Molecular Biology Commons^™

Palmitoyl Acyltransferase Dhhc21 Mediates Endothelial Dysfunction In Systemic Inflammatory Response Syndrome, Richard S. Beard Jr.

Biomedical Research Institute Publications and Presentations

Endothelial dysfunction is a hallmark of systemic inflammatory response underlying multiple organ failure. Here we report a novel function of DHHC-containing palmitoyl acyltransferases (PATs) in mediating endothelial inflammation. Pharmacological inhibition of PATs attenuates barrier leakage and leucocyte adhesion induced by endothelial junction hyperpermeability and ICAM-1 expression during inflammation. Among 11 DHHCs detected in vascular endothelium, DHHC21 is required for barrier response. Mice with DHHC21 function deficiency (Zdhhc21^dep/dep) exhibit marked resistance to injury, characterized by reduced plasma leakage, decreased leucocyte adhesion and ameliorated lung pathology, culminating in improved survival. Endothelial cells from Zdhhc21^dep/dep display blunted barrier dysfunction and …

Serum Proteins Enhance Dispersion Stability And Influence The Cytotoxicity And Dosimetry Of Zno Nanoparticles In Suspension And Adherent Cancer Cell Models, Catherine B. Anders, Jordan J. Chess, Denise G. Wingett, Alex Punnoose

Biomedical Research Institute Publications and Presentations

Agglomeration and sedimentation of nanoparticles (NPs) within biological solutions is a major limitation in their use in many downstream applications. It has been proposed that serum proteins associate with the NP surface to form a protein corona that limits agglomeration and sedimentation. Here, we investigate the effect of fetal bovine serum (FBS) proteins on the dispersion stability, dosimetry, and NP-induced cytotoxicity of cationic zinc oxide nanoparticles (nZnO) synthesized via forced hydrolysis with a core size of 10 nm. Two different in vitro cell culture models, suspension and adherent, were evaluated by comparing a phosphate buffered saline (PBS) nZnO dispersion (nZnO/PBS) …

Wintering Bald Eagle Count Trends In The Conterminous United States, 1986-2010, Wade L. Eakle, Laura Bond, Mark R. Fuller, Richard A. Fischer, Karen Steenhof

Biomedical Research Institute Publications and Presentations

We analyzed counts from the annual Midwinter Bald Eagle Survey to examine state, regional, and national trends in counts of wintering Bald Eagles (Haliaeetus leucocephalus) within the conterminous 48 United States from 1986 to 2010. Using hierarchical mixed model methods, we report trends in counts from 11 729 surveys along 844 routes in 44 states. Nationwide Bald Eagle counts increased 0.6% per yr over the 25-yr period, compared to an estimate of 1.9% per yr from 1986 to 2000. Trend estimates for Bald Eagles were significant (P ≤ 0.05) and positive in the northeastern and northwestern U.S. …

The Effect Of Osm On Mc3t3-E1 Osteoblastic Cells In Simulated Microgravity With Radiation, Jake Goyden, Ken Tawara, Danielle Hedeen, Jeffrey S. Willey, Julia Thom Oxford, Cheryl L. Jorcyk

Biomedical Research Institute Publications and Presentations

Bone deterioration is a challenge in long-term spaceflight with significant connections to patients experiencing disuse bone loss. Prolonged unloading and radiation exposure, defining characteristics of space travel, have both been associated with changes in inflammatory signaling via IL-6 class cytokines in bone. While there is also evidence for perturbed IL-6 class signaling in spaceflight, there has been scant examination of the connections between microgravity, radiation, and inflammatory stimuli in bone. Our lab and others have shown that the IL-6 class cytokine oncostatin M (OSM) is an important regulator of bone remodeling. We hypothesize that simulated microgravity alters osteoblast OSM signaling, …

Developing An Application For Evolutionary Search For Computational Models Of Cellular Development, Nicolas Scott Cornia

Boise State University Theses and Dissertations

VPEvolve is a free and open source application that utilizes a Visual Programming Environment (VPE) for the setup of the Genetic Algorithm (GA), for optimization of computational models. Specifically, the User Interface uses connected glyphs to represent the genetic operators of mutation, reproduction, fitness and selection. These glyphs give the user an intuitive way to set the parameters for the GA, and better visualization of the population's flow through these operators.

VPEvolve is currently being developed alongside research being done in Biocomputing to create models of cellular regeneration based on the regenerative properties of Planaria or flatworms. Since these models …

Trends In Midwinter Counts Of Bald Eagles In The Conterminous United States, 1986-2005, Karen Steenhof, Laura Bond, Leah L. Dunn

Biomedical Research Institute Publications and Presentations

Each January, several hundred individuals count eagles along standard, non-overlapping survey routes as part of a nationwide Midwinter Bald Eagle survey. Nationwide counts of eagles were coordinated by the National Wildlife Federation from 1979 until 1992, when the Bureau of Land Management’s Raptor Research and Technical Assistance Center assumed responsibility for overseeing the count. Responsibility for count coordination shifted to the National Biological Survey (1993-1996) and later to the U.S. Geological Survey (USGS), Forest and Rangeland Ecosystem Science Center, Snake River Field Station.

Initial objectives of the survey were to establish an index to the total wintering Bald Eagle population …

Exploration Into The Cellular Effects Of Aziridinomitosenes, Christopher M. Mallory

Boise State University Theses and Dissertations

Aziridinomitosenes (AZMs) are organic compounds structurally related to the mitomycins, a class of anti-tumor agents and antibiotics. The cytotoxicity of the mitomycins is correlated to their ability to covalently link complimentary strands of DNA, forming DNA interstrand cross-links (ICLs). Currently, there has been limited investigation into the biological activity of AZMs, likely due to difficulties in their synthesis. Our lab has synthesized and evaluated the cellular effects of two AZMs, (1S, 2S)-6-desmethyl(methylaziridino)mitosene (H/H-AZM) and (1S, 2S)-6-methyl(methylaziridino)mitosene (Me/H-AZM). We hypothesize that AZMs exhibit their cytotoxicity and cellular effects following a similar pathway to that of mitomycin C (MC) including …

A Lipid-Rich Gestational Diet Predisposes Offspring To Nonalcoholic Fatty Liver Disease: A Potential Sequence Of Events, Alexandria N. Hughes, Julia Thom Oxford

Biomedical Research Institute Publications and Presentations

Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome. It affects 20%–30% of the US population, and it is increasing worldwide. Recently, the role of lipid-rich maternal gestational nutrition in spurring the development of NAFLD among offspring has been indicated. Fetal predisposition to NAFLD involves numerous physiological reroutings that are initiated by increased delivery of nonesterified fatty acids to the fetal liver. Hampered ß-oxidation, uncontrolled oxidative stress, increased triacylglycerol synthesis, and the endoplasmic reticulum unfolded protein response are all implicated in sculpting a hepatic phenotype with a propensity to develop NAFLD in the postnatal state. This review …

A Genetic Analysis Of Bald Eagles In The Pacific Northwest: Retained Genetic Diversity Following A Large-Scale Population Bottleneck, Andrew Joseph Nadeau

Boise State University Theses and Dissertations

Bald eagle (Haliaeetus leucocephalus) populations in the continental United States experienced a dramatic population decline during the twentieth century. Populations across the species’ range have largely recovered, thanks in part to the ban of DDT, rapidly enacted conservation measures, and reintroduction efforts. Using six microsatellite loci, I tested the genetic variation of bald eagles across six states in the Pacific Northwest. Genetic analysis revealed that, despite undergoing a population-wide decline, the bald eagles in the locations sampled outside of Idaho did not exhibit the characteristics typically associated with a genetic bottleneck (i.e., a reduced number of alleles and …

Minor Fibrillar Collagens, Variable Regions Alternative Splicing, Intrinsic Disorder, And Tyrosine Sulfation, Ming Fang, Reed B. Jacob, Owen Mcdougal, Julia Oxford

Biomedical Research Institute Publications and Presentations

Minor fibrillar collagen types V and XI, are those less abundant than the fibrillar collagens types I, II and III. The alpha chains share a high degree of similarity with respect to protein sequence in all domains except the variable region. Genomic variation and, in some cases, extensive alternative splicing contribute to the unique sequence characteristics of the variable region. While unique expression patterns in tissues exist, the functions and biological relevance of the variable regions have not been elucidated. In this review, we summarize the existing knowledge about expression patterns and biological functions of the collagen types V and …

Inhibition Of Proprotein Convertase Ski-1 Blocks Transcription Of Key Extracellular Matrix Genes Regulating Osteoblastic Mineralization, Jeff P. Gorski, Nichole T. Huffman, Sridar Chittur, Ronald J. Midura, Claudine Black, Julia Oxford, Nabil G. Seidah

Biomedical Research Institute Publications and Presentations

Mineralization, a characteristic phenotypic property of osteoblastic lineage cells, was blocked by AEBSF and dec-RRLL-cmk, inhibitors of SKI-1 (site 1; subtilisin kexin like-1) protease. Since SKI-1 is required for activation of SREBP and CREB/ATF family transcription factors, we tested the effect of these inhibitors on gene expression. AEBSF decreased expression of 140 genes by 1.5- to 3.0-fold including Phex, Dmp1, COL1A1, COL11A1 and fibronectin. Direct comparison of AEBSF and dec-RRLL-cmk, a more specific SKI-1 inhibitor, demonstrated that expression of Phex, Dmp1, COL11A1 and fibronectin was reduced by both while COL1A2 and HMGCS1 were reduced …

The Expression Patterns Of Minor Fibrillar Collagens During Development In Zebrafish, Ming Fang, Jason S. Adams, B. Lane Memahhan, Raquel J. Brown, Julia Oxford

Biomedical Research Institute Publications and Presentations

Minor fibrillar collagens are recognized as the organizers and nucleators during collagen fibrillogenesis but likely serve additional functions. The minor fibrillar collagens include collagens type V and type XI. Mutations of collagen type V and XI can cause Ehlers Danlos, Stickler's, and Marshall's syndromes in human. We have characterized the spatiotemporal expression patterns of Col11a1, Col11a2, Col5a1 as well as Col5a3 in zebrafish embryos by in situ hybridization. Col5a1 is expressed in developing somites, neural crest, the head mesenchyme, developing cranial cartilage, pharyngeal arches and vertebrae. Col5a3 is detected in the notochord, mesenchyme cells in the eyes and lens. Both …

Differential Expression Of Collagen Type V And Xi Α-1 In Human Ascending Thoracic Aortic Aneurysms, Julia Thom Oxford

Biomedical Research Institute Publications and Presentations

Background—The molecular mechanisms leading to ascending thoracic aortic aneurysms (ATAAs) remain unknown. We hypothesized that alterations in expression levels of specific fibrillar collagens occur during the aneurysmal process.

Methods—Surgical samples from ascending aortas from patients with degenerative ATAAs were subdivided by aneurysm diameter: small, 5 to 6 cm; medium, 6 to 7 cm; and large, greater than 7 cm; and compared with nonaneurysmal aortas (mean diameter, 2.3 cm).

Results—Histology, immunofluorescence, and electron microscopy demonstrated greater disorganization of extracellular matrix constituents in ATAAs as compared with control with an increase in collagen α1(XI) within regions of cystic medial …

Collagen 11a1 Is Indirectly Activated By Lymphocyte Enhancer-Binding Factor 1 (Lef1) And Negatively Regulates Osteoblast Maturation, Rachel A. Kahler, Sorcha M.C. Yingst, Luke H. Hoeppner, Eric D. Jensen, David Krawczak, Julia T. Oxford, Jennifer J. Westendorf

Biomedical Research Institute Publications and Presentations

Alpha 1 (XI) collagen (Col11a1) is essential for normal skeletal development. Mutations in Col11a1 cause Marshall and Stickler syndromes, characterized by craniofacial abnormalities, nearsightedness and hearing abnormalities. Despite its link to human diseases, few studies have characterized the factors that control Col11a1 transcription. We previously identified Col11a1 as a differentially expressed gene in Lef1-suppressed MC3T3 preosteoblasts. Here we report that Lef1 activates the Col11a1 promoter. This activation is dependent upon the DNA binding domain of Lef1, but does not require the ß-catenin interaction domain, suggesting that it is not responsive to Wnt signals. Targeted deletion of Col11a1 with an antisense …