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Unidentified Mechanism (unidentified + mechanism)
Selected AbstractsRearrangement of microtubule polarity orientation during conversion of dendrites to axons in cultured pyramidal neuronsCYTOSKELETON, Issue 5 2007Daisuke Takahashi Abstract Axons and dendrites of neurons differ in the polarity orientation of their microtubules. Whereas the polarity orientation of microtubules in axons is uniform, with all plus ends distal, that in dendrites is nonuniform. The mechanisms responsible for establishment and maintenance of microtubule polarity orientation in neuronal processes remain unclear, however. We previously described a culture system in which dendrites of rat cortical neurons convert to axons. In the present study, we examined changes in microtubule polarity orientation in such dendrites. With the use of the hooking procedure and electron microscopy, we found that microtubule polarity orientation changed from nonuniform to uniform, with a plus end-distal arrangement, in dendrites that gave rise to axons during culture of neurons for 24 h. Microtubule polarity orientation remained nonuniform in dendrites that did not elongate. Axon regeneration at the dendritic tip thus triggered the disappearance of minus end-distal microtubules from dendrites. These minus end-distal microtubules also disappeared from dendrites during axon regeneration in the presence of inhibitors of actin polymerization, suggesting that actin-dependent transport of microtubules is not required for this process and implicating a previously unidentified mechanism in the establishment and maintenance of microtubule polarity orientation in neuronal processes. Cell Motil. Cytoskeleton 2007. © 2007 Wiley-Liss, Inc. [source] Secretion of the Escherichia coli K-12 SheA hemolysin is independent of its cytolytic activityFEMS MICROBIOLOGY LETTERS, Issue 2 2001Francisco J del Castillo Abstract The Escherichia coli K-12 sheA gene encodes a pore-forming hemolysin that is secreted to the medium by a hitherto unidentified mechanism. To study SheA secretion, we constructed fusions between SheA and the mature form of the periplasmic enzyme ,-lactamase, and performed site-directed mutagenesis on these constructs. The SheA-Bla and Bla-SheA hybrid proteins displayed hemolytic activity and were efficiently exported to the extracellular medium. Our results with mutant hybrid proteins show that secretion of SheA is independent of its cytolytic activity, that secretion is paralleled by a transient leakage of periplasmic contents to the extracellular medium, and that deletion of the 11 C-terminal residues of SheA has no effect on its secretion and cytolytic activity. [source] ,-Arrestin2 Regulates the Differential Response of Cortical and Trabecular Bone to Intermittent PTH in Female Mice,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 4 2005Mary L Bouxsein PhD Abstract Cytoplasmic arrestins regulate PTH signaling in vitro. We show that female ,-arrestin2,/, mice have decreased bone mass and altered bone architecture. The effects of intermittent PTH administration on bone microarchitecture differed in ,-arrestin2,/, and wildtype mice. These data indicate that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH at endosteal and periosteal bone surfaces. Introduction: The effects of PTH differ at endosteal and periosteal surfaces, suggesting that PTH activity in these compartments may depend on some yet unidentified mechanism(s) of regulation. The action of PTH in bone is mediated primarily by intracellular cAMP, and the cytoplasmic molecule ,-arrestin2 plays a central role in this signaling regulation. Thus, we hypothesized that arrestins would modulate the effects of PTH on bone in vivo. Materials and Methods: We used pDXA, ,CT, histomorphometry, and serum markers of bone turnover to assess the skeletal response to intermittent PTH (0, 20, 40, or 80 ,g/kg/day) in adult female mice null for ,-arrestin2 (,-arr2,/,) and wildtype (WT) littermates (7-11/group). Results and Conclusions: ,-arr2,/, mice had significantly lower total body BMD, trabecular bone volume fraction (BV/TV), and femoral cross-sectional area compared with WT. In WT females, PTH increased total body BMD, trabecular bone parameters, and cortical thickness, with a trend toward decreased midfemoral medullary area. In ,-arr2,/, mice, PTH not only improved total body BMD, trabecular bone architecture, and cortical thickness, but also dose-dependently increased femoral cross-sectional area and medullary area. Histomorphometry showed that PTH-stimulated periosteal bone formation was 2-fold higher in ,-arr2,/, compared with WT. Osteocalcin levels were significantly lower in ,-arr2,/, mice, but increased dose-dependently with PTH in both ,-arr2,/, and WT. In contrast, whereas the resorption marker TRACP5B increased dose-dependently in WT, 20-80 ,g/kg/day of PTH was equipotent with regard to stimulation of TRACP5B in ,-arr2,/,. In summary, ,-arrestin2 plays an important role in bone mass acquisition and remodeling. In estrogen-replete female mice, the ability of intermittent PTH to stimulate periosteal bone apposition and endosteal resorption is inhibited by arrestins. We therefore infer that arrestin-mediated regulation of intracellular signaling contributes to the differential effects of PTH on cancellous and cortical bone. [source] Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol IntoxicationMICROCIRCULATION, Issue 7 2010FLAVIA M. SOUZA-SMITH Please cite this paper as: Souza-Smith, Kurtz, Molina and Breslin (2010). Adaptation of Mesenteric Collecting Lymphatic Pump Function Following Acute Alcohol Intoxication. Microcirculation17(7), 514,524. Abstract Objective:, Acute alcohol intoxication increases intestinal lymph flow by unknown mechanisms, potentially impacting mucosal immunity. We tested the hypothesis that enhanced intrinsic pump function of mesenteric lymphatics contributes to increased intestinal lymph flow during alcohol intoxication. Methods:, Acute alcohol intoxication was produced by intragastric administration of 30% alcohol to conscious, unrestrained rats through surgically implanted catheters. Time-matched controls received either no bolus, vehicle, or isocaloric dextrose. Thirty minutes after alcohol administration, rats were anesthetized and mesenteric collecting lymphatics were isolated and cannulated to study intrinsic pumping parameters. In separate experiments, mesenteric lymphatics were isolated to examine direct effects of alcohol on intrinsic pump activity. Results:, Lymphatics isolated from alcohol-intoxicated animals displayed significantly decreased CF compared to the dextrose group, elevated SVI versus all other groups, and decreased myogenic responsiveness compared to sham. Elevating pressure from 2 to 4 cm H2O increased the volume flow index 2.4-fold in the alcohol group versus 1.4-fold for shams. Isolated lymphatics exposed to 20 mM alcohol had reduced myogenic tone, without changes in CF or SVI. Conclusions:, Alcohol intoxication enhances intrinsic pumping by mesenteric collecting lymphatics. Alcohol directly decreases lymphatic myogenic tone, but effects on phasic contractions occur by an unidentified mechanism. [source] Inhibitory effect of bionic fungicide 2-allylphenol on Botrytis cinerea (Pers. ex Fr.) in vitro,PEST MANAGEMENT SCIENCE (FORMERLY: PESTICIDE SCIENCE), Issue 12 2009Shuangjun Gong Abstract BACKGROUND: 2-Allylphenol is a registered fungicide in China to control fungal diseases on tomato, strawberry and apple. It is synthetic and structurally resembles the active ingredient ginkgol isolated from Ginkgo biloba L. bark. 2-Allylphenol has been used in China for 10 years. However, its biochemical mode of action remains unclear. An in vitro study was conducted on the biochemical mechanism of 2-allyphenol inhibiting Botrytis cinerea (Pers. ex Fr.). RESULTS: The inhibition was approximately 3 times stronger when the fungus was grown on non-fermentable source, glycerol, than that on a fermentable carbon source, glucose. Inhibition of B. cinerea and Magnaporthe oryzae (Hebert) Barr mycelial growth was markedly potentiated in the presence of salicylhydroxamic acid (SHAM), an inhibitor of mitochondrial alternative oxidase. Furthermore, at 3 h after treatment with 2-allylphenol, oxygen consumption had recovered, but respiration was resistant to potassium cyanide and sensitive to SHAM, indicating that 2-allylphenol had the ability to induce cyanide-resistant respiration. The mycelium inhibited in the presence of 2-allylphenol grew vigorously after being transferred to a fungicide-free medium, indicating that 2-allylphenol is a fungistatic compound. Adenine nucleotide assay showed that 2-allylphenol depleted ATP content and decreased the energy charge values, which confirmed that 2-allylphenol is involved in the impairment of the ATP energy generation system. CONCLUSION: These results suggested that 2-allylphenol induces cyanide-resistant respiration and causes ATP decrease, and inhibits respiration by an unidentified mechanism. Copyright © 2009 Society of Chemical Industry [source] Thalidomide inhibits UVB-induced mouse keratinocyte apoptosis by both TNF-,-dependent and TNF-,-independent pathwaysPHOTODERMATOLOGY, PHOTOIMMUNOLOGY & PHOTOMEDICINE, Issue 6 2003Kurt Q. Lu Background: Thalidomide is an anti-inflammatory pharmacologic agent that has been utilized as a therapy for a number of dermatologic diseases. Its anti-inflammatory properties have been attributed to its ability to antagonize tumor necrosis factor-alfa (TNF-,) production by monocytes. However, its mechanism of action in the skin is not known. Purpose: To test our hypothesis that thalidomide may antagonize TNF-, production in the skin, we used a mouse model for acute ultraviolet-B (UVB) exposure, a known stimulus for inducing this cytokine. Results: A single bolus dose of thalidomide (either 100 or 400 mg/kg) given immediately before UVB exposure (40,120 mJ/cm2) inhibited, in a dose-dependent manner, sunburn cell formation (i.e. keratinocyte (KC) apoptosis as defined by histologic appearance and confirmed by terminal transferase mediated biotinylated dUTP nick end labelling staining) in mouse skin biopsy specimens. However, this agent did not affect the formation of cyclobutane pyrimidine dimers, a measure of UVB-induced DNA damage, which is an early event associated with apoptosis. RNase protection assays confirmed that high (400 mg/kg), but not low (100 mg/kg), doses of thalidomide inhibited the UVB-induced increase in steady-state TNF-, mRNA. Additionally, our in vitro data using neonatal mouse KCs showed that thalidomide prevented UVB-induced cell death (JAM assay). The antiapoptotic effects of thalidomide can be reversed by the addition of exogenous recombinant mouse TNF-, and hence reconstituting UVB-induced programmed cell death. The inhibition of sunburn cell formation by low-dose thalidomide in the absence of TNF-, inhibition suggests that other, unidentified mechanisms of apoptosis inhibition are active. Conclusions: These data suggest that the anti-inflammatory effects of thalidomide can affect UVB injury, and may, in part, explain its action in photosensitivity diseases such as cutaneous lupus erythematosus. [source] | |||||||||||||