Refine
Year of publication
Document Type
- Article (138)
- Preprint (45)
- Part of a Book (1)
- Conference Proceeding (1)
- Part of Periodical (1)
Has Fulltext
- yes (186)
Is part of the Bibliography
- no (186)
Keywords
- LHC (8)
- environmental tobacco smoke (4)
- particulate matter (4)
- ALICE (3)
- ALICE experiment (3)
- Hadron-Hadron Scattering (3)
- Knowledge (3)
- Malaria (3)
- pp collisions (3)
- Aedes aegypti (2)
- Aedes albopictus (2)
- Attitude (2)
- Beauty production (2)
- Bibliometrics (2)
- Clinical Trials and Observations (2)
- Dengue (2)
- Heavy Ions (2)
- Heavy-ion collisions (2)
- Mountain (2)
- RNF4 (2)
- Single electrons (2)
- Zika virus (2)
- additives (2)
- second-hand smoke (2)
- 900 GeV (1)
- ALICE LHC (1)
- Akaike information criterion (AIC) (1)
- Amateurfilm (1)
- Anandamide (1)
- Anti-seizure medication (1)
- Archiv (1)
- Archivierung (1)
- Ausstellung (1)
- Awareness (1)
- BCOR (1)
- BCORL1 (1)
- BG-index (1)
- Balance function (1)
- Biomarker (1)
- Bone cancer (1)
- Breast cancer (1)
- CCL2 (1)
- CVID (1)
- Calorimeters (1)
- Cancer genetics (1)
- Cellular microbiology (1)
- Charge correlations (1)
- Charged-particle density (1)
- Charm physics (1)
- Chemical biology (1)
- Chemical ecology (1)
- Chikungunya (1)
- Chikungunya virus (1)
- Cigarettes (1)
- Citation analysis (1)
- Climate inequity (1)
- Cognitive impairment (1)
- Cold hardiness (1)
- Cold tolerance (1)
- Community health services (1)
- Comparison with QCD (1)
- Computer hardware (1)
- Computer software (1)
- Computers (1)
- Cryoelectron microscopy (1)
- Cryoelectron tomography (1)
- Culicidae (1)
- DNA sequencing (1)
- Dengue fever (1)
- Dengue virus (1)
- Digital breast tomosynthesis (DBT) (1)
- Digital mammography (1)
- Diptera (1)
- Distance to water (1)
- Distribution limits (1)
- Elevation (1)
- Environmental chemistry (1)
- Environmental sciences (1)
- Epilepsy (1)
- European Society for Immunodeficiencies (ESID) (1)
- Everolimus (1)
- Femtoscopy (1)
- Filariasis (1)
- General practitioner (1)
- Genetics (1)
- Genome-wide association studies (1)
- Geographically weighted regression (GWR) (1)
- German PID-NET registry (1)
- Gewebetypen (1)
- Global warming (1)
- Greenhouse effect (1)
- HBT (1)
- HDAC4 (1)
- HNSCC (1)
- Hadron production (1)
- Healthcare worker (1)
- Heavy flavor production (1)
- Heavy flavour production (1)
- Heavy ions (1)
- Heavy-flavour production (1)
- Heldenepos (1)
- Hepatitis B (1)
- Hepatitis B infection (1)
- Hepatitis B vaccination (1)
- High altitude (1)
- Himalayas (1)
- Hindu Kush Himalayas (1)
- Iceland (1)
- IgG substitution therapy (1)
- Inclusive spectra (1)
- Indoor air pollution (1)
- Inflammation (1)
- Intensity interferometry (1)
- Internet (1)
- Interspecific competition (1)
- Irrall, Elfriede (1)
- Jets (1)
- KAP (1)
- Kontamination <Literatur> (1)
- Kuratieren (1)
- Large Hadron Collider (1)
- Lee-type (1)
- Leishmaniasis (1)
- Livestock (1)
- Local climate (1)
- Loco-regional control (1)
- Lymphoid Neoplasia (1)
- Machine learning (1)
- Magnetic resonance imaging (1)
- Malaria prevalence (1)
- Microalgae (1)
- Mid-rapidity (1)
- Monte Carlo (1)
- Mosquito (1)
- Multi-strange baryons (1)
- Multienzyme complexes (1)
- Multivariable analysis (1)
- Myeloid Neoplasia (1)
- NCoR1 (1)
- NMDA IgA/IgM antibodies (1)
- NMDA antibody (1)
- NR4A2 (1)
- Nibelungenlied (1)
- Niche differentiation (1)
- Nuclear modification factor (1)
- Ordinary least squares (OLS) (1)
- Overwintering (1)
- PID prevalence (1)
- PML (1)
- PYTHIA (1)
- Paediatrics (1)
- Parkinson disease (1)
- Particulate matter (1)
- Pb–Pb (1)
- Performance of High Energy Physics Detectors (1)
- Phenotypic plasticity (1)
- Physical environment (1)
- PolySUMOylation (1)
- Population-based screening (1)
- Poverty (1)
- Practice (1)
- Proton–proton (1)
- Prototypes (1)
- RBC (1)
- Radiomics (1)
- Rainfall (1)
- Recall rate (1)
- Relativistic heavy ion physics (1)
- Research investment (1)
- Resource competition (1)
- Rhabdomyoma (1)
- Risk factors (1)
- Rural area (1)
- SARS-CoV-2 (1)
- SENP6 (1)
- SUMO (1)
- SUMO chains (1)
- Sandfly (1)
- Scientific publishing (1)
- Scientists (1)
- Seizure (1)
- Single muons (1)
- Social epidemiology (1)
- Social health determinants (1)
- Socioeconomic indices (1)
- StUbL (1)
- Stem-cell therapies (1)
- Sub-zero exposure (1)
- Sumatra (1)
- Systematic Uncertainty (1)
- Textgeschichte (1)
- Time Projection Chamber (1)
- Transportation (1)
- Transverse Momentum (1)
- Transverse momentum (1)
- Validation (1)
- Viral infection (1)
- Water chemistry (1)
- Wide rapidity coverage (1)
- Winter survival (1)
- Zika (1)
- Zika vaccine (1)
- Zoopotentation (1)
- Zooprophylaxis (1)
- academic medicine (1)
- acute coronary syndrome (1)
- acute myeloid leukaemia (1)
- acute myeloid leukemia (1)
- antibodies (1)
- apex (1)
- aromatics (1)
- automatic environmental tobacco smoke emitter (1)
- b-cell lymphomas (1)
- bendamustine (1)
- career promotion (1)
- chemotherapy regimen (1)
- chimeric antigen receptor t-cell therapy (1)
- chimeric antigen receptors (1)
- cigarette strength (1)
- climate change (1)
- climate change genomics (1)
- copeptin (1)
- declaration of tobacco ingredients (1)
- dementia (1)
- dengue vector (1)
- diffusion tensor imaging (1)
- disasters (1)
- egg sampling (1)
- epidemics (1)
- functional outcome (1)
- gender (1)
- gender difference (1)
- hatching (1)
- health (1)
- hematopoietic stem cell transplantation (1)
- humectant agents (1)
- image-based risk modelling (1)
- in-cabin exposure (1)
- indoor air pollution (1)
- induction chemotherapy (1)
- infectious disease (1)
- international transport (1)
- latent factor mixed model (1)
- leukapheresis (1)
- loss-of-function (1)
- lymphoma (1)
- mTOR inhibitor (1)
- machine learning (1)
- magnetic resonance imaging (1)
- membrane-less organelles (1)
- membranous urethra (1)
- mental health (1)
- menthol (1)
- mid-term urinary continence (1)
- mild cognitive impairment (1)
- mobile air quality study (1)
- monitoring (1)
- monsoon (1)
- mortality (1)
- mountain (1)
- myocardial infarction (1)
- neurodegeneration (1)
- non-communicable disease (1)
- nuclear receptor-related 1 (1)
- nucleolus (1)
- oviposition (1)
- oviposition substrate (1)
- ovitrap (1)
- particle size distribution (1)
- personalised therapy (1)
- pharmacophore model (1)
- postmonsoon (1)
- primary immunodeficiency (PID) (1)
- promotion index (1)
- prostate cancer (1)
- public health (1)
- radiation oncology (1)
- radical prostatectomy (1)
- radiomic (1)
- range expansion (1)
- registry (1)
- registry for primary immunodeficiency (1)
- risk stratification (1)
- rituximab (1)
- size of cigarettes (1)
- spectra (1)
- splicing (1)
- stress granules (1)
- survival (1)
- tobacco control (1)
- tobacco products (1)
- traffic emissions (1)
- transcription factor (1)
- transfusion (1)
- troponin (1)
- vaccine acceptance (1)
- vaccine trial (1)
- ventilation modes (1)
- whole genome pooled sequencing (1)
- willingness to participate (1)
- yellow fever mosquito (1)
- √sN N = 2.76 TeV (1)
Institute
- Physik (112)
- Frankfurt Institute for Advanced Studies (FIAS) (101)
- Informatik (99)
- Medizin (64)
- Biochemie und Chemie (6)
- Senckenbergische Naturforschende Gesellschaft (3)
- Biodiversität und Klima Forschungszentrum (BiK-F) (2)
- Geowissenschaften (2)
- Geowissenschaften / Geographie (2)
- Biochemie, Chemie und Pharmazie (1)
Measurements of cross sections of inelastic and diffractive processes in proton--proton collisions at LHC energies were carried out with the ALICE detector. The fractions of diffractive processes in inelastic collisions were determined from a study of gaps in charged particle pseudorapidity distributions: for single diffraction (diffractive mass MX<200 GeV/c2) σSD/σINEL=0.21±0.03,0.20+0.07−0.08, and 0.20+0.04−0.07, respectively at centre-of-mass energies s√=0.9,2.76, and 7~TeV; for double diffraction (for a pseudorapidity gap Δη>3) σDD/σINEL=0.11±0.03,0.12±0.05, and 0.12+0.05−0.04, respectively at s√=0.9,2.76, and 7~TeV. To measure the inelastic cross section, beam properties were determined with van der Meer scans, and, using a simulation of diffraction adjusted to data, the following values were obtained: σINEL=62.8+2.4−4.0(model)±1.2(lumi) mb at s√= 2.76~TeV and 73.2+2.0−4.6(model)±2.6(lumi) mb at s√ = 7~TeV. The single- and double-diffractive cross sections were calculated combining relative rates of diffraction with inelastic cross sections. The results are compared to previous measurements at proton--antiproton and proton--proton colliders at lower energies, to measurements by other experiments at the LHC, and to theoretical models.
We report the first measurement of the net-charge fluctuations in Pb-Pb collisions at sNN−−−√ = 2.76 TeV, measured with the ALICE detector at the CERN Large Hadron Collider. The dynamical fluctuations per unit entropy are observed to decrease when going from peripheral to central collisions. An additional reduction in the amount of fluctuations is seen in comparison to the results from lower energies. We examine the dependence of fluctuations on the pseudorapidity interval, which may account for the dilution of fluctuations during the evolution of the system. We find that the fluctuations at LHC are smaller compared to the measurements at the Relativistic heavy Ion Collider (RHIC), and as such, closer to what has been theoretically predicted for the formation of Quark-Gluon Plasma (QGP).
In this Letter we report the first results on π±, K±, p and pp¯¯¯ production at mid-rapidity (|y|<0.5) in central Pb-Pb collisions at sNN−−−√ = 2.76 TeV, measured by the ALICE experiment at the LHC. The pT distributions and yields are compared to previous results at sNN−−−√ = 200 GeV and expectations from hydrodynamic and thermal models. The spectral shapes indicate a strong increase of the radial flow velocity with sNN−−−√, which in hydrodynamic models is expected as a consequence of the increasing particle density. While the K/π ratio is in line with predictions from the thermal model, the p/π ratio is found to be lower by a factor of about 1.5. This deviation from thermal model expectations is still to be understood.
The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at sqrt{s}=7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L_int = 5.6nb-1. The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p_t>1.3 GeV/c and rapidity |y|<0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the Psi(2S) and Csi_c resonances, is sigma_prompt-J/psi(pt > 1.3 GeV/c, |y| < 0.9) = 8.3 +- 0.8(stat.) +- 1.1(syst.) + 1.5 - 1.4(syst. pol.) micro barn. The cross section for the production of b-hadrons decaying to J/psi with p_t>1.3 GeV/c and |y|<0.9 is sigma_{J/psi<-h_B} = 1.46 +- 0.38(stat.) + 0.26 -0.32(syst.) micro barn. The results are compared to QCD model predictions. The shape of the p_t and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b-bbar pair total cross section and dsigma/dy at mid-rapidity.
The ALICE Collaboration has measured the inclusive production of muons from heavy flavour decays at forward rapidity, 2.5 < y < 4, in pp and Pb-Pb collisions at sNN−−−−√ = 2.76 TeV. The pT-differential inclusive cross section of muons from heavy flavour decays in pp collisions is compared to perturbative QCD calculations. The nuclear modification factor is studied as a function of pt and collision centrality. A weak suppression is measured in peripheral collisions. In the most central collisions, a suppression of a factor of about 3-4 is observed in 6 < pT < 10 GeV/c. The suppression shows no significant pT dependence.
Measurement of electrons from semileptonic heavy-flavor hadron decays in pp collisions at √s = 7 TeV
(2012)
The differential production cross section of electrons from semileptonic heavy-flavour hadron decays has been measured at mid-rapidity (|y|<0.5) in proton-proton collisions at s√=7 TeV with ALICE at the LHC. Electrons were measured in the transverse momentum range 0.5 <pT< 8 GeV/c. Predictions from a fixed order perturbative QCD calculation with next-to-leading-log resummation agree with the data within the theoretical and experimental uncertainties.
Measurement of charm production at central rapidity in proton-proton collisions at √s = 2.76 TeV
(2012)
The pT-differential production cross sections of the prompt (B feed-down subtracted) charmed mesons D0, D+, and D∗+ in the rapidity range |y|<0.5, and for transverse momentum 1<pT<12 GeV/c, were measured in proton-proton collisions at s√=2.76 TeV with the ALICE detector at the Large Hadron Collider. The analysis exploited the hadronic decays D0→Kπ, D+→Kππ, D∗+→D0π, and their charge conjugates, and was performed on a Lint=1.1 nb−1 event sample collected in 2011 with a minimum-bias trigger. The total charm production cross section at s√=2.76 TeV and at 7 TeV was evaluated by extrapolating to the full phase space the pT-differential production cross sections at s√=2.76 TeV and our previous measurements at s√=7 TeV. The results were compared to existing measurements and to perturbative-QCD calculations. The fraction of cdbar D mesons produced in a vector state was also determined.
Rapidity and transverse momentum dependence of inclusive J/ψ production in pp collisions at √s=7 TeV
(2011)
The ALICE experiment at the LHC has studied inclusive J/ψ production at central and forward rapidities in pp collisions at √s=7 TeV. In this Letter, we report on the first results obtained detecting the J/ψ through the dilepton decay into e+e− and μ+μ− pairs in the rapidity ranges |y|<0.9 and 2.5<y<4, respectively, and with acceptance down to zero pT. In the dielectron channel the analysis was carried out on a data sample corresponding to an integrated luminosity Lint=5.6 nb−1 and the number of signal events is NJ/ψ=352±32(stat.)±28(syst.); the corresponding figures in the dimuon channel are Lint=15.6 nb−1 and NJ/ψ=1924±77(stat.)±144(syst.). The measured production cross sections are σJ/ψ(|y|<0.9)=10.7±1.0(stat.)±1.6(syst.)−2.3+1.6(syst.pol.)μb and σJ/ψ(2.5<y<4)=6.31±0.25(stat.)±0.76(syst.)−1.96+0.95(syst.pol.)μb. The differential cross sections, in transverse momentum and rapidity, of the J/ψ were also measured.
The first measurement of two-pion Bose–Einstein correlations in central Pb–Pb collisions at √sNN=2.76 TeV at the Large Hadron Collider is presented. We observe a growing trend with energy now not only for the longitudinal and the outward but also for the sideward pion source radius. The pion homogeneity volume and the decoupling time are significantly larger than those measured at RHIC.
The inclusive charged particle transverse momentum distribution is measured in proton–proton collisions at s=900 GeV at the LHC using the ALICE detector. The measurement is performed in the central pseudorapidity region (|η|<0.8) over the transverse momentum range 0.15<pT<10 GeV/c. The correlation between transverse momentum and particle multiplicity is also studied. Results are presented for inelastic (INEL) and non-single-diffractive (NSD) events. The average transverse momentum for |η|<0.8 is 〈pT〉INEL=0.483±0.001 (stat.)±0.007 (syst.) GeV/c and 〈pT〉NSD=0.489±0.001 (stat.)±0.007 (syst.) GeV/c, respectively. The data exhibit a slightly larger 〈pT〉 than measurements in wider pseudorapidity intervals. The results are compared to simulations with the Monte Carlo event generators PYTHIA and PHOJET.
Inclusive transverse momentum spectra of primary charged particles in Pb–Pb collisions at √sNN=2.76 TeV have been measured by the ALICE Collaboration at the LHC. The data are presented for central and peripheral collisions, corresponding to 0–5% and 70–80% of the hadronic Pb–Pb cross section. The measured charged particle spectra in |η|<0.8 and 0.3<pT<20 GeV/c are compared to the expectation in pp collisions at the same sNN, scaled by the number of underlying nucleon–nucleon collisions. The comparison is expressed in terms of the nuclear modification factor RAA. The result indicates only weak medium effects (RAA≈0.7) in peripheral collisions. In central collisions, RAA reaches a minimum of about 0.14 at pT=6–7 GeV/c and increases significantly at larger pT. The measured suppression of high-pT particles is stronger than that observed at lower collision energies, indicating that a very dense medium is formed in central Pb–Pb collisions at the LHC.
Mutations of the isocitrate dehydrogenase-1 (IDH1) and IDH2 genes are among the most frequent alterations in acute myeloid leukemia (AML) and can be found in ∼20% of patients at diagnosis. Among 4930 patients (median age, 56 years; interquartile range, 45-66) with newly diagnosed, intensively treated AML, we identified IDH1 mutations in 423 (8.6%) and IDH2 mutations in 575 (11.7%). Overall, there were no differences in response rates or survival for patients with mutations in IDH1 or IDH2 compared with patients without mutated IDH1/2. However, distinct clinical and comutational phenotypes of the most common subtypes of IDH1/2 mutations could be associated with differences in outcome. IDH1-R132C was associated with increased age, lower white blood cell (WBC) count, less frequent comutation of NPM1 and FLT3 internal tandem mutation (ITD) as well as with lower rate of complete remission and a trend toward reduced overall survival (OS) compared with other IDH1 mutation variants and wild-type (WT) IDH1/2. In our analysis, IDH2-R172K was associated with significantly lower WBC count, more karyotype abnormalities, and less frequent comutations of NPM1 and/or FLT3-ITD. Among patients within the European LeukemiaNet 2017 intermediate- and adverse-risk groups, relapse-free survival and OS were significantly better for those with IDH2-R172K compared with WT IDH, providing evidence that AML with IDH2-R172K could be a distinct entity with a specific comutation pattern and favorable outcome. In summary, the presented data from a large cohort of patients with IDH1/2 mutated AML indicate novel and clinically relevant findings for the most common IDH mutation subtypes.
SUMO : glue or solvent for phase-separated ribonucleoprotein complexes and molecular condensates?
(2021)
Spatial organization of cellular processes in membranous or membrane-less organelles (MLOs, alias molecular condensates) is a key concept for compartmentalizing biochemical pathways. Prime examples of MLOs are the nucleolus, PML nuclear bodies, nuclear splicing speckles or cytosolic stress granules. They all represent distinct sub- cellular structures typically enriched in intrinsically disordered proteins and/or RNA and are formed in a process driven by liquid-liquid phase separation. Several MLOs are critically involved in proteostasis and their formation, disassembly and composition are highly sensitive to proteotoxic insults. Changes in the dynamics of MLOs are a major driver of cell dysfunction and disease. There is growing evidence that post-translational modifications are critically involved in controlling the dynamics and composition of MLOs and recent evidence supports an important role of the ubiquitin-like SUMO system in regulating both the assembly and disassembly of these structures. Here we will review our current understanding of SUMO function in MLO dynamics under both normal and pathological conditions.
Osteosarcomas are aggressive bone tumours with a high degree of genetic heterogeneity, which has historically complicated driver gene discovery. Here we sequence exomes of 31 tumours and decipher their evolutionary landscape by inferring clonality of the individual mutation events. Exome findings are interpreted in the context of mutation and SNP array data from a replication set of 92 tumours. We identify 14 genes as the main drivers, of which some were formerly unknown in the context of osteosarcoma. None of the drivers is clearly responsible for the majority of tumours and even TP53 mutations are frequently mapped into subclones. However, >80% of osteosarcomas exhibit a specific combination of single-base substitutions, LOH, or large-scale genome instability signatures characteristic of BRCA1/2-deficient tumours. Our findings imply that multiple oncogenic pathways drive chromosomal instability during osteosarcoma evolution and result in the acquisition of BRCA-like traits, which could be therapeutically exploited.
Background: Ever since it was discovered that zoophilic vectors can transmit malaria, zooprophylaxis has been used to prevent the disease. However, zoopotentiation has also been observed. Thus, the presence of livestock has been widely accepted as an important variable for the prevalence and risk of malaria, but the effectiveness of zooprophylaxis remained subject to debate. This study aims to critically analyse the effects of the presence of livestock on malaria prevalence using a large dataset from Indonesia.
Methods: This study is based on data from the Indonesia Basic Health Research ("Riskesdas") cross-sectional survey of 2007 organized by the National Institute of Health Research and Development of Indonesia’s Ministry of Health. The subset of data used in the present study included 259,885 research participants who reside in the rural areas of 176 regencies throughout the 15 provinces of Indonesia where the prevalence of malaria is higher than the national average. The variable "existence of livestock" and other independent demographic, social and behavioural variables were tested as potential determinants for malaria prevalence by multivariate logistic regressions.
Results: Raising medium-sized animals in the house was a significant predictor of malaria prevalence (OR = 2.980; 95% CI 2.348–3.782, P < 0.001) when compared to keeping such animals outside of the house (OR = 1.713; 95% CI 1.515–1.937, P < 0.001). After adjusting for gender, age, access to community health facility, sewage canal condition, use of mosquito nets and insecticide-treated bed nets, the participants who raised medium-sized animals inside their homes were 2.8 times more likely to contract malaria than respondents who did not (adjusted odds ratio = 2.809; 95% CI 2.207–3.575; P < 0.001).
Conclusions: The results of this study highlight the importance of livestock for malaria transmission, suggesting that keeping livestock in the house contributes to malaria risk rather than prophylaxis in Indonesia. Livestock-based interventions should therefore play a significant role in the implementation of malaria control programmes, and focus on households with a high proportion of medium-sized animals in rural areas. The implementation of a "One Health" strategy to eliminate malaria in Indonesia by 2030 is strongly recommended.
In Germany, orthopedic workforce planning relies on population-to-provider-ratios represented by the "official degree of care provision". However, with geographic information systems (GIS), more sophisticated measurements are available. By utilizing GIS-based technologies we analyzed the current state of demand and supply of the orthopedic workforce in Germany (orthopedic accessibility) with the integrated Floating Catchment Area method. The analysis of n = 153,352,220 distances revealed significant geographical variations on national scale: 5,617,595 people (6.9% of total population) lived in an area with significant low orthopedic accessibility (average z-score = -4.0), whereas 31,748,161 people (39.0% of total population) lived in an area with significant high orthopedic accessibility (average z-score = 8.0). Accessibility was positively correlated with the degree of urbanization (r = 0.49; p<0.001) and the official degree of care provision (r = 0.33; p<0.001) and negatively correlated with regional social deprivation (r = -0.47; p<0.001). Despite advantages of simpler measures regarding implementation and acceptance in health policy, more sophisticated measures of accessibility have the potential to reduce costs as well as improve health care. With this study, significant geographical variations were revealed that show the need to reduce oversupply in less deprived urban areas in order to enable adequate care in more deprived rural areas.
HDL, through sphingosine-1-phosphate (S1P), exerts direct cardioprotective effects on ischemic myocardium. It remains unclear whether other HDL-associated sphingophospholipids have similar effects. We therefore examined if HDL-associated sphingosylphosphorylcholine (SPC) reduces infarct size in a mouse model of transient myocardial ischemia/reperfusion. Intravenously administered SPC dose-dependently reduced infarct size after 30 minutes of myocardial ischemia and 24 hours reperfusion compared to controls. Infarct size was also reduced by postischemic, therapeutical administration of SPC. Immunohistochemistry revealed reduced polymorphonuclear neutrophil recruitment to the infarcted area after SPC treatment, and apoptosis was attenuated as measured by TUNEL. In vitro, SPC inhibited leukocyte adhesion to TNFα-activated endothelial cells and protected rat neonatal cardiomyocytes from apoptosis. S1P3 was identified as the lysophospholipid receptor mediating the cardioprotection by SPC, since its effect was completely absent in S1P3-deficient mice. We conclude that HDL-associated SPC directly protects against myocardial reperfusion injury in vivo via the S1P3 receptor.
A wide variety of enzymatic pathways that produce specialized metabolites in bacteria, fungi and plants are known to be encoded in biosynthetic gene clusters. Information about these clusters, pathways and metabolites is currently dispersed throughout the literature, making it difficult to exploit. To facilitate consistent and systematic deposition and retrieval of data on biosynthetic gene clusters, we propose the Minimum Information about a Biosynthetic Gene cluster (MIBiG) data standard.
Simple Summary: Acute myeloid leukemia (AML) is a genetically heterogeneous disease. Clinical phenotypes of frequent mutations and their impact on patient outcome are well established. However, the role of rare mutations often remains elusive. We retrospectively analyzed 1529 newly diagnosed and intensively treated AML patients for mutations of BCOR and BCORL1. We report a distinct co-mutational pattern that suggests a role in disease progression rather than initiation, especially affecting mechanisms of DNA-methylation. Further, we found loss-of-function mutations of BCOR to be independent markers of poor outcomes in multivariable analysis. Therefore, loss-of-function mutations of BCOR need to be considered for AML management, as they may influence risk stratification and subsequent treatment allocation.
Abstract: Acute myeloid leukemia (AML) is characterized by recurrent genetic events. The BCL6 corepressor (BCOR) and its homolog, the BCL6 corepressor-like 1 (BCORL1), have been reported to be rare but recurrent mutations in AML. Previously, smaller studies have reported conflicting results regarding impacts on outcomes. Here, we retrospectively analyzed a large cohort of 1529 patients with newly diagnosed and intensively treated AML. BCOR and BCORL1 mutations were found in 71 (4.6%) and 53 patients (3.5%), respectively. Frequently co-mutated genes were DNTM3A, TET2 and RUNX1. Mutated BCORL1 and loss-of-function mutations of BCOR were significantly more common in the ELN2017 intermediate-risk group. Patients harboring loss-of-function mutations of BCOR had a significantly reduced median event-free survival (HR = 1.464 (95%-Confidence Interval (CI): 1.005–2.134), p = 0.047), relapse-free survival (HR = 1.904 (95%-CI: 1.163–3.117), p = 0.01), and trend for reduced overall survival (HR = 1.495 (95%-CI: 0.990–2.258), p = 0.056) in multivariable analysis. Our study establishes a novel role for loss-of-function mutations of BCOR regarding risk stratification in AML, which may influence treatment allocation.