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Peptidomimetic SH2 domain antagonists for targeting signal transduction
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Year: 2001

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Does c-Src activation by a growth factor-receptor tyrosine kinase leads to its recruitment on rafts?

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Etude de la sensibilité des cardiomyocytes à l'insuline
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Insulin is a hormone involved in glucose homeostasis and in the control of lipid metabolism. In 1981, frank and his co-workers found that the glycogen metabolism, in isolated hepatocytes, was more sensitive to insulin than the insulin receptor. They explained this phenomenon by the presence of “spare receptors”. It involved that a slight activation of the insulin signalling pathway was sufficient to obtain maximal metabolic responses. Similar experiments performed in other tissues indicated that spare receptors were not present everywhere. This first aim of my work was to determine if the spare receptor phenomenon exists in the heart. Moreover, several experiments realised in our laboratory showed a difference in sensitivity between protein kinase B and the metabolic effect of insulin. This questioned the participation of this enzyme in the metabolic effect of insulin.
To answer these two questions, we incubated rat cardiomyocytes with various concentration of insulin. Dose-responses curves were established, describing the effects of insulin on its signalling pathway and on metabolism. The targets studied in the signalling pathway were the insulin receptor, phosphatidylinositol-3 kinase, protein kinase B and glycogen synthase kinase-3. The metabolic responses studied here were glucose uptake and fructose-2;6-P2 concentration. The final step was to compare the ED50 obtained for each target studied. The ED50 represents the concentration of ligand that causes 50% of the maximal effect. A similar ED50 value (± 17 nM) was obtained for all elements of the insulin signalling pathway, from IR to GSK-3. By contrast, the two metabolic responses studied here were more sensitive (± 1.2 nM). From these results, we can conclude that spare receptors for insulin indeed exist in the heart and that a role of PKB in the metabolic effects of insulin can not be excluded L’insuline joue un rôle essentiel dans l’homéostasie du glucose et dans le contrôle du métabolisme des lipides. En 1981, Frank et collaborateurs ont mis en évidence, dans des hépatocytes en suspension, la présence d’une différence de sensibilité à l’insuline entre le récepteur insulinique et le métabolisme du glycogène, ce dernier étant le plus sensible. Ils avaient, à l’époque, expliqué ce phénomène par l’existence de « récepteurs de réserve » ou « spare receptors ». La présence de ces récepteurs de réserve impliquait qu’une petit activation au départ de la voie de signalisation de l’insuline était suffisante pour obtenir des réponses métaboliques maximales. Des expériences similaires ont ensuite été effectuées dans d’autres tissus et ont montré que la présence d’une telle différence de sensibilité à l’insuline varie en fonction du tissu étudié. Le premier objectif de mon travail a été par conséquent de savoir qu’est-ce qu’il en était du tissu cardiaque. D’autre part, des expériences réalisées dans notre laboratoire avaient mis en évidence l’existence d’une différence de sensibilité à l’insuline entre la protéine kinase B et les effets métaboliques de cette hormone, dans le cœur. Cela remettait en question la participation de cette enzyme aux effets métaboliques de l’insuline. Pur pouvoir répondre à ces deux questions, la première étape a été d’incuber des cardiomyocytes de rats aves des concentrations croissantes en insuline. Des courbes doses-réponses ont ensuite été établies, celles-ci décrivant les effets de l’insuline sur sa voie de signalisation et sur le métabolisme glucidique. Les cibles qui ont été étudiées dans la voie de signalisation sont le récepteur insulinique, la phosphatidylinositol 3-kinase, la protéine kinase B et la glycogène synthase kinase-3. D’autre part, les deux réponses métaboliques qui ont été choisies sont le captage du glucose et l’augmentation de la concentration en fructose-2,6-P2. Enfin, la dernière étape a été de déterminer et de comparer les ED50 obtenues pour chacune des courbes. La ED50 désigne la concentration en ligand nécessaire pour obtenir 50% de l’effet maximal. Les ED50 sont semblables pour tous les constituants de la voie de signalisation de l’insuline (± 17 nM). Les effets métaboliques, quant à eux, sont caractérisés par une sensibilité plus élevée envers l’insuline (± 1,2 nM). Ce travail montre donc que le phénomène de récepteurs de réserve est bien présent dans le cœur. De plus, nous ne pouvons pas exclure la participation de la PKB aux effets métaboliques de l’insuline, dans le cœur


Book
Risk Factors for Pancreatic Cancer: Underlying Mechanisms and Potential Targets
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Year: 2015 Publisher: Frontiers Media SA

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Pancreatic Cancer has been and still is one of the deadliest types of human malignancies. The annual mortality rates almost equal incidence rates making this disease virtually universally fatal. The 5-year survival of patients with pancreatic cancer is a dismal 5% or less. Therapeutic strategies are extremely limited with gemcitabine extending the survival by a disappointing few weeks. The failure of several randomized clinical trials in the past decade investigating the therapeutic efficacy of different mono- and combination therapies reflects our limited knowledge of pancreatic cancer biology. In addition, biomarkers for early detection are sorely missing. Several pancreatic cancer risk factors have been identified. Unfortunately, the underlying mechanisms linking these risk factors to cancer development are poorly understood. Well known possible and probable risk factors for the development of pancreatic cancer are age, smoking, chronic pancreatitis, obesity, and type-2 diabetes mellitus. Age is certainly of the most important risk factors as most cases of pancreatic cancer occur in the elderly population. Smoking ten cigarettes a day increases the risk by 2.6 times and smoking a pack per day increases it by 5 folds. Chronic pancreatitis increases the risk of pancreatic cancer by up to 13 times. Patients with hereditary forms of chronic pancreatitis have an even higher risk. Obesity, a growing global health problem, increases the risk of pancreatic cancer by about 1.5 fold. Type-2 diabetes mellitus is also associated with an increased risk of pancreatic cancer by at least two-fold. The more recent the onset of diabetes, the stronger the correlation with pancreatic cancer is. In addition, heavy alcohol drinking, a family history of the disease, male gender and African American ethnicity are other risk factors for pancreatic cancer. Pancreatic cancer is characterized by several genetic alterations including mutations in the Kras proto-oncogene and mutations in the tumor suppressor genes p53 and p16. While Kras mutations are currently thought as early events present in a certain percentage of pancreatic intraepithelial neoplasias (PanINs), known precursor lesions of pancreatic ductal adenocarcinomas, mutations in tumor suppressor genes, e.g. p53, seem to accumulate later during progression. In addition, several intracellular signaling pathways are amplified or enhanced, including the MAPK/ERK and PI3K/AKT signaling modules. Overall, these genetic alterations lead to enhanced and sustained proliferation, resistance to cell death, invasive and metastatic potential, and angiogenesis, all hallmarks of cancers. The scope of this Research Topic is to collect data and knowledge of how risk factors increase the risk of initiation/progression of pancreatic cancer. Of particular interest are potential underlying molecular mechanisms. Understanding the molecular mechanisms and driving signaling pathways will ultimately allow the development of targeted interventions to disrupt the risk factor-induced cancer development. This Research Topic is interested in a broad range of risk factors, including genetic and environmental, and welcomes original papers, mini and full reviews, and hypothesis papers. Manuscripts that address the effect of combination of risk factors on pancreatic cancer development and progression are of great interest as well.


Book
Everyone says no
Author:
ISBN: 0773587101 9780773587106 0773539336 9780773539334 0773539344 9780773539341 077358711X Year: 2011 Publisher: Montreal [Que.] McGill-Queen's University Press

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"Quebec has never signed on to Canada's constitution. After both major attempts to win Quebec's approval - the Meech Lake and Charlottetown Accords - failed, Quebec came within a fraction of a percentage point of voting for independence. Everyone Says No examines how the failure of these accords was depicted in French and English media and the ways in which journalists' reporting failed to translate the differences between Quebec and the rest of Canada. Focusing on the English- and French-language networks of the Canadian Broadcasting Corporation, Kyle Conway draws on the CBC/Radio Canada rich print and video archive as well as journalists' accounts of their reporting to revisit the story of the accords and the furor they stirred in both French and English Canada. He shows that CBC/Radio Canada attempts to translate language and culture and encourage understanding among Canadians actually confirmed viewers' pre-existing assumptions rather than challenging them. The first book to examine translation in Canadian news, Everyone Says No also provides insight into Canada's constitutional history and the challenges faced by contemporary public service broadcasters in increasingly multilingual and multicultural communities."--Publisher's website.


Periodical
Rapport annuel

Physics and the rise of scientific research in Canada
Author:
ISBN: 1282855514 9786612855511 0773562818 9780773562813 0773508236 9780773508231 Year: 1991 Publisher: Montreal, Que. McGill-Queen's University Press

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The teaching of engineering and a change in liberal arts curricula, both stimulated by industrial growth, encouraged the creation of specialized courses in the sciences. By the 1890s, Gingras argues, trained researchers had begun to appear in Canadian universities. The technological demands of the First World War and the founding, in 1916, of the National Research Council of Canada (NRC) accelerated the growth of scientific research. The Transactions of the Royal Society of Canada could no longer publish everything submitted to it because of the disproportionately large number of research papers from the fields of science. In response, the NRC created the Canadian Journal of Research, a journal specifically dedicated to the publication of scientific research. By 1930, a stable, national system of scientific research was in place in Canada. Following the dramatic increase in the national importance of their disciplines, scientists faced the problem of social identity. Gingras demonstrates that in the case of physics this took the form of a conflict between those who promoted a professional orientation, necessary to compete successfully with engineers in the labour market, and those, mainly in the universities, who were concerned with problems of the discipline such as publication, internal management, and awards. Physics and the Rise of Scientific Research in Canada is the first book to provide a general analysis of the origins of scientific research in Canadian universities. Gingras proposes a sociological model of the formation of scientific disciplines, distinguishing the profession from the discipline, two notions often confused by historians and sociologists of science.

Protein tyrosine kinases : from inhibitors to useful drugs
Authors: ---
ISBN: 9781588293848 158829384X 9781592599622 9786610358779 1280358777 1592599621 Year: 2006 Publisher: Totowa, N.J. : Humana Press,

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Protein kinases function as components of signal transduction pathways, playing a central role in the control of cell growth, metabolism, differentiation, and apoptosis. The development of selective protein tyrosine kinase (PTK) inhibitors that can block or modulate diseases, such as cancer, with abnormalities in these signaling pathways is considered a promising approach for drug development. Currently, more than 20 different PTKs are being considered as potential therapeutic targets in oncology. In Protein Tyrosine Kinases: From Inhibitors to Useful Drugs, leading researchers from the Novartis group that pioneered Gleevec/Glivec™ and from around the world comprehensively survey the state-of-the-art in the drug discovery processes (bio- and chemoinformatics, structural biology, profiling, generation of resistance, etc.) aimed at generating PTK inhibitors for the treatment of various diseases, including cancer. Highlights include a discussion of the rationale and the progress made toward generating "selective" low molecular-weight kinase inhibitors; an analysis of the normal function, role in disease, and application of platelet-derived growth factor antagonists; and a summary of the factors involved in successful structure-based drug design. Additional chapters address the advantages and disadvantages of in vivo preclinical models for testing PTK inhibitors with antitumor activity and the utility of different methods in the drug discovery and development process for determining "on-target" vs "off-target" effects of kinase inhibitors. Authoritative and state-of-the-art, Protein Tyrosine Kinases: From Inhibitors to Useful Drugs details the key stages in the design of PTK inhibitors and their development into useful drugs.


Book
Growth and Development of Short Rotation Woody Crops for Rural and Urban Applications
Authors: ---
Year: 2022 Publisher: Basel MDPI - Multidisciplinary Digital Publishing Institute

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Integrating biomass production of short rotation woody crops (SRWCs), with their use in environmental applications to produce income, sequester carbon, and clean the environment, provides an opportunity to enhance livelihoods and increase ecosystem services in rural and urban communities. This book consists of 20 papers from the special issue on the Growth and Development of SRWCs for Rural and Urban Applications highlighting four genera (Phalaris L., Populus L., Robinia L., Salix L.) from 13 countries. In addition to the development and management of a Salix cultivar database, rural and urban applications represented in the book included: a) forest buffers, b) forest health screening, c) phytoremediation, d) short rotation coppice, e) volume production, and f) wastewater reuse.

Keywords

Research & information: general --- Biology, life sciences --- Forestry & related industries --- cutback --- mulch --- Salix --- short-rotation coppice --- weed control --- woody biomass --- intensive silviculture --- Populus maximowiczii × P. deltoides × P. trichocarpa --- fast-growing tree species --- severe soil disturbance --- foliar nutrition --- soil inorganic N --- deer browsing --- short rotation coppice --- yield loss --- bioenergy plantation --- Populus --- renewable energy --- Populus × euramericana --- Lonsdalea populi --- canker diseases --- poplar diseases --- bacterial canker of poplars --- die-back of poplars --- MLSA --- short rotation coppice (SRC) --- biomass --- white poplar --- black locust --- monocultures --- mixture --- leaf litter --- SRC (Short Rotation Coppice) --- short rotation woody crops --- sustainability --- Mediterranean conditions --- management --- review --- fuelwood --- seasoning --- log diameter --- splitting --- heating value --- moisture content --- agroforestry --- red maple --- white ash --- trembling aspen --- fast growing trees --- poplar hybrids --- poplar clones --- tree height --- DBH --- stem volume --- yield --- Kyrgyzstan --- Kazakhstan --- Tajikistan --- ecosystem services --- multi-environmental trials (MET) --- phenotypic plasticity --- phyto buffers --- phyto-recurrent selection --- phytotechnologies --- poplars --- effluent water treatment --- short rotation coppice willow --- irrigation --- growth response --- biomass crops --- mineral content --- tree growth --- tree biomass --- volume forest stand --- thickness classes --- clonal selection --- genotype × environment (G × E) interactions --- evapotranspirative willow system --- resource recovery --- sustainable wastewater treatment --- oil sands reclamation --- end-pit lake --- balsam poplar --- salt tolerance --- Populus sp. --- bioenergy --- SRC --- financial analysis --- break-even-point --- net present value --- proof-of-concept: use case --- spreadsheet --- CSV file --- SQL --- database --- data integrity --- GitHub --- Linux --- poplar --- salt stress --- gene expression analyses --- radical scavenger capacity --- osmolytes --- cottonwood leaf beetle (Chrysomela scripta) --- stand density --- fertilizer application --- soil quality --- Melampsora rust --- energy crops --- land use --- reed canary grass (RCG) --- Phalaris arundinacea L. --- n/a


Book
Growth and Development of Short Rotation Woody Crops for Rural and Urban Applications
Authors: ---
Year: 2022 Publisher: Basel MDPI - Multidisciplinary Digital Publishing Institute

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Abstract

Integrating biomass production of short rotation woody crops (SRWCs), with their use in environmental applications to produce income, sequester carbon, and clean the environment, provides an opportunity to enhance livelihoods and increase ecosystem services in rural and urban communities. This book consists of 20 papers from the special issue on the Growth and Development of SRWCs for Rural and Urban Applications highlighting four genera (Phalaris L., Populus L., Robinia L., Salix L.) from 13 countries. In addition to the development and management of a Salix cultivar database, rural and urban applications represented in the book included: a) forest buffers, b) forest health screening, c) phytoremediation, d) short rotation coppice, e) volume production, and f) wastewater reuse.

Keywords

cutback --- mulch --- Salix --- short-rotation coppice --- weed control --- woody biomass --- intensive silviculture --- Populus maximowiczii × P. deltoides × P. trichocarpa --- fast-growing tree species --- severe soil disturbance --- foliar nutrition --- soil inorganic N --- deer browsing --- short rotation coppice --- yield loss --- bioenergy plantation --- Populus --- renewable energy --- Populus × euramericana --- Lonsdalea populi --- canker diseases --- poplar diseases --- bacterial canker of poplars --- die-back of poplars --- MLSA --- short rotation coppice (SRC) --- biomass --- white poplar --- black locust --- monocultures --- mixture --- leaf litter --- SRC (Short Rotation Coppice) --- short rotation woody crops --- sustainability --- Mediterranean conditions --- management --- review --- fuelwood --- seasoning --- log diameter --- splitting --- heating value --- moisture content --- agroforestry --- red maple --- white ash --- trembling aspen --- fast growing trees --- poplar hybrids --- poplar clones --- tree height --- DBH --- stem volume --- yield --- Kyrgyzstan --- Kazakhstan --- Tajikistan --- ecosystem services --- multi-environmental trials (MET) --- phenotypic plasticity --- phyto buffers --- phyto-recurrent selection --- phytotechnologies --- poplars --- effluent water treatment --- short rotation coppice willow --- irrigation --- growth response --- biomass crops --- mineral content --- tree growth --- tree biomass --- volume forest stand --- thickness classes --- clonal selection --- genotype × environment (G × E) interactions --- evapotranspirative willow system --- resource recovery --- sustainable wastewater treatment --- oil sands reclamation --- end-pit lake --- balsam poplar --- salt tolerance --- Populus sp. --- bioenergy --- SRC --- financial analysis --- break-even-point --- net present value --- proof-of-concept: use case --- spreadsheet --- CSV file --- SQL --- database --- data integrity --- GitHub --- Linux --- poplar --- salt stress --- gene expression analyses --- radical scavenger capacity --- osmolytes --- cottonwood leaf beetle (Chrysomela scripta) --- stand density --- fertilizer application --- soil quality --- Melampsora rust --- energy crops --- land use --- reed canary grass (RCG) --- Phalaris arundinacea L. --- n/a

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