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

Room-temperature deformation of single crystals of transition-metal disilicides (TMSi₂) with the C11b (TM = Mo) and C40 (TM = V, Cr, Nb and Ta) structures investigated by micropillar compression

The room-temperature deformation behavior of single crystals of transition-metal (TM) disilicides with the tetragonal C11b (TM=Mo) and hexagonal C40 (TM = V, Cr, Nb and Ta) structures has been investigated by micropillar compression as a function of specimen size, paying special attention to the deformation behavior of the equivalent slip ({110} and (0001), respectively for the two structures). In contrast to bulk single crystals, in which high temperature at least exceeding 400 °C is usually needed for the operation of the equivalent slip, plastic flow is observed by the operation of the equivalent slip at room temperature for all these TM disilicides in the micropillar form. The critical resolved shear stress (CRSS) value exhibits the ‘smaller is stronger’ behavior following an inverse power-law relationship for all these TM disilicides. The bulk CRSS values at room temperature estimated from the specimen size dependence are 620 ± 40, 240 ± 20, 1, 440 ± 10, 640 ± 20 and 1, 300 ± 30 MPa for MoSi₂, VSi₂, CrSi₂, NbSi₂ and TaSi₂, respectively. Transmission electron microscopy reveals that the equivalent slip at room temperature occurs by a conventional shear mechanism for all TM disilicides, indicating the change in deformation mechanism from synchroshear in bulk to conventional shear in micropillars occurs in CrSi₂ with decreasing temperature

Observation of the magnetoelectric reversal process of the antiferromagnetic domain

We investigated the switching process of the perpendicular exchange bias, which is driven by the magnetoelectric effect, by conducting magnetic domain observations using scanning soft X-ray magnetic circular dichroism microscopy. Isothermal and simultaneous application of magnetic and electric fields switches the perpendicular exchange bias polarity. The switching process proceeds by the nucleation and growth of reversed domains. The correspondence among the ferromagnetic/antiferromagnetic domains and exchange bias polarity indicates that interfacial antiferromagnetic spin/domain reversal is responsible for the magnetoelectric switching of the perpendicular exchange bias polarity.Yu Shiratsuchi, Shunsuke Watanabe, Hiroaki Yoshida, Noriaki Kishida, Ryoichi Nakatani, Yoshinori Kotani, Kentaro Toyoki, and Tetsuya Nakamura, Appl. Phys. Lett. 113, 242404 (2018); https://doi.org/10.1063/1.5053925

Beyond water homeostasis:diverse functional roles of mammalian aquaporins

Background - Aquaporin (AQP) water channels are best known as passive transporters of water that are vital for water homeostasis. Scope of review - AQP knockout studies in whole animals and cultured cells, along with naturally occurring human mutations suggest that the transport of neutral solutes through AQPs has important physiological roles. Emerging biophysical evidence suggests that AQPs may also facilitate gas (CO2) and cation transport. AQPs may be involved in cell signalling for volume regulation and controlling the subcellular localization of other proteins by forming macromolecular complexes. This review examines the evidence for these diverse functions of AQPs as well their physiological relevance. Major conclusions - As well as being crucial for water homeostasis, AQPs are involved in physiologically important transport of molecules other than water, regulation of surface expression of other membrane proteins, cell adhesion, and signalling in cell volume regulation. General significance - Elucidating the full range of functional roles of AQPs beyond the passive conduction of water will improve our understanding of mammalian physiology in health and disease. The functional variety of AQPs makes them an exciting drug target and could provide routes to a range of novel therapies

Identification of Disease-Promoting HLA Class I and Protective Class II Modifiers in Japanese Patients with Familial Mediterranean Fever

Objectives: The genotype-phenotype correlation of MEFV remains unclear for the familial Mediterranean fever (FMF) patients, especially without canonical MEFV mutations in exon 10. The risk of FMF appeared to be under the influence of other factors in this case. The contribution of HLA polymorphisms to the risk of FMF was examined as strong candidates of modifier genes. Methods: Genotypes of HLA-B and -DRB1 loci were determined for 258 mutually unrelated Japanese FMF patients, who satisfied modified Tel-Hashomer criteria, and 299 healthy controls. The effects of carrier status were evaluated for the risk of FMF by odds ratio (OR). The HLA effects were also assessed for clinical forms of FMF, subsets of FMF with certain MEFV genotypes and responsiveness to colchicine treatment. Results: The carriers of B?39:01 were increased in the patients (OR = 3.25, p = 0.0012), whereas those of DRB1?15:02 were decreased (OR = 0.45, p = 0.00050), satisfying Bonferroni\u27s correction for multiple statistical tests (n = 28, p<0.00179). The protective effect of DRB1?15:02 was completely disappeared in the co-existence of B?40:01. The HLA effects were generally augmented in the patients without a canonical MEFV variant allele M694I, in accordance with the notion that the lower penetrance of the mutations is owing to the larger contribution of modifier genes in the pathogenesis, with a few exceptions. Further, 42.9% of 14 colchicine-resistant patients and 13.5% of 156 colchicine-responders possessed B?35:01 allele, giving OR of 4.82 (p = 0.0041). Conclusions: The differential effects of HLA class I and class II polymorphisms were identified for Japanese FMF even in those with high-penetrance MEFV mutations