The orthologue of the "acatalytic" mammalian ART4 in chicken is an arginine-specific mono-ADP-ribosyltransferase

<p>Abstract</p> <p>Background</p> <p>Human ART4, carrier of the GPI-(glycosyl-phosphatidylinositol) anchored Dombrock blood group antigens, is an apparently inactive member of the mammalian mono-ADP-ribosyltransferase (ART) family named after the enzymatic transfer of a single ADP-ribose moiety from NAD⁺to arginine residues of extracellular target proteins. All known mammalian ART4 orthologues are predicted to lack ART activity because of one or more changes in essential active site residues that make up the R-S-EXE motif. So far, no other function has been detected.</p> <p>Results</p> <p>Here we report the identification and characterisation of ART4 in chicken, which to our knowledge is the first true non-mammalian orthologue of a mammalian ART family member. The chicken <it>ART4 </it>gene has the same physical structure as its mammalian counterparts (three coding exons separated by two introns in phase 0 and phase 1, respectively) and maps to a region of conserved linkage synteny on chromosome 1. Its mRNA encodes a 289 amino acid protein with predicted N-terminal signal peptide and C-terminal GPI-anchor sequences and 47% sequence identity to human ART4. However, in striking contrast to its mammalian orthologues, the chicken protein contains an intact R-S-EXE motif. Upon ectopic expression in C-33A cells, recombinant chicken ART4 localized at the cell surface as a GPI-anchored, highly glycosylated protein, which displayed arginine-specific ART activity (apparent K_mof the recombinant protein for etheno-NAD⁺1.0 ± 0.18 μM).</p> <p>Conclusion</p> <p>The avian orthologue of the "acatalytic" mammalian ART4 is a mono-ADP-ribosyltransferase with enzymatic activity comparable to that of other, catalytically active and GPI-anchored members of the mammalian ART family.</p

Drivers with Dementia: Environment, Errors and Performance Outcomes

The current non-experimental observational study adds to the body of evidence and literature by describing, from a person – environment – occupation model, the on-road performance of 115 licensed drivers who had dementia. The purpose is to potentially prescribe the essential criteria of environmental and driving tasks for on-road assessment inclusion

Терапия болезней периодонта с использованием шинирующих волоконных систем

периодонта болезн

Studies on the influence of ochratoxin A administration on Salmonella typhimurium infection in pigs

The aim of the study was to assess whether immunomodulating effects produced by ochratoxin A (OTA) may influence the course of an experimental infection of pigs with Salmonella Typhimurium 27 Nat (STM 27 Nair). 8-week old pigs were administered 50 g OTA per kg body weight per day via feed. Either 7 or 14 days after beginning of OTA application, these pigs and untreated controls were challenged orally with STM 27 Nair. Different systemic immune parameters in blood and OT A concentration in serum and organs were examined. The number of STM 27 Nair was detected in faecal samples of the pigs. Despite high concentrations of OTA in sera and organs, systemic immune parameters were not modified compared with controls. Significant changes in these parameters were induced only by the Salmonella infection. Pigs pretreated with OTA excreted STM 27 Nair in slightly higher (not significant) concentrations than untreated controls. As the immunomodul ating effects produced by OT A after oral administration seem to be considerably lower than the effects induced by a challenge with Salmonella Typhimurium in a high dose, experiments using reduced doses for infection should give further information on the effect on Salmonella shedding

An Introduction To Marine Invasive Species

Countless marine species are invading new environments with devastating effects on the ecosystem, the local and global economy, and on human health. The frequency of marine invasions has been increasing in recent decades with a respective raised interest of invasive species in the scientific community, and the general public. The Aquatic Invasive Species class (MAR442) at the University of New England offers an informative overview of invasive species, targeting educated readers with a general interest in invasive species biology. Students in the MAR 442 class have worked on identifying the most important topics on marine invasive species, have reviewed the respective literature and written chapters that provide both a broad overview of the general aspects on marine invasions, as well as a set of individual case studies that illustrate different specific aspects of marine invasions. The class, comprised of fifteen junior and senior marine biology students, selected the different topics, presented the material, wrote the drafts, edited the drafts and assembled the final versions into this book. With a wealth of information on invasive species assembled in peer-reviewed articles, books, other literature, websites, data-bases and more, this book cannot claim to be all inclusive. However, we think that this book will provide an excellent broad overview of the most important aspects of marine invasion biology, and will furthermore provide very specific information on selected topics.https://dune.une.edu/marinesci_studproj/1000/thumbnail.jp

Fine-mapping identifies multiple prostate cancer risk loci at 5p15, one of which associates with TERT expression

Associations between single nucleotide polymorphisms (SNPs) at 5p15 and multiple cancer types have been reported. We have previously shown evidence for a strong association between prostate cancer (PrCa) risk and rs2242652 at 5p15, intronic in the telomerase reverse transcriptase (TERT) gene that encodes TERT. To comprehensively evaluate the association between genetic variation across this region and PrCa, we performed a fine-mapping analysis by genotyping 134 SNPs using a custom Illumina iSelect array or Sequenom MassArray iPlex, followed by imputation of 1094 SNPs in 22 301 PrCa cases and 22 320 controls in The PRACTICAL consortium. Multiple stepwise logistic regression analysis identified four signals in the promoter or intronic regions of TERT that independently associated with PrCa risk. Gene expression analysis of normal prostate tissue showed evidence that SNPs within one of these regions also associated with TERT expression, providing a potential mechanism for predisposition to disease

A genome-wide association study identifies protein quantitative trait loci (pQTLs)

There is considerable evidence that human genetic variation influences gene expression. Genome-wide studies have revealed that mRNA levels are associated with genetic variation in or close to the gene coding for those mRNA transcripts - cis effects, and elsewhere in the genome - trans effects. The role of genetic variation in determining protein levels has not been systematically assessed. Using a genome-wide association approach we show that common genetic variation influences levels of clinically relevant proteins in human serum and plasma. We evaluated the role of 496,032 polymorphisms on levels of 42 proteins measured in 1200 fasting individuals from the population based InCHIANTI study. Proteins included insulin, several interleukins, adipokines, chemokines, and liver function markers that are implicated in many common diseases including metabolic, inflammatory, and infectious conditions. We identified eight Cis effects, including variants in or near the IL6R (p = 1.8×10 -57), CCL4L1 (p = 3.9×10-21), IL18 (p = 6.8×10-13), LPA (p = 4.4×10-10), GGT1 (p = 1.5×10-7), SHBG (p = 3.1×10-7), CRP (p = 6.4×10-6) and IL1RN (p = 7.3×10-6) genes, all associated with their respective protein products with effect sizes ranging from 0.19 to 0.69 standard deviations per allele. Mechanisms implicated include altered rates of cleavage of bound to unbound soluble receptor (IL6R), altered secretion rates of different sized proteins (LPA), variation in gene copy number (CCL4L1) and altered transcription (GGT1). We identified one novel trans effect that was an association between ABO blood group and tumour necrosis factor alpha (TNF-alpha) levels (p = 6.8×10-40), but this finding was not present when TNF-alpha was measured using a different assay , or in a second study, suggesting an assay-specific association. Our results show that protein levels share some of the features of the genetics of gene expression. These include the presence of strong genetic effects in cis locations. The identification of protein quantitative trait loci (pQTLs) may be a powerful complementary method of improving our understanding of disease pathways. © 2008 Melzer et al

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression