An observational investigation of the faecal microbiota and metabonome of gastrostomy fed children, on blended and formula diets

Gastrostomy fed children traditionally have a Formulae diet (FD), which fulfills nutritional requirements; however, many families are adopting Blended diets (BD), which are what the whole family would eat. We undertook an observational investigation of the colonic microbiota and metabonome in a small group of gastrostomy fed children, who were either on an FD or BD, and compared, where possible to their siblings (17 FD, 28 BD, 19 HS). There was no increase in complications in tube blockage or infection rates, but a significant improvement in the prevalence of bowel problems, a reduction in medication and an increase in quality of life. Metataxonomic analysis showed that the FD group was significantly different to the Sibling group, and that families did not cluster together. Whole sample metabonomics showed no differences between groups; however, univariate analysis of biologically important metabolites did differ. Changing to a BD resulted in no increase in complications or risks, but improved the overall quality of life for the children and families

Tempo and mode of performance evolution across multiple independent origins of adhesive toe pads in lizards

Understanding macroevolutionary dynamics of trait evolution is an important endeavor in evolutionary biology. Ecological opportunity can liberate a trait as it diversifies through trait space, while genetic and selective constraints can limit diversification. While many studies have examined the dynamics of morphological traits, diverse morphological traits may yield the same or similar performance and as performance is often more proximately the target of selection, examining only morphology may give an incomplete understanding of evolutionary dynamics. Here, we ask whether convergent evolution of pad‐bearing lizards has followed similar evolutionary dynamics, or whether independent origins are accompanied by unique constraints and selective pressures over macroevolutionary time. We hypothesized that geckos and anoles each have unique evolutionary tempos and modes. Using performance data from 59 species, we modified Brownian motion (BM) and Ornstein–Uhlenbeck (OU) models to account for repeated origins estimated using Bayesian ancestral state reconstructions. We discovered that adhesive performance in geckos evolved in a fashion consistent with Brownian motion with a trend, whereas anoles evolved in bounded performance space consistent with more constrained evolution (an Ornstein–Uhlenbeck model). Our results suggest that convergent phenotypes can have quite distinctive evolutionary patterns, likely as a result of idiosyncratic constraints or ecological opportunities

Fabrication of Microstripline Wiring for Large Format Transition Edge Sensor Arrays

We have developed a process to integrate microstripline wiring with transition edge sensors (TES). The process includes additional layers for metal-etch stop and dielectric adhesion to enable recovery of parameters achieved in non-microstrip pixel designs. We report on device parameters in close-packed TES arrays achieved with the microstrip process including R(sub n), G, and T(sub c) uniformity. Further, we investigate limits of this method of producing high-density, microstrip wiring including critical current to determine the ultimate scalability of TES arrays with two layers of wiring

Reptile remains from Tiga (Tokanod), Loyalty Islands, New Caledonia

Archaeological excavations on Tiga provide the first vouchered herpetological records for this small island between Lifou and Maré in the Loyalty Islands. Eighty-three skeletal elements from four sites yielded material assignable to skinks (Emoia loyaltiensis, Lioscincus nigrofasciolatus), geckos (Bavayia crass i-collis, B. sp., Gehyra georgpotthasti, Nactus pelagicus), and a boid snake (Candoia bihroni) all known from elsewhere in the Loyalties, as well as undetermined material consistent with these and other Loyalties lizards. Diagnostic features of geckos versus skinks for elements commonly recovered from archaeological sites and from owl pellets are discussed. Gehyra georgpotthasti has a limited distribution in the Loyalties and its occurrence on Tiga clarifies its range. The boid snake is the only reptile likely to have been harvested by human inhabitants of Tiga. The presence of gekkonid geckos in pre-European times is confirmed and contrasts with the situation of Grande Terre fossil sites, where only diplodactylid geckos have been recovered. Although it is anticipated that all species recovered from archaeological sites are still present on the island, a modern herpetofaunal survey is needed

Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis

BACKGROUND: Osteoporosis, a disease of decreased bone mineral density represents a significant and growing burden in the western world. Aging population structure and therapeutic use of glucocorticoids have contributed in no small way to the increase in the incidence of this disease. Despite substantial investigative efforts over the last number of years the exact molecular mechanism underpinning the initiation and progression of osteoporosis remain to be elucidated. This has meant that no significant advances in therapeutic strategies have emerged, with joint replacement surgery being the mainstay of treatment. METHODS: In this study we have used an integrated genomics profiling and computational biology based strategy to identify the key osteoblast genes and gene clusters whose expression is altered in response to dexamethasone exposure. Primary human osteoblasts were exposed to dexamethasone in vitro and microarray based transcriptome profiling completed. RESULTS: These studies identified approximately 500 osteoblast genes whose expression was altered. Functional characterization of the transcriptome identified developmental networks as being reactivated with 106 development associated genes found to be differentially regulated. Pathway reconstruction revealed coordinate alteration of members of the WNT signaling pathway, including frizzled-2, frizzled-7, DKK1 and WNT5B, whose differential expression in this setting was confirmed by real time PCR. CONCLUSION: The WNT pathway is a key regulator of skeletogenesis as well as differentiation of bone cells. Reactivation of this pathway may lead to altered osteoblast activity resulting in decreased bone mineral density, the pathological hallmark of osteoporosis. The data herein lend weight to the hypothesis that alterations in developmental pathways drive the initiation and progression of osteoporosis

Metalloprotease Meprinβ in Rat Kidney: Glomerular Localization and Differential Expression in Glomerulonephritis

Meprin (EC 3.4.24.18) is an oligomeric metalloendopeptidase found in microvillar membranes of kidney proximal tubular epithelial cells. Here, we present the first report on the expression of meprinβ in rat glomerular epithelial cells and suggest a potential involvement in experimental glomerular disease. We detected meprinβ in glomeruli of immunostained rat kidney sections on the protein level and by quantitative RT-PCR of laser-capture microdissected glomeruli on the mRNA level. Using immuno-gold staining we identified the membrane of podocyte foot processes as the main site of meprinβ expression. The glomerular meprinβ expression pattern was altered in anti-Thy 1.1 and passive Heymann nephritis (PHN). In addition, the meprinβ staining pattern in the latter was reminiscent of immunostaining with the sheep anti-Fx1A antiserum, commonly used in PHN induction. Using Western blot and immunoprecipitation assays we demonstrated that meprinβ is recognized by Fx1A antiserum and may therefore represent an auto-antigen in PHN. In anti-Thy 1.1 glomerulonephritis we observed a striking redistribution of meprinβ in tubular epithelial cells from the apical to the basolateral side and the cytosol. This might point to an involvement of meprinβ in this form of glomerulonephritis

A Genome-Wide Association Study of Diabetic Kidney Disease in Subjects With Type 2 Diabetes

dentification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined T1D+T2D GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 subjects with diabetes (18,582 with DKD). Analysis of specific DKD phenotypes identified a novel signal near GABRR1 (rs9942471, P = 4.5 x 10(-8)) associated with microalbuminuria in European T2D case subjects. However, no replication of this signal was observed in Asian subjects with T2D or in the equivalent T1D analysis. There was only limited support, in this substantially enlarged analysis, for association at previously reported DKD signals, except for those at UMOD and PRKAG2, both associated with estimated glomerular filtration rate. We conclude that, despite challenges in addressing phenotypic heterogeneity, access to increased sample sizes will continue to provide more robust inference regarding risk variant discovery for DKD.Peer reviewe

Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies

) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification. (sister taxon to Phalacrocoracidae). These relationships are invariant when ‘backbone’ constraints based on recent avian phylogenies are imposed.Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several “stem fossil + crown family” clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms