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11.
Thibaut Crepin Vyacheslav F. Shalak Anna D. Yaremchuk Dmytro O. Vlasenko Andrew McCarthy Boris S. Negrutskii Michail A. Tukalo Anna V. El'skaya 《Nucleic acids research》2014,42(20):12939-12948
Eukaryotic elongation factor eEF1A transits between the GTP- and GDP-bound conformations during the ribosomal polypeptide chain elongation. eEF1A*GTP establishes a complex with the aminoacyl-tRNA in the A site of the 80S ribosome. Correct codon–anticodon recognition triggers GTP hydrolysis, with subsequent dissociation of eEF1A*GDP from the ribosome. The structures of both the ‘GTP’- and ‘GDP’-bound conformations of eEF1A are unknown. Thus, the eEF1A-related ribosomal mechanisms were anticipated only by analogy with the bacterial homolog EF-Tu. Here, we report the first crystal structure of the mammalian eEF1A2*GDP complex which indicates major differences in the organization of the nucleotide-binding domain and intramolecular movements of eEF1A compared to EF-Tu. Our results explain the nucleotide exchange mechanism in the mammalian eEF1A and suggest that the first step of eEF1A*GDP dissociation from the 80S ribosome is the rotation of the nucleotide-binding domain observed after GTP hydrolysis. 相似文献
12.
We used simulated data to investigate a number of properties of maximum-
likelihood (ML) phylogenetic tree estimation for the case of four taxa.
Simulated data were generated under a broad range of conditions, including
wide variation in branch lengths, differences in the ratio of transition
and transversion substitutions, and the absence of presence of
gamma-distributed site-to-site rate variation. Data were analyzed in the ML
framework with two different substitution models, and we compared the
ability of the two models to reconstruct the correct topology. Although
both models were inconsistent for some branch-length combinations in the
presence of site-to-site variation, the models were efficient predictors of
topology under most simulation conditions. We also examined the performance
of the likelihood ratio (LR) test for significant positive interior branch
length. This test was found to be misleading under many simulation
conditions, rejecting too often under some simulation conditions. Under the
null hypothesis of zero length internal branch, LR statistics are assumed
to be asymptotically distributed chi 2(1); with limited data, the
distribution of LR statistics under the null hypothesis varies from chi
2(1).
相似文献
13.
Tian-Yi?Chi George?G?Chen Lok-Kee?Ho Paul?BS?LaiEmail author 《Cancer cell international》2005,5(1):27
p53 is important in the development of hepatocellular carcinoma (HCC) and in therapeutic approaches, but the mechanism whereby
it inhibits HCC growth is still unclear. The aim of the present study was to establish a HCC cell system in which p53 levels
can be regulated. Full-length wild-type p53 cDNA obtained by PCR was cloned into a retroviral response vector controlled by
the tetracycline responsive element (RevTRE-p53). The regulatory vectors RevTet-Off and RevTRE-p53 were transfected into a
packaging cell line, PT67. Hep3B cells in which the p53 gene was deleted were infected with RevTet-Off viral particles from
the PT67. Three G418-resistant cell clones with high luciferase expression and low background were infected with RevTRE-p53.
By screening dozens of RevTRE-p53-infected clones with hygromycin we identified the one with the highest expression of p53
and the lowest background after doxycycline treatment. The results showed that p53 expression in this cell clone could be
simply turned on or off by removing or adding doxycycline. Furthermore, it was found that the level of p53 protein was negatively
and sensitively related to the doxycycline concentration. In conclusion, we have established a HCC cell line in which p53
expression can be switched on or off and regulated in a dose- and time-dependent manner. 相似文献
14.
Likelihood-ratio statistics are proposed to test for heterogeneity in
nucleotide substitution rate among regions of a DNA sequence. The tests
examine three-sequence phylogenies, and two specific tests are proposed: a
test to detect rate heterogeneity among genic regions within a sequence,
over all evolutionary lineages; and a test to detect rate heterogeneity
among regions in a specific evolutionary lineage. Simulations examine the
ability of tests to detect a single region that varies in nucleotide
substitution rate relative to the remainder of the sequence. A 50-bp region
with a fivefold substitution-rate increase can be detected > or = 90% of
the time when it is found in all three lineages of the phylogeny, and a
50-bp region of fivefold rate increase can be detected with approximately
70% power when it is found in only one evolutionary lineage. Simulation
also examines the effect of transition- and transversion-rate differences.
The tests are applied to published DNA sequences. While the tests are
powerful, significant results can be difficult to interpret biologically.
相似文献
15.
16.
Niels de Fine Olivarius Volkert Siersma Anni BS Nielsen Lars J Hansen Lotte Rosenvinge Carl Erik Mogensen 《BMC endocrine disorders》2010,10(1):1-12
Background
At diabetes diagnosis major decisions about life-style changes and treatments are made based on characteristics measured shortly after diagnosis. The predictive value for mortality of these early characteristics is widely unknown. We examined the predictive value of patient characteristics measured shortly after diabetes diagnosis for 5-year all-cause and cardiovascular mortality with special reference to self-rated general health.Methods
Data were from a population-based sample of 1,323 persons newly diagnosed with clinical diabetes and aged 40 years or over. Possible predictors of mortality were investigated in Cox regression models.Results
Multivariately patients who rated their health less than excellent experienced increased all-cause and cardiovascular mortality. These end-points also increased with sedentary life-style, relatively young age at diagnosis and presence of cardiovascular disease (CVD) at diagnosis. Further predictors of all-cause mortality were male sex, low body mass index and cancer, while cardiovascular mortality increased with urinary albumin concentration.Conclusions
We found that patients who rated their health as less than excellent had increased 5-year mortality, similar to that of patients with prevalent CVD, even when biochemical, clinical and life-style variables were controlled for. This finding could motivate doctors to discuss perceptions of health with newly diagnosed diabetic patients and be attentive to patients with suboptimal health ratings. Our findings also confirm that life-style changes and optimizing treatment are particularly relevant for relatively young and inactive patients and those who already have CVD or (micro)albuminuria at the time of diabetes diagnosis. 相似文献17.
Background: In the past, type 2 diabetes mellitus (DM) was regarded as a progressive, incurable disease for which palliative therapy could not, over the long term, prevent the associated amputations, blindness, renal failure, and early mortality. This is no longer true. Full and durable remission of type 2 DM, with major decreases in morbidity and mortality, is now achieved regularly with several types of surgery that reduce contact between food and the foregut.Objectives: The aims of this article are to review the impact of bariatric surgery on obesity, remission of DM, and obesity-related morbidity and mortality, and the possible mechanisms for this advance.Methods: This article is based on our 2 meta-analyses of the literature published through April 30, 2006, as well as the most significant reports in the bariatric surgical literature that have been published in English since April 30, 2006. The studies included in our second meta-analysis provided the details of the methodology for the present literature review, including the levels of evidence.Results: Results of our 2 meta-analyses were published previously. Briefly, the analyses revealed that the clinical and laboratory manifestations of type 2 DM resolved or improved in most of the patients who underwent bariatric surgery; the responses were greatest in the patients who lost the most excess body weight; and the improvements were maintained for ≥2 years. The studies reported that intestinal operations such as gastric bypass reduced contact between food and the foregut, produced full and durable remission of DM, reduced mortality, and reversed other comorbidities associated with severe obesity (eg, asthma, gastroesophageal reflux, hypertension, stress incontinence). Insulin levels decreased markedly after surgery, as did glycosylated hemoglobin (A1C) and fasting blood glucose levels. Although these effects were initially attributed to weight loss, the rapid reversal of DM within a matter of days after surgery suggest that bariatric surgery changes the signaling mechanism of the gut with pancreatic islet cells, muscles, fat, the liver, and other organs.Conclusions: Bariatric surgery has opened new vistas, producing durable full remission of type 2 DM—a breakthrough previously considered impossible—with normalization of A1C levels over time and discontinuation of all antidiabetes medication for many patients. These advances create new opportunities for exploring the mechanisms of type 2 DM and its control through pharmaceutical approaches. DM is no longer an irreversible, incurable, or hopeless disease. 相似文献
18.
Literature data and authors' results on the structural and functional organization of the translation apparatus in higher eukaryotes are considered. Proofs are presented of the channeling of tRNA/aminoacyl-tRNA in the course of eukaryotic protein synthesis. The concept of the shuttle role of eEF1A is grounded; the factor, being in a GTP-bound form, delivers aminoacyl-tRNA to the ribosome and then, in the having undergone to a GDP -form after hydrolysis of GTP on the ribosome, forms a complex with the deacylated tRNA and delivers it to the aminoacyl-tRNA synthetase. The notion of a translational compartment is defined. 相似文献
19.
Background
We present an analysis of the utility of multispectral versus standard RGB imagery for routine H&;E stained histopathology images, in particular for pixel-level classification of nuclei. Our multispectral imagery has 29 spectral bands, spaced 10 nm within the visual range of 420–700 nm. It has been hypothesized that the additional spectral bands contain further information useful for classification as compared to the 3 standard bands of RGB imagery. We present analyses of our data designed to test this hypothesis.Results
For classification using all available image bands, we find the best performance (equal tradeoff between detection rate and false alarm rate) is obtained from either the multispectral or our "ccd" RGB imagery, with an overall increase in performance of 0.79% compared to the next best performing image type. For classification using single image bands, the single best multispectral band (in the red portion of the spectrum) gave a performance increase of 0.57%, compared to performance of the single best RGB band (red). Additionally, red bands had the highest coefficients/preference in our classifiers. Principal components analysis of the multispectral imagery indicates only two significant image bands, which is not surprising given the presence of two stains.Conclusion
Our results indicate that multispectral imagery for routine H&;E stained histopathology provides minimal additional spectral information for a pixel-level nuclear classification task than would standard RGB imagery.20.
Lewis Landsberg MD Louis J. Aronne MD Lawrence J. Beilin MB BS MD MA Valerie Burke MD Leon I. Igel MD Donald Lloyd‐Jones MD ScM James Sowers MD 《Obesity (Silver Spring, Md.)》2013,21(1):8-24
In light of the worldwide epidemic of obesity, and in recognition of hypertension as a major factor in the cardiovascular morbidity and mortality associated with obesity, The Obesity Society and The American Society of Hypertension agreed to jointly sponsor a position paper on obesity‐related hypertension to be published jointly in the journals of each society. The purpose is to inform the members of both societies, as well as practicing clinicians, with a timely review of the association between obesity and high blood pressure, the risk that this association entails, and the options for rational, evidenced‐based treatment. The position paper is divided into six sections plus a summary as follows: pathophysiology, epidemiology and cardiovascular risk, the metabolic syndrome, lifestyle management in prevention and treatment, pharmacologic treatment of hypertension in the obese, and the medical and surgical treatment of obesity in obese hypertensive patients. Obesity (2012) 相似文献