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Search Results: 1 - 10 of 1864 matches for " Bertrand Daignan-Fornier "
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5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-Monophosphate (AICAR), a Highly Conserved Purine Intermediate with Multiple Effects
Bertrand Daignan-Fornier,Beno?t Pinson
Metabolites , 2012, DOI: 10.3390/metabo2020292
Abstract: AICAR (5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranosyl 5'-monophosphate) is a natural metabolic intermediate of purine biosynthesis that is present in all organisms. In yeast, AICAR plays important regulatory roles under physiological conditions, notably through its direct interactions with transcription factors. In humans, AICAR accumulates in several metabolic diseases, but its contribution to the symptoms has not yet been elucidated. Further, AICAR has highly promising properties which have been recently revealed. Indeed, it enhances endurance of sedentary mice. In addition, it has antiproliferative effects notably by specifically inducing apoptosis of aneuploid cells. Some of the effects of AICAR are due to its ability to stimulate the AMP-activated protein kinase but some others are not. It is consequently clear that AICAR affects multiple targets although only few of them have been identified so far. This review proposes an overview of the field and suggests future directions.
Proliferation/Quiescence: When to start? Where to stop? What to stock?
Bertrand Daignan-Fornier, Isabelle Sagot
Cell Division , 2011, DOI: 10.1186/1747-1028-6-20
Abstract: The restriction point is defined as a point in G1 phase of the cell cycle after which cells are committed to cell division [1]. Indeed, it is commonly accepted that once cells have passed this point, they proceed through all the phases of the cell cycle until completion, i.e. until they reach the restriction point again. But cells may individually "decide" to engage themselves in another round of cell division or enter a non-dividing state. This non-dividing state may be non-reversible (senescence, apoptosis...) or, alternatively, cells can enter quiescence, a cellular state defined as a temporary and reversible absence of proliferation. In all cases, it is thought that cells integrate a combination of external and internal signals before committing to the cell division cycle. In multi-cellular eukaryotes, external signals emanate from the entire organism. These extremely complex physiological conditions are difficult to reproduce in a laboratory. By contrast, in single cell eukaryotes like budding yeast, these external cues can be easily monitored since entry into-and exit from the cell cycle apparently rely solely on nutrient availability in the growth medium. As mammalian cells, yeast cells, once they have passed a point called Start (originally defined as a point in G1 after which cells are resistant to mating pheromone [2]) are committed to proceed through all the phases of the cell cycle until G1 [3].The molecular nature of Start has been extensively investigated and a fair amount of key proteins, including cyclins and cyclin-dependent kinases, together with crucial signalling networks have been discovered. However, in yeast, as in metazoa, how these regulators integrate external and internal signals to trigger either the re-entry into the cell cycle or the transition to non-dividing cellular states remains largely mysterious.Recently, using budding yeast as a model organism, transitions from proliferation to quiescence have been revisited by means of several
Proliferation/quiescence: the controversial "aller-retour"
Bertrand Daignan-Fornier, Isabelle Sagot
Cell Division , 2011, DOI: 10.1186/1747-1028-6-10
Abstract: Quiescence is the most common cellular state on earth. While it is relatively easy to describe a proliferating cell, defining a quiescent cell is rather difficult. A commonly accepted, yet highly operational, definition of quiescence is "a reversible absence of proliferation". Consequently, a cell that is not dividing but eventually will when conditions become appropriate, is considered as a bona fide quiescent cell. But this definition is rather vague and probably encompasses various cellular situations. Therefore, instead of a single quiescent state, one can imagine that there may be distinct quiescent states depending on the cell's history before entry into quiescence, and/or depending on the time spent in quiescence (early quiescence, deep quiescence..., see Figure 1). This raises the delicate question of the existence of a quiescence "program". In other words, does quiescence result from a dedicated gene expression pattern that commits cells to the quiescent state or is quiescence an ultimate form of slow growth which would be a passive consequence of a cell's adaptation to unfavorable external conditions?One major problem for studying quiescence comes from the fact that in multi-cellular organisms, environmental signals that control quiescence emanate from the entire organism - conditions that are difficult to reproduce in a lab. By contrast, in single cell eukaryotes like budding yeast, quiescence entry and exit are solely conditioned by nutrient availability. Using this model, the nature of proliferation/quiescence transitions has recently been revisited.Budding yeast is THE model in which genetics has proven its power, and not surprisingly, using this organism, several genetic approaches have been developed in order to identify a dedicated mechanism that drives cells into quiescence. Many mutants were found to be specifically sensitive to one nutrient limitation [1-5], but only very few of them died upon all the starvation conditions tested [1,2]. At the pr
Polarized Growth in the Absence of F-Actin in Saccharomyces cerevisiae Exiting Quiescence
Annelise Sahin, Bertrand Daignan-Fornier, Isabelle Sagot
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002556
Abstract: Background Polarity establishment and maintenance are crucial for morphogenesis and development. In budding yeast, these two intricate processes involve the superposition of regulatory loops between polarity landmarks, RHO GTPases, actin-mediated vesicles transport and endocytosis. Deciphering the chronology and the significance of each molecular step of polarized growth is therefore very challenging. Principal Findings We have taken advantage of the fact that yeast quiescent cells display actin bodies, a non polarized actin structure, to evaluate the role of F-actin in bud emergence. Here we show that upon exit from quiescence, actin cables are not required for the first steps of polarized growth. We further show that polarized growth can occur in the absence of actin patch-mediated endocytosis. We finally establish, using latrunculin-A, that the first steps of polarized growth do not require any F-actin containing structures. Yet, these structures are required for the formation of a bona fide daughter cell and cell cycle completion. We propose that upon exit from quiescence in the absence of F-actin, secretory vesicles randomly reach the plasma membrane but preferentially dock and fuse where polarity cues are localized, this being sufficient to trigger polarized growth.
Guanylic nucleotide starvation affects Saccharomyces cerevisiae mother-daughter separation and may be a signal for entry into quiescence
Isabelle Sagot, Jacques Schaeffer, Bertrand Daignan-Fornier
BMC Cell Biology , 2005, DOI: 10.1186/1471-2121-6-24
Abstract: To gain insight into the molecular relationships connecting intracellular guanylic nucleotide levels and cellular proliferation, we have studied the consequences of guanylic nucleotide limitation on Saccharomyces cerevisiae cell cycle progression. We first utilized mycophenolic acid, an immunosuppressive drug that specifically inhibits inosine monophosphate dehydrogenase, the enzyme catalyzing the first committed step in de novo GMP biosynthesis. To approach this system physiologically, we next developed yeast mutants for which the intracellular guanylic nucleotide pools can be modulated through changes of growth conditions. In both the pharmacological and genetic approaches, we found that guanylic nucleotide limitation generated a mother-daughter separation defect, characterized by cells with two unseparated daughters. We then showed that this separation defect resulted from cell wall perturbations but not from impaired cytokinesis. Importantly, cells with similar separation defects were found in a wild type untreated yeast population entering quiescence upon nutrient limitation.Our results demonstrate that guanylic nucleotide limitation slows budding yeast cell cycle progression, with a severe pause in telophase. At the cellular level, guanylic nucleotide limitation causes the emergence of cells with two unseparated daughters. By fluorescence and electron microscopy, we demonstrate that this phenotype arises from defects in cell wall partition between mother and daughter cells. Because cells with two unseparated daughters are also observed in a wild type population entering quiescence, our results reinforce the hypothesis that guanylic nucleotide intracellular pools contribute to a signal regulating both cell proliferation and entry into quiescence.Guanylic nucleotides are critical for multiple crucial cellular processes such as replication, transcription, translation and signalization via small GTPases. Most cell types recycle GMP from guanosine or guanine, which
The yeast ISN1 (YOR155c) gene encodes a new type of IMP-specific 5'-nucleotidase
Roichi Itoh, Christelle Saint-Marc, Stéphane Chaignepain, Riko Katahira, Jean-Marie Schmitter, Bertrand Daignan-Fornier
BMC Biochemistry , 2003, DOI: 10.1186/1471-2091-4-4
Abstract: Mass spectrometry analysis of several peptides of this enzyme purified from yeast allowed identification of the corresponding gene as YOR155c, an open reading frame of unknown function, renamed ISN1. The deduced Isn1p sequence was clearly not homologous to 5'-nucleotidases from other species. However, significant similarities to Isn1p were found in proteins of unknown function from Neurospora crassa, Plasmodium falciparum and several yeast species. Knock-out of ISN1 resulted in the total loss of IMP-specific 5'-nucleotidase activity, thus confirming that the ISN1 gene indeed encodes the enzymatic activity purified from yeast. In vivo studies revealed that, when IMP is overproduced through constitutive activation of the IMP de novo synthesis pathway, ISN1 is required for excretion of inosine and hypoxanthine in the medium.We have identified a new yeast gene, ISN1 (YOR155c), as encoding IMP-specific 5'-nucleotidase activity. The ISN1 gene defines a new type of 5'-nucleotidase which was demonstrated to be functional in vivo.Purine salvage pathway allows interconversion of bases, nucleosides and nucleotides. Importance of this pathway in humans has been clearly established since several defects in purine salvage enzymes have been associated to pathologies such as mental retardation and severe immunodeficiencies [1,2]. In yeast, mutations in several purine salvage genes lead to deregulation of AMP biosynthesis [3] and purine excretion. Taking advantage of complete genome sequencing of Saccharomyces cerevisiae we were able to identify several new purine salvage genes such as adenosine kinase or purine nucleoside phosphorylase [4,5] which are highly homologous to their mammalian counterpart. Strikingly, no 5'-nucleotidase encoding gene could be inferred from comparison of the completely sequenced yeast genome with 5'-nucleotidase genes from other species, although several lines of evidence argued for the presence of 5'-nucleotidase in yeast. First, an IMP-specific 5'-nucle
Leading from the Middle: Innovation as a Grassroots Effort
Lisa Fornier
Strategic Leadership Review , 2011,
Abstract: Innovation is the creative process of design, development and implementation of new products, processes or services to improve efficiency, effectiveness, or to build a differentiator for sustainable competitive advantage. Innovation insists on disrupting the market, industry, and organization, spawning change and disturbing the status quo. Innovation requires a strategic approach of thinking and planning throughout the organization, facilitated by strategic leaders and embraced within the ecosystem of stakeholders. A cursory glance across the Internet for “innovation organization” provides the reader tens of millions of possible links to companies promoting their claim to being “innovative.” Gaining insight on innovation in an organization requires in-depth investigation into the perceptions of the people and underlying frameworks of the organization. This article is a qualitative research study with three director-level learning leaders who embrace strategy in an innovation-promoting organization. The study explores essential strategic components, including: 1) vision-sharing, 2) diversity, 3) knowledge management, 4) innovation programs, and 5) communication to determine if and how these leaders embrace strategic thinking, strategic planning, and socio-technical systems to foster an innovative culture.
Dose-dense adjuvant chemotherapy for primary breast cancer
Monica Fornier, Larry Norton
Breast Cancer Research , 2005, DOI: 10.1186/bcr1007
Abstract: Breast cancer is the most commonly diagnosed form of cancer and is the second most common cause of cancer-related death in women, both in Europe and in the USA. It was estimated that in the year 2004 about 40,100 patients would die from metastatic breast carcinoma in the USA [1,2]. Although increased patient awareness and improved screening techniques (including mammography, ultrasound, and breast magnetic resonance imaging) now permit early detection of localized and resectable tumors, many women still die from recurrent breast carcinoma, suggesting that a substantial number of patients already have distant micrometastasis at the time of diagnosis. With time, a significant number of patients will develop metastatic disease, even after seemingly curative surgery and radiotherapy. Systemic adjuvant chemotherapy for early-stage breast cancer is utilized to eradicate microscopic deposits of cancer cells that may have spread or metastasized from the primary breast cancer, and so it is recommended in large groups of patients to prevent or delay progression, based on risk assessment.In the 1990s, the Early Breast Cancer Trialists' Collaborative Group published overviews, consolidating data from the randomized trials using meta-analytical techniques. This methodology has the advantage of being able to combine data from many small under-powered trials, consideration of the individual results from which might have led to negative or positive conclusions [3]. Adjuvant chemotherapy has been proven to reduce significantly the risk for relapse and death in women with operable breast cancer, and therapy with anthracycline-containing regimens has been shown to confer a small but significant benefit over the classic CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) combinations (Table 1). The most recent Early Breast Cancer Trialists' Collaborative Group meta-analysis [3] showed reductions in the annual hazard rate for recurrence and death of 23.5% and 14.3%, respectively. H
Minimum Penalized Hellinger Distance for Model Selection in Small Samples  [PDF]
Papa Ngom, Bertrand Ntep
Open Journal of Statistics (OJS) , 2012, DOI: 10.4236/ojs.2012.24045
Abstract: In statistical modeling area, the Akaike information criterion AIC, is a widely known and extensively used tool for model choice. The φ-divergence test statistic is a recently developed tool for statistical model selection. The popularity of the divergence criterion is however tempered by their known lack of robustness in small sample. In this paper the penalized minimum Hellinger distance type statistics are considered and some properties are established. The limit laws of the estimates and test statistics are given under both the null and the alternative hypotheses, and approximations of the power functions are deduced. A model selection criterion relative to these divergence measures are developed for parametric inference. Our interest is in the problem to testing for choosing between two models using some informational type statistics, when independent sample are drawn from a discrete population. Here, we discuss the asymptotic properties and the performance of new procedure tests and investigate their small sample behavior.
Relativistic Gauge Invariant Wave Equation of the Electron-Neutrino  [PDF]
Claude Daviau, Jacques Bertrand
Journal of Modern Physics (JMP) , 2014, DOI: 10.4236/jmp.2014.511102
Abstract:

With the right and the left waves of an electron, plus the left wave of its neutrino, we write the tensorial densities coming from all associations of these three spinors. We recover the wave equation of the electro-weak theory. A new non linear mass term comes out. The wave equation is form invariant, then relativistic invariant, and it is gauge invariant under the U(1)×SU(2), Lie group of electro-weak interactions. The invariant form of the wave equation has the Lagrangian density as real scalar part. One of the real equations equivalent to the invariant form is the law of conservation of the total current.

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