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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.
Relative apparent synapomorphy analysis (RASA). I: The statistical measurement of phylogenetic signal 总被引:10,自引:9,他引:1
We have developed a new approach to the measurement of phylogenetic signal
in character state matrices called relative apparent synapomorphy analysis
(RASA). RASA provides a deterministic, statistical measure of natural
cladistic hierarchy (phylogenetic signal) in character state matrices. The
method works by determining whether a measure of the rate of increase of
cladistic similarity among pairs of taxa as a function of phenetic
similarity is greater than a null equiprobable rate of increase. Our
investigation of the utility and limitations of RASA using simulated and
bacteriophage T7 data sets indicates that the method has numerous
advantages over existing measures of signal. A first advantage is
computational efficiency. A second advantage is that RASA employs known
methods of statistical inference, providing measurable sensitivity and
power. The performance of RASA is examined under various conditions of
branching evolution as the number of characters, character states per
character, and mutations per branch length are varied. RASA appears to
provide an unbiased and reliable measure of phylogenetic signal, and the
general approach promises to be useful in the development of new techniques
that should increase the rigor and reliability of phylogenetic estimates.
相似文献
3.
4.
Variation in heat-shock proteins among species of desert fishes (Poeciliidae, Poeciliopsis) 总被引:4,自引:0,他引:4
Analysis of the heat-shock proteins (hsps) of six closely related species
of Poeciliopsis demonstrated the existence of biochemical diversity in the
hsp100, hsp70, hsp60, and hsp30 protein families among species. Each
species expressed five to seven hsp70-related isoforms. Constitutive 70-kD
isoforms were identical among species, but four different patterns of
heat-inducible isoforms were seen in these six species. Members of the
hsp70 family of molecular chaperones are included among the most highly
conserved proteins known, and the possibility of variation in hsp70 among
closely related species has rarely been addressed. The hsp30 family is
known to be less conserved than the hsp70 family, and, as expected, the
Poeciliopsis hsp30 patterns showed more variation. Most of the hsp30
isoforms characteristic of a particular species were unique to that
species. Hsp100 and hsp60 were identical in five of the species, but
alternate isoforms were found in P. monacha. The small size and limited
geographical distribution of the P. monacha population have probably
contributed to the uniqueness of the monacha pattern. Two of the species
were shown to acquire thermotolerance, the ability to withstand normally
lethal temperatures when subjected to a gradual temperature increase.
Rapid-heating protocols commonly used to establish critical thermal maxima
of organisms do not include this inducible component of thermoresistance
and therefore do not adequately assess an organism's capacity to withstand
thermal stress.
相似文献
5.
Variation in heat shock proteins within tropical and desert species of poeciliid fishes 总被引:8,自引:0,他引:8
Norris CE; diIorio PJ; Schultz RJ; Hightower LE 《Molecular biology and evolution》1995,12(6):1048-1062
The 70-kilodalton heat shock protein (hsp70) family of molecular
chaperones, which contains both stress-inducible and normally abundant
constitutive members, is highly conserved across distantly related taxa.
Analysis of this protein family in individuals from an outbred population
of tropical topminnows, Poeciliopsis gracilis, showed that while
constitutive hsp70 family members showed no variation in protein isoforms,
inducibly synthesized hsp70 was polymorphic. Several species of
Poeciliopsis adapted to desert environments exhibited lower levels of
inducible hsp70 polymorphism than the tropical species, but constitutive
forms were identical to those in P. gracilis, as they were in the
confamilial species Gambusia affinis. These differences suggest that
inducible and constitutive members of this family are under different
evolutionary constraints and may indicate differences in their function
within the cell. Also, northern desert species of Poeciliopsis synthesize a
subset of the inducible hsp70 isoforms seen in tropical species. This
distribution supports the theory that ancestral tropical fish migrated
northward and colonized desert streams; the subsequent decrease in
variation of inducible hsp70 may have been due to genetic drift or a
consequence of adaptation to the desert environment. Higher levels of
variability were found when the 30- kilodalton heat shock protein (hsp30)
family was analyzed within different strains of two desert species of
Poeciliopsis and also in wild-caught individuals of Gambusia affinis. In
both cases the distribution of hsp30 isoform diversity was similar to that
seen previously with allozyme polymorphisms.
相似文献
6.
7.
8.
Engineering tumor-targeted gadolinium hexanedione nanoparticles for potential application in neutron capture therapy 总被引:5,自引:0,他引:5
Microemulsions (oil-in-water) have been employed as templates to engineer nanoparticles containing high concentrations of gadolinium for potential application in neutron capture therapy of tumors. Gadolinium hexanedione (GdH), synthesized by complexation of Gd(3+) with 2,4-hexanedione, was used as the nanoparticle matrix alone or in combination with either emulsifying wax or PEG-400 monostearate. Solid nanoparticles (<125 nm size) were obtained by simple cooling of the microemulsions prepared at 60 degrees C to room temperature in one vessel. The feasibility of tumor targeting via folate receptors was studied. A folate ligand was synthesized by chemically linking folic acid to distearoylphosphatidylethanolamine (DSPE) via a poly(ethylene glycol) (PEG; MW 3350) spacer. To obtain folate-coated nanoparticles, the folate ligand (0.75% w/w to 15% w/w) was added to either the microemulsion templates at 60 degrees C or nanoparticle suspensions at 25 degrees C. Efficiencies of folate ligand attachment/adsorption to nanoparticle formulations were monitored by gel permeation chromatography. Cell uptake studies were carried out in KB cells (human nasopharyngeal epidermal carcinoma cell line), known to overexpress folate receptors. The uptake of folate-coated nanoparticles was about 10-fold higher than uncoated nanoparticles after 30 min at 37 degrees C. The uptake of folate-coated nanoparticles at 4 degrees C was 20-fold lower than the uptake at 37 degrees C and comparable to the uptake of uncoated nanoparticles at 37 degrees C. Folate-mediated endocytosis was further verified by the inhibition of folate-coated nanoparticles uptake by free folic acid. It was observed that folate-coated nanoparticles uptake decreased to approximately 2% of its initial value with the coincubation of 0.001 mM of free folic acid. The results suggested that these tumor-targeted nanoparticles containing high concentrations of Gd may have potential for neutron capture therapy. 相似文献
9.
A high population of dendritic cells in the skin makes intradermal (ID) immunization an attractive route. We sought to further enhance immune responses from a previously reported novel nanoparticle-based DNA vaccine delivery system by administering the system intradermally into mouse skin using Biojector 2000, a needle-free jet injection device. Two mouse studies were carried out. Balb/C mice (n=5-6) were immunized on day 0, 7, and 14 by subcutaneous injection or via the Biojector 2000 with pDNA alone (CMV-beta-galactosidase, 5 micro g), pDNA-coated nanoparticles, or beta-galactosidase protein (10 micro g) adjuvanted with 'Alum' (15 micro g). On day 28, mice were sacrificed and specific serum IgG and IgA titer, in vitro cytokine release, and cell proliferation of isolated splenocytes were determined. Similar to previous reports, in both mouse studies, SC immunization with pDNA-coated nanoparticles led to over a log increase in specific serum IgG titer as compared to immunization with pDNA alone. For pDNA alone, jet and SC injection did not result in significant differences in IgG titer. In contrast, for pDNA-coated nanoparticles, jet injection led to as high as a 20-fold enhancement in IgG titer over SC injection. In addition, jet injection of pDNA-coated nanoparticles enhanced the IgG titer by more than 200-fold over jet injection of pDNA alone. Also, jet injection of pDNA-coated nanoparticles resulted in significantly enhanced specific serum IgA titer. For in vitro cytokine release, immunization with pDNA-coated nanoparticles by jet injection enhanced IFN-gamma and IL-4 release over pDNA alone by 6- and 5-fold, respectively. SC injection of pDNA-coated nanoparticles also resulted in enhanced IFN-gamma and IL-4 release over pDNA alone although with less magnitude. Finally, immunization with pDNA-coated nanoparticles, by both jet injection and SC injection, led to improved splenocyte proliferation over pDNA alone. In conclusion, a combination of a novel cationic nanoparticle-based DNA delivery system with ID jet injection led to enhanced antibody production, Th-1/Th-2 balanced cytokine release, and enhanced splenocyte proliferation. 相似文献
10.
Preparation and characterization of novel coenzyme Q<Subscript>10</Subscript> nanoparticles engineered from microemulsion precursors 总被引:2,自引:0,他引:2
The purpose of these studies was to prepare and characterize nanoparticles into which Coenzyme Q10 (CoQ10) had been incorporated (CoQ10-NPs) using a simple and potentially scalable method. CoQ10-NPs were prepared by cooling warm microemulsion precursors composed of emulsifying wax, CoQ10, Brij 78, and/or Tween 20. The nanoparticles were lyophilized, and the stability of CoQ10-NPs in both lyophilized form and aqueous suspension was monitored over 7 days. The release of CoQ10 from the nanoparticles was investigated at 37°C. Finally, an in vitro study of the uptake of CoQ10-NPs by mouse macrophage, J774A.1, was completed. The incorporation efficiency of CoQ10 was approximately 74%±5%. Differential Scanning Calorimetry (DSC) showed that the nanoparticle was not a physical mixture
of its individual components. The size of the nanoparticles increased over time if stored in aqueous suspension. However,
enhanced stability was observed when the nanoparticles were stored at 4°C. Storage in lyophilized form demonstrated the highest
stability. The in vitro release profile of CoQ10 from the nanoparticles showed an initial period of rapid release in the first 9 hours followed by a period of slower and
extended release. The uptake of CoQ10-NPs by the J774A.1 cells was over 4-fold higher than that of the CoQ10-free nanoparticles (P<.05). In conclusion, CoQ10-NPs with potential application for oral CoQ10 delivery were engineered readily from microemulsion precursors. 相似文献