1,720,998 research outputs found
Specific fate decisions in adult hepatic progenitor cells driven by MET and EGFR signaling
No full textMitsuteru Kitade, Valentina M. Factor, Jesper B. Andersen, Akira Tomokuni, Kosuke Kaji, Hirofumi Akita, Agnes Holczbauer, Daekwan Seo, Jens U. Marquardt, Elizabeth A. Conner, Seung-Bum Lee, Yun-Han Lee, and Snorri S. Thorgeirssonope
Electro-hyperthermia inhibits glioma tumorigenicity through the induction of E2F1-mediated apoptosis
No full textModulated electro-hyperthermia (mEHT), also known as oncothermia, shows remarkable treatment efficacies for various types of tumours, including glioma. The aim of the present study was to investigate the molecular mechanism underlying phenotypic changes in oncothermic cancer cells. Materials and methods: U87-MG and A172 human glioma cells were exposed to mEHT (42 °C/60 min) three times with a 2-day interval and subsequently tested for growth inhibition using MTS, FACS and microscopic analysis. To obtain insights into the molecular changes in response to mEHT, global changes in gene expression were examined using RNA sequencing. For in vivo evaluation of mEHT, we used U87-MG glioma xenografts grown in nude mice. Results: mEHT inhibited glioma cell growth through the strong induction of apoptosis. The transcriptomic analysis of differential gene expression under mEHT showed that the anti-proliferative effects were induced through a subset of molecular alterations, including the up-regulation of E2F1 and CPSF2 and the down-regulation of ADAR and PSAT1. Subsequent Western blotting revealed that mEHT increased the levels of E2F1 and p53 and decreased the level of PARP-1, accelerating apoptotic signalling in glioma cells. mEHT significantly suppressed the growth of human glioma xenografts in nude mice. We also observed that mEHT dramatically reduced the portion of CD133+ glioma stem cell population and suppressed cancer cell migration and sphere formation. Conclusions: These findings suggest that mEHT suppresses glioma cell proliferation and mobility through the induction of E2F1-mediated apoptosis and might be an effective treatment for eradicating brain tumours. © 2015 Taylor and Francis1661sciescopu
Sex hormones establish a reserve pool of adult muscle stem cells
No full textQuiescent satellite cells, known as adult muscle stem cells, possess a remarkable ability to regenerate skeletal muscle following injury throughout life. Although they mainly originate from multipotent stem/progenitor cells of the somite, the mechanism underlying the establishment of quiescent satellite cell populations is unknown. Here, we show that sex hormones induce Mind bomb 1 (Mib1) expression in myofibres at puberty, which activates Notch signalling in cycling juvenile satellite cells and causes them to be converted into adult quiescent satellite cells. Myofibres lacking Mib1 fail to send Notch signals to juvenile satellite cells, leading to impaired cell cycle exit and depletion. Our findings reveal that the hypothalamic-pituitary-gonadal axis drives Mibi expression in the myofibre niche. Moreover, the same axis regulates the re-establishment of quiescent satellite cell populations following injury. Our data show that sex hormones establish adult quiescent satellite cell populations by regulating the myofibre niche at puberty and re-establish them during regeneration
© 2016 Macmillan Publishers Limited, part of springer Nature All rights reserved.111
Temporal Landscape of MicroRNA-Mediated Host-Virus Crosstalk during Productive Human Cytomegalovirus Infection
No full textTemporal profiles of miRNA activity during productive
virus infection can provide fundamental insights
into host-virus interactions. Most reported miRNA
targetome analyses in the context of virus infection
have been performed in latently infected cells and
lack reliable models for quantifying the suppression
efficacy at specific miRNA target sites. Here, we
identified highly competent temporal miRNA targetomes
during lytic HCMV infection by using AGOCLIP-
seq together with a bioinformatic method that
quantifies miRNA functionality at a specific target
site, called ACE-scoring. The repression efficiency
at target sites correlates with the magnitude of the
ACE-score, and temporal HCMV-encoded miRNA
targetomes identified by ACE-scoring were significantly
enriched in functional categories involved in
pathways central for HCMV biology. Furthermore,
comparative analysis between human and viral
miRNA targetomes supports the existence of intimate
cooperation and co-targeting between them.
Our holistic survey provides a valuable resource for
understanding host-virus interactions during lytic
HCMV infection. ⓒ2015 Elsevier Inc.11091sciescopu
Deletion of Human tarbp2 Reveals Cellular MicroRNA Targets and Cell-Cycle Function of TRBP
Full text linkTRBP functions as both a Dicer cofactor and a PKR
inhibitor. However, the role of TRBP in microRNA
(miRNA) biogenesis is controversial and its regulation
of PKR in mitosis remains unexplored. Here,
we generate TRBP knockout cells and find altered
Dicer-processing sites in a subset of miRNAs but
no effect on Dicer stability, miRNA abundance, or
Argonaute loading. By generating PACT, another
Dicer interactor, and TRBP/PACT double knockout
(KO) cells, we further show that TRBP and PACT do
not functionally compensate for one another and
that only TRBP contributes to Dicer processing. We
also report that TRBP is hyperphosphorylated by
JNK in M phase when PKR is activated by cellular
double-stranded RNAs (dsRNAs). Hyperphosphorylation
potentiates the inhibitory activity of TRBP on
PKR, suppressing PKR in M-G1 transition. By generating
human TRBP KO cells, our study clarifies the
role of TRBP and unveils negative feedback regulation
of PKR through TRBP phosphorylation.138391sciescopu
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Optimization of AAV expression cassettes to improve packaging capacity and transgene expression in neurons
Full text linkAdeno-associated virus (AAV) vectors can deliver transgenes to diverse cell types and are therefore useful for basic research and gene therapy. Although AAV has many advantages over other viral vectors, its relatively small packaging capacity limits its use for delivering large genes. The available transgene size is further limited by the existence of additional elements in the expression cassette without which the gene expression level becomes much lower. By using alternative combinations of shorter elements, we generated a series of AAV expression cassettes and systematically evaluated their expression efficiency in neurons to maximize the transgene size available within the AAV packaging capacity while not compromising the transgene expression. We found that the newly developed smaller expression cassette shows comparable expression efficiency with an efficient vector generally used for strong gene expression. This new expression cassette will allow us to package larger transgenes without compromising expression efficiency.120261sciescopu
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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