Morphological Transformations of Galaxies in the A901/02 Supercluster from STAGES

We present a study of galaxies in the Abell 901/902 Supercluster at z~0.165, based on HST ACS F606W, COMBO-17, Spitzer 24um, XMM-Newton X-ray, and gravitational lensing maps, as part of the STAGES survey. We characterize galaxies with strong externally-triggered morphological distortions and normal relatively undisturbed galaxies, using visual classification and quantitative CAS parameters. We compare normal and distorted galaxies in terms of their frequency, distribution within the cluster, star formation properties, and relationship to dark matter (DM) or surface mass density, and intra-cluster medium (ICM) density. We revisit the morphology density relation, which postulates a higher fraction of early type galaxies in dense environments, by considering separately galaxies with a low bulge-to-disk (B/D) ratio and a low gas content as these two parameters may not be correlated in clusters. We report here on our preliminary analysis.Comment: To appear in the ASP conference proceedings of the "Frank N. Bash Symposium 2007: New Horizons in Astronomy", Eds. A. Frebel, J. Maund, J. Shen, M. Siegel. 4 pages, 4 figure

Male reproductive health and environmental xenoestrogens

EHP is a publication of the U.S. government. Publication of EHP lies in the public domain and is therefore without copyright. Research articles from EHP may be used freely; however, articles from the News section of EHP may contain photographs or figures copyrighted by other commercial organizations and individuals that may not be used without obtaining prior approval from both the EHP editors and the holder of the copyright. Use of any materials published in EHP should be acknowledged (for example, "Reproduced with permission from Environmental Health Perspectives") and a reference provided for the article from which the material was reproduced.Male reproductive health has deteriorated in many countries during the last few decades. In the 1990s, declining semen quality has been reported from Belgium, Denmark, France, and Great Britain. The incidence of testicular cancer has increased during the same time incidences of hypospadias and cryptorchidism also appear to be increasing. Similar reproductive problems occur in many wildlife species. There are marked geographic differences in the prevalence of male reproductive disorders. While the reasons for these differences are currently unknown, both clinical and laboratory research suggest that the adverse changes may be inter-related and have a common origin in fetal life or childhood. Exposure of the male fetus to supranormal levels of estrogens, such as diethlylstilbestrol, can result in the above-mentioned reproductive defects. The growing number of reports demonstrating that common environmental contaminants and natural factors possess estrogenic activity presents the working hypothesis that the adverse trends in male reproductive health may be, at least in part, associated with exposure to estrogenic or other hormonally active (e.g., antiandrogenic) environmental chemicals during fetal and childhood development. An extensive research program is needed to understand the extent of the problem, its underlying etiology, and the development of a strategy for prevention and intervention.Supported by EU Contract BMH4-CT96-0314

From little things, big things grow: trends and fads in 110 years of Australian ornithology

Publishing histories can reveal changes in ornithological effort, focus or direction through time. This study presents a bibliometric content analysis of Emu (1901–2011) which revealed 115 trends (long-term changes in publication over time) and 18 fads (temporary increases in publication activity) from the classification of 9,039 articles using 128 codes organised into eight categories (author gender, author affiliation, article type, subject, main focus, main method, geographical scale and geographical location). Across 110 years, private authorship declined, while publications involving universities and multiple institutions increased; from 1960, female authorship increased. Over time, question-driven studies and incidental observations increased and decreased in frequency, respectively. Single species and ‘taxonomic group’ subjects increased while studies of birds at specific places decreased. The focus of articles shifted from species distribution and activities of the host organisation to breeding, foraging and other biological/ecological topics. Site- and Australian-continental-scales slightly decreased over time; non-Australian studies increased from the 1970s. A wide variety of fads occurred (e.g. articles on bird distribution, 1942–1951, and using museum specimens, 1906–1913) though the occurrence of fads decreased over time. Changes over time are correlated with technological, theoretical, social and institutional changes, and suggest ornithological priorities, like those of other scientific disciplines, are temporally labil

Enantioselective, intermolecular benzylic C–H amination catalysed by an engineered iron-haem enzyme

C–H bonds are ubiquitous structural units of organic molecules. Although these bonds are generally considered to be chemically inert, the recent emergence of methods for C–H functionalization promises to transform the way synthetic chemistry is performed. The intermolecular amination of C–H bonds represents a particularly desirable and challenging transformation for which no efficient, highly selective, and renewable catalysts exist. Here we report the directed evolution of an iron-containing enzymatic catalyst—based on a cytochrome P450 monooxygenase—for the highly enantioselective intermolecular amination of benzylic C–H bonds. The biocatalyst is capable of up to 1,300 turnovers, exhibits excellent enantioselectivities, and provides access to valuable benzylic amines. Iron complexes are generally poor catalysts for C–H amination: in this catalyst, the enzyme's protein framework confers activity on an otherwise unreactive iron-haem cofactor

Gaze-grasp coordination in obstacle avoidance: differences between binocular and monocular viewing

Most adults can skillfully avoid potential obstacles when acting in everyday cluttered scenes. We examined how gaze and hand movements are normally coordinated for obstacle avoidance and whether these are altered when binocular depth information is unavailable. Visual fixations and hand movement kinematics were simultaneously recorded, while 13 right-handed subjects reached-to-precision grasp a cylindrical household object presented alone or with a potential obstacle (wine glass) located to its left (thumb's grasp side), right or just behind it (both closer to the finger's grasp side) using binocular or monocular vision. Gaze and hand movement strategies differed significantly by view and obstacle location. With binocular vision, initial fixations were near the target's centre of mass (COM) around the time of hand movement onset, but usually shifted to end just above the thumb's grasp site at initial object contact, this mainly being made by the thumb, consistent with selecting this digit for guiding the grasp. This strategy was associated with faster binocular hand movements and improved end-point grip precision across all trials than with monocular viewing, during which subjects usually continued to fixate the target closer to its COM despite a similar prevalence of thumb-first contacts. While subjects looked directly at the obstacle at each location on a minority of trials and their overall fixations on the target were somewhat biased towards the grasp side nearest to it, these gaze behaviours were particularly marked on monocular vision-obstacle behind trials which also commonly ended in finger-first contact. Subjects avoided colliding with the wine glass under both views when on the right (finger side) of the workspace by producing slower and straighter reaches, with this and the behind obstacle location also resulting in 'safer' (i.e. narrower) peak grip apertures and longer deceleration times than when the goal object was alone or the obstacle was on its thumb side. But monocular reach paths were more variable and deceleration times were selectively prolonged on finger-side and behind obstacle trials, with this latter condition further resulting in selectively increased grip closure times and corrections. Binocular vision thus provided added advantages for collision avoidance, known to require intact dorsal cortical stream processing mechanisms, particularly when the target of the grasp and potential obstacle to it were fairly closely separated in depth. Different accounts of the altered monocular gaze behaviour converged on the conclusion that additional perceptual and/or attentional resources are likely engaged compared to when continuous binocular depth information is available. Implications for people lacking binocular stereopsis are briefly considered

Gut microbiota functions: metabolism of nutrients and other food components

The diverse microbial community that inhabits the human gut has an extensive metabolic repertoire that is distinct from, but complements the activity of mammalian enzymes in the liver and gut mucosa and includes functions essential for host digestion. As such, the gut microbiota is a key factor in shaping the biochemical profile of the diet and, therefore, its impact on host health and disease. The important role that the gut microbiota appears to play in human metabolism and health has stimulated research into the identification of specific microorganisms involved in different processes, and the elucidation of metabolic pathways, particularly those associated with metabolism of dietary components and some host-generated substances. In the first part of the review, we discuss the main gut microorganisms, particularly bacteria, and microbial pathways associated with the metabolism of dietary carbohydrates (to short chain fatty acids and gases), proteins, plant polyphenols, bile acids, and vitamins. The second part of the review focuses on the methodologies, existing and novel, that can be employed to explore gut microbial pathways of metabolism. These include mathematical models, omics techniques, isolated microbes, and enzyme assays

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects

Over the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is likely to become an option for routine care of a subset of severe inherited genetic/metabolic liver diseases in the relatively near term. In this review, we aim to summarise the milestones in the development of gene therapy, present the different vector tools and their clinical applications for liver-directed gene therapy. AAV-derived vectors are emerging as the leading candidates for clinical translation of gene delivery to the liver. Therefore, we focus on clinical applications of AAV vectors in providing the most recent update on clinical outcomes of completed and ongoing gene therapy trials and comment on the current challenges that the field is facing for large-scale clinical translation. There is clearly an urgent need for more efficient therapies in many severe monogenic liver disorders, which will require careful risk-benefit analysis for each indication, especially in paediatrics

Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.