Intellectual property strategies for improving profitability -A case study of the leading pharmaceutical companies-

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How to Balance the Intellectual Property Conflict-a Case Study of Japanese Pharmaceutical Companies in Emerging Countries-

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From adhesion complex to signaling hub: the dual role of dystroglycan

Dystroglycan (DG) is a transmembrane protein widely expressed in multiple cells and tissues. It is formed by two subunits, alpha- and beta-DG, and represents a molecular bridge between the outside and the inside of the cell, which is essential for the mechanical and structural stability of the plasma membrane. The alpha-subunit is a cell-surface protein that binds to the extracellular matrix (ECM) and is tightly associated with the plasma membrane via a non-covalent interaction with the beta-subunit, which, in turn, is a transmembrane protein that binds to the cytoskeletal actin. DG is a versatile molecule acting not only as a mechanical building block but also as a modulator of outside-inside signaling events. The cytoplasmic domain of beta-DG interacts with different adaptor and cytoskeletal proteins that function as molecular switches for the transmission of ECM signals inside the cells. These interactions can modulate the involvement of DG in different biological processes, ranging from cell growth and survival to differentiation and proliferation/regeneration. Although the molecular events that characterize signaling through the ECM-DG-cytoskeleton axis are still largely unknown, in recent years, a growing list of evidence has started to fill the gaps in our understanding of the role of DG in signal transduction. This mini-review represents an update of recent developments, uncovering the dual role of DG as an adhesion and signaling molecule that might inspire new ideas for the design of novel therapeutic strategies for pathologies such as muscular dystrophy, cardiomyopathy, and cancer, where the DG signaling hub plays important roles

大手製薬会社の知的財産戦略 -研究開発の収益性向上の視点から-

明治大学博士（経営学）Article2018doctoral thesi

Molecular mechanisms underlying muscle wasting in huntington’s disease

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disorder caused by pathogenic expansions of the triplet cytosine-adenosine-guanosine (CAG) within the Huntingtin gene. These expansions lead to a prolongation of the poly-glutamine stretch at the N-terminus of Huntingtin causing protein misfolding and aggregation. Huntingtin and its pathological variants are widely expressed, but the central nervous system is mainly affected, as proved by the wide spectrum of neurological symptoms, including behavioral anomalies, cognitive decline and motor disorders. Other hallmarks of HD are loss of body weight and muscle atrophy. This review highlights some key elements that likely provide a major contribution to muscle atrophy, namely, alteration of the transcriptional processes, mitochondrial dysfunction, which is strictly correlated to loss of energy homeostasis, inflammation, apoptosis and defects in the processes responsible for the protein quality control. The improvement of muscular symptoms has proven to slow the disease progression and extend the life span of animal models of HD, underlining the importance of a deep comprehension of the molecular mechanisms driving deterioration of muscular tissue

Verbascoside Elicits Its Beneficial Effects by Enhancing Mitochondrial Spare Respiratory Capacity and the Nrf2/HO-1 Mediated Antioxidant System in a Murine Skeletal Muscle Cell Line

Muscle weakness and muscle loss characterize many physio-pathological conditions, including sarcopenia and many forms of muscular dystrophy, which are often also associated with mitochondrial dysfunction. Verbascoside, a phenylethanoid glycoside of plant origin, also named acteoside, has shown strong antioxidant and anti-fatigue activity in different animal models, but the molecular mechanisms underlying these effects are not completely understood. This study aimed to investigate the influence of verbascoside on mitochondrial function and its protective role against H2O2-induced oxidative damage in murine C2C12 myoblasts and myotubes pre-treated with verbascoside for 24 h and exposed to H2O2. We examined the effects of verbascoside on cell viability, intracellular reactive oxygen species (ROS) production and mitochondrial function through high-resolution respirometry. Moreover, we verified whether verbascoside was able to stimulate nuclear factor erythroid 2-related factor (Nrf2) activity through Western blotting and confocal fluorescence microscopy, and to modulate the transcription of its target genes, such as heme oxygenase-1 (HO-1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), by Real Time PCR. We found that verbascoside (1) improved mitochondrial function by increasing mitochondrial spare respiratory capacity; (2) mitigated the decrease in cell viability induced by H2O2 and reduced ROS levels; (3) promoted the phosphorylation of Nrf2 and its nuclear translocation; (4) increased the transcription levels of HO-1 and, in myoblasts but not in myotubes, those of PGC-1α. These findings contribute to explaining verbascoside’s ability to relieve muscular fatigue and could have positive repercussions for the development of therapies aimed at counteracting muscle weakness and mitochondrial dysfunction

大学剣道における女子競技者の踏み込み音が打突の評価に及ぼす影響

鹿屋体育大学博士（体育スポーツ学）平成30年度doctoral thesi

キリスト教宣教団の影響力 : 旧ゴールドコーストにおけるメソジスト宣教団の事例

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測定の問題(Ⅱ)

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Industrial Development and Japanese Spinners’ Management\nActivities

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