An Association Analysis between Mitochondrial DNA A10398G Polymorphism and Temperament in Japanese Young Adults

The mitochondrial (mt) DNA C5178A and A10398G polymorphisms have been reported to be associated with mental disorders such as bipolar disorder. However, the effects of these polymorphisms on temperament in healthy people are poorly understood. Evaluating healthy subjects can have the advantage of providing new strategies for maintaining psychological health and preventing mental illness. We examined the association between mtDNA polymorphisms and temperament in Japanese students. There was no significant difference in examined temperament when analysed by genotypes, 5178–10398 haplotypes, or sex. The subgroup analysis based on sex indicated that there was an interactive effect of the mtDNA A10398G polymorphism and sex on anxiety and obsession. This finding is preliminary and cannot exclude the possibility of false-positive due to small sample size (144 subjects) and multiple statistical testing. Further studies involving a larger sample size or other ethnic groups are necessary to confirm that mtDNA A10398G polymorphism can be a genetic factor for temperament

Inhibitory effects of resistant maltodextrin on rat disaccharidases: Overestimation by the method measuring released glucose

Resistant maltodextrin (RMD) attenuates the blood glucose response in healthy adults, as supported by meta-analysis. One of the potential mechanisms is disaccharidase inhibition. We hypothesized that the conventional method determining released glucose might lead to misestimation of the inhibitory effects because RMD is partly digested and the glucose amount released from RMD could change in the presence or absence of substrates. We examined digestibility change of RMD and compared the inhibitory effects by determination of released glucose (Glu method), fructose (Fru method), and p-nitrophenol from p-nitrophenyl- α -D-glucopyranoside (pNPG method). The Glu method overestimated the inhibition rate (18.9 to 60.2% for maltase). The Fru method showed inhibition for sucrase by 6.46 to 10.9% and isomaltase by 14.4 to 28.6%. The pNPG method showed α-glucosidase inhibition of 11.0 to 28.1%. These results indicate that the Glu method is not suitable for inhibition assay of partially digestible dextrin and that RMD has disaccharidase inhibition

Involvement of ASK1 in Ca(2+)-induced p38 MAP kinase activation

The mammalian mitogen-activated protein (MAP) kinase kinase kinase apoptosis signal-regulating kinase 1 (ASK1) is a pivotal component in cytokine- and stress-induced apoptosis. It also regulates cell differentiation and survival through p38 MAP kinase activation. Here we show that Ca(2+) signalling regulates the ASK1–p38 MAP kinase cascade. Ca(2+) influx evoked by membrane depolarization in primary neurons and synaptosomes induced activation of p38, which was impaired in those derived from ASK1-deficient mice. Ca(2+)/calmodulin-dependent protein kinase type II (CaMKII) activated ASK1 by phosphorylation. Moreover, p38 activation induced by the expression of constitutively active CaMKII required endogenous ASK1. Thus, ASK1 is a critical intermediate of Ca(2+) signalling between CaMKII and p38 MAP kinase

Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types

Abstract Background Mammalian small intestinal tight junctions (TJ) link epithelial cells to one another and function as a permselective barrier, strictly modulating the passage of ions and macromolecules through the pore and leak pathways, respectively, thereby preventing the absorption of harmful compounds and microbes while allowing regulated transport of nutrients and electrolytes. Small intestinal epithelial permeability is ascribed primarily to the properties of TJs between adjoining enterocytes (ENTs), because there is almost no information on TJ composition and the paracellular permeability of nonenterocyte cell types that constitute a small but significant fraction of the intestinal epithelia. Results Here we directed murine intestinal crypts to form specialized organoids highly enriched in intestinal stem cells (ISCs), absorptive ENTs, secretory goblet cells, or Paneth cells. The morphological and morphometric characteristics of these cells in organoids were similar to those in vivo. The expression of certain TJ proteins varied with cell type: occludin and tricellulin levels were high in both ISCs and Paneth cells, while claudin-1, -2, and -7 expression was greatest in Paneth cells, ISCs, and ENTs, respectively. In contrast, the distribution of claudin-15, zonula occludens 1 (ZO-1), and E-cadherin was relatively homogeneous. E-cadherin and claudin-7 marked mainly the basolateral membrane, while claudin-2, ZO-1, and occludin resided in the apical membrane. Remarkably, organoids enriched in ENTs or goblet cells were over threefold more permeable to 4 and 10 kDa dextran compared to those containing stem and Paneth cells. The TJ-regulator larazotide prevented the approximately tenfold increases in dextran flux induced by the TJ-disrupter AT1002 into organoids of different cell types, indicating that this ZO toxin nonselectively increases permeability. Forced dedifferentiation of mature ENTs results in the reacquisition of ISC-like characteristics in TJ composition and dextran permeability, suggesting that the post-differentiation properties of TJs are not hardwired. Conclusions Differentiation of adult intestinal stem cells into mature secretory and absorptive cell types causes marked, but potentially reversible, changes in TJ composition, resulting in enhanced macromolecular permeability of the TJ leak pathway between ENTs and between goblet cells. This work advances our understanding of how cell differentiation affects the paracellular pathway of epithelia

UPI scores calculated on the basis of mitochondrial DNA A10398G genotypes and sex.

<p>Values are expressed as means±S.D.s.</p><p>Higher scores indicate stronger status.</p><p>Statistical analysis was carried out using the Mann-Whitney U-test.</p>*<p>P<0.05 vs. female with 10398A.</p>†<p>P<0.05 vs. female with 10398G.</p>††<p>P<0.01 vs. female with 10398G.</p