Search results for " beta"
showing 10 items of 1438 documents
The HLA-DQβ1 insertion is a strong achalasia risk factor and displays a geospatial north-south gradient among Europeans.
2016
Idiopathic achalasia is a severe motility disorder of the esophagus and is characterized by a failure of the lower esophageal sphincter to relax due to a loss of neurons in the myenteric plexus. Most recently, we identified an eight-amino-acid insertion in the cytoplasmic tail of HLA-DQβ1 as strong achalasia risk factor in a sample set from Central Europe, Italy and Spain. Here, we tested whether the HLA-DQβ1 insertion also confers achalasia risk in the Polish and Swedish population. We could replicate the initial findings and the insertion shows strong achalasia association in both samples (Poland P=1.84 × 10(-04), Sweden P=7.44 × 10(-05)). Combining all five European data sets - Central E…
Multicomponent Training Prevents Memory Deficit Related to Amyloid-β Protein-Induced Neurotoxicity.
2021
Background: Alzheimer’s disease (AD) is characterized by the accumulation of the amyloid-β peptide in the brain, leading to early oxidative stress and neurotoxicity. It has been suggested that physical exercise could be beneficial in preventing AD, but studies with multicomponent training are scanty. Objective: Verify the effects of multicomponent exercise training to prevent deficits in recognition memory related to Aβ neurotoxicity. Methods: We subjected Wistar rats to multicomponent training (including aerobic and anaerobic physical exercise and cognitive exercise) and then infused amyloid-β peptide into their hippocampus. Results: We show that long-term multicomponent training prevents …
Autosomal-Recessive Mutations in AP3B2, Adaptor-Related Protein Complex 3 Beta 2 Subunit, Cause an Early-Onset Epileptic Encephalopathy with Optic At…
2016
International audience; Early-onset epileptic encephalopathy (EOEE) represents a heterogeneous group of severe disorders characterized by seizures, interictal epileptiform activity with a disorganized electroencephalography background, developmental regression or retardation, and onset before 1 year of age. Among a cohort of 57 individuals with epileptic encephalopathy, we ascertained two unrelated affected individuals with EOEE associated with developmental impairment and autosomal-recessive variants in AP3B2 by means of whole-exome sequencing. The targeted sequencing of AP3B2 in 86 unrelated individuals with EOEE led to the identification of an additional family. We gathered five addition…
Diagnostic accuracy of cerebrospinal fluid biomarkers measured by chemiluminescent enzyme immunoassay for Alzheimer disease diagnosis.
2020
In the last decades, an important role of cerebrospinal fluid (CSF) biomarkers for Alzheimer disease (AD) diagnosis has emerged. The evaluation of the triad consisting of 42 aminoacid-long amyloid-beta peptide (Aβ42), total Tau (tTau) and Tau phosphorylated at threonine 181 (pTau) have been recently integrated into the research diagnostic criteria of AD. For a long time, the enzyme-linked immunosorbent assay (ELISA) has represented the most commonly used method for the measurement of CSF biomarkers levels. This study aimed to assess the diagnostic accuracy of CSF biomarkers, namely Aβ42, tTau and pTau and their ratio, measured by fully automated CLEIA assay (Lumipulse). We included 96 patie…
Short-Term Effects of Microglia-Specific Mitochondrial Dysfunction on Amyloidosis in Transgenic Models of Alzheimer's Disease.
2018
Reduction of mitochondrial activity is a subtle and early event in the pathogenesis of Alzheimer’s disease. Mitochondrial damage and consequentially enhanced production of reactive oxygen species is particularly occurring in the vicinity of amyloid plaques. Since all cells are affected by mitochondrial damage, analyses of cell type-specific effects are challenging. To study the impact of mitochondrial alterations on microglial activity in a homogeneous genetic background, we generated bone marrow chimeras of irradiated 46-days-old APP-transgenic mice. For reconstitution, bone marrow from CX3CR1-eGFP mice with mitochondria of either non-obese diabetic or C57BL/6J animals was utilized. Succes…
Fasciola hepatica reinfection potentiates a mixed Th1/Th2/Th17/Treg response and correlates with the clinical phenotypes of anemia.
2016
Background: Fascioliasis is a severe zoonotic disease of worldwide extension caused by liver flukes. In human fascioliasis hyperendemic areas, reinfection and chronicity are the norm and anemia is the main sign. Herein, the profile of the Th1/Th2/Th17/Treg expression levels is analyzed after reinfection, correlating them with their corresponding hematological biomarkers of morbidity. Methodology/Principal findings: The experimental design reproduces the usual reinfection/chronicity conditions in human fascioliasis endemic areas and included Fasciola hepatica primo-infected Wistar rats (PI) and rats reinfected at 8 weeks (R8), and at 12 weeks (R12), and negative control rats. In a cross-sect…
Mutations in SKI in Shprintzen-Goldberg syndrome lead to attenuated TGF-β responses through SKI stabilization.
2020
ABSTRACTShprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional corepressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This resul…
Homocysteine concentration in coronary artery disease: Influence of three common single nucleotide polymorphisms.
2017
Whether single nucleotide polymorphisms (SNPs) of homocysteine metabolism enzymes influence the rate of cardiovascular (CV) events in coronary artery disease (CAD) patients remains controversial.In this analysis, 1126 subjects from the AtheroGene study with CAD and 332 control subjects without known CAD were included. The following SNPs were investigated: methylentetrahydrofolate reductase (MTHFR-C667T), methionin synthetase (MS-D919G), and cystathionin beta synthetase (CBS-I278T). The endpoint was the combination of cardiovascular death, stroke, and non-fatal myocardial infarction (N = 286). The median follow-up time was 6.4 years. Kaplan-Meier curve analysis showed an increasing event rat…
Altered Gut Microbiome Composition and Tryptic Activity of the 5xFAD Alzheimer's Mouse Model.
2017
The regulation of physiological gut functions such as peristalsis or secretion of digestive enzymes by the central nervous system via the Nervus vagus is well known. Recent investigations highlight that pathological conditions of neurological or psychiatric disorders might directly interfere with the autonomous neuronal network of the gut - the enteric nervous system, or even derive from there. By using a murine Alzheimer's disease model, we investigated a potential influence of disease-associated changes on gastrointestinal properties. 5xFAD mice at three different ages were compared to wild type littermates in regard to metabolic parameters and enzymes of the gut by fluorimetric enzyme as…
Age-related regulation of bone formation by the sympathetic cannabinoid CB1 receptor.
2017
The endocannabinoid (eCB) system, including its receptors, ligands, and their metabolizing enzymes, plays an important role in bone physiology. Skeletal cannabinoid type 1 (CB1) receptor signaling transmits retrograde signals that restrain norepinephrine (NE) release, thus transiently stimulating bone formation following an acute challenge, suggesting a feedback circuit between sympathetic nerve terminals and osteoblasts. To assess the effect of chronic in vivo occurrence of this circuit, we characterized the skeletal phenotype of mice with a conditional deletion of the CB1 receptor in adrenergic/noradrenergic cells, including sympathetic nerves. Whereas the deletion of the CB1 receptor did…