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1.
Trimethyloxonium modification of single batrachotoxin-activated sodium channels in planar bilayers. Changes in unit conductance and in block by saxitoxin and calcium 总被引:13,自引:9,他引:4 下载免费PDF全文
Single batrachotoxin-activated sodium channels from rat brain were modified by trimethyloxonium (TMO) after incorporation in planar lipid bilayers. TMO modification eliminated saxitoxin (STX) sensitivity, reduced the single channel conductance by 37%, and reduced calcium block of inward sodium currents. These effects always occurred concomitantly, in an all-or-none fashion. Calcium and STX protected sodium channels from TMO modification with potencies similar to their affinities for block. Calcium inhibited STX binding to rat brain membrane vesicles and relieved toxin block of channels in bilayers, apparently by competing with STX for the toxin binding site. These results suggest that toxins, permeant cations, and blocking cations can interact with a common site on the sodium channel near the extracellular surface. It is likely that permeant cations transiently bind to this superficial site, as the first of several steps in passing inward through the channel. 相似文献
2.
Extreme differences in rates of molecular evolution of foraminifera revealed by comparison of ribosomal DNA sequences and the fossil record 总被引:5,自引:3,他引:5
Pawlowski J; Bolivar I; Fahrni JF; de Vargas C; Gouy M; Zaninetti L 《Molecular biology and evolution》1997,14(5):498-505
Foraminifera have one of the best known fossil records among the
unicellular eukaryotes. However, the origin and phylogenetic relationships
of the extant foraminiferal lineages are poorly understood. To test the
current paleontological hypotheses on evolution of foraminifera, we
sequenced about 1,000 base pairs from the 3' end of the small subunit rRNA
gene (SSU rDNA) in 22 species representing all major taxonomic groups.
Phylogenies were derived using neighbor- joining, maximum-parsimony, and
maximum-likelihood methods. All analyses confirm the monophyletic origin of
foraminifera. Evolutionary relationships within foraminifera inferred from
rDNA sequences, however, depend on the method of tree building and on the
choice of analyzed sites. In particular, the position of planktonic
foraminifera shows important variations. We have shown that these changes
result from the extremely high rate of rDNA evolution in this group. By
comparing the number of substitutions with the divergence times inferred
from the fossil record, we have estimated that the rate of rDNA evolution
in planktonic foraminifera is 50 to 100 times faster than in some benthic
foraminifera. The use of the maximum-likelihood method and limitation of
analyzed sites to the most conserved parts of the SSU rRNA molecule render
molecular and paleontological data generally congruent.
相似文献
3.
Jolanda?HM?van Bilsen Josée?PA?Wagenaar-Hilbers Maarten?JF?van der Cammen Mariska?EA?van Dijk Willem?van Eden Marca?HM?WaubenEmail author 《Arthritis research & therapy》2002,4(4):R2
We have recently found that matrix metalloproteinases (MMPs) are targets for T-cell and B-cell reactivity in experimental
arthritis. In the present article, we investigate whether modulation of MMP-specific T-cell responses could influence the
course of adjuvant arthritis (AA). Lewis rats were treated nasally with MMP peptides prior to or after AA induction. Administration
of the MMP-10 or the MMP-16 peptide prior to AA induction reduced the arthritic symptoms. In contrast, administration of the
MMP-10 peptide after AA induction aggravated the arthritic symptoms. The present study shows the possible usefulness of MMP
peptides for immunotherapy. However, a clear understanding of proper timing of peptide administration is crucial for the development
of such therapies. 相似文献
4.
L C Schenkels W M Rathman E C Veerman A V Nieuw Amerongen 《Biological chemistry Hoppe-Seyler》1991,372(5):325-329
With a highly specific monoclonal antibody against a previously isolated and characterized human salivary 19-20-kDa glycoprotein, designated as extra-parotid glycoprotein [Rathman et al. (1989) J. Biol. Buccale 17, 199-208], a common epitope was detected on proteins in several excretory human body fluids. With a quantitative ELISA the EP-GP epitope was measured in widely different concentrations in several secretory human body fluids in the descending order of seminal plasma much greater than tears approximately nasal mucus approximately sweat much greater than saliva. Crossreactivity was also observed in cerumen but not in milk, cerebrospinal fluid, blood plasma and urine. The relative amount of EP-GP in the positively reacting secretions was however, in the same order in each fluid per mg of protein on an average of 1% of the total protein amount. The EP-GP-epitope bearing proteins found in the various human secretions were further characterized by means of electrophoresis and immunoblotting. The molecular masses and the isoelectric points of the proteins in the different secretions display strong resemblance to values found for the salivary glycoprotein EP-GP (molecular masses 19 and 20 kDa; pI values between 4.8 and 5.4). All these findings point to the presence of proteins related to EP-GP in human secretions other than saliva. 相似文献
5.
Clogston J Rathman J Tomasko D Walker H Caffrey M 《Chemistry and physics of lipids》2000,107(2):191-220
The phase behavior of Myverol 18-99K, a food emulsifier rich in monoacylglycerols, in combination with water has been determined. X-ray diffraction and polarized light microscopy (PLM) were used for phase identification and structure characterization. Phase behavior was established in the temperature range from -15 to 50 degrees C and in the composition range from dry to full hydration. Phases identified include the solid lamellar crystal (Lc) phase, the liquid fluid isotropic phase and three liquid crystal phases, the lamellar liquid crystal, the cubic-Ia3d and the cubic-Pn3m phase. Phase information is reported in the form of temperature-composition phase diagrams. It was collected under equilibrium conditions where measurements were made in the heating direction beginning with the Lc phase at -15 degrees C. Phase metastability was also examined in which the natural tendency of the liquid crystal phases to undercool was facilitated. Under this condition, both cubic phases were found to remain free of the solid Lc phase over a relatively wide range of hydration values down to 0 degrees C. The microstructure of the different phases and its dependence on temperature and hydration has been determined. Compositional analysis using thin layer chromatography and gas chromatography/mass spectrometry shows that Myverol 18-99K consists of 82% monoacylglycerols (86.6% monoolein, 7. 0% monostearin, 3.5% monopalmitin, 0.9% monoarachidin, 2.0% unidentified). The equilibrium and metastable phase diagrams of the Myverol 18-99K/water system show remarkable similarity to those reported for the monoolein/water system (Qiu, H., Caffrey, M., 2000. The phase diagram of the monoolein/water system: metastability and equilibrium aspects Biomaterials 21, 223-594.). 相似文献
6.
The alpha-like globin gene cluster in rabbits contains embryonic zeta-
globin genes, an adult alpha-globin gene, and theta-globin genes of
undetermined function. The basic arrangement of genes, deduced from
analysis of cloned DNA fragments, is 5'-zeta 0-zeta 1-alpha 1-theta 1- zeta
2-zeta 3-theta 2-3'. However, the pattern of restriction fragments
containing zeta- and theta-globin genes varies among individual rabbits.
Analysis of BamHI fragments of genomic DNA from 24 New Zealand white
rabbits revealed eight different patterns of fragments containing
zeta-globin genes. The large BamHI fragments containing genes zeta 0 and
zeta 1 are polymorphic in length, whereas a 1.9-kb fragment containing the
zeta 2 gene and the 3.5-kb fragment containing the zeta 3 gene do not vary
in size. In contrast to this constancy in the size of the restriction
fragments, the copy number of the zeta 2 and zeta 3 genes does vary among
different rabbits. No length polymorphism was detected in the BamHI
fragments containing the theta-globin genes, but again the copy number
varies for restriction fragments containing the theta 2 gene. The alpha 1-
and theta 1-globin genes are located in a nonpolymorphic 7.2-kb BamHI
fragment. The combined data from hybridization with both zeta and theta
probes shows that the BamHI cleavage pattern does not vary within the
region 5'-alpha 1-theta 1- zeta 2-zeta 3-theta 2-3', but the pattern
genomic blot-hybridization patterns for the progeny of parental rabbits
with different zeta-globin gene patterns shows that the polymorphic
patterns are inherited in a Mendelian fashion. Two different haplotypes
have been mapped based on the genomic blot-hybridization data. The
variation in the alpha-like globin gene cluster in the rabbit population
results both from differences in the copy number of the duplication block
containing the zeta-zeta-theta gene set and from the presence or absence of
polymorphic BamHI sites.
相似文献
7.
Charlie Strange Felix JF Herth Kevin L Kovitz Geoffrey McLennan Armin Ernst Jonathan Goldin Marc Noppen Gerard J Criner Frank C Sciurba 《BMC pulmonary medicine》2007,7(1):1-12
Background
Lung volume reduction surgery is effective at improving lung function, quality of life, and mortality in carefully selected individuals with advanced emphysema. Recently, less invasive bronchoscopic approaches have been designed to utilize these principles while avoiding the associated perioperative risks. The Endobronchial Valve for Emphysema PalliatioN Trial (VENT) posits that occlusion of a single pulmonary lobe through bronchoscopically placed Zephyr® endobronchial valves will effect significant improvements in lung function and exercise tolerance with an acceptable risk profile in advanced emphysema.Methods
The trial design posted on Clinical trials.gov, on August 10, 2005 proposed an enrollment of 270 subjects. Inclusion criteria included: diagnosis of emphysema with forced expiratory volume in one second (FEV1) < 45% of predicted, hyperinflation (total lung capacity measured by body plethysmography > 100%; residual volume > 150% predicted), and heterogeneous emphysema defined using a quantitative chest computed tomography algorithm. Following standardized pulmonary rehabilitation, patients were randomized 2:1 to receive unilateral lobar placement of endobronchial valves plus optimal medical management or optimal medical management alone. The co-primary endpoint was the mean percent change in FEV1 and six minute walk distance at 180 days. Secondary end-points included mean percent change in St. George's Respiratory Questionnaire score and the mean absolute changes in the maximal work load measured by cycle ergometry, dyspnea (mMRC) score, and total oxygen use per day. Per patient response rates in clinically significant improvement/maintenance of FEV1 and six minute walk distance and technical success rates of valve placement were recorded. Apriori response predictors based on quantitative CT and lung physiology were defined.Conclusion
If endobronchial valves improve FEV1 and health status with an acceptable safety profile in advanced emphysema, they would offer a novel intervention for this progressive and debilitating disease.Trial Registration
ClinicalTrials.gov: NCT00129584 相似文献8.
Charles E Chalfant Kristin Rathman Ryan L Pinkerman Rachel E Wood Lina M Obeid Besim Ogretmen Yusuf A Hannun 《The Journal of biological chemistry》2002,277(15):12587-12595
Previous studies have demonstrated that several splice variants are derived from both the caspase 9 and Bcl-x genes in which the Bcl-x splice variant, Bcl-x(L) and the caspase 9 splice variant, caspase 9b, inhibit apoptosis in contrast to the pro-apoptotic splice variants, Bcl-x(s) and caspase 9. In a recent study, we showed that ceramide induces the dephosphorylation of SR proteins, a family of protein factors that regulate alternative splicing. In this study, the regulation of the alternative processing of pre-mRNA of both caspase 9 and Bcl-x(L) was examined in response to ceramide. Treatment of A549 lung adenocarcinoma cells with cell-permeable ceramide, D-e-C(6) ceramide, down-regulated the levels of Bcl-x(L) and caspase 9b mRNA and immunoreactive protein with a concomitant increase in the mRNA and immunoreactive protein levels of Bcl-x(s) and caspase 9 in a dose- and time-dependent manner. Pretreatment with calyculin A (5 nm), an inhibitor of protein phosphatase-1 (PP1) and protein phosphatase 2A (PP2A) blocked ceramide-induced alternative splicing in contrast to okadaic acid (10 nm), a specific inhibitor of PP2A at this concentrations in cells, demonstrating a PP1-mediated mechanism. A role for endogenous ceramide in regulating the alternative splicing of caspase 9 and Bcl-x was demonstrated using the chemotherapeutic agent, gemcitabine. Treatment of A549 cells with gemcitabine (1 microm) increased ceramide levels 3-fold via the de novo sphingolipid pathway as determined by pulse labeling experiments and inhibition studies with myriocin (50 nm), a specific inhibitor of serine palmitoyltransferase (the first step in de novo synthesis of ceramide). Treatment of A549 cells with gemcitabine down-regulated the levels of Bcl-x(L) and caspase 9b mRNA with a concomitant increase in the mRNA levels of Bcl-x(s) and caspase 9. Again, inhibitors of ceramide synthesis blocked this effect. We also demonstrate that the change in the alternative splicing of caspase 9 and Bcl-x occurred prior to apoptosis following treatment with gemcitabine. Furthermore, doses of D-e-C(6) ceramide that induce the alternative splicing of both caspase 9 and Bcl-x-sensitized A549 cells to daunorubicin. These data demonstrate a role for protein phosphatases 1 (PP1) and endogenous ceramide generated via the de novo pathway in regulating this mechanism. This is the first report on the dynamic regulation of RNA splicing of members of the Bcl-2 and caspase families in response to regulators of apoptosis. 相似文献
9.
Background
Most studies examining the commensal human oral microbiome are focused on disease or are limited in methodology. In order to diagnose and treat diseases at an early and reversible stage an in-depth definition of health is indispensible. The aim of this study therefore was to define the healthy oral microbiome using recent advances in sequencing technology (454 pyrosequencing). 相似文献10.
RP Tucker K Drabikowski JF Hess J Ferralli R Chiquet-Ehrismann JC Adams 《BMC evolutionary biology》2006,6(1):60-17