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151.
The fluoropyrimidines 5-fluorouracil (5-FU) and FdUrd (5-fluorodeoxyuridine; floxuridine) are the backbone of chemotherapy regimens for colon cancer and other tumors. Despite their widespread use, it remains unclear how these agents kill tumor cells. Here, we have analyzed the checkpoint and DNA repair pathways that affect colon tumor responses to 5-FU and FdUrd. These studies demonstrate that both FdUrd and 5-FU activate the ATR and ATM checkpoint signaling pathways, indicating that they cause genotoxic damage. Notably, however, depletion of ATM or ATR does not sensitize colon cancer cells to 5-FU, whereas these checkpoint pathways promote the survival of cells treated with FdUrd, suggesting that FdUrd exerts cytotoxicity by disrupting DNA replication and/or inducing DNA damage, whereas 5-FU does not. We also found that disabling the base excision (BER) repair pathway by depleting XRCC1 or APE1 sensitized colon cancer cells to FdUrd but not 5-FU. Consistent with a role for the BER pathway, we show that small molecule poly(ADP-ribose) polymerase 1/2 (PARP) inhibitors, AZD2281 and ABT-888, remarkably sensitized both mismatch repair (MMR)-proficient and -deficient colon cancer cell lines to FdUrd but not to 5-FU. Taken together, these studies demonstrate that the roles of genotoxin-induced checkpoint signaling and DNA repair differ significantly for these agents and also suggest a novel approach to colon cancer therapy in which FdUrd is combined with a small molecule PARP inhibitor. 相似文献
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Jody L. Clasey Claude Bouchard Laurie Wideman Jill Kanaley C. David Teates Michael O. Thorner Mark L. Hartman Arthur Weltman 《Obesity (Silver Spring, Md.)》1997,5(5):395-401
CLASEY, JODY L, CLAUDE BOUCHARD, LAURIE WIDEMAN, JILL KANALEY, C DAVID TEATES, MICHAEL O THORNER, MARK L HARTMAN, ARTHUR WELTMAN. The influence of anatomical boundaries, age, and sex on the assessment of abdominal visceral fat. Single-slice abdominal computed tomography (CT) scanning has been used extensively for the measurement of abdominal visceral fat (AYF). Optimal anatomical scan location and pixel density ranges have been proposed and are specifically reported to allow for the replication and standardization of AVF measurements. Standardization of the anatomical boundaries for CT measurement of AVF and the influence of age and gender on results obtained with different boundary locations have received much less attention. To determine the influence of three boundary analysis methods (AVF-1, AVF-2, and AVF-3) on the measurement of AVF by CT, 54 older (60 years to 79 years) and 37 younger (20 years to 29 years) healthy men and women were examined. The measurement boundary for AVF-1 was the internal most aspect of the abdominal and oblique muscle walls, and the posterior aspect of the vertebral body. AVF-2 used fat measurements enclosed in a boundary formed by the midpoint of the abdominal and oblique muscle walls, and the most posterior aspect of the spinous process. AVF-3 used fat measurements enclosed in a boundary formed by the external border of the abdominal and oblique muscle walls, and the external border of the erector spinae. Greater AVF measures were obtained with AVF-2 and AVF-3 compared with AVF-1 (p<0.0001). These differences were greater in older compared with younger subjects (p<0.0001) and greater in women compared with men (p<0.02). The significantly greater AVF measurements obtained with AVF-2 and AVF-3 resulted from the inclusion of larger amounts of fat that are not drained by the portal circulation. This included retroperitoneal, intermuscular, and intramuscular lipid droplets, which increase with aging. On the basis of these results, we recommend the AVF-1 anatomical boundaries for the measurement of AVF in clinical investigations, particularly with older subjects. These data demonstrate the importance of precise and reproducible anatomical boundaries for the measurement of AVF, particularly in longitudinal studies. 相似文献
154.
Ann Pa Jill S. Craven Xiaotao T. Bi Staffan Melin Shahab Sokhansanj 《The International Journal of Life Cycle Assessment》2012,17(2):220-231
Purpose
Environmental footprints of wood pellets produced in British Columbia (BC) of Canada are to be estimated based on industry surveys and published emission factor data. 相似文献155.
Climate change poses critical challenges for population persistence in natural communities, for agriculture and environmental sustainability, and for food security. In this review, we discuss recent progress in climatic adaptation in plants. We evaluate whether climate change exerts novel selection and disrupts local adaptation, whether gene flow can facilitate adaptive responses to climate change, and whether adaptive phenotypic plasticity could sustain populations in the short term. Furthermore, we discuss how climate change influences species interactions. Through a more in‐depth understanding of these eco‐evolutionary dynamics, we will increase our capacity to predict the adaptive potential of plants under climate change. In addition, we review studies that dissect the genetic basis of plant adaptation to climate change. Finally, we highlight key research gaps, ranging from validating gene function to elucidating molecular mechanisms, expanding research systems from model species to other natural species, testing the fitness consequences of alleles in natural environments, and designing multifactorial studies that more closely reflect the complex and interactive effects of multiple climate change factors. By leveraging interdisciplinary tools (e.g., cutting‐edge omics toolkits, novel ecological strategies, newly developed genome editing technology), researchers can more accurately predict the probability that species can persist through this rapid and intense period of environmental change, as well as cultivate crops to withstand climate change, and conserve biodiversity in natural systems. 相似文献
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Stefano Potter Kylen Solvik Angela Erb Scott J. Goetz Jill F. Johnstone Michelle C. Mack James T. Randerson Miguel O. Romn Crystal L. Schaaf Merritt R. Turetsky Sander Veraverbeke Xanthe J. Walker Zhuosen Wang Richard Massey Brendan M. Rogers 《Global Change Biology》2020,26(3):1592-1607
Fire is a primary disturbance in boreal forests and generates both positive and negative climate forcings. The influence of fire on surface albedo is a predominantly negative forcing in boreal forests, and one of the strongest overall, due to increased snow exposure in the winter and spring months. Albedo forcings are spatially and temporally heterogeneous and depend on a variety of factors related to soils, topography, climate, land cover/vegetation type, successional dynamics, time since fire, season, and fire severity. However, how these variables interact to influence albedo is not well understood, and quantifying these relationships and predicting postfire albedo becomes increasingly important as the climate changes and management frameworks evolve to consider climate impacts. Here we developed a MODIS‐derived ‘blue sky’ albedo product and a novel machine learning modeling framework to predict fire‐driven changes in albedo under historical and future climate scenarios across boreal North America. Converted to radiative forcing (RF), we estimated that fires generate an annual mean cooling of ?1.77 ± 1.35 W/m2 from albedo under historical climate conditions (1971–2000) integrated over 70 years postfire. Increasing postfire albedo along a south–north climatic gradient was offset by a nearly opposite gradient in solar insolation, such that large‐scale spatial patterns in RF were minimal. Our models suggest that climate change will lead to decreases in mean annual postfire albedo, and hence a decreasing strength of the negative RF, a trend dominated by decreased snow cover in spring months. Considering the range of future climate scenarios and model uncertainties, we estimate that for fires burning in the current era (2016) the cooling effect from long‐term postfire albedo will be reduced by 15%–28% due to climate change. 相似文献
158.
Darren R. Grafius Stephen Hall Nicola McHugh Jill L. Edmondson 《Global Change Biology Bioenergy》2020,12(1):118-132
Biofuel provides a globally significant opportunity to reduce fossil fuel dependence; however, its sustainability can only be meaningfully explored for individual cases. It depends on multiple considerations including: life cycle greenhouse gas emissions, air quality impacts, food versus fuel trade‐offs, biodiversity impacts of land use change and socio‐economic impacts of energy transitions. One solution that may address many of these issues is local production of biofuel on non‐agricultural land. Urban areas drive global change, for example, they are responsible for 70% of global energy use, but are largely ignored in their resource production potential; however, underused urban greenspaces could be utilized for biofuel production near the point of consumption. This could avoid food versus fuel land conflicts in agricultural land and long‐distance transport costs, provide ecosystem service benefits to urban dwellers and increase the sustainability and resilience of cities and towns. Here, we use a Geographic Information System to identify urban greenspaces suitable for biofuel production, using exclusion criteria, in 10 UK cities. We then model production potential of three different biofuels: Miscanthus grass, short rotation coppice (SRC) willow and SRC poplar, within the greenspaces identified and extrapolate up to a UK‐scale. We demonstrate that approximately 10% of urban greenspace (3% of built‐up land) is potentially suitable for biofuel production. We estimate the potential of this to meet energy demand through heat generation, electricity and combined heat and power (CHP) operations. Our findings show that, if fully utilized, urban biofuel production could meet nearly a fifth of demand for biomass in CHP systems in the United Kingdom's climate compatible energy scenarios by 2030, with potentially similar implications for other comparable countries and regions. 相似文献
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