Search results for "131"
showing 10 items of 342 documents
Ticagrelor, but not clopidogrel, reduces arterial thrombosis via endothelial tissue factor suppression
2017
The P2Y12 antagonist ticagrelor reduces mortality in patients with acute coronary syndrome (ACS), compared with clopidogrel, and the mechanisms underlying this effect are not clearly understood. Arterial thrombosis is the key event in ACS; however, direct vascular effects of either ticagrelor or clopidogrel with focus on arterial thrombosis and its key trigger tissue factor have not been previously investigated.Methods and results: Human aortic endothelial cells were treated with ticagrelor or clopidogrel active metabolite (CAM) and stimulated with tumour necrosis factor-alpha (TNF-α); effects on procoagulant tissue factor (TF) expression and activity, its counter-player TF pathway inhibito…
Origin of modern syphilis and emergence of a pandemic Treponema pallidum cluster
2016
The abrupt onslaught of the syphilis pandemic that started in the late fifteenth century established this devastating infectious disease as one of the most feared in human history1 . Surprisingly, despite the availability of effective antibiotic treatment since the mid-twentieth century, this bacterial infection, which is caused by Treponema pallidum subsp. pallidum (TPA), has been re-emerging globally in the last few decades with an estimated 10.6 million cases in 2008 (ref. 2). Although resistance to penicillin has not yet been identified, an increasing number of strains fail to respond to the secondline antibiotic azithromycin3. Little is known about the genetic patterns in current infec…
Fasciola hepatica eggs in paleofaeces of the Persian onager Equus hemionus onager, a donkey from Chehrabad archaeological site, dating back to the Sa…
2018
Fascioliasis is a highly pathogenic zoonotic disease caused by the liver trematodes Fasciola hepatica and F. gigantica. Within the multidisciplinary initiative against this disease, there is the aim of understanding how this disease reached a worldwide distribution, with important veterinary and medical repercussions, by elucidating the spreading steps followed by the two fasciolids from their paleobiogeograhical origins. Fasciola eggs were detected in paleofaeces of a donkey, probably the present-day endangered Persian onager Equus hemionus onager, found in the Chehrabad salt mine archaeological site, Zanjan province, northwestern Iran. The biological remains dated back to the Sassanid per…
The anti-oxidative role of cytoglobin in podocytes: implications for a role in chronic kidney disease
2020
Abstract: Aims: Cytoglobin (CYGB) is a member of the mammalian globin family of respiratory proteins. Despite extensive research efforts, its physiological role remains largely unknown, but potential functions include reactive oxygen species (ROS) detoxification and signaling. Accumulating evidence suggests that ROS play a crucial role in podocyte detachment and apoptosis during diabetic kidney disease. This study aimed to explore the potential antioxidative renal role of CYGB both in vivo and in vitro. Results: Using a Cygb-deficient mouse model, we demonstrate a Cygb-dependent reduction in renal function, coinciding with a reduced number of podocytes. To specifically assess the putative a…
Assessing statistical significance in multivariable genome wide association analysis
2016
Motivation: Although Genome Wide Association Studies (GWAS) genotype a very large number of single nucleotide polymorphisms (SNPs), the data are often analyzed one SNP at a time. The low predictive power of single SNPs, coupled with the high significance threshold needed to correct for multiple testing, greatly decreases the power of GWAS. Results: We propose a procedure in which all the SNPs are analyzed in a multiple generalized linear model, and we show its use for extremely high-dimensional datasets. Our method yields P-values for assessing significance of single SNPs or groups of SNPs while controlling for all other SNPs and the family wise error rate (FWER). Thus, our method tests whe…
An overview of the molecular mechanisms underlying development and progression of bicuspid aortic valve disease
2019
Bicuspid aortic valve (BAV) is a common congenital heart malformation frequently associated with the development of aortic valve diseases and severe aortopathy, such as aortic dilatation, aneurysm and dissection. To date, different genetic loci have been identified in syndromic and non- syndromic forms of BAV. Among these, genes involved in the regulation of extracellular matrix remodelling, epithelial to mesenchymal transition and nitric oxide metabolism appear to be the main contributors to BAV pathogenesis. However, no- single gene model explains BAV inheritance, suggesting that more factors are simultaneously involved. In this regard, characteristic epigenetic and immunological profiles…
A Library-Based Screening Strategy for the Identification of DARPins as Ligands for Receptor-Targeted AAV and Lentiviral Vectors
2021
Delivering genes selectively to the therapeutically relevant cell type is among the prime goals of vector development. Here, we present a high-throughput selection and screening process that identifies designed ankyrin repeat proteins (DARPins) optimally suited for receptor-targeted gene delivery using adeno-associated viral (AAV) and lentiviral (LV) vectors. In particular, the process includes expression, purification, and in situ biotinylation of the extracellular domains of target receptors as Fc fusion proteins in mammalian cells and the selection of high-affinity binders by ribosome display from DARPin libraries each covering more than 1012 variants. This way, DARPins specific for the …
Outcome of Patients With Differentiated Thyroid Cancer Treated With 131-Iodine on the Basis of a Detectable Serum Thyroglobulin Level After Initial T…
2019
Background: In patients with differentiated thyroid cancer (DTC) and raising serum thyroglobulin (Tg) after total or near-total thyroidectomy and 131I remnant ablation an empiric 131I therapy may be considered. However, outcome data after empiric therapy in did not show a clear evidence of improved survival. We assessed the efficacy of such empiric 131I therapy in patients with DTC and evaluated the long-term outcome.Methods: A total of 100 patients with DTC showing raised Tg level during follow-up after thyroidectomy and 131I ablation were treated with a further 131I therapy (6.1 ± 1.7 GBq). Whole-body scan (WBS) was performed 5–7 days after therapy. Tg value at 12 months after 131I therap…
Development and validation of the Healthy-Unhealthy Music Scale.
2015
Background Music is an integral part of life in youth, and although it has been acknowledged that musical behavior reflects broader psychosocial aspects of adolescent behavior, no measurement instruments have been specifically designed for assessing musical engagement as an indicator of adolescent wellbeing and/or symptomatology. This study was conducted in order to develop and validate a scale for assessing musical engagement as an indicator of proneness for depression in youth. Method Items were developed based on the literature and a prior grounded theory analysis and three surveys (N = 54, N = 187, N = 211) were conducted to select, refine, test, and validate the items. Scale structure …
Metabolic detoxification: implications for thresholds.
2000
The fact that chemical carcinogenesis involves single, isolated, essentially irreversible molecular events as discrete steps, several of which must occur in a row to finally culminate in the development of a malignancy, rather suggests that an absolute threshold for chemical carcinogens may not exist. However, practical thresholds may exist due to saturable pathways involved in the metabolic processing, especially in the metabolic inactivation, of such compounds. An important example for such a pathway is the enzymatic hydrolysis of epoxides via epoxide hydrolases, a group of enzymes for which the catalytic mechanism has recently been established. These enzymes convert their substrates via…