Study of Dramaturgical Elements in Three of Robert Browning's Closet Dramas

Englis

BIOL 404- Dual nature of phytoestrogens as both procancer and anticancer agents

Phytoestrogens are plant-derived, xenoestrogenic dietary compounds found in various fruits, vegetables, soy products, teas, grains, beans, and more. There are different classes of phytoestrogens, including flavonoids, isoflavonoids, lignans, and coumestans, all of which can affect estrogen-mediated responses in different ways (Bilal et al, 2014). The aim of this project is to investigate the potential duality of phytoestrogens as both estrogen receptor antagonists in cancer cells, but also as potential activators of myeloid-derived suppressor cells. Understanding the complex role phytoestrogens play in cancer progression will prove valuable in the potential development of novel phytoestrogen-base cancer drug therapies

Increased gene expression of a facilitated diffusion urea transporter in the skin of the African lungfish (Protopterus annectens) during massively elevated post-terrestrialization urea excretion

The full-length cDNA sequence of a putative urea transporter (IfUl) of the facilitated diffusion UT-A type has been cloned from the African lungfish Protopterus annectens. The IFUTcDNA is 1990bp in length and its open reading frame encodes a 409 amino acid long protein, with a calculated molecular mass of 44,723 Da. The sequence is closest to those of amphibians (∼65% amino acid homology), followed by mammals and elasmobranchs (∼60%), and then teleosts (∼50%). IfUT was clearly expressed in gill, kidney, liver, skeletal muscle and skin. Upon re-immersion in water after 33days of air exposure (\u27terrestrialization\u27), lungfish exhibited a massive rise in urea-N excretion which peaked at 12-30h with rates of 2000-5000μmol-N kg-1 h -1 (versus normal aquatic rates of \u3c130μmol-Nkg -1h-1) and persisted until 70h. This appears to occur mainly through the skin. Total \u27excess\u27 urea-N excretion amounted to ∼81,000-91,000 μmol-N kg-1 over 3 days. By real-time PCR, there was no difference in IfUT expression in the ventral abdominal skin between aquatic ammoniotelic controls and terrestrialized lungfish immediately after return to water (0h), and no elevation of urea-N excretion at this time. However, skin biopsies revealed a significant 2.55-fold elevation of IfUT expression at 14h, coincident with peak urea-N excretion. At 48h, there was no longer any significant difference in IFUT mRNA levels from those at 0 and 14h, or from aquatic fed controls. In accordance with earlier studies, which identified elevated urea-N excretion w\u27athe skin of P. dolloi with pharmacology typical of UT-A carriers, these results argue that transcriptional activation of a facilitated diffusion type urea transporter (IfUT) occurs in the skin during re-immersion. This serves to clear the body burden of urea-N accumulated during terrestrialization

Immunostimulatory Membrane Proteins Potentiate \u3cem\u3eH. pylori-\u3c/em\u3eInduced Carcinogenesis by Enabling CagA Translocation

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, depletion of Hp0305 and Hp1564 significantly reduced levels of gastric cell-associated bacteria and markedly impaired the ability of H. pylori to stimulate pro-inflammatory cytokine production. Remarkably, our studies revealed that Hp1564 is required for translocation of the oncoprotein CagA into gastric epithelial cells. Our data provide experimental insight into the molecular mechanisms governing novel H. pylori pathogenicity factors that are strongly associated with gastric disease and highlight the potential of Hp0305 and Hp1564 as robust molecular tools that can improve identification of individuals that are highly susceptible to gastric cancer. We demonstrate that Hp0305 and Hp1564 augment H. pylori-mediated inflammation and gastric cancer risk by promoting key bacteria-gastric cell interactions that facilitate delivery of oncogenic microbial cargo to target cells. Thus, therapeutically targeting microbial interactions driven by Hp0305/Hp1564 may enable focused H. pylori eradication strategies to prevent development of gastric malignancies in high-risk populations

Understanding stakeholder views regarding the design of an intervention trial to reduce anticholinergic burden : a qualitative study

Funding statement This research was supported by the Chief Scientist Office under their Catalytic Research Grants Scheme, CSO reference number: CGA/18/47. Acknowledgments We gratefully acknowledge the support from the Alliance, the Glasgow Stroke Group and NKS in recruiting focus group participants and conducting the focus groups and Scottish Primary Care Research Network for recruiting patients from primary care. Special thanks to Irene Oldfather from Alliance and Naseem Suleman from NKS for their help in setting up interviews and focus groups. We gratefully acknowledge the research participants who provided their views and insights.Peer reviewedPublisher PD

The Unknown and Awakening Europe

Program for the fourth annual RISD Cabaret held in the Cellar at the top of the Waterman Building. Design by Daniel Kraft.https://digitalcommons.risd.edu/liberalarts_cabaret_programs/1003/thumbnail.jp

In Situ Imaging of Bacterial Outer Membrane Projections and Associated Protein Complexes Using Electron Cryo-Tomography

The ability to produce outer membrane projections in the form of tubular membrane extensions (MEs) and membrane vesicles (MVs) is a widespread phenomenon among diderm bacteria. Despite this, our knowledge of the ultrastructure of these extensions and their associated protein complexes remains limited. Here, we surveyed the ultrastructure and formation of MEs and MVs, and their associated protein complexes, in tens of thousands of electron cryo-tomograms of ~90 bacterial species that we have collected for various projects over the past 15 years (Jensen lab database), in addition to data generated in the Briegel lab. We identified outer MEs and MVs in 13 diderm bacterial species and classified several major ultrastructures: (1) tubes with a uniform diameter (with or without an internal scaffold), (2) tubes with irregular diameter, (3) tubes with a vesicular dilation at their tip, (4) pearling tubes, (5) connected chains of vesicles (with or without neck-like connectors), (6) budding vesicles and nanopods. We also identified several protein complexes associated with these MEs and MVs which were distributed either randomly or exclusively at the tip. These complexes include a secretin-like structure and a novel crown-shaped structure observed primarily in vesicles from lysed cells. In total, this work helps to characterize the diversity of bacterial membrane projections and lays the groundwork for future research in this field

Performance deficits of NK1 receptor knockout mice in the 5 choice serial reaction time task: effects of d Amphetamine, stress and time of day.

Background The neurochemical status and hyperactivity of mice lacking functional substance P-preferring NK1 receptors (NK1R-/-) resemble abnormalities in Attention Deficit Hyperactivity Disorder (ADHD). Here we tested whether NK1R-/- mice express other core features of ADHD (impulsivity and inattentiveness) and, if so, whether they are diminished by d-amphetamine, as in ADHD. Prompted by evidence that circadian rhythms are disrupted in ADHD, we also compared the performance of mice that were trained and tested in the morning or afternoon. Methods and Results The 5-Choice Serial Reaction-Time Task (5-CSRTT) was used to evaluate the cognitive performance of NK1R-/- mice and their wildtypes. After training, animals were tested using a long (LITI) and a variable (VITI) inter-trial interval: these tests were carried out with, and without, d-amphetamine pretreatment (0.3 or 1 mg/kg i.p.). NK1R-/- mice expressed greater omissions (inattentiveness), perseveration and premature responses (impulsivity) in the 5-CSRTT. In NK1R-/- mice, perseveration in the LITI was increased by injection-stress but reduced by d-amphetamine. Omissions by NK1R-/- mice in the VITI were unaffected by d-amphetamine, but premature responses were exacerbated by this psychostimulant. Omissions in the VITI were higher, overall, in the morning than the afternoon but, in the LITI, premature responses of NK1R-/- mice were higher in the afternoon than the morning. Conclusion In addition to locomotor hyperactivity, NK1R-/- mice express inattentiveness, perseveration and impulsivity in the 5-CSRTT, thereby matching core criteria for a model of ADHD. Because d-amphetamine reduced perseveration in NK1R-/- mice, this action does not require functional NK1R. However, the lack of any improvement of omissions and premature responses in NK1R-/- mice given d-amphetamine suggests that beneficial effects of this psychostimulant in other rodent models, and ADHD patients, need functional NK1R. Finally, our results reveal experimental variables (stimulus parameters, stress and time of day) that could influence translational studies

Familial pulmonary alveolar proteinosis caused by mutations in CSF2RA

Primary pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by accumulation of surfactant in the lungs that is presumed to be mediated by disruption of granulocyte/macrophage colony-stimulating factor (GM-CSF) signaling based on studies in genetically modified mice. The effects of GM-CSF are mediated by heterologous receptors composed of GM-CSF binding (GM-CSF-Rα) and nonbinding affinity-enhancing (GM-CSF-Rβ) subunits. We describe PAP, failure to thrive, and increased GM-CSF levels in two sisters aged 6 and 8 yr with abnormalities of both GM-CSF-Rα–encoding alleles (CSF2RA). One was a 1.6-Mb deletion in the pseudoautosomal region of one maternal X chromosome encompassing CSF2RA. The other, a point mutation in the paternal X chromosome allele encoding a G174R substitution, altered an N-linked glycosylation site within the cytokine binding domain and glycosylation of GM-CSF-Rα, severely reducing GM-CSF binding, receptor signaling, and GM-CSF–dependent functions in primary myeloid cells. Transfection of cloned cDNAs faithfully reproduced the signaling defect at physiological GM-CSF concentrations. Interestingly, at high GM-CSF concentrations similar to those observed in the index patient, signaling was partially rescued, thereby providing a molecular explanation for the slow progression of disease in these children. These results establish that GM-CSF signaling is critical for surfactant homeostasis in humans and demonstrate that mutations in CSF2RA cause familial PAP

LSST Science Book, Version 2.0

A survey that can cover the sky in optical bands over wide fields to faint magnitudes with a fast cadence will enable many of the exciting science opportunities of the next decade. The Large Synoptic Survey Telescope (LSST) will have an effective aperture of 6.7 meters and an imaging camera with field of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over 20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a total point-source depth of r~27.5. The LSST Science Book describes the basic parameters of the LSST hardware, software, and observing plans. The book discusses educational and outreach opportunities, then goes on to describe a broad range of science that LSST will revolutionize: mapping the inner and outer Solar System, stellar populations in the Milky Way and nearby galaxies, the structure of the Milky Way disk and halo and other objects in the Local Volume, transient and variable objects both at low and high redshift, and the properties of normal and active galaxies at low and high redshift. It then turns to far-field cosmological topics, exploring properties of supernovae to z~1, strong and weak lensing, the large-scale distribution of galaxies and baryon oscillations, and how these different probes may be combined to constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at http://www.lsst.org/lsst/sciboo