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21.
Bax loss impairs Myc-induced apoptosis and circumvents the selection of p53 mutations during Myc-mediated lymphomagenesis 下载免费PDF全文
Eischen CM Roussel MF Korsmeyer SJ Cleveland JL 《Molecular and cellular biology》2001,21(22):7653-7662
The ARF and p53 tumor suppressors mediate Myc-induced apoptosis and suppress lymphoma development in E mu-myc transgenic mice. Here we report that the proapoptotic Bcl-2 family member Bax also mediates apoptosis triggered by Myc and inhibits Myc-induced lymphomagenesis. Bax-deficient primary pre-B cells are resistant to the apoptotic effects of Myc, and Bax loss accelerates lymphoma development in E mu-myc transgenics in a dose-dependent fashion. Eighty percent of lymphomas arising in wild-type E mu-myc transgenics have alterations in the ARF-Mdm2-p53 tumor suppressor pathway characterized by deletions in ARF, mutations or deletions of p53, and overexpression of Mdm2. The absence of Bax did not alter the frequency of biallelic deletion of ARF in lymphomas arising in E mu-myc transgenic mice or the rate of tumorigenesis in ARF-null mice. Furthermore, Mdm2 was overexpressed at the same frequency in lymphomas irrespective of Bax status, suggesting that Bax resides in a pathway separate from ARF and Mdm2. Strikingly, lymphomas from Bax-null E mu-myc transgenics lacked p53 alterations, whereas 27% of the tumors in Bax(+/-) E mu-myc transgenic mice contained p53 mutations or deletions. Thus, the loss of Bax eliminates the selection of p53 mutations and deletions, but not ARF deletions or Mdm2 overexpression, during Myc-induced tumorigenesis, formally demonstrating that Myc-induced apoptotic signals through ARF/Mdm2 and p53 must bifurcate: p53 signals through Bax, whereas this is not necessarily the case for ARF and Mdm2. 相似文献
22.
Aldair JW Pinto Maria M Figueiredo Fabiana L Silva Trycia Martins Marilene SM Michalick Washington L Tafuri Wagner L Tafuri 《Acta veterinaria Scandinavica》2011,53(1):1-8
Background
A nationwide survey on the microbial etiology of cases of subclinical mastitis in dairy cows was carried out on dairy farms in Sweden. The aim was to investigate the microbial panorama and the occurrence of antimicrobial resistance. Moreover, differences between newly infected cows and chronically infected cows were investigated.Methods
In total, 583 quarter milk samples were collected from 583 dairy cows at 226 dairy farms from February 2008 to February 2009. The quarter milk samples were bacteriological investigated and scored using the California Mastitis Test. Staphylococci were tested for betalactamase production and presence of resistance was evaluated in all specific udder pathogens. Differences between newly infected cows and chronically infected cows were statistically investigated using logistic regression analysis.Results
The most common isolates of 590 bacteriological diagnoses were Staphylococcus (S) aureus (19%) and coagulase-negative staphylococci (CNS; 16%) followed by Streptococcus (Str) dysgalactiae (9%), Str. uberis (8%), Escherichia (E.) coli (2.9%), and Streptococcus spp. (1.9%). Samples with no growth or contamination constituted 22% and 18% of the diagnoses, respectively. The distribution of the most commonly isolated bacteria considering only bacteriological positive samples were: S. aureus - 31%, CNS - 27%, Str. dysgalactiae - 15%, Str. uberis - 14%, E. coli - 4.8%, and Streptococcus spp. - 3.1%. There was an increased risk of finding S. aureus, Str. uberis or Str. dysgalactiae in milk samples from chronically infected cows compared to findings in milk samples from newly infected cows. Four percent of the S. aureus isolates and 35% of the CNS isolates were resistant to penicillin G. Overall, resistance to other antimicrobials than penicillin G was uncommon.Conclusions
Staphylococcus aureus and CNS were the most frequently isolated pathogens and resistance to antimicrobials was rare. 相似文献23.
Inactivation of the Arf-Mdm2-p53 tumor suppressor pathway is a necessary event for tumorigenesis. Arf controls Mdm2, which in turn regulates p53, but Arf and Mdm2 also have p53-independent functions that affect tumor development. Moreover, inhibition of oncogene-induced tumorigenesis relies on Arf and p53, but the requirements of Arf and p53 in tumor development initiated in the absence of overt oncogene overexpression and the role of Mdm2 in this process remain unclear. In a series of genetic experiments in mice with defined deficiencies in Arf, Mdm2 and/or p53, we show Mdm2 haploinsufficiency significantly delayed tumorigenesis in mice deficient in Arf and p53. Mdm2 heterozygosity significantly inhibited tumor development in the absence of Arf, and in contrast to Myc oncogene-driven cancer, this delay in tumorigenesis could not be rescued with the presence of one allele of Arf. Notably, Mdm2 haploinsufficieny blocked the accelerated tumor development in Arf deficient mice caused by p53 heterozygosity. However, tumorigenesis was not inhibited in Mdm2 heterozygous mice lacking both alleles of p53 regardless of Arf status. Surprisingly, loss of Arf accelerated tumor development in p53-null mice. Tumor spectrum was largely dictated by Arf and p53 status with Mdm2 haploinsufficiency only modestly altering the tumor type in some of the genotypes and not the number of primary tumors that arose. Therefore, the significant effects of Mdm2 haploinsufficiency on tumor latency were independent of Arf and required at least one allele of p53, and an Mdm2 deficiency had minor effects on the types of tumors that developed. These data also demonstrate that decreased levels of Mdm2 are protective in the presence of multiple genetic events in Arf and p53 genes that normally accelerate tumorigenesis. 相似文献
24.
Krause DA Smith AM Holmes LC Klebe CR Lee JB Lundquist KM Eischen JJ Hollman JH 《Journal of strength and conditioning research / National Strength & Conditioning Association》2012,26(5):1423-1430
The purpose of this study was to examine the relationship of off-ice performance measures with on-ice turning, crossover, and forward skating performance in high school male hockey players. Thirty-eight players aged 15-18 (mean age ± SD: 16.4 ± 1.1 years; height: 177.9 ± 6.8 cm; weight: 72.5 ± 8.9 kg) participated in this study. On-ice tests included a forward sprint, short radius turns, and crossover turns. Off-ice tests included a 40-yd sprint, vertical jumps, horizontal jumps, and a dynamic balance test using a Y balance testing device. Five off-ice variables correlated with all on-ice performance measures. These variables included the 40-yd sprint, lateral bound right to left limb, double limb horizontal hop, balance on right in posterolateral direction, and composite balance performance on the right. Hierachical regression demonstrated that off-ice sprint time was most predictive of on-ice skating performance, accounting for 65.4% of the variability in forward skate time, 45.0% of the variability in left short radius time, 21.8% of the variance in right short radius time, 36.2% of the variance in left crossover time, and 30.8% of the variability in right crossover time. When using off-ice tests to evaluate hockey players, the 40-yd sprint is the best predictor of skating performance. Based on our regression equation, for every 1-second difference in the 40-yd sprint time, there will be approximately a 0.6-second difference in the 34.5-m on-ice sprint. The 40-yd sprint predicts forward skating performance and to a lesser degree; it also predicts crossover and tuning performance. 相似文献
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26.
Positions of multiple insertions in SSU rDNA of lichen-forming fungi 总被引:11,自引:3,他引:8
Lichen-forming fungi, in symbiotic associations with algae, frequently have
nuclear small subunit ribosomal DNA (SSU rDNA) longer than the 1,800
nucleotides typical for eukaryotes. The lichen-forming ascomycetous fungus
Lecanora dispersa contains insertions at eight distinct positions of its
SSU rDNA; the lichen-forming fungi Calicium tricolor and Porpidia
crustulata each contain one insertion. Insertions are not limited to fungi
that form lichens; the lichen ally Mycocalicium albonigrum also contains
two insertions. Of the 11 insertion positions now reported for
lichen-forming fungi and this ally, 6 positions are known only from
lichen-forming fungi. Including the 4 newly reported in this study,
insertions are now known from at least 17 positions among all reported SSU
rDNA sequences. Insertions, most of which are Group I introns, are reported
in fungal and protistan lineages and occur at corresponding positions in
genomes as phylogenetically distant as the nuclei of fungi, green algae,
and red algae. Many of these positions are exposed in the mature rRNA
tertiary structure and may be subject to independent insertion of introns.
Insertion of introns, accompanied by their sporadic loss, accounts for the
scattered distribution of insertions observed within the SSU rDNA of these
diverse organisms.
相似文献
27.
The extent of polylactosamine glycosylation of MDCK LAMP-2 is determined by its Golgi residence time 总被引:2,自引:1,他引:1
The increased polylactosamine glycosylation of LAMP-2 in MDCK cells
cultured for 1 day relative to cells cultured for 3 days has been
correlated with its slower rate of Golgi transit (Nabi and Rodriguez-
Boulan, 1993, Mol. Biol. Cell., 4, 627-635). To determine if the
differential polylactosamine glycosylation of LAMP-2 is a consequence of
glycosyltransferase expression levels, the activities of beta1- 6GlcNAc-TV,
beta1-3GlcNAc-T(i), beta1-2GlcNAc-TI, beta1, 4Gal-T, alpha2- 6sialyl-T, and
alpha2-3sialyl-T were assayed and no significant differences in the
activities of these enzymes in 1 and 3 day cell extracts were detected.
During MDCK epithelial polarization, the Golgi apparatus undergoes
morphological changes and apiconuclear Golgi networks were more evident in
3 day cells. Treatment with nocodazole disrupted Golgi networks and
generated numerous Golgi clusters in both 1 day and 3 day cells. In the
presence of nocodazole the differential migration of LAMP-2 in 1 and 3 day
MDCK cells was maintained and could be eliminated by treatment with
endo-beta-galactosidase, indicating that gross Golgi morphology did not
influence the extent of LAMP-2 polylactosamine glycosylation. Nocodazole
treatment did, however, result in the faster migration of LAMP-2 which was
not due to modification of core N-glycans as the precursor form of the
glycoprotein migrated with an identical molecular size. Following
incubation at 20 degrees C, which prevents the exit of proteins from the
trans-Golgi network, the molecular size of LAMP-2 increased to a similar
extent in both 1 and 3 day MDCK cells. Extending the time of incubation at
20 degrees C did not influence the size of LAMP-2, demonstrating that its
glycosylation is modified not by its retention within the Golgi but rather
by its equivalent slower Golgi passage at the lower temperature in both 1
and 3 day cells. An identical effect was observed in nocodazole treated
cells, demonstrating that Golgi residence time determines the extent of
LAMP-2 polylactosamine glycosylation, even in isolated Golgi clusters.
相似文献
28.
Incorporation of axonally transported glycoproteins into axolemma during nerve regeneration 总被引:14,自引:4,他引:10 下载免费PDF全文
The insertion of axonally transported fucosyl glycoproteins into the axolemma of regenerating nerve sprouts was examined in rat sciatic motor axons at intervals after nerve crush. [(3)H]Fucose was injected into the lumbar ventral horns and the nerves were removed at intervals between 1 and 14 d after labeling. To follow the fate of the “pulse- labeled” glycoproteins, we examined the nerves by correlative radiometric and EM radioautographic approaches. The results showed, first, that rapidly transported [(3)H]fucosyl glycoproteins were inserted into the axolemma of regenerating sprouts as well as parent axons. At 1 d after delivery, in addition to the substantial mobile fraction of radioactivity still undergoing bidirectional transport within the axon, a fraction of label was already associated with the axolemma. Insertion of labeled glycoproteins into the sprout axolemma appeared to occur all along the length of the regenerating sprouts, not just in sprout terminals. Once inserted, labeled glycoproteins did not undergo extensive redistribution, nor did they appear in sprout regions that formed (as a result of continued outgrowth) after their insertion. The amount of radioactivity in the regenerating nerves decreased with time, in part as a result of removal of transported label by retrograde transport. By 7-14 d after labeling, radioautography showed that almost all the remaining radioactivity was associated with axolemma. The regenerating sprouts retained increased amounts of labeled glycoproteins; 7 or 14 d after labeling, the regenerating sprouts had over twice as much of radioactivity as comparable lengths of control nerves or parent axons. One role of fast axonal transport in nerve regeneration is the contribution to the regenerating sprout of glycoproteins inserted into the axolemma; these membrane elements are added both during longitudinal outgrowth and during lateral growth and maturation of the sprout. 相似文献
29.
JW Mills ADC MacKnight JA Jarrell JM Dayer DA Ausiello 《The Journal of cell biology》1981,88(3):637-643
To determine the specificity and efficacy of [(3)H]ouabain binding as a quantitative measure of the Na(+) pump (Na(+), K(+)-ATPase) and as a marker for the localization of pumps involved in transepithelial Na(+)-transport, we analyzed the interaction of [(3)H]ouabain with its receptor in pig kidney epithelial (LLC-PK(1)) cells. When these epithelial cells are depleted of Na(+) and exposed to 2 muM [(3)H]ouabain in a Na(+)-free medium, binding is reduced by 90 percent. When depleted of K(+) and incubated in a K(+)- free medium, the ouabain binding rate is increase compared with that measured at 5 mM. This increase is only demonstable when Na(+) is present. The increased rate could be attributed to the predominance of the Na(+)-stimulated phosphorylated form of the pump, as K(+) is not readily available to stimulate dephosphorylation. However, some binding in the K(+)-free medium is attributable to pump turnover (and therefore, recycling of K(+)), because analysis of K(+)-washout kinetics demonstrated that addition of 2 muM ouabain to K(+)-depleted cells increased the rate of K(+) loss. These results indicate that in intact epithelial cells, unlike isolated membrane preparations, the most favorable condition for supporting ouabain binding occurs when the Na(+), K(+)-ATPase is operating in the Na(+)-pump mode or is phosphorylated in the presence of Na(+). When LLC-PK(1) cells were exposed to ouabain at 4 degrees C, binding was reduced by 97 percent. Upon rewarming, the rate of binding was greater than that obtained on cells kept at a constant 37 degrees C. However, even at this accelerated rate, the time to reach equilibrium was beyond what is required for cells, swollen by exposure to cold, to recover normal volume. Thus, results from studies that have attempted to use ouabain to eliminate the contribution of the conventional Na(+) pump to volume recovery must be reevaluated if the exposure to ouabain was done in the cold or under conditions in which the Na(+) pump is not operating. 相似文献
30.