Transcriptomic Profiling of Virus-Host Cell Interactions following Chicken Anaemia Virus (CAV) Infection in an In Vivo Model.

Chicken Anaemia Virus (CAV) is an economically important virus that targets lymphoid and erythroblastoid progenitor cells leading to immunosuppression. This study aimed to investigate the interplay between viral infection and the host's immune response to better understand the pathways that lead to CAV-induced immunosuppression. To mimic vertical transmission of CAV in the absence of maternally-derived antibody, day-old chicks were infected and their responses measured at various time-points post-infection by qRT-PCR and gene expression microarrays. The kinetics of mRNA expression levels of signature cytokines of innate and adaptive immune responses were determined by qRT-PCR. The global gene expression profiles of mock-infected (control) and CAV-infected chickens at 14 dpi were also compared using a chicken immune-related 5K microarray. Although in the thymus there was evidence of induction of an innate immune response following CAV infection, this was limited in magnitude. There was little evidence of a Th1 adaptive immune response in any lymphoid tissue, as would normally be expected in response to viral infection. Most cytokines associated with Th1, Th2 or Treg subsets were down-regulated, except IL-2, IL-13, IL-10 and IFNγ, which were all up-regulated in thymus and bone marrow. From the microarray studies, genes that exhibited significant (greater than 1.5-fold, false discovery rate <0.05) changes in expression in thymus and bone marrow on CAV infection were mainly associated with T-cell receptor signalling, immune response, transcriptional regulation, intracellular signalling and regulation of apoptosis. Expression levels of a number of adaptor proteins, such as src-like adaptor protein (SLA), a negative regulator of T-cell receptor signalling and the transcription factor Special AT-rich Binding Protein 1 (SATB1), were significantly down-regulated by CAV infection, suggesting potential roles for these genes as regulators of viral infection or cell defence. These results extend our understanding of CAV-induced immunosuppression and suggest a global immune dysregulation following CAV infection

Phase-separated lipid-based nanoparticles: selective behavior at the nano-bio interface

Solid state NMR/Biophysical Organic Chemistr

An untargeted multi-technique metabolomics approach to studying intracellular metabolites of HepG2 cells exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

<p>Abstract</p> <p>Background</p> <p><it>In vitro </it>cell systems together with omics methods represent promising alternatives to conventional animal models for toxicity testing. Transcriptomic and proteomic approaches have been widely applied <it>in vitro </it>but relatively few studies have used metabolomics. Therefore, the goal of the present study was to develop an untargeted methodology for performing reproducible metabolomics on <it>in vitro </it>systems. The human liver cell line HepG2, and the well-known hepatotoxic and non-genotoxic carcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), were used as the <it>in vitro </it>model system and model toxicant, respectively.</p> <p>Results</p> <p>The study focused on the analysis of intracellular metabolites using NMR, LC-MS and GC-MS, with emphasis on the reproducibility and repeatability of the data. State of the art pre-processing and alignment tools and multivariate statistics were used to detect significantly altered levels of metabolites after exposing HepG2 cells to TCDD. Several metabolites identified using databases, literature and LC-nanomate-Orbitrap analysis were affected by the treatment. The observed changes in metabolite levels are discussed in relation to the reported effects of TCDD.</p> <p>Conclusions</p> <p>Untargeted profiling of the polar and apolar metabolites of <it>in vitro </it>cultured HepG2 cells is a valid approach to studying the effects of TCDD on the cell metabolome. The approach described in this research demonstrates that highly reproducible experiments and correct normalization of the datasets are essential for obtaining reliable results. The effects of TCDD on HepG2 cells reported herein are in agreement with previous studies and serve to validate the procedures used in the present work.</p

The influence of some pterins on the circadian rhythmicity of hydroxyindole-O-methyl transferase in the pineal gland of 42-day old male Wistar rats

International audienc

Potential cofactors in accidental food allergic reactions are frequently present but may not influence severity and occurrence

Background: Cofactors, such as physical exercise and alcohol intake, might be associated with the severity or occurrence of food allergic reactions. Objective: To gain insight into the frequency of presence of potential cofactors in accidental food allergic reactions in adults and to what extent these factors influence the severity and occurrence of allergic reactions. Methods: A prospective cohort study was conducted, with a 1-year follow-up in adult patients with a physician-diagnosed food allergy. Patients were required to fill in a questionnaire after every accidental allergic reactions to food over a 1-year period. The primary outcome measure was the frequency that potential cofactors were present in these allergic reactions. Results: A total of 157 patients were included, of which 46% reported a total of 153 reactions during a 1-year follow-up period. In 74% of the reactions, ≥1 potential cofactor was reported to be present: tiredness (38%), alcohol intake (16%), stress (14%), symptoms of pollinosis (16%), symptoms of asthma (9%), sickness/flu (3%), physical exercise (3%) and use of analgesics (2%). More than one potential cofactor was reported in almost half of all reactions (47%). There was no significant difference in the presence of these factors between mild, moderate and severe reactions (P = 0.522). In the total study population, 9% of the patients used medication that might act as cofactor (antacids, angiotensin receptor blockers [ARBs], beta blockers and angiotensin-converting enzyme inhibitors [ACEIs]) on a daily basis, which however did not influence the occurrence of reactions. Furthermore, 38% daily used allergy-suppressing medication. Conclusions: Although factors suggested to be cofactors were frequently present during accidental food allergic reactions, we found no evidence for an association between the potential cofactors examined and reaction severity, in a population where most reactions were of mild to moderate severity