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Modeling of single noninactivating Na+ channels: evidence for two open and several fast inactivated states 下载免费PDF全文
Voltage-gated Na(+) channels play a fundamental role in the excitability of nerve and muscle cells. Defects in fast Na(+) channel inactivation can cause hereditary muscle diseases with hyper- or hypoexcitability of the sarcolemma. To explore the kinetics and gating mechanisms of noninactivating muscle Na(+) channels on a molecular level, we analyzed single channel currents from wild-type and five mutant Na(+) channels. The mutations were localized in different protein regions which have been previously shown to be important for fast inactivation (D3-D4-linker, D3/S4-S5, D4/S4-S5, D4/S6) and exhibited distinct grades of defective fast inactivation with varying levels of persistent Na(+) currents caused by late channel reopenings. Different gating schemes were fitted to the data using hidden Markov models with a correction for time interval omission and compared statistically. For all investigated channels including the wild-type, two open states were necessary to describe our data. Whereas one inactivated state was sufficient to fit the single channel behavior of wild-type channels, modeling the mutants with impaired fast inactivation revealed evidence for several inactivated states. We propose a single gating scheme with two open and three inactivated states to describe the behavior of all five examined mutants. This scheme provides a biological interpretation of the collected data, based on previous investigations in voltage-gated Na(+) and K(+) channels. 相似文献
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The ClC family encompasses two classes of proteins with distinct transport functions: anion channels and transporters. ClC-type transporters usually mediate secondary active anion–proton exchange. However, under certain conditions they assume slippage mode behavior in which proton and anion transport are uncoupled, resulting in passive anion fluxes without associated proton movements. Here, we use patch clamp and intracellular pH recordings on transfected mammalian cells to characterize exchanger and slippage modes of human ClC-4, a member of the ClC transporter branch. We found that the two transport modes differ in transport mechanisms and transport rates. Nonstationary noise analysis revealed a unitary transport rate of 5 × 105 s−1 at +150 mV for the slippage mode, indicating that ClC-4 functions as channel in this mode. In the exchanger mode, unitary transport rates were 10-fold lower. Both ClC-4 transport modes exhibit voltage-dependent gating, indicating that there are active and non-active states for the exchanger as well as for the slippage mode. ClC-4 can assume both transport modes under all tested conditions, with exchanger/channel ratios determined by the external anion. We propose that binding of transported anions to non-active states causes transition from slippage into exchanger mode. Binding and unbinding of anions is very rapid, and slower transitions of liganded and non-liganded states into active conformations result in a stable distribution between the two transport modes. The proposed mechanism results in anion-dependent conversion of ClC-type exchanger into an anion channel with typical attributes of ClC anion channels. 相似文献
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Shi Yu Tillmann Falck Anneleen Daemen Leon-Charles Tranchevent Johan AK Suykens Bart De Moor Yves Moreau 《BMC bioinformatics》2010,11(1):309
Background
This paper introduces the notion of optimizing different norms in the dual problem of support vector machines with multiple kernels. The selection of norms yields different extensions of multiple kernel learning (MKL) such as L ∞, L 1, and L 2 MKL. In particular, L 2 MKL is a novel method that leads to non-sparse optimal kernel coefficients, which is different from the sparse kernel coefficients optimized by the existing L ∞ MKL method. In real biomedical applications, L 2 MKL may have more advantages over sparse integration method for thoroughly combining complementary information in heterogeneous data sources. 相似文献6.
The Indian black berry (Syzygium cumini Skeels) has a great nutraceutical and medicinal properties. As in other fruit crops, the
fruit characteristics are important attributes for differentiation were also determined for different accessions of S. cumini. The fruit
weight, length, breadth, length: breadth ratio, pulp weight, pulp content, seed weight and pulp: seed ratio significantly varied in
different accessions. Molecular characterization was carried out using PCR based RAPD technique. Out of 80 RAPD primers, only
18 primers produced stable polymorphisms that were used to examine the phylogenetic relationship. A sum of 207 loci were
generated out of which 201 loci found polymorphic. The average genetic dissimilarity was 97 per cent among jamun accessions.
The phylogenetic relationship was also determined by principal coordinates analysis (PCoA) that explained 46.95 per cent
cumulative variance. The two-dimensional PCoA analysis showed grouping of the different accessions that were plotted into four
sub-plots, representing clustering of accessions. The UPGMA (r = 0.967) and NJ (r = 0.987) dendrogram constructed based on the
dissimilarity matrix revealed a good degree of fit with the cophenetic correlation value. The dendrogram grouped the accessions
into three main clusters according to their eco-geographical regions which given useful insight into their phylogenetic
relationships. 相似文献
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不同耕作措施对冬小麦-夏玉米复种连作系统土壤有机碳和水分利用效率的影响 总被引:2,自引:1,他引:1
在连续8年田间定位试验的基础上,分析了关中平原冬小麦 夏玉米复种连作系统2008—2009年连续两个生长季期间不同耕作措施(结合秸秆还田和不还田)对土壤有机碳和水分利用率的影响.结果表明: 相对于传统耕作,保护性耕作有利于土壤有机碳、水分利用效率和作物产量的提高,其中在“深松+秸秆还田”耕作模式下的增幅最高,土壤有机碳含量在0~30 cm土层增幅达到19.5%,水分利用效率和作物产量提高了16.9%和20.5%,而免耕模式则有效提高了0~10 cm土层有机碳含量.在该地区土壤和气候条件下,深松结合秸秆粉碎还田是最理想的耕作模式,最有利于土壤有机碳累积,并提高水分利用效率和作物产量. 相似文献
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K Michałek M Laszczyńska AK Ciechanowicz A Herosimczyk I Rotter M Oganowska 《Biotechnic & histochemistry》2014,89(5):342-347
Aquaporin 2 (AQP2) is a small, integral tetrameric plasma membrane protein that is expressed in mammalian kidneys. The specific constitution of this protein and its selective permeability to water means that AQP2 plays an important role in hypertonic urine production. Immunolocalization of AQP2 has been studied in humans, monkeys, sheep, dogs, rabbits, rats, mice and adult cattle. We analyzed the expression of AQP2 in kidneys of 7-month-old Polish-Friesian var. black and white male calves. AQP2 was localized in the principal cells of collecting ducts in medullary rays penetrating the renal cortex and in the collecting ducts of renal medulla. AQP2 was expressed most strongly in the apical plasma membrane, but expression was observed also in the intracellular vesicles and basolateral plasma membrane. Our study provides new information concerning the immunolocalization of AQP2 in calf kidneys. 相似文献
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The sequences of the 5' long-terminal repeat (LTR) and adjacent leader
regions of 27 full-length copia elements isolated from natural populations
of Drosophila melanogaster, D. simulans, and D. mauritiana are presented.
Phylogenetic analyses indicate that although D. melanogaster copia elements
are distinct from those of D. simulans and D. mauritiana, the elements of
these latter two species are not distinguishable from one another. LTRs and
adjacent 5' leader regions of elements isolated from D. simulans and D.
mauritiana are structurally similar to one another and carry substantial
deletional variation mapping to regions previously identified as being of
potential importance for copia expression.
相似文献