Lottery Action, August 9-22, 2004, Vol. 11, no. 15

Iowa Lottery Authority Retailer Information Newsletter

The E3 ubiquitin ligase Itch regulates sorting nexin 9 through an unconventional substrate recognition domain.

The level of intracellular proteins is mainly regulated through modifications by ubiquitin ligases that target them for degradation. Members of the NEDD4 family of E3 ubiquitin ligases, such as Itch (atrophin-1 interacting protein 4), possess up to four WW domains for specific association with PY motif-containing substrates. We have identified sorting nexin 9 (SNX9), a protein involved in endocytic processes, as a new substrate of Itch. Itch ubiquitylates SNX9 and regulates intracellular SNX9 levels. Using truncated proteins, we found that the interaction with SNX9 is mediated by the proline-rich domain (PRD) of Itch, a domain distinct from the conventional WW recognition domain, and the SH3 domain of SNX9. Interaction with the PRD of Itch is essential for SNX9 ubiquitylation and degradation. Furthermore, this effect is specific for Itch, as NEDD4, a related PRD-containing E3 ligase, does not bind SNX9. SNX18, a second member of the SNX family containing an SH3 domain, was also found to bind to Itch. Our results indicate that the pool of substrates of NEDD4 family E3 ubiquitin ligases extends beyond proteins containing PY motifs.

Histoire du dix-neuvième siècle depuis les traités de Vienne. Tome 9 / G. G. Gervinus,... ; traduit de l'allemand par J.-F. Minssen,...

Collection : Collection d'historiens contemporains

Credit Union Division Activities, December 2003, Issue 9

Newsletter for Iowa Credit Union Division

Footnotes, September-October 2004, Vol. 28, no. 9-10

Monthly newsletter of the State Library

Footnotes, July/August 2004, Vol. 28, no. 7-9

Monthly newsletter of the State Library

Lottery Action, August 23-September 9, 2004, Vol. 11, no. 16

Iowa Lottery Retailer Newsletter

The Security Blanket, June/July 2002, Vol.1, no.9

Newsletter for Information Technology Department

Iowa African-American Journal, Spring 2004, Vol. 9, no. 1

Newsletter for the Iowa Commission on the Status of African-Americans

Discrepancies between office and ambulatory blood pressure: clinical implications.

BACKGROUND: Recent trials have documented no benefit from small reductions in blood pressure measured in the clinical office. However, ambulatory blood pressure is a better predictor of cardiovascular events than office-based blood pressure. We assessed control of ambulatory blood pressure in treated hypertensive patients at high cardiovascular risk. METHODS: We selected 4729 patients from the Spanish Ambulatory Blood Pressure Monitoring Registry. Patients were aged >/=55 years and presented with at least one of the following co-morbidities: coronary heart disease, stroke, and diabetes with end-organ damage. An average of 2 measures of blood pressure in the office was used for analyses. Also, 24-hour ambulatory blood pressure was recorded at 20-minute intervals with a SpaceLabs 90207 device. RESULTS: Patients had a mean age of 69.6 (+/-8.2) years, and 60.8% of them were male. Average time from the diagnosis of hypertension to recruitment into the Registry was 10.9 (+/-8.4) years. Mean blood pressure in the office was 152.3/82.3 mm Hg, and mean 24-hour ambulatory blood pressure was 133.3/72.4 mm Hg. About 60% of patients with an office-pressure of 130-139/85-89 mm Hg, 42.4% with office-pressure of 140-159/90-99 mm Hg, and 23.3% with office-pressure > or =160/100 mm Hg were actually normotensive, according to 24-hour ambulatory blood pressure criteria (<130/80 mm Hg). CONCLUSION: We suggest that the lack of benefit of antihypertensive therapy in some trials may partly be due to some patients having normal pressure at trial baseline. Ambulatory monitoring of blood pressure may allow for a better assessment of trial eligibility.

Absence of delta-9-tetrahydrocannabinol dysphoric effects in dynorphin-deficient mice

The involvement of dynorphin on Delta-9-tetrahydrocannabinol (THC) and morphine responses has been investigated by using mice with a targeted inactivation of the prodynorphin (Pdyn) gene. Dynorphin-deficient mice show specific changes in the behavioral effects of THC, including a reduction of spinal THC analgesia and the absence of THC-induced conditioned place aversion. In contrast, acute and chronic opioid effects were normal. The lack of negative motivational effects of THC in the absence of dynorphin demonstrates that this endogenous opioid peptide mediates the dysphoric effects of marijuana.