Histone Chaperone Asf1 Plays an Essential Role in Maintaining Genomic Stability in Fission Yeast

The histone H3-H4 chaperone Asf1 is involved in chromatin assembly (or disassembly), histone exchange, regulation of transcription, and chromatin silencing in several organisms. To investigate the essential functions of Asf1 in Schizosaccharomyces pombe, asf1-ts mutants were constructed by random mutagenesis using PCR. One mutant (asf1-33(ts)) was mated with mutants in 77 different kinase genes to identify synthetic lethal combinations. The asf1-33 mutant required the DNA damage checkpoint factors Chk1 and Rad3 for its survival at the restrictive temperature. Chk1, but not Cds1, was phosphorylated in the asf1-33 mutant at the restrictive temperature, indicating that the DNA damage checkpoint was activated in the asf1-33 mutant. DNA damage occured in the asf1-33 mutant, with degradation of the chromosomal DNA observed through pulse-field gel electrophoresis and the formation of Rad22 foci. Sensitivity to micrococcal nuclease in the asf1-33 mutant was increased compared to the asf1+ strain at the restrictive temperature, suggesting that asf1 mutations also caused a defect in overall chromatin structure. The Asf1-33 mutant protein was mislocalized and incapable of binding histones. Furthermore, histone H3 levels at the centromeric outer repeat region were decreased in the asf1-33 mutant and heterochromatin structure was impaired. Finally, sim3, which encodes a CenH3 histone chaperone, was identified as a strong suppressor of the asf1-33 mutant. Taken together, these results clearly indicate that Asf1 plays an essential role in maintaining genomic stability in S. pombe

High Speed And Large Capacity Compressor-Driving Turbines For Chemical Plants

LecturePg. 59-69.This paper gives a brief description of compressor-driving steam turbines for use in chemical plants. Turbines used for ethylene plants, ammonia plants and LNG plants, in particular, are large-capacity, high-speed variable-speed steam turbines. Their present state and the state of their development are described. Rotor dynamics technique which is the basic design technique for the attainment of their stable operation and blade design and manufacturing techniques are described in detail. Further, the construction of each component part is described in full

Statins Activate Human PPARα Promoter and Increase PPARα mRNA Expression and Activation in HepG2 Cells

Statins increase peroxisome proliferator-activated receptor α (PPARα) mRNA expression, but the mechanism of this increased PPARα production remains elusive. To examine the regulation of PPARα production, we examined the effect of 7 statins (atorvastatin, cerivastatin, fluvastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin) on human PPARα promoter activity, mRNA expression, nuclear protein levels, and transcriptional activity. The main results are as follows. (1) Majority of statins enhanced PPARα promoter activity in a dose-dependent manner in HepG2 cells transfected with the human PPARα promoter. This enhancement may be mediated by statin-induced HNF-4α. (2) PPARα mRNA expression was increased by statin treatment. (3) The PPARα levels in nuclear fractions were increased by statin treatment. (4) Simvastatin, pravastatin, and cerivastatin markedly enhanced transcriptional activity in 293T cells cotransfected with acyl-coenzyme A oxidase promoter and PPARα/RXRα expression vectors. In summary, these data demonstrate that PPARα production and activation are upregulated through the PPARα promoter activity by statin treatment

Early-term birth and hypoglycaemia

Background : The effect of early-term birth on the development of hypoglycaemia in large-for gestational-age (LGA) neonates is yet to be clarified. This study aimed to clarify the association between hypoglycaemia and early-term birth in LGA neonates. Methods : This single-centre retrospective cohort study evaluated LGA neonates born at term at Tsurugi Municipal Handa Hospital, Japan. Blood glucose levels were measured immediately and at 1, 2, and 4 hours after birth. The association between early-term birth and hypoglycaemia was evaluated using logistic regression analysis. The prevalence of severe hypoglycaemia and hypoglycaemia according to its timing of development was analysed using Fisher’s exact test. Results : In total, 295 neonates were included. Among them, 113 neonates (38.3%) were born at early term and 91 infants (30.8%) had hypoglycaemia. Logistic regression analysis showed a significant association between early-term birth and hypoglycaemia (adjusted odds ratio [95% confidence interval] : 2.691 [1.597 to 4.535]). However, there was no significant between-group difference among those with severe hypoglycaemia. Conclusions : Among LGA neonates, early-term birth is positively associated with neonatal hypoglycaemia. This indicates that among LGA neonates, those born at early term require more careful observation for hypoglycaemia than do those born at later term

Sulfur assimilation using gaseous carbonyl sulfideby the soil fungus Trichoderma harzianum

Fungi have the capacity to assimilate a diverse range of both inorganic and organic sulfur compounds. It has been recognized that all sulfur sources taken up by fungi are in soluble forms. In this study, we present evidence that fungi can utilize gaseous carbonyl sulfide(COS) for the assimilation of a sulfur compound. We found that the filamentousfungus Trichoderma harzianum strain THIF08, which has constitutively high COS-degrading activity, was able to grow with COS as the sole sulfur source. Cultivation with 34S-labeled COS revealed that sulfur atom from COS was incorporated into intracellular metabolites such as glutathione and ergothioneine. COS degradation by strain THIF08, in which as much of the moisture derived from the agar medium as possible was removed, indicated that gaseous COS was taken up directly into the cell. Escherichia coli transformed with a COS hydrolase (COSase) gene, which is clade D of the β-class carbonic anhydrase subfamily enzyme with high specificity for COS but low activity for CO2 hydration, showed that the COSase is involved in COS assimilation. Comparison of sulfur metabolites of strain THIF08 revealed a higher relative abundance of reduced sulfur compounds under the COS-supplemented condition than the sulfate-supplemented condition, suggesting that sulfur assimilation is more energetically efficient with COS than with sulfate because there is no redox change of sulfur. Phylogenetic analysis of the genes encoding COSase, which are distributed in a wide range of fungal taxa, suggests that the common ancestor of Ascomycota, Basidiomycota, and Mucoromycota acquired COSase at about 790-670 Ma. © 2024 Iizuka et al

Albumin-conjugated PEG liposome enhances tumor distribution of liposomal doxorubicin in rats

To evaluate the effect of coupling of recombinant human serum albumin (rHSA) onto the surface of poly(ethylene glycol)-modified liposorne (PEG liposome) on the in vivo disposition characteristics of liposomal doxorubicin (DXR), the pharmacokinetics and tissue distribution of DXR were evaluated after intravenous administration of rHSA-modified PEG (rHSA/PEG) liposomal DXR into tumor-bearing rats. rHSA/PEG liposome prepared using a hetero-bifunctional cross-linker, N- succinimidyl 3-(2-pyridyldithio) propionate (SPDP), efficiently encapsulated DXR (over 95%). rHSA/PEG liposomal DXR showed longer blood-circulating property than PEG liposornal DXR and the hepatic and splenic clearances of rHSA/PEG liposornal DXR were significantly smaller than those of PEG liposomal DXR. It was also demonstrated that the disposition of DXR to the heart, one of the organs for DXR-related side-effects, was significantly smaller than free DXR. Furthermore, the tumor accumulation of rHSA/PEG liposomal DXR was significantly larger than that of PEG liposomal DXR. The &#34;therapeutic index&#34;, a criterion for therapeutic outcome, for rHSA/PEG fiposornal DXR was significantly higher than PEG liposomal DXR. These results clearly indicate that rHSA-conjugation onto the surface of PEG liposome would be a useful approach to increase the effectiveness and safety of PEG liposomal DXR.</p