CFTR p.Arg117His associated with CBAVD and other CFTR-related disorders.

Background: The high frequency of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene mutation p.Arg117His in patients with congenital bilateral absence of the vas deferens (CBAVD) and in newborns screened for CF has created a dilemma.

Methods: Phenotypic and genotypic data were retrospectively collected in 179 non-newborn French individuals carrying p.

Bridging neuroscience and clinical psychology: cognitive behavioral and psychophysiological models in the evaluation and treatment of Gilles de la Tourette syndrome.

Cognitive neuroscience and clinical psychology have long been considered to be separate disciplines. However, the phenomenon of brain plasticity in the context of a psychological intervention highlights the mechanisms of brain compensation and requires linking both clinical cognition and cognitive psychophysiology. A quantifiable normalization of brain activity seems to be correlated with an improvement of the tic symptoms after cognitive behavioral therapy in patients with Gilles de la Tourette syndrome (GTS).

Role of the Salmonella enterica serovar Typhi Fur regulator and small RNAs RfrA and RfrB in iron homeostasis and interaction with host cells.

Iron is an essential element but can be toxic at high concentrations. Therefore, its acquisition and storage require tight control. Salmonella encodes the global regulator Fur (ferric uptake regulator) and the small regulatory non-coding RNAs (sRNAs) RfrA and RfrB, homologues of RyhB.

Lysozyme transport in p-HEMA hydrogel contact lenses.

Protein binding in hydrogels adversely affects their performance and can interfere with their usage in several biomedical applications including contact lenses. In this study we focus on understanding and modeling the mechanisms of protein transport in hydrogels, specifically focusing on the effect of protein concentration and gel crosslinking on transport. Specifically, we focus on lysozyme, the most abundant protein in tear fluid, and hydrogels of poly-hydroxyethyl methacrylate (p-HEMA), a common contact lens material.

Xenobiotic metabolism and disposition in human lung cell models: comparison with in vivo expression profiles.

Numerous lung cell lines are currently used as in vitro models for pharmacological and toxicological studies. However, no exhaustive report about the metabolic capacities of these models in comparison with those of lung tissues is available. In the present study, we used a high-throughput quantitative real-time reverse transcription-polymerase chain reaction strategy to characterize the expression profiles of 380 genes encoding proteins involved in the metabolism and disposition of xenobiotics in 10 commonly used lung cell lines (A549, H292, H358, H460, H727, Calu-1, 16HBE, 1 HAEO, BEAS-2B, and L-132) and four primary cultures of human bronchial epithelial cells.

Genome-wide somatic copy number alterations in low-grade PanINs and IPMNs from individuals with a family history of pancreatic cancer.

Purpose: Characterizing the earliest chromosomal alterations of pancreatic precursor neoplasms from individuals with a familial aggregation of pancreatic cancer may provide clues as to the loci of pancreatic cancer susceptibility genes.

Experimental Design: We used Illumina 370/660K SNP arrays to conduct genome-wide copy number analysis in 60 benign neoplasms [58 mostly low-grade pancreatic intraepithelial neoplasias (PanIN) and intraductal papillary mucinous neoplasms (IPMN) and two pancreatic neuroendocrine tumors (PNET)] and matched normal tissues from 16 individuals with a family history of pancreatic cancer. PanINs and IPMNs were analyzed for KRAS codon 12/13 mutations.

Genomic analysis of immune response against Vibrio cholerae hemolysin in Caenorhabditis elegans.

Vibrio cholerae cytolysin (VCC) is among the accessory V. cholerae virulence factors that may contribute to disease pathogenesis in humans. VCC, encoded by hlyA gene, belongs to the most common class of bacterial toxins, known as pore-forming toxins (PFTs).

Inactivation of AMPKα1 induces asthenozoospermia and alters spermatozoa morphology.

AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis, is present in metabolic tissues (muscle and liver) and has been identified as a modulator of the female reproductive functions. However, its function in the testis has not yet been clearly defined. We have investigated the potential role of AMPK in male reproduction by using transgenic mice lacking the activity of AMPK catalytic subunit α1 gene [α1AMPK knockout (KO)].

Can we predict a difficult intubation in cleft lip/palate patients?

Objective: To find predictors of a difficult intubation in infants with an isolated or a syndromic cleft lip/palate.

Study Design: Retrospective review: single-blind trial.

Settings: Tertiary care centre.

Radon measurement in schools located in three priority investigation areas in the province of Quebec, Canada.

The purpose of this study was to measure radon concentration in public primary schools located in priority investigation areas, with the aim of decreasing occupants' exposure to radon in public buildings where concentrations exceed the Canadian Federal guidelines (i.e. 200 Bq m(-3)).

Discovery of potent and liver-targeted stearoyl-CoA desaturase (SCD) inhibitors in a bispyrrolidine series.

Inhibition of stearoyl-CoA desaturase (SCD) activity represents a potential novel mechanism for the treatment of metabolic disorders including obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed SCD inhibitors, our research efforts have been focused on the search for new and structurally diverse liver-targeted SCD inhibitors. This work has led to the discovery of novel, potent and structurally diverse liver-targeted bispyrrolidine SCD inhibitors.

Genomic anatomy of Escherichia coli O157:H7 outbreaks.

The rapid emergence of Escherichia coli O157:H7 from an unknown strain in 1982 to the dominant hemorrhagic E. coli serotype in the United States and the cause of widespread outbreaks of human food-borne illness highlights a need to evaluate critically the extent to which genomic plasticity of this important enteric pathogen contributes to its pathogenic potential and its evolution as well as its adaptation in different ecological niches. Aimed at a better understanding of the evolution of the E.

Cellular and molecular mechanisms of metformin: an overview.

Considerable efforts have been made since the 1950s to better understand the cellular and molecular mechanisms of action of metformin, a potent antihyperglycaemic agent now recommended as the first-line oral therapy for T2D (Type 2 diabetes). The main effect of this drug from the biguanide family is to acutely decrease hepatic glucose production, mostly through a mild and transient inhibition of the mitochondrial respiratory chain complex I. In addition, the resulting decrease in hepatic energy status activates AMPK (AMP-activated protein kinase), a cellular metabolic sensor, providing a generally accepted mechanism for the action of metformin on hepatic gluconeogenesis.

Discovery of potent and liver-selective stearoyl-CoA desaturase (SCD) inhibitors in an acyclic linker series.

Elevated levels of stearoyl-CoA desaturase (SCD) activity have been implicated in metabolic disorders such as obesity and type II diabetes. To circumvent skin and eye adverse events observed in rodents with systemically-distributed inhibitors, our research efforts have been focused on the search for new liver-targeting compounds. This work has led to the discovery of novel, potent and liver-selective acyclic linker SCD inhibitors.

Accumulation of Cu, Pb, Ni and Zn in the halophyte plant Atriplex grown on polluted soil.

Background: Three annual Atriplex species-A. hortensis var. purpurea, A.

Conversion of systemically-distributed triazole-based stearoyl-CoA desaturase (SCD) uHTS hits into liver-targeted SCD inhibitors.

It has been demonstrated that once-a-day dosing of systemically-distributed SCD inhibitors leads to adverse events in eye and skin. Herein, we describe our efforts to convert a novel class of systemically-distributed potent triazole-based uHTS hits into liver-targeted SCD inhibitors as a means to circumvent chronic toxicity.

Structure and pH-induced alterations of recombinant and natural spider silk proteins in solution.

The spinning process of spiders can modulate the mechanical properties of their silk fibers. It is therefore of primary importance to understand what are the key elements of the spider spinning process to develop efficient industrial spinning processes. We have exhaustively investigated the native conformation of major ampullate silk (MaS) proteins by comparing the content of the major ampullate gland of Nephila clavipes, solubilized MaS (SolMaS) fibers and the recombinant proteins rMaSpI and rMaSpII using (1) H solution NMR spectroscopy.

Uncertainty forecasts improve weather-related decisions and attenuate the effects of forecast error.

Although uncertainty is inherent in weather forecasts, explicit numeric uncertainty estimates are rarely included in public forecasts for fear that they will be misunderstood. Of particular concern are situations in which precautionary action is required at low probabilities, often the case with severe events. At present, a categorical weather warning system is used.

Bicyclic heteroaryl inhibitors of stearoyl-CoA desaturase: from systemic to liver-targeting inhibitors.

Optimization of a lead thiazole amide MF-152 led to the identification of potent bicyclic heteroaryl SCD1 inhibitors with good mouse pharmacokinetic profiles. In a view to target the liver for efficacy and to avoid SCD1 inhibition in the skin and eyes where adverse effects were previously observed in rodents, representative systemically-distributed SCD1 inhibitors were converted into liver-targeting SCD1 inhibitors.

Antagonistic control of muscle cell size by AMPK and mTORC1.

Nutrition and physical activity have profound effects on skeletal muscle metabolism and growth. Regulation of muscle mass depends on a thin balance between growth-promoting and growth-suppressing factors. Over the past decade, the mammalian target of rapamycin (mTOR) kinase has emerged as an essential factor for muscle growth by mediating the anabolic response to nutrients, insulin, insulin-like growth factors and resistance exercise.

Investigating the global genomic diversity of Escherichia coli using a multi-genome DNA microarray platform with novel gene prediction strategies.

Background: The gene content of a diverse group of 183 unique Escherichia coli and Shigella isolates was determined using the Affymetrix GeneChip® E. coli Genome 2.0 Array, originally designed for transcriptome analysis, as a genotyping tool.

A community-based clinical trial of Intra-Venous zOledRonic acid once Yearly in comparison to oral bisphosphonates in postmenopausal women with osteoporosis: the IVORY trial Methodological considerations.

Background: Zoledronic acid is an intravenous once yearly bisphosphonate that has been shown to be effective and safe in improving BMD (bone mineral density) and reducing fracture risk in controlled clinical trials. IVORY is a Canadian post marketing study aiming at assessing real-life effectiveness, health care resource utilization, safety and compliance to treatment with zoledronic acid in comparison to orally administered bisphosphonates (OBP).

Methods: IVORY is a prospective two cohort observational study of patients treated with zoledronic acid or OBP.