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Search Results: 1 - 10 of 726 matches for " Elke Ericson "
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Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast
Elke Ericson,Marinella Gebbia,Lawrence E. Heisler,Jan Wildenhain,Mike Tyers,Guri Giaever,Corey Nislow
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000151
Abstract: To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes.
Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action
Maureen E Hillenmeyer, Elke Ericson, Ronald W Davis, Corey Nislow, Daphne Koller, Guri Giaever
Genome Biology , 2010, DOI: 10.1186/gb-2010-11-3-r30
Abstract: Yeast competitive fitness data constitute a unique, genome-wide assay of the cellular response to environmental and chemical perturbations [1-8]. Here, we systematically analyzed the largest fitness dataset available, comprising measurements of the growth rates of barcoded, pooled deletion strains in the presence of over 400 unique perturbations [1] and show that the dataset reveals novel aspects of cellular physiology and provides a valuable resource for systems biology. In the haploinsufficiency profiling (HIP) assay consisting of all 6,000 heterozygous deletions (where one copy of each gene is deleted), most strains (97%) grow at the rate of wild type [9] when assayed in parallel. In the presence of a drug, the strain deleted for the drug target is specifically sensitized (as measured by a decrease in growth rate) as a result of a further decrease in 'functional' gene dosage by the drug binding to the target protein. In this way, fitness data allow identification of the potential drug target [3,4,10]. In the homozygous profiling (HOP) assay (applied to non-essential genes), both copies of the gene are deleted in a diploid strain to produce a complete loss-of-function allele. This assay identifies genes required for growth in the presence of compound, often identifying functions that buffer the drug target pathway [5-8].The field of functional genomics aims to predict gene functions using high-throughput datasets that interrogate functional genetic relationships. To address the value of fitness data as a resource for functional genomics, we asked how well co-fitness (correlated growth of gene deletion strains in compounds) predicts gene function compared to other large-scale datasets, including co-expression, protein-protein interactions, and synthetic lethality [11-13]. Interestingly, co-fitness predicts cellular functions not evident in these other datasets. We also investigated the theory that genes are essential because they belong to essential complexes [14,1
The Recollection of Morning Sickness and Their Support System as Documented by Women Post Pregnancy  [PDF]
Hanna Ericson, Malin Sunnergren, Annsofie Adolfsson
Advances in Sexual Medicine (ASM) , 2013, DOI: 10.4236/asm.2013.34011
Abstract: Nausea during pregnancy affects about ten percent of all pregnant women. The causes of nausea and vomiting during pregnancy are unclear. The condition can lead to dehydration, electrolyte derangement, impaired organ function and lead to serious health issues or even death if left untreated. The treatment conducted today is symptomatic and is not completely satisfactory. Objective: The purpose of the study was to describe women’s experience of morning sickness and their experience of support. Design: Data was collected through a semi-structured questionnaire and analyzed by qualitative content analysis. Participants: Nine women responded to the survey. Results: The result shows that women who suffer from morning sickness during pregnancy feel a loss of control over their lives which has a significant impact on their mental and physical health making it difficult to function normally. Feelings of isolation, loneliness and alienation are common. It is essential that midwives are attentive in order to provide the help and support that these women require. Conclusion: It is essential that the personnel providing the care are knowledgeable about the condition. More research is necessary to find the root cause of the condition in order to develop effective strategies for treatment.
Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells
Lisa Yu equal contributor,Andres Lopez equal contributor,Abderrahmane Anaflous,Brahim El Bali,Abdellah Hamal,Elke Ericson,Lawrence E. Heisler,Angus McQuibban,Guri Giaever,Corey Nislow,Charles Boone,Grant W. Brown ,Mohammed Bellaoui
PLOS Genetics , 2008, DOI: 10.1371/journal.pgen.1000284
Abstract: Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships.
Pion and neutron production by cosmic-ray muons underground
Jean Delorme,Magda Ericson,Torleif Ericson
Physics , 1995, DOI: 10.1103/PhysRevC.52.2222
Abstract: The production of positive pions and neutrons by cosmic muons at underground sites of various depths is investigated. We first test the equivalent photon method in the particular case of $\Delta$ excitation by the muon. We find that this method, when it neglects the momentum dependence of the transverse response, reproduces remarkably well the theoretical muon cross-section. This success has lead us to apply the method to higher energies, where it has not been tested. We evaluate in this way the production of positive pions in liquid scintillator from known photo-absorption cross-sections. At a shallow depth of 20 meters our estimate reproduces the measurement. As for the neutron emission, we include the obvious sources, such as the giant-resonance excitation, the quasi-deuteron process, the quasi- free pion production as well as neutrons emitted following pion capture. Our evaluation underestimates the number of neutrons produced and finds a too weak dependence on the depth. This suggests that secondary neutron production is important at all depths.
História ocupacional
Bagatin, Ericson;Kitamura, Satoshi;
Jornal Brasileiro de Pneumologia , 2006, DOI: 10.1590/S1806-37132006000800004
Abstract: just as a complete patient history is fundamental to making any diagnosis, the history of environmental exposure in the workplace forms the informational base needed in order to understand occupational respiratory diseases. it is estimated that 20% of all cases of interstitial or airway disease are related to such exposure. however, information regarding potential environmental exposure is rarely included in the patient history, nor is job/occupation/function taken into consideration. therefore, this theme has become pivotal to the discussion among health care professionals working in this area, who must decide whether evaluating and estimating the magnitude of this problem are truly desirable goals.
Visual Odometry System for Agricultural Field Robots
Stefan Ericson,Bjorn Astrand
Lecture Notes in Engineering and Computer Science , 2008,
A Pintura como um Paradigma da Percep o
Ericson Sávio Falabretti
DoisPontos , 2012,
Abstract: The reflections on the paint across the whole itinerary of the work of Merleau-Ponty and seem to indicate the reasons for the movement and the unity of his thought, especially when we seek to understand the scope of perception as a significant pre-reflective event. The experience of perception is radicalized on painting that express a “primordial level” - "leads to their last power is a delusion that same vision" - with all the charactersthat phenomenology sought to achieve in describing the different forms of perceptive experience, is through the description of pre-reflective experience of the body itself or, finally, the conception of perceptual faith as a "donation in flesh." The painting holds the most genuine intention of a philosophy dedicated to the description of the pre-reflective, and asks the witness to be. The painter, as indicated by the analysis of Cezanne, the original remains in the soil, without the need for justification or foundation, free of the obligation to announce a thesis or a convention on the world, expressed the significance of the crudest sense: what makes the visible visible.
Merleau-Ponty: o sentido e o uso da no o de estrutura
Ericson Savio Falabretti
DoisPontos , 2008,
Abstract: This work discusses the reach of the considerations of Merleau-Ponty for a formulation of a theory of the behavior. We sought, before everything, to show in that felt Merleau-Ponty refuses the interpretations of the schools intellectual and empirical about the behavior. Then, in a second moment, having in view the current problems of those classic theories, we pointed the foundations to a phenomenological description of the behavior: mainly from the structure notion. We look for, also, to establish the genealogy, the different uses and sense of the term structure in human sciences, especially for the GestaltPsychology. Finally, we argue the direction given for Merleau-Ponty to the term structure and as this notion became possible a phenomenological reading of the behavior.
Ericson Saint Clair
Brazilian Journalism Research , 2012,
Abstract: We investigate evidence of the cultural construction of depression in Brazilian media. To this end, we have explored its definition as a journalistic subject by examining the corpus of research materials from Folha Group’s newspapers, especially Folha de S. Paulo, over the past forty years. Our approach to the news archives has allowed us to outline four main strategic regions of discourse production, revealed and exemplified in the article. Based on these observations, we have advocated a new perspective for the analysis of the press’s role in publishing materials for dissemination of scientific research regarding depression. We will interpret its role not simply as the automatic disseminator of scientific truth, but as the explorer of a gray area of the field of opinion, regarded as a representation of the rubble of circulating knowledge, where what is at stake is the production of the current nature itself of the disorder.
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