In the Shadow of the Transiting Disk: Imaging epsilon Aurigae in Eclipse

Eclipses of the single-line spectroscopic binary star, epsilon Aurigae, provide an opportunity to study the poorly-defined companion. We used the MIRC beam combiner on the CHARA array to create interferometric images during eclipse ingress. Our results demonstrate that the eclipsing body is a dark disk that is opaque and tilted, and therefore exclude alternative models for the system. These data constrain the geometry and masses of the components, providing evidence that the F-star is not a massive supergiant star.Comment: As submitted to Nature. Published in Nature April 8, 2010

Global Analysis of Genes Essential for Francisella tularensis Schu S4 Growth In Vitro and for Fitness during Competitive Infection of Fischer 344 Rats

This is the final version. Available from American Society for Microbiology via the DOI in this record The highly virulent intracellular pathogen Francisella tularensis is a Gram-negative bacterium that has a wide host range, including humans, and is the causative agent of tularemia. To identify new therapeutic drug targets and vaccine candidates and investigate the genetic basis of Francisella virulence in the Fischer 344 rat, we have constructed an F. tularensis Schu S4 transposon library. This library consists of more than 300,000 unique transposon mutants and represents a transposon insertion for every 6 bp of the genome. A transposon-directed insertion site sequencing (TraDIS) approach was used to identify 453 genes essential for growth in vitro Many of these essential genes were mapped to key metabolic pathways, including glycolysis/gluconeogenesis, peptidoglycan synthesis, fatty acid biosynthesis, and the tricarboxylic acid (TCA) cycle. Additionally, 163 genes were identified as required for fitness during colonization of the Fischer 344 rat spleen. This in vivo selection screen was validated through the generation of marked deletion mutants that were individually assessed within a competitive index study against the wild-type F. tularensis Schu S4 strain.IMPORTANCE The intracellular bacterial pathogen Francisella tularensis causes a disease in humans characterized by the rapid onset of nonspecific symptoms such as swollen lymph glands, fever, and headaches. F. tularensis is one of the most infectious bacteria known and following pulmonary exposure can have a mortality rate exceeding 50% if left untreated. The low infectious dose of this organism and concerns surrounding its potential as a biological weapon have heightened the need for effective and safe therapies. To expand the repertoire of targets for therapeutic development, we initiated a genome-wide analysis. This study has identified genes that are important for F. tularensis under in vitro and in vivo conditions, providing candidates that can be evaluated for vaccine or antibacterial development.Biotechnology & Biological Sciences Research Council (BBSRC)Defence Science and Technology Laboratory (DSTL

Tennis Service Stroke Benefits Humerus Bone: Is Torsion the Cause?

Regular tennis play is associated with impressive asymmetries in bone strength in favor of the racquet arm, particularly in the humerus. However, the relative effects of service and ground strokes are not known. Serendipitously, we encountered a 46-year-old regular tennis player who has played service and ground strokes with different arms for over 30 years, and thus allowed differentiation of stroke effects. Grip strength and peripheral quantitative computed tomography scans of both arms of radius at 4 % distal–proximal ulna length, radius and ulna at 60 % distal–proximal ulna length, and at distal (35 % length) humerus were analyzed in this player, and 12 male veteran players of similar age, height, and mass who played a conventional single-sided style. Confidence intervals (95 %) were calculated for asymmetries and bone, muscle and force parameters in the control players—values in the case study player were compared to these intervals. Sizeable differences in bone strength in favor of the serving arm humerus were observed in this player—comparable to those found in the control players. While asymmetries in favor of the ground stroke arm ulna were also evident, no sizeable asymmetry was found in proximal or distal radius, forearm or upper arm muscle size or hand grip force. These results suggest that the service stroke is responsible for the humeral hypertrophy observed in tennis players, and that ulna adaptation may be attributable to the ground strokes. The osteogenic potential of the service stroke may be related to the large torsional stresses it produces

Molecular Regulation of Noradrenaline in Bovine Corpus Luteum

Noradrenergic stimulation increases progesterone, oxytocin and prostaglandins in the bovine luteal tissue. Better understanding of noradrenaline (NA) role in bovine the corpus luteum (CL) can advance our current knowledge on the regulatory mechanism of CL function. The present study was conducted to explore the source of noradrenaline and further to investigate whether nerve growth factor (NGF), insulin like growth factor 1 (IGF1) and transforming growth factor b1 (TGFb1) influence the expression of dopamine-b-hydroxylase (DBH), biosynthetic enzyme of NA in cultured bovine luteal cells. Corpora lutea were collected and classified into stages of early, developing, mid, late, and regressed. Messenger RNA (mRNA) and protein expression of DBH were studied throughout the estrous cycle. Additionally, DBH protein expression was examined in cultured mid luteal cells after tumour necrosis factor alpha/interferon gamma (TNFa/IFNg)-induced apoptosis or after treatment with NGF, IGF1, and TGFb1. DBH mRNA and protein expressions were detected throughout the cycle without significant changes in the protein level while mRNA showed a decrease at the developing stage (P < 0.05). Interestingly, NGF, IGF1, and TGFb1 increased DBH expression in cultured luteal cells (P < 0.05). The overall findings suggest non-neural source of noradrenaline in the bovine CL which appears to be regulated by NGF, IGF1, and TGFb1 indicating intraluteal molecules play an important and unrecognized role in the CL function

Modelling the Health Impact of an English Sugary Drinks Duty at National and Local Levels

Increasing evidence associates excess refined sugar intakes with obesity, Type 2 diabetes and heart disease. Worryingly, the estimated volume of sugary drinks purchased in the UK has more than doubled between 1975 and 2007, from 510ml to 1140ml per person per week. We aimed to estimate the potential impact of a duty on sugar sweetened beverages (SSBs) at a local level in England, hypothesising that a duty could reduce obesity and related diseases. Methods and Findings We modelled the potential impact of a 20% sugary drinks duty on local authorities in England between 2010 and 2030. We synthesised data obtained from the British National Diet and Nutrition Survey (NDNS), drinks manufacturers, Office for National Statistics, and from previous studies. This produced a modelled population of 41 million adults in 326 lower tier local authorities in England. This analysis suggests that a 20% SSB duty could result in approximately 2,400 fewer diabetes cases, 1,700 fewer stroke and coronary heart disease cases, 400 fewer cancer cases, and gain some 41,000 Quality Adjusted Life Years (QALYs) per year across England. The duty might have the biggest impact in urban areas with young populations. Conclusions This study adds to the growing body of evidence suggesting health benefits for a duty on sugary drinks. It might also usefully provide results at an area level to inform local price interventions in England

Mindfulness Training for Improving Attention Regulation in University Students: Is It Effective? and Do Yoga and Homework Matter?

The present study examined the effects of mindfulness training on attention regulation in university students and whether the potential benefits of implementation are influenced by the yoga component of mindfulness-based interventions (MBIs) and/or by MBI homework practice. In a non-randomized trial with pre- and post-assessments, n = 180 university students were allocated to either mindfulness training (experimental groups), awareness activities (active control group), or no training (passive control group). Mindfulness was taught through two MBIs, one including yoga and the other excluding yoga. Attention regulation was operationalized via behavioral indicators, namely sustained attention, cognitive flexibility, cognitive inhibition, and data-driven information processing. With the exception of speed in a cognitive flexibility task, the results indicated no systematic or differential advantage arising from mindfulness training, with or without yoga, regarding the aspects of attention regulation. There was no consistent influence of homework quantity or quality. The implications for mindfulness training in academic contexts are discussed

Natural products in modern life science

With a realistic threat against biodiversity in rain forests and in the sea, a sustainable use of natural products is becoming more and more important. Basic research directed against different organisms in Nature could reveal unexpected insights into fundamental biological mechanisms but also new pharmaceutical or biotechnological possibilities of more immediate use. Many different strategies have been used prospecting the biodiversity of Earth in the search for novel structure–activity relationships, which has resulted in important discoveries in drug development. However, we believe that the development of multidisciplinary incentives will be necessary for a future successful exploration of Nature. With this aim, one way would be a modernization and renewal of a venerable proven interdisciplinary science, Pharmacognosy, which represents an integrated way of studying biological systems. This has been demonstrated based on an explanatory model where the different parts of the model are explained by our ongoing research. Anti-inflammatory natural products have been discovered based on ethnopharmacological observations, marine sponges in cold water have resulted in substances with ecological impact, combinatory strategy of ecology and chemistry has revealed new insights into the biodiversity of fungi, in depth studies of cyclic peptides (cyclotides) has created new possibilities for engineering of bioactive peptides, development of new strategies using phylogeny and chemography has resulted in new possibilities for navigating chemical and biological space, and using bioinformatic tools for understanding of lateral gene transfer could provide potential drug targets. A multidisciplinary subject like Pharmacognosy, one of several scientific disciplines bridging biology and chemistry with medicine, has a strategic position for studies of complex scientific questions based on observations in Nature. Furthermore, natural product research based on intriguing scientific questions in Nature can be of value to increase the attraction for young students in modern life science

Host-Adaptation of Francisella tularensis Alters the Bacterium's Surface-Carbohydrates to Hinder Effectors of Innate and Adaptive Immunity

The gram-negative bacterium Francisella tularensis survives in arthropods, fresh water amoeba, and mammals with both intracellular and extracellular phases and could reasonably be expected to express distinct phenotypes in these environments. The presence of a capsule on this bacterium has been controversial with some groups finding such a structure while other groups report that no capsule could be identified. Previously we reported in vitro culture conditions for this bacterium which, in contrast to typical methods, yielded a bacterial phenotype that mimics that of the bacterium's mammalian, extracellular phase.SDS-PAGE and carbohydrate analysis of differentially-cultivated F. tularensis LVS revealed that bacteria displaying the host-adapted phenotype produce both longer polymers of LPS O-antigen (OAg) and additional HMW carbohydrates/glycoproteins that are reduced/absent in non-host-adapted bacteria. Analysis of wildtype and OAg-mutant bacteria indicated that the induced changes in surface carbohydrates involved both OAg and non-OAg species. To assess the impact of these HMW carbohydrates on the access of outer membrane constituents to antibody we used differentially-cultivated bacteria in vitro to immunoprecipitate antibodies directed against outer membrane moieties. We observed that the surface-carbohydrates induced during host-adaptation shield many outer membrane antigens from binding by antibody. Similar assays with normal mouse serum indicate that the induced HMW carbohydrates also impede complement deposition. Using an in vitro macrophage infection assay, we find that the bacterial HMW carbohydrate impedes TLR2-dependent, pro-inflammatory cytokine production by macrophages. Lastly we show that upon host-adaptation, the human-virulent strain, F. tularensis SchuS4 also induces capsule production with the effect of reducing macrophage-activation and accelerating tularemia pathogenesis in mice.F. tularensis undergoes host-adaptation which includes production of multiple capsular materials. These capsules impede recognition of bacterial outer membrane constituents by antibody, complement, and Toll-Like Receptor 2. These changes in the host-pathogen interface have profound implications for pathogenesis and vaccine development