Search results for "DK"

Strategies for structuring interdisciplinary education in Systems Biology: an European perspective

2016

Systems Biology is an approach to biology and medicine that has the potential to lead to a better understanding of how biological properties emerge from the interaction of genes, proteins, molecules, cells and organisms. The approach aims at elucidating how these interactions govern biological function by employing experimental data, mathematical models and computational simulations. As Systems Biology is inherently multidisciplinary, education within this field meets numerous hurdles including departmental barriers, availability of all required expertise locally, appropriate teaching material and example curricula. As university education at the Bachelor’s level is traditionally built upon…

2021

Familial pancreatic cancer (FPC) is an established but rare inherited tumor syndrome that accounts for approximately 5% of pancreatic ductal adenocarcinoma (PDAC) cases. No major causative gene defect has yet been identified, but germline mutations in predisposition genes BRCA1/2, CDKN2A and PALB2 could be detected in 10–15% of analyzed families. Thus, the genetic basis of disease susceptibility in the majority of FPC families remains unknown. In an attempt to identify new candidate genes, we performed whole-genome sequencing on affected patients from 15 FPC families, without detecting BRCA1/2, CDKN2A or PALB2 mutations, using an Illumina based platform. Annotations from CADD, PolyPhen-2, S…

Rett‐like phenotypes: expanding the genetic heterogeneity to the KCNA2 gene and first familial case of CDKL5 ‐related disease

2016

Several genes have been implicated in Rett syndrome (RTT) in its typical and variant forms. We applied next-generation sequencing (NGS) to evaluate for mutations in known or new candidate genes in patients with variant forms of Rett or Rett-like phenotypes of unknown molecular aetiology. In the first step, we used NGS with a custom panel including MECP2, CDKL5, FOXG1, MEF2C and IQSEC2. In addition to a FOXG1 mutation in a patient with all core features of the congenital variant of RTT, we identified a missense (p.Ser240Thr) in CDKL5 in a patient who appeared to be seizure free. This missense was maternally inherited with opposite allele expression ratios in the proband and her mother. In th…

The prevalence of malnutrition according to the new ESPEN definition in four diverse populations

2016

© 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism.Background & aims: Consensus on the definition of malnutrition has not yet been reached. Recently, The European Society for Clinical Nutrition and Metabolism (ESPEN) proposed a consensus definition of malnutrition. The aim of the present study was to describe the prevalence of malnutrition according to the ESPEN definition in four diverse populations. Methods: In total, 349 acutely ill middle-aged patients, 135 geriatric outpatients, 306 healthy old individuals and 179 healthy young individuals were included in the study. Subjects were screened for risk of malnutrition using the SNAQ. The ESPEN definition of maln…

Synthesis, antitumor activity and CDK1 inhibiton of new thiazole nortopsentin analogues

2017

A new series of thiazole nortopsentin analogues was conveniently synthesized with fair overall yields. The antiproliferative activity of the new derivatives was tested against different human tumor cell lines of the NCI full panel. Four of them showed good antitumor activity with GI(50) values from micro to nanomolar level. The mechanism of the antiproliferative effect of these derivatives, was pro-apoptotic, being associated with externalization of plasma membrane phosphatidylserine and DNA fragmentation. The most active and selective of the new thiazoles confined viable cells in G2/M phase and markedly inhibited in vitro CDK1 activity. (C) 2017 Elsevier Masson SAS.

Molecular Biology of Atherosclerotic Ischemic Strokes

2020

Among the causes of global death and disability, ischemic stroke (also known as cerebral ischemia) plays a pivotal role, by determining the highest number of worldwide mortality, behind cardiomyopathies, affecting 30 million people. The etiopathogenetic burden of a cerebrovascular accident could be brain ischemia (~80%) or intracranial hemorrhage (~20%). The most common site when ischemia occurs is the one is perfused by middle cerebral arteries. Worse prognosis and disablement consequent to brain damage occur in elderly patients or affected by neurological impairment, hypertension, dyslipidemia, and diabetes. Since, in the coming years, estimates predict an exponential increase of people w…

Predicting and mapping human risk of exposure to ixodes ricinus nymphs using climatic and environmental data, Denmark, Norway and Sweden, 2016

2019

Background Tick-borne diseases have become increasingly common in recent decades and present a health problem in many parts of Europe. Control and prevention of these diseases require a better understanding of vector distribution. Aim Our aim was to create a model able to predict the distribution of Ixodes ricinus nymphs in southern Scandinavia and to assess how this relates to risk of human exposure. Methods We measured the presence of I. ricinus tick nymphs at 159 stratified random lowland forest and meadow sites in Denmark, Norway and Sweden by dragging 400 m transects from August to September 2016, representing a total distance of 63.6 km. Using climate and remote sensing environmental…

A selective inhibitor of the Polo-box domain of Polo-like kinase 1 identified by virtual screening

2018

Graphical abstract

Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy

2019

Supplemental Digital Content is available in the text.

Somatic copy number alterations are associated with EGFR amplification and shortened survival in patients with primary glioblastoma.

2019

Glioblastoma (GBM) is the most common malignant primary tumor of the central nervous system. With no effective therapy, the prognosis for patients is terrible poor. It is highly heterogeneous and EGFR amplification is its most frequent molecular alteration. In this light, we aimed to examine the genetic heterogeneity of GBM and to correlate it with the clinical characteristics of the patients. For that purpose, we analyzed the status of EGFR and the somatic copy number alterations (CNAs) of a set of tumor suppressor genes and oncogenes. Thus, we found GBMs with high level of EGFR amplification, low level and with no EGFR amplification. Highly amplified tumors showed histological features of…