994 resultados para Hunter, Charles G.


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Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

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Glutamine is conditionally essential in cancer cells, being utilized as a carbon and nitrogen source for macromolecule production, as well as for anaplerotic reactions fuelling the tricarboxylic acid (TCA) cycle. In this study, we demonstrated that the glutamine transporter ASCT2 (SLC1A5) is highly expressed in prostate cancer patient samples. Using LNCaP and PC-3 prostate cancer cell lines, we showed that chemical or shRNA-mediated inhibition of ASCT2 function in vitro decreases glutamine uptake, cell cycle progression through E2F transcription factors, mTORC1 pathway activation and cell growth. Chemical inhibition also reduces basal oxygen consumption and fatty acid synthesis, showing that downstream metabolic function is reliant on ASCT2-mediated glutamine uptake. Furthermore, shRNA knockdown of ASCT2 in PC-3 cell xenografts significantly inhibits tumour growth and metastasis in vivo, associated with the down-regulation of E2F cell cycle pathway proteins. In conclusion, ASCT2-mediated glutamine uptake is essential for multiple pathways regulating the cell cycle and cell growth, and is therefore a putative therapeutic target in prostate cancer.

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BACKGROUND: Glyphosate-resistant cotton varieties are an important tool for weed control in Australian cotton production systems. To increase the sustainability of this technology and to minimise the likelihood of resistance evolving through its use, weed scientists, together with herbicide regulators, industry representatives and the technology owners, have developed a framework that guides the use of the technology. Central to this framework is a crop management plan (CMP) and grower accreditation course. A simulation model that takes into account the characteristics of the weed species, initial gene frequencies and any associated fitness penalties was developed to ensure that the CMP was sufficiently robust to minimise resistance risks. RESULTS: The simulations showed that, when a combination of weed control options was employed in addition to glyphosate, resistance did not evolve over the 30 year period of the simulation. CONCLUSION: These simulations underline the importance of maintaining an integrated system for weed management to prevent the evolution of glyphosate resistance, prolonging the use of glyphosate-resistant cotton.

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Weed management practices in cotton systems that were based on frequent cultivation, residual herbicides, and some post-emergent herbicides have changed. The ability to use glyphosate as a knockdown before planting, in shielded sprayers, and now over-the-top in glyphosate-tolerant cotton has seen a significant reduction in the use of residual herbicides and cultivation. Glyphosate is now the dominant herbicide in both crop and fallow. This reliance increases the risk of shifts to glyphosate-tolerant species and the evolution of glyphosate-resistant weeds. Four surveys were undertaken in the 2008-09 and 2010-11 seasons. Surveys were conducted at the start of the summer cropping season (November-December) and at the end of the same season (March-April). Fifty fields previously surveyed in irrigated and non-irrigated cotton systems were re-surveyed. A major species shift towards Conyza bonariensis was observed. There was also a minor increase in the prevalence of Sonchus oleraceus. Several species were still present at the end of the season, indicating either poor control and/or late-season germinations. These included C. bonariensis, S. oleraceus, Hibiscus verdcourtii and Hibiscus tridactylites, Echinochloa colona, Convolvulus sp., Ipomea lonchophylla, Chamaesyce drummondii, Cullen sp., Amaranthus macrocarpus, and Chloris virgata. These species, with the exception of E. colona, H. verdcourtii, and H. tridactylites, have tolerance to glyphosate and therefore are likely candidates to either remain or increase in dominance in a glyphosate-based system.

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Thousands of hectares of native plants and shallow open water habitat have been displaced in Lake Okeechobee’s marsh by the invasive exotic species torpedograss ( Panicum repens L.). The rate of torpedograss expansion, it’s areal distribution and the efficacy of herbicide treatments used to control torpedograss in the lake’s marsh were quantified using aerial color infra red (IR) photography.(PDF has 6 pages.)

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Studies were conducted to evaluate whether the herbicide imazapyr or a combination of imazapyr and fluridone could be used effectively to control torpedograss ( Panicum repens L.), an exotic perennial plant that has replaced more than 6,000 ha of native vegetation and degraded quality wildlife habitat in Lake Okeechobee, Florida. Torpedograss was controlled for more than one year in some areas following a single aerial treatment using 0.56, 0.84, or 1.12 kg acid equivalents (ae) imazapyr/ha. Combining imazapyr and fluridone did not increase the level of torpedograss control. In areas where plant biomass was reduced by fire prior to being treated with 0.84 or 1.12 kg ae imazapyr/ha, torpedograss was controlled for more than two years and native plant species, including duck potato ( Sagittaria lancifolia L.) and pickerelweed ( Pontederia cordata L.) became the dominant vegetation in less than one year. Although torpedograss was controlled in some areas, little or no long-term control was observed at 16 of the 26 treatment locations. To reduce the uncertainty associated with predicting long-term treatment affects, additional studies are needed to determine whether environmental factors such as periphyton mats, plant thatch, hydroperiod and water depth affect treatment efficacy. , he

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The crinoid fauna of the continental margin (0-1500 m) of northeastern North America (Georgia to Canada) includes 14 species in 13 genera and 5 families. We introduce the external morphology and natural history of crinoids and include a glossary of terms, an illustrated key to local taxa, annotated systematic list, and an index. The fauna includes 2 species found no further south than New England and 8 that occur no further north than the Carolinas and Blake Plateau. Comactinia meridionalis (Agassiz) is the only species commonly found in shallow water «50 m). No taxa are endemic to the area. (PDF file contains 34 pages.)

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Gemstone Team Organ Storage and Hibernation

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A section of the Niagara Historical Society No. 20 titled Reminiscences of the Fenian Raid 1866. A brief account of the time of the Fenian Raid in three parts with a focus on Dunville in Part II.

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La disminución del sacrificio durante dos años seguidos en gran medida obedece al comportamiento que ha venido teniendo la economía del país y a la debilidad de la demanda interna además del bajo movimiento que han tenido las exportaciones del sector