A unique homologue of the eukaryotic protein-modifier ubiquitin present in the bacterium Bacteroides fragilis, a predominant resident of the human gastrointestinal tract

In the complete genome sequences of Bacteroides fragilis NCTC9343 and 638R, we have discovered a gene, ubb, the product of which has 63 % identity to human ubiquitin and cross-reacts with antibodies raised against bovine ubiquitin. The sequence of ubb is closest in identity (76 %) to the ubiquitin gene from a migratory grasshopper entomopoxvirus, suggesting acquisition by inter-kingdom horizontal gene transfer. We have screened clinical isolates of B. fragilis from diverse geographical regions and found that ubb is present in some, but not all, strains. The gene is transcribed and the mRNA is translated in B. fragilis, but deletion of ubb did not have a detrimental effect on growth. BfUbb has a predicted signal sequence; both full-length and processed forms were detected in whole-cell extracts, while the processed form was found in concentrated culture supernatants. Purified recombinant BfUbb inhibited in vitro ubiquitination and was able to covalently bind the human E1 activating enzyme, suggesting it could act as a suicide substrate in vivo. B. fragilis is one of the predominant members of the normal human gastrointestinal microbiota with estimates of up to >1011 cells per g faeces by culture. These data indicate that the gastro-intestinal tract of some individuals could contain a significant amount of aberrant ubiquitin with the potential to inappropriately activate the host immune system and/or interfere with eukaryotic ubiquitin activity. This discovery could have profound implications in relation to our understanding of human diseases such as inflammatory bowel and autoimmune diseases

CE20006

The 2020 Irish Anglerfish and Megrim Survey (IAMS) took place from 23rd February to 18th March (area 7bcjk) and 12-21st April 2020 (area 6a) on RV Celtic Explorer. The main objective of the survey is to obtain biomass and abundance indices for anglerfish (Lophius piscatorius and L. budegassa) and megrim (Lepidorhombus whiffiagonis and L. boscii) in areas 6a (south of 58°N) and 7 (west of 8°W). Secondary objectives are to collect data on the distribution, relative abundance and biology of other commercially exploited species. For the second year, additional sampling took place in deep water (up to 1,500m) in order to monitor the recovery of exploited deep-water species following the decline of the deep-water fisheries in Irish waters. The IAMS survey is coordinated with the Scottish Anglerfish and Megrim Survey (SIAMISS) and uses the same gear and fishing practices

Lifelogging user study:bystander privacy

Automatically and passively taking pictures (using lifelogging devices such as wearable cameras) of people who don’t know they’re having their picture taken raises a number of privacy concerns (from a bystander’s perspective). We conducted a study focussing on the bystanders’ concerns to the presence of augmented reality wearable devices in two contexts (one formal and one informal). The results suggests the need to embed privacy enhancing techniques into the design of lifelogging applications, which are likely to depend upon an array of factors, but not limited to the context of use, scenario (and surroundings), and content

Spatial and seasonal variation of peatland-fed riverine macroinvertebrate and benthic diatom assemblages and implications for assessment: a case study from Ireland

Blanket peat catchments are important biodiversity refugia. Key pressures on peatland catchment water bodies include artificial drainage, forestry, over-grazing, wind farm development and climate change, and assessment of these pressures requires sensitive monitoring programmes. This study, undertaken in two neighbouring blanket peat catchments, examined the variability in macroinvertebrate and diatom assemblages and related indices in response to spatial and seasonal variability. Multivariate analysis revealed significant trends in the taxa distribution of both groups and the indices downstream and away from the constraining influence of the peat. However, the ecological quality ratios and status assessments for the associated water bodies were consistent irrespective of spatial variability in assemblages and raw indices. Significant seasonal trends emerged only in the macroinvertebrate assemblages and indices. This study contributes to the understanding of sources of uncertainty in ecological assessment and thus provides valuable information for the calibration of assessment protocols for sensitive peatland catchments

Implantable Therapeutic Reservoir Systems for Diverse Clinical Applications in Large Animal Models

Regenerative medicine approaches, specifically stem cell technologies, have demonstrated significant potential to treat a diverse array of pathologies. However, such approaches have resulted in a modest clinical benefit, which may be attributed to poor cell retention/survival at the disease site. A delivery system that facilitates regional and repeated delivery to target tissues can provide enhanced clinical efficacy of cell therapies when localized delivery of high doses of cells is required. In this study, a new regenerative reservoir platform (Regenervoir) is described for use in large animal models, with relevance to cardiac, abdominal, and soft tissue pathologies. Regenervoir incorporates multiple novel design features essential for clinical translation, with a focus on scalability, mechanism of delivery, fixation to target tissue, and filling/refilling with a therapeutic cargo, and is demonstrated in an array of clinical applications that are easily translated to human studies. Regenervoir consists of a porous reservoir fabricated from a single material, a flexible thermoplastic polymer, capable of delivering cargo via fill lines to target tissues. A radiopaque shear thinning hydrogel can be delivered to the therapy reservoir and multiple fixation methods (laparoscopic tacks and cyanoacrylate bioadhesive) can be used to secure Regenervoir to target tissues through a minimally invasive approach.In this study, a new regenerative reservoir platform (Regenervoir) is described for use in large animal models that are easily translated to human studies, with relevance to cardiac, abdominal, and soft tissue pathologies. Regenervoir incorporates multiple novel design features essential for clinical translation, with a focus on scalability, mechanism of delivery, fixation, and filling/refilling with a therapeutic cargo.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155890/1/adhm202000305.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155890/2/adhm202000305_am.pd

Improving validity of informed consent for biomedical research in Zambia using a laboratory exposure intervention.

BACKGROUND: Complex biomedical research can lead to disquiet in communities with limited exposure to scientific discussions, leading to rumours or to high drop-out rates. We set out to test an intervention designed to address apprehensions commonly encountered in a community where literacy is uncommon, and where complex biomedical research has been conducted for over a decade. We aimed to determine if it could improve the validity of consent. METHODS: Data were collected using focus group discussions, key informant interviews and observations. We designed an intervention that exposed participants to a detailed demonstration of laboratory processes. Each group was interviewed twice in a day, before and after exposure to the intervention in order to assess changes in their views. RESULTS: Factors that motivated people to participate in invasive biomedical research included a desire to stay healthy because of the screening during the recruitment process, regular advice from doctors, free medical services, and trust in the researchers. Inhibiting factors were limited knowledge about samples taken from their bodies during endoscopic procedures, the impact of endoscopy on the function of internal organs, and concerns about the use of biomedical samples. The belief that blood can be used for Satanic practices also created insecurities about drawing of blood samples. Further inhibiting factors included a fear of being labelled as HIV positive if known to consult heath workers repeatedly, and gender inequality. Concerns about the use and storage of blood and tissue samples were overcome by a laboratory exposure intervention. CONCLUSION: Selecting a group of members from target community and engaging them in a laboratory exposure intervention could be a useful tool for enhancing specific aspects of consent for biomedical research. Further work is needed to determine the extent to which improved understanding permeates beyond the immediate group participating in the intervention

Determinants of suicide and accidental or violent death in the Australian HIV Observational Database

Background: Rates of suicide and accidental or violent death remain high in HIV-positive populations despite significantly improved prognosis since the introduction of cART. Methods: We conducted a nested case-control study of suicide and accidental or violent death in the Australian HIV Observational Database (AHOD) between January 1999 and March 2012. For each case, 2 controls were matched by clinic, age, sex, mode of exposure and HIV-positive date to adjust for potential confounding by these covariates. Risk of suicide and accidental or violent death was estimated using conditional logistic regression. Results: We included 27 cases (17 suicide and 10 violent/accidental death) and 54 controls. All cases were men who have sex with men (MSM) or MSM/ injecting drug use (IDU) mode of exposure. Increased risk was associated with unemployment (Odds Ratio (OR) 5.86, 95% CI: 1.69–20.37), living alone (OR 3.26, 95% CI: 1.06–10.07), suicidal ideation (OR 6.55, 95% CI: 1.70–25.21), and >2 psychiatric/cognitive risk factors (OR 4.99, 95% CI: 1.17–30.65). CD4 cell count of >500 cells/mL (OR 0.25, 95% CI: 0.07–0.87) and HIV-positive date ≥1990 (1990–1999 (OR 0.31, 95% CI: 0.11–0.89), post-2000 (OR 0.08, 95% CI: 0.01– 0.84)) were associated with decreased risk. CD4 cell count ≥500 cells/mL remained a significant predictor of reduced risk (OR 0.15, 95% CI: 0.03–0.70) in a multivariate model adjusted for employment status, accommodation status and HIV-positive date. Conclusions: After adjustment for psychosocial factors, the immunological status of HIV-positive patients contributed to the risk of suicide and accidental or violent death. The number of psychiatric/cognitive diagnoses contributed to the level of risk but many psychosocial factors were not individually significant. These findings indicate a complex interplay of factors associated with risk of suicide and accidental or violent death.Hamish McManus, Kathy Petoumenos, Teo Franic, Mark D. Kelly, Jo Watson, Catherine C. O’Connor, Mark Jeanes, Jennifer Hoy, David A. Cooper, Matthew G. Law, M. Boyd on behalf of the Australian HIV Observational Databas

DCE-MRI perfusion and permeability parameters as predictors of tumor response to CCRT in patients with locally advanced NSCLC

In this prospective study, 36 patients with stage III non-small cell lung cancers (NSCLC), who underwent dynamic contrast-enhanced MRI (DCE-MRI) before concurrent chemo-radiotherapy (CCRT) were enrolled. Pharmacokinetic analysis was carried out after non-rigid motion registration. The perfusion parameters including Blood Flow (BF), Blood Volume (BV), Mean Transit Time (MTT) and permeability parameters including endothelial transfer constant (Ktrans), reflux rate (Kep), fractional extravascular extracellular space volume (Ve), fractional plasma volume (Vp) were calculated, and their relationship with tumor regression was evaluated. The value of these parameters on predicting responders were calculated by receiver operating characteristic (ROC) curve. Multivariate logistic regression analysis was conducted to find the independent variables. Tumor regression rate is negatively correlated with V e and its standard variation V e-SD and positively correlated with K trans and Kep. Significant differences between responders and non-responders existed in Ktrans, Kep, Ve, Ve-SD, MTT, BV-SD and MTT-SD (P < 0.05). ROC indicated that Ve < 0.24 gave the largest area under curve of 0.865 to predict responders. Multivariate logistic regression analysis also showed Ve was a significant predictor. Baseline perfusion and permeability parameters calculated from DCE-MRI were seen to be a viable tool for predicting the early treatment response after CCRT of NSCLC. © 2016 The Author(s)