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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.
The endoplasmic reticulum–mitochondria encounter structure (ERMES) connects the mitochondrial outer membrane with the ER. Multiple functions have been linked to ERMES, including maintenance of mitochondrial morphology, protein assembly and phospholipid homeostasis. Since the mitochondrial distribution and morphology protein Mdm10 is present in both ERMES and the mitochondrial sorting and assembly machinery (SAM), it is unknown how the ERMES functions are connected on a molecular level. Here we report that conserved surface areas on opposite sides of the Mdm10 β-barrel interact with SAM and ERMES, respectively. We generated point mutants to separate protein assembly (SAM) from morphology and phospholipid homeostasis (ERMES). Our study reveals that the β-barrel channel of Mdm10 serves different functions. Mdm10 promotes the biogenesis of α-helical and β-barrel proteins at SAM and functions as integral membrane anchor of ERMES, demonstrating that SAM-mediated protein assembly is distinct from ER-mitochondria contact sites.
Broadly neutralizing antibodies (bNAbs) represent a promising approach to prevent and treat HIV-1 infection. However, viral escape through mutation of the HIV-1 envelope glycoprotein (Env) limits clinical applications. Here we describe 1-18, a new VH1-46-encoded CD4 binding site (CD4bs) bNAb with outstanding breadth (97%) and potency (GeoMean IC50 = 0.048 μg/mL). Notably, 1-18 is not susceptible to typical CD4bs escape mutations and effectively overcomes HIV-1 resistance to other CD4bs bNAbs. Moreover, mutational antigenic profiling uncovered restricted pathways of HIV-1 escape. Of most promise for therapeutic use, even 1-18 alone fully suppressed viremia in HIV-1-infected humanized mice without selecting for resistant viral variants. A 2.5-Å cryo-EM structure of a 1-18-BG505SOSIP.664 Env complex revealed that these characteristics are likely facilitated by a heavy-chain insertion and increased inter-protomer contacts. The ability of 1-18 to effectively restrict HIV-1 escape pathways provides a new option to successfully prevent and treat HIV-1 infection.
In statistics, samples are drawn from a population in a data-generating process (DGP). Standard errors measure the uncertainty in sample estimates of population parameters. In science, evidence is generated to test hypotheses in an evidence-generating process (EGP). We claim that EGP variation across researchers adds uncertainty: non-standard errors. To study them, we let 164 teams test six hypotheses on the same sample. We find that non-standard errors are sizeable, on par with standard errors. Their size (i) co-varies only weakly with team merits, reproducibility, or peer rating, (ii) declines significantly after peer-feedback, and (iii) is underestimated by participants.
Background: Liver cirrhosis is a relevant comorbidity with increasing prevalence. Postoperative decompensation and development of complications in patients with cirrhosis remains a frequent clinical problem. Surgery has been discussed as a precipitating event for decompensation and complications of cirrhosis, but the underlying pathomechanisms are still obscure. The aim of this study was to analyze the role of abdominal extrahepatic surgery in cirrhosis on portal pressure and fibrosis in a preclinical model. Methods: Compensated liver cirrhosis was induced using tetrachlormethane (CCL4) inhalation and bile duct ligation (BDL) models in rats, non-cirrhotic portal hypertension by partial portal vein ligation (PPVL). Intestinal manipulation (IM) as a model of extrahepatic abdominal surgery was performed. 2 and 7 days after IM, portal pressure was measured in-vivo. Hydroxyproline measurements, Sirius Red staining and qPCR measurements of the liver were performed for evaluation of fibrosis development and hepatic inflammation. Laboratory parameters of liver function in serum were analyzed. Results: Portal pressure was significantly elevated 2 and 7 days after IM in both models of cirrhosis. In the non-cirrhotic model the trend was the same, while not statistically significant. In both cirrhotic models, IM shows strong effects of decompensation, with significant weight loss, elevation of liver enzymes and hypoalbuminemia. 7 days after IM in the BDL group, Sirius red staining and hydroxyproline levels showed significant progression of fibrosis and significantly elevated mRNA levels of hepatic inflammation compared to the respective control group. A progression of fibrosis was not observed in the CCL4 model. Conclusion: In animal models of cirrhosis with continuous liver injury (BDL), IM increases portal pressure, and development of fibrosis. Perioperative portal pressure and hence inflammation processes may be therapeutic targets to prevent post-operative decompensation in cirrhosis.
The ALICE Collaboration reports the measurement of semi-inclusive distributions of charged-particle jets recoiling from a high transverse momentum (high pT) hadron trigger in proton−proton and central Pb−Pb collisions at sNN−−−√=5.02 TeV. A data-driven statistical method is used to mitigate the large uncorrelated background in central Pb−Pb collisions. Recoil jet distributions are reported for jet resolution parameter R=0.2, 0.4, and 0.5 in the range 7<pT,jet<140 GeV/c and trigger−recoil jet azimuthal separation π/2<Δφ<π. The measurements exhibit a marked medium-induced jet yield enhancement at low pT and at large azimuthal deviation from Δφ∼π. The enhancement is characterized by its dependence on Δφ, which has a slope that differs from zero by 4.7σ. Comparisons to model calculations incorporating different formulations of jet quenching are reported. These comparisons indicate that the observed yield enhancement arises from the response of the QGP medium to jet propagation.
The ALICE Collaboration reports measurements of the semi-inclusive distribution of charged-particle jets recoiling from a high transverse momentum (high pT) charged hadron, in pp and central Pb−Pb collisions at center of mass energy per nucleon−nucleon collision sNN−−−√=5.02 TeV. The large uncorrelated background in central Pb−Pb collisions is corrected using a data-driven statistical approach, which enables precise measurement of recoil jet distributions over a broad range in pT,chjet and jet resolution parameter R. Recoil jet yields are reported for R=0.2, 0.4, and 0.5 in the range 7<pT,chjet<140 GeV/c and π/2<Δφ<π, where Δφ is the azimuthal angular separation between hadron trigger and recoil jet. The low pT,chjet reach of the measurement explores unique phase space for studying jet quenching, the interaction of jets with the quark-gluonnplasma generated in high-energy nuclear collisions. Comparison of pT,chjet distributions from pp and central Pb−Pb collisions probes medium-induced jet energy loss and intra-jet broadening, while comparison of their acoplanarity distributions explores in-medium jet scattering and medium response. The measurements are compared to theoretical calculations incorporating jet quenching.
The ALICE Collaboration reports measurements of the semi-inclusive distribution of charged-particle jets recoiling from a high transverse momentum (high pT) charged hadron, in pp and central Pb−Pb collisions at center of mass energy per nucleon−nucleon collision sNN−−−√=5.02 TeV. The large uncorrelated background in central Pb−Pb collisions is corrected using a data-driven statistical approach, which enables precise measurement of recoil jet distributions over a broad range in pT,chjet and jet resolution parameter R. Recoil jet yields are reported for R=0.2, 0.4, and 0.5 in the range 7<pT,chjet<140 GeV/c and π/2<Δφ<π, where Δφ is the azimuthal angular separation between hadron trigger and recoil jet. The low pT,chjet reach of the measurement explores unique phase space for studying jet quenching, the interaction of jets with the quark-gluonnplasma generated in high-energy nuclear collisions. Comparison of pT,chjet distributions from pp and central Pb−Pb collisions probes medium-induced jet energy loss and intra-jet broadening, while comparison of their acoplanarity distributions explores in-medium jet scattering and medium response. The measurements are compared to theoretical calculations incorporating jet quenching.
The first measurements of skewness and kurtosis of mean transverse momentum (⟨pT⟩) fluctuations are reported in Pb−Pb collisions at sNN−−−√ = 5.02 TeV, Xe−Xe collisions at sNN−−−√ = 5.44 TeV and pp collisions at s√=5.02 TeV using the ALICE detector. The measurements are carried out as a function of system size ⟨dNch/dη⟩1/3|η|<0.5, using charged particles with transverse momentum (pT) and pseudorapidity (η), in the range 0.2<pT<3.0 GeV/c and |η|<0.8, respectively. In Pb−Pb and Xe−Xe collisions, positive skewness is observed in the fluctuations of ⟨pT⟩ for all centralities, which is significantly larger than what would be expected in the scenario of independent particle emission. This positive skewness is considered a crucial consequence of the hydrodynamic evolution of the hot and dense nuclear matter created in heavy-ion collisions. Furthermore, similar observations of positive skewness for minimum bias pp collisions are also reported here. Kurtosis of ⟨pT⟩ fluctuations is found to be in good agreement with the kurtosis of Gaussian distribution, for most central Pb−Pb collisions. Hydrodynamic model calculations with MUSIC using Monte Carlo Glauber initial conditions are able to explain the measurements of both skewness and kurtosis qualitatively from semicentral to central collisions in Pb--Pb system. Color reconnection mechanism in PYTHIA8 model seems to play a pivotal role in capturing the qualitative behavior of the same measurements in pp collisions.
Deuterons are atomic nuclei composed of a neutron and a proton held together by the strong interaction. Unbound ensembles composed of a deuteron and a third nucleon have been investigated in the past using scattering experiments and they constitute a fundamental reference in nuclear physics to constrain nuclear interactions and the properties of nuclei. In this work K+−d and p−d femtoscopic correlations measured by the ALICE Collaboration in proton−proton (pp) collisions at s√=13 TeV at the Large Hadron Collider (LHC) are presented. It is demonstrated that correlations in momentum space between deuterons and kaons or protons allow us to study three-hadron systems at distances comparable with the proton radius. The analysis of the K+−d correlation shows that the relative distances at which deuterons and proton/kaons are produced are around 2 fm. The analysis of the p−d correlation shows that only a full three-body calculation that accounts for the internal structure of the deuteron can explain the data. In particular, the sensitivity of the observable to the short-range part of the interaction is demonstrated. These results indicate that correlations involving light nuclei in pp collisions at the LHC will also provide access to any three-body systems in the strange and charm sectors.
The ALICE Collaboration reports a search for jet quenching effects in high-multiplicity (HM) proton−proton collisions at s√ = 13 TeV, using the semi-inclusive azimuthal-difference distribution Δφ of charged-particle jets recoiling from a high transverse momentum (high-pT,trig) trigger hadron. Jet quenching may broaden the Δφ distribution measured in HM events compared to that in minimum bias (MB) events. The measurement employs a pT,trig-differential observable for data-driven suppression of the contribution of multiple partonic interactions, which is the dominant background. While azimuthal broadening is indeed observed in HM compared to MB events, similar broadening for HM events is observed for simulations based on the PYTHIA 8 Monte Carlo generator, which does not incorporate jet quenching. We elucidate the origin of the broadening by comparing biases induced by HM selection in the data and simulations, and discuss its implications for the study of jet quenching in small collision systems.
The first measurements of K∗(892)0 resonance production as a function of charged-particle multiplicity in Xe−Xe collisions at sNN−−−√= 5.44 TeV and pp collisions at s√= 5.02 TeV using the ALICE detector are presented. The resonance is reconstructed at midrapidity (|y|<0.5) using the hadronic decay channel K∗0→K±π∓. Measurements of transverse-momentum integrated yield, mean transverse-momentum, nuclear modification factor of K∗0, and yield ratios of resonance to stable hadron (K∗0/K) are compared across different collision systems (pp, p−Pb, Xe−Xe, and Pb−Pb) at similar collision energies to investigate how the production of K∗0 resonances depends on the size of the system formed in these collisions. The hadronic rescattering effect is found to be independent of the size of colliding systems and mainly driven by the produced charged-particle multiplicity, which is a proxy of the volume of produced matter at the chemical freeze-out. In addition, the production yields of K∗0 in Xe−Xe collisions are utilized to constrain the dependence of the kinetic freeze-out temperature on the system size using HRG-PCE model.
Results on the transverse spherocity dependence of light-flavor particle production (π, K, p, ϕ, K∗0, K0S, Λ, Ξ) at midrapidity in high-multiplicity pp collisions at s√=13 TeV were obtained with the ALICE apparatus. The transverse spherocity estimator (SpT=1O) categorizes events by their azimuthal topology. Utilizing narrow selections on SpT=1O, it is possible to contrast particle production in collisions dominated by many soft initial interactions with that observed in collisions dominated by one or more hard scatterings. Results are reported for two multiplicity estimators covering different pseudorapidity regions. The SpT=1O estimator is found to effectively constrain the hardness of the events when the midrapidity (|η|<0.8) estimator is used. The production rates of strange particles are found to be slightly higher for soft isotropic topologies, and severely suppressed in hard jet-like topologies. These effects are more pronounced for hadrons with larger mass and strangeness content, and observed when the topological selection is done within a narrow multiplicity interval. This demonstrates that an important aspect of the universal scaling of strangeness enhancement with final-state multiplicity is that high-multiplicity collisions are dominated by soft, isotropic processes. On the contrary, strangeness production in events with jet-like processes is significantly reduced. The results presented in this article are compared with several QCD-inspired Monte Carlo event generators. Models that incorporate a two-component phenomenology, either through mechanisms accounting for string density, or thermal production, are able to describe the observed strangeness enhancement as a function of SpT=1O.
Long- and short-range correlations for pairs of charged particles are studied via two-particle angular correlations in pp collisions at s√=13 TeV and p−Pb collisions at sNN−−−√=5.02 TeV. The correlation functions are measured as a function of relative azimuthal angle Δφ and pseudorapidity separation Δη for pairs of primary charged particles within the pseudorapidity interval |η|<0.9 and the transverse-momentum interval 1<pT<4 GeV/c. Flow coefficients are extracted for the long-range correlations (1.6<|Δη|<1.8) in various high-multiplicity event classes using the low-multiplicity template fit method. The method is used to subtract the enhanced yield of away-side jet fragments in high-multiplicity events. These results show decreasing flow signals toward lower multiplicity events. Furthermore, the flow coefficients for events with hard probes, such as jets or leading particles, do not exhibit any significant changes compared to those obtained from high-multiplicity events without any specific event selection criteria. The results are compared with hydrodynamic-model calculations, and it is found that a better understanding of the initial conditions is necessary to describe the results, particularly for low-multiplicity events.
Modification of charged-particle jets in event-shape engineered Pb–Pb collisions at √sNN = 5.02 TeV
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Charged-particle jet yields have been measured in semicentral Pb−Pb collisions at center-of-mass energy per nucleon-nucleon collision sNN−−−√=5 TeV with the ALICE detector at the LHC. These yields are reported as a function of the jet transverse momentum, and further classified by their angle with respect to the event plane and the event shape, characterized by ellipticity, in an effort to study the path-length dependence of jet quenching. Jets were reconstructed at midrapidity from charged-particle tracks using the anti-kT algorithm with resolution parameters R= 0.2 and 0.4, with event-plane angle and event-shape values determined using information from forward scintillating detectors. The results presented in this letter show that, in semicentral Pb−Pb collisions, there is no significant difference between jet yields in predominantly isotropic and elliptical events. However, out-of-plane jets are observed to be more suppressed than in-plane jets. Further, this relative suppression is greater for low transverse momentum (< 50 GeV/c) R= 0.2 jets produced in elliptical events, with out-of-plane to in-plane jet-yield ratios varying up to 5.2σ between different event-shape classes. These results agree with previous studies indicating that jets experience azimuthally anisotropic suppression when traversing the QGP medium, and can provide additional constraints on the path-length dependence of jet energy loss.
This Letter presents the first measurement of event-by-event fluctuations of the net number (difference between the particle and antiparticle multiplicities) of multistrange hadrons Ξ− and Ξ¯¯¯¯+ and its correlation with the net-kaon number using the data collected by the ALICE Collaboration in pp, p−Pb, and Pb−Pb collisions at a center-of-mass energy per nucleon pair sNN−−−√=5.02 TeV. The statistical hadronization model with a correlation over three units of rapidity between hadrons having the same and opposite strangeness content successfully describes the results. On the other hand, string-fragmentation models that mainly correlate strange hadrons with opposite strange quark content over a small rapidity range fail to describe the data.
he first measurement of 3ΛH and 3Λ¯¯¯¯H¯¯¯¯ differential production with respect to transverse momentum and centrality in Pb−Pb collisions at sNN−−−√=5.02~TeV is presented. The 3ΛH has been reconstructed via its two-charged-body decay channel, i.e., 3ΛH→3He+π−. A Blast-Wave model fit of the pT-differential spectra of all nuclear species measured by the ALICE collaboration suggests that the 3ΛH kinetic freeze-out surface is consistent with that of other nuclei. The ratio between the integrated yields of 3ΛH and 3He is compared to predictions from the statistical hadronisation model and the coalescence model, with the latter being favoured by the presented measurements.
First measurements of hadron(h)−Λ azimuthal angular correlations in p−Pb collisions at sNN−−−√ = 5.02 TeV using the ALICE detector at the LHC are presented. These correlations are used to separate the production of associated Λ baryons into three different kinematic regions, namely those produced in the direction of the trigger particle (near-side), those produced in the opposite direction (away-side), and those whose production is uncorrelated with the jet-axis (underlying event). The per-trigger associated Λ yields in these regions are extracted, along with the near- and away-side azimuthal peak widths, and the results are studied as a function of associated particle pT and event multiplicity. Comparisons with the DPMJET event generator and previous measurements of the ϕ(1020) meson are also made. The final results indicate that strangeness production in the highest multiplicity p−Pb collisions is enhanced relative to low multiplicity collisions in the jet-like regions, as well as the underlying event. The production of Λ relative to charged hadrons is also enhanced in the underlying event when compared to the jet-like regions. Additionally, the results hint that strange quark production in the away-side of the jet is modified by soft interactions with the underlying event.
Measurements of (anti)deuteron and (anti)3He production in the rapidity range |y|< 0.5 as a function of the transverse momentum and event multiplicity in Xe−Xe collisions at a center-of-mass energy per nucleon−nucleon pair of sNN−−−√ = 5.44 TeV are presented. The coalescence parameters B2 and B3 are measured as a function of the transverse momentum per nucleon. The ratios between (anti)deuteron and (anti)3He yields and those of (anti)protons and pions are reported as a function of the mean charged-particle multiplicity density, and compared with two implementations of the statistical hadronization model (SHM) and with coalescence predictions. The elliptic flow of (anti)deuterons is measured for the first time in Xe−Xe collisions and shows features similar to those already observed in Pb−Pb collisions, i.e., the mass ordering at low transverse momentum and the meson−baryon grouping at intermediate transverse momentum. The production of nuclei is particularly sensitive to the chemical freeze-out temperature of the system created in the collision, which is extracted from a grand-canonical-ensemble-based thermal fit, performed for the first time including light nuclei along with light-flavor hadrons in Xe−Xe collisions. The extracted chemical freeze-out temperature Tchem = (154.2 ± 1.1) MeV in Xe−Xe collisions is similar to that observed in Pb−Pb collisions and close to the crossover temperature predicted by lattice QCD calculations.