Simple Shared Motifs (SSM) in conserved region of promoters: a new approach to identify co-regulation patterns

<p>Abstract</p> <p>Background</p> <p>Regulation of gene expression plays a pivotal role in cellular functions. However, understanding the dynamics of transcription remains a challenging task. A host of computational approaches have been developed to identify regulatory motifs, mainly based on the recognition of DNA sequences for transcription factor binding sites. Recent integration of additional data from genomic analyses or phylogenetic footprinting has significantly improved these methods.</p> <p>Results</p> <p>Here, we propose a different approach based on the compilation of Simple Shared Motifs (SSM), groups of sequences defined by their length and similarity and present in conserved sequences of gene promoters. We developed an original algorithm to search and count SSM in pairs of genes. An exceptional number of SSM is considered as a common regulatory pattern. The SSM approach is applied to a sample set of genes and validated using functional gene-set enrichment analyses. We demonstrate that the SSM approach selects genes that are over-represented in specific biological categories (Ontology and Pathways) and are enriched in co-expressed genes. Finally we show that genes co-expressed in the same tissue or involved in the same biological pathway have increased SSM values.</p> <p>Conclusions</p> <p>Using unbiased clustering of genes, Simple Shared Motifs analysis constitutes an original contribution to provide a clearer definition of expression networks.</p

A genome-wide association scan implicates <i>DCHS2, RUNX2, GLI3, PAX1</i> and <i>EDAR</i> in human facial variation

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values−8) at single-nucleotide polymorphisms (SNPs) in four genomic regions for three nose-related traits: columella inclination (4q31), nose bridge breadth (6p21) and nose wing breadth (7p13 and 20p11). In a subsample of ∼3,000 individuals we obtained quantitative traits related to 9 of the ordinal phenotypes and, also, a measure of nasion position. Quantitative analyses confirmed the ordinal-based associations, identified SNPs in 2q12 associated to chin protrusion, and replicated the reported association of nasion position with SNPs in PAX3. Strongest association in 2q12, 4q31, 6p21 and 7p13 was observed for SNPs in the EDAR, DCHS2, RUNX2 and GLI3 genes, respectively. Associated SNPs in 20p11 extend to PAX1. Consistent with the effect of EDAR on chin protrusion, we documented alterations of mandible length in mice with modified Edar function

ADAM9 is highly expressed in renal cell cancer and is associated with tumour progression

<p>Abstract</p> <p>Background</p> <p><b>A D</b>isintegrin <b>A</b>nd <b>M</b>etalloprotease (ADAM) 9 has been implicated in tumour progression of various solid tumours, however, little is known about its role in renal cell carcinoma. We evaluated the expression of ADAM9 on protein and transcript level in a clinico-pathologically characterized renal cell cancer cohort.</p> <p>Methods</p> <p>108 renal cancer cases were immunostained for ADAM9 on a tissue-micro-array. For 30 additional cases, ADAM9 mRNA of microdissected tumour and normal tissue was analyzed via quantitative RT-PCR. SPSS 14.0 was used to apply crosstables (Fisher's exact test and χ²-test), correlations and univariate as well as multivariate survival analyses.</p> <p>Results</p> <p>ADAM9 was significantly up-regulated in renal cancer in comparison to the adjacent normal tissue on mRNA level. On protein level, ADAM9 was significantly associated with higher tumour grade, positive nodal status and distant metastasis. Furthermore, ADAM9 protein expression was significantly associated with shortened patient survival in the univariate analysis.</p> <p>Conclusion</p> <p>ADAM9 is strongly expressed in a large proportion of renal cell cancers, concordant with findings in other tumour entities. Additionally, ADAM9 expression is significantly associated with markers of unfavourable prognosis. Whether the demonstrated prognostic value of ADAM9 is independent from other tumour parameters will have to be verified in larger study cohorts.</p

Effect of continuous versus intermittent subglottic suctioning on tracheal mucosa by the mallinckrodt taperguard evac oral tracheal tube in intensive care unit ventilated patients A prospective randomized study

International audienceBackground and Aims: A risk of tracheal mucosa injury induced by subglottic suctioning has been raised. Therefore, this prospective randomized study aims to compare the effect of continuous suctioning of subglottic secretions versus intermittent suctioning of subglottic secretions (CSSS vs. ISSS) secretions on tracheal mucosa in front of the suctioning port of the endotracheal tube.Patients and Methods: Patients requiring intubation or reintubation in Intensive Care Unit with an expected ventilation duration > 24 h were eligible. Participants received CSSS at -20 mmHg or ISSS at -100 mmHg during 15 s and no suction during 8 s. The effect on tracheal mucosa in front of the suction port was assessed after intubation (T0) and before extubation (T1) using bronchoscopy. Tracheal mucosa damages were graded into five categories (no injury, erythema, edema, ulceration, or necrosis). The occurrence (no injury observed at T0 but present at T1) or the worsening (injury observed at T0 exacerbating at T1) was studied.Results: Seventy-three patients were included and 53 patients (CSSS, n = 26 and ISSS, n = 27) were evaluable on the primary endpoint. The occurrence or worsening of tracheal mucosal damages did not differ between the two groups (CSSS, n = 7 [27%] vs. ISSS, n = 5 [17%], P = 0.465). Daily average volume of suctioned secretion was higher with ISSS (74 ± 100 ml vs. 20 ± 25 ml, P < 0.001). Impossibility to aspirate was higher with CSSS (0.14 ± 0.16 per day vs. 0.03 ± 0.07 per day, P < 0.001).Conclusions: Our results suggest that tracheal mucosal damages did not differ between CSSS and ISSS. The aspirated volume was higher and impossibility to aspirate was lower with ISSS.Clinical Trial Registration: ClinicalTrials.gov Identifier: NCT01555229

Expression of a disintegrin and metalloprotease (ADAM and ADAMTS) enzymes in human non-small-cell lung carcinomas (NSCLC)

A Disintegrin and Metalloprotease (ADAM) are transmembrane proteases displaying multiple functions. ADAM with ThromboSpondin-like motifs (ADAMTS) are secreted proteases characterised by thrombospondin (TS) motifs in their C-terminal domain. The aim of this work was to evaluate the expression pattern of ADAMs and ADAMTS in non small cell lung carcinomas (NSCLC) and to investigate the possible correlation between their expression and cancer progression. Reverse transcriptase-polymerase chain reaction (RT-PCR), Western blot and immunohistochemical analyses were performed on NSCLC samples and corresponding nondiseased tissue fragments. Among the ADAMs evaluated (ADAM-8, -9, -10, -12, -15, -17, ADAMTS-1, TS-2 and TS-12), a modulation of ADAM-12 and ADAMTS-1 mRNA expression was observed. Amounts of ADAM-12 mRNA transcripts were increased in tumour tissues as compared to the corresponding controls. In sharp contrast, ADAMTS-1 mRNA levels were significantly lower in tumour tissues when compared to corresponding nondiseased lung. These results were corroborated at the protein level by Western blot and immunohistochemistry. A positive correlation was observed between the mRNA levels of ADAM-12 and those of two vascular endothelial growth factor (VEGF)-A isoforms (VEGF-A(165) and VEGF-A(121)). Taken together, these results providing evidence for an overexpression of ADAM-12 and a lower expression of ADAMTS-1 in non-small-cell lung cancer suggest that these proteases play different functions in cancer progression

Recommandations pour la prescription et l’interprétation des examens biologiques utilisables dans le cadre du diagnostic ou du suivi des allergies, disponibles en France. Partie 1 : préambule

International audienc