Resting cells rely on the DNA helicase component MCM2 to build cilia

Minichromosome maintenance (MCM) proteins facilitate replication by licensing origins and unwinding the DNA double strand. Interestingly, the number of MCM hexamers greatly exceeds the number of firing origins suggesting additional roles of MCMs. Here we show a hitherto unanticipated function of MCM2 in cilia formation in human cells and zebrafish that is uncoupled from replication. Zebrafish depleted of MCM2 develop ciliopathy-phenotypes including microcephaly and aberrant heart looping due to malformed cilia. In non-cycling human fibroblasts, loss of MCM2 promotes transcription of a subset of genes, which cause cilia shortening and centriole overduplication. Chromatin immunoprecipitation experiments show that MCM2 binds to transcription start sites of cilia inhibiting genes. We propose that such binding may block RNA polymerase II-mediated transcription. Depletion of a second MCM (MCM7), which functions in complex with MCM2 during its canonical functions, reveals an overlapping cilia-deficiency phenotype likely unconnected to replication, although MCM7 appears to regulate a distinct subset of genes and pathways. Our data suggests that MCM2 and 7 exert a role in ciliogenesis in post-mitotic tissues

Perceptions of Weight, Diabetes and Willingness to Participate in Randomised Controlled Trials of Bariatric Surgery for Patients With Type 2 Diabetes Mellitus and Body Mass Index 30-39.9 kg/m(2)

Purpose: Evidence from high-quality randomised controlled trials (RCTs) is needed to establish the long-term benefit of bariatric surgery in people with type 2 diabetes mellitus (T2DM) and body mass index (BMI) 30–39.9 kg/m2. However, willingness amongst this group to be randomised and undergo surgery is uncertain. This study assessed UK patients’ perceptions of their weight and diabetes, and associations with willingness to participate in RCTs involving bariatric surgery, amongst this population. Materials and Methods: Postal survey of 1820 patients from four regions in England. Eligible patients were as follows: BMI 30–39.9 kg/m2, 18–74 years, diagnosis of T2DM ≥2 years. A reminder survey was sent after 4 weeks. Independent predictors influencing patients’ willingness to consider RCT participation were identified using multiple logistic regression analysis. Results: Thirty-four per cent (614/1820) of patients responded. Weight was considered to be harder to control than diabetes [468/584 (80 %) vs. 107/600 (17 %)]. More people reported a negative impact on life for weight rather than diabetes [379/579 (63 %) vs. 180/574 (31 %)]. Feeling unsatisfied/very unsatisfied with weight loss ability was common 261/578 (45 %). Sixty-four per cent (379/594, CI = 60–68) were willing to consider participating in an RCT. In multivariate analysis, negative impact of weight on life (OR = 2.55, 95 % CI = 1.68–3.89, P < 0.001) and feeling unsatisfied with weight loss ability (OR = 2.47, 95 % CI = 1.55–3.95, P < 0.001) positively influenced patients’ willingness to participate in an RCT. Conclusion: Strong patient interest supports the feasibility of such trials for this group. Perceptions of obesity negatively impacting on life and difficulties in achieving weight loss were common and influenced attitudes to potential participation in bariatric surgery RCTs

Comparison of anthropometric measurements of adiposity in relation to cancer risk: a systematic review of prospective studies

Purpose: In epidemiology, the relationship between increased adiposity and cancer risk has long been recognized. However, whether the association is the same for measures of abdominal or whole body adiposity is unclear. The aim of this systematic review is to compare cancer risk, associated with body mass index (BMI), an indicator of whole body adiposity, with indicators of abdominal adiposity in studies in which these indicators have been directly measured. Methods: We conducted a systematic search from 1974 (EMBASE) and 1988 (PubMed) to September 2015 with keywords related to adiposity and cancer. Included studies were limited to cohort studies reporting directly measured anthropometry and performing mutually adjusted analyses. Results: Thirteen articles were identified, with two reporting on breast cancer, three on colorectal cancer, three on endometrial cancer, two on gastro-oesophageal cancer, two on renal cancer, one on ovarian cancer, one on bladder cancer, one on liver and biliary tract cancer and one on leukaemia. Evidence suggests that abdominal adiposity is a stronger predictor than whole body adiposity for gastro-oesophageal, leukaemia and liver and biliary tract cancer in men and women and for renal cancer in women. Abdominal adiposity was a stronger predictor for bladder and colorectal cancer in women, while only BMI was a predictor in men. In contrast, BMI appears to be a stronger predictor for ovarian cancer. For breast and endometrial cancer, both measures were predictors for cancer risk in postmenopausal women. Conclusions: Only few studies used mutually adjusted and measured anthropometric indicators when studying adiposity-cancer associations. Further research investigating cancer risk and adiposity should include more accurate non-invasive indicators of body fat deposition and focus on the understudied cancer types, namely leukaemia, ovarian, bladder and liver and biliary tract cancer