401 research outputs found
âI Found It Again. My Home.â: The Role of Art in the Mediation of Trauma and Loss in Station Eleven
This project examines the role of the fictional graphic novel â âStation Elevenâ â at the center of HBOâs Station Eleven as a form of trauma mediation. The graphic novel serves as a central, physical object in the show through which the characters Miranda, Kirsten, and Tyler process trauma, find comfort, and connect with others. I trace the creation process of âStation Eleven,â from Mirandaâs original doodles as a child to the surviving physical copies in the hands of Kirsten and Tyler, exploring how each character engages with the artwork. Situating my analysis within a theoretical framework of contemporary trauma theory, expanding the Freudian, Euro-centric, individualized model, I argue art in Station Eleven serves as a reparative, spiritual, and collective medium through which the individual characters directly and their communities cope with trauma and grieve loss. Through my analysis of how âStation Elevenâ is used by Miranda, Kirsten, and Tyler as a mediator for trauma, I argue that, when the global scale of communication becomes inoperable, local collectives, collective memory, and shared storytelling become essential parts of trauma mediation
Le rÎle des étudiants en médecine dans la réponse à la pandémie de la COVID-19 : un appel pour des directives éthiques
Oral serum-derived bovine immunoglobulin improves duodenal immune reconstitution and absorption function in patients with HIV enteropathy.
ObjectivesTo examine the impact of serum-derived bovine immunoglobulin, an oral medical food known to neutralize bacterial antigen and reduce intestinal inflammation, on restoration of mucosal immunity and gastrointestinal function in individuals with HIV enteropathy.DesignOpen-label trial with intensive 8-week phase of bovine serum immunoglobulin (SBI) 2.5âg twice daily with a 4-week washout period and an optional 9-month extension study.MethodsHIV enteropathy was defined as chronic gastrointestinal symptoms including frequent loose or watery stools despite no identifiable, reversible cause. Upper endoscopy for tissue immunofluorescent antibody assay and disaccharide gut permeability/absorption studies were performed before and after 8 weeks of SBI to test mucosal immunity and gastrointestinal function. Blood was collected for markers of microbial translocation, inflammation, and collagen kinetics. A validated gastrointestinal questionnaire assessed changes in symptoms.ResultsAll eight participants experienced profound improvement in symptoms with reduced bowel movements/day (Pâ=â0.008) and improvements in stool consistency (Pâ=â0.008). Gut permeability was normal before and after the intervention, but D-xylose absorption increased in seven of eight participants. Mucosal CD4 lymphocyte densities increased by a median of 139.5âcells/mm2 from 213 to 322âcells/mm2 (Pâ=â0.016). Intestinal-fatty acid binding protein (I-FABP), a marker of enterocyte damage, initially rose in seven of eight participants after 8 weeks (Pâ=â0.039), and then fell below baseline in four of five who continued receiving SBI (Pâ=â0.12). Baseline serum I-FABP levels were negatively correlated with subsequent rise in mucosal CD4 lymphocyte densities (râ=â-0.74, Pâ=â0.046).ConclusionSBI significantly increases intestinal mucosal CD4 lymphocyte counts, improves duodenal function, and showed evidence of promoting intestinal repair in the setting of HIV enteropathy
Evolutionary conservation of ABA signaling for stomatal closure in ferns
ABA-driven stomatal regulation reportedly evolved after the divergence of ferns, during the early evolution of seed plants approximately 360 Mya. This hypothesis is based on the observation that the stomata of certain fern species are unresponsive to ABA, but exhibit passive hydraulic control. However, ABA-induced stomatal closure was detected in some mosses and lycophytes. Here, we observed that a number of ABA signaling and membrane transporter protein families diversified over the evolutionary history of land plants. The aquatic ferns Azolla filiculoides and Salvinia cucullata have representatives of 23 families of proteins orthologous to those of Arabidopsis thaliana and all other land plant species studied. Phylogenetic analysis of the key ABA signaling proteins indicates an evolutionarily conserved stomatal response to ABA. Moreover, comparative transcriptomic analysis has identified a suite of ABA responsive genes that differentially expressed in a terrestrial fern species, Polystichum proliferum. These genes encode proteins associated with ABA biosynthesis, transport, reception, transcription, signaling, and ion and sugar transport, which fit the general ABA signaling pathway constructed from Arabidopsis thaliana and Hordeum vulgare. The retention of these key ABA-responsive genes could have had a profound effect on the adaptation of ferns to dry conditions. Furthermore, stomatal assays have shown the primary evidence for ABA-induced closure of stomata in two terrestrial fern species P. proliferum and Nephrolepis exaltata. In summary, we report new molecular and physiological evidence for the presence of active stomatal control in ferns
Waterproofed Photomultiplier Tube Assemblies for the Daya Bay Reactor Neutrino Experiment
In the Daya Bay Reactor Neutrino Experiment 960 20-cm-diameter waterproof
photomultiplier tubes are used to instrument three water pools as Cherenkov
detectors for detecting cosmic-ray muons. Of these 960 photomultiplier tubes,
341 are recycled from the MACRO experiment. A systematic program was undertaken
to refurbish them as waterproof assemblies. In the context of passing the water
leakage check, a success rate better than 97% was achieved. Details of the
design, fabrication, testing, operation, and performance of these waterproofed
photomultiplier-tube assemblies are presented.Comment: 16 pages, 11 figures. Submitted to Nucl. Instr. Met
Neural EGFL-Like 1 Regulates Cartilage Maturation through Runt-Related Transcription Factor 3âMediated Indian Hedgehog Signaling
The pro-chondrogenic function of runt-related transcription factor 2 (Runx2) was previously considered to be dependent on direct binding with the promoter of Indian hedgehog (Ihh)âthe major regulator of chondrocyte differentiation, proliferation, and maturation. The authorsâ previous studies identified neural EGFL like 1 (Nell-1) as a Runx2-responsive growth factor for chondrogenic differentiation and maturation. In this study, it was further revealed that the pro-chondrogenic activities of Nell-1 also rely on Ihh signaling, by showing: i) Nell-1 significantly elevated Ihh signal transduction; ii) Nell-1 deficiency markedly reduced Ihh activation in chondrocytes; and iii) Nell-1âstimulated chondrogenesis was significantly reduced by the specific hedgehog inhibitor cyclopamine. Importantly, the authors demonstrated that Nell-1âresponsive Ihh signaling and chondrogenic differentiation extended to Runx2 â/â models in vitro and in vivo. In Runx2 â/â chondrocytes, Nell-1 stimulated the expression and signal transduction of Runx3, another transcription factor required for complete chondrogenic differentiation and maturation. Furthermore, knocking down Runx3 in Runx2 â/â chondrocytes abolished Nell-1\u27s stimulation of Ihh-associated molecule expression, which validates Runx3 as a major mediator of Nell-1âstimulated Ihh activation. For the first time, the Runx2âNell-1âRunx3âIhh signaling cascade during chondrogenic differentiation and maturation has been identified as an alternative, but critical, pathway for Runx2 to function as a pro-chondrogenic molecule via Nell-1. © 2018 American Society for Investigative Patholog
Adapting AlphaLISA high throughput screen to discover a novel small-molecule inhibitor targeting protein arginine methyltransferase 5 in pancreatic and colorectal cancers
Pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) are notoriously challenging for treatment. Hyperactive nuclear factor ÎșB (NF-ÎșB) is a common culprit in both cancers. Previously, we discovered that protein arginine methyltransferase 5 (PRMT5) methylated and activated NF-ÎșB. Here, we show that PRMT5 is highly expressed in PDAC and CRC. Overexpression of PRMT5 promoted cancer progression, while shRNA knockdown showed an opposite effect. Using an innovative AlphaLISA high throughput screen, we discovered a lead compound, PR5-LL-CM01, which exhibited robust tumor inhibition effects in both cancers. An in silico structure prediction suggested that PR5-LL-CM01 inhibits PRMT5 by binding with its active pocket. Importantly, PR5-LL-CM01 showed higher anti-tumor efficacy than the commercial PRMT5 inhibitor, EPZ015666, in both PDAC and CRC. This study clearly highlights the significant potential of PRMT5 as a therapeutic target in PDAC and CRC, and establishes PR5-LL-CM01 as a promising basis for new drug development in the future
Recommended from our members
Neural EGFL Like 1 as a Potential Pro-Chondrogenic, Anti-Inflammatory Dual-Functional Disease-Modifying Osteoarthritis Drug
Arthritis, an inflammatory condition that causes pain and cartilage destruction in joints, affects over 54.4 million people in the US alone. Here, for the first time, we demonstrated the emerging role of neural EGFL like 1 (NELL-1) in arthritis pathogenesis by showing that Nell-1-haploinsufficient (Nell-1+/6R) mice had accelerated and aggravated osteoarthritis (OA) progression with elevated inflammatory markers in both spontaneous primary OA and chemical-induced secondary OA models. In the chemical-induced OA model, intra-articular injection of interleukin (IL)1ÎČ induced more severe inflammation and cartilage degradation in the knee joints of Nell-1+/6R mice than in wildtype animals. Mechanistically, in addition to its pro-chondrogenic potency, NELL-1 also effectively suppressed the expression of inflammatory cytokines and their downstream cartilage catabolic enzymes by upregulating runt-related transcription factor (RUNX)1 in mouse and human articular cartilage chondrocytes. Notably, NELL-1 significantly reduced IL1ÎČ-stimulated inflammation and damage to articular cartilage in vivo. In particular, NELL-1 administration markedly reduced the symptoms of antalgic gait observed in IL1ÎČ-challenged Nell-1+/6R mice. Therefore, NELL-1 is a promising pro-chondrogenic, anti-inflammatory dual-functional disease-modifying osteoarthritis drug (DMOAD) candidate for preventing and suppressing arthritis-related cartilage damage. © 2019 Elsevier Lt
- âŠ