迷失的世界(18)

正[前情回顾]米鲁在能量豆制造工厂发现了一株奇特的巨魔芋,奋不顾身想要带走它,却因此落入兔人长老院惩罚重要罪犯的奇幻森林,还遇到了被控制的伽马。在与伽马对抗的过程中,原本并肩作战的小怪物突然变脸,将米鲁和伽马一起推下了悬崖。     

一例罕见的t(6;18) del(18)综合征

Gouw等于1973年首次报道了t(6;18)(p22;q12)病例。同年,Nakagme等也发现了t(6;18)(q27;q11)核型。迄今国外共发现至少9种关于t(6;18)核型。而国内尚未见公开报道。 作者从遗传咨询门诊病人中,检出一例至今未见报道过的t(6;18)del(18)综合征患者。现简要报告如下。     

成纤维细胞生长因子18(FGF18)的研究进展

成纤维细胞生长因子18 (fibroblast growth factor 18,FGF18)是成纤维细胞生长因子家族( FGFs)的成员之一.研究发现,FGF 18不仅在骨骼发育和生长期对软骨形成和成骨生成起着重要的作用,其功能也已延伸至其他许多生物过程,尽管对FGF18作为一个有用治疗靶点发挥作用的功能和机制仍有待进一步的发现及研究.现针对FGF18的特点,及其在骨骼发育中的功能,特别其在未来具有潜在应用领域上的研究进展进行综述.     

一例罕见的t(6;18) del(18）综合征

Gouw 等于1973年首次报道了t(6; 18) (p22;g12）病例。同年，Nakagme等也发现 了t(6;18)(g27;qll）核型。迄今国外共发现 至少9种关于t(6;18）核型。而国内尚未见公 开报道。     

[18F]DAA1106: Automated radiosynthesis using spirocyclic iodonium ylide and preclinical evaluation for positron emission tomography imaging of translocator protein (18 kDa)

DAA1106 (N-(2,5-dimethoxybenzyl)-N-(5-fluoro-2-phenoxyphenyl)acetamide), is a potent and selective ligand for the translocator protein (18?kDa, TSPO) in brain mitochondrial fractions of rats and monkey (K_i?=?0.043 and 0.188?nM, respectively). In this study, to translate [¹⁸F]DAA1106 for clinical studies, we performed automated syntheses of [¹⁸F]DAA1106 using the spirocyclic iodonium ylide (1) as a radiolabelling precursor and conducted preclinical studies including positron emission tomography (PET) imaging of TSPO in ischemic rat brains. Radiofluorination of the ylide precursor 1 with [¹⁸F]F^?, followed by HPLC separation and formulation, produced the [¹⁸F]DAA1106 solution for injection in 6% average (n?=?10) radiochemical yield (based on [¹⁸F]F^?) with >98% radiochemical purity and molar activity of 60–100?GBq/μmol at the end of synthesis. The synthesis time was 87?min from the end of bombardment. The automated synthesis achieved [¹⁸F]DAA1106 with sufficient radioactivity available for preclinical and clinical use. Biodistribution study of [¹⁸F]DAA1106 showed a low uptake of radioactivity in the mouse bones. Metabolite analysis showed that >96% of total radioactivity in the mouse brain at 60?min after the radiotracer injection was unmetabolized [¹⁸F]DAA1106. PET study of ischemic rat brains visualized ischemic areas with a high uptake ratio (1.9?±?0.3) compared with the contralateral side. We have provided evidence that [¹⁸F]DAA1106 could be routinely produced for clinical studies.     

泥鳅角蛋白18(K18)基因的克隆与表达分析

角蛋白18(K18)是角蛋白的一种,为中间纤维蛋白,是细胞骨架的组成部分。为了解泥鳅(Misgurnus anguillicaudatus)K18序列特征及其在不同组织中的表达,研究采用3'-和5'-RACE法克隆K18基因c DNA全长序列,并运用实时荧光定量PCR技术探讨其在不同组织中的表达。结果表明,泥鳅K18基因c DNA全长序列1 694 bp,其中包含开放阅读框1 299bp,编码432个氨基酸,其序列具有Ⅰ型角蛋白序列DGKVVS,以及非常相似序列DNA(R/K)LAADDF。相似度分析显示,泥鳅K18与大鳞副泥鳅(Paramisgurnus dabryanus)的相似度最高为98%,与其它物种K18也存在不同程度的相似度。系统进化分析表明,泥鳅与其他物种的K18系统发育同源,且同陆生脊椎动物和硬骨鱼类同源,并与大鳞副泥鳅的关系最为密切。通过定量分析,K18基因在泥鳅肠、肌肉、心脏、胃、肝脏、精巢、卵巢、脾脏等8种组织都有表达,其中,肠表达最高,心脏最低。统计学分析表明,K18基因的表达在不同组织间存在显著性差异。     

Development of novel liver X receptor modulators based on a 1,2,4-triazole scaffold

Liver?X?Receptor (LXR) agonists have been reported as a potential treatment for atherosclerosis, Alzheimer’s disease and hepatitis C virus (HCV) infection. We have designed and synthesized a series of potent compounds based on a 1,2,4-triazole scaffold as novel LXR modulators. In cell-based cotransfection assays these compounds generally functioned as LXR agonists and we observed compounds with selectivity towards LXRα (7-fold) and LXRβ (7-fold) in terms of potency. Assessment of the effects of selected compounds on LXR target gene expression in HepG2 cells revealed that compounds 6a-b and 8a-b behaved as inverse agonists on FASN expression even though they were agonists in the LXRα and LXRβ cotransfection assays. Interestingly, these compounds had no effect on the expression of SREBP-1c confirming a unique LXR modulator pharmacology. Molecular docking studies and evaluation of ADME properties in-silico show that active compounds possess favorable binding modes and ADME profiles. Thus, these compounds may be useful for in vivo characterization of LXR modulators with unique profiles and determination of their potential clinical utility.     

3D-pharmacophore model for RXRγ agonists

Three-dimensional pharmacophore models were generated for retinoid X receptor (RXR_γ) agonists using quantitative approach (CATALYST HypoRefine). One optimal pharmacophore model for selective RXR_γ agonists was determined through careful validation processes. The best quantitative model (Hypo-1) had five features and five excluded volumes: three hydrophobic aliphatic groups (HAL1, HAL2, and HAL3), one hydrophobic aromatic ring (HAR), and one hydrogen bond acceptor (HBA). The model was validated using a wide range of test molecules. It could predict agonist activity and identify highly potent molecules. The present results are valuable to discover and develop specific RXR_γ agonists with desired biological activities.     

C_(18)H_(29)SO_3Na降解菌的降解能力测定

本实验从环境中提取表面活性剂(C18H29SO3Na)降解菌,进行富集分离,测定其降解能力,并研究不同起始浓度C18H29SO3Na对微生物降解度的影响。实验表明,随着起始浓度增加,其毒性增强,菌株的降解度逐渐减小。     

Stathmin/Oncoprotein 18(Op18)基因在人骨肉瘤中的表达及其意义

目的:探讨stathmin/oncoprotein 18(Op18)基因在人骨肉瘤中的表达规律及意义。方法:分别采用免疫组化法和Western blot法检测10例正常骨组织和56例骨肉瘤中stathmin蛋白的表达。结果:免疫组化法检测stathmin蛋白在正常骨组织、低级别骨肉瘤(G1级组)及高级别骨肉瘤(G2级组)中阳性表达率分别为20%、65%、100%。正常骨组织分别与G1级组、G2级组比较,均有显著性差异(P﹤0.05);G1级组与G2级组比较,有显著差异(P<0.05)。Western blot法检测显示,stathmin蛋白在正常骨组织、G1级组、G2级组表达相对值分别为(0.34±0.15)、(0.68±0.21)、(0.90±0.17)。正常骨组织分别与G1级级组、G2级组比较,差异均有显著性(P<0.01),G1级组与G2级组比较,差异有显著性(P<0.01)。结论:Stathmin在骨肉瘤中过表达,与骨肉瘤的发生及发展密切相关。     

Incidentalomes parotidiens en TEP-18F-FDG : prévalence,diagnostic et impact thérapeutique

Objective

Parotid gland incidentalomas are unexpected hypermetabolic foci in the parotid region that can be found when scanning the whole-body by PET/CT. The role of SUVmax is controversial to differentiate benign or malignant tumours in this indication. The aim of this study was to determine PET/CT features of malignant parotid incidentaloma, in order to improve medical care.

人白介素18(IL-18)RGD模体抗黑色素瘤细胞B16活性研究

利用定点突变及DNA重组技术,在人白细胞介素18(IL-18)的cDNA序列中插入了GGC序列,使IL-18第39精氨酸残基和第40天冬氨酸残基之间插入一个甘氨酸残基,从而构建了RGD模体。此重组的cDNA序列构建入表达质粒pPIC9K,并转化Pichia Pastoris酵母GS115,利用表达系统进行了高效表达。用Sephadex G-100凝胶过滤纯化表达产物,获得初步纯化的蛋白。研究表明,IL-18在体外对黑色素瘤细胞株B16没有作用,而IL-18-RGD抑制作用明显,IC50 = 8.10μmol/L;应用小鼠动物模型研究结果显示,IL-18及IL-18-RGD均对黑色素瘤细胞B16有抑制作用,且IL-18-RGD比IL-18的作用强;同时,对鸡胚绒毛尿囊膜(chicken chorioallantoic membrane,CAM)血管生成的抑制实验发现,IL-18-RGD 对CAM血管生成的抑制作用也比IL-18强。但IL-18-RGD仍保存对PBMC诱导产生IFN-γ能力。结果提示,IL-18-RGD在具有抗炎,抗感染作用的同时增添了抑制肿瘤血管新的功能。     

Association between carbonyl sulfide uptake and (18)Δ during gas exchange in C(3) and C(4) leaves

Carbonyl sulfide (COS) and C(18)OO exchange by leaves provide potentially powerful tracers of biosphere-atmosphere CO(2) exchange, and both are assumed to depend on carbonic anhydrase (CA) activity and conductance along the diffusive pathway in leaves. We investigated these links using C(3) and C(4) plants, hypothesizing that the rates of COS and C(18)OO exchange by leaves respond in parallel to environmental and biological drivers. Using CA-deficient antisense lines of C(4) and C(3) plants, COS uptake was essentially eliminated and discrimination against C(18)OO exchange ((18)Δ) greatly reduced, demonstrating CA's key role in both processes. (18)Δ showed a positive linear correlation with leaf relative uptake (LRU; ratio of COS to CO(2) assimilation rates, A(s)/A(c), normalized to their respective ambient concentrations), which reflected the effects of stomatal conductance on both COS and C(18)OO exchange. Unexpectedly, a decoupling between A(s) and (18)Δ was observed in comparing C(4) and C(3) plants, with a large decrease in (18)Δ but no parallel reduction in A(s) in the former. This could be explained by C(4) plants having higher COS concentrations at the CA site (maintaining high A(s) with reduced CA) and a high phosphoenolpyruvate carboxylase/CA activity ratio (reducing (18)O exchange efficiency between CO(2) and water, but not A(s)). Similar A(s) but higher A(c) in C(4) versus C(3) plants resulted in lower LRU values in the former (1.16 ± 0.20 and 1.82 ± 0.18 for C(4) and C(3), respectively). LRU was, however, relatively constant in both plant types across a wide range of conditions, except low light (<191 μmol photon m(-2) s(-1)).     

No-carrier-added (NCA) (±)-N-(3-[18F]fluoropropyl)-N-normetazocine-Synthesis and PET studies in a baboon

No-carrier-added (NCA) (±)-N-(3-[¹⁸F]Fluoropropyl)-N-normetazocine (2) was synthesized by N-alkylation of (±)-N-normetazocine (1) with NCA 1-[¹⁸F]fluoro-3-iodopropane in an overall radiochemical yield of 10% (EOB) with a mass of 3.5 nmol in a synthesis time of 90 min from end of bombardment (EOB). PET studies of 2 in a baboon did not indicate specificity for opiate receptor sites alone: The activity declined rapidly in the striatum the frontal cortex and the cerebellum. The baboon total arterial plasma radioactivity clearance was very rapid and the metabolism of compound 2 in plasma was also very rapid. These results suggest that compound 2 is not a suitable radioligand for imaging opiate receptors in the human brain by positron tomography.     

《细胞生物学杂志》第18卷总目录(1996)

怀念庄孝德教授····························································································……张小云工:(1) 永远怀念庄孝德先生···················································································……翟中和皿:(封二)专论与综述、细胞谱系研究中的一种标记基因—Lacz基因···············…     

2007年第18届国际生物学奥林匹克竞赛(7)

问题46～48.下图示不同物质以不同方式通过生物膜。问题46.将图中的字母代号填到相应的空格内。(4分)运输机制