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121.
Giordano Mancini Ilda D’Annessa Andrea Coletta Giovanni Chillemi Yves Pommier Mark Cushman Alessandro Desideri 《PloS one》2012,7(12)
Long-duration comparative molecular dynamics simulations of the DNA-topoisomerase binary and DNA-topoisomerase-indenoisoquinoline ternary complexes have been carried out. The analyses demonstrated the role of the drug in conformationally stabilizing the protein-DNA interaction. In detail, the protein lips, clamping the DNA substrate, interact more tightly in the ternary complex than in the binary one. The drug also reduces the conformational space sampled by the protein linker domain through an increased interaction with the helix bundle proximal to the active site. A similar alteration of linker domain dynamics has been observed in a precedent work for topotecan but the molecular mechanisms were different if compared to those described in this work. Finally, the indenoisoquinoline keeps Lys532 far from the DNA, making it unable to participate in the religation reaction, indicating that both short- and long-range interactions contribute to the drug poisoning effect. 相似文献
122.
LL Matos AB Del Giglio CO Matsubayashi ML Farah A Del Giglio MA Pinhal 《Diagnostic pathology》2012,7(1):97
ABSTRACT: BACKGROUND: To distinguish between malignant and benign lesions of the thyroid gland histological demonstration is often required since the fine-needle aspiration biopsy method applied pre-operatively has some limitations. In an attempt to improve diagnostic accuracy, markers using immunocytochemistry and immunohistochemistry techniques have been studied, mainly cytokeratin-19 (CK-19), galectin-3 (Gal-3) and Hector Battifora mesothelial-1 (HBME-1). However, current results remain controversial. The aim of the present article was to establish the diagnostic accuracy of CK-19, Gal-3 and HBME-1 markers, as well as their associations, in the differentiation of malignant and benign thyroid lesions. METHODS: A systematic review of published articles on MEDLINE and The Cochrane Library was performed. After establishing inclusion and exclusion criteria, 66 articles were selected. The technique of meta-analysis of diagnostic accuracy was employed and global values of sensitivity, specificity, area under the summary ROC curve, and diagnostic odds ratio (dOR) were calculated. RESULTS: For the immunohistochemistry technique, the positivity of CK-19 for the diagnosis of malignant thyroid lesions demonstrated global sensitivity of 81% and specificity of 73%; for Gal-3, sensitivity of 82% and specificity of 81%; and for HBME-1, sensitivity of 77% and specificity of 83%. The association of the three markers determined sensitivity of 85%, specificity of 97%, and diagnostic odds ratio of 95.1. Similar results were also found for the immunocytochemistry assay. CONCLUSION: This meta-analysis demonstrated that the three immunomarkers studied are accurate in pre- and postoperative diagnosis of benign and malignant thyroid lesions. Nevertheless, the search for other molecular markers must continue in order to enhance this diagnostic accuracy since the results found still show a persistency of false-negative and false-positive tests.Virtual slidesHttp://www.diagnosticpathology.diagnomx.eu/vs/3436263067345159. 相似文献
123.
Mendes AI Matos P Moniz S Luz S Amaral MD Farinha CM Jordan P 《Molecular and cellular biology》2011,31(19):4076-4086
Members of the WNK (with-no-lysine [K]) subfamily of protein kinases regulate various ion channels involved in sodium, potassium, and chloride homeostasis by either inducing their phosphorylation or regulating the number of channel proteins expressed at the cell surface. Here, we describe findings demonstrating that the cell surface expression of the cystic fibrosis transmembrane conductance regulator (CFTR) is also regulated by WNK4 in mammalian cells. This effect of WNK4 is independent of the presence of kinase and involves interaction with and inhibition of spleen tyrosine kinase (Syk), which phosphorylates Tyr512 in the first nucleotide-binding domain 1 (NBD1) of CFTR. Transfection of catalytically active Syk into CFTR-expressing baby hamster kidney cells reduces the cell surface expression of CFTR, whereas that of WNK4 promotes it. This is shown by biotinylation of cell surface proteins, immunofluorescence microscopy, and functional efflux assays. Mutation of Tyr512 to either glutamic acid or phenylalanine is sufficient to alter CFTR surface levels. In human airway epithelial cells, downregulation of endogenous Syk and WNK4 confirms their roles as physiologic regulators of CFTR surface expression. Together, our results show that Tyr512 phosphorylation is a novel signal regulating the prevalence of CFTR at the cell surface and that WNK4 and Syk perform an antagonistic role in this process. 相似文献
124.
The red death meets the abdominal bristle: Polygenic mutation for susceptibility to a bacterial pathogen in Caenorhabditis elegans 下载免费PDF全文
Veronique Etienne Erik C. Andersen José Miguel Ponciano Dustin Blanton Analucia Cadavid Joanna Joyner‐Matos Chikako Matsuba Brandon Tabman Charles F. Baer 《Evolution; international journal of organic evolution》2015,69(2):508-519
Understanding the genetic basis of susceptibility to pathogens is an important goal of medicine and of evolutionary biology. A key first step toward understanding the genetics and evolution of any phenotypic trait is characterizing the role of mutation. However, the rate at which mutation introduces genetic variance for pathogen susceptibility in any organism is essentially unknown. Here, we quantify the per‐generation input of genetic variance by mutation (VM) for susceptibility of Caenorhabditis elegans to the pathogenic bacterium Pseudomonas aeruginosa (defined as the median time of death, LT50). VM for LT50 is slightly less than VM for a variety of life‐history and morphological traits in this strain of C. elegans, but is well within the range of reported values in a variety of organisms. Mean LT50 did not change significantly over 250 generations of mutation accumulation. Comparison of VM to the standing genetic variance (VG) implies a strength of selection against new mutations of a few tenths of a percent. These results suggest that the substantial standing genetic variation for susceptibility of C. elegans to P. aeruginosa can be explained by polygenic mutation coupled with purifying selection. 相似文献
125.
This editorial highlights a study by Rodriguez, Sanchez‐Moran et al. (2019) in the current issue of the Journal of Neurochemistry, in which the authors describe a microcephalic boy carrying the novel heterozygous de novo missense mutation c.560A> G; p.Asp187Gly in Cdh1/Fzr1 encoding the APC/C E3‐ubiquitin ligase cofactor CDH1. A functional characterization of mutant APC/CCDH1 confirms an aberrant division of neural progenitor cells, a condition known to determine the mouse brain cortex size. These data suggest that APC/CCDH1 may contribute to the regulation of the human brain size.
126.
M.C. Matos A.A. Matos A. Mantas V. Cordeiro J.B. Vieira Da Silva 《Photosynthetica》1997,34(2):249-256
Five cultivars of Prunus amygdalus Batsch (Ferragnes, Ferrastar, Marcona, Garrigues, and Non Pareil) grafted on two different
rootstocks (Garrigues and GF677), and two cultivars (Ferraduel and Casa Nova) grafted on GF677, were grown for three years
under rainfed conditions in an orchard in northeast Portugal. Net photosynthetic rate (PN), leaf conductance for water vapour
(gs), leaf water potential (Ψ), instantaneous water use efficiency (WUE), and internal CO2 concentration (Ci) were measured
at three periods of the growing season: spring, summer (June or July) and late summer (September) over two years. Ferraduel,
Ferrastar, and Marcona presented the best performance in the periods when environmental conditions were not very hard (May
or September). Casa Nova and Non Pareil were well adapted to high air evaporative demand, preventing the increase of leaf
temperature (T1). Ferrastar, although having a good performance in May and September, did well adapt to hard climatic conditions
in June 1994. In the following year, although it presented the highest T1, the values were not limiting (30.6 ± 2.1 °C), and
PN was only decreased from May to July. Marcona was highly dependent on T1, but prevented its increasing. Garrigues showed
lower PN in most measurement periods. GF677 frequently induced the highest PN, WUE, and Ψ. PN was mainly dependent on T1,
radiation, Ci, month, and year. WUE depended on the same factors. Ψ depended mainly on gs, air temperature, month, and year.
This revised version was published online in June 2006 with corrections to the Cover Date. 相似文献
127.
128.
A procedure for rapid induction of mycelial to yeast phase (M→Y) conversion ofHistoplasma capsulatum has been devised. Exposure of mycelial fragments to low oxidation-reduction (O/R) potentials (+5 to+65 mv) either aerobically (ascorbic acid treatment) or anaerobically (nitrogen atmosphere) for 18 to 24 hours at 37° C resulted in induction of the M→Y conversion process whether or not an organic sulfur source was available. However, aerobic conditions and a suitable organic sulfur source, such as cysteine, cystine or lanthionine were found essential for outgrowth and maintenance in the yeastlike phase. 相似文献
129.
Rosilia Silva Souza William Morais Machado Caline Santana da Frana Lopes Csar Mugabe Emmanuel Emydio Gomes Pinheiro Isabella de Matos Brando Carneiro Laiara Fernandes Rocha Larissa Pires Barbosa 《Animal Reproduction》2021,18(3)
The effects of docosahexaenoic acid (DHA) in the diluent for cryopreservation of goat semen on seminal quality and the optimal levels to be used were evaluated. After collection, semen was pooled and physically evaluated, then divided into four aliquots with different DHA levels in the diluent: 0, 10, 20, and 30 ng mL-1. The semen was cryopreserved in a TK 3000® freezing machine and then thawed for assessment at 37 °C. Sperm motility and vigor, membrane integrity, acrosomal integrity, mitochondrial activity, and sperm chromatin compaction were evaluated after thawing. A completely randomized design was used. For normally distributed variables, ANOVA and regression analysis were used to test for differences between treatments, and for non-parametric data, the Kruskal Wallis test was used at the 5% significance level. There were no differences among groups in terms of membrane integrity, acrosomal integrity, or chromatin compaction. There was a decrease in class I mitochondrial activity with increasing DHA level (P<0.05), but no differences in classes II, III, and IV (P>0.05). The inclusion of 10 to 30 ng mL-1 of DHA in the diluent did not result in improvements in seminal quality parameters after thawing, with some impairment observed in the mitochondrial activity of the sperm cells. 相似文献
130.
Reactions of the adduct UCl3·(THF)x (THF = tetrahydrofuran) with compounds of the type K[HnBL4?n], where L = pyrazole or 3,5-dimethylpyrazole, are presented. Based on the results obtained the two compounds UCl2H2BPz2·THF and UCl2HBPz3·THF were isolated. 相似文献