Association of common variation in the <Emphasis Type="Italic">PPARA</Emphasis>gene with incident myocardial infarction in individuals with type 2 diabetes: A Go-DARTS study

Background

Common variants of the PPARA gene have been found to associate with ischaemic heart disease in non diabetic men. The L162V variant was found to be protective while the C2528G variant increased risk. L162V has also been associated with altered lipid measures. We therefore sought to determine the effect of PPARA gene variation on susceptibility to myocardial infarction in patients with type 2 diabetes. 1810 subjects with type 2 diabetes from the prospective Go-DARTS study were genotyped for the L162V and C2528G variants in the PPARA gene and the association of the variants with incident non-fatal myocardial infarction was examined. Cox's proportional hazards was used to interrogate time to event from recruitment, and linear regression for analysing association of genotype with quantitative clinical traits.

Results

The V162 allele was associated with decreased risk of non-fatal myocardial infarction (HR = 0.31, 95%CI 0.10–0.93 p = 0.037) whereas the C2528 allele was associated with increased risk (HR = 2.77 95%CI 1.34–5.75 p = 0.006). Similarly V162 was associated with a later mean age of diagnosis with type 2 diabetes and C2582 an earlier age of diagnosis. C2528 was also associated with increased total cholesterol and LDL cholesterol, which did not account for the observed increased risk. Haplotype analysis demonstrated that when both rare variants occurred on the same haplotype the effect of each was abrogated.

Conclusion

Genetic variation at the PPARA locus is important in determining cardiovascular risk in both male and female patients with diabetes. This genotype associated risk appears to be independent of the effect of these genotypes on lipid profiles and age of diagnosis with diabetes.

     

Development and standardization of multiplexed antibody microarrays for use in quantitative proteomics

BACKGROUND: Quantitative proteomics is an emerging field that encompasses multiplexed measurement of many known proteins in groups of experimental samples in order to identify differences between groups. Antibody arrays are a novel technology that is increasingly being used for quantitative proteomics studies due to highly multiplexed content, scalability, matrix flexibility and economy of sample consumption. Key applications of antibody arrays in quantitative proteomics studies are identification of novel diagnostic assays, biomarker discovery in trials of new drugs, and validation of qualitative proteomics discoveries. These applications require performance benchmarking, standardization and specification. RESULTS: Six dual-antibody, sandwich immunoassay arrays that measure 170 serum or plasma proteins were developed and experimental procedures refined in more than thirty quantitative proteomics studies. This report provides detailed information and specification for manufacture, qualification, assay automation, performance, assay validation and data processing for antibody arrays in large scale quantitative proteomics studies. CONCLUSION: The present report describes development of first generation standards for antibody arrays in quantitative proteomics. Specifically, it describes the requirements of a comprehensive validation program to identify and minimize antibody cross reaction under highly multiplexed conditions; provides the rationale for the application of standardized statistical approaches to manage the data output of highly replicated assays; defines design requirements for controls to normalize sample replicate measurements; emphasizes the importance of stringent quality control testing of reagents and antibody microarrays; recommends the use of real-time monitors to evaluate sensitivity, dynamic range and platform precision; and presents survey procedures to reveal the significance of biomarker findings.     

Distribution of Pirhemocyton Chatton & Blanc and other, Possibly Related, Infections of Poikilotherms

SYNOPSIS. Data for host and geographic distribution are listed for Pirhemocyton and for apparently similar infections of poikilothermic vertebrates. The list was compiled from published accounts of Pirhemocyton, Toddia, Cytamoeba, Bertarellia , Piscine erythrocytic necrosis, Immanoplasma, Haematractidium, Sauroplasma, Sauromella, Serpentoplasma, Tunetella, Haemohormidium and unnamed infections. New records are included for Pirhemocyton and Haematractidium. The probability that some may be viruses and not protozoa is discussed; Haematractidium is shown by electron microscopy to be a eukaryote whereas Immanoplasma is not a eukaryote.     

Species of street tree is important for southern hemisphere bird trophic guilds

Abstract Urban environments are highly modified with unique assemblages of bird species. Much of the research on urban bird assemblages comes from the northern hemisphere. Southern hemisphere bird assemblages differ from northern hemisphere assemblages in that they contain a large proportion of nectarivores. In this study we focus on bird use of street trees in Australia. We investigate the relative influence of tree species (plane tree, Platanus x acerifolia; red gums, Eucalyptus camaldulensis; jacaranda, Jacaranda mimosifolia; bottlebrush, Callistemon citrinus), season and the environment surrounding street trees, on the abundance and species richness of birds in Adelaide, South Australia. Our study considers birds in terms of granivore, nectarivore and insectivore trophic guilds. Nectarivores accounted for the greatest proportion of observations, in terms of abundance, in each of the tree species investigated. Species of street tree was a significant influence on bird use of the trees for all birds and each dietary guild. Red gums were used more than the other tree species by nectarivores, while plane trees were used more than the other trees by insectivores. Use of the tree species by granivores varied with the season. The measures of the environment surrounding street trees were largely unimportant with the exception of traffic for nectarivores in some cases. Urban avifauna use street trees and the species of tree will strongly influence its use by birds. However, the pattern of use of street tree species varied at different times of year and differed between different trophic guilds of birds. The dominance of nectarivores in the southern avifauna will likely produce different patterns of urban environment use to northern hemisphere avifaunas.     

A note on the use of dextran in blood cultures monitored by conductance methods

The incorporation of dextran into broth for the detection of bacteraemia by conductance monitoring is recommended to eliminate the effect of sedimenting blood cells which may mask early signals from bacteria. Broth containing ten times the recommended concentration of dextran was tested with a wide range of bacteria without demonstrating any reduction in growth or rate of change of conductance.     

Fetal microchimerism in kidney biopsies of lupus nephritis patients may be associated with a beneficial effect

IntroductionMicrochimeric male fetal cells (MFCs) have been associated with systemic lupus erythematosus, and published studies have further correlated MFC with lupus nephritis (LN). In the present study, we evaluated the frequency of MFC in the renal tissue of patients with LN.MethodsTwenty-seven renal biopsies were evaluated: Fourteen were from women with clinical and laboratory findings of LN, and thirteen were from controls. Genomic DNA was extracted from kidney biopsies, and the male fetal DNA was quantified using real-time quantitative polymerase chain reactions for the detection of specific Y chromosome sequences.ResultsMFCs were detected in 9 (64%) of 14 of patients with LN, whereas no MFCs were found in the control group (P = 0.0006). No differences in pregnancy history were found between patients with LN and the control group. Significantly higher amounts of MFCs were found in patients with LN with serum creatinine ≤1.5 mg/dl. Furthermore, women with MFCs had significantly better renal function at the time of biopsy (P = 0.03). In contrast, patients with LN without MFCs presented with more severe forms of glomerulonephritis (World Health Organization class IV = 60% and class V = 40%).ConclusionsOur data indicate a high prevalence of MFCs in renal biopsy specimens from women with LN, suggesting a role for MFCs in the etiology of LN. The present report also provides some evidence that MFCs could have a beneficial effect in this disease.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0615-4) contains supplementary material, which is available to authorized users.     

Growth and survivorship as proximate causes of sexual size dimorphism in peninsula dragon lizards Ctenophorus fionni

Males and females differ in body size in many animals, but the direction and extent of this sexual size dimorphism (SSD) varies widely. Males are larger than females in most lizards of the iguanian clade, which includes dragon lizards (Agamidae). I tested whether the male larger pattern of SSD in the peninsula dragon lizard, Ctenophorus fionni, is a result of sexual selection for large male size or relatively higher mortality among females. Data on growth and survivorship were collected from wild lizards during 1991–1994. The likelihood of differential predation between males and females was assessed by exposing pairs of male and female lizards to a predator in captivity, and by comparing the frequency of tail damage in wild‐caught males and females. Male and female C. fionni grew at the same rate, but males grew for longer than females and reached a larger asymptotic size (87 mm vs. 78 mm). Large males were under‐represented in the population because they suffered higher mortality than females. Predation may account for some of this male‐biased mortality. The male‐biased SSD in C. fionni resulted from differences in growth pattern between the sexes. The male‐biased SSD was not the result of proximate factors reducing female body size. Indeed SSD in this species remained male‐biased despite high mortality among large males. SSD in C. fionni is consistent with the ultimate explanation of sexual selection for large body size in males.