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1.
Ivana Tonic Wan-Ni Yu Youngku Park Chia-Chen Chen Nissim Hay 《The Journal of biological chemistry》2010,285(31):23790-23798
Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage. 相似文献
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WHO Collaborating Centres (CCs) form part of an international collaborative network set up by WHO in support of its mandated programme at the country, intercountry, regional, interregional and global levels, as appropriate. As part of its mandate in the area of biologicals, WHO has broadened the scope of its work and has expanded the range of activities devoted to the establishment of international standards for vaccines. In line with global immunization goals, the need for standards for evaluation of quality, safety and efficacy of new vaccines, as well as those that have been in use for a long time, has significantly increased. Furthermore, complex issues related to new production methodologies, more sophisticated techniques for characterization and laboratory testing, and for nonclinical and clinical evaluation of vaccines have raised a number of regulatory challenges for WHO when requested to assist its Member States. In this context, CCs in the area of standardization of vaccines and biotherapeutics (excluding blood products) have provided technical assistance and have broadened the scope of their work over time. In the area of standardization and regulatory evaluation of vaccines, WHO currently has six CCs as well as one candidate centre for which the designation process has been initiated and a further three candidate centres with great potential. The purpose of the meeting held on 24–26 April 2012 was to improve understanding of WHO's priorities in setting standards, to facilitate their implementation, and to increase transparency of the roles and responsibilities of CCs. The meeting was also an excellent opportunity to explore possibilities for improving collaboration between WHO and CCs, as well as among CCs themselves by working as a CC network. All CCs expressed a wish for increased interaction, information-sharing, collaboration and other ways of working together that may lead to cross-fertilization between the CCs. Synergy was recognized as a significant mechanism for leveraging existing resources in responding to global public health challenges and in addressing WHO's priorities. Agreement was reached for operating as a network of CCs. 相似文献
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Abstract. Numbers of plant species were recorded in species‐rich meadows in the Bílé Karpaty Mts., SE Czech Republic, with the aim to evaluate the sampling error made by well‐trained observers. Five observers recorded vascular plants in seven plots ranging from 9.8 cm2 to 4 m2 independently and were not time‐limited. In larger plots a discrepancy of 10–20% was found between individual estimates, in smaller plots discrepancy increased to 33%, on average. The gain in observed species richness by combining records of individual observers (in comparison with the mean numbers estimated by single observers) decreased from the smallest plot (27–82% for two to five observers) to the largest one (13–25%). However, after misidentified and suspicious records were eliminated, the gain was much lower and became scale‐independent; two observers added 12% species, on average, and the increase by combining species lists made by three or more observers was negligible (3% more on average). It is concluded that most discrepancies between individual observers were caused by misidentification of rare seedlings and young plants. We suggest that in species‐rich meadows plants should be recorded by at least three observers together and that they should consult all problematic plant specimens together in the field, to minimize errors. 相似文献
6.
Increased p50/p50 NF-κB Activation in Human Papillomavirus Type 6- or Type 11-Induced Laryngeal Papilloma Tissue 下载免费PDF全文
We have observed elevated NF-kappaB DNA-binding activity in nuclear extracts from human papillomavirus type 6- and 11-infected laryngeal papilloma tissues. The predominant DNA-binding species is the p50/p50 homodimer. The elevated NF-kappaB activity could be correlated with a reduced level of cytoplasmic IkappaBbeta and could be associated with the overexpression of p21(CIP1/WAF1) in papilloma cells. Increased NF-kappaB activity and cytoplasmic accumulation of p21(CIP1/WAF1) might counteract death-promoting effects elicited by overexpressed PTEN and reduced activation of Akt and STAT3 previously noted in these tissues. 相似文献
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Pavol Svorc Ivana Bacova Sona Gresova Pavol Svorc Jr. 《Biological Rhythm Research》2017,48(3):343-351
The specific aim of the present study, with respect to dependence on the light–dark (LD) cycle under in vivo conditions in spontaneously breathing rats was to review initial state in electrophysiological parameters that may predict the development of heart rhythm disorders in pentobarbital (40 mg/kg), ketamine–xylazine (100 + 15 mg/kg) and zoletil (30 mg/kg) anaesthetized animals. The study was performed using female Wistar rats that were adaptated to an LD cycle (12 h:12 h). Heart rate, PQ and QT intervals were evaluated for their dependence on the LD cycle. The longest PQ interval duration is under zoletil anaesthesia in the light period and the longest QT interval duration is under ketamine–xylazine anaesthesia in both light periods. We concluded that the most significant predisposition toward the development of ventricular arrhythmias originating from disorders of impulse production and conduction occurred under zoletil anaesthesia in the light period; those resulting from disorders in the dispersion of refractory periods occurred under ketamine–xylazine anaesthesia in both the light periods. 相似文献
9.
Ivana Rosenzweig Matthew J. Kempton William R. Crum Martin Glasser Milan Milosevic Sandor Beniczky Douglas R. Corfield Steven C. Williams Mary J. Morrell 《PloS one》2013,8(12)
The full impact of multisystem disease such as obstructive sleep apnoea (OSA) on regions of the central nervous system is debated, as the subsequent neurocognitive sequelae are unclear. Several preclinical studies suggest that its purported major culprits, intermittent hypoxia and sleep fragmentation, can differentially affect adult hippocampal neurogenesis. Although the prospective biphasic nature of chronic intermittent hypoxia in animal models of OSA has been acknowledged, so far the evidence for increased ‘compensatory’ neurogenesis in humans is uncertain. In a cross-sectional study of 32 patients with mixed severity OSA and 32 non-apnoeic matched controls inferential analysis showed bilateral enlargement of hippocampi in the OSA group. Conversely, a trend for smaller thalami in the OSA group was noted. Furthermore, aberrant connectivity between the hippocampus and the cerebellum in the OSA group was also suggested by the correlation analysis. The role for the ischemia/hypoxia preconditioning in the neuropathology of OSA is herein indicated, with possible further reaching clinical implications. 相似文献
10.
Perennial plant Mentha pulegium L. (pennyroyal, Lamiaceae) can be found in Europe and Mediterranean. In areas where it thrives, M. pulegium is used in nutrition and as medicinal plant. Essential oil of M. pulegium is also a frequent constituent of foods and fragrances, because of mint-like odor. Regarding the use of M. pulegium in traditional medicine and nutrition, as well as fact that essential oils are potential sources of bioactive components, this study was conducted to examine the chemical composition of essential oil of M. pulegium wild growing in Bosnia and Herzegovina and its biological activity. The chemical profile testing was made using GC/MS and GC/FID technique. Potential of cholinesterase inhibition was tested by Ellman's assay. The antioxidant activity was tested by DPPH and FRAP assay. The dominant components in analyzed oil were pulegone 54.4 %, p-menthone 14.0 % and piperitenone 12.8 %. Good antioxidant activity and moderate cholinesterase inhibition potential of tested essential oil indicates to possibility of its use in treatment of diseases related to free radicals, Alzheimer disease and as lipid protecting antioxidant. 相似文献