A specific case in the classification of woods by FTIR and chemometric: discrimination of Fagales from Malpighiales

Fourier transform infrared (FTIR) spectroscopic data was used to classify wood samples from nine species within the Fagales and Malpighiales using a range of multivariate statistical methods. Taxonomic classification of the family Fagaceae and Betulaceae from Angiosperm Phylogenetic System Classification (APG II System) was successfully performed using supervised pattern recognition techniques. A methodology for wood sample discrimination was developed using both sapwood and heartwood samples. Ten and eight biomarkers emerged from the dataset to discriminate order and family, respectively. In the species studied FTIR in combination with multivariate analysis highlighted significant chemical differences in hemicelluloses, cellulose and guaiacyl (lignin) and shows promise as a suitable approach for wood sample classification

Large meta-analysis of multiple cancers reveals a common, compact and highly prognostic hypoxia metagene

BACKGROUND: There is a need to develop robust and clinically applicable gene expression signatures. Hypoxia is a key factor promoting solid tumour progression and resistance to therapy; a hypoxia signature has the potential to be not only prognostic but also to predict benefit from particular interventions. METHODS: An approach for deriving signatures that combine knowledge of gene function and analysis of in vivo co-expression patterns was used to define a common hypoxia signature from three head and neck and five breast cancer studies. Previously validated hypoxia-regulated genes (seeds) were used to generate hypoxia co-expression cancer networks. RESULTS: A common hypoxia signature, or metagene, was derived by selecting genes that were consistently co-expressed with the hypoxia seeds in multiple cancers. This was highly enriched for hypoxia-regulated pathways, and prognostic in multivariate analyses. Genes with the highest connectivity were also the most prognostic, and a reduced metagene consisting of a small number of top-ranked genes, including VEGFA, SLC2A1 and PGAM1, outperformed both a larger signature and reported signatures in independent data sets of head and neck, breast and lung cancers. CONCLUSION: Combined knowledge of multiple genes' function from in vitro experiments together with meta-analysis of multiple cancers can deliver compact and robust signatures suitable for clinical application

Spatial distribution of the risk of dengue fever in southeast Brazil, 2006-2007

Background: Many factors have been associated with circulation of the dengue fever virus and vector, although the dynamics of transmission are not yet fully understood. The aim of this work is to estimate the spatial distribution of the risk of dengue fever in an area of continuous dengue occurrence. Methods: This is a spatial population-based case-control study that analyzed 538 cases and 727 controls in one district of the municipality of Campinas, Sao Paulo, Brazil, from 2006-2007, considering socio-demographic, ecological, case severity, and household infestation variables. Information was collected by in-home interviews and inspection of living conditions in and around the homes studied. Cases were classified as mild or severe according to clinical data, and they were compared with controls through a multinomial logistic model. A generalized additive model was used in order to include space in a non-parametric fashion with cubic smoothing splines. Results: Variables associated with increased incidence of all dengue cases in the multiple binomial regression model were: higher larval density (odds ratio (OR) = 2.3 (95%CI: 2.0-2.7)), reports of mosquito bites during the day (OR = 1.8 (95%CI: 1.4-2.4)), the practice of water storage at home (OR = 2.5 (95%CI: 1.4, 4.3)), low frequency of garbage collection (OR = 2.6 (95%CI: 1.6-4.5)) and lack of basic sanitation (OR = 2.9 (95%CI: 1.8-4.9)). Staying at home during the day was protective against the disease (OR = 0.5 (95%CI: 0.3-0.6)). When cases were analyzed by categories (mild and severe) in the multinomial model, age and number of breeding sites more than 10 were significant only for the occurrence of severe cases (OR = 0.97, (95%CI: 0.96-0.99) and OR = 2.1 (95%CI: 1.2-3.5), respectively. Spatial distribution of risks of mild and severe dengue fever differed from each other in the 2006/2007 epidemic, in the study area. Conclusions: Age and presence of more than 10 breeding sites were significant only for severe cases. Other predictors of mild and severe cases were similar in the multiple models. The analyses of multinomial models and spatial distribution maps of dengue fever probabilities suggest an area-specific epidemic with varying clinical and demographic characteristics

Exhaustive prediction of disease susceptibility to coding base changes in the human genome

<p>Abstract</p> <p>Background</p> <p>Single Nucleotide Polymorphisms (SNPs) are the most abundant form of genomic variation and can cause phenotypic differences between individuals, including diseases. Bases are subject to various levels of selection pressure, reflected in their inter-species conservation.</p> <p>Results</p> <p>We propose a method that is not dependant on transcription information to score each coding base in the human genome reflecting the disease probability associated with its mutation. Twelve factors likely to be associated with disease alleles were chosen as the input for a support vector machine prediction algorithm. The analysis yielded 83% sensitivity and 84% specificity in segregating disease like alleles as found in the Human Gene Mutation Database from non-disease like alleles as found in the Database of Single Nucleotide Polymorphisms. This algorithm was subsequently applied to each base within all known human genes, exhaustively confirming that interspecies conservation is the strongest factor for disease association. For each gene, the length normalized average disease potential score was calculated. Out of the 30 genes with the highest scores, 21 are directly associated with a disease. In contrast, out of the 30 genes with the lowest scores, only one is associated with a disease as found in published literature. The results strongly suggest that the highest scoring genes are enriched for those that might contribute to disease, if mutated.</p> <p>Conclusion</p> <p>This method provides valuable information to researchers to identify sensitive positions in genes that have a high disease probability, enabling them to optimize experimental designs and interpret data emerging from genetic and epidemiological studies.</p

Satellite Cells Senescence in Limb Muscle of Severe Patients with COPD

Centre de recherche de l’Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada Rationale: The maintenance of peripheral muscle mass may be compromised in chronic obstructive pulmonary disease (COPD) due to premature cellular senescence and exhaustion of the regenerative potential of the muscles. Methods: Vastus lateralis biopsies were obtained from patients with COPD (n = 16) and healthy subjects (n = 7). Satellite cell number and the proportion of central nuclei, as a marker of muscle regenerative events, were assessed on cryosections. Telomere lengths, used as a marker of cellular senescence, were determined using Southern blot analyses. Results: Central nuclei proportion was significantly higher in patients with COPD with a preserved muscle mass compared to controls and patients with COPD with muscle atrophy (p,0.001). In COPD, maximal telomere length was significantly decreased compared to controls (p,0.05). Similarly, minimal telomere length was significantly reduced in GOLD III–IV patients with muscle atrophy compared to controls (p,0.005). Minimal, mean and maximum telomere lengths correlated with mid-thigh muscle cross-sectional area (MTCSA) (R = 0.523, p = 0.005; R = 0.435, p = 0.019 and R = 0.491, p = 0.009, respectively). Conclusions: Evidence of increased regenerative events was seen in GOLD III–IV patients with preserved muscle mass. Shortening of telomeres in GOLD III–IV patients with muscle atrophy is consistent with an increased number of senescen

Predicting Human Nucleosome Occupancy from Primary Sequence

Nucleosomes are the fundamental repeating unit of chromatin and comprise the structural building blocks of the living eukaryotic genome. Micrococcal nuclease (MNase) has long been used to delineate nucleosomal organization. Microarray-based nucleosome mapping experiments in yeast chromatin have revealed regularly-spaced translational phasing of nucleosomes. These data have been used to train computational models of sequence-directed nuclesosome positioning, which have identified ubiquitous strong intrinsic nucleosome positioning signals. Here, we successfully apply this approach to nucleosome positioning experiments from human chromatin. The predictions made by the human-trained and yeast-trained models are strongly correlated, suggesting a shared mechanism for sequence-based determination of nucleosome occupancy. In addition, we observed striking complementarity between classifiers trained on experimental data from weakly versus heavily digested MNase samples. In the former case, the resulting model accurately identifies nucleosome-forming sequences; in the latter, the classifier excels at identifying nucleosome-free regions. Using this model we are able to identify several characteristics of nucleosome-forming and nucleosome-disfavoring sequences. First, by combining results from each classifier applied de novo across the human ENCODE regions, the classifier reveals distinct sequence composition and periodicity features of nucleosome-forming and nucleosome-disfavoring sequences. Short runs of dinucleotide repeat appear as a hallmark of nucleosome-disfavoring sequences, while nucleosome-forming sequences contain short periodic runs of GC base pairs. Second, we show that nucleosome phasing is most frequently predicted flanking nucleosome-free regions. The results suggest that the major mechanism of nucleosome positioning in vivo is boundary-event-driven and affirm the classical statistical positioning theory of nucleosome organization

The Association of Antarctic Krill Euphausia superba with the Under-Ice Habitat

The association of Antarctic krill Euphausia superba with the under-ice habitat was investigated in the Lazarev Sea (Southern Ocean) during austral summer, autumn and winter. Data were obtained using novel Surface and Under Ice Trawls (SUIT), which sampled the 0–2 m surface layer both under sea ice and in open water. Average surface layer densities ranged between 0.8 individuals m−2 in summer and autumn, and 2.7 individuals m−2 in winter. In summer, under-ice densities of Antarctic krill were significantly higher than in open waters. In autumn, the opposite pattern was observed. Under winter sea ice, densities were often low, but repeatedly far exceeded summer and autumn maxima. Statistical models showed that during summer high densities of Antarctic krill in the 0–2 m layer were associated with high ice coverage and shallow mixed layer depths, among other factors. In autumn and winter, density was related to hydrographical parameters. Average under-ice densities from the 0–2 m layer were higher than corresponding values from the 0–200 m layer collected with Rectangular Midwater Trawls (RMT) in summer. In winter, under-ice densities far surpassed maximum 0–200 m densities on several occasions. This indicates that the importance of the ice-water interface layer may be under-estimated by the pelagic nets and sonars commonly used to estimate the population size of Antarctic krill for management purposes, due to their limited ability to sample this habitat. Our results provide evidence for an almost year-round association of Antarctic krill with the under-ice habitat, hundreds of kilometres into the ice-covered area of the Lazarev Sea. Local concentrations of postlarval Antarctic krill under winter sea ice suggest that sea ice biota are important for their winter survival. These findings emphasise the susceptibility of an ecological key species to changing sea ice habitats, suggesting potential ramifications on Antarctic ecosystems induced by climate change

A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level

<p>Abstract</p> <p>Background</p> <p>Serum creatinine (S_CR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in S_CRlevel is explicable by genetic factors.</p> <p>Methods</p> <p>We performed a meta-analysis of genome-wide association studies of S_CRundertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with S_CR(candidate loci) were replicated in two additional population-based samples ('replication cohorts').</p> <p>Results</p> <p>After the discovery meta-analysis, 29 loci were selected for replication. Association between S_CRlevel and polymorphisms in the collagen type XXII alpha 1 (<it>COL22A1</it>) gene, on chromosome 8, and in the synaptotagmin-1 (<it>SYT1</it>) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 × 10^-6and 1.7 × 10^-4, respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (<it>GABRR2</it>) gene and the ubiquitin-conjugating enzyme E2-J1 (<it>UBE2J1</it>) gene (replication p value = 3.6 × 10^-3). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (<it>UMOD</it>) gene and in the schroom family member 3 (<it>SCHROOM3</it>) gene were also replicated.</p> <p>Conclusions</p> <p>While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes <it>SYT1 </it>and <it>GABRR2 </it>corroborate previous findings that highlighted a possible role of the neurotransmitters GABA_Areceptors in the regulation of the glomerular basement membrane and a possible interaction between GABA_Areceptors and synaptotagmin-I at the podocyte level.</p

The Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort study: Assessment of environmental exposures

The Canadian Healthy Infant Longitudinal Development birth cohort was designed to elucidate interactions between environment and genetics underlying development of asthma and allergy. Over 3600 pregnant mothers were recruited from the general population in four provinces with diverse environments. The child is followed to age 5 years, with prospective characterization of diverse exposures during this critical period. Key exposure domains include indoor and outdoor air pollutants, inhalation, ingestion and dermal uptake of chemicals, mold, dampness, biological allergens, pets and pests, housing structure, and living behavior, together with infections, nutrition, psychosocial environment, and medications. Assessments of early life exposures are focused on those linked to inflammatory responses driven by the acquired and innate immune systems. Mothers complete extensive environmental questionnaires including time-activity behavior at recruitment and when the child is 3, 6, 12, 24, 30, 36, 48, and 60 months old. House dust collected during a thorough home assessment at 3–4 months, and biological specimens obtained for multiple exposure-related measurements, are archived for analyses. Geo-locations of homes and daycares and land-use regression for estimating traffic-related air pollution complement time-activity-behavior data to provide comprehensive individual exposure profiles. Several analytical frameworks are proposed to address the many interacting exposure variables and potential issues of co-linearity in this complex data set