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排序方式: 共有432条查询结果,搜索用时 15 毫秒
41.
Conditional deletion of focal adhesion kinase leads to defects in ventricular septation and outflow tract alignment 总被引:1,自引:0,他引:1 下载免费PDF全文
Hakim ZS DiMichele LA Doherty JT Homeister JW Beggs HE Reichardt LF Schwartz RJ Brackhan J Smithies O Mack CP Taylor JM 《Molecular and cellular biology》2007,27(15):5352-5364
To examine a role for focal adhesion kinase (FAK) in cardiac morphogenesis, we generated a line of mice with a conditional deletion of FAK in nkx2-5-expressing cells (herein termed FAKnk mice). FAKnk mice died shortly after birth, likely resulting from a profound subaortic ventricular septal defect and associated malalignment of the outflow tract. Additional less penetrant phenotypes included persistent truncus arteriosus and thickened valve leaflets. Thus, conditional inactivation of FAK in nkx2-5-expressing cells leads to the most common congenital heart defect that is also a subset of abnormalities associated with tetralogy of Fallot and the DiGeorge syndrome. No significant differences in proliferation or apoptosis between control and FAKnk hearts were observed. However, decreased myocardialization was observed for the conal ridges of the proximal outflow tract in FAKnk hearts. Interestingly, chemotaxis was significantly attenuated in isolated FAK-null cardiomyocytes in comparison to genetic controls, and these effects were concomitant with reduced tyrosine phosphorylation of Crk-associated substrate (CAS). Thus, it is possible that ventricular septation and appropriate outflow tract alignment is dependent, at least in part, upon FAK-dependent CAS activation and subsequent induction of polarized myocyte movement into the conal ridges. Future studies will be necessary to determine the precise contributions of the additional nkx2-5-derived lineages to the phenotypes observed. 相似文献
42.
Plutonium(IV) Reduction by the Metal-Reducing Bacteria Geobacter metallireducens GS15 and Shewanella oneidensis MR1 下载免费PDF全文
Hakim Boukhalfa Gary A. Icopini Sean D. Reilly Mary P. Neu 《Applied microbiology》2007,73(18):5897-5903
The bacterial reduction of actinides has been suggested as a possible remedial strategy for actinide-contaminated environments, and the bacterial reduction of Pu(VI/V) has the potential to produce highly insoluble Pu(IV) solid phases. However, the behavior of plutonium with regard to bacterial reduction is more complex than for other actinides because it is possible for Pu(IV) to be further reduced to Pu(III), which is relatively more soluble than Pu(IV). This work investigates the ability of the metal-reducing bacteria Geobacter metallireducens GS15 and Shewanella oneidensis MR1 to enzymatically reduce freshly precipitated amorphous Pu(IV) (OH)4 [Pu(IV)(OH)4(am)] and soluble Pu(IV)(EDTA). In cell suspensions without added complexing ligands, minor Pu(III) production was observed in cultures containing S. oneidensis, but little or no Pu(III) production was observed in cultures containing G. metallireducens. In the presence of EDTA, most of the Pu(IV)(OH)4(am) present was reduced to Pu(III) and remained soluble in cell suspensions of both S. oneidensis and G. metallireducens. When soluble Pu(IV)(EDTA) was provided as the terminal electron acceptor, cell suspensions of both S. oneidensis and G. metallireducens rapidly reduced Pu(IV)(EDTA) to Pu(III)(EDTA) with nearly complete reduction within 20 to 40 min, depending on the initial concentration. Neither bacterium was able to use Pu(IV) (in any of the forms used) as a terminal electron acceptor to support growth. These results have significant implications for the potential remediation of plutonium and suggest that strongly reducing environments where complexing ligands are present may produce soluble forms of reduced Pu species. 相似文献
43.
Antczak C Shum D Escobar S Bassit B Kim E Seshan VE Wu N Yang G Ouerfelli O Li YM Scheinberg DA Djaballah H 《Journal of biomolecular screening》2007,12(4):521-535
The human mitochondrial peptide deformylase (HsPDF) provides a potential new target for broadly acting antiproliferative agents. To identify novel nonpeptidomimetic and nonhydroxamic acid-based inhibitors of HsPDF, the authors have developed a high-throughput screening (HTS) strategy using a fluorescence polarization (FP)-based binding assay as the primary assay for screening chemical libraries, followed by an enzymatic-based assay to confirm hits, prior to characterization of their antiproliferative activity against established tumor cell lines. The authors present the results and performance of the established strategy tested in a pilot screen of 2880 compounds and the identification of the 1st inhibitors. Two common scaffolds were identified within the hits. Furthermore, cytotoxicity studies revealed that most of the confirmed hits have antiproliferative activity. These findings demonstrate that the designed strategy can identify novel functional inhibitors and provide a powerful alternative to the use of functional assays in HTS and support the hypothesis that HsPDF inhibitors may constitute a new class of antiproliferative agent. 相似文献
44.
Maraldi T Prata C Fiorentini D Zambonin L Landi L Hakim G 《Free radical research》2007,41(12):1348-1357
In M07e cells, a human megakaryocytic leukaemia line, reactive oxygen species (ROS) are generated in response to cytokines acting as intracellular messengers to modulate glucose transport. The aim of this work was to study the signal cascade involved in the acute glucose transport activation in cells exposed to growth factors, such as granulocyte macrophage-colony stimulation factor (GM-CSF) and thrombopoietin (TPO), to better understand some aspects of the aberrant proliferation in leukaemia. Results confirm ROS involvement in modulation of glucose transport in this cell line. Furthermore, GM-CSF and TPO produced changes in Glut1 phosphorylation and specific inhibitors employed to identify protein kinases involved in Glut activation by these cytokines proved that Akt, PLCγ, Syk and the Src family take part in signal transduction leading to Glut1 activation. 相似文献
45.
Altindag O Gur A Calgan N Soran N Celik H Selek S 《Redox report : communications in free radical research》2007,12(3):134-138
We aimed to evaluate the association of serum paraoxonase and arylesterase activities and oxidative/antioxidative status in patients with fibromyalgia. Forty-two patients with fibromyalgia and 53 healthy controls were included in the study. Serum paraoxonase and arylesterase activities were measured spectrophotometrically. Oxidative and antioxidative status were evaluated by measuring serum lipid hydroperoxide (LOOH) levels, total antioxidant status (TAS) and free sulfhydryl groups (-SH = total thiol). Lipid parameters were determined by routine laboratory methods. Serum paraoxonase and arylesterase activities, and TAS were lower in patients with fibromyalgia than in controls (P < 0.001, for all), and the -SH level was also lower in the patient group (P = 0.03). LOOH levels were higher in the patient group than in controls (P = 0.01). Our results suggest that patients with fibromyalgia were exposed to oxidative stress, and paraoxonase and arylesterase activities were decreased in these patients. Patients with fibromyalgia might be prone to development of atherosclerosis with reduced paraoxonase and arylesterase activities. 相似文献
46.
Hakim RS Blackburn MB Corti P Gelman DB Goodman C Elsen K Loeb MJ Lynn D Soin T Smagghe G 《Archives of insect biochemistry and physiology》2007,64(2):63-73
In insects, developmental responses are organ- and tissue-specific. In previous studies of insect midgut cells in primary tissue cultures, growth-promoting and differentiation factors were identified from the growth media, hemolymph, and fat body. Recently, it was determined that the mitogenic effect of a Manduca sexta fat body extract on midgut stem cells of Heliothis virescens was due to the presence of monomeric alpha-arylphorin. Here we report that in primary midgut cell cultures, this same arylphorin stimulates stem cell proliferation in the lepidopterans M. sexta and Spodoptera littoralis, and in the beetle Leptinotarsa decemlineata. Studies using S. littoralis cells confirm that the mitogenic effect is due to free alpha-arylphorin subunits. In addition, feeding artificial diets containing arylphorin increased the growth rates of several insect species. When tested against continuous cell lines, including some with midgut and fat body origins, arylphorin had no effect; however, a cell line derived from Lymantria dispar fat body grew more rapidly in medium containing a chymotryptic digest of arylphorin. 相似文献
47.
Ramajayam R Giridhar R Yadav MR Djaballah H Shum D Radu C 《Journal of enzyme inhibition and medicinal chemistry》2007,22(6):716-721
Novel substituted 5,7-diaryl-2,3-dihydro-1,4-diazepines and 4,6-diaryl-2-aminopyrimidines were synthesized and tested for their antiproliferative activity. Title compounds were obtained by cyclocondensation of a substituted flavone with ethylenediamine and guanidine respectively. The cytotoxicity in vitro against various human leukemic cancer cell lines viz., Jurkat, HL60, MOLT3, NCEB-1, K562 was determined. 相似文献
48.
Hakim Bouamar Daifeng Jiang Long Wang An-Ping Lin Manoela Ortega Ricardo C. T. Aguiar 《Molecular and cellular biology》2015,35(8):1329-1340
In biological processes, the balance between positive and negative inputs is critical for an effective physiological response and to prevent disease. A case in point is the germinal center (GC) reaction, wherein high mutational and proliferation rates are accompanied by an obligatory suppression of the DNA repair machinery. Understandably, when the GC reaction goes awry, loss of immune cells or lymphoid cancer ensues. Here, we detail the functional interactions that make microRNA 155 (miR-155) a key part of this process. Upon antigen exposure, miR-155−/− mature B cells displayed significantly higher double-strand DNA break (DSB) accumulation and p53 activation than their miR-155+/+ counterparts. Using B cell-specific knockdown strategies, we confirmed the role of the miR-155 target Aicda (activation-induced cytidine deaminase) in this process and, in combination with a gain-of-function model, unveiled a previously unappreciated role for Socs1 in directly modulating p53 activity and the DNA damage response in B lymphocytes. Thus, miR-155 controls the outcome of the GC reaction by modulating its initiation (Aicda) and termination (Socs1/p53 response), suggesting a mechanism to explain the quantitative defect in germinal center B cells found in mice lacking or overexpressing this miRNA. 相似文献
49.
Soudani N Ben Amara I Troudi A Hakim A Bouaziz H Ayadi Makni F Zeghal KM Zeghal N 《Journal of physiology and biochemistry》2011,67(4):577-588
Excess chromium (Cr) exposure is associated with various pathological conditions including hematological dysfunction. The
generation of oxidative stress is one of the plausible mechanisms behind Cr-induced cellular deteriorations. The efficacy
of selenium (Se) to combat Cr-induced oxidative damage in the erythrocytes of adult rats was investigated in the current study.
Female Wistar rats were randomly divided into four groups of six each: group I served as controls which received standard
diet, group II received in drinking water K2Cr2O7 alone (700 ppm), group III received both K2Cr2O7 and Se (0.5 Na2SeO3 mg/kg of diet), and group IV received Se (0.5 mg/kg of diet) for 3 weeks. Rats exposed to K2Cr2O7 showed an increase of malondialdehyde and protein carbonyl levels and a decrease of sulfhydryl content, glutathione, non-protein
thiol, and vitamin C levels. A decrease of enzyme activities like catalase, glutathione peroxidase, and superoxide dismutase
activities was also noted. Co-administration of Se with K2Cr2O7 restored the parameters cited above to near-normal values. Therefore, our investigation revealed that Se was a useful element
preventing K2Cr2O7-induced erythrocyte damages. 相似文献
50.
Gana ML Kebbouche-Gana S Touzi A Zorgani MA Pauss A Lounici H Mameri N 《Journal of industrial microbiology & biotechnology》2011,38(3):391-404
The present study enlightens the role of the antagonistic potential of nonpathogenic strain B21 against sulfate-reducing bacteria
(SRB) consortium. The inhibitor effects of strain B21 were compared with those of the chemical biocide tetrakishydroxymethylphosphonium
sulfate (THPS), generally used in the petroleum industry. The biological inhibitor exhibited much better and effective performance.
Growth of SRB in coculture with bacteria strain B21 antagonist exhibited decline in SRB growth, reduction in production of
sulfides, with consumption of sulfate. The observed effect seems more important in comparison with the effect caused by the
tested biocide (THPS). Strain B21, a dominant facultative aerobic species, has salt growth requirement always above 5% (w/v)
salts with optimal concentration of 10–15%. Phylogenetic analysis based on partial 16S rRNA gene sequences showed that strain B21
is a member of the genus Bacillus, being most closely related to Bacillus qingdaonensis DQ115802 (94.0% sequence similarity), Bacillus aidingensis DQ504377 (94.0%), and Bacillus salarius AY667494 (92.2%). Comparative analysis of partial 16S rRNA gene sequence data plus physiological, biochemical, and phenotypic
features of the novel isolate and related species of Bacillus indicated that strain B21 may represent a novel species within the genus Bacillus, named Bacillus sp. (EMBL, FR671419). The results of this study indicate the application potential of Bacillus strain B21 as a biocontrol agent to fight corrosion in the oil industry. 相似文献