Dietary moderately oxidized oil activates the Nrf2 signaling pathway in the liver of pigs

<p>Abstract</p> <p>Background</p> <p>Previous studies have shown that administration of oxidized oils increases gene expression and activities of various enzymes involved in xenobiotic metabolism and stress response in the liver of rats and guinea pigs. As these genes are controlled by nuclear factor erythroid-derived 2-like 2 (Nrf2), we investigated the hypothesis that feeding of oxidized fats causes an activation of that transcription factor in the liver which in turn activates the expression of antioxidant, cytoprotective and detoxifying genes.</p> <p>Methods</p> <p>Twenty four crossbred pigs were allocated to two groups of 12 pigs each and fed nutritionally adequate diets with either fresh rapeseed oil (fresh fat group) or oxidized rapeseed oil prepared by heating at a temperature of 175°C for 72 h (oxidized fat group).</p> <p>Results</p> <p>After 29 days of feeding, pigs of the oxidized fat group had a markedly increased nuclear concentration of the transcription factor Nrf2 and a higher activity of cellular superoxide dismutase and T4-UDP glucuronosyltransferase in liver than the fresh fat group (<it>P </it>< 0.05). In addition, transcript levels of antioxidant and phase II genes in liver, like superoxide dismutase 1, heme oxygenase 1, glutathione peroxidase 1, thioredoxin reductase 1, microsomal glutathione-S-transferase 1, UDP glucuronosyltransferase 1A1 and NAD(P)H:quinone oxidoreductase 1 in the liver were higher in the oxidized fat group than in the fresh fat group (<it>P </it>< 0.05). Moreover, pigs of the oxidized fat group had an increased hepatic nuclear concentration of the transcription factor NF-κB which is also an important transcription factor mediating cellular stress response.</p> <p>Conclusion</p> <p>The present study shows for the first time that administration of an oxidized fat activates the Nrf2 in the liver of pigs which likely reflects an adaptive mechanism to prevent cellular oxidative damage. Activation of the NF-κB pathway might also contribute to this effect of oxidized fat.</p

Using Murine Bone Marrow Transplantation to Understand Hematopoietic Stem Cell Development and to Explore Possible Treatments for Blood Disorders

Blood cells keep us alive by fighting off infection and providing oxygen to every cell in our body. Every blood cell is derived from hematopoietic stem cells (HSCs) which can self-renew to maintain a constant HSC pool throughout a lifetime, engraft long-term in a conditioned recipient, and give rise to all the lineage blood cells. These characteristics are key for carrying out the lifesaving therapy HSC transplantation (HSCT), also known as hematopoietic cell transplantation (HCT) or bone marrow transplantation (BMT). A form of HCT called allogeneic HCT (allo-HCT) is a therapeutic strategy that eradicates a defective blood system, often with radiation therapy or chemotherapy conditioning, then replaces it with a healthy one using non-identical donor HSCs. It is effective against hematological malignancies like leukemia, and lymphoma, the 7th and 8th leading cause of death among cancers. Unfortunately, allo-HCT is used as a last resort treatment due to the complications associated with it including suboptimal allo-HSC recipient engraftment and the major complication Graft-vs-Host disease (GvHD). Resolving these limitations could increase the shortage of much needed donor cells and expand the patient pool to patients with milder blood cancer cases and other diseases such as autoimmune diseases. GvHD occurs when donor immune cells, or graft cells, recognize the host as a foreign threat, thus engendering host tissue damage and organ failure. Many have strived to prevent GvHD after allo-HCT, however, there is still a high incidence of GvHD seen in the clinic. Currently, we face the complex challenge of minimizing GvHD while conserving the benefit of the Graft-vs-Leukemia (GvL) effect elicited by donor immune cells. There is currently no strategy that fully satisfies all these issues plaguing allo-HCT. There is a need for a new approach to safely and efficiently eliminate GvHD while preserving GvL and HSC engraftment in allo-HCT. Here we explore a new proof-of-principle method that prevents GvHD after allo-HCT by using the glucocorticoid fluticasone propionate (Flonase) on a mouse model. We treated donor cells isolated from spleen and bone marrow with the glucocorticoid fluticasone propionate (Flonase) then transplanted them into lethally irradiated fully major histocompatibility complex (MHC) mismatched allogeneic recipients to prevent GvHD. We provide evidence on Flonase efficacy that addresses multiple issues associated with allo-HCT. Here we show that Flonase treatment increases HSC chemotaxis to the bone marrow through increased C-X-C chemotactic receptor type 4 (CXCR4) expression. We also show that pre-treating donor cells with Flonase decreases GvHD in allo-HCT and creates donor T cell immune tolerance. Our results demonstrate a possible mechanism underlying Flonase-induced immune tolerance involving regulatory T cell suppression of alloreactive cells. We also utilize HCT to learn more about pre-HSCs, the HSC precursor. Altogether, we explore potential ways of improving HCT by shedding light on the pre-HSC and showing proof of concept that Flonase donor cell pre-treatment can prevent GvHD. We also investigate using HCT to treat the autoimmune disease Idiopathic Thrombocytopenic Purpura (ITP) by first developing a new mouse model to allow us to test HCT

Understanding Youth Perspectives: Opportunities for Civic Engagement in the Thermi Youth Council

Working with the Directorate of Social and Educational Policy in Thermi, Greece, our team determined the interests and concerns of Thermi youth to identify opportunities for broader civic youth engagement and increased participation in the Thermi Youth Council. Through interviews, surveys, and activities with 122 Thermi youth, we explored their interests, commitments, and concerns. Our findings indicate that the youth council’s strong relationship with the municipality may deter new members because of negative perceptions of the Greek bureaucracy. We also suggest promotional events and programs the council can organize to encourage youth engagement and participation with the organization.

Microsatellite characterization and marker development for the fungus Penicillium digitatum, causal agent of green mold of citrus.

Penicillium digitatum is one of the most important postharvest pathogens of citrus on a global scale causing significant annual losses due to fruit rot. However, little is known about the diversity of P.&nbsp;digitatum populations. The genome of P.&nbsp;digitatum has been sequenced, providing an opportunity to determine the microsatellite distribution within P.&nbsp;digitatum to develop markers that could be valuable tools for studying the population biology of this pathogen. In the analyses, a total of 3,134 microsatellite loci were detected; 66.73%, 23.23%, 8.23%, 1.24%, 0.16%, and 0.77% were detected as mono-, di-, tri-, tetra-, penta-, and hexanucleotide repeats, respectively. As consistent with other ascomycete fungi, the genome size of P.&nbsp;digitatum does not seem to correlate with the density of microsatellite loci. However, significantly longer motifs of mono-, di-, and tetranucleotide repeats were identified in P.&nbsp;digitatum compared to 10 other published ascomycete species with repeats of over 800, 300, and 900 motifs found, respectively. One isolate from southern California and five additional isolates from other countries ("global isolates") were used to initially screen microsatellite markers developed in this study. Twelve additional isolates, referred to as the "local isolates," were also collected from citrus at the University of California Riverside agricultural experiment station and were subsequently used to screen the primers that sequenced well and were polymorphic based on the global isolates. Thirty-six primers were screened, and nine trinucleotide loci and one hexanucleotide locus were chosen as robust markers. These loci yielded two to seven alleles and will be useful to study population genetic structure of P.&nbsp;digitatum populations

Design, Fabrication, and Testing of Surface Undersea Kite Prototypes

In this project, Surface Undersea Kite (SUSK) prototypes were designed, fabricated and tested. SUSK systems use a vertical wing and turbine beneath a streamlined hull that slaloms across a water current to enhance power output. The work extends previous WPI efforts by developing new hull, hydrofoil, vertical wing, rudder and support frame designs. A wireless servo-based control system and a winglet device were also added. The concurrent development of WPI's ODE-based SUSK simulation was aided by improving the characterization of the new hull cross-section shape for drag calculations. A 1/3 scale prototype achieved the desired slalom motions in the WPI swimming pool during initial tow tests. Components for a larger full-scale prototype were fabricated using an infinite axis 3D printer

A Molecular and Cellular Context-Dependent Role for Ir76b in Detection of Amino Acid Taste

Amino acid taste is expected to be a universal property among animals. Although sweet, bitter, salt, and water tastes have been well characterized in insects, the mechanisms underlying amino acid taste remain elusive. From a Drosophila RNAi screen, we identify an ionotropic receptor, Ir76b, as necessary for yeast preference. Using calcium imaging, we identify Ir76b+ amino acid taste neurons in legs, overlapping partially with sweet neurons but not those that sense other tastants. Ir76b mutants have reduced responses to amino acids, which are rescued by transgenic expression of Ir76b and a mosquito ortholog AgIr76b. Co-expression of Ir20a with Ir76b is sufficient for conferring amino acid responses in sweet-taste neurons. Notably, Ir20a also serves to block salt response of Ir76b. Our study establishes the role of a highly conserved receptor in amino acid taste and suggests a mechanism for mutually exclusive roles of Ir76b in salt- and amino-acid-sensing neurons