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Currently, the genus Polypedates comprises 26 species distributed in South, Southeast, and East Asia. Because of their relatively low dispersal capability and intolerance to seawater, this genus is ideal for the study of terrestrial range evolution that extends into the island archipelagos of southeastern Asia. In this study, based on data compiled for Polypedates from previous studies and partial mitochondrial and nuclear genes collected in this study, we performed systematic biogeographical analysis. We confirmed a Sundaland origin for the extant genus and showed northward dispersal into mainland Southeast Asia and Asia, which coincided with the timing of paleoclimatic change from the Oligocene to Middle Miocene. Climate fluctuations had a profound impact on species diversification within the genus Polypedates. Furthermore, the Red River did not mediate species exchange between Southeast Asia and mainland Asia until the end of the Miocene, with the sudden onset of northward dispersal in several clades independently at that time. Alternatively, the lineage of widespread insular P. leucomystax strongly supports the hypothesis of terrestrial connection between island archipelagos of Southeast Asia during the Mid-Pleistocene paleoclimate fluctuations. Our biogeographical analysis also supports the recent introduction of P. leucomystax to the Philippines and Ryukyus, as previously suggested.
Box C/D snoRNAs are known to guide site-specific ribose methylation of ribosomal RNA. Here, we demonstrate a novel and unexpected role for box C/D snoRNAs in guiding 18S rRNA acetylation in yeast. Our results demonstrate, for the first time, that the acetylation of two cytosine residues in 18S rRNA catalyzed by Kre33 is guided by two orphan box C/D snoRNAs–snR4 and snR45 –not known to be involved in methylation in yeast. We identified Kre33 binding sites on these snoRNAs as well as on the 18S rRNA, and demonstrate that both snR4 and snR45 establish extended bipartite complementarity around the cytosines targeted for acetylation, similar to pseudouridylation pocket formation by the H/ACA snoRNPs. We show that base pairing between these snoRNAs and 18S rRNA requires the putative helicase activity of Kre33, which is also needed to aid early pre-rRNA processing. Compared to yeast, the number of orphan box C/D snoRNAs in higher eukaryotes is much larger and we hypothesize that several of these may be involved in base-modifications.
The ALICE Collaboration reports the first fully-corrected measurements of the N-subjettiness observable for track-based jets in heavy-ion collisions. This study is performed using data recorded in pp and Pb-Pb collisions at centre-of-mass energies of s√ = 7 TeV and sNN−−−√ = 2.76 TeV, respectively. In particular the ratio of 2-subjettiness to 1-subjettiness, τ2/τ1, which is sensitive to the rate of two-pronged jet substructure, is presented. Energy loss of jets traversing the strongly interacting medium in heavy-ion collisions is expected to change the rate of two-pronged substructure relative to vacuum. The results are presented for jets with a resolution parameter of R = 0.4 and charged jet transverse momentum of 40 ≤ pT,jet ≤ 60 GeV/c, which constitute a larger jet resolution and lower jet transverse momentum interval than previous measurements in heavy-ion collisions. This has been achieved by utilising a semi-inclusive hadron-jet coincidence technique to suppress the larger jet combinatorial background in this kinematic region. No significant modification of the τ2/τ1 observable for track-based jets in Pb-Pb collisions is observed relative to vacuum PYTHIA6 and PYTHIA8 references at the same collision energy. The measurements of τ2/τ1, together with the splitting aperture angle ∆R, are also performed in pp collisions at s√ = 7 TeV for inclusive jets. These results are compared with PYTHIA calculations at s√ = 7 TeV, in order to validate the model as a vacuum reference for the Pb-Pb centre-of-mass energy. The PYTHIA references for τ2/τ1 are shifted to larger values compared to the measurement in pp collisions. This hints at a reduction in the rate of two-pronged jets in Pb-Pb collisions compared to pp collisions.
Background: Misconceptions about ADHD stigmatize affected people, reduce credibility of providers, and prevent/delay treatment. To challenge misconceptions, we curated findings with strong evidence base. Methods: We reviewed studies with more than 2000 participants or meta-analyses from five or more studies or 2000 or more participants. We excluded meta-analyses that did not assess publication bias, except for meta-analyses of prevalence. For network meta-analyses we required comparison adjusted funnel plots. We excluded treatment studies with waiting-list or treatment as usual controls. From this literature, we extracted evidence-based assertions about the disorder. Results: We generated 208 empirically supported statements about ADHD. The status of the included statements as empirically supported is approved by 80 authors from 27 countries and 6 continents. The contents of the manuscript are endorsed by 366 people who have read this document and agree with its contents. Conclusions: Many findings in ADHD are supported by meta-analysis. These allow for firm statements about the nature, course, outcome causes, and treatments for disorders that are useful for reducing misconceptions and stigma.
The spirochete Borrelia burgdorferi is the causative agent of Lyme disease, the most common tick-borne disease in the US and Europe. No potent human vaccine is currently available. The innate immune complement system is vital to host defense against pathogens, as complement activation on the surface of spirochetes results in bacterial killing. Complement system is inhibited by the complement regulator factor H (FH). To escape killing, B. burgdorferi produces an outer surface protein CspZ that binds FH to inhibit complement activation on the cell surface. Immunization with CspZ alone does not protect mice from infection, which we speculate is because FH-binding cloaks potentially protective epitopes. We modified CspZ by conjugating to virus-like particles (VLP-CspZ) and eliminating FH binding (modified VLP-CspZ) to increase immunogenicity. We observed greater bactericidal antibody titers in mice vaccinated with modified VLP-CspZ: A serum dilution of 1:395 (modified VLP-CspZ) vs 1:143 (VLP-CspZ) yielded 50% borreliacidal activity. Immunizing mice with modified VLP-CspZ cleared spirochete infection, as did passive transfer of elicited antibodies. This work developed a novel Lyme disease vaccine candidate by conjugating CspZ to VLP and eliminating FH-binding ability. Such a strategy of conjugating an antigen to a VLP and eliminating binding to the target ligand can serve as a general model for developing vaccines against other bacterial infectious agents.
Measurements of event-by-event fluctuations of charged-particle multiplicities in Pb–Pb collisions at sNN−−−√ = 2.76 TeV using the ALICE detector at the CERN Large Hadron Collider (LHC) are presented in the pseudorapidity range |η|<0.8 and transverse momentum 0.2<pT<2.0 GeV/c. The amplitude of the fluctuations is expressed in terms of the variance normalized by the mean of the multiplicity distribution. The η and pT dependences of the fluctuations and their evolution with respect to collision centrality are investigated. The multiplicity fluctuations tend to decrease from peripheral to central collisions. The results are compared to those obtained from HIJING and AMPT Monte Carlo event generators as well as to experimental data at lower collision energies. Additionally, the measured multiplicity fluctuations are discussed in the context of the isothermal compressibility of the high-density strongly-interacting system formed in central Pb–Pb collisions.
The p300/CBP‐associated factor (PCAF) and related GCN5 bromodomain‐containing lysine acetyl transferases are members of subfamily I of the bromodomain phylogenetic tree. Iterative cycles of rational inhibitor design and biophysical characterization led to the discovery of the triazolopthalazine‐based L‐45 (dubbed L‐Moses) as the first potent, selective, and cell‐active PCAF bromodomain (Brd) inhibitor. Synthesis from readily available (1R,2S)‐(−)‐norephedrine furnished L‐45 in enantiopure form. L‐45 was shown to disrupt PCAF‐Brd histone H3.3 interaction in cells using a nanoBRET assay, and a co‐crystal structure of L‐45 with the homologous Brd PfGCN5 from Plasmodium falciparum rationalizes the high selectivity for PCAF and GCN5 bromodomains. Compound L‐45 shows no observable cytotoxicity in peripheral blood mononuclear cells (PBMC), good cell‐permeability, and metabolic stability in human and mouse liver microsomes, supporting its potential for in vivo use.
We have identified a mistake in how Fig. 1 is referenced in the text of the article Eur. Phys. J. C 77 (2017) no. 8, 569 which affected three paragraphs of the results section. The corrected three paragraphs as well as the unmodified accompanying figure are reproduced in this document with the correct labeling.
In addition, an editing issue led to a missing acknowledgements section. The missing section is reproduced at the end of this document in the manner in which it should have appeared in the published article.
The pT-differential production cross sections of prompt and non-prompt (produced in beauty-hadron decays) D mesons were measured by the ALICE experiment at midrapidity (|y| < 0.5) in proton-proton collisions at s√ = 5.02 TeV. The data sample used in the analysis corresponds to an integrated luminosity of (19.3 ± 0.4) nb−1. D mesons were reconstructed from their decays D0 → K−π+, D+ → K−π+π+, and D+s→φπ+→K−K+π+ and their charge conjugates. Compared to previous measurements in the same rapidity region, the cross sections of prompt D+ and D+s mesons have an extended pT coverage and total uncertainties reduced by a factor ranging from 1.05 to 1.6, depending on pT, allowing for a more precise determination of their pT-integrated cross sections. The results are well described by perturbative QCD calculations. The fragmentation fraction of heavy quarks to strange mesons divided by the one to non-strange mesons, fs/(fu + fd), is compatible for charm and beauty quarks and with previous measurements at different centre-of-mass energies and collision systems. The bb¯¯¯ production cross section per rapidity unit at midrapidity, estimated from non-prompt D-meson measurements, is dσbb¯¯¯/dy∣∣|y|<0.5=34.5±2.4(stat)+4.7−2.9(tot.syst) μb. It is compatible with previous measurements at the same centre-of-mass energy and with the cross section pre- dicted by perturbative QCD calculations.
Higher harmonic non-linear flow modes of charged hadrons in Pb-Pb collisions at √sNN = 5.02 TeV
(2020)
Anisotropic flow coefficients, vn, non-linear flow mode coefficients, χn,mk, and correlations among different symmetry planes, ρn,mk are measured in Pb-Pb collisions at sNN−−−√ = 5.02 TeV. Results obtained with multi-particle correlations are reported for the transverse momentum interval 0.2 < pT < 5.0 GeV/c within the pseudorapidity interval 0.4 < |η| < 0.8 as a function of collision centrality. The vn coefficients and χn,mk and ρn,mk are presented up to the ninth and seventh harmonic order, respectively. Calculations suggest that the correlations measured in different symmetry planes and the non-linear flow mode coefficients are dependent on the shear and bulk viscosity to entropy ratios of the medium created in heavy-ion collisions. The comparison between these measurements and those at lower energies and calculations from hydrodynamic models places strong constraints on the initial conditions and transport properties of the system.