👤 Anja Weise

Since apolipoprotein E4 (ApoE4) is associated with therapy-related adverse effects of anti-amyloid-β monoclonal antibodies in Alzheimer's disease, such as amyloid-related imaging abnormalities, methods for determining the ApoE4 status are needed. The Lumipulse Plasma and serum obtained from a single blood draw from 157 patients were analyzed using ApoE4 and Pan-ApoE chemiluminescent enzyme immunoassays. The ApoE4, Pan-ApoE, and the resulting ApoE4/Pan-ApoE ratio showed minimal bias, strong positive correlation and linearity between plasma and serum. Using matrix-specific thresholds, plasma- and serum-derived ApoE4/Pan-ApoE ratios accurately classified the ApoE4 phenotypes in concordance with Using matrix-specific thresholds, the ApoE4/Pan-ApoE ratio in plasma and serum accurately classified the ApoE4 phenotype in concordance with Show less

Refugees and asylum seekers encounter numerous post-migration living difficulties (PMLDs) that can substantially affect their mental health. However, the role of PMLDs remains insufficiently explored, particularly in clinical refugee populations. This study aimed to identify subgroups based on patterns of PMLD by examining their relationship with depressive symptoms and determining which stressors function as key bridges. This study reports a secondary analysis of baseline data from the ReTreat trial. Data were collected from 141 refugees and asylum seekers enrolled in a multicentre randomized controlled trial of a culturally adapted CBT program in Germany. Participants completed measures of depressive symptoms (PHQ-9) and post-migration stressors (27-item checklist). Latent Profile Analysis (LPA) was used to identify distinct burden profiles. Exploratory Factor Analysis (EFA) examined the dimensionality of PMLDs. Network analysis was conducted to investigate symptom-stressor connectivity. Three latent profiles emerged: Class 1 showed elevated distress across all domains; Class 2 was characterized by family separation and homesickness; and Class 3 exhibited minimal post-migration stress. EFA of PMLDS supported a four-factor solution: institutional/legal stressors, structural hardship, health/service access, and emotional/family-related strain. Depressive symptoms differed significantly across profiles, with highest scores in the high burden group (Class 1). Network analysis identified institutional/legal and emotional/family-related stressors as central bridge nodes linking PMLDs to depressive symptoms. PMLDs are multidimensional and heterogeneously distributed among forcibly displaced individuals. Legal insecurity and emotional strain are particularly influential in connecting environmental hardship to depressive symptoms. This study uses baseline data from a registered randomized controlled trial (DRKS00021536). Show less

Guanine-quadruplex (G-quadruplex) structures in mRNAs have been shown to modulate gene expression. However, the overall biological relevance of this process is under debate, as cellular helicases unwind G-quadruplex structures. The helicase Rhau (encoded by the DHX36 gene) was reported to be the major source of RNA G-quadruplex resolving activity in lysates of human cells. In the current study, we depleted Rhau by RNAi-mediated silencing and analyzed the effect on proteins whose mRNAs harbor a G-quadruplex motif in their 5'-UTRs. A targeted investigation of the proto-oncogenes Bcl-2 and NRAS, which are well-known examples for the translational repression of G-quadruplex structures, did not reveal effects caused by Rhau silencing. We therefore carried out a global analysis of changes in protein levels by label-free quantification using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Following Rhau knockdown, of all the identified proteins, only 1.9% were significantly downregulated to at least 70%. According to a bioinformatic analysis with the QGRS mapper, 33% of the downregulated proteins were predicted to harbor a G-quadruplex motif in the 5'-UTR of their respective mRNAs, compared to only 11% in the complete dataset. This indicates that in an unexpectedly small set of genes, in which G-quadruplex motifs are unusually common in the 5'-UTR of their mRNAs, Rhau helicase is responsible for the regulation of their expression. Show less

To assess potential effects of variants in six lipid modulating genes (SORT1, HMGCR, MLXIPL, FADS2, APOE and MAFB) on early development of dyslipidemia independent of the degree of obesity in children, we investigated their association with total (TC), low density lipoprotein (LDL-C), high density lipoprotein (HDL-C) cholesterol and triglyceride (TG) levels in 594 children. Furthermore, we evaluated the expression profile of the candidate genes during human adipocyte differentiation. Expression of selected genes increased 10(1) to >10(4) fold during human adipocyte differentiation, suggesting a potential link with adipogenesis. In genetic association studies adjusted for age, BMI SDS and sex, we identified significant associations for rs599839 near SORT1 with TC and LDL-C and for rs4420638 near APOE with TC and LDL-C. We performed Bayesian modelling of the combined lipid phenotype of HDL-C, LDL-C and TG to identify potentially causal polygenic effects on this multi-dimensional phenotype and considering obesity, age and sex as a-priori modulating factors. This analysis confirmed that rs599839 and rs4420638 affect LDL-C. We show that lipid modulating genes are dynamically regulated during adipogenesis and that variants near SORT1 and APOE influence lipid levels independent of obesity in children. Bayesian modelling suggests causal effects of these variants. Show less