Clustering protein sequences with a novel metric transformed from sequence similarity scores and sequence alignments with neural networks

BACKGROUND: The sequencing of the human genome has enabled us to access a comprehensive list of genes (both experimental and predicted) for further analysis. While a majority of the approximately 30000 known and predicted human coding genes are characterized and have been assigned at least one function, there remains a fair number of genes (about 12000) for which no annotation has been made. The recent sequencing of other genomes has provided us with a huge amount of auxiliary sequence data which could help in the characterization of the human genes. Clustering these sequences into families is one of the first steps to perform comparative studies across several genomes. RESULTS: Here we report a novel clustering algorithm (CLUGEN) that has been used to cluster sequences of experimentally verified and predicted proteins from all sequenced genomes using a novel distance metric which is a neural network score between a pair of protein sequences. This distance metric is based on the pairwise sequence similarity score and the similarity between their domain structures. The distance metric is the probability that a pair of protein sequences are of the same Interpro family/domain, which facilitates the modelling of transitive homology closure to detect remote homologues. The hierarchical average clustering method is applied with the new distance metric. CONCLUSION: Benchmarking studies of our algorithm versus those reported in the literature shows that our algorithm provides clustering results with lower false positive and false negative rates. The clustering algorithm is applied to cluster several eukaryotic genomes and several dozens of prokaryotic genomes

Combined endo-β-1,4-xylanase and α-L-arabinofuranosidase increases butyrate concentration during broiler cecal fermentation of maize glucurono-arabinoxylan

Solubilisation of prebiotic arabinoxylooligosaccharides from complex arabinoxylans in e.g. maize by xylanases may be increased by addition of auxiliary debranching enzymes. In this study, the hydrolysis and fermentation of maize fibre was investigated in vitro using a xylanase and an alpha-L-arabinofuranosidase. Combining the enzymes induced a higher (P < .001) xylose solubilisation and higher (P < .05) butyrate production during in vitro fermentation of maize fibre with cecal broiler inoculum compared to applying enzymes separately after 48 h. Subsequently, fibre degradation and fermentation was investigated in ROSS 308 broiler chickens supplemented with the enzyme combination to test the effects on gut morphology and microbiota composition along with performance. However, to address the relevance of combining the enzymes in vivo, further full factorial studies using individual enzymes at lower dosages are needed. Birds were fed a maize/soy based diet with 100 g/kg maize DDGS and 50 g/kg rapeseed meal. Enzymes supplementation increased (P < .001) body weight (+ 5.4%) and improved (P < .001) feed conversion ratio (-5.8%) after 29 days compared to control birds. Non-starch polysaccharide analysis and confocal microscopy of jejunum digesta visualised and confirmed solubilisation of the insoluble maize (glucurono)arabinoxylan. Birds receiving enzyme supplementation had increased (P < .001) duodenum villi length (+120 mu m) and reduced (P < .002) CD3 T-cell infiltration (-22.1%) after 29 days. Cecal butyrate levels were increased (P < .05) compared to controls. Although the microbiota composition was not significantly altered, numerical increases in cecal Ruminococcaceae and Lachnospiraceae genera were observed in birds supplemented with enzymes

Weapon injuries in the crusader mass graves from a 13th century attack on the port city of Sidon (Lebanon).

Archaeological excavations close to St Louis' castle in Sidon, Lebanon have revealed two mass grave deposits containing partially articulated and disarticulated human skeletal remains. A minimum of 25 male individuals have been recovered, with no females or young children. Radiocarbon dating of the human remains, a crusader coin, and the design of Frankish belt buckles strongly indicate they belong to a single event in the mid-13th century CE. The skeletal remains demonstrate a high prevalence of unhealed sharp force, penetrating force and blunt force trauma consistent with medieval weaponry. Higher numbers of wounds on the back of individuals than the front suggests some were attacked from behind, possibly as they fled. The concentration of blade wounds to the back of the neck of others would be compatible with execution by decapitation following their capture. Taphonomic changes indicate the skeletal remains were left exposed for some weeks prior to being collected together and re-deposited in the defensive ditch by a fortified gateway within the town wall. Charring on some bones provides evidence of burning of the bodies. The findings imply the systematic clearance of partially decomposed corpses following an attack on the city, where adult and teenage males died as a result of weapon related trauma. The skeletons date from the second half of the Crusader period, when Christian-held Sidon came under direct assault from both the Mamluk Sultanate (1253 CE) and the Ilkhanate Mongols (1260 CE). It is likely that those in the mass graves died during one of these assaults

Rural to Urban Migration and Changes in Cardiovascular risk Factors in Tanzania: A Prospective Cohort Study.

High levels of rural to urban migration are a feature of most African countries. Our aim was to investigate changes, and their determinants, in cardiovascular risk factors on rural to urban migration in Tanzania. Men and women (15 to 59 years) intending to migrate from Morogoro rural region to Dar es Salaam for at least 6 months were identified. Measurements were made at least one week but no more than one month prior to migration, and 1 to 3 monthly after migration. Outcome measures included body mass index, blood pressure, fasting lipids, and self reported physical activity and diet. One hundred and three men, 106 women, mean age 29 years, were recruited and 132 (63.2%) followed to 12 months. All the figures presented here refer to the difference between baseline and 12 months in these 132 individuals. Vigorous physical activity declined (79.4% to 26.5% in men, 37.8% to 15.6% in women, p < 0.001), and weight increased (2.30 kg men, 2.35 kg women, p < 0.001). Intake of red meat increased, but so did the intake of fresh fruit and vegetables. HDL cholesterol increased in men and women (0.24, 0.25 mmoll-1 respectively, p < 0.001); and in men, not women, total cholesterol increased (0.42 mmoll-1, p = 0.01), and triglycerides fell (0.31 mmoll-1, p = 0.034). Blood pressure appeared to fall in both men and women. For example, in men systolic blood pressure fell by 5.4 mmHg, p = 0.007, and in women by 8.6 mmHg, p = 0.001. The lower level of physical activity and increasing weight will increase the risk of diabetes and cardiovascular disease. However, changes in diet were mixed, and may have contributed to mixed changes in lipid profiles and a lack of rise in blood pressure. A better understanding of the changes occurring on rural to urban migration is needed to guide preventive measures

Genotoxic agents promote the nuclear accumulation of annexin A2: role of annexin A2 in mitigating DNA damage

Annexin A2 is an abundant cellular protein that is mainly localized in the cytoplasm and plasma membrane, however a small population has been found in the nucleus, suggesting a nuclear function for the protein. Annexin A2 possesses a nuclear export sequence (NES) and inhibition of the NES is sufficient to cause nuclear accumulation. Here we show that annexin A2 accumulates in the nucleus in response to genotoxic agents including gamma-radiation, UV radiation, etoposide and chromium VI and that this event is mediated by the nuclear export sequence of annexin A2. Nuclear accumulation of annexin A2 is blocked by the antioxidant agent N-acetyl cysteine (NAC) and stimulated by hydrogen peroxide (H2O2), suggesting that this is a reactive oxygen species dependent event. In response to genotoxic agents, cells depleted of annexin A2 show enhanced phospho-histone H2AX and p53 levels, increased numbers of p53-binding protein 1 nuclear foci and increased levels of nuclear 8-oxo-2'-deoxyguanine, suggesting that annexin A2 plays a role in protecting DNA from damage. This is the first report showing the nuclear translocation of annexin A2 in response to genotoxic agents and its role in mitigating DNA damage.Natural Sciences and Engineering Research Council of Canada (NSERC); European Union [PCOFUND-GA-2009-246542]; Foundation for Science and Technology of Portugal; Beatrice Hunter Cancer Research Institute; Terry Fox Foundationinfo:eu-repo/semantics/publishedVersio

Population-Level Benefits from Providing Effective HIV Prevention Means to Pregnant Women in High Prevalence Settings

Background:HIV prevalence among pregnant women in Southern Africa is extremely high. Epidemiological studies suggest that pregnancy increases the risk of HIV sexual acquisition and that HIV infections acquired during pregnancy carry higher risk of mother-to-child transmission (MTCT). We analyze the potential benefits from extending the availability of effective microbicide to pregnant women (in addition to non-pregnant women) in a wide-scale intervention.Methods and Findings:A transmission dynamic model was designed to assess the impact of microbicide use in high HIV prevalence settings and to estimate proportions of new HIV infections, infections acquired during pregnancy, and MTCT prevented over 10 years. Our analysis suggests that consistent use of microbicide with 70% efficacy by 60% of non-pregnant women may prevent approximately 40% and 15% of new infections in women and men respectively over 10 years, assuming no additional increase in HIV risk to either partner during pregnancy (RRHIV/preg = 1). It may also prevent 8-15% MTCT depending on the increase in MTCT risk when HIV is acquired during pregnancy compared to before pregnancy (RRMTCT/preg). Extending the microbicides use during pregnancy may improve the effectiveness of the intervention by 10% (RRHIV/preg = 1) to 25% (RRHIV/preg = 2) and reduce the number of HIV infections acquired during pregnancy by 40% to 70% in different scenarios. It may add between 6% (RRHIV/preg = 1, RRMTCT/preg = 1) and 25% (RRHIV/preg = 2, RRMTCT/preg = 4) to the reduction in the residual MTCT.Conclusion:Providing safe and effective microbicide to pregnant women in the context of wide-scale interventions would be desirable as it would increase the effectiveness of the intervention and significantly reduce the number of HIV infections acquired during pregnancy. The projected benefits from covering pregnant women by the HIV prevention programs is more substantial in communities in which the sexual risk during pregnancy is elevated. © 2013 Dimitrov et al

Methods for comprehensive chromosome screening of oocytes and embryos: capabilities, limitations, and evidence of validity

Preimplantation aneuploidy screening of cleavage stage embryos using fluorescence in situ hybridization (FISH) may no longer be considered the standard of care in reproductive medicine. Over the last few years, there has been considerable development of novel technologies for comprehensive chromosome screening (CCS) of the human genome. Among the notable methodologies that have been incorporated are whole genome amplification, metaphase and array based comparative genomic hybridization, single nucleotide polymorphism microarrays, and quantitative real-time PCR. As these methods become more integral to treating patients with infertility, it is critical that clinicians and scientists obtain a better understanding of their capabilities and limitations. This article will focus on reviewing these technologies and the evidence of their validity