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Search Results: 1 - 10 of 4155 matches for " Jacques Lapointe "
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Mechanism and evolution of multidomain aminoacyl-tRNA synthetases revealed by their inhibition by analogues of a reaction intermediate, and by properties of truncated forms  [PDF]
Jacques Lapointe
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.610115
Abstract: Many enzymes which catalyze the conversion of large substrates are made of several structural domains belonging to the same polypeptide chain. Transfer RNA (tRNA), one of the substrates of the multidomain aminoacyl-tRNA synthetases (aaRS), is an L-shaped molecule whose size in one dimension is similar to that of its cognate aaRS. Crystallographic structures of aaRS/tRNA complexes show that these enzymes use several of their structural domains to interact with their cognate tRNA. This mini review discusses first some aspects of the evolution and of the flexibility of the pentadomain bacterial glutamyl-tRNA synthetase (GluRS) revealed by kinetic and interaction studies of complementary truncated forms, and then illustrates how stable analogues of aminoacyl-AMP intermediates have been used to probe conformational changes in the active sites of Escherichia coli GluRS and of the nondiscriminating aspartyl-tRNA synthetase (ND-AspRS) of Pseudomonas aeruginosa.
Theoretical and experimental biology in one
—A symposium in honour of Professor Kuo-Chen Chou’s 50th anniversary and Professor Richard Giegé’s 40th anniversary of their scientific careers
 [PDF]

Sheng-Xiang Lin, Jacques Lapointe
Journal of Biomedical Science and Engineering (JBiSE) , 2013, DOI: 10.4236/jbise.2013.64054
Abstract:

It has been a dream that theoretical biology can be extensively applied in experimental biology to accelerate the understanding of the sophiscated movements in living organisms. A brave assay and an excellent example were represented by enzymology, in which the well-established physico-chemistry is used to describe, to fit, to predict and to improve enzyme reactions. Before the modern bioinformatics, the developments of the combination of theoretical biology and experimental biology have been mainly limited to various classic formulations. The systematic use of graphic rules by Prof. Kuo-Chen Chou and his co-workers has significantly facilitated to deal with complicated enzyme systems. With the recent fast progress of bioinformatics, prediction of protein structures and various protein attributes have been well established by Chou and co-workers, stimulating the experimental biology. For example, their recent method for predicting protein subcellular localization (one of the important attributes of proteins) has been extensively applied by scientific colleagues, yielding many new results with thousands of citations. The research by Prof. Chou is characterized by introducing novel physical concepts as well as powerful and elegant mathematical methods into important biomedical problems, a focus throughout his career, even when facing enormous difficulties. His efforts in 50 years have greatly helped us to realize the dream to make “theoretical and experimental biology in one”. Prof. Richard Giege is well known for his multi-disciplinary research combining physics, chemistry, enzymology and molecular biology. His major focus of study is on the identity of tRNAs and their interactions with aminoacyl-tRNA synthetases (aaRS), which are of critical importance to the fidelity of protein biosynthesis. He and his colleagues have carried out the first crystallization of a tRNA/aaRS complex, that between

A Comparison of Invasive Acer platanoides and Native A. saccharum First-Year Seedlings: Growth, Biomass Distribution and the Influence of Ecological Factors in a Forest Understory
Marie Lapointe,Jacques Brisson
Forests , 2012, DOI: 10.3390/f3020190
Abstract: Invasive shade tolerant species can have profound and long-lasting detrimental effects even on previously undisturbed forests. In North American forests, the invasive Acer platanoides is capable of dominating the understory where it could displace the native Acer saccharum. To understand the relative importance of various ecological factors in a forest understory on their establishment, we transplanted A. platanoides and A. saccharum seedlings in an urban sugar maple forest understory and their growth and survival were compared over a growing season. Seedlings did not differ in height, but biomass growth and assimilation rates were twice as high for the invasive species. Ecological variables accounted for only 23–24% of variation in growth. Seedlings of A. platanoides appeared to capture light more efficiently, with over 150% greater foliage biomass and surface area. A. saccharum seedlings were more negatively affected by herbivory. The more robust A. platanoides seedlings presented characteristics that could allow them to better grow and survive in shaded understories than their native congeners.
Uma atividade "sexo" que faz relfletir
Bujold, Francine;Dionne, Jacques;Lapointe, Claire;
Paidéia (Ribeir?o Preto) , 2000, DOI: 10.1590/S0103-863X2000000100009
Abstract: in this paper, it is intended to describe the characteristics of an adolescents sample living in institutions, their problems, and the concepts behind the program proposed, based on a reorganization of activities. in a second phase it is explained the way the information about sex begin to be transmitted, the orientation to talk about this subject, specially the experiences the adolescents had and the opportunity to reflect; the activity about sexual education included to form a group to help the adolescents that had been abused.
The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis
Bernard Têtu, Jacques Brisson, Chang Wang, Hélène Lapointe, Geneviève Beaudry, Caty Blanchette, Dominique Trudel
Breast Cancer Research , 2006, DOI: 10.1186/bcr1503
Abstract: MMP-2, MMP-14 and TIMP-2 expression has been evaluated by 35S mRNA in situ hybridization on paraffin material of 539 breast cancers without distant metastasis at diagnosis and with a median follow-up of 9.2 years.MMP-2 and MMP-14 mRNA was detected primarily in reactive stromal cells whereas TIMP-2 mRNA was expressed by both stromal and cancer cells. Of the three molecules, an adjusted Cox model revealed that high MMP-14 mRNA (≥ 10% cells) alone predicted a significantly shorter overall survival (p = 0.031) when adjusted for clinical factors (tumor size and number of involved lymph nodes). Prognostic significance was lost when further adjusted for Her-2/neu and urokinase-type plasminogen activator (p = 0.284). Furthermore, when all three components were analyzed together, the survival was worst for patients with high MMP-2/high MMP-14/low TIMP-2 (5 year survival = 60%) and best with low MMP-2/low MMP-14/high TIMP-2 (5 year survival = 74%), but the difference did not reach statistical significance (p = 0.3285).Of the MMP-14/TIMP-2/MMP-2 complex, MMP-14 was the factor most significantly associated with the outcome of breast cancer and was an independent factor of poor overall survival when adjusted for clinical prognostic factors, but not for certain ancillary markers.In breast cancer, matrix metalloproteinase (MMP)-2 is a protease produced essentially by stromal cells. In vitro studies have clearly demonstrated that it degrades molecules that are abundant in the extracellular matrix (ECM) [1]. MMP-2 is also one of the major targets of recently developed synthetic MMP inhibitors [2,3]. However, recent literature demonstrates that the mechanism of action of MMP-2 is complex and that other molecules modulate its activity [4,5].MMP-2 is secreted in an inactive pro-enzymatic form and, unlike other MMPs, its activity is modulated by tissue inhibitor of metalloproteases (TIMP)-2 [6] and the membrane type 1 MMP (MMP-14) [7]. Using zymography, breast cancers were found to expr
Iron supplementation in the intensive care unit: when, how much, and by what route?
Marc Lapointe
Critical Care , 2004, DOI: 10.1186/cc2825
Abstract: The development of anemia during critical illness is hematologically similar to the anemia of chronic disease/inflammation (ACD), except that the onset is generally acute. Blunting of endogenous erythropoietin production, mediated through the action of inflammatory cytokines, is thought to be the most important cause of this common syndrome [1]. Because low serum iron and elevated serum ferritin levels are also clinical features of ACD, investigators once believed that altered iron metabolism was responsible for this condition. This early hypothesis has merit because iron utilization plays a key role in anemia and can affect the response to endogenous or exogenously administered erythropoietin [2]. Nutritional deficiencies (folic acid, vitamin B12, and iron) can possibly contribute to the etiology of early anemia in the intensive care unit (ICU). In a study conducted by Rodriguez and colleagues [3], 13% of critically ill patients were identified as having potentially correctable nutritional abnormalities, with 9% having laboratory values consistent with iron deficiency (i.e. iron/total iron binding capacity <15%, with a ferritin level <100 ng/ml).The relevant iron parameters that characterize anemia in chronic disease or critical illness, as compared with those in iron deficiency anemia and normal individuals, are summarized in Table 1. In ACD-type disorders, absorption of iron is actually stimulated and there are adequate stores of iron in the bone marrow. Stored iron may not be effectively utilized, however. Release of iron from macrophages in the reticulo-endothelial system is defective, ferritin concentrations are increased, and serum transferrin levels are normal, rather than elevated [4]. This 'functional iron deficiency', when diagnosed by cytometry, is present in 35% of patients on admission to the ICU [5]. Disturbed iron metabolism from enhanced immune activation has also been documented in surgical ICU patients [6] and in patients with multiple organ dysfu
Spectral properties of bipolar minimal surfaces in S^4
Hugues Lapointe
Mathematics , 2005,
Abstract: The i-th eigenvalue of the Laplacian on a surface can be viewed as a functional on the space of Riemannian metrics of fixed area. Extremal points of these functionals correspond to surfaces admitting minimal isometric immersions into spheres. Recently, critical metrics for the first eigenvalue were classified on tori and on Klein bottles. The present paper is concerned with extremal metrics for higher eigenvalues on these surfaces. We apply a classical construction due to Lawson. The ranks of the extremal eigenvalues are obtained for the bipolar surfaces $\tilde \tau_{r,k}$ of the corresponding Lawson's tori or Klein bottles. Furthermore, we find explicitly the $S^1$-equivariant minimal immersion of the bipolar surfaces into $S^4$ by the corresponding eigenfunctions.
A remainder estimate for Weyl's law on Liouville tori
Hugues Lapointe
Mathematics , 2009,
Abstract: The paper is concerned with the asymptotic distribution of Laplace eigenvalues on Liouville tori. Liouville metrics are the largest known class of integrable metrics on two-dimensional tori; they contain flat metrics and metrics of revolution as special cases. Using separation of variables, we reduce the eigenvalue counting problem to the problem of counting lattice points in certain planar domains. This allows us to improve the remainder estimate in Weyl's law on a large class of Liouville tori. For flat metrics, such an estimate has been known for more than a century due to classical results of W. Sierpinski and J.G. van der Corput. Our proof combines the method of Y. Colin de Verdiere, who proved an analogous result for metrics of revolution on a sphere, with the techniques developed by P. Bleher, D. Kosygin, A. Minasov and Y. Sinai in their study of the almost periodic properties of the remainder in Weyl's law on Liouville tori.
A Tri-Marker Proliferation Index Predicts Biochemical Recurrence after Surgery for Prostate Cancer
Sameer Malhotra,Jacques Lapointe,Keyan Salari,John P. Higgins,Michelle Ferrari,Kelli Montgomery,Matt van de Rijn,James D. Brooks,Jonathan R. Pollack
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0020293
Abstract: Prostate cancer exhibits tremendous variability in clinical behavior, ranging from indolent to lethal disease. Better prognostic markers are needed to stratify patients for appropriately aggressive therapy. By expression profiling, we can identify a proliferation signature variably expressed in prostate cancers. Here, we asked whether one or more tissue biomarkers might capture that information, and provide prognostic utility. We assayed three proliferation signature genes: MKI67 (Ki-67; also a classic proliferation biomarker), TOP2A (DNA topoisomerase II, alpha), and E2F1 (E2F transcription factor 1). Immunohistochemical staining was evaluable on 139 radical prostatectomy cases (in tissue microarray format), with a median clinical follow-up of eight years. Each of the three proliferation markers was by itself prognostic. Notably, combining the three markers together as a “proliferation index” (0 or 1, vs. 2 or 3 positive markers) provided superior prognostic performance (hazard ratio = 2.6 (95% CI: 1.4–4.9); P = 0.001). In a multivariate analysis that included preoperative serum prostate specific antigen (PSA) levels, Gleason grade and pathologic tumor stage, the composite proliferation index remained a significant predictor (P = 0.005). Analysis of receiver-operating characteristic (ROC) curves confirmed the improved prognostication afforded by incorporating the proliferation index (compared to the clinicopathologic data alone). Our findings highlight the potential value of a multi-gene signature-based diagnostic, and define a tri-marker proliferation index with possible utility for improved prognostication and treatment stratification in prostate cancer.
Healthcare professionals' intentions to use wiki-based reminders to promote best practices in trauma care: a survey protocol
Patrick M Archambault, France Légaré, André Lavoie, Marie-Pierre Gagnon, Jean Lapointe, Sylvie St-Jacques, Julien Poitras, Karine Aubin, Sylvain Croteau, Martin Pham-Dinh
Implementation Science , 2010, DOI: 10.1186/1748-5908-5-45
Abstract: Using the Theory of Planned Behavior, we will conduct semi-structured interviews of healthcare professionals to identify salient beliefs that may affect their future use of wikis. These beliefs will inform our questionnaire on intended behavior. A test-retest of the survey will verify the questionnaire's stability over time. We will interview 50 healthcare professionals (25 physicians and 25 allied health professionals) working in the emergency departments of three trauma centers in Quebec, Canada. We will analyze the content of the interviews and construct and pilot a questionnaire. We will then test the revised questionnaire with 30 healthcare professionals (15 physicians and 15 allied health professionals) and retest it two weeks later. We will assess the internal consistency of the questionnaire constructs using Cronbach's alpha coefficients and determine their stability with the intra-class correlation (ICC).To our knowledge, this study will be the first to develop and test a theory-based survey that measures healthcare professionals' intentions to use a wiki-based intervention. This study will identify professionals' salient beliefs qualitatively and will quantify the psychometric capacities of the questionnaire based on those beliefs.Clinical practice does not always reflect best evidence, and high proportions of inappropriate care have been reported in different healthcare systems and settings [1]. Inappropriate care significantly impacts patient outcomes and healthcare costs. In emergency departments, unconscious acts of omission and information overload [2] contribute to inappropriate care. Systematic reviews have indicated that reminders to healthcare professionals can be effective in promoting change in healthcare professionals' practices in a variety of clinical areas and environments [3-6]. These reminders can take the form of protocols with check boxes, admission order sets, care maps, clinical decision rules, patient handouts, or decision aids. To in
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