3,422 research outputs found
Molecular mechanisms and therapeutic interventions in sarcopenia
No full textSarcopenia is the degenerative loss of muscle mass and function with aging. Recently sarcopenia was recognized as a clinical disease by the International Classification of Disease, 10th revision, Clinical Modification. An imbalance between protein synthesis and degradation causes a gradual loss of muscle mass, resulting in a decline of muscle function as a progress of sarcopenia. Many mechanisms involved in the onset of sarcopenia include age-related factors as well as activity-, disease-, and nutrition-related factors. The stage of sarcopenia reflecting the severity of conditions assists clinical management of sarcopenia. It is important that systemic descriptions of the disease conditions include age, sex, and other environmental risk factors as well as levels of physical function. To develop a new therapeutic intervention needed is the detailed understanding of molecular and cellular mechanisms by which apoptosis, autophagy, atrophy, and hypertrophy occur in the muscle stem cells, myotubes, and/or neuromuscular junction. The new strategy to managing sarcopenia will be signal-modulating small molecules, natural compounds, repurposing of old drugs, and muscle-specific microRNAs
First-principles calculation of terahertz absorption with dispersion correction of 2,2′-bithiophene as model compound
No full textTerahertz absorption of organic materials is closely linked to molecular arrangements and their intermolecular interactions and is important for material identification as well as THz generation. Theoretical calculations of solid-state vibrations known as phonons help to understand intermolecular interactions responsible for THz absorption but frequently are of limited use without considering dispersion interaction. In this study, we have calculated the THz phonon modes of an organic model crystal 2,2′-bithiophene, considering dispersion intermolecular interactions assuming the fixed cell dimensions. Both energies and intensities of phonon modes at low frequencies were interpreted concentrating on the intermolecular level in conjunction with hydrogen bonds and showed an excellent agreement with the experimental results. This approach to identify the phonon modes responsible for strong THz absorptions and to interpret those modes in terms of intermolecular vibrations is also expected to be applicable to the field of THz generation using nonlinear optical organic crystals
PI3Kγ contributes to MEK1/2 activation in oxidative glutamate toxicity via PDK1
No full textThe role of phosphoinositide 3-kinase (PI3K) in oxidative glutamate toxicity is not clear. Here, we investigate its role in HT22 mouse hippocampal cells and primary cortical neuronal cultures, showing that inhibitors of PI3K, LY294002, and wortmannin suppress extracellular hydrogen peroxide (H 2O2) generation and increase cell survival during glutamate toxicity in HT22 cells. The mitogen-activated protein kinase kinase (MEK) inhibitor U0126 also reduced glutamate-induced H2O2 generation and inhibited phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. LY294002 was seen to abolish phosphorylation of both ERK1/2 and Akt. A small interfering RNA (siRNA) study showed that PI3Kβ and PI3Kγ, rather than PI3Kα and PI3Kδ, contribute to glutamate-induced H2O2 generation and cell death. PI3Kγ knockdown also inhibited glutamate-induced ERK1/2 phosphorylation, whereas transfection with the constitutively active form of human PI3Kγ (PI3Kγ-CAAX) triggered MEK1/2 and ERK1/2 phosphorylation and H 2O2 generation without glutamate exposure. This H 2O2 generation was reduced by inhibition of MEK. Transfection with kinase-dead 3-phosphoinositide-dependent protein kinase 1 (PDK1-KD) reduced glutamate-induced ERK1/2 phosphorylation and H 2O2 generation. Accordingly, cotransfection of cells with PDK1-KD and PI3Kγ-CAAX suppressed PI3Kγ-CAAX-triggered ERK1/2 phosphorylation and H2O2 generation. These results suggest that activation of PI3Kγ induces ERK1/2 phosphorylation, leading to extracellular H2O2 generation via PDK1 in oxidative glutamate toxicity. Glutamate induces extracellular H2O2 generation by NADPH oxidase 4 (Nox4), leading to cell death in neurons. Our experiments, using siRNAs and chemical inhibitors, showed the PI3Kγ-PDK1-MEK axis but not Akt1, mTOR, or S6K to be involved in the glutamate-induced H2O2 generation and the subsequent toxicity in neurons. Glutamate induces extracellular H2O2 generation by NADPH oxidase 4 (Nox4), leading to cell death in neurons. Our experiments, using siRNAs and chemical inhibitors, showed the PI3Kγ-PDK1-MEK axis but not Akt1, mTOR, or S6K to be involved in the glutamate-induced H2O2 generation and the subsequent toxicity in neurons.open
Prediction of 1-year Graft Survival Rates in Kidney Transplantation: A Bayesian Network Model
No full textThis article is confirmed to be submitted through the review and edition of the Korean Operations Research and Management Science Society. Please enter the title (Journal/Proceedings), volume, number, and pages properly when citing the article.A Bayesian network model was developed to predict 1-year graft survival rates after kidney transplantation. The data from a random sample of 90% of 35,366 kidney transplants performed in the United States between 1987 and 1991 were used to build a Bayesian network model. The discriminating power and the accuracy of the model predicting 1-year graft survival rates was demonstrated using the remaining 10% test sample. By more accurately predicting graft survival, such models may be used to refine existing rule-based transplant-allocation systems and, thus, improve patient and transplant outcomes
Effects of Fe content in Al-Fe alloys on the microstructures and their hydrogen generation properties in alkaline water
No full textEffects of Co electroplating on the corrosion resistance of 310S cathode current collector in MCFC
No full textDevelopment of Al-Cu alloys with high performance for hydrogen generation in alkaline water
No full textAlloy design of Al-Cu alloys for fast hydrogen generation from hydrolysis in alkaline water
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