Periostin in inflammation and allergy

We found for the first time that IL-4 and IL-13, signature type 2 cytokines, are able to induce periostin expression. We and others have subsequently shown that periostin is highly expressed in chronic inflammatory diseases―asthma, atopic dermatitis, eosinophilc chronic sinusitis/chronic rhinosinusitis with nasal polyp, and allergic conjunctivitis—and that periostin plays important roles in the pathogenesis of these diseases. The epithelial/mesenchymal interaction via periostin is important for the onset of allergic inflammation, in which periostin derived from fibroblasts acts on epithelial cells or fibroblasts, activating their NF-κB. Moreover, the immune cell/non-immune cell interaction via periostin may be also involved. Now the significance of periostin has been expanded into other inflammatory or fibrotic diseases such as scleroderma and pulmonary fibrosis. The cross-talk of periostin with TGF-β or pro-inflammatory cytokines is important for the underlying mechanism of these diseases. Because of its pathogenic importance and broad expression, diagnostics or therapeutic drugs can be potentially developed to target periostin as a means of treating these diseases.     

“魔术蘑菇”(MagicMushroom)与药物滥用

"魔术蘑菇"广泛存在于自然界中,其所含裸盖菇素具有致幻作用,可使服用者产生欣快感并产生依赖性和神经毒性,在许多国家已被列为违禁物品。我国有些研究在蘑菇中毒的诊断及治疗方面取得一些成果,但还未从药物滥用方面引起人们足够认识。通过综述"魔术蘑菇"对人体的作用、国内外流通现状及常用检验方法,使从法庭科学的角度重新认识"魔术蘑菇",以期引起重视,防患于未然。     

具有对称不均等负重合量的气动伺服阀特性

分析了具有负重合量的气动伺服阀特性及各节流口的流动形式.理论分析和实验结果表明：具有均等负重合量的气动伺服阀的零位压力约为供气压力的80%；当供气侧对称不均等负重合量小于排气侧负重合量时，零位压力小于供气压力的80%；当供气侧对称不均等负重合量大于排气侧负重合量时，零位压力大于供气压力的80%；具有对称均等负重合量或对称不均等负重合量的伺服阀的最大泄漏量发生在零位附近.     

Enzymatic catalysis of anti-Baldwin ring closure in polyether biosynthesis

Polycyclic polyether natural products have fascinated chemists and biologists alike owing to their useful biological activity, highly complex structure and intriguing biosynthetic mechanisms. Following the original proposal for the polyepoxide origin of lasalocid and isolasalocid and the experimental determination of the origins of the oxygen and carbon atoms of both lasalocid and monensin, a unified stereochemical model for the biosynthesis of polyether ionophore antibiotics was proposed. The model was based on a cascade of nucleophilic ring closures of postulated polyepoxide substrates generated by stereospecific oxidation of all-trans polyene polyketide intermediates. Shortly thereafter, a related model was proposed for the biogenesis of marine ladder toxins, involving a series of nominally disfavoured anti-Baldwin, endo-tet epoxide-ring-opening reactions. Recently, we identified Lsd19 from the Streptomyces lasaliensis gene cluster as the epoxide hydrolase responsible for the epoxide-opening cyclization of bisepoxyprelasalocid A to form lasalocid A. Here we report the X-ray crystal structure of Lsd19 in complex with its substrate and product analogue to provide the first atomic structure-to our knowledge-of a natural enzyme capable of catalysing the disfavoured epoxide-opening cyclic ether formation. On the basis of our structural and computational studies, we propose a general mechanism for the enzymatic catalysis of polyether natural product biosynthesis.     

油菜秸秆比例对好氧堆肥过程及产品特性的影响

采用堆肥工艺将农作物秸秆转化为有机肥还田是秸秆资源化利用的有效手段.本研究以油菜秸秆为主要原料,按不同比例同辅料混合(三组实验R1、R2和R3中的油菜秸秆比例(湿重)分别为45%、65%和85%),研究了油菜秸秆比例对高温好氧堆肥过程及产品特性的影响.结果表明,在72d的堆肥过程中,R1、R2和R3的有机物降解主要发生在堆肥过程前期,堆肥结束时分别达到34.06%、35.57%和39.78%.通过比较三组实验过程中样品的理化性质,可知R3最终样品满足了堆肥腐熟的各项指标,且堆肥过程中氮损失最少;其最终堆肥产品中未检测出NH_4~+,总N含量、NO_3~-浓度和GI值分别达到2.17%、1,844.93mg·kg~(-1)干重和102.66%.     

Fras1 deficiency results in cryptophthalmos,renal agenesis and blebbed phenotype in mice

Loss of tight association between epidermis and dermis underlies several blistering disorders and is frequently caused by impaired function of extracellular matrix (ECM) proteins. Here we describe a new protein in mouse, Fras1, that is specifically detected in a linear fashion underlying the epidermis and the basal surface of other epithelia in embryos. Loss of Fras1 function results in the formation of subepidermal hemorrhagic blisters as well as unilateral or bilateral renal agenesis during mouse embryogenesis. Postnatally, homozygous Fras1 mutants have fusion of the eyelids and digits and unilateral renal agenesis or dysplasia. The defects observed in Fras1-/- mice phenocopy those of the existing bl (blebbed) mouse mutants, which have been considered a model for the human genetic disorder Fraser syndrome. We show that bl/bl homozygous embryos are devoid of Fras1 protein, consistent with the finding that Fras1 is mutated in these mice. In sum, our data suggest that perturbations in the composition of the extracellular space underlying epithelia could account for the onset of the blebbed phenotype in mouse and Fraser syndrome manifestation in human.     

Insight into a natural Diels-Alder reaction from the structure of macrophomate synthase

The Diels-Alder reaction, which forms a six-membered ring from an alkene (dienophile) and a 1,3-diene, is synthetically very useful for construction of cyclic products with high regio- and stereoselectivity under mild conditions. It has been applied to the synthesis of complex pharmaceutical and biologically active compounds. Although evidence on natural Diels-Alderases has been accumulated in the biosynthesis of secondary metabolites, there has been no report on the structural details of the natural Diels-Alderases. The function and catalytic mechanism of the natural Diels-Alderase are of great interest owing to the diversity of molecular skeletons in natural Diels-Alder adducts. Here we present the 1.70 A resolution crystal structure of the natural Diels-Alderase, fungal macrophomate synthase (MPS), in complex with pyruvate. The active site of the enzyme is large and hydrophobic, contributing amino acid residues that can hydrogen-bond to the substrate 2-pyrone. These data provide information on the catalytic mechanism of MPS, and suggest that the reaction proceeds via a large-scale structural reorganization of the product.     

Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.