Contents of volume 16, 2006

EOITORIALA journey to a brighter futureGang Pei尺石功石的呀3 GATA·3PromotesTh2resPonsesthroughthreedifferentmeehanisms:inductionofThZeytokine Production,Selective growth of ThZ cells and inhibition of Thl eell·sPecific怕etors Jinfang Zhu,刀友论hiro Yamane,Javiel’ Cole一Sierra.Liying Guo,川llia脚E Paul1 1 The quantal theory of immunity 人治ndallA肠力ith20 Cytokines as critieal eo·stimulatory moleeules in modulating the immune resPonse of natural k川6F C6!!S Howa)汀A Young,…     

World Antibody-Drug Conjugate Summit,October 15–16, 2013, San Francisco,CA

The World Antibody-Drug Conjugate (WADC) Summits organized by Hanson Wade are currently the largest meetings fully dedicated to ADCs. The first global ADC Summit was organized in Boston in October 2010. Since 2011, two WADC are held every year in Frankfurt and San Francisco, respectively. The 2013 WADC San Francisco event was structured around plenary sessions with keynote speakers from AbbVie, Agensys, ImmunoGen, Immunomedics, Genentech, Pfizer and Seattle Genetics. Parallel tracks were also organized addressing ADC discovery, development and optimization of chemistry, manufacturing and control (CMC) issues. Discovery and process scientists, regulatory experts (US Food and Drug Administration), academics and clinicians were present, including representatives from biotechnology firms (Concortis, CytomX Therapeutics, Glykos, Evonik, Igenica, Innate Pharma, Mersana Therapeutics, Polytherics, Quanta Biodesign, Redwood Bioscience, Sutro Biopharma, SynAffix), pharmaceutical companies (Amgen, Genmab, Johnson and Johnson, MedImmune, Novartis, Progenics, Takeda) and contract research or manufacturing organizations (Baxter, Bayer, BSP Pharmaceuticals, Fujifilm/Diosynth, Lonza, Pierre Fabre Contract Manufacturing, Piramal, SAFC, SafeBridge).     

World Antibody-Drug Conjugate Summit,October 15–16, 2013, San Francisco,CA

The World Antibody-Drug Conjugate (WADC) Summits organized by Hanson Wade are currently the largest meetings fully dedicated to ADCs. The first global ADC Summit was organized in Boston in October 2010. Since 2011, two WADC are held every year in Frankfurt and San Francisco, respectively. The 2013 WADC San Francisco event was structured around plenary sessions with keynote speakers from AbbVie, Agensys, ImmunoGen, Immunomedics, Genentech, Pfizer and Seattle Genetics. Parallel tracks were also organized addressing ADC discovery, development and optimization of chemistry, manufacturing and control (CMC) issues. Discovery and process scientists, regulatory experts (US Food and Drug Administration), academics and clinicians were present, including representatives from biotechnology firms (Concortis, CytomX Therapeutics, Glykos, Evonik, Igenica, Innate Pharma, Mersana Therapeutics, Polytherics, Quanta Biodesign, Redwood Bioscience, Sutro Biopharma, SynAffix), pharmaceutical companies (Amgen, Genmab, Johnson and Johnson, MedImmune, Novartis, Progenics, Takeda) and contract research or manufacturing organizations (Baxter, Bayer, BSP Pharmaceuticals, Fujifilm/Diosynth, Lonza, Pierre Fabre Contract Manufacturing, Piramal, SAFC, SafeBridge).     

特色桑资源ITS, TrnL-F, rps16序列与亲缘关系分析

为了更好地开发利用特色桑树品种,分析了龙桑、龙须桑等12个特色桑资源ITS、TrnL-F、rps16碱基序列的长度、G+C含量、亲缘关系、遗传距离及信息变异位点。结果表明,ITS间隔区(包括5.8S)全长为576~590 bp,G+C含量59.38%~60.17%;TrnL-F间隔区(包括TrnL内含子)全长为920~923 bp,G+C含量为34.02%~34.24%;rps16内含子全长为929~947 bp,G+C含量为32.51%~33.26%。亲缘关系分析显示,分支图首先将外类群—构树分出,紧接着分出的是新疆黑桑。再依次为咸丰长穗桑、钦州长果桑、神农华桑、广东大10、雅安白桑、斯里兰卡1号、湖北蒙桑4号、龙桑、和田白桑,龙须桑、剑持、小冠桑在分支树的最顶层。根据外类群确定法,新疆黑桑为原始类型,龙须桑、剑持、小冠桑为最进化类型。遗传距离分析显示,新疆黑桑、剑持、咸丰长穗桑、钦州长果桑、小冠桑与其他桑属材料的遗传距离分别为1.0~1.3、0.2~0.3、0.1~0.4、0.1~0.2、0~0.3,龙桑、斯里兰卡1号、雅安白桑、和田白桑、广东大10、龙须桑、湖北蒙桑4号与其他桑属材料间遗传距离差异不大。信息变异位点分析显示共有14个信息位点,占总位点数的0.5564%。变异主要发生在外类群—构树和新疆黑桑,且变异大多集中在ITS区域。ITS、TrnL-F和rps16三片段分析桑属的亲缘关系,信息位点不足,有待深入研究。     

Unusual oxidative transformations of a steroidal 16α,17α,22-triol

A number of unexpected reactions were observed during attempts to invert configuration at C16 in 16α,17α,22-triol 3a. The PDC oxidation of 3a produced the D-seco-aldehyde 4a. Analogous compound 4b was obtained by Swern oxidation of the 16α,17α-dihydroxy-22-O-TES-ether 3b in addition to the desired 16-ketone 7. The unprotected triol 3a yielded pentacyclic products 5 and 6 under similar conditions. The Mitsunobu reaction of the triol 3a afforded 16-ketone 8 with inverted configuration of the side chain. During heating of a solution of 3a in THF with NaH at reflux autoxidation to the 16-ketone cyclic hemiketal 5, identical to one of the Swern oxidation products, took place.     

The microbiological transformation of epicandicandiol,ent-7α,18-dihydroxykaur-16-ene,by Gibberella fujikuroi

Incubation of ent-7α,18-dihydroxykaur-16-ene with Gibberella fujikuroi affords ent-7α,18,19-trihydroxykaur-16-ene and ent-7α,18-dihydroxykaur-16-en-19-oic acid. There was no transformation into 7,18-dihydroxykaurenolide.     

The microbiological transformation of candidiol,ent-15β,18-dihydroxy-kaur-16-ene,by gibberella fujikuroi

Incubation of candidiol, ent-15β,18-dihydroxy-kaur-16-ene, with Gibberella fujikuroi affords ent-11α,15β,18-trihydroxy-kaur-16-ene. Its structure was determined by X-ray analysis.     

The chemokine,CXCL16, and its receptor,CXCR6, are constitutively expressed in human annulus fibrosus and expression of CXCL16 is up-regulated by exposure to IL-1ß in vitro

Chemokines are an important group of soluble molecules with specialized functions in inflammation. The roles of many specialized chemokines and their receptors remain poorly understood in the human intervertebral disc. We investigated CXCL16 and its receptor, CXCR6, to determine their immunolocalization in disc tissue and their presence following exposure of cultured human annulus fibrosus cells to proinflammatory cytokines. CXCL16 is a marker for inflammation; it also can induce hypoxia-inducible factor 1α (HIF-1α), which is a phenotypic marker of heathy nucleus pulposus tissue. We found CXCL16 and CXCR6 immunostaining in many cells of the annulus portion of the disc. Molecular studies showed that annulus fibrosus cells exposed to IL-1ß, but not TNF-α, exhibited significant up-regulation of CXCL16 expression vs. control cells. There was no significant difference in the percentage of annulus cells that exhibited immunolocalization of CXCL16 in grade I/II, grade III or grade IV/V specimens. The presence of CXCL16 and its receptor, CXCR6, in the annulus in vivo suggests the need for future research concerning the role of this chemokine in proinflammatory functions, HIF-1α expression and disc vascularization.     

Synthesis, aggregation behavior and cholesterol solubilization studies of 16-epi-pythocholic acid (3α,12α,16β-trihydroxy-5β-cholan-24-oic acid)

Synthesis, aggregation behavior and in vitro cholesterol solubilization studies of 16-epi-pythocholic acid (3α,12α,16β-trihydroxy-5β-cholan-24-oic acid, EPCA) are reported. The synthesis of this unnatural epimer of pythocholic acid (3α,12α,16α-trihydroxy-5β-cholan-24-oic acid, PCA) involves a series of simple and selective chemical transformations with an overall yield of 21% starting from readily available cholic acid (CA). The critical micellar concentration (CMC) of 16-epi-pythocholate in aqueous media was determined using pyrene as a fluorescent probe. In vitro cholesterol solubilization ability was evaluated using anhydrous cholesterol and results were compared with those of other natural di- and trihydroxy bile acids. These studies showed that 16-epi-pythocholic acid (16β-hydroxy-deoxycholic acid) behaves similar to cholic acid (CA) and avicholic acid (3α,7α,16α-trihydroxy-5β-cholan-24-oic acid, ACA) in its aggregation behavior and cholesterol dissolution properties.     

The new ParaDIgm: IgM from bench to clinic: November 15–16, 2011, Frankfurt,Germany

The inaugural IgM event entitled “The new ParaDIgm: IgM from bench to clinic” brought together the increasingly active and growing IgM antibody community to discuss recent advances and challenges facing the discovery and development of IgM antibody therapies and technologies. Researchers, clinicians and biomanufacturing experts delivered 21 talks on the basic science and isolation of IgM, upstream and downstream development, and formulation and clinical development of the molecules. Participants networked around topics aimed at exploring the full potential of IgM antibodies. The meeting was held at DECHEMA Gesellschaft für Chemische Technik und Biotechnologie e. V. (Society for Chemical Engineering and Biotechnology), a non-profit scientific and technical society based in Frankfurt am Main, Germany. The meeting was sponsored by Patrys, Laureate Biopharma, Bio-Rad Laboratories, BIA Separations, Percivia and the Bio Affinity Company (BAC). The second New ParaDIgm: IgM from bench to clinic meeting, will be held on April 23–24, 2013 in Frankfurt, Germany.     

F16,一种以线粒体为靶点的抗癌分子

寻找以线粒体为靶点的抗癌新药,是近年来的研究热点。研究在探讨HER-2／ErbB-2下游信号传导通路的过程中,发现了一种新的抗癌分子——F16。这是一种高度疏水、电子移位亲脂性阳离子,能够靶向聚集于肿瘤细胞线粒体基质内,引起线粒体渗透性转换孔开放,导致肿瘤细胞凋亡;同时,在肿瘤细胞过度表达抗凋亡蛋白的情况下,能够通过干扰肿瘤细胞能量代谢、增加活性氧中间产物产生等途径,诱导肿瘤细胞坏死。     

Capture, mark and re-capture workshop Hannover 16–17 March 2006

Announcement

Capture, mark and re-capture workshop Hannover 16–17 March 2006     

拟诺卡氏菌16S rRNA,gyrB,sod和rpoB基因的系统发育分析

为了更好地了解拟诺卡氏菌属(Nocardiopsis)各物种间的系统发育关系,该属现有有效描述种的gyrB,sod和rpoB基因的部分序列被测定,结合16S rRNA基因,对拟诺卡氏菌属进行了系统发育重建。研究发现拟诺卡氏菌属gyrB,sod和rpoB基因的平均相似性分别为87.7%、87.3%和94.1%,而16S rRNA基因的平均相似性则达到96.65%,3个看家基因均比16S rRNA具有更高的分歧度。比较基于不同基因的系统树发现,由gyrB基因得到的系统树拓扑结构与16S rRNA得到的结构在亚群上基本一致。因此,gyrB基因在拟诺卡氏菌属的系统分类上比16S rRNA基因更具优越性。