Connexin-43 hemichannels contribute to the propagation of μ-calpain-mediated neuronal death in a cortical ablation injury model

We investigated the role of the astrocytic and neuronal hemichannels (HCs) in the spread of cortical neuronal death in a rat cortical injury model. Over time (by 6 h), propidium iodide (PI)-positive cells with labeling either with anti-neuron specific enolase or anti-parvalbumin (indicating GABAnergic interneurons) antibody spread in the deep cortical layers adjacent to the injury and co-localized with activated μ-calpain. Connexin (Cx)-43, glial fibrillary acidic protein (GFAP), activated μ-calpain and α-fodrin breakdown product (FBP) increased post-injury, peaking at 1 h, in the injury and adjacent areas. GFAP-Cx43-positive reactivated astrocytes exhibited similar distribution to the dead neurons. Cx43 and Cx36 primarily comprise HCs in the astrocyte and neuron, respectively. Ethidium bromide (EtBr) uptake was enhanced post-injury, and confirmed in the Cx43- and Cx36-positive cells. A Cx43-HC inhibitor Gap26 prevented the opening of the Cx43-HC and Cx36-HC, μ-calpain activation, α-fodrin proteolysis and death in the deep cortical neurons. Collectively, opening of the astrocytic Cx43-HC and neuronal Cx36-HC would induce the regional spread of cortical neuronal death through μ-calpain activation in the rat brain injury model.     

Mangrove stilt root morphology modeling for estimating hydraulic drag in tsunami inundation simulation

The submerged tree volume and the projection area of mangroves play a significant role in damping tsunami inundation flow with a distinct root formation above ground. We modeled the stilt root morphology of the Rhizophora sp., especially to incorporate into a hydraulic drag of tsunami inundation simulation. The equivalent Manning’s roughness coefficient has been used as the hydraulic drag of mangroves for the computation of inundation flow [Yanagisawa et al. (Coast Shelf Sci 81: 27–37, 2009)], but it could not elucidate the effectiveness under different tree conditions. The field data from 18 sample trees in Ranong Province, Thailand, were measured. The total number of primary roots, the root height at trunk, and the root-spread distance, the root diameter, and the vertical root angle from trunk could be estimated with the diameter of the breast height. The quadratic equation expressed the root curve of the primary stilt root, and functions to estimate root volume and projected area were derived by the integration of the equation that will be used to calculate drag force in tsunami simulation.     

Formation of long-chain N-vanillyl-acylamides from plant oils

Long-chain N-vanillyl-acylamides (LCNVAs) were generated from plant oils and vanillylamine (VA) by nucleophilic amidation without any catalytic reagents. The resulting LCNVAs varied according to the fatty acid composition of the plant oil used. Therefore, the LCNVAs contained in Capsicum oleoresins were products that were spontaneously generated from the oleoresin during storage.     

Identification of Highly Selective and Potent Histone Deacetylase 3 Inhibitors Using Click Chemistry-Based Combinatorial Fragment Assembly

To find histone deacetylase 3 (HDAC3)-selective inhibitors, a series of 504 candidates was assembled using “click chemistry”, by reacting nine alkynes bearing a zinc-binding group with 56 azide building blocks in the presence of Cu(I) catalyst. Screening of the 504-member triazole library against HDAC3 and other HDAC isozymes led to the identification of potent and selective HDAC3 inhibitors T247 and T326. These compounds showed potent HDAC3 inhibition with submicromolar IC₅₀s, whereas they did not strongly inhibit other isozymes. Compounds T247 and T326 also induced a dose-dependent selective increase of NF-κB acetylation in human colon cancer HCT116 cells, indicating selective inhibition of HDAC3 in the cells. In addition, these HDAC3-selective inhibitors induced growth inhibition of cancer cells, and activated HIV gene expression in latent HIV-infected cells. These findings indicate that HDAC3-selective inhibitors are promising candidates for anticancer drugs and antiviral agents. This work also suggests the usefulness of the click chemistry approach to find isozyme-selective HDAC inhibitors.     

Association between Smoking Status and Obesity in a Nationwide Survey of Japanese Adults

Objective

A positive association between the number of cigarettes smoked per day and obesity has been reported, whereas how other smoking-related indices, such as pack-years and duration of smoking, are related with obesity has been less investigated. We analyzed the age-adjusted cross-sectional association between smoking and obesity in a general Japanese population.

Methods

We used data from a nationwide epidemiological study of Japanese adults (N = 23,106). We compared the prevalence of obesity (defined as body mass index ≥ 25kg/m²) among groups classified by smoking behavior, pack-years, number of cigarettes per day, duration of smoking, and duration and time of smoking cessation.

Results

In men, current smokers had a lower odds ratio (OR) for obesity of 0.80 (95% confidence interval (CI): 0.72–0.88) compared to non-smokers, whereas past smokers had a higher OR of 1.23 (95% CI: 1.09–1.37) compared to current smokers. In women, there were no differences in obesity between the three groups classified by smoking behavior. However, in both sexes, the prevalence of obesity tended to increase with pack-years and the number of cigarettes per day, but not with duration of smoking in current and past smokers. Further, in male smokers, the risks for obesity were markedly higher in short-term heavy smokers compared with long-term light smokers, even with the same number of pack-years. Regarding the impact of smoking cessation, female past smokers who quit smoking at an age > 55-years had an elevated OR of 1.60 (95% CI:1.05–2.38) for obesity.

Conclusions

In a general Japanese population, obesity is progressively associated with pack-years and number of cigarettes per day, but not with the duration of smoking. When investigating the association between obesity and cigarette smoking, the daily smoking burden and the duration of smoking require to be independently considered.     

Preparation of reminiscent aroma mixture of Japanese soy sauce

To prepare an aroma mixture of Japanese soy sauce by fewest components, the aroma concentrate of good sensory attributes was prepared by polyethylene membrane extraction, which could extract only the volatiles with diethyl ether. GC-MS-Olfactometry was done with the aroma concentrate, and 28 odor-active compounds were detected. Application of aroma extract dilution analysis to the separated fraction revealed high flavor dilution factors with respect to acetic acid, 4-hydroxy-2(or5)-ethyl-5(or2)-methyl-3(2H)-furanone (HEMF), 3-methyl-1-butanol (isoamyl alcohol), and 3-(methylsulfanyl)propanal (methional). A model aroma mixture containing above four odorants showed a good similarity with the aroma of the soy sauce itself. Consequently, the reminiscent aroma mixture of soy sauce was prepared in water. The ratio of acetic acid, HEMF, isoamyl alcohol, and methional was 2500:300:100:1.