TASK DEFINITION: In this task, you are given an abstract of article. Your task is to generate title for this article. Preferred titles are under thirty words.
PROBLEM: P19 cells are a line of pluripotent embryonal carcinoma able to grow continuously in serum-supplemented media. The differentiation of these cells can be controlled by nontoxic drugs. Retinoic acid effectively induces the development of neurons, astroglia and microglia--cell types normally derived from the neuroectoderm. Aggregates of P19 cells exposed to dimethyl sulfoxide differentiate into endodermal and mesodermal derivatives including cardiac and skeletal muscle. P19 cells can be effectively transfected with DNA encoding recombinant genes and stable lines expressing these genes can be readily isolated. These manipulations make P19 cells suitable material for investigating the molecular mechanisms governing developmental decision made by differentiating pluripotent cells.

SOLUTION: P19 embryonal carcinoma cells.

PROBLEM: Uncoupling protein 1 (Ucp1), which is localized in the mitochondrial inner membrane of mammalian brown adipose tissue (BAT), generates heat by uncoupling oxidative phosphorylation. Upon cold exposure or nutritional abundance, sympathetic neurons stimulate BAT to express Ucp1 to induce energy dissipation and thermogenesis. Accordingly, increased Ucp1 expression reduces obesity in mice and is correlated with leanness in humans. Despite this significance, there is currently a limited understanding of how Ucp1 expression is physiologically regulated at the molecular level. Here, we describe the involvement of Sestrin2 and reactive oxygen species (ROS) in regulation of Ucp1 expression. Transgenic overexpression of Sestrin2 in adipose tissues inhibited both basal and cold-induced Ucp1 expression in interscapular BAT, culminating in decreased thermogenesis and increased fat accumulation. Endogenous Sestrin2 is also important for suppressing Ucp1 expression because BAT from Sestrin2(-/-) mice exhibited a highly elevated level of Ucp1 expression. The redox-inactive mutant of Sestrin2 was incapable of regulating Ucp1 expression, suggesting that Sestrin2 inhibits Ucp1 expression primarily through reducing ROS accumulation. Consistently, ROS-suppressing antioxidant chemicals, such as butylated hydroxyanisole and N-acetylcysteine, inhibited cold- or cAMP-induced Ucp1 expression as well. p38 MAPK, a signaling mediator required for cAMP-induced Ucp1 expression, was inhibited by either Sestrin2 overexpression or antioxidant treatments. Taken together, these results suggest that Sestrin2 and antioxidants inhibit Ucp1 expression through suppressing ROS-mediated p38 MAPK activation, implying a critical role of ROS in proper BAT metabolism.

SOLUTION: Sestrin2 inhibits uncoupling protein 1 expression through suppressing reactive oxygen species.

PROBLEM: BACKGROUND An increased volume of patients is associated with improved survival in numerous high-risk medical and surgical conditions. The relationship between the number of patients admitted (hospital volume) and outcome among patients with critical illnesses is unknown.
METHODS We analyzed data from 20,241 nonsurgical patients receiving mechanical ventilation at 37 acute care hospitals in the Acute Physiology and Chronic Health Evaluation clinical information system from 2002 through 2003. Multivariate analyses were performed to adjust for the severity of illness and other differences in the case mix.
RESULTS An increase in hospital volume was associated with improved survival among patients receiving mechanical ventilation in the intensive care unit (ICU) and in the hospital. Admission to a hospital in the highest quartile according to volume (i.e., >400 patients receiving mechanical ventilation per year) was associated with a 37 percent reduction in the adjusted odds of death in the ICU as compared with admission to hospitals in the lowest quartile (< or =150 patients receiving mechanical ventilation per year, P<0.001). In-hospital mortality was similarly reduced (adjusted odds ratio, 0.66; 95 percent confidence interval, 0.52 to 0.83; P<0.001). A typical patient in a hospital in a low-volume quartile would have an adjusted in-hospital mortality of 34.2 percent as compared with 25.5 percent in a hospital in a high-volume quartile. Among survivors, there were no significant trends in the length of stay in the ICU or the hospital.
CONCLUSIONS Mechanical ventilation of patients in a hospital with a high case volume is associated with reduced mortality. Further research is needed to determine the mechanism of the relationship between volume and outcome among patients with a critical illness.

SOLUTION:
Hospital volume and the outcomes of mechanical ventilation.