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排序方式: 共有153条查询结果,搜索用时 203 毫秒
101.
Sexton KE Lee HT Massa M Padia J Patt WC Liao P Pontrello JK Roth BD Spahr MA Ramharack R 《Bioorganic & medicinal chemistry》2003,11(22):4827-4845
Compounds of the general structure A and B were investigated for their activity as lipoprotein(a), [Lp(a)], assembly (coupling) inhibitors. SAR around the amino acid derivatives (structure A) gave compound 14-6 as a potent coupling inhibitor. Oral dosing of compound 14-6 to Lp(a) transgenic mice and cymologous monkeys resulted in a>30% decrease in plasma Lp(a) levels after 1-2 weeks of treatment at 100 mg/kg/day. 相似文献
102.
Background
Cancer of the oral tongue is the second most common cancer among males in various parts of India. Despite advances in diagnosis and treatment the failure rates in cancer of the oral tongue are high and survival poor. Majority of these failures occur in untreated neck. 相似文献103.
Raw milk was artificially contaminated with declumped cells of Mycobacterium avium subsp. paratuberculosis at a concentration of 10(4) to 10(5) CFU/ml and was used to manufacture model hard (Swiss Emmentaler) and semihard (Swiss Tisliter) cheese. Two different strains of M. avium subsp. paratuberculosis were tested, and for each strain, two model hard and semihard cheeses were produced. The survival of M. avium subsp. paratuberculosis cells was monitored over a ripening period of 120 days by plating out homogenized cheese samples onto 7H10-PANTA agar. In both the hard and the semihard cheeses, counts decreased steadily but slowly during cheese ripening. Nevertheless, viable cells could still be detected in 120-day cheese. D values were calculated at 27.8 days for hard and 45.5 days for semihard cheese. The most important factors responsible for the death of M. avium subsp. paratuberculosis in cheese were the temperatures applied during cheese manufacture and the low pH at the early stages of cheese ripening. Since the ripening period for these raw milk cheeses lasts at least 90 to 120 days, the D values found indicate that 10(3) to 10(4) cells of M. avium subsp. paratuberculosis per g will be inactivated. 相似文献
104.
Mutations in Rous sarcoma virus nucleocapsid protein p12 (NC): deletions of Cys-His boxes. 总被引:41,自引:33,他引:8
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Rous sarcoma virus nucleocapsid protein p12 (NC) contains two conserved amino acid motifs, the Cys-His boxes, which constitute potential metal-binding domains. To try to understand the function of NC and of each of its Cys-His boxes during the viral life cycle, particularly in viral RNA packaging, we have used synthetic oligonucleotides to delete precisely either the proximal or the distal box, or both Cys-His boxes. The mutant DNAs were transfected into chicken embryo fibroblasts, and the virions produced in a transient assay were characterized biochemically for production of viral proteins and particles, RNA packaging, and infectivity. The results indicated the following. (i) The deletion of either the proximal or the distal box decreases the amount of viral RNA packaged in the particles and results in incomplete 70S dimer formation. (ii) The deletion of both boxes inhibits viral RNA packaging. (iii) The deletion of the proximal, but not the distal, box suppresses any detectable infectivity, while the deletion of the distal, but not the proximal, box lowers infectivity 100 to 200 times. 相似文献
105.
106.
Effect of rearrangements and duplications of the Cys-His motifs of Rous sarcoma virus nucleocapsid protein. 总被引:18,自引:17,他引:1
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It has been widely documented that the nucleocapsid protein p12 (NC) of Rous sarcoma virus (RSV) has a role in the encapsidation and maturation of the virus genomic RNA during particle formation, and particularly important appear to be the Cys-His motifs of this protein. Since some retroviruses only have one such motif, we have investigated the significance of the two distinct Cys-His motifs of RSV NC. The analysis of the phenotype of virus NC mutants with precise rearrangements or duplications of the motifs highlights the following features. (i) The two motifs are not functionally equivalent. (ii) The order and number of Cys-His motifs are less important for RSV NC than the presence of two distinct motifs for both the encapsidation of virus genomic RNA and maintenance of the integrity of the RNA after particle formation. (iii) The proximal motif has a distinct function in the virus replication cycle other than RNA encapsidation and dimerization. (iv) The presence of three Cys-His motifs reduces virus infectivity and leads to high-frequency deletion events (of one of the motifs) after infection: the resulting RNA species encode a wild type-like NC protein restoring full infectivity to the progeny virus particles. Additionally, the data suggest that this occurs only after infection. The deletion probably arises by intramolecular displacement of the replication complex between repeat sequences. 相似文献
107.
Tonic GABAergic inhibition of taste-responsive neurons in the nucleus of the solitary tract 总被引:4,自引:1,他引:3
The effects of gamma-aminobutyric acid (GABA) and the GABAA receptor
antagonist bicuculline methiodide (BICM) on the activity of taste-
responsive neurons in the nucleus of the solitary tract (NST) were examined
electrophysiologically in urethane-anesthetized hamsters. Single neurons in
the NST were recorded extracellularly and drugs (21 nl) were microinjected
into the vicinity of the cell via a multibarrel pipette. The response of
each cell was recorded to lingual stimulation with 0.032 M NaCl, 0.032 M
sucrose, 0.0032 M citric acid and 0.032 M quinine hydrochloride (QHCl).
Forty-six neurons were tested for the effects of GABA; the activity of 29
cells (63%) was inhibited by 5 mM GABA. Whether activity was elicited in
these cells by repetitive anodal current stimulation (25 microA, 0.5 s, 0.1
Hz) of the tongue (n = 13 cells) or the cells were spontaneously active (n
= 13 cells), GABA produced a dose-dependent (1, 2 and 5 mM) decrement in
activity. Forty- seven NST neurons were tested for the effects of BICM on
their responses to chemical stimulation of the tongue; the responses of 28
cells (60%) were enhanced by 10 mM BICM. The gustatory responses of 26 of
these cells were tested with three concentrations (0.2, 2 and 10 mM) of
BICM, which produced a dose-dependent increase in both spontaneous activity
and taste-evoked responses. Nine of these neurons were sucrose- best, seven
were NaCl-best, eight were acid-best and two responded best to QHCl. The
responses to all four tastants were enhanced, with no difference among
neuron types. For 18 cells that were tested with two or more gustatory
stimuli, BICM increased their breadth of responsiveness to their two most
effective stimuli. These data show that approximately 60% of the
taste-responsive neurons in the rostral NST are inhibited by GABA and/or
subject to a tonic inhibitory influence, which is mediated by GABAA
receptors. The modulation of these cells by GABA provides a mechanism by
which the breadth of tuning of the cell can be sharpened. Modulation of
gustatory activity following a number of physiological changes could be
mediated by such a GABAergic circuit.
相似文献
108.
Molecular evolution of the Sex-Ratio inversion complex in Drosophila pseudoobscura: analysis of the Esterase-5 gene region 总被引:2,自引:0,他引:2
The Sex-Ratio chromosome in Drosophila pseudoobscura is subject to meiotic
drive. It is associated with a series of three nonoverlapping paracentric
inversions on the right arm of the X chromosome. The esterase-5 gene region
has been localized to section 23 within the subbasal inversion of the
Sex-Ratio inversion complex, making esterase- 5 a convenient locus for
molecular evolutionary analyses of the Sex- Ratio inversion complex and the
associated drive system. A 504-bp fragment of noncoding, intergenic DNA
from the esterase-5 gene region was amplified and sequenced from 14
Sex-Ratio and 14 Standard X chromosomes of D. pseudoobscura, and from 9 X
chromosomes of its two sibling species, Drosophila persimilis and
Drosophila miranda. There is extensive sequence differentiation between the
Sex-Ratio and Standard chromosomal types. The common Standard chromosome is
highly polymorphic, while, as expected from either the neutral mutation
theory or the selective sweep hypothesis, the rarer Sex-Ratio chromosome
has much less within-chromosome nucleotide polymorphism. We estimate that
the Standard and Sex-Ratio chromosomes in D. pseudoobscura diverged between
700,000 and 1.3 Mya, or at least 2 million generations ago. The clustering
of D. pseudoobscura Sex-Ratio chromosomes in a neighbor- joining phylogeny
indicates a fairly old, monophyletic origin in this species. It appears
from these data that Sex-Ratio genes were present prior to the divergence
of D. pseudoobscura and D. persimilis and that both the Standard and
Sex-Ratio chromosomes of D. persimilis were derived from the Standard
chromosome of D. pseudoobscura after the inversion events that isolated the
D. pseudoobscura Sex-Ratio chromosome.
相似文献
109.
Although it is now apparent that the intracellular pH may rise considerably above neutrality under physiological conditions, information on the effect of alkaline pH on microtubule assembly and disassembly is still quite fragmentay. We have studied the assembly/disassembly of bovine brain microtubule protein at alkaline pH in vitro. When microtubules are assembled to a new steady state at pH less than 7 and pH is then made more alkaline, they undergo a rapid disassembly to a new steady state. This disassembly is reversed by acidification. The degree of disassembly is determined largely by the pH- dependence of the critical concentration, which increases five to eight times, from pH 7 to 8. A fraction of assembly-incompetent tubulin is identified that increases with pH, but its incompetency is largely reversed with acidification. Measurements of microtubule lengths are used to indicate that disassembly occurs by uniform shortening of microtubules. A comparison of shortening by alkalinization with dilution suggests that the intrinsic rate of disassembly is accelerated by increasing pH. The capacity for initiating assembly is progressively lost with incubation at alkaline pH (although some protection is afforded by sulfhydryl-reducing agents). However, direct assembly from depolymerized mixtures is possible at least up to pH 8.3, and the steady state achieved at these alkaline pH values is stable. Such preparations are readily disassembled by cold and podophyllotoxin (PLN). Disassembly induced by PLN is also markedly enhanced at alkaline pH, suggesting a corresponding enhancement of “treadmilling.” The implications of physiological events leading to alkaline shifts of pH for microtubule assembly/disassembly are discussed, particularly in the light of recent hypotheses regarding treadmilling and its role in controlling the distribution of microtubules in vivo. 相似文献
110.
The polycistronic RNAs from both bacteriophage R17 and Qβ are translated in a mammalian cell-free system of purified and partially purified components. The requirement of one of the partially purified initiation factors (IF-E3 from rabbit reticulocytes) for the phage RNA translation is strikingly different from that for rabbit globin messenger RNA translation. The phage RNA-directed products are characterized by acrylamide gel electrophoresis and compared with those synthesized in an Escherichia coli cell-free system. There is good agreement between the respective coat proteins and the presumptive synthetase proteins. R17 RNA directs the synthesis of two additional defined polypeptides. However, their possible relationship with the A-protein cistron has not yet been investigated. The RNA from the amB2 mutant of R17, which carries an amber triplet at position 6 in the coat protein cistron, directs the synthesis of the same polypeptides as the wild-type RNA with the exception of the coat protein which is completely abolished. This identifies the product made with wild-type RNA as coat protein and provides a direct in vitro assay for the suppression of nonsense mutations in eukaryotic cells. 相似文献