Structure- and context-based analysis of the GxGYxYP family reveals a new putative class of glycoside hydrolase.

BackgroundGut microbiome metagenomics has revealed many protein families and domains found largely or exclusively in that environment. Proteins containing the GxGYxYP domain are over-represented in the gut microbiota, and are found in Polysaccharide Utilization Loci in the gut symbiont Bacteroides thetaiotaomicron, suggesting their involvement in polysaccharide metabolism, but little else is known of the function of this domain.ResultsGenomic context and domain architecture analyses support a role for the GxGYxYP domain in carbohydrate metabolism. Sparse occurrences in eukaryotes are the result of lateral gene transfer. The structure of the GxGYxYP domain-containing protein encoded by the BT2193 locus reveals two structural domains, the first composed of three divergent repeats with no recognisable homology to previously solved structures, the second a more familiar seven-stranded β/α barrel. Structure-based analyses including conservation mapping localise a presumed functional site to a cleft between the two domains of BT2193. Matching to a catalytic site template from a GH9 cellulase and other analyses point to a putative catalytic triad composed of Glu272, Asp331 and Asp333.ConclusionsWe suggest that GxGYxYP-containing proteins constitute a novel glycoside hydrolase family of as yet unknown specificity

Impacts of indoor surface finishes on bacterial viability.

Microbes in indoor environments are constantly being exposed to antimicrobial surface finishes. Many are rendered non-viable after spending extended periods of time under low-moisture, low-nutrient surface conditions, regardless of whether those surfaces have been amended with antimicrobial chemicals. However, some microorganisms remain viable even after prolonged exposure to these hostile conditions. Work with specific model pathogens makes it difficult to draw general conclusions about how chemical and physical properties of surfaces affect microbes. Here, we explore the survival of a synthetic community of non-model microorganisms isolated from built environments following exposure to three chemically and physically distinct surface finishes. Our findings demonstrated the differences in bacterial survival associated with three chemically and physically distinct materials. Alkaline clay surfaces select for an alkaliphilic bacterium, Kocuria rosea, whereas acidic mold-resistant paint favors Bacillus timonensis, a Gram-negative spore-forming bacterium that also survives on antimicrobial surfaces after 24 hours of exposure. Additionally, antibiotic-resistant Pantoea allii did not exhibit prolonged retention on antimicrobial surfaces. Our controlled microcosm experiment integrates measurement of indoor chemistry and microbiology to elucidate the complex biochemical interactions that influence the indoor microbiome

Accelerated Calvarial Healing in Mice Lacking Toll-Like Receptor 4

The bone and immune systems are closely interconnected. The immediate inflammatory response after fracture is known to trigger a healing cascade which plays an important role in bone repair. Toll-like receptor 4 (TLR4) is a member of a highly conserved receptor family and is a critical activator of the innate immune response after tissue injury. TLR4 signaling has been shown to regulate the systemic inflammatory response induced by exposed bone components during long-bone fracture. Here we tested the hypothesis that TLR4 activation affects the healing of calvarial defects. A 1.8 mm diameter calvarial defect was created in wild-type (WT) and TLR4 knockout (TLR4-/-) mice. Bone healing was tested using radiographic, histologic and gene expression analyses. Radiographic and histomorphometric analyses revealed that calvarial healing was accelerated in TLR4-/- mice. More bone was observed in TLR4-/- mice compared to WT mice at postoperative days 7 and 14, although comparable healing was achieved in both groups by day 21. Bone remodeling was detected in both groups on postoperative day 28. In TLR4-/- mice compared to WT mice, gene expression analysis revealed that higher expression levels of IL-1β, IL-6, TNF-α,TGF-β1, TGF-β3, PDGF and RANKL and lower expression level of RANK were detected at earlier time points (≤ postoperative 4 days); while higher expression levels of IL-1β and lower expression levels of VEGF, RANK, RANKL and OPG were detected at late time points (> postoperative 4 days). This study provides evidence of accelerated bone healing in TLR4-/- mice with earlier and higher expression of inflammatory cytokines and with increased osteoclastic activity. Further work is required to determine if this is due to inflammation driven by TLR4 activation. © 2012 Wang et al

A method for exploratory repeated-measures analysis applied to a breast-cancer screening study

When a model may be fitted separately to each individual statistical unit, inspection of the point estimates may help the statistician to understand between-individual variability and to identify possible relationships. However, some information will be lost in such an approach because estimation uncertainty is disregarded. We present a comparative method for exploratory repeated-measures analysis to complement the point estimates that was motivated by and is demonstrated by analysis of data from the CADET II breast-cancer screening study. The approach helped to flag up some unusual reader behavior, to assess differences in performance, and to identify potential random-effects models for further analysis.Comment: Published in at http://dx.doi.org/10.1214/11-AOAS481 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

The impact of increased food availability on reproduction in a long-distance migratory songbird: implications for environmental change?

Many populations of migratory songbirds are declining or shifting in distribution. This is likely due to environmental changes that alter factors such as food availability that may have an impact on survival and/or breeding success. We tested the impact of experimentally supplemented food on the breeding success over three years of northern wheatears (Oenanthe oenanthe), a species in decline over much of Europe. The number of offspring fledged over the season was higher for food-supplemented birds than for control birds. The mechanisms for this effect were that food supplementation advanced breeding date, which, together with increased resources, allowed further breeding attempts. While food supplementation did not increase the clutch size, hatching success or number of chicks fledged per breeding attempt, it did increase chick size in one year of the study. The increased breeding success was greater for males than females; males could attempt to rear simultaneous broods with multiple females as well as attempting second broods, whereas females could only increase their breeding effort via second broods. Multiple brooding is rare in the study population, but this study demonstrates the potential for changes in food availability to affect wheatear breeding productivity, primarily via phenotypic flexibility in the number of breeding attempts. Our results have implications for our understanding of how wheatears may respond to natural changes in food availability due to climate changes or changes in habitat management

Draft Genome Sequences of Six Ruminant Coxiella burnetii Isolates of European Origin

Coxiella burnetii is responsible for Q fever, a worldwide zoonosis attributed to the inhalation of aerosols contaminated by livestock birth products. Six draft genome sequences of European C. burnetii isolates from ruminants are presented here. The availability of these genomes will help in understanding the potential host specificity and pathogenicity and in identifying pertinent markers for surveillance and tracing

Complete and Prolonged Response to Immune Checkpoint Blockade in POLE-Mutated Colorectal Cancer

Enid Robertson Logan Faculty Fellowship Fund6 month embargo; published online: 21 June 2019This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Glycoprotein hormone receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database

Glycoprotein hormone receptors (provisional nomenclature [45]) are activated by a non-covalent heterodimeric glycoprotein made up of a common α chain (glycoprotein hormone common alpha subunit CGA, P01215), with a unique β chain that confers the biological specificity to FSH, LH, hCG or TSH. There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [120]

Glycoprotein hormone receptors in GtoPdb v.2023.1

Glycoprotein hormone receptors (provisional nomenclature [47]) are activated by a non-covalent heterodimeric glycoprotein made up of a common α chain (glycoprotein hormone common alpha subunit CGA, P01215), with a unique β chain that confers the biological specificity to FSH, LH, hCG or TSH. There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [122, 31]

Glycoprotein hormone receptors (version 2020.4) in the IUPHAR/BPS Guide to Pharmacology Database

Glycoprotein hormone receptors (provisional nomenclature [45]) are activated by a non-covalent heterodimeric glycoprotein made up of a common α chain (glycoprotein hormone common alpha subunit CGA, P01215), with a unique β chain that confers the biological specificity to FSH, LH, hCG or TSH. There is binding cross-reactivity across the endogenous agonists for each of the glycoprotein hormone receptors. The deglycosylated hormones appear to exhibit reduced efficacy at these receptors [120]