Global ETD Search

91	Nuclear translation Baboo, Sabyasachi January 2012 (has links) In bacteria, protein synthesis can occur tightly coupled to transcription. In eukaryotes, it is believed that translation occurs solely in the cytoplasm; I test whether some occurs in nuclei and find: (1) L-azidohomoalanine (Aha) – a methionine analogue (detected by microscopy after attaching a fluorescent tag using ‘click’ chemistry) – is incorporated within 5 s into nuclei in a process sensitive to the translation inhibitor, anisomycin. (2) Puromycin – another inhibitor that end-labels nascent peptides (detected by immuno-fluorescence) – is similarly incorporated in a manner sensitive to a transcriptional inhibitor. (3) CD2 – a non-nuclear protein – is found in nuclei close to the nascent RNA that encodes it (detected by combining indirect immuno-labelling with RNA fluorescence in situ hybridization using intronic probes); faulty (nascent) RNA is destroyed by a quality-control mechanism sensitive to translational inhibitors. I conclude that substantial translation occurs in the nucleus, with some being closely coupled to transcription and the associated proof-reading. Moreover, most peptides made in both the nucleus and cytoplasm are degraded soon after they are made with half-lives of about one minute. I also collaborated on two additional projects: the purification of mega-complexes (transcription ‘factories’) containing RNA polymerases I, II, or III (I used immuno-fluorescence to confirm that each contained the expected constituents), and the demonstration that some ‘factories’ specialize in transcribing genes responding to tumour necrosis factor α – a cytokine that signals through NFκB (I used RNA fluorescence in situ hybridization coupled with immuno-labelling to show active NFκB is found in factories transcribing responsive genes). 572
92	Filozofie přirozeného jazyka - její úpadek a co po něm / Philosophy of Ordinary Language - its Decline and What to Do After It Ivan, Michal January 2019 (has links) The general topic of the thesis is the history of the Ordinary Language Philosophy. To be more precise, it deals with the critical arguments, which were raised against is. The thesis offers a short historical and sociological review of the Ordinary Language Philosophy. Critical analysis shows two things: 1) the main reason for the rejection was a different understanding of meaning (and consequences of such a understanding); 2) critics begged the question and already assumed the justification of these rejections in their arguments. The area of this criticism was: the paradigm case argument, the empirical nature of the statements of meaning produced by the Ordinary Language Philosophy, the structural elements of meaning and the political implications of the theory of meaning. The thesis criticizes the Ordinary Language Philosophy in those parts (and in such interpretations), where its understanding of meaning does not differ from the understanding of the critics and where they share common assumptions. On the other hand, the thesis argues for an interpretation, which avoids classical understanding of meaning in all its consequences. Finally, the thesis asks how the Ordinary Language Philosophy can be useful for contemporary debates.
93	Gothic Agents Of Revolt: The Female Rebel In Pan's Labyrinth, Alice's Adventures In Wonderland And Through The Looking Glass Markodimitrakis, Michail-Chrysovalantis 21 April 2016 (has links) No description available. Literature American Studies Film Studies Gender Studies Cinematography Comparative Literature Political Science Philosophy Gothic gothic literature horror film fascism theory violence cinema victorian literature nonsense children state of exception fairies Nazism Guillermo Del Toro Lewis Carroll Wonderland Pan Labyrinth ideology homo sacer gender death
94	Stoichiometric imbalance in the receptor complex contributes to dysfunctional BMPR-II mediated signalling in pulmonary arterial hypertension Nasim, Md. Talat, Ghouri, A., Patel, B., James, V., Rudarakanchana, N., Morrell, N.W., Trembath, R.C. January 2008 (has links) No / Heterozygous germline defects in a gene encoding a type II receptor for bone morphogenetic proteins (BMPR-II) underlie the majority of inherited cases of the vascular disorder known as pulmonary arterial hypertension (PAH). However, the precise molecular consequences of PAH causing mutations on the function of the receptor complex remain unclear. We employed novel enzymatic and fluorescence activity based techniques to assess the impact of PAH mutations on pre-mRNA splicing, nonsense-mediated decay (NMD) and receptor complex interactions. We demonstrate that nonsense and frameshift mutations trigger NMD, providing further evidence that haplo-insufficiency is a major molecular consequence of disease-related BMPR2 mutations. We identified heterogeneous functional defects in BMPR-II activity, including impaired type I receptor phosphorylation, receptor interactions and altered receptor complex stoichiometry leading to perturbation of downstream signalling pathways. Importantly, these studies demonstrate that the intracellular domain of BMPR-II is both necessary and sufficient for receptor complex interaction. Finally and to address the potential for resolution of stoichiometric balance, we investigated an agent that promotes translational readthrough of a BMPR2 nonsense reporter construct without interfering with the NMD pathway. We propose that stoichiometric imbalance, due to either haplo-insufficiency or loss of optimal receptor-receptor interactions impairs BMPR-II mediated signalling in PAH. Taken together, these studies have identified an important target for early therapeutic intervention in familial PAH. Aminoglycosides Pharmacology Bone morphogenetic protein receptors Type I Metabolism Bone morphogenetic protein receptors Type II Genetics Codon Nonsense Exons Genes Reporter Humans Hypertension Pulmonary Enzymology Introns Phosphorylation Protein biosynthesis RNA precursors RNA splicing RNA stability RNA messenger Signal transduction Transcription Drug effects REF 2014

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