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131.
Arthur Beyder Peter R. Strege Cheryl Bernard Gianrico Farrugia 《Channels (Austin, Tex.)》2012,6(4):308-316
Voltage-gated sodium selective ion channel NaV1.5 is expressed in the heart and the gastrointestinal tract, which are mechanically active organs. NaV1.5 is mechanosensitive at stimuli that gate other mechanosensitive ion channels. Local anesthetic and antiarrhythmic drugs act upon NaV1.5 to modulate activity by multiple mechanisms. This study examined whether NaV1.5 mechanosensitivity is modulated by local anesthetics. NaV1.5 channels wereexpressed in HEK-293 cells, and mechanosensitivity was tested in cell-attached and excised inside-out configurations. Using a novel protocol with paired voltage ladders and short pressure pulses, negative patch pressure (-30 mmHg) in both configurations produced a hyperpolarizing shift in the half-point of the voltage-dependence of activation (V1/2a) and inactivation (V1/2i) by about -10 mV. Lidocaine (50 µM) inhibited the pressure-induced shift of V1/2a but not V1/2i. Lidocaine inhibited the tonic increase in pressure-induced peak current in a use-dependence protocol, but it did not otherwise affect use-dependent block. The local anesthetic benzocaine, which does not show use-dependent block, also effectively blocked a pressure-induced shift in V1/2a. Lidocaine inhibited mechanosensitivity in NaV1.5 at the local anesthetic binding site mutated (F1760A). However, a membrane impermeable lidocaine analog QX-314 did not affect mechanosensitivity of F1760A NaV1.5 when applied from either side of the membrane. These data suggest that the mechanism of lidocaine inhibition of the pressure-induced shift in the half-point of voltage-dependence of activation is separate from the mechanisms of use-dependent block. Modulation of NaV1.5 mechanosensitivity by the membrane permeable local anesthetics may require hydrophobic access and may involve membrane-protein interactions. 相似文献
132.
Lentil root statoliths reach a stable state in microgravity 总被引:3,自引:0,他引:3
The kinetics of the movement of statoliths in gravity-perceiving root cap cells of Lens culinaris L. and the force responsible for it have been analysed under 1 g and under microgravity conditions (S/MM-03 mission of Spacehab 1996). At the beginning of the experiment in space, the amyloplasts
were grouped at the distal pole of the statocytes by a root-tip-directed 1-g centrifugal acceleration. The seedlings were then placed in microgravity for increasing periods of time (13, 29, 46 or 122 min)
and chemically fixed. During the first 29 min of microgravity there were local displacements (mean velocity: 0.154 μm min−1) of some amyloplasts (first at the front of the group and then at the rear). Nevertheless, the group of amyloplasts tended
to reconstitute. After 122 min in microgravity the bulk of amyloplasts had almost reached the proximal pole where further
movement was blocked by the nucleus. After a longer period in microgravity (4 h; experiment carried out 1994 during the IML
2 mission) the statoliths reached a stable position due to the fact that they were stopped by the nucleus. The position was
similar to that observed in roots grown continuously in microgravity. Treatment with cytochalasin D (CD) did not stop the
movement of the amyloplasts but slowed down the velocity of their displacement (0.019 μm min−1). Initial movement patterns were the same as in control roots in water. Comparisons of mean velocities of amyloplast movements
in roots in space and in inverted roots on earth showed that the force responsible for the movement in microgravity (Fc) was about 86% less (Fc = 0.016 pN) than the gravity force (Fg = 0.11 pN). Treatment with CD reduced Fc by two-thirds. The apparent viscosity of the statocyte cytoplasm was found to be 1 Pa s or 3.3 Pa s for control roots or
CD treated roots, respectively. Brownian motion or elastic forces due to endoplasmic reticulum membranes do not cause the
movement of the amyloplasts in microgravity. It is concluded that the force transporting the statoliths is caused by the actomyosin
system.
Received: 22 March 1999 / Accepted: 18 December 1999 相似文献
133.
134.
Hao-Han Chang Bernard Choong Anthony RJ Phillips Kerry M Loomes 《Experimental biology and medicine (Maywood, N.J.)》2015,240(1):8-14
Diabetic nephropathy is a serious complication of diabetes mellitus with a pressing need for effective metabolic markers to detect renal impairment. Of potential significance are the inositol compounds, myo-inositol (MI), and the less abundant stereoisomer, D-chiro-inositol (DCI), which are excreted at increased levels in the urine in diabetes mellitus, a phenomenon known as inosituria. There is also a selective urinary excretion of DCI compared to MI. As the biological origins of altered inositol metabolism in diabetes mellitus are unknown, the aim of this study was to determine whether the diabetic kidney was directly responsible. Kidneys isolated from four-week streptozotocin-induced diabetic rats were characterized by a 3-fold reduction in glomerular filtration rate (GFR) compared to matched non-diabetic kidneys. When perfused with fixed quantities of MI (50 µM) and DCI (5 µM) under normoglycemic conditions (5 mM glucose), GFR-normalized urinary excretion of MI was increased by 1.7-fold in diabetic vs. non-diabetic kidneys. By comparison, GFR-normalized urinary excretion of DCI was increased by 4-fold. Perfusion conditions replicating hyperglycemia (20 mM glucose) potentiated DCI but not MI urinary excretion in both non-diabetic and diabetic kidneys. Overall, there was a 2.4-fold increase in DCI urinary excretion compared to MI in diabetic kidneys that was independent of glucose ambience. This increased urinary excretion of DCI and MI in diabetic kidneys occurred despite increased renal expression of the inositol transporters, sodium myo-inositol transporter subtype 1 and 2 (SMIT1 and SMIT2). These findings show that the diabetic kidney primarily mediates inosituria and altered urinary partitioning of MI and DCI. Urinary inositol levels might therefore serve as an indicator of impaired renal function in diabetes mellitus with wider implications for monitoring chronic kidney disease. 相似文献
135.
Hutchinson–Gilford progeria syndrome (HGPS) is caused by an LMNA mutation that results in the production of the abnormal progerin protein. Children with HGPS display phenotypes of premature aging and have an average lifespan of 13 years. We found earlier that the targeting of the transmembrane protein PLA2R1 overcomes senescence and improves phenotypes in a mouse model of progeria. PLA2R1 is regulating the JAK/STAT signaling, but we do not yet know whether targeting this pathway directly would influence cellular and in vivo progeria phenotypes. Here, we show that JAK1/2 inhibition with ruxolitinib rescues progerin‐induced cell cycle arrest, cellular senescence, and misshapen nuclei in human normal fibroblasts expressing progerin. Moreover, ruxolitinib administration reduces several premature aging phenotypes: bone fractures, bone mineral content, grip strength, and a trend to increase survival in a mouse model of progeria. Thus, we propose that ruxolitinib, an FDA‐approved drug, should be further evaluated as a drug candidate in HGPS therapy. 相似文献
136.
Paul L. Drake Daniel S. Mendham Don A. White Gary N. Ogden Bernard Dell 《Plant and Soil》2012,350(1-2):221-235
Aims
Growers of Eucalyptus globulus Labill. plantations can establish second and later rotations from coppice or by replanting with seedlings. At most locations where E. globulus is grown commercially, water availability is a major driver for productivity. Thus growers must consider which reestablishment technique will maximize productivity whilst sustaining site resources for subsequent rotations. In this study we aimed to compare the stand-scale water balance components of young coppice and seedling E. globulus.Methods
A second rotation E. globulus coppice and seedling trial was monitored for two successive seasonal cycles. Coppice and seedling plots were instrumented with sap flow- and meteorological-sensors so that stand-scale water balance components could be estimated on a daily time step.Results
Stand-scale transpiration rate (E) and rate of interception (E I) were larger in coppice compared to seedlings, but the rate of soil evaporation (E S) was lower. At approximately 2?years of age each coppice stump was reduced to a single dominant stem, a standard management practice for E. globulus growers, which reduced stem biomass by approximately 70% and caused E to fall to a value approximating that in seedlings. The cumulative transpiration of coppice was 425?mm greater than seedlings up to 34?months of age. Without the coppice reduction (down to one stem/stump), we estimate that the difference would have been much greater. The water-use efficiency of stem production (WUEstem) was greater in young coppice compared to seedlings but this benefit is likely to be offset by the loss of biomass (and thus transpired water) during coppice stem reduction.Conclusion
Under the conditions of this study, which included reducing coppice to a single stem, reestablishment with seedling E. globulus resulted in a higher water-use efficiency of stem biomass production compared to coppice of a similar age. 相似文献137.
Arnaud Foulquier Florian Mermillod-Blondin Bernard Montuelle Sylvain Dolédec Bernadette Volat Janine Gibert 《Ecosystems》2011,14(8):1339-1353
Groundwaters are increasingly viewed as resource-limited ecosystems in which fluxes of dissolved organic carbon (DOC) from
surface water are efficiently mineralized by a consortium of microorganisms which are grazed by invertebrates. We tested for
the effect of groundwater recharge on resource supply and trophic interactions by measuring physico-chemistry, microbial activity
and biomass, structure of bacterial communities and invertebrate density at three sites intensively recharged with surface
water. Comparison of measurements made in recharge and control well clusters at each site showed that groundwater recharge
significantly increased fluxes of DOC and phosphate, elevated groundwater temperature, and diminished dissolved oxygen (DO).
Microbial biomass and activity were significantly higher in recharge well clusters but stimulation of autochthonous microorganisms
was not associated with a major shift in bacterial community structure. Invertebrate assemblages were not significantly more
abundant in recharge well clusters and did not show any relationship with microbial biomass and activity. Microbial communities
were bottom-up regulated by DOC and nutrient fluxes but trophic interactions between microorganisms and invertebrates were
apparently limited by environmental stresses, particularly DO depletion and groundwater warming. Hydrological connectivity
is a key factor regulating the function of DOC-based groundwater food webs as it influences both resource availability for
microorganisms and environmental stresses which affect energy transfer to invertebrates and top-down control on microorganisms. 相似文献
138.
Maria Polikandritou Lambros Cyrus Parsa HariChandana Mulamalla Robert Orlando Bernard Lau Ying Huang Doreen Pon Moses Chow 《Biochemical and biophysical research communications》2011,405(1):102
Mucositis is a debilitating adverse effect of chemotherapy and radiation treatment. It is important to develop a simple and reliable in vitro model, which can routinely be used to screen new drugs for prevention and treatment of mucositis. Furthermore, identifying cell and molecular stresses especially in the initiation phase of mucositis in this model will help towards this end. We evaluated a three-dimensional (3-D) human oral cell culture that consisted of oral keratinocytes and fibroblasts as a model of oral mucositis. The 3-D cell culture model was irradiated with 12 or 2 Gy. Six hours after the irradiation we evaluated microscopic sections of the cell culture for evidence of morphologic changes including apoptosis. We used microarrays to compare the expression of several genes from the irradiated tissue with identical genes from tissue that was not irradiated. We found that irradiation with 12 Gy induced significant histopathologic effects including cellular apoptosis. Irradiation significantly affected the expression of several genes of the NF-kB pathway and several inflammatory cytokines, such as IL-1B, 1L-8, NF-kB1, and FOS compared to tissue that was not irradiated. We identified significant upregulation of several genes that belong to damage-associated molecular patterns (DAMPs) such as HMB1, S100A13, SA10014, and SA10016 in the 3-D tissues that received 12 Gy but not in tissues that received 2 Gy. In conclusion, this model quantifies radiation damage and this is an important first step towards the development 3-D tissue as a screening tool. 相似文献
139.
Glycosylation in the CH2 domain of Fc is required for immunoglobulins G (IgGs) to exhibit immune effector functions including complement-dependent cytotoxicity (CDC) and antibody-dependent (Ab-dependent) cellular cytotoxicity (ADCC). We recently established that glycosylated Abs are more resistant to papain digestion than non-glycosylated IgGs (Biochem. Biophys. Res. Commun. 2006, 341, 797-803). To test whether specific Fc glycan structures affect Ab resistance to papain, we used in vitro glycoengineering methods to prepare homogeneous Ab glycoforms terminated with either sialic acid (G2S2), beta-galactose (G2), or N-acetylglucosamine (G0) and subjected them to papain digestions. Analyses of aliquots taken at different times during the digestions by matrix-assisted laser desorption-time-of-flight-mass spectroscopy (MALDI-TOF-MS) and high-performance liquid chromatography (HPLC) methods showed that the G0 glycoform was at least two times more resistant to papain digestion than the G2 and G2S2 glycoforms. The increased resistance of the G0 glycoform over the G2 and G2S2 glycoforms was independent of the specific Ab analyzed. A mouse/human chimeric version of Ab1, a fully human version of Ab2, and a humanized version of Ab3 exhibited a similar pattern of glycoform-dependent resistance. These data suggest that terminal sugars of Fc glycans may play important roles in Ab stability and affect resistance to proteases in addition to impacting Ab effector functions. 相似文献
140.
Michel de Bandt Bruno Fautrel Jean Francis Maillefert Jean Marie Berthelot Bernard Combe René-Marc Flipo Frédéric Lioté Olivier Meyer Alain Saraux Daniel Wendling Xavier Le Loët Francis Guillemin 《Arthritis research & therapy》2009,11(5):1-8