Concentration and proteolysis of CX3CL1 may regulate the microglial response to CX3CL1.

Fractalkine (FKN) is a membrane-bound chemokine that can be cleaved by proteases such as ADAM 10, ADAM 17, and cathepsin S to generate soluble fragments. Studies using different forms of the soluble FKN yield conflicting results in vivo. These observations prompted us to investigate the function and pharmacology of two commonly used isoforms of FKN, a human full-length soluble FKN (sFKN), and a human chemokine domain only FKN (cdFKN).

Generation of a Novel Rat Model of Angelman Syndrome with a Complete Ube3a Gene Deletion.

Angelman syndrome (AS) is a rare genetic disorder characterized by severe intellectual disability, seizures, lack of speech, and ataxia. The gene responsible for AS was identified as Ube3a and it encodes for E6AP, an E3 ubiquitin ligase. Currently, there is very little known about E6AP's mechanism of action in vivo or how the lack of this protein in neurons may contribute to the AS phenotype.

The Disease-Associated Chaperone FKBP51 Impairs Cognitive Function by Accelerating AMPA Receptor Recycling.

Increased expression of the FK506-binding protein 5 () gene has been associated with a number of diseases, but most prominently in connection to psychiatric illnesses. Many of these psychiatric disorders present with dementia and other cognitive deficits, but a direct connection between these issues and alterations in remains unclear. We generated a novel transgenic mouse to selectively overexpress which encodes the FKBP51 protein, in the corticolimbic system, which had no overt effects on gross body weight, motor ability, or general anxiety.

Respiratory syncytial virus (RSV) infection in elderly mice results in altered antiviral gene expression and enhanced pathology.

Elderly persons are more susceptible to RSV-induced pneumonia than young people, but the molecular mechanism underlying this susceptibility is not well understood. In this study, we used an aged mouse model of RSV-induced pneumonia to examine how aging alters the lung pathology, modulates antiviral gene expressions, and the production of inflammatory cytokines in response to RSV infection. Young (2-3 months) and aged (19-21 months) mice were intranasally infected with mucogenic or non-mucogenic RSV strains, lung histology was examined, and gene expression was analyzed.

BAD phosphorylation determines ovarian cancer chemosensitivity and patient survival.

Purpose: Despite initial sensitivity to chemotherapy, ovarian cancers (OVCA) often develop drug resistance, which limits patient survival. Using specimens and/or genomic data from 289 patients and a panel of cancer cell lines, we explored genome-wide expression changes that underlie the evolution of OVCA chemoresistance and characterized the BCL2 antagonist of cell death (BAD) apoptosis pathway as a determinant of chemosensitivity and patient survival.

Experimental Design: Serial OVCA cell cisplatin treatments were performed in parallel with measurements of genome-wide expression changes.

Trafficking CD11b-positive blood cells deliver therapeutic genes to the brain of amyloid-depositing transgenic mice.

A major question for gene therapy in brain concerns methods to administer therapeutic genes in a uniform manner over major portions of the brain. A second question in neuroimmunology concerns the extent to which monocytes migrate to the CNS in degenerative disorders. Here we show that CD11b+ cells (largely monocytes) isolated from the bone marrow of GFP (green fluorescent protein)-expressing donors spontaneously home to compacted amyloid plaques in the brain.

Genomic-directed targeted therapy increases endometrial cancer cell sensitivity to doxorubicin.

Objective: We aimed to utilize genome-wide expression analysis to identify molecular pathways that may contribute to endometrial cancer resistance to doxorubicin (DOX) and that also represent therapeutic targets to increase DOX sensitivity.

Study Design: Ten endometrial cancer cell lines were subjected to gene expression analysis. Sensitivity of each endometrial cell line to DOX was quantified by dimethylthiazoldiphenyltetrazoliumbromide cell proliferation assay.

Gedunin, a novel natural substance, inhibits ovarian cancer cell proliferation.

The discovery of more active therapeutic compounds is essential if the outcome for patients with advanced-stage epithelial ovarian cancer is to be improved. Gedunin, an extract of the neem tree, has been used as a natural remedy for centuries in Asia. Recently, gedunin has been shown to have potential in vitro antineoplastic properties; however, its effect on ovarian cancer cells is unknown.

MicroRNAs and their target messenger RNAs associated with ovarian cancer response to chemotherapy.

Objective: Few successful therapeutic options exist for patients with recurrent ovarian cancer (OVCA). This is due in part to an incomplete understanding of the molecular determinants of chemotherapy-response. Recently, it has been shown that microRNAs (miRNAs) influence messenger-RNA (mRNA) post-transcriptional control and can contribute to human carcinogenesis.

MicroRNAs and their target messenger RNAs associated with endometrial carcinogenesis.

Objective: Recent advances in gene expression technology have provided insights into global messenger RNA (mRNA) expression changes associated with endometrial cancer development. However, the post-transcriptional events that may also have phenotypic consequences remain to be completely delineated. MicroRNAs (miRNAs) are small non-coding RNA transcripts, that influence cell function via modulation of post-transcriptional activity of multiple target mRNA genes.

Trophic factor induction of human umbilical cord blood cells in vitro and in vivo.

The mononuclear fraction of human umbilical cord blood (HUCBmnf) is a mixed cell population that multiple research groups have shown contains cells that can express neural proteins. In these studies, we have examined the ability of the HUCBmnf to express neural antigens after in vitro exposure to defined media supplemented with a cocktail of growth and neurotrophic factors. It is our hypothesis that by treating the HUCBmnf with these developmentally-relevant factors, we can expand the population, enhance the expression of neural antigens and increase cell survival upon transplantation.

Transcriptional profile of NeuroD expression in a human fetal astroglial cell line.

NeuroD1, a member of the basic helix-loop-helix (bHLH) protein family, is a transcription factor that plays a pivotal role in terminal differentiation of neural progenitors. The primary objective was to generate an early transcriptional profile triggered by NeuroD1 to guide future studies on mechanisms of neuronal differentiation. The human NeuroD1 coding region was amplified from human fetal brain RNA using specific primers and cloned into a CMV expression vector (CT-GFP-TOPO/pcDNA3.