Generation of thiocillin ring size variants by prepeptide gene replacement and in vivo processing by Bacillus cereus

The thiocillins from Bacillus cereus ATCC 14579 are natural products from the broader class of thiazolyl peptides. Their biosynthesis proceeds via extensive post-translational modification of a ribosomally encoded precursor peptide. This post-translational tailoring involves a key step formal cycloaddition between two distal serine residues. In the wild-type structure, this cycloaddition forms a major macrocycle circumscribed by 26-atoms (shortest path). Results presented herein demonstrate the promiscuity of this last step by means of a set of "competition" experiments. Cyclization proceeds in many cases to provide altered ring sizes, giving access to several variant rings sizes that have not previously been observed in nature

Intensive care utilisation and outcomes after high-risk surgery in Scotland: a population based cohort study.

Chief Scientist’s Office Scotland (grant no. CHZ/821/4)

Family systemic psychosocial support for at-risk adolescents in Lebanon: study protocol for a multi-site randomised controlled trial

Background: Adolescents growing up in communities characterised by adversity face multiple risk factors for poor mental health and wellbeing. There is currently a scarcity of research on effective approaches for preventing and treating psychological distress in this population, particularly in humanitarian settings. The powerful impact of the home environment and family support is well known; however, approaches targeting the family are seldom developed or evaluated in such settings. We developed a brief family systemic psychosocial support intervention to be delivered through existing child protection systems with non-specialist facilitators. This paper outlines the study protocol for a randomised controlled trial of the intervention in Lebanon.Methods: We will conduct a single-blind hybrid effectiveness-implementation multi-site RCT comparing the locally developed systemic family intervention to a waitlist control group for families residing in vulnerable regions in North Lebanon and Beqaa governorates (including families of Syrian, Palestinian, and Lebanese backgrounds). Outcomes on a range of family, adolescent, and caregiver measures will be assessed at baseline (T0) and post-intervention (T1), and at a 3-month follow-up for the treatment arm (T2). Families will be eligible for the trial if they are identified by implementing organisations as being medium-to-high risk for child protection concerns and have one or more adolescent aged 12–17 who demonstrates significant psychological distress on a self-report brief screening tool. Families will be randomly assigned to a treatment or a waitlist control condition. Families in the waitlist condition will receive a group version of the programme after completion of the study, to allow us to assess feasibility, acceptability, and preliminary indications of intervention effects of this modality. The primary outcome is reduction in overall adolescent-reported psychological distress over time, with post-intervention (T1) as the primary endpoint. Secondary adolescent-reported outcomes include family functioning, psychosocial wellbeing, and emotional regulation difficulties. Secondary caregiver-reported outcomes include parenting style, family functioning, psychological distress, and emotional regulation difficulties. Discussion: This trial will provide the first assessment of the effectiveness of the family systemic psychosocial support intervention for use in Lebanon, with important implications for the use of systemic, low-cost, non-specialist interventions for this age range. Trial registration: Local registry: National Mental Health Program, Ministry of Public Health, Lebanese Republic. Registered on 19 October 2021 Lebanese Clinical Trial Registry LBCTR2021104870

Selenium status and its determinants in very old adults: insights from the Newcastle 85+ Study

There is a dearth of data on Se status in very old adults. The aims of this study were to assess Se status and its determinants in 85-year-olds living in the Northeast of England by measuring serum Se and selenoprotein P (SELENOP) concentrations and glutathione peroxidase 3 (GPx3) activity. A secondary aim was to examine the interrelationships between each of the biomarkers. In total, 757 participants (463 women, 293 men) from the Newcastle 85+ Study were included. Biomarker concentrations were compared with selected cut-offs (serum Se: suboptimal 70 µg/l and deficient 45 µg/l; SELENOP: suboptimal 4·5 mg/l and deficient 2·6 mg/l). Determinants were assessed using linear regressions, and interrelationships were assessed using restricted cubic splines. Median (inter-quartile range) concentrations of serum Se, SELENOP and of GPx3 activity were 53·6 (23·6) µg/l, 2·9 (1·9) mg/l and 142·1 (50·7) U/l, respectively. Eighty-two percentage and 83 % of participants had suboptimal serum Se (< 70 µg/l) and SELENOP (< 4·5 mg/l), and 31 % and 40 % of participants had deficient serum Se (< 45 µg/l) and SELENOP (< 2·6 mg/l), respectively. Protein intake was a significant determinant of Se status. Additional determinants of serum Se were sex, waist:hip ratio, self-rated health and disease, while sex, BMI and physical activity were determinants of GPx3 activity. There was a linear association between serum Se and SELENOP, and nonlinear associations between serum Se and GPx3 activity and between SELENOP and GPx3 activity. These findings indicate that most participants had suboptimal Se status to saturate circulating SELENOP

Time-integrated luminosity recorded by the BABAR detector at the PEP-II e+e- collider

This article is the Preprint version of the final published artcile which can be accessed at the link below.We describe a measurement of the time-integrated luminosity of the data collected by the BABAR experiment at the PEP-II asymmetric-energy e+e- collider at the ϒ(4S), ϒ(3S), and ϒ(2S) resonances and in a continuum region below each resonance. We measure the time-integrated luminosity by counting e+e-→e+e- and (for the ϒ(4S) only) e+e-→μ+μ- candidate events, allowing additional photons in the final state. We use data-corrected simulation to determine the cross-sections and reconstruction efficiencies for these processes, as well as the major backgrounds. Due to the large cross-sections of e+e-→e+e- and e+e-→μ+μ-, the statistical uncertainties of the measurement are substantially smaller than the systematic uncertainties. The dominant systematic uncertainties are due to observed differences between data and simulation, as well as uncertainties on the cross-sections. For data collected on the ϒ(3S) and ϒ(2S) resonances, an additional uncertainty arises due to ϒ→e+e-X background. For data collected off the ϒ resonances, we estimate an additional uncertainty due to time dependent efficiency variations, which can affect the short off-resonance runs. The relative uncertainties on the luminosities of the on-resonance (off-resonance) samples are 0.43% (0.43%) for the ϒ(4S), 0.58% (0.72%) for the ϒ(3S), and 0.68% (0.88%) for the ϒ(2S).This work is supported by the US Department of Energy and National Science Foundation, the Natural Sciences and Engineering Research Council (Canada), the Commissariat à l’Energie Atomique and Institut National de Physique Nucléaire et de Physiquedes Particules (France), the Bundesministerium für Bildung und Forschung and Deutsche Forschungsgemeinschaft (Germany), the Istituto Nazionale di Fisica Nucleare (Italy), the Foundation for Fundamental Research on Matter (The Netherlands), the Research Council of Norway, the Ministry of Education and Science of the Russian Federation, Ministerio de Ciencia e Innovación (Spain), and the Science and Technology Facilities Council (United Kingdom). Individuals have received support from the Marie-Curie IEF program (European Union) and the A.P. Sloan Foundation (USA)

Subclinical Thyroid Dysfunction and Fracture Risk: A Meta-analysis

IMPORTANCE Associations between subclinical thyroid dysfunction and fractures are unclear and clinical trials are lacking. OBJECTIVE To assess the association of subclinical thyroid dysfunction with hip, nonspine, spine, or any fractures. DATA SOURCES AND STUDY SELECTION The databases of MEDLINE and EMBASE (inception to March 26, 2015) were searched without language restrictions for prospective cohort studies with thyroid function data and subsequent fractures. DATA EXTRACTION Individual participant data were obtained from 13 prospective cohorts in the United States, Europe, Australia, and Japan. Levels of thyroid function were defined as euthyroidism (thyroid-stimulating hormone [TSH], 0.45-4.49 mIU/L), subclinical hyperthyroidism (TSH <0.45 mIU/L), and subclinical hypothyroidism (TSH ≥4.50-19.99 mIU/L) with normal thyroxine concentrations. MAIN OUTCOME AND MEASURES The primary outcome was hip fracture. Any fractures, nonspine fractures, and clinical spine fractures were secondary outcomes. RESULTS Among 70,298 participants, 4092 (5.8%) had subclinical hypothyroidism and 2219 (3.2%) had subclinical hyperthyroidism. During 762,401 person-years of follow-up, hip fracture occurred in 2975 participants (4.6%; 12 studies), any fracture in 2528 participants (9.0%; 8 studies), nonspine fracture in 2018 participants (8.4%; 8 studies), and spine fracture in 296 participants (1.3%; 6 studies). In age- and sex-adjusted analyses, the hazard ratio (HR) for subclinical hyperthyroidism vs euthyroidism was 1.36 for hip fracture (95% CI, 1.13-1.64; 146 events in 2082 participants vs 2534 in 56,471); for any fracture, HR was 1.28 (95% CI, 1.06-1.53; 121 events in 888 participants vs 2203 in 25,901); for nonspine fracture, HR was 1.16 (95% CI, 0.95-1.41; 107 events in 946 participants vs 1745 in 21,722); and for spine fracture, HR was 1.51 (95% CI, 0.93-2.45; 17 events in 732 participants vs 255 in 20,328). Lower TSH was associated with higher fracture rates: for TSH of less than 0.10 mIU/L, HR was 1.61 for hip fracture (95% CI, 1.21-2.15; 47 events in 510 participants); for any fracture, HR was 1.98 (95% CI, 1.41-2.78; 44 events in 212 participants); for nonspine fracture, HR was 1.61 (95% CI, 0.96-2.71; 32 events in 185 participants); and for spine fracture, HR was 3.57 (95% CI, 1.88-6.78; 8 events in 162 participants). Risks were similar after adjustment for other fracture risk factors. Endogenous subclinical hyperthyroidism (excluding thyroid medication users) was associated with HRs of 1.52 (95% CI, 1.19-1.93) for hip fracture, 1.42 (95% CI, 1.16-1.74) for any fracture, and 1.74 (95% CI, 1.01-2.99) for spine fracture. No association was found between subclinical hypothyroidism and fracture risk. CONCLUSIONS AND RELEVANCE Subclinical hyperthyroidism was associated with an increased risk of hip and other fractures, particularly among those with TSH levels of less than 0.10 mIU/L and those with endogenous subclinical hyperthyroidism. Further study is needed to determine whether treating subclinical hyperthyroidism can prevent fractures

Spatiotemporal variability of hydrologic soil properties and the implications for overland flow and land management in a peri-urban Mediterranean catchment

Planning of semi-urban developments is often hindered by a lack of knowledge on how changes in landuse affect catchment hydrological response. The temporal and spatial patterns of overland flow source areas and their connectivity in the landscape, particularly in a seasonal climate, remain comparatively poorly understood. This study investigates seasonal variations in factors influencing runoff response to rainfall in a peri-urban catchment in Portugal characterized by a mosaic of landscape units and a humid Mediterranean climate. Variations in surface soil moisture, hydrophobicity and infiltration capacity were measured in six different landscape units (defined by land-use on either sandstone or limestone) in nine monitoring campaigns at key times over a one-year period. Spatiotemporal patterns in overland flow mechanisms were found. Infiltration-excess overland flow was generated in rainfalls during the dry summer season in woodland on both sandstone and limestone and on agricultural soils on limestone due probably in large part to soil hydrophobicity. In wet periods, saturation overland flow occurred on urban and agricultural soils located in valley bottoms and on shallow soils upslope. Topography, water table rise and soil depth determined the location and extent of saturated areas. Overland flow generated in upslope source areas potentially can infiltrate in other landscape units downslope where infiltration capacity exceeds rainfall intensity. Hydrophilic urban and agricultural-sandstone soils were characterized by increased infiltration capacity during dry periods, while forest soils provided potential sinks for overland flow when hydrophilic in the winter wet season. Identifying the spatial and temporal variability of overland flow sources and sinks is an important step in understanding and modeling flow connectivity and catchment hydrologic response. Such information is important for land managers in order to improve urban planning to minimize flood risk

Measurement of the B0-anti-B0-Oscillation Frequency with Inclusive Dilepton Events

The $B^0$-$\bar B^0$ oscillation frequency has been measured with a sample of 23 million \B\bar B pairs collected with the BABAR detector at the PEP-II asymmetric B Factory at SLAC. In this sample, we select events in which both B mesons decay semileptonically and use the charge of the leptons to identify the flavor of each B meson. A simultaneous fit to the decay time difference distributions for opposite- and same-sign dilepton events gives $\Delta m_d = 0.493 \pm 0.012{(stat)}\pm 0.009{(syst)}$ ps$^{-1}$.Comment: 7 pages, 1 figure, submitted to Physical Review Letter

Multiple drivers of decline in the global status of freshwater crayfish (Decapoda: Astacidea)

International audienceRates of biodiversity loss are higher in freshwater ecosystems than in most terrestrial or marine ecosystems, making freshwater conservation a priority. However, prioritization methods are impeded by insufficient knowledge on the distribution and conservation status of freshwater taxa, particularly invertebrates. We evaluated the extinction risk of the world's 590 freshwater crayfish species using the IUCN Categories and Criteria and found 32% of all species are threatened with extinction. The level of extinction risk differed between families, with proportionally more threatened species in the Parastacidae and Astacidae than in the Cambaridae. Four described species were Extinct and 21% were assessed as Data Deficient. There was geographical variation in the dominant threats affecting the main centres of crayfish diversity. The majority of threatened US and Mexican species face threats associated with urban development, pollution, damming and water management. Conversely, the majority of Australian threatened species are affected by climate change, harvesting, agriculture and invasive species. Only a small proportion of crayfish are found within the boundaries of protected areas, suggesting that alternative means of long-term protection will be required. Our study highlights many of the significant challenges yet to come for freshwater biodiversity unless conservation planning shifts from a reactive to proactive approach

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters