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921.
922.
Chris J. Cotsapas Rohan B.H. Williams Jeremy N. Pulvers David J. Nott Eva K.F. Chan Mark J. Cowley Peter F.R. Little 《Mammalian genome》2006,17(6):490-495
The analysis of the influence of genetic variation on regulation of gene expression at a near-genome-wide level has become
the focus of much recent interest. It is widely appreciated that many genes are expressed in a tissue-specific manner and
that others are more ubiquitously expressed but relatively little is known about how genetic variation might influence these
tissue patterns of gene expression. In this review we discuss what is known about the tissue specificity of the influence
of genetic variation and review the challenges that we face in combining hugely parallel, microarray-based gene analysis with
equally expensive genetic analysis. We conclude that the available data suggest that genetic variation is essentially tissue
specific in its effects upon gene expression and this has important implications for experimental analysis. 相似文献
923.
924.
G protein-coupled receptors (GPCRs) mediate cellular responses to a variety of stimuli, but how specific responses are regulated has been elusive, as the types of GPCRs vastly outnumber the classes of G protein heterotrimers available to initiate downstream signaling. In our analysis of signaling proteins containing DEP domains ( approximately 90 residue sequence motifs first recognized in fly Dishevelled, worm EGL-10, and mammalian Pleckstrin), we find that DEP domains are responsible for specific recognition of GPCRs. We examined the yeast regulator of G protein signaling (RGS) protein Sst2 and demonstrate that the DEP domains in Sst2 mediate binding to its cognate GPCR (Ste2). DEP-domain-mediated tethering promotes downregulation by placing the RGS protein in proximity to its substrate (receptor-activated Galpha subunit). Sst2 docks to the Ste2 cytosolic tail, but only its unphosphorylated state, allowing for release and recycling of this regulator upon receptor desensitization and internalization. DEP-domain-mediated targeting of effectors and regulators to specific GPCRs provides a means to dictate the nature, duration, and specificity of the response. 相似文献
925.
Burton JP Wescombe PA Moore CJ Chilcott CN Tagg JR 《Applied and environmental microbiology》2006,72(4):3050-3053
Streptococcus salivarius is a prominent member of the oral microbiota and has excellent potential for use as a probiotic targeting the oral cavity. In this report we document safety data relating to S. salivarius K12, including assessment of its antibiogram, metabolic profiles, and virulence determinants, and we examine the microbial composition of saliva following the dosing of subjects with K12. 相似文献
926.
Dissolved H2 and CO2 were measured by an improved manual headspace-gas chromatographic method during fermentative H2 production with N2 sparging. Sparging increased the yield from 1.3 to 1.8 mol H2/mol glucose converted, although H2 and CO2 were still supersaturated regardless of sparging. The common assumption that sparging increases the H2 yield because of lower dissolved H2 concentrations may be incorrect, because H2 was not lowered into the range necessary to affect the relevant enzymes. More likely, N2 sparging decreased the rate of H2 consumption via lower substrate concentrations. 相似文献
927.
Zheng W Kollmeyer J Symolon H Momin A Munter E Wang E Kelly S Allegood JC Liu Y Peng Q Ramaraju H Sullards MC Cabot M Merrill AH 《Biochimica et biophysica acta》2006,1758(12):1864-1884
Sphingolipids are comprised of a backbone sphingoid base that may be phosphorylated, acylated, glycosylated, bridged to various headgroups through phosphodiester linkages, or otherwise modified. Organisms usually contain large numbers of sphingolipid subspecies and knowledge about the types and amounts is imperative because they influence membrane structure, interactions with the extracellular matrix and neighboring cells, vesicular traffic and the formation of specialized structures such as phagosomes and autophagosomes, as well as participate in intracellular and extracellular signaling. Fortunately, "sphingolipidomic" analysis is becoming feasible (at least for important subsets such as all of the backbone "signaling" subspecies: ceramides, ceramide 1-phosphates, sphingoid bases, sphingoid base 1-phosphates, inter alia) using mass spectrometry, and these profiles are revealing many surprises, such as that under certain conditions cells contain significant amounts of "unusual" species: N-mono-, di-, and tri-methyl-sphingoid bases (including N,N-dimethylsphingosine); 3-ketodihydroceramides; N-acetyl-sphingoid bases (C2-ceramides); and dihydroceramides, in the latter case, in very high proportions when cells are treated with the anticancer drug fenretinide (4-hydroxyphenylretinamide). The elevation of DHceramides by fenretinide is befuddling because the 4,5-trans-double bond of ceramide has been thought to be required for biological activity; however, DHceramides induce autophagy and may be important in the regulation of this important cellular process. The complexity of the sphingolipidome is hard to imagine, but one hopes that, when partnered with other systems biology approaches, the causes and consequences of the complexity will explain how these intriguing compounds are involved in almost every aspect of cell behavior and the malfunctions of many diseases. 相似文献
928.
Seven top amateur or professional skateboarders (BW=713 N+/-83 N) performed Ollie maneuvers onto and off an elevated wooden platform (45.7 cm high). We recorded ground reaction force (GRF) data for three Ollie Up (OU) and Ollie Down (OD) trials per participant. The vertical GRF (VGRF) during the OU has a characteristic propulsive peak (M=2.22 body weight [BW]+/-0.22) resulting from rapidly rotating the tail of the board into the ground to propel the skater and board up and forward. The anterior-posterior (A-P) GRF also shows a pronounced peak (M=0.05+/-0.01 BW) corresponding with this propulsive VGRF peak. The initial phase of landing in the OD shows an impact peak in VGRF rising during the first 30 to 80 ms to a mean of 4.74+/-0.46 BW. These impact peaks are higher than expected given the relatively short drop of 45.7 cm and crouched body position. But we observed that our participants intentionally affected a firm landing to stabilize the landing position; and the Ollie off the platform raised the center of mass, also contributing to higher forces. 相似文献
929.
Another step along the road towards determining the subcellular localization of a complete mammalian proteome has been taken with a study using cellular fractionation and protein correlation profiling to identify and localize organellar proteins. Here we discuss this new work in the context of other strategies for large-scale subcellular localization. 相似文献
930.
The DExD/H-box ATPase Dbp5 is essential for nuclear mRNA export, although its precise role in this process remains poorly understood. Here, we identify the nuclear pore protein Gle1 as a cellular activator of Dbp5. Dbp5 alone is unable to stably bind RNA or effectively hydrolyse ATP under physiological conditions, but addition of Gle1 dramatically stimulates these activities. A gle1 point mutant deficient for Dbp5 stimulation in vitro displays an mRNA export defect in vivo, indicating that activation of Dbp5 is an essential function of Gle1. Interestingly, Gle1 binds directly to inositol hexakisphosphate (InsP6) and InsP6 potentiates the Gle1-mediated stimulation of Dbp5. Dominant mutations in DBP5 and GLE1 that rescue mRNA export phenotypes associated with the lack of InsP6 mimic the InsP6 effects in vitro. Our results define specific functions for Gle1 and InsP6 in mRNA export and suggest that local activation of Dbp5 at the nuclear pore is critical for mRNA export. 相似文献