25 hasil untuk "Douglas Strathdee"
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Artikel Jurnal Teks lengkap
Expression of transgenes targeted to the Gt(ROSA)26Sor locus is orientation dependent.
Targeting transgenes to a chosen location in the genome has a number of advantages. A single copy of the DNA construct can be inserted by targeting into regions of chromatin that allow the desired developmental and tissue-specific expression of the transgene.In order to develop a reliable system…
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Morphogenesis of extra-embryonic tissues directs the remodelling of the mouse embryo at implantation
How the shape of the pre-implantation murine embryo changes dramatically upon implantation is unclear. Here, the authors use live imaging with a cdx2-GFP reporter line in combination with loss of function experiments to demonstrate that FGF signalling mediated trophectoderm morphogenesis…
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Artikel Jurnal Teks lengkap
Phenotypic Characterization of Male Tafazzin-Knockout Mice at 3, 6, and 12 Months of Age
Barth syndrome (BTHS) is an X-linked mitochondrial disease caused by mutations in the gene encoding for tafazzin (TAZ), a key enzyme in the remodeling of cardiolipin. Mice with a germline deficiency in Taz have been generated (Taz-KO) but not yet fully characterized. We performed physiological…
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Artikel Jurnal Teks lengkap
Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis.
Barth syndrome is an X-linked mitochondrial disease, symptoms of which include neutropenia and cardiac myopathy. These symptoms are the most significant clinical consequences of a disease, which is increasingly recognised to have a variable presentation. Mutation in the Taz gene in Xq28 is thought…
Juga tersedia di: PLOS
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RNA helicase EIF4A1-mediated translation is essential for the GC response
Conditional mouse knock-out models show that EIF4A1, but not its cofactors EIF4B or EIF4H, is essential in B cells for their development, the GC response, and increased translation after activation. EIF4A1 and cofactors EIF4B and EIF4H have been well characterised in cancers, including B cell…
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Artikel Jurnal Teks lengkap
Phenotypic Characterization of Female Carrier Mice Heterozygous for Tafazzin Deletion
Barth syndrome (BTHS) is caused by mutations in tafazzin resulting in deficits in cardiolipin remodeling that alter major metabolic processes. The tafazzin gene is encoded on the X chromosome, and therefore BTHS primarily affects males. Female carriers are typically considered asymptomatic, but…
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Artikel Jurnal
Plaat1 deficiency reduces cardiac cardiolipin content and impairs exercise tolerance
Phospholipase A and acyltransferase 1 (PLAAT1) catalyzes O-transacylase, N-transacylase, and phospholipase A1/2 reactions. We have demonstrated that PLAAT1 has O-transacylase activity in vitro using phosphatidylcholine as an acyl donor and monolysocardiolipin (MLCL) as an acyl acceptor, generating…
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The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma
The cell's repertoire of transfer RNAs (tRNAs) has been linked to cancer. Recently, the level of the initiator methionine tRNA (tRNAiMet) in stromal fibroblasts has been shown to influence extracellular matrix (ECM) secretion to drive tumour growth and angiogenesis. Here we show that increased…
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Development of an inducible mouse model of iRFP713 to track recombinase activity and tumour development in vivo
Abstract While the use of bioluminescent proteins for molecular imaging is a powerful technology to further our understanding of complex processes, fluorescent labeling with visible light fluorescent proteins such as GFP and RFP suffers from poor tissue penetration and high background…
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STEF/TIAM2-mediated Rac1 activity at the nuclear envelope regulates the perinuclear actin cap
The perinuclear actin cap determines nuclear morphology but its regulation is currently poorly understood. Here, the authors find that an activator of the Rac1 GTPase, STEF/TIAM2, localises to the nuclear envelope and contributes to perinuclear actin and myosin tension, which in turn regulates the…
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Artikel Jurnal
Characterisation of cold-selective lamina I spinal projection neurons in the mouse
Skin cooling is detected by primary afferents that express the Trpm8 channel, but how this information is conveyed to the brain remains poorly understood. We have previously identified a population of lamina I projection neurons belonging to the anterolateral system (ALS) that receive numerous…
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Artikel Jurnal
Tafazzin regulates neutrophil maturation and inflammatory response
Abstract Barth syndrome (BTHS) is a rare genetic disease caused by mutations in the TAFAZZIN gene. It is characterized by neutropenia, cardiomyopathy and skeletal myopathy. Neutropenia in BTHS is associated with life-threatening infections, yet there is little understanding of the molecular and…
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KRAS allelic imbalance drives tumour initiation yet suppresses metastasis in colorectal cancer in vivo
Abstract Oncogenic KRAS mutations are well-described functionally and are known to drive tumorigenesis. Recent reports describe a significant prevalence of KRAS allelic imbalances or gene dosage changes in human cancers, including loss of the wild-type allele in KRAS mutant cancers. However, the…
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Removing physiological motion from intravital and clinical functional imaging data
Intravital microscopy can provide unique insights into the function of biological processes in a native context. However, physiological motion caused by peristalsis, respiration and the heartbeat can present a significant challenge, particularly for functional readouts such as fluorescence lifetime…
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Artikel Jurnal
RAC1B modulates intestinal tumourigenesis via modulation of WNT and EGFR signalling pathways
RAC1 is a downstream target of the Wnt signaling that promotes intestinal stem cell expansion and tumorigenesis. Here, the authors identify the specific splice variant RAC1B as an important mediator of colorectal tumourigenesis and a potential target for enhancing the efficacy of EGFR inhibitor…
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Increased mRNA translation delays tumour initiation and exposes a therapeutic vulnerability in lung cancer
Abstract Background Although inhibitors of mRNA translation are being evaluated as anti-cancer agents, the dynamics of protein synthesis throughout tumour progression are still poorly understood. Here we assess how alterations in mRNA translation during early tumorigenesis affect tumour development…
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Artikel Jurnal
Oncogenic BRAF, unrestrained by TGFβ-receptor signalling, drives right-sided colonic tumorigenesis
Right-sided colorectal cancer (rCRC) has a different mutational spectrum to the left-sided counterpart. Here the authors develop a mouse model of rCRC that recapitulates human BRAF-mutant rCRC and show that loss of TGFβ-receptor signalling and inflammation induce the development of colonic tumours…