Improved ability of biological and previous caries multimarkers to predict caries disease as revealed by multivariate PLS modelling

<p>Abstract</p> <p>Background</p> <p>Dental caries is a chronic disease with plaque bacteria, diet and saliva modifying disease activity. Here we have used the PLS method to evaluate a multiplicity of such biological variables (n = 88) for ability to predict caries in a cross-sectional (baseline caries) and prospective (2-year caries development) setting.</p> <p>Methods</p> <p>Multivariate PLS modelling was used to associate the many biological variables with caries recorded in thirty 14-year-old children by measuring the numbers of incipient and manifest caries lesions at all surfaces.</p> <p>Results</p> <p>A wide but shallow gliding scale of one fifth caries promoting or protecting, and four fifths non-influential, variables occurred. The influential markers behaved in the order of plaque bacteria > diet > saliva, with previously known plaque bacteria/diet markers and a set of new protective diet markers. A differential variable patterning appeared for new versus progressing lesions. The influential biological multimarkers (n = 18) predicted baseline caries better (ROC area 0.96) than five markers (0.92) and a single lactobacilli marker (0.7) with sensitivity/specificity of 1.87, 1.78 and 1.13 at 1/3 of the subjects diagnosed sick, respectively. Moreover, biological multimarkers (n = 18) explained 2-year caries increment slightly better than reported before but predicted it poorly (ROC area 0.76). By contrast, multimarkers based on previous caries predicted alone (ROC area 0.88), or together with biological multimarkers (0.94), increment well with a sensitivity/specificity of 1.74 at 1/3 of the subjects diagnosed sick.</p> <p>Conclusion</p> <p>Multimarkers behave better than single-to-five markers but future multimarker strategies will require systematic searches for improved saliva and plaque bacteria markers.</p

Characterization of globulin storage proteins of a low prolamin cereal species in relation to celiac disease

Brachypodium distachyon, a small annual grass with seed storage globulins as primary protein reserves was used in our study to analyse the toxic nature of non-prolamin seed storage proteins related to celiac disease. The main storage proteins of B. distachyon are the 7S globulin type proteins and the 11S, 12S seed storage globulins similar to oat and rice. Immunoblot analyses using serum samples from celiac disease patients were carried out followed by the identification of immune-responsive proteins using mass spectrometry. Serum samples from celiac patients on a gluten-free diet, from patients with Crohn's disease and healthy subjects, were used as controls. The identified proteins with intense serum-IgA reactivity belong to the 7S and 11-12S seed globulin family. Structure prediction and epitope predictions analyses confirmed the presence of celiac disease-related linear B cell epitope homologs and the presence of peptide regions with strong HLA-DQ8 and DQ2 binding capabilities. These results highlight that both MHC-II presentation and B cell response may be developed not only to prolamins but also to seed storage globulins. This is the first study of the non-prolamin type seed storage proteins of Brachypodium from the aspect of the celiac disease

An Evolutionarily Conserved Arginine Is Essential for Tre1 G Protein-Coupled Receptor Function During Germ Cell Migration in Drosophila melanogaster

BACKGROUND: G protein-coupled receptors (GPCRs) play central roles in mediating cellular responses to environmental signals leading to changes in cell physiology and behaviors, including cell migration. Numerous clinical pathologies including metastasis, an invasive form of cell migration, have been linked to abnormal GPCR signaling. While the structures of some GPCRs have been defined, the in vivo roles of conserved amino acid residues and their relationships to receptor function are not fully understood. Trapped in endoderm 1 (Tre1) is an orphan receptor of the rhodopsin class that is necessary for primordial germ cell migration in Drosophila melanogaster embryos. In this study, we employ molecular genetic approaches to identify residues in Tre1 that are critical to its functions in germ cell migration. METHODOLOGY/PRINCIPAL FINDINGS: First, we show that the previously reported scattershot mutation is an allele of tre1. The scattershot allele results in an in-frame deletion of 8 amino acids at the junction of the third transmembrane domain and the second intracellular loop of Tre1 that dramatically impairs the function of this GPCR in germ cell migration. To further refine the molecular basis for this phenotype, we assayed the effects of single amino acid substitutions in transgenic animals and determined that the arginine within the evolutionarily conserved E/N/DRY motif is critical for receptor function in mediating germ cell migration within an intact developing embryo. CONCLUSIONS/SIGNIFICANCE: These structure-function studies of GPCR signaling in native contexts will inform future studies into the basic biology of this large and clinically important family of receptors

SpiroESTdb: a transcriptome database and online tool for sparganum expressed sequences tags

<p>Abstract</p> <p>Background</p> <p>Sparganum (plerocercoid of <it>Spirometra erinacei</it>) is a parasite that possesses the remarkable ability to survive by successfully modifying its physiology and morphology to suit various hosts and can be found in various tissues, even the nervous system. However, surprisingly little is known about the molecular function of genes that are expressed during the course of the parasite life cycle. To begin to decipher the molecular processes underlying gene function, we constructed a database of expressed sequence tags (ESTs) generated from sparganum.</p> <p>Findings</p> <p>SpiroESTdb is a web-based information resource that is built upon the annotation and curation of 5,655 ESTs data. SpiroESTdb provides an integrated platform for expressed sequence data, expression dynamics, functional genes, genetic markers including single nucleotide polymorphisms and tandem repeats, gene ontology and KEGG pathway information. Moreover, SpiroESTdb supports easy access to gene pages, such as (i) curation and query forms, (ii) <it>in </it><it>silico </it>expression profiling and (iii) BLAST search tools. Comprehensive descriptions of the sparganum content of all sequenced data are available, including summary reports. The contents of SpiroESTdb can be viewed and downloaded from the web (<url>http://pathod.cdc.go.kr/spiroestdb</url>).</p> <p>Conclusions</p> <p>This integrative web-based database of sequence data, functional annotations and expression profiling data will serve as a useful tool to help understand and expand the characterization of parasitic infections. It can also be used to identify potential industrial drug targets and vaccine candidate genes.</p

Assessment of clusters of transcription factor binding sites in relationship to human promoter, CpG islands and gene expression

BACKGROUND: Gene expression is regulated mainly by transcription factors (TFs) that interact with regulatory cis-elements on DNA sequences. To identify functional regulatory elements, computer searching can predict TF binding sites (TFBS) using position weight matrices (PWMs) that represent positional base frequencies of collected experimentally determined TFBS. A disadvantage of this approach is the large output of results for genomic DNA. One strategy to identify genuine TFBS is to utilize local concentrations of predicted TFBS. It is unclear whether there is a general tendency for TFBS to cluster at promoter regions, although this is the case for certain TFBS. Also unclear is the identification of TFs that have TFBS concentrated in promoters and to what level this occurs. This study hopes to answer some of these questions. RESULTS: We developed the cluster score measure to evaluate the correlation between predicted TFBS clusters and promoter sequences for each PWM. Non-promoter sequences were used as a control. Using the cluster score, we identified a PWM group called PWM-PCP, in which TFBS clusters positively correlate with promoters, and another PWM group called PWM-NCP, in which TFBS clusters negatively correlate with promoters. The PWM-PCP group comprises 47% of the 199 vertebrate PWMs, while the PWM-NCP group occupied 11 percent. After reducing the effect of CpG islands (CGI) against the clusters using partial correlation coefficients among three properties (promoter, CGI and predicted TFBS cluster), we identified two PWM groups including those strongly correlated with CGI and those not correlated with CGI. CONCLUSION: Not all PWMs predict TFBS correlated with human promoter sequences. Two main PWM groups were identified: (1) those that show TFBS clustered in promoters associated with CGI, and (2) those that show TFBS clustered in promoters independent of CGI. Assessment of PWM matches will allow more positive interpretation of TFBS in regulatory regions

Awareness and acceptability of human papillomavirus vaccine: an application of the instrumental variables bivariate probit model

<p>Abstract</p> <p>Background</p> <p>Although lower uptake rates of the human papillomavirus (HPV) vaccine among socioeconomically disadvantaged populations have been documented, less is known about the relationships between awareness and acceptability, and other factors affecting HPV vaccine uptake.</p> <p>The current study aimed to estimate the potential effectiveness of increased HPV vaccine awareness on the acceptability of HPV vaccination in a nationally representative sample of women, using a methodology that controlled for potential non-random selection.</p> <p>Methods</p> <p>This study used a population-based sample from the 2007 Health Information National Trends Survey, a cross-sectional study of the US population aged 18 years or older, and focused on the subsample of 742 women who have any female children under the age of 18 years in the household. An instrumental variables bivariate probit model was used to jointly estimate HPV vaccine awareness and acceptability.</p> <p>Results</p> <p>The proportion of HPV vaccine acceptability among the previously aware and non-aware groups was 58% and 47%, respectively. Results from the instrumental variables bivariate probit model showed that the estimated marginal effect of awareness on acceptability was 46 percentage points, an effect that was even greater than observed.</p> <p>Conclusions</p> <p>Among populations who are not currently aware of the HPV vaccine, the potential impact of raising awareness on acceptability of HPV vaccination is substantial. This finding provides additional support to strengthening public health programs that increase awareness and policy efforts that address barriers to HPV vaccination.</p

Comprehensive Survey of SNPs in the Affymetrix Exon Array Using the 1000 Genomes Dataset

Microarray gene expression data has been used in genome-wide association studies to allow researchers to study gene regulation as well as other complex phenotypes including disease risks and drug response. To reach scientifically sound conclusions from these studies, however, it is necessary to get reliable summarization of gene expression intensities. Among various factors that could affect expression profiling using a microarray platform, single nucleotide polymorphisms (SNPs) in target mRNA may lead to reduced signal intensity measurements and result in spurious results. The recently released 1000 Genomes Project dataset provides an opportunity to evaluate the distribution of both known and novel SNPs in the International HapMap Project lymphoblastoid cell lines (LCLs). We mapped the 1000 Genomes Project genotypic data to the Affymetrix GeneChip Human Exon 1.0ST array (exon array), which had been used in our previous studies and for which gene expression data had been made publicly available. We also evaluated the potential impact of these SNPs on the differentially spliced probesets we had identified previously. Though the 1000 Genomes Project data allowed a comprehensive survey of the SNPs in this particular array, the same approach can certainly be applied to other microarray platforms. Furthermore, we present a detailed catalogue of SNP-containing probesets (exon-level) and transcript clusters (gene-level), which can be considered in evaluating findings using the exon array as well as benefit the design of follow-up experiments and data re-analysis

CyclinPred: A SVM-Based Method for Predicting Cyclin Protein Sequences

Functional annotation of protein sequences with low similarity to well characterized protein sequences is a major challenge of computational biology in the post genomic era. The cyclin protein family is once such important family of proteins which consists of sequences with low sequence similarity making discovery of novel cyclins and establishing orthologous relationships amongst the cyclins, a difficult task. The currently identified cyclin motifs and cyclin associated domains do not represent all of the identified and characterized cyclin sequences. We describe a Support Vector Machine (SVM) based classifier, CyclinPred, which can predict cyclin sequences with high efficiency. The SVM classifier was trained with features of selected cyclin and non cyclin protein sequences. The training features of the protein sequences include amino acid composition, dipeptide composition, secondary structure composition and PSI-BLAST generated Position Specific Scoring Matrix (PSSM) profiles. Results obtained from Leave-One-Out cross validation or jackknife test, self consistency and holdout tests prove that the SVM classifier trained with features of PSSM profile was more accurate than the classifiers based on either of the other features alone or hybrids of these features. A cyclin prediction server- CyclinPred has been setup based on SVM model trained with PSSM profiles. CyclinPred prediction results prove that the method may be used as a cyclin prediction tool, complementing conventional cyclin prediction methods

Molecular and cellular mechanisms underlying the evolution of form and function in the amniote jaw.

The amniote jaw complex is a remarkable amalgamation of derivatives from distinct embryonic cell lineages. During development, the cells in these lineages experience concerted movements, migrations, and signaling interactions that take them from their initial origins to their final destinations and imbue their derivatives with aspects of form including their axial orientation, anatomical identity, size, and shape. Perturbations along the way can produce defects and disease, but also generate the variation necessary for jaw evolution and adaptation. We focus on molecular and cellular mechanisms that regulate form in the amniote jaw complex, and that enable structural and functional integration. Special emphasis is placed on the role of cranial neural crest mesenchyme (NCM) during the species-specific patterning of bone, cartilage, tendon, muscle, and other jaw tissues. We also address the effects of biomechanical forces during jaw development and discuss ways in which certain molecular and cellular responses add adaptive and evolutionary plasticity to jaw morphology. Overall, we highlight how variation in molecular and cellular programs can promote the phenomenal diversity and functional morphology achieved during amniote jaw evolution or lead to the range of jaw defects and disease that affect the human condition

Corrigendum: An ethnically relevant consensus Korean reference genome is a step towards personal reference genomes.

This corrects the article DOI: 10.1038/ncomms13637