In JoVE (1)
Other Publications (9)
- Molecular and Cellular Neurosciences
- Cell Motility and the Cytoskeleton
- Developmental Biology
- American Journal of Physiology. Cell Physiology
- American Journal of Physiology. Cell Physiology
- Tissue Engineering. Part A
- Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry
- Frontiers in Oncology
Articles by Powrnima Joshi in JoVE
Other articles by Powrnima Joshi on PubMed
Β 淀粉样肽不利影响脊椎数目和海马神经元的动力。 Molecular and Cellular Neurosciences. Nov, 2006 | Pubmed ID: 16962789 － β － 淀粉样蛋白肽 （Abeta） 水平升高是发现唐氏综合征患者和阿尔茨海默病的早期阶段改变突触功能。树突棘，站点的大多数兴奋性突触联系，被认为是重要的场所，为编码突触可塑性。我们的海马锥体神经元的延时双光子成像中用于器官切片研究 Abeta 树突棘的发展的影响。我们报告海马神经元接触到致命水平下降 Abeta 脊柱密度、 增加的脊柱长度与疲弱的脊柱动力。对脊柱密度 Abeta 的影响是可逆的。此外，由于咯利普兰，暗示的营地的依赖通路参与磷酸二酯酶类型 IV 抑制剂而受阻对树突棘密度 Abeta 的影响。这些研究结果提高 Abeta 诱导脊柱改建可作为基础认知缺陷的唐氏综合征和阿尔茨海默病的可能性。
细胞膜中的胆固醇水平的变化调节细胞内信号传递及调节细胞粘附和迁移对纤维连接蛋白。 Cell Motility and the Cytoskeleton. Mar, 2007 | Pubmed ID: 17238130 数量和分布的脂质分子，包括胆固醇特别细胞质膜，可发挥关键作用调节细胞中的几个生理过程。我们调查的膜胆固醇调节细胞形状、 粘附和运动性的作用。胆固醇是好分散和能动性的纤维连接蛋白的细胞的细胞质膜从急性枯竭造成这些单元格的舍入和减少其对附着力和纤维连接蛋白对动力。这些修改不是那么突出镀金层粘连蛋白、 与受精关系或塑料，指示介导胆固醇粘附和运动性的变化有更具体的特定于纤维连接蛋白整合素，如 alpha5beta1 介导的粘附的单元格中。这些变化相伴随的肌动蛋白细胞骨架，桩蛋白膜，和向 alpha5 整合素和桩蛋白富焦粘连的动态变化的空间重组重塑。酪氨酸磷酸化在水平位置的 FAK 576/577 和 Erk1/Erk2 MAP 激酶活性水平都较低的胆固醇-贫比控制单元格中。胆固醇重新成为细胞膜这些级别就归一化仅在纤维上。因此，膜胆固醇含量有某些具体地参与调节细胞运动纤维连接蛋白和肌动蛋白细胞骨架的组织上的信号传导通路的具体影响。
淀粉样前体蛋白在斑马鱼开发过程中是必需的收敛推广运动。 Developmental Biology. Nov, 2009 | Pubmed ID: 19664615 淀粉样前体蛋白 (APP) 一直紧张调查的重点由于在阿尔茨海默病 (AD)，其作用但是，其生物功能仍不明朗。应用程序和应用程序类似的蛋白质的损失会导致产后致死小鼠，表明在胚胎发生过程的作用。在这里我们表明在斑马鱼模型系统中，击倒的应用程序结果大大减少的体长与短，卷曲的尾巴鱼的代中。基因表达的原位检测表明 APP morphant 胚胎有缺陷的收敛推广运动。我们还表明野生型人类 APP 营救 morphant 表型，但瑞典突变 APP，这将导致家族性 AD (时尚)，救不发育的缺陷。集体，这项工作演示的斑马鱼模型是一个强大的系统，在胚胎发育过程中定义应用程序的作用，并评估功能活动的时尚突变体的应用程序。
CDK5 Slo 进行交互，并对其表面表达和通过直接磷酸化动力学的影响。 American Journal of Physiology. Cell Physiology. Nov, 2011 | Pubmed ID: 22094329 大电导钙激活钾 (BK) 通道是无处不在在一些疾病中发挥着重要的作用。耳毛细胞他们发挥关键作用，电调谐，频率歧视的一种机制。这些渠道显示变量的动力学和沿 tonotopic 轴的表达。虽然不甚了解到其功能的毛细胞的分子基础建立浅滩渠道由孔形成 α 亚基 (Slo) 和大量的辅助亚基组成。在这里我们查明 CDK5，作为斯洛伐克相互作用合作伙伴的细胞周期蛋白依赖性激酶家族成员。我们显示 CDK5 存在于毛细胞，并表示角质层板和环区的浓度很高。曼浦汉克的单元格中我们显示 CDK5 抑制 Slo 通过直接磷酸化 Slo 的表面表达。同样，我们注意到 CDK5 通过直接磷酸化 T847 影响 Slo 电压激活和取消激活动力学。再加上沿 tonotopic 轴及其越来越多的表达，这些数据表明 CDK5 可能发挥着关键的作用，在电调谐和斯洛伐克毛细胞的表面表达。关键词： BK 通道、 CDK5、 表面表达及动力学。
Hair Cell BK Channels Interact with RACK1, and PKC Increases Its Expression on the Cell Surface by Indirect Phosphorylation American Journal of Physiology. Cell Physiology. Jul, 2012 | Pubmed ID: 22538239 Large conductance (BK) calcium activated potassium channels (Slo) are ubiquitous and implicated in a number of human diseases including hypertension and epilepsy. BK channels consist of a pore forming α-subunit (Slo) and a number of accessory subunits. In hair cells of nonmammalian vertebrates these channels play a critical role in electrical resonance, a mechanism of frequency selectivity. Hair cell BK channel clusters on the surface and currents increase along the tonotopic axis and contribute significantly to the responsiveness of these hair cells to sounds of high frequency. In contrast, messenger RNA levels encoding the Slo gene show an opposite decrease in high frequency hair cells. To understand the molecular events underlying this paradox, we used a yeast two-hybrid screen to isolate binding partners of Slo. We identified Rack1 as a Slo binding partner and demonstrate that PKC activation increases Slo surface expression. We also establish that increased Slo recycling of endocytosed Slo is at least partially responsible for the increased surface expression of Slo. Moreover, analysis of several PKC phosphorylation site mutants confirms that the effects of PKC on Slo surface expression are likely indirect. Finally, we show that Slo clusters on the surface of hair cells are also increased by increased PKC activity and may contribute to the increasing amounts of channel clusters on the surface of high-frequency hair cells.
In Vivo Transplantation of Autogenous Marrow-derived Cells Following Rapid Intraoperative Magnetic Separation Based on Hyaluronan to Augment Bone Regeneration Tissue Engineering. Part A. Jan, 2013 | Pubmed ID: 23082937 This project was designed to test the hypothesis that rapid intraoperative processing of bone marrow based on hyaluronan (HA) could be used to improve the outcome of local bone regeneration if the concentration and prevalence of marrow-derived connective tissue progenitors (CTPs) could be increased and nonprogenitors depleted before implantation.
A Quantitative Determination of Magnetic Nanoparticle Separation Using On-off Field Operation of Quadrupole Magnetic Field-flow Fractionation (QMgFFF) Analytical Sciences : the International Journal of the Japan Society for Analytical Chemistry. 2013 | Pubmed ID: 23842422 Quadrupole Magnetic Field-Flow Fractionation (QMgFFF) is a technique for characterization of sub-micrometer magnetic particles based on their retention in the magnetic field from flowing suspensions. Different magnetic field strengths and volumetric flow rates were tested using on-off field application and two commercial nanoparticle preparations that significantly differed in their retention parameter, λ (by nearly 8-fold). The fractograms showed a regular pattern of higher retention (98.6% v. 53.3%) for the larger particle (200 nm v. 90 nm) at the higher flow rate (0.05 mL/min v. 0.01 mL/min) at the highest magnetic field (0.52 T), as expected because of its lower retention parameter. The significance of this approach is a demonstration of a system that is simpler in operation than a programmed field QMgFFF in applications to particle mixtures consisting of two distinct particle fractions. This approach could be useful for detection of unwanted particulate contaminants, especially important in industrial and biomedical applications.
Enrichment of Circulating Melanoma Cells (CMCs) Using Negative Selection from Patients with Metastatic Melanoma Oncotarget. May, 2014 | Pubmed ID: 24811334 Circulating tumor cells have emerged as prognostic biomarkers in the treatment of metastatic cancers of epithelial origins viz., breast, colorectal and prostate. These tumors express Epithelial Cell Adhesion Molecule (EpCAM) on their cell surface which is used as an antigen for immunoaffinity capture. However, EpCAM capture technologies are of limited utility for non-epithelial cancers such as melanoma. We report a method to enrich Circulating Melanoma Cells (CMCs) that does not presuppose malignant cell characteristics. CMCs were enriched by centrifugation of blood samples from healthy (N = 10) and patient (N = 11) donors, followed by RBC lysis and immunomagnetic depletion of CD45-positive leukocytes in a specialized magnetic separator. CMCs were identified by immunocytochemistry using Melan-A or S100B as melanoma markers and enumerated using automated microscopy image analyses. Separation was optimized for maximum sensitivity and recovery of CMCs. Our results indicate large number of CMCs in Stage IV melanoma patients. Analysis of survival suggested a trend toward decreased survival with increased number of CMCs. Moreover, melanoma-associated miRs were found to be higher in CMC-enriched fractions in two patients when compared with the unseparated samples, validating this method as applicable for molecular analyses. Negative selection is a promising approach for isolation of CMCs and other EpCAM -negative CTCs, and is amenable to molecular analysis of CMCs. Further studies are required to validate its efficacy at capturing specific circulating cells for genomic analysis, and xenograft studies.