TGFβ1 single-nucleotide polymorphism C-509T alters mucosal cell function in pediatric eosinophilic esophagitis.

Eosinophilic esophagitis (EoE) is a chronic Th2 antigen-driven disorder associated with tissue remodeling. Inflammation and remodeling lead to esophageal rigidity, strictures, and dysphagia. TGFβ1 drives esophageal remodeling including epithelial barrier dysfunction and subepithelial fibrosis. A functional SNP in the TGFβ1 gene that increases its transcription (C-509T) is associated with elevated numbers of esophageal TGFβ1-expressing cells. We utilized esophageal biopsies and fibroblasts from TT-genotype EoE children to understand if TGFβ1 influenced fibroblast and epithelial cell function in vivo. Genotype TT EoE esophageal fibroblasts had higher baseline TGFβ1, collagen1α1, periostin, and MMP2 (p < 0.05) gene expression and distinct contractile properties compared with CC genotype (n = 6 subjects per genotype). In vitro TGFβ1 exposure caused greater induction of target gene expression in genotype CC fibroblasts (p < 0.05). Esophageal biopsies from TT-genotype subjects had significantly less epithelial membrane-bound E-cadherin (p < 0.01) and wider cluster distribution at nanometer resolution. TGFβ1 treatment of stratified primary human esophageal epithelial cells and spheroids disrupted transepithelial resistance (p < 0.001) and E-cadherin localization (p < 0.0001). A TGFβ1-receptor-I inhibitor improved TGFβ1-mediated E-cadherin mislocalization. These data suggest that EoE severity can depend on genotypic differences that increase in vivo exposure to TGFβ1. TGFβ1 inhibition may be a useful therapy in subsets of EoE patients

Chemical Cues Influence Pupation Behavior of Drosophila simulans and Drosophila buzzatii in Nature and in the Laboratory

In the wild, larvae of several species of Drosophila develop in heterogeneous and rapidly changing environments sharing resources as food and space. In this scenario, sensory systems contribute to detect, localize and recognize congeners and heterospecifics, and provide information about the availability of food and chemical features of environments where animals live. We investigated the behavior of D. simulans and D. buzzatii larvae to chemicals emitted by conspecific and heterospecific larvae. Our goal was to understand the role of these substances in the selection of pupation sites in the two species that cohabit within decaying prickly pear fruits (Opuntia ficus-indica). In these breeding sites, larvae of D. simulans and D. buzzatii detect larvae of the other species changing their pupation site preferences. Larvae of the two species pupated in the part of the fruit containing no or few heterospecifics, and spent a longer time in/on spots marked by conspecifics rather than heterospecifics. In contrast, larvae of the two species reared in isolation from conspecifics pupated randomly over the substrate and spent a similar amount of time on spots marked by conspecifics and by heterospecifics. Our results indicate that early chemically-based experience with conspecific larvae is critical for the selection of the pupation sites in D. simulans and D. buzzatii, and that pupation site preferences of Drosophila larvae depend on species-specific chemical cues. These preferences can be modulate by the presence of larvae of the same or another species

A review of elliptical and disc galaxy structure, and modern scaling laws

A century ago, in 1911 and 1913, Plummer and then Reynolds introduced their models to describe the radial distribution of stars in `nebulae'. This article reviews the progress since then, providing both an historical perspective and a contemporary review of the stellar structure of bulges, discs and elliptical galaxies. The quantification of galaxy nuclei, such as central mass deficits and excess nuclear light, plus the structure of dark matter halos and cD galaxy envelopes, are discussed. Issues pertaining to spiral galaxies including dust, bulge-to-disc ratios, bulgeless galaxies, bars and the identification of pseudobulges are also reviewed. An array of modern scaling relations involving sizes, luminosities, surface brightnesses and stellar concentrations are presented, many of which are shown to be curved. These 'redshift zero' relations not only quantify the behavior and nature of galaxies in the Universe today, but are the modern benchmark for evolutionary studies of galaxies, whether based on observations, N-body-simulations or semi-analytical modelling. For example, it is shown that some of the recently discovered compact elliptical galaxies at 1.5 < z < 2.5 may be the bulges of modern disc galaxies.Comment: Condensed version (due to Contract) of an invited review article to appear in "Planets, Stars and Stellar Systems"(www.springer.com/astronomy/book/978-90-481-8818-5). 500+ references incl. many somewhat forgotten, pioneer papers. Original submission to Springer: 07-June-201

Immigration, Acculturation and Chronic Back and Neck Problems Among Latino-Americans

Higher acculturation is associated with increased obesity and depression among Latino-Americans, but not much is known about how acculturation is related to their prevalence of back and neck problems. This study examines whether acculturation is associated with the 12-month prevalence of self-reported chronic back or neck problems among US-born and immigrant Latinos. We performed multivariable logistic regression analysis of data from 2,553 noninstitutionalized Latino adults from the 2002–2003 National Latino and Asian American Survey (NLAAS). After adjusting for demographic, physical and mental health indicators, English proficiency, nativity and higher generational status were all significantly positively associated with the report of chronic back or neck problems. Among immigrants, the proportion of lifetime in the US was not significantly associated. Our findings suggest that the report of chronic back or neck problems is higher among more acculturated Latino-Americans independent of health status, obesity, and the presence of depression

Micro-combs: a novel generation of optical sources

The quest towards the integration of ultra-fast, high-precision optical clocks is reflected in the large number of high-impact papers on the topic published in the last few years. This interest has been catalysed by the impact that high-precision optical frequency combs (OFCs) have had on metrology and spectroscopy in the last decade [1–5]. OFCs are often referred to as optical rulers: their spectra consist of a precise sequence of discrete and equally-spaced spectral lines that represent precise marks in frequency. Their importance was recognised worldwide with the 2005 Nobel Prize being awarded to T.W. Hänsch and J. Hall for their breakthrough in OFC science [5]. They demonstrated that a coherent OFC source with a large spectrum – covering at least one octave – can be stabilised with a self-referenced approach, where the frequency and the phase do not vary and are completely determined by the source physical parameters. These fully stabilised OFCs solved the challenge of directly measuring optical frequencies and are now exploited as the most accurate time references available, ready to replace the current standard for time. Very recent advancements in the fabrication technology of optical micro-cavities [6] are contributing to the development of OFC sources. These efforts may open up the way to realise ultra-fast and stable optical clocks and pulsed sources with extremely high repetition-rates, in the form of compact and integrated devices. Indeed, the fabrication of high-quality factor (high-Q) micro-resonators, capable of dramatically amplifying the optical field, can be considered a photonics breakthrough that has boosted not only the scientific investigation of OFC sources [7–13] but also of optical sensors and compact light modulators [6,14]

Novel inhibitors of the calcineurin/NFATc hub - alternatives to CsA and FK506?

The drugs cyclosporine A (CsA) and tacrolimus (FK506) revolutionized organ transplantation. Both compounds are still widely used in the clinic as well as for basic research, even though they have dramatic side effects and modulate other pathways than calcineurin-NFATc, too. To answer the major open question - whether the adverse side effects are secondary to the actions of the drugs on the calcineurin-NFATc pathway - alternative inhibitors were developed. Ideal inhibitors should discriminate between the inhibition of (i) calcineurin and peptidyl-prolyl cis-trans isomerases (PPIases; the matchmaker proteins of CsA and FK506), (ii) calcineurin and the other Ser/Thr protein phosphatases, and (iii) NFATc and other transcription factors. In this review we summarize the current knowledge about novel inhibitors, synthesized or identified in the last decades, and focus on their mode of action, specificity, and biological effects