Regulation of alpha1 Na/K-ATPase expression by cholesterol

We have reported that α1 Na/K-ATPase regulates the trafficking of caveolin-1 and consequently alters cholesterol distribution in the plasma membrane. Here, we report the reciprocal regulation of α1 Na/K-ATPase by cholesterol. Acute exposure of LLC-PK1 cells to methyl β-cyclodextrin led to parallel decreases in cellular cholesterol and the expression of α1 Na/K-ATPase. Cholesterol repletion fully reversed the effect of methyl β-cyclodextrin. Moreover, inhibition of intracellular cholesterol trafficking to the plasma membrane by compound U18666A had the same effect on α1 Na/K-ATPase. Similarly, the expression of α1, but not α2 and α3, Na/K-ATPase was significantly reduced in the target organs of Niemann-Pick type C mice where the intracellular cholesterol trafficking is blocked. Mechanistically, decreases in the plasma membrane cholesterol activated Src kinase and stimulated the endocytosis and degradation of α1 Na/K-ATPase through Src- and ubiquitination-dependent pathways. Thus, the new findings, taken together with what we have already reported, revealed a previously unrecognized feed-forward mechanism by which cells can utilize the Src-dependent interplay among Na/K-ATPase, caveolin-1, and cholesterol to effectively alter the structure and function of the plasma membrane.     

抗冻蛋白结构与抗冻机制

抗冻蛋白(amifreeze proteins,AFPs)是20世纪60年代从极地鱼血淋巴中分离的一种大分子抗冻剂,迄今为止科学工作者已从陆地昆虫、植物、细菌和真菌等各类生物中分离到多种抗冻蛋白,并测得了它们的基因序列及一些晶体结构,近些年的工作主要集中在该类蛋白质抗冻机制的研究上。抗冻蛋白具有广泛的应用前景,它不但可以应用于食物的冷鲜贮存及移植器官的低温保存,还可通过转基因提高经济作物的抗冻能力。     

An Efficient Supervised Training Algorithm for Multilayer Spiking Neural Networks

The spiking neural networks (SNNs) are the third generation of neural networks and perform remarkably well in cognitive tasks such as pattern recognition. The spike emitting and information processing mechanisms found in biological cognitive systems motivate the application of the hierarchical structure and temporal encoding mechanism in spiking neural networks, which have exhibited strong computational capability. However, the hierarchical structure and temporal encoding approach require neurons to process information serially in space and time respectively, which reduce the training efficiency significantly. For training the hierarchical SNNs, most existing methods are based on the traditional back-propagation algorithm, inheriting its drawbacks of the gradient diffusion and the sensitivity on parameters. To keep the powerful computation capability of the hierarchical structure and temporal encoding mechanism, but to overcome the low efficiency of the existing algorithms, a new training algorithm, the Normalized Spiking Error Back Propagation (NSEBP) is proposed in this paper. In the feedforward calculation, the output spike times are calculated by solving the quadratic function in the spike response model instead of detecting postsynaptic voltage states at all time points in traditional algorithms. Besides, in the feedback weight modification, the computational error is propagated to previous layers by the presynaptic spike jitter instead of the gradient decent rule, which realizes the layer-wised training. Furthermore, our algorithm investigates the mathematical relation between the weight variation and voltage error change, which makes the normalization in the weight modification applicable. Adopting these strategies, our algorithm outperforms the traditional SNN multi-layer algorithms in terms of learning efficiency and parameter sensitivity, that are also demonstrated by the comprehensive experimental results in this paper.     

Age validation,and comparison of otolith,vertebra and opercular bone for estimating age of <Emphasis Type="BoldItalic">Schizothorax o’connori</Emphasis> in the Yarlung Tsangpo River,Tibet

A collection of 514 Schizothorax o’connori was made between August 2008 and August 2009 from Yarlung Tsangpo River to assess the suitability of three bony structures for age estimation. The annulus characteristics of otolith, vertebra and opercular bone were described. Location of the first annulus was validated by daily growth increment (DGI) analysis in the otoliths. Annual periodicity was verified by marginal increment ratio (MIR) analysis in otoliths and edge analysis in vertebrae and opercular bones. Annuli formed, once a year, between March and May for all three bony structures. Otoliths, vertebrae and opercular bones were examined to determine which structure produced the most precise and accurate age estimates in S. o’connori. Vertebrae and otoliths matched closely for the first 21 years of life, while opercular bones appeared to underestimate age. For older fish, the counts diverged and otoliths consistently providing higher age estimates. Sectioned otoliths proved to be the most precise and accurate structure for age estimation. The oldest observed schizothoracine fish was 50, more than twice the longevity previously accepted in S. o’connori.     

微生物NAD合成酶及其抑制剂的研究进展

NAD(P)生物代谢在能量代谢,维持氧化还原稳态以及调节细胞寿命等许多细胞进程中有重要作用。因此,NAD生物合成途径的关键酶的抑制剂就成为备受关注的候选新药,如NAD合成酶抑制剂。本文对微生物中的NAD合成酶的催化活性特征,晶体结构,调控因子以及基于晶体结构的抑制剂设计方面进行了综述,以期为基于NAD的治疗领域打开新的思路。     

Efficient Passivation of Hybrid Perovskite Solar Cells Using Organic Dyes with COOH Functional Group

Organic–inorganic halide perovskites are efficient absorbers for solar cells. Nevertheless, the trap states at the surfaces and grain boundaries are a detrimental factor compromising the device performance. Here, an organic dye (AQ310) is employed as passivator to reduce the trap states of the perovskites and promote better stability. The results demonstrate that the trap states of perovskite are minimized by the presence of AQ310's ?COOH group and the formation of coordination with under‐coordinated Pb²⁺ ions. The resulting carrier recombination time is prolonged and verified by the photoluminescence and open‐circuit voltage decay measurements. Consequently, the best average power conversion efficiency (PCE) of 19.43% is achieved for the perovskite solar cell (PSC) with AQ310 passivation, as compared with a low average PCE of 17.98% for the PSC without AQ310 passivation.     

Mechanism of ammonium adsorption from wastewater by modified bentonite and optimization by response surface

Three modified bentonites, dry alkali modification, thermal modification, and acid modification, were prepared and characterized by XRD and FTIR. Batch experiments were performed to evaluate their efficiency as adsorbent for ammonium removal. Multi-variables interaction effects were evaluated by Response Surface Methodology. The results showed that the adsorption efficiency of ammonium by dry alkali modification bentonite was the best in three modified methods; the next was that of thermal modification. The crystalline structure of bentonite was significantly changed with dry alkali modification. Na₂SiO₃ and Na₂AlSi₃O₈(OH) were achieved by bentonite with powder NaOH modification. The increase in the mole ratio of exchangeable cations indicated that the adsorption efficiency of ammonium increased; while the layer spacing of bentonite expanded with the amount of the adsorbed water and hydrated water increased by thermal modification. In multi-variables interaction effects (holding time, calcination temperature, pH, dosage), the most significant factors were calcination temperature and dosage.     

Design,synthesis and biological evaluation of novel human monoamine oxidase B inhibitors based on a fragment in an X-ray crystal structure

Herein we report our efforts of developing reversible selective hMAO-B inhibitors based on isatin, a fragment in an X-ray crystal structure. Five different scaffolds were designed and many compounds were synthesized. Among them, compound A3 demonstrated very high potency and isoform selectivity against hMAO-B, 11 and 13 times more potent (IC₅₀?=?3?nM) and 23.64 and 6.8 times more selective than the marked drugs, selegiline and safinamide. However, the endeavors to modify the polar 3-one group of isatin, that is in a hydrophobic environment in the binding site of hMAO-B, to small nonpolar hydrophobic groups did not bring about improved hMAO-B inhibitors, which may challenge our understanding of molecular interactions and molecular recognition in biological systems.