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991.
The development of a three-dimensional finite element model of a posteriorly plated canine cervical spine (C3-C6) including contact nonlinearities is described. The model was created from axial CT scans and the material properties were derived from the literature. The model demonstrated sufficient accuracy from the results of a mesh convergence test. Significant steps were taken toward establishing model validation by comparison of plate surface strains with a posteriorly plated canine cervical spine under three-point bending. This model was developed to better characterize the contact pressures at the various interfaces under average physiologic canine loading. The analysis showed that the screw-plate interfaces had the highest values of all the mechanical parameters evaluated. 相似文献
992.
993.
Srikanth Sampathkumar Franklin Christopher C. Duke Richard C. Kraft Andrew S. 《Molecular and cellular biochemistry》1999,199(1-2):169-178
Recent studies have suggested that MAP kinase phosphatase 1 (MKP-1) is overexpressed in prostate cancer. To evaluate the role of MKP-1 in regulating cell death and tumor growth in prostate cancer, MKP-1 was conditionally overexpressed in the human prostate cancer cell line DU145. Overexpression of MKP-1 in DU145 cells blocked activation of stress-activated protein kinase (SAPK/JNK). MKP-1 overexpression in DU-145 cells was also found to inhibit Fas ligand (FasL)-induced apoptosis, as well as block the activation of caspases by Fas engagement. In addition, MKP-1 blocked the activation of apoptosis by transfected MEKK-1 and ASK-1, presumably through its inhibition of the SAPK/JNK family of enzymes. MKP-1 blocked the ability of FasL to induce loss of mitochondrial transmembrane potential (m), suggesting that MKP-1 acts upstream of mitochondrial pro-apoptotic events induced by FasL and that the SAPK/JNK pathway may form the signaling link between Fas receptor and mitochondrial dysfunction. Thus, MKP-1 overexpression in prostate cancer may play a role in promoting prostate carcinogenesis by inhibiting FasL-induced cell death. 相似文献
994.
Mycopathologia - It was previously shown that the presence of estrogen enhances survival of Candida albicans under heat and oxidative stresses. A 92-kDa protein is inducible by heat shock and... 相似文献
995.
Effects of a 12-day “live high, train low” camp on reticulocyte production and haemoglobin mass in elite female road cyclists 总被引:10,自引:0,他引:10
Michael J. Ashenden Christopher J. Gore David T. Martin Geoffrey P. Dobson Allan G. Hahn 《European journal of applied physiology and occupational physiology》1999,80(5):472-478
The aim of this study was to document the effect of "living high, training low" on the red blood cell production of elite female cyclists. Six members of the Australian National Women's road cycling squad slept for 12 nights at a simulated altitude of 2650 m in normobaric hypoxia (HIGH), while 6 team-mates slept at an altitude of 600 m (CONTROL). HIGH and CONTROL subjects trained and raced as a group throughout the 70-day study. Baseline levels of reticulocyte parameters sensitive to changes in erythropoeisis were measured 21 days and 1 day prior to sleeping in hypoxia (D1 and D20, respectively). These measures were repeated after 7 nights (D27) and 12 nights (D34) of simulated altitude exposure, and again 15 days (D48) and 33 days (D67) after leaving the altitude house. There was no increase in reticulocyte production, nor any change in reticulocyte parameters in either the HIGH or CONTROL groups. This lack of haematological response was substantiated by total haemoglobin mass measures (CO-rebreathing), which did not change when measured on D1, D20, D34 or D67. We conclude that in elite female road cyclists, 12 nights of exposure to normobaric hypoxia (2650 m) is not sufficient to either stimulate reticulocyte production or increase haemoglobin mass. 相似文献
996.
997.
Mutations linked to leukoencephalopathy with vanishing white matter impair the function of the eukaryotic initiation factor 2B complex in diverse ways 下载免费PDF全文
Leukoencephalopathy with vanishing white matter (VWM) is a severe inherited human neurodegenerative disorder that is caused by mutations in the genes for the subunits of eukaryotic initiation factor 2B (eIF2B), a heteropentameric guanine nucleotide exchange factor that regulates both global and mRNA-specific translation. Marked variability is evident in the clinical severity and time course of VWM in patients. Here we have studied the effects of VWM mutations on the function of human eIF2B. All the mutations tested cause partial loss of activity. Frameshift mutations in genes for eIF2Bepsilon or eIF2Bbeta lead to truncated polypeptides that fail to form complexes with the other subunits and are effectively null mutations. Certain point mutations also impair the ability of eIF2Bbeta or -epsilon to form eIF2B holocomplexes and also diminish the intrinsic nucleotide exchange activity of eIF2B. A point mutation in the catalytic domain of eIF2Bepsilon impairs its ability to bind the substrate, while two mutations in eIF2Bbeta actually enhance eIF2 binding. We provide evidence that expression of VWM mutant eIF2B may enhance the translation of specific mRNAs. The variability of the clinical phenotype in VWM may reflect the multiple ways in which VWM mutations affect eIF2B function. 相似文献
998.
RPA alleviates the inhibitory effect of vinylphosphonate internucleotide linkages on DNA unwinding by BLM and WRN helicases 总被引:3,自引:1,他引:2
Garcia PL Bradley G Hayes CJ Krintel S Soultanas P Janscak P 《Nucleic acids research》2004,32(12):3771-3778
Bloom (BLM) and Werner (WRN) syndrome proteins are members of the RecQ family of SF2 DNA helicases. In this paper, we show that restricting the rotational DNA backbone flexibility, by introducing vinylphosphonate internucleotide linkages in the translocating DNA strand, inhibits efficient duplex unwinding by these enzymes. The human single-stranded DNA binding protein replication protein A (RPA) fully restores the unwinding activity of BLM and WRN on vinylphosphonate-containing substrates while the heterologous single-stranded DNA binding protein from Escherichia coli (SSB) restores the activity only partially. Both RPA and SSB fail to restore the unwinding activity of the SF1 PcrA helicase on modified substrates, implying specific interactions of RPA with the BLM and WRN helicases. Our data highlight subtle differences between SF1 and SF2 helicases and suggest that although RecQ helicases belong to the SF2 family, they are mechanistically more similar to the SF1 PcrA helicase than to other SF2 helicases that are not affected by vinylphosphonate modifications. 相似文献
999.
RB signaling prevents replication-dependent DNA double-strand breaks following genotoxic insult 总被引:7,自引:0,他引:7
Cell cycle checkpoints induced by DNA damage play an integral role in preservation of genomic stability by allowing cells to limit the propagation of deleterious mutations. The retinoblastoma tumor suppressor (RB) is crucial for the maintenance of the DNA damage checkpoint function because it elicits cell cycle arrest in response to a variety of genotoxic stresses. Although sporadic loss of RB is characteristic of most cancers and results in the bypass of the DNA damage checkpoint, the consequence of RB loss upon chemotherapeutic responsiveness has been largely uninvestigated. Here, we employed a conditional knockout approach to ablate RB in adult fibroblasts. This system enabled us to examine the DNA damage response of adult cells following acute RB deletion. Using this system, we demonstrated that loss of RB disrupted the DNA damage checkpoint elicited by either cisplatin or camptothecin exposure. Strikingly, this bypass was not associated with enhanced repair, but rather the accumulation of phosphorylated H2AX (γH2AX) foci, which indicate DNA double-strand breaks. The formation of γH2AX foci was due to ongoing replication following chemotherapeutic treatment in the RB-deficient cells. Additionally, peak γH2AX accumulation occurred in S-phase cells undergoing DNA replication in the presence of damage, and these γH2AX foci co-localized with replication foci. These results demonstrate that acute RB loss abrogates DNA damage-induced cell cycle arrest to induce γH2AX foci formation. Thus, secondary genetic lesions induced by RB loss have implications for the chemotherapeutic response and the development of genetic instability. 相似文献
1000.
Deppmann CD Acharya A Rishi V Wobbes B Smeekens S Taparowsky EJ Vinson C 《Nucleic acids research》2004,32(11):3435-3445
Basic region-leucine zipper (B-ZIP) proteins are a class of dimeric sequence-specific DNA-binding proteins unique to eukaryotes. We have identified 67 B-ZIP proteins in the Arabidopsis thaliana genome. No A.thaliana B-ZIP domains are homologous with any Homo sapiens B-ZIP domains. Here, we predict the dimerization specificity properties of the 67 B-ZIP proteins in the A.thaliana genome based on three structural properties of the dimeric alpha-helical leucine zipper coiled coil structure: (i) length of the leucine zipper, (ii) placement of asparagine or a charged amino acid in the hydrophobic interface and (iii) presence of interhelical electrostatic interactions. Many A.thaliana B-ZIP leucine zippers are predicted to be eight or more heptads in length, in contrast to the four or five heptads typically found in H.sapiens, a prediction experimentally verified by circular dichroism analysis. Asparagine in the a position of the coiled coil is typically observed in the second heptad in H.sapiens. In A.thaliana, asparagine is abundant in the a position of both the second and fifth heptads. The particular placement of asparagine in the a position helps define 14 families of homodimerizing B-ZIP proteins in A.thaliana, in contrast to the six families found in H.sapiens. The repulsive interhelical electrostatic interactions that are used to specify heterodimerizing B-ZIP proteins in H.sapiens are not present in A.thaliana. Instead, we predict that plant leucine zippers rely on charged amino acids in the a position to drive heterodimerization. It appears that A.thaliana define many families of homodimerizing B-ZIP proteins by having long leucine zippers with asparagine judiciously placed in the a position of different heptads. 相似文献