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1.
  总被引:8,自引:0,他引:8  
Acrylamide, an animal carcinogen and germ cell mutagen present at low (ppm) levels in heated carbohydrate-containing foodstuffs, is oxidized by cytochrome P4502E1 (CYP2E1) to the epoxide glycidamide, which is believed to be responsible for the mutagenic and carcinogenic activity of acrylamide. We recently reported a comparison of the effects of acrylamide on the genetic integrity of germ cells of male wild-type and CYP2E1-null mice [B.I. Ghanayem, K.L. Witt, L. El-Hadri, U. Hoffler, G.E. Kissling, M.D. Shelby, J.B. Bishop, Comparison of germ-cell mutagenicity in male CYP2E1-null and wild-type mice treated with acrylamide: evidence supporting a glycidamide-mediated effect, Biol. Reprod. 72 (2005) 157-163]. In those experiments, dose-related increases in dominant lethal mutations were detected in uterine contents of female mice mated to acrylamide-treated wild-type males but not CYP2E1-null males, clearly implicating CYP2E1-mediated formation of glycidamide in the induction of genetic damage in male germ cells. We hypothesized that acrylamide-induced somatic cell damage is also caused by glycidamide. Therefore, to examine this hypothesis, female wild-type and CYP2E1-null mice were administered acrylamide (0, 25, 50mg/kg) by intraperitoneal injection once daily for 5 consecutive days. Twenty-four hours after the final treatment, blood and tissue samples were collected. Erythrocyte micronucleus frequencies were determined using flow cytometry and DNA damage was assessed in leukocytes, liver, and lung using the alkaline (pH>13) single cell gel electrophoresis (Comet) assay. Results were consistent with the earlier observations in male germ cells: significant dose-related increases in micronucleated erythrocytes and DNA damage in somatic cells were induced in acrylamide-treated wild-type but not in the CYP2E1-null mice. These results support the hypothesis that genetic damage in somatic and germ cells of mice-treated with acrylamide is dependent upon metabolism of the parent compound by CYP2E1. This dependency on metabolism has implications for the assessment of human risks resulting from occupational or dietary exposure to acrylamide. CYP2E1 polymorphisms and variability in CYP2E1 activity associated with, for example, diabetes, obesity, starvation, and alcohol consumption, may result in altered metabolic efficiencies leading to differential susceptibilities to acrylamide toxicities in humans.  相似文献   
2.
The development of nasal tumors in humans and rodents is likely mediated through the accumulation of genetic alterations in genes that regulate cell proliferation, cell death and differentiation (oncogenes and tumor suppressor genes). By examination of the relationship between genetic alterations that are known to occur in human cancers with those induced in rodent tumors with defined carcinogenic exposures, biologically relevant mechanistic linkages of molecular events leading to tumors in rodents and humans can be established. Molecular genetic studies on nasal squamous cell carcinomas (SCC) in rats thus far have indicated the presence of oncogenes unrelated to the ras oncogene family and that p53 mutation occurs at a high frequency among the nasal SCC examined. The finding of p53 mutations in rat nasal SCC and the high prevalence of p53 mutations among human SCC, indicates that a common molecular alteration is shared between rodent and human SCC.  相似文献   
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Background  

The Beijing lineage of Mycobacterium tuberculosis is causing concern due to its global distribution and its involvement in severe outbreaks. Studies focused on this lineage are mainly restricted to geographical settings where its prevalence is high, whereas those in other areas are scarce. In this study, we analyze Beijing isolates in the Mediterranean area, where this lineage is not prevalent and is mainly associated with immigrant cases.  相似文献   
5.
Poaceae pollen is one of the most prevalent aeroallergens causing allergenic reactions. The aim of this study was to characterise the grass pollen season in Tetouan during the years 2008–2010, to analyse the effect of some meteorological parameters on the incidence of the airborne Poaceae pollen, and to establish forecasting variables for daily pollen concentrations. Aerobiological sampling was undertaken over three seasons using the volumetric method. The pollen season started in April and showed the highest pollen index in May and June, when the maximum temperature ranged from 23 to 27 °C, respectively. The annual pollen score recorded varied from year to year between 2,588 and 5,404. The main pollen season lasted 114–173 days, with peak days occurring mainly in May; the highest concentration reached 308 pollen grains/m3. Air temperature was the most important meteorological parameter and correlated positively to daily pollen concentration increase. An increase in relative humidity and precipitation was usually related to a decrease in airborne pollen content. External validation of the models performed using data from 2011 showed that Poaceae pollen concentration can be highly predicted (64.2–78.6 %) from the maximum temperature, its mean concentration for the same day in other years, and its concentration recorded on the previous day. Sensitive patients suffering allergy to Poaceae pollen are at moderate to highest risk of manifesting allergic symptoms to grass pollen over 33–42 days. The results obtained provide new information on the quantitative contribution of the Poaceae pollen to the airborne pollen of Tetouan and on its temporal distribution. Airborne pollen can be surveyed and forecast in order to warn the atopic population.  相似文献   
6.
Marmosets (genus Callithrix) are a diverse group of platyrrhine primates with 13-15 purported taxa, many of them considered endangered. Morphological analyses constitute most of the basis for recognition of these forms as distinct taxa. The purpose of this study was to provide a molecular view, based on mitochondrial control region sequences, of the evolutionary history of the marmosets, concomitant with a molecular phylogenetic perspective on species diversity within the group. An additional purpose was to provide the first comparative examination of a complete New World monkey control region sequence with those of other mammals. The phylogenetic analyses provide convincing support for a split between the Atlantic forest and Amazonian marmosets, with the inclusion of the pygmy marmoset (Cebuella pygmaea) at the base of the Amazonian clade. The earliest branch of the Atlantic forest group was C. aurita. In the Amazonian group, the analyses do not support the recognition of C. humeralifer and the recently described C mauesi as distinct taxa. They do, however, support a clear distinction between C. argentata and a strongly supported mixed clade of C. humeralifer and C. mauesi. In the Atlantic forest group, the phylogenetic tree suggests mixing between C. penicillata, C. kuhli, and possibly C. jacchus. Most of the sequence features characteristic of other mammal control regions were also evident in marmosets, with the exception that conserved sequence blocks (CSBs) 2 and 3 were not clearly identifiable. Tandem repeat units often associated with heteroplasmy in a variety of other mammals were not evident in the marmoset sequences.   相似文献   
7.
The first two genes of the threonine pathway, ask and asd, were cloned and sequenced from the aminoethoxyvinylglycine-producing Streptomyces sp. NRRL 5331. The two genes are organized in a bicistronic operon. ask, encoding the apartokinase (ASK), is located upstream from asd. The presence of a ribosome-binding site within the ask sequence suggests that this open reading frame encodes two overlapping proteins. The formation of both subunits of the aspartokinase from a single gene was studied using antibodies raised against the C-terminal end of the aspartokinase subunits. Disruption of asd results in a significant decrease of aminoethoxyvinylglycine production, thus supporting the involvement of the ask–asd operon in the biosynthesis of this metabolite. This is the first report in which a gene cluster for the first two steps of aminoethoxyvinylglycine biosynthesis is characterized.Abbreviations ASD Aspartate semialdehyde dehydrogenase - ASK Aspartokinase - AVG Aminoethoxyvinylglycine  相似文献   
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The in vivo [1-14C]acetate incorporation into free and esterified cholesterol in rat ventral prostate depends on the animal developmental process, and it is the highest in the puberty stage. The relationship between free cholesterol and total lipids is 12-14% and that between esterified cholesterol and total lipids is 4-5%, both of the two being maintained during the animal development. The [1-14C]-acetate incorporation into free and esterified cholesterol in castrated animals decreases as compared with that in normal rats and it does not depend on the age of the animal.  相似文献   
10.
    
Mutations at protein–protein recognition sites alter binding strength by altering the chemical nature of the interacting surfaces. We present a simple surface energy model, parameterized with empirical values, yielding mean energies of ?48 cal mol?1 Å?2 for interactions between hydrophobic surfaces, ?51 to ?80 cal mol?1 Å?2 for surfaces of complementary charge, and 66–83 cal mol?1 Å?2 for electrostatically repelling surfaces, relative to the aqueous phase. This places the mean energy of hydrophobic surface burial at ?24 cal mol?1 Å?2. Despite neglecting configurational entropy and intramolecular changes, the model correlates with empirical binding free energies of a functionally diverse set of rigid‐body interactions (r = 0.66). When used to rerank docking poses, it can place near‐native solutions in the top 10 for 37% of the complexes evaluated, and 82% in the top 100. The method shows that hydrophobic burial is the driving force for protein association, accounting for 50–95% of the cohesive energy. The model is available open‐source from http://life.bsc.es/pid/web/surface_energy/ and via the CCharpPPI web server http://life.bsc.es/pid/ccharppi/ . Proteins 2015; 83:640–650. © 2015 Wiley Periodicals, Inc.  相似文献   
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