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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.
Summary Isolated crayfish retinas were incubated for 8 h in the light in a medium containing either 3H-fucose or 3H-mannose. Following this incubation, the rhabdom membranes were isolated, the pigment reduced with boranedimethylamine, and extracted with SDS detergent. The membrane-protein extract was separated by SDS-polyacrylamide gel electrophoresis. The photopigment band on the gels was identified by its fluorescence upon exposure to long wavelength ultraviolet light. Determination of the distribution of radioactivity in the gels indicated that both fucose and mannose labeled the photopigment and other glycoproteins. Hydrolysis of the sugars from the labeled photopigment bands, followed by thin layer chromatography, further confirmed that both sugars were incorporated into newly synthesized photopigment without modification. These results provide the first reported data on the partial composition of the carbohydrate moiety of an invertebrate photopigment. These findings on the crayfish photopigment are compared with data from vertebrate rhodopsin and photopigment of other invertebrates.Supported by a grant from the National Science Foundation (BNS 80-04587) and by BRSG Grant 507 RR07031 awarded by the Biomedical Research Support Grant Program, Division of Research Resources, NIH 相似文献
3.
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 下载免费PDF全文
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
4.
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
5.
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
6.
Misra RN Xiao HY Williams DK Kim KS Lu S Keller KA Mulheron JG Batorsky R Tokarski JS Sack JS Kimball SD Lee FY Webster KR 《Bioorganic & medicinal chemistry letters》2004,14(11):2973-2977
N-Aryl aminothiazoles 6-9 were prepared from 2-bromothiazole 5 and found to be CDK inhibitors. In cells they act as potent cytotoxic agents. Selectivity for CDK1, CDK2, and CDK4 was dependent of the nature of the N-aryl group and distinct from the CDK2 selective N-acyl analogues. The N-2-pyridyl analogues 7 and 19 showed pan CDK inhibitory activity. Elaborated analogues 19 and 23 exhibited anticancer activity in mice against P388 murine leukemia. The solid-state structure of 7 bound to CDK2 shows a similar binding mode to the N-acyl analogues. 相似文献
7.
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
8.
The results described in the accompanying article support the model in
which glucosylphosphoryldolichol (Glc-P-Dol) is synthesized on the
cytoplasmic face of the ER, and functions as a glucosyl donor for three
Glc-P-Dol:Glc0-2Man9-GlcNAc2-P-P-Dol glucosyltransferases (GlcTases) in the
lumenal compartment. In this study, the enzymatic synthesis and structural
characterization by NMR and electrospray-ionization tandem mass
spectrometry of a series of water-soluble beta-Glc-P-Dol analogs containing
2-4 isoprene units with either the cis - or trans - stereoconfiguration in
the beta-position are described. The water- soluble analogs were (1) used
to examine the stereospecificity of the Glc-P-Dol:Glc0-2Man9GlcNAc2-P-P-Dol
glucosyltransferases (GlcTases) and (2) tested as potential substrates for
a membrane protein(s) mediating the transbilayer movement of Glc-P-Dol in
sealed ER vesicles from rat liver and pig brain. The Glc-P-Dol-mediated
GlcTases in pig brain microsomes utilized [3H]Glc-labeled Glc-P-Dol10,
Glc-P-(omega, c )Dol15, Glc-P(omega, t,t )Dol20, and Glc-P-(omega, t,c
)Dol20as glucosyl donors with [3H]Glc3Man9GlcNAc2-P-P-Dol the major product
labeled in vitro. A preference was exhibited for C15-20 substrates
containing an internal cis -isoprene unit in the beta-position. In
addition, the water-soluble analog, Glc-P-Dol10, was shown to enter the
lumenal compartment of sealed microsomal vesicles from rat liver and pig
brain via a protein-mediated transport system enriched in the ER. The
properties of the ER transport system have been characterized. Glc-
P-Dol10was not transported into or adsorbed by synthetic PC-liposomes or
bovine erythrocytes. The results of these studies indicate that (1) the
internal cis -isoprene units are important for the utilization of Glc-P-Dol
as a glucosyl donor and (2) the transport of the water- soluble analog may
provide an experimental approach to assay the hypothetical "flippase"
proposed to mediate the transbilayer movement of Glc-P-Dol from the
cytoplasmic face of the ER to the lumenal monolayer.
相似文献
9.
10.
Fink BE Vite GD Mastalerz H Kadow JF Kim SH Leavitt KJ Du K Crews D Mitt T Wong TW Hunt JT Vyas DM Tokarski JS 《Bioorganic & medicinal chemistry letters》2005,15(21):4774-4779
A novel series of dual EGFR and HER2 inhibitors based on the pyrrolo[2,1-f][1,2,4]triazine nucleus is described. A general route toward their synthesis, which enables functionalization at multiple sites, has been developed. Biological evaluation in enzymatic and cell-based assays has identified a series of C-6 carbamates with potent biochemical and cellular activities. 相似文献