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51.
Rebecca A. Capel Emma L. Bolton Wee K. Lin Daniel Aston Yanwen Wang Wei Liu Xin Wang Rebecca-Ann B. Burton Duncan Bloor-Young Kai-Ting Shade Margarida Ruas John Parrington Grant C. Churchill Ming Lei Antony Galione Derek A. Terrar 《The Journal of biological chemistry》2015,290(50):30087-30098
Ca2+-permeable type 2 two-pore channels (TPC2) are lysosomal proteins required for nicotinic acid adenine dinucleotide phosphate (NAADP)-evoked Ca2+ release in many diverse cell types. Here, we investigate the importance of TPC2 proteins for the physiology and pathophysiology of the heart. NAADP-AM failed to enhance Ca2+ responses in cardiac myocytes from Tpcn2−/− mice, unlike myocytes from wild-type (WT) mice. Ca2+/calmodulin-dependent protein kinase II inhibitors suppressed actions of NAADP in myocytes. Ca2+ transients and contractions accompanying action potentials were increased by isoproterenol in myocytes from WT mice, but these effects of β-adrenoreceptor stimulation were reduced in myocytes from Tpcn2−/− mice. Increases in amplitude of L-type Ca2+ currents evoked by isoproterenol remained unchanged in myocytes from Tpcn2−/− mice showing no loss of β-adrenoceptors or coupling mechanisms. Whole hearts from Tpcn2−/− mice also showed reduced inotropic effects of isoproterenol and a reduced tendency for arrhythmias following acute β-adrenoreceptor stimulation. Hearts from Tpcn2−/− mice chronically exposed to isoproterenol showed less cardiac hypertrophy and increased threshold for arrhythmogenesis compared with WT controls. Electron microscopy showed that lysosomes form close contacts with the sarcoplasmic reticulum (separation ∼25 nm). We propose that Ca2+-signaling nanodomains between lysosomes and sarcoplasmic reticulum dependent on NAADP and TPC2 comprise an important element in β-adrenoreceptor signal transduction in cardiac myocytes. In summary, our observations define a role for NAADP and TPC2 at lysosomal/sarcoplasmic reticulum junctions as unexpected but major contributors in the acute actions of β-adrenergic signaling in the heart and also in stress pathways linking chronic stimulation of β-adrenoceptors to hypertrophy and associated arrhythmias. 相似文献
52.
Jessica A. Wisniewski Wee L. Teng Trudi L. Bannam Julian I. Rood 《Journal of bacteriology》2015,197(4):774-781
The anaerobic pathogen Clostridium perfringens encodes either toxin genes or antibiotic resistance determinants on a unique family of conjugative plasmids that have a novel conjugation region, the tcp locus. Studies of the paradigm conjugative plasmid from C. perfringens, the 47-kb tetracycline resistance plasmid pCW3, have identified several tcp-encoded proteins that are involved in conjugative transfer and form part of the transfer apparatus. In this study, the role of the conserved hypothetical proteins TcpD, TcpE, and TcpJ was examined. Mutation and complementation analyses showed that TcpD and TcpE were essential for the conjugative transfer of pCW3, whereas TcpJ was not required. To analyze the TcpD and TcpE proteins in C. perfringens, functional hemagglutinin (HA)-tagged derivatives were constructed. Western blots showed that TcpD and TcpE localized to the cell envelope fraction independently of the presence of other pCW3-encoded proteins. Finally, examination of the subcellular localization of TcpD and TcpE by immunofluorescence showed that these proteins were concentrated at both poles of C. perfringens donor cells, where they are postulated to form essential components of the multiprotein complex that comprises the transfer apparatus. 相似文献
53.
54.
Males of certain species belonging to the Bactrocera
dorsalis complex are strongly attracted to, and readily feed on methyl eugenol (ME), a plant secondary compound that is found in over 480 plant species worldwide. Amongst those species is one of the world’s most severe fruit pests the Oriental fruit fly, Bactrocera
dorsalis
s.s., and the former taxonomic species Bactrocera
invadens, Bactrocera
papayae and Bactrocera
philippinensis. The latter species have been recently synonymised with Bactrocera
dorsalis based on their very similar morphology, mating compatibility, molecular genetics and identical sex pheromones following consumption of ME. Previous studies have shown that male fruit fly responsiveness to lures is a unique phenomenon that is dose species-specific, besides showing a close correlation to sexual maturity attainment. This led us to use ME sensitivity as a behavioural parameter to test if Bactrocera
dorsalis and the three former taxonomic species had similar sensitivity towards odours of ME. Using Probit analysis, we estimated the median dose of ME required to elicit species’ positive response in 50% of each population tested (ED50). ED50 values were compared between Bactrocera
dorsalis and the former species. Our results showed no significant differences between Bactrocera
dorsalis
s.s., and the former Bactrocera
invadens, Bactrocera
papayae and Bactrocera
philippinensis in their response to ME. We consider that the Bactrocera males’ sensitivity to ME may be a useful behavioural parameter for species delimitation and, in addition to other integrative taxonomic tools used, provides further supportive evidence that the four taxa belong to one and the same biological species, Bactrocera
dorsalis. 相似文献
55.
56.
Hum Yan Chai Lai Khin Wee Tan Tian Swee Sh-Hussain Salleh Lim Yee Chea 《Biomedical engineering online》2011,10(1):1-22
Background
Guidewire (GW) size and stenosis dimensions are the two major factors affecting the translesional pressure drop. Studying the combined effect of these parameters on the mean pressure drop (Δp) across the stenosis is of high practical importance.Methods
In this study, time averaged mass and momentum conservation equations are solved analytically to obtain pressure drop-flow, Δp-Q, curves for three different percentage area blockages corresponding to moderate (64%), intermediate (80%), and severe (90%) stenoses. Stenosis is considered to be axisymmetric consisting of three different sections namely converging, throat, and diverging regions. Analytical expressions for pressure drop are obtained for each of these regions separately. Using this approach, effects of lesion length and GW insertion on the mean translesional pressure drop and its component (loss due to momentum change and viscous loss) are analyzed.Results and Conclusion
It is observed that for a given percent area stenosis (AS), increase in the throat length only increases the viscous loss. However, increase in the severity of stenosis and GW insertion increase both loss due to momentum change and viscous loss. GW insertion has greater contribution to the rise in viscous loss (increase by 2.14 and 2.72 times for 64% and 90% AS, respectively) than loss due to momentum change (1.34% increase for 64% AS and 25% decrease for 90% AS). It also alters the hyperemic pressure drop in moderate (48% increase) to intermediate (30% increase) stenoses significantly. However, in severe stenoses GW insertion has a negligible effect (0.5% increase) on hyperemic translesional pressure drop. It is also observed that pressure drop in a severe stenosis is less sensitive to lesion length variation (4% and 14% increase in Δp for without and with GW, respectively) as compared to intermediate (10% and 30% increase in Δp for without and with GW, respectively) and moderate stenoses (22% and 48% increase in Δp for without and with GW, respectively). Based on the contribution of pressure drop components to the total translesional pressure drop, it is found that viscous losses are dominant in moderate stenoses, while in severe stenoses losses due to momentum changes are significant. It is also shown that this simple analytical solution can provide valuable information regarding interpretation of coronary diagnostic parameters such as fractional flow reserve (FFR). 相似文献57.
58.
Folli F Okada T Perego C Gunton J Liew CW Akiyama M D'Amico A La Rosa S Placidi C Lupi R Marchetti P Sesti G Hellerstein M Perego L Kulkarni RN 《PloS one》2011,6(11):e28050
Insulin resistance, reduced β-cell mass, and hyperglucagonemia are consistent features in type 2 diabetes mellitus (T2DM). We used pancreas and islets from humans with T2DM to examine the regulation of insulin signaling and cell-cycle control of islet cells. We observed reduced β-cell mass and increased α-cell mass in the Type 2 diabetic pancreas. Confocal microscopy, real-time PCR and western blotting analyses revealed increased expression of PCNA and down-regulation of p27-Kip1 and altered expression of insulin receptors, insulin receptor substrate-2 and phosphorylated BAD. To investigate the mechanisms underlying these findings, we examined a mouse model of insulin resistance in β-cells--which also exhibits reduced β-cell mass, the β-cell-specific insulin receptor knockout (βIRKO). Freshly isolated islets and β-cell lines derived from βIRKO mice exhibited poor cell-cycle progression, nuclear restriction of FoxO1 and reduced expression of cell-cycle proteins favoring growth arrest. Re-expression of insulin receptors in βIRKO β-cells reversed the defects and promoted cell cycle progression and proliferation implying a role for insulin-signaling in β-cell growth. These data provide evidence that human β- and α-cells can enter the cell-cycle, but proliferation of β-cells in T2DM fails due to G1-to-S phase arrest secondary to defective insulin signaling. Activation of insulin signaling, FoxO1 and proteins in β-cell-cycle progression are attractive therapeutic targets to enhance β-cell regeneration in the treatment of T2DM. 相似文献
59.
The leaf protein content for 17 species of legumes ranges from 2.8 to 9.4 g% fr. wt, with an average of 5.3 g % fr. wt. Taxonomic pattern is detectable in leaf amino acid patterns, those of the Mimosoideae being distinguishable from those of the Papilionoideae and Caesalpinioideae. 相似文献
60.
A Rab-E GTPase mutant acts downstream of the Rab-D subclass in biosynthetic membrane traffic to the plasma membrane in tobacco leaf epidermis
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Zheng H Camacho L Wee E Batoko H Legen J Leaver CJ Malhó R Hussey PJ Moore I 《The Plant cell》2005,17(7):2020-2036
The function of the Rab-E subclass of plant Rab GTPases in membrane traffic was investigated using a dominant-inhibitory mutant (RAB-E1(d)[NI]) of Arabidopsis thaliana RAB-E1(d) and in vivo imaging approaches that have been used to characterize similar mutants in the plant Rab-D2 and Rab-F2 subclasses. RAB-E1(d)[NI] inhibited the transport of a secreted green fluorescent protein marker, secGFP, but in contrast with dominant-inhibitory RAB-D2 or RAB-F2 mutants, it did not affect the transport of Golgi or vacuolar markers. Quantitative imaging revealed that RAB-E1(d)[NI] caused less intracellular secGFP accumulation than RAB-D2(a)[NI], a dominant-inhibitory mutant of a member of the Arabidopsis Rab-D2 subclass. Furthermore, whereas RAB-D2(a)[NI] caused secGFP to accumulate exclusively in the endoplasmic reticulum, RAB-E1(d)[NI] caused secGFP to accumulate additionally in the Golgi apparatus and a prevacuolar compartment that could be labeled by FM4-64 and yellow fluorescent protein (YFP)-tagged Arabidopsis RAB-F2(b). Using the vacuolar protease inhibitor E64-d, it was shown that some secGFP was transported to the vacuole in control cells and in the presence of RAB-E1(d)[NI]. Consistent with the hypothesis that secGFP carries a weak vacuolar-sorting determinant, it was shown that a secreted form of DsRed reaches the apoplast without appearing in the prevacuolar compartment. When fused to RAB-E1(d), YFP was targeted specifically to the Golgi via a saturable nucleotide- and prenylation-dependent mechanism but was never observed on the prevacuolar compartment. We propose that RAB-E1(d)[NI] inhibits the secretory pathway at or after the Golgi, causing an accumulation of secGFP in the upstream compartments and an increase in the quantity of secGFP that enters the vacuolar pathway. 相似文献