Autism NPCs from both idiopathic and CNV 16p11.2 deletion patients exhibit dysregulation of proliferation and mitogenic responses.

Neural precursor cell (NPC) dysfunction has been consistently implicated in autism. Induced pluripotent stem cell (iPSC)-derived NPCs from two autism groups (three idiopathic [I-ASD] and two 16p11.2 deletion [16pDel]) were used to investigate if proliferation is commonly disrupted.

Using iPSC-Based Models to Understand the Signaling and Cellular Phenotypes in Idiopathic Autism and 16p11.2 Derived Neurons.

Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that is remarkably heterogeneous at the clinical, neurobiological, and genetic levels. ASD can also affect language, a uniquely human capability, and is caused by abnormalities in brain development. Traditionally obtaining biologically relevant human cells to study ASD has been extremely difficult, but new technologies including iPSC-derived neurons and high-throughput omic techniques now provide new, exciting tools to uncover the cellular and signaling basis of ASD etiology.

The glutamate release inhibitor riluzole increases DNA damage and enhances cytotoxicity in human glioma cells, and .

Purpose: High-grade gliomas are lethal malignancies that cause morbidity and mortality due to local progression rather than metastatic spread. Our group has previously demonstrated that human GRM1 (hGRM1) is ectopically expressed in melanocytes leading to a transformed phenotype. Riluzole, a glutamate release inhibitor, leads to apoptotic cell death via DNA damage.

Non-canonical activation of CREB mediates neuroprotection in a Caenorhabditis elegans model of excitotoxic necrosis.

Excitotoxicity, caused by exaggerated neuronal stimulation by Glutamate (Glu), is a major cause of neurodegeneration in brain ischemia. While we know that neurodegeneration is triggered by overstimulation of Glu-receptors (GluRs), the subsequent mechanisms that lead to cellular demise remain controversial. Surprisingly, signaling downstream of GluRs can also activate neuroprotective pathways.

Radiosensitization of Primary Human Glioblastoma Stem-like Cells with Low-Dose AKT Inhibition.

Glioblastoma (GBM) is the most frequent and lethal brain cancer. The lack of early detection methods, the presence of rapidly growing tumor cells, and the high levels of recurrence due to chemo- and radioresistance make this cancer an extremely difficult disease to treat. Emerging studies have focused on inhibiting AKT activation; here, we demonstrate that in primary GBM tumor samples, full-dose inhibition of AKT activity leads to differential responses among samples in the context of cell death and self-renewal, reinforcing the notion that GBM is a heterogeneous disease.

Autophagy inhibition by chloroquine sensitizes HT-29 colorectal cancer cells to concurrent chemoradiation.

Aim: To investigate whether the inhibition of autophagy by chloroquine (CQ) sensitizes rectal tumors to radiation therapy (RT) or concurrent chemoradiation (chemoRT).

Methods: In vitro, HCT-116 and HT-29 colorectal cancer (CRC) cell lines were treated as following: (1) PBS; (2) CQ; (3) 5-fluorouracil (5-FU); (4) RT; (5) CQ and RT; (6) 5-FU and RT; (7) CQ and 5-FU; and (8) 5-FU and CQ and RT. Each group was then exposed to various doses of radiation (0-8 Gy) depending on the experiment.

Quantitative analysis of forward and backward second-harmonic images of collagen fibers using Fourier transform second-harmonic-generation microscopy.

Fourier transform second-harmonic generation (SHG) microscopy has been applied to quantitatively compare the information content between SHG images obtained from the forward and backward direction for three tissue types: porcine tendon, sclera, and ear cartilage. Both signal types yield consistent information on the preferred orientation of collagen fibers. For all specimens, the Fourier transform of the forward and backward SHG images produces several overlapping peaks in the magnitude spectrum at various depths into the tissues, indicating that some information present in the forward SHG images can be extracted from the backward SHG images.

Fourier transform-second-harmonic generation imaging of biological tissues.

Fourier transform-second-harmonic generation imaging is employed to obtain quantitative metrics of collagen fibers in biological tissues. In particular, the preferred orientation and maximum spatial frequency of collagen fibers for selected regions of interest in porcine trachea, ear, and cornea are determined. These metrics remain consistent when applied to collagen fibers in the ear, which can be expected from observation.