Interactions of the Bacillus subtilis DnaE polymerase with replisomal proteins modulate its activity and fidelity

During Bacillus subtilis replication two replicative polymerases function at the replisome to collectively carry out genome replication. In a reconstituted in vitro replication assay, PolC is the main polymerase while the lagging strand DnaE polymerase briefly extends RNA primers synthesized by the primase DnaG prior to handing-off DNA synthesis to PolC. Here, we show in vivo that (i) the polymerase activity of DnaE is essential for both the initiation and elongation stages of DNA replication, (ii) its error rate varies inversely with PolC concentration, and (iii) its misincorporations are corrected by the mismatch repair system post-replication. We also found that the error rates in cells encoding mutator forms of both PolC and DnaE are significantly higher (up to 15-fold) than in PolC mutants. In vitro, we showed that (i) the polymerase activity of DnaE is considerably stimulated by DnaN, SSB and PolC, (ii) its error-prone activity is strongly inhibited by DnaN, and (iii) its errors are proofread by the 30 . 50 exonuclease activity of PolC in a stable template-DnaE –PolC complex. Collectively our data show that protein –protein interactions within the replisome modulate the activity and fidelity of DnaE, and confirm the prominent role of DnaE during B. subtilis replication

Reported appetite, taste and smell changes following Roux-en-Y gastric bypass and sleeve gastrectomy: Effect of gender, type 2 diabetes and relationship to post-operative weight loss.

Reduced energy intake drives weight loss following Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) procedures. Post-operative changes in subjective appetite, taste, and smell and food preferences are reported and suggested to contribute to reduced energy intake. We aimed to investigate the prevalence of these changes following RYGB and SG and to evaluate their relationship with weight loss. 98 patients post-RYGB and 155 post-SG from a single bariatric centre were recruited to a cross-sectional study. Participants completed a questionnaire, previously utilised in post-operative bariatric patients, to assess the prevalence of post-operative food aversions and subjective changes in appetite, taste and smell. Anthropometric data were collected and percentage weight loss (%WL) was calculated. The relationship between food aversions, changes in appetite, taste and smell and %WL was assessed. The influence of time post-surgery, gender and type 2 diabetes (T2D) were evaluated. Following RYGB and SG the majority of patients reported food aversions (RYGB = 62%, SG = 59%), appetite changes (RYGB = 91%, SG = 91%) and taste changes (RYGB = 64%, SG = 59%). Smell changes were more common post-RYGB than post-SG (RYGB = 41%, SG = 28%, p = 0.039). No temporal effect was observed post-RYGB. In contrast, the prevalence of appetite changes decreased significantly with time following SG. Post-operative appetite changes associated with and predicted higher %WL post-SG but not post-RYGB. Taste changes associated with and predicted higher %WL following RYGB but not post-SG. There was no gender effect post-RYGB. Post-SG taste changes were less common in males (female = 65%, males = 40%, p = 0.008). T2D status in females did not influence post-operative subjective changes. However, in males with T2D, taste changes were less common post-SG than post-RYGB together with lower %WL (RYGB = 27.5 ± 2.7, SG = 14.6 ± 2.1, p = 0.003). Further research is warranted to define the biology underlying these differences and to individualise treatments

Protocol for a 1-year prospective, longitudinal cohort study of patients undergoing Roux-en-Y gastric bypass and sleeve gastrectomy: the BARI-LIFESTYLE observational study

INTRODUCTION: Roux-en-Y gastric bypass and sleeve gastrectomy are the two most common bariatric surgery performed in the UK that result in comparable weight loss and remission of obesity-associated comorbidities. However, there is a paucity of studies examining the impact of these procedures on body composition, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life and costs. METHODS AND ANALYSIS: The BARI-LIFESTYLE observational study is a 1-year prospective, longitudinal cohort study within a real-world routine clinical care setting aiming to recruit 100 patients with severe obesity undergoing either primary Roux-en-Y gastric bypass or sleeve gastrectomy from two bariatric centres in London, UK. Participants will be followed up four times during the study period; presurgery baseline (T0) and at 3 (T1), 6 (T2) and 12 months (T3) postsurgery. In addition to the standard follow-up investigations, assessments including dual-energy X-ray absorptiometry scan, bioelectric impedance analysis, 6 min walk test, sit-to-stand test and handgrip test will be undertaken together with completion of questionnaires. Physical activity levels and sedentary behaviour will be assessed using accelerometer, and dietary intake will be recorded using a 3-day food diary. Outcome measures will include body weight, body fat mass, lean muscle mass, bone mineral density, physical activity levels, sedentary behaviour, physical function and strength, dietary intake, health-related quality of life, remission of comorbidities, healthcare resource utilisation and costs. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable ethical opinion by London-Dulwich Research Ethics Committee (17/LO/0950). The results will be presented to stakeholder groups locally, nationally and internationally and published in peer-reviewed medical journals. The lay-person summary of the findings will be published on the Centre for Obesity Research, University College London website (http://www.ucl.ac.uk/obesity)

A case of severe anorexia, excessive weight loss and high peptide YY levels after sleeve gastrectomy

Sleeve gastrectomy (SG) is the second most commonly performed bariatric procedure worldwide. Altered circulating gut hormones have been suggested to contribute post-operatively to appetite suppression, decreased caloric intake and weight reduction. In the present study, we report a 22-year-old woman who underwent laparoscopic SG for obesity (BMI 46 kg/m2). Post-operatively, she reported marked appetite reduction, which resulted in excessive weight loss (1-year post-SG: BMI 22 kg/m2, weight loss 52%, >99th centile of 1-year percentage of weight loss from 453 SG patients). Gastrointestinal (GI) imaging, GI physiology/motility studies and endoscopy revealed no anatomical cause for her symptoms, and psychological assessments excluded an eating disorder. Despite nutritional supplements and anti-emetics, her weight loss continued (BMI 19 kg/m2), and she required nasogastric feeding. A random gut hormone assessment revealed high plasma peptide YY (PYY) levels. She underwent a 3 h meal study following an overnight fast to assess her subjective appetite and circulating gut hormone levels. Her fasted nausea scores were high, with low hunger, and these worsened with nutrient ingestion. Compared to ten other post-SG female patients, her fasted circulating PYY and nutrient-stimulated PYY and active glucagon-like peptide 1 (GLP1) levels were markedly elevated. Octreotide treatment was associated with suppressed circulating PYY and GLP1 levels, increased appetite, increased caloric intake and weight gain (BMI 22 kg/m2 after 6 months). The present case highlights the value of measuring gut hormones in patients following bariatric surgery who present with anorexia and excessive weight loss and suggests that octreotide treatment can produce symptomatic relief and weight regain in this setting

Patients' views and experiences of live supervised tele-exercise classes following bariatric surgery during the COVID-19 pandemic: The BARI-LIFESTYLE qualitative study

The BARI-LIFESTYLE trial is a randomized controlled trial evaluating the efficacy of a post-surgery nutritional and behavioural tele-counselling, and supervised exercise programme to maximize the health benefits of bariatric surgery. Due to the coronavirus disease 2019 (COVID-19) pandemic, the in-person supervised exercise component had to be converted to remote tele-exercise. However, patients' acceptability of this method of exercise provision is unknown. Between 3 and 6 months following bariatric surgery, 13 adults participated in weekly, structured, 60-min supervised exercise classes delivered via Zoom by a trained exercise therapist. A total of 12 participants (n = 8 female), with a mean age of 46.3 (range 33–63) years, who had undergone either sleeve gastrectomy (n = 8) or Roux-en-Y gastric bypass (n = 4) surgery, participated in one-to-one semi-structured interviews following the tele-exercise classes. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Participants described how the tele-exercise classes helped them to cope with the changes to their lives brought about by the COVID-19 pandemic. Participants found the tele-exercise schedule, content and intensity to be acceptable, and were satisfied with the privacy, security and safety of the technology and classes. Professional supervision and guidance from an exercise therapist were described as central to the tele-exercise provision. Importantly, participation in the tele-exercise provided physical, emotional and social benefits. Few participants reported barriers to participation. Overall, the tele-exercise classes were deemed acceptable and compared favourably to in-person exercise classes

Linking public health agencies and hospitals for improved emergency preparedness: North Carolina's public health epidemiologist program

<p>Abstract</p> <p>Background</p> <p>In 2003, 11 public health epidemiologists were placed in North Carolina's largest hospitals to enhance communication between public health agencies and healthcare systems for improved emergency preparedness. We describe the specific services public health epidemiologists provide to local health departments, the North Carolina Division of Public Health, and the hospitals in which they are based, and assess the value of these services to stakeholders.</p> <p>Methods</p> <p>We surveyed and/or interviewed public health epidemiologists, communicable disease nurses based at local health departments, North Carolina Division of Public Health staff, and public health epidemiologists' hospital supervisors to 1) elicit the services provided by public health epidemiologists in daily practice and during emergencies and 2) examine the value of these services. Interviews were transcribed and imported into ATLAS.ti for coding and analysis. Descriptive analyses were performed on quantitative survey data.</p> <p>Results</p> <p>Public health epidemiologists conduct syndromic surveillance of community-acquired infections and potential bioterrorism events, assist local health departments and the North Carolina Division of Public Health with public health investigations, educate clinicians on diseases of public health importance, and enhance communication between hospitals and public health agencies. Stakeholders place on a high value on the unique services provided by public health epidemiologists.</p> <p>Conclusions</p> <p>Public health epidemiologists effectively link public health agencies and hospitals to enhance syndromic surveillance, communicable disease management, and public health emergency preparedness and response. This comprehensive description of the program and its value to stakeholders, both in routine daily practice and in responding to a major public health emergency, can inform other states that may wish to establish a similar program as part of their larger public health emergency preparedness and response system.</p

Co-evolution of density and topology in a simple model of city formation

We study the influence that population density and the road network have on each others' growth and evolution. We use a simple model of formation and evolution of city roads which reproduces the most important empirical features of street networks in cities. Within this framework, we explicitely introduce the topology of the road network and analyze how it evolves and interact with the evolution of population density. We show that accessibility issues -pushing individuals to get closer to high centrality nodes- lead to high density regions and the appearance of densely populated centers. In particular, this model reproduces the empirical fact that the density profile decreases exponentially from a core district. In this simplified model, the size of the core district depends on the relative importance of transportation and rent costs.Comment: 13 pages, 13 figure

Transit Photometry as an Exoplanet Discovery Method

Photometry with the transit method has arguably been the most successful exoplanet discovery method to date. A short overview about the rise of that method to its present status is given. The method's strength is the rich set of parameters that can be obtained from transiting planets, in particular in combination with radial velocity observations; the basic principles of these parameters are given. The method has however also drawbacks, which are the low probability that transits appear in randomly oriented planet systems, and the presence of astrophysical phenomena that may mimic transits and give rise to false detection positives. In the second part we outline the main factors that determine the design of transit surveys, such as the size of the survey sample, the temporal coverage, the detection precision, the sample brightness and the methods to extract transit events from observed light curves. Lastly, an overview over past, current and future transit surveys is given. For these surveys we indicate their basic instrument configuration and their planet catch, including the ranges of planet sizes and stellar magnitudes that were encountered. Current and future transit detection experiments concentrate primarily on bright or special targets, and we expect that the transit method remains a principal driver of exoplanet science, through new discoveries to be made and through the development of new generations of instruments.Comment: Review chapte