• 【孕妇1型糖尿病的胎盘甘油三酸酯蓄积与脂肪酶基因表达增加有关。】 复制标题 收藏 收藏
    DOI:10.1194/jlr.M600236-JLR200 复制DOI
    作者列表:Lindegaard ML,Damm P,Mathiesen ER,Nielsen LB
    BACKGROUND & AIMS: :Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport in placenta is largely unknown. To examine whether maternal type 1 diabetes affects placental lipid metabolism, we measured lipids and mRNA expression of lipase-encoding genes in placentas from women with type 1 diabetes (n = 27) and a control group (n = 21). The placental triglyceride (TG) concentration and mRNA expression of endothelial lipase (EL) and hormone-sensitive lipase (HSL) were increased in placentas from women with diabetes. The differences were more pronounced in women with diabetes and suboptimal metabolic control than in women with diabetes and good metabolic control. Placental mRNA expression of lipoprotein lipase and lysosomal lipase were similar in women with diabetes and the control group. Immunohistochemistry showed EL protein in syncytiotrophoblasts facing the maternal blood and endothelial cells facing the fetal blood in placentas from both normal women and women with diabetes. These results suggest that maternal type 1 diabetes is associated with TG accumulation and increased EL and HSL gene expression in placenta and that optimal metabolic control reduces these effects.
    背景与目标: 孕产妇糖尿病会导致胎儿巨大儿,并在后代成年后增加肥胖,糖尿病和心血管疾病的风险。尽管可能涉及胎盘脂质转运的增加,但母体1型糖尿病对胎盘脂质转运分子机制的影响尚不清楚。为了检查母体1型糖尿病是否影响胎盘脂质代谢,我们测量了1型糖尿病女性(n = 27)和对照组(n = 21)的胎盘中脂质和脂肪酶编码基因的mRNA表达。糖尿病女性胎盘中胎盘甘油三酸酯(TG)的浓​​度和内皮脂肪酶(EL)和激素敏感性脂肪酶(HSL)的mRNA表达增加。糖尿病和代谢控制欠佳的女性比糖尿病和代谢控制良好的女性更明显。糖尿病女性和对照组胎盘脂蛋白脂肪酶和溶酶体脂肪酶的mRNA表达相似。免疫组织化学显示,正常妇女和糖尿病妇女的胎盘中母体血液中的合体滋养层细胞和胎儿血中的内皮细胞中的EL蛋白。这些结果表明,孕妇1型糖尿病与TG积累和胎盘中EL和HSL基因表达增加有关,最佳的代谢控制可降低这些影响。
  • 【鸡原始生殖细胞ESTs的基因表达谱。】 复制标题 收藏 收藏
    DOI:10.1186/1471-2164-7-220 复制DOI
    作者列表:Han JY,Park TS,Kim JN,Kim MA,Lim D,Lim JM,Kim H
    BACKGROUND & AIMS: BACKGROUND:Germ cells are the only cell type that can penetrate from one generation to next generation. At the early embryonic developmental stages, germ cells originally stem from primordial germ cells, and finally differentiate into functional gametes, sperm in male or oocyte in female, after sexual maturity. This study was conducted to investigate a large-scale expressed sequence tag (EST) analysis in chicken PGCs and compare the expression of the PGC ESTs with that of embryonic gonad. RESULTS:We constructed 10,851 ESTs from a chicken cDNA library of a collection of highly separated embryonic PGCs. After chimeric and problematic sequences were filtered out using the chicken genomic sequences, there were 5,093 resulting unique sequences consisting of 156 contigs and 4,937 singlets. Pearson chi-square tests of gene ontology terms in the 2nd level between PGC and embryonic gonad set showed no significance. However, digital gene expression profiling using the Audic's test showed that there were 2 genes expressed significantly with higher number of transcripts in PGCs compared with the embryonic gonads set. On the other hand, 17 genes in embryonic gonads were up-regulated higher than those in the PGC set. CONCLUSION:Our results in this study contribute to knowledge of mining novel transcripts and genes involved in germline cell proliferation and differentiation at the early embryonic stages.
    背景与目标: 背景:生殖细胞是唯一可以从一代渗透到下一代的细胞类型。在胚胎发育的早期阶段,生殖细胞最初起源于原始生殖细胞,并在性成熟后分化为功能性配子,雄性精子或雌性卵母细胞。进行这项研究以调查鸡PGC中的大规模表达序列标签(EST)分析,并将PGC EST与胚胎性腺的表达进行比较。
    结果:我们从鸡的高度分离的胚胎PGC的cDNA文库中构建了10,851个EST。使用鸡基因组序列过滤掉嵌合和有问题的序列后,共有5,093个得到的独特序列,由156个重叠群和4,937个单重态组成。 PGC和胚胎性腺集之间第二级的基因本体项的皮尔逊卡方检验没有意义。但是,使用Audic's测试进行的数字基因表达谱分析显示,与胚胎性腺相比,PGC中有2个基因表达显着,且转录本数量更高。另一方面,胚胎性腺中的17个基因上调的程度高于PGC中的基因。
    结论:我们在这项研究中的结果有助于了解在胚胎早期阶段涉及生殖细胞增殖和分化的新转录本和基因。
  • 【链霉菌A3(2)中的一种隐秘的I型聚酮化合物合酶(cpk)基因簇。】 复制标题 收藏 收藏
    DOI:10.1007/s00203-006-0176-7 复制DOI
    作者列表:Pawlik K,Kotowska M,Chater KF,Kuczek K,Takano E
    BACKGROUND & AIMS: :The chromosome of Streptomyces coelicolor A3(2), a model organism for the genus Streptomyces, contains a cryptic type I polyketide synthase (PKS) gene cluster which was revealed when the genome was sequenced. The ca. 54-kb cluster contains three large genes, cpkA, cpkB and cpkC, encoding the PKS subunits. In silico analysis showed that the synthase consists of a loading module, five extension modules and a unique reductase as a terminal domain instead of a typical thioesterase. All acyltransferase domains are specific for a malonyl extender, and have a B-type ketoreductase. Tailoring and regulatory genes were also identified within the gene cluster. Surprisingly, some genes show high similarity to primary metabolite genes not commonly identified in any antibiotic biosynthesis cluster. Using western blot analysis with a PKS subunit (CpkC) antibody, CpkC was shown to be expressed in S. coelicolor at transition phase. Disruption of cpkC gave no obvious phenotype.
    背景与目标: :Streptomyces coelicolor A3(2)(Streptomyces属的一种模式生物)的染色体包含一个隐秘的I型聚酮化合物合酶(PKS)基因簇,该基因簇在对基因组进行测序时就显示出来。的ca。 54kb的簇包含三个大基因,编码PKS亚基的cpkA,cpkB和cpkC。在计算机分析中,该合成酶由一个加载模块,五个扩展模块和一个独特的还原酶(而不是典型的硫酯酶)作为末端结构域组成。所有酰基转移酶结构域都对丙二酰增量剂具有特异性,并具有B型酮还原酶。还可以在基因簇中鉴定出剪裁和调节基因。出乎意料的是,一些基因显示出与任何抗生素生物合成簇中未普遍鉴定的初级代谢产物基因高度相似。使用具有PKS亚基(CpkC)抗体的Western印迹分析,显示CpkC在过渡阶段在天蓝色链霉菌中表达。 cpkC的破坏没有明显的表型。
  • 【哪些血栓形成性基因突变是复发性流产的危险因素?】 复制标题 收藏 收藏
    DOI:10.1111/j.1600-0897.2006.00419.x 复制DOI
    作者列表:Goodman CS,Coulam CB,Jeyendran RS,Acosta VA,Roussev R
    BACKGROUND & AIMS: PROBLEM:Thrombophilia has been associated with poor obstetrical outcomes. To determine the association of specific inherited thrombophilias and recurrent pregnancy loss, 10 thrombophilic genes were investigated. METHOD OF STUDY:A total of 550 women with a history of recurrent pregnancy loss had buccal swabs taken for DNA analyses of the following gene mutations: factor V G1691A, factor V H1299R (R2), factor V Y1702C, factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), methylenetetrahydrofolate reductase (MTHFR) C677T, MTHFR A1298C. The frequencies of these mutations were compared with controls published in the literature. RESULTS:When examined individually, PAI-1 4G/5G (P = 0.009), factor XIII V34L (P < 0.0001), and homozygous MTHFR C667T (P < 0.0001) correlated significantly with recurrent pregnancy loss compared with controls. The frequency of the factor V Y1702C mutation was extremely low in patients and controls; thus, this gene was removed from further calculations. The remaining six mutated genes, when analyzed cumulatively, also corresponded with recurrent pregnancy loss (P < 0.0001). CONCLUSION:A panel of thrombogenic gene mutations consisting of factor V G1691A, factor V H1299R (R2), factor II prothrombin G20210A, factor XIII V34L, beta-fibrinogen -455G>A, PAI-1 4G/5G, HPA1 a/b(L33P), MTHFR C677T, and MTHFR A1298C can identify individuals at risk for recurrent pregnancy loss.
    背景与目标: 问题:血友病与产科预后不良有关。为了确定特定遗传性血栓形成症与复发性流产的关联,研究了10个血栓形成性基因。
    研究方法:总共550名有反复性流产史的妇女接受了口腔拭子以进行以下基因突变的DNA分析:因子V G1691A,因子V H1299R(R2),因子V Y1702C,因子II凝血酶原G20210A,因子XIII V34L,β-纤维蛋白原-455G> A,PAI-1 4G / 5G,HPA1a / b(L33P),亚甲基四氢叶酸还原酶(MTHFR)C677T,MTHFR A1298C。将这些突变的频率与文献中发表的对照进行了比较。
    结果:当单独检查时,与对照组相比,PAI-1 4G / 5G(P = 0.009),XIII因子V34L(P <0.0001)和纯合MTHFR C667T(P <0.0001)与复发性流产显着相关。在患者和对照组中,V Y1702C因子突变的频率非常低。因此,该基因已从进一步的计算中删除。当进行累积分析时,剩下的六个突变基因也与复发性流产相对应(P <0.0001)。
    结论:一组血栓形成基因突变,由因子V G1691A,因子V H1299R(R2),因子II凝血酶原G20210A,因子XIII V34L,β-纤维蛋白原-455G> A,PAI-1 4G / 5G,HPA1 a / b( L33P),MTHFR C677T和MTHFR A1298C可以识别有复发性流产风险的个体。
  • 【大鼠角膜缘和中央角膜上皮中基因表达(SAGE)的系列分析。】 复制标题 收藏 收藏
    DOI:10.1167/iovs.06-0216 复制DOI
    作者列表:Adachi W,Ulanovsky H,Li Y,Norman B,Davis J,Piatigorsky J
    BACKGROUND & AIMS: PURPOSE:To identify genes preferentially expressed in the stem-cell-rich limbal epithelium of the rat cornea. METHODS:The limbal and central corneal epithelial cells of 6-week-old rats were isolated by microdissection. Serial analysis of gene expression (SAGE) libraries were constructed and analyzed, and in situ hybridization, reverse transcription-polymerase chain reaction (RT-PCR) and cDNA cloning were conducted by conventional procedures. RESULTS:The rat limbal and central corneal epithelial SAGE libraries consisted of 41,894 and 40,691 tags, respectively. After annotation, this was reduced to 759 transcripts specific for the limbal library and 844 transcripts specific for the central corneal library; 2292 transcripts overlapped. Transcripts encoding proteins with metabolic functions comprised the major functional category in both libraries. In situ hybridization and/or RT-PCR results of 12 of the most abundant, highly enriched transcripts in the limbal epithelium were in general agreement with the SAGE data and showed that these proteins are also expressed in the conjunctival epithelium. Interesting limbal-enriched transcripts encode WDNM1-like protein (similar to WDNM1/Expi, a putative secreted proteinase and inhibitor of metastasis), mesothelin (a cancer marker), marapsin (a trypsin-like serine protease that may control cell growth and migration), K4 and K15 (both cytokeratins), and membrane-spanning four-domain subfamily A member 8B. WDNM1-like protein was cloned and confirmed as a member of the four-disulfide core family. CONCLUSIONS:The SAGE results extend the database of genes expressed in the rodent cornea and suggest an association between several genes preferentially expressed in the limbal epithelium with cellular proliferation and migration.
    背景与目标: 目的:鉴定在大鼠角膜的富含干细胞的角膜缘上皮细胞中优先表达的基因。
    方法:采用显微解剖技术分离6周龄大鼠角膜缘和角膜上皮细胞。构建并分析基因表达(SAGE)库的序列分析,并通过常规方法进行原位杂交,逆转录-聚合酶链反应(RT-PCR)和cDNA克隆。
    结果:大鼠角膜缘和角膜上皮SAGE文库分别由41,894和40,691个标签组成。注释后,该数目减少为角膜缘文库特异的759个转录物和中央角膜文库特异的844个转录物。 2292个成绩单重叠。编码具有代谢功能的蛋白质的转录本在两个文库中均属于主要功能类别。角膜缘上皮细胞中12种最丰富,高度富集的转录本的原位杂交和/或RT-PCR结果与SAGE数据基本一致,表明这些蛋白也在结膜上皮细胞中表达。有趣的角膜缘丰富的转录本编码WDNM1样蛋白(类似于WDNM1 / Expi,一种假定的分泌蛋白酶和转移抑制剂),间皮素(一种癌症标志物),marapsin(一种胰蛋白酶样丝氨酸蛋白酶,可以控制细胞的生长和迁移)。 ,K4和K15(均为细胞角蛋白)和跨膜四结构域亚家族A成员8B。克隆了类似WDNM1的蛋白质,并确认其为四-二硫键核心家族的成员。
    结论:SAGE结果扩展了在啮齿动物角膜中表达的基因数据库,并暗示了在角膜缘上皮中优先表达的几个基因与细胞增殖和迁移之间的关联。
  • 【与人神经胶质瘤有关的人核糖体蛋白L14.22的全长新基因。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Qi ZY,Hui GZ,Li Y,Zhou ZX,Gu SH,Xie Y
    BACKGROUND & AIMS: BACKGROUND:This study was undertaken to obtain differentially expressed genes related to human glioma by cDNA microarray and the characterization of a novel full-length gene. METHODS:Total RNA was extracted form human glioma and normal brain tissue, and mRNA was used as a probe. The results of hybridization procedure were scanned with the computer system. The gene named 507E08 cone was subsequently analyzed by northern blot, bioinformatic approach, and protein expression. RESULTS:Fifteen differentially expressed genes were obtained from human glioma by hybridization and scanning for four times. Northern blot analysis confirmed that the 507E08 clone was low expressed in human brain tissue and over expressed in human glioma tissues. The analysis of BLASTn and BLASTx showed that the 507E08 clone was a novel full-length gene, which codes 203 amino acid of protein and is called human ribosomal protein 14.22 gene. The nucleotide sequence had been submitted to the GenBank with the accession number of AF329277. After expression in E. coli., protein yielded a major band of apparent molecular mass 22 kDa on an SDS-PAGE gel. CONCLUSIONS:cDNA microarray technology can be successfully used to identify differentially expressed genes. The novel full-length gene of human ribosomal protein 13.22 may be correlated with the development of human glioma.
    背景与目标: 背景:本研究旨在通过cDNA微阵列技术获得与人神经胶质瘤相关的差异表达基因,并鉴定一个新的全长基因。
    方法:从人脑胶质瘤和正常脑组织中提取总RNA,并以mRNA为探针。杂交程序的结果用计算机系统扫描。随后通过Northern印迹,生物信息学方法和蛋白质表达来分析名为507E08视锥细胞的基因。
    结果:通过杂交和扫描4次,从人脑胶质瘤中获得了15个差异表达基因。 Northern印迹分析证实507E08克隆在人脑组织中低表达而在人脑胶质瘤组织中高表达。对BLASTn和BLASTx的分析表明,507E08克隆是一个新颖的全长基因,其编码蛋白质的203个氨基酸,被称为人核糖体蛋白质14.22基因。该核苷酸序列已提交给GenBank,登录号为AF329277。在大肠杆菌中表达后,蛋白质在SDS-PAGE凝胶上产生一条表观分子量为22 kDa的主带。
    结论:cDNA微阵列技术可成功用于鉴定差异表达的基因。人核糖体蛋白13.22的新的全长基因可能与人脑胶质瘤的发展有关。
  • 【罕见的母体mRNA编码调控蛋白,这些蛋白控制着海胆胚胎中谱系特异性基因的表达。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.20.7953 复制DOI
    作者列表:Cutting AE,Höög C,Calzone FJ,Britten RJ,Davidson EH
    BACKGROUND & AIMS: :The prevalence of mRNAs coding for the sea urchin embryo regulatory factors P3A1 and P3A2 was measured by single-strand probe excess solution hybridization. P3A1 and P3A2 are not homologous proteins, though they both bind specifically to a particular cis-regulatory sequence. Interaction at this target site is known to be required for lineage-specific expression of an aboral ectoderm-specific gene and probably for several other genes as well. Genome blot hybridizations show that both factors are encoded by single-copy genes. Maternal mRNAs for both factors are present at less than 10(3) molecules per egg, which places them in the rare mRNA class. During development to the mesenchyme blastula stage, the amount of P3A1 mRNA (per embryo) increases severalfold while that of P3A2 remains approximately constant. Specification of the aboral ectoderm founder cells and of their initial patterns of gene expression must occur during early to mid-cleavage stage. Therefore, the regulatory proteins needed for this process must be produced by this stage. We show that the quantities of the P3A proteins that can be synthesized from the numbers of mRNA molecules present in the large blastomeres of the early embryo are sufficient to be functional, because these proteins will be accumulated in the nuclei. Thus maternal P3A1 or P3A2 proteins asre not required, nor were these detected in earlier studies. Furthermore, differential spatial (as well as temporal) distribution of both of these newly synthesized factor species could result from the unequal cleavage pattern utilized in the sea urchin egg.
    背景与目标: :通过单链探针过量溶液杂交测量编码海胆胚胎调节因子P3A1和P3A2的mRNA的发生率。尽管P3A1和P3A2都与特定的顺式调控序列特异性结合,但它们不是同源蛋白。已知该靶标位点的相互作用是特定于宗族的外胚层特异性基因的谱系表达所必需的,并且可能还需要其他几个基因。基因组印迹杂交显示这两个因子均由单拷贝基因编码。每个鸡蛋的母体mRNA均少于10(3)个分子,这使它们处于罕见的mRNA类中。在发育到间充质囊阶段期间,P3A1 mRNA(每个胚胎)的数量增加了几倍,而P3A2的数量保持近似恒定。胎盘外胚层基础细胞及其基因表达的初始模式的规范必须在卵裂早期至中期进行。因此,必须在该阶段生产该过程所需的调节蛋白。我们表明,可以从早期胚胎的大型卵裂球中存在的mRNA分子数量合成的P3A蛋白数量足以发挥功能,因为这些蛋白将积聚在细胞核中。因此,不需要母体P3A1或P3A2蛋白,也不需要在早期研究中检测到这些蛋白。此外,这两种新合成的因子物种在空间(以及时间)上的差异分布可能是由于海胆卵中使用的不均等卵裂模式造成的。
  • 【上颌骨成骨术中的载体比对。】 复制标题 收藏 收藏
    DOI:10.1097/01.scs.0000234980.76992.69 复制DOI
    作者列表:Uckan S,Arman A,Bayram B,Celik E
    BACKGROUND & AIMS: :Maxillary distraction osteogenesis is an alternative treatment of cleft patients with severe maxillary hypoplasia. The aim of this paper is to present the combined surgical/orthodontic treatment of a cleft lip and palate patient and to evaluate the maxillary distraction procedure and the distraction vector in high Le Fort I osteotomy.
    背景与目标: :上颌骨牵张成骨是严重上颌骨发育不全的left裂患者的另一种治疗方法。本文的目的是介绍唇裂和pa裂患者的手术/正畸综合治疗,并评价上Le Fort I截骨术的上颌牵张方法和牵张向量。
  • 【肺鱼是化石吗?阿片/孤儿蛋白基因家族进化的观察。】 复制标题 收藏 收藏
    DOI:10.1016/j.ygcen.2006.07.010 复制DOI
    作者列表:Lee J,Alrubaian J,Dores RM
    BACKGROUND & AIMS: :This minireview considers the possibility that there is a correlation between the slow rate of morphological change and speciation events that has been occurred within the lungfish lineage since the Permian period, and the apparent slow rate of divergence in the amino acid sequences of lungfish opioid precursor sequences. The status of lungfish as "living fossils" is considered.
    背景与目标: :本篇小型综述认为,二叠纪以来在肺鱼谱系内发生的形态变化和物种形成的缓慢速率与形态上的缓慢变化与肺鱼阿片样物质前体的氨基酸序列的明显缓慢速率之间存在相关性的可能性序列。考虑到肺鱼作为“活化石”的地位。
  • 【全前脑和单纯性下垂病的连续基因综合征:与18p11.3缺失相关。】 复制标题 收藏 收藏
    DOI:10.1002/ajmg.a.31386 复制DOI
    作者列表:Kantaputra PN,Limwongse C,Tochareontanaphol C,Mutirangura A,Mevatee U,Praphanphoj V
    BACKGROUND & AIMS: :We report a patient with a unique combination of features, including microcephaly; mental retardation; poorly developed frontal lobes; hypoplastic pituitary gland; hypothyroidism; alopecia universalis; single maxillary central incisor; taurodontism; median palatal ridge; longitudinally grooved nails; and scoliosis. His unbalanced karyotype was found to be 45,XY,der(15;18)(q10;q10). The constellation of anomalies appears to represent a contiguous gene syndrome caused, at least in part, by deletion of TGIF and the gene responsible for hereditary hypotrichosis simplex. The phenotype of our patient differs other reported patients with del(18p). Possible explanations include (1) the effects of a different deleted region, (2) a positional effect caused by a gene close by, or (3) by interruption of a different gene resulting from chromosomal translocation.
    背景与目标: :我们报告的患者具有独特的功能组合,包括小头畸形;智力低下;额叶发育不良;垂体发育不全甲状腺功能减退;普遍性脱发;单上颌中切牙;牛头牙症pa中纵向开槽的指甲;和脊柱侧弯。发现他的不平衡核型为45,XY,der(15; 18)(q10; q10)。异常群似乎代表着一种连续的基因综合征,这种综合征至少部分地是由于TGIF的缺失和负责遗传性单毛发生的基因所致。我们患者的表型与其他报道的del(18p)患者不同。可能的解释包括(1)不同缺失区域的作用;(2)由附近基因引起的位置作用;或(3)由染色体易位引起的不同基因的中断。
  • 【躁狂抑郁症与GABRbeta-1基因高度多态性标记之间的遗传关联研究。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1096-8628(19970531)74:3<342::aid-ajm 复制DOI
    作者列表:Puertollano R,Visedo G,Zapata C,Fernández-Piqueras J
    BACKGROUND & AIMS: We report on an association study between a tetranucleotide repeat polymorphism in the GABR beta1 gene and manic-depressive illness in a Spanish population. This gene may be an important candidate for bipolar affective disorders since severe GABergic alterations have been described in patients. Although our results do not reveal a clear evidence for association between manic-depressive illness and GABR beta1, we have found significant differences between patients and controls in the female subpopulation.

    背景与目标: 我们报告了GABR beta1基因中的四核苷酸重复多态性与西班牙人群的躁狂抑郁症之间的关联研究。该基因可能是双相情感障碍的重要候选者,因为已在患者中描述了严重的GABergic改变。尽管我们的结果并未显示出躁狂抑郁症与GABR beta1之间存在关联的明确证据,但我们发现女性亚人群中的患者与对照组之间存在显着差异。

  • 【通过气管内施用编码人血小板生成素cDNA的腺病毒载体来提高血小板水平。】 复制标题 收藏 收藏
    DOI:10.1038/nbt0697-570 复制DOI
    作者列表:Cannizzo SJ,Frey BM,Raffi S,Moore MA,Eaton D,Suzuki M,Singh R,Mack CA,Crystal RG
    BACKGROUND & AIMS: :This study was designed to evaluate the hypothesis that administration of a replication-deficient, recombinant adenovirus vector to the epithelial surface of the respiratory tract can be used to deliver a recombinant protein to the systemic circulation in sufficient quantities to evoke a systemic response appropriate to the recombinant protein. We administered AdCMV.TPO-an adenovirus vector containing an expression cassette coding for the human thrombopoietin (TPO) cDNA-to the respiratory epithelium of immunocompetent Balb/c mice. Over the following week, serum human TPO levels were elevated, platelet levels increased more than sixfold, and megakaryocytosis was evident in bone marrow. This strategy may be a useful approach to the nonparenteral administration of a variety of therapeutic recombinant proteins, such as those relevant to clotting, endocrine function, and bone-marrow function.
    背景与目标: :这项研究旨在评估以下假设:向呼吸道上皮表面施用复制缺陷型重组腺病毒载体可将重组蛋白以足够的量递送至全身循环,以引起适当的全身反应。重组蛋白。我们将AdCMV.TPO-一种含有编码人血小板生成素(TPO)cDNA的表达盒的腺病毒载体施用于具有免疫功能的Balb / c小鼠的呼吸道上皮。在接下来的一周中,人的血清TPO水平升高,血小板水平升高了六倍以上,并且在骨髓中发现了巨核细胞增多。该策略可能是非胃肠道给药多种治疗性重组蛋白(例如与凝血,内分泌功能和骨髓功能相关的蛋白)的有用途径。
  • 【拟南芥中吸收氢酶的调控和氢利用对基因表达的影响。】 复制标题 收藏 收藏
    DOI:10.1128/JB.00381-06 复制DOI
    作者列表:Rey FE,Oda Y,Harwood CS
    BACKGROUND & AIMS: :Rhodopseudomonas palustris is a purple, facultatively phototrophic bacterium that uses hydrogen gas as an electron donor for carbon dioxide fixation during photoautotrophic growth or for ammonia synthesis during nitrogen fixation. It also uses hydrogen as an electron supplement to enable the complete assimilation of oxidized carbon compounds, such as malate, into cell material during photoheterotrophic growth. The R. palustris genome predicts a membrane-bound nickel-iron uptake hydrogenase and several regulatory proteins to control hydrogenase synthesis. There is also a novel sensor kinase gene (RPA0981) directly adjacent to the hydrogenase gene cluster. Here we show that the R. palustris regulatory sensor hydrogenase HupUV acts in conjunction with the sensor kinase-response regulator protein pair HoxJ-HoxA to activate hydrogenase expression in response to hydrogen gas. Transcriptome analysis indicated that the HupUV-HoxJA regulatory system also controls the expression of genes encoding a predicted dicarboxylic acid transport system, a putative formate transporter, and a glutamine synthetase. RPA0981 had a small effect in repressing hydrogenase synthesis. We also determined that the two-component system RegS-RegR repressed expression of the uptake hydrogenase, probably in response to changes in intracellular redox status. Transcriptome analysis indicated that about 30 genes were differentially expressed in R. palustris cells that utilized hydrogen when growing photoheterotrophically on malate under nitrogen-fixing conditions compared to a mutant strain that lacked uptake hydrogenase. From this it appears that the recycling of reductant in the form of hydrogen does not have extensive nonspecific effects on gene expression in R. palustris.
    背景与目标: :Rhodopseudomonas palustris是一种紫色的兼性光养细菌,它利用氢气作为电子供体,在光养植物生长过程中固定二氧化碳,或在固氮过程中合成氨气。它还使用氢作为电子补充剂,以在光异养生长期间将氧化的碳化合物(例如苹果酸)完全同化到细胞材料中。 R. palustris基因组预测膜结合的镍铁摄取氢化酶和几种调节蛋白来控制氢化酶的合成。与氢化酶基因簇直接相邻的还有一个新的传感器激酶基因(RPA0981)。在这里,我们显示帕氏疟原虫调节传感器氢化酶HupUV与传感器激酶响应调节蛋白对HoxJ-HoxA共同作用,以响应氢气激活氢化酶表达。转录组分析表明,HupUV-HoxJA调节系统还控制编码预测的二羧酸转运系统,推定的甲酸盐转运蛋白和谷氨酰胺合成酶的基因的表达。 RPA0981在抑制氢化酶合成方面作用很小。我们还确定了两组分系统RegS-RegR抑制摄取氢化酶的表达,可能是响应细胞内氧化还原状态的变化。转录组分析表明,与缺乏摄取氢酶的突变菌株相比,当在固氮条件下在苹果酸上光异养地生长时,利用氢的Pal。R. palustris细胞中约有30个基因差异表达。由此看来,还原剂以氢的形式的循环利用对R. palustris的基因表达没有广泛的非特异性影响。
  • 【P53基因的等位基因缺失与膀胱癌的肿瘤分级,分期和恶性进展的相关性。】 复制标题 收藏 收藏
    DOI:10.1111/j.1442-2042.1997.tb00144.x 复制DOI
    作者列表:Tsutsumi M,Sugano K,Yamaguchi K,Kakizoe T,Akaza H
    BACKGROUND & AIMS: BACKGROUND:We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined. METHODS:LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis. RESULTS:Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors. CONCLUSIONS:The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.
    背景与目标: 背景:我们检查了膀胱癌中P53基因的杂合性(LOH)缺失,并研究了P53基因在乳头状瘤恶性进展中的作用。另外,检查了复发性膀胱癌的克隆性。
    方法:分析了47例患者的67例膀胱癌中P53基因的LOH。从福尔马林固定,石蜡包埋的组织中提取DNA,在P53基因的3个多态性位点处通过聚合酶链反应(PCR)进行扩增,并通过非放射性同位素单链构象多态性(Non-RI SSCP)分析。
    结果:在40个信息量样本中,在13个样本中检测到LOH,其中3个7级中有4个(57%),2个23级中有9个(39%),1个10级中没有10个(10%)。在1级和2级以及1级和3级的LOH之间观察到统计学意义。对5例恶性进展的分析表明,3例(60%)在原发性肿瘤中显示LOH,2例在复发性肿瘤中显示LOH。 ,而在3例19例(16%)未发现恶性进展的LOH中则相反。 4例异时复发表现为LOH。在复发性肿瘤中2个,仅在初始肿瘤中1个,在两个肿​​瘤中1个。
    结论:P53基因的改变被认为与肿瘤的分级有关,并有助于膀胱癌的恶性进展。 P53基因中的LOH可作为浅表性膀胱癌预后的临床指标。
  • 【使用支持向量机进行虚拟筛选的药效基核。】 复制标题 收藏 收藏
    DOI:10.1021/ci060138m 复制DOI
    作者列表:Mahé P,Ralaivola L,Stoven V,Vert JP
    BACKGROUND & AIMS: :We introduce a family of positive definite kernels specifically optimized for the manipulation of 3D structures of molecules with kernel methods. The kernels are based on the comparison of the three-point pharmacophores present in the 3D structures of molecules, a set of molecular features known to be particularly relevant for virtual screening applications. We present a computationally demanding exact implementation of these kernels, as well as fast approximations related to the classical fingerprint-based approaches. Experimental results suggest that this new approach is competitive with state-of-the-art algorithms based on the 2D structure of molecules for the detection of inhibitors of several drug targets.
    背景与目标: :我们介绍了一系列正定内核,这些内核已针对使用内核方法处理分子的3D结构进行了专门优化。内核基于分子3D结构中存在的三点药效基团的比较,这是已知与虚拟筛选应用特别相关的一组分子特征。我们提出了对这些内核的计算要求很高的精确实现,以及与基于经典指纹的方法有关的快速逼近。实验结果表明,这种新方法与基于分子2D结构的最新算法可检测多种药物靶标的抑制剂相比具有竞争优势。

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