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141.
142.
Connie R. Jimenez Jaco C. Knol Gerrit A. Meijer Remond J.A. Fijneman 《Journal of Proteomics》2010,73(10):1873-1895
Colorectal cancer (CRC) is a common cause of cancer-related mortality in the developed world. Improved methods for early detection and disease management are urgently needed. Many efforts in the past 5 years have been devoted to protein biomarker discovery for early detection of CRC. Here, we discuss identity-based studies employing tandem mass spectrometry that analyzed clinical material as well as model systems. Through meta-analysis we provide a list of CRC-associated tissue proteins discovered in multiple studies, with the greater majority being 2D gel-based discoveries coupled to MS/MS. So far only a limited number of CRC-associated proteins have been validated in serum for non-invasive testing for CRC. This list includes several intracellular and nuclear proteins that a priori would not have been considered candidate biomarkers based on their predicted subcellular localization. Finally, we highlight promising new directions that combine targeted analyses of subcellular proteomes, like the cell surface, secretome, exosome, and nuclear matrix, with nanoLC-MS/MS-based proteomics. We anticipate that in the near future, these novel mass spectrometry-based in-depth approaches will uncover many novel, specific CRC marker candidates in clinical tissues and that their targeted validation with multi-reaction monitoring MS will speed up development of non-invasive tests in feces and serum/plasma. 相似文献
143.
Direct fitness benefits explain mate preference,but not choice,for similarity in heterozygosity levels 下载免费PDF全文
Under sexual selection, mate preferences can evolve for traits advertising fitness benefits. Observed mating patterns (mate choice) are often assumed to represent preference, even though they result from the interaction between preference, sampling strategy and environmental factors. Correlating fitness with mate choice instead of preference will therefore lead to confounded conclusions about the role of preference in sexual selection. Here we show that direct fitness benefits underlie mate preferences for genetic characteristics in a unique experiment on wild great tits. In repeated mate preference tests, both sexes preferred mates that had similar heterozygosity levels to themselves, and not those with which they would optimise offspring heterozygosity. In a subsequent field experiment where we cross fostered offspring, foster parents with more similar heterozygosity levels had higher reproductive success, despite the absence of assortative mating patterns. These results support the idea that selection for preference persists despite constraints on mate choice. 相似文献
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Pérez-Pérez JM Rubio-Díaz S Dhondt S Hernández-Romero D Sánchez-Soriano J Beemster GT Ponce MR Micol JL 《Plant, cell & environment》2011,34(12):2200-2211
Despite the large number of genes known to affect leaf shape or size, we still have a relatively poor understanding of how leaf morphology is established. For example, little is known about how cell division and cell expansion are controlled and coordinated within a growing leaf to eventually develop into a laminar organ of a definite size. To obtain a global perspective of the cellular basis of variations in leaf morphology at the organ, tissue and cell levels, we studied a collection of 111 non-allelic mutants with abnormally shaped and/or sized leaves, which broadly represent the mutational variations in Arabidopsis thaliana leaf morphology not associated with lethality. We used image-processing techniques on these mutants to quantify morphological parameters running the gamut from the palisade mesophyll and epidermal cells to the venation, whole leaf and rosette levels. We found positive correlations between epidermal cell size and leaf area, which is consistent with long-standing Avery's hypothesis that the epidermis drives leaf growth. In addition, venation parameters were positively correlated with leaf area, suggesting that leaf growth and vein patterning share some genetic controls. Positional cloning of the genes affected by the studied mutations will eventually establish functional links between genotypes, molecular functions, cellular parameters and leaf phenotypes. 相似文献
146.
Siemerink MA Kuit W López Contreras AM Eggink G van der Oost J Kengen SW 《Applied and environmental microbiology》2011,77(8):2582-2588
Acetoin reductase (ACR) catalyzes the conversion of acetoin to 2,3-butanediol. Under certain conditions, Clostridium acetobutylicum ATCC 824 (and strains derived from it) generates both d- and l-stereoisomers of acetoin, but because of the absence of an ACR enzyme, it does not produce 2,3-butanediol. A gene encoding ACR from Clostridium beijerinckii NCIMB 8052 was functionally expressed in C. acetobutylicum under the control of two strong promoters, the constitutive thl promoter and the late exponential adc promoter. Both ACR-overproducing strains were grown in batch cultures, during which 89 to 90% of the natively produced acetoin was converted to 20 to 22 mM d-2,3-butanediol. The addition of a racemic mixture of acetoin led to the production of both d-2,3-butanediol and meso-2,3-butanediol. A metabolic network that is in agreement with the experimental data is proposed. Native 2,3-butanediol production is a first step toward a potential homofermentative 2-butanol-producing strain of C. acetobutylicum. 相似文献
147.
The p24 proteins function in early secretory pathway transport processes, but their exact role is unclear. In physiologically activated Xenopus melanotrope cells, a representative of each p24 subfamily (p24α3, -β1, -γ3, -δ2) is upregulated coordinately with the major melanotrope cargo, proopiomelanocortin (POMC), whereas two other p24s (p24γ2 and -δ1) are also expressed, but not coordinately with POMC. Using melanotrope-specific transgene expression, we here find that the roles of both p24γ2 and p24δ1 in the transport, glycosylation, sulphation and cleavage of POMC are different from those of their upregulated subfamily relatives (p24γ3 and p24δ2, respectively). Thus, even p24 proteins from the same subfamily have distinct functions in secretory cargo biosynthesis. 相似文献
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Drew BG Carey AL Natoli AK Formosa MF Vizi D Reddy-Luthmoodoo M Weir JM Barlow CK van Hall G Meikle PJ Duffy SJ Kingwell BA 《Journal of lipid research》2011,52(3):572-581
We recently demonstrated that reconstituted high-density lipoprotein (rHDL) modulates glucose metabolism in humans via both AMP-activated protein kinase (AMPK) in muscle and by increasing plasma insulin. Given the key roles of both AMPK and insulin in fatty acid metabolism, the current study investigated the effect of rHDL infusion on fatty acid oxidation and lipolysis. Thirteen patients with type 2 diabetes received separate infusions of rHDL and placebo in a randomized, cross-over study. Fatty acid metabolism was assessed using steady-state tracer methodology, and plasma lipids were measured by mass spectrometry (lipidomics). In vitro studies were undertaken in 3T3-L1 adipocytes. rHDL infusion inhibited fasting-induced lipolysis (P = 0.03), fatty acid oxidation (P < 0.01), and circulating glycerol (P = 0.04). In vitro, HDL inhibited adipocyte lipolysis in part via activation of AMPK, providing a possible mechanistic link for the apparent reductions in lipolysis observed in vivo. In contrast, circulating NEFA increased after rHDL infusion (P < 0.01). Lipidomic analyses implicated phospholipase hydrolysis of rHDL-associated phosphatidylcholine as the cause, rather than lipolysis of endogenous fat stores. rHDL infusion inhibits fasting-induced lipolysis and oxidation in patients with type 2 diabetes, potentially through both AMPK activation in adipose tissue and elevation of plasma insulin. The phospholipid component of rHDL also has the potentially undesirable effect of increasing circulating NEFA. 相似文献