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961.
Endogenous prenylation with sesquiterpene or diterpene isoprenoids facilitates membrane localization and functional activation of small monomeric GTP-binding proteins. A direct effect of isoprenoids on regulation of gene expression and protein stability has also been proposed. In this study, we determined the role of sesquiterpene or diterpene isoprenoids on the regulation of Rho G-protein expression, activation, and stability in human trabecular meshwork (TM) cells. In both primary and transformed human TM cells, limiting endogenous isoprenoid synthesis with lovastatin, a potent HMG-CoA reductase inhibitor, elicited marked increases in RhoA and RhoB mRNA and protein content. The effect of lovastatin was dose-dependent with newly synthesized inactive protein accumulating in the cytosol. Supplementation with geranylgeranyl pyrophosphate (GGPP) prevented, while inhibition of geranylgeranyl transferase-I mimicked, the effects of lovastatin on RhoA and RhoB protein content. Similarly, lovastatin-dependent increases in RhoA and RhoB mRNA expression were mimicked by geranylgeranyl transferase-I inhibition. Interestingly, GGPP supplementation selectively promoted the degradation of newly synthesized Rho proteins which was mediated, in part, through the 20S proteasome. Functionally, GGPP supplementation prevented lovastatin-dependent decreases in actin stress fiber organization while selectively facilitating the subcellular redistribution of accumulated Rho proteins from the cytosol to the membrane and increasing RhoA activation. Post-translational prenylation with geranylgeranyl diterpenes selectively facilitates the expression, membrane translocation, functional activation, and turnover of newly synthesized Rho proteins. Geranylgeranyl prenylation represents a novel mechanism by which active Rho proteins are targeted to the 20S proteasome for degradation in human TM cells. 相似文献
962.
To sustain plants’ postembryonic growth and development in a structure of cells fixed in cell walls, a tightly controlled short distance cell–cell communication is required. The focus on phytohormones, such as auxin, has historically overshadowed the importance of small peptide signals, but it is becoming clear that secreted peptide signals are important in cell–cell communication to coordinate and integrate cellular functions. However, of the more than 1000 potential secreted peptides, so far only very few have been functionally characterized or matched to a receptor. Here, we will describe our current knowledge on how small peptide signals can be identified, how they are modified and processed, which roles they play in Arabidopsis thaliana development, and through which receptors they act. 相似文献
963.
The role of algae in the metabolism of northern peatlands is largely unknown, as is how algae will respond to the rapid climate change being experienced in this region. In this study, we examined patterns in algal productivity, nutrients, and dissolved organic carbon (DOC) during an uncharacteristically wet summer in an Alaskan rich fen. Our sampling was conducted in three large-scale experimental plots where water table position had been manipulated (including both drying and wetting plots and a control) for the previous 4 years. This study allowed us to explore how much ecosystem memory of the antecedent water table manipulations governed algal responses to natural flooding. Despite no differences in water table position between the manipulated plots at the time of sampling, algal primary productivity was consistently higher in the lowered water table plot compared to the control or raised water table plots. In all plots, algal productivity peaked immediately following seasonal maxima in nutrient concentrations. We found a positive relationship between algal productivity and water-column DOC concentrations (r (2) = 0.85, P < 0.001). Using these data, we estimate that algae released approximately 19% of fixed carbon into the water column. Algal exudates were extremely labile in biodegradability assays, decreasing by more than 55% within the first 24 h of incubation. We suggest that algae can be an important component of the photosynthetic community in boreal peatlands and may become increasingly important for energy flow in a more variable climate with more intense droughts and flooding. 相似文献
964.
Tepper O Hirsch D Levine J Garfein E 《Plastic and reconstructive surgery》2012,130(1):192e-194e; author reply 194e-195e
965.
Breedlove EL Robinson M Talavage TM Morigaki KE Yoruk U O'Keefe K King J Leverenz LJ Gilger JW Nauman EA 《Journal of biomechanics》2012,45(7):1265-1272
Concussion is a growing public health issue in the United States, and chronic traumatic encephalopathy (CTE) is the chief long-term concern linked to repeated concussions. Recently, attention has shifted toward subconcussive blows and the role they may play in the development of CTE. We recruited a cohort of high school football players for two seasons of observation. Acceleration sensors were placed in the helmets, and all contact activity was monitored. Pre-season computer-based neuropsychological tests and functional magnetic resonance imaging (fMRI) tests were also obtained in order to assess cognitive and neurophysiological health. In-season follow-up scans were then obtained both from individuals who had sustained a clinically-diagnosed concussion and those who had not. These changes were then related through stepwise regression to history of blows recorded throughout the football season up to the date of the scan. In addition to those subjects who had sustained a concussion, a substantial portion of our cohort who did not sustain concussions showed significant neurophysiological changes. Stepwise regression indicated significant relationships between the number of blows sustained by a subject and the ensuing neurophysiological change. Our findings reinforce the hypothesis that the effects of repetitive blows to the head are cumulative and that repeated exposure to subconcussive blows is connected to pathologically altered neurophysiology. 相似文献
966.
Whiting RJ Payne CJ Satiaputra J Kucera N Qiu TW Irtegun S Gunn NJ Slavova-Azmanova NS Lavova-Azmanova NS Mulhern TD Ingley E 《The Biochemical journal》2012,442(3):611-620
The tyrosine kinase Lyn is involved in oncogenic signalling in several leukaemias and solid tumours, and we have previously identified a pathway centred on Cbp [Csk (C-terminal Src kinase)-binding protein] that mediates both enzymatic inactivation, as well as proteasomal degradation of Lyn via phosphorylation-dependent recruitment of Csk (responsible for phosphorylating the inhibitory C-terminal tyrosine of Lyn) and SOCS1 (suppressor of cytokine signalling 1; an E3 ubiquitin ligase). In the present study we show that fusing specific functional motifs of Cbp and domains of SOCS1 together generates a novel molecule capable of directing the proteasomal degradation of Lyn. We have characterized the binding of pY (phospho-tyrosine) motifs of Cbp to SFK (Src-family kinase) SH2 (Src homology 2) domains, identifying those with high affinity and specificity for the SH2 domain of Lyn and that are preferred substrates of active Lyn. We then fused them to the SB (SOCS box) of SOCS1 to facilitate interaction with the ubiquitination-promoting elongin B/C complex. As an eGFP (enhanced green fluorescent protein) fusion, these proteins can direct the polyubiquitination and proteasomal degradation of active Lyn. Expressing this fusion protein in DU145 cancer cells (but not LNCaP or MCF-7 cells), that require Lyn signalling for survival, promotes loss of Lyn, loss of caspase 3, appearance of an apoptotic morphology and failure to survive/expand. These findings show how functional domains of Cbp and SOCS1 can be fused together to generate molecules capable of inhibiting the growth of cancer cells that express high levels of active Lyn. 相似文献
967.
While genetically encoded Ca(2+) indicators (GECIs) allow Ca(2+) imaging in model organisms, the gene expression is often under the control of a single promoter that may drive expression beyond, the cell types of interest. To enable more cell-type specific targeting, GECIs can be brought under the, control of the intersecting expression from two promoters. Here, we present the splitting and, reassembly of two representative GECIs (TN-XL and GCaMP2) mediated by the split intein from Nostoc, punctiforme (NpuDnaE). While the split TN-XL biosensor offered ratiometric Ca(2+) imaging, it had a, diminished Ca(2+) response relative to the native TN-XL biosensor. In contrast, the split GCaMP2, biosensor retained similar Ca(2+) response to the native GCaMP2. The split GCaMP2 biosensor was, further targeted to the pharyngeal muscles of Caenorhabditis elegans where Ca(2+) signals from feeding C. elegans, were imaged. Thus, we envision that increased cell-type targetability of GECIs is feasible with two, complementary promoters. 相似文献
968.
969.
Visser EM Oliveira Filho D Tótola MR Martins MA Guimarães VM 《Bioprocess and biosystems engineering》2012,35(5):801-807
Jatropha curcas has great potential as an oil crop for use in biodiesel applications, and the outer shell is rich in lignocellulose that
may be converted to ethanol, giving rise to the concept of a biorefinery. In this study, two dilute pretreatments of 0.5%
H2SO4 and 1.0% NaOH were performed on Jatropha shells with subsequent simultaneous saccharification and fermentation (SSF) of the
pretreated water-insoluble solids (WIS) to evaluate the effect of inhibitors in the pretreatment slurry. A cellulase loading
of 15 FPU/g WIS, complimented with an excess of cellobiase (19.25 U/g), was used for SSF of either the washed WIS or the original
slurry to determine the effect of inhibitors. Ethanol and glucose were monitored during SSF of 20 g of pretreated biomass.
The unwashed slurry showed to have a positive effect on SSF efficiency for the NaOH-pretreated biomass. Maximum efficiencies
of glucan conversion to ethanol in the WIS were 40.43% and 41.03% for the H2SO4- and NaOH-pretreated biomasses, respectively. 相似文献
970.
Karakoc E Alkan C O'Roak BJ Dennis MY Vives L Mark K Rieder MJ Nickerson DA Eichler EE 《Nature methods》2012,9(2):176-178
We report an algorithm to detect structural variation and indels from 1 base pair (bp) to 1 Mbp within exome sequence data sets. Splitread uses one end-anchored placements to cluster the mappings of subsequences of unanchored ends to identify the size, content and location of variants with high specificity and sensitivity. The algorithm discovers indels, structural variants, de novo events and copy number-polymorphic processed pseudogenes missed by other methods. 相似文献