CCAR-1 is a negative regulator of the heat-shock response in Caenorhabditis elegans.

Defects in protein quality control during aging are central to many human diseases, and strategies are needed to better understand mechanisms of controlling the quality of the proteome. The heat-shock response (HSR) is a conserved survival mechanism mediated by the transcription factor HSF1 which functions to maintain proteostasis. In mammalian cells, HSF1 is regulated by a variety of factors including the prolongevity factor SIRT1. SIRT1 promotes the DNA-bound state of HSF1 through deacetylation of the DNA-binding domain of HSF1, thereby enhancing the HSR. SIRT1 is also regulated by various factors, including negative regulation by the cell-cycle and apoptosis regulator CCAR2. CCAR2 negatively regulates the HSR, possibly through its inhibitory interaction with SIRT1. We were interested in studying conservation of the SIRT1/CCAR2 regulatory interaction in Caenorhabditis elegans, and in utilizing this model organism to observe the effects of modulating sirtuin activity on the HSR, longevity, and proteostasis. The HSR is highly conserved in C. elegans and is mediated by the HSF1 homolog, HSF-1. We have uncovered that negative regulation of the HSR by CCAR2 is conserved in C. elegans and is mediated by the CCAR2 ortholog, CCAR-1. This negative regulation requires the SIRT1 homolog SIR-2.1. In addition, knockdown of CCAR-1 via ccar-1 RNAi works through SIR-2.1 to enhance stress resistance, motility, longevity, and proteostasis. This work therefore highlights the benefits of enhancing sirtuin activity to promote the HSR at the level of the whole organism.

Fluorodeoxyuridine enhances the heat shock response and decreases polyglutamine aggregation in an HSF-1-dependent manner in Caenorhabditis elegans.

The heat shock response (HSR) protects cells from protein-denaturing stress through the induction of chaperones. The HSR is conserved in all organisms and is mediated by the transcription factor HSF-1. We show here that a compound commonly used to prevent larval development in Caenorhabditis elegans, 5-fluoro-2'-deoxyuridine (FUdR), can enhance heat shock induction of hsp mRNA in an HSF-1-dependent manner. Treatment with FUdR can also decrease age-dependent polyglutamine aggregation in a Huntington's disease model, and this effect depends on HSF-1 as well. Therefore, FUdR treatment can modulate the HSR and proteostasis, and should be used with caution when used to inhibit reproduction.

Microbial growth on the anesthesia machine.

The purpose of this study was to determine the amount of microbial growth that develops on the anesthesia machine after a full day's use in the operating room. This descriptive bacteriology study is relevant to anesthesia practice because of the proximity of the oropharynx and multiple body fluids to anesthesia equipment and the potential for cross-contamination to patients and staff. The Wilcoxon signed rank test was used to evaluate the change in colony-forming units (CFUs) before and after use of equipment. The resulting P value of 0.12 indicated that the observed CFU increase was not statistically significant at the .05 level. The study identified many organisms that survive on the anesthesia machine tabletop, namely, coagulase-negative Staphylococcus, Bacillus, alpha Streptococcus, Acinetobacter, Staphylococcus aureus, and gram-negative rods. Several were expected to be found; however, alpha Streptococcus, Acinetobacter, S aureus, and gram-negative rods are pathogenic organisms causing respiratory infections and bacteremia, especially in patients with compromised conditions. Terminal cleaning methods may have changed during the course of the study, thereby contributing to the volume of microbes present before use and distorting the change in the number of CFUs before and after use.