140 research outputs found

    Regulation of TGF-β signal transduction by mono- and deubiquitylation of Smads

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    Polyubiquitylation leading to proteasomal degradation is a well-established mechanism for regulat- ing TGF-b signal transduction components such as receptors and Smads. Recently, an equally impor- tant role was suggested for monoubiquitylation of both Smad4 and receptor-associated Smads that regulates their function without protein degradation. Monoubiquitylation of Smads was discovered following the identification of deubiquitylases required for TGF-b signaling, suggesting that contin- uous cycles of Smad mono- and deubiquitylation are required for proper TGF-b signal transduction. Here we summarize and discuss recent work on Smad mono- and deubiquitylation

    MicroRNA control of signal transduction

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    MicroRNAs (miRNAs) are integral elements in the post-transcriptional control of gene expression. After the identification of hundreds of miRNAs, the challenge is now to understand their specific biological function. Signalling pathways are ideal candidates for miRNA-mediated regulation owing to the sharp dose-sensitive nature of their effects. Indeed, emerging evidence suggests that miRNAs affect the responsiveness of cells to signalling molecules such as transforming growth factor-beta, WNT, Notch and epidermal growth factor. As such, miRNAs serve as nodes of signalling networks that ensure homeostasis and regulate cancer, metastasis, fibrosis and stem cell biology

    Remark on blow-up of the threshold solutions to the nonlinear Schrödinger equation with the repulsive Dirac delta potential (Harmonic Analysis and Nonlinear Partial Differential Equations)

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    We consider the focusing ²-supercritical nonlinear Schrödinger equation with the repulsive Dirac delta potential. The global dynamics below the ground state standing waves was obtained by Ikeda and the author [18]. Recently, Ardila and the author [3] gave a sufficient condition for the threshold solutions to scatter. In the present paper, we are interested in a sufficient condition for the threshold solutions to blow up

    Protocadherin-1 is expressed in the notochord of mouse embryo but is dispensable for its formation

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    Notochord is an embryonic midline structure that serves as mechanical support for axis elongation and the signaling center for the surrounding tissues. Precursors of notochord are initially induced in the dorsal most mesoderm region in gastrulating embryo and separate from the surrounding mesoderm/endoderm tissue to form an elongated rod-like structure, suggesting that cell adhesion molecules may play an important role in this step. In Xenopus embryo, axial protocadherin (AXPC), an orthologue of mammalian Protocadherin-1 (PCDH1), is indispensable for the assembly and separation from the surrounding tissue of the notochord cells. However, the role of PCDH1 in mammalian notochord remains unknown. We herein report that PCDH1 is expressed in the notochord of mouse embryo and that PCDH1-deficient mice form notochord normally. First, we examined the temporal expression pattern of pcdh1 and found that pcdh1 mRNA was expressed from embryonic day (E) 7.5, prior to the stage when notochord cells detach from the surrounding endoderm tissue. Second, we found that PCDH1 protein is expressed in the notochord of mouse embryos in addition to the previously reported expression in endothelial cells. To further investigate the role of PCDH1 in embryonic development, we generated PCDH1-deficient mice using the CRISPR-Cas9 system. In PCDH1-deficient embryos, notochord formation and separation from the surrounding tissue were normal. Structure and marker gene expression of notochord were also unaffected by loss of PCDH1. Major vascular patterns in PCDH1-deficient embryo were essentially normal. These results suggest that PCDH1 is dispensable for notochord formation, including the tissue separation process, in mammalian embryos. We successfully identified the evolutionary conserved expression of PCDH1 in notochord, but its function may differ among species

    Xapelin and Xmsr are required for cardiovascular development in Xenopus laevis

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    AbstractThe cardiovascular development is the elaborate process, and despite the extensive studies, the mechanisms underlying endothelial, hematopoietic, and cardiac developments, as well as the interrelation between these processes, are not fully understood. In this study, we demonstrated that Xenopus apelin and Xmsr play pivotal roles in cardiovascular development. Apelin is a recently identified ligand for an orphan G-protein-coupled receptor APJ and is involved in fluid homeostasis in mammals. Xenopus preproapelin (Xpreproapelin) was isolated and its mRNA localized to the region around the presumptive blood vessels, which are overlapping or adjacent to those expressing Xmsr, the Xenopus homologue of APJ. Overexpression of Xpreproapelin disorganized the expression of the endothelial precursor cell marker XlFli and the hematopoietic precursor cell marker SCL at the neurula, whereas embryos injected with morpholino antisense oligonucleotides for Xapelin and Xmsr displayed attenuated expression of Tie2, α-globin, XPOX2, and cTnI, markers of endothelium, erythrocytes, myeloid cells, and cardiomyocytes, respectively. XlFli morpholino had similar effects to Xapelin and Xmsr morpholinos on cardiac differentiation, suggesting an unexpected potential relationship between the endothelium and cardiac differentiation. Forced expression of constitutive active Gαi rescued the phenotypes of Xmsr morpholino-injected embryos, indicating that the i/o type of G protein α subunit acts downstream of Xmsr

    Malaria parasites of long-tailed macaques in Sarawak, Malaysian Borneo: A novel species and demographic and evolutionary histories

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    Background: Non-human primates have long been identified to harbour different species of Plasmodium. Long-tailed macaques (Macaca fascicularis), in particular, are reservoirs for P. knowlesi, P. inui, P. cynomolgi, P. coatneyi and P. fieldi. A previous study conducted in Sarawak, Malaysian Borneo, however revealed that long-tailed macaques could potentially harbour novel species of Plasmodium based on sequences of small subunit ribosomal RNA and circumsporozoite genes. To further validate this finding, the mitochondrial genome and the apicoplast caseinolytic protease M genes of Plasmodium spp. were sequenced from 43 long-tailed macaque blood samples. Results: Apart from several named species of malaria parasites, long-tailed macaques were found to be potentially infected with novel species of Plasmodium, namely one we refer to as "P. inui-like." This group of parasites bifurcated into two monophyletic clades indicating the presence of two distinct sub-populations. Further analyses, which relied on the assumption of strict co-phylogeny between hosts and parasites, estimated a population expansion event of between 150,000 to 250,000 years before present of one of these sub-populations that preceded that of the expansion of P. knowlesi. Furthermore, both sub-populations were found to have diverged from a common ancestor of P. inui approximately 1.5 million years ago. In addition, the phylogenetic analyses also demonstrated that long-tailed macaques are new hosts for P. simiovale. Conclusions: Malaria infections of long-tailed macaques of Sarawak, Malaysian Borneo are complex and include a novel species of Plasmodium that is phylogenetically distinct from P. inui. These macaques are new natural hosts of P. simiovale, a species previously described only in toque monkeys (Macaca sinica) in Sri Lanka. The results suggest that ecological factors could affect the evolution of malaria parasites. © 2018 The Author(s)

    Remarks on the global dynamics for solutions with an infinite group invariance to the nonlinear Schrödinger equation (Harmonic Analysis and Nonlinear Partial Differential Equations)

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    "Harmonic Analysis and Nonlinear Partial Differential Equations". July 3~5, 2017. edited by Hideo Takaoka and Hideo Kubo. The papers presented in this volume of RIMS Kôkyûroku Bessatsu are in final form and refereed.We consider the focusing mass-supercritical and energy-subcritical nonlinear Schrödinger equation (NLS). The global dynamics below the ground state standing waves is known (see [6, 1, 9]). Recently, the author [12] gave the global dynamics above the ground state standing waves for finite group invariant solutions. In the present paper, we are interested in the global dynamics for the solutions with an infinite group invariance
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