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T granules in human platelets function in TLR9 organization and signaling

Human and murine platelets (PLTs) variably express toll-like receptors (TLRs), which link the innate and adaptive immune responses during infectious inflammation and atherosclerotic vascular disease. In this paper, we show that the TLR9 transcript is specifically up-regulated during pro-PLT production and is distributed to a novel electron-dense tubular system-related compartment we have named the

Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia

Immune thrombocytopenia (ITP) is a bleeding disorder in which antibodies and/or T cells lead to enhanced peripheral platelet destruction and reduced bone marrow platelet production. Several reports have observed that ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP, we analyzed Tregs in the spleen and thymu

HLA alloimmunization against platelet transfusions : pathophysiology, significance, prevention and management

Approximately five decades ago, alloimmunization to human leukocyte antigens (HLA) and platelet refractoriness were recognized as potentially serious complications of platelet transfusions. The mechanisms that result in stimulating immunity against blood products are still incompletely understood but are related to both the composition of the donor product transfused and the immune status of the r

Single nucleotide polymorphism (SNP) analysis demonstrates a significant association of tumour necrosis factor-alpha (TNFA) with primary immune thrombocytopenia among Caucasian adults

T-helper 1 polarization in patients with primary immune thrombocytopenia (ITP) is well documented. However, the genetic contribution to this imbalance remains unclear. To address this question, we selected six candidate single nucleotide polymorphisms within cytokine or cytokine receptor genes for association testing among Caucasian adults. Patients from the United Kingdom Adult ITP Registry were

Management of immune thrombocytopenic purpura in children : potential role of novel agents

The treatment of immune thrombocytopenic purpura (ITP) in children is controversial, requiring individualized assessment of the patient and consideration of treatment options. If the platelet count is >10 000/μL and the patient is asymptomatic, a 'watch and wait' strategy is appropriate since most children with ITP will recover completely without pharmacotherapy. If therapy is indicated because of

Platelets and the immune continuum

Platelets are anucleate cells that are crucial mediators of haemostasis. Most immunologists probably don't think about platelets every day, and may even consider these cells to be 'nuisances' in certain in vitro studies. However, it is becoming increasingly clear that platelets have inflammatory functions and can influence both innate and adaptive immune responses. Here, we discuss the mechanisms

Platelets and innate immunity

Although platelets are best known as primary mediators of hemostasis, this function intimately associates them with inflammatory processes, and it has been increasingly recognized that platelets play an active role in both innate and adaptive immunity. For example, platelet adhesive interactions with leukocytes and endothelial cells via P-selectin can lead to several pro-inflammatory events, inclu

A murine model of severe immune thrombocytopenia is induced by antibody- and CD8+ T cell-mediated responses that are differentially sensitive to therapy

Immune thrombocytopenia (ITP) is a bleeding disorder characterized by antibody-opsonized platelets being prematurely destroyed in the spleen, although some patients with ITP may have a cell-mediated form of thrombocytopenia. Although several animal models of ITP have been developed, few mimic primary chronic ITP nor have any shown cell-mediated platelet destruction. To create this type of model, s

Civil Defence (Re)Emerged : A Multi-Level Perspective on Policy Developments in Post-Crimea Europe

Denna avhandling undersöker (åter)uppbyggnaden av civilt försvar i Europa efter Rysslands annektering av Krim 2014. Mer specifikt analyserar den befintliga uppfattningar om civilt försvar och hur dessa formas i ett flernivåsammanhang, med fokus på samspelet mellan nationella, regionala och internationella institutioner. Genom ett diskursivt institutionellt perspektiv betonar avhandlingen den dynamThis dissertation examines the (re)emergence of civil defence in Europe in the aftermath of Russia's annexation of Crimea in 2014. More specifically, it investigates the existing conceptions of civil defence and how these are shaped in a multi-level institutional context, focusing on the interplay between national, regional, and international levels. Through the lens of discursive institutionalism

Antibiotic prophylaxis and incidence of infection following elbow arthroplasty : a nationwide study

BACKGROUND AND PURPOSE: Periprosthetic joint infection (PJI) after elbow arthroplasty is a serious complication. Evidence of the best antibiotic prophylaxis for elbow arthroplasty is lacking. We aimed to investigate the regimens presently used in Sweden, incidence of PJI, and the bacteria most frequently found in elbow PJI.METHODS: A questionnaire was sent out to all Swedish units performing elbow

Integrating machine learning with process-based glacio-hydrological model for improving the performance of runoff simulation in cold regions

Hydrological modelling is essential for effective water resources management, as it represents complex physical processes through mathematical equations to improve our understanding of the water cycle. FLEXG is a glacio-hydrological model that has been successfully applied and found to perform well in glacierized regions. This study seeks to improve the capability of classical FLEXG model for glac

Super-resolution imaging pinpoints the periodic ultrastructure at the human node of Ranvier and its disruption in patients with polyneuropathy

The node of Ranvier is the key element in saltatory conduction along myelinated axons, but its specific protein organization remains elusive in the human species. To shed light on nanoscale anatomy of the human node of Ranvier in health and disease, we assessed human nerve biopsies of patients with polyneuropathy by super-resolution fluorescence microscopy. We applied direct stochastic optical rec

Parent-of-origin effects in the life-course evolution of cardiometabolic traits

AIMS/HYPOTHESIS: Cardiometabolic traits are heritable, and some display parent-of-origin effects, which indicates preferential inheritance from one parent or parental bias. Most studies of these phenomena have focused on adult populations. We aimed to investigate the heritability and parent-of-origin effects on cardiometabolic traits in a birth cohort with serial measurements to determine whether

Epigenome-wide association study of objectively measured physical activity in peripheral blood leukocytes

BACKGROUND: Few studies have explored the association between DNA methylation and physical activity. The aim of this study was to evaluate the association of objectively measured hours of sedentary behavior (SB) and moderate physical activity (MPA) with DNA methylation. We further aimed to explore the association between SB or MPA related CpG sites and cardiometabolic traits, gene expression, and

Clinical use of polygenic scores in type 2 diabetes: challenges and possibilities

Resulting from a combination of genetic and environmental factors, type 2 diabetes is highly heterogeneous in manifestation and disease progression, with the only common feature being chronic hyperglycaemia. In spite of vigorous efforts to elucidate the pathogenetic origins and natural course of the disease, there is still a lack of biomarkers and tools for prevention, disease stratification and t