Kumamoto University

About: Kumamoto University is a education organization based out in Kumamoto, Kumamoto, Japan. It is known for research contribution in the topics: Population & Cancer. The organization has 19602 authors who have published 35513 publications receiving 901260 citations. The organization is also known as: Kumamoto Daigaku.

The Src/c-Abl pathway is a potential therapeutic target in amyotrophic lateral sclerosis.

Abstract: Amyotrophic lateral sclerosis (ALS), a fatal disease causing progressive loss of motor neurons, still has no effective treatment We developed a phenotypic screen to repurpose existing drugs using ALS motor neuron survival as readout Motor neurons were generated from induced pluripotent stem cells (iPSCs) derived from an ALS patient with a mutation in superoxide dismutase 1 (SOD1) Results of the screen showed that more than half of the hits targeted the Src/c-Abl signaling pathway Src/c-Abl inhibitors increased survival of ALS iPSC-derived motor neurons in vitro Knockdown of Src or c-Abl with small interfering RNAs (siRNAs) also rescued ALS motor neuron degeneration One of the hits, bosutinib, boosted autophagy, reduced the amount of misfolded mutant SOD1 protein, and attenuated altered expression of mitochondrial genes Bosutinib also increased survival in vitro of ALS iPSC-derived motor neurons from patients with sporadic ALS or other forms of familial ALS caused by mutations in TAR DNA binding protein (TDP-43) or repeat expansions in C9orf72 Furthermore, bosutinib treatment modestly extended survival of a mouse model of ALS with an SOD1 mutation, suggesting that Src/c-Abl may be a potentially useful target for developing new drugs to treat ALS

Solar wind proton reflection at the lunar surface: Low energy ion measurement by MAP‐PACE onboard SELENE (KAGUYA)

Abstract: [1] Interaction between the solar wind and objects in the solar system varies largely according to the settings, such as the existence of a global intrinsic magnetic field and/or thick atmosphere. The Moon's case is characterized by the absence of both of them. Low energy ion measurements on the lunar orbit is realized more than 30 years after the Apollo period by low energy charged particle analyzers MAP-PACE on board SELENE(KAGUYA). MAP-PACE ion sensors have found that 0.1%∼1% of the solar wind protons are reflected back from the Moon instead of being absorbed by the lunar surface. Some of the reflected ions are accelerated above solar wind energy as they are picked-up by the solar wind convection electric field. The proton reflection that we have newly discovered around the Moon should be a universal process that characterizes the environment of an airless body.

A study protocol for quantitative targeted absolute proteomics (QTAP) by LC-MS/MS: application for inter-strain differences in protein expression levels of transporters, receptors, claudin-5, and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice

Abstract: Proteomics has opened a new horizon in biological sciences. Global proteomic analysis is a promising technology for the discovery of thousands of proteins, post-translational modifications, polymorphisms, and molecular interactions in a variety of biological systems. The activities and roles of the identified proteins must also be elucidated, but this is complicated by the inability of conventional proteomic methods to yield quantitative information for protein expression. Thus, a variety of biological systems remain “black boxes”. Quantitative targeted absolute proteomics (QTAP) enables the determination of absolute expression levels (mol) of any target protein, including low-abundance functional proteins, such as transporters and receptors. Therefore, QTAP will be useful for understanding the activities and roles of individual proteins and their differences, including normal/disease, human/animal, or in vitro/in vivo. Here, we describe the study protocols and precautions for QTAP experiments including in silico target peptide selection, determination of peptide concentration by amino acid analysis, setup of selected/multiple reaction monitoring (SRM/MRM) analysis in liquid chromatography–tandem mass spectrometry, preparation of protein samples (brain capillaries and plasma membrane fractions) followed by the preparation of peptide samples, simultaneous absolute quantification of target proteins by SRM/MRM analysis, data analysis, and troubleshooting. An application of QTAP in biological sciences was introduced that utilizes data from inter-strain differences in the protein expression levels of transporters, receptors, tight junction proteins and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice. Among 18 molecules, 13 (abcb1a/mdr1a/P-gp, abcc4/mrp4, abcg2/bcrp, slc2a1/glut1, slc7a5/lat1, slc16a1/mct1, slc22a8/oat3, insr, lrp1, tfr1, claudin-5, Na+/K+-ATPase, and γ-gtp) were detected in the isolated brain capillaries, and their protein expression levels were within a range of 0.637-101 fmol/μg protein. The largest difference in the levels between the three strains was 2.2-fold for 13 molecules, although bcrp and mct1 displayed statistically significant differences between C57BL/6J and the other strain(s). Highly sensitive simultaneous absolute quantification achieved by QTAP will increase the usefulness of proteomics in biological sciences and is expected to advance the new research field of pharmacoproteomics (PPx).

Prevalence of dry eye in Japanese eye centers

Abstract: • Background: The purpose of the investigation was to ascertain the prevalence of dry eye in new outpatients. • Methods: A total of 2127 consecutive new outpatients seen in eight Japanese centers from April 1992 to January 1993 underwent comprehensive examinations, including double vital staining and measurement of tear film break-up time, basal tear secretion, and tear clearance. Dry eye was diagnosed if patients had abnormalities of both the tear film and the ocular surface. • Results: Three hundred fifty-nine patients (17%) had dry eye. There was no seasonal pattern for dry eye. The condition was significantly more common in Tokyo than in suburban areas (P < 0.01). The prevalence of dry eye in visual display terminal (VDT) users and contact lens (CL) wearers was significantly higher than in non-VDT users and non-CL wearers (P < 0.05 and P < 0.02, respectively). • Conclusion: Our findings suggest that dry eye is one of the most common ocular disorders encountered by physicians. Furthermore, if patients use VDTs or wear CLs, the likelihood of dry eye occurring is higher.