Neuregulin signaling regulates neural precursor growth and the generation of oligodendrocytes in vitro

Peer reviewe

Exile Vol. XXXI No. 2

Plenty of Space by Carol Contiguglia (cover) Dénouement by Jeff Masten 3 The Ballad of Old Bill Brown by Amy Becker 4-5 Elegy by Ann Townsend 6 Untitled by Karen Koch 7 Dénouement by Carol Mason 9-14 Untitled by N. R. B. III 15 A Lot in Common We Two, by David Zivan 17 The Sidewalk Taken, Kate Anthony 18 Upon Hearing Two Male Poets Read by Karen J. Hall 19 Leaves by Amy Becker 20 To Dad by Carrie Jordan 21 Attie Mae by Theresa Copeland 23-25 Oh, Henry by T. S. Elliott 26-38 Solitude; Normandy, France by Margie Boll 39 In Edgartown, Drunk, Stranded in the A.M. by Karen Kearney 41 Pink Feet by Catherine DuBois 42 Ensign in the Naval Corps of Engineers by Betsy Oster 43 Morning Haze by Stephanie Athey 44-45 Just Thought You\u27d Like to Know by Joan DeWitt 46-53 Art Class, A Study of Still-Lifes by Margie Boll 55 Contributor Notes 57 Editorial decision is shared equally among the Editorial Board members -cover page (credited here as editors ) PRINTING BY / PRINTING ARTS PRESS / MOUNT VERNON, OHIO -back cove

The role of cholesterol and mitochondrial bioenergetics in activation of the inflammasome in IBD

Inflammatory Bowel Disease (IBD) is characterized by a loss of intestinal barrier function caused by an aberrant interaction between the immune response and the gut microbiota. In IBD, imbalance in cholesterol homeostasis and mitochondrial bioenergetics have been identified as essential events for activating the inflammasome-mediated response. Mitochondrial alterations, such as reduced respiratory complex activities and reduced production of tricarboxylic acid (TCA) cycle intermediates (e.g., citric acid, fumarate, isocitric acid, malate, pyruvate, and succinate) have been described in in vitro and clinical studies. Under inflammatory conditions, mitochondrial architecture in intestinal epithelial cells is dysmorphic, with cristae destruction and high dynamin-related protein 1 (DRP1)-dependent fission. Likewise, these alterations in mitochondrial morphology and bioenergetics promote metabolic shifts towards glycolysis and down-regulation of antioxidant Nuclear erythroid 2-related factor 2 (Nrf2)/Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) signaling. Although the mechanisms underlying the mitochondrial dysfunction during mucosal inflammation are not fully understood at present, metabolic intermediates and cholesterol may act as signals activating the NLRP3 inflammasome in IBD. Notably, dietary phytochemicals exhibit protective effects against cholesterol imbalance and mitochondrial function alterations to maintain gastrointestinal mucosal renewal in vitro and in vivo conditions. Here, we discuss the role of cholesterol and mitochondrial metabolism in IBD, highlighting the therapeutic potential of dietary phytochemicals, restoring intestinal metabolism and function

IL-33 alarmin and its active proinflammatory fragments are released in small intestine in Celiac disease

Initially described as Th2 promoter cytokine, more recently, IL-33 has been recognized as an alarmin, mainly in epithelial and endothelial cells. While localized in the nucleus acts as a gene regulator, it can be also released after injury, stress or inflammatory cell death. As proinflammatory signal, IL-33 binds to the surface receptor ST2, which enhances mast cell, Th2, regulatory T cell, andinnate lymphoid cell type 2 functions. Besides these Th2 roles, free IL-33 can activate CD8+ T cells during ongoing Th1 immune responses to potentiate its cytotoxic function. Celiac Disease (CD) is a chronic inflammatory disorder characterized by a predominant Th1 response responsible for multiple pathways of mucosal damage in the proximal small intestine. By immunofluorescence and western blot analysis of duodenal tissues, we found an increased expression of IL-33 in duodenal mucosa of active CD (ACD) patients. Particularly, locally digested IL-33 releases active 18/21kDa fragments which can contribute to expand the proinflammatory signal. Endothelial (CD31+) and mesenchymal, myofibroblast and pericytes, cells from microvascular structures in villi and crypts, showed IL-33 nuclear location; while B cells (CD20+) showed a strong cytoplasmic staining.Both ST2 forms, ST2L and sST2, were also upregulated in duodenal mucosa of CD patients. This was accompanied by increased number of CD8+ST2+ T cells and the expression of T-bet in some ST2+ intraepithelial lymphocytes and lamina propria cells. IL-33 and sST2 mRNA levels correlated with IRF1, an IFN induced factor relevant in responses to viral infections and interferon mediatedproinflammatory responses highly represented in duodenal tissues in ACD. These findings highlight the potential contribution of IL-33 and its fragments to exacerbate the proinflammatory circuit and potentiate the cytotoxic activity of CD8+ T cells in CD pathology.Fil: Perez, Federico. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Ruera, Carolina Naymé. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Miculán, Emanuel Gonzalo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Carasi, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Dubois Camacho, Karen. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomedicas.; ChileFil: Garbi, Laura. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martín; ArgentinaFil: Guzman, Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Hermoso, Marcela A.. Universidad de Chile. Facultad de Medicina. Institutos de Ciencias Biomedicas.; ChileFil: Chirdo, Fernando Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentin

Comparing the resident populations of private and public long-term care facilities over a fifteen-year period: a study from Quebec, Canada

In the province of Quebec, Canada, long-term residential care is provided by two types of facilities: privately-owned facilities in which care is privately financed and delivered, and publicly-subsidised accredited facilities. There are few comparative data on the residents served by the private and public sectors, and none on whether their respective population has changed over time. Such knowledge would help plan services for older adults who can no longer live at home due to increased disabilities. This study compared 1) the resident populations currently served by private and public facilities and 2) how they have evolved over time. The data come from two cross-sectional studies conducted in 1995-2000 and 2010-2012. In both studies, we randomly selected care settings in which we randomly selected older residents. In total, 451 residents from 145 settings assessed in 1995-2000 were compared to 329 residents from 102 settings assessed in 2010-2012. In both study periods, older adults housed in the private sector had fewer cognitive and functional disabilities than those in public facilities. Between the two study periods, the proportion of residents with severe disabilities decreased in private facilities while it remained over 80% in their public counterparts. Findings indicate that private facilities care today for less-disabled older adults, leaving to public facilities the heavy responsibility of caring for those with more demanding needs. These trends may impact both sectors’ ability to deliver proper residential care

High refractive index composite materials for THz waveguides: trade-off between index contrast and absorption loss

Polymer compounds from titania-doped polyethylene are fabricated and their linear optical properties characterized by THz-TDS. We show that high concentration of dopants not only enhances the refractive index of the composite material, but also can dramatically raise its absorption coefficient. We demonstrate that the design of Bragg reflectors based on lossy composite polymers depends on finding a compromise between index contrast and corresponding losses. A small absorption value is also shown to be favorable, compared to an ideal lossless reflector, as it enables to smooth the transmission passbands. Transmission measurements of a fabricated hollowcore Bragg fiber confirm simulation results

Parkinson's disease biomarkers: perspective from the NINDS Parkinson's Disease Biomarkers Program

Biomarkers for Parkinson's disease (PD) diagnosis, prognostication and clinical trial cohort selection are an urgent need. While many promising markers have been discovered through the National Institute of Neurological Disorders and Stroke Parkinson's Disease Biomarker Program (PDBP) and other mechanisms, no single PD marker or set of markers are ready for clinical use. Here we discuss the current state of biomarker discovery for platforms relevant to PDBP. We discuss the role of the PDBP in PD biomarker identification and present guidelines to facilitate their development. These guidelines include: harmonizing procedures for biofluid acquisition and clinical assessments, replication of the most promising biomarkers, support and encouragement of publications that report negative findings, longitudinal follow-up of current cohorts including the PDBP, testing of wearable technologies to capture readouts between study visits and development of recently diagnosed (de novo) cohorts to foster identification of the earliest markers of disease onset

Advertising in Medical Journals: Should Current Practices Change?

Fugh-Berman and colleagues surveyed medical journals' policies and practices on advertising. Pharmaceutical products, they say, dominate journals' advertising pages, creating conflicts of interests

Landscapes and bacterial signatures of mucosa-associated intestinal microbiota in Chilean and Spanish patients with inflammatory bowel disease

Inflammatory bowel diseases (IBDs), which include ulcerative colitis (UC) and Crohn’s disease (CD), cause chronic inflammation of the gut, affecting millions of people worldwide. IBDs have been frequently associated with an alteration of the gut microbiota, termed dysbiosis, which is generally characterized by an increase in abundance of Proteobacteria such as Escherichia coli, and a decrease in abundance of Firmicutes such as Faecalibacterium prausnitzii (an indicator of a healthy colonic microbiota). The mechanisms behind the development of IBDs and dysbiosis are incompletely understood. Using samples from colonic biopsies, we studied the mucosa-associated intestinal microbiota in Chilean and Spanish patients with IBD. In agreement with previous studies, microbiome comparison between IBD patients and non-IBD controls indicated that dysbiosis in these patients is characterized by an increase of pro-inflammatory bacteria (mostly Proteobacteria) and a decrease of commensal beneficial bacteria (mostly Firmicutes). Notably, bacteria typically residing on the mucosa of healthy individuals were mostly obligate anaerobes, whereas in the inflamed mucosa an increase of facultative anaerobe and aerobic bacteria was observed. We also identify potential co-occurring and mutually exclusive interactions between bacteria associated with the healthy and inflamed mucosa, which appear to be determined by the oxygen availability and the type of respiration. Finally, we identified a panel of bacterial biomarkers that allow the discrimination between eubiosis from dysbiosis with a high diagnostic performance (96% accurately), which could be used for the development of non-invasive diagnostic methods. Thus, this study is a step forward towards understanding the landscapes and alterations of mucosa-associated intestinal microbiota in patients with IBDs.This study was supported by Fondo Nacional De Desarrollo Científico y Tecnológico FONDECYT grant 1161161 to R. Vidal, CONICYT-PCHA/2014-21140975 fellowship to N. Chamorro, FONDECYT 1120577 and 1170648 to Hermoso MA and the Spanish Ministry of Economy projects CLG2015 66686-C3-1-P to Rosselló-Mora R., as well as funds from the European Regional Development Fund (FEDER) and NSF Dimensions in Biodiversity grant OCE-1342694. Support was also provided by a Millennium Science Initiative grant from the Ministry of Economy, Development and Tourism to Paredes-Sabja D