The human lens is comprised largely of crystallin proteins assembled into a highly ordered, interactive macro-structure essential for lens transparency and refractive index. Any disruption of intra- or inter-protein interactions will alter this delicate structure, exposing hydrophobic surfaces, with consequent protein aggregation and cataract formation. Cataracts are the most common cause of blindness worldwide, affecting tens of millions of people, and currently the only treatment is surgical removal of cataractous lenses. The precise mechanisms by which lens proteins both prevent aggregation and maintain lens transparency are largely unknown. Lanosterol is an amphipathic molecule enriched in the lens. It is synthesized by lanosterol synthase (LSS) in a key cyclization reaction of a cholesterol synthesis pathway. Here we identify two distinct homozygous LSS missense mutations (W581R and G588S) in two families with extensive congenital cataracts. Both of these mutations affect highly conserved amino acid residues and impair key catalytic functions of LSS. Engineered expression of wild-type, but not mutant, LSS prevents intracellular protein aggregation of various cataract-causing mutant crystallins. Treatment by lanosterol, but not cholesterol, significantly decreased preformed protein aggregates both in vitro and in cell-transfection experiments. We further show that lanosterol treatment could reduce cataract severity and increase transparency in dissected rabbit cataractous lenses in vitro and cataract severity in vivo in dogs. Our study identifies lanosterol as a key molecule in the prevention of lens protein aggregation and points to a novel strategy for cataract prevention and treatment.
The development of high specific surface area amidoxime-based polymeric (H-ABP) fibers presents a new technology for the synthesis of highly efficient adsorbents for uranium extraction from seawater (UES), thus opening a whole new means of nuclear fuel production from the ocean.
Viruses interfere with and usurp host machinery and circumvent defense responses to create a suitable cellular environment for successful infection. This is usually achieved through interactions between viral proteins and host factors. Geminiviruses are a group of plant-infecting DNA viruses, of which some contain a betasatellite, known as DNAβ. Here, we report that Cotton leaf curl Multan virus (CLCuMuV) uses its sole satellite-encoded protein βC1 to regulate the plant ubiquitination pathway for effective infection. We found that CLCuMu betasatellite (CLCuMuB) βC1 interacts with NbSKP1, and interrupts the interaction of NbSKP1s with NbCUL1. Silencing of either NbSKP1s or NbCUL1 enhances the accumulation of CLCuMuV genomic DNA and results in severe disease symptoms in plants. βC1 impairs the integrity of SCFCOI1 and the stabilization of GAI, a substrate of the SCFSYL1 to hinder responses to jasmonates (JA) and gibberellins (GA). Moreover, JA treatment reduces viral accumulation and symptoms. These results suggest that CLCuMuB βC1 inhibits the ubiquitination function of SCF E3 ligases through interacting with NbSKP1s to enhance CLCuMuV infection and symptom induction in plants.
Solid alkaline fuel cells with anion exchange membranes (AEMs) have drawn wide attention and have become an important focus in the field of renewable energy cells in recent years due to their high electrode activity, potential application of non‐precious metal catalysts, and relatively low requirements for fuel purity. AEM is the central component in solid alkaline fuel cells, and plays the role of conducting ions, blocking fuel crossover and providing catalyst support in fuel cells. Its performance directly affects the efficiency and service life of fuel cells. With some exceptions, the majority of AEMs have relatively low hydroxide conductivity and poor durability, which cannot meet the requirements of practical applications. The past decade has witnessed great progress in AEM designs and stability. Various kinds of AEMs with different cationic structures have been designed, and their properties and application in fuel cells are investigated. This review provides a comparative investigation and summary of highlights from the design of cationic structures for AEMs, including cyclic and spirocyclic quaternary ammonium cations, modified quaternary phosphonium, modified imidazoles, guanidinium, and metal cations. The authors’ perspective on the remaining challenges and directions of AEMs research for future development are also discussed.
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