Downstream events initiated by expression of FSHD-associated DUX4: Studies of nucleocytoplasmic transport, γH2AX accumulation, and Bax/Bak-dependence
Biology Open
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2y ago
ABSTRACT Abnormal expression in skeletal muscle of the double homeobox transcription factor DUX4 underlies pathogenesis in facioscapulohumeral muscular dystrophy (FSHD). Though multiple changes are known to be initiated by aberrant DUX4 expression, the downstream events initiated by DUX4 remain incompletely understood. In this study, we examined plausible downstream events initiated by DUX4. First, we found that nucleocytoplasmic protein export appeared to be decreased upon DUX4 expression as indicated by nuclear accumulation of a shuttle-GFP reporter. Second, building on studies from other la ..read more
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First person – Kerry Roby
Biology Open
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2y ago
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Kerry Roby is first author on ‘ Loss of p19Arf Promotes Fibroblast Survival During Leucine Deprivation’, published in BiO. Kerry conducted the research described in this article while a postgraduate student in Sandra Ryeom's lab at the Perlman School of Medicine, University of Pennsylvania. He is now a Postdoc in the lab of Joseph McCarty at the MD Anderson Cancer Center, University of Texas, inves ..read more
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First person – Takuma Kozono
Biology Open
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2y ago
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Takuma Kozono is first author on ‘ Novel protocol to observe the intestinal tuft cell using transmission electron microscopy’, published in BiO. Takuma is a project assistant professor in the lab of Atsushi Nishikawa at Tokyo University of Agriculture and Technology, investigating the morphology and functions of organelles in the cells ..read more
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First person – Tom Carruthers
Biology Open
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2y ago
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Tom Carruthers is first author on ‘ exTREEmaTIME: a method for incorporating uncertainty into divergence time estimates’, published in BiO. Tom conducted the research described in this article while a PhD student in Professor Robert Scotland's lab in the Department of Plant Sciences, University of Oxford. He is now a postdoc in the lab of Dr William Baker at the Royal Botanic Gardens, Kew, working ..read more
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First person – Kelly Diamond
Biology Open
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2y ago
ABSTRACT First Person is a series of interviews with the first authors of a selection of papers published in Biology Open, helping early-career researchers promote themselves alongside their papers. Kelly Diamond is first author on ‘ Computational anatomy and geometric shape analysis enables analysis of complex craniofacial phenotypes in zebrafish’, published in BiO. Kelly is a postdoc in the lab of Dr Murat Maga at the Center for Developmental Biology and Regenerative Medicine, Seattle Children's Research Institute, Seattle, USA, investigating which combination of factors contribute to organi ..read more
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Computational anatomy and geometric shape analysis enables analysis of complex craniofacial phenotypes in zebrafish
Biology Open
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2y ago
ABSTRACT Due to the complexity of fish skulls, previous attempts to classify craniofacial phenotypes have relied on qualitative features or sparce 2D landmarks. In this work we aim to identify previously unknown 3D craniofacial phenotypes with a semiautomated pipeline in adult zebrafish mutants. We first estimate a synthetic ‘normative’ zebrafish template using MicroCT scans from a sample pool of wild-type animals using the Advanced Normalization Tools (ANTs). We apply a computational anatomy (CA) approach to quantify the phenotype of zebrafish with disruptions in bmp1a, a gene implicated in l ..read more
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Loss of p19Arf promotes fibroblast survival during leucine deprivation
Biology Open
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2y ago
ABSTRACT Fibroblasts are quiescent and tumor suppressive in nature but become activated in wound healing and cancer. The response of fibroblasts to cellular stress has not been extensively investigated, however the p53 tumor suppressor has been shown to be activated in fibroblasts during nutrient deprivation. Since the p19 Alternative reading frame (p19Arf) tumor suppressor is a key regulator of p53 activation during oncogenic stress, we investigated the role of p19Arf in fibroblasts during nutrient deprivation. Here, we show that prolonged leucine deprivation results in increased expression a ..read more
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Novel protocol to observe the intestinal tuft cell using transmission electron microscopy
Biology Open
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2y ago
ABSTRACT The tuft cell is a chemosensory cell, a specific cell type sharing the taste transduction system with a taste cell on the tongue, of which the existence has been discovered in various tissues including the gastrointestinal tract, gall bladder, trachea and pancreatic duct. To date, electron microscopic approaches have shown various morphological features of the tuft cell, such as long and thick microvilli, tubulovesicular network at the apical side and prominent skeleton structures. Recently, it has been reported that the small intestinal tuft cell functions to initiate type-2 immunity ..read more
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Construction of a human hTERT RPE-1 cell line with inducible Cre for editing of endogenous genes
Biology Open
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2y ago
ABSTRACT The human retinal pigment epithelial RPE-1 cell line immortalized with hTERT retains a stable karyotype with a modal chromosome number of 46 and has been widely used to study physiological events in human cell culture systems. To facilitate inducible knock-out or knock-in experiments in this cell line, we have modified the AAVS1 locus to harbour a DNA fragment encoding ERT2-Cre-ERT2 fusion protein under regulation of a Tet-On expression system. In the generated cell line, active Cre recombinase was induced by simple addition of doxycycline and tamoxifen to the culture medium. As proof ..read more
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ExTREEmaTIME: a method for incorporating uncertainty into divergence time estimates
Biology Open
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2y ago
ABSTRACT We present a method of divergence time estimation (exTREEmaTIME) that aims to effectively account for uncertainty in divergence time estimates. The method requires a minimal set of assumptions, and, based on these assumptions, estimates the oldest possible divergence times and youngest possible divergence times that are consistent with the assumptions. We use a series of simulations and empirical analyses to illustrate that exTREEmaTIME is effective at representing uncertainty. We then describe how exTREEmaTIME can act as a basis to determine the implications of the more stringent ass ..read more
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