Potential climate change effects on the habitat of Antarctic krill in the Weddell Quadrant of the Southern Ocean

Antarctic krill is a cold water species, an increasingly important fishery resource and a major prey item for many fish, birds and mammals in the Southern Ocean. The fishery and the summer foraging sites of many of these predators are concentrated between 0° and 90°W. Parts of this quadrant have experienced recent localised sea surface warming of up to 0.2°C per decade, and projections suggest that further widespread warming of 0.27° to 1.08°C will occur by the late 21st century. We assessed the potential influence of this projected warming on Antarctic krill habitat with a statistical model that links growth to temperature and chlorophyll concentration. The results divide the quadrant into two zones: a band around the Antarctic Circumpolar Current in which habitat quality is particularly vulnerable to warming, and a southern area which is relatively insensitive. Our analysis suggests that the direct effects of warming could reduce the area of growth habitat by up to 20%. The reduction in growth habitat within the range of predators, such as Antarctic fur seals, that forage from breeding sites on South Georgia could be up to 55%, and the habitat’s ability to support Antarctic krill biomass production within this range could be reduced by up to 68%. Sensitivity analysis suggests that the effects of a 50% change in summer chlorophyll concentration could be more significant than the direct effects of warming. A reduction in primary production could lead to further habitat degradation but, even if chlorophyll increased by 50%, projected warming would still cause some degradation of the habitat accessible to predators. While there is considerable uncertainty in these projections, they suggest that future climate change could have a significant negative effect on Antarctic krill growth habitat and, consequently, on Southern Ocean biodiversity and ecosystem services

Injury Alcohol-Attributable Fractions: Methodological Issues and Developments

Background: Alcohol-attributable fractions (AAFs) are routinely used to estimate the burden of injury resulting from alcohol. Recent methodological advances allow AAFs to be estimated using national survey data. However, this requires assuming that the drinking patterns are equivalent to those used by epidemiological studies estimating the relative risk of injury. This study explores the implications of this assumption and presents an improved method of estimating injury AAFs. Methods: Diary survey is used to describe individuals’ drinking occasions and estimate AAFs. Statistical methods and numerical integration are used to combine the evidence on the risk of injury when intoxicated with the diary data. Alternative assumptions are chosen to explore the implications of using national survey data. Results:Overall, an estimated 27% of road traffic accident (RTA) and 23% of non-RTA injuries in Britain are attributable to alcohol. AAF estimates for RTAs range from 54% to 2% and for non-RTAs from 36% to 8% in men aged 16-24 and women aged 55-64 respectively. Two potentially more realistic assumptions relating to the use of national survey data resulted in substantially lower AAF estimates for RTAs. Conclusion: Current methods of estimating injury AAFs using national survey data are flawed for some harms, particularly RTAs, where the data is not consistent with the epidemiological literature. Our findings indicate that the burden of injuries from RTAs in England has been previously overestimated. Further research into the prevalence of risky behaviours when intoxicated is required to refine these methods and produce more robust burden of injury estimates

Development and validation of multivariable clinical diagnostic models to identify type 1 diabetes requiring rapid insulin therapy in adults aged 18-50 years

This is the final version. Available on open access from BMJ Publishing Group via the DOI in this recordObjective: To develop and validate multivariable clinical diagnostic models to assist distinguishing between type 1 and type 2 diabetes in adults aged 18 to 50. Design: Multivariable logistic regression analysis was used to develop classification models integrating five pre-specified predictor variables, including clinical features (age of diagnosis, BMI) and clinical biomarkers (GADA and Islet Antigen 2 islet autoantibodies, Type 1 Diabetes Genetic Risk Score), to identify type 1 diabetes with rapid insulin requirement using data from existing cohorts. Setting: United Kingdom cohorts recruited from primary and secondary care. Participants: 1,352 (model development) and 582 (external validation) participants diagnosed with diabetes between the age of 18 and 50 years of white European origin. Main outcome measures: Type 1 diabetes was defined by rapid insulin requirement (within 3 years of diagnosis) and severe endogenous insulin deficiency (C-peptide <200pmol/L). Type 2 diabetes was defined by either a lack of rapid insulin requirement or, where insulin treated within 3 years, retained endogenous insulin secretion (C-peptide >600pmol/L at ≥5 years diabetes duration). Model performance was assessed using area under the receiver operating characteristic curve (ROC AUC), and internal and external validation. 4 Results: Type 1 diabetes was present in 13% of participants in the development cohort. All five predictor variables were discriminative and independent predictors of type 1 diabetes (p<0.001 for all) with individual ROC AUC ranging from 0.82 to 0.85. Model performance was high: ROC AUC range 0.90 [95%CI 0.88, 0.93] (clinical features only) to 0.97 [0.96, 0.98] (all predictors) with low prediction error. Results were consistent in external validation (clinical features and GADA ROC AUC 0.93 [0.90, 0.96]). Conclusions: Clinical diagnostic models integrating clinical features with biomarkers have high accuracy for identifying type 1 diabetes with rapid insulin requirement, and could assist clinicians and researchers in accurately identifying patients with type 1 diabetes.National Institute for Health Research (NIHR)European Community FP7Oxford Hospitals Charitable FundWellcome TrustMedical Research Council (MRC

Architecture of the chromatin remodeler RSC and insights into its nucleosome engagement.

Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The Saccharomyces cerevisiae RSC (Remodeling the Structure of Chromatin) complex, a member of the SWI/SNF chromatin remodeler family, plays critical roles in genome maintenance, transcription, and DNA repair. Here, we report cryo-electron microscopy (cryo-EM) and crosslinking mass spectrometry (CLMS) studies of yeast RSC complex and show that RSC is composed of a rigid tripartite core and two flexible lobes. The core structure is scaffolded by an asymmetric Rsc8 dimer and built with the evolutionarily conserved subunits Sfh1, Rsc6, Rsc9 and Sth1. The flexible ATPase lobe, composed of helicase subunit Sth1, Arp7, Arp9 and Rtt102, is anchored to this core by the N-terminus of Sth1. Our cryo-EM analysis of RSC bound to a nucleosome core particle shows that in addition to the expected nucleosome-Sth1 interactions, RSC engages histones and nucleosomal DNA through one arm of the core structure, composed of the Rsc8 SWIRM domains, Sfh1 and Npl6. Our findings provide structural insights into the conserved assembly process for all members of the SWI/SNF family of remodelers, and illustrate how RSC selects, engages, and remodels nucleosomes

The BAH domain of Rsc2 is a histone H3 binding domain

Bromo-adjacent homology (BAH) domains are commonly found in chromatin-associated proteins and fall into two classes; Remodels the Structure of Chromatin (RSC)-like or Sir3-like. Although Sir3-like BAH domains bind nucleosomes, the binding partners of RSC-like BAH domains are currently unknown. The Rsc2 subunit of the RSC chromatin remodeling complex contains an RSC-like BAH domain and, like the Sir3-like BAH domains, we find Rsc2 BAH also interacts with nucleosomes. However, unlike Sir3-like BAH domains, we find that Rsc2 BAH can bind to recombinant purified H3 in vitro, suggesting that the mechanism of nucleosome binding is not conserved. To gain insight into the Rsc2 BAH domain, we determined its crystal structure at 2.4 Å resolution. We find that it differs substantially from Sir3-like BAH domains and lacks the motifs in these domains known to be critical for making contacts with histones. We then go on to identify a novel motif in Rsc2 BAH that is critical for efficient H3 binding in vitro and show that mutation of this motif results in defective Rsc2 function in vivo. Moreover, we find this interaction is conserved across Rsc2-related proteins. These data uncover a binding target of the Rsc2 family of BAH domains and identify a novel motif that mediates this interaction

Humanistic psychotherapy research 1990-2015 : from methodological innovation to evidence-supported treatment outcomes and beyond

Over the past twenty five years, humanistic psychotherapy (HP) researchers have actively contributed to the development and implementation of innovative practice-informed research measures and coding systems. Qualitative and quantitative research findings, including meta-analyses, support the identification of HP approaches as evidence-based treatments for a variety of psychological conditions. Implications for future psychotherapy research, training and practice are discussed in terms of addressing the persistent disjunction between significant HP research productivity and relatively low support for HP approaches in university-based clinical training programs, funding agencies and government-supported clinical guidelines. Finally, specific recommendations are provided to further enhance and expand the impact of humanistic psychotherapy research for clinical training programs and the development of treatment guidelines

Early Retained C-peptide is Associated with Markedly Reduced Hospital Admissions and Improved Glycaemic Control in Adult-Onset Type 1 Diabetes but Does Not impact Quality of Life (QOL) Measures

Background: Emerging therapies aim to preserve insulin secretion (measured using cpeptide) in type 1 diabetes. The impact of preserved insulin secretion in adult-onset diabetes, and on non glycemic outcomes, is unclear.Aims: To determine the impacts of retained endogenous insulin secretion on glycemic control, healthcare utilisation and patient quality of life (QOL) in adult on-set type 1 diabetes.Methods: StartRight Study is a prospective study.Results: Participants with retained insulin secretion (c-peptide ≥ 200 pmol/L), incomparison to those with c-peptide &lt;200pmol/L had significantly:- Better glycaemic control: mean HbA1c 6.5 mmol/mol lower than those with severe insulin deficiency (c-peptide &lt; 200 pmol/L) (58.0 vs 64.5 mmol/mol, p&lt; 0.001)- Fewer hospital admissions over the prior year for any cause in comparison to the severe insulin deficient group: (4% vs 13%, p&lt; 0.01)Where ≥1 admission:- Less nights in hospital (mean 2.2 vs 4.9 nights, p= 0.001) and less likely to report ketoacidosis (0% vs 32.4% of admissions, p= 0.001) compared to participants with severe insulin deficiency.Conclusion: - Participants with severe insulin deficiency (c-peptide &lt; 200pmol/L) attended fewer outpatient healthcare appointments (including general practitioners, diabetes specialist doctors, diabetes specialist nurses, community diabetes nurses, community diabetes clinics) over the previous 12 months (3.5 vs 4.3appointments, p&gt; 0.05).- QOL did not differ by c-peptide status (mean SF-12 102 vs 101, p= 0.5).Conclusions: - In adult-onset type 1 diabetes, retained c-peptide level &gt;200pmol/L four yearspost-diagnosis is associated with significantly better glycemic control, fewer hospital admissions, reduced total nights in hospital, fewer episodes of diabetic ketoacidosis and reduction in outpatient contact with healthcare professionals. - This supports the commissioning of therapies to preserve beta cell functionto shift adult-onset type 1 diabetes management and reduce strain on healthcare resources

The SWI/SNF complex acts to constrain distribution of the centromeric histone variant Cse4

In order to gain insight into the function of the Saccharomyces cerevisiae SWI/SNF complex, we have identified DNA sequences to which it is bound genomewide. One surprising observation is that the complex is enriched at the centromeres of each chromosome. Deletion of the gene encoding the Snf2 subunit of the complex was found to cause partial redistribution of the centromeric histone variant Cse4 to sites on chromosome arms. Cultures of snf2Δ yeast were found to progress through mitosis slowly. This was dependent on the mitotic checkpoint protein Mad2. In the absence of Mad2, defects in chromosome segregation were observed. In the absence of Snf2, chromatin organisation at centromeres is less distinct. In particular, hypersensitive sites flanking the Cse4 containing nucleosomes are less pronounced. Furthermore, SWI/SNF complex was found to be especially effective in the dissociation of Cse4 containing chromatin in vitro. This suggests a role for Snf2 in the maintenance of point centromeres involving the removal of Cse4 from ectopic sites