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61.
Onizuka T Yuasa S Kusumoto D Shimoji K Egashira T Ohno Y Kageyama T Tanaka T Hattori F Fujita J Ieda M Kimura K Makino S Sano M Kudo A Fukuda K 《Journal of molecular and cellular cardiology》2012,52(3):650-659
The efficient induction of cardiomyocyte differentiation from embryonic stem (ES) cells is crucial for cardiac regenerative medicine. Although Wnts play important roles in cardiac development, complex questions remain as to when, how and what types of Wnts are involved in cardiogenesis. We found that Wnt2 was strongly up-regulated during cardiomyocyte differentiation from ES cells. Therefore, we investigated when and how Wnt2 acts in cardiogenesis during ES cell differentiation. Wnt2 was strongly expressed in the early developing murine heart. We applied this embryonic Wnt2 expression pattern to ES cell differentiation, to elucidate Wnt2 function in cardiomyocyte differentiation. Wnt2 knockdown revealed that intrinsic Wnt2 was essential for efficient cardiomyocyte differentiation from ES cells. Moreover, exogenous Wnt2 increased cardiomyocyte differentiation from ES cells. Interestingly, the effects on cardiogenesis of intrinsic Wnt2 knockdown and exogenous Wnt2 addition were temporally restricted. During cardiomyocyte differentiation from ES cells, Wnt2 didn't activate canonical Wnt pathway but utilizes JNK/AP-1 pathway which is required for cardiomyocyte differentiation from ES cells. Therefore we conclude that Wnt2 plays strong positive stage-specific role in cardiogenesis through non-canonical Wnt pathway in murine ES cells. 相似文献
62.
Noda Y Niwa S Homma N Fukuda H Imajo-Ohmi S Hirokawa N 《Proceedings of the National Academy of Sciences of the United States of America》2012,109(5):1725-1730
Neuronal morphology is regulated by cytoskeletons. Kinesin superfamily protein 2A (KIF2A) depolymerizes microtubules (MTs) at growth cones and regulates axon pathfinding. The factors controlling KIF2A in neurite development remain totally elusive. Here, using immunoprecipitation with an antibody specific to KIF2A, we identified phosphatidylinositol 4-phosphate 5-kinase alpha (PIPKα) as a candidate membrane protein that regulates the activity of KIF2A. Yeast two-hybrid and biochemical assays demonstrated direct binding between KIF2A and PIPKα. Partial colocalization of the clusters of punctate signals for these two molecules was detected by confocal microscopy and photoactivated localization microscopy. Additionally, the MT-depolymerizing activity of KIF2A was enhanced in the presence of PIPKα in vitro and in vivo. PIPKα suppressed the elongation of axon branches in a KIF2A-dependent manner, suggesting a unique PIPK-mediated mechanism controlling MT dynamics in neuronal development. 相似文献
63.
Hosen N Ichihara H Mugitani A Aoyama Y Fukuda Y Kishida S Matsuoka Y Nakajima H Kawakami M Yamagami T Fuji S Tamaki H Nakao T Nishida S Tsuboi A Iida S Hino M Oka Y Oji Y Sugiyama H 《British journal of haematology》2012,156(2):213-224
Monoclonal antibody (mAb) drugs are desirable for the improvement of multiple myeloma (MM) treatment. In this study, we found for the first time that CD48 was highly expressed on MM plasma cells. In 22 out of 24 MM patients, CD48 was expressed on more than 90% of MM plasma cells at significantly higher levels than it was on normal lymphocytes and monocytes. CD48 was only weakly expressed on some CD34(+) haematopoietic stem/progenitor cells, and not expressed on erythrocytes or platelets. We next examined whether CD48 could serve as a target antigen for mAb therapy against MM. A newly generated in-house anti-CD48 mAb induced mild antibody-dependent cell-mediated cytotoxicity and marked complement-dependent cytotoxicity against not only MM cell lines but also primary MM plasma cells in vitro. Administration of the anti-CD48 mAb significantly inhibited tumour growth in severe combined immunodeficient mice inoculated subcutaneously with MM cells. Furthermore, anti-CD48 mAb treatment inhibited growth of MM cells transplanted directly into murine bone marrow. Finally and importantly, we demonstrated that the anti-CD48 mAb did not damage normal CD34(+) haematopoietic stem/progenitor cells. These results suggest that the anti-CD48 mAb has the potential to become an effective therapeutic mAb against MM. 相似文献
64.
Egashira T Yuasa S Suzuki T Aizawa Y Yamakawa H Matsuhashi T Ohno Y Tohyama S Okata S Seki T Kuroda Y Yae K Hashimoto H Tanaka T Hattori F Sato T Miyoshi S Takatsuki S Murata M Kurokawa J Furukawa T Makita N Aiba T Shimizu W Horie M Kamiya K Kodama I Ogawa S Fukuda K 《Cardiovascular research》2012,95(4):419-429
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Linda Lee Mikako Sakurai Shinsuke Matsuzaki Ottavio Arancio Paul Fraser 《Neuromolecular medicine》2013,15(4):720-736
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline and is the most common cause of dementia in the elderly. Histopathologically, AD features insoluble aggregates of two proteins in the brain, amyloid-β (Aβ) and the microtubule-associated protein tau, both of which have been linked to the small ubiquitin-like modifier (SUMO). A large body of research has elucidated many of the molecular and cellular pathways that underlie AD, including those involving the abnormal Aβ and tau aggregates. However, a full understanding of the etiology and pathogenesis of the disease has remained elusive. Consequently, there are currently no effective therapeutic options that can modify the disease progression and slow or stop the decline of cognitive functioning. As part of the effort to address this lacking, there needs a better understanding of the signaling pathways that become impaired under AD pathology, including the regulatory mechanisms that normally control those networks. One such mechanism involves SUMOylation, which is a post-translational modification (PTM) that is involved in regulating many aspects of cell biology and has also been found to have several critical neuron-specific roles. Early studies have indicated that the SUMO system is likely altered with AD-type pathology, which may impact Aβ levels and tau aggregation. Although still a relatively unexplored topic, SUMOylation will likely emerge as a significant factor in AD pathogenesis in ways which may be somewhat analogous to other regulatory PTMs such as phosphorylation. Thus, in addition to the upstream effects on tau and Aβ processing, there may also be downstream effects mediated by Aβ aggregates or other AD-related factors on SUMO-regulated signaling pathways. Multiple proteins that have functions relevant to AD pathology have been identified as SUMO substrates, including those involved in synaptic physiology, mitochondrial dynamics, and inflammatory signaling. Ongoing studies will determine how these SUMO-regulated functions in neurons and glial cells may be impacted by Aβ and AD pathology. Here, we present a review of the current literature on the involvement of SUMO in AD, as well as an overview of the SUMOylated proteins and pathways that are potentially dysregulated with AD pathogenesis. 相似文献
68.
Noriyuki Koizumi Shinsuke Morioka Atsushi Mori Bounsong Vongvichith Koichi Shibukawa Kazuya Nishida Keiji Watabe Takeshi Takemura 《Conservation Genetics Resources》2013,5(3):711-713
Twenty-four microsatellite loci were isolated and characterized from the genome of Rasbora borapetensis. Flanking polymerase chain reaction primers were designed and used to amplify these loci in 32 individuals. All loci were polymorphic with allele numbers ranging from 2 to 27, observed heterozygosity from 0.031 to 1.000 and expected heterozygosity from 0.031 to 0.965. All loci conformed to the Hardy–Weinberg equilibrium and no evidence of null alleles was observed. Pairwise comparisons between alleles did not detect any linkage disequilibrium. The high level of polymorphisms observed in these microsatellite loci will enhance future investigations on the genetic differentiation and structure of populations of Rasbora borapetensis. 相似文献
69.
Toshitetsu Hayashi M.D. Ph.D. Reiji Haba M.D. Ph.D. Yoshio Kushida M.D. Ph.D. Kyuichi Kadota M.D. Ph.D. Naomi Katsuki M.D. Yumi Miyai M.D. Ph.D. Shinsuke Shibuya M.D. Makiko Sasaki M.D. Ph.D. Kenji Bando M.D. Ph.D. Toru Matsunaga C.T. Toshiyuki Hata M.D. Ph.D. 《Diagnostic cytopathology》2013,41(9):812-816
Primary strumal carcinoid tumor of the ovary (SCTO) is an extremely rare entity, though the survival rate is excellent if the disease is confined to one ovary. A case is presented here in which intraoperative squash smears in a 45‐year‐old woman with a left adnexal mass revealed dispersed or small clusters of neoplastic cells forming loosely cohesive gland‐like structures with abundant cytoplasm. The nuclear chromatin was finely granular with a “salt and pepper” appearance and occasional tiny nucleoli. The position of the nucleus presented a vaguely plasmacytoid appearance. Small fragments of thyroidal colloid‐like structures were also identified. A cytopathologic diagnosis of a SCTO was suggested. Further evaluation and immunohistochemical studies were conducted on formalin‐fixed, paraffin‐embedded material. Cords or nests of uniform cells with abundant cytoplasm, and eccentric nuclei with coarse chromatin and occasional colloidal tissue were identified on H&E sections. The tumor cells showed diffuse and strong cytoplasmic staining for chromogranin A, synaptophysin, CD56, and vimentin but were negative for calretinin, α‐inhibin or CDX2. The proliferative index with MIB‐1 was around 3%. Thyroidal colloid‐like structures were immunoreactive for thyroglobulin and TTF‐1 stains. The diagnosis of primary SCTO was confirmed based on cytopathologic, histopathological, and immunohistochemical results, and the location of the tumor. Awareness of the cytopathological findings of SCTO can assist in diagnosing this rare entity correctly. Diagn. Cytopathol. 2013;41:812–816. © 2011 Wiley Periodicals, Inc. 相似文献
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