Publications by authors named "Karl Schafer"

The developing nervous system is highly vulnerable to environmental toxicants especially pesticides. Glyphosate pesticide induces neurotoxicity both in humans and rodents, but so far only when exposed to higher concentrations. A few studies, however, have also reported the risk of general toxicity of glyphosate at concentrations comparable to allowable limits set up by environmental protection authorities.

View Article and Find Full Text PDF

Intensive agriculture activities, industrialization and growing numbers of wastewater treatment plants along river banks collectively contribute to the elevated levels of neurotoxic pollutants in natural water reservoirs across Europe. We established an in vitro bioassay based upon neural stem cells isolated from the subventricular zone of the postnatal mouse to evaluate the neurotoxic potential of raw wastewater, treated sewage effluent, groundwater and drinking water. The toxic potential of water samples was evaluated employing viability, proliferation, differentiation and migration assays.

View Article and Find Full Text PDF

Troxerutin (TRX) is a water-soluble flavonoid which occurs commonly in the edible plants. Recent studies state that TRX improves the functionality of the nervous system and neutralizes Amyloid-ß induced neuronal toxicity. In this study, an in vitro assay based upon Neural stem cell (NSCs) isolated from the subventricular zone of the postnatal balb/c mice was established to explore the impact of TRX on individual neurogenesis processes in general and neuroprotective effect against ß-amyloid 1-42 (Aß42) induced inhibition in differentiation in particular.

View Article and Find Full Text PDF

Alzheimer's disease (AD) is the leading cause of dementia with very limited therapeutic options. Amyloid β (Aβ) and phosphorylated Tau (p-Tau) are key pathogenic molecules in AD. P38α-MAPK is specifically activated in AD lesion sites.

View Article and Find Full Text PDF

Purpose: To report on 10 years of high-risk service screening with annual MRI in the German Consortium for Hereditary Breast and Ovarian Cancer (GC-HBOC).

Methods: A cohort of 4,573 high-risk, previously unaffected women (954 BRCA1 carriers, 598 BRCA2 carriers, 3021 BRCA1/2 non-carriers) participating in the GC-HBOC surveillance program was prospectively followed. Screening outcomes for 14,142 screening rounds with MRI between 2006 and 2015 were analyzed and stratified by risk group, type of screening round, and age.

View Article and Find Full Text PDF

Nanosizing represents a straight forward technique to unlock the biological activity of complex plant materials. The aim of this study was to develop herbal nanoparticles with medicinal value from dried leaves and stems of with the aid of ball-milling, high speed stirring, and high-pressure homogenization techniques. The milled nanoparticles were characterized using laser diffraction analysis, photon correlation spectroscopy analysis, and light microscopy.

View Article and Find Full Text PDF

In several gut inflammatory or cancer diseases, cell-cell interactions are compromised, and an increased cytoplasmic expression of β-catenin is observed. Over the last decade, numerous studies provided compelling experimental evidence that the loss of cadherin-mediated cell adhesion can promote β-catenin release and signaling without any specific activation of the canonical Wnt pathway. In the present work, we took advantage of the ability of lipofectamine-like reagent to cause a synchronous dissociation of adherent junctions in cells isolated from the rat enteric nervous system (ENS) for obtaining an in vitro model of deregulated β-catenin signaling.

View Article and Find Full Text PDF

Background: In the last years, Wnt signaling was demonstrated to regulate inflammatory processes. In particular, an increased expression of Wnts and Frizzled receptors was reported in inflammatory bowel disease (IBD) and ulcerative colitis to exert both anti- and pro-inflammatory functions regulating the intestinal activated nuclear factor κB (NF-кB), TNFa release, and IL10 expression.

Methods: To investigate the role of Wnt pathway in the response of the enteric nervous system (ENS) to inflammation, neurons and glial cells from rat myenteric plexus were treated with exogenous Wnt3a and/or LPS with or without supporting neurotrophic factors such as basic fibroblast growth factor (bFGF), epithelial growth factor (EGF), and glial cell-derived neurotrophic factor (GDNF).

View Article and Find Full Text PDF

Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning.

View Article and Find Full Text PDF

An atmospheric pressure laser desorption/ionization mass spectrometry imaging ion source has been developed that combines high spatial resolution and high mass resolution for the in situ analysis of biological tissue. The system is based on an infrared laser system working at 2.94 to 3.

View Article and Find Full Text PDF

Cell responses to surface and contact cell guidance are of great interest in bio-applications especially on nano- and micro scale features. Recently we showed selective cell responses on Al/Al2O3, bi-phasic nanowires (NWs). In this context, Al/Al2O3 NWs were synthesized by the chemical vapor deposition of (tBuOAIH2)2.

View Article and Find Full Text PDF

Success in discovering bioactive peptide mimetics is often limited by the difficulties in correctly transposing known binding elements of the active peptide onto a small and metabolically more stable scaffold while maintaining bioactivity. Here we describe a scanning approach using a library of pyranose-based peptidomimetics that is structurally diverse in a systematic manner, designed to cover all possible conformations of tripeptide motifs containing two aromatic groups and one positive charge. Structural diversity was achieved by efficient selection of various chemoforms, characterized by a choice of pyranose scaffold of defined chirality and substitution pattern.

View Article and Find Full Text PDF

Objectives: Imbalanced apoptosis of enterocytes is likely to be 1 of the mechanisms underlying Crohn's disease (CD). Apoptosis of enterocytes is regulated by glial-derived neurotrophic factor (GDNF), which is increased in CD. The cellular source of GDNF during gut inflammation is unclear.

View Article and Find Full Text PDF

Few reported inhibitors of secretory phospholipase A(2) enzymes truly inhibit the IIa human isoform (hnpsPLA(2)-IIa) noncovalently at submicromolar concentrations. Herein, the simple chiral precursor D-tyrosine was derivatised to give a series of potent new inhibitors of hnpsPLA(2)-IIa. A 2.

View Article and Find Full Text PDF

An efficient method for preparing conformationally restricted cyclopentenyl-glutamate analogues in a regioselective and diastereoselective manner has been developed using a formal [3 + 2] cycloaddition reaction of dehydroamino acids. Methods for preparing optically active versions of these compounds have also been devised. Of these compounds, (S)-2 is an agonist at the mGlu5 (EC(50) 18 microM) and mGlu2 (EC(50) 45 microM) receptors.

View Article and Find Full Text PDF