Insights into Metabolite Diagnostic Biomarkers for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a persistent and unexplained pathological state characterized by exertional and severely debilitating fatigue, with/without infectious or neuropsychiatric symptoms, and with a minimum duration of 6 consecutive months. Its pathogenesis is not fully understood. There are no firmly established diagnostic biomarkers or treatment, due to incomplete understanding of the etiology of ME/CFS and diagnostic uncertainty. Establishing a biomarker for the objective diagnosis is urgently needed to treat a lot of patients. Recently, research on ME/CFS using metabolome analysis methods has been increasing. Here, we overview recent findings concerning the metabolic features in patients with ME/CFS and the animal models which contribute to the development of diagnostic biomarkers for ME/CFS and its treatment. In addition, we discuss future perspectives of studies on ME/CFS.     

Direct Injection of CRISPR/Cas9-Related mRNA into Cytoplasm of Parthenogenetically Activated Porcine Oocytes Causes Frequent Mosaicism for Indel Mutations

Some reports demonstrated successful genome editing in pigs by one-step zygote microinjection of mRNA of CRISPR/Cas9-related components. Given the relatively long gestation periods and the high cost of housing, the establishment of a single blastocyst-based assay for rapid optimization of the above system is required. As a proof-of-concept, we attempted to disrupt a gene (GGTA1) encoding the α-1,3-galactosyltransferase that synthesizes the α-Gal epitope using parthenogenetically activated porcine oocytes. The lack of α-Gal epitope expression can be monitored by staining with fluorescently labeled isolectin BS-I-B₄ (IB4), which binds specifically to the α-Gal epitope. When oocytes were injected with guide RNA specific to GGTA1 together with enhanced green fluorescent protein (EGFP) and human Cas9 mRNAs, 65% (24/37) of the developing blastocysts exhibited green fluorescence, although almost all (96%, 23/24) showed a mosaic fluorescent pattern. Staining with IB4 revealed that the green fluorescent area often had a reduced binding activity to IB4. Of the 16 samples tested, six (five fluorescent and one non-fluorescent blastocysts) had indel mutations, suggesting a correlation between EGFP expression and mutation induction. Furthermore, it is suggested that zygote microinjection of mRNAs might lead to the production of piglets with cells harboring various mutation types.     

The microwave effect on the properties of silica-coated TiO2 fine particles prepared using sol-gel method

The silica coating of TiO₂ fine particle was conducted using microwave assisted sol-gel method and conventional sol-gel method to suppress its photo-catalytic activity. The amount and uniformity of silica coating on TiO₂ surface were characterized by X-ray photoelectron spectroscopy (XPS), X-ray fluorescence spectroscopy (XRF), infrared spectroscopy (IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and zeta potential measurements. XPS and XRF results showed that the presence of catalyst and reaction time were important factors to reach high silica amounts. SEM, TEM, and zeta potential results indicated that dense film coating of SiO₂ layer formed on TiO₂ surface in conventional sol-gel method, whereas the nucleation coating was observed on sample prepared by microwave assisted sol-gel method. When photo-catalytic activities and ultraviolet (UV) shielding abilities of these samples were evaluated, the sample prepared by microwave processing showed higher inhibition of photo-catalytic activity and better UV shielding ability than the sample prepared by conventional method. These results suggested that the coating method significantly affected the photo-catalytic activity and UV shielding ability of coated TiO₂.     

Simulation of transverse crack formation on continuously cast peritectic medium carbon steel slabs

Reliable data are limited to the critical strain for the formation of transverse cracks on the slabs, owing to experimental difficulty to simulate temperature gradient in solidified shell in continuous casting mold. The present study is to determine the critical strain, ?_c, for the formation of transverse cracks on continuously cast slabs. A convenient and simple hot tensile test using rectangular test pieces with either V-notch or semi-circle notch or oscillation marks has been developed by placing the specimen under similar temperature gradient to that in solidified shell in the mold. The ?_c has been determined at a better accuracy and reproducibility, and the ?_c at a strain rate of 5?10^?4s^?1 is found to be a high 35% for test pieces without notch. It sharply decreases, however, to 10% for those with V- and semi-circle-notches, slightly decreases with increasing notch depth, and further decreases for those with oscillation marks that accompany solute segregation. Reduction of the oscillation mark depth is shown to be important measure to prevent the occurrence of transverse cracking of continuously cast slabs.     

Gas sensitiveness of polypyrrole films doped chemically in the gas phase

Electropolymerized polypyrrole films were electrochemically reduced and then chemically doped with one of PCl₃, SO₂, NO₂ or iodine vapour in the gas phase. These chemically-doped polypyrrole films showed a resistance decrease when they were exposed to electron-acceptor gases having electron affinities larger than those used in the chemical doping, except for one case of exposure of iodine-doped polypyrrole films to NO₂, where (although iodine has reportedly a larger electron affinity than NO₂) a resistance increase was seen, which was caused by a partial substitution of the doped iodine with exposed NO₂. The phenomenon is discussed in terms of the stabilization of gaseous species on adsorption. The present study suggests that a selective gas sensitivity may be attached to polypyrrole films if they are doped with an appropriate gas in advance.     

Re-passivation current of amorphous Zr65Al7.5Ni10Cu17.5 alloy in a Hanks’ balanced solution

To evaluate the repassivation behavior of amorphous phase with chemical and structural homogeneity, time transient of re-passivation current density was measured on amorphous Zr₆₅Al_7.5Ni₁₀Cu_17.5 alloy and crystalline pure Zr with a momentary fracture of a ribbon shaped specimen in an artificial body fluid. Current density abruptly increased to a peak, J_peak, and exponentially decreased to the constant value, J_∞, J_peak and J_∞ on the amorphous specimen were smaller than those on the crystalline specimen, indicating that the amorphous phase would show the smaller dissolution rate from bare metal surface and from a re-passive film than the crystalline specimen, respectively. On the other hand, decrease rate of the current density on the amorphous specimen was smaller than that on the crystalline specimen, indicating the regeneration of passive film on the amorphous specimen was delayed probably because the amount of metal ions dissolved at the initial stage, i.e. the source of re-passive film, was smaller on the amorphous specimen. Consequently, the total charge for the re-passivation of the amorphous specimen was smaller than that of the crystalline specimen, supposing that the amount of dissolved metal ions during re-passivation was smaller on the amorphous specimen than the crystalline specimen.     

Japanese research and development on metallic biomedical,dental, and healthcare materials

There is considerable demand for metallic materials for use in medical and dental devices. Metals and alloys are widely used as biomedical materials and are indispensable in the medical field. In dentistry, metal is used for restorations, orthodontic wires, and dental implants. This article describes R&D on metallic biomaterials primarily conducted by the members of the Japan Institute of Metals. For more information, contact Mitsuo Niinomi, Toyohashi University of Technology, Department of Production Systems Engineering, 1-1 Hibarigaoka, Tempaku-cho.Toyohashi 441-8580, Japan     

Early effects of sodium iodate injection on ERG in mice

The electroretinogram (ERG) was recorded in 15 ICR albino mice before and 2, 4 and 24 h after injection of 40 mg/kg of NaIO3 and the results were compared with the corresponding ultrastructural findings. Both a- and b-wave amplitudes decreased at 2 h after injection and increased at 4 h to the levels before injection and further increased at 24 h after injection. The b-wave threshold intensity increased by 2.1 log units at 2 h after injection. Thereafter, it decreased once at 4 h and significantly increased at 24 h by 3.4 log units. Electron microscopic examination showed swollen cytoplasmic organelles of the retinal pigment epithelial cells at 4 h after injection. It was thus demonstrated that an early effect of NaIO3 on the electrical response of the mouse retina was more conspicuous than histopathological changes.