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981.
Akavia UD Litvin O Kim J Sanchez-Garcia F Kotliar D Causton HC Pochanard P Mozes E Garraway LA Pe'er D 《Cell》2010,143(6):1005-1017
Systematic characterization of cancer genomes has revealed a staggering number of diverse aberrations that differ among individuals, such that the functional importance and physiological impact of most tumor genetic alterations remain poorly defined. We developed a computational framework that integrates chromosomal copy number and gene expression data for detecting aberrations that promote cancer progression. We demonstrate the utility of this framework using a melanoma data set. Our analysis correctly identified known drivers of melanoma and predicted multiple tumor dependencies. Two dependencies, TBC1D16 and RAB27A, confirmed empirically, suggest that abnormal regulation of protein trafficking contributes to proliferation in melanoma. Together, these results demonstrate the ability of integrative Bayesian approaches to identify candidate drivers with biological, and possibly therapeutic, importance in cancer. 相似文献
982.
983.
Dylan K. Kosma Eugene P. Parsons Tal Isaacson Shiyou Lü Jocelyn K. C. Rose Matthew A. Jenks 《Physiologia plantarum》2010,139(1):107-117
Recent studies suggest that fruit cuticle is an important contributing factor to tomato (Solanum lycopersicum) fruit shelf life and storability. Moreover, it has been hypothesized that variation in fruit cuticle composition may underlie differences in traits such as fruit resistance to desiccation and microbial infection. To gain a better understanding of cuticle lipid composition diversity during fruit ontogeny and to assess if there are common features that correlate with ripening, we examined developmental changes in fruit cuticle wax and cutin monomer composition of delayed‐ripening tomato fruit mutants, ripening inhibitor (rin) and non‐ripening (nor) and delayed‐ripening landrace Alcobaça. Previous reports show that fruit ripening processes such as climacteric ethylene production, cell wall degradation and color change are significantly delayed, or do not occur, in these lines. In the study presented here, however, we show that fruits from rin, nor and Alcobaça have cuticle lipid compositions that differ significantly from normal fruits of Ailsa Craig (AC) even at very early stages in fruit development, with continuing impacts throughout ripening. Moreover, rin, nor and the Alcobaça lines show quite different wax profiles from AC and each other throughout fruit development. Although cutin monomer composition differed much less than wax composition among the genotypes, all delayed‐ripening lines possessed higher relative amounts of C18 monomers than AC. Together, these results reveal new genetic associations between cuticle and fruit development processes and define valuable genetic resources to further explore the importance of cuticle in fruit shelf life. 相似文献
984.
985.
Funmei Yang Jacqueline G. Stonehuerner Judy H. Richards Ngoc-Bich Nguyen Kimberly D. Callaghan David J. Haile Andrew J. Ghio 《Biometals》2010,23(4):657-667
Exposure to bleomycin can result in an inflammatory lung injury. The biological effect of this anti-neoplastic agent is dependent
on its coordination of iron with subsequent oxidant generation. In lung cells, divalent metal transporter 1 (DMT1) can participate
in metal transport resulting in control of an oxidative stress and tissue damage. We tested the postulate that metal import
by DMT1 would participate in preventing lung injury after exposure to bleomycin. Microcytic anemia (mk/mk) mice defective in DMT1 and wild-type mice were exposed to either bleomycin or saline via intratracheal instillation and
the resultant lung injury was compared. Twenty-four h after instillation, the number of neutrophils and protein concentrations
after bleomycin exposure were significantly elevated in the mk/mk mice relative to the wild-type mice. Similarly, levels of a pro-inflammatory mediator were significantly increased in the
mk/mk mice relative to wild-type mice following bleomycin instillation. Relative to wild-type mice, mk/mk mice demonstrated lower non-heme iron concentrations in the lung, liver, spleen, and splenic, peritoneal, and liver macrophages.
In contrast, levels of this metal were elevated in alveolar macrophages from mk/mk mice. We conclude that DMT1 participates in the inflammatory lung injury after bleomycin with mk/mk mice having increased inflammation and damage following exposure. This finding supports the hypothesis that DMT1 takes part
in iron detoxification and homeostasis in the lung. 相似文献
986.
Maristela Pereira Zhihong Song Ludier Kesser Santos-Silva Mathew H. Richards Thi Thuy Minh Nguyen JiaLin Liu Celia Maria de Almeida Soares Aline Helena da Silva Cruz Kulothungan Ganapathy W. David Nes 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(10):1163-1174
The first committed step in the formation of 24-alkylsterols in the ascomycetous fungus Paracoccidiodes brasiliensis (Pb) has been shown to involve C24-methylation of lanosterol to eburicol (24(28)-methylene-24,25-dihydro-lanosterol) on the basis of metabolite co-occurrence. A similarity-based cloning strategy was employed to obtain the cDNA clone corresponding to the sterol C24-methyltransferase (SMT) implicated in the C24-methylation reaction. The resulting catalyst, prepared as a recombinant fusion protein (His/Trx/S), was expressed in Escherichia coli BL21(C43) and shown to possess a substrate specificity for lanosterol and to generate a single exocyclic methylene product. The full-length cDNA has an open reading frame of 1131 base pairs and encodes a protein of 377 residues with a calculated molecular mass of 42,502 Da. The enzymatic C24-methylation gave a Kmapp of 38 μM and kcatapp of 0.14 min−1. Quite unexpectedly, “plant” cycloartenol was catalyzed in high yield to 24(28)-methylene cycloartanol consistent with conformational arguments that favor that both cycloartenol and lanosterol are bound pseudoplanar in the ternary complex. Incubation of [27-13C]- or [24-2H]cycloartenol with PbSMT and analysis of the enzyme-generated product by a combination of 1H and 13CNMR and mass spectroscopy established the regiospecific conversion of the pro-Z methyl group of the Δ24(25)-substrate to the pro-R isopropyl methyl group of the product and the migration of H24 to C25 on the Re-face of the original substrate double bond undergoing C24-methylation. Inhibition kinetics and products formed from the substrate analogs 25-azalanosterol (Ki 14 nM) and 26,27-dehydrolanosterol (Ki 54 μM and kinact of 0.24 min−1) provide direct evidence for distinct reaction channeling capitalized by structural differences in the C24- and C26-sterol acceptors. 25-Azalanosterol was a potent inhibitor of cell growth (IC50, 30 nM) promoting lanosterol accumulation and 24-alkyl sterol depletion. Phylogenetic analysis of PbSMT with related SMTs of diverse origin together with the results of the present study indicate that the enzyme may have a similar complement of active-site amino acid residues compared to related yeast SMTs affording monofunctional C1-transfer behavior, yet there are sufficient differences in its overall amino acid composition and substrate-dependent partitioning pathways to group PbSMT into a fourth and new class of SMT. 相似文献
987.
Shifts in the seasonal timing of rainfall have the potential to substantially affect the immense terrestrial stores of soil
organic carbon (C, SOC). It remains unclear, however, how changes in the timing of rainfall are influencing SOC storage. We
hypothesized that a sustained shift in rainfall timing from winter to a spring-summer regime would reduce desert SOC stores
by creating moist and warm soil conditions, thus promoting decomposition. To investigate this, we evaluated how an 11-year
seasonal shift in rainfall (winter to spring-summer regime) affected SOC storage (that is, dissolved organic C, light SOC,
and heavy SOC) in soils beneath dominant shrub and perennial grass species in a cold desert sagebrush-steppe ecosystem. We
also measured the soil C to nitrogen (N) ratios, standing litter stocks, and root biomass C to help interpret the long-term
changes in SOC stores. As predicted, a seasonal shift in rainfall caused heavy SOC to decline beneath Artemisia tridentata ssp. wyomingensis by 14%, from 3.1 to 2.7 kg C m−2, and Pseudoroegneria spicata by 19%, from 3.0 to 2.4 kg C m−2. Neither dissolved organic C, nor the light fraction, responded to changes in rainfall. The C to N ratio of heavy SOC beneath
Artemisia declined by at least 6% under the warmer and moister conditions of the spring-summer regime, suggesting that alterations
in decomposition dynamics contributed to the loss of SOC. Unexpectedly, coarse litter and root C in Artemisia soils were lower under the spring-summer than winter rainfall regime, suggesting that a decline in litter inputs may also
have contributed to the loss of SOC. The C to N ratio of heavy SOC, litter stores (that is, coarse litter and thatch), and
root C in Pseudoroegneria soils demonstrated similar responses as in Artemisia soils, but these variables were at best only marginally significant. Our results suggest that a sustained seasonal shift
in rainfall from winter to spring-summer will reduce heavy SOC across cold deserts, and that this reduction will stem from
alterations in decomposition dynamics and net primary production by plants. Further, as global temperatures rise we may see
more overlap of moist and warm soil conditions, especially in ecosystems with winter rainfall regimes (for example, Mediterranean-climate
ecosystems and temperate forests), that may reduce SOC in the absence of rainfall changes. 相似文献
988.
The bee tribe Ceratinini provides important insights into the early stages of sociality. Many arthropods exhibit behaviours
precursory to social life, including adult longevity, parental care, nest loyalty and mutual tolerance, yet the origins of
social behaviour are few. Here we describe the biology of a facultatively social bee, Ceratina (Neoceratina) australensis, which exhibits all of the preadaptations for successful group living, yet presents ecological and behavioural characteristics
that seemingly disfavour frequent colony formation. This species is socially polymorphic with both solitary and social nests
collected in sympatry. Social colonies consist of two foundresses, one contributing both foraging and reproductive effort
and the second which remains at the nest as a passive guard. Cooperative nesting provides no overt reproductive benefits over
solitary nesting in this population, although brood survival tends to be greater in social colonies. Maternal longevity, subsociality
and bivoltine nesting phenology in this species favour colony formation, while dispersal habits and offspring longevity may
inhibit more frequent social nesting in this and other ceratinines. 相似文献
989.
990.
Richards KA Topham D Chaves FA Sant AJ 《Journal of immunology (Baltimore, Md. : 1950)》2010,185(9):4998-5002
The unexpected emergence of pandemic H1N1 influenza has generated significant interest in understanding immunological memory to influenza and how previous encounters with seasonal strains influence our ability to respond to novel strains. In this study, we evaluate the memory T cell repertoire in healthy adults to determine the abundance and protein specificity of influenza-reactive CD4 T cells, using an unbiased and empirical approach, and assess the ability of CD4 T cells to recognize epitopes naturally generated by infection with pandemic H1N1 virus. Our studies revealed that most individuals have abundant circulating CD4 T cells that recognize influenza-encoded proteins and that a strikingly large number of CD4 T cells can recognize autologous cells infected with live H1N1 virus. Collectively, our results indicate that a significant fraction of CD4 T cells generated from priming with seasonal virus and vaccines can be immediately mobilized upon infection with pandemic influenza strains derived from antigenic shift. 相似文献