The 3-ketoacyl-CoA synthase WFL is involved in lateral organ development and cuticular wax synthesis in Medicago truncatula

Plant Molecular Biology - A 3-ketoacyl-CoA synthase involved in biosynthesis of very long chain fatty acids and cuticular wax plays a vital role in aerial organ development in M. truncatula....     

运用重叠延伸PCR技术构建在甘丙肽全长cDNA嵌入第二内含子的重构分子

构建嵌入第二内含子的甘丙肽(Galanin,GAL)全长基因组cDNA的重构分子。通过RT-PCR扩增出cDNA编区的序列,分别从基因组中扩增出cDNA的5′和3′端部分非编码序列;使用重叠延伸PCR(overlap extention PCR,OE-PCR)方法将三个片段重叠获得全长cDNA序列;再将全长cDNA从第三外显子第15个碱基处分成两部分,分开的cDNA前半部分和后半部分以及第二内含子进行重叠延伸获得重构分子,含有第二内含子的甘丙肽(GAL)全长基因组cDNA;将重构分子连入pMDI9-Tsimple载体。电泳分析观察到清晰的重构分子片段;测序显示重构分子由所设计的序列组成,第二内含子插入的位置准确,且无移码。使用重叠延伸PCR能够成功在cDNA中插入内含子获得一段重构基因。     

An interpretable boosting model to predict side effects of analgesics for osteoarthritis

Background

Osteoarthritis (OA) is the most common disease of arthritis. Analgesics are widely used in the treat of arthritis, which may increase the risk of cardiovascular diseases by 20% to 50% overall.There are few studies on the side effects of OA medication, especially the risk prediction models on side effects of analgesics. In addition, most prediction models do not provide clinically useful interpretable rules to explain the reasoning process behind their predictions. In order to assist OA patients, we use the eXtreme Gradient Boosting (XGBoost) method to balance the accuracy and interpretability of the prediction model.

Results

In this study we used the XGBoost model as a classifier, which is a supervised machine learning method and can predict side effects of analgesics for OA patients and identify high-risk features (RFs) of cardiovascular diseases caused by analgesics. The Electronic Medical Records (EMRs), which were derived from public knee OA studies, were used to train the model. The performance of the XGBoost model is superior to four well-known machine learning algorithms and identifies the risk features from the biomedical literature. In addition the model can provide decision support for using analgesics in OA patients.

Conclusion

Compared with other machine learning methods, we used XGBoost method to predict side effects of analgesics for OA patients from EMRs, and selected the individual informative RFs. The model has good predictability and interpretability, this is valuable for both medical researchers and patients.

     

Efficient enzymatic production of rebaudioside A from stevioside

Stevioside and rebaudioside A are the chief diterpene glycosides present in the leaves of Stevia rebaudiana. Rebaudioside A imparts a desirable sweet taste, while stevioside produces a residual bitter aftertaste. Enzymatic synthesis of rebaudioside A from stevioside can increase the ratio of rebaudioside A to stevioside in steviol glycoside products, providing a conceivable strategy to improve the organoleptic properties of steviol glycoside products. Here, we demonstrate the efficient conversion of stevioside to rebaudioside A by coupling the activities of recombinant UDP-glucosyltransferase UGT76G1 from S. rebaudiana and sucrose synthase AtSUS1 from Arabidopsis thaliana. The conversion occurred via regeneration of UDP-glucose by AtSUS1. UDP was applicable as the initial material instead of UDP-glucose for UDP-glucose recycling. The amount of UDP could be greatly reduced in the reaction mixture. Rebaudioside A yield in 30?h with 2.4?mM stevioside, 7.2?mM sucrose, and 0.006?mM UDP was 78%.     

Gating mechanism of mechanosensitive channel of large conductance: a coupled continuum mechanical-continuum solvation approach

Gating transition of the mechanosensitive channel of large conductance (MscL) represents a good example of important biological processes that are difficult to describe using atomistic simulations due to the large (submicron) length scale and long (millisecond) time scale. Here we develop a novel computational framework that tightly couples continuum mechanics with continuum solvation models to study the detailed gating behavior of E. coli-MscL. The components of protein molecules are modeled by continuum elements that properly describe their shape, material properties and physicochemical features (e.g., charge distribution). The lipid membrane is modeled as a three-layer material in which the lipid head group and tail regions are treated separately, taking into account the fact that fluidic lipid bilayers do not bear shear stress. Coupling between mechanical and chemical responses of the channel is realized by an iterative integration of continuum mechanics (CM) modeling and continuum solvation (CS) computation. Compared to previous continuum mechanics studies, the present model is capable of capturing the most essential features of the gating process in a much more realistic fashion: due mainly to the apolar solvation contribution, the membrane tension for full opening of MscL is reduced substantially to the experimental measured range. Moreover, the pore size stabilizes constantly during gating because of the intricate interactions of the multiple components of the system, implying the mechanism for sub-conducting states of MscL gating. A significant fraction (\(\sim \)2/3) of the gating membrane strain is required to reach the first sub-conducting state of our model, which is featured with a relative conductance of 0.115 to the fully opened state. These trends agree well with experimental observations. We anticipate that the coupled CM/CS modeling framework is uniquely suited for the analysis of many biomolecules and their assemblies under external mechanical stimuli.     

Discovery of a novel protein kinase B inhibitor by structure-based virtual screening

Protein kinase B (PKB/AKT) is a promising and attractive therapeutic target in anticancer drug development. Herein, we report the findings of virtual screening for novel ATP-competitive inhibitors of AKT-2 using 2D- and 3D-similarity searching and sequential molecular docking with two crystal structures of AKT-2. Our multistep approach led to the identification of a low micromolar AKT-2 inhibitor (IC₅₀ = 1.5 μM) with a novel scaffold. The experimentally validated inhibitor represents the starting point for an optimization program.     

The Association of Thyroid Nodule with Non-Iodized Salt among Chinese Children

Objective

The controversy that iodized salt may increase the risk of thyroid disorders has been aroused in China during the past decade. Most of studies focused on adult rather than children. We aimed to explore whether iodized salt was associated with an increased risk of thyroid nodule in Chinese children.

Methods

The cross-sectional study was conducted in Hangzhou, China, in 2010. Iodized salt intake, urine iodine concentration (UIC) and thyroid nodule (by ultrasonography) were measured in 3026 children. The associations of iodized salt with thyroid nodule were evaluated using multiple logistic regression models.

Results

The prevalence of thyroid nodule was 10.59% among Chinese children. Girls (11.89%) had higher prevalence of thyroid nodule than boys (9.26%). No significant association was observed between type of salt and thyroid nodule in pooled samples, boys and girls, respectively. Similar associations were observed between UIC and thyroid nodule. There was no significant association between milk consumption and thyroid nodule as well.

Conclusion

The present study indicated that non-iodized salt may not increase the risk of thyroid nodules among Chinese children. Similar associations were observed between milk consumption, UIC and thyroid nodules.     

Biosynthesis of a water solubility-enhanced succinyl glucoside derivative of luteolin and its neuroprotective effect

The natural flavonoids luteolin and luteoloside have anti-bacterial, anti-inflammatory, anti-oxidant, anti-tumour, hypolipidemic, cholesterol lowering and neuroprotective effects, but their poor water solubility limits their application in industrial production and the pharmaceutical industry. In this study, luteolin-7-O-β-(6″-O-succinyl)-d -glucoside, a new compound that was prepared by succinyl glycosylation of luteolin by the organic solvent tolerant bacterium Bacillus amyloliquefaciens FJ18 in an 8.0% DMSO (v/v) system, was obtained and identified. Its greater water solubility (2293 times that of luteolin and 12 232 times that of luteoloside) provides the solution to the application problems of luteolin and luteoloside. The conversion rate of luteolin (1.0 g l⁻¹) was almost 100% at 24 h, while the yield of luteolin-7-O-β-(6″-O-succinyl)-d -glucoside reached 76.2%. In experiments involving the oxygen glucose deprivation/reoxygenation injury model of mouse hippocampal neuron cells, the cell viability was significantly improved with luteolin-7-O-β-(6″-O-succinyl)-d -glucoside dosing, and the expressions of the anti-oxidant enzyme HO-1 in the nucleus increased, providing a neuroprotective effect for ischemic cerebral cells. The availability of biosynthetic luteolin-7-O-β-(6″-O-succinyl)-d -glucoside, which is expected to replace luteolin and luteoloside, would effectively expand the clinical application value of luteolin derivatives.     

<Emphasis Type="Italic">Plantactinospora solaniradicis</Emphasis> sp. nov., a novel actinomycete isolated from the root of a tomato plant (<Emphasis Type="Italic">Solanum lycopersicum</Emphasis> L.)

A Gram-positive, non-motile actinomycete, designated strain NEAU-FJL1^T, was isolated from tomato root (Solanum lycopersicum L.) collected from Harbin, Heilongjiang province, north China. The strain formed single spores with smooth surfaces from substrate mycelia. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-FJL1^T should be affiliated with the genus Plantactinospora and forms a distinct branch with its close neighbour Plantactinospora soyae NEAU-gxj3^T (99.2% sequence similarity). The cell wall was found to contain meso-diaminopimelic acid and the whole cell sugars were identified as xylose, glucose, arabinose and galactose. The predominant menaquinones were identified as MK-10(H₆) and MK-10(H₄). The phospholipid profile was found to consist of diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. The major fatty acids were identified as C_15:0, iso-C_16:0, anteiso-C_17:0, C_17:0 and iso-C_15:0. With reference to phenotypic characteristics, phylogenetic data and DNA–DNA hybridization results, strain NEAU-FJL1^T can be distinguished from its most closely related strain and classified as a new species, for which the name Plantactinospora solaniradicis sp. nov. is proposed. The type strain is NEAU-FJL1^T (= DSM 100596^T = CGMCC 4.7284^T).