Studies on disaccharide nucleoside synthesis. Mechanism of the formation of trisaccharide purine nucleosides.

The unexpected formation of trisaccharide nucleosides during synthesis of purine 5'-O-beta-D-ribofuranosylnucleosides in the presence of Lewis acids was observed.     

Nucleotide variation at the hypervariable esterase 6 isozyme locus of Drosophila simulans

Esterase 6 (Est-6/EST6) is polymorphic in both Drosophila melanogaster and D. simulans for two common allozyme forms, as well as for several other less common variants. Parallel latitudinal clines in the frequencies of the common EST6-F and EST6-S allozymes in these species have previously been interpreted in terms of a shared amino acid polymorphism that distinguishes the two variants and is subject to selection. Here we compare the sequences of four D. simulans Est-6 isolates and show that overall estimates of nucleotide heterozygosity in both coding and 5' flanking regions are more than threefold higher than those obtained previously for this gene in D. melanogaster. Nevertheless, the ratio of replacement to exon silent-site polymorphism in D. simulans is less than the ratio of replacement to silent divergence between D. simulans and D. melanogaster, which could be the result of increased efficiency of selection against replacement polymorphisms in D. simulans or to divergent selection between the two species. We also find that the amino acid polymorphisms separating EST6- F and EST6-S in D. simulans are not the same as those that separate these allozymes in D. melanogaster, implying that the shared clines do not reflect shared molecular targets for selection. All comparisons within and between the two species reveal a remarkable paucity of variation in a stretch of nearly 400 bp immediately 5' of the gene, indicative of strong selective constraint to retain essential aspects of Est-6 promoter function.      

The distribution and evolutionary history of the PRP8 intein

Background  

We recently described a mini-intein in the PRP8 gene of a strain of the basidiomycete Cryptococcus neoformans, an important fungal pathogen of humans. This was the second described intein in the nuclear genome of any eukaryote; the first nuclear encoded intein was found in the VMA gene of several saccharomycete yeasts. The evolution of eukaryote inteins is not well understood. In this report we describe additional PRP8 inteins (bringing the total of these to over 20). We compare and contrast the phylogenetic distribution and evolutionary history of the PRP8 intein and the saccharomycete VMA intein, in order to derive a broader understanding of eukaryote intein evolution. It has been suggested that eukaryote inteins undergo horizontal transfer and the present analysis explores this proposal.     

Smoking and γ-Glutamyltransferase: Opposite Interactions with Alcohol Consumption and Body Mass Index

Background

Smoking has recently been suggested to synergistically interact with alcohol intake as a determinant of serum gamma-glutamyltransferase (γ-GT), an emergent powerful predictor of disease and mortality. This study investigated whether this also applies to higher smoking and alcohol exposure ranges and to body mass index (BMI), which likewise is strongly associated with γ-GT.

Methodology/Principal Findings

Analyses were based on occupational health examinations of more than 15,000 German male workers aged 16–64 years, predominantly from the construction industry. Sociodemographics and other health-related information were collected during the exam. Joint associations of smoking and alcohol consumption or BMI with elevated or log-transformed γ-GT were examined by tabulation and multiple adjusted regression models. Cigarette smoking exerted no effect on γ-GT in teetotalers, but there was a statistically significant effect of smoking among participants with higher alcohol consumption intensity, odds of elevated γ-GT being increased by 24% and 27% per additional 10 cigarettes smoked per day in subjects drinking 61–90 and >90 gram alcohol per day, respectively (P for interaction = 0.039). The interaction was opposite for BMI, where no association was seen in obese subjects, whereas odds of elevated γ-GT were increased by 24% per 10 cigarettes below 25 kg/m² (P for interaction = 0.040). This novel interaction was replicable in an independent cohort.

Conclusion

The evidence for opposite interactions of smoking with alcohol and BMI as determinants of serum γ-GT suggests that different physiological pathways are responsible for the associations between these factors.     

Helicobacter pylori infection and colorectal cancer risk: a meta-analysis

BACKGROUND: Several studies suggested an association between Helicobacter pylori infection and colorectal carcinoma or adenoma risk. However, different authors reported quite varying estimates. We carried out a systematic review and meta-analysis of published studies investigating this association and paid special attention to the possibility of publication bias and sources of heterogeneity between studies. Materials and METHODS: An extensive literature search and cross-referencing were performed to identify all published studies. Summary estimates were obtained using random-effects models. The presence of possible publication bias was assessed using different statistical approaches. RESULTS: In a meta-analysis of the 11 identified human studies, published between 1991 and 2002, a summary odds ratio of 1.4 (95% CI, 1.1-1.8) was estimated for the association between H. pylori infection and colorectal cancer risk. The graphical funnel plot appeared asymmetrical, but the formal statistical evaluations did not provide strong evidence of publication bias. The proportion of variation of study results because of heterogeneity was small (36.5%). CONCLUSIONS: The results of our meta-analysis are consistent with a possible small increase in risk of colorectal cancer because of H. pylori infection. However, the possibility of some publication bias cannot be ruled out, although it could not be statistically confirmed. Larger, better designed and better controlled studies are needed to clarify the situation.     

Contemporary epidemiology of gout in the UK general population

Introduction  

The objective of this study was to investigate the contemporary incidence of gout, examine potential risk factors, and evaluate specific gout treatment patterns in the general population.     

Objectively Measured Walking Duration and Sedentary Behaviour and Four-Year Mortality in Older People

BackgroundPhysical activity is an important component of health. Recommendations based on sensor measurements are sparse in older people. The aim of this study was to analyse the effect of objectively measured walking and sedentary duration on four-year mortality in community-dwelling older people.MethodsBetween March 2009 and April 2010, physical activity of 1271 participants (≥65 years, 56.4% men) from Southern Germany was measured over one week using a thigh-worn uni-axial accelerometer (activPAL; PAL Technologies, Glasgow, Scotland). Mortality was assessed during a four-year follow-up. Cox-proportional-hazards models were used to estimate the associations between walking (including low to high intensity) and sedentary duration with mortality. Models were adjusted for age and sex, additional epidemiological variables, and selected biomarkers.ResultsAn inverse relationship between walking duration and mortality with a minimum risk for the 3rd quartile (102.2 to128.4 minutes walking daily) was found even after multivariate adjustment with HRs for quartiles 2 to 4 compared to quartile 1 of 0.45 (95%-CI: 0.26; 0.76), 0.18 (95%-CI: 0.08; 0.41), 0.39 (95%-CI: 0.19; 0.78), respectively. For sedentary duration an age- and sex-adjusted increased mortality risk was observed for the 4th quartile (daily sedentary duration ≥1137.2 min.) (HR 2.05, 95%-CI: 1.13; 3.73), which diminished, however, after full adjustment (HR 1.63, 95%-CI: 0.88; 3.02). Furthermore, our results suggest effect modification between walking and sedentary duration, such that in people with low walking duration a high sedentary duration was noted as an independent factor for increased mortality.ConclusionsIn summary, walking duration was clearly associated with four-year overall mortality in community-dwelling older people.