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1.
Phylogenetic distribution in the genus Mus of t-complex-specific DNA and protein markers: inferences on the origin of t-haplotypes 总被引:8,自引:0,他引:8
Delarbre C; Kashi Y; Boursot P; Beckmann JS; Kourilsky P; Bonhomme F; Gachelin G 《Molecular biology and evolution》1988,5(2):120-133
We have examined the phylogenetic distribution of two t-specific markers
among representatives of various taxa belonging to the genus Mus. The
centromeric TCP-1a marker (a testicular protein variant specific for all
t-haplotypes so far studied) has also been apparently detected in several
non-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolor
species. By contrast, a t-specific restriction- fragment-length
polymorphism allele (RFLP) of the telomeric alpha- globin pseudogene DNA
marker alpha-psi-4 was found only in animals belonging to the M.
musculus-complex species either bearing genuine t- haplotypes or, like the
M. m. bactrianus specimen studied here, likely to do so. This t-specific
alpha-psi-4 RFLP allele was found to be as divergent from the RFLP alleles
of the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, or
M. spretus ones. These results suggest the presence of t-haplotypes and of
t-specific markers in populations other than those belonging to the M. m.
domesticus and M. m. musculus subspecies, implying a possible origin for
t-haplotypes prior to the radiation of the most recent offshoot of the Mus
genus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago.
相似文献
2.
Monoclonal antibody-based immunoassay for type A Clostridium botulinum toxin is comparable to the mouse bioassay 总被引:3,自引:0,他引:3
C Shone P Wilton-Smith N Appleton P Hambleton N Modi S Gatley J Melling 《Applied and environmental microbiology》1985,50(1):63-67
A monoclonal antibody (BA11) has been produced against Clostridium botulinum type A neurotoxin by the fusion of myeloma cells (P3 NS1/1-Ag4-1) with spleen cells from BALB/c mice immunized with botulinum type A neurotoxoid. The antibody bound specifically to botulinum type A neurotoxin, showing no cross-reactivity with types B and E botulinum toxins or with any of several other bacterial toxins tested. The monoclonal antibody did not bind to botulinum type A neurotoxin which had been denatured with sodium dodecyl sulfate and bound only weakly to each of the separated heavy and light subunits of the neurotoxin, suggesting a conformational requirement for the antigenic determinant of the antibody. A sensitive immunoassay for C. botulinum type A toxin with monoclonal antibody BA11 in conjunction with an enzyme amplication system has been developed which allows detection of 5 to 10 mouse 50% lethal doses ml-1 of purified neurotoxin. The assay was equally sensitive when applied to the detection of crude toxin in food stuffs; the average value for the minimum level of detectable toxin in extracts of tinned salmon or corned beef was 9 +/- 3.1 mouse 50% lethal doses ml-1. 相似文献
3.
S. John Gatley Ding-Wei Yu Joanna S. Fowler Robert R. MacGregor David J. Schlyer Stephen L. Dewey Alfred P. Wolf Thomas Martin Colleen E. Shea Nora D. Volkow 《Journal of neurochemistry》1994,62(3):1154-1162
Abstract: The psychostimulant drug of abuse, cocaine (benzoylecgonine methyl ester), is rapidly metabolized by cleavage of its two ester groups, to give benzoylecgonine (BE) and ecgonine methyl ester, and by N-demethylation, to give N-norcocaine (NC). The recent use of [N-methyl-11CH3]cocaine to image brain cocaine binding sites with positron emission tomography (PET) raises the question of whether PET images partially reflect the distribution and kinetics of labeled cocaine metabolites. We prepared [O-metty/-11CH3]cocaine by methylation of the sodium salt of BE with [11C]CH3l, and showed that PET baboon brain scans, as well as regional brain kinetics and plasma time-activity curves corrected for the presence of labeled metabolites, are nearly identical to those seen with [N-methyl-11CH3]cocaine. This strongly suggests that 11C metabolites do not significantly affect PET images, because the metabolite pattern is different for the two labeled forms of cocaine. In particular, nearly half the 11C in blood plasma at 30 min was [11C]CO2 when [N-methy/-11CH3]cocaine was administered, whereas [11C]CO2 was not formed from [O-methy/-11CH3]cocaine. Only a trace of [11C]NC was detected in plasma after [O-methyl-11CH3]cocaine administration. Nearly identical brain PET data were also obtained when 4′-[N-methy/-11CH3]fluorococaine and 4′-[18F]fluoro-cocaine (prepared by nucleophilic aromatic substitution from [18F]fluoride-and 4′-nitrococaine) were compared with [N-methy/-11CH3]cocaine. In vitro assays with rat brain membranes showed that cocaine and 4′-fluoroco-caine were equipotent at the dopamine reuptake site, but that 4′-fluorococaine was about 100 times more potent at the 5-hydroxytryptamine reuptake site. The studies with positron-emitting 4′-fluorococaines thus support the lack of significance of labeled metabolites or of binding to 5-hydroxytryptamine reuptake sites to PET images taken with [N-methy/-11CH3]cocaine. [11C]NC prepared by O-methylation of norbenzoylecgonine gave PET images with preferential uptake in striatum, but slower clearance from all brain regions than [O-methy/-11CH3]cocaine. [11C]BE prepared by N-methylation of norbenzoylecgonine did not show brain uptake. 相似文献
4.
The contractile basis of amoeboid movement: V. The control of gelation, solation, and contraction in extracts from dictyostelium discoideum 总被引:29,自引:22,他引:7
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Motile extracts have been prepared from Dictyostelium discoideum by homogenization and differential centrifugation at 4 degrees C in a stabilization solution (60). These extracts gelled on warming to 25 degrees Celsius and contracted in response to micromolar Ca++ or a pH in excess of 7.0. Optimal gelation occurred in a solution containing 2.5 mM ethylene glycol-bis (β-aminoethyl ether)N,N,N',N'-tetraacetate (EGTA), 2.5 mM piperazine-N-N'-bis [2-ethane sulfonic acid] (PIPES), 1 mM MgC1(2), 1 mM ATP, and 20 mM KCI at ph 7.0 (relaxation solution), while micromolar levels of Ca++ inhibited gelation. Conditions that solated the gel elicited contraction of extracts containing myosin. This was true regardless of whether chemical (micromolar Ca++, pH >7.0, cytochalasin B, elevated concentrations of KCI, MgC1(2), and sucrose) or physical (pressure, mechanical stress, and cold) means were used to induce solation. Myosin was definitely required for contraction. During Ca++-or pH-elicited contraction: (a) actin, myosin, and a 95,000-dalton polypeptide were concentrated in the contracted extract; (b) the gelation activity was recovered in the material sqeezed out the contracting extract;(c) electron microscopy demonstrated that the number of free, recognizable F-actin filaments increased; (d) the actomyosin MgATPase activity was stimulated by 4- to 10-fold. In the absense of myosin the Dictyostelium extract did not contract, while gelation proceeded normally. During solation of the gel in the absense of myosin: (a) electron microscopy demonstrated that the number of free, recognizable F- actin filaments increased; (b) solation-dependent contraction of the extract and the Ca++-stimulated MgATPase activity were reconstituted by adding puried Dictyostelium myosin. Actin purified from the Dictyostelium extract did not gel (at 2 mg/ml), while low concentrations of actin (0.7-2 mg/ml) that contained several contaminating components underwent rapid Ca++ regulated gelation. These results indicated : (a) gelation in Dictyostelium extracts involves a specific Ca++-sensitive interaction between actin and several other components; (b) myosin is an absolute requirement for contraction of the extract; (c) actin-myosin interactions capable of producing force for movement are prevented in the gel, while solation of the gel by either physical or chemical means results in the release of F-actin capable of interaction with myosin and subsequent contraction. The effectiveness of physical agents in producting contraction suggests that the regulation of contraction by the gel is structural in nature. 相似文献
5.
Distribution of nitrogen-13 from labeled nitrate and nitrite in germfree and conventional-flora rats
The in vivo distribution of physiological concentrations of NO3- and NO2- labeled with 13N was studied in germfree and conventional-flora Sprague-Dawley rats after gastric intubation (gavage), intravenous (cardiac or tail vein), or intraluminal (intestinal) injection. Some in vitro studies were performed to determine the influence of the bacterial flora on ion distribution. After gavage with 13NO3-, essentially all of the label passed into the upper small intestine, where most was absorbed; however, up to 24% of the 13N could reach the ileum within 1 h. Gavage with 13NO2- resulted in some gastric absorption of the label, but most seemed to exit the stomach via passage into the duodenum. The exit of 13NO2- from the stomach was slower, and less 13N appeared to be absorbed from the small intestine than with 13NO3-. Movement of label through the gastrointestinal tract could be enhanced by inducing diarrhea. Absorbed 13N was either excreted in the urine, reentered the gastrointestinal tract at various points, or was temporarily stored in the eviscerated carcass. The bacterial flora, either by incorporation or chemical alteration, appeared to have some influence on the distribution of 13N from 13NO3- or 13NO2-. 相似文献
6.
The observation that increased muscular activity leads to muscle hypertrophy is well known, but identification of the biochemical and physiological mechanisms by which this occurs remains an important problem. Experiments have been described (5, 6) which suggest that creatine, an end product of contraction, is involved in the control of contractile protein synthesis in differentiating skeletal muscle cells and may be the chemical signal coupling increased muscular activity and the increased muscular mass. During contraction, the creatine concentration in muscle transiently increases as creatine phosphate is hydrolyzed to regenerate ATP. In isometric contraction in skeletal muscle for example, Edwards and colleagues (3) have found that nearly all of the creatine phosphate is hydrolyzed. In this case, the creatine concentration is increased about twofold, and it is this transient change in creatine concentration which is postulated to lead to increased contractile protein synthesis. If creatine is found in several intracellular compartments, as suggested by Lee and Vissher (7), local changes in concentration may be greater then twofold. A specific effect on contractile protein synthesis seems reasonable in light of the work of Rabinowitz (13) and of Page et al. (11), among others, showing disproportionate accumulation of myofibrillar and mitochondrial proteins in response to work-induced hypertrophy and thyroxin-stimulated growth. Previous experiments (5, 6) have shown that skeletal muscles cells which have differentiated in vitro or in vivo synthesize myosin heavy-chain and actin, the major myofibrillar polypeptides, faster when supplied creatine in vitro. The stimulation is specific for contractile protein synthesis since neither the rate of myosin turnover nor the rates of synthesis of noncontractile protein and DNA are affected by creatine. The experiments reported in this communication were undertaken to test whether creatine selectively stimulates contractile protein synthesis in heart as it does in skeletal muscle. 相似文献
7.
Microengineered systems with iPSC-derived cardiac and hepatic cells to evaluate drug adverse effects
Hepatic and cardiac drug adverse effects are among the leading causes of attrition in drug development programs, in part due to predictive failures of current animal or in vitro models. Hepatocytes and cardiomyocytes differentiated from human induced pluripotent stem cells (iPSCs) hold promise for predicting clinical drug effects, given their human-specific properties and their ability to harbor genetically determined characteristics that underlie inter-individual variations in drug response. Currently, the fetal-like properties and heterogeneity of hepatocytes and cardiomyocytes differentiated from iPSCs make them physiologically different from their counterparts isolated from primary tissues and limit their use for predicting clinical drug effects. To address this hurdle, there have been ongoing advances in differentiation and maturation protocols to improve the quality and use of iPSC-differentiated lineages. Among these are in vitro hepatic and cardiac cellular microsystems that can further enhance the physiology of cultured cells, can be used to better predict drug adverse effects, and investigate drug metabolism, pharmacokinetics, and pharmacodynamics to facilitate successful drug development. In this article, we discuss how cellular microsystems can establish microenvironments for these applications and propose how they could be used for potentially controlling the differentiation of hepatocytes or cardiomyocytes. The physiological relevance of cells is enhanced in cellular microsystems by simulating properties of tissue microenvironments, such as structural dimensionality, media flow, microfluidic control of media composition, and co-cultures with interacting cell types. Recent studies demonstrated that these properties also affect iPSC differentiations and we further elaborate on how they could control differentiation efficiency in microengineered devices. In summary, we describe recent advances in the field of cellular microsystems that can control the differentiation and maturation of hepatocytes and cardiomyocytes for drug evaluation. We also propose how future research with iPSCs within engineered microenvironments could enable their differentiation for scalable evaluations of drug effects. 相似文献
8.
The CB1 cannabinoid receptor is expressed in the brain at levels sufficient to serve as potential target for in vivo imaging using positron emission tomography (PET) or single photon emission computed tomography methodology. To date, the most promising radioligands for the in vivo imaging of this receptor have structures based on that of the cannabinoid antagonist, SR141716A. Rodent data obtained using these in vivo radiotracers has demonstrated that both the behavioral and neurochemical effects of cannabinoids occur at very low levels of receptor occupancy. More recently, an agonist radiotracer based on the structure of aminoalkylindole cannabinoids has also been examined for in vivo labeling of CB1 receptors. Although rodent studies have indicated that in vivo imaging of CB1 receptors is feasible, at the present time this receptor has still to be successful imaged in a human PET study. 相似文献
9.
Presence or absence of N-acetylneuraminic acid (Neu5Ac) can change a
sialylated glycoprotein's serum half-life and possibly its function. We
evaluated the linearity, sensitivity, reproducibility, and accuracy of a
HPAEC/PAD method to determine its suitability for routine simultaneous
analysis of Neu5Ac and N-glycolylneuraminic acid (Neu5Gc). An effective
internal standard for this analysis is 3-deoxy-d-glycero-d-
galacto-2-nonulosonic acid (KDN). We investigated the effect of the Au
working electrode recession and determined that linear range and
sensitivity were dependent on electrode recession. Using an electrode that
was 350 &mgr;m recessed from the electrode block, the minimum detection
limits of Neu5Ac, KDN, and Neu5Gc were 2, 5, and 2 pmol, respectively, and
were reduced to 1, 2, and 0.5 pmol using a new electrode. The response of
standards was linear from 10 to 500 pmol (r2>0.99) regardless of
electrode recession. When Neu5Ac, KDN, and Neu5Gc (200 pmol each) were
analyzed repetitively for 48 h, area RSDs were <3%. Reproducibility was
unaffected when injections of glycoprotein neuraminidase and acid
digestions were interspersed with standard injections. Area RSDs of Neu5Ac
and Neu5Gc improved when the internal standard was used. We determined the
precision and accuracy of this method for both a recessed and a new working
electrode by analyzing Neu5Ac and Neu5Gc contents of bovine fetuin and
bovine and human transferrins. Results were consistent with published
values and independent of the working electrode. The sensitivity,
reproducibility, and accuracy of this method make it suitable for direct
routine analysis of glycoprotein Neu5Ac and Neu5Gc contents.
相似文献
10.