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951.
952.
Saigusa T Reichert R Guare J Siroky BJ Gooz M Steele S Fenton RA Bell PD Kolb RJ 《American journal of physiology. Renal physiology》2012,302(7):F801-F808
Polycystic kidney disease (PKD) is a ciliopathy characterized by renal cysts and hypertension. These changes are presumably due to altered fluid and electrolyte transport in the collecting duct (CD). This is the site where vasopressin (AVP) stimulates vasopressin-2 receptor (V2R)-mediated aquaporin-2 (AQP2) insertion into the apical membrane. Since cysts frequently occur in the CD, we studied V2R and AQP2 trafficking and function in CD cell lines with stunted and normal cilia [cilia (-), cilia (+)] derived from the orpk mouse (hypomorph of the Tg737/Ift88 gene). Interestingly, only cilia (-) cells grown on culture dishes formed domes after apical AVP treatment. This observation led to our hypothesis that V2R mislocalizes to the apical membrane in the absence of a full-length cilium. Immunofluorescence indicated that AQP2 localizes to cilia and in a subapical compartment in cilia (+) cells, but AQP2 levels were elevated in both apical and basolateral membranes in cilia (-) cells after apical AVP treatment. Western blot analysis revealed V2R and glycosylated AQP2 in biotinylated apical membranes of cilia (-) but not in cilia (+) cells. In addition, apical V2R was functional upon apical desmopressin (DDAVP) treatment by demonstrating increased cAMP, water transport, and benzamil-sensitive equivalent short-circuit current (I(sc)) in cilia (-) cells but not in cilia (+) cells. Moreover, pretreatment with a PKA inhibitor abolished DDAVP stimulation of I(sc) in cilia (-) cells. Thus we propose that structural or functional loss of cilia leads to abnormal trafficking of AQP2/V2R leading to enhanced salt and water absorption. Whether such apical localization contributes to enhanced fluid retention and hypertension in PKD remains to be determined. 相似文献
953.
Ohsaki Y O'Connor P Mori T Ryan RP Dickinson BC Chang CJ Lu Y Ito S Cowley AW 《American journal of physiology. Renal physiology》2012,302(1):F95-F102
The mitochondria-rich epithelial cells of the renal medullary thick ascending limb (mTAL) reabsorb nearly 25% of filtered sodium (Na(+)) and are a major source of cellular reactive oxygen species. Although we have shown that delivery of Na(+) to the mTAL of rats increases superoxide (O(2)(·-)) production in mTAL, little is known about H(2)O(2) production, given the lack of robust and selective fluorescent indicators for determining changes within the whole cell, specifically in the mitochondria. The present study determined the effect of increased tubular flow and Na(+) delivery to mTAL on the production of mitochondrial H(2)O(2) in mTAL. H(2)O(2) responses were determined in isolated, perfused mTAL of Sprague-Dawley rats using a novel mitochondrial selective fluorescent H(2)O(2) indicator, mitochondria peroxy yellow 1, and a novel, highly sensitive and stable cytosolic-localized H(2)O(2) indicator, peroxyfluor-6 acetoxymethyl ester. The results showed that mitochondrial H(2)O(2) and cellular fluorescent signals increased progressively over a period of 30 min following increased tubular perfusion (5-20 nl/min), reaching levels of statistical significance at ~10-12 min. Responses were inhibited with rotenone or antimycin A (inhibitors of the electron-transport chain), polyethylene glycol-catalase and by reducing Na(+) transport with furosemide or ouabain. Inhibition of membrane NADPH-oxidase with apocynin had no effect on mitochondrial H(2)O(2) production. Cytoplasmic H(2)O(2) (peroxyfluor-6 acetoxymethyl ester) increased in parallel with mitochondrial H(2)O(2) (mitochondria peroxy yellow 1) and was partially attenuated (~65%) by rotenone and completely inhibited by apocynin. The present data provide clear evidence that H(2)O(2) is produced in the mitochondria in response to increased flow and delivery of Na(+) to the mTAL, and that whole cell H(2)O(2) levels are triggered by the mitochondrial reactive oxygen species production. The mitochondrial production of H(2)O(2) may represent an important target for development of more effective antioxidant therapies. 相似文献
954.
Recent research has demonstrated that the topography of defensive reactions depends on factors that are extraneous to the stimulus that elicits the defensive response. For example, hermit crabs will withdraw more slowly to the approach of a simulated visual predator (i.e., the eliciting stimulus) when in the presence of a coincident acoustic stimulus. Multiple properties related to the magnitude (e.g., duration, amplitude) of the acoustic stimulus have been found to modulate the crabs' withdrawal response (Chan et al., 2010b). We demonstrate that the proximity in spatial location between a threatening visual stimulus and a potentially distracting extraneous auditory stimulus is an important determinant of anti-predator behavior in hermit crabs. We suggest that a distal relationship between the eliciting stimulus and an unrelated signal may produce greater distraction. This marks the first reported experimental evidence of this relationship in an invertebrate species. 相似文献
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957.
Lamour KH Mudge J Gobena D Hurtado-Gonzales OP Schmutz J Kuo A Miller NA Rice BJ Raffaele S Cano LM Bharti AK Donahoo RS Finley S Huitema E Hulvey J Platt D Salamov A Savidor A Sharma R Stam R Storey D Thines M Win J Haas BJ Dinwiddie DL Jenkins J Knight JR Affourtit JP Han CS Chertkov O Lindquist EA Detter C Grigoriev IV Kamoun S Kingsmore SF 《Molecular plant-microbe interactions : MPMI》2012,25(10):1350-1360
The oomycete vegetable pathogen Phytophthora capsici has shown remarkable adaptation to fungicides and new hosts. Like other members of this destructive genus, P. capsici has an explosive epidemiology, rapidly producing massive numbers of asexual spores on infected hosts. In addition, P. capsici can remain dormant for years as sexually recombined oospores, making it difficult to produce crops at infested sites, and allowing outcrossing populations to maintain significant genetic variation. Genome sequencing, development of a high-density genetic map, and integrative genomic or genetic characterization of P. capsici field isolates and intercross progeny revealed significant mitotic loss of heterozygosity (LOH) in diverse isolates. LOH was detected in clonally propagated field isolates and sexual progeny, cumulatively affecting >30% of the genome. LOH altered genotypes for more than 11,000 single-nucleotide variant sites and showed a strong association with changes in mating type and pathogenicity. Overall, it appears that LOH may provide a rapid mechanism for fixing alleles and may be an important component of adaptability for P. capsici. 相似文献
958.
Peripheral axons from auditory spiral ganglion neurons (SGNs) form an elaborate series of radially and spirally oriented projections that interpret complex aspects of the auditory environment. However, the developmental processes that shape these axon tracts are largely unknown. Radial bundles are comprised of dense SGN fascicles that project through otic mesenchyme to form synapses within the cochlea. Here, we show that radial bundle fasciculation and synapse formation are disrupted when Pou3f4 (DFNX2) is deleted from otic mesenchyme. Further, we demonstrate that Pou3f4 binds to and directly regulates expression of Epha4, Epha4?/? mice present similar SGN defects, and exogenous EphA4 promotes SGN fasciculation in the absence of Pou3f4. Finally, Efnb2 deletion in SGNs leads to similar fasciculation defects, suggesting that ephrin-B2/EphA4 interactions are critical during this process. These results indicate a model whereby Pou3f4 in the otic mesenchyme establishes an Eph/ephrin-mediated fasciculation signal that promotes inner radial bundle formation. 相似文献
959.
Stability of the spinal column is critical to bear loads, allow movement, and at the same time avoid injury and pain. However, there has been a debate in recent years as to how best to define and quantify spine stability, with the outcome being that different methods are used without a clear understanding of how they relate to one another. Therefore, the goal of the present study was to directly compare lumbar spine rotational stiffness, calculated with an EMG-driven biomechanical model, to local dynamic spine stability calculated using Lyapunov analyses of kinematic data, during a series of continuous dynamic lifting challenges. Twelve healthy male subjects performed 30 repetitive lifts under three varying load and three varying rate conditions. With an increase in the load lifted (constant rate) there was a significant increase in mean, maximum, and minimum spine rotational stiffness (p<0.001) and a significant increase in local dynamic stability (p<0.05); both stability measures were moderately to strongly related to one another (r=-0.55 to -0.71). With an increase in lifting rate (constant load), there was also a significant increase in mean and maximum spine rotational stiffness (p<0.01); however, there was a non-significant decrease in the minimum rotational stiffness and a non-significant decrease in local dynamic stability (p>0.05). Weak linear relationships were found for the varying rate conditions (r=-0.02 to -0.27). The results suggest that spine rotational stiffness and local dynamic stability are closely related to one another, as they provided similar information when movement rate was controlled. However, based on the results from the changing lifting rate conditions, it is evident that both models provide unique information and that future research is required to completely understand the relationship between the two models. Using both techniques concurrently may provide the best information regarding the true effects of (in) stability under different loading and movement scenarios, and in comparing healthy and clinical populations. 相似文献
960.
Babiker MH Gonzalez LF Ryan J Albuquerque F Collins D Elvikis A Frakes DH 《Journal of biomechanics》2012,45(3):440-447
Embolic coiling is the most popular endovascular treatment available for cerebral aneurysms. Nevertheless, the embolic coiling of wide-neck aneurysms is challenging and, in many cases, ineffective. Use of highly porous stents to support coiling of wide-neck aneurysms has become a common procedure in recent years. Several studies have also demonstrated that high porosity stents alone can significantly alter aneurysmal hemodynamics, but differences among different stent configurations have not been fully characterized. As a result, it is usually unclear which stent configuration is optimal for treatment. In this paper, we present a flow study that elucidates the influence of stent configuration on cerebral aneurysm fluid dynamics in an idealized wide-neck basilar tip aneurysm model. Aneurysmal fluid dynamics for three different stent configurations (half-Y, Y and, cross-bar) were first quantified using particle image velocimetry and then compared. Computational fluid dynamics (CFD) simulations were also conducted for selected stent configurations to facilitate validation and provide more detailed characterizations of the fluid dynamics promoted by different stent configurations. In vitro results showed that the Y stent configuration reduced cross-neck flow most significantly, while the cross-bar configuration reduced velocity magnitudes within the aneurysmal sac most significantly. The half-Y configuration led to increased velocity magnitudes within the aneurysmal sac at high parent-vessel flow rates. Experimental results were in strong agreement with CFD simulations. Simulated results indicated that differences in fluid dynamic performance among the different stent configurations can be attributed primarily to protruding struts within the bifurcation region. 相似文献