簇素在急性胰腺炎发病机制中的研究进展

簇素是一种普遍存在的异源二聚体硫酸化糖蛋白,目前研究推测簇素参与调节急性胰腺炎发病中胰腺细胞的凋亡、拮抗细胞坏死及抑制补体对细胞膜的攻击,进而减轻炎症反应,同时参与损伤胰腺细胞的再生和修复,最终保护胰腺组织。现认为,簇素在急性胰腺炎中是一种保护细胞的蛋白质。

A pair of two－component regulatory genes ecrA1／A2 in S. coelicolor

Two-component genes are kinds of genetic elements involved in regulation of antibiotic production in Streptomyces coelicolor. DNA microarray analysis revealed that ecrA1/A2, which mapped at distant sites from red locus and encode respectively the kinase and regulator, expressed coordinately with genes of Red specific biosynthetic pathway, ecrA1 and ecrA2 gene-disruptive mutants were constructed using homogenotisation by reciprocal double crossover. Fermentation data showed that the undecylprodigiosin (Red) level of production was lower than that of wild-type strain. However, the change of the actinorhodin (Act) production level was not significant compared with wild type. Thus, these experiment results confirmed that the two-component system ecrA 1/A2 was positive regulatory element for red gene cluster.

Complete genome sequence of the rifamycin SV-producing Amycolatopsis mediterranei U32 revealed its genetic characteristics in phylogeny and metabolism

Amycolatopsis mediterranei is used for industry-scale production of rifamycin, which plays a vital role in antimyco- bacterial therapy. As the first sequenced genome of the genus Amycolatopsis, the chromosome of strain U32 comprising 10 236 715 base pairs, is one of the largest prokaryotic genomes ever sequenced so far. Unlike the linear topology found in streptomycetes, this chromosome is circular, particularly similar to that of Saccharopolyspora erythraea and Nocardia farcinica, representing their close relationship in phylogeny and taxonomy. Although the predicted 9 228 protein-coding genes in the A. mediterranei genome shared the greatest number of orthologs with those of S. erythraea, it was unexpectedly followed by Streptomyces coelicolor rather than N. farcinica, indicating the distinct metabolic characteristics evolved via adaptation to diverse ecological niches. Besides a core region analogous to that common in streptomycetes, a novel ＇quasicore＇ with typical core characteristics is defined within the non-core region, where 21 out of the total 26 gene clusters for secondary metabolite production are located. The rifamycin biosynthesis gene cluster located in the core encodes a cytochrome P450 enzyme essential for the conversion of rifamycin SV to B, revealed by comparing to the highly homologous cluster of the rifamycin B-producing strain S699 and further confirmed by genetic complementation. The genomic information of A. mediterranei demonstrates a metabolic network orchestrated not only for extensive utilization of various carbon sources and inorganic nitrogen compounds but also for effective funneling of metabolic intermediates into the secondary antibiotic synthesis process under the control of a seemingly complex regulatory mechanism.

Expression of microRNA-29b2-c Cluster is Positively Regulated by MyoD in L6 Cells

Objectives To evaluate the expression profile of myoD microRNA-29 （miR-29） family in L6 myoblast differentiated to myotube or L6 myotube treated by glucose and insulin, and to further probe the molecular mechanism of myoD regulating the expression of miR-29 clusters.

Gound State Properties of Nuclei in ^(295)118 α-Decay Chain

The properties of nuclei belonging to the α-decay chain of superheavy element ^295118 have been studied in the framework of axially deformed relativistic mean field （RMF） theory with the parameter set of NL-Z2 in the blocked BCS approximation. Some ground state properties such as binding energies, deformations, and α-decay energies Qα have been obtained and agree well with those from finite-range droplet model （FRDM）. The single-particle spectra of nuclei in ^295118 α-decay chain show that the shell gaps present obviously nucleon number dependence. The root-mean-square （rms） radii of proton, neutron and matter distributions change slowly from ^283112 to ^295118 but dramatically from ^279110 to ^283112, which may be due to the subshell closure at Z = 110 in ^279110. The α-decay half-lives in 295118 decay chain are evaluated by employing the cluster model and the generalized liquid drop model （GLDM）, and the overall agreement is found when they are compared with the known experimental data. The α-decay lifetimes obtained from the cluster model are slightly larger than those of GLDM ones. Finally, we predict the α-decay half-lives of Z=118, 116, 114, 112 isotopes using the cluster model and GLDM, which also indicate these two models can corroborate each other in studies on superheavy nuclei. The results from GLDM are always lower than those obtained from the cluster model.

Effects of Small Water Clusters on the Growth and Microcystin Production of Microcystis aeruginosa

Mierocystis aeruginosa FACHB 905 was used as a model organism to study the ellects oI small water clusters （SWCs） on the growth and microcystin （MC） production of toxic cyanobacteria. The results showed that SWCs were able to stimulate the growth of Microcystis aeruginosa, which resulted in increased cell numbers and higher specific growth rates after a 30-d treatment. The cell morphology indicated that Microcystis aeruginosa was in a better state of growth, and it was more prone to divide in SWCs than in normal water clusters. The SWCs treatment up-regulated MC synthesis and exudation in 10 d in Microcystis aeruginosa, and the intra-cellular MC content de- creased after the 20th day subsequently. Moreover, the cellular photosynthetic pigment contents were temporarily stimulated by SWCs. A possible reason is that SWCs stimulated the growth by promoting photosynthesis, whereas the increased MC production was relevant to pigment contents.

Reconstruction of a hybrid nucleoside antibiotic gene cluster based on scarless modification of large DNA fragments

Genetic modification of large DNA fragments(gene clusters) is of great importance in synthetic biology and combinatorial biosynthesis as it facilitates rational design and modification of natural products to increase their value and productivity.In this study,we developed a method for scarless and precise modification of large gene clusters by using RecET/RED-mediated polymerase chain reaction(PCR) targeting combined with Gibson assembly.In this strategy,the biosynthetic genes for peptidyl moieties(HPHT) in the nikkomycin biosynthetic gene cluster were replaced with those for carbamoylpolyoxamic acid(CPOAA)from the polyoxin biosynthetic gene cluster to generate a^40 kb hybrid gene cluster in Escherichia coli with a reusable targeting cassette.The reconstructed cluster was introduced into Streptomyces lividans TK23 for heterologous expression and the expected hybrid antibiotic,polynik A,was obtained and verified.This study provides an efficient strategy for gene cluster reconstruction and modification that could be applied in synthetic biology and combinatory biosynthesis to synthesize novel bioactive metabolites or to improve antibiotic production.

Quantum phase transition in quarter-filled nanoclusters of manganite induced by element substitution at B site

In the present paper,we study the effect of element substitution for quarter-filled nanoclusters of perovskite manganite by introducing Jahn-Teller type of perturbation interaction to the double-exchange Hamiltonian.Using the unrestricted real-space Hartree-Fock approximation method we find that,the Jahn-Teller electron-phonon interaction plays the central role in producing the phase transition from ferromagnetic phase to CE type antiferromagnetic phase.Not only the Jahn-Teller interaction benefits antiferromagnetic correlation,it also increases the charge density order parameter.These theoretical results provide a guidance to predict the properties and modify the composition of particles of perovskite manganite under nano-scale.

Conversion of the high-yield salinomycin producer Streptomyces albus BK3-25 into a surrogate host for polyketide production

An ideal surrogate host for heterologous production of various natural products is expected to have efficient nutrient utilization,fast growth,abundant precursors and energy supply,and a pronounced gene expression.Streptomyces albus BK3-25 is a high-yield industrial strain producing type-Ⅰ polyketide sahnomycin,with a unique ability of bean oil utilization.Its potential of being a surrogate host for heterologous production of PKS was engineered and evaluated herein.Firstly,introduction of a three-gene cassette for the biosynthesis of ethylmalonyl-CoA resulted in accumulation of ethylmalonyl-CoA precursor and sahnomycin,and subsequent deletion of the sahnomycin biosynthetic gene cluster resulted in a host with rich supplies of common polyketide precursors,including malonyl-CoA,methylmalonyl-CoA,and ethylmalonyl-CoA.Secondly,the energy and reducing force were measured,and the improved accumulation of ATP and NADPH was observed in the mutant.Furthermore,the strength of a series of selected endogenous promoters based on microarray data was assessed at different growth phases,and a strong constitutive promoter was identified,providing a useful tool for further engineered gene expression.Finally,the potential of the BK3-25 derived host ZXJ-6 was evaluated with the introduction of the actinorhodin biosynthetic gene cluster from Streptomyces coelicolor,and the heterologous production of actinorhodin was obtained.This work clearly indicated the potential of the high-yield sahnomycin producer as a surrogate host for heterologous production of polyketides,although more genetic manipulation should be conducted to streamline its performance.

Anti-CD69 monoclonal antibody treatment inhibits airway inflammation in a mouse model of asthma

Objective： Airway inflammation and airway hyper-responsiveness（AHR） are principle pathological manifestations of asthma. Cluster of differentiation 69（CD69） is a well-known co-stimulatory factor associated with the activation, proliferation as well as apoptosis of immune cells. This study aims to examine the effect of anti-CD69 monoclonal antibody（m Ab） on the pathophysiology of a mouse model of asthma. Methods： A murine model of ovalbumin（OVA）-induced allergic airway inflammation was used in this study. Briefly, mice were injected with 20 μg chicken OVA intraperitoneally on Days 0 and 14, followed by aerosol provocation with 1%（0.01 g/ml） OVA on Days 24, 25, and 26. Anti-CD69 m Ab or isotype Ig G was injected intraperitoneally after OVA challenge; dexamethasone（DXM） was administrated either before or after OVA challenge. AHR, mucus production, and eosinophil infiltration in the peribronchial area were examined. The levels of granulocyte-macrophage colony-stimulating factor（GM-CSF） and interleukin-5（IL-5） in bronchoalveolar lavage fluid（BALF） were also assayed as indices of airway inflammation on Day 28 following OVA injection. Results： Pretreatment with DXM together with anti-CD69 m Ab treatment after OVA provocation completely inhibited AHR, eosinophil infiltration and mucus overproduction, and significantly reduced BALF IL-5. However, treatment with DXM alone after OVA challenge only partially inhibited AHR, eosinophil infiltration and mucus overproduction, and did not diminish BALF IL-5. Treatment with either DXM or anti-CD69 m Ab did not alter the concentration of BALF GM-CSF. Conclusions： Anti-CD69 m Ab treatment inhibits established airway inflammation as effectively as DXM pretreatment. This study provides a potential alternative therapeutic opportunity for the clinical management of asthma and its exacerbation.

Biosynthesis of tetronate antibiotics:A growing family of natural products with broad biological activities

Tetronate antibiotics, a growing family of natural products featuring a characteristic tetronic acid moiety, are of importance and of particular interest for their typical structures, especially the spirotetronate structure, and corresponding versatile biolog- ical activities. Considerable efforts have persistently performed since the first tetronate was isolated, to elucidate the biosyn- thesis of natural tetronate products, by isotope-labeled feeding experiments, genetical characterization of biosynthetic gene clusters, and biochemical reconstitution of key enzymatic catalyzed reactions. Accordingly, the biosynthesis of spirotetronates has been gradually determined, including biosynthesis of a polyketide-derived backbone for spirotetronate aglycone, incorpo- ration of a glycerol-derived three-carbon unit into tetronic acid moiety, formation of mature aglycone via Diels-AIder-like re- action, and decorations of aglycone with various deoxysugar moieties. In this paper, the biosynthetic investigations of natural tetronates are well documented and a common biosynthetic route for this group of natural products is summarized accordingly.