Pro-inflammatory miR-223 mediates the cross-talk between the IL23 pathway and the intestinal barrier in inflammatory bowel disease

Genes that showed greater than four-fold upregulation in IBD. (XLSX 28 kb

Impact of inter- and intra-individual variation, sample storage and sampling fraction on human stool microbial community profiles

Stools are commonly used as proxies for studying human gut microbial communities as sample collection is straightforward, cheap and non-invasive. In large-scale human population surveys, however, sample integrity becomes an issue as it is not logistically feasible for researchers to personally collect stools from every participant. Instead, participants are usually given guidelines on sample packaging and storage, and asked to deliver their stools to a centralised facility. Here, we tested a number of delivery conditions (temperature, duration and addition of preservative medium) and assessed their effects on stool microbial community composition using 16S rRNA gene amplicon sequencing. The largest source of variability in stool community composition was attributable to inter-individual differences regardless of delivery condition. Although the relative effect of delivery condition on community composition was small compared to inter-individual variability (1.6% vs. 60.5%, permutational multivariate analysis of variance [PERMANOVA]) and temporal variation within subjects over 10 weeks (5.2%), shifts in microbial taxa associated with delivery conditions were non-systematic and subject-specific. These findings indicated that it is not possible to model or accurately predict shifts in stool community composition associated with sampling logistics. Based on our findings, we recommend delivery of fresh, preservative-free stool samples to laboratories within 2 hr either at ambient or chilled temperatures to minimise perturbations to microbial community composition. In addition, subsamples from different fractions of the same stool displayed a small (3.3% vs. 72.6% inter-individual variation, PERMANOVA) but significant effect on community composition. Collection of larger sample volumes for homogenisation is recommended

Minimal SUSY SO(10) model and predictions for neutrino mixings and leptonic CP violation

We discuss a minimal Supersymmetric SO(10) model where B-L symmetry is broken by a {\bf 126} dimensional Higgs multiplet which also contributes to fermion masses in conjunction with a {\bf 10} dimensional superfield. This minimal Higgs choice provides a partial unification of neutrino flavor structure with that of quarks and has been shown to predict all three neutrino mixing angles and the solar mass splitting in agreement with observations, provided one uses the type II seesaw formula for neutrino masses. In this paper we generalize this analysis to include arbitrary CP phases in couplings and vevs. We find that (i) the predictions for neutrino mixings are similar with $U_{e3}\simeq 0.18$ as before and other parameters in a somewhat bigger range and (ii) that to first order in the quark mixing parameter $\lambda$ (the Cabibbo angle), the leptonic mixing matrix is CP conserving. We also find that in the absence of any higher dimensional contributions to fermion masses, the CKM phase is different from that of the standard model implying that there must be new contributions to quark CP violation from the supersymmetry breaking sector. Inclusion of higher dimensional terms however allows the standard model CKM phase to be maintained.Comment: 22 pages, 6 figure

The association between new generation oral contraceptive pill and the development of inflammatory bowel diseases

Background/AimsTo examine the association between use of oral contraceptive pills (OCPs) and the risk of developing inflammatory bowel diseases (IBD), in a modern cohort.MethodsA prospective nested case-control study across sites in the Asia-Pacific region was conducted; involving female IBD cases and asymptomatic controls. Subjects completed a questionnaire addressing questions related to OCP use. Primary outcome was the risk of development of IBD of those exposed to OCP versus non-exposure. Secondary outcomes were development of Crohn's disease (CD) versus ulcerative colitis (UC), and whether age of first use of OCP use may be associated with risk of IBD.ResultsThree hundred and forty-eight female IBD cases (41% CD, median age: 43 years) and 590 female age-matched controls were recruited. No significant association was found between OCP use and the risk of IBD (odds ratio [OR], 1.65; 95% confidence interval, 0.77–3.13; P=0.22), CD (OR, 1.55) or UC (OR, 1.01). The lack of association persisted when results were adjusted for age and smoking. IBD cases commenced OCP use at a younger age than controls (18 years vs. 20 years, P=0.049).ConclusionsIn this large cohort of subjects from the Asia-Pacific region, we found a modest but not significantly increased risk of developing IBD amongst OCP users

Pectin at the oil-water interface: Relationship of molecular composition and structure to functionality

The present review examines how macromolecular structure and functional groups of pectin affect its functionality with particular focus on its interfacial activity. We venture into a description of the particularly complex pectin structure and describe the major building blocks and their properties. In the following section, the role of each structural parameter is discussed with particular attention to protein, degree of acetylation and methylation, molecular weight, and branching. Finally, we discuss how modification of the extraction conditions could be tailored to obtain pectin with the desired emulsification properties. It is proposed that pectin with protein content in the range of 3%, with degree of acetylation greater than 10%, molecular weight between 100 and 200 x103 g mol-1 and enriched in RG-I segments is more likely to perform well as an emulsifier. To tailor such a structure, an aqueous extraction protocol with low pH values (between 2.5-3.5) with a strong monoprotic acid (e.g., HCl) and one-step solvent precipitation should be selected. The proposed set of extraction conditions could be used as a first step towards rational design of pectin with desirable interfacial functionality

Linear B-cell epitopes in the spike and nucleocapsid proteins as markers of SARS-CoV-2 exposure and disease severity

BACKGROUND Given the unceasing worldwide surge in COVID-19 cases, there is an imperative need to develop highly specific and sensitive serology assays to define exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). METHODS Pooled plasma samples from PCR positive COVID-19 patients were used to identify linear B-cell epitopes from a SARS-CoV-2 peptide library of spike (S), envelope (E), membrane (M), and nucleocapsid (N) structural proteins by peptide-based ELISA. Hit epitopes were further validated with 79 COVID-19 patients with different disease severity status, 13 seasonal human CoV, 20 recovered SARS patients and 22 healthy donors. FINDINGS Four immunodominant epitopes, S14P5, S20P2, S21P2 and N4P5, were identified on the S and N viral proteins. IgG responses to all identified epitopes displayed a strong detection profile, with N4P5 achieving the highest level of specificity (100%) and sensitivity (>96%) against SARS-CoV-2. Furthermore, the magnitude of IgG responses to S14P5, S21P2 and N4P5 were strongly associated with disease severity. INTERPRETATION IgG responses to the peptide epitopes can serve as useful indicators for the degree of immunopathology in COVID-19 patients, and function as higly specific and sensitive sero-immunosurveillance tools for recent or past SARS-CoV-2 infections. The flexibility of these epitopes to be used alone or in combination will allow for the development of improved point-of-care-tests (POCTs)

Impact of globalization on strategic human resource management : the mediating role of CEO in HR.

Globalization and Strategic Human Resource Management (SHRM) are worldwide phenomena that have changed the face of both the global and corporate world. However, the links between the two have not been extensively researched. This exploratory study seeks to investigate the relationship between the degree of globalization and the degree of SHRM in a firm. Secondly, we examine to what extent does the chief executive officer’s (CEO) influences HRM practices to become more strategic. The results of this study show that the degree of globalization is significantly and positively related to the degree of SHRM in a firm. In addition, CEO’s role in HR is found to be a partial mediator. These results suggest that a firm’s degree of globalization should correspond to the degree of SHRM practised in the firm, and the CEO plays a vital role in influencing the practice of SHRM