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Ekaterina Maidji Galina Kosikova Pheroze Joshi Cheryl A. Stoddart 《Journal of virology》2012,86(23):12795-12805
Human cytomegalovirus (HCMV) is the leading viral cause of birth defects and life-threatening lung-associated diseases in premature infants and immunocompromised children. Although the fetal lung is a major target organ of the virus, HCMV lung pathogenesis has remained unexplored, possibly as a result of extreme host range restriction. To overcome this hurdle, we generated a SCID-hu lung mouse model that closely recapitulates the discrete stages of human lung development in utero. Human fetal lung tissue was implanted into severe combined immunodeficient (CB17-scid) mice and inoculated by direct injection with the VR1814 clinical isolate of HCMV. Virus replication in the fetal lung was assessed by the quantification of infectious virus titers and HCMV genome copies and the detection of HCMV proteins by immunohistochemistry and Western blotting. We show that HCMV efficiently replicated in the lung implants during a 2-week period, forming large viral lesions. The virus productively infected alveolar epithelial and mesenchymal cells, imitating congenital infection of the fetal lung. HCMV replication triggered apoptosis near and within the viral lesions and impaired the production of surfactant proteins in the alveolar epithelium. Our findings highlight that congenital and neonatal HCMV infection can adversely impact lung development, leading to pneumonia and acute lung injury. We have successfully developed a small-animal model that closely recapitulates fetal and neonatal lung development and provides a valuable, biologically relevant tool for an understanding of the lung pathogenesis of HCMV as well as other human respiratory viruses. Additionally, this model would greatly facilitate the development and testing of new antiviral therapies for HCMV along with select human pulmonary pathogens. 相似文献
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The mechanism of the vanadate (V(v))-dependent oxidation of NADH was different in phosphate buffers and in phosphate-free media. In phosphate-free media (aqueous medium or HEPES buffer) the vanadyl (V(v)) generated by the direct V(v)-dependent oxidation of NADH formed a complex with V(v). In phosphate buffers V(v) autoxidized instead of forming a complex with V(v). The generated superoxide radical (O2−) initiated, in turn, a high-rate free radical chain oxidation of NADH. Phosphate did not stimulate the V(v)-dependent NADH oxidation catalyzed by O2−-generating systems. Monovanadate proved to be a stronger catalyzer of NADH oxidation as compared to polyvanadate. 相似文献
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Membrane preparations, capable of high rates of respiration-linked ATP synthesis, have been obtained from a gram-positive methylotrophic bacterium Bacillus sp. MGA3. NADH, succinate, reduced TMPD and methanol were shown to be suitable substrates for the oxidative phosphorylation. Esterification of orthophosphate was dependent on electron transfer, as evidenced by the requirement for both substrate and oxygen. Phosphorylation was also dependent on ADP and was destroyed by boiling the membrane preparation. The phosphorylation was markedly uncoupled by carbonyl cyanide p-(trichloromethoxy)-phenylhydrazone (CCCP) and was inhibited by N,N-dicyclohexylcarbodiimide (DCCD). KCN caused strong inhibition of substrate oxidation as well as phosphorylation for all substrates tested. Rotenone, amytal and antimycin A caused inhibition when NADH or methanol were used as substrates. Antimycin A inhibited respiration and ATP synthesis with succinate as substrate and had no effect on ascorbate —N,N,N,N-tetramethyl-p-phenylenediimide (TMPD) oxidation by membrane preparations of Bacillus sp. MGA3. P/O ratios determined were 2.4 with NADH, 1.7 with succinate and 0.8 with reduced TMPD. The measured P/O ratio with methanol-oxidizing system was similar to that with NADH (about 2.4).Abbreviations CCCP
Carbonyl cyanide p-(trichloromethoxy)-phenylhydrazone
- DCCD
N,N-dicyclohexylcarbodiimide
- TMPD
N,N,N,N-tetramethyl-p-phenylenediimide
- Q
ubiquinone Q 相似文献
5.
Vanadyl caused a time- and dose-dependent degradation of deoxyribose to carbonyl products detectable with thiobarbituric acid. This process was inhibited by catalase, ethanol or HEPES; whereas superoxide dismutase was without effect. Vanadate did not substitute for vanadyl even in the presence of a source of O2- plus H2 O 2; but it did so in the presence of reductants such as thiols or NADH. It appears that hydrogen peroxide, generated by the autoxidation of vanadyl, is reduced by vanadyl to the hydroxyl radical; which, in turn, was responsible for the degradation of deoxyribose. A similar process might contribute to the toxic and pharmacological effects of vanadium salts. 相似文献
6.
Chromosome polymorphism in populations of the grasshopper Trimerotropis pallidipennis from southern Argentina 总被引:1,自引:0,他引:1
Three populations of the grasshopper Trimerotropis pallidipennis from southern Argentina have been studied cytologically. A very characteristic B-chromosome was found in all three. They also showed geographical variability in respect of the presence of pericentric inversions, and the inversion system was found to influence chiasma frequency. The Laguna Blanca population, which is on the hypothetical pathway the species is believed to have followed during its migration from northern to southern latitudes, has the same karyotype composition as the N. American form, with fixed inversions in the 3 largest autosomes and the X-chromosome. Its members have a high total chiasma frequency and a great number of interstitial chiasmata. The Sierra de la Ventana population, situated at the absolute eastern border of the species distribution is highly polymorphic with respect to the presence of inversions in the medium chromosomes. Its members have the lowest total chiasma frequency and a greatly reduced number of interstitial chiasmata. Situated geographically between the other two, the Choele-Choel population has the highest frequency of inversions and many of them are homozygous. Its members have a higher total chiasma frequency than that observed in specimens from Sierra de la Ventana, and a greatly reduced number of interstitial chiasmata, similar to that observed in individuals from the latter population. 相似文献
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I.A. Manuilova L.E. Murashko N.D. Fanchenko V.G. Kolodjko E.A. Chernukha S.A. Rahman M. Bygdeman S.Z. Cekan E. Diczfalusy 《Prostaglandins & other lipid mediators》1979,17(2):313-322
Ten pregnant women (7th–8th week of pregnancy) obtained an intravenous infusion of 15-methyl-prostaglandin-F2α (2.5 μg/min) until clinical signs of abortion occurred or up to 7 hours. Surgical removal of the products of conception was performed 4–7 hours after the start of the infusion. Blood samples were taken prior to and during the infusion and then during the post-abortion period. The plasma levels of both progesterone and estradiol exhibited a significant decrease (p<0.001 and p<0.05, respectively) one hour after the beginning of infusion and remained reduced by approximately 35 and 45 per cent, respectively, during the entire infusion period. A drop in the levels of both steroids was seen after surgical interruption. This was followed by a gradual decrease to non-pregnancy levels. The levels of cortisol increased significantly (p<0.01) by approximately 60 per cent, starting with the second hour of infusion. Following surgical interruption, the levels dropped to pre-infusion values. 17-Hydroxyprogesterone levels increased (p<0.05) above the pretreatment levels by approximately 25 per cent, starting with the third hour of infusion. These levels were not correlated with those of cortisol during the infusion period. Following surgical interruption the plasma levels of 17-hydroxyprogesterone returned to non-pregnancy levels. 相似文献
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Syatkin Sergey P. Neborak Ekaterina V. Khlebnikov Andrei I. Komarova Marina V. Shevkun Natalia A. Kravtsov Eduard G. Blagonravov Mikhail L. Agostinelli Enzo 《Amino acids》2020,52(2):199-211
Amino Acids - The polyamine (PA) metabolism is involved in cell proliferation and differentiation. Increased cellular PA levels are observed in different types of cancers. Products of PA oxidation... 相似文献