TAK1 is required for survival of mouse fibroblasts treated with TRAIL, and does so by NF-kappaB dependent induction of cFLIPL.

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is known as a "death ligand"-a member of the TNF superfamily that binds to receptors bearing death domains. As well as causing apoptosis of certain types of tumor cells, TRAIL can activate both NF-kappaB and JNK signalling pathways. To determine the role of TGF-beta-Activated Kinase-1 (TAK1) in TRAIL signalling, we analyzed the effects of adding TRAIL to mouse embryonic fibroblasts (MEFs) derived from TAK1 conditional knockout mice. TAK1-/- MEFs were significantly more sensitive to killing by TRAIL than wild-type MEFs, and failed to activate NF-kappaB or JNK. Overexpression of IKK2-EE, a constitutive activator of NF-kappaB, protected TAK1-/- MEFs against TRAIL killing, suggesting that TAK1 activation of NF-kappaB is critical for the viability of cells treated with TRAIL. Consistent with this model, TRAIL failed to induce the survival genes cIAP2 and cFlipL in the absence of TAK1, whereas activation of NF-kappaB by IKK2-EE restored the levels of both proteins. Moreover, ectopic expression of cFlipL, but not cIAP2, in TAK1-/- MEFs strongly inhibited TRAIL-induced cell death. These results indicate that cells that survive TRAIL treatment may do so by activation of a TAK1-NF-kappaB pathway that drives expression of cFlipL, and suggest that TAK1 may be a good target for overcoming TRAIL resistance.

Audit report on the City of Maxwell, Iowa for the year ended June 30, 2008

Audit report on the City of Maxwell, Iowa for the year ended June 30, 2008

Audit report on the City of Anita, Iowa for the year ended June 30, 2008

Audit report on the City of Anita, Iowa for the year ended June 30, 2008

Audit report on the Iowa Turkey Marketing Council for the years ended December 31, 2008 and 2007

Audit report on the Iowa Turkey Marketing Council for the years ended December 31, 2008 and 2007

Audit report of the Department of Corrections for the year ended June 30, 2008

Audit report of the Department of Corrections for the year ended June 30, 2008

Audit report on Delaware Township, located in Polk County, Iowa, for the year ended June 30, 2008

Audit report on Delaware Township, located in Polk County, Iowa, for the year ended June 30, 2008

Audit report on the Iowa Department of Transportation for the year ended June 30, 2008

Audit report on the Iowa Department of Transportation for the year ended June 30, 2008

Audit report of Iowa State Prison Industries – Farms for the year ended June 30, 2008

Audit report of Iowa State Prison Industries – Farms for the year ended June 30, 2008

The trail making test as a screening instrument for driving performance in older drivers; a translational research.

BACKGROUND: In many countries, primary care physicians determine whether or not older drivers are fit to drive. Little, however, is known regarding the effects of cognitive decline on driving performance and the means to detect it. This study explores to what extent the trail making test (TMT) can provide indications to clinicians about their older patients' on-road driving performance in the context of cognitive decline. METHODS: This translational study was nested within a cohort study and an exploratory psychophysics study. The target population of interest was constituted of older drivers in the absence of important cognitive or physical disorders. We therefore recruited and tested 404 home-dwelling drivers, aged 70 years or more and in possession of valid drivers' licenses, who volunteered to participate in a driving refresher course. Forty-five drivers also agreed to undergo further testing at our lab. On-road driving performance was evaluated by instructors during a 45 minute validated open-road circuit. Drivers were classified as either being excellent, good, moderate, or poor depending on their score on a standardized evaluation of on-road driving performance. RESULTS: The area under the receiver operator curve for detecting poorly performing drivers was 0.668 (CI95% 0.558 to 0.778) for the TMT-A, and 0.662 (CI95% 0.542 to 0.783) for the TMT-B. TMT was related to contrast sensitivity, motion direction, orientation discrimination, working memory, verbal fluency, and literacy. Older patients with a TMT-A ≥ 54 seconds or a TMT-B ≥ 150 seconds have a threefold (CI95% 1.3 to 7.0) increased risk of performing poorly during the on-road evaluation. TMT had a sensitivity of 63.6%, a specificity of 64.9%, a positive predictive value of 9.5%, and a negative predictive value of 96.9%. CONCLUSION: In screening settings, the TMT would have clinicians uselessly consider driving cessation in nine drivers out of ten. Given the important negative impact this could have on older drivers, this study confirms the TMT not to be specific enough for clinicians to justify driving cessation without complementary investigations on driving behaviors.

Audit report on the Iowa Communications Network (ICN) for the year ended June 30, 2008

Audit report on the Iowa Communications Network (ICN) for the year ended June 30, 2008

Audit report on the Student Health Facility Revenue Bond Funds of Iowa State University of Science and Technology for the year ended June 30, 2009

Audit report on the Student Health Facility Revenue Bond Funds of Iowa State University of Science and Technology for the year ended June 30, 2009

Audit report on the City of Murray, Iowa for the year ended June 30, 2009

Audit report on the City of Murray, Iowa for the year ended June 30, 2009

Audit report on the Office of Treasurer of State, Iowa Educational Savings Plan Trust for the year ended June 30, 2009

Audit report on the Office of Treasurer of State, Iowa Educational Savings Plan Trust for the year ended June 30, 2009

Audit report on the City of Denison, Iowa for the year ended June 30, 2009

Audit report on the City of Denison, Iowa for the year ended June 30, 2009