Molecular pharmacology of a Novel NR2B-selective NMDA Receptor Antagonist

The NMDA receptor is a heteromeric ligand-gated ion channel in the central nervous system (CNS). There are three families of NMDA receptor subunits with various combinations of NRl, NR2A-D and NR3A֊B subunits producing unique receptors with distinctive pharmacological and biochemical properties. Pharmacological and functional properties of the NMDA receptor are highly dependent on the composition of the receptor complex. The NMDA receptor is the focus of drug development for therapy and prevention of numerous neurological and psychiatric disorders. The focus of this thesis was to investigate NMDA receptor subtype selectivity of NMDA antagonists, in particular, RGH-896, a novel NR2B֊selective antagonist. The study has utilised radioligand binding competition binding assays with RGH-896 in native, recombinant and immunopurified NMDA receptor preparations. In addition, ligand autoradiography has been employed to quantify and delineate the regional distribution of [^3H] RGH-896 binding sites in rodent and human brain tissue. This study provides the first evidence that [3H] RGH-896 binds to a distinct binding site which displays a significantly lower affinity for spermidine compared to the [^3H] Ro 25,6981 binding site. In addition, the low sensitivity of [^3H] MK-801 for unlabelled RGH-896 compared to prototypical NR2B ligand ifenprodil is further evidence for the difference in binding sites. Novel immunopurification studies using [3H] RGH-896, in contrast to [3H] CP 101,606, binds to NR2B-containing receptors irrespective of NMDA receptor subunit combinations. Ligand autoradiography in human brain has shown a surprising overall preservation of NR2B receptors in dementia with Lewy bodies (DLB) patients compared to age matched controls in the anterior cingulate cortex (ACC). However, this study has revealed the first evidence of an upregulation of NR2B receptors in ACC of DLB cases related to severity of auditory, but not visual hallucinations

Boston Hospitality Review: Fall 2014

Boston Market Hotel Review by Andrea Foster -- The Prevalence of Longevity Amongst Leading Brands by Bradford Hudson -- European River Cruising On The Rise Among American Tourists by Melinda Jàszbernèny -- Building A Spirit of Inclusion: Pan Am and The Cultural Revolution by Mirembe B. Birigwa -- Re-imagining The Hotel Guestroom for The Millennial Business Traveler by Alexis Oliver -- Introducing RevPASH: The Free Webtool Application by Peter Szend

Determination of convergence rates across the Ventura Basin, Southern California, using GPS and historical triangulation

Comparison of angles from historical triangulation observations dating as far back as 1932 with Global Positions System (GPS) measurements taken in 1987 indicates that rapid convergence may be taking place on decade timescales in the central and eastern part of the Ventura basin, an east-west trending trough bounded by thrust faults. Changes in angles over this time were analyzed using Prescott's modified Frank's method and in terms of a model which assumes that the regions to the north and south of the basin are rigid blocks undergoing relative motion. For the two block model, inversion of the observed angle changes over the last 28 years for the relative motion vector leads to north-south convergence across the basin of 30 + or - 5 mm/yr, with a left lateral component of 10 + or - 1 mm/yr in the Fillmore-Santa Paula area in the central part of the basin. The modified Frank's method yields strain rates of approximately 2 microrad/yr in both the east and central parts of the basin for measurements spanning the 1971 San Fernando earthquake. Assuming no east-west strain yeilds north-south compression of approximately 3.5 + or - .2 cm/yr. Comparison of triangulation data prior to the earthquake shows no strain outside the margin of error. The convergence rates determined by geodetic techniques are consistent with geologic observations in the area. Such large geodetic deformation rates, with no apparent near-surface creep on the major thrust, can be understood if these faults become subhorizontal at relatively shallow depths and if the subhorizontal portions of the faults are creeping. An alternative explanation of the large displacement rates might be that the pumping of oil in the vicinity of the benchmarks caused large horizontal motions, although it is unlikely that meter scale horizontal motions are due to oil withdrawal. These and other hypotheses are evaluated to better constrain the tectonics of this active region

Boston Hospitality Review: Fall 2016

The Heart of Successful Hotels: Going Beyond the Monopoly Game Strategy By Joseph Khairallah and Andrea Foster -- Fragments of the Past By Peter Szende and Annie Holcombe -- Hospitality Branding in the Age of the Millennial By Allen Adamson and Chekitan S. Dev -- In 2017 What Will a Restaurant Actually Be? A New Taxonomy By Christopher Muller -- The Unreal Thing: Faux Heritage at Disney By Bradford Hudson -- An Insider’s Look at the 2016 Philadelphia Democratic National Convention: Hospitality and Inclusion at Work By Erin Tucker, Leora Halpern Lanz, and Juan Lesme

Animal models of rheumatoid pain: experimental systems and insights.

Severe chronic pain is one of the hallmarks and most debilitating manifestations of inflammatory arthritis. It represents a significant problem in the clinical management of patients with common chronic inflammatory joint conditions such as rheumatoid arthritis, psoriatic arthritis and spondyloarthropathies. The functional links between peripheral inflammatory signals and the establishment of the neuroadaptive mechanisms acting in nociceptors and in the central nervous system in the establishment of chronic and neuropathic pain are still poorly understood, representing an area of intense study and translational priority. Several well-established inducible and spontaneous animal models are available to study the onset, progression and chronicization of inflammatory joint disease, and have been instrumental in elucidating its immunopathogenesis. However, quantitative assessment of pain in animal models is technically and conceptually challenging, and it is only in recent years that inflammatory arthritis models have begun to be utilized systematically in experimental pain studies using behavioral and neurophysiological approaches to characterize acute and chronic pain stages. This article aims primarily to provide clinical and experimental rheumatologists with an overview of current animal models of arthritis pain, and to summarize emerging findings, challenges and unanswered questions in the field

Boston Hospitality Review: Winter 2015

In Hotels, Health and Spas Equals Wealth by Andrea Foster and Jenna Finkelstein -- Cunard in Boston by Bradford Hudson -- Product Life Cycle: Moving from Theory to Practice by Stanley I. Buchin, D.B.A. -- I Dream of Doughnuts: One Family’s Sweet Saga of the American Dream by Rachel DeSimone -- Delivering Food to the Front Door: A New, Or Very Old, Convenience? by Christopher Muller, Ph.D. -- Thoughts: Field Notes on the Future of Food by Nicco Murator

Maackia amurensis Seed Lectin (MASL) Increases Movement Velocity of Mice with TNFα Induced Rheumatoid Arthritis

Up to 70 million people around the world suffer from rheumatoid arthritis. Current treatment options have varied efficacy and can cause unwanted side effects. New approaches are needed to treat this condition. Sialic acid modifications on chondrocyte receptors have been associated with arthritic inflammation and joint destruction. The transmembrane mucin receptor protein podoplanin (PDPN) has been identified as a functionally relevant receptor that presents extracellular sialic acid motifs. PDPN signaling promotes inflammation and invasion associated with arthritis and, therefore, has emerged as a target that can be used to inhibit arthritic inflammation. Maackia amurensis seed lectin (MASL) can target PDPN on chondrocytes to decrease inflammatory signaling cascades and reduce cartilage destruction in a lipopolysaccharide induced osteoarthritis mouse model. Here, we investigated the effects of MASL on rheumatoid arthritis progression in a TNFα transgenic (TNF-Tg) mouse model. Results from this study indicate that MASL can be administered orally to ameliorate joint malformation and increase velocity of movement exhibited by these TNF-Tg mice. These data support the consideration of MASL as a potential treatment for rheumatoid arthritis

Bidirectional associations between body dissatisfaction and depressive symptoms from adolescence through early adulthood

Body dissatisfaction and depressive symptoms are commonly experienced during adolescence and increase the risk of adverse health outcomes, especially eating disorders. However, the dominant temporal associations between these two experiences (i.e., whether one is a risk factor for the other or the two are mutually reinforcing) has yet to be fully explored. We examined the associations between body dissatisfaction and depressive symptoms assessed at baseline and 5- and 10-year follow-up in younger (M age = 12.9 years at baseline, 56% female, n = 577) and older (M age = 15.9 years at baseline, 57% female, n = 1,325) adolescent cohorts assessed as part of Project Eating Among Teens and Young Adults. Associations between body dissatisfaction and depressive symptoms were examined using cross-lagged models. For females, the dominant directionality was for body dissatisfaction predicting later depressive symptoms. For males, the picture was more complex, with developmentally sensitive associations in which depressive symptoms predicted later body dissatisfaction in early adolescence and early adulthood, but the reverse association was dominant during middle adolescence. These findings suggest that interventions should be tailored to dynamic risk profiles that shift over adolescence and early adulthood, and that targeting body dissatisfaction at key periods during development may have downstream impacts on depressive symptoms

Uma revisão crítica da política pública para a melhoria das práticas de governança em IES na Colômbia

Good governance practices in Higher Education Institutions (heis) in Colombia have been a subject of discussion during the past decade. The Ministry of Education, key actors in heis’ governance systems, and researchers with studies in this subject have participated in this dialogue. It was due to this debate that in November 2017 the National Council of Higher Education (cesu, by its acronym in Spanish) established the Public Policy for the improvement of Colombian heis’ governance. This policy highlights relevant aspects for good governance at Colombian heis but leaves behind many others that we want to bring to discussion. This paper undertakes a critical review to the public policy enacted in 2017 and suggests to the Colombian Ministry of Education new issues to be considered in establishinggovernance guidelines for Colombian heis.Las prácticas de gobierno en las instituciones de educación superior (ies) en Colombia han sido objeto de debate en la década actual. En este diálogo han participado el Ministerio de Educación Nacional, actores en los sistemas de gobierno de las ies e investigadores que han desarrollado estudios sobre el tema en particular. En el marco de este debate, el Consejo Nacional de Educación Superior estableció la política pública para el mejoramiento del gobierno en las ies en noviembre de 2017. Esta política expresa aspectos relevantes para un buen gobierno en las ies del país, pero deja de lado otros que consideramos fundamentales traer a discusión. Este artículo realiza un análisis crítico a la política pública promulgada en el año 2017 y sugiere al Ministerio de Educación Nacional nuevos aspectos que deben ser considerados en el establecimiento de lineamientos de gobierno para las ies colombianas.As práticas de governança em instituições de ensino superior (ies) na Colômbia foram objeto de debate na década atual. Este diálogo teve a participação do Ministério da Educação Nacional, atores dos sistemas de governo das ies e pesquisadores, que desenvolveram estudos sobre o tema em particular. Como resultado desse debate, o Conselho Nacional de Educação Superior estabeleceu a política pública para o melhoramento de governança nas ies em novembro de 2017. Esta política expressa aspectos relevantes para uma boa governança nas ies do país, mas deixa de lado outros que consideramos fundamentais para debate. Este artigo realiza uma análise crítica da política pública promulgada no ano de 2017 e sugere ao Ministério da Educação Nacional novos aspectos que devem ser considerados no estabelecimento de diretrizes de governança para as ies colombianas