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61.
David Rheubottom Peter Gow Eytan Avital Eva Jablonka S. Scott C. J. Duncan Cecilia Gatto Trocchi P. C. Lee Lynne E. Miller Dean Falk Kathleen R. Gibson Bernard Rosner W. R. Leonard M. H. Crawford Alex Roche Shumei Sun Mark Harris S. Boinsky P. A. Garber Peter M. Kappeler 《Human Evolution》2003,18(3-4):255-264
62.
Background
In many microarray experiments, analysis is severely hindered by a major difficulty: the small number of samples for which expression data has been measured. When one searches for differentially expressed genes, the small number of samples gives rise to an inaccurate estimation of the experimental noise. This, in turn, leads to loss of statistical power. 相似文献63.
Marilyn Gordon Mohamed El-Kalla Yuewen Zhao Yahya Fiteih Jennifer Law Natalia Volodko Anwar Mohamed Ayman O. S. El-Kadi Lei Liu Jeff Odenbach Aducio Thiesen Christina Onyskiw Haya Abu Ghazaleh Jikyoung Park Sean Bong Lee Victor C. Yu Carlos Fernandez-Patron R. Todd Alexander Eytan Wine Shairaz Baksh 《PloS one》2015,10(6)
64.
A computational study of the Warburg effect identifies metabolic targets inhibiting cancer migration 下载免费PDF全文
Vasiliki Maria Rogkoti Franziska Baenke Vincent C de Boer Christian Frezza Almut Schulze Eytan Ruppin 《Molecular systems biology》2014,10(8)
Over the last decade, the field of cancer metabolism has mainly focused on studying the role of tumorigenic metabolic rewiring in supporting cancer proliferation. Here, we perform the first genome‐scale computational study of the metabolic underpinnings of cancer migration. We build genome‐scale metabolic models of the NCI‐60 cell lines that capture the Warburg effect (aerobic glycolysis) typically occurring in cancer cells. The extent of the Warburg effect in each of these cell line models is quantified by the ratio of glycolytic to oxidative ATP flux (AFR), which is found to be highly positively associated with cancer cell migration. We hence predicted that targeting genes that mitigate the Warburg effect by reducing the AFR may specifically inhibit cancer migration. By testing the anti‐migratory effects of silencing such 17 top predicted genes in four breast and lung cancer cell lines, we find that up to 13 of these novel predictions significantly attenuate cell migration either in all or one cell line only, while having almost no effect on cell proliferation. Furthermore, in accordance with the predictions, a significant reduction is observed in the ratio between experimentally measured ECAR and OCR levels following these perturbations. Inhibiting anti‐migratory targets is a promising future avenue in treating cancer since it may decrease cytotoxic‐related side effects that plague current anti‐proliferative treatments. Furthermore, it may reduce cytotoxic‐related clonal selection of more aggressive cancer cells and the likelihood of emerging resistance. 相似文献
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Lisa Kish Naomi Hotte Gilaad G. Kaplan Renaud Vincent Robert Tso Michael G?nzle Kevin P. Rioux Aducio Thiesen Herman W. Barkema Eytan Wine Karen L. Madsen 《PloS one》2013,8(4)
Background
Particulate matter (PM) is a key pollutant in ambient air that has been associated with negative health conditions in urban environments. The aim of this study was to examine the effects of orally administered PM on the gut microbiome and immune function under normal and inflammatory conditions.Methods
Wild-type 129/SvEv mice were gavaged with Ottawa urban PM10 (EHC-93) for 7–14 days and mucosal gene expression analyzed using Ingenuity Pathways software. Intestinal permeability was measured by lactulose/mannitol excretion in urine. At sacrifice, segments of small and large intestine were cultured and cytokine secretion measured. Splenocytes were isolated and incubated with PM10 for measurement of proliferation. Long-term effects of exposure (35 days) on intestinal cytokine expression were measured in wild-type and IL-10 deficient (IL-10−/−) mice. Microbial composition of stool samples was assessed using terminal restriction fragment length polymorphism. Short chain fatty acids were measured in caecum.Results
Short-term treatment of wild-type mice with PM10 altered immune gene expression, enhanced pro-inflammatory cytokine secretion in the small intestine, increased gut permeability, and induced hyporesponsiveness in splenocytes. Long-term treatment of wild-type and IL-10−/− mice increased pro-inflammatory cytokine expression in the colon and altered short chain fatty acid concentrations and microbial composition. IL-10−/− mice had increased disease as evidenced by enhanced histological damage.Conclusions
Ingestion of airborne particulate matter alters the gut microbiome and induces acute and chronic inflammatory responses in the intestine. 相似文献68.
Gorshtein A Strenov Y Mor E Shimon I Grozinsky-Glasberg S 《Neuro endocrinology letters》2011,32(6):735-740
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have been rarely reported in patients with Crohn's disease, being usually small and incidentally detected in areas uninvolved by the inflammatory process. We describe the case of a young female patient with Crohn's disease and a fulminant Cushing's syndrome induced by the ectopic secretion of adrenocorticotropic hormone (ACTH) by an aggressive gastrointestinal neuroendocrine carcinoma (NEC). Despite a multi-therapeutic approach, including the administration of multiple courses of chemotherapy, hypo-cortisolemic agents, somatostatin analogues, as well as the performance of bilateral adrenal vein embolization followed by bilateral adrenalectomy, patient's condition progressively deteriorated and she died nine months after the diagnosis of NEC due to liver failure. The available literature addressing the possible connection between Crohn's disease and NEC is discussed in detail. 相似文献
69.
Association between translation efficiency and horizontal gene transfer within microbial communities
Tuller T Girshovich Y Sella Y Kreimer A Freilich S Kupiec M Gophna U Ruppin E 《Nucleic acids research》2011,39(11):4743-4755
Horizontal gene transfer (HGT) is a major force in microbial evolution. Previous studies have suggested that a variety of factors, including restricted recombination and toxicity of foreign gene products, may act as barriers to the successful integration of horizontally transferred genes. This study identifies an additional central barrier to HGT-the lack of co-adaptation between the codon usage of the transferred gene and the tRNA pool of the recipient organism. Analyzing the genomic sequences of more than 190 microorganisms and the HGT events that have occurred between them, we show that the number of genes that were horizontally transferred between organisms is positively correlated with the similarity between their tRNA pools. Those genes that are better adapted to the tRNA pools of the target genomes tend to undergo more frequent HGT. At the community (or environment) level, organisms that share a common ecological niche tend to have similar tRNA pools. These results remain significant after controlling for diverse ecological and evolutionary parameters. Our analysis demonstrates that there are bi-directional associations between the similarity in the tRNA pools of organisms and the number of HGT events occurring between them. Similar tRNA pools between a donor and a host tend to increase the probability that a horizontally acquired gene will become fixed in its new genome. Our results also suggest that frequent HGT may be a homogenizing force that increases the similarity in the tRNA pools of organisms within the same community. 相似文献
70.
Bursztyn L Eytan O Jaffa AJ Elad D 《American journal of physiology. Cell physiology》2007,292(5):C1816-C1829
Uterine contractility is generated by contractions of myometrial smooth muscle cells (SMCs) that compose most of the myometrial layer of the uterine wall. Calcium ion (Ca2+) entry into the cell can be initiated by depolarization of the cell membrane. The increase in the free Ca2+ concentration within the cell initiates a chain of reactions, which lead to formation of cross bridges between actin and myosin filaments, and thereby the cell contracts. During contraction the SMC shortens while it exerts forces on neighboring cells. A mathematical model of myometrial SMC contraction has been developed to study this process of excitation and contraction. The model can be used to describe the intracellular Ca2+ concentration and stress produced by the cell in response to depolarization of the cell membrane. The model accounts for the operation of three Ca2+ control mechanisms: voltage-operated Ca2+ channels, Ca2+ pumps, and Na+/Ca2+ exchangers. The processes of myosin light chain (MLC) phosphorylation and stress production are accounted for using the cross-bridge model of Hai and Murphy (Am J Physiol Cell Physiol 254: C99C106, 1988) and are coupled to the Ca2+ concentration through the rate constant of myosin phosphorylation. Measurements of Ca2+, MLC phosphorylation, and force in contracting cells were used to set the model parameters and test its ability to predict the cell response to stimulation. The model has been used to reproduce results of voltage-clamp experiments performed in myometrial cells of pregnant rats as well as the results of simultaneous measurements of MLC phosphorylation and force production in human nonpregnant myometrial cells. cellular calcium control mechanisms; myometrial contractions; myosin light chain phosphorylation 相似文献