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An embryotoxicological investigation using embryonic stem cells : a molecular and cellular approachBigot, Karine January 2000 (has links)
No description available.
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Studies of cutaneous sensitisation to dinitrochlorobenzene in manMoss, C. January 1983 (has links)
No description available.
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A light and electron microscope investigation of the host-parasite relationship in the brains of mice with congenital toxoplasmosisSims, Thomas Anthony January 1992 (has links)
Impregnation of the wall of intact tissue cysts in the brains of mice with congenital toxoplasmosis, with reduced silver salts and protargol silver suggested that it was composed, at least in part, of components derived from the neuronal cytoskeleton. Electron microscopy extended these observations and revealed that intact tissue cysts were separated from the extra-cellular compartment by a layer of neurofibrillae enclosed within the host cell membranes. Immunohistochemical staining confirmed that this layer contained neurofilament protein. Interior to this layer was a much convoluted parasitophorous vacuole membrane; exterior was the host cell membrane. In most cases, synaptic plates were noted on the outer plasma membrane. In no instance were tissue cysts observed either within neuroglial cells or in the absence of a host cell. Electron immunocytochemistry, using a rabbit polyclonal antiToxoplasma IgG as the primary layer in immunogold staining, revealed that Toxoplasma antigenwas widely distributed within the matrix of the cyst, being most concentrated in the proximity of the inner surface of the parasitophorous vacuole membrane. Relatively little Toxoplasma antigen was detected directly associated with cystozoites. Small amounts of antigen were detected directly associated with cystozoites, within host cell components exterior to the parasitophorous vacuole membrane and in the host neuropil, immediately adjacent to the tissue cyst. The inter-relationship between inflammatory lesions associated with small vessels, in close proximity to intact tissue cysts, suggest that there may be 'migration' of these cells, in an ordered sequence, towards the Toxoplasma antigen secreted from the tissue cysts.
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Some studies on the toxic effects of heavy metals to a polychaete Hediste diversicolor (Muller) with particular reference to zincFernandez, T. V. January 1983 (has links)
No description available.
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Studies on some of the effects of pesticides on earthwormsKhan, Farrukh Humayoon Rafique January 1998 (has links)
No description available.
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The accumulation and toxicity of copper, zinc and manganese in the farmed snail Helix aspersa maximaBradley, Matthew Darren January 1995 (has links)
No description available.
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297 |
Structural aspects of tetanus toxinBritton, Paul January 1981 (has links)
No description available.
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298 |
Targeting Enzymes Involved in Protein Translation and Quality Control as Potential Cancer TherapeuticsTillotson, Joseph, Tillotson, Joseph January 2016 (has links)
Activation of pathways resulting in an overexpression of oncoproteins, reliant on cap-dependent translation, or mutations of key proteins in a pathway can be advantageous to cancer cells but creates heightened protein quality control pressure. Because of this, there has been an interest in targeting enzymes involved in protein synthesis and protein quality control: such as the eukaryotic initiation factor, eIF4A, a DEAD-box RNA helicase involved in translation initiation, and p97, an AAA+ chaperone involved in protein quality control. Despite some successes in discovering both eIF4A and p97 inhibitors, many of these compounds have pharmacological setbacks. The work in this dissertation defines new inhibitors of eIF4A and p97 with unique mechanisms of action. As described in chapter 2, we demonstrated that a marine-derived sesquiterpene, elatol, can modulate the ATPase activity of eIF4A. We provide further evidence that this molecule inhibits cap-dependent translation. Because there is no clear consensus on the mechanism of action for elatol, we hypothesized that the mechanism of toxicity attributed to elatol is likely through inhibition of cap-dependent translation initiation by targeting eIF4A. In chapter 3, we adapted a colorimetric assay to identify natural products that modulate the ATPase activity of p97 from which withaferin A (WFA) was identified. Because proteostasis modulation can connect each of the reported modes of action of WFA, we hypothesized that the primary mode of cytotoxic action of WFA is through inhibition of protein quality control machinery. Through medicinal chemistry efforts, we were able to improve WFA's biochemical and cellular activities as well as shifting the activity toward p97 and away from the proteasome. The work described in chapter 4 reports that dehydrocurvularin (DHC) and its chlorinated analogs are covalent modifiers of p97 and that the selectivity toward p97 can be attributed, in part, to the electronic effects of the chlorines. Taken together, this work highlights the significance of targeting protein translation and quality control, by modulation of eIF4A and p97 activity respectively, as promising anticancer therapeutics.
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Generation of DNA-damaging reactive oxygen species via the autoxidation of hydrogen sulfide under physiologically relevant conditionsHoffman, Marjorie A. 18 November 2016 (has links)
<p> Hydrogen sulfide (H<sub>2</sub>S) is more commonly known for its toxic properties; however, recently, there has been evidence that this small, gaseous molecule could serve as an endogenous cell-signaling agent. Surprisingly, a number of studies have also provided evidence that H<sub> 2</sub>S is a DNA-damaging mutagen. Using a plasmid-based DNA strand cleavage assay, we examined the chemical mechanisms of DNA damage by H<sub>2</sub>S. We found single-strand DNA cleavage was caused by micromolar concentrations of H<sub>2</sub>S. The mechanistic process was studied and was shown to involve the autoxidation of H<sub>2</sub>S to generate superoxide, hydrogen peroxide, and ultimately hydroxyl radical, a well-known DNA-damaging agent, via a trace metal-mediated Fenton-type reaction. In the presence of physiological thiol concentrations, DNA strand cleavage by H<sub>2</sub>S still occurred. The oxidation byproducts of H<sub>2</sub>S, such as thiosulfate, sulfite, and sulfate, do not contribute to DNA strand cleavage. However, the initially generated oxidation products, like persulfide (S<sub>2</sub><sup>2-</sup>), most likely go through rapid autoxidation reactions, which contribute to superoxide generation. This autoxidation process is of potential relevance to both the genotoxic and cell signaling properties of H<sub>2</sub>S.</p>
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Chronic lead exposure : effects on behaviour and development in miceDonald, James M. January 1985 (has links)
No description available.
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