Epidemiology of Pathogenic Retroviruses and Domestic Cat Hepadnavirus in Community and Client-Owned Cats in Hong Kong

Understanding the local epidemiology of feline leukaemia virus (FeLV) and feline immunodeficiency virus (FIV) in Hong Kong will inform retrovirus prevention strategies. Domestic cat hepadnavirus (DCH), a novel hepatitis-B-like virus, is commonly detected among client-owned cats in Hong Kong, but community cats have not been studied. The aims of this study were to investigate the frequency and potential risk factors for (i) FeLV and FIV among community and client-owned cats and (ii) perform molecular detection of DCH among community cats in Hong Kong. Blood samples from 713 cats were obtained from client-owned (n = 415, residual diagnostic) and community cats (n = 298, at trap-neuter-return). Point-of-care (POC) testing for FeLV antigen and feline immunodeficiency virus (FIV) anti-p15 and p24 antibodies was performed. FeLV-positive samples were progressed to p27 sandwich enzyme-linked immunosorbent assay. Whole blood DNA was tested with qPCRs for FeLV U3 and gag, and nested PCRs where additional information was required. DCH qPCR was performed on a subset of community cats (n = 193). A single, regressive, FeLV infection was detected in a client-owned cat (1/415 FeLV U3 qPCR positive, 0.2%, 95% CI 0.0–1.3%). Five/415 client-owned cats tested presumably false FeLV-antigen positive (qPCR negative). No markers of FeLV infection were detected in community cats (0/298; 0%). FIV seroprevalence was much higher in community cats (46/298, 15.4%) than in client-owned cats (13/415, 3.1%) (p < 0.001). Mixed breed was a risk factor for FIV infection in client-owned cats. Neither sex nor age were associated with FIV infection. DCH DNA was detected in 34/193 (17.6%) community cats (median viral load 6.32 × 103 copies/reaction). FeLV infection is rare in Hong Kong, negatively impacting the positive predictive value of diagnostic tests. FeLV-antigen testing remains the screening test of choice, but confirmation of a positive result using FeLV qPCR is essential. FIV infection is common in community cats and the absence of a sex predisposition, seen previously in cats managed similarly, raises questions about virus-transmission dynamics in these groups. DCH infection is very common in Hong Kong, both in client-owned and community cats, highlighting the importance of understanding the pathogenic potential of this virus for cats

Waist circumference and waist-to-height ratio of Hong Kong Chinese children

<p>Abstract</p> <p>Background</p> <p>Central body fat is a better predictor than overall body fat for cardiovascular (CV) risk factors in both adults and children. Waist circumference (WC) has been used as a proxy measure of central body fat. Children at high CV risk may be identified by WC measurements. Waist-to-height ratio (WHTR) has been proposed as an alternative, conveniently age-independent measure of CV risk although WHTR percentiles have not been reported. We aim to provide age- and sex-specific reference values for WC and WHTR in Hong Kong Chinese children.</p> <p>Methods</p> <p>Cross sectional study in a large representative sample of 14,842 children aged 6 to 18 years in 2005/6. Sex-specific descriptive statistics for whole-year age groups and smoothed percentile curves of WC and WHTR were derived and presented.</p> <p>Results</p> <p>WC increased with age, although less after age 14 years in girls. WHTR decreased with age (particularly up to age 14). WHTR correlated less closely than WC with BMI (r = 0.65, 0.59 cf. 0.93, 0.91, for boys and girls respectively).</p> <p>Conclusion</p> <p>Reference values and percentile curves for WC and WHRT of Chinese children and adolescents are provided. Both WC and WHTR are age dependent. Since the use of WHRT does not obviate the need for age-related reference standards, simple WC measurement is a more convenient method for central fat estimation than WHRT.</p

Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+/Calcineurin Signaling in the Rice Blast Fungus

Significant progress has been made in defining the central signaling networks in many organisms, but collectively we know little about the downstream targets of these networks and the genes they regulate. To reconstruct the regulatory circuit of calcineurin signal transduction via MoCRZ1, a Magnaporthe oryzae C2H2 transcription factor activated by calcineurin dephosphorylation, we used a combined approach of chromatin immunoprecipitation - chip (ChIP-chip), coupled with microarray expression studies. One hundred forty genes were identified as being both a direct target of MoCRZ1 and having expression concurrently differentially regulated in a calcium/calcineurin/MoCRZ1 dependent manner. Highly represented were genes involved in calcium signaling, small molecule transport, ion homeostasis, cell wall synthesis/maintenance, and fungal virulence. Of particular note, genes involved in vesicle mediated secretion necessary for establishing host associations, were also found. MoCRZ1 itself was a target, suggesting a previously unreported autoregulation control point. The data also implicated a previously unreported feedback regulation mechanism of calcineurin activity. We propose that calcium/calcineurin regulated signal transduction circuits controlling development and pathogenicity manifest through multiple layers of regulation. We present results from the ChIP-chip and expression analysis along with a refined model of calcium/calcineurin signaling in this important plant pathogen

Pharmaceuticals and personal care products in the environment: What are the big questions?

Background: Over the past 10-15 years, a substantial amount of work has been done by the scientific, regulatory, and business communities to elucidate the effects and risks of pharmaceuticals and personal care products (PPCPs) in the environment. Objective: This review was undertaken to identify key outstanding issues regarding the effects of PPCPs on human and ecological health in order to ensure that future resources will be focused on the most important areas. Data sources: To better understand and manage the risks of PPCPs in the environment, we used the "key question" approach to identify the principle issues that need to be addressed. Initially, questions were solicited from academic, government, and business communities around the world. A list of 101 questions was then discussed at an international expert workshop, and a top-20 list was developed. Following the workshop, workshop attendees ranked the 20 questions by importance. Data synthesis: The top 20 priority questions fell into seven categories: a) prioritization of substances for assessment, b) pathways of exposure, c) bioavailability and uptake, d) effects characterization, e) risk and relative risk, f) antibiotic resistance, and g) risk management. Conclusions: A large body of information is now available on PPCPs in the environment. This exercise prioritized the most critical questions to aid in development of future research programs on the topic.Centro de Investigaciones del Medioambient

De novo mutations in histone modifying genes in congenital heart disease

Congenital heart disease (CHD) is the most frequent birth defect, affecting 0.8% of live births1. Many cases occur sporadically and impair reproductive fitness, suggesting a role for de novo mutations. By analysis of exome sequencing of parent-offspring trios, we compared the incidence of de novo mutations in 362 severe CHD cases and 264 controls. CHD cases showed a significant excess of protein-altering de novo mutations in genes expressed in the developing heart, with an odds ratio of 7.5 for damaging mutations. Similar odds ratios were seen across major classes of severe CHD. We found a marked excess of de novo mutations in genes involved in production, removal or reading of H3K4 methylation (H3K4me), or ubiquitination of H2BK120, which is required for H3K4 methylation2–4. There were also two de novo mutations in SMAD2; SMAD2 signaling in the embryonic left-right organizer induces demethylation of H3K27me5. H3K4me and H3K27me mark `poised' promoters and enhancers that regulate expression of key developmental genes6. These findings implicate de novo point mutations in several hundred genes that collectively contribute to ~10% of severe CHD

Evaluation of genetic susceptibility to childhood allergy and asthma in an African American urban population

<p>Abstract</p> <p>Background</p> <p>Asthma and allergy represent complex phenotypes, which disproportionately burden ethnic minorities in the United States. Strong evidence for genomic factors predisposing subjects to asthma/allergy is available. However, methods to utilize this information to identify high risk groups are variable and replication of genetic associations in African Americans is warranted.</p> <p>Methods</p> <p>We evaluated 41 single nucleotide polymorphisms (SNP) and a deletion corresponding to 11 genes demonstrating association with asthma in the literature, for association with asthma, atopy, testing positive for food allergens, eosinophilia, and total serum IgE among 141 African American children living in Detroit, Michigan. Independent SNP and haplotype associations were investigated for association with each trait, and subsequently assessed in concert using a genetic risk score (GRS).</p> <p>Results</p> <p>Statistically significant associations with asthma were observed for SNPs in <it>GSTM1, MS4A2</it>, and <it>GSTP1 </it>genes, after correction for multiple testing. Chromosome 11 haplotype CTACGAGGCC (corresponding to <it>MS4A2 </it>rs574700, rs1441586, rs556917, rs502581, rs502419 and <it>GSTP1 </it>rs6591256, rs17593068, rs1695, rs1871042, rs947895) was associated with a nearly five-fold increase in the odds of asthma (Odds Ratio (OR) = 4.8, <it>p </it>= 0.007). The GRS was significantly associated with a higher odds of asthma (OR = 1.61, 95% Confidence Interval = 1.21, 2.13; <it>p </it>= 0.001).</p> <p>Conclusions</p> <p>Variation in genes associated with asthma in predominantly non-African ethnic groups contributed to increased odds of asthma in this African American study population. Evaluating all significant variants in concert helped to identify the highest risk subset of this group.</p

Mouse Sphingosine Kinase 1a Is Negatively Regulated through Conventional PKC-Dependent Phosphorylation at S373 Residue

Sphingosine kinase is a lipid kinase that converts sphingosine into sphingosine-1-phosphate, an important signaling molecule with intracellular and extracellular functions. Although diverse extracellular stimuli influence cellular sphingosine kinase activity, the molecular mechanisms underlying its regulation remain to be clarified. In this study, we investigated the phosphorylation-dependent regulation of mouse sphingosine kinase (mSK) isoforms 1 and 2. mSK1a was robustly phosphorylated in response to extracellular stimuli such as phorbol ester, whereas mSK2 exhibited a high basal level of phosphorylation in quiescent cells regardless of agonist stimulation. Interestingly, phorbol ester-induced phosphorylation of mSK1a correlated with suppression of its activity. Chemical inhibition of conventional PKCs (cPKCs) abolished mSK1a phosphorylation, while overexpression of PKC alpha, a cPKC isoform, potentiated the phosphorylation, in response to phorbol ester. Furthermore, an in vitro kinase assay showed that PKC alpha directly phosphorylated mSK1a. In addition, phosphopeptide mapping analysis determined that the S373 residue of mSK1a was the only site phosphorylated by cPKC. Interestingly, alanine substitution of S373 made mSK1a refractory to the inhibitory effect of phorbol esters, whereas glutamate substitution of the same residue resulted in a significant reduction in mSK1a activity, suggesting the significant role of this phosphorylation event. Taken together, we propose that mSK1a is negatively regulated through cPKC-dependent phosphorylation at S373 residueopen

A Novel Pathogenicity Gene Is Required in the Rice Blast Fungus to Suppress the Basal Defenses of the Host

For successful colonization and further reproduction in host plants, pathogens need to overcome the innate defenses of the plant. We demonstrate that a novel pathogenicity gene, DES1, in Magnaporthe oryzae regulates counter-defenses against host basal resistance. The DES1 gene was identified by screening for pathogenicity-defective mutants in a T-DNA insertional mutant library. Bioinformatic analysis revealed that this gene encodes a serine-rich protein that has unknown biochemical properties, and its homologs are strictly conserved in filamentous Ascomycetes. Targeted gene deletion of DES1 had no apparent effect on developmental morphogenesis, including vegetative growth, conidial germination, appressorium formation, and appressorium-mediated penetration. Conidial size of the mutant became smaller than that of the wild type, but the mutant displayed no defects on cell wall integrity. The Δdes1 mutant was hypersensitive to exogenous oxidative stress and the activity and transcription level of extracellular enzymes including peroxidases and laccases were severely decreased in the mutant. In addition, ferrous ion leakage was observed in the Δdes1 mutant. In the interaction with a susceptible rice cultivar, rice cells inoculated with the Δdes1 mutant exhibited strong defense responses accompanied by brown granules in primary infected cells, the accumulation of reactive oxygen species (ROS), the generation of autofluorescent materials, and PR gene induction in neighboring tissues. The Δdes1 mutant displayed a significant reduction in infectious hyphal extension, which caused a decrease in pathogenicity. Notably, the suppression of ROS generation by treatment with diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases, resulted in a significant reduction in the defense responses in plant tissues challenged with the Δdes1 mutant. Furthermore, the Δdes1 mutant recovered its normal infectious growth in DPI-treated plant tissues. These results suggest that DES1 functions as a novel pathogenicity gene that regulates the activity of fungal proteins, compromising ROS-mediated plant defense

The DRUID study: racism and self-assessed health status in an indigenous population

BackgroundThere is now considerable evidence from around the world that racism is associated with both mental and physical ill-health. However, little is known about the mediating factors between racism and ill-health. This paper investigates relationships between racism and self-assessed mental and physical health among Indigenous Australians as well as potential mediators of these relationships.MethodsA total of 164 adults in the Darwin Region Urban Indigenous Diabetes (DRUID) study completed a validated instrument assessing interpersonal racism and a separate item on discrimination-related stress. Self-assessed health status was measured using the SF-12. Stress, optimism, lack of control, social connections, cultural identity and reactions/responses to interpersonal racism were considered as mediators and moderators of the relationship between racism/discrimination and self-assessed health status.ResultsAfter adjusting for socio-demographic factors, interpersonal racism was significantly associated with the SF-12 mental (but not the physical) health component. Stress, lack of control and feeling powerless as a reaction to racism emerged as significant mediators of the relationship between racism and general mental health. Similar findings emerged for discrimination-related stress.ConclusionsRacism/discrimination is significantly associated with poor general mental health among this indigenous population. The mediating factors between racism and mental health identified in this study suggest new approaches to ameliorating the detrimental effects of racism on health. In particular, the importance of reducing racism-related stress, enhancing general levels of mastery, and minimising negative social connections in order to ameliorate the negative consequences of racism