Search results for "tolerance"
showing 10 items of 956 documents
Tolerance through Education: How Tolerogenic Dendritic Cells Shape Immunity
2017
Dendritic cells (DCs) are central players in the initiation and control of responses, regulating the balance between tolerance and immunity. Tolerogenic DCs are essential in the maintenance of central and peripheral tolerance by induction of clonal T cell deletion and T cell anergy, inhibition of memory and effector T cell responses, and generation and activation of regulatory T cells. Therefore, tolerogenic DCs are promising candidates for specific cellular therapy of allergic and autoimmune diseases and for treatment of transplant rejection. Studies performed in rodents have demonstrated the efficacy and feasibility of tolerogenic DCs for tolerance induction in various inflammatory diseas…
eIF2α confers cellular tolerance to S. aureus α-toxin
2015
We report on the role of conserved stress-response pathways for cellular tolerance to a pore forming toxin. First, we observed that small molecular weight inhibitors including of eIF2α-phosphatase, jun-N-terminal kinase (JNK), and PI3-kinase sensitized normal mouse embryonal fibroblasts (MEFs) to the small pore forming S. aureus α-toxin. Sensitization depended on expression of mADAM10, the murine ortholog of a proposed high-affinity receptor for α-toxin in human cells. Similarly, eIF2α (S51A/S51A) MEFs, which harbor an Ala knock-in mutation at the regulated Ser51 phosphorylation site of eukaryotic translation initiation factor 2α, were hyper-sensitive to α-toxin. Inhibition of translation w…
Neuro-endocrine networks controlling immune system in health and disease
2014
The nervous and immune systems have long been considered as compartments that perform separate and different functions. However, recent clinical, epidemiological, and experimental data have suggested that the pathogenesis of several immune-mediated disorders, such as multiple sclerosis (MS), might involve factors, hormones, and neural mediators that link the immune and nervous system. These molecules are members of the same superfamily, which allow the mutual and bi-directional neural–immune interaction. More recently, the discovery of leptin, one of the most abundant adipocyte-derived hormones that control food intake and metabolism, has suggested that nutritional/metabolic status, acting …
Tolerogenic Dendritic Cells for Regulatory T Cell Induction in Man.
2015
Dendritic cells are (DC) highly specialized professional antigen-presenting cells (APC) that regulate immune responses, maintaining the balance between tolerance and immunity. Mechanisms via which they can promote central and peripheral tolerance include clonal deletion, inhibition of memory T cell responses, T cell anergy and induction of regulatory T cells. These properties have led to the analysis of human tolerogenic DC as a therapeutic strategy for induction or re-establishment of tolerance. In the recent years, numerous protocols for the generation of human tolerogenic DC have been developed and their tolerogenic mechanisms, including induction of regulatory T cells, are relatively we…
Relationship Between the Critical Power Test and a 20-min Functional Threshold Power Test in Cycling.
2021
To investigate the agreement between critical power (CP) and functional threshold power (FTP), 17 trained cyclists and triathletes (mean ± SD: age 31 ± 9 years, body mass 80 ± 10 kg, maximal aerobic power 350 ± 56 W, peak oxygen consumption 51 ± 10 mL⋅min–1⋅kg–1) performed a maximal incremental ramp test, a single-visit CP test and a 20-min time trial (TT) test in randomized order on three different days. CP was determined using a time-trial (TT) protocol of three durations (12, 7, and 3 min) interspersed by 30 min passive rest. FTP was calculated as 95% of 20-min mean power achieved during the TT. Differences between means were examined using magnitude-based inferences and a paired-samples…
Node co-activations as a means of error detection : Towards fault-tolerant neural networks
2022
Context: Machine learning has proved an efficient tool, but the systems need tools to mitigate risks during runtime. One approach is fault tolerance: detecting and handling errors before they cause harm. Objective: This paper investigates whether rare co-activations – pairs of usually segregated nodes activating together – are indicative of problems in neural networks (NN). These could be used to detect concept drift and flagging untrustworthy predictions. Method: We trained four NNs. For each, we studied how often each pair of nodes activates together. In a separate test set, we counted how many rare co-activations occurred with each input, and grouped the inputs based on whether its class…
The Life Cycle of the Mu-Opioid Receptor
2020
Opioid receptors (ORs) are undisputed targets for the treatment of pain. Unfortunately, targeting these receptors therapeutically poses significant challenges including addiction, dependence, tolerance, and the appearance of side effects, such as respiratory depression and constipation. Moreover, misuse of prescription and illicit narcotics has resulted in the current opioid crisis. The mu-opioid receptor (MOR) is the cellular mediator of the effects of most commonly used opioids, and is a prototypical G protein-coupled receptor (GPCR) where new pharmacological, signalling and cell biology concepts have been coined. This review summarises the knowledge of the life cycle of this therapeutic …
The impact of coffee on health
2013
Abstract Objective Coffee is a beverage used worldwide. It includes a wide array of components that can have potential implication on health. We have reviewed publications on the impact of coffee on a series of health outcomes. Methods Articles published between January 1990 and December 2012 were selected after crossing coffee or caffeine with a list of keywords representative of the most relevant health areas potentially affected by coffee intake. Results Caffeine, chlorogenic acids and diterpenes are important components of coffee. Tolerance often acts as a modulator of the biological actions of coffee. There is a significant impact of coffee on the cardiovascular system, and on the meta…
Novel Approaches for Immunosuppression in Graves’ Hyperthyroidism and Associated Orbitopathy
2020
<b><i>Background:</i></b> Both Graves’ hyperthyroidism (GH) and Graves’ orbitopathy (GO) are associated with significant adverse health consequences. All conventional treatment options have limitations regarding efficacy and safety. Most importantly, they do not specifically address the underlying immunological mechanisms. We aim to review the latest development of treatment approaches in these two closely related disorders. <b><i>Summary:</i></b> Immunotherapies of GH have recently demonstrated clinical efficacy in preliminary studies. They include ATX-GD-59, an antigen-specific immunotherapy which restores immune tolerance to the thyrotropin…
Role of FODMAPs in Patients With Irritable Bowel Syndrome.
2015
Irritable bowel syndrome (IBS) is a condition characterized by abdominal pain, bloating, flatus, and altered bowel habits. The role of dietary components in inducing IBS symptoms is difficult to explore. To date, foods are not considered a cause but rather symptom-triggering factors. Particular interest has been given to the so-called FODMAPs (fermentable oligo-, di-, and monosaccharides and polyols). We aimed to summarize the evidence from the most common approaches to manage suspected food intolerance in IBS, with a particular interest in the role of FODMAPs and the effects of a low FODMAP diet. We reviewed literature, consulting PubMed and Medline by using the search terms FODMAP(s), fru…