The PRL2 Phosphatase Upregulates miR-21 through Activation of the JAK2/STAT3 Pathway to Downregulate the PTEN Tumor Suppressor.

The Phosphatases of Regenerating Liver (PRLs) are members of the protein tyrosine phosphatase (PTP) superfamily that play pro-oncogenic roles in cell proliferation, migration, and survival. We previously demonstrated that PRLs can post-translationally downregulate PTEN, a tumor suppressor frequently inactivated in human cancers, by dephosphorylating PTEN at Tyr336, which promotes the NEDD4-mediated PTEN ubiquitination and proteasomal degradation. Here we report that PRLs can also reduce PTEN expression by upregulating MicroRNA-21 (miR-21), which is one of the most frequently overexpressed miRNAs in solid tumors.

Sirtuin 6 is required for the integrated stress response and resistance to inhibition of transcriptional cyclin-dependent kinases.

Pancreatic ductal adenocarcinoma (PDAC) is classified into two key subtypes, classical and basal, with basal PDAC predicting worse survival. Using in vitro drug assays, genetic manipulation experiments, and in vivo drug studies in human patient-derived xenografts (PDXs) of PDAC, we found that basal PDACs were uniquely sensitive to transcriptional inhibition by targeting cyclin-dependent kinase 7 (CDK7) and CDK9, and this sensitivity was recapitulated in the basal subtype of breast cancer. We showed in cell lines, PDXs, and publicly available patient datasets that basal PDAC was characterized by inactivation of the integrated stress response (ISR), which leads to a higher rate of global mRNA translation.

Admission Peripheral Edema, Central Venous Pressure, and Survival in Critically Ill Patients.

Rationale: The clinical significance of peripheral edema has not been well described in critical illness.

Objectives: To assess the clinical significance of peripheral edema detected on physical examination at the time of hospital admission for patients who were treated in an intensive care unit (ICU).

Methods: Using a large inception cohort of critically ill patients, we examined the association of peripheral edema, as documented on hospital admission physical examination, with hospital and 1-year survival.

Peripheral Edema, Central Venous Pressure, and Risk of AKI in Critical Illness.

Background And Objectives: Although venous congestion has been linked to renal dysfunction in heart failure, its significance in a broader context has not been investigated.

Design, Setting, Participants, & Measurements: Using an inception cohort of 12,778 critically ill adult patients admitted to an urban tertiary medical center between 2001 and 2008, we examined whether the presence of peripheral edema on admission physical examination was associated with an increased risk of AKI within the first 7 days of critical illness. In addition, in those with admission central venous pressure (CVP) measurements, we examined the association of CVPs with subsequent AKI.

The effects of acetazolamide in albino rabbits, pigmented rabbits, and humans.

In three separate experiments albino rabbits, pigmented rabbits, and humans were tested following administration of acetazolamide and without acetazolamide. In all three experiments, we recorded electroretinograms (ERGs) under dark adapted and light adapted conditions and measured the b-wave amplitudes. Dark adapted ERG b-wave amplitudes were increased following administration of acetazolamide as compared to control conditions, in albino rabbits, pigmented rabbits and humans.