Refine
Has Fulltext
- yes (61)
Is part of the Bibliography
- yes (61)
Year of publication
Document Type
- Journal article (59)
- Conference Proceeding (2)
Keywords
- CML (3)
- Chirurgie (3)
- gene expression (3)
- Biochemie (2)
- Virologie (2)
- activation (2)
- brain (2)
- density (2)
- epithelial cells (2)
- psychiatry (2)
- reactive electrophilic species (2)
- salt stress (2)
- 12-oxo-phytodienoic acid (1)
- 5-HTTLPR (1)
- 53BP1 (1)
- ABCG2 (1)
- ADHD (1)
- AcrAB-TolC efflux pump (1)
- Affenimmundefizienzvirus (1)
- Alpha therapy (1)
- Alzheimer's disease (1)
- Apoptosis (1)
- Autoimmune diseases (1)
- B cells (1)
- BCR‐ABL (1)
- Biomarker (1)
- Bone marrow transplantantation (1)
- Bullous pemphigoid (1)
- CD74 (1)
- CXCR4 (1)
- Calcineurin-NFATsignaling (1)
- Cancer (1)
- Ceramide (1)
- Cognitive control (1)
- DNA damage (1)
- DNA methylation (1)
- Dickkopf proteins (1)
- Down syndrome (1)
- Dual 3'seq (1)
- Expression (1)
- Factor receptor (1)
- Golgi (1)
- Graft-versus-leukemia (1)
- HIV-Infektion (1)
- HLA class II (1)
- HLA peptidome (1)
- Hamburg (1)
- Human Physiome (1)
- Imatinib (1)
- Immunbiologie (1)
- Immunoadsorption (1)
- Immunoapheresis (1)
- Japanese population (1)
- Jurkat cells (1)
- Kongress (1)
- LASP1 (1)
- LRP6 (1)
- M1/M2 macrophages (1)
- MACE (1)
- MFM (1)
- MTCH2 (1)
- N-oleoyl serinol (1)
- N170 (1)
- NHX1 (1)
- NK cells (1)
- NaCl transport (1)
- Neisseria gonorrhoeae (1)
- P100 (1)
- Pakistan (1)
- Prediction (1)
- RNA-Seq (1)
- Regulatory-cells (1)
- Retroviren-Infektion (1)
- Rheumatoid arthritis (1)
- SLC6A4 (1)
- SUMO2 (1)
- Salmonella Typhimurium (1)
- Salmonella enterica Typhimurium strain SL1344 (1)
- Salt Overly Sensitive pathway (1)
- Selective attention (1)
- Staphylococcus aureus (1)
- SuperSAGE (1)
- Suppression (1)
- T cells (1)
- TH1-induced senescence (1)
- TH17 cells (1)
- TIC disorders (1)
- TIMP-1 (1)
- Tiermodell (1)
- Tierversuch (1)
- Tumor-necrosis-factor (1)
- WNT (1)
- Working memory (1)
- [\(^{223}\)Ra]RaCl\(_{2}\) (1)
- abscisic acid (ABA) (1)
- acquired thermotolerance (1)
- acquisition (1)
- allogeneic hematopoietic stem cell transplantation (1)
- amino acid transporter (1)
- animal behaviour (1)
- animal experimentation (1)
- antibodies (1)
- antidepressant (1)
- apolipoprotein-E4 (1)
- apoptosis (1)
- arabidopsis-thaliana (1)
- ash dieback (1)
- association (1)
- atypical tetracyclines (1)
- autism (1)
- autotoxicity (1)
- auxin (1)
- bcl-2 associated athanogene protein 3 (1)
- beetle (1)
- beetle communities (1)
- biokinetics (1)
- biomarkers Myelomas (1)
- bipartite metabolism (1)
- bird communities (1)
- bone imaging (1)
- bone morphogenetic proteins (1)
- bone regeneration (1)
- brain metastasis (1)
- broad-spectrum antibiotics (1)
- brucei genome (1)
- calcium signaling (1)
- cancer (1)
- cancer-targeted IL-12 (1)
- candidate gene (1)
- cardiac hypertrophy (1)
- cartilage induction (1)
- cell death (1)
- chelocardins (1)
- chronic myeloid leukemia (1)
- clinical isolates (1)
- colorectal carcinoma (1)
- common SNPS (1)
- complete genome sequence (1)
- complex diseases (1)
- consanguinity (1)
- conservation (1)
- conservation biology (1)
- correlate (1)
- cytosolic pH (1)
- cytotoxicity (1)
- data acquisition (1)
- deepSuperSAGE (1)
- detoxification (1)
- developmental dyscalculia (1)
- diarrhea (1)
- differentiation (1)
- disability (1)
- disorders (1)
- distance-dependent decay (1)
- diversity (1)
- dosimetry (1)
- drug design/partial agonists (1)
- drug treatment (1)
- dyscalculia (1)
- dyslexia (1)
- early respiratory-failure (1)
- echo planar imaging (1)
- ecosystem function (1)
- efficacy (1)
- elderly (1)
- enzyme-linked immunoassays (1)
- epigenetics in the nervous system (1)
- epigenomics (1)
- evaluation (1)
- exome sequencing (1)
- expression (1)
- family (1)
- fear conditioning (1)
- fetal brain development (1)
- fire (1)
- fluorescence microscopy (1)
- fluorescent dyes (1)
- forest (1)
- forest conversion (1)
- forest ecology (1)
- forestry (1)
- frontal cortex (1)
- functional magnetic resonance imaging (1)
- gene (1)
- gene expression profiling (1)
- gene-expression (1)
- genetic diagnosis (1)
- genome architecture (1)
- genome wide (1)
- genome-wide association (1)
- genome-wide linkage analysis (1)
- genomic imaging (1)
- genotype (1)
- gilles (1)
- glial fate modulation (1)
- glycophyte Arabidopsis (1)
- guard cell (1)
- halophyte Thellungiella/Eutrema (1)
- hearing impairment (1)
- hearing loss (1)
- heart (1)
- heart failure (1)
- heat shock response (1)
- heat stress (1)
- helimagnets (1)
- histone variants (1)
- host cells (1)
- host pathogen interaction (1)
- human macrophages (1)
- humanized mice (1)
- identification (1)
- imaging techniques (1)
- immunocytokine (1)
- immunotherapy (1)
- impact (1)
- increases bone-formation (1)
- inelastic neutron scattering (1)
- infection (1)
- ion transport (1)
- isothiocyanates (1)
- jasmonates (1)
- kidneys (1)
- leaf response (1)
- learning (1)
- ligand (1)
- macrophages (1)
- management (1)
- managing big data (1)
- mass casualties (1)
- matched filters (1)
- mathematics (1)
- mechanism of resistance (1)
- medial prefrontal cortex (mPFC) (1)
- memory B cells (1)
- memory consolidation and extinction (1)
- mesenchymal stem cells (1)
- microparticles (1)
- missing heritability (1)
- model (1)
- mucosal inflammation (1)
- multiparametric magnetic resonance imaging (1)
- multiple myeloma Lesions (1)
- muscular-dystrophy (1)
- mustard oil bomb (1)
- myasthenia gravis (1)
- myelin (1)
- myeloma cells (1)
- myopathy (1)
- natural disturbance (1)
- near-infrared spectroscopy (1)
- neophyte trees (1)
- neovascularization, physiologic (1)
- neural stem cells (1)
- neurological disorders (1)
- neuropsychiatric disorders (1)
- neutralizing antibodies (1)
- neutrophils (1)
- next generation sequencing (1)
- nilotinib (1)
- nuclear medicine (1)
- oligodendroglia (1)
- osmotic effects (1)
- permeation and transport (1)
- pharmacogenetics (1)
- physics (1)
- phytoprostanes (1)
- plants (1)
- polyneuropathy (1)
- postmenopausal osteoporosis (1)
- posttranscriptional regulation (1)
- precursor cells (1)
- prelevance (1)
- prostate cancer (1)
- protein aggregation (1)
- protocadherin gamma cluster (1)
- quality indicators (1)
- quantitative trait (1)
- rat model (1)
- receptor (1)
- receptor signalling (1)
- receptors (1)
- red blood cells (1)
- redox homeostasis (1)
- repositories (1)
- reproducible science (1)
- rescue mission (1)
- resistance-breaking properties (1)
- rhabdomyosarcoma (1)
- sRNA (1)
- secretion systems (1)
- secretome (1)
- serovar Typhimurium (1)
- service infrastructure (1)
- shock response (1)
- signal filtering (1)
- simultaneous (1)
- single molecule real time (SMRT) (1)
- skeletal myopathy (1)
- soil (1)
- spin waves (1)
- spinal cord (1)
- standards (1)
- statistical data (1)
- stem cell transplantation (1)
- stomata (1)
- sulcal morphology (1)
- sulforaphane (1)
- tag based (1)
- targeted (1)
- terror attack (1)
- thermotolerance (1)
- thymic carcinoma (1)
- thymoma (1)
- thymus (1)
- tissue engineering (1)
- tolerability (1)
- transcranial magnetic stimulation (TMS) (1)
- transcriptome (1)
- transfusion (1)
- translational medical research (1)
- transplantation (1)
- transposable elements (1)
- trisomy 21 (1)
- tumor infiltrating lymphocytes (1)
- tumor-infiltrating lymphocytes (1)
- tumor-suppressor gene (1)
- tyrosine kinase inhibitors (1)
- unfolded protein response (1)
- urinary tract infection (UTI) (1)
- uropathogens (1)
- verbal fluency task (1)
- windthrow (1)
- α-Emitter (1)
- γ-H2AX (1)
Institute
- Theodor-Boveri-Institut für Biowissenschaften (15)
- Institut für Virologie und Immunbiologie (10)
- Julius-von-Sachs-Institut für Biowissenschaften (7)
- Klinik und Poliklinik für Allgemein-, Viszeral-, Gefäß- und Kinderchirurgie (Chirurgische Klinik I) (6)
- Klinik und Poliklinik für Psychiatrie, Psychosomatik und Psychotherapie (6)
- Institut für Humangenetik (5)
- Institut für Molekulare Infektionsbiologie (5)
- Pathologisches Institut (4)
- Medizinische Klinik und Poliklinik II (3)
- Deutsches Zentrum für Herzinsuffizienz (DZHI) (2)
The direct estimation of heritability from genome-wide common variant data as implemented in the program Genome-wide Complex Trait Analysis (GCTA) has provided a means to quantify heritability attributable to all interrogated variants. We have quantified the variance in liability to disease explained by all SNPs for two phenotypically-related neurobehavioral disorders, obsessive-compulsive disorder (OCD) and Tourette Syndrome (TS), using GCTA. Our analysis yielded a heritability point estimate of 0.58 (se = 0.09, p = 5.64e-12) for TS, and 0.37 (se = 0.07, p = 1.5e-07) for OCD. In addition, we conducted multiple genomic partitioning analyses to identify genomic elements that concentrate this heritability. We examined genomic architectures of TS and OCD by chromosome, MAF bin, and functional annotations. In addition, we assessed heritability for early onset and adult onset OCD. Among other notable results, we found that SNPs with a minor allele frequency of less than 5% accounted for 21% of the TS heritability and 0% of the OCD heritability. Additionally, we identified a significant contribution to TS and OCD heritability by variants significantly associated with gene expression in two regions of the brain (parietal cortex and cerebellum) for which we had available expression quantitative trait loci (eQTLs). Finally we analyzed the genetic correlation between TS and OCD, revealing a genetic correlation of 0.41 (se = 0.15, p = 0.002). These results are very close to previous heritability estimates for TS and OCD based on twin and family studies, suggesting that very little, if any, heritability is truly missing (i.e., unassayed) from TS and OCD GWAS studies of common variation. The results also indicate that there is some genetic overlap between these two phenotypically-related neuropsychiatric disorders, but suggest that the two disorders have distinct genetic architectures.
A recent genome-wide association study in patients with panic disorder (PD) identified a risk haplotype consisting of two single-nucleotide polymorphisms (SNPs) (rs7309727 and rs11060369) located in intron 3 of TMEM132D to be associated with PD in three independent samples. Now we report a subsequent confirmation study using five additional PD case-control samples (n = 1670 cases and n 2266 controls) assembled as part of the Panic Disorder International Consortium (PanIC) study for a total of 2678 cases and 3262 controls in the analysis. In the new independent samples of European ancestry (EA), the association of rs7309727 and the risk haplotype rs7309727-rs11060369 was, indeed, replicated, with the strongest signal coming from patients with primary PD, that is, patients without major psychiatric comorbidities (n 1038 cases and n 2411 controls). This finding was paralleled by the results of the meta-analysis across all samples, in which the risk haplotype and rs7309727 reached P-levels of P = 1.4e-8 and P = 1.1e-8, respectively, when restricting the samples to individuals of EA with primary PD. In the Japanese sample no associations with PD could be found. The present results support the initial finding that TMEM132D gene contributes to genetic susceptibility for PD in individuals of EA. Our results also indicate that patient ascertainment and genetic background could be important sources of heterogeneity modifying this association signal in different populations.
Abstract
Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity.
We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line.
We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected.
In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.
The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.
Stimulating the immune system to attack cancer is a promising approach, even for the control of advanced cancers. Several cytokines that promote interferon-γ-dominated immune responses show antitumor activity, with interleukin 12 (IL-12) being of major importance. Here, we used an antibody-IL-12 fusion protein (NHS-IL12) that binds histones of necrotic cells to treat human sarcoma in humanized mice. Following sarcoma engraftment, NHS-IL12 therapy was combined with either engineered IL-7 (FcIL-7) or IL-2 (IL-2MAB602) for continuous cytokine bioavailability. NHS-IL12 strongly induced innate and adaptive antitumor immunity when combined with IL-7 or IL-2. NHS-IL12 therapy significantly improved survival of sarcoma-bearing mice and caused long-term remissions when combined with IL-2. NHS-IL12 induced pronounced cancer cell senescence, as documented by strong expression of senescence-associated p16\(^{INK4a}\) and nuclear translocation of p-HP1γ, and permanent arrest of cancer cell proliferation. In addition, this cancer immunotherapy initiated the induction of myogenic differentiation, further promoting the hypothesis that efficient antitumor immunity includes mechanisms different from cytotoxicity for efficient cancer control in vivo.
Rhesus monkeys (M. mulatta) were i. v. infected with SIV mac251. Three phases of lymph node changes were observed. 1: physiological follicular hyperplasia (3 and 6 weeks p.i.). 2: Alterations of germinal centers: loss of follicular mantle zone, fragmentation or sclerosis (12 and 24 weeks p.i.). 3: Partial depletion of T-lymphocytes, accumulation of plasma cells, increased numbers of syncytial giant cells, hemophgocytosis in the sinuses (about 1 year p.i.). The thymus of the juvenile animals showed first changes 12 and 24 weeks after infection with focalloss of immature (and Ki-67 positive) cortical thymocytes, leading to severe accidental involution of the thymuses one year after infection and reduced numbers of Hassalls corpuscles. These investigations show the value of this animal model for the study of morphology and pathogenesis of AIDS.
The role of the thymus in the pathogenesis of simian acquired immunodeficiency syndrome was investigated in 18 juvenile rhesus monkeys (Macaca mulatta). The thymus was infected from the first week post-SIVmac inoculation, but the amount of virus-positive cells was very low « 1 in 1 04 T cells) as demonstrated by polymerase chain reaction and in situ hybridization. First morphological alteration was a narrowing of the cortex at 12 and 24 wpi. Morphometry revealed no increase of pyknotic T cells but a decrease of the proliferation rate andflow cytometry showed a reduction of the immature \(CD4^+/CD8^+\) double-positive T cells. Ultrastructural analysis revealed vacuolization, shrinkage, andfinally cytolysis of the cortical epithelial cells and the interdigitating dendritic cells. Immunofluorescence staining exhibited a widespread loss of cortical epithelial cells. This damage to the thymic microenvironment could explain the breakdown of the intrathymic T cell proliferation. It preceded fully developed simian acquired immunodeficiency syndrome and is therefore considered to play a major role in its pathogenesis.
The thymus in SIV infection
(1993)
no abstract available
Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR‐ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR‐ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1‐mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell‐mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.