Poloxomer 188 Has a Deleterious Effect on Dystrophic Skeletal Muscle Function

Duchenne muscular dystrophy (DMD) is an X-linked, fatal muscle wasting disease for which there is currently no cure and limited palliative treatments. Poloxomer 188 (P188) is a tri-block copolymer that has been proposed as a potential treatment for cardiomyopathy in DMD patients. Despite the reported beneficial effects of P188 on dystrophic cardiac muscle function, the effects of P188 on dystrophic skeletal muscle function are relatively unknown. Mdx mice were injected intraperitoneally with 460 mg/kg or 30 mg/kg P188 dissolved in saline, or saline alone (control). The effect of single-dose and 2-week daily treatment was assessed using a muscle function test on the Tibialis Anterior (TA) muscle in situ in anaesthetised mice. The test comprises a warm up, measurement of the force-frequency relationship and a series of eccentric contractions with a 10% stretch that have previously been shown to cause a drop in maximum force in mdx mice. After 2 weeks of P188 treatment at either 30 or 460 mg/kg/day the drop in maximum force produced following eccentric contractions was significantly greater than that seen in saline treated control mice (P = 0.0001). Two week P188 treatment at either dose did not significantly change the force-frequency relationship or maximum isometric specific force produced by the TA muscle. In conclusion P188 treatment increases susceptibility to contraction-induced injury following eccentric contractions in dystrophic skeletal muscle and hence its suitability as a potential therapeutic for DMD should be reconsidered

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz

On pains and fear in childbirth: dimensions of listening

OBJETIVOS: desenvolver algumas reflexões sobre os possíveis efeitos benéficos de uma escuta responsiva à verbalização da presença de dor, medos e seus correlatos na cena do parto tomando como base dados empíricos de pesquisa realizada em maternidade situada na cidade de São Paulo, Brasil. MÉTODOS: estudo descritivo, de metodologia qualitativa, referenciado no quadro teórico da Psicologia Social, Psicanálise e Lingüística, utilizando entrevistas semi-estruturadas com 20 parturientes e sete doulas e observação de rotinas da maternidade. RESULTADOS: a análise, apoiada em categorias estabelecidas (subjetividade auto-referida, intersubjetividade, acolhimento, apropriação da experiência) mostrou, entre outros pontos, a importância e a valorização da interlocução qualificada no processo da parturição. Processo esse referido pelas parturientes como experiência de elevado grau de estresse, com vivências de dor, medos e ansiedades, porém mitigados pelo apoio recebido. CONCLUSÕES: a análise permitiu compreender as relações interpessoais como campo de interlocução e acolhimento percebidos pelas mulheres do estudo capazes de produzir efeitos favoráveis sobre as vivências do estresse materno, configurando-se como recurso técnico, qualificado e valioso, oferecido à parturienteOBJECTIVES: to reflect on the possibilities raised by listening to the life-experiences related by parturient women concerning pain on delivery, using empirical data from research carried out in a Maternity ward in the city of São Paulo, Brazil. METHODS: a descriptive study, with a qualitative methodology, based on the theoretical framework of Social Psychology, Psychoanalysis and Linguistics was carried out, by means of semi-structured interviews with parturient women and midwives, in addition to observation of maternity routines. RESULTS: one of the findings of the analysis, based on established categories (self-referred subjectivity, intersubjectivity, the appropriation of experience), was the importance of accurate interlocution in the course of the parturition process. This process was mentioned by the parturient women as an experience accompanied by a high level of stress, involving pain, fear and anxiety, although these may be mitigated by the support received. CONCLUSIONS: the analysis shed light on the role of interpersonal relationships involving dialogue and physical contact experienced by these women in reducing the stress of childbirth, suggesting that these constitute a valuable and effective resource that should be offered to parturient woma

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Thermorheological and textural behaviour of gluten-free gels obtained from chestnut and rice flours

Nowadays, as celiac disease is becoming more common the consumers’ demand for gluten-free products with high nutritional and taste quality is increasing. This work deals with the study of the impact of four novelty gluten-free sources: chestnut flour (Cf), whole rice flour (Rw), Carolino rice flour (Rc) and Agulha rice flour (Ra). Textural, thermorheological and stability performance of gluten-free gels using different experimental techniques were evaluated. Mixed gels were also produced for comparison. Texture parameters were determined from the texture profile analysis using a texturometer. Thermorheological oscillatory measurements were conducted in a stresscontrolled rheometer in order to clarify the kinetics of gel formation and to characterise the structure of the matured gels. The stability of the gels was evaluated using transmittance profiling of the gels under gravitational fields (LUMiSizer®). Texture studies suggested that gels from mixtures of chestnut flour at 30 % and rice flour at 20 % showed the right texture to develop gel-based new desserts. Rheological results showed that the thermal profiles on heating of Cf gels were similar to those obtained for Rw and Ra, whereas Rc gels exhibited a particular pattern. Once the final gelatinisation temperature was achieved, no significant differences on the viscoelastic properties were noticed for all the tested gels. Stability tests showed that gels with Rc should present an industrial advantage over the other assayed formulations, since the stability of these gels is of the order of four times larger

Quivers as calculators: counting, correlators and Riemann surfaces

86 figures (84 pages + Appendices

A Search for Dark Higgs Bosons

Recent astrophysical and terrestrial experiments have motivated the proposal of a dark sector with GeV-scale gauge boson force carriers and new Higgs bosons. We present a search for a dark Higgs boson using 516 fb-1 of data collected with the BABAR detector. We do not observe a significant signal and we set 90% confidence level upper limits on the product of the Standard Model-dark sector mixing angle and the dark sector coupling constant.Comment: 7 pages, 5 postscript figures, published version with improved plots for b/w printin

Heavy and light roles: myosin in the morphogenesis of the heart

Myosin is an essential component of cardiac muscle, from the onset of cardiogenesis through to the adult heart. Although traditionally known for its role in energy transduction and force development, recent studies suggest that both myosin heavy-chain and myosin lightchain proteins are required for a correctly formed heart. Myosins are structural proteins that are not only expressed from early stages of heart development, but when mutated in humans they may give rise to congenital heart defects. This review will discuss the roles of myosin, specifically with regards to the developing heart. The expression of each myosin protein will be described, and the effects that altering expression has on the heart in embryogenesis in different animal models will be discussed. The human molecular genetics of the myosins will also be reviewed

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe

A historical overview of the classification, evolution, and dispersion of Leishmania parasites and sandflies

Background The aim of this study is to describe the major evolutionary historical events among Leishmania, sandflies, and the associated animal reservoirs in detail, in accordance with the geographical evolution of the Earth, which has not been previously discussed on a large scale. Methodology and Principal Findings Leishmania and sandfly classification has always been a controversial matter, and the increasing number of species currently described further complicates this issue. Despite several hypotheses on the origin, evolution, and distribution of Leishmania and sandflies in the Old and New World, no consistent agreement exists regarding dissemination of the actors that play roles in leishmaniasis. For this purpose, we present here three centuries of research on sandflies and Leishmania descriptions, as well as a complete description of Leishmania and sandfly fossils and the emergence date of each Leishmania and sandfly group during different geographical periods, from 550 million years ago until now. We discuss critically the different approaches that were used for Leishmana and sandfly classification and their synonymies, proposing an updated classification for each species of Leishmania and sandfly. We update information on the current distribution and dispersion of different species of Leishmania (53), sandflies (more than 800 at genus or subgenus level), and animal reservoirs in each of the following geographical ecozones: Palearctic, Nearctic, Neotropic, Afrotropical, Oriental, Malagasy, and Australian. We propose an updated list of the potential and proven sandfly vectors for each Leishmania species in the Old and New World. Finally, we address a classical question about digenetic Leishmania evolution: which was the first host, a vertebrate or an invertebrate? Conclusions and Significance We propose an updated view of events that have played important roles in the geographical dispersion of sandflies, in relation to both the Leishmania species they transmit and the animal reservoirs of the parasites