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91.
Stationary-phase mutagenesis in nondividingE. coli cells exposed to a nonlethal stress was, a few years ago, claimed to be a likely case of a Lamarckian mechanism capable of
producing exclusively useful mutations in a directed manner. After a heated debate over the last decade it now appears to
involve a Darwinian mechanism that generates a transient state of hypermutagenesis, operating on a large number of sites spread
over the entire genome, at least in a proportion of the resting cells. Most of the studies that clarified this position were
on the reversion of a frameshift mutation present in alacI-lacZ fusion inE. coli strain FC40. Several groups have extensively examined both the sequence changes associated with these reversions and the
underlying genetic requirements. On the basis of our studies on the genomic sequence analysis, we recently proposed a model
to explain the specific changes associated with the reversion hotspots. Here we propose a more detailed version of this model
that also takes into account the observed genetic requirements of stationary-state mutagenesis. Briefly, G:T/U mismatches
produced at methylatable cytosines are preferentially repaired in nondividing cells by the very short patch mismatch repair
(VSPMR) mechanism which is itself mutagenic and can produce mutations in very short stretches located in the immediate vicinity
of these cytosine methylation sites. This mechanism requires a homologous or homeologous strand invasion step and an error-prone
DNA synthesis step and is dependent on RecA, RecBCD and a DNA polymerase. The process is initiated near sequences recognized
by Dcm and Vsr enzymes and further stimulated if these sequences are a part of CHI or CHI-like sequences, but a double-strand-break-dependent
recombination mediated by the RecBCD pathways proposed by others seems to be nonessential. The strand transfer step is proposed
to depend on RecA, RuvA, RuvB and RuvC and is opposed by RecG and MutS. The model also gives interesting insights into the
evolution of theE. coli genome. 相似文献
92.
Brett A. Shook Jessica B. Lennington Rebecca L. Acabchuk Meredith Halling Ye Sun John Peters Qian Wu Amit Mahajan Douglas W. Fellows Joanne C. Conover 《Aging cell》2014,13(2):340-350
Age‐associated ventriculomegaly is typically attributed to neurodegeneration; however, additional factors might initiate or contribute to progressive ventricular expansion. By directly linking postmortem human MRI sequences with histological features of periventricular tissue, we show that substantial lateral ventricle surface gliosis is associated with ventriculomegaly. To examine whether loss of ependymal cell coverage resulting in ventricle surface glial scarring can lead directly to ventricle enlargement independent of any other injury or degenerative loss, we modeled in mice the glial scarring found along the lateral ventricle surface in aged humans. Neuraminidase, which cleaves glycosidic linkages of apical adherens junction proteins, was administered intracerebroventricularly to denude areas of ependymal cells. Substantial ependymal cell loss resulted in reactive gliosis rather than stem cell‐mediated regenerative repair of the ventricle lining, and the gliotic regions showed morphologic and phenotypic characteristics similar to those found in aged humans. Increased levels of aquaporin‐4, indicative of edema, observed in regions of periventricular gliosis in human tissue were also replicated in our mouse model. 3D modeling together with volume measurements revealed that mice with ventricle surface scarring developed expanded ventricles, independent of neurodegeneration. Through a comprehensive, comparative analysis of the lateral ventricles and associated periventricular tissue in aged humans and mouse, followed by modeling of surface gliosis in mice, we have demonstrated a direct link between lateral ventricle surface gliosis and ventricle enlargement. These studies highlight the importance of maintaining an intact ependymal cell lining throughout aging. 相似文献
93.
94.
The binding of cyclosporin A and ovine prolactin to rabbit mammary gland membranes was determined. CsA bound with a Kd of 2.2 X 10(-6)M whereas prolactin bound with a Kd of 2 X 10(-10)M. The binding of each ligand was an independent event and neither ligand influenced the binding of the other ligand showing that CsA does not inhibit the binding of prolactin to its specific receptor in this system. 相似文献
95.
96.
Roles of the sequence encoding tobacco etch virus capsid protein in genome amplification: requirements for the translation process and a cis-active element. 总被引:6,自引:2,他引:4
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The roles of the capsid protein (CP) and the CP coding sequence of tobacco etch potyvirus (TEV) in genome amplification were analyzed. A series of frameshift-stop codon mutations that interrupted translation of the CP coding sequence at various positions were introduced into the TEV genome. A series of 3' deletion mutants that lacked the CP coding sequence beyond each of the frameshift-stop codon mutations were also produced. In addition, a series of 5' CP deletion mutants were generated. Amplification of genomes containing either frameshift-stop codon insertions after codons 1, 59, 103, and 138 or genomes containing the corresponding 3' deletions of the CP coding sequence was reduced by 100- to 1,000-fold relative to that of the parental genome in inoculated protoplasts. In contrast, a mutant containing a frameshift-stop codon after CP position 189 was amplified to 27% of the level of the parental virus, but the corresponding 3' deletion mutant lacking codons 190 to 261 was nonviable. Deletion mutants lacking CP codons 2 to 100, 2 to 150, 2 to 189, and 2 to 210 were amplified relatively efficiently in protoplasts, but a deletion mutant lacking codons 2 to 230 was nonviable. None of the amplification-defective frameshift-stop codon or deletion mutants was rescued in transgenic cells expressing TEV CP, although the transgenic CP was able to rescue intercellular movement defects of replication-competent CP mutants. Coupled with previous results, these data led to the conclusions that (i) TEV genome amplification requires translation to a position between CP codons 138 and 189 but does not require the CP product and (ii) the TEV CP coding sequence contains a cis-active RNA element between codons 211 and 246. The implications of these findings on mechanisms of RNA replication and genome evolution are discussed. 相似文献
97.
A recently silenced, duplicate PgiC locus in Clarkia 总被引:1,自引:0,他引:1
Previous electrophoretic analysis showed that 17 diploid species of the
wildflower Clarkia (Onagraceae) have two cytosolic isozymes of
phosphoglucose isomerase (PGIC; EC 5.3.1.9), whereas 15 other diploid
species have a single PGIC. Molecular studies revealed that the two
isozymes in the former species are encoded by duplicate genes, PgiC1 and
PgiC2, whereas the single isozyme in the latter is always encoded by PgiC1.
Phylogenetic analysis of the nucleotide sequences implied that PgiC2 was
silenced four times independently in the genus. Here we describe a psi
PgiC2 from C. mildrediae, a species in which only PgiC1 is expressed. The
discovery of the psi PgiC2 is significant because it confirms a formal
prediction of the phylogenetic analysis. The psi PgiC2 includes 5,039
nucleotides corresponding to 18 of the 23 exons of PgiC, as well as the
intervening introns and 3' nontranslated region. The absence of an increase
of nucleotide substitutions in its "exons" suggests that the gene was
silenced recently. The present study appears to be the first to establish
that a specific duplicate gene locus regularly expressed in a group of
related plant species has been silenced in one of them. The multiple
independent silencings of PgiC2 suggest that it remained functional but
inessential in ancestral lineages. We discuss the possibility that PgiC2
may have been preserved in these lineages by selection against mutants
causing defective PGIC1- PGIC2 heterodimers.
相似文献
98.
Hieng Chiong Tie Divyanshu Mahajan Bing Chen Li Cheng Antonius M. J. VanDongen Lei Lu 《Molecular biology of the cell》2016,27(5):848-861
Cellular functions of the Golgi are determined by the unique distribution of its resident proteins. Currently, electron microscopy is required for the localization of a Golgi protein at the sub-Golgi level. We developed a quantitative sub-Golgi localization method based on centers of fluorescence masses of nocodazole-induced Golgi ministacks under conventional optical microscopy. Our method is rapid, convenient, and quantitative, and it yields a practical localization resolution of ∼30 nm. The method was validated by the previous electron microscopy data. We quantitatively studied the intra-Golgi trafficking of synchronized secretory membrane cargoes and directly demonstrated the cisternal progression of cargoes from the cis- to the trans-Golgi. Our data suggest that the constitutive efflux of secretory cargoes could be restricted at the Golgi stack, and the entry of the trans-Golgi network in secretory pathway could be signal dependent. 相似文献
99.
In 1949, Fowler (J. Appl. Physiol. 2: 283-299) advocated calculation of a "dilution index" from data of the alveolar plateau of single-breath tests; the calculation provides an estimate of the dilution of resident gas in the lung that gave rise to the observed concentrations. In this communication, we show that the calculation can be applied to conventional single-breath tests where O2 is inhaled by air-breathing persons, and we illustrate the principle with vital capacity breaths of a mixture that contained a low concentration of neon. The dilution was approximately 3:1 in young subjects (20-30 yr), as if a vital capacity of 6 liters were mixed with a residual volume of 2 liters. The dilution was less, 2:1, in older subjects (56 yr) and tended to become as low as 1:1 during emptying of the closing volume. In addition to being more informative, the dilution index format allows common sense comparison of alveolar plateau levels and slopes when single-breath tests are done by various methods. 相似文献
100.
Seven strains of Mycoplasma mycoides subsp. mycoides (LC, Y-Goat) were isolated from 4 of 85 (4.7%) cases of bovine abortion. The biochemical characters of all the isolates were homogenous (except for one sucrose negative isolate), but variation in sensitivity to neomycin, kanamycin and streptomycin were noted. The only gross lesions of internal organs in aborted fetuses were congestion of liver and lungs, and hemorrhagic patches on the heart surface. Significant microscopic lesions were encountered in lungs (edema of the interlobular septae, thickened alveolar wall, lymphocytic infiltration, septal hyperplasia and alveolar infiltration with neutrophils and macrophages), liver (mild lymphocytic infiltration in the hepatic triad, hypertrophy of Von-kupffer cells), kidney (degenerative necrosis and desquamation of tubular epithelium, and the marked lymphocytic infiltration in the interstitium), spleen (depleted lymphoid tissues, infiltration of lymphocytes, macrophage and plasma cells in the red pulp) and heart (lymphocytic myocarditis). The observations of this study focus on the role of M. mycoides subsp. mycoides (LC variant) in bovine abortions. 相似文献