黑色素母细胞沿神经的迁移

黑色素细胞是皮肤中的特殊细胞,它产生黑色素,并将其传递给周围的角质形成细胞,从而决定皮肤的颜色等,其来源于黑色素母细胞.因此,了解黑色素母细胞如何迁移至靶点,对改善个体肤色以及诊断和治疗黑色素瘤等都具有重要意义.文章通过对黑色素母细胞沿神经迁移这一模式的过程和相关机制进行综述,希望为个体肤色改善以及黑色素瘤术后复发机制...     

The combined use of photoaffinity labeling and surface plasmon resonance‐based technology identifies multiple salicylic acid‐binding proteins

Salicylic acid (SA) is a small phenolic molecule that not only is the active ingredient in the multi‐functional drug aspirin, but also serves as a plant hormone that affects diverse processes during growth, development, responses to abiotic stresses and disease resistance. Although a number of SA‐binding proteins (SABPs) have been identified, the underlying mechanisms of action of SA remain largely unknown. Efforts to identify additional SA targets, and thereby elucidate the complex SA signaling network in plants, have been hindered by the lack of effective approaches. Here, we report two sensitive approaches that utilize SA analogs in conjunction with either a photoaffinity labeling technique or surface plasmon resonance‐based technology to identify and evaluate candidate SABPs from Arabidopsis. Using these approaches, multiple proteins, including the E2 subunit of α‐ketoglutarate dehydrogenase and the glutathione S‐transferases GSTF2, GSTF8, GSTF10 and GSTF11, were identified as SABPs. Their association with SA was further substantiated by the ability of SA to inhibit their enzymatic activity. The photoaffinity labeling and surface plasmon resonance‐based approaches appear to be more sensitive than the traditional approach for identifying plant SABPs using size‐exclusion chromatography with radiolabeled SA, as these proteins exhibited little to no SA‐binding activity in such an assay. The development of these approaches therefore complements conventional techniques and helps dissect the SA signaling network in plants, and may also help elucidate the mechanisms through which SA acts as a multi‐functional drug in mammalian systems.     

A mass spectrometry-based high-throughput screening method for engineering fatty acid synthases with improved production of medium-chain fatty acids

Microbial cell factories have been extensively engineered to produce free fatty acids (FFAs) as key components of crucial nutrients, soaps, industrial chemicals, and fuels. However, our ability to control the composition of microbially synthesized FFAs is still limited, particularly, for producing medium-chain fatty acids (MCFAs). This is mainly due to the lack of high-throughput approaches for FFA analysis to engineer enzymes with desirable product specificity. Here we report a mass spectrometry (MS)-based method for rapid profiling of MCFAs in Saccharomyces cerevisiae by using membrane lipids as a proxy. In particular, matrix-assisted laser desorption/ionization time-of-flight (MALDI-ToF) MS was used to detect shorter acyl chain phosphatidylcholines from membrane lipids and a higher m/z peak ratio at 730 and 758 was used as an indication for improved MCFA production. This colony-based method can be performed at a rate of ~2 s per sample, representing a substantial improvement over gas chromatography-MS (typically >30 min per sample) as the gold standard method for FFA detection. To demonstrate the power of this method, we performed site-saturation mutagenesis of the yeast fatty acid synthase and identified nine missense mutations that resulted in improved MCFA production relative to the wild-type strain. Colony-based MALDI-ToF MS screening provides an effective approach for engineering microbial fatty acid compositions in a high-throughput manner.     

云南景颇族的体质特征

本文调查了云南景颇族261人（男105人,女156人）。年龄为成年人（男24－60岁,女23－55岁）。主要测量均值与现代中国汉族和云南省各少数民族比较和聚类分析的结果表明,景颇族属黄种人的东亚类型,但也有南亚类型特征表现。体质特征与傣族、哈尼族和彝族接近,与基诺族和布郎族较远。     

Effects of various straw incorporation strategies on soil phosphorus fractions and transformations

Returning straw to the field is an effective method for optimizing the soil phosphorus (P) availability, in which bacteria play an important role. However, the effects of various straw incorporation strategies on P transformation between different soil P pools remain unclear. In this study, variations in soil P fractions, phosphatase activities and the abundance of phosphatase genes (phoD, phoX and phoC) as well as a P-solubilizing gene (pqqC) at DNA (total) and cDNA (transcribed) levels were analysed in three straw incorporation treatments, including chopped straw (StrawD), straw compost (Compost) and straw-derived biochar (Biochar), and control (no straw, CK). Compared with the CK, the moderately labile inorganic P (NaOH I-P_i) content significantly decreased and the non-available P (Residual P) content significantly increased in the StrawD treatment. At the same time, phosphodiesterase (PD) activity and the transcribed phoC and phoX genes as well as total pqqC gene abundance significantly increased in the StrawD treatment, suggesting that the input of chopped straw stimulated P transformations from both organic and inorganic P pools. In addition, the stable P_i (NaOH II-P_i) content and total pqqC gene abundance in the Biochar treatment were significantly higher than that in the CK, indicating that the input of biochar increased the NaOH II-P_i that could release available P by Pi-solubilizing bacteria. In comparison to the CK, the Compost input significantly decreased one labile Pi (resin-P_i) only. However, its P fractions were significantly different from that of CK, Biochar and StrawD treatments, suggesting that the effects of compost input on P should not be ignored. In conclusion, chopped straw input increased soil P transformation but not available P, biochar input may promote inorganic P transformation, and compost input has a latent effect on P transformation. The study provided a comprehensive understanding of straw incorporation strategies for regulating soil P availability.     

A screening of inhibitors targeting the receptor kinase FERONIA reveals small molecules that enhance plant root immunity

Receptor-like kinases (RLKs) constitute the largest receptor family involved in the regulation of plant immunity and growth, but small-molecule inhibitors that target RLKs to improve agronomic traits remain unexplored. The RLK member FERONIA (FER) negatively regulates plant resistance to certain soil-borne diseases that are difficult to control and cause huge losses in crop yields and economy. Here, we identified 33 highly effective FER kinase inhibitors from 1494 small molecules by monitoring FER autophosphorylation in vitro. Four representative inhibitors (reversine, cenisertib, staurosporine and lavendustin A) inhibited the kinase activity of FER and its homologues in several crops by targeting the conserved ATP pocket in the kinase structure. FER contributes to the physiological impact of representative inhibitors in plants. The treatment of roots with reversine, staurosporine and lavendustin A enhanced innate immunity in plant roots and thus alleviated soil-borne diseases in tobacco, tomato and rice without growth penalties. Consistently, RNA sequencing assays showed that lavendustin A and reversine exert profound impacts on immunity-related gene expression. Our results will set a new milestone in the development of the plant RLK kinase regulation theory and provide a novel strategy for the prevention and control of plant soil-borne diseases without growth penalties.     

Compositional Characterization and Pyrolysis of Loblolly Pine and Douglas-fir Bark

Two potential biofuel resources, Douglas-fir and Loblolly pine bark, were subjected to extensive chemical and compositional analysis. The barks were initially extracted with dichloromethane, and the resulting extracted compounds were characterized by gas chromatography coupled with mass spectrometric analysis. Characterization of the major bark biocomponents indicated that Douglas-fir and Loblolly pine bark contained 22.5 and 13.2 % tannins, 44.2 and 43.5 % lignin, 16.5 and 23.1 % cellulose, and 7.6 and 14.1 % hemicellulose, respectively. Of particular interest is the high content of tannins and lignin, which make these barks excellent potential precursors for bio-oils and/or other value-added chemicals. ¹³C nuclear magnetic resonance (NMR) was used to characterize the chemical structure of the lignin and tannins. These samples were also analyzed by ³¹P NMR after phosphitylation of the hydroxyl groups in lignin and tannins. The NMR spectral data indicated that the lignin in both barks contained p-hydroxyphenyl (h) and guaiacyl (g) of lignin monomers with an h/g ratio of 10:90 and 22:78 for Douglas-fir and Loblolly pine bark, respectively. Gel permeation chromatography was used to analyze the molecular weight distributions of extracted tannins, isolated cellulose, and ball-milled lignin. The pyrolysis of Douglas-fir and pine bark at 500°C in a tubular reactor generated 48.2 and 45.2 % of total oil, of which the light oil contents are 14.1 and 20.7 % and heavy oil are 34.1 and 24.4 %. Similarly, fast pyrolysis at 375°C yielded 56.1 and 49.8 % of total oil for Douglas-fir and pine bark, respectively.     

The association between CD14 gene C-260T polymorphism and coronary heart disease risk: a meta-analysis

Monocyte differentiation antigen CD14 is considered an important cell-activating mediator of inflammatory responses that may result in atherosclerosis, coronary heart disease (CHD), thrombus formation, and myocardial infarction (MI). A common C-260T polymorphism in the promoter of the CD14 gene, the trans-membrane receptor of lipopolysaccharides, has been inconsistently associated with CHD. To investigate this inconsistency, we performed a meta-analysis of 28 studies involving a total of 13,335 CHD cases and 7,979 controls for C-260T of the CD14 gene to evaluate the effect of CD14 on genetic susceptibility for CHD. An overall random effects odds ratio of 1.24 (95 % CI: 1.12–1.36, P < 10^?5) was found for T allele. Significant results were also observed using dominant (OR = 1.34, 95 % CI: 1.17–1.54, P < 10^?4) or recessive genetic model (OR = 1.25, 95 % CI: 1.10–1.41, P = 0.0004). There was strong evidence of heterogeneity (P < 10^?5), which largely disappeared after stratification by ethnicity. After stratified by ethnicity, significant results were found in East Asians; whereas no significant associations were found among Caucasians and other ethnic populations in all genetic models. In the stratified analysis according to sample size, CHD endpoints, and HWE status, significantly increased risks for the polymorphism were found in all genetic models. In conclusion, our results indicate that the CD14 C-260T polymorphism is a risk factor of CHD, especially in East Asians. However, additional very large-scale studies are warranted to confirm our results.     

Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity

Mammalian brain contains high levels of d-serine, an endogenous co-agonist of N-methyl D-aspartate type of glutamate receptors. D-Serine is synthesized by serine racemase, a brain enriched enzyme converting L- to D-serine. Degradation of D-serine is achieved by D-amino acid oxidase, but this enzyme is not present in forebrain areas that are highly enriched in D-serine. We now report that serine racemase catalyzes the degradation of cellular D-serine itself, through the alpha,beta-elimination of water. The enzyme also catalyzes water alpha,beta-elimination with L-serine and L-threonine. alpha,beta-Elimination with these substrates is observed both in vitro and in vivo. To investigate further the role of alpha,beta-elimination in regulating cellular D-serine, we generated a serine racemase mutant displaying selective impairment of alpha,beta-elimination activity (Q155D). Levels of D-serine synthesized by the Q155D mutant are several-fold higher than the wild-type both in vitro and in vivo. This suggests that the alpha,beta-elimination reaction limits the achievable D-serine concentration in vivo. Additional mutants in vicinal residues (H152S, P153S, and N154F) similarly altered the partition between the alpha,beta-elimination and racemization reactions. alpha,beta-Elimination also competes with the reverse serine racemase reaction in vivo. Although the formation of L- from D-serine is readily detected in Q155D mutant-expressing cells incubated with physiological D-serine concentrations, reversal with wild-type serine racemase-expressing cells required much higher D-serine concentration. We propose that alpha,beta-elimination provides a novel mechanism for regulating intracellular D-serine levels, especially in brain areas that do not possess D-amino acid oxidase activity. Extracellular D-serine is more stable toward alpha,beta-elimination, likely due to physical separation from serine racemase and its elimination activity.