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941.
942.
H Inuzuka D Gao LW Finley W Yang L Wan H Fukushima YR Chin B Zhai S Shaik AW Lau Z Wang SP Gygi K Nakayama J Teruya-Feldstein A Toker MC Haigis PP Pandolfi W Wei 《Cell》2012,150(1):179-193
Aberrant Skp2 signaling has been implicated as a driving event in tumorigenesis. Although the underlying molecular mechanisms remain elusive, cytoplasmic Skp2 correlates with more aggressive forms of breast and prostate cancers. Here, we report that Skp2 is acetylated by p300 at K68 and K71, which is a process that can be antagonized by the SIRT3 deacetylase. Inactivation of SIRT3 leads to elevated Skp2 acetylation, which leads to increased Skp2 stability through impairment of the Cdh1-mediated proteolysis pathway. As a result, Skp2 oncogenic function is increased, whereby cells expressing an acetylation-mimetic mutant display enhanced cellular proliferation and tumorigenesis in vivo. Moreover, acetylation of Skp2 in the nuclear localization signal (NLS) promotes its cytoplasmic retention, and cytoplasmic Skp2 enhances cellular migration through ubiquitination and destruction of E-cadherin. Thus, our study identifies an acetylation-dependent regulatory mechanism governing Skp2 oncogenic function and provides insight into how cytoplasmic Skp2 controls cellular migration. 相似文献
943.
Ross KA Feazel LM Robertson CE Fathepure BZ Wright KE Turk-Macleod RM Chan MM Held NL Spear JR Pace NR 《Microbial ecology》2012,64(1):162-170
The mesothermal outflow zones (50-65°C) of geothermal springs often support an extensive zone of green and orange laminated microbial mats. In order to identify and compare the microbial inhabitants of morphologically similar green-orange mats from chemically and geographically distinct springs, we generated and analyzed small-subunit ribosomal RNA (rRNA) gene amplicons from six mesothermal mats (four previously unexamined) in Yellowstone National Park. Between three and six bacterial phyla dominated each mat. While many sequences bear the highest identity to previously isolated phototrophic genera belonging to the Cyanobacteria, Chloroflexi, and Chlorobi phyla, there is also frequent representation of uncultured, unclassified members of these groups. Some genus-level representatives of these dominant phyla were found in all mats, while others were unique to a single mat. Other groups detected at high frequencies include candidate divisions (such as the OP candidate clades) with no cultured representatives or complete genomes available. In addition, rRNA genes related to the recently isolated and characterized photosynthetic acidobacterium "Candidatus Chloracidobacterium thermophilum" were detected in most mats. In contrast to microbial mats from well-studied hypersaline environments, the mesothermal mats in this study accrue less biomass and are substantially less diverse, but have a higher proportion of known phototrophic organisms. This study provides sequences appropriate for accurate phylogenetic classification and expands the molecular phylogenetic survey of Yellowstone microbial mats. 相似文献
944.
Benavides JA Godreuil S Bodenham R Ratiarison S Devos C Petretto MO Raymond M Escobar-Páramo P 《Applied and environmental microbiology》2012,78(12):4281-4287
The intensification of human activities within the habitats of wild animals is increasing the risk of interspecies disease transmission. This risk is particularly important for great apes, given their close phylogenetic relationship with humans. Areas of high human density or intense research and ecotourism activities expose apes to a high risk of disease spillover from humans. Is this risk lower in areas of low human density? We determined the prevalence of Escherichia coli antibiotic-resistant isolates in a population of the critically endangered western lowland gorilla (Gorilla gorilla gorilla) and other wild mammals in Lopé National Park (LNP), Gabon, and we tested whether the observed pattern could be explained by bacterial transmission from humans and domestic animals into wildlife populations. Our results show a high prevalence of antibiotic-resistant bacterial isolates in humans and low levels in gorillas and other wildlife. The significant differences in the genetic background of the resistant bacteria isolated from humans and gorillas suggest that transmission is low or does not occur between these two species. These findings indicate that the presence of antibiotic-resistant strains in wildlife do not imply direct bacteria transmission from humans. Thus, in areas of low human density, human-wildlife E. coli transmission seems to be low. The presence of antibiotic-resistant isolates in gorillas may be better explained by other mechanisms for resistance acquisition, such as horizontal gene exchange among bacteria or naturally acquired resistance. 相似文献
945.
McKinley JW Parzen RE Mercado Guzmán Á 《Applied and environmental microbiology》2012,78(15):5133-5137
Viable ova of Ascaris lumbricoides, an indicator organism for pathogens, are frequently found in feces-derived compost produced from ecological toilets, demonstrating that threshold levels of time, temperature, pH, and moisture content for pathogen inactivation are not routinely met. Previous studies have determined that NH(3) has ovicidal properties for pathogens, including Ascaris ova. This research attempted to achieve Ascaris inactivation via NH(3) under environmental conditions commonly found in ecological toilets and using materials universally available in an ecological sanitation setting, including compost (feces and sawdust), urine, and ash. Compost mixed with stored urine and ash produced the most rapid inactivation, with significant inactivation observed after 2 weeks and with a time to 99% ovum inactivation (T(99)) of 8 weeks. Compost mixed with fresh urine and ash achieved a T(99) of 15 weeks, after a 4-week lag phase. Both matrices had relatively high total-ammonia concentrations and pH values of >9.24 (pK(a) of ammonia). In compost mixed with ash only, and in compost mixed with fresh urine only, inactivation was observed after an 11-week lag phase. These matrices contained NH(3) concentrations of 164 to 173 and 102 to 277 mg/liter, respectively, when inactivation occurred, which was below the previously hypothesized threshold for inactivation (280 mg/liter), suggesting that a lower threshold NH(3) concentration may be possible with a longer contact time. Other significant results include the hydrolysis of urea to ammonia between pH values of 10.4 and 11.6, above the literature threshold pH of 10. 相似文献
946.
Yong-Ming Zhang Jeyanthi Rebecca Livingstone Eiji Hirasawa 《Acta Physiologiae Plantarum》2012,34(4):1411-1419
FAD-containing monoamine oxidase (MAO; EC 1.4.3.4) oxidises monoamines to their corresponding aldehydes, H2O2, and NH3. It has been purified to homogeneity in mammals, but to our knowledge, there have been no reports of the enzyme in plants. MAO activity was detected in Avena sativa seedlings during germination using benzylamine as substrate. The enzyme was purified to homogeneity (as assessed by native PAGE) by Sephadex G-25, DEAE Sephacel, hydroxyapatite, Mono Q, and TSK-GEL column chromatographies. The molecular mass estimated by gel filtration using the TSK-GEL column was 220?kDa. SDS-PAGE yielded four distinct protein bands of 78, 58, 55, and 32?kDa molecular masses. The pI value of the enzyme was 6.3. The enzyme showed high substrate specificity for an endogenous amine, phenethylamine, which was oxidised to phenylacetaldehde, but not for ethylamine, propylamine, butylamine, pentylamine, dopamine, serotonin, tryptamine, or tyramine. The K m values for benzylamine and phenethylamine were 2.7?×?10?4 and 7.1?×?10?4?M, respectively. Enzyme activity was not inhibited by pargyline, clorgyline, semicarbazide, or Na-diethyldithiocarbamate. Benzaldehyde, the product of benzylamine oxidation, exhibited strong competitive inhibition of enzyme activity with a Ki of 3???M. FAD was identified by ODS-column chromatography as an enzyme cofactor. The enzyme contained 2?mol of FAD per 220,000?g of enzyme. 相似文献
947.
McCranor BJ Bozym RA Vitolo MI Fierke CA Bambrick L Polster BM Fiskum G Thompson RB 《Journal of bioenergetics and biomembranes》2012,44(2):253-263
The role of zinc ion in cytotoxicity following ischemic stroke, prolonged status epilepticus, and traumatic brain injury remains
controversial, but likely is the result of mitochondrial dysfunction. We describe an excitation ratiometric fluorescence biosensor
based on human carbonic anhydrase II variants expressed in the mitochondrial matrix, permitting free zinc levels to be quantitatively
imaged therein. We observed an average mitochondrial matrix free zinc concentration of 0.2 pM in the PC12 rat pheochromacytoma cell culture line. Cytoplasmic and mitochondrial free zinc levels were imaged in a cellular
oxygen glucose deprivation (OGD) model of ischemia/reperfusion. We observed a significant increase in mitochondrial zinc 1 h
following 3 h OGD, at a time point when cytosolic zinc levels were depressed. Following the increase, mitochondrial zinc levels
returned to physiological levels, while cytosolic zinc increased gradually over a 24 h time period in viable cells. The increase
in intramitochondrial zinc observed during reoxygenation after OGD may contribute to bioenergetic dysfunction and cell death
that occurs with both in vitro and in vivo models of reperfusion. 相似文献
948.
Because hydrodynamic regimes influence community assemblages, commercial ferry traffic can directly affect neighboring marine ecosystems by altering water movement. One of the largest ferry fleets in the world traverses the calm, protected waters of the Canadian Gulf Islands (British Columbia). To address the effects of ferry wakes on rocky marine intertidal communities, we examined community assemblages in sites impacted by ferry wakes (N?=?5) relative to geographically similar control sites not directly exposed to ferry wakes (N?=?6). Intertidal communities were significantly different between wake-influenced and control sites. Further analyses revealed that community level differences resulted from differences in seaweed assemblages, while invertebrate assemblages were similar. Sites exposed to ferry traffic displayed significantly greater overall seaweed abundance and seaweed species richness. Nitrate and nitrite concentrations, salinity, fetch, and tidal zonation were not significantly different between wake-impacted and control sites. However, dissolution blocks revealed that wake-impacted sites experienced increased overall water movement. Furthermore, block dissolution was negatively associated with distance from nearest ferry route and not fetch. Although dissolution block cannot disentangle effects of increased flow versus waves resulting from ferry wakes, we conclude that increased overall water movement from frequent and proximate ferry traffic stimulates primary production in rocky intertidal marine seaweeds by ameliorating mass transfer limitation. 相似文献
949.
Biofilms of microbial cells encased in an exopolymeric matrix can form on solid surfaces, but how bacteria sense a solid surface and upregulate biofilm genes is largely unknown. We investigated the role of the Bacillus subtilis signal peptidase, SipW, which has a unique role in forming biofilms on a solid surface and is not required at an air-liquid interface. Surprisingly, we found that the signal peptidase activity of SipW was not required for solid-surface biofilms. Furthermore, a SipW mutant protein was constructed that lacks the ability to form a solid-surface biofilm but still retains signal peptidase activity. Through genetic and gene expression tests, the non-signal peptidase role of SipW was found to activate biofilm matrix genes specifically when cells were on a solid surface. These data provide the first evidence that a signal peptidase is bifunctional and that SipW has a regulatory role in addition to its role as a signal peptidase. 相似文献
950.
The forces driving extra-pair reproduction by socially monogamous females, and the resulting genetic polyandry, remain unclear. A testable prediction of the hypothesis that extra-pair reproduction partly reflects indirect selection on females is that extra-pair young (EPY) will be fitter than their within-pair young (WPY) maternal half-siblings. This prediction has not been comprehensively tested in a wild population, requiring data on the lifetime reproductive success (LRS) of maternal half-sib EPY and WPY. We used 17 years of genetic parentage data from song sparrows, Melospiza melodia, to compare the LRS of hatched EPY and WPY maternal half-siblings measured as their lifetime number of hatched offspring, recruited offspring, and hatched grandoffspring. EPY hatchlings were not significantly fitter than WPY hatchlings for any of three measures of LRS. Furthermore, opposite to prediction, EPY hatchlings tended to have lower LRS than their maternal half-sibling WPY hatchlings on average. EPY also tended to be less likely to survive to hatch than their maternal half-sibling WPY. Taken together, these results fail to support one key hypothesis explaining the evolution of genetic polyandry by socially monogamous females and suggest there may be weak indirect selection against female extra-pair reproduction in song sparrows. 相似文献