Reproducibility of CBF using pCASL

Purpose : To determine the reproducibility of corrected quantitative cerebral blood flow (qCBF) through measurement of transit flow time using multi-delay three-dimensional pseudo-continuous arterial spin labeling (pCASL) in healthy men and women and to evaluate the differences in qCBF between not only men and women, but also the follicular and luteal phases of the women’s menstrual cycle. Methods : The participants were 16 healthy volunteers (8 men and 8 women ; mean age, 25.3 years). Two MRI were conducted for all participants ; female participants were conducted in the follicular and luteal phases. The reproducibility of qCBF values was evaluated by the intraclass correlation coefficient (ICC) and differences between the two groups were estimated by voxel-based morphometry (VBM) analysis. Results : The qCBF values were lower in men than in women, and those in females were significantly different between the follicular and luteal phases (P < 0.05). In VBM analysis, the qCBF values of the lower frontal lobes were significantly higher in women than in men (P < 0.05). The qCBF values of the frontal pole were significantly higher in the follicular phase than in the luteal phase (P < 0.01). Conclusion : Multi-delay pCASL can reveal physiological and sex differences in cerebral perfusion

Comparison of ocean deoxygenation between CMIP models and an observational dataset in the North Pacific from 1958 to 2005

This study investigated the relationship between the observed and simulated dissolved oxygen (O2) inventory changes in the North Pacific by analyzing an observational dataset and the outputs of Coupled Model Intercomparison Project Phase 5 and 6 (CMIP5/6) between 1958 and 2005. A total of 204 ensembles from 20 models were analyzed. Many of the models in the North Pacific subarctic region have higher climatological O2 concentrations than observed at deeper water depths. Therefore, the negative trend of O2 inventories tends to be larger, and in fact, several model ensemble members have a larger negative trend in O2 inventories than observed. The variability among model ensemble members is more influenced by the uncertainty due to internal variability than by the uncertainty resulting from model dependency. An inter-model empirical orthogonal function (EOF) analysis revealed that the different simulated magnitudes of the negative O2 trend is closely associated with the first EOF mode, and ensemble members with strong negative trends are characterized by large oxygen reduction in the subarctic North Pacific, especially around the boundaries between the North Pacific Ocean and the Sea of Okhotsk as well as the Bering Seas. The modeled strong O2 decrease in the subarctic North Pacific is consistent with the spatial pattern of the observed O2 trend. Further analysis of climate models indicated that the O2 decrease in the subarctic region was primarily caused by physical factors. This conclusion is supported by the significantly high correlation is present between the potential temperature and O2 inventory trend in the subarctic region, whereas an insignificant correlation coefficient is present between dissolved organic carbon and the O2 inventory trend. However, the observations have a larger ratio of O2 inventory trend to temperature trend than any of the ensembles, and thus the relationship between O2 and temperature change in the subarctic North Pacific seen in the CMIP5/6 simulations is not exact

Sesamin catechol glucuronides exert anti-inflammatory effects by suppressing IFN-β and iNOS expression through the deconjugation in macrophage-like J774.1 cells

Sesamin, a representative sesame lignan, has health-promoting activities. Sesamin is converted into catechol derivatives and further into their glucuronides or sulfates in vivo, whereas the biological activities of sesamin metabolites remain unclear. We examined the inhibitory effects of sesamin metabolites on the lipopolysaccharide (LPS)-induced NO production in mouse macrophage-like J774.1 cells and found that a mono-catechol derivative SC1, (7α,7'α,8α,8'α)-3,4-dihydroxy-3',4'-methylenedioxy-7,9':7',9-diepoxylignane, has a much higher activity than sesamin and other metabolites. The inhibitory effects of SC1 glucuronides were time-dependently enhanced, associated with the intracellular accumulation of SC1 and the methylated form. SC1 glucuronides and SC1 attenuated the expression of inducible NO synthase (iNOS) and upstream interferon-β (IFN-β) in the LPS-stimulated macrophages. The inhibitory effects of SC1 glucuronides against NO production were canceled by the β-glucuronidase inhibitor and enhanced by the catechol- O-methyltransferase inhibitor. Our results suggest that SC1 glucuronides exert the anti-inflammatory effects by inhibiting the IFN-β/iNOS signaling through macrophage-mediated deconjugation

Formation of meso, N-diphenylprotoporphyrin IX by an aerobic reaction of phenylhydrazine with oxyhemoglobins.

Administration of phenylhydrazine to rabbits resulted in the denaturation of hemoglobins in erythrocytes, causing the formation of intracellular precipitates known as Heinz bodies, severe hemolytic anemia, and reticulocytosis. To elucidate the molecular mechanism of the destabilization, we allowed human oxyhemoglobins to react aerobically with phenylhydrazine. After treatment with acetic acid/HCl and H2SO4/methanol, the chloroform extract contained blue-green pigments of major products accompanied by different minor products. Each product was isolated by column chromatography. By fast-atom-bombardment mass spectrometry (FAB-MS) and proton nuclear magnetic resonance (1H-NMR) spectrometry, dimethyl esters of N-phenylprotoporphyrin IX and meso, N-diphenylprotoporphyrin IX were determined. Other major products also were determined to be dimethyl esters of triphenyl-and tetraphenyl-substituted protoporphyrins by FAB-MS. The formation of meso, N-diphenylprotoporphyrin indicated that the addition of a phenyl radical to the meso-carbon atom of the protoporphyrin ring occurred. Triphenyl and tetraphenyl adducts also indicated the formation of phenyl radicals in the aerobic reaction of phenylhydrazine with oxyhemoglobins. From these results, we suggest that the formation of phenyl radicals and the replacement of heme with phenyl-substituted protoporphyrins cause the destabilization of hemoglobins to induce Heinz bodies and hemolytic anemia with phenylhydrazine.</p

BMP4 in Diabetic Nephropathy

Podocyte injury and loss have been indicated as constituting the crucial pathogenesis of glomerular injury ; however, it remains necessary to elucidate the detailed molecular mechanisms and cell-to-cell response because multiple factors may cause podocyte injury. In the glomerulus, three kinds of cells (endothelial, mesangial, and parietal epithelial) react to podocyte injury. Endothelial and mesangial cells are connected with podocyte cells across the glomerular basement membrane. However, the detailed mechanisms regarding the interaction of the mesangium and podocyte injury are unclear. Diabetic nephropathy is characterized by mesangial matrix expansion caused by an excessive deposition of extracellular matrix proteins in the mesangial area, which can be observed through the increased expression of type IV collagen. We have shown that bone morphogenetic protein 4 (BMP4) signaling leads to the glomerular changes characteristic of this disorder. To analyze the effect of BMP4 was investigated in vitro and in vivo using streptozotocin (STZ)-induced and Bmp4 heterozygous knockout (Bmp4+/-) diabetic mice or podocyte-specific Bmp4 knockout mice, and Bmp4-induced or podocyte-specific transgenic mice. BMP4 positive area and mesangial area fraction showed positively correlation. Furthermore, mesangial area fraction was significantly and negatively correlated with,WT1-positive cell number, and nephrin-positive area. We also demonstrated that the induction of podocyte apoptosis by BMP4 may be mediated by p38 activation and that of caspase 3 through cleavage. In mesangial cells, BMP4 stimulation also induced phosphorylation of p38 and Smad1 and increased cleaved caspase 3, with similar significant inhibition of Smad1 activation and decreased cleaved caspase 3 mediated by dorsomorphin. These data suggest that the BMP4 signaling pathway plays important roles for the development of both podocyte injury and mesangial expansion in diabetic nephropathy

Essential functions of the CNOT7/8 catalytic subunits of the CCR4-NOT complex in mRNA regulation and cell viability

Shortening of mRNA poly(A) tails (deadenylation) to trigger their decay is mediated mainly by the CCR4-NOT deadenylase complex. While four catalytic subunits (CNOT6, 6L 7, and 8) have been identified in the mammalian CCR4-NOT complex, their individual biological roles are not fully understood. In this study, we addressed the contribution of CNOT7/8 to viability of primary mouse embryonic fibroblasts (MEFs). We found that MEFs lacking CNOT7/8 expression [Cnot7/8-double knockout (dKO) MEFs] undergo cell death, whereas MEFs lacking CNOT6/6L expression (Cnot6/6l-dKO MEFs) remain viable. Co-immunoprecipitation analyses showed that CNOT6/6L are also absent from the CCR4-NOT complex in Cnot7/8-dKO MEFs. In contrast, either CNOT7 or CNOT8 still interacts with other subunits in the CCR4-NOT complex in Cnot6/6l-dKO MEFs. Exogenous expression of a CNOT7 mutant lacking catalytic activity in Cnot7/8-dKO MEFs cannot recover cell viability, even though CNOT6/6L exists to some extent in the CCR4-NOT complex, confirming that CNOT7/8 is essential for viability. Bulk poly(A) tail analysis revealed that mRNAs with longer poly(A) tails are more numerous in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Consistent with elongated poly(A) tails, more mRNAs are upregulated and stabilized in Cnot7/8-dKO MEFs than in Cnot6/6l-dKO MEFs. Importantly, Cnot6/6l-dKO mice are viable and grow normally to adulthood. Taken together, the CNOT7/8 catalytic subunits are essential for deadenylation, which is necessary to maintain cell viability, whereas CNOT6/6L are not

Biased Bowl-Direction of Monofluorosumanene in the Solid State

Yakiyama Y., Li M., Zhou D., et al. Biased Bowl-Direction of Monofluorosumanene in the Solid State. Journal of the American Chemical Society 146, 5224 (2024); https://doi.org/10.1021/jacs.3c11311.A new curved π-conjugated molecule 1-fluorosumanene (1) was designed and synthesized that possesses one fluorine atom on the benzylic carbon of sumanene. This compound can exhibit bowl inversion in solution, leading to the formation of two diastereomers, 1endo and 1exo, with different dipole moments. Experimental and theoretical investigation revealed an energetical relationship among 1exo, 1endo, and solvent to realize the various endo:exo ratios in the single crystals of 1 depending on the crystallization solvent. Significantly, the molecular dynamics (MD) simulations revealed that 1exo positively worked for the elongation of the stacking structure and the final endo:exo ratio was affected by the relative stability difference between 1endo and 1exo derived by solvation. Such an arrangeable endo:exo ratio of 1 realized the preparation of unique materials showing a different dielectric response from the same molecule 1 just by changing the crystallization solvent

骨卒中予防みそ汁が握力と血清25(OH)D濃度に及ぼす影響

We examined the nutritional effects of miso soup supplemented with vitamin D on serum level of ２５‐hydroxyvitamin D（２５（OH）D）and grip strength in sixty-seven inpatients（２６ males, ４１ females）of vitamin D insufficiency. The average age was ８４．６ years old and average body mass index was ２０．５kg/m２. These inpatients were divided into two groups, miso soup supplemented with vitamin D group（D group）（n=３５）and control group（n＝３２）. Nyucal Kouso FiberⓇ, NUTRI Co, Ltd, easily dissolved in miso soup. The D group ingested ２g of Nyucal Kouso FiberⓇ containing １０μg of vitamin D once a day. The daily diet included １７．５μg of vitamin D. As a result, D group and control group ingested ２７．５ μg and １７．５ μg per day of vitamin D, respectively. These results showed that both serum level of ２５（OH）D and grip strength of D group were significantly higher for one month than before（p<0.001）. In contrast, in control group, serum level of ２５（OH）D also higher than before, whereas grip strength did not change so much. These findings suggest that vitamin D-added diet is nutritionally effective to improve serum level of ２５（OH）D and grip strength of patients with vitamin D insufficiency