Immunohistochemical Studies of Experimental Diabetic Neuropathy

Accumulations of substance P, somatostatin, vasoactive intestinal polypeptide (VIP) and dopamine-/3-hydroxylase (DBH) after ligation of the ischiadic nerve of streptozotocininduced diabetic rats were observed by an immunohistochemical technique and the results were examined both qualitatively and quantitatively. Besides, effects of administration of an aldose reductase inhibitor (ONO 2235), a key enzyme for polyol synthesis, on these accumulation patterns were studied. Immunofluorescent positiveness of these biological active substances was intensely observed along the axon in nerves of control animals. In the ischiadic nerves of diabetic rats, it was weakly observed in irregular shapes. On the other hand, in the ischiadic nerve of the diabetic rat treated with the aldose reductase inhibitor, substance P-, DBH- and VIP- immunoreactive positiveness was recovered in both distribution pattern and accumulation length. Our findings show that there are abnormalities of the axonal flow of the peripheral nerve in diabetic animals. These results also suggest that polyol pathway activity may contribute to the pathogenesis of diabetic neuropathy and ONO-2235 may be useful in preventing diabetic complications

Susceptibility of Influenza Viruses to the Novel Cap-Dependent Endonuclease Inhibitor Baloxavir Marboxil

The novel cap-dependent endonuclease inhibitor baloxavir marboxil was approved for the treatment of influenza A and B virus infections in February 2018 in Japan. Because of the need to monitor influenza viruses for reduced susceptibility to this drug, we used two cell-based screening systems – a conventional plaque reduction assay and a focus reduction assay – to evaluate the susceptibility of influenza viruses to baloxavir. First, we generated a reference virus possessing an I38T substitution in the polymerase acidic subunit (PA), which is known to be associated with reduced susceptibility to baloxavir, and demonstrated the validity of our systems using this reference virus. We then determined the susceptibility of a panel of neuraminidase (NA) inhibitor-resistant viruses and their sensitive counterparts to baloxavir. No significant differences in baloxavir susceptibilities were found between the NA inhibitor-resistant and -sensitive viruses. We also examined seasonal influenza viruses isolated during the 2017–2018 influenza season in Japan and found that no currently circulating A(H1N1)pdm09, A(H3N2), or B viruses had significantly reduced susceptibility to baloxavir and none of the viruses possessed an amino acid substitution at PA residue 38. Use of a combination of methods to analyze antiviral susceptibility and detect amino acid substitutions is valuable for monitoring the emergence of baloxavir-resistant viruses

Dietary fiber intake and risk of incident disabling dementia: the Circulatory Risk in Communities Study

OBJECTIVES: It has been hypothesized that dietary fiber intake has a beneficial impact on prevention of dementia, but the epidemiological evidence is scant. We sought to examine whether dietary fiber intake is inversely associated with risk of dementia requiring care under the national insurance (disabling dementia). METHODS: The study setting was the Circulatory Risk in Communities Study, involving 3739 Japanese individuals aged 40-64 years at the dietary surveys (1985-99). Dietary fiber intake was estimated using the 24-hour dietary recall method. Incident disabling dementia was followed up from 1999 through 2020. Disabling dementia was further classified into that with or without a history of stroke. Hazard ratios of disabling dementia according to quartiles of total, soluble, and insoluble fiber intake were calculated using the Cox proportional hazards model. RESULTS: During a median 19.7-year follow-up, a total of 670 cases of disabling dementia developed. Dietary fiber intake was inversely associated with risk of dementia: the multivariate hazards ratios (95% confidence intervals) were 0.83 (0.67-1.04), 0.81 (0.65-1.02), and 0.74 (0.57-0.96) for individuals with the second, third, and highest quartiles of dietary fiber intake, respectively, as compared with the lowest quartile (P for trend = 0.03). The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke. As for fiber-containing foods, potatoes, but not vegetables or fruits, showed a similar association. CONCLUSIONS: Dietary fiber intake, especially soluble fiber, was inversely associated with risk of disabling dementia in a general Japanese population

ニホンゴ ジュギョウ ニ オケル ILL リネン ノ グゲンカ ニ ムケタ トリクミ -エイガキョウザイ 『シアワセ カゾク ケイカク』 ヲ モチイタ キョウシケンシュウ セイカ カラ-

本稿は、1990年代後半以降、オーストラリアの学校教育において言語学習に不可欠の理念となったILL(Intercultural Language Learning)に着目し、近年の動向とその理念に基づく授業デザインを示した国際交流基金シドニー日本文化センターでの教師研修成果をまとめた実践報告である。 まず関係資料を整理した結果、ILLは導入予定のナショナルカリキュラム(Australian Curriculum)にも散見され、将来に向けた教育政策にその理念が継承されていることがわかった。次にILLを取り入れ作成した映画教材『しあわせ家族計画』を用いた教師研修では、参加者がその場でILLを体験していることがうかがえ、さらにILLを日々の授業に照らし合わせ、自らの実践を振り返っていたことが研修の記録や任意の聞き取りによって確認された。This paper focuses on the ILL (Intercultural Language Learning) approach, which has been a fundamental element of language education in Australia since the late 1990s. From an investigation of the reference material it was evident that ILL is included in the draft of the new Australian Curriculum for languages, and that ILL principles will continue to feature in education policy in the future. In this paper we report on the results of a teacher professional development seminar conducted by the Japan Foundation, Sydney which demonstrates ILL teaching practices. For the professional development seminar we used the film resource `Happy Family Plan\u27 which incorporates aspects of ILL. Through the participants\u27 responses to questioning, we were able to confirm that they gained an experience in ILL, which led them to make comparisons with and reflect on their own daily teaching practices

Food and Habitat Selection of Lepus brachyurus lyoni

We determined the environmental requirements for Lepus brachyurus lyoni on Sado Island, Japan. during the winter when food resources are low Flare track survey sites were classified by vegetation type. The movement distances of hares, which indicated habitat preference, were evaluated as the relative length of tracks in a I-ha area In addition, we examined browse marks on plants and the protein content of plants to determine the preferred plant species. Movement distances of hares decreased significantly with increasing tree stand height, mean tree diameter. basal area of the tree stand, and forest canopy closure, but increased with branch-and-stem density. The percentage of browse marks Oil the branches of tree/shrub species decreased significantly with increasing branch-and-stem diameter The rate of feeding increased significantly with increased protein content in the branches These findings suggest that hares prefer shrub stands with high branch-and-stem density to mature forests. which have lower branch-and-stem densities Hares also prefer branches and stems containing large amounts of protein Young stands offering many shrub species as food resources and shelter constitute preferable environments for hare

Association between Vitamin A and E Forms and Prostate Cancer Risk in the Singapore Prostate Cancer Study

Purpose: This study aimed to assess associations between forms of vitamin A and E (both individually and collectively) and the risk of prostate cancer, as well as identify potential effect modifiers. Methods: Utilizing data from the Singapore Prostate Cancer Study, a hospital-based case-control study, we measured the serum concentrations of 15 different forms of vitamins A and E in 156 prostate cancer patients and 118 control subjects, using a high-performance liquid chromatography technique. These forms included retinol, lutein, zeaxanthin, α-cryptoxanthin, β-cryptoxanthin, α-carotene, β-carotene, lycopene, ubiquinone, δ-tocopherol, γ-tocopherol, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol. The odds ratio and 95% confidence interval for associations between vitamin A and E and prostate cancer risk were estimated using logistic regression models after adjustment for potential confounders. The analyses were further stratified by smoking and alcohol consumption status. The mixture effect of micronutrient groups was evaluated using weighted quantile sum regression. Results: Higher concentrations of retinol, lutein, α-carotene, β-carotene, ubiquinone, α-tocopherol, δ-tocotrienol, γ-tocotrienol, and α-tocotrienol were significantly and positively associated with overall prostate cancer risk. Among ever-smokers, associations were stronger for lutein, β-cryptoxanthin and β-carotene compared with never-smokers. Among regular alcohol drinkers, associations were stronger for lutein, β-cryptoxanthin, ubiquinone, γ-tocotrienol and α-tocotrienol compared with non-regular alcohol drinkers. Retinol and α-tocotrienol contributed most to the group indices ‘vitamin A and provitamin A carotenoids’ and ‘vitamin E’, respectively. Conclusions: Several serum vitamin A and E forms were associated with prostate cancer risk, with significant effect modification by smoking and alcohol consumption status. Our findings shed light on prostate cancer etiology

Metabolic engineering of Schizosaccharomyces pombe via CRISPR-Cas9 genome editing for lactic acid production from glucose and cellobiose

Modification of the Schizosaccharomyces pombe genome is often laborious, time consuming due to the lower efficiency of homologous recombination. Here, we constructed metabolically engineered S. pombe strains using a CRISPR-Cas9 system and also demonstrated D-lactic acid (D-LA) production from glucose and cellobiose. Genes encoding two separate pyruvate decarboxylases (PDCs), an L-lactic acid dehydrogenase (L-LDH), and a minor alcohol dehydrogenase (SPBC337.11) were disrupted, thereby attenuating ethanol production. To increase the cellular supply of acetyl-CoA, an important metabolite for growth, we introduced genes encoding bacterial acetylating acetaldehyde dehydrogenase enzymes (Escherichia coli MhpF and EutE). D-LA production by the resulting strain was achieved by expressing a Lactobacillus plantarum gene encoding D-lactate dehydrogenase. The engineered strain efficiently consumed glucose and produced D-LA at 25.2 g/L from 35.5 g/L of consumed glucose with a yield of 0.71 g D-LA / g glucose. We further modified this strain by expressing beta-glucosidase by cell surface display; the resulting strain produced D-LA at 24.4 g/L from 30 g/L of cellobiose in minimal medium, with a yield of 0.68 g D-LA / g glucose. To our knowledge, this study represents the first report of a S. pombe strain that was metabolically engineered using a CRISPR-Cas9 system, and demonstrates the possibility of engineering S. pombe for the production of value-added chemicals

Enhancing 3-hydroxypropionic acid production in combination with sugar supply engineering by cell surface-display and metabolic engineering of Schizosaccharomyces pombe

Abstract Background Economical production of value-added chemicals from renewable biomass is a promising path to sustainability. 3-Hydroxypropionic acid (3-HP) is an important chemical for building a bio-sustainable society. Establishment of 3-HP production from renewable resources such as glucose would provide a bio-sustainable alternative to the production of acrylic acid from fossil resources. Results Here, we describe metabolic engineering of the fission yeast Schizosaccharomyces pombe to enhance 3-HP production from glucose and cellobiose via the malonyl-CoA pathway. The mcr gene, encoding the malonyl-CoA reductase of Chloroflexus aurantiacus, was dissected into two functionally distinct fragments, and the activities of the encoded protein were balanced. To increase the cellular supply of malonyl-CoA and acetyl-CoA, we introduced genes encoding endogenous aldehyde dehydrogenase, acetyl-CoA synthase from Salmonella enterica, and endogenous pantothenate kinase. The resulting strain produced 3-HP at 1.0 g/L from a culture starting at a glucose concentration of 50 g/L. We also engineered the sugar supply by displaying beta-glucosidase (BGL) on the yeast cell surface. When grown on 50 g/L cellobiose, the beta-glucosidase-displaying strain consumed cellobiose efficiently and produced 3-HP at 3.5 g/L. Under fed-batch conditions starting from cellobiose, this strain produced 3-HP at up to 11.4 g/L, corresponding to a yield of 11.2% (g-3-HP/g-glucose; given that 1 g cellobiose corresponds to 1.1 g glucose upon digestion). Conclusions In this study, we constructed a series of S. pombe strains that produced 3-HP via the malonyl-CoA pathway. Our study also demonstrated that BGL display using cellobiose and/or cello-oligosaccharides as a carbon source has the potential to improve the titer and yield of malonyl-CoA- and acetyl-CoA-derived compounds