p53-Dependent suppression of genome instability in germ cells.

Radiation increases mutation frequencies at tandem repeat loci. Germline mutations in γ-ray-irradiated medaka fish (Oryzias latipes) were studied, focusing on the microsatellite loci. Mismatch-repair genes suppress microsatellite mutation by directly removing altered sequences at the nucleotide level, whereas the p53 gene suppresses genetic alterations by eliminating damaged cells. The contribution of these two defense mechanisms to radiation-induced microsatellite instability was addressed. The spontaneous mutation frequency was significantly higher in msh2(-/-) males than in wild-type fish, whereas there was no difference in the frequency of radiation-induced mutations between msh2(-/-) and wild-type fish. By contrast, irradiated p53(-/-) fish exhibited markedly increased mutation frequencies, whereas their spontaneous mutation frequency was the same as that of wild-type fish. In the spermatogonia of the testis, radiation induced a high level of apoptosis both in wild-type and msh2(-/-) fish, but negligible levels in p53(-/-) fish. The results demonstrate that the msh2 and p53 genes protect genome integrity against spontaneous and radiation-induced mutation by two different pathways: direct removal of mismatches and elimination of damaged cells.

Heat stress impact on the expression patterns of different reproduction related genes in Malabari goats.

A study was conducted to evaluate the effect of heat stress on the expression pattern of reproduction related genes in Malabari breed of goat. The study was conducted during 45 days using twelve 10 months to one year old Malabari goats. The goats were randomly allocated into two groups: MC (n = 6; Malabari control) and MHS (n = 6; Malabari heat stress). Goats were stall-fed with a diet composed of 60% roughage and 40% concentrate. All animals had access to ad-libitum feed and water and they were fed and watered individually. The MC goats were placed in the shaded pens while MHS goats were exposed to heat stress in outside environment between 10.00 h and 16.00 h. At the end of study period, all 12 animals were slaughtered and their uterus tissues were collected for gene expression and histopathological studies. The temperature humidity index (THI) inside shed (74.9) proved that the animals were not stressed while in the outside environment (86.5) the animals were extremely distressed. Heat stress significantly (P < 0.05) influenced the expression patterns of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR), estrogen receptor α (ESTRα), prostaglandin F2 α (PGF2α) and cyclooxygenase-2 (COX-2). However, prostaglandin E2 (PGE2) did not differed between the groups. Further, a strong positive correlation (P < 0.01) was established for THI with both FSHR gene expression. A negative correlation was also established between THI and ESTRα (P < 0.01), PGF2α (P < 0.01), PGE2 (P < 0.05) genes. However, heat stress did not influence the expression patterns of LHR; COX-2 genes. The histopathological section of uterine epithelial cells showed degenerative changes (P < 0.05) with less differentiation in MHS group as compared to MC group. The results from the study clearly indicated that heat stress was able to alter the reproductive activity related gene expressions at uterine level and this could be an indication of reduced reproductive efficiency in Malabari goats.

Transferred multipolar atom model for 10ß,17ß-dihydroxy-17α-methylestr-4-en-3-one dihydrate obtained from the biotransformation of methyloestrenolone.

Biotransformation is the structural modification of compounds using enzymes as the catalysts and it plays a key role in the synthesis of pharmaceutically important compounds. 10ß,17ß-Dihydroxy-17α-methylestr-4-en-3-one dihydrate, C19H28O3·2H2O, was obtained from the fungal biotransformation of methyloestrenolone. The structure was refined using the classical independent atom model (IAM) and a transferred multipolar atom model using the ELMAM2 database. The results from the two refinements have been compared. The ELMAM2 refinement has been found to be superior in terms of the refinement statistics. It has been shown that certain electron-density-derived properties can be calculated on the basis of the transferred parameters for crystals which diffract to ordinary resolution.

In utero exposure to nanosized carbon black (Printex90) does not induce tandem repeat mutations in female murine germ cells.

Inhalation of particles has been shown to induce mutations in the male germline in mice following both prenatal and adult exposures in several experiments. In contrast, the effects of particles on female germ cell mutagenesis are not well established. Germline mutations are induced during active cell division, which occurs during fetal development in females. We investigated the effects of prenatal exposure to carbon black nanoparticles (CB) on induction of mutations in the female mouse germline during fetal development, spanning the critical developmental stages of oogenesis. Pregnant C57BL/6J mice were exposed four times during gestation by intratracheal instillation of 67µg/animal of nanosized carbon black Printex90 or vehicle (gestation days 7, 10, 15 and 18). Female offspring were raised to maturity and mated with unexposed CBA males. Expanded simple tandem repeat (ESTR) germline mutation rates in the resulting F2 generation were determined from full pedigrees (mother, father, offspring) of F1 female mice (178 CB-exposed and 258 control F2 offspring). ESTR mutation rates in CB-exposed F2 female offspring were not statistically different from those of F2 female control offspring.

Study on the Fermentation Condition of Steroid 15?-Hydroxylation by Penicillium raistrickii / 微生物学通报

The fermentation conditions which affect C-15? hydroxylation o f 18-methyl-estr- 4-ene-3,17-dione were investigated. As the key step in the Hydroxylation, the dissolution of substrate was focused on. Tween80, MeOH, DMSO,?-CD and 2-HP?CD were studied to improve the dissolvability of 18-met hyl-estr-4-ene-3,17-dione.The other factors such as pH, substrate concent ration and aeration strategies which affected conversion rate were also resea rched. As a result, the conversion rate can be up to 60% in shake flask and ach i(eve 50% in fermentor,which would overcome the disadvantage of 15?-hydroxyl -18-methyl-estr-4-ene-3,17-dione chemosynthesis and provide a good techn ics to industry.