Search for CPCP violation through an amplitude analysis of D0→K+K−π+π−D^0 \to K^+ K^- \pi^+ \pi^- decays

International audienceA search for CP violation in the Cabibbo-suppressed D$^{0}$ → K$^{+}$K$^{−}$π$^{+}$π$^{−}$ decay mode is performed using an amplitude analysis. The measurement uses a sample of pp collisions recorded by the LHCb experiment during 2011 and 2012, corresponding to an integrated luminosity of 3.0 fb$^{−1}$. The D$^{0}$ mesons are reconstructed from semileptonic b-hadron decays into D$^{0}$μ$^{−}$X final states. The selected sample contains more than 160 000 signal decays, allowing the most precise amplitude modelling of this D$^{0}$ decay to date. The obtained amplitude model is used to perform the search for CP violation. The result is compatible with CP symmetry, with a sensitivity ranging from 1% to 15% depending on the amplitude considered

Measurement of the Omega(0)(c) Baryon Lifetime

We report a measurement of the lifetime of the $\Omega_c^0$ baryon using proton-proton collision data at center-of-mass energies of 7 and 8~TeV, corresponding to an integrated luminosity of 3.0 fb$^{-1}$ collected by the LHCb experiment. The sample consists of about 1000 $\Omega_b^-\to\Omega_c^0\mu^-\bar{\nu}_{\mu} X$ signal decays, where the $\Omega_c^0$ baryon is detected in the $pK^-K^-\pi^+$ final state and $X$ represents possible additional undetected particles in the decay. The $\Omega_c^0$ lifetime is measured to be $\tau_{\Omega_c^0} = 268\pm24\pm10\pm2$ fs, where the uncertainties are statistical, systematic, and from the uncertainty in the $D^+$ lifetime, respectively. This value is nearly four times larger than, and inconsistent with, the current world-average value.Comment: 7 pages, 2 figures. All figures and tables, along with any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/lhcbproject/Publications/LHCbProjectPublic/LHCb-PAPER-2018-028.htm

psi-Footprinting approach for the identification of protein synthesis inhibitor producers

Handel F, Kulik A, Wex KW, et al. psi-Footprinting approach for the identification of protein synthesis inhibitor producers. NAR: Genomics and Bioinformatics . 2022;4(3): lqac055.Today, one of the biggest challenges in antibiotic research is a targeted prioritization of natural compound producer strains and an efficient dereplication process to avoid undesired rediscovery of already known substances. Thereby, genome sequence-driven mining strategies are often superior to wet-lab experiments because they are generally faster and less resource-intensive. In the current study, we report on the development of a novel in silico screening approach to evaluate the genetic potential of bacterial strains to produce protein synthesis inhibitors (PSI), which was termed the protein synthesis inhibitor ('psi') target gene footprinting approach = psi-footprinting. The strategy is based on the occurrence of protein synthesis associated self-resistance genes in genome sequences of natural compound producers. The screening approach was applied to 406 genome sequences of actinomycetes strains from the DSMZ strain collection, resulting in the prioritization of 15 potential PSI producer strains. For twelve of them, extract samples showed protein synthesis inhibitory properties in in vitro transcription/translation assays. For four strains, namely Saccharopolyspora flava DSM 44771, Micromonospora aurantiaca DSM 43813, Nocardioides albertanoniae DSM 25218, and Geodermatophilus nigrescens DSM 45408, the protein synthesis inhibitory substance amicoumacin was identified by HPLC-MS analysis, which proved the functionality of the in silico screening approach

Early-phase [18F]PI-2620 tau-PET imaging as a surrogate marker of neuronal injury

PurposeSecond-generation tau radiotracers for use with positron emission tomography (PET) have been developed for visualization of tau deposits in vivo. For several β-amyloid and first-generation tau-PET radiotracers, it has been shown that early-phase images can be used as a surrogate of neuronal injury. Therefore, we investigated the performance of early acquisitions of the novel tau-PET radiotracer [18F]PI-2620 as a potential substitute for [18F]fluorodeoxyglucose ([18F]FDG).MethodsTwenty-six subjects were referred with suspected tauopathies or overlapping parkinsonian syndromes (Alzheimer’s disease, progressive supranuclear palsy, corticobasal syndrome, multi-system atrophy, Parkinson’s disease, multi-system atrophy, Parkinson's disease, frontotemporal dementia) and received a dynamic [18F]PI-2620 tau-PET (0–60 min p.i.) and static [18F]FDG-PET (30–50 min p.i.). Regional standardized uptake value ratios of early-phase images (single frame SUVr) and the blood flow estimate (R1) of [18F]PI-2620-PET were correlated with corresponding quantification of [18F]FDG-PET (global mean/cerebellar normalization). Reduced tracer uptake in cortical target regions was also interpreted visually using 3-dimensional stereotactic surface projections by three more and three less experienced readers. Spearman rank correlation coefficients were calculated between early-phase [18F]PI-2620 tau-PET and [18F]FDG-PET images for all cortical regions and frequencies of disagreement between images were compared for both more and less experienced readers.ResultsHighest agreement with [18F]FDG-PET quantification was reached for [18F]PI-2620-PET acquisition from 0.5 to 2.5 min p.i. for global mean (lowest R = 0.69) and cerebellar scaling (lowest R = 0.63). Correlation coefficients (summed 0.5–2.5 min SUVr & R1) displayed strong agreement in all cortical target regions for global mean (RSUVr 0.76, RR1 = 0.77) and cerebellar normalization (RSUVr 0.68, RR1 = 0.68). Visual interpretation revealed high regional correlations between early-phase tau-PET and [18F]FDG-PET. There were no relevant differences between more and less experienced readers.ConclusionEarly-phase imaging of [18F]PI-2620 can serve as a surrogate biomarker for neuronal injury. Dynamic imaging or a dual time-point protocol for tau-PET imaging could supersede additional [18F]FDG-PET imaging by indexing both the distribution of tau and the extent of neuronal injury

Assessment of F-18-PI-2620 as a Biomarker in Progressive Supranuclear Palsy

Importance Progressive supranuclear palsy (PSP) is a 4-repeat tauopathy. Region-specific tau aggregates establish the neuropathologic diagnosis of definite PSP post mortem. Future interventional trials against tau in PSP would strongly benefit from biomarkers that support diagnosis. Objective To investigate the potential of the novel tau radiotracer F-18-PI-2620 as a biomarker in patients with clinically diagnosed PSP. Design, Setting, and Participants In this cross-sectional study, participants underwent dynamic F-18-PI-2620 positron emission tomography (PET) from 0 to 60 minutes after injection at 5 different centers (3 in Germany, 1 in the US, and 1 in Australia). Patients with PSP (including those with Richardson syndrome [RS]) according to Movement Disorder Society PSP criteria were examined together with healthy controls and controls with disease. Four additionally referred individuals with PSP-RS and 2 with PSP-non-RS were excluded from final data analysis owing to incomplete dynamic PET scans. Data were collected from December 2016 to October 2019 and were analyzed from December 2018 to December 2019. Main Outcomes and Measures Postmortem autoradiography was performed in independent PSP-RS and healthy control samples. By in vivo PET imaging, F-18-PI-2620 distribution volume ratios were obtained in globus pallidus internus and externus, putamen, subthalamic nucleus, substantia nigra, dorsal midbrain, dentate nucleus, dorsolateral, and medial prefrontal cortex. PET data were compared between patients with PSP and control groups and were corrected for center, age, and sex. Results Of 60 patients with PSP, 40 (66.7%) had RS (22 men [55.0%]; mean [SD] age, 71 [6] years; mean [SD] PSP rating scale score, 38 [15]; score range, 13-71) and 20 (33.3%) had PSP-non-RS (11 men [55.0%]; mean [SD] age, 71 [9] years; mean [SD] PSP rating scale score, 24 [11]; score range, 11-41). Ten healthy controls (2 men; mean [SD] age, 67 [7] years) and 20 controls with disease (of 10 [50.0%] with Parkinson disease and multiple system atrophy, 7 were men; mean [SD] age, 61 [8] years; of 10 [50.0%] with Alzheimer disease, 5 were men; mean [SD] age, 69 [10] years). Postmortem autoradiography showed blockable F-18-PI-2620 binding in patients with PSP and no binding in healthy controls. The in vivo findings from the first large-scale observational study in PSP with F-18-PI-2620 indicated significant elevation of tracer binding in PSP target regions with strongest differences in PSP vs control groups in the globus pallidus internus (mean [SD] distribution volume ratios: PSP-RS, 1.21 [0.10]; PSP-non-RS, 1.12 [0.11]; healthy controls, 1.00 [0.08]; Parkinson disease/multiple system atrophy, 1.03 [0.05]; Alzheimer disease, 1.08 [0.06]). Sensitivity and specificity for detection of PSP-RS vs any control group were 85% and 77%, respectively, when using classification by at least 1 positive target region. Conclusions and Relevance This multicenter evaluation indicates a value of F-18-PI-2620 to differentiate suspected patients with PSP, potentially facilitating more reliable diagnosis of PSP. Question Can tau-positron emission tomography imaging with the novel tau radiotracer F-18-PI-2620 differentiate patients with progressive supranuclear palsy (PSP) from healthy controls and controls with disease? Findings In this cross-sectional study of 60 patients with PSP, 10 healthy controls, and 20 controls with disease, there was significantly higher F-18-PI-2620 binding in target regions of patients with PSP compared with controls regardless of disease severity. Individual patients with PSP with Richardson syndrome were separated with high sensitivity and specificity. Meaning F-18-PI-2620 tau-positron emission tomography differentiates patients with PSP from controls at the single-patient level, potentially facilitating a more reliable diagnosis. This cross-sectional study investigates the potential of novel tau radiotracer F-18-PI-2620 as a biomarker in patients with clinically diagnosed progressive supranuclear palsy