Autoubiquitination of the 26S proteasome on Rpn13 regulates breakdown of ubiquitin conjugates.

Degradation rates of most proteins in eukaryotic cells are determined by their rates of ubiquitination. However, possible regulation of the proteasome's capacity to degrade ubiquitinated proteins has received little attention, although proteasome inhibitors are widely used in research and cancer treatment. We show here that mammalian 26S proteasomes have five associated ubiquitin ligases and that multiple proteasome subunits are ubiquitinated in cells, especially the ubiquitin receptor subunit, Rpn13.

Continuous venovenous hemodiafiltration in patients with multiple organ dysfunction syndrome in an intensive care unit.

Introduction: Continuous venovenous hemodiafiltration, generally used in patients with acute renal failure, enables elimination of humoral mediators of systemic inflammatory response and sepsis from blood. This effect should improve treatment results in patients with multiple organ dysfunction, but evidence of improved survival is insufficient.

Objectives: Describe the effect of continuous venovenous hemodiaflitration on patients with multiple organ dysfunction syndrome in terms of systemic and brain hemodynamics, oxygenation, metabolism and status on ICU separation.

The JAMM motif of human deubiquitinase Poh1 is essential for cell viability.

Poh1 deubiquitinase activity is required for proteolytic processing of polyubiquitinated substrates by the 26S proteasome, linking deubiquitination to complete substrate degradation. Poh1 RNA interference (RNAi) in HeLa cells resulted in a reduction in cell viability and an increase in polyubiquitinated protein levels, supporting the link between Poh1 and the ubiquitin proteasome pathway. To more specifically test for any requirement of the zinc metalloproteinase motif of Poh1 to support cell viability and proteasome function, we developed a RNAi complementation strategy.

Characterization of Staphylococcus aureus enterotoxin L.

Staphylococcus aureus causes a wide variety of diseases. Major virulence factors of this organism include enterotoxins (SEs) that cause both food poisoning and toxic shock syndrome. Recently, a novel SE, tentatively designated SEL, was identified in a pathogenicity island from a bovine mastitis isolate.

Femoral central venous catheter-associated deep venous thrombosis in children with diabetic ketoacidosis.

Objective: To describe the incidence of clinical deep venous thrombosis associated with femoral central venous catheters (CVC-DVT) in children with diabetic ketoacidosis (DKA).

Design: Retrospective case-matched control series.

Setting: Pediatric intensive care units of two university-affiliated hospitals.

Assessment of the effects of D-003, a new antiplatelet and lipid-lowering compound, in healthy volunteers. A phase I clinical study.

Objective: To investigate the effects of D-003 on the bleeding time (BT) and lipid profile of healthy human volunteers.

Methods: This single-blind, randomised, placebo-controlled, parallel-group study was conducted in healthy volunteers. Step 1 investigated the effects of single doses of D-003 5, 25 or 50 mg on BT in comparison with placebo.

Streptococcus mutans ffh, a gene encoding a homologue of the 54 kDa subunit of the signal recognition particle, is involved in resistance to acid stress.

The ability of Streptococcus mutans, a bacterial pathogen associated with dental caries, to tolerate rapid drops in plaque pH (acidurance), is considered an important virulence factor. To study this trait, Tn917 mutants of S. mutans strain JH1005 which display acid sensitivity have been isolated and partially characterized.