Search results for " complex"

Ferritin and C-reactive protein are predictive biomarkers of mortality and macrophage activation syndrome in adult onset Still's disease. Analysis of…

2020

ObjectiveTo assess the predictive role of ferritin and C-reactive protein (CRP) on occurrence of macrophage activation syndrome (MAS) and mortality in patients with adult onset Still's disease (AOSD), a rare and severe disease, included in the multicentre Gruppo Italiano di Ricerca in Reumatologia Clinica e Sperimentale (GIRRCS) cohort.MethodsThe predictive role, at the time of diagnosis, of serum levels of ferritin and CRP on occurrence of MAS and mortality, was evaluated by logistic regression analyses and receiver-operating characteristic (ROC) curves were built to identify patients at high risk of MAS and mortality, respectively.ResultsIn assessed 147 patients with AOSD, levels of ferri…

Evidence of gene orthology and trans-species polymorphism, but not of parallel evolution, despite high levels of concerted evolution in the major his…

2016

17 pages; International audience; The major histocompatibility complex (MHC) is a cornerstone in the study of adaptive genetic diversity. Intriguingly, highly polymorphic MHC sequences are often not more similar within species than between closely related species. Divergent selection of gene duplicates, balancing selection maintaining trans-species polymorphism (TSP) that predate speciation and parallel evolution of species sharing similar selection pressures can all lead to higher sequence similarity between species. In contrast, high rates of concerted evolution increase sequence similarity of duplicated loci within species. Assessing these evolutionary models remains difficult as related…

Preproinsulin designer antigens excluded from endoplasmic reticulum suppressed diabetes development in nod mice by dna vaccination

2019

DNA vaccines against autoimmune type 1 diabetes (T1D) contain a nonpredictable risk to induce autoreactive T cell responses rather than a protective immunity. Little is known if (and how) antigen expression and processing requirements favor the induction of autoreactive or protective immune responses by DNA immunization. Here, we analyzed whether structural properties of preproinsulin (ppins) variants and/or subcellular targeting of ppins designer antigens influence the priming of effector CD8+ T cell responses by DNA immunization. Primarily, we used H-2b RIP-B7.1 tg mice, expressing the co-stimulator molecule B7.1 in beta cells, to identify antigens that induce or fail to induce autoreacti…

Protoparvovirus Knocking at the Nuclear Door

2017

Protoparvoviruses target the nucleus due to their dependence on the cellular reproduction machinery during the replication and expression of their single-stranded DNA genome. In recent years, our understanding of the multistep process of the capsid nuclear import has improved, and led to the discovery of unique viral nuclear entry strategies. Preceded by endosomal transport, endosomal escape and microtubule-mediated movement to the vicinity of the nuclear envelope, the protoparvoviruses interact with the nuclear pore complexes. The capsids are transported actively across the nuclear pore complexes using nuclear import receptors. The nuclear import is sometimes accompanied by structural chan…

The quality of life - an indicator for assessing the recovery program in patients diagnosed with degenerative disorders

2020

Introduction. Osteoarthritis is a chronic joint disease, a progressive non-inflammatory arthropathy-type. Globally, around 1.7 billion people are affected by musculoskeletal and rheumatic diseases, which indicates an increase in the last 20 years of around 45%. Material and method. The objectives of the treatment of patients diagnosed with osteoarthritis were: decreasing the pain, increasing joint mobility, muscle strength, trophic and muscle tone, increasing the quality of life and reintegration into the social and family environment. Demographic data and the functional status were assessed using the VAS scale, the WOMAC scale, the QOL scale. Results and discussions. The pain, the most imp…

Exploring the association between extra-cardiac troponin elevations and risk of future mortality

2019

Although the measurement of cardiac troponin I (cTnI) and T (cTnT) has now become the cornerstone for diagnosing cardiac injury, both ischemic and non-ischemic, recent evidence has become available that many patients display extra-cardiac causes of cTn elevations and carry a considerably enhanced risk of future mortality. The current literature data suggests that cTn elevations may be equally common in patients with cardiac and extra-cardiac diseases. Among the latter cohort of patients, the leading extra-cardiac diseases which may be responsible for either cTnI or cTnT elevations include infectious diseases/sepsis, pulmonary disorders, renal failure, malignancy, as well as gastrointestinal…

2019

Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activ…

Generation of TCR-engineered reference cell samples to control T-cell assay performance

2020

In vitro cellular assays analyzing antigen-specific T cells are characterized by their high complexity and require controlled conditions to lower experimental variations. Without standard cellular reagents, it is difficult to compare results over time and across institutions. To overcome this problem, a simple and robust technology was developed to generate TCR-engineered reference samples (TERS) containing defined numbers of antigen-specific T cells. Utilization of TERS enables performance control of three main T-cell assays: MHC-peptide multimer staining, IFN-gamma ELISpot and cytokine flow cytometry. TERS continuously deliver stable results and can be stored for longer periods of time. H…

Local adaptation in populations ofMycobacterium tuberculosisendemic to the Indian Ocean Rim

2020

AbstractLineage 1 (L1) and 3 (L3) are two lineages of theMycobacterium tuberculosiscomplex (MTBC), causing tuberculosis (TB) in humans. L1 and L3 are endemic to the Rim of the Indian Ocean, the region that accounts for most of the world’s new TB cases. Despite their relevance for this region, L1 and L3 remain understudied. Here we analyzed 2,938 L1 and 2,030 L3 whole genome sequences originating from 69 countries. We show that South Asia played a central role in the dispersion of these two lineages to neighboring regions. Moreover, we found that L1 exhibits signatures of local adaptation at theesxHlocus, a gene coding for a secreted effector that targets the human endosomal sorting complex,…

The Multiple Sclerosis Genomic Map: Role of peripheral immune cells and resident microglia in susceptibility

2017

Abstract:We assembled and analyzed genetic data of 47,351 multiple sclerosis (MS) subjects and 68,284 control subjects and establish a reference map of the genetic architecture of MS that includes 200 autosomal susceptibility variants outside the major histocompatibility complex (MHC), one chromosome X variant, and 32 independent associations within the extended MHC. We used an ensemble of methods to prioritize up to 551 potentially associated MS susceptibility genes, that implicate multiple innate and adaptive pathways distributed across the cellular components of the immune system. Using expression profiles from purified human microglia, we do find enrichment for MS genes in these brain -…