Microbial genomics amidst the Arctic crisis

The Arctic is warming – fast. Microbes in the Arctic play pivotal roles in feedbacks that magnify the impacts of Arctic change. Understanding the genome evolution, diversity and dynamics of Arctic microbes can provide insights relevant for both fundamental microbiology and interdisciplinary Arctic science. Within this synthesis, we highlight four key areas where genomic insights to the microbial dimensions of Arctic change are urgently required: the changing Arctic Ocean, greenhouse gas release from the thawing permafrost, 'biological darkening' of glacial surfaces, and human activities within the Arctic. Furthermore, we identify four principal challenges that provide opportunities for timely innovation in Arctic microbial genomics. These range from insufficient genomic data to develop unifying concepts or model organisms for Arctic microbiology to challenges in gaining authentic insights to the structure and function of low-biomass microbiota and integration of data on the causes and consequences of microbial feedbacks across scales. We contend that our insights to date on the genomics of Arctic microbes are limited in these key areas, and we identify priorities and new ways of working to help ensure microbial genomics is in the vanguard of the scientific response to the Arctic crisis

The specialty choices of graduates from Brighton and Sussex Medical School: a longitudinal cohort study

BACKGROUND Since 2007 junior doctors in the UK have had to make major career decisions at a point when previously many had not yet chosen a specialty. This study examined when doctors in this new system make specialty choices, which factors influence choices, and whether doctors who choose a specialty they were interested in at medical school are more confident in their choice than those doctors whose interests change post-graduation. METHODS Two cohorts of students in their penultimate year at one medical school (n = 227/239) were asked which specialty interested them as a career. Two years later, 210/227 were sent a questionnaire measuring actual specialty chosen, confidence, influence of perceptions of the specialty and experiences on choice, satisfaction with medicine, personality, self-efficacy, and demographics. Medical school and post-graduation choices in the same category were deemed 'stable'. Predictors of stability, and of not having chosen a specialty, were calculated using bootstrapped logistic regression. Differences between specialties on questionnaire factors were analysed. RESULTS 50% responded (n = 105/277; 44% of the 239 Year 4 students). 65% specialty choices were 'stable'. Factors univariately associated with stability were specialty chosen, having enjoyed the specialty at medical school or since starting work, having first considered the specialty earlier. A regression found doctors who chose psychiatry were more likely to have changed choice than those who chose general practice. Confidence in the choice was not associated with stability. Those who chose general practice valued lifestyle factors. A psychiatry choice was associated with needing a job and using one's intellect to help others. The decision to choose surgical training tended to be made early. Not having applied for specialty training was associated with being lower on agreeableness and conscientiousness. CONCLUSION Medical school experiences are important in specialty choice but experiences post-graduation remain significant, particularly in some specialties (psychiatry in our sample). Career guidance is important at medical school and should be continued post-graduation, with senior clinicians supported in advising juniors. Careers advice in the first year post-graduation may be particularly important, especially for specialties which have difficulty recruiting or are poorly represented at medical school

smokeSALUD: exploring the effect of demographic change on the smoking prevalence at municipality level in Austria

Background: Reducing the smoking population is still high on the policy agenda, as smoking leads to many preventable diseases, such as lung cancer, heart disease, diabetes, and more. In Austria, data on smoking prevalence only exists at the federal state level. This provides an interesting overview about the current health situation, but for regional planning authorities these data are often insufficient as they can hide pockets of high and low smoking prevalence in certain municipalities. Methods: This paper presents a spatial-temporal change of estimated smokers for municipalities from 2001 and 2011. A synthetic dataset of smokers is built by combining individual large-scale survey data and small area census data using a deterministic spatial microsimulation approach. Statistical analysis, including chi-square test and binary logistic regression, are applied to find the best variables 24 for the simulation model and to validate its results. Results: As no easy-to-use spatial microsimulation software for non-programmers is available yet, a flexible web-based spatial microsimulation application for health decision support (called simSALUD) has been developed and used for these analyses. The results of the simulation show in general a decrease of smoking prevalence within municipalities between 2001 and 2011 and 29 differences within areas are identified. These results are especially valuable to policy decision makers for future planning strategies. Conclusions: This case study shows the application of smokeSALUD to model the spatial-temporal changes in the smoking population in Austria between 2001 and 2011. This is important as no data on smoking exists at this geographical scale (municipality). However, spatial microsimulation models are useful tools to estimate small area health data and to overcome these problems. The simulations and analysis should support health decision makers to identify hot spots of smokers and this should 36 help to show where to spend health resources best in order to reduce health inequalities

Influence of association state and DNA binding on the O2-reactivity of [4Fe-4S] fumarate and nitrate reduction (FNR) regulator

The fumarate and nitrate reduction (FNR) regulator is the master switch for the transition between anaerobic and aerobic respiration in Escherichia coli. Reaction of dimeric [4Fe-4S] FNR with O2 results in conversion of the cluster into a [2Fe-2S] form, via a [3Fe-4S] intermediate, leading to the loss of DNA binding through dissociation of the dimer into monomers. In the present paper, we report studies of two previously identified variants of FNR, D154A and I151A, in which the form of the cluster is decoupled from the association state. In vivo studies of permanently dimeric D154A FNR show that DNA binding does not affect the rate of cluster incorporation into the apoprotein or the rate of O2-mediated cluster loss. In vitro studies show that O2-mediated cluster conversion for D154A and the permanent monomer I151A FNR is the same as in wild-type FNR, but with altered kinetics. Decoupling leads to an increase in the rate of the [3Fe-4S]1+ into [2Fe-2S]2+ conversion step, consistent with the suggestion that this step drives association state changes in the wild-type protein. We have also shown that DNA-bound FNR reacts more rapidly with O2 than FNR free in solution, implying that transcriptionally active FNR is the preferred target for reaction with O2

Heterogenous late Holocene climate in the Eastern Mediterranean – the Kocain Cave record from SW Turkey

Palaeoclimate variability must be constrained to predict the nature and impacts of future climate change in the Eastern Mediterranean. Here, we present a late Holocene high-resolution multiproxy data set from Kocain Cave, the first of its kind from SW Turkey. Regional fluctuations in effective-moisture are recorded by variations in magnesium, strontium, phosphorous and carbon isotopes, with oxygen isotopes reacting to changes in precipitation and effective-moisture. The new record shows a double-peak of arid conditions at 1150 and 800 BCE, a wet period 330–460 CE followed by a rapid shift to dry conditions 460–830 CE, and a dry/wet Medieval Climate Anomaly/Little Ice Age pattern. Large discrepancies exist between Turkish records and the Kocain record, which shares more similarities with other Eastern Mediterranean coastal records. Heterogeneity of regional climate and palaeoclimate proxy records are emphasized

Leptin interacts with glucagon-like peptide-1 neurons to reduce food intake and body weight in rodents

AbstractThe adipose tissue hormone, leptin, and the neuropeptide glucagon-like peptide-1 (7–36) amide (GLP-1) both reduce food intake and body weight in rodents. Using dual in situ hybridization, long isoform leptin receptor (OB-Rb) was localized to GLP-1 neurons originating in the nucleus of the solitary tract. ICV injection of the specific GLP-1 receptor antagonist, exendin(9–39), at the onset of dark phase, did not affect feeding in saline pre-treated controls, but blocked the reduction in food intake and body weight of leptin pre-treated rats. These findings suggest that GLP-1 neurons are a potential target for leptin in its control of feeding

Significance of left ventricular apical-basal muscle bundle identified by cardiovascular magnetic resonance imaging in patients with hypertrophic cardiomyopathy

Aims Cardiovascular magnetic resonance (CMR) has improved diagnostic and management strategies in hypertrophic cardiomyopathy (HCM) by expanding our appreciation for the diverse phenotypic expression. We sought to characterize the prevalence and clinical significance of a recently identified accessory left ventricular (LV) muscle bundle extending from the apex to the basal septum or anterior wall (i.e. apical-basal). Methods and results CMR was performed in 230 genotyped HCM patients (48 ± 15 years, 69% male), 30 genotype-positive/phenotype-negative (G+/P−) family members (32 ± 15 years, 30% male), and 126 controls. Left ventricular apical-basal muscle bundle was identified in 145 of 230 (63%) HCM patients, 18 of 30 (60%) G+/P− family members, and 12 of 126 (10%) controls (G+/P− vs. controls; P < 0.01). In HCM patients, the prevalence of an apical-basal muscle bundle was similar among those with disease-causing sarcomere mutations compared with patients without mutation (64 vs. 62%; P = 0.88). The presence of an LV apical-basal muscle bundle was not associated with LV outflow tract obstruction (P = 0.61). In follow-up, 33 patients underwent surgical myectomy of whom 22 (67%) were identified to have an accessory LV apical-basal muscle bundle, which was resected in all patients. Conclusion Apical-basal muscle bundles are a unique myocardial structure commonly present in HCM patients as well as in G+/P− family members and may represent an additional morphologic marker for HCM diagnosis in genotype-positive statu

Development and stability of Th17 cells in ovarian cancer requires nitric oxide and endogenous NOS2 activity in cancer-associated CD4+ T cells

Th17 cells play reciprocal roles in different forms and at different stages of cancer. We report that the presence of Th17 cells in ovarian cancer ascites correlates with local expression of nitric oxide synthase-2 (NOS2). Furthermore, the development of RORγt+IL-23R+IL-17+ Th17 cells from human naive-, memory- or tumor-infiltrating CD4+ T cells critically depends on NO and endogenous NOS2 induced in CD4+ T cells by Th17-inducing cytokines (IL-1β/IL-6/IL-23) or by cancer-associated IL-1β/IL-6/IL-23/NO-producing MDSCs. Inhibition of NOS2 or its downstream cGMP/cGK signaling pathway abolishes de novo induction of Th17 cells. Moreover, even short-term blockade of NOS/cGMP suppresses the IL-17 production by established Th17 cells isolated from ovarian cancer patients, demonstrating the novel key role of NOS/cGMP in Th17 cell physiology and providing for new therapeutic targets to manipulate Th17- and NOS/cGMP-associated immunity in precancerous lesions and advanced cancer

The writing on the wall: the concealed communities of the East Yorkshire horselads

This paper examines the graffiti found within late nineteenth and early-twentieth century farm buildings in the Wolds of East Yorkshire. It suggests that the graffiti were created by a group of young men at the bottom of the social hierarchy - the horselads – and was one of the ways in which they constructed a distinctive sense of communal identity, at a particular stage in their lives. Whilst it tells us much about changing agricultural regimes and social structures, it also informs us about experiences and attitudes often hidden from official histories and biographies. In this way, the graffiti are argued to inform our understanding, not only of a concealed community, but also about their hidden histor