Photoinduced reduction of thymine glycol in oligodeoxynucleotides was investigated using either a reduced form of flavin adenine dinucleotide (FADH(-)) as an intermolecular electron donor or covalently linked phenothiazine (PTZ) as an intramolecular electron donor. Intermolecular electron donation from photoexcited flavin (FADH(-)) to free thymidine glycol generated thymidine in high yield, along with a small amount of 6-hydroxy-5,6-dihydrothymidine. In the case of photoreduction of 4-mer long single-stranded oligodeoxynucleotides containing thymine glycol by *FADH(-), the restoration yield of thymine was varied depending on the sequence of oligodeoxynucleotides. Time-resolved spectroscopic study on the photoreduction by laser-excited N,N-dimethylaniline (DMA) suggested elimination of a hydroxyl ion from the radical anion of thymidine glycol with a rate constant of approximately 10(4) s(-1) generates 6-hydroxy-5,6-dihydrothymidine (6-HOT(*)) as a key intermediate, followed by further reduction of 6-HOT(*) to thymidine or 6-hydroxy-5,6-dihydrothymdine (6-HOT). On the other hand, an excess electron injected into double-stranded DNA containing thymine glycol was not trapped at the lesion but was further transported along the duplex. Considering redox properties of the nucleobases and PTZ, competitive excess electron trapping at pyrimidine bases (thymine, T and cytosine, C) which leads to protonation of the radical anion (T(-)(*), C(-)(*)) or rapid back electron transfer to the radical cation of PTZ (PTZ(+)(*)), is presumably faster than elimination of the hydroxyl ion from the radical anion of thymine glycol in DNA.
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Blood eosinophil count is a useful measure in asthma or COPD management. Recent epidemiological studies revealed that body mass index (BMI) is positively associated with eosinophil counts. However, few studies focused on the role of adiposity and fatty acid-related metabolites on eosinophil counts, including the effect of genetic polymorphism. In this community-based study involving 8265 participants (30–74 year old) from Nagahama city, we investigated the relationship between eosinophil counts and serum levels of fatty acid-related metabolites. The role of MDC1, a gene that is related to eosinophil counts in our previous study and encodes a protein that is thought to be involved in the repair of deoxyribonucleic acid damage, was also examined taking into account its interaction with adiposity. Serum levels of linoleic acid (LA) and β-hydroxybutyric acid (BHB) were negatively associated with eosinophil counts after adjustment with various confounders; however, there were positive interactions between serum LA and BMI and between serum BHB and BMI/body fat percentages in terms of eosinophil counts. In never-smokers, there was positive interaction for eosinophil counts between the CC genotype of MDC1 rs4713354 and BMI/body fat percentages. In conclusion, both serum LA and BHB have negative impacts on eosinophil counts, while adiposity shows robust positive effects on eosinophil counts, partly via genetic background in never-smokers.
The main focus of this study is the optimal administration period concerning toxic effects on male fertility in rats. To assess functional and morphological changes induced in the testis by nitrazepam, male rats were administered the drug at doses of 0, 20, 40 or 80 mg/kg during pre-mating periods of 2, 4 or 9 weeks and then the 2 weeks of mating. At the end of the administration period the animals were sacrificed and sperm number, motility, abnormalities and histopathological changes in the testis were examined. Decreases in testis weight, epididymis weight, number of sperm in the testis and sperm motility were observed in the 40 and 80 mg/kg sections of the 2, 4 and 9 week pre-mating treated groups. Mating with untreated females revealed no adverse effects on copulation rate in any group; however, a remarkable decrease in pregnancy rate was noted in the 80 mg/kg section of the 2, 4 and 9 week treated groups. On histological examination, various degrees of localized necrosis in the seminiferous epithelium and Leydig cell hyperplasia were observed in the testis. No clear changes were observed in the 20 mg/kg section of the 2 week pre-mating administration group, but at the 4 week time point, necrosis of spermatogenic cells began to appear. The primary morphological event was evident in spermatocytes with necrosis of the cytoplasm observed from 4 weeks after administration of nitrazepam, although sperm motility and sperm head counts were unaffected. From these findings, examination of sperm characteristics and histopathological changes in the testis are important parameters for evaluation of drugs inducing testicular damage. We conclude that a 4 week administration period is sufficient to detect effects of nitrazepam on male fertility.
Background Botrytis species are well known fungal pathogens of various plants but have not been reported as human pathogens, except as allergenic precipitants of asthma and hypersensitivity pneumonitis. Case presentation The asymptomatic patient was referred because of a nodule revealed by chest X-ray. Computed tomography (CT) showed a cavitary nodule in the right upper lobe of the lung. He underwent wedge resection of the nodule, which revealed necrotizing granulomas and a fungus ball containing Y-shaped filamentous fungi, which was confirmed histopathologically. Culture of the specimen yielded white to grayish cotton-like colonies with black sclerotia. We performed multilocus gene sequence analyses including three single-copy nuclear DNA genes encoding glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and DNA-dependent RNA polymerase subunit II. The analyses revealed that the isolate was most similar to Botrytis elliptica . To date, the pulmonary Botrytis sp. infection has not recurred after lung resection and the patient did not require any additional medication. Conclusions We report the first case of an immunocompetent patient with pulmonary Botrytis sp. infection, which has not recurred after lung resection without any additional medication. Precise evaluation is necessary for the diagnosis of pulmonary Botrytis infection because it is indistinguishable from other filamentous fungi both radiologically and by histopathology. The etiology and pathophysiology of pulmonary Botrytis infection remains unclear. Further accumulation and analysis of Botrytis cases is warranted. Electronic supplementary material The online version of this article (10.1186/s12879-019-4319-2) contains supplementary material, which is available to authorized users.
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