Search results for "Mod"
showing 10 items of 39605 documents
Consequences of single-locus and tightly linked genomic architectures for evolutionary responses to environmental change
2020
AbstractGenetic and genomic architectures of traits under selection are key factors influencing evolutionary responses. Yet, knowledge of their impacts has been limited by a widespread assumption that most traits are controlled by unlinked polygenic architectures. Recent advances in genome sequencing and eco-evolutionary modelling are unlocking the potential for integrating genomic information into predictions of population responses to environmental change. Using eco-evolutionary simulations, we demonstrate that hypothetical single-locus control of a life history trait produces highly variable and unpredictable harvesting-induced evolution relative to the classically applied multi-locus mo…
Retinoic Acid affects Lung Adenocarcinoma growth by inducing differentiation via GATA6 activation and EGFR and Wnt inhibition
2016
AbstractA fundamental task in cancer research aims at the identification of new pharmacological therapies that can affect tumor growth. Differentiation therapy might exploit this function not only for hematological diseases, such as acute promyelocytic leukemia (APML) but also for epithelial tumors, including lung cancer. Here we show that Retinoic Acid (RA) arrests in vitro and in vivo the growth of Tyrosine Kinase Inhibitors (TKI) resistant Non Small Cell Lung Cancer (NSCLC). In particular, we found that RA induces G0/G1 cell cycle arrest in TKI resistant NSCLC cells and activates terminal differentiation programs by modulating the expression of GATA6, a key transcription factor involved …
Engineering of a DNA Polymerase for Direct m6A Sequencing
2017
Methods for the detection of RNA modifications are of fundamental importance for advancing epitranscriptomics. N6-methyladenosine (m6A) is the most abundant RNA modification in mammalian mRNA and is involved in the regulation of gene expression. Current detection techniques are laborious and rely on antibody-based enrichment of m6A-containing RNA prior to sequencing, since m6A modifications are generally "erased" during reverse transcription (RT). To overcome the drawbacks associated with indirect detection, we aimed to generate novel DNA polymerase variants for direct m6A sequencing. Therefore, we developed a screen to evolve an RT-active KlenTaq DNA polymerase variant that sets a mark for…
New Therapeutic Implications of Endothelial Nitric Oxide Synthase (eNOS) Function/Dysfunction in Cardiovascular Disease
2019
The Global Burden of Disease Study identified cardiovascular risk factors as leading causes of global deaths and life years lost. Endothelial dysfunction represents a pathomechanism that is associated with most of these risk factors and stressors, and represents an early (subclinical) marker/predictor of atherosclerosis. Oxidative stress is a trigger of endothelial dysfunction and it is a hall-mark of cardiovascular diseases and of the risk factors/stressors that are responsible for their initiation. Endothelial function is largely based on endothelial nitric oxide synthase (eNOS) function and activity. Likewise, oxidative stress can lead to the loss of eNOS activity or even “uncoupli…
Type of chromosome abnormality affects embryo morphology dynamics.
2016
Objective To study the differences in the cleavage time between types of embryo chromosomal abnormalities and elaborate algorithm to exclude aneuploid embryos according to the likelihood to be euploid. Design Retrospective cohort study. Setting University affiliated private center. Patient(s) Preimplantational genetic screening patients (n = 112) including cases of advanced maternal age, repeated implantation failure, and recurrent miscarriage. A total of 485 embryos were analyzed. Intervention(s) None. Main Outcome Measure(s) All biopsied embryos were cultured in an incubator with time-lapse technology, cleavage timing from insemination to day 3 and all kinetic parameters that have been de…
Dynamic clonal remodelling in breast cancer metastases is associated with subtype conversion
2019
Background: Changes in the clinical subtype (CS) and intrinsic subtype (IS) between breast cancer (BC) metastases and corresponding primary tumours have been reported. However, their relationship with tumour genomic changes remains poorly characterised. Here, we analysed the association between genomic remodelling and subtype conversion in paired primary and metastatic BC samples. Methods: A total of 57 paired primary and metastatic tumours from GEICAM/2009-03 (ConvertHER, NCT01377363) study participants with centrally assessed CS (n = 57) and IS (n = 46) were analysed. Targeted capture and next-generation sequencing of 202 genes on formalin-fixed paraffin-embedded samples was performed. Th…
A single preoperative pain neuroscience education: Is it an effective strategy for patients with carpal tunnel syndrome?
2019
Patients undergoing carpal tunnel release surgery may continue to experience pain despite the intervention. This symptom may be modulated by psychosocial factors including depression, catastrophic thinking, and kinesiophobia. Pain neuroscience education (PNE) has been found to be effective when combined with therapeutic exercise in patients with chronic pain, but this strategy has not been evaluated in patients with persistent hand pain. The findings of this study indicate that a single preoperative PNE session in combination with therapeutic exercise does not provide added benefits in comparison to standard preoperative care plus therapeutic exercise. Future studies should evaluate if pati…
Hepatitis delta virus infection in a large cohort of chronic hepatitis B patients in Ethiopia.
2017
Background Hepatitis D Virus (HDV)-infection is associated with a more severe outcome in patients with chronic hepatitis B (CHB); however, little is known about the presence of HDV in sub-Saharan Africa. We aimed to determine the prevalence of HDV-infection, as well as its clinical, biological and virological characteristics, in a large CHB cohort in Ethiopia. Methods In total, 1267 HIV-negative CHB patients at St. Paul's Hospital Millennium Medical College in Addis Ababa were screened for anti-HDV antibodies using ELISA assays. Confirmed positive samples were further tested for HDV RNA using a consensus commercial real-time RT-PCR assay. HDV genotypes were also determined for RNA positive …
Are the Motives for Food Choices Different in Orthorexia Nervosa and Healthy Orthorexia?
2019
Recent research points to the bidimensional nature of orthorexia, with one dimension related to interest in healthy eating (healthy orthorexia) and another dimension related to a pathological preoccupation with eating healthily (orthorexia nervosa). Research was needed to provide further support for this differentiation. We examined the food-choice motives related to both aspects of orthorexia. Participants were 460 students from a Spanish university who completed the Teruel Orthorexia Scale and the Food Choice Questionnaire. By means of structural equation modeling, we analyzed the relationship between orthorexia, food-choice motives, gender, body mass index, and age. The motives predictin…
Succinate receptor mediates intestinal inflammation and fibrosis.
2018
Succinate, an intermediate of the tricarboxylic acid cycle, is accumulated in inflamed areas and its signaling through succinate receptor (SUCNR1) regulates immune function. We analyze SUCNR1 expression in the intestine of Crohn's disease patients and its role in murine intestinal inflammation and fibrosis. We show that both serum and intestinal succinate levels and SUCNR1 expression in intestinal surgical resections were higher in CD patients than in controls. SUCNR1 co-localized with CD86, CD206, and alpha-SMA(+) cells in human intestine and we found a positive and significant correlation between SUCNR1 and alpha-SMA expression. In human isolated fibroblasts from CD patients SUCNR1 expres…