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Kalt W.,Agriculture and Agri Food Canada | Hanneken A.,Scripps Institute | Milbury P.,Tufts University | Tremblay F.,Dalhousie University
Journal of Agricultural and Food Chemistry

A long-standing yet controversial bioactivity attributed to polyphenols is their beneficial effects in vision. Although anecdotal case reports and in vitro research studies provide evidence for the visual benefits of anthocyanin-rich berries, rigorous clinical evidence of their benefits is still lacking. Recent in vitro studies demonstrate that anthocyanins and other flavonoids interact directly with rhodopsin and modulate visual pigment function. Additional in vitro studies show flavonoids protect a variety of retinal cell types from oxidative stress-induced cell death, a neuroprotective property of significance because the retina has the highest metabolic rate of any tissue and is particularly vulnerable to oxidative injury. However, more information is needed on the bioactivity of in vivo conjugates and the accumulation of flavonoids in ocular tissues. The direct and indirect costs of age-related vision impairment provide a powerful incentive to explore the potential for improved vision health through the intake of dietary polyphenolics. © 2010 American Chemical Society. Source

Kaatz M.,Institute for Novel and Emerging Infectious Diseases | Fast C.,Institute for Novel and Emerging Infectious Diseases | Ziegler U.,Institute for Novel and Emerging Infectious Diseases | Balkema-Buschmann A.,Institute for Novel and Emerging Infectious Diseases | And 5 more authors.
American Journal of Pathology

An experimental oral bovine spongiform encephalopathy (BSE) challenge study was performed to elucidate the route of infectious prions from the gut to the central nervous system in preclinical and clinical infected animals. Tissue samples collected from the gut and the central and autonomic nervous system from animals sacrificed between 16 and 44 months post infection (mpi) were examined for the presence of the pathological prion protein (PrPSc) by IHC. Moreover, parts of these samples were also bioassayed using bovine cellular prion protein (PrPC) overexpressing transgenic mice (Tgbov XV) that lack the species barrier for bovine prions. A distinct accumulation of PrP Sc was observed in the distal ileum, confined to follicles and/or the enteric nervous system, in almost all animals. BSE prions were found in the sympathetic nervous system starting at 16 mpi, and in the parasympathetic nervous system from 20 mpi. A clear dissociation between prion infectivity and detectable PrPSc deposition became obvious. The earliest presence of infectivity in the brain stem was detected at 24 mpi, whereas PrPSc accumulation was first detected after 28 mpi. In summary, our results decipher the centripetal spread of BSE prions along the autonomic nervous system to the central nervous system, starting already halfway in the incubation time. © 2012 American Society for Investigative Pathology. Source

Falzone M.,Drew University | Martens E.,Drew University | Tynan H.,Drew University | Maggio C.,Drew University | And 12 more authors.
Applied Microbiology and Biotechnology

The actinomycete Streptomyces platensis produces two compounds that display antibacterial activity: platensimycin and platencin. These compounds were discovered by the Merck Research Laboratories, and a complex insoluble production medium was reported. We have used this medium as our starting point in our studies. In a previous study, we developed a semi-defined production medium, i.e., PM5. In the present studies, by varying the concentration of the components of PM5, we were able to develop a superior semi-defined medium, i.e., PM6, which contains a higher concentration of lactose. Versions of PM6, containing lower concentrations of all components, were also found to be superior to PM5. The new semi-defined production media contain dextrin, lactose, MOPS buffer, and ammonium sulfate in different concentrations. We determined antibiotic production capabilities using agar diffusion assays and chemical assays via thin-layer silica chromatography and high-performance liquid chromatography. We reduced crude nutrient carryover from the seed medium by washing the cells with distilled water. Using these semi-defined media, we determined that addition of the semi-defined component soluble starch stimulated antibiotic production and that it and dextrin could both be replaced with glucose, resulting in the chemically defined medium, PM7. © 2013 Springer-Verlag Berlin Heidelberg. Source

Yi C.,Georgetown University | Shen Z.,University of Pennsylvania | Stemmer-Rachamimov A.,Massachusetts General Hospital | Dawany N.,Wistar Institute | And 9 more authors.
Science Signaling

The Hippo-Yap signaling pathway regulates a number of developmental and adult cellular processes, including cell fate determination, tissue growth, and tumorigenesis. Members of the scaffold protein angiomotin (Amot) family interact with several Hippo pathway components, including Yap (Yes-associated protein), and either stimulate or inhibit Yap activity. We used a combination of genetic, biochemical, and transcriptional approaches to assess the functional consequences of the Amot-Yap interaction in mice and in human cells. Mice with a liver-specific Amot knockout exhibited reduced hepatic "oval cell" proliferation and tumorigenesis in response to toxin-induced injury or when crossed with mice lacking the tumor suppressor Nf2. Biochemical examination of the Amot-Yap interaction revealed that the p130 splicing isoform of Amot (Amot-p130) and Yap interacted in both the cytoplasm and nucleus, which involved binding of PPxY and LPxY motifs in Amot-p130 to WW domains of Yap. In the cytoplasm, Amotp130 prevented the phosphorylation of Yap by blocking access of the WW domains to the kinase Lats1. Within the nucleus, Amot-p130 was associated with the transcriptional complex containing Yap and Teads (TEA domain family members) and contributed to the regulation of a subset of Yap target genes, many of which are associated with tumorigenesis. These findings indicated that Amot acts as a Yap cofactor, preventing Yap phosphorylation and augmenting its activity toward a specific set of genes that facilitate tumorigenesis. Copyright © 2008 by the American Association for the Advancement of Science. Source

Abdel-Wahab M.,University of Miami | Rengan R.,University of Pennsylvania | Curran B.,Brown University | Swerdloff S.,Elekta | And 5 more authors.
International Journal of Radiation Oncology Biology Physics

Purpose: To describe the processes and benefits of the integrating healthcare enterprises in radiation oncology (IHE-RO). Methods: The IHE-RO process includes five basic steps. The first step is to identify common interoperability issues encountered in radiation treatment planning and the delivery process. IHE-RO committees partner with vendors to develop solutions (integration profiles) to interoperability problems. The broad application of these integration profiles across a variety of vender platforms is tested annually at the Connectathon event. Demonstration of the seamless integration and transfer of patient data to the potential users are then presented by vendors at the public demonstration event. Users can then integrate these profiles into requests for proposals and vendor contracts by institutions. Results: Incorporation of completed integration profiles into requests for proposals can be done when purchasing new equipment. Vendors can publish IHE integration statements to document the integration profiles supported by their products. As a result, users can reference integration profiles in requests for proposals, simplifying the systems acquisition process. These IHE-RO solutions are now available in many of the commercial radiation oncology-related treatment planning, delivery, and information systems. They are also implemented at cancer care sites around the world. Conclusions: IHE-RO serves an important purpose for the radiation oncology community at large. © 2010 Elsevier Inc. All rights reserved. Source

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