Showing papers by "Laval University published in 2006"

The human obesity gene map: the 2005 update.

Abstract: This paper presents the 12th update of the human obesity gene map, which incorporates published results up to the end of October 2005. Evidence from single-gene mutation obesity cases, Mendelian disorders exhibiting obesity as a clinical feature, transgenic and knockout murine models relevant to obesity, quantitative trait loci (QTL) from animal cross-breeding experiments, association studies with candidate genes, and linkages from genome scans is reviewed. As of October 2005, 176 human obesity cases due to single-gene mutations in 11 different genes have been reported, 50 loci related to Mendelian syndromes relevant to human obesity have been mapped to a genomic region, and causal genes or strong candidates have been identified for most of these syndromes. There are 244 genes that, when mutated or expressed as transgenes in the mouse, result in phenotypes that affect body weight and adiposity. The number of QTLs reported from animal models currently reaches 408. The number of human obesity QTLs derived from genome scans continues to grow, and we now have 253 QTLs for obesity-related phenotypes from 61 genome-wide scans. A total of 52 genomic regions harbor QTLs supported by two or more studies. The number of studies reporting associations between DNA sequence variation in specific genes and obesity phenotypes has also increased considerably, with 426 findings of positive associations with 127 candidate genes. A promising observation is that 22 genes are each supported by at least five positive studies. The obesity gene map shows putative loci on all chromosomes except Y. The electronic version of the map with links to useful publications and relevant sites can be found at http://obesitygene.pbrc.edu.

Psychological and behavioral treatment of insomnia:update of the recent evidence (1998-2004).

Abstract: Background Recognition that psychological and behavioral factors play an important role in insomnia has led to increased interest in therapies targeting these factors. A review paper published in 1999 summarized the evidence regarding the efficacy of psychological and behavioral treatments for persistent insomnia. The present review provides an update of the evidence published since the original paper. As with the original paper, this review was conducted by a task force commissioned by the American Academy of Sleep Medicine in order to update its practice parameters on psychological and behavioral therapies for insomnia. Methods A systematic review was conducted on 37 treatment studies (N = 2246 subjects/patients) published between 1998 and 2004 inclusively and identified through Psyclnfo and Medline searches. Each study was systematically reviewed with a standard coding sheet and the following information was extracted: Study design, sample (number of participants, age, gender), diagnosis, type of treatments and controls, primary and secondary outcome measures, and main findings. Criteria for inclusion of a study were as follows: (a) the main sleep diagnosis was insomnia (primary or comorbid), (b) at least 1 treatment condition was psychological or behavioral in content, (c) the study design was a randomized controlled trial, a nonrandomized group design, a clinical case series or a single subject experimental design with a minimum of 10 subjects, and (d) the study included at least 1 of the following as dependent variables: sleep onset latency, number and/or duration of awakenings, total sleep time, sleep efficiency, or sleep quality. Results Psychological and behavioral therapies produced reliable changes in several sleep parameters of individuals with either primary insomnia or insomnia associated with medical and psychiatric disorders. Nine studies documented the benefits of insomnia treatment in older adults or for facilitating discontinuation of medication among chronic hypnotic users. Sleep improvements achieved with treatment were well sustained over time; however, with the exception of reduced psychological symptoms/ distress, there was limited evidence that improved sleep led to clinically meaningful changes in other indices of morbidity (e.g., daytime fatigue). Five treatments met criteria for empirically-supported psychological treatments for insomnia: Stimulus control therapy, relaxation, paradoxical intention, sleep restriction, and cognitive-behavior therapy. Discussion These updated findings provide additional evidence in support of the original review's conclusions as to the efficacy and generalizability of psychological and behavioral therapies for persistent insomnia. Nonetheless, further research is needed to develop therapies that would optimize outcomes and reduce morbidity, as would studies of treatment mechanisms, mediators, and moderators of outcomes. Effectiveness studies are also needed to validate those therapies when implemented in clinical settings (primary care), by non-sleep specialists. There is also a need to disseminate more effectively the available evidence in support of psychological and behavioral interventions to health-care practitioners working on the front line.

Food protein-based materials as nutraceutical delivery systems

Abstract: Incorporation of bioactive compounds–such as vitamins, probiotics, bioactive peptides, and antioxidants etc.–into food systems provide a simple way to develop novel functional foods that may have physiological benefits or reduce the risks of diseases. As a vital macronutrient in food, proteins possess unique functional properties including their ability to form gels and emulsions, which allow them to be an ideal material for the encapsulation of bioactive compounds. Based on the knowledge of protein physical–chemistry properties, this review describes the potential role of food proteins as substrate for the development of nutraceutical delivery systems in the form of hydrogel, micro-, or nano- particles. Applications of these food protein matrices to protect and delivery-sensitive nutraceutical compounds are illustrated, and the impacts of particle size on release properties are emphasized.

Management control systems and strategy: A resource-based perspective

Abstract: The aim of this study is to examine, from a resource-based perspective, the relationships between the use of management control systems (MCS) and organizational capabilities. More specifically, the study focuses on the diagnostic and interactive uses of one important aspect of MCS, namely performance measurement systems (PMS), and four capabilities leading to strategic choices (i.e., market orientation, entrepreneurship, innovativeness, and organizational learning). Three research questions are investigated in this study: (i) to what extent do the diagnostic and interactive uses of MCS contribute specifically to the creation and maintenance of capabilities leading to strategic choices? (ii) To what extent do the diagnostic and interactive uses of MCS act in combination to produce dynamic tension which contributes to the creation and maintenance of these capabilities? (iii) To what extent does the use of MCS contribute to organizational performance? The results suggest that an interactive use of PMS fosters the four capabilities by focusing organizational attention on strategic priorities and stimulating dialogue. Also, by creating constraints to ensure compliance with orders, the diagnostic use of PMS exerts negative pressure on these capabilities. Furthermore, some evidence suggests the influence of dynamic tension resulting from the balanced use of PMS in a diagnostic and interactive fashion on capabilities and performance.

Recommendations for a standard research assessment of insomnia.

Abstract: Study objectives To present expert consensus recommendations for a standard set of research assessments in insomnia, reporting standards for these assessments, and recommendations for future research. Participants N/A. Interventions N/A. Methods and results An expert panel of 25 researchers reviewed the available literature on insomnia research assessments. Preliminary recommendations were reviewed and discussed at a meeting on March 10-11, 2005. These recommendations were further refined during writing of the current paper. The resulting key recommendations for standard research assessment of insomnia disorders include definitions/diagnosis of insomnia and comorbid conditions; measures of sleep and insomnia, including qualitative insomnia measures, diary, polysomnography, and actigraphy; and measures of the waking correlates and consequences of insomnia disorders, such as fatigue, sleepiness, mood, performance, and quality of life. Conclusions Adoption of a standard research assessment of insomnia disorders will facilitate comparisons among different studies and advance the state of knowledge. These recommendations are not intended to be static but must be periodically revised to accommodate further developments and evidence in the field.

ING2 PHD domain links histone H3 lysine 4 methylation to active gene repression

Abstract: Dynamic regulation of diverse nuclear processes is intimately linked to covalent modifications of chromatin. Much attention has focused on methylation at lysine 4 of histone H3 (H3K4), owing to its association with euchromatic genomic regions. H3K4 can be mono-, di- or tri-methylated. Trimethylated H3K4 (H3K4me3) is preferentially detected at active genes, and is proposed to promote gene expression through recognition by transcription-activating effector molecules. Here we identify a novel class of methylated H3K4 effector domains--the PHD domains of the ING (for inhibitor of growth) family of tumour suppressor proteins. The ING PHD domains are specific and highly robust binding modules for H3K4me3 and H3K4me2. ING2, a native subunit of a repressive mSin3a-HDAC1 histone deacetylase complex, binds with high affinity to the trimethylated species. In response to DNA damage, recognition of H3K4me3 by the ING2 PHD domain stabilizes the mSin3a-HDAC1 complex at the promoters of proliferation genes. This pathway constitutes a new mechanism by which H3K4me3 functions in active gene repression. Furthermore, ING2 modulates cellular responses to genotoxic insults, and these functions are critically dependent on ING2 interaction with H3K4me3. Together, our findings establish a pivotal role for trimethylation of H3K4 in gene repression and, potentially, tumour suppressor mechanisms.

The E-NTPDase family of ectonucleotidases: Structure function relationships and pathophysiological significance

Abstract: Ectonucleotidases are ectoenzymes that hydrolyze extracellular nucleotides to the respective nucleosides. Within the past decade, ectonucleotidases belonging to several enzyme families have been discovered, cloned and characterized. In this article, we specifically address the cell surface-located members of the ecto-nucleoside triphosphate diphosphohydrolase (E-NTPDase/CD39) family (NTPDase1,2,3, and 8). The molecular identification of individual NTPDase subtypes, genetic engineering, mutational analyses, and the generation of subtype-specific antibodies have resulted in considerable insights into enzyme structure and function. These advances also allow definition of physiological and patho-physiological implications of NTPDases in a considerable variety of tissues. Biological actions of NTPDases are a consequence (at least in part) of the regulated phosphohydrolytic activity on extracellular nucleotides and consequent effects on P2-receptor signaling. It further appears that the spatial and temporal expression of NTPDases by various cell types within the vasculature, the nervous tissues and other tissues impacts on several patho-physiological processes. Examples include acute effects on cellular metabolism, adhesion, activation and migration with other protracted impacts upon developmental responses, inclusive of cellular proliferation, differentiation and apoptosis, as seen with atherosclerosis, degenerative neurological diseases and immune rejection of transplanted organs and cells. Future clinical applications are expected to involve the development of new therapeutic strategies for transplantation and various inflammatory cardiovascular, gastrointestinal and neurological diseases.

Lessons from Innovation Empirical Studies in the Manufacturing Sector: A Systematic Review of the Literature from 1993-2003

Abstract: Provides a systematic review of empiricalarticles published in scholarly periodicals between 1993 and 2003 on the topicof technological innovations in the manufacturing sector. The goals of thisreview are to identify the variables that determine the innovative behavior andcapacity of firms and to explore how the authors of the articles approached andmeasure innovation. A careful study of 108 articles uncovers various internal variables (i.e.,specific to the firm) and contextual variables (i.e., related to the firm'senvironment) that shape a firm's innovative activities. The internal variablescan be grouped into such categories as general firm characteristics,strategies, structure, control, organizational culture, the management team andfunctional assets. Among the external variables are such types asindustry, region, networking, knowledge and technology acquisition and publicpolicies. Results show that the relationship linking several of these variableswith innovation is often moderated by an interaction with other variables. Firmmanagers and policy makers wishing to foster innovation more effectively canlearn from the results of this study. (SAA)

Apoptosis-inducing factor mediates poly(ADP-ribose) (PAR) polymer-induced cell death

Abstract: Apoptosis-inducing factor (AIF), a mitochondrial oxidoreductase, is released into the cytoplasm to induce cell death in response to poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) activation. How PARP-1 activation leads to AIF release is not known. Here we identify PAR polymer as a cell death signal that induces release of AIF. PAR polymer induces mitochondrial AIF release and translocation to the nucleus. PAR glycohydrolase, which degrades PAR polymer, prevents PARP-1-dependent AIF release. Cells with reduced levels of AIF are resistant to PARP-1-dependent cell death and PAR polymer cytotoxicity. These results reveal PAR polymer as an AIF-releasing factor that plays important roles in PARP-1-dependent cell death.

A Social-Neuroscience Perspective on Empathy

Abstract: In recent years, abundant evidence from be- havioral and cognitive studies and functional-imaging experiments has indicated that individuals come to un- derstand the emotional and affective states expressed by others with the help of the neural architecture that pro- duces such states in themselves. Such a mechanism gives rise to shared representations, which constitutes one im- portant aspect of empathy, although not the sole one. We suggestthatothercomponents,includingpeople'sabilityto monitor and regulate cognitive and emotional processes to prevent confusion between self and other, are equally necessary parts of a functional model of empathy. We dis- cuss data from recent functional-imaging studies in sup- port of such a model and highlight the role of specific brain regions, notably the insula, the anterior cingulate cortex, and the right temporo-parietal region. Because this model assumes that empathy relies on dissociable information- processing mechanisms, it predicts a variety of structural or functional dysfunctions, depending on which mecha- nism is disrupted. KEYWORDS—empathy;intersubjectivity;affectivesharing; perspective taking; emotion regulation Empathy refers to the capacity to understand and respond to the unique affective experiences of another person. At an experi- ential level of description, this psychological construct denotes a sense of similarity between one's own feelings and those ex- pressed by another person. At a basic level of description, em- pathy can be conceived of as an interaction between any two individuals, with one experiencing and sharing the feeling of the other. This sharing of feelings does not necessarily imply that one will act or even feel impelled to act in a supportive or sympathetic way. The social and emotional situations eliciting empathy can be quite complex, depending on the feelings ex- perienced by the observed person (target), the relationship of the target to the observer, and the context in which they socially interact. In recent years, there has been a growing interest in the cognitive-affective neuroscience of empathy. In this article, we first discuss what the components of this psychological construct are and then present empirical data that can cast some light on the neurocognitive mechanisms subserving empathy, with a special emphasis on the perception of pain in others.

Organizational culture and performance measurement systems

Abstract: The aim of this study is to articulate and test the relationships between organizational culture and two attributes of performance measurement systems (PMS), namely the diversity of measurement and the nature of use. The results of a survey reveal that top managers of firms reflecting a flexibility dominant type tend to use more performance measures and to use PMS to focus organizational attention, support strategic decision-making and legitimate actions to a greater extent than top managers of firms reflecting a control dominant type.

Poly(ADP-ribose) (PAR) polymer is a death signal

Abstract: Excessive activation of the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP-1) plays a prominent role in various of models of cellular injury. Here, we identify poly(ADP-ribose) (PAR) polymer, a product of PARP-1 activity, as a previously uncharacterized cell death signal. PAR polymer is directly toxic to neurons, and degradation of PAR polymer by poly(ADP-ribose) glycohydrolase (PARG) or phosphodiesterase 1 prevents PAR polymer-induced cell death. PARP-1-dependent, NMDA excitotoxicity of cortical neurons is reduced by neutralizing antibodies to PAR and by overexpression of PARG. Neuronal cultures with reduced levels of PARG are more sensitive to NMDA excitotoxicity than WT cultures. Transgenic mice overexpressing PARG have significantly reduced infarct volumes after focal ischemia. Conversely, mice with reduced levels of PARG have significantly increased infarct volumes after focal ischemia compared with WT littermate controls. These results reveal PAR polymer as a signaling molecule that induces cell death and suggests that interference with PAR polymer signaling may offer innovative therapeutic approaches for the treatment of cellular injury.

Human let-7a miRNA blocks protein production on actively translating polyribosomes

Abstract: MicroRNAs (miRNAs) regulate gene expression at a post-transcriptional level through base-pairing to 3' untranslated regions (UTRs) of messenger RNAs. The mechanism by which human let-7a miRNA regulates mRNA translation was examined in HeLa cells expressing reporter mRNAs containing the Caenorhabditis elegans lin-41 3' UTR. let-7a miRNA strongly repressed translation, yet the majority of control and lin-41-bearing RNAs sedimented with polyribosomes in sucrose gradients; these polyribosomes, together with let-7a miRNA and the miRISC protein AGO, were released from those structures by puromycin. RNA containing the lin-41 3' UTR and an iron response element in the 5' UTR sedimented with polysomes when cells were incubated with iron, but showed ribosome run-off when the iron was chelated. These data indicate that let-7a miRNA inhibits actively translating polyribosomes. Nascent polypeptide coimmunoprecipitation experiments further suggest that let-7a miRNA interferes with the accumulation of growing polypeptides.

Prosthesis‐patient mismatch: definition, clinical impact, and prevention

Abstract: Prosthesis-patient mismatch (PPM) is present when the effective orifice area of the inserted prosthetic valve is too small in relation to body size Its main haemodynamic consequence is to generate higher than expected gradients through normally functioning prosthetic valves This review updates the present knowledge about the impact of PPM on clinical outcomes PPM is common (20-70% of aortic valve replacements) and has been shown to be associated with worse haemodynamic function, less regression of left ventricular hypertrophy, more cardiac events, and lower survival Moreover, as opposed to most other risk factors, PPM can largely be prevented by using a prospective strategy at the time of operation

Preparation of ready-to-use, storable and reconstituted type I collagen from rat tail tendon for tissue engineering applications

Abstract: Collagen is a widely investigated extracellular matrix material with extensive potentials in the field of tissue engineering. This protocol describes a method to prepare reconstituted collagen that can be ready-to-use, storable and suitable for further in vitro and in vivo investigations. Type I collagen was extracted from rat tail tendons and processed in acetic acid solution to obtain sterile soluble collagen. At first, crude collagen was dissolved in acetic acid, then frozen at -20 degrees C and lyophilized to obtain a sponge, which could be stored at -80 degrees C. Lyophilized collagen was then dispersed in acetic acid to obtain a sterile solution of collagen at targeted concentrations. The whole low-cost process from the extraction to the final sterile solution takes around 2-3 weeks. The collagen solution, once neutralized, has the potential to be used to produce gels or scaffolds, to deposit thin films on supports and to develop drug delivery systems.

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

Abstract: There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

Anodizing Treatments for Magnesium Alloys and Their Effect on Corrosion Resistance in Various Environments

Abstract: This paper reviews various aspects of anodizing of magnesium alloys, such as the basics, processes, properties and applications. It systematically summarises the existing fundamental studies and technical developments of anodizing of magnesium alloys, and concludes that new anodizing processes based on electrolytic plasma anodizing that convert the surface of a magnesium alloy into a hard ceramic coating in an electrolytic bath using high energy electric discharges can offer improved wear and corrosion resistance. These new anodized coatings are often claimed to perform better than the traditional ones obtained through older anodizing processes, such as DOW17 or HAE. The new anodizing techniques are chromate free and hence environment friendly. It is expected that more cost-effective, environment-friendly and non-toxic anodizing techniques will be developed and applied to magnesium alloy components in the future.

Goodness‐of‐fit Procedures for Copula Models Based on the Probability Integral Transformation

Abstract: Wang & Wells [J Amer Statist Assoc 95 (2000) 62] describe a non-parametric approach for checking whether the dependence structure of a random sample of censored bivariate data is appropriately modelled by a given family of Archimedean copulas Their procedure is based on a truncated version of the Kendall process introduced by Genest & Rivest [J Amer Statist Assoc 88 (1993) 1034] and later studied by Barbe et al [J Multivariate Anal 58 (1996) 197] Although Wang & Wells (2000) determine the asymptotic behaviour of their truncated process, their model selection method is based exclusively on the observed value of its L2-norm This paper shows how to compute asymptotic p-values for various goodness-of-fit test statistics based on a non-truncated version of Kendall's process Conditions for weak convergence are met in the most common copula models, whether Archimedean or not The empirical behaviour of the proposed goodness-of-fit tests is studied by simulation, and power comparisons are made with a test proposed by Shih [Biometrika 85 (1998) 189] for the gamma frailty family

V-ATPase interacts with ARNO and Arf6 in early endosomes and regulates the protein degradative pathway

Abstract: The recruitment of the small GTPase Arf6 and ARNO from cytosol to endosomal membranes is driven by V-ATPase-dependent intra-endosomal acidification. The molecular mechanism that mediates this pH-sensitive recruitment and its role are unknown. Here, we demonstrate that Arf6 interacts with the c-subunit, and ARNO with the a2-isoform of V-ATPase. The a2-isoform is targeted to early endosomes, interacts with ARNO in an intra-endosomal acidification-dependent manner, and disruption of this interaction results in reversible inhibition of endocytosis. Inhibition of endosomal acidification abrogates protein trafficking between early and late endosomal compartments. These data demonstrate the crucial role of early endosomal acidification and V-ATPase/ARNO/Arf6 interactions in the regulation of the endocytic degradative pathway. They also indicate that V-ATPase could modulate membrane trafficking by recruiting and interacting with ARNO and Arf6; characteristics that are consistent with the role of V-ATPase as an essential component of the endosomal pH-sensing machinery.

Chromogranin-mediated secretion of mutant superoxide dismutase proteins linked to amyotrophic lateral sclerosis.

Abstract: Here we report that chromogranins, components of neurosecretory vesicles, interact with mutant forms of superoxide dismutase (SOD1) that are linked to amyotrophic lateral sclerosis (ALS), but not with wild-type SOD1. This interaction was confirmed by yeast two-hybrid screen and by co-immunoprecipitation assays using either lysates from Neuro2a cells coexpressing chromogranins and SOD1 mutants or lysates from spinal cord of ALS mice. Confocal and immunoelectron microscopy revealed a partial colocalization of mutant SOD1 with chromogranins in spinal cord of ALS mice. Mutant SOD1 was also found in immuno-isolated trans-Golgi network and in microsome preparations, suggesting that it can be secreted. Indeed we report evidence that chromogranins may act as chaperone-like proteins to promote secretion of SOD1 mutants. From these results, and our finding that extracellular mutant SOD1 can trigger microgliosis and neuronal death, we propose a new ALS pathogenic model based on the toxicity of secreted SOD1 mutants.

Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer.

Abstract: Purpose Radical cystectomy and pelvic lymphadenectomy (PLND) remains the standard treatment for localized and regionally advanced invasive bladder cancers We have constructed an international bladder cancer database from centers of excellence in the management of bladder cancer consisting of patients treated with radical cystectomy and PLND The goal of this study was the development of a prognostic outcomes nomogram to predict the 5-year disease recurrence risk after radical cystectomy Patients and Methods Institutional radical cystectomy databases containing detailed information on bladder cancer patients were obtained from 12 centers of excellence worldwide Data were collected on more than 9,000 postoperative patients and combined into a relational database formatted with patient characteristics, pathologic details of the pre- and postcystectomy specimens, and recurrence and survival status Patients with available information for all selected study criteria were included in the formation of the final prognostic nomogram designed to predict 5-year progression-free probability Results The final nomogram included information on patient age, sex, time from diagnosis to surgery, pathologic tumor stage and grade, tumor histologic subtype, and regional lymph node status The predictive accuracy of the constructed international nomogram (concordance index, 075) was significantly better than standard American Joint Committee on Cancer TNM (concordance index, 068; P 001) or standard pathologic subgroupings (concordance index, 062; P 001) Conclusion We have developed an international bladder cancer nomogram predicting recurrence risk after radical cystectomy for bladder cancer The nomogram outperformed prognostic models that use standard pathologic subgroupings and should improve our ability to provide accurate risk assessments to patients after the surgical management of bladder cancer J Clin Oncol 24:3967-3972 © 2006 by American Society of Clinical Oncology