The HIV capsid mimics karyopherin engagement of FG-nucleoporins.

HIV can infect non-dividing cells because the viral capsid can overcome the selective barrier of the nuclear pore complex and deliver the genome directly into the nucleus1,2. Remarkably, the intact HIV capsid is more than 1,000 times larger than the size limit prescribed by the diffusion barrier of the nuclear pore3. This barrier in the central channel of the nuclear pore is composed of intrinsically disordered nucleoporin domains enriched in phenylalanine-glycine (FG) dipeptides. Through multivalent FG interactions, cellular karyopherins and their bound cargoes solubilize in this phase to drive nucleocytoplasmic transport4. By performing an in vitro dissection of the nuclear pore complex, we show that a pocket on the surface of the HIV capsid similarly interacts with FG motifs from multiple nucleoporins and that this interaction licences capsids to penetrate FG-nucleoporin condensates. This karyopherin mimicry model addresses a key conceptual challenge for the role of the HIV capsid in nuclear entry and offers an explanation as to how an exogenous entity much larger than any known cellular cargo may be able to non-destructively breach the nuclear envelope.

CRP Genotypes Predict Increased Risk to Co-Present with Low Vitamin D and Elevated CRP in a Group of Healthy Black South African Women.

Low 25-hydroxyvitamin D (25(OH)D) and elevated C-reactive protein (CRP) concentrations are independently associated with adverse health outcomes, including cardiovascular disease (CVD). Although an inverse association between these factors has been described, the underlying mechanisms remain unknown. We postulate that environment-gene interactions, through which 25(OH)D interacts with single nucleotide polymorphisms (SNPs) within the CRP gene, modulate CRP; that certain CRP genotypes predispose individuals to a co-phenotype of low 25(OH)D and elevated CRP concentrations; and that this co-phenotype is associated with higher CVD risk. Twelve CRP SNPs were genotyped, and both 25(OH)D and CRP were quantified, in 505 black South African women. Alarmingly, 66% and 60% of the women presented with deficient/insufficient 25(OH)D and elevated CRP concentrations, respectively. CRP concentrations were higher in individuals with lower 25(OH)D concentrations. However, no 25(OH)D-CRP genotype interactions were evident. Several genotypes were associated with an altered risk of presenting with the co-phenotype, indicating a genetic predisposition. Women presenting with this co-phenotype had higher blood pressure and increased anthropometric measures, which may predispose them to develop CVD. We recommend increasing vitamin D fortification and supplementation efforts to reduce inflammation among black women with vitamin D deficiency, thereby possibly curbing diseases contingent on the co-phenotype described here.

Associations between Common Variants in Iron-Related Genes with Haematological Traits in Populations of African Ancestry.

BACKGROUND: Large genome-wide association (GWA) studies of European ancestry individuals have identified multiple genetic variants influencing iron status. Studies on the generalizability of these associations to African ancestry populations have been limited. These studies are important given interethnic differences in iron status and the disproportionate burden of iron deficiency among African ancestry populations. METHODS: We tested the associations of 20 previously identified iron status-associated single nucleotide polymorphisms (SNPs) in 628 Kenyans, 609 Tanzanians, 608 South Africans and 228 African Americans. In each study, we examined the associations present between 20 SNPs with ferritin and haemoglobin, adjusting for age, sex and CRP levels. RESULTS: In the meta analysis including all 4 African ancestry cohorts, we replicated previously reported associations with lowered haemoglobin concentrations for rs2413450 (ß = -0.19, P = 0.02) and rs4820268 (ß = -0.16, P = 0.04) in TMPRSS6. An association with increased ferritin concentrations was also confirmed for rs1867504 in TF (ß = 1.04, P = <0.0001) in the meta analysis including the African cohorts only. CONCLUSIONS: In all meta analyses, we only replicated 4 of the 20 single nucleotide polymorphisms reported to be associated with iron status in large GWA studies of European ancestry individuals. While there is now evidence for the associations of a number of genetic variants with iron status in both European and African ancestry populations, the considerable lack of concordance highlights the importance of continued ancestry-specific studies to elucidate the genetic underpinnings of iron status in ethnically diverse populations.

Common Variants and Haplotypes in the TF, TNF-α, and TMPRSS6 Genes Are Associated with Iron Status in a Female Black South African Population.

BACKGROUND: It is unknown whether single nucleotide polymorphisms (SNPs), associated with iron status in European and Asian populations, have the same relation within the African population. OBJECTIVES: We investigated associations of reported SNPs with iron markers in a South African cohort. METHODS: Hemoglobin concentration, serum ferritin (SF) and soluble transferrin receptor (sTfR) concentrations, and body iron (BI) stores were measured in women (n = 686; range, 32-86 y) who were part of the Prospective Urban and Rural Epidemiology study. Thirty-two SNPs in 12 genes were selected based on existing genome-wide association study data. RESULTS: In the transferrin (TF) gene, SF and BI were significantly lower in the heterozygote genotype (AG) of reference SNP (rs) 1799852 (P = 0.01 and 0.03, respectively) and sTfR concentrations were significantly higher (P = 0.004) than the homozygote minor allele genotype (AA), whereas transferrin receptor and BI concentrations were significantly lower in the heterozygote genotype (AG) of rs3811647 (both P = 0.03) than the homozygote wild-type (AA) and minor allele groups (GG). The chromosome 6 allele combination (AAA) consisting of rs1799964 and rs1800629 both in tumor necrosis factor-α (TNF-α) and rs2071592 in nuclear factor κB inhibitor-like protein 1 (NFKBIL1) was associated with higher odds for low SF concentrations (SF < 15 µg/L; OR: 1.86; 95% CI: 1.23, 2.79) than the allele combinations AGA, GGT, and AGT. The chromosome 22 allele combination (GG) consisting of rs228918 and rs228921 in the transmembrane protease serine 6 (TMPRSS6) gene was associated with lower odds for increased sTfR concentrations (sTfR > 8.3mg/L; OR: 0.79; 95% CI: 0.63, 0.98) than the allele combination AA. CONCLUSIONS: Various SNPs and allele combinations in the TF, TNF-α, and TMPRSS6 genes are associated with iron status in black South African women; however, these association patterns are different compared with European ancestry populations. This stresses the need for population-specific genomic data.

Inter-ethnic differences in genetic variants within the transmembrane protease, serine 6 (TMPRSS6) gene associated with iron status indicators: a systematic review with meta-analyses.

Transmembrane protease, serine 6 (TMPRSS6), is likely to be involved in iron metabolism through its pleiotropic effect on hepcidin concentrations. Recently, genome-wide association studies have identified common variants in the TMPRSS6 gene to be linked to anaemia and low iron status. To get a more precise evaluation of identified TMPRSS6 single nucleotide polymorphism associations with iron status in cohorts of differing continental ancestry, we conducted a systematic review with meta-analyses. We searched the literature using HuGE Navigator, Pubmed and Scopus databases for primarily genome-wide association studies using TMPRSS6 as a free term. Fixed-effects meta-analysis was used to obtain summary estimates of associations. Eleven studies comprised Caucasian populations, four included an Asian population and one study included an African-American population. Differences in minor allele frequencies of 8 TMPRSS6 SNPs (rs855791, rs4820268, rs2111833, rs1421312, rs228921, rs228918, rs228919 and rs575620) across ethnic groups were observed, with the MAF of rs855791 significantly higher in Asian populations than in Caucasians (0.55 vs 0.42, P < 0.0001). In the meta-analysis, the A allele of rs855791 was associated with lower Hb and ferritin concentrations in all populations. This allele was also associated with increased serum transferrin receptor and transferrin concentrations. We observed similar associations for the G allele in rs4820268. Clear disparities in associations were found for the African-American population, although not statistically significant. Associations between TMPRSS6 SNPs and anaemia are consistent across Caucasian and Asian populations. This study highlights the need to conduct studies in African populations where iron deficiency is of utmost public health significance.

Interactions between C-reactive protein genotypes with markers of nutritional status in relation to inflammation.

Inflammation, as indicated by C-reactive protein concentrations (CRP), is a risk factor for chronic diseases. Both genetic and environmental factors affect susceptibility to inflammation. As dietary interventions can influence inflammatory status, we hypothesized that dietary effects could be influenced by interactions with single nucleotide polymorphisms (SNPs) in the CRP gene. We determined 12 CRP SNPs, as well as various nutrition status markers in 2010 black South Africans and analyzed their effect on CRP. Interactions were observed for several genotypes with obesity in determining CRP. Lipid intake modulated the pro-inflammatory effects of some SNPs, i.e., an increase in both saturated fatty acid and monounsaturated fatty acid intake in those homozygous for the polymorphic allele at rs2808630 was associated with a larger increase in CRP. Those harboring the minor alleles at rs3093058 and rs3093062 presented with significantly higher CRP in the presence of increased triglyceride or cholesterol intake. When harboring the minor allele of these SNPs, a high omega-6 to -3 ratio was, however, found to be anti-inflammatory. Carbohydrate intake also modulated CRP SNPs, as HbA1C and fasting glucose levels interacted with some SNPs to influence the CRP. This investigation highlights the impact that nutritional status can have on reducing the inherent genetic susceptibility to a heightened systemic inflammatory state.

Lack of Association of Glycated Haemoglobin with Blood Pressure and Subclinical Atherosclerosis in Black South Africans: a Five-Year Prospective Study

Objectives: Hypertension and diabetes are common in rapidly urbanising sub-Saharan African communities. However; lack of longitudinal data in these regions prevents adequate analysis of the link between measures of glycaemia and cardiovascular disease. Therefore; we examined the relationships of fasting glucose and glycated haemoglobin (HbA1c) with brachial and central blood pressure (BP); and measures of vascular structure and function after five years in black South Africans.Setting and subjects: Nine hundred and twenty-eight participants were included as part of the Prospective Urban Rural Epidemiological (PURE) study in the North West Province.Outcome measures: Fasting glucose; HbA1c and brachial BP at two time points were determined. Central BP; augmentation index (AI) and carotid intima-media thickness (CIMT) were taken at follow-up. Results: Fasting glucose [4.78 (3.50; 6.30) vs. 5 mmol/l (3.96; 6.42)]; HbA1c [5.6 (4.9; 6.3) vs. 5.9 (5.2; 6.9) and (37 vs. 41 mmol/mol)]; and BP (134/88.1 vs. 138/89.5 mmHg) increased significantly over five years (p-value 0.05). However; an association was absent between BP; AI or CIMT and either baseline or the five-year change in glucose or HbA1c. Multivariate analyses confirmed that neither glucose or HbA1c predicted changes in BP; CIMT or AI; but factors that did associate significantly were age; male gender; rural location; abdominal obesity; alcohol intake; total cholesterol to high-density lipoprotein ratio; C-reactive protein and antihypertensive medication (R2; ranging from 0.24-0.36).Conclusion: Although both BP and measures of glycaemia increased significantly over five years in black South Africans; glucose was not independently associated with BP or measures of large artery structure or function. We suggest that fasting glucose and HbA1c below the threshold of diagnosing diabetes should not be used in isolation to predict cardiovascular risk in African individuals

Gene-environment and gene-gene interactions of specific MTHFR, MTR and CBS gene variants in relation to homocysteine in black South Africans.

The methylenetetrahydrofolate reductase (MTHFR), cystathione-ß-synthase (CBS) and methionine synthase (MTR) genes interact with each other and the environment. These interactions could influence homocysteine (Hcy) and diseases contingent thereon. We determined single nucleotide polymorphisms (SNPs) within these genes, their relationships and interactions with total Hcy concentrations within black South Africans to address the increased prevalence of diseases associated with Hcy. The MTHFR 677 TT and MTR 2756 AA genotypes were associated with higher Hcy concentrations (16.6 and 10.1 µmol/L; p<0.05) compared to subjects harboring the MTHFR 677 CT/CC and the MTR 2756 AG genotypes (10.5, 9.7 and 9.5 µmol/L, respectively). The investigated CBS genotypes did not influence Hcy. We demonstrated interactions between the area of residence and the CBS T833C/844ins68 genotypes (p=0.005) so that when harboring the wildtype allele, rural subjects had significantly higher Hcy than their urban counterparts, but when hosting the variant allele the environment made no difference to Hcy. Between the CBS T833C/844ins68 or G9276A and MTHFR C677T genotypes, there were two-way interactions (p=0.003 and=0.004, respectively), with regard to Hcy. Subjects harboring the MTHFR 677 TT genotype in combination with the CBS 833 TT/homozygous 844 non-insert or the MTHFR 677 TT genotype in combination with the CBS 9276 GA/GG displayed higher Hcy concentrations. Therefore, some of the investigated genotypes affected Hcy; residential area changed the way in which the CBS T833C/844ins68 SNPs influenced Hcy concentrations highlighting the importance of environmental factors; and gene-gene interactions allude to epistatic effects.

Nutritional genetics: the case of alcohol and the MTHFR C677T polymorphism in relation to homocysteine in a black South African population.

BACKGROUND/AIMS: It is unknown whether the effect of alcohol consumption on homocysteine (Hcy) is modulated by the methylenetetrahydrofolate reductase (MTHFR) C677T. We explored this hypothesized effect by analyzing cross-sectional data of 1,827 black South Africans. METHODS: Total Hcy concentrations were determined by fluorescence polarization immunoassay and the genotype through polymerase chain reaction-based RFLP analysis. RESULTS: Subjects harboring the 677 TT genotype had the highest Hcy. Among subjects harboring the 677 CC genotype, men had higher Hcy (p = 0.04). Age and gamma-glutamyltransferase (GGT) correlated best (r = 0.26 and r = 0.27; p < 0.05), while the percentage carbohydrate-deficient transferrin and the B vitamins correlated weakly (r < 0.1; p < 0.05) with Hcy. Hcy was positively associated with the reported alcohol intake (p ≤ 0.01). There was no interaction between alcohol consumption and the MTHFR 677 CC or CT genotypes (p > 0.05) for Hcy concentrations; however, an interaction was determined for GGT and the MTHFR genotype (p = 0.02). Age, GGT, gender, MTHFR and vitamin B6 explained 16.8% of the variation in Hcy (p < 0.01). CONCLUSION: The determined interactions might result in differences in the risk conveyed through Hcy with regard to disease development in those with unfavorable GGT concentrations.

Are behavioural risk factors to be blamed for the conversion from optimal blood pressure to hypertensive status in Black South Africans? A 5-year prospective study.

BACKGROUND: Longitudinal cohort studies in sub-Saharan Africa are urgently needed to understand cardiovascular disease development. We, therefore, explored health behaviours and conventional risk factors of African individuals with optimal blood pressure (BP) (≤ 120/80 mm Hg), and their 5-year prediction for the development of hypertension. METHODS: The Prospective Urban Rural Epidemiology study in the North West Province, South Africa, started in 2005 and included African volunteers (n = 1994; aged > 30 years) from a sample of 6000 randomly selected households in rural and urban areas. RESULTS: At baseline, 48% of the participants were hypertensive (≥ 140/90 mmHg). Those with optimal BP (n = 478) were followed at a success rate of 70% for 5 years (213 normotensive, 68 hypertensive, 57 deceased). Africans that became hypertensive smoked more than the normotensive individuals (68.2% vs 49.8%), and they also had a greater waist circumference [ratio of geometric means of 0.94 cm (95% CI: 0.86-0.99)] and greater amount of γ-glutamyltransferase [0.74 U/l (95% CI: 0.62-0.88)] at baseline. The 5-year change in BP was independently explained by baseline γ-glutamyltransferase [R(2) = 0.23, ß = 0.13 U/l (95% CI: 0.01-0.19)]. Alcohol intake also predicted central systolic BP and carotid cross-sectional wall area (CSWA) at follow-up. Waist circumference was another predictor of BP changes [ß = 0.18 cm (95% CI: 0.05-0.24)] and CSWA. HIV infection was inversely associated with increased BP. CONCLUSIONS: During the 5 years, 24% of Africans with optimal BP developed hypertension. The surge in hypertension in Africa is largely explained by modifiable risk factors. Public health strategies should focus aggressively on lifestyle to prevent a catastrophic burden on the national health system.

Ovine TRIM5α can restrict visna/maedi virus.

The restrictive properties of tripartite motif-containing 5 alpha (TRIM5α) from small ruminant species have not been explored. Here, we identify highly similar TRIM5α sequences in sheep and goats. Cells transduced with ovine TRIM5α effectively restricted the lentivirus visna/maedi virus DNA synthesis. Proteasome inhibition in cells transduced with ovine TRIM5α restored restricted viral DNA synthesis, suggesting a conserved mechanism of restriction. Identification of TRIM5α active molecular species may open new prophylactic strategies against lentiviral infections.

Compound heterozygosity in a South African patient with facioscapulohumeral muscular dystrophy.

Facioscapulohumeral muscular dystrophy (FSHD) is characterised by weakness and atrophy of the facial and shoulder girdle muscles. The FSHD phenotype segregates as an autosomal dominant trait and is caused by a deletion of an integral number of 3.3 kilobase pair (kb) repeat units on chromosome 4q35. Haplotype and Southern blot analyses of chromosome 4 resulted in the detection of two BlnI resistant deletion fragments, of 24 kb and 34 kb respectively, in a single individual from a South African FSHD family. The patient had moderate facial weakness and marked winging and high-riding of the scapulae with prominent pectoral and proximal arm muscle atrophy and weakness. Quadriceps and anterior tibial muscles were weak and the patient had bilateral foot drop. Although none of his children were symptomatic yet and only two showed very mild clinical signs, one had inherited the 24 kb deletion fragment, while the other two had the 34 kb deletion fragment. Molecular analysis conclusively identified the first compound heterozygous case in the South African FSHD population. However, in accordance with other studies of compound heterozygotes and clinical findings, no direct correlation between the clinical severity of this patient and the number of deletion fragments was observed.

Antimicrobial activity of flavonoids from Piper lanceaefolium and other Colombian medicinal plants against antibiotic susceptible and resistant strains of Neisseria gonorrhoeae.

BACKGROUND: The successful treatment of Neisseria gonorrhoeae (NG) infections is increasingly problematic because of the resistance of this pathogen to multiple antimicrobial agents. This development underscores the need for new antimicrobial sources. In the current study, 21 crude methanol extracts, from 19 plants used in Colombian traditional medicine for cutaneous infections, were screened for antimicrobial activity against NG. METHODS: Extracts were screened by disc susceptibility assay. In addition, the minimum inhibitory concentrations of active compounds from P. lanceaefolium were assayed using a panel of 26 NG strains comprising 12 antibiotic-resistant phenotypes. RESULTS: In all, 71% of the crude extracts exhibited antibacterial activity against the antibiotic susceptible NG strain WHO V, whereas 10% of the extracts inhibited penicillinase-producing NG strain GC1-182. The crude extract of Piper lanceaefolium was the only extract to show significant activity without ultraviolet (UV) light activation. Preliminary screening identified 3 compounds in this plant possessing antimicrobial activity: the flavonoids 5,7-dihydroxyflavanone (pinocembrin), 2',4',6'-trihydroxychalcone (pinocembrin chalcone), and the prenylated benzoic acid derivative cyclolanceaefolic acid methyl ester. Pinocembrin and pinocembrin chalcone inhibited 100% of the NG panel at 64 µg/mL and 128 µg/mL, respectively, whereas cyclolanceaefolic acid methyl ester inhibited 44% of the strains at 128 µg/mL. CONCLUSIONS: This is the first report of the antibacterial activity of Columbian plants against NG. The activity of the 2 flavonoids, pinocembrin, and pinocembrin chalcone, toward both susceptible and resistant NG strains makes them promising candidates for further research.

First Report of Brown Ring Patch Caused by Waitea circinata var. circinata on Creeping Bentgrass in Arizona.

A disease resembling brown ring (Waitea) patch was observed on a 'Dominant Extreme' creeping bentgrass (Agrostis stolonifera) green on a golf course in Maricopa County, Arizona in February 2010. The green was 17 months old and built with 95% sand and 5% peat moss. The superintendent reported seeing yellow rings, 12 to 16 cm in diameter, on several greens as early as 3 months postinstallation; the yellow rings developed into brown, necrotic rings. Symptoms started in the cool, cloudy, and moist conditions of December (5.0 to 6.7°C) and became persistent into the spring. Symptoms on the samples appeared to be yellowing of leaves and stems with the development of a dark, water-soaked appearance of the whole plant on older affected portions. The samples were incubated in a moist chamber at 22 to 25°C for 24 h. Foliar mycelium developed on the symptomatic leaves, and upon microscopic examination, the mycelium appeared to have the characteristics of Rhizoctonia spp.; i.e., a right-angled branching pattern, constriction of the hyphal branch near its point of origin, and the presence of a septum near the point of origin. The pathogen was recovered from chlorotic tissue by plating the symptomatic tissue on one-quarter-strength acidified potato dextrose agar (9.90 g of PDA and 11.26 g of granulated agar [Fisher, Lenexa, KS] and 600 ml of lactic acid [Sigma, St. Louis, MO] per liter of water) and incubating at ~27°C in light. A Rhizoctonia-like pathogen emerged from the tissue within 48 h and was tentatively identified as Waitea circinata var. circinata based on colony and bulbil morphology after 10 days of incubation (3). The recovered isolate was used for DNA extraction and subsequent amplification and sequencing of the rDNA internally transcribed spacer (ITS) region using ITS1F and ITS4 primers (2). The recovered sequence (HM807352) was compared with the National Center for Biotechnology Information (NCBI) nucleic acid database and was found to show 100% similarity to W. circinata var. circinata (FJ755879). To confirm pathogenicity, the isolate was used to fulfill Koch's postulates. The isolate was grown on autoclaved sand and corn meal (250 g of sand and 50 g of corn meal) for 4 weeks to produce inoculum. Eight grams of colonized sand and corn meal was broadcast on 4-week-old creeping bentgrass seedlings ('Penncross') planted in a 90:10 peat moss/sand mixture in 10-cm-diameter pots. There were three replications and the experiment was repeated twice. Negative controls consisted of plants inoculated with sand and corn meal only. Pots were maintained at 28 to 33°C in the greenhouse with ambient light. Within 4 days of inoculation, the plants showed chlorosis and necrosis, while noninoculated plants showed no symptoms. The pathogen was successfully reisolated from several plants from each replication using the method described above. This pathogen has been known to cause disease on annual and rough bluegrass (1,2) in the United States, but not confirmed as a pathogen on creeping bentgrass here. To our knowledge, this is the first report of brown ring patch on creeping bentgrass in Arizona. References: (1) C. M. Chen et al. Plant Dis. 91:1687, 2007. (2) K. de la Cerda et al. Plant Dis. 91:791, 2007. (3) T. Toda et al. Plant Dis. 89:536, 2005.

Colorectal cancer follow-up: patient satisfaction and amenability to telephone after care.

PURPOSE: To explore patient satisfaction on different aspects of follow-up service provision following treatment for colorectal cancer and amenability to an alternative strategy for follow-up care. METHODS AND SAMPLE: A postal survey was administered to 297 eligible patients who had been treated for colorectal cancer at a large hospital in the North West of England. Patients were asked to indicate responses to questions comprising likert scales, including views on organisation of care, information and advice, personal experience of care, satisfaction with information and care, views on specialist nursing services and amenability to telephone follow-up. KEY RESULTS: One hundred and eighty-seven completed surveys were returned (62.97% response rate). Analysis of scale data indicated high levels of satisfaction on all outcome measures but sub-optimal rates of satisfaction on some items. Respondents indicated high levels of satisfaction with information related to disease and treatment but lower levels of satisfaction for items related to genetic risk, sexual attractiveness and self care. Colorectal nurse specialists were highly rated, especially in terms of information provision and personal experience of care. Patients were generally amenable to telephone follow-up, although male patients indicated higher levels of willingness to accept this approach than females. CONCLUSIONS: Satisfaction with traditional medical based follow-up is generally high in this patient cohort but there is room for improvement in terms of service delivery. High levels of satisfaction with the care delivered by colorectal nurse specialists and patient acceptance of telephone follow-up suggests nurse-led telephone follow-up is a viable alternative to traditional hospital based follow-up.

Global meta-analysis of the C-11377G alteration in the ADIPOQ gene indicates the presence of population-specific effects: challenge for global health initiatives.

Type II diabetes mellitus is currently globally one of the fastest growing non-communicable diseases, especially in developing countries. This investigation reports on a meta-analysis undertaken of the C-11377G locus within the adiponectin gene in a black South African, a Cuban Hispanic and a German Caucasian cohort. Genotyping was performed via a real-time PCR strategy. Both fixed- and random-effects models were tested to describe the diabetes risk at both the cohort and population levels. The 2,2 genotype may only be associated with increased diabetes risk in the Cuban Hispanic cohort. Population-specific effects may have masked these associations upon meta-analytical analysis, as no significant odds ratio could be determined. Thus, to examine diabetes risk, a more global approach including the design of population-specific experimental strategies should be used, which will be crucial in developing health education and policies in a global health programme.

Identification of a RELIK orthologue in the European hare (Lepus europaeus) reveals a minimum age of 12 million years for the lagomorph lentiviruses.

The retroviral genus Lentivirus comprises retroviruses characterised from five mammalian orders. Lentiviruses typically undergo rapid rates of evolution, a feature that has allowed recent evolutionary relationships to be elucidated, but has also obscured their distant evolutionary past. However, the slowdown in the rate of evolution associated with genome invasion, as has occurred in the European rabbit, enables longer-term lentiviral evolutionary history to be inferred. Here we report the identification of orthologous RELIK proviruses in the European hare, demonstrating a minimum age of 12 million years for the lagomorph lentiviruses. This finding indicates an association between lentiviruses and their hosts covering much of the evolutionary history of the lagomorphs, and taking place within species with a worldwide distribution.

Genetic polymorphisms of beta2- and beta3-adrenergic receptor genes associated with characteristics of the metabolic syndrome in black South African women.

BACKGROUND: Genetic variation in the beta2 (ADRB2) and beta3 (ADRB3) adrenergic receptor genes are associated with obesity and insulin resistance. To further elucidate the role of these genes in the pathophysiology of obesity the present study investigated associations between certain polymorphisms in ADRB2 and ADRB3 and parameters of carbohydrate and lipid metabolism in a population of African origin. MATERIAL AND METHODS: Data of 102 black South African women obtained in the POWIRS (Profile of Obese Women with the Insulin Resistance Syndrome) study were used. Endpoint measurements included several anthropometric variables, resting blood pressure, plasma glucose, insulin, free fatty acids (FFA), ghrelin, leptin and lipids, and insulin resistance as estimated by the homeostasis model assessment (HOMA-IR) index. Polymorphisms were analyzed via PCR based methods. RESULTS: The percentage body fat was significantly lower (p< or =0.05) and the FFA significantly higher (p< or =0.05) in lean subjects (BMI< or =25 kg/m2) with the Glu27 variant allele compared to subjects with the Gln27 wildtype allele of the ADRB2 gene. In contrast, the variant allele of the ADRB2 gene was significantly positive associated (p< or =0.05) with the HOMA-IR-index in overweight black African women (BMI>25 kg/m2). No significant differences in parameters of the metabolic syndrome were apparent between subjects with the wildtype and variant alleles in the ADRB3 gene. CONCLUSION: The presence of the Glu27 and Arg64 polymorphisms of the ADRB2 and ADRB3 genes are not directly related to indices of the metabolic syndrome.

Bioactivity-guided isolation of the active compounds from Rosa nutkana and quantitative analysis of ascorbic acid by HPLC.

Rosa nutkana Presl. (Rosaceae) is distributed abundantly throughout central and southern areas of British Columbia, Canada. Aboriginal people in the Pacific Northwest have traditionally used R. nutkana as a food, medicine, and source of cultural material. The methanolic extract of the fruits of R. nutkana was previously found to have inhibitory activity against methicillin-resistant Staphylococcus aureus (MRSA). In our study, bioactivity-guided fractionation of the methanol extract from R. nutkana led to the isolation of the following 10 compounds: (i) tormentic acid, (ii) euscaphic acid, (iii) ursolic acid, (iv) maslinic acid, (v) quercetin, (vi) catechin gallate, (vii) quercetin-3-O-glucoside, (viii) 1,2,3,4,6-penta-O-galloyl-beta-D-glucoside, (ix) L-ascorbic acid (vitamin C), and (x) 1,6-digalloyl-beta-D-glucoside. Structures were elucidated by ultraviolet, infrared, mass spectrometry, and nuclear magnetic resonance data, as well as by comparison with those of the literature. The compounds quercetin, catechin gallate, quercetin-3-O-glucoside, 1,2,3,4,6-penta-O-galloyl-beta-D-glucoside, and 1,6-digalloyl-beta-D-glucoside exhibited weak antibacterial activity against MRSA. Our research demonstrates the value of traditional knowledge held by Aboriginal people in the Pacific Northwest with respect to uses of R. nutkana. Some described uses in the ethnobotanical literature correspond to activities observed under laboratory conditions. Further work on British Columbia Rosa spp. may contribute to identifying other potential therapeutic uses.