Pax3 expression enhances PDGF-B-induced brainstem gliomagenesis and characterizes a subset of brainstem glioma.

High-grade Brainstem Glioma (BSG), also known as Diffuse Intrinsic Pontine Glioma (DIPG), is an incurable pediatric brain cancer. Increasing evidence supports the existence of regional differences in gliomagenesis such that BSG is considered a distinct disease from glioma of the cerebral cortex (CG). In an effort to elucidate unique characteristics of BSG, we conducted expression analysis of mouse PDGF-B-driven BSG and CG initiated in Nestin progenitor cells and identified a short list of expression changes specific to the brainstem gliomagenesis process, including abnormal upregulation of paired box 3 (Pax3). In the neonatal mouse brain, Pax3 expression marks a subset of brainstem progenitor cells, while it is absent from the cerebral cortex, mirroring its regional expression in glioma. Ectopic expression of Pax3 in normal brainstem progenitors in vitro shows that Pax3 inhibits apoptosis. Pax3-induced inhibition of apoptosis is p53-dependent, however, and in the absence of p53, Pax3 promotes proliferation of brainstem progenitors. In vivo, Pax3 enhances PDGF-B-driven gliomagenesis by shortening tumor latency and increasing tumor penetrance and grade, in a region-specific manner, while loss of Pax3 function extends survival of PDGF-B-driven;p53-deficient BSG-bearing mice by 33%. Importantly, Pax3 is regionally expressed in human glioma as well, with high PAX3 mRNA characterizing 40% of human BSG, revealing a subset of tumors that significantly associates with PDGFRA alterations, amplifications of cell cycle regulatory genes, and is exclusive of ACVR1 mutations. Collectively, these data suggest that regional Pax3 expression not only marks a novel subset of BSG but also contributes to PDGF-B-induced brainstem gliomagenesis.

A systematic review of evidence for silver nanoparticle-induced mitochondrial toxicity

© The Royal Society of Chemistry 2016.Silver nanoparticles (AgNPs) are extensively used for their antibacterial properties in a diverse set of applications, ranging from the treatment of municipal wastewater to infection control in hospitals. However, the properties of AgNPs that render them conducive to bactericidal use in commerce may influence their potential toxicity to non-bacterial organisms. Based on the physiological and phylogenetic similarities between bacteria and mitochondria within eukaryotic cells, mitochondria are a likely intracellular target of AgNP toxicity. Mitochondria-specific outcomes of AgNP exposures have been identified in multiple cell types, including (but not limited to) loss of membrane potential, inhibition of enzymes involved in oxidative phosphorylation, and changes in calcium sequestration. However, the biological significance of mitochondrial toxicity due to AgNP exposure is currently incompletely understood. This review examines the existing evidence of mitochondrial toxicity induced by AgNP exposure, with discussions of the role of the physicochemical properties of the nanoparticles themselves in mitochondrial toxicity. The impacts of potentially differential cell- and tissue-specific significance of AgNP-induced mitochondrial dysfunction are also discussed.

Optical Control of Magnetic Feshbach Resonances by Closed-Channel Electromagnetically Induced Transparency

Optical control of interactions in ultracold gases opens new fields of research by creating ``designer" interactions with high spatial and temporal resolution. However, previous optical methods using single optical fields generally suffer from atom loss due to spontaneous scattering. This thesis reports new optical methods, employing two optical fields to control interactions in ultracold gases, while suppressing spontaneous scattering by quantum interference. In this dissertation, I will discuss the experimental demonstration of two optical field methods to control narrow and broad magnetic Feshbach resonances in an ultracold gas of $^6$Li atoms. The narrow Feshbach resonance is shifted by $30$ times its width and atom loss suppressed by destructive quantum interference. Near the broad Feshbach resonance, the spontaneous lifetime of the atoms is increased from $0.5$ ms for single field methods to $400$ ms using our two optical field method. Furthermore, I report on a new theoretical model, the continuum-dressed state model, that calculates the optically induced scattering phase shift for both the broad and narrow Feshbach resonances by treating them in a unified manner. The continuum-dressed state model fits the experimental data both in shape and magnitude using only one free parameter. Using the continuum-dressed state model, I illustrate the advantages of our two optical field method over single-field optical methods.