56016 research outputs found
Sort by
Nigericin protects obesity-induced insulin resistance by reducing endotrophin generation via MMP activatio
No full textEndotrophin, a cleavage product of collagen VI??3 (COL6A3), is a major contributor of adipose fibro-inflammation and exacerbates metabolic derangements such as insulin resistance. Previously we demonstrated that endotrophin was generated from the COL6A3 through the action of hypoxia-induced matrix metalloproteinases (MMPs) in obese adipose tissue. We reasoned that inhibition of MMPs activity may ameliorate the vicious phenotypes of obese adipose environment. In this study, we identified nigericin as an inhibitor of MMPs to suppress the endotrophin generation. The metabolic effects of nigericin were validated with HFD-fed obese mice compared to those in lean controls. Nigericen markedly improved metabolic parameters such as glucose intolerance and insulin responsiveness in CoCl2-stimulated adipocytes and in the obese mice. Also, nigericin-treated obese mice have reduced fibrosis and inflammation in adipose tissues. This was accompanied by decreased levels of endotrophin and its MMPs??? cleavage activities in adipose tissue. In vitro studies have revealed that nigericin effectively suppresses MMPs activation (MMP9 and MMP16) in HEK293T cells, and the action of nigericin was partly mediated by the disruption of endotrophin/MMP9 interaction. Our findings strongly suggest that nigericin protects local fibro-inflammation in adipose tissues and systemic insulin resistance in HFD-fed obese mice, and that is mediated by inhibition of endotrophin cleavage activities via blocking interactions between MMP9 and endotrophin, at least in part. Therefore, Nigericin could be a potential drug candidate to treat for the obesity-related complications
????????? ?????????????????? ?????? ?????? ?????? ????????? ????????? ??????????????? ?????? ?????? ?????? ??????
No full text
?????? 3D ????????? ???????????? ??????, ?????? ??? ?????? ????????? ??????????????? ????????? ??????????????? ????????? ????????? ????????????
No full text
Robust membrane protein tweezers reveal the folding speed limit of helical membrane proteins
No full textSingle-molecule tweezers, such as magnetic tweezers, are powerful tools for probing nm-scale structural changes in single membrane proteins under force. However, the weak molecular tethers used for the membrane protein studies have limited the observation of long-time, repetitive molecular transitions due to force-induced bond breakage. The prolonged observation of numerous transitions is critical in reliable characterizations of structural states, kinetics, and energy barrier properties. Here, we present a robust single-molecule tweezer method that uses dibenzocyclooctyne cycloaddition and traptavidin binding, enabling the estimation of the folding ???speed limit??? of helical membrane proteins. This method is >100 times more stable than a conventional linkage system regarding the lifetime, allowing for the survival for ~12 hr at 50 pN and ~1000 pulling cycle experiments. By using this method, we were able to observe numerous structural transitions of a designer single-chained transmembrane homodimer for 9 hr at 12 pN and reveal its folding pathway including the hidden dynamics of helix-coil transitions. We characterized the energy barrier heights and folding times for the transitions using a model-independent deconvolution method and the hidden Markov modeling analysis, respectively. The Kramers rate framework yields a considerably low-speed limit of 21 ms for a helical hairpin formation in lipid bilayers, compared to ??s scale for soluble protein folding. This large discrepancy is likely due to the highly viscous nature of lipid membranes, retarding the helix-helix interactions. Our results offer a more valid guideline for relating the kinetics and free energies of membrane protein folding
Vectorial Electron Transfer for Dye-Sensitized Solar Cells and Their Applications into Power Sources
No full textImprovement potential detection of integrated biomethane liquefaction and liquid air energy storage system
No full textBiomethane (BM) is highly competitive bio-energy alternatives for lowering the dependency on fossil fuels globally. The form of BM that is most suitable for storage as well as shipping to far-flung areas of the world is liquefied biomethane (LBM). However, due to the significant power consumption by compressors used in BM liquefaction process (like natural gas), it is a cost-and energy-intensive operation. Additionally, because bio-methane is created at atmospheric pressure, unlike ordinary natural gas, liquefaction requires more power consumption because the pressure at which BM is produced is much less than corresponding critical pressure. Therefore, an integrated system of liquid air energy storage (LAES) system discharging end and a biomethane liquefaction process is introduced that is both economical and efficient in terms of energy use. The sub-cooling and liquefaction processes of biomethane are aided by the cold-exergy of liquid air at the time of regasification mode of LAES, which eventually lowers the refrigeration cycle duty of LBM process. On the other hand, gaining the additional advantage, the expansion stage of liquid air is aided by the thermal exergy of a compressed mixed refrigerant (MR). On the basis of conventional exergy analysis, composite curves analysis, advanced exergy analysis, and sustainability index, the impacts of novel integration of LBM and LAES are estimated in this study. Conventional exergy analysis determines that 15.9 % of exergy destruction is decreased in the proposed LBM-LAES system having additional power production of 4529 kW using gas turbine. Results based on advanced exergy analysis conclude that avoidable, endogenous and exogenous portions of exergy destructions are decreased by 28.9 %, 39.9 % and 43 %, respectively; which implies the significant improvement potential. Composite curves analysis depicts that the efficiency of primary cryogenic heat exchanger is improved in the proposed integrated scheme. Additionally, the overall sustainability index is increased from 1.55 to 2.13 for LBM-LAES process