TREM-1 links dyslipidemia to inflammation and lipid deposition in atherosclerosis.

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses, but its significance in non-infectious diseases remains unclear. Here, we demonstrate that TREM-1 promotes cardiovascular disease by exacerbating atherosclerosis. TREM-1 is expressed in advanced human atheromas and is highly upregulated under dyslipidemic conditions on circulating and on lesion-infiltrating myeloid cells in the Apoe(-/-) mouse model. TREM-1 strongly contributes to high-fat, high-cholesterol diet (HFCD)-induced monocytosis and synergizes with HFCD serum-derived factors to promote pro-inflammatory cytokine responses and foam cell formation of human monocyte/macrophages. Trem1(-/-)Apoe(-/-) mice exhibit substantially attenuated diet-induced atherogenesis. In particular, our results identify skewed monocyte differentiation and enhanced lipid accumulation as novel mechanisms through which TREM-1 can promote atherosclerosis. Collectively, our findings illustrate that dyslipidemia induces TREM-1 surface expression on myeloid cells and subsequently synergizes with TREM-1 to enhance monopoiesis, pro-atherogenic cytokine production and foam cell formation

J., C., G., C. , I., S. Kopp

Freigang F, Klett S, Kopp S. Pragmatic multimodality: Effects of nonverbal cues of focus and certainty in a virtual human. In: Beskow J, Peters C, Castellano G, O'Sullivan C, Leite I, Kopp S, eds. The Seventeenth International Conference on Intelligent Virtual Agents (IVA 2017). Lecture Notes in Computer Science. Vol 10498. Springer International Publishing; 2017: 142-155

Hereditary Hemorrhagic Telangiectasia: Success of the Osler Calendar for Documentation of Treatment and Course of Disease

Hereditary hemorrhagic telangiectasia (HHT; Rendu-Osler-Weber syndrome) affects the capillary and larger vessels, leading to arteriovenous shunts. Epistaxis is the main symptom impairing quality of life. The aim of the Osler Calendar is to offer information about the extent of the systemic disease and the current state of treatment. A care plan with information on the rare disease and self-treatment of epistaxis was created. Organ examinations and ongoing treatments were recorded. A questionnaire documents the treatment success, including patient satisfaction, frequency of hemorrhage and hemoglobin levels. The patients using the Osler Calendar for at least one year (n = 54) were surveyed. Eighty-five percent of patients (n = 46) used the calendar to gain information about HHT. Seventy-two percent (n = 39) used the Osler Calendar for instructions on the self-treatment of nosebleeds. The calendar increased patients’ understanding for the need for organ screenings from 48% (n = 26) to 81% (n = 44). Seventy-nine percent (n = 43) of patients confirmed that the Osler Calendar documented their therapeutic process either well or very well. Fifty-two percent (n = 28) saw an improvement in the therapeutic process due to the documentation. The Osler Calendar records the individual intensity of the disease and facilitates the communication between attending physicians. It is a tool for specialists to review treatment strategies. Furthermore, the calendar enhances patients’ comprehension of their condition

Requirement for neutralizing antibodies to control bone marrow transplantation-associated persistent viral infection and to reduce immunopathology

Bone marrow transplantation (BMT) is commonly used in the treatment of leukemia, however its therapeutic application is partly limited by the high incidence of associated opportunistic infections. We modeled this clinical situation by infecting mice that underwent BMT with lymphocytic choriomeningitis virus (LCMV) and investigated the potential of immunotherapeutic strategies to counter such infections. All mice that received BMT survived LCMV infection and developed a virus carrier status. Immunotherapy by adoptive transfer of naive splenocytes protected against low (200 PFU), but not high (2 x 10(6) PFU), doses of LCMV. Attempts to control infection of high viral titers using strongly elevated frequencies of activated LCMV-specific T cells failed to control virus and resulted in immunopathology and death. In contrast, virus neutralizing Abs combined with naive splenocytes were able to efficiently control high-dose LCMV infection without associated side effects. Thus, cell transfer combined with neutralizing Abs represented the most effective means of controlling BMT-associated opportunistic viral infection in our in vivo model. These data underscore the in vivo efficacy and immunopathological "safety" of neutralizing antibodies

Toll-like receptor engagement converts T-cell autoreactivity into overt autoimmune disease

Autoimmune diabetes mellitus in humans is characterized by immunological destruction of pancreatic beta islet cells. We investigated the circumstances under which CD8(+) T cells specific for pancreatic beta-islet antigens induce disease in mice expressing lymphocytic choriomeningitis virus (LCMV) glycoprotein (GP) as a transgene under the control of the rat insulin promoter. In contrast to infection with LCMV, immunization with LCMV-GP derived peptide did not induce autoimmune diabetes despite large numbers of autoreactive cytotoxic T cells. Only subsequent treatment with Toll-like receptor ligands elicited overt autoimmune disease. This difference was critically regulated by the peripheral target organ itself, which upregulated class I major histocompatibility complex (MHC) in response to systemic Toll-like receptor-triggered interferon-alpha production. These data identify the 'inflammatory status' of the target organ as a separate and limiting factor determining the development of autoimmune disease

'Ain't it a Ripping Night': Alcoholism and the Legacies of Empire in Salman Rushdie's Midnight's Children.

In the era of decolonisation that followed the Second World War, various authors sought to engage with India and the Empire’s past anew throughout their novels, identifying medicine and illness as key parts of Imperial authority and colonial experience. Salman Rushdie’s approach to the Raj in Midnight’s Children (1981) focused on the broad sweep of colonial life, juxtaposing the political and the personal. This article argues that Rushdie explores the history of colonial India by employing alcohol and alcoholism as lenses through which to explore the cultural, political and medical legacies of Empire. Through analysis of Midnight’s Children as well as a range of medical sources related to alcohol and inebriation, it will illustrate how drinking is central to Rushdie’s approach to secular and religious identities in newly independent India, as well as a means of satirising and undermining the supposed benefit that Empire presented to India and Indians

Электроснабжение установки перекачки нефти п. Пионерный ОАО «Томскнефть»

РЕФЕРАТ Выпускная квалификационная работа 149 с., 23 рис., 32 табл., 29 источников, 6 прил. Ключевые слова: нефтепровод, насос, электрооборудование, схема электроснабжения, линия, сеть, электроприемник, нагрузка, оборудование, защита, ток, напряжение, мощность. Объектом исследования является электрическая часть УПН п. Пионерный ОАО «Томскенефть». Цель работы – проектирование схемы электроснабжения предприятия, выбор оборудования. В процессе исследования проводился сбор исходных данных в ходе производственной практики на объекте исследования. В результате была спроектирована схема электроснабжения от подстанции энергосистемы, до конечного электроприемника. Были выбраны кабели и провода, коммутационное оборудование, были сделаны необходимые проверки. Также результатом работы сталESSAY Final qualifying work 149 p., 23 fig., 32 tab., 29 sources, 6 adj. Keywords: oil, pump, electrical equipment, power supply circuit, line, network, power-consuming equipment, load equipment, protection, current, voltage, power. The object of research is the electrical part of UPN claim. Pionerny of "Tomskeneft". The purpose of work - designing enterprise power scheme, the choice of equipment. The study was conducted to collect baseline data in the course of practical training on the subject of the study. As a result, power supply circuit has been designed from the substation grid, appliance, to the end. Were selected cables and wires, switching equipment, the necessary checks have been made. It is also the result of the work became an economic calculation of capital costs for the con

Murid Herpesvirus-4 Exploits Dendritic Cells to Infect B Cells

Dendritic cells (DCs) play a central role in initiating immune responses. Some persistent viruses infect DCs and can disrupt their functions in vitro. However, these viruses remain strongly immunogenic in vivo. Thus what role DC infection plays in the pathogenesis of persistent infections is unclear. Here we show that a persistent, B cell-tropic gamma-herpesvirus, Murid Herpesvirus-4 (MuHV-4), infects DCs early after host entry, before it establishes a substantial infection of B cells. DC-specific virus marking by cre-lox recombination revealed that a significant fraction of the virus latent in B cells had passed through a DC, and a virus attenuated for replication in DCs was impaired in B cell colonization. In vitro MuHV-4 dramatically altered the DC cytoskeleton, suggesting that it manipulates DC migration and shape in order to spread. MuHV-4 therefore uses DCs to colonize B cells