The epigenetic regulator ATF7ip inhibits Il2 expression, regulating Th17 responses.

T helper 17 cells (Th17) are critical for fighting infections at mucosal surfaces; however, they have also been found to contribute to the pathogenesis of multiple autoimmune diseases and have been targeted therapeutically. Due to the role of Th17 cells in autoimmune pathogenesis, it is important to understand the factors that control Th17 development. Here we identify the activating transcription factor 7 interacting protein (ATF7ip) as a critical regulator of Th17 differentiation. Mice with T cell-specific deletion of Atf7ip have impaired Th17 differentiation secondary to the aberrant overproduction of IL-2 with T cell receptor (TCR) stimulation and are resistant to colitis in vivo. ChIP-seq studies identified ATF7ip as an inhibitor of Il2 gene expression through the deposition of the repressive histone mark H3K9me3 in the Il2-Il21 intergenic region. These results demonstrate a new epigenetic pathway by which IL-2 production is constrained, and this may open up new avenues for modulating its production

Pdl1 Is a Putative Lipase that Enhances Photorhabdus Toxin Complex Secretion

The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of pathogens, including those of humans. These complexes comprise three protein subunits, A, B and C which in the Xenorhabdus toxin are found in a 4∶1∶1 stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to insects and have the potential to be developed as a pest control technology. The lack of recognisable signal sequences in the three large component proteins hinders an understanding of their mode of secretion. Nevertheless, we have shown the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with the bacteria's surface, although some strains can also release it into the surrounding milieu. The large number of tc gene homologues in Pl make study of the export process difficult and as such we have developed and validated a heterologous Escherichia coli expression model to study the release of these important toxins. In addition to this model, we have used comparative genomics between a strain that releases high levels of Tcd into the supernatant and one that retains the toxin on its surface, to identify a protein responsible for enhancing secretion and release of these toxins. This protein is a putative lipase (Pdl1) which is regulated by a small tightly linked antagonist protein (Orf53). The identification of homologues of these in other bacteria, linked to other virulence factor operons, such as type VI secretion systems, suggests that these genes represent a general and widespread mechanism for enhancing toxin release in Gram negative pathogens

An integrated functional genomic study of acute phenobarbital exposure in the rat.

BACKGROUND: Non-genotoxic carcinogens are notoriously difficult to identify as they do not damage DNA directly and have diverse modes of action, necessitating long term in vivo studies. The early effects of the classic rodent non-genotoxic hepatocarcinogen phenobarbital have been investigated in the Fisher rat using a combination of metabolomics and transcriptomics, to investige early stage mechanistic changes that are predictive of longer term pathology. RESULTS: Liver and blood plasma were profiled across 14 days, and multivariate statistics used to identify perturbed pathways. Both metabolomics and transcriptomics detected changes in the liver which were dose dependent, even after one day of exposure. Integration of the two datasets associated perturbations with specific pathways. Hepatic glycogen was decreased due to a decrease in synthesis, and plasma triglycerides were decreased due to an increase in fatty acid uptake by the liver. Hepatic succinate was increased and this was associated with increased heme biosynthesis. Glutathione synthesis was also increased, presumably in response to oxidative stress. Liquid Chromatography Mass Spectrometry demonstrated a remodeling of lipid species, possibly resulting from proliferation of the smooth endoplasmic reticulum. CONCLUSIONS: The data fusion of metabolomic and transcriptomic changes proved to be a highly sensitive approach for monitoring early stage changes in altered hepatic metabolism, oxidative stress and cytochrome P450 induction simultaneously. This approach is particularly useful in interpreting changes in metabolites such as succinate which are hubs of metabolism.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Isolation and characterization of Clostridioides difficile spores from contaminated single-used surgical gowns

Clostridium difficile is the primary cause of antibiotic associated diarrhoea globally. In the UK there has been a decline in the prevalence of C. difficile due to implementation of surveillance and infection control procedures. At Rideout Hospital, USA, however, there is a high incidence of C. difficile infection, which has been partly attributed to poor infection control measures. Other factors include the ability of spores to adhere to fomites such as surgical gowns. It has been demonstrated that the single-use polypropylene surgical gowns used at Rideout can ‘trap’ hydrophobic epidemic spores of C. difficile within the fibres, which can then be transferred to stainless steel surfaces and hospital floor vinyl; even with use of appropriate sporicides such as sodium dichloroisocyanurate. This study sought to establish the strains of C. difficile present on the gowns and thus inside the nosocomial environment. Contaminated gowns from Rideout were cultured for 5 days anaerobically in Brain –Heart Infusion broth supplemented with 0.1 % Sodium taurocholate. Broth culture was screened for the presence of C. difficile using CCFA media, C. DIFF QUIK CHEK COMPLETE®, 16 s-23s RNA analysis and toxin PCR. Once isolated, strains were sequenced and tested for biocide susceptibility to in-use concentrations of Sodium dichloroisocyanurate. In total 23 suspected C. difficile samples were isolated from the gowns; of which 8 were confirmed. Sporicide susceptibility testing is ongoing. Once infective strains have been identified measures can be taken to enforce appropriate infection control procedures in order to limit the prevalence of spores and reduce infection rates

HIV clinical stage progression of patients at 241 outpatient clinics in Democratic Republic of Congo: Disparities by gender, TB status and rurality

Background: HIV clinical care programs are increasingly cognizant of the importance of customizing services according to patients’ clinical stage progression (WHO\u27s four-tiered staging) and other risk assessments. Understanding factors associated with Persons Living with HIV (PLHIV) patients’ progression through the treatment cascade and clinical stages is essential for programs to provide patient-centered, evidence-based services. Methods and materials: To analyze patient characteristics associated with disease progression stages for PLHIV on antiretroviral therapy (ART), this quantitative study used data, from January 2014–June 2019, from 49,460 PLHIV on ART from 241 HIV/AIDS outpatient clinics in 23 health zones in Haut-Katanga and Kinshasa provinces, Democratic Republic of Congo. To assess bivariate and multivariate associations, we performed Chi-square and multinomial logistic regression. Results: Among PLHIV receiving ART, 4.4% were at stage 4, and 30.7% at stage 3. Those at the less severe stages 2 and 1 constituted 22.9% and 41.9%. After controlling for covariates, patients with no TB were significantly more likely than those with TB (p\u3c = .05) to be at stage 1, rather than 3 or 4 (adjusted odds ratio or AOR, 5.73; confidence interval or CI, 4.98–6.59). Other characteristics significantly associated with higher odds of being at stage 1 included being female (AOR, 1.35; CI, 1.29–1.42), and shorter duration on ART (vs. \u3e 40.37 months); for ART duration less than 3.23 months the AOR was 2.47, for 3.23–14.52 months duration the AOR was 2.60, and for 14.53–40.37 months duration the AOR was 1.77 (quartile cut points used). Compared to patients in urban health zones, those in rural (AOR, 0.32) and semi-rural health zones (AOR, 0.79) were less likely to be at stage 1. Conclusion: Significant and substantial variation in HIV clinical progression stage by geographic location and demographic characteristics existed, indicative of the need for targeted efforts to improve the effectiveness of HIV care. Patients with TB coinfection compared to those without coinfection had a much greater risk of being at stage 3 or 4, implying a need for customized approaches and clinical regimens for this high-risk population

When digital capital is not enough: reconsidering the digital lives of disabled university students.

publication-status: Publishedtypes: ArticleThe relationship that disabled university students have with both their technologies and institutions is poorly understood. This paper seeks to illuminate this relationship using the conceptual lens of digital capital. The results from a study that explored the technology experiences of 31 disabled students studying in one university were analysed with a view to revealing evidence for both cultural and social digital capital. The analysis suggests that disabled students possess significant levels of both cultural and social capital, but that there are times when this capital is compromised or insufficient to enable students to fully benefit from technologies. Possessing digital capital does not appear to guarantee complete inclusion into university life

Perineal resuturing versus expectant management following vaginal delivery complicated by a dehisced wound (PREVIEW): a nested qualitative study

Objective: To explore women's lived experiences of a dehisced perineal wound following childbirth and how they felt participating in a pilot and feasibility randomised controlled trial (RCT). Design: A nested qualitative study using semistructured interviews, underpinned by descriptive phenomenology. Participants and setting: A purposive sample of six women at 6-9 months postnatal who participated in the RCT were interviewed in their own homes. Results: Following Giorgi's analytical framework the verbatim transcripts were analysed for key themes. Women's lived experiences revealed 4 emerging themes: (1) Physical impact, with sub-themes focusing upon avoiding infection, perineal pain and the impact of the wound dehiscence upon daily activities; (2) Psychosocial impact, with sub-themes of denial, sense of failure or self-blame, fear, isolation and altered body image; (3) Sexual impact; and (4) Satisfaction with wound healing. A fifth theme 'participating in the RCT' was 'a priori' with sub-themes centred upon understanding the randomisation process, completing the trial questionnaires, attending for hospital appointments and acceptability of the treatment options. Conclusions: To the best of our knowledge, this is the first qualitative study to grant women the opportunity to voice their personal experiences of a dehisced perineal wound and their views on the management offered. The powerful testimonies presented disclose the extent of morbidity experienced while also revealing a strong preference for a treatment option.sch_die7pub5266pub

Evaluation of epidermal growth factor receptors in bladder tumours.

Epidermal growth factor (EGF) receptor expression in 31 primary human bladder tumours was quantitated using both structural and functional assays and the EGF receptor gene in the same tumours was analyzed by Southern blot analysis. Immunocytochemical studies using the EGFR1 monoclonal antibody (Mab) showed a significant correlation between EGF receptor levels and the stage and grade of the tumours. Autophosphorylation assays employed to evaluate the receptor's tyrosine kinase activity gave results which in general were consistent with the immunocytochemical data. Using internally controlled immunocytochemical studies with two Mabs and Southern blot analysis of DNA isolated from the tumours, no evidence was obtained for the production of truncated receptors similar to those encoded by the v-erb-B oncogene. Gene amplification was not found in any of the superficial tumours, but one invasive tumour with high EGF receptor expression had an 8-10 fold amplification of the EGF receptor gene. The EGF receptor isolated from this tumour showed a normal pattern of tyrosine phosphorylation at all three major autophosphorylation sites. Our detailed study is consistent with the correlation previously found between EGF receptor expression and stage and grade of bladder tumours, and suggests that at this level of analysis EGF receptors in bladder tumours are not abnormal in structure or size, autophosphorylation activity, or gene structure

The introduction and refinement of the assessment of digitally recorded audio presentations

This case study critically evaluates benefits and challenges of a form of assessment included in a final year undergraduate Religious Studies Open University module, which combines a written essay task with a digital audio recording of a short oral presentation. Based on the analysis of student and tutor feedback and sample assignments, this study critically examines how teaching and learning practices linked to this novel form of assessment have been iteratively developed in light of the project findings over a period of two years. It concludes that while this form of assessment poses a number of challenges, it can create valuable opportunities for the development of transferable twenty-first-century graduate employability skills as well as deep, effective learning experiences, particularly – though not exclusively – in distance learning settings

In-situ real time monitoring of the polymerization in gel-cast ceramic processes

Gelcasting requires making a mixture of a slurry of ceramic powder in a solution of organic monomers and casting it in a mold. Gelcasting is different from injection molding in that it separates mold filling from setting during conversion of the ceramic slurry to a formed green part. In this work, NMR spectroscopy and imaging were used for in-situ monitoring of the gelation process and gelcasting of alumina. {sup 1}H NMR spectra and images are obtained during polymerization of a mixture of soluble reactive acrylamide monomers. Polymerization was initiated by adding an initiator and an accelerator to form long- chain, crosslinked polymers. Multidimensional NMR imaging was used for in-situ monitoring of the process and for verification of homogeneous polymerization. Comparison of the modeled intensities with acquired images shows a direction extraction of T{sub 1} data from the images