Effects of Early Neonatal Infection on Adult Cerebrovascular Health

Denman Undergraduate Research Forum, 2nd place winner, Division of PsychologyTransient focal ischemia occurs when a portion of the brain is cut off from oxygen. Damage occurs in two phases: the initial phase, during which cell death by necrosis occurs, and the secondary phase, during which cell death by apoptosis and inflammation occurs. Exposure to lipopolysaccharide (LPS), a component of the Gram-negative bacteria, initiates an innate immune response resulting in inflammation. Specifically, LPS activates cytokines which then induce cyclooxygenase-2 (COX-2) to synthesize PGE2, a prostaglandin that causes inflammation. COX-2 also contributes to the activation of the glutamate receptors during the initial stages of ischemic damage. Early LPS exposure up-regulates the basal levels of COX-2 in adulthood. To determine the role of COX-2 in stroke Escherichia coli LPS was administered to fourteen-day-old male and female neonatal mice and transient focal ischemia was later induced in adulthood. The control group was given an equal amount of pyrogen-free sterile saline solution. It was hypothesized that after induction of experimental stroke mice administered LPS would show greater stroke damage, both initially and secondarily, compared to their vehicle counterparts. To assess initial damage 24 h post-surgery mice were perfused and level of edema was determined. To assess secondary damage 72 h post-surgery infarct was measured. Behavioral deficits occurring at both 24 h and 72 h post-surgery were determined by preferential paw use and level of anxiety. Females neonatally treated with LPS had a significant decrease in infarct size 72 h post-surgery compared to their vehicle counterparts. These results are indicative of LPS acting as a neuroprotective agent against ischemic stroke. The 72 h survival females, however, showed a significant decrease in contralateral paw use compared to the vehicle suggesting that the LPS had a negative effect on behavioral outcome despite its neuroprotective capability. There was no significant effect of LPS on any of the other experimental groups. The study was reproduced with a doubled dose of LPS and no significant effect was seen across the board. This suggests that the amount of LPS administered is a critical factor. An effect only on females indicates a gender bias.University Honors & Scholars Center, Pressey Honors Student Research Grant, 2006Denman Undergraduate Research Forum, 2006Undergraduate Student Government Academic Committee, 2005 & 2006A three-year embargo was granted for this item

Marital satisfaction among newly married couples: Associations with religiosity and romantic attachment style.

The marriage and family literature has identified a host of factors that contribute to a satisfactory marital union. For example, research on religious congruency has indicated that the more similar partners are in their religious beliefs the higher their reported marital satisfaction. Another construct studied in conjunction with marital satisfaction is adult attachment style. The attachment literature has consistently shown that secure couples tend to report higher marital satisfaction than couples with at least one insecure partner. The purpose of this study was to examine the combined role of religious commitment and attachment in marital satisfaction. Heterosexual couples (N = 184; 92 husbands, 92 wives) without children and married 1-5 years were administered a background information questionnaire, the Religious Commitment Inventory-10, the Dyadic Adjustment Scale, and the Experiences in Close Relationships Inventory. Results indicated that couples with congruent religious commitment reported higher marital satisfaction than couples with large discrepancies in religious commitment. Religious commitment did not mediate the relationship between attachment and marital satisfaction, but instead was found to moderate this relationship. Results of this study will benefit clinicians working in the field to help newly married couples negotiate the marital relationship

Near-Complete Genome Sequences of Vesicular Stomatitis Virus Indiana Laboratory Strains HR and T1026R1 and Plaque Isolates 22-20 and 22-25

We report four near-complete genome sequences of vesicular stomatitis virus (VSV) Indiana obtained with Sanger and Illumina next-generation sequencing, namely, laboratory strains HR (heat resistant) and T1026R1 and isolates 22-20 and 22-25. Previously, only the M gene of these viruses had been sequenced, and these sequences were not deposited in GenBank

The board of directors in agricultural marketing businesses

Published March 1972. Facts and recommendations in this publication may no longer be valid. Please look for up-to-date information in the OSU Extension Catalog: http://extension.oregonstate.edu/catalo

Antibodies to C1q in systemic lupus erythematosus: Characteristics and relation to FcγRIIA alleles

Antibodies to C1q in systemic lupus erythematosus: Characteristics and relation to FcγRIIA alleles. Autoantibodies to the collagen-like region of the first complement component (C1qAB) are found in patients with systemic lupus erythematosus (SLE), particularly those with renal disease. In a cohort of 46 SLE patients with diffuse proliferative glomerulonephritis, we found declining C1qAB titers in 77% of treatment responders and in only 38% of treatment non-responders (P < 0.03). To further characterize this autoantibody, we tested 240 SLE patients for the presence of C1qAB. Positive titers were found in 44% of patients with renal disease and 18% of patients without renal disease (χ2 P < 0.0003). Analysis of IgG subclass revealed IgG2 C1qAB alone in 34%, IgG1 C1qAB alone in 20%, and both IgG1 and IgG2 in 46% of patients. Fewer than 10% of patients had measurable titers of IgG3 or IgG4 C1qAB. The pathogenic role of these IgG2-skewed C1qAB may relate to impaired immune complex clearance by the mononuclear phagocyte system: IgG2 antibodies are efficiently recognized by only one IgG receptor, the H131 allele of FcγRIIa (FcγRIIa-H131). In contrast, FcγRIIa-R131, which is characterized by minimal IgG2 binding, has recently been associated with lupus nephritis. In our C1qAB positive patients, the presence of FcγRIIA-R131 was associated with an increased risk for renal disease. Autoantibodies to C1q may have pathogenic significance in SLE patients with genetic defects in the ability to clear IgG2 containing immune complexes

Glioblastoma cellular cross-talk converges on NF-κB to attenuate EGFR inhibitor sensitivity

Funding Information: We thank Dr. David James, Dr. Frederick Lang, Dr. Cameron Brennan, and Dr. Harley Kornblum for GBM-PDX neurospheres. We thank Dr. Karen Arden for continuous support and critical evaluation of the results. We thank Dr. Robert Davis, Dr. German Gomez, Dr. Tiffany Taylor, Dr. Rachel Reed, Dr. Melissa Mcalonis, and Dr. Sora Lee for technical support. In memory of Rosa Lupo. This work was supported by the Defeat GBM Research Collaborative, a subsidiary of the National Brain Tumor Society (F.B.F. and P.S.M.), R01-NS080939 (F.B.F.), the James S. McDonnell Foundation (F.B.F.), the National Cancer Institute (2T32CA009523-29A1) (A.H.T), and 1RO1NS097649-01 (C.C.C.). C.Z. was partially supported by an American-Italian Cancer Foundation post-doctoral research fellowship. F.L. received a Gao Feng Gao Yuan Scholarship Award. T.C.G., A.K.S., P.S.M., W.K.C., and F.B.F. receive salary and additional support from the Ludwig Institute for Cancer Research. Publisher Copyright: © 2017 Zanca et al.In glioblastoma (GBM), heterogeneous expression of amplified and mutated epidermal growth factor receptor (EGFR) presents a substantial challenge for the effective use of EGFR-directed therapeutics. Here we demonstrate that heterogeneous expression of the wild-type receptor and its constitutively active mutant form, EGFRvIII, limits sensitivity to these therapies through an interclonal communication mechanism mediated by interleukin-6 (IL-6) cytokine secreted from EGFRvIII-positive tumor cells. IL-6 activates a NF-κB signaling axis in a paracrine and autocrine manner, leading to bromodomain protein 4 (BRD4)-dependent expression of the prosurvival protein survivin (BIRC5) and attenuation of sensitivity to EGFR tyrosine kinase inhibitors (TKIs). NF-κB and survivin are coordinately up-regulated in GBM patient tumors, and functional inhibition of either protein or BRD4 in in vitro and in vivo models restores sensitivity to EGFR TKIs. These results provide a rationale for improving anti-EGFR therapeutic efficacy through pharmacological uncoupling of a convergence point of NF-κB-mediated survival that is leveraged by an interclonal circuitry mechanism established by intratumoral mutational heterogeneity.publishersversionPeer reviewe

The Stem Cell Commons: an exemplar for data integration in the biomedical domain driven by the ISA framework

Comparisons of stem cell experiments at both molecular and semantic levels remain challenging due to inconsistencies in results, data formats, and descriptions among biomedical research discoveries. The Harvard Stem Cell Institute (HSCI) has created the Stem Cell Commons (stemcellcommons.org), an open, community-based approach to data sharing. Experimental information is integrated using the Investigation-Study-Assay tabular format (ISA-Tab) used by over 30 organizations (ISA Commons, isacommons.org). The early adoption of this format permitted the novel integration of three independent systems to facilitate stem cell data storage, exchange and analysis: the Blood Genomics Repository, the Stem Cell Discovery Engine, and the new Refinery platform that links the Galaxy analytical engine to data repositories

A verified genomic reference sample for assessing performance of cancer panels detecting small variants of low allele frequency

BackgroundOncopanel genomic testing, which identifies important somatic variants, is increasingly common in medical practice and especially in clinical trials. Currently, there is a paucity of reliable genomic reference samples having a suitably large number of pre-identified variants for properly assessing oncopanel assay analytical quality and performance. The FDA-led Sequencing and Quality Control Phase 2 (SEQC2) consortium analyze ten diverse cancer cell lines individually and their pool, termed Sample A, to develop a reference sample with suitably large numbers of coding positions with known (variant) positives and negatives for properly evaluating oncopanel analytical performance.ResultsIn reference Sample A, we identify more than 40,000 variants down to 1% allele frequency with more than 25,000 variants having less than 20% allele frequency with 1653 variants in COSMIC-related genes. This is 5-100x more than existing commercially available samples. We also identify an unprecedented number of negative positions in coding regions, allowing statistical rigor in assessing limit-of-detection, sensitivity, and precision. Over 300 loci are randomly selected and independently verified via droplet digital PCR with 100% concordance. Agilent normal reference Sample B can be admixed with Sample A to create new samples with a similar number of known variants at much lower allele frequency than what exists in Sample A natively, including known variants having allele frequency of 0.02%, a range suitable for assessing liquid biopsy panels.ConclusionThese new reference samples and their admixtures provide superior capability for performing oncopanel quality control, analytical accuracy, and validation for small to large oncopanels and liquid biopsy assays.Peer reviewe