SUMMARY The import of superoxide dismutase-2 (SOD2) into mitochondria is vital for the survival of eukaryotic cells. SOD2 is encoded within the nuclear genome and translocated into mitochondria for activation after translation in the cytosol. The molecular chaperone Hsp70 modulates SOD2 activity by promoting import of SOD2 into mitochondria. In turn, the activity of Hsp70 is controlled by co-chaperones, particularly CHIP, which directs Hsp70-bound proteins for degradation in the proteasomes. We investigated the mechanisms controlling the activity of SOD2 to signal activation and maintain mitochondrial redox balance. We demonstrate that Akt1 binds to and phosphorylates the C terminus of Hsp70 on Serine631, which inhibits CHIP-mediated SOD2 degradation thereby stabilizing and promoting SOD2 import. Conversely, increased mitochondrial-H2O2 formation disrupts Akt1-mediated phosphorylation of Hsp70, and non-phosphorylatable Hsp70 mutants decrease SOD2 import, resulting in mitochondrial oxidative stress. Our findings identify Hsp70 phosphorylation as a physiological mechanism essential for regulation of mitochondrial redox balance.

Laparoscopic appendectomy (LA) is preferred to open appendectomy (OA), as it is less invasive. However, it is debatable whether LA is more cost-effective. We compared the cost-benefits of LA with OA, using the entire pediatric inpatient hospital data in the USA. The Kids' Inpatient Database (KID) shows that 51,007 pediatric patients were subjected to laparoscopic appendectomy and 12,668 to open appendectomy during 2010-12 across the USA. This dataset was used to assess the cost-effectiveness of LA and OA while controlling for the demographic characteristics of patients (e.g. age and gender), their background (e.g., place of residence), and complexity of surgery (e.g., number of procedures). We found that patients with laparoscopic surgery saved ~0.46 days of hospital stay, but paid $3641 more compared to patients with open surgery. Surgeons prefer to use the technologically advanced laparoscopic appendectomy (80% of patients). Our analysis shows that the cost-benefit of laparoscopic appendectomy is marginal. Hence, for making a fully informed decision, patients should be provided with both clinical and cost comparison data.

Structural modifications of the existing ampicillin are much needed for saving patients from ampicillin-resistant microorganisms. A number of new molecules were generated by side chain modification of the existing ampicillin structure. Armed with molecular docking softwares like FlexiDOC, GLIDE, and AutoDOCK, a docking study was performed. Interaction between new molecules and target protein (1W2N) was also executed. Finally, we arranged new molecules according to docking scores, which directly reflects the binding affinity to the receptor protein.