572 Biochemie
Refine
Has Fulltext
- yes (95)
Is part of the Bibliography
- yes (95)
Year of publication
Document Type
- Doctoral Thesis (51)
- Journal article (39)
- Master Thesis (2)
- Preprint (2)
- Book article / Book chapter (1)
Keywords
- Transkriptionsfaktor (5)
- DNS-Reparatur (4)
- Ubiquitin (4)
- Regulation (3)
- SMN (3)
- Saccharomyces cerevisiae (3)
- TFIIH (3)
- Thrombozyt (3)
- gene expression (3)
- mass spectrometry (3)
- platelet (3)
- ALS (2)
- Antibody (2)
- Antikörper (2)
- Cancer (2)
- Cytokine (2)
- DNA-Reparatur (2)
- Expression (2)
- Fluoreszenz (2)
- G-Protein gekoppelte Rezeptoren (2)
- Genexpression (2)
- Immunreaktion (2)
- Interleukin 4 (2)
- Messenger-RNP (2)
- Messenger-RNS (2)
- Monoklonaler bispezifischer Antikörper (2)
- Nanopartikel (2)
- Röntgenkristallographie (2)
- Signaltransduktion (2)
- Transkription (2)
- Ubiquitin-Protein-Ligase (2)
- Ubiquitinierung (2)
- Vaccinia-Virus (2)
- apoptosis (2)
- binding (2)
- identification (2)
- immunoprecipitation (2)
- inflammation (2)
- magnetic resonance imaging (2)
- messenger RNA (2)
- mouse models (2)
- neuroblastoma (2)
- pICln (2)
- phosphorylation (2)
- protein (2)
- regulation (2)
- 26S proteasome (1)
- 5-HT1A (1)
- 5-HT2C (1)
- 7,8-dihydroxyflavone (7,8-DHF) (1)
- A2a-R receptor (1)
- AD5 mutation (1)
- AMP-activated protein kinase (AMPK) (1)
- Ackerschmalwand (1)
- Activation (1)
- Adhesion and degranulation promoting adapter protein (1)
- Affinity probe (1)
- Antigen CD40 (1)
- Antigen CD95 (1)
- Antigenrezeptor (1)
- Apoptose (1)
- Aptamer (1)
- Arrestine (1)
- Arzneimitteldesign (1)
- Assembly (1)
- AuNPs (1)
- Aurora-A (1)
- Automation (1)
- B-Zell-Lymphom (1)
- BCMA (1)
- BRAF mutations (1)
- BRCA1 (1)
- BRM (1)
- BRN-3A (1)
- BTB domain (1)
- Baff (1)
- Bakteriorhodopsin (1)
- Bauchspeicheldrüsenkrebs (1)
- Beige adipocytes (1)
- Bierhefe (1)
- Bioanorganische Chemie (1)
- Bioconjugate (1)
- Biologie (1)
- Biomarker (1)
- Bispecific T-cell engager (1)
- Bortezomib (1)
- Brahma (1)
- Breast-cancer (1)
- Bäckerhefe (1)
- C-MYC (1)
- C/EBP (1)
- CGG repeat (1)
- CLIP-seq (1)
- CPG Island (1)
- Cancer Metabolism (1)
- Candida albicans (1)
- Cdc48 (1)
- Chaetomium thermophilum (1)
- Chemotherapie (1)
- Chemotherapy (1)
- Chimeric Antigen Receptor (1)
- Chimärer Antigenrezeptor (1)
- Chinese family (1)
- Cholesterinstoffwechsel (1)
- Chromatin-remodeling complexes (1)
- Chromophor (1)
- Chromosomal Passenger Complex (1)
- Colorectal Cancer (1)
- Combination therapy (1)
- Cyclophosphamide (1)
- Cytoskeleton Chromosomal Passenger Complex Interaction GAR Domain (1)
- DHX30 (1)
- DNA (1)
- DNA Sekundärstruktur (1)
- DNA damage (1)
- DNA methylferase homolog (1)
- DNA repair (1)
- DNA secondary structure (1)
- DNA-binding proteins (1)
- DNS-Bindung (1)
- DNS-Bindungsproteine (1)
- DUB (1)
- Decapping (1)
- Deubiquitination (1)
- Deuteriumaustausch (1)
- Dickdarmkrebs (1)
- Differentiation (1)
- Dihydroisochinolinderivate (1)
- Dihydroisochinolinonderivate (1)
- Diphenylether (1)
- Disease (1)
- Distinct (1)
- Drosophila melanogaster (1)
- Drug delivery platform (1)
- Drug delivery system (DDS) (1)
- Dualstere Liganden (1)
- Dualsteric Ligands (1)
- E2 (1)
- Echinococcus (1)
- Enzym (1)
- Excitatory/inhibitory imbalance (1)
- Exons (1)
- FMR1 (1)
- FMR2 (1)
- FMRP (1)
- FRET (1)
- FXR1 (1)
- FXR2 (1)
- Factor gene PRPF31 (1)
- FcgR (1)
- Fettsäurestoffwechsel (1)
- Fluorescence microscopy (1)
- Fluoreszenz-Resonanz-Energie-Transfer (1)
- Fluoreszenzmikroskopie (1)
- Fragiles-X-Syndrom (1)
- Fuchsbandwurm (1)
- G3BP (1)
- GAS2L3 (1)
- GLV-1H68 (1)
- Ganzkörperbestrahlung (1)
- Gen BRCA 1 (1)
- Gen notch (1)
- Gene Expression (1)
- Gene regulation (1)
- General Transcription Factor II H (1)
- Genes (1)
- Genexpressionsmaschinerie (1)
- Genome Instability (1)
- Genregulation (1)
- Gephyrin (1)
- Gold Nanoparticles (1)
- HUWE1 (1)
- Halobacterium halobium (1)
- Helikasen (1)
- Hemibodies (1)
- Hemibody (1)
- Hey Proteine (1)
- Hey proteins (1)
- Hitzeschockproteine (1)
- Hitzestress (1)
- Homebox gene (1)
- Hsc70 (1)
- Human Sodium/Iodide symporter (1)
- IN-VIVO (1)
- Ifn-gamma (1)
- In-Vivo (1)
- In-vivo (1)
- Induzierte pluripotente Stammzelle (1)
- Inhibitor (1)
- Inhibitorische Synapse (1)
- Inhibitory synapse (1)
- Insulinsekretion (1)
- Interferon <alpha-2a-> (1)
- KSR1 (1)
- Knochenmark (1)
- Knochenmarktransplantation (1)
- Kolorektales Karzinom (1)
- Konjugation (1)
- Kontrollierte Wirkstofffreisetzung (1)
- Krebs <Medizin> (1)
- Kristallstruktur (1)
- LCK (1)
- Library Screening (1)
- Lipidumbau (1)
- Lung cancer (1)
- Lung squamous cancer cells (1)
- MAP-Kinase (1)
- MAPK (1)
- MDSCs (1)
- MIZ1 (1)
- MYCN (1)
- Macromolecular Assembly (1)
- Macromolecular Crystallography (1)
- Mechanismus (1)
- Megakaryocyte (1)
- Megakaryozyt (1)
- Metabolismus (1)
- Mevalonate Pathway (1)
- Modifikation (1)
- Molecular Chaperone (1)
- Molekulargenetik (1)
- MscS (1)
- Multidrug-Resistenz (1)
- Multiple Myeloma (1)
- Multiples Myelom (1)
- Muscarinrezeptor (1)
- Mutations (1)
- Myc (1)
- N-MYC (1)
- N-Myc (1)
- NA+/I-symporter (1)
- NEDMIAL (1)
- NFkB-Signalling (1)
- NO (1)
- NPY (1)
- Nanodiamant (1)
- Nanodiamond (1)
- Nanoparticles (1)
- Nekroptose (1)
- Nekrose (1)
- Neural precursor cells (1)
- Neuroblastom (1)
- Neuroblastoma (1)
- Neurodevelopmental diseases (1)
- Neuropeptide Hormone (1)
- Neuropeptidhormon (1)
- Notch Signalweg (1)
- Notch signalling (1)
- Nucleinsäuren (1)
- Nucleosidanaloga (1)
- Nucleoside (1)
- Nucleotide excision repair (1)
- Nude-mice (1)
- Nukleotid-Exzisions-Reparatur (1)
- Oligomerisation (1)
- OmoMYC (1)
- Oncolysis (1)
- Oncolytic vaccinia virus (1)
- Onkogen (1)
- Onkolyse (1)
- Opiatrezeptor (1)
- Opioide (1)
- P53 (1)
- P97 (1)
- PAR-CLIP (1)
- PDXP inhibitors (1)
- PGAS (1)
- PRPF31 (1)
- Partial Agonists (1)
- Partialagonismus (1)
- Particle analytics (1)
- Partikelanalytik (1)
- Pathway (1)
- Peptide (1)
- Peptidsynthese (1)
- Pharmakodynamik (1)
- Platelet (1)
- Pockenviren (1)
- Polo-like kinase 1 (1)
- Polyethylenglykole (1)
- Polyglycerol (1)
- Polymere (1)
- Polypeptidketten bindende Proteine (1)
- Poxviridae (1)
- Progenitor cells (1)
- Protease-sensitive release (1)
- Proteasom (1)
- Proteasome (1)
- Protein (1)
- Protein kinase D1 (PKD1) (1)
- Protein kinase D3 (PKD3) (1)
- Proteinbiosynthese (1)
- Protonenpumpe (1)
- Purpurmembran (1)
- Quadruplex-DNS (1)
- RIP3 (1)
- RNA (1)
- RNA binding protein (1)
- RNA binding proteins (1)
- RNA helicase (1)
- RNA interference (1)
- RNA metabolism (1)
- RNA splicing (1)
- RNA-Polymerase (1)
- RNA-polymerase-II (1)
- RNA-seq (1)
- RNS (1)
- RP11 (1)
- RecQ helicase (1)
- Rekonstitution (1)
- Reporter Cells (1)
- Reporter gene (1)
- Reporterzellen (1)
- Retinitis pigmentosa (RP) (1)
- Retinoic acid (1)
- Rezeptorpharmakologie (1)
- Rothmund-Thomson-Syndrome (1)
- SM proteins (1)
- SP117 mutation (1)
- SPION (1)
- Salmonella enterica (1)
- Schizophrenie (1)
- Schizosaccharomyces pombe (1)
- Screening (1)
- SdsR (1)
- Sekundärstruktur (1)
- Signalweg (1)
- Site-specific protein conjugation (1)
- Small nuclear RNP (1)
- Solid-phase peptide synthesis (1)
- Spleißosom (1)
- Squamous cell carcinoma (1)
- Ssl1 (1)
- Stammzelle (1)
- Structural Biology (1)
- Struktur (1)
- Strukturbiologie (1)
- Strumpellin (1)
- Subunit (1)
- T cells (1)
- T-Lymphozyt (1)
- T-cell engager (1)
- T-lymphocytes (1)
- TDRD3 (1)
- TFIIIC (1)
- TIAR (1)
- TNF (1)
- TOP mRNA (1)
- TOP3b (1)
- TRAF2 (1)
- TRI-SNRNP (1)
- TRNA(ASP) (1)
- TTF complex (1)
- TWEAK (1)
- Targeted drug delivery (1)
- Targeted therapies (1)
- Terminal Oligopyrimidine Tract (1)
- Tfb4 (1)
- Therapy (1)
- Thermotoleranz (1)
- Thiolase (1)
- Tissue Engineering (1)
- Transcription (1)
- Transcription factor (1)
- Transgenic zebrafish (1)
- Transkription <Genetik> (1)
- Translation <Genetik> (1)
- Translationsinitiation (1)
- Translationskontrolle (1)
- Transporter (1)
- Triglyceride (1)
- Trithorax (1)
- Tritiumaustausch (1)
- Tuberkulose (1)
- Tumor (1)
- Tumor models (1)
- Tumour (1)
- U snRNPs (1)
- UBE2S (1)
- USP (1)
- USP28 (1)
- Ubiquitin-conjugating enzyme (1)
- VACV (1)
- Vaccinia virus (1)
- Verweildauer (1)
- Virotherapie (1)
- Virotherapy (1)
- WASH complex (1)
- X-ray crystallography (1)
- YnaI (1)
- Zellteilung (1)
- Zellzyklus (1)
- Zink-Finger-Proteine (1)
- adaptive immunity (1)
- adsorption (1)
- alpha-IIb beta-3 (1)
- animal behavior (1)
- anti-sigma factor (1)
- antigen expression (1)
- antitumor immune response (1)
- antiviral immunity (1)
- aquired resistance (1)
- arginine (1)
- arterial elasticity (1)
- ascites (1)
- assembly chaperone (1)
- atherosclerosis (1)
- autoantibodies (1)
- autophagy (1)
- bacterial fatty-acid biosynthesis (1)
- biased agonism (1)
- binding mode (1)
- biochemistry (1)
- bispecific (1)
- bispezifisch (1)
- blood (1)
- bone marrow (1)
- breast cancer (1)
- cancer microenvironment (1)
- cancer treatment (1)
- cations (1)
- cell carcinoma (1)
- cholesterol (1)
- circadian rhythms (1)
- coexpression (1)
- cohesin (1)
- colorectal cancer (1)
- coloteral cancer (1)
- comparative genomic hybridization (1)
- complexity (1)
- cyanelle (1)
- cytokinin (1)
- cytokinin kinetin (1)
- cytoskeleton (1)
- deep sequencing (1)
- delipidation (1)
- density gradient centrifugation (1)
- deubiquitinase (1)
- diabetes (1)
- diacylglycerol (DAG) (1)
- differential centrifugation (1)
- diversity (1)
- domain (1)
- dominant-negative (1)
- down regulation (1)
- drospophila (1)
- dual targeting (1)
- ectopic release (1)
- electron cryomicroscopy (1)
- electron microscopy (1)
- embryos (1)
- endosomal trafficking (1)
- enoyl-ACP reductase (1)
- enzyme (1)
- eukaryotic gene expression (1)
- evolutionary genetics (1)
- expression (1)
- extracellular domain (1)
- family (1)
- fluorescence (1)
- fluorescence imaging (1)
- fluorescence microscopy (1)
- fraxe mental retardation (1)
- genes (1)
- genome integrity (1)
- genome stability (1)
- genome-wide analysis (1)
- genomics (1)
- glycerol (1)
- glycine receptor (1)
- glycosylation (1)
- granulophagy (1)
- granulostasis (1)
- haploinsufficiency (1)
- histology (1)
- homeostasis (1)
- humanized tumor (1)
- hyperexpression techniques (1)
- iNOS (1)
- iPSCs (1)
- in vitro (1)
- in vivo imaging (1)
- in vivo toxicity (1)
- in-vitro (1)
- in-vivo (1)
- inhibition (1)
- inhibitor residence time (1)
- innate immune system (1)
- innate immunity (1)
- insulin (1)
- interaction networks (1)
- label-free quantification (1)
- limiting dilution cloning (1)
- lipid bilayer (1)
- lipid remodeling (1)
- liver (1)
- living cells (1)
- lymph nodes (1)
- mRNA metabolism (1)
- macrophages (1)
- males (1)
- malignant melanoma (1)
- mechanism (1)
- mechanosensing (1)
- mechanosensitive channels (1)
- melanoma (1)
- membrane potential (1)
- membrane proteins (1)
- membrane structures (1)
- metabolism (1)
- metastatic tumors (1)
- miR-181 (1)
- modulatory effects (1)
- molecular evolution (1)
- molecular mass (1)
- monoclonal stable cell (1)
- motor-neuron protein (1)
- mouse model (1)
- mutation (1)
- myeloablation (1)
- myeloma (1)
- ncuCyte\(^®\)S3 (1)
- neural crest factors (1)
- neurons (1)
- oligomerization (1)
- oncogene-induced senescence (1)
- oncolytic virus therapy (1)
- oncolytic viruses (1)
- organellar mapping (1)
- p34 (1)
- p44 (1)
- p97/VCP (1)
- pancreas (1)
- partial purification (1)
- peptide (1)
- permutation (1)
- peroxisome purification (1)
- phase transition (1)
- photooxidative stress (1)
- photosynthesis genes (1)
- plant hormones (1)
- plant-microbe interaction (1)
- poly(2-ethyl-2-oxazoline) (1)
- posttranscriptional gene regulation (1)
- prognostic biomarkers (1)
- prognostic relevance (1)
- promoter invasion (1)
- prostate cancer (1)
- protein argentine methyltranserase (1)
- protein domains (1)
- protein interactions (1)
- protein localization (1)
- protein subunit (1)
- protein synthesis (1)
- protein-lipid interactions (1)
- pulse wave velocity (1)
- pyridoxal phosphatase (PDXP) (1)
- quality control (1)
- quanititative proteomics (1)
- red blood cells (1)
- regulatory RNA (1)
- replication (1)
- rhodobacter sphaeroides (1)
- ribonuclease-P (1)
- ribosome (1)
- ribosome profiling (1)
- rod degeneration (1)
- sRNA (1)
- schizophrenia (1)
- separation (1)
- sequence (1)
- signaling (1)
- signalling (1)
- singlet oxygen stress (1)
- small RNA (1)
- snRNPs (1)
- spatial proteomics (1)
- spliceosomes (1)
- splicing defect (1)
- splicing factor (1)
- stem cells (1)
- structural mechanism (1)
- structure-based drug design (1)
- subcutaneous human tumors (1)
- systems biology (1)
- thermotolerance (1)
- thrombopoiesis (1)
- tissue microarray (1)
- toxins (1)
- transcription factors (1)
- transcription/replication conflicts (1)
- translation initiation (1)
- translational regulation (1)
- triple in situ hybridization (1)
- trispecific (1)
- tumors (1)
- tumourigenesis (1)
- tyrosine phosphorylation (1)
- ubiquitin chain formation (1)
- ubiquitin linkage specificity (1)
- ubiquitin recognition (1)
- ubiquitination (1)
- vitamin B6 (1)
- wall shear stress (1)
- zebrafish (1)
- zinc-finger (1)
- ΔNp63 (1)
- β cell (1)
- β3 adrenergic receptor (ADRB3) (1)
Institute
- Graduate School of Life Sciences (35)
- Lehrstuhl für Biochemie (32)
- Theodor-Boveri-Institut für Biowissenschaften (22)
- Rudolf-Virchow-Zentrum (13)
- Institut für Molekulare Infektionsbiologie (7)
- Institut für Experimentelle Biomedizin (4)
- Fakultät für Chemie und Pharmazie (3)
- Institut für Pharmazie und Lebensmittelchemie (3)
- Medizinische Klinik und Poliklinik II (3)
- Fakultät für Biologie (2)
Schriftenreihe
Sonstige beteiligte Institutionen
ResearcherID
No abstract available.
Rekonstitution des Chromophors und der Funktion von Bakteriorhodopsin aus Halobacterium halobium
(1976)
Ein Modell der lichtgetriebenen Protonenpumpe Bakteriorhodopsin postulierte die direkte Beteiligung der Wasserstoffe in der 4-Stellung des Cyclohexenringes des Retinalchromophors an dem Vorgang der Protonenverschiebung. Mittels Blockaden der Retroform-Bildung von Retinal durch chemische Modifizierungen des Cyclohexenringes (4-Hydroxy-Retinal, 5,6-Epoxy-Retinal) konnten nach Einbau der modifizierten Moleküle in die isolierte Purpurmembran und nach Zugabe zu Halobakterien mit unterdrückter Retinalsynthese die direkte Beteiligung des Cyclohexenringes an der Protonenpumpe mit großer Wahrscheinlichkeit ausgeschlossen werden.
Background:
The SWI/SNF chromatin remodeling factors have the ability to remodel nucleosomes and play essential roles in key developmental processes. SWI/SNF complexes contain one subunit with ATPase activity, which in Drosophila melanogaster is called Brahma (Brm). The regulatory activities of SWI/SNF have been attributed to its influence on chromatin structure and transcription regulation, but recent observations have revealed that the levels of Brm affect the relative abundances of transcripts that are formed by alternative splicing and/or polyadenylation of the same pre-mRNA.
Results:
We have investigated whether the function of Brm in pre-mRNA processing in Drosophila melanogaster is mediated by Brm alone or by the SWI/SNF complex. We have analyzed the effects of depleting individual SWI/SNF subunits on pre-mRNA processing throughout the genome, and we have identified a subset of transcripts that are affected by depletion of the SWI/SNF core subunits Brm, Snr1 or Mor. The fact that depletion of different subunits targets a subset of common transcripts suggests that the SWI/SNF complex is responsible for the effects observed on pre-mRNA processing when knocking down Brm. We have also depleted Brm in larvae and we have shown that the levels of SWI/SNF affect the pre-mRNA processing outcome in vivo.
Conclusions:
We have shown that SWI/SNF can modulate alternative pre-mRNA processing, not only in cultured cells but also in vivo. The effect is restricted to and specific for a subset of transcripts. Our results provide novel insights into the mechanisms by which SWI/SNF regulates transcript diversity and proteomic diversity in higher eukaryotes.
Background:
Retinitis pigmentosa (RP) is an inherited eye disease characterized by the progressive degeneration of rod photoreceptor cells. Mutations in pre-mRNA splicing factors including PRPF31 have been identified as cause for RP, raising the question how mutations in general factors lead to tissue specific defects.
Results:
We have recently shown that the zebrafish serves as an excellent model allowing the recapitulation of key events of RP. Here we use this model to investigate two pathogenic mutations in PRPF31, SP117 and AD5, causing the autosomal dominant form of RP. We show that SP117 leads to an unstable protein that is mislocalized to the rod cytoplasm. Importantly, its overexpression does not result in photoreceptor degeneration suggesting haploinsufficiency as the underlying cause in human RP patients carrying SP117. In contrast, overexpression of AD5 results in embryonic lethality, which can be rescued by wild-type Prpf31. Transgenic retina-specific expression of AD5 reveals that stable AD5 protein is initially localized in the nucleus but later found in the cytoplasm concurrent with progressing rod outer segment degeneration and apoptosis. Importantly, we show for the first time in vivo that retinal transcripts are wrongly spliced in adult transgenic retinas expressing AD5 and exhibiting increased apoptosis in rod photoreceptors.
Conclusion:
Our data suggest that distinct mutations in Prpf31 can lead to photoreceptor degeneration through different mechanisms, by haploinsufficiency or dominant-negative effects. Analyzing the AD5 effects in our animal model in vivo, our data imply that aberrant splicing of distinct retinal transcripts contributes to the observed retina defects.
Introduction:
Oncolytic viruses show promise for treating cancer. However, to assess therapeutic efficacy and potential toxicity, a noninvasive imaging modality is needed. This study aimed to determine if insertion of the human sodium iodide symporter (hNIS) cDNA as a marker for non-invasive imaging of virotherapy alters the replication and oncolytic capability of a novel vaccinia virus, GLV-1h153.
Methods:
GLV-1h153 was modified from parental vaccinia virus GLV-1h68 to carry hNIS via homologous recombination. GLV-1h153 was tested against human pancreatic cancer cell line PANC-1 for replication via viral plaque assays and flow cytometry. Expression and transportation of hNIS in infected cells was evaluated using Westernblot and immunofluorescence. Intracellular uptake of radioiodide was assessed using radiouptake assays. Viral cytotoxicity and tumor regression of treated PANC-1tumor xenografts in nude mice was also determined. Finally, tumor radiouptake in xenografts was assessed via positron emission tomography (PET) utilizing carrier-free (124)I radiotracer.
Results:
GLV-1h153 infected, replicated within, and killed PANC-1 cells as efficiently as GLV-1h68. GLV-1h153 provided dose-dependent levels of hNIS expression in infected cells. Immunofluorescence detected transport of the protein to the cell membrane prior to cell lysis, enhancing hNIS-specific radiouptake (P < 0.001). In vivo, GLV-1h153 was as safe and effective as GLV-1h68 in regressing pancreatic cancer xenografts (P < 0.001). Finally, intratumoral injection of GLV-1h153 facilitated imaging of virus replication in tumors via (124)I-PET.
Conclusion:
Insertion of the hNIS gene does not hinder replication or oncolytic capability of GLV-1h153, rendering this novel virus a promising new candidate for the noninvasive imaging and tracking of oncolytic viral therapy.
Background:
Over 90% of low risk (LR) neuroblastoma patients survive whereas less than 30% of high risk (HR) patients are long term survivors. Age (children younger than 18 months old) is associated with LR disease. Considering that adaptive immune system is well developed in older children, and that T cells were shown to be involved in tumor escape and progression of cancers, we sought to determine whether HR patients may tend to show a signature of adaptive immune responses compared to LR patients who tend to have diminished T-cell responses but an intact innate immune response.
Methods:
We performed microarray analysis of RNA extracted from the tumor specimens of HR and LR patients. Flow cytometry was performed to determine the cellular constituents in the blood while multiplex cytokine array was used to detect the cytokine profile in patients' sera. A HR tumor cell line, SK-N-SH, was also used for detecting the response to IL-1 beta, a cytokines which is involved in the innate immune responses.
Results:
Distinct patterns of gene expression were detected in HR and LR patients indicating an active T-cell response and a diminished adaptive immune response, respectively. A diminished adaptive immune response in LR patients was evident by higher levels of IL-10 in the sera. In addition, HR patients had lower levels of circulating myeloid derived suppressor cells (MDSC) compared with a control LR patient. LR patients showed slightly higher levels of cytokines of the innate immune responses. Treatment of the HR tumor line with IL-1b induced expression of cytokines of the innate immune responses.
Conclusions:
This data suggests that adaptive immune responses may play an important role in the progression of HR disease whereas innate immune responses may be active in LR patients.
Multiple fluorescence in situ hybridization is the method of choice for studies aimed at determining simultaneous production of signal transduction molecules and neuromodulators in neurons. In our analyses of the monoamine receptor mRNA expression of peptidergic neurons in the rat telencephalon, double tyramide-signal-amplified fluorescence in situ hybridization delivered satisfactory results for coexpression analysis of neuropeptide Y (NPY) and serotonin receptor 2C (5-HT2C) mRNA, a receptor subtype expressed at high-to-moderate abundance in the regions analyzed. However, expression of 5-HT1A mRNA, which is expressed at comparatively low abundance in many telencephalic areas, could not be unequivocally identified in NPY mRNA-reactive neurons due to high background and poor signal-to-noise ratio in fluorescent receptor mRNA detections. Parallel chromogenic in situ hybridization provided clear labeling for 5-HT1A mRNA and additionally offered the possibility to monitor the chromogen deposition at regular time intervals to determine the optimal signal-to-noise ratio. We first developed a double labeling protocol combining fluorescence and chromogenic in situ hybridization and subsequently expanded this variation to combine double fluorescence and chromogenic in situ hybridization for triple labelings. With this method, we documented expression of 5-HT2C and/or 5-HT1A in subpopulations of telencephalic NPY-producing neurons. The method developed in the present study appears suitable for conventional light and fluorescence microscopy, combines advantages of fluorescence and chromogenic in situ hybridization protocols and thus provides a reliable non-radioactive alternative to previously published multiple labeling methods for coexpression analyses in which one mRNA species requires highly sensitive detection.
Agrobacterium species are capable of interkingdom gene transfer between bacteria and plants. The genome of Agrobacterium tumefaciens consists of a circular and a linear chromosome, the At-plasmid and the Ti-plasmid, which harbors bacterial virulence genes required for tumor formation in plants. Little is known about promoter sequences and the small RNA (sRNA) repertoire of this and other α-proteobacteria. We used a differential RNA sequencing (dRNA-seq) approach to map transcriptional start sites of 388 annotated genes and operons. In addition, a total number of 228 sRNAs was revealed from all four Agrobacterium replicons. Twenty-two of these were confirmed by independent RNA gel blot analysis and several sRNAs were differentially expressed in response to growth media, growth phase, temperature or pH. One sRNA from the Ti-plasmid was massively induced under virulence conditions. The presence of 76 cis-antisense sRNAs, two of them on the reverse strand of virulence genes, suggests considerable antisense transcription in Agrobacterium. The information gained from this study provides a valuable reservoir for an in-depth understanding of sRNA-mediated regulation of the complex physiology and infection process of Agrobacterium.
Background: The weight that gene copy number plays in transcription remains controversial; although in specific cases gene expression correlates with copy number, the relationship cannot be inferred at the global level. We hypothesized that genes steadily expressed by 15 melanoma cell lines (CMs) and their parental tissues (TMs) should be critical for oncogenesis and their expression most frequently influenced by their respective copy number.
Results: Functional interpretation of 3,030 transcripts concordantly expressed (Pearson's correlation coefficient p-value < 0.05) by CMs and TMs confirmed an enrichment of functions crucial to oncogenesis. Among them, 968 were expressed according to the transcriptional efficiency predicted by copy number analysis (Pearson's correlation coefficient p-value < 0.05). We named these genes, "genomic delegates" as they represent at the transcriptional level the genetic footprint of individual cancers. We then tested whether the genes could categorize 112 melanoma metastases. Two divergent phenotypes were observed: one with prevalent expression of cancer testis antigens, enhanced cyclin activity, WNT signaling, and a Th17 immune phenotype (Class A). This phenotype expressed, therefore, transcripts previously associated to more aggressive cancer. The second class (B) prevalently expressed genes associated with melanoma signaling including MITF, melanoma differentiation antigens, and displayed a Th1 immune phenotype associated with better prognosis and likelihood to respond to immunotherapy. An intermediate third class (C) was further identified. The three phenotypes were confirmed by unsupervised principal component analysis.
Conclusions: This study suggests that clinically relevant phenotypes of melanoma can be retraced to stable oncogenic properties of cancer cells linked to their genetic back bone, and offers a roadmap for uncovering novel targets for tailored anti-cancer therapy.
The Epstein-Barr Virus (EBV) -encoded EBNA2 protein, which is essential for the in vitro transformation of B-lymphocytes, interferes with cellular processes by binding to proteins via conserved sequence motifs. Its Arginine-Glycine (RG) repeat element contains either symmetrically or asymmetrically di-methylated arginine residues (SDMA and ADMA, respectively). EBNA2 binds via its SDMA-modified RG-repeat to the survival motor neurons protein (SMN) and via the ADMA-RG-repeat to the NP9 protein of the human endogenous retrovirus K (HERV-K (HML-2) Type 1). The hypothesis of this work was that the methylated RG-repeat mimics an epitope shared with cellular proteins that is used for interaction with target structures. With monoclonal antibodies against the modified RG-repeat, we indeed identified cellular homologues that apparently have the same surface structure as methylated EBNA2. With the SDMA-specific antibodies, we precipitated the Sm protein D3 (SmD3) which, like EBNA2, binds via its SDMA-modified RG-repeat to SMN. With the ADMA-specific antibodies, we precipitated the heterogeneous ribonucleoprotein K (hnRNP K). Specific binding of the ADMA-antibody to hnRNP K was demonstrated using E. coli expressed/ADMA-methylated hnRNP K. In addition, we show that EBNA2 and hnRNP K form a complex in EBV-infected B-cells. Finally, hnRNP K, when co-expressed with EBNA2, strongly enhances viral latent membrane protein 2A (LMP2A) expression by an unknown mechanism as we did not detect a direct association of hnRNP K with DNA-bound EBNA2 in gel shift experiments. Our data support the notion that the methylated surface of EBNA2 mimics the surface structure of cellular proteins to interfere with or co-opt their functional properties.