Search results for "cept"
showing 10 items of 15508 documents
Experienced Migratory Bats Integrate the Sun's Position at Dusk for Navigation at Night.
2019
Summary From bats to whales, millions of mammals migrate every year. However, their navigation capacity for accomplishing long-distance movements remains remarkably understudied and lags behind by five decades compared to other animals [ 1 , 2 ]—partly because, unlike for other taxa, such as birds and sea turtles, no small-scale orientation assay has so far been developed. Yet recently, bats became a model to investigate which cues mammals use for long-range navigation, and, surprisingly for nocturnal animals, sunset cues, and particularly polarized-light cues, appear to be crucial for calibration of the magnetic-compass system in non-migratory bats [ 3 , 4 , 5 ]. This does not appear to ho…
Protective and causative killer Ig-like receptor (KIR) and metalloproteinase genetic patterns associated with Herpes simplex virus 1 (HSV-1) encephal…
2020
Abstract Background The cerebral innate immune system has a critical role in control processes of viral replication in the brain after primary infactivo and immunologic disregulation and inflammation has been reported as a primary determinant of pathogenesis and prognosis of subsequent HSV-1 related encephalitis (HSE). Interaction linking LTR3-activated DCs is also represented by the killer Ig-like receptor (KIR) + pathways on NK cells. Only a few studies analyzed the role of of MMP-9 activity regulating genetic polymorphism on clinical outcome of viral infections. Susceptibility to symptomatic encephalitis depends on SNC viral invasion and BBB disruption. We hypothesize that certain KIR ge…
Inflammasome activation in Ankylosing Spondylitis is associated to gut dysbiosis
2021
Objective: We undertook this study to evaluate the activation and functional relevance of inflammasome pathways in ankylosing spondylitis (AS) patients and rodent models and their relationship to dysbiosis. Methods: An inflammasome pathway was evaluated in the gut and peripheral blood from 40 AS patients using quantitative reverse transcriptase–polymerase chain reaction (qRT-PCR), immunohistochemistry (IHC), flow cytometry, and confocal microscopy, and was compared to that of 20 healthy controls and 10 patients with Crohn’s disease. Bacteria was visualized using silver stain in human samples, and antibiotics were administered to HLA–B27–transgenic rats. The NLRP3 inhibitor MCC950 was admini…
Plasmacytoid dendritic cells promote systemic sclerosis with a key role for TLR8
2018
Systemic sclerosis (SSc) is a multisystem life-threatening fibrosing disorder that lacks effective treatment. The link between the inflammation observed in organs such as the skin and profibrotic mechanisms is not well understood. The plasmacytoid dendritic cell (pDC) is a key cell type mediating Toll-like receptor (TLR)-induced inflammation in autoimmune disease patients, including lupus and skin diseases with interface dermatitis. However, the role of pDCs in fibrosis is less clear. We show that pDCs infiltrate the skin of SSc patients and are chronically activated, leading to secretion of interferon-α (IFN-α) and CXCL4, which are both hallmarks of the disease. We demonstrate that the s…
Genome-Wide Association Study of the Modified Stumvoll Insulin Sensitivity Index Identifies BCL2 and FAM19A2 as Novel Insulin Sensitivity Loci.
2016
Genome-wide association studies (GWAS) have found few common variants that influence fasting measures of insulin sensitivity. We hypothesized that a GWAS of an integrated assessment of fasting and dynamic measures of insulin sensitivity would detect novel common variants. We performed a GWAS of the modified Stumvoll Insulin Sensitivity Index (ISI) within the Meta-Analyses of Glucose and Insulin-Related Traits Consortium. Discovery for genetic association was performed in 16,753 individuals, and replication was attempted for the 23 most significant novel loci in 13,354 independent individuals. Association with ISI was tested in models adjusted for age, sex, and BMI and in a model analyzing t…
Differential role of interleukin-1β in neuroinflammation-induced impairment of spatial and nonspatial memory in hyperammonemic rats.
2019
Activated microglia and increased brain IL-1β play a main role in cognitive impairment in much pathology. We studied the role of IL-1β in neuroinflammation-induced impairment of the following different types of learning and memory: novel object recognition (NOR), novel object location (NOL), spatial learning, reference memory (RM), and working memory (WM). All these processes are impaired in hyperammonemic rats. We assessed which of these types of learning and memory are restored by blocking the IL-1 receptor in vivo in hyperammonemic rats and the possible mechanisms involved. Blocking the IL-1 receptor reversed microglial activation in the hippocampus, perirhinal cortex, and prefrontal cor…
New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics
2017
Item does not contain fulltext Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic ne…
Repurposing of the Antiepileptic Drug Levetiracetam to Restrain Neuroendocrine Prostate Cancer and Inhibit Mast Cell Support to Adenocarcinoma
2021
A relevant fraction of castration-resistant prostate cancers (CRPC) evolve into fatal neuroendocrine (NEPC) tumors in resistance to androgen deprivation and/or inhibitors of androgen receptor pathway. Therefore, effective drugs against both CRPC and NEPC are needed. We have previously described a dual role of mast cells (MCs) in prostate cancer, being capable to promote adenocarcinoma but also to restrain NEPC. This finding suggests that a molecule targeting both MCs and NEPC cells could be effective against prostate cancer. Using an in silico drug repurposing approach, here we identify the antiepileptic drug levetiracetam as a potential candidate for this purpose. We found that the protein…
The significance of epidermal growth factor receptor uncommon mutations in non-small cell lung cancer: A systematic review and critical appraisal
2020
Uncommon epidermal growth factor receptor (EGFR) mutations collectively account for 10% of EGFR mutations, harboring heterogeneous molecular alterations within exons 18-21 with clinically variable responses to EGFR tyrosine kinase inhibitors (TKIs) in advanced Non-Small Cell Lung Cancer (NSCLC) patients. In addition, with the introduction of different NGS gene approach an improvement of EGFR mutations detection was reported. Today, no specific studies have prospectively evaluated uncommon sensitizing mutations in detail and no firm standard of care has been established in the first-line setting. The aim of this comprehensive review is to critically consider the clinical role of uncommon EGF…
Increased PD-1 Expression and Altered T Cell Repertoire Diversity Predict Mortality in Patients with Septic Shock: A Preliminary Study
2017
Sepsis causes impairment of innate and adaptive immunity by multiple mechanisms, including depletion of immune effector cells and T cell exhaustion. Although lymphocyte dysfunction is associated with increased mortality and potential reactivation of latent viral infection in patients with septic shock, the relation between viral reactivation and lymphocyte dysfunction is obscure. The objectives of this study were 1) to determine the relation of lymphocyte dysfunction to viral reactivation and mortality, and 2) to evaluate recovery of lymphocyte function during septic shock, including T cell receptor (TCR) diversity and the expression of programmed death 1 (PD-1). In 18 patients with septic …