Introduction: Conformational diseases are caused by structurally abnormal proteins that cannot fold properly and achieve their native conformation. Misfolded proteins frequently originate from genetic mutations that may lead to loss-of-function diseases involving a variety of structurally diverse proteins including enzymes, ion channels, and membrane receptors. Pharmacoperones are small molecules that cross the cell surface plasma membrane and reach their target proteins within the cell, serving as molecular scaffolds to stabilize the native conformation of misfolded or well-folded but destabilized proteins, to prevent their degradation and promote correct trafficking to their functional site of action. Because of their high specificity toward the target protein, pharmacoperones are currently the focus of intense investigation as therapy for several conformational diseases.
Areas covered: This review summarizes data on the mechanisms leading to protein misfolding and the use of pharmacoperone drugs as an experimental approach to rescue function of distinct misfolded/misrouted proteins associated with a variety of diseases, such as lysosomal storage diseases, channelopathies, and G protein-coupled receptor misfolding diseases.
Expert commentary: The fact that many misfolded proteins may retain function, offers a unique therapeutic opportunity to cure disease by directly correcting misrouting through administering pharmacoperone drugs thereby rescuing function of disease-causing, conformationally abnormal proteins. 相似文献
Coherence is a major caveat in quantum computing. While phonons and electrons are weakly coupled in a glass, topological insulators strongly depend on the electron-phonon coupling. Knowledge of the electron−phonon interaction at conducting surfaces is relevant from a fundamental point of view as well as for various applications, such as two-dimensional and quasi-1D superconductivity in nanotechnology. Similarly, the electron−phonon interaction plays a relevant role in other transport properties e.g., thermoelectricity, low-dimensional systems as layered Bi and Sb chalcogenides, and quasi-crystalline materials. Glass-electrolyte ferroelectric energy storage cells exhibit self-charge and self-cycling related to topological superconductivity and electron-phonon coupling; phonon coherence is therefore important. By recurring to ab initio molecular dynamics, it was demonstrated the tendency of the Li3ClO, Li2.92Ba0.04ClO, Na3ClO, and Na2.92Ba0.04ClO ferroelectric-electrolytes to keep phonon oscillation coherence for a short lapse of time in ps. Double-well energy potentials were obtained while the electrolyte systems were thermostatted in a heat bath at a constant temperature. The latter occurrences indicate ferroelectric type behavior but do not justify the coherent self-oscillations observed in all types of cells containing these families of electrolytes and, therefore, an emergent type phenomenon where the full cell works as a feedback system allowing oscillations coherence must be realized. A comparison with amorphous SiO2 was performed and the specific heats for the various species were calculated. 相似文献
The use of phase change materials (PCMs) is an attractive method for energy storage and utilization in building envelopes. Here, shape-stabilized phase change materials (SS-PCMs) were prepared via direct adsorption using mesoporous silica (MS) with different pore diameters as the support matrix. The leakage properties, microstructure, chemical structure, thermophysical properties, activation energy, thermal stability and thermal storage-release characteristics of paraffin and SS-PCMs were investigated. The results show that the maximum mass proportion of paraffin in SS-PCMs is 70% when the average pore diameter of mesoporous silica is 15 nm, and the phase change temperature and latent heat of the corresponding SS-PCM are 23.6 °C and 135.4 kJ/kg, respectively. No chemical reaction occurs between mesoporous silica and paraffin and the SS-PCMs exhibit high thermal stability. The high activation energy of the paraffin (70%)/MS1 SS-PCM verifies that the shape and thermal properties can be maintained stably during phase change conversions. The time required for SS-PCMs to complete the thermal storage and release process is reduced by up to 34.0% compared with that for pure paraffin, showing a decline in the thermal conductivity of SS-PCMs after the addition of mesoporous silica. Hence, the prepared paraffin/MS SS-PCMs, in particular paraffin (70%)/MS1 SS-PCM, can be used for storing thermal energy and regulating indoor temperature in buildings. 相似文献
Magnesium-based alloys are attractive as hydrogen storage materials due to their lightweight and high absorption, but their high operating temperatures and very slow kinetics are obstacles to practical applications. Therefore, the effect of CaO has improved the hydrogenation kinetics and slowed down the degradation. The Mg2NiHx–CaO composites were prepared by hydrogen-induced mechanical alloying (HIMA). Hydrogenation kinetics was performed by using an Automatic PCT Measuring System and evaluated in the temperature range of 423, 523, and 623 K. As a result of calculating the hydrogen absorption amounts through the hydrogenation kinetics curve, they were calculated as about 0.52 wt%, 1.21 wt%, and 1.59 wt% (Mg2NiHx–10 wt% CaO). In this study, the material environmental aspects of Mg2NiHx–CaO composites were investigated through life cycle assessment (LCA). LCA was performed analyzing the environmental impact characteristics of the manufacturing process by using Gabi software and the Eco-Indicator 99’ and Centrum voor Milieuweten schappen (CML 2001) methodology. As a result, the contents of global warming potential (GWP) and fossil fuels were found to have a higher impact than other impact categories. 相似文献