Refine
Year of publication
Document Type
- Preprint (776)
- Article (580)
- Working Paper (1)
Language
- English (1357)
Has Fulltext
- yes (1357)
Is part of the Bibliography
- no (1357)
Keywords
- Heavy Ion Experiments (21)
- BESIII (15)
- Hadron-Hadron Scattering (11)
- Hadron-Hadron scattering (experiments) (11)
- Branching fraction (9)
- LHC (9)
- e +-e − Experiments (9)
- Heavy-ion collision (6)
- Particle and Resonance Production (6)
- Quarkonium (6)
- Hadronic decays (5)
- ALICE experiment (4)
- Branching fractions (4)
- Charm physics (4)
- Collective Flow (4)
- Electroweak interaction (4)
- Jets (4)
- Lepton colliders (4)
- QCD (4)
- Quark-Gluon Plasma (4)
- ALICE (3)
- Charm Physics (3)
- Charmed mesons (3)
- Charmonium (3)
- Elastic scattering (3)
- Exotics (3)
- Experimental nuclear physics (3)
- Experimental particle physics (3)
- Heavy Ions (3)
- Heavy Quark Production (3)
- Initial state radiation (3)
- Jets and Jet Substructure (3)
- Particle and resonance production (3)
- Polarization (3)
- Spectroscopy (3)
- e+-e− Experiments (3)
- pp collisions (3)
- Beauty production (2)
- Bhabha (2)
- Collectivity (2)
- Correlation (2)
- Cross section (2)
- Diffraction (2)
- Electroweak Interaction (2)
- Elliptic flow (2)
- Hadronic cross section (2)
- Heavy-ion collisions (2)
- Lepton-Nucleon Scattering (experiments) (2)
- Leptonic, semileptonic & radiative decays (2)
- Muon anomaly (2)
- Particle Correlations and Fluctuations (2)
- Particle correlations and fluctuations (2)
- Particle decays (2)
- Pb–Pb collisions (2)
- Pion form factor (2)
- RHIC (2)
- Shear viscosity (2)
- Single electrons (2)
- mass spectrometry (2)
- 900 GeV (1)
- ALICE detector (1)
- Angular distribution (1)
- Annihilation (1)
- Anti-nuclei (1)
- Atmospheric chemistry (1)
- B-slope (1)
- BESIII detector (1)
- BET inhibitor (1)
- Boosted Jets (1)
- Born cross section measurement (1)
- CP violation (1)
- Centrality Class (1)
- Centrality Selection (1)
- Charged-particle multiplicity (1)
- Charm quark spatial diffusion coefficient (1)
- Charmonia (1)
- Charmonium (-like) (1)
- Climate-change impacts (1)
- Coalescence (1)
- Cold nuclear matter effects (1)
- Collective Flow, (1)
- Comparison with QCD (1)
- Computational models (1)
- Covariance matrix (1)
- Critical point (1)
- Cross section measurements (1)
- Cryoelectron microscopy (1)
- D meson (1)
- D0 and D+ mesons (1)
- DNA damage response (1)
- Dalitz decay (1)
- Dark photon (1)
- Dark sector (1)
- Deuteron production (1)
- Di-hadron correlations (1)
- D⁰ meson (1)
- Electromagnetic amplitude (1)
- Electromagnetic form factor (1)
- Electromagnetic form factors (1)
- Electron-pion identification (1)
- FOS: Physical sciences (1)
- Femtoscopy (1)
- Fibre/foam sandwich radiator (1)
- Flavor changing neutral currents (1)
- Flavor symmetries (1)
- Flavour Physics (1)
- Flow (1)
- Form factors (1)
- Groomed jet radius (1)
- HBT (1)
- HDAC inhibitor (1)
- Hadron production (1)
- Hadron-Hadron Scattering Heavy (1)
- Hadron-hadron interactions (1)
- Hadronization (1)
- Hadrons (1)
- Hard Scattering (1)
- Heavy Ion Experiment (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ion collisions (1)
- Heavy ions (1)
- Heavy-Ion Collision (1)
- Heavy-flavor decay electron (1)
- Heavy-flavour decay muons (1)
- Heavy-flavour production (1)
- Heavy-ion (1)
- High Energy Physics - Experiment (hep-ex) (1)
- Higher moments (1)
- Highwire (1)
- Hyperons (1)
- Inclusive spectra (1)
- Intensity interferometry (1)
- Interference fragmentation function (1)
- Invariant Mass Distribution (1)
- Invisible decays (1)
- Ionisation energy loss (1)
- J/ψ suppression (1)
- Jet Physics (1)
- Jet Substructure (1)
- Jet substructure (1)
- MYCBP2 (1)
- Material budget (1)
- Membrane proteins (1)
- Mid-rapidity (1)
- Minimum Bias (1)
- Monte Carlo (1)
- Multi-Parton Interactions (1)
- Multi-strange baryons (1)
- Multi-wire proportional drift chamber (1)
- Multiple parton interactions (1)
- Net-charge correlations (1)
- Net-charge fluctuations (1)
- Neural network (1)
- Neuron (1)
- Neutrinos (1)
- Nonflow (1)
- Nuclear modification factor (1)
- PAM (1)
- PHR1 (1)
- PYTHIA (1)
- Pain (1)
- Particle phenomena (1)
- Pb–Pb (1)
- Phase (1)
- Production Cross Section (1)
- Properties of Hadrons (1)
- Protein folding (1)
- Proton (1)
- Proton-proton collisions (1)
- Proton–proton (1)
- Proton–proton collisions (1)
- Quantum chromodynamics (1)
- Quark Deconfinement (1)
- Quark Gluon Plasma (1)
- Quark Production (1)
- Quark gluon plasma (1)
- R value (1)
- RNA PT (1)
- RNA modification (1)
- Radiative decay (1)
- Rapidity Range (1)
- Rare decays (1)
- Relativistic heavy ion physics (1)
- Relativistic heavy-ion collisions (1)
- Resolution Parameter (1)
- SF-36 (1)
- STAR (1)
- Semi-leptonic decays (1)
- Single muons (1)
- SoftDrop (1)
- Spin alignment (1)
- Splitting function (1)
- Strong amplitude (1)
- Systematic Uncertainty (1)
- TR (1)
- TRP Channels (1)
- Techniques Electromagnetic calorimeters (1)
- Thermal model (1)
- Time Projection Chamber (1)
- Tracking (1)
- Trafficking (1)
- Transcription factors (1)
- Transition radiation detector (1)
- Transverse momentum (1)
- Transversity (1)
- Trigger (1)
- Triple quarkonia (1)
- Tumour-suppressor proteins (1)
- Ubiquitin Ligase (1)
- Vector Boson Production (1)
- WHO-5 (1)
- X-ray crystallography (1)
- Xenon-based gas mixture (1)
- Y (4260) (1)
- Y states (1)
- branching fractions (1)
- burnout (1)
- center-of-mass energy (1)
- charmed baryon (1)
- charmonium-like states (1)
- chemical biology (1)
- combined therapy (1)
- coronavirus (1)
- cross-cultural leadership (1)
- cross-cultural study (1)
- dE/dx (1)
- decay (1)
- decays (1)
- detector (1)
- deubiquitylating enzymes (1)
- digestion artifact (1)
- dimuon (1)
- diphoton (1)
- dual BET/HDAC inhibitor (1)
- e+e − annihilation (1)
- e+e⁻ − Experiments (1)
- e+e− Experiments (1)
- e+e− annihilation (1)
- ectosomes (1)
- electron-positron collision (1)
- exhaustion (1)
- exosomes (1)
- experimental results (1)
- extracellular vesicles (1)
- guidelines (1)
- hadron spectroscopy (1)
- hadronic events (1)
- heavy ion experiments (1)
- helicity amplitude analysis (1)
- identity leadership (1)
- inclusive J/ψ decays (1)
- innovative behavior (1)
- isoforms (1)
- lockdowns (1)
- luminosity (1)
- microparticles (1)
- microvesicles (1)
- minimal information requirements (1)
- multilevel modeling (1)
- nucleoside analysis (1)
- number of J/ψ events (1)
- p+p collisions (1)
- p38 MAPK (1)
- pain (1)
- pancreatic ductal adenocarcinoma (1)
- positive leadership (1)
- proteomics (1)
- psychological health (1)
- quark gluon plasma (1)
- reproducibility (1)
- rigor (1)
- social identification (1)
- spectra (1)
- standardization (1)
- team identification (1)
- tetraquark (1)
- trigger efficiency (1)
- ubiquitin specific proteases (1)
- Λ+c baryon (1)
- Σ hyperon (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (1301)
- Frankfurt Institute for Advanced Studies (FIAS) (989)
- Informatik (917)
- Medizin (6)
- Informatik und Mathematik (3)
- Psychologie und Sportwissenschaften (3)
- Biochemie und Chemie (2)
- Biochemie, Chemie und Pharmazie (2)
- Hochschulrechenzentrum (2)
- MPI für Biophysik (2)
Comprehensive landscape of active deubiquitinating enzymes profiled by advanced chemoproteomics
(2019)
Enzymes that bind and process ubiquitin, a small 76-amino-acid protein, have been recognized as pharmacological targets in oncology, immunological disorders, and neurodegeneration. Mass spectrometry technology has now reached the capacity to cover the proteome with enough depth to interrogate entire biochemical pathways including those that contain DUBs and E3 ligase substrates. We have recently characterized the breast cancer cell (MCF7) deep proteome by detecting and quantifying ~10,000 proteins, and within this data set, we can detect endogenous expression of 65 deubiquitylating enzymes (DUBs), whereas matching transcriptomics detected 78 DUB mRNAs. Since enzyme activity provides another meaningful layer of information in addition to the expression levels, we have combined advanced mass spectrometry technology, pre-fractionation, and more potent/selective ubiquitin active-site probes with propargylic-based electrophiles to profile 74 DUBs including distinguishable isoforms for 5 DUBs in MCF7 crude extract material. Competition experiments with cysteine alkylating agents and pan-DUB inhibitors combined with probe labeling revealed the proportion of active cellular DUBs directly engaged with probes by label-free quantitative (LFQ) mass spectrometry. This demonstrated that USP13, 39, and 40 are non-reactive to probe, indicating restricted enzymatic activity under these cellular conditions. Our extended chemoproteomics workflow increases depth of covering the active DUBome, including isoform-specific resolution, and provides the framework for more comprehensive cell-based small-molecule DUB selectivity profiling.
Background: In patients with genotype 1 chronic hepatitis C infection, telaprevir (TVR) in combination with peginterferon and ribavirin (PR) significantly increased sustained virologic response (SVR) rates compared with PR alone. However, genotypic changes could be observed in TVR-treated patients who did not achieve an SVR.
Methods: Population sequence analysis of the NS3•4A region was performed in patients who did not achieve SVR with TVR-based treatment.
Results: Resistant variants were observed after treatment with a telaprevir-based regimen in 12% of treatment-naïve patients (ADVANCE; T12PR arm), 6% of prior relapsers, 24% of prior partial responders, and 51% of prior null responder patients (REALIZE, T12PR48 arms). NS3 protease variants V36M, R155K, and V36M+R155K emerged frequently in patients with genotype 1a and V36A, T54A, and A156S/T in patients with genotype 1b. Lower-level resistance to telaprevir was conferred by V36A/M, T54A/S, R155K/T, and A156S variants; and higher-level resistance to telaprevir was conferred by A156T and V36M+R155K variants. Virologic failure during telaprevir treatment was more common in patients with genotype 1a and in prior PR nonresponder patients and was associated with higher-level telaprevir-resistant variants. Relapse was usually associated with wild-type or lower-level resistant variants. After treatment, viral populations were wild-type with a median time of 10 months for genotype 1a and 3 weeks for genotype 1b patients.
Conclusions: A consistent, subtype-dependent resistance profile was observed in patients who did not achieve an SVR with telaprevir-based treatment. The primary role of TVR is to inhibit wild-type virus and variants with lower-levels of resistance to telaprevir. The complementary role of PR is to clear any remaining telaprevir-resistant variants, especially higher-level telaprevir-resistant variants. Resistant variants are detectable in most patients who fail to achieve SVR, but their levels decline over time after treatment.
The extremophile Alvinella pompejana, an annelid worm living on the edge of hydrothermal vents in the Pacific Ocean, is an excellent model system for studying factors that govern protein stability. Low intrinsic stability is a crucial factor for the susceptibility of the transcription factor p53 to inactivating mutations in human cancer. Understanding its molecular basis may facilitate the design of novel therapeutic strategies targeting mutant p53. By analyzing expressed sequence tag (EST) data, we discovered a p53 family gene in A. pompejana. Protein crystallography and biophysical studies showed that it has a p53/p63-like DNA-binding domain (DBD) that is more thermostable than all vertebrate p53 DBDs tested so far, but not as stable as that of human p63. We also identified features associated with its increased thermostability. In addition, the A. pompejana homolog shares DNA-binding properties with human p53 family DBDs, despite its evolutionary distance, consistent with a potential role in maintaining genome integrity. Through extensive structural and phylogenetic analyses, we could further trace key evolutionary events that shaped the structure, stability, and function of the p53 family DBD over time, leading to a potent but vulnerable tumor suppressor in humans.
The E3 ubiquitin ligase MYCBP2 negatively regulates neuronal growth, synaptogenesis, and synaptic strength. More recently it was shown that MYCBP2 is also involved in receptor and ion channel internalization. We found that mice with a MYCBP2-deficiency in peripheral sensory neurons show prolonged thermal hyperalgesia. Loss of MYCBP2 constitutively activated p38 MAPK and increased expression of several proteins involved in receptor trafficking. Surprisingly, loss of MYCBP2 inhibited internalization of transient receptor potential vanilloid receptor 1 (TRPV1) and prevented desensitization of capsaicin-induced calcium increases. Lack of desensitization, TRPV internalization and prolonged hyperalgesia were reversed by inhibition of p38 MAPK. The effects were TRPV-specific, since neither mustard oil-induced desensitization nor behavioral responses to mechanical stimuli were affected. In summary, we show here for the first time that p38 MAPK activation can inhibit activity-induced ion channel internalization and that MYCBP2 regulates internalization of TRPV1 in peripheral sensory neurons as well as duration of thermal hyperalgesia through p38 MAPK.
In this report, we perform structure validation of recently reported RNA phosphorothioate (PT) modifications, a new set of epitranscriptome marks found in bacteria and eukaryotes including humans. By comparing synthetic PT-containing diribonucleotides with native species in RNA hydrolysates by high-resolution mass spectrometry (MS), metabolic stable isotope labeling, and PT-specific iodine-desulfurization, we disprove the existence of PTs in RNA from E. coli, S. cerevisiae, human cell lines, and mouse brain. Furthermore, we discuss how an MS artifact led to the initial misidentification of 2′-O-methylated diribonucleotides as RNA phosphorothioates. To aid structure validation of new nucleic acid modifications, we present a detailed guideline for MS analysis of RNA hydrolysates, emphasizing how the chosen RNA hydrolysis protocol can be a decisive factor in discovering and quantifying RNA modifications in biological samples.
Human feline leukemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and 2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN, and Fowler syndrome2–7. Earlier studies concluded that FLVCR1 may function as a putative heme exporter8–12, while FLVCR2 was suggested to act as a heme importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14–17. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across human plasma membranes, utilizing a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unraveled the coordination chemistry underlying their substrate interactions. Within the binding pocket of both transporters, we identify fully conserved tryptophan and tyrosine residues holding a central role in the formation of cation-π interactions, essential for choline and ethanolamine selectivity. Our findings not only clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhancing our comprehension of disease-associated mutations that interfere with these vital processes, but also shed light on the conformational dynamics of these MFS-type proteins during the transport cycle.
Human feline leukaemia virus subgroup C receptor-related proteins 1 and 2 (FLVCR1 and FLVCR2) are members of the major facilitator superfamily1. Their dysfunction is linked to several clinical disorders, including PCARP, HSAN and Fowler syndrome2,3,4,5,6,7. Earlier studies concluded that FLVCR1 may function as a haem exporter8,9,10,11,12, whereas FLVCR2 was suggested to act as a haem importer13, yet conclusive biochemical and detailed molecular evidence remained elusive for the function of both transporters14,15,16. Here, we show that FLVCR1 and FLVCR2 facilitate the transport of choline and ethanolamine across the plasma membrane, using a concentration-driven substrate translocation process. Through structural and computational analyses, we have identified distinct conformational states of FLVCRs and unravelled the coordination chemistry underlying their substrate interactions. Fully conserved tryptophan and tyrosine residues form the binding pocket of both transporters and confer selectivity for choline and ethanolamine through cation–π interactions. Our findings clarify the mechanisms of choline and ethanolamine transport by FLVCR1 and FLVCR2, enhance our comprehension of disease-associated mutations that interfere with these vital processes and shed light on the conformational dynamics of these major facilitator superfamily proteins during the transport cycle.