Ј,7Ј-dichlorofluorescein, suggestive of higher MRP2 activity, was observed in the 3-day 100 nM 1,25(OH) 2 D 3 -treated cells over controls. Higher protein expression of CYP3A4, MRP2, P-gp, and MRP4 was also observed after a 6-day treatment with other vitamin D analogs (100 nM 1␣-hydroxyvitamin D 3 , 1␣-hydroxyvitamin D 2 or Hectorol, and 25-hydroxyvitamin D 3 ) in Caco-2 cells, suggesting a role of 1,25(OH) 2 D 3 and analogs in the activation of enzymes and transporters via the vitamin D receptor. The intestine plays an important role in the absorption of orally administered drugs. The expression and proximity of metabolic enzymes and efflux transporters in the enterocyte contribute to intestinal first-pass removal and delimit the tissue accumulation of endo-and xenobiotics. In the small intestine, cytochrome P450 3A4 (CYP3A4) accounts for approximately 70% of total cytochrome P450 content and is responsible for the metabolism of approximately 50% of drugs currently in us

Envelope Determinants of Equine Lentiviral Vaccine Protection

Lentiviral envelope (Env) antigenic variation and associated immune evasion present major obstacles to vaccine development. The concept that Env is a critical determinant for vaccine efficacy is well accepted, however defined correlates of protection associated with Env variation have yet to be determined. We reported an attenuated equine infectious anemia virus (EIAV) vaccine study that directly examined the effect of lentiviral Env sequence variation on vaccine efficacy. The study identified a significant, inverse, linear correlation between vaccine efficacy and increasing divergence of the challenge virus Env gp90 protein compared to the vaccine virus gp90. The report demonstrated approximately 100% protection of immunized ponies from disease after challenge by virus with a homologous gp90 (EV0), and roughly 40% protection against challenge by virus (EV13) with a gp90 13% divergent from the vaccine strain. In the current study we examine whether the protection observed when challenging with the EV0 strain could be conferred to animals via chimeric challenge viruses between the EV0 and EV13 strains, allowing for mapping of protection to specific Env sequences. Viruses containing the EV13 proviral backbone and selected domains of the EV0 gp90 were constructed and in vitro and in vivo infectivity examined. Vaccine efficacy studies indicated that homology between the vaccine strain gp90 and the N-terminus of the challenge strain gp90 was capable of inducing immunity that resulted in significantly lower levels of post-challenge virus and significantly delayed the onset of disease. However, a homologous N-terminal region alone inserted in the EV13 backbone could not impart the 100% protection observed with the EV0 strain. Data presented here denote the complicated and potentially contradictory relationship between in vitro virulence and in vivo pathogenicity. The study highlights the importance of structural conformation for immunogens and emphasizes the need for antibody binding, not neutralizing, assays that correlate with vaccine protection. © 2013 Craigo et al

IL-15 trans-presentation by pulmonary dendritic cells promotes effector CD8 T cell survival during influenza virus infection

We have recently demonstrated that peripheral CD8 T cells require two separate activation hits to accumulate to high numbers in the lungs after influenza virus infection: a primary interaction with mature, antigen-bearing dendritic cells (DCs) in the lymph node, and a second, previously unrecognized interaction with MHC I–viral antigen–bearing pulmonary DCs in the lungs. We demonstrate that in the absence of lung-resident DC subsets, virus-specific CD8 T cells undergo significantly increased levels of apoptosis in the lungs; however, reconstitution with pulmonary plasmacytoid DCs and CD8α+ DCs promotes increased T cell survival and accumulation in the lungs. Further, our results show that the absence of DCs after influenza virus infection results in significantly reduced levels of IL-15 in the lungs and that pulmonary DC–mediated rescue of virus-specific CD8 T cell responses in the lungs requires trans-presentation of IL-15 via DC-expressed IL-15Rα. This study demonstrates a key, novel requirement for DC trans-presented IL-15 in promoting effector CD8 T cell survival in the respiratory tract after virus infection, and suggests that this trans-presentation could be an important target for the development of unique antiviral therapies and more effective vaccine strategies

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 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

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