Special investigation of the Newell Ambulance Service for the period August 1, 2004 through September 30, 2009

Special investigation of the Newell Ambulance Service for the period August 1, 2004 through September 30, 2009

Report on a special investigation of the Food Service Department of the Springville Community School District for the period July 1, 2005 through March 31, 2009

Report on a special investigation of the Food Service Department of the Springville Community School District for the period July 1, 2005 through March 31, 2009

Report on a special investigation of the Muscatine County Drug Task Force for the period January 1, 2004 through November 30, 2009

Report on a special investigation of the Muscatine County Drug Task Force for the period January 1, 2004 through November 30, 2009

Report on a review of selected general and application controls over the Iowa Department of Transportation’s Internal Billing System for the period April 6, 2009 through July 31, 2009

Report on a review of selected general and application controls over the Iowa Department of Transportation’s Internal Billing System for the period April 6, 2009 through July 31, 2009

Report on a review of selected general and application controls over the Iowa State University of Science and Technology (Iowa State University) Purchase Order/Requisition System for the period of March 20 through April 28, 2009

Report on a review of selected general and application controls over the Iowa State University of Science and Technology (Iowa State University) Purchase Order/Requisition System for the period of March 20 through April 28, 2009

Report on the review of selected general and application controls over the State University of Iowa (University of Iowa) ePro System for the period June 15, 2009 through July 31, 2009

Report on the review of selected general and application controls over the State University of Iowa (University of Iowa) ePro System for the period June 15, 2009 through July 31, 2009

ON THE ROLE OF PERIOD-2 IN THE CIRCADIAN AND HOMEOSTATIC REGULATION OF SLEEP

Humans spend one third of their life sleeping, then we could raise the basic question: Why do we sleep? Despite the fact that we still don't fully understand its function, we made much progress in understanding at different levels how sleep is regulated. One model suggests that sleep is regulated by two processes: a homeostatic process that tracks the need for sleep and by a circadian rhythm that determines the preferred time-of-day sleep occurs. At the molecular level circadian rhythms are a property of interlocking transcriptional regula-tors referred to as clock genes. The heterodimeric transcription factors BMAL1::CLOCK/NPAS2 drive the transcription of many target genes including the clock genes Cryptochome1 (Cry1), Cry2, Period1 (Per1), and Per2. The encoded CRY/PER proteins are transcriptional inhibitors of BMAL1::CLOCK/NPAS2 thereby providing negative feedback to their own transcription. These genes seem, however, also involved in sleep homeostasis because the brain expression of clock genes, es-pecially that of Per2, increase as a function of time-spent-awake and because mice lacking clock genes display altered sleep homeostasis. The aim of first part of my doctoral work has been to advance our understanding the link that exists between sleep homeostasis and circadian rhythms investigating a possible mechanism by which sleep deprivation could alter clock gene expression by quantifying DNA-binding of the core-clock genes BMAL1, CLOCK and NPAS2 to their target chromatin loci including the E-box enhancers of the Per2 promoter. We made use of chromatin immunoprecipitation (ChIP) and quantitative poly-merase chain reaction (qPCR) to show that DNA-binding of CLOCK and BMAL1 to their target genes changes as a function of time-of-day in both liver and cerebral cortex. We then performed a 6h sleep deprivation (SD) and observed a significant decrease in DNA-binding of CLOCK and BMAL1 to Dbp. This is consistent with a decrease in Dbp mRNA levels after SD. The DNA-binding of NPAS2 and BMAL1 to Per2 was similarly decreased following SD. However, SD has been previously shown to in-crease Per2 expression in the cortex which seems paradoxical. Our results demonstrate that sleep-wake history can affect the molecular clock machinery directly at the level of the chromatin thereby altering the cortical expression of Dbp and Per2, and likely other targets. However, the precise dy-namic relationship between DNA-binding and mRNA expression, especially for Per2, remains elusive. The second aim of my doctoral work has been to perform an in depth characterization of cir-cadian rhythmicity, sleep architecture, analyze the response to SD in full null-Per2 knock-out (Per2-/-) mice, and Per1-/- mice, as well as their double knock-out offspring (Per1,2-/-) and littermate wildtype (Wt) mice. The techniques used include locomotor activity recording by passive infrared (PIR) sen-sors, EEG/EMG surgery, recording, and analysis, and cerebral cortex extraction and quantification of mRNA levels by qPCR. Under standard LD12:12 conditions, we found that wakefulness onset, as well as the time courses of clock gene expression in the brain and corticosterone plasma levels were ad-vanced by about 2h in Per2-/- mice compared to Wt mice. When released under constant dark condi-tions almost all Per2-/- mice (97%) became arrhythmic immediately. From these observations, we conclude that while Per2-/- mice seem to be able to anticipate dark onset, this does not result from a self-sustained circadian clock. Our results suggest instead that the earlier onset of activity results from a labile, not-self sustained 22h rhythm linked to light onset suggesting the existence of a light-driven rhythm. Analyses of sleep under LD12:12 conditions revealed that in both Per2-/- and Per1,2-/- mice the same sleep phenotypes are observed compared to Wt mice: increased NREM sleep frag-mentation and inability to adequately compensate the loss of NREM sleep. That suggests a possible role of PER2 in sleep consolidation and recovery.

Report on a review of selected general and application controls over the University of Northern Iowa Accounts Payable/Purchasing System for the period of June 10, 2009 through August 20, 2009

Report on a review of selected general and application controls over the University of Northern Iowa Accounts Payable/Purchasing System for the period of June 10, 2009 through August 20, 2009

Report on a special investigation of the Clinton Community School District for the period July 1, 2005 through February 28, 2010

Report on a special investigation of the Clinton Community School District for the period July 1, 2005 through February 28, 2010

Report on a special investigation of certain driver’s license collections at the Sioux County Treasurer’s Office for the period July 1, 2009 through May 31, 2010

Report on a special investigation of certain driver’s license collections at the Sioux County Treasurer’s Office for the period July 1, 2009 through May 31, 2010

Report on a special investigation of the City of Alburnett for the period January 1, 2006 through December 31, 2009

Report on a special investigation of the City of Alburnett for the period January 1, 2006 through December 31, 2009

Special investigation of the Country Living Care Center in Toledo, Iowa for the period July 1, 2007 through April 30, 2009

Special investigation of the Country Living Care Center in Toledo, Iowa for the period July 1, 2007 through April 30, 2009

Special investigation of the Iowa Department of Economic Development Film Office and the Film, Television and Video Production Promotion Program for the period May 17, 2007 through September 21, 2009

Special investigation of the Iowa Department of Economic Development Film Office and the Film, Television and Video Production Promotion Program for the period May 17, 2007 through September 21, 2009

Letter to the Colo-Nesco Community School District as a result of reaudit procedures performed at the request of the Superintendent pursuant to Chapter 11.6(4)(a)(2) of the Code of Iowa for the period July 1, 2007 through June 30, 2008

Letter to the Colo-Nesco Community School District as a result of reaudit procedures performed at the request of the Superintendent pursuant to Chapter 11.6(4)(a)(2) of the Code of Iowa for the period July 1, 2007 through June 30, 2008

Report on the Local Public Health Services Grant administered by the Bureau of Local Public Health Services, a division of Health Promotion and Chronic Disease Prevention of the Iowa Department of Public Health for the period July 1, 2006 through June 30, 2008

Report on the Local Public Health Services Grant administered by the Bureau of Local Public Health Services, a division of Health Promotion and Chronic Disease Prevention of the Iowa Department of Public Health for the period July 1, 2006 through June 30, 2008