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《Expert opinion on therapeutic targets》2013,17(11):1249-1266
Introduction: Stathmin is a microtubule-destabilizing phosphoprotein, firstly identified as the downstream target of many signal transduction pathways. Several studies then indicated that stathmin is overexpressed in many types of human malignancies, thus deserving the name of Oncoprotein 18 (Op18). At molecular level, stathmin depolymerizes microtubules by either sequestering free tubulin dimers or directly inducing microtubule-catastrophe. A crucial role for stathmin in the control of mitosis has been proposed, since both its overexpression and its downregulation induce failure in the correct completion of cell division. Accordingly, stathmin is an important target of the main regulator of M phase, cyclin-dependent kinase 1. Areas covered: Recent evidences support a role for stathmin in the regulation of cell growth and motility, both in vitro and in vivo, and indicate its involvement in advanced, invasive and metastatic cancer more than in primary tumors. Expert opinion: Many studies suggest that high stathmin expression levels in cancer negatively influence the response to microtubule-targeting drugs. These notions together with the fact that stathmin is expressed at very low levels in most adult tissues strongly support the use of stathmin as marker of prognosis and as target for novel anti-tumoral and anti-metastatic therapies. 相似文献
905.
Paula S. Mckinley Arlene R. King Peter A. Shapiro Iordan Slavov Yixin Fang Ivy S. Chen Larry D. Jamner Richard P. Sloan 《Psychophysiology》2009,46(4):904-911
This study investigated menstrual cycle phase differences in heart rate (HR) and RR interval variability (RRV) in 49 healthy, premenopausal, eumenorrheic women (age 30.2±6.2 years). HR and RRV were computed from ambulatory 24-h electrocardiogram, collected for up to 6 days, with at least 1 day each during early to midfollicular and midluteal menstrual phases. Phase effects on HR and RRV were assessed using linear mixed effects models with a random intercept to account for the correlation of observations within each subject as well as intrasubject variation. During follicular phase monitoring, women had significantly lower average HR (−2.33 bpm), and higher standard deviation, the root mean squared successive difference, and high frequency (0.04–0.15 Hz) and low frequency (0.15–0.40 Hz) RRV than during the luteal phase. These results provide strong support for the influence of menstrual phase on cardiac autonomic regulation in premenopausal women. 相似文献
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Pradyumna Kumar Mishra Venkata Raghuram Gorantla Nabila Akhtar Priyanka Tamrakar Subodh Kumar Jain Kewal Krishan Maudar 《Environmental and molecular mutagenesis》2009,50(4):328-336
Isocyanates (R? N?C?O), one of the highly reactive industrial intermediates, possess the capability to modulate the bio‐molecules by forming toxic metabolites and adducts which may cause adverse health effects. Some of their toxic degradations have previously been unknown and overlooked; of which, molecular repercussions underlying their genetic hazards upon occupational/accidental exposures still remain as an intricate issue and are hitherto unknown. To assess the genotoxic potential of methyl isocyanate in cultured mammalian cells after in vitro exposure, we performed a study in three different normal cell lines MM55.K (mouse kidney epithelial), B/CMBA.Ov (mouse ovarian epithelial), and NIH/3T3 (primary mouse embryonic fibroblast). Cellular DNA damage response was studied for qualitative phosphorylation states of ATM, γH2AX proteins and quantitative state of p53 phosphorylation; DNA cell cycle analysis and measure of cellular apoptotic index before and after treatment were also investigated. Our results demonstrate that methyl isocyanate by negatively regulating the DNA damage response pathway, might promote cell cycle arrest, and apoptosis in cultured mammalian cells suggestive of causing genetic alterations. We anticipate that these data along with other studies reported in the literature would help to design better approaches in risk assessment of occupational and accidental exposure to isocyanates. We also predict that increasing knowledge on DNA damage‐triggered signaling leading to cell death could provide new strategies for investigating the effects of DNA repair disorders and decreased repair capacity on the toxicity and carcinogenic properties of environmental toxins. Environ. Mol. Mutagen., 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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909.
Ansgar Gruber Till Weber Carolina Río Brtulos Sascha Vugrinec Peter G. Kroth 《Journal of basic microbiology》2009,49(1):58-72
Diatoms contribute a large proportion to the worldwide primary production and are particularly effective in fixing carbon dioxide. Possibly because diatom plastids originate from a secondary endocytobiosis, their cellular structure is more complex and metabolic pathways are rearranged within diatom cells compared to cells containing primary plastids. We annotated genes encoding isozymes of the reductive and oxidative pentose phosphate pathways in the genomes of the centric diatom Thalassiosira pseudonana and the pennate diatom Phaeodactylum tricornutum and bioinformatically inferred their intracellular distribution. Prediction results were confirmed by fusion of selected presequences to Green Fluorescent Protein and expression of these constructs in P. tricornutum. Calvin cycle enzymes for the carbon fixation and reduction of 3‐phosphoglycerate are present in single isoforms, while we found multiple isoenzymes involved in the regeneration of ribulose‐1,5‐bisphosphate. We only identified one cytosolic sedoheptulose‐1,7‐bisphosphatase in both investigated diatoms. The oxidative pentose phosphate pathway seems to be restricted to the cytosol in diatoms, since we did not find stromal glucose‐6‐phosphate dehydrogenase and 6‐phosphogluconolactone dehydrogenase isoforms. However, the two species apparently possess a plastidic phosphogluconolactonase. A 6‐phosphogluconolactone dehydrogenase is apparently plastid associated in P. tricornutum and might be active in the periplastidic compartment, suggesting that this compartment might be involved in metabolic processes in diatoms. Abbreviations: AL: aldolase, ATP: adenosine triphosphate, Chl: Chlorophyll, DIC: Normanski differential interference contrast, ER: endoplasmic reticulum, EST: expressed sequence tag, FBA: fructose‐1,6‐bisphosphate aldolase, FBPase: fructose‐1,6‐bisphosphatase, GAPDH: glycerinaldehyd‐3‐phosphate dehydrogenase, GFP: enhanced Green Fluorescent Protein, GPDH: glucose‐6‐phosphate dehydrogenase, GPI: glucose‐6‐phosphate isomerase, HMM: Hidden Markov Models, JGI: Joint Genome Institute, NADPH: nicotinamide adenine dinucleotide phosphate, NN: Neuronal networks, OPP: oxidative pentose phosphate pathway, PCR: Polymerase Chain Reaction, PGDH: 6‐phosphogluconolactone dehydrogenase, PGK: phosphoglycerate kinase, PGL: phosphogluconolactonase, Phatr2: version 2.0 of the Phaeodactylum tricornutum genome, PRK: phosphoribulokinase, RPE: ribulose‐phosphate epimerase, RPI: ribose‐5‐phosphate isomerase, RuBisCO: ribulose‐1,5‐bisphosphate carboxylase/oxygenase, SBPase: sedoheptulose‐1,7‐bisphosphatase, TAL: transaldolase, Thaps3: version 3.0 of the Thalassiosira pseudonana genome, TKL: transketolase, TPI: triosephosphate isomerase, UGGtransferase: UDP glucose‐starch glycosyl transferase. (© 2009 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim) 相似文献
910.
Alexi I. Goranov Michael Cook Marketa Ricicova Giora Ben-Ari Christian Gonzalez Carl Hansen Mike Tyers Angelika Amon 《Genes & development》2009,23(12):1408-1422
Cell growth is an essential requirement for cell cycle progression. While it is often held that growth is independent of cell cycle position, this relationship has not been closely scrutinized. Here we show that in budding yeast, the ability of cells to grow changes during the cell cycle. We find that cell growth is faster in cells arrested in anaphase and G1 than in other cell cycle stages. We demonstrate that the establishment of a polarized actin cytoskeleton—either as a consequence of normal cell division or through activation of the mating pheromone response—potently attenuates protein synthesis and growth. We furthermore show by population and single-cell analysis that growth varies during an unperturbed cell cycle, slowing at the time of polarized growth. Our study uncovers a fundamental relationship whereby cell cycle position regulates growth. 相似文献