Virtually nothing is known about the biochemical adaptations in eukaryotic cells that may enhance survival at low temperatures or upon freezing. Here we demonstrate an adaptive response in yeast that is activated below 10 degrees C and increases tolerance to low temperatures and freezing. This response involves a dramatic accumulation of the chemical chaperone trehalose and induction of trehalose-synthesizing enzymes (Tps1, Tps2) and certain heat shock proteins (Hsp104, Hsp42, Hsp12, Ssa4). mRNAs for these proteins increase dramatically below 10 degrees C and even at 0 degrees C. Their expression requires Msn2,4 transcription factors but also involves marked mRNA stabilization. Upon return to 30 degrees C, TPS1, TPS2, and HSP104 mRNAs, trehalose levels and tolerance to freezing fall dramatically within minutes. Mutants lacking trehalose or Msn2,4 die more rapidly at 0 degrees C and upon freezing. Thus, below 10 degrees C, yeast show an adaptive response that sustains viability at low or freezing temperatures, which are commonly encountered in natural environments and laboratory refrigerators.

Since its introduction into the endourologist's armamentarium almost 40 years ago, percutaneous nephrolithotomy (PCNL) has become the standard of care for patients with large-volume nephrolithiasis. Postoperative infection is one of the most common complications of the procedure, and postoperative sepsis is one of the most detrimental. A number of factors have been found to increase the risk of postoperative sepsis. These include patient characteristics that are known preoperatively, such as urine culture obtained from the bladder or from the renal pelvis if percutaneous access to the renal pelvis is obtained in advance to the procedure. Neurogenic bladder dysfunction secondary to spinal cord injury and anatomical renal abnormalities, such as pelvicalyceal dilatation, have also been associated with increased incidence of fever and sepsis after the procedure. Several intraoperative factors, such as the average renal pressure sustained during PCNL and the operative time, also seem to increase the risk of sepsis. Finally, the contribution of postoperative factors, such as presence of a nephrostomy tube or a urethral catheter, has also been investigated. A short preoperative course of antibiotics has been found to significantly decrease the rate of postoperative fever and sepsis. Novel agents targeted at sepsis prevention and treatment, such as anti-endotoxin antibodies and cholesterol-lowering drugs statins, are currently under investigation.

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