Interleukin-1 polymorphisms associated with increased risk of gastric cancer

Helicobacter pylori infection is associated with a variety of clinical outcomes including gastric cancer and duodenal ulcer disease. The reasons for this variation are not clear, but the gastric physiological response is influenced by the severity and anatomical distribution of gastritis induced by H. pylori. Thus, individuals with gastritis predominantly localized to the antrum retain normal (or even high) acid secretion, whereas individuals with extensive corpus gastritis develop hypochlorhydria and gastric atrophy, which are presumptive precursors of gastric cancer. Here we report that interleukin-1 gene cluster polymorphisms suspected of enhancing production of interleukin-1-beta are associated with an increased risk of both hypochlorhydria induced by H. pylori and gastric cancer. Two of these polymorphism are in near-complete linkage disequilibrium and one is a TATA-box polymorphism that markedly affects DNA-protein interactions in vitro. The association with disease may be explained by the biological properties of interleukin-1-beta, which is an important pro-inflammatory cytokine and a powerful inhibitor of gastric acid secretion. Host genetic factors that affect interleukin-1-beta may determine why some individuals infected with H. pylori develop gastric cancer while others do no

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Rarity of monodominance in hyperdiverse Amazonian forests.

Tropical forests are known for their high diversity. Yet, forest patches do occur in the tropics where a single tree species is dominant. Such "monodominant" forests are known from all of the main tropical regions. For Amazonia, we sampled the occurrence of monodominance in a massive, basin-wide database of forest-inventory plots from the Amazon Tree Diversity Network (ATDN). Utilizing a simple defining metric of at least half of the trees ≥ 10 cm diameter belonging to one species, we found only a few occurrences of monodominance in Amazonia, and the phenomenon was not significantly linked to previously hypothesized life history traits such wood density, seed mass, ectomycorrhizal associations, or Rhizobium nodulation. In our analysis, coppicing (the formation of sprouts at the base of the tree or on roots) was the only trait significantly linked to monodominance. While at specific locales coppicing or ectomycorrhizal associations may confer a considerable advantage to a tree species and lead to its monodominance, very few species have these traits. Mining of the ATDN dataset suggests that monodominance is quite rare in Amazonia, and may be linked primarily to edaphic factors

Ucma/GRP inhibits phosphate-induced vascular smooth muscle cell calcification via SMAD-dependent BMP signalling

Vascular calcification (VC) is the process of deposition of calcium phosphate crystals in the blood vessel wall, with a central role for vascular smooth muscle cells (VSMCs). VC is highly prevalent in chronic kidney disease (CKD) patients and thought, in part, to be induced by phosphate imbalance. The molecular mechanisms that regulate VC are not fully known. Here we propose a novel role for the mineralisation regulator Ucma/GRP (Upper zone of growth plate and Cartilage Matrix Associated protein/Gla Rich Protein) in phosphate-induced VSMC calcification. We show that Ucma/GRP is present in calcified atherosclerotic plaques and highly expressed in calcifying VSMCs in vitro. VSMCs from Ucma/GRP(-/-) mice showed increased mineralisation and expression of osteo/chondrogenic markers (BMP-2, Runx2, beta-catenin, p-SMAD1/5/8, ALP, OCN), and decreased expression of mineralisation inhibitor MGP, suggesting that Ucma/GRP is an inhibitor of mineralisation. Using BMP signalling inhibitor noggin and SMAD1/5/8 signalling inhibitor dorsomorphin we showed that Ucma/GRP is involved in inhibiting the BMP-2-SMAD1/5/8 osteo/chondrogenic signalling pathway in VSMCs treated with elevated phosphate concentrations. Additionally, we showed for the first time evidence of a direct interaction between Ucma/GRP and BMP-2. These results demonstrate an important role of Ucma/GRP in regulating osteo/chondrogenic differentiation and phosphate-induced mineralisation of VSMCs.NWO ZonMw [MKMD 40-42600-98-13007]; FCT [SFRH/BPD/70277/2010]info:eu-repo/semantics/publishedVersio

A Comprehensive Analysis of Electric Dipole Moment Constraints on CP-violating Phases in the MSSM

We analyze the constraints placed on individual, flavor diagonal CP-violating phases in the minimal supersymmetric extension of the Standard Model (MSSM) by current experimental bounds on the electric dipole moments (EDMs) of the neutron, Thallium, and Mercury atoms. We identify the four CP-violating phases that are individually highly constrained by current EDM bounds, and we explore how these phases and correlations among them are constrained by current EDM limits. We also analyze the prospective implications of the next generation of EDM experiments. We point out that all other CP-violating phases in the MSSM are not nearly as tightly constrained by limits on the size of EDMs. We emphasize that a rich set of phenomenological consequences is potentially associated with these generically large EDM-allowed phases, ranging from B physics, electroweak baryogenesis, and signals of CP-violation at the CERN Large Hadron Collider and at future linear colliders. Our numerical study takes into account the complete set of contributions from one- and two-loop EDMs of the electron and quarks, one- and two-loop Chromo-EDMs of quarks, the Weinberg 3-gluon operator, and dominant 4-fermion CP-odd operator contributions, including contributions which are both included and not included yet in the CPsuperH2.0 package. We also introduce an open-source numerical package, 2LEDM, which provides the complete set of two-loop electroweak diagrams contributing to the electric dipole moments of leptons and quarks.Comment: 23 pages, 11 figures; v2: references added, minor change

Microspatial variability in community structure and photophysiology of calcified macroalgal microbiomes revealed by coupling of hyperspectral and high-resolution fluorescence imaging

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. The attached file is the published version of the article

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America

Background: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. Methods: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. Results: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. Conclusion: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.Radium Hospital Foundation (Oslo, Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, Helse Sør-Øst (Norway) in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript, the French Association Recherche contre le Cancer (ARC) in the analysis, and interpretation of data, the Groupement des Entreprises Françaises dans la Lutte contre le Cancer (Gefluc) in the analysis, and interpretation of data, the Association Nationale de la Recherche et de la Technologie (ANRT, CIFRE PhD fellowship to H.T.) in the analysis, and interpretation of data and by the OpenHealth Institute in the analysis, and interpretation of data. Barretos Cancer Hospital received financial support by FINEP-CT-INFRA (02/2010)info:eu-repo/semantics/publishedVersio

Design principles in housing for people with complex physical and cognitive disability: towards an integrated framework for practice

To develop a research-based environmental framework to guide the design and construction of suitable residential dwellings for individuals with complex disability. An environmental approach to housing design and development recognises that there are physical, psychological and social components relating to housing design, dwelling location and the neighbourhood context, and that these elements interact to affect the physical, psychological, and social wellness of individuals. Following theoretical review and synthesis, a comprehensive set of design features that are conducive to residents’ wellness and quality of life are described. It is clear that housing design and development for people with complex disability ought to consider the physical, social, natural, symbolic, and care environment in relation to housing design, dwelling location, and the neighbourhood context for improved housing outcomes. An integrated housing design and development framework is presented. It is hoped this practical matrix/evaluative tool will inform future inclusive housing design and development decisions in Australia and internationally. The application of this framework is especially relevant to political climates striving to achieve design innovation to increase housing choice for people with complex disability

Early predictors of impaired social functioning in male rhesus macaques (Macaca mulatta)

Autism spectrum disorder (ASD) is characterized by social cognition impairments but its basic disease mechanisms remain poorly understood. Progress has been impeded by the absence of animal models that manifest behavioral phenotypes relevant to ASD. Rhesus monkeys are an ideal model organism to address this barrier to progress. Like humans, rhesus monkeys are highly social, possess complex social cognition abilities, and exhibit pronounced individual differences in social functioning. Moreover, we have previously shown that Low-Social (LS) vs. High-Social (HS) adult male monkeys exhibit lower social motivation and poorer social skills. It is not known, however, when these social deficits first emerge. The goals of this study were to test whether juvenile LS and HS monkeys differed as infants in their ability to process social information, and whether infant social abilities predicted later social classification (i.e., LS vs. HS), in order to facilitate earlier identification of monkeys at risk for poor social outcomes. Social classification was determined for N = 25 LS and N = 25 HS male monkeys that were 1–4 years of age. As part of a colony-wide assessment, these monkeys had previously undergone, as infants, tests of face recognition memory and the ability to respond appropriately to conspecific social signals. Monkeys later identified as LS vs. HS showed impairments in recognizing familiar vs. novel faces and in the species-typical adaptive ability to gaze avert to scenes of conspecific aggression. Additionally, multivariate logistic regression using infant social ability measures perfectly predicted later social classification of all N = 50 monkeys. These findings suggest that an early capacity to process important social information may account for differences in rhesus monkeys’ motivation and competence to establish and maintain social relationships later in life. Further development of this model will facilitate identification of novel biological targets for intervention to improve social outcomes in at-risk young monkeys

Low temperature exposure induces browning of bone marrow stem cell derived adipocytes in vitro

Brown and beige adipocytes are characterised as expressing the unique mitochondrial uncoupling protein (UCP)1 for which the primary stimulus in vivo is cold exposure. The extent to which cold-induced UCP1 activation can also be achieved in vitro, and therefore perform a comparable cellular function, is unknown. We report an in vitro model to induce adipocyte browning using bone marrow (BM) derived mesenchymal stem cells (MSC), which relies on differentiation at 32°C instead of 37°C. The low temperature promoted browning in adipogenic cultures, with increased adipocyte differentiation and upregulation of adipogenic and thermogenic factors, especially UCP1. Cells exhibited enhanced uncoupled respiration and metabolic adaptation. Cold-exposed differentiated cells showed a marked translocation of leptin to adipocyte nuclei, suggesting a previously unknown role for leptin in the browning process. These results indicate that BM-MSC can be driven to forming beige-like adipocytes in vitro by exposure to a reduced temperature. This in vitro model will provide a powerful tool to elucidate the precise role of leptin and related hormones in hitherto functions in the browning process