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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.
Mouse blastocysts hatch in vitro by using a trypsin-like proteinase associated with cells of mural trophectoderm 总被引:7,自引:0,他引:7
The mammalian blastocyst must hatch from its extracellular coat, or zona pellucida, to implant in the uterus and continue development normally. Results of experiments described here strongly suggest that a proteinase (74K Mr), called "strypsin," is directly involved in hatching of isolated mouse blastocysts in vitro. Strypsin is a trypsin-like proteinase, based on its substrate specificity and sensitivity to inhibitors, that is present in mouse blastocysts and exhibits certain properties characteristic of membrane-associated enzymes. Histochemical and autoradiographic evidence suggests that, prior to hatching of blastocysts, strypsin is found with cells of mural trophectoderm; not with polar trophectoderm or inner cell mass. Following hatching, strypsin is also found associated with empty zonae pellucidae, specifically at the opening through which the embryo emerged. These and other observations suggest that hatching of mouse blastocysts in vitro is initiated by limited proteolysis of the region of zona pellucida overlying mural trophectoderm. 相似文献
3.
Laser Doppler blood flow measurements of common cutaneous donor sites for reconstructive surgery 总被引:1,自引:0,他引:1
J Goldberg R S Sepka B P Perona W C Pederson B Klitzman 《Plastic and reconstructive surgery》1990,85(4):581-586
The purpose of this study was to evaluate cutaneous blood flow in regions commonly used as donor sites in reconstructive surgery in order to better establish normal flow ranges. Flow was measured with the TSI Laserflo BPM 403 in 27 healthy volunteers and compared to the flow in uncomplicated postoperative autologous tissue transplants. The forehead produced the highest flow, with an average value of 6.50 +/- 0.31 (mean +/- SE), and the dorsalis pedis had the lowest flow, with an average value of 0.60 +/- 0.04. Gender differences were noted in the latissimus dorsi, pectoralis major, and rectus abdominis areas. There were no significant differences between smokers and nonsmokers, hand dominance, musculocutaneous and fasciocutaneous tissues, or supine and sitting body positions. Flow levels in volunteers were similar to those in postoperative surviving autologous tissue transplants. The site-specific flow and flow changes over long time periods (hours) have helped clinical monitoring of 77 patients in the last 24 months. In every case identified by the flowmeter as decreased perfusion, a definite etiology for low reduction was documented. Complications occurred in 12 patients, and the rate of salvaging compromised tissue has increased from 50 percent using temperature monitoring and clinical observation to 83 percent with the computerized laser Doppler flowmeter. 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.
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
6.
Structure-based mutational analysis of serine protease specificity has produced a large database of information useful in addressing biological function and in establishing a basis for targeted design efforts. Critical issues examined include the function of water molecules in providing strength and specificity of binding, the extent to which binding subsites are interdependent, and the roles of polypeptide chain flexibility and distal structural elements in contributing to specificity profiles. The studies also provide a foundation for exploring why specificity modification can be either straightforward or complex, depending on the particular system. 相似文献
7.
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
8.
The accuracy of protein synthesis relies on the ability of aminoacyl-tRNA synthetases (aaRSs) to discriminate among true and near cognate substrates. To date, analysis of aaRSs function, including identification of residues of aaRS participating in amino acid and tRNA discrimination, has largely relied on the steady state kinetic pyrophosphate exchange and aminoacylation assays. Pre-steady state kinetic studies investigating a more limited set of aaRS systems have also been undertaken to assess the energetic contributions of individual enzyme-substrate interactions, particularly in the adenylation half reaction. More recently, a renewed interest in the use of rapid kinetics approaches for aaRSs has led to their application to several new aaRS systems, resulting in the identification of mechanistic differences that distinguish the two structurally distinct aaRS classes. Here, we review the techniques for thermodynamic and kinetic analysis of aaRS function. Following a brief survey of methods for the preparation of materials and for steady state kinetic analysis, this review will describe pre-steady state kinetic methods employing rapid quench and stopped-flow fluorescence for analysis of the activation and aminoacyl transfer reactions. Application of these methods to any aaRS system allows the investigator to derive detailed kinetic mechanisms for the activation and aminoacyl transfer reactions, permitting issues of substrate specificity, stereochemical mechanism, and inhibitor interaction to be addressed in a rigorous and quantitative fashion. 相似文献
9.
Olga P. Nyssen Angeles Perez‐Aisa Luis Rodrigo Manuel Castro Pilar Mata Romero Juan Ortuo Jesus Barrio Jose Maria Huguet Ines Modollel Noelia Alcaide Alfredo Lucendo Xavier Calvet Monica Perona Barbara Gomez Blas Jose Gomez Rodriguez Pilar Varela Manuel Jimenez‐Moreno Manuel Dominguez‐Cajal Liliana Pozzati Diego Burgos Luis Bujanda Jenifer Hinojosa Javier Molina‐Infante Tommaso Di Maira Luis Ferrer Luis Fernndez‐Salazar Ariadna Figuerola Llucia Tito Cristobal de la Coba Judith Gomez‐Camarero Nuria Fernandez Maria Caldas Ana Garre Elena Resina Ignasi Puig Colm OMorain Francis Megraud Javier P. Gisbert 《Helicobacter》2020,25(5)
10.
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