Vanadyl bisacetylacetonate protects β cells from palmitate-induced cell death through the unfolded protein response pathway

Endoplasmic reticulum (ER) stress induced by free fatty acids (FFA) is important to β-cell loss during the development of type 2 diabetes. To test whether vanadium compounds could influence ER stress and the responses in their mechanism of antidiabetic effects, we investigated the effects and the mechanism of vanadyl bisacetylacetonate [VO(acac)₂] on β cells upon treatment with palmitate, a typical saturated FFA. The experimental results showed that VO(acac)₂ could enhance FFA-induced signaling pathways of unfolded protein responses by upregulating the prosurvival chaperone immunoglobulin heavy-chain binding protein/78-kDa glucose-regulated protein and downregulating the expression of apoptotic C/EBP homologous protein, and consequently the reduction of insulin synthesis. VO(acac)₂ also ameliorated FFA-disturbed Ca²⁺ homeostasis in β cells. Overall, VO(acac)₂ enhanced stress adaption, thus protecting β cells from palmitate-induced apoptosis. This study provides some new insights into the mechanisms of antidiabetic vanadium compounds.     

Equivalent potential of water for the electronic structure of glycine

First-principles, all-electron, ab initio calculations have been performed to construct an equivalent potential of water for the electronic structure of glycine (Gly) in solution. The calculation involved three steps. The first step was to search for the minimum-energy geometric structure of the Gly + nH₂O system. The second step was to calculate the electronic structure of Gly with the potential of water molecules via the self-consistent cluster-embedding method (SCCE), based on the result obtained in the first step. The last step was to calculate the electronic structure of Gly with the potential of dipoles after replacing the water molecules with dipoles. The results show that the occupied molecular orbitals of Gly are raised by about 0.0524 Ry on average due to the effect of water. The effect of water can be simulated well using the dipole potential. The equivalent potential obtained can be applied directly to electronic structure calculations of proteins in solution using the SCCE method.     

A New Statistic to Evaluate Imputation Reliability

Background

As the amount of data from genome wide association studies grows dramatically, many interesting scientific questions require imputation to combine or expand datasets. However, there are two situations for which imputation has been problematic: (1) polymorphisms with low minor allele frequency (MAF), and (2) datasets where subjects are genotyped on different platforms. Traditional measures of imputation cannot effectively address these problems.

Methodology/Principal Findings

We introduce a new statistic, the imputation quality score (IQS). In order to differentiate between well-imputed and poorly-imputed single nucleotide polymorphisms (SNPs), IQS adjusts the concordance between imputed and genotyped SNPs for chance. We first evaluated IQS in relation to minor allele frequency. Using a sample of subjects genotyped on the Illumina 1 M array, we extracted those SNPs that were also on the Illumina 550 K array and imputed them to the full set of the 1 M SNPs. As expected, the average IQS value drops dramatically with a decrease in minor allele frequency, indicating that IQS appropriately adjusts for minor allele frequency. We then evaluated whether IQS can filter poorly-imputed SNPs in situations where cases and controls are genotyped on different platforms. Randomly dividing the data into “cases” and “controls”, we extracted the Illumina 550 K SNPs from the cases and imputed the remaining Illumina 1 M SNPs. The initial Q-Q plot for the test of association between cases and controls was grossly distorted (λ = 1.15) and had 4016 false positives, reflecting imputation error. After filtering out SNPs with IQS<0.9, the Q-Q plot was acceptable and there were no longer false positives. We then evaluated the robustness of IQS computed independently on the two halves of the data. In both European Americans and African Americans the correlation was >0.99 demonstrating that a database of IQS values from common imputations could be used as an effective filter to combine data genotyped on different platforms.

Conclusions/Significance

IQS effectively differentiates well-imputed and poorly-imputed SNPs. It is particularly useful for SNPs with low minor allele frequency and when datasets are genotyped on different platforms.     

Two‐Dimensional Materials for Beyond‐Lithium‐Ion Batteries

Lithium‐ion batteries (LIBs) have dominated the portable electronics industry and solid‐state electrochemical research and development for the past two decades. In light of possible concerns over the cost and future availability of lithium, sodium‐ion batteries (SIBs) and other new technologies have emerged as candidates for large‐scale stationary energy storage. Research in these technologies has increased dramatically with a focus on the development of new materials for both the positive and negative electrodes that can enhance the cycling stability, rate capability, and energy density. Two‐dimensional (2D) materials are showing promise for many energy‐related applications and particularly for energy storage, because of the efficient ion transport between the layers and the large surface areas available for improved ion adsorption and faster surface redox reactions. Recent research highlights on the use of 2D materials in these future ‘beyond‐lithium‐ion’ battery systems are reviewed, and strategies to address challenges are discussed as well as their prospects.     

Characterization of VAMP-2 gene from marine teleostean, Lateolabrax japonicus

The whole length SPV2 gene of 715 bp, encoding VAMP-2 protein of 110 amino acids from Japanese sea perch, Lateolabrax japonicus, was obtained by using both RT-PCR and anchored PCR strategies while we initiated the structural and functional study on SNARE proteins in marine teleostean. Analysis of the deduced amino acid sequence indicated that SPV2 has its core arginine residue, a potential N-linked glycosylation site near its N-terminal, and one transmembrane domain in its C-terminal. Advanced structural analysis of bioinformatics approach predicts a coiled-coil α-helix backbone as the characteristic of SPV2 main conformational structure, identical to the structure of rat VAMP-2 obtained by crystallography. Semi-quantitative RT-PCR revealed that SPV2 was generally expressed in 10 neural and non-neural tissues, with the highest concentration in brain and the least in muscle.     

Research progress on the immune mechanism of the silkworm Bombyx mori

The silkworm Bombyx mori L., representing an important economic insect and one of the best models for studying insect immunity, possesses an efficient and sophisticated innate immune system against invasive microorganisms. The innate immune system basically includes humoural immunity and cellular immunity. The humoural immunity, which functions via molecules including humoural factors, lysozymes, phenoloxidase, hemolin, lectins and, in particular, antimicrobial peptides, plays a central role in eliminating the invading pathogens. The cellular immunity is primarily carried out and mediated by plasmatocytes and granular cells of haemocytes in the haemolymph, usually followed by melanization. Additionally, apoptosis, a primary viral defence for insects lacking adaptive immunity, comprises an important part of the silkworm immune system. Currently, there is still the lack of a comprehensive and systematic understanding of the molecular mechanisms of silkworm immunity. We review the latest research progress on silkworm immune mechanisms, including phenoloxidase‐dependent melanization and apoptosis, which is conducive to improving our understanding of the silkworm immune mechanism, clarifying the relationship of various immune mechanisms, and also providing a theoretical basis and reference for the future research of insect immunity.     

Structure-based design of thioether-bridged cyclic phosphopeptides binding to Grb2-SH2 domain

A series of phosphotyrosine containing cyclic peptides was designed and synthesized based upon the phage library derived cyclopeptide, G1TE. Considering the type-I beta-turn feature of peptidic ligand binding to Grb2 SH2 domain, we introduce alpha,alpha-disubstituted cyclic amino acid, Ach, into the 4th position of the cyclic peptide to induce a local right handed 3(10) helical conformation. In order to stabilize the favorable binding conformation, the bulky and hydrophobic amino acids, neopentylglycine (NPG) and phenylalanine, were introduced into the 8th and 2nd positions of the peptide ligand, respectively. To facilitate the sidechain of pTyr3 reaching into the phosphotyrosine binding pocket, a less bulky alanine was preferred in position 1. Based upon these global modifications, a highly potent peptide ligand 12 was discovered with an IC(50)=1.68 nM, evaluated by ELISA binding essay. Ligand 12 is at least 10(5) more potent than the lead peptide, termed G1TE.     

环境参数变化对γ射线诱变微生物的影响

报告了在非自然环境中培养选育青霉菌菌株的一些结论。实验表明随着辐射剂量的增加菌株的致死率也相应增加;当辐照剂量相同时,与自然环境相比其致死率有所提高,且随着非自然环境参数值的增加而增加。当电场强度为３００ｋＶ／ｍ、磁场强度为６００Ｇｓ时,正变率有一极大值。