Compositions and methods for bone formation and remodeling
    3.
    发明申请
    Compositions and methods for bone formation and remodeling 有权
    用于骨形成和重塑的组合物和方法

    公开(公告)号:US20100298308A1

    公开(公告)日:2010-11-25

    申请号:US11598916

    申请日:2006-11-14

    摘要: The mechanism by which the high bone mass (HBM) mutation (G171V) of the Wnt coreceptor LRP5 regulates the canonical Wnt signaling was investigated. The mutation was previously shown to reduce Dkk protein-1-mediated antagonism, suggesting that the first YWTD repeat domain where G171 is located may be responsible for Dkk protein-mediated antagonism. However, we found that the third YWTD repeat, but not the first repeat domain, is required for DKK1-mediated antagonism. Instead, we found that the G171V mutation disrupted the interaction of LRP5 with Mesd, a chaperon protein for LRP5/6 that is required for the coreceptors' transport to cell surfaces, resulting in less LRP5 molecules on the cell surface. Although the reduction in the level of cell surface LRP5 molecules led to a reduction in Wnt signaling in a paracrine paradigm, the mutation did not appear to affect the activity of coexpressed Wnt in an autocrine paradigm. Together with the observation that osteoblast cells produce autocrine canonical Wnt, Wnt7b, and that osteocytes produce paracrine Dkk1, we believe that the G171V mutation may cause an increase in Wnt activity in osteoblasts by reducing the number of targets for paracrine Dkk1 to antagonize without affecting the activity of autocrine Wnt.

    摘要翻译: 研究了Wnt共同受体LRP5的高骨量(HBM)突变(G171V)调节规范Wnt信号传导的机制。 以前显示突变可以降低Dkk蛋白-1介导的拮抗作用,这表明G171位于第一个YWTD重复结构域可能是Dkk蛋白介导的拮抗作用的原因。 然而,我们发现第三个YWTD重复,但不是第一个重复结构域,是DKK1介导的拮抗作用所必需的。 相反,我们发现G171V突变破坏了LRP5与Mesd的相互作用,Mesd是共受体转运到细胞表面所需的LRP5 / 6的伴侣蛋白,导致细胞表面上较少的LRP5分子。 尽管细胞表面LRP5分子水平的降低导致旁分泌范例中Wnt信号传导的降低,但突变似乎不影响共表达Wnt在自分泌范式中的活性。 连同观察到成骨细胞产生自分泌的正常Wnt,Wnt7b,并且该骨细胞产生旁分泌的Dkk1,我们认为G171V突变可能通过减少旁分泌Dkk1靶向拮抗的数目而引起成骨细胞中Wnt活性的增加,而不影响 自分泌Wnt的活性。

    Independent helper virus packaging cell line for propagating viral vectors
    5.
    发明授权
    Independent helper virus packaging cell line for propagating viral vectors 失效
    用于传播病毒载体的独立的辅助病毒包装细胞系

    公开(公告)号:US07439060B1

    公开(公告)日:2008-10-21

    申请号:US09046833

    申请日:1998-03-24

    IPC分类号: C12N5/10 A61K48/00 C12N15/63

    摘要: Provided are novel vectors and viral vectors capable of expressing exogenous gene or exogenous nucleic acid sequences in a target cell of interest, such as T cells, bone marrow cells, epithelial cells, liver cells and the like. The nucleic acid components of the vectors may include one or more native promoter/enhancer regions having modified sequence segments, one or more non-native promoter/enhancer or non-native promoter's gene or gene segment, and a native viral vector terminator or processing signal or segment thereof. The viral vectors comprise a virus or viral portion having on the surfaces or envelopes adsorption components, one for a packaging cell line and the other for delivery to a target cell. Packaging cell lines for propagating the vectors and viral vectors are also provided, as are novel processes for propagating any of the disclosed vectors or viral vectors.

    摘要翻译: 提供能够在靶细胞中表达外源基因或外源核酸序列的新载体和病毒载体,例如T细胞,骨髓细胞,上皮细胞,肝细胞等。 载体的核酸组分可以包括一个或多个具有修饰的序列区段的天然启动子/增强子区域,一个或多个非天然启动子/增强子或非天然启动子的基因或基因区段,以及天然病毒载体终止子或处理信号 或其片段。 病毒载体包含在表面或包膜上具有吸附组分的病毒或病毒部分,一个用于包装细胞系,另一个用于递送至靶细胞。 还提供用于繁殖载体和病毒载体的包装细胞系,以及用于繁殖任何所公开的载体或病毒载体的新方法。

    Optimized real time nucleic acid detection processes
    8.
    发明授权
    Optimized real time nucleic acid detection processes 有权
    优化的实时核酸检测过程

    公开(公告)号:US09353405B2

    公开(公告)日:2016-05-31

    申请号:US13436174

    申请日:2012-03-30

    IPC分类号: C12Q1/68 C12Q1/70

    摘要: This invention provides for compositions for use in real time nucleic acid detection processes. Such real time nucleic acid detection processes are carried out with energy transfer elements attached to nucleic acid primers, nucleotides, nucleic acid probes or nucleic acid binding agents. Real time nucleic acid detection allows for the qualitative or quantitative detection or determination of single-stranded or double-stranded nucleic acids of interest in a sample. Other processes are provided by this invention including processes for removing a portion of a homopolymeric sequence, e.g., poly A sequence or tail, from an analyte or library of analytes. Compositions useful in carrying out such removal processes are also described and provided. Paneling and multiplex analyzes of more than one nucleic acid analyte using one sample are also provided.

    摘要翻译: 本发明提供用于实时核酸检测过程的组合物。 这种实时核酸检测方法是用连接于核酸引物,核苷酸,核酸探针或核酸结合剂的能量转移元件进行的。 实时核酸检测允许定性或定量检测或测定样品中感兴趣的单链或双链核酸。 本发明提供了其它方法,包括从被分析物或分析物库中除去一部分均聚物序列,例如聚A序列或尾部的方法。 还描述和提供了用于进行这种去除方法的组合物。 还提供了使用一个样品的多于一种核酸分析物的镶板和多重分析。