Genome-Wide Transcriptomic Analysis of Intestinal Tissue to Assess the Impact of Nutrition and a Secondary Nematode Challenge in Lactating Rats

Gastrointestinal nematode infection is a major challenge to the health and welfare of mammals. Although mammals eventually acquire immunity to nematodes, this breaks down around parturition, which renders periparturient mammals susceptible to re-infection and an infection source for their offspring. Nutrient supplementation reduces the extent of periparturient parasitism, but the underlying mechanisms remain unclear. Here, we use a genome wide approach to assess the effects of protein supplementation on gene expression in the small intestine of periparturient rats following nematode re-infection.The use of a rat whole genome expression microarray (Affymetrix Gene 1.0ST) showed significant differential regulation of 91 genes in the small intestine of lactating rats, re-infected with Nippostrongylus brasiliensis compared to controls; affected functions included immune cell trafficking, cell-mediated responses and antigen presentation. Genes with a previously described role in immune response to nematodes, such as mast cell proteases, and intelectin, and others newly associated with nematode expulsion, such as anterior gradient homolog 2 were identified. Protein supplementation resulted in significant differential regulation of 64 genes; affected functions included protein synthesis, cellular function and maintenance. It increased cell metabolism, evident from the high number of non-coding RNA and the increased synthesis of ribosomal proteins. It regulated immune responses, through T-cell activation and proliferation. The up-regulation of transcription factor forkhead box P1 in unsupplemented, parasitised hosts may be indicative of a delayed immune response in these animals.This study provides the first evidence for nutritional regulation of genes related to immunity to nematodes at the site of parasitism, during expulsion. Additionally it reveals genes induced following secondary parasite challenge in lactating mammals, not previously associated with parasite expulsion. This work is a first step towards defining disease predisposition, identifying markers for nutritional imbalance and developing sustainable measures for parasite control in domestic mammals

The future of monetary arrangements in Europe

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Comparison of Actinarian and HEG phylogenies.

<div><p> <b>A.</b> The numbers above each branch are the Bayesian posterior probabilities (again after burn-in trees discarded), and those below the branch are the support generated from a likelihood bootstrap analysis (n = 1000).</p> <p>The HEG tree is unrooted (it is unknown) and displayed in such a way as to minimise the differences with the host tree.</p> <p> <b>B.</b> The null distribution for the likelihood ratio test generated by evaluating δ for 1000 non-parametric bootstrap resampled data sets, 50% of which are drawn entirely from the host data and 50% from the HEG data.</p> <p>The likelihood ratio for the observed partition is shown.</p></div

Cnidaria host genome phylogeny reconstructed using Bayesian methods from 18S, 5.8S and ITS data, and is a 50% majority rule consensus taken from the MCMC analyses after plateau (i.e. ‘burn-in’ trees discarded).

<div><p>The Bayesian posterior probabilities are given for each node.</p> <p>Taxa containing a HEG are highlighted; the non-functional HEG is boxed.</p> <p>Taxonomic classification is also distinguished; O(A)  =  Octocorallia (Alcyonaria); C  =  Corrimorpharia; S  =  Scleratinia; Z  =  Zoanthiniaria.</p></div

Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 Diabetes (SCORE-IT): study protocol for the development of a core outcome set

Type 2 diabetes is characterised by abnormal glucose metabolism, and treatment is aimed at normalising glycaemia. Outcomes measured in clinical trials should be meaningful to patients, health care professionals and researchers, yet there is heterogeneity in the outcomes used across trials of glucose-lowering interventions. This inconsistency affects the ability to compare findings and may mean that the results have little importance to health care professionals and the patients for whom they care. The SCORE-IT study aims to develop a core outcome set (COS) for use in all trials of glucose-lowering interventions for people with type 2 diabetes.This study will involve three key stages in the development of a COS: (1) A list of outcomes will be identified from multiple sources, specifically registered clinical trials, online patient resources, the qualitative literature and landmark studies identified by a Study Steering Committee. (2) The list of outcomes will be scored by multiple stakeholder groups in a two-round online international Delphi survey. (3) The results of the online Delphi will be summarised and discussed at a face-to-face consensus meeting with representation from all stakeholder groups.The SCORE-IT study aims to develop an internationally relevant set of core outcomes for use in future trials of glucose-lowering interventions for type 2 diabetes. The use of a COS will improve the consistency of outcomes, allowing results of studies to be compared and combined and for new effective treatments to made available more quickly.The COS study, of which this is a part, is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database, http://www.comet-initiative.org/studies/details/956 . Registered January 2017

Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes (SCORE-IT):a patient and healthcare professional consensus on a core outcome set for type 2 diabetes

Objectives Heterogeneity in outcomes measured across trials of glucose-lowering interventions for people with type 2 diabetes impacts on the ability to compare findings and may mean that the results have little importance to healthcare professionals and the patients that they care for. The SCORE-IT study (Selecting Core Outcomes for Randomised Effectiveness trials In Type 2 diabetes) has addressed this issue by establishing consensus on the most important outcomes for non-surgical interventions for hyperglycemia in type 2 diabetes. Research design and methods A comprehensive list of outcomes was developed from registered clinical trials, online patient resources, qualitative literature and long-term studies in the field. This list was then scored in a two-round online Delphi survey completed by healthcare professionals, people with type 2 diabetes, researchers in the field and healthcare policymakers. The results of this online Delphi were discussed and ratified at a face-to-face consensus meeting. Results 173 people completed both rounds of the online survey (116 people with type 2 diabetes, 37 healthcare professionals, 14 researchers and 6 policymakers), 20 of these attended the consensus meeting (13 people with type 2 diabetes and 7 healthcare professionals). Consensus was reached on 18 core outcomes across five domains, which include outcomes related to diabetes care, quality of life and long-term diabetes-related complications. Conclusions Implementation of the core outcome set in future trials will ensure that outcomes of importance to all stakeholders are measured and reported, enhancing the relevance of trial findings and facilitating the comparison of results across trials