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At least 757 records · Page 42Linked to original sources
PubMed2005

Induction of OGG1 gene expression by HIV-1 Tat.

To identify the cellular gene target for Tat, we performed gene expression profile analysis and found that Tat up-regulates the expression of the OGG1 (8-oxoguanine-DNA glycosylase-1) gene, which encodes an enzyme responsible for repairing the oxidatively damaged guanosine, 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG). We observed that Tat induced OGG1 gene expression by enhancing its promoter activity without changing its mRNA stability. We found that the upstream AP-4 site within the OGG1 promoter is responsible and that Tat interacted with AP-4 and removed AP-4 from the OGG1 promoter by in vivo chromatin immunoprecipitation assay. Thus, Tat appears to activate OGG1 expression by sequestrating AP-4. Interestingly, although Tat induces oxidative stress known to generate 8-oxo-dG, which causes the G:C to T:A transversion, we observed that the amount of 8-oxo-dG was reduced by Tat. When OGG1 was knocked down by small interfering RNA, Tat increased the amount of 8-oxo-dG, thus confirming the role of OGG1 in preventing the formation of 8-oxo-dG. These findings collectively indicate the possibility that Tat may play a role in maintenance of the genetic integrity of the proviral and host cellular genomes by up-regulating OGG1 as a feed-forward mechanism.

Binding Sites↗
PubMed1981

The inheritance of plasma and red blood cell magnesium and zinc levels studied from twin and family data.

The variability of magnesium and zinc concentrations in plasma and erythrocytes was investigated by twin and family studies. Twins were sampled in two distinct ways and in two different West-European regions. In one of the samples, a distinction was made between twins liver together and twins living apart. Two series of families were studied, one in a homogeneous environment, the other in a more diverse environment. Samples were compared by variance analysis. The results show 1) that genetic variability is significant for red blood cell (RBC) magnesium and zinc, minor for plasma magnesium and absent for plasma zinc; 2) that the family environment affects the extent of resemblance between twins and between siblings more for plasma levels than for RBC levels of magnesium and zinc. Furthermore, the intercorrelation analysis suggests that the genetic regulation systems of RBC magnesium and zinc are different, whereas some of the environmental regulation systems of plasma magnesium and zinc are the same. Biological interpretations are brought forward and discussed.

Adolescent↗
PubMedDate not supplied

Near-optimal region selection for feature space reduction: novel preprocessing methods for classifying MR spectra.

We introduce a global feature extraction method specifically designed to preprocess magnetic resonance spectra of biomedical origin. Such preprocessing is essential for the accurate and reliable classification of diseases or disease stages manifest in the spectra. The new method is genetic algorithm-guided. It is compared with our enhanced version of the standard forward selection algorithm. Both seek and select optimal spectral subregions. These subregions necessarily retain spectral information, thus aiding the eventual identification of the biochemistry of disease presence and progression. The power of the methods is demonstrated on two biomedical examples: the discrimination between meningioma and astrocytoma in brain tissue biopsies, and the classification of colorectal biopsies into normal and tumour classes. Both preprocessing methods lead to classification accuracies over 97% for the two examples.

Algorithms↗
PubMed1996

Tumorous calcinosis: a disease of its own?

Tumorous calcinosis has been considered as a disease of its own. A survey of the literature shows that only its clinical and radiological appearances are universally agreed upon, while its epidemiology and etiology are still under discussion. A genetic disorder, recurrent soft-tissue microtrauma and terminal renal failure have been put forward as causes. All of them may lead to a localized or generalized disturbance of the calcium-phosphate metabolism, which in turn could produce tumorous calcinosis. Therefore, tumorous calcinosis should be regarded as a rare manifestation of a metabolic disorder rather than a disease of own.

Adult↗
PubMed1981

Estimation of genetic risks of alkylating agents. VI. Exposure of mice and bacteria to methyl bromide.

Methyl bromide was studied in a forward mutation system of E. coli to evaluate the relationship between dose and mutagenic response. The compound had a high toxicity and a low mutagenic efficiency, as expected from the high s value. The mutagenic effectiveness was estimated to be 1 mutation per 10(8) surviving bacteria per mM . h, in reasonable agreement with expectation from reaction kinetic data. To study the possibilities of using hemoglobin alkylation for an estimation of DNA alkylation in vivo, mice were treated with 14C-labeled methyl bromide. The degree of alkylation of DNA, determined in liver and spleen, was considerably lower than expected (200 and 20 times, respectively) from the degree of alkylation of hemoglobin and from the relative reactivities of DNA and hemoglobin towards methyl bromide in vitro. when hemoglobin alkylation is used for quantitative risk estimations, a correction factor has to be applied by taking into account the difference between the dose in red blood cells and the dose in the compartments of DNA.

Alkylation↗
PubMed2005

Analysis of Salmonella spp. with resistance to extended-spectrum cephalosporins and fluoroquinolones isolated in North America and Latin America: report from the SENTRY Antimicrobial Surveillance Program (1997-2004).

Emerging antimicrobial-resistant Salmonella spp. requires increased efforts to appropriately test susceptibility. The SENTRY Antimicrobial Surveillance Program monitored Salmonella spp. and detected nalidixic acid-resistant strains with elevated fluoroquinolone minimum inhibitory concentration (MIC) results and strains with extended-spectrum beta-lactamase (ESBL) "phenotypes" over the last 8 years. A total of 786 stool and bloodstream isolates from North American and Latin American medical centers (2001-2003) were tested by reference broth microdilution methods. Genetic analysis was used to further characterize the resistance mechanisms. Twenty-one sites forwarded 89 (11.3%) nalidixic acid-resistant (MIC, > or =32 microg/mL) strains. Nineteen of these isolates were studied to determine mutations in the quinolone resistance-determining region (QRDR). Among the nalidixic acid-resistant Salmonella spp. isolates, fluoroquinolone MIC values were also elevated (8- to 32-fold) compared with "wild-type" strains. Ciprofloxacin and gatifloxacin (MIC(90), 0.5 microg/mL) were more potent than levofloxacin and garenoxacin (1 microg/mL) against nalidixic acid-resistant strains. Single gyrA mutations were responsible for elevated fluoroquinolone MIC values and included D87Y (5), S83F (7), D87N (5), and S83Y (2). During 2001, 9 sites contributed 11 (2.9%) strains that met ESBL screening criteria (> or =2 microg/mL) for aztreonam or ceftazidime or ceftriaxone. ESBL confirmation was evaluated by Etest (AB BIODISK, Solna, Sweden) ESBL strips and the enzymes were characterized by polymerase chain reaction and gene sequencing. The ESBL phenotype isolates had the following MIC patterns: ceftazidime (> or =16 microg/mL), aztreonam (4 to >16 microg/mL), and ceftriaxone (8-32 microg/mL). All strains were susceptible to cefepime, carbapenems, gentamicin, and fluoroquinolones. No strains were inhibited by clavulanic acid consistent with all isolates producing the identified CMY-2, AmpC-like enzyme. Fluoroquinolones may be compromised among isolates with QRDR mutations detected using nalidixic acid as a screening agent. Salmonella spp. with ESBL phenotypes were likely to harbor CMY-2 (not an ESBL) and remain susceptible to cefepime, carbapenems, and fluoroquinolones, which can be used for serious invasive Salmonella spp. infections. Compared with the stool culture isolates, the blood culture isolates had higher QRDR mutations, but remained susceptible to the fluoroquinolones. The blood culture isolates were more susceptible to penicillins (ampicillin and ticarcillin) and not significantly different for ceftriaxone or trimethoprim/sulfamethoxazole susceptibility patterns. No QRDR trends over time were detected in North America, but increased resistance was observed in Latin America.

Anti-Bacterial Agents↗
PubMed1979

An unstable allele of the am locus of Neurospora crassa.

The mutant strain am126 was isolated, using the direct selection procedure, after nitrous acid mutagenesis. It produced neither measurable NADP-dependent glutamate dehydrogenase (GDH) nor immunologically cross-reacting material. That the am126 strain produced some form of GDH product was shown by the fact that it complemented several other am mutant strains. The GDH formed by complementation between am126 and each of two other am mutants was relatively thermolabile, but could not be distinguished from wild-type GDH formed by electrophoresis in polyacrylamide gels. This, together with the relatively high yield of the complementation enzymes, suggest that the am126 product is a polypeptide chain not grossly abnormal in structure. The spontaneous revertant frequency was between 0.3 and 3 prototrophic revertants per 10(5) live cells. This frequency was at least 40 times greater than that for am19, which had the second highest spontaneous revertant frequency among the mutants tested. Neither meiosis nor mutagenesis increased the revertant frequency, nor did incubation at elevated temperatures lower it. Sixty-eight revertant strains were examined for thermostability of their GHD. All appeared to be identical to wild type. Seven of the revertant strains were also tested for instability with regard to forward mutation to am auxtrophy. None was found to be unstable. Models for the genetic instability of the am126 mutation are discussed.

Cross Reactions↗
PubMed2005

Sampling rare switching events in biochemical networks.

Bistable biochemical switches are widely found in gene regulatory networks and signal transduction pathways. Their switching dynamics are difficult to study, however, because switching events are rare, and the systems are out of equilibrium. We present a simulation method for predicting the rate and mechanism of the flipping of these switches. We apply it to a genetic switch and find that it is highly efficient. The path ensembles for the forward and reverse processes do not coincide. The method is widely applicable to rare events and nonequilibrium processes.

Bacteriophage lambda↗
PubMed1985

[Etiological evaluation of deafness in children].

In relation to cochlear implants, the authors review the various etiologies of deafness in infancy and childhood, either genetic or acquired in order to determine the criteria for advising implantation. They put forward the necessity of complete evaluation of all the auditory pathways involved to determine if a premature who has sustained hypoxicischemic encephalopathy and a full term baby have the same chance to benefit from cochlear implants after meningitis. Defined criteria are urgent needs for patients and parents.

Auditory Pathways↗
PubMed1995

[Cellular and molecular mechanisms of insulin resistance].

In the submitted review the authors give an account of contemporary knowledge regarding the mechanism of insulin action, including a brief account of pathological conditions associated with insulin resistance. The development of knowledge of problems of insulin resistance syndromes was always very dynamic, and due to the introduction of techniques of molecular biology and genetics at the turn of the eighties and nineties, a further very marked step forward was made. Despite this it will take some time before molecular mechanisms which will confirm (or rule out?) the etiopathogenetic importance of insulin resistance not only for diabetes but also for hypertension, dyslipidaemia, IHD will be revealed.

Humans↗
PubMedDate not supplied

Analysis of HLA haplotype segregation in the Schmiedeleut Hutterites of South Dakota.

HLA data from 1,085 South Dakotan Schmiedeleut Hutterites were examined for evidence of nonrandom transmission of haplotypes. The inheritance of haplotypes was viewed as a series of genetic contests between competing pairs of parental haplotypes using a maximum likelihood approach first put forward by Carlisle and Woodbury. Haplotype transmission probabilities were expressed in terms of weights, and the null hypothesis that the inheritance pattern was a random stochastic process, equivalent to the equality of the weights, was tested via the likelihood ratio. A total of 1,517 competitions was subjected to analysis, first globally using all data, and then for particular haplotypes of interest. Transmission of haplotype observed to compete with only a single other haplotype was also assessed using an exact procedure. No evidence of preferential transmission of HLA haplotypes was found. These results do not rule out transmission biases that may arise because of selection against homozygotes, mechanisms specifically affecting particular alleles or haplotypes not considered in the present study, or biases arising from maternal-fetal interactions.

Consanguinity↗
PubMed2004

[Genetics of bipolar disorder].

Bipolar disorder (BD) is a worldwide highly prevalent mental disease. This disorder has a genetic inheritance characterized by complex transmission mechanisms involving multiple genes. Many investigation strategies have been put forward in order to identify BD susceptibility genes. Linkage studies reveal markers and candidate genes for the association studies. Monoaminergic system genes and intracellular signaling pathway genes are also important candidates to be investigated in the etiology of this disorder. Recent techniques of gene expression mapping suggest novel genes whose mutations may be responsible for BD. Due to the complexity of the transmission pattern for BD and its phenotypic heterogeneity many difficulties have emerged to exactly define bipolar susceptibility genes. There is currently only preliminary results of genes associated with BD. However, the increasing understanding of gene expression regulation by epigenetic mechanisms and the dimensional approach to mental disorders can give directions for further research in psychiatric genetics.

Bipolar Disorder↗
PubMed2005

Functional ingredient production: application of global metabolic models.

The biotechnology industry continuously explores new ways to improve the performance of microbial strains in fermentation processes. Recent focus has been on new genome-wide modelling approaches in functional genomics, which aim to take full advantage of genome sequence data, transcription profiling, proteomics and metabolite profiling for strain improvement. The integration of global metabolic models with genetic and regulatory models will be essential for the practice of metabolic engineering for strain improvement to move forward, simply because we cannot rely on our intuition to grasp the complexity of the biological systems involved.

Bacterial Physiological Phenomena↗
PubMed2000

Towards a circuit engineering discipline.

Genetic circuits can now be engineered that perform moderately complicated switching functions or exhibit predictable dynamical behavior. These 'forward engineering' techniques may have to be combined with directed evolution techniques to produce robustness comparable with naturally occurring circuits.

Escherichia coli↗
PubMed2001

Genetic models of hypertension in experimental animals.

Genetic animal models are central to ongoing efforts to elucidate the pathophysiology and genetic basis of hypertension. The rat is the leading species in experimental hypertension. Several rat models of hypertension are available for research, including inbred strains, congenic lines, transgenic animals and recombinant inbred strains. Each of these models has been designed to express different phenotypes, including spontaneous hypertension, salt sensitivity, stress sensitivity and susceptibility to end-organ damage. All these models have been extremely useful in the search for the physiological mechanisms that underlie hypertension, but some of them have been specifically designed for detecting the hypertension genes. This latter task is extremely complex in spontaneous hypertension, but genetic animal models may simplify the task by enabling to focus on specific phenotypes. Despite intensive efforts over nearly 3 decades, the genetic basis of hypertension has not been unveiled so far in the rat or in other species. Recent dense mapping of the rat genome, the development of new strategies and technologies in molecular genetics including differential gene expression, expressed sequence tags and DNA biochips render hope that the formidable task of identification of new candidate genes in hypertension will move another major step forward. Once these genes are identified, their function and role in hypertension will have to be determined, utilizing functional genomic strategies and bioinformatics. Finally, the findings in genetic animal models of hypertension will have to be extrapolated to humans by homology and syntenic mapping strategies.

Animals↗
PubMed2000

[Structural organization and evolution of t-complex in Mus genus].

Modern data on the structure and evolution of the t complex are discussed. The t complex is a series of inversions in the proximal region of murine chromosome 17; it contains a set of genes that determine its predominant transmission to the offspring of heterozygous males. Variants of structural organization of this genetic system (t haplotypes) have been found in wild populations of four species of genus Mus (M. domesticus, M. musculus, M. molossinus, and M. castaneus), but not in representatives of other, evolutionarily remote species of this genus. The so-called vertical, horizontal, and introgressive hypotheses are discussed of the origin and evolution of the t complex. Based on population genetic studies and molecular analysis a new hypothesis on the origin of the t-complex is put forward. This hypothesis is a synthesis between the vertical and horizontal models and assumes that all known t haplotypes had a common ancestral chromosome 17 carrying a proximal inversion.

Animals↗
PubMed1993

Comparison of the spectra of genetic damage in N4-hydroxycytidine-induced ad-3 mutations between nucleotide excision repair-proficient and -deficient heterokaryons of Neurospora crassa.

A comparison has been made of the mutagenic effects of N4-hydroxycytidine (HC) in the adenine-3 (ad-3) region of two-component heterokaryons of Neurospora crassa: nucleotide excision repair-proficient (uvs-2+/uvs-2+) heterokaryon 12 (H-12) and nucleotide excision repair-deficient (uvs-2/uvs-2) heterokaryon 59 (H-59). HC was found to produce mutations predominantly, if not exclusively, by AT to GC base-pair transitions in Escherichia coli strain K12 by Janion and Glickman (1980, Mutation Res., 72, 43-47) and Sledziewska-Gojska et al. (1992, Mutagenesis, 7, 41-46). The ad-3 forward-mutation, specific-locus assay system permits the recovery of ad-3A and/or ad-3B mutants resulting from gene/point mutation, multiple-locus mutation, and multilocus deletion mutation. Uvs-2, which is homokaryotic in H-59, results in a recovery of HC-induced ad-3 forward mutations at a frequency in H-59 that is comparable to that found in H-12. Genetic analysis of ad-3 mutants recovered from experiments with HC treatment demonstrates that predominantly gene/point mutations were found in both strains: 99.3% (540/544) in H-12, and 97.4% (531/545) in H-59. Genetic analysis of allelic complementation among the ad-3BR mutations demonstrated that HC induced the highest percentage of complementing mutants ever found with base analogs both in H-12 (99.7% [328/329]) and H-59 (91.2% [290/318]). As a result of these findings, the majority of HC-induced ad-3 mutations are postulated to have resulted from missense mutations. Thus, we conclude that the results in Neurospora are consistent with the observations in E. coli strain K-12, where HC induces predominantly AT to GC base-pair transitions.

Adenine↗
PubMed2004

In utero gene therapy: prospect and future.

Many genetic disorders are reported to cause irreversible damage to the fetus before birth. In utero gene therapy may be an effective tool for correction of genetic disorders by replacing defective gene with normal one. There are many reasons for moving forward with in utero gene therapy. The most important reason is to provide early intervention as to prevent or slow dysfunction and morbidity. This approach may prove to be advantageous in rapidly replicating fetal cells, and less sensitive to immune response to vector or transgene product due to underdeveloped immune system. In addition, the developing fetus may be a better candidate for gene therapy than the adult because gene engraftment may be more feasible in early fetal life, where stem cells or pleuripotent progenitor cells are more accessible to vectors. Some reports are available on successful in utero gene transfer in animal models but many questions remain to be answered before in utero gene therapy can be considered a viable solution to human. The real moral challenge facing in utero gene therapy is finding ways to insure that the review of protocols is adequate, and that those undertaking trials are competent to do so. Present review article analyzes the overall progress of the field, and the research that still needs to be performed before it can be considered to human clinical trials.

Animals↗