Metformin Promotes Antitumor Immunity via Endoplasmic-Reticulum-Associated Degradation of PD-L1.

Metformin has been reported to possess antitumor activity and maintain high cytotoxic T lymphocyte (CTL) immune surveillance. However, the functions and detailed mechanisms of metformin's role in cancer immunity are not fully understood. Here, we show that metformin increases CTL activity by reducing the stability and membrane localization of programmed death ligand-1 (PD-L1).

In silico and in vitro methods to identify ebola virus VP35-dsRNA inhibitors.

Ebola virus continues to be problematic as sporadic outbreaks in Africa continue to arise, and as terrorist organizations have considered the virus for bioterrorism use. Several proteins within the virus have been targeted for antiviral chemotherapy, including VP35, a dsRNA binding protein that promotes viral replication, protects dsRNA from degradation, and prevents detection of the viral genome by immune complexes. To augment the scope of our antiviral research, we have now employed molecular modeling techniques to enrich the population of compounds for further testing in vitro.

Leptin dependent changes in the expression of tropomyosin receptor kinase B protein in nucleus of the solitary tract to acute intermittent hypoxia.

To investigate the possibility that leptin exerts an effect in NTS by inducing changes in the expression of pre- and/or post-synaptic proteins, experiments were done in Sprague-Dawley wild-type rats (WT) rats and leptin-deficient rats (Lep(Δ151/Δ151); KILO rat) exposed to 8h of continuous intermittent hypoxia (IH) or normoxia. Protein was extracted from the caudal medial NTS and analyzed by western blot for the expression of brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), synaptophysin, synaptopodin and growth-associated protein-43 (GAP-43). In WT rats, BDNF and GAP 43 protein expression levels were not altered after IH or normoxia, although there was a trend towards an increase in BDNF expression.

Phenotypic characterization of recessive gene knockout rat models of Parkinson's disease.

Recessively inherited loss-of-function mutations in the PTEN-induced putative kinase 1(Pink1), DJ-1 (Park7) and Parkin (Park2) genes are linked to familial cases of early-onset Parkinson's disease (PD). As part of its strategy to provide more tools for the research community, The Michael J. Fox Foundation for Parkinson's Research (MJFF) funded the generation of novel rat models with targeted disruption ofPink1, DJ-1 or Parkin genes and determined if the loss of these proteins would result in a progressive PD-like phenotype.

Resolution of enantiomers of a series of chiral alkoxy-modified phthalocyaninato nickel(II) complexes by enantioselective HPLC.

We have resolved the enantiomers of a series of chiral modified metallophthalocyaninato complexes of nickel bearing alkoxy groups at the 14 and 28 positions on what would otherwise be a normal phthalocyaninato ligand and conforming to the general formula [14,28-(RO)(2)Pc]Ni(ii), where R = Me, Et, or n-Pr. The complex for which R = n-Pr is reported here for the first time. Resolution of the enantiomers of these complexes was accomplished via HPLC utilizing an immobilized carbohydrate-based stationary phase, resulting in baseline resolution of peaks corresponding to enantiomers of the complexes, with R(s) values in excess of five.

Efficient catalytic cycloalkane oxidation employing a "helmet" phthalocyaninato iron(III) complex.

We have examined the catalytic activity of an iron(III) complex bearing the 14,28-[1,3-diiminoisoindolinato]phthalocyaninato (diiPc) ligand in oxidation reactions with three substrates (cyclohexane, cyclooctane, and indan). This modified metallophthalocyaninato complex serves as an efficient and selective catalyst for the oxidation of cyclohexane and cyclooctane, and to a far lesser extent indan. In the oxidations of cyclohexane and cyclooctane, in which hydrogen peroxide is employed as the oxidant under inert atmosphere, we have observed turnover numbers of 100.