Shriners Hospitals for Children - Galveston

About: Shriners Hospitals for Children - Galveston is a healthcare organization based out in Galveston, Texas, United States. It is known for research contribution in the topics: Burn injury & Lean body mass. The organization has 249 authors who have published 420 publications receiving 15311 citations.

Developmental changes in expression and subcellular localization of the DNA repair glycosylase, MYH, in the rat brain.

Abstract: Mammalian cells employ a network of DNA repair pathways. DNA repair is required during development to ensure accuracy of DNA replication in the rapidly dividing embryonic cells and to maintain genomic integrity in the mature organism. An enzyme involved in repair of replication errors generated on either normal or oxidatively damaged DNA templates, is the mammalian ortholog of the Escherichia coli MutY DNA glycosylase (MYH). We show that levels of MYH isoform, detected at the E14 embryonic stage, decrease during embryonic and neonatal rat development, while new isoforms appear and gradually increase in the neonate and adult brain. The temporally declining expression of embryonic MYH resembles the pattern of proliferating cell nuclear antigen (PCNA) decline during this period. Immunohistochemical analyses of the embryonic brain show that cells staining for MYH initially coincide with cells staining for PCNA. At later stages PCNA declines, while MYH is detected primarily outside the nucleus. MutY-like glycosylase activity for adenines misincorporated opposite oxidized guanines is detected in both, embryonic and adult brain extracts. Together, these findings suggest that in proliferating embryonic cells, MYH might be primarily involved in post replicative repair of nuclear DNA, whereas in post mitotic neurons, in the repair of mitochondrial DNA.

Comparison of Gene Expression by Sheep and Human Blood Stimulated with the TLR4 Agonists Lipopolysaccharide and Monophosphoryl Lipid A.

Abstract: Background Animal models that mimic human biology are important for successful translation of basic science discoveries into the clinical practice. Recent studies in rodents have demonstrated the efficacy of TLR4 agonists as immunomodulators in models of infection. However, rodent models have been criticized for not mimicking important characteristics of the human immune response to microbial products. The goal of this study was to compare genomic responses of human and sheep blood to the TLR4 agonists lipopolysaccharide (LPS) and monophosphoryl lipid A (MPLA). Methods Venous blood, withdrawn from six healthy human adult volunteers (~ 28 years old) and six healthy adult female sheep (~3 years old), was mixed with 30 μL of PBS, LPS (1μg/mL) or MPLA (10μg/mL) and incubated at room temperature for 90 minutes on a rolling rocker. After incubation, 2.5 mL of blood was transferred to Paxgene Blood RNA tubes. Gene expression analysis was performed using an Agilent Bioanalyzer with the RNA6000 Nano Lab Chip. Agilent gene expression microarrays were scanned with a G2565 Microarray Scanner. Differentially expressed genes were identified. Results 11,431 human and 4,992 sheep probes were detected above background. Among them 1,029 human and 175 sheep genes were differentially expressed at a stringency of 1.5-fold change (p 1.5-fold changes in human samples. Genes of major inflammatory mediators, such as IL-1, IL-6 and IL-8, TNF alpha, NF-kappaB, ETS2, PTGS2, PTX3, CXCL16, KYNU, and CLEC4E were similarly (>2-fold) upregulated by LPS and MPLA in both species. Conclusion The genomic responses of peripheral blood to LPS and MPLA in sheep are quite similar to those observed in humans, supporting the use of the ovine model for translational studies that mimic human inflammatory diseases and the study of TLR-based immunomodulators.