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We assessed the efficiency and limitations of using a 10-point self-check sheet on the day of participation in an athletic event to prevent medical accidents in the Kakitsubata Marathon. In 2003, 633 completed the self-check sheet, 17 (2.7%)canceled participation in the race and 617 participated and completed the race. In 2004, 758 completed the self-check sheet, 37 (4.8%)canceled participation in the race, 725 participated and 724 completed the race. The one person that did not complete the race was a 57-year old male, who collapsed with heat stroke and had to receive first aid treatment. The number of people who enjoy sports is increasing, but many accidents happen during such activities. This self-assessment is useful as a screening tool to confirm the physical condition of the participants from the administration perspective in order to provide medical support, and as an opportunity to check one's own physical condition on the day of participation in a marathon race from the participants' perspective. [ABSTRACT FROM AUTHOR]

We experienced stress fractures of the lower third of the fibula. These were possibly caused by a "rope-skipping" activity in a first-grade gymnastics class. We consider that cases of stress fracture in children should be recognized by sports instructors and medical personnel to ensure early detection and treatment. [ABSTRACT FROM AUTHOR]

Because of the advent of genome-editing technology, gene knockout (KO) hamsters have become attractive research models for diverse diseases in humans. This study established a new KO model of diabetes by disrupting the insulin receptor substrate-2 (Irs2) gene in the golden (Syrian) hamster. Homozygous KO animals were born alive but with delayed postnatal growth until adulthood. They showed hyperglycemia, high HbA1c, and impaired glucose tolerance. However, they normally responded to insulin stimulation, unlike Irs2 KO mice, an obese type 2 diabetes (T2D) model. Consistent with this, Irs2 KO hamsters did not increase serum insulin levels upon glucose administration and showed β-cell hypoplasia in their pancreas. Thus, our Irs2 KO hamster provide a unique T2D animal model that is distinct from the obese T2D models. This model may contribute to a better understanding of the pathophysiology of human non-obese T2D with β-cell dysfunction, the most common type of T2D in East Asian countries, including Japan., (© 2024. The Author(s).)

Removal of somatic histone H3 lysine 9 trimethylation (H3K9me3) from the embryonic genome can improve the efficiency of mammalian cloning using somatic cell nuclear transfer (SCNT). However, this strategy involves the injection of histone demethylase mRNA into embryos, which is limiting because of its invasive and labor-consuming nature. Here, we report that treatment with an inhibitor of G9a (G9ai), the major histone methyltransferase that introduces H3K9me1/2 in mammals, greatly improved the development of mouse SCNT embryos. Intriguingly, G9ai caused an immediate reduction of H3K9me1/2, a secondary loss of H3K9me3 in SCNT embryos, and increased the birth rate of cloned pups about 5-fold (up to 3.9%). G9ai combined with the histone deacetylase inhibitor trichostatin A further improved this rate to 14.5%. Mechanistically, G9ai and TSA synergistically enhanced H3K9me3 demethylation and boosted zygotic genome activation. Thus, we established an easy, highly effective SCNT protocol that would enhance future cloning research and applications., Competing Interests: Declaration of interests F.S., A.I., and M.Y. are inventors on a PCT international patent application (WO/2021/106988) that covers RK-701, a compound studied in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Alzheimer's disease (AD) is characterized by the extensive deposition of amyloid-β peptide (Aβ) in the brain. Brain Aβ level is regulated by a balance between Aβ production and clearance. The clearance rate of Aβ is decreased in the brains of sporadic AD patients, indicating that the dysregulation of Aβ clearance mechanisms affects the pathologic process of AD. Astrocytes are among the most abundant cells in the brain and are implicated in the clearance of brain Aβ via their regulation of the blood-brain barrier, glymphatic system, and proteolytic degradation. The cellular morphology and activity of astrocytes are modulated by several molecules, including ω3 polyunsaturated fatty acids, such as docosahexaenoic acid, which is one of the most abundant lipids in the brain, via the G protein-coupled receptor GPR120/FFAR4. In this study, we analyzed the role of GPR120 signaling in the Aβ-degrading activity of astrocytes. Treatment with the selective antagonist upregulated the matrix metalloproteinase (MMP) inhibitor-sensitive Aβ-degrading activity in primary astrocytes. Moreover, the inhibition of GPR120 signaling increased the levels of Mmp2 and Mmp14 mRNAs, and decreased the expression levels of tissue inhibitor of metalloproteinases 3 ( Timp3 ) and Timp4 , suggesting that GPR120 negatively regulates the astrocyte-derived MMP network. Finally, the intracerebral injection of GPR120-specific antagonist substantially decreased the levels of TBS-soluble Aβ in male AD model mice, and this effect was canceled by the coinjection of an MMP inhibitor. These data indicate that astrocytic GPR120 signaling negatively regulates the Aβ-degrading activity of MMPs. SIGNIFICANCE STATEMENT The level of amyloid β (Aβ) in the brain is a crucial determinant of the development of Alzheimer's disease. Here we found that astrocytes, which are the most abundant cell type in the CNS, harbor degrading activity against Aβ, which is regulated by GPR120 signaling. GPR120 is involved in the inflammatory response and obesity in peripheral organs. However, the pathophysiological role of GPR120 in Alzheimer's disease remains unknown. We found that selective inhibition of GPR120 signaling in astrocytes increased the Aβ-degrading activity of matrix metalloproteases. Our results suggest that GPR120 in astrocytes is a novel therapeutic target for the development of anti-Aβ therapeutics., (Copyright © 2021 the authors.)

In the design of solar-energy conversion electrochemical systems, it is important to consider that natural sunlight fluctuates. By taking nitrous acid photoreduction as an example, this study has shown that the reaction pathway, and hence the reaction products, dynamically respond to variations in light intensity. Under irradiation, the photooxidation of methanol (as sacrificial agent) on TiO 2 and the reduction of HNO 2 on a Cu-modified covalent triazine framework (Cu-CTF) are electrically coupled, which leads to the photoreduction of HNO 2 without an external bias. The major product of the reaction changes from N 2 O to NH 4 + with an increase in the light intensity. The operating potential also shifts negatively (or positively) when the light intensity is increased (or decreased). These results indicate that a change in the reaction pathway is triggered by a change in the operating potential of the Cu-CTF catalyst under varying light intensity. Such a light-intensity-dependent change in the reaction pathway is particularly important in systems that use photoresponsive electrodes and where multiple products can be obtained, such as the solar-driven reduction of carbon dioxide and nitrogen oxides., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We proposed and demonstrated a wavelength-division multiplexing (WDM) optical beam-steering device consisting of a thermally controlled doubly periodic Si two-dimensional bulk photonic crystal waveguide and coupled microring multiplexers. Beam forming and steering while maintaining a sharp profile is much easier in this device than with optical phased arrays which need the fine phase control. By dividing the range of beam-steering angles into different wavelength channels, it is possible to cover a wide range of angles, even when each angle is small. In this study, we fabricated a device with four wavelength channels, each of which showed beam steering of 4°-5° as a result of heating, resulting in a total of 16°. Two-dimensional steering is also achieved by loading a collimator lens and selecting one waveguide from those arrayed. We evaluated 112 resolution points with four wavelengths and 448 points in total by switching four waveguides. If this WDM concept is introduced into light detection and ranging and the number of wavelengths is increased, it will be possible to increase the sensing throughput, which is usually constrained by the round-trip time of light, by simultaneous parallel operation.

Photo-induced electron-transfer reactions occurring at the interface between titanium dioxide modified with hexacyanoferrate(iii) (Fe(iii)-CN-TiO2) were characterized. After the modification of TiO2 with [Fe(CN)6]3- ions, a new absorption appeared in the visible light region (410 to 700 nm). Absorption spectroscopy measurements showed that Fe(iii)-CN-TiO2 was converted to Fe(ii)-CN-TiO2 under visible light irradiation (>520 nm), which indicates that the new absorption was assignable to direct charge transfer from the valence band to the modified Fe(iii) ions.

Deposition of amyloid-β (Aβ) as senile plaques is one of the pathological hallmarks in the brains of Alzheimer's disease (AD) patients. In addition, glial activation has been found in AD brains, although the precise pathological role of astrocytes remains unclear. Here, we identified kallikrein-related peptidase 7 (KLK7) as an astrocyte-derived Aβ degrading enzyme. Expression of KLK7 mRNA was significantly decreased in the brains of AD patients. Ablation of Klk7 exacerbated the thioflavin S-positive Aβ pathology in AD model mice. The expression of Klk7 was upregulated by Aβ treatment in the primary astrocyte, suggesting that Klk7 is homeostatically modulated by Aβ-induced responses. Finally, we found that the Food and Drug Administration-approved anti-dementia drug memantine can increase the expression of Klk7 and Aβ degradation activity specifically in the astrocytes. These data suggest that KLK7 is an important enzyme in the degradation and clearance of deposited Aβ species by astrocytes involved in the pathogenesis of AD., (© 2018 The Authors. Published under the terms of the CC BY 4.0 license.)

Amyloid-β protein (Aβ) is the main component of senile plaques in the brains of Alzheimer disease (AD) patients. Aβ is proteolytically derived from amyloid-β precursor protein by β- and γ-secretases. Secreted Aβ is then eliminated from the central nervous system by multiple clearance mechanisms, including phagocytosis, immune responses, and proteolytic degradation. These dynamic metabolic processes, which are referred to as Aβ economy, regulate steady-state brain Aβ levels. Familial AD-linked genetic mutations augment the production and aggregation of Aβ. In contrast, rare genetic variants that reduce Aβ production were protective against AD. Moreover, decreased Aβ clearance has been demonstrated in sporadic AD patients, suggesting that dysregulation of Aβ economy contributes to the development of AD. Thus, several approaches to inhibit the production as well as to enhance the clearance of Aβ have been investigated as potential therapeutics against AD. In this manuscript, we introduce the molecules and cellular mechanisms involved in the regulation of Aβ economy and discuss the current understanding of these processes in the development of therapeutics against AD. J. Cell. Biochem. 118: 4183-4190, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Compact non-mechanical beam steering devices are desired not only for current common applications, but also for advanced applications such as light detection and ranging. We use a Si photonic crystal slow-light waveguide with a diffraction grating, which radiates the guided mode to free space and steers a fan beam by sweeping the wavelength. Due to its large angular dispersion, slow light enhances the steering range without degrading the beam quality, resulting in more resolution points. We fabricated 600 μm devices and observed a 23° steering range and a beam divergence of 0.23°, which resulted in 100 resolution points.

Memantine, an uncompetitive glutamatergic N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used as medication for the treatment of Alzheimer's disease (AD). It has been reported that memantine reduces amyloid-β peptide (Aβ) levels in both neuronal cultures and in brains of animal models of AD. However, the underlying mechanism of these effects is unclear. Here we examined the effect of memantine on Aβ production. Memantine was administered to 9-month-old Tg2576 mice, a transgenic mouse model of AD, at 10 or 20mg/kg/day in drinking water for 1 month. Memantine significantly reduced the amounts of both CHAPS-soluble and CHAPS-insoluble Aβ in the brains of Tg2576 mice. Memantine at 10mg/kg/day for 1 month also reduced the levels of insoluble Aβ42 in the brains of aged F344 rats. Moreover, memantine reduced Aβ and sAPPβ levels in conditioned media from rat primary cortical cultures without affecting the enzymatic activities of α-secretase, β-secretase, or γ-secretase. Notably, in a cell-surface biotinylation assay, memantine increased the amount of amyloid precursor protein (APP) at the cell surface without changing the total amount of APP. Collectively, our results indicate that chronic treatment with memantine reduces the levels of Aβ both in AD models and in aged animals, and that memantine affects the endocytosis pathway of APP, which is required for β-secretase-mediated cleavage. This leads to a reduction in Aβ production. These results suggest that memantine reduces Aβ production and plaque deposition through the regulation of intracellular trafficking of APP., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Naturally occurring chlorophyll-a was chemically modified to methyl 3-aminomethyl-pyropheophorbides-a including primary, secondary, and tertiary amines. Reductive amination of methyl pyropheophorbide-d possessing the 3-formyl group with ammonia efficiently gave a chlorin dimer covalently linked with CH2NHCH2 at the 3-position, which was transformed into a trimer through the substitution at the amino group. Conformational analyses by (1)H NMR spectroscopic observation and molecular modeling estimation indicated that the dimer and trimer were apt to form closely packed structures. Chlorin chromophores in the dimer and trimer were weakly interacted in dichloromethane to shift their Qy absorption bands to longer wavelengths by 4-6nm than the maxima of the corresponding monomer. In the red-shifted Qy region, the trimer gave an S-shaped circular dichroism band by exciton coupling of composite chlorin units. All the semi-synthetic chlorophyll derivatives were highly fluorescent and no intramolecular quenching was observed even in the trimer. The behaviors would be ascribable to the formation of compact conformers and suppression of intramolecular motion, which are important to construct light-harvesting antenna complexes in phototrophs and their model systems., (Copyright © 2015 Elsevier Ltd. All rights reserved.)