Divergent GW182 functional domains in the regulation of translational silencing

MicroRNA (miRNA)-mediated gene regulation has become a major focus in many biological processes. GW182 and its long isoform TNGW1 are marker proteins of GW/P bodies and bind to Argonaute proteins of the RNA induced silencing complex. The goal of this study is to further define and distinguish the repression domain(s) in human GW182/TNGW1. Two non-overlapping regions, Δ12 (amino acids 896–1219) containing the Ago hook and Δ5 (amino acids 1670–1962) containing the RRM, both induced comparable silencing in a tethering assay. Mapping data showed that the RRM and its flanking sequences in Δ5, but not the Ago hook in Δ12, were important for silencing. Repression mediated by Δ5 or Δ12 was not differentially affected when known endogenous repressors RCK/p54, GW182/TNGW1, TNRC6B were depleted. Transfected Δ5, but not Δ12, enhanced Ago2-mediated repression in a tethering assay. Transfected Δ12, but not Δ5, released endogenous miRNA reporter silencing without affecting siRNA function. Alanine substitution showed that GW/WG motifs in Δ12 (Δ12a, amino acids 896–1045) were important for silencing activity. Although Δ12 appeared to bind PABPC1 more efficiently than Δ5, neither Δ5 nor Δ12 significantly enhanced reporter mRNA degradation. These different functional characteristics of Δ5 and Δ12 suggest that their roles are distinct, and possibly dynamic, in human GW182-mediated silencing

The Correlates of Leisure Time Physical Activity among an Adults Population from Southern Taiwan

<p>Abstract</p> <p>Background</p> <p>Assessing the correlates of practicing physical activity during leisure time is important with regard to planning and designing public health strategies to increase beneficial behaviors among adult populations. Although the importance of leisure time physical activity (LTPA) is highlighted in many Western countries, there are not many publications on physical activity patterns, and even less on their correlates, in non-Western societies. The goal of this study was thus to explore the determinants influencing adults' leisure time physical activity (LTPA) in a city in southern Taiwan.</p> <p>Methods</p> <p>A cross-sectional population-based study was conducted in 2007, using a standardized questionnaire. Energy expenditure was dichotomized into two groups based on the recommended levels of moderate physical activity from LTPA: ≥10 or < 10 MET·hr·wk^-1. Logistic regression analyses were applied to the results.</p> <p>Results</p> <p>A total of 762 subjects with valid data took part in the study (mean age 53.8 ± 13.8 years). In multivariate logistic regression analysis, we found the following results: Age was positively associated with LTPA. Adults with stronger perceived convenience of exercise facilities (OR = 2.04; 95%CI = 1.28-3.24) and past exercise experience in school (OR = 1.86; 95%CI= 1.19-2.91) participated in more LTPA. Subjects with more general social support (OR = 1.66;95%CI = 1.13-2.44), greater knowledge about the health benefits of exercise (OR = 1.85;95%CI = 1.25-2.74), more sports media consumption (OR = 1.94;95%CI = 1.26-2.98), and higher self-efficacy (OR = 3.99;95%CI = 2.67-5.97) were more likely to engage in LTPA. Further analysis comparing different sources of social support showed only social support from friends had a significant positive association (OR = 1.73;95%CI = 1.14-2.63) with increased LTPA.</p> <p>Conclusions</p> <p>LTPA in southern city of Taiwan showed some unique associations with age, socioeconomic status and media consumption that are not commonly reported in the Western World and similar associations with regards to psychosocial correlates of LTPA participation. Further studies from developing countries are warranted to highlight culture-specific differences in physical activity participation.</p

Deep underground laboratory measurement of 13^{13}C(α\alpha,nn)16^{16}O in the Gamow windows of the ss- and ii-processes

The $^{13}$C($\alpha$,$n$)$^{16}$O reaction is the main neutron source for the slow-neutron-capture (s-) process in Asymptotic Giant Branch stars and for the intermediate (i-) process. Direct measurements at astrophysical energies in above-ground laboratories are hindered by the extremely small cross sections and vast cosmic-ray induced background. We performed the first consistent direct measurement in the range of $E_{\rm c.m.}=$0.24 MeV to 1.9 MeV using the accelerators at the China Jinping Underground Laboratory (CJPL) and Sichuan University. Our measurement covers almost the entire i-process Gamow window in which the large uncertainty of the previous experiments has been reduced from 60\% down to 15\%, eliminates the large systematic uncertainty in the extrapolation arising from the inconsistency of existing data sets, and provides a more reliable reaction rate for the studies of the s- and i-processes along with the first direct determination of the alpha strength for the near-threshold state

Molecular mechanisms and cellular functions of cGAS-STING signalling

The cGAS–STING signalling axis, comprising the synthase for the second messenger cyclic GMP–AMP (cGAS) and the cyclic GMP–AMP receptor stimulator of interferon genes (STING), detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections. Notably however, besides sensing microbial DNA, the DNA sensor cGAS can also be activated by endogenous DNA, including extranuclear chromatin resulting from genotoxic stress and DNA released from mitochondria, placing cGAS–STING as an important axis in autoimmunity, sterile inflammatory responses and cellular senescence. Initial models assumed that co-localization of cGAS and DNA in the cytosol defines the specificity of the pathway for non-self, but recent work revealed that cGAS is also present in the nucleus and at the plasma membrane, and such subcellular compartmentalization was linked to signalling specificity of cGAS. Further confounding the simple view of cGAS–STING signalling as a response mechanism to infectious agents, both cGAS and STING were shown to have additional functions, independent of interferon response. These involve non-catalytic roles of cGAS in regulating DNA repair and signalling via STING to NF-κB and MAPK as well as STING-mediated induction of autophagy and lysosome- dependent cell death. We have also learnt that cGAS dimers can multimerize and undergo liquid–liquid phase separation to form biomolecular condensates that could importantly regulate cGAS activation. Here, we review the molecular mechanisms and cellular functions underlying cGAS–STING activation and signalling, particularly highlighting the newly emerging diversity of this signalling pathway and discussing how the specificity towards normal, damage-induced and infection-associated DNA could be achieved

Enhanced production of Λb0\Lambda_{b}^{0} baryons in high-multiplicity pppp collisions at s=13\sqrt{s} = 13 TeV

The production rate of $\Lambda_{b}^{0}$ baryons relative to $B^{0}$ mesons in $pp$ collisions at a center-of-mass energy $\sqrt{s} = 13$ TeV is measured by the LHCb experiment. The ratio of $\Lambda_{b}^{0}$ to $B^{0}$ production cross-sections shows a significant dependence on both the transverse momentum and the measured charged-particle multiplicity. At low multiplicity, the ratio measured at LHCb is consistent with the value measured in $e^{+}e^{-}$ collisions, and increases by a factor of $\sim2$ with increasing multiplicity. At relatively low transverse momentum, the ratio of $\Lambda_{b}^{0}$ to $B^{0}$ cross-sections is higher than what is measured in $e^{+}e^{-}$ collisions, but converges with the $e^{+}e^{-}$ ratio as the momentum increases. These results imply that the evolution of heavy $b$ quarks into final-state hadrons is influenced by the density of the hadronic environment produced in the collision. Comparisons with a statistical hadronization model and implications for the mechanisms enforcing quark confinement are discussed.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-027.html (LHCb public pages

Studies of η\eta and η′\eta' production in pppp and ppPb collisions

The production of $\eta$ and $\eta'$ mesons is studied in proton-proton and proton-lead collisions collected with the LHCb detector. Proton-proton collisions are studied at center-of-mass energies of $5.02$ and $13~{\rm TeV}$, and proton-lead collisions are studied at a center-of-mass energy per nucleon of $8.16~{\rm TeV}$. The studies are performed in center-of-mass rapidity regions $2.5<y_{\rm c.m.}<3.5$ (forward rapidity) and $-4.0<y_{\rm c.m.}<-3.0$ (backward rapidity) defined relative to the proton beam direction. The $\eta$ and $\eta'$ production cross sections are measured differentially as a function of transverse momentum for $1.5<p_{\rm T}<10~{\rm GeV}$ and $3<p_{\rm T}<10~{\rm GeV}$, respectively. The differential cross sections are used to calculate nuclear modification factors. The nuclear modification factors for $\eta$ and $\eta'$ mesons agree at both forward and backward rapidity, showing no significant evidence of mass dependence. The differential cross sections of $\eta$ mesons are also used to calculate $\eta/\pi^0$ cross section ratios, which show evidence of a deviation from the world average. These studies offer new constraints on mass-dependent nuclear effects in heavy-ion collisions, as well as $\eta$ and $\eta'$ meson fragmentation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://lhcbproject.web.cern.ch/Publications/p/LHCb-PAPER-2023-030.html (LHCb public pages

Observation of Cabibbo-suppressed two-body hadronic decays and precision mass measurement of the Ωc0\Omega_{c}^{0} baryon

The first observation of the singly Cabibbo-suppressed $\Omega_{c}^{0}\to\Omega^{-}K^{+}$ and $\Omega_{c}^{0}\to\Xi^{-}\pi^{+}$ decays is reported, using proton-proton collision data at a centre-of-mass energy of $13\,{\rm TeV}$, corresponding to an integrated luminosity of $5.4\,{\rm fb}^{-1}$, collected with the LHCb detector between 2016 and 2018. The branching fraction ratios are measured to be $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}K^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.0608\pm0.0051({\rm stat})\pm 0.0040({\rm syst})$, $\frac{\mathcal{B}(\Omega_{c}^{0}\to\Xi^{-}\pi^{+})}{\mathcal{B}(\Omega_{c}^{0}\to\Omega^{-}\pi^{+})}=0.1581\pm0.0087({\rm stat})\pm0.0043({\rm syst})\pm0.0016({\rm ext})$. In addition, using the $\Omega_{c}^{0}\to\Omega^{-}\pi^{+}$ decay channel, the $\Omega_{c}^{0}$ baryon mass is measured to be $M(\Omega_{c}^{0})=2695.28\pm0.07({\rm stat})\pm0.27({\rm syst})\pm0.30({\rm ext})\,{\rm MeV}/c^{2}$, improving the precision of the previous world average by a factor of four.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-011.html (LHCb public pages

Fraction of χc\chi_c decays in prompt J/ψJ/\psi production measured in pPb collisions at sNN=8.16\sqrt{s_{NN}}=8.16 TeV

The fraction of $\chi_{c1}$ and $\chi_{c2}$ decays in the prompt $J/\psi$ yield, $F_{\chi c}=\sigma_{\chi_c \to J/\psi}/\sigma_{J/\psi}$, is measured by the LHCb detector in pPb collisions at $\sqrt{s_{NN}}=8.16$ TeV. The study covers the forward ($1.5<y^*<4.0$) and backward ($-5.0<y^*<-2.5$) rapidity regions, where $y^*$ is the $J/\psi$ rapidity in the nucleon-nucleon center-of-mass system. Forward and backward rapidity samples correspond to integrated luminosities of 13.6 $\pm$ 0.3 nb$^{-1}$ and 20.8 $\pm$ 0.5 nb$^{-1}$, respectively. The result is presented as a function of the $J/\psi$ transverse momentum $p_{T,J/\psi}$ in the range 1$<p_{T, J/\psi}<20$ GeV/$c$. The $F_{\chi c}$ fraction at forward rapidity is compatible with the LHCb measurement performed in $pp$ collisions at $\sqrt{s}=7$ TeV, whereas the result at backward rapidity is 2.4 $\sigma$ larger than in the forward region for $1<p_{T, J/\psi}<3$ GeV/$c$. The increase of $F_{\chi c}$ at low $p_{T, J/\psi}$ at backward rapidity is compatible with the suppression of the $\psi$(2S) contribution to the prompt $J/\psi$ yield. The lack of in-medium dissociation of $\chi_c$ states observed in this study sets an upper limit of 180 MeV on the free energy available in these pPb collisions to dissociate or inhibit charmonium state formation.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-028.html (LHCb public pages

A measurement of ΔΓs\Delta \Gamma_{s}

Using a dataset corresponding to $9~\mathrm{fb}^{-1}$ of integrated luminosity collected with the LHCb detector between 2011 and 2018 in proton-proton collisions, the decay-time distributions of the decay modes $B_s^0 \rightarrow J/\psi \eta'$ and $B_s^0 \rightarrow J/\psi \pi^{+} \pi^{-}$ are studied. The decay-width difference between the light and heavy mass eigenstates of the $B_s^0$ meson is measured to be $\Delta \Gamma_s = 0.087 \pm 0.012 \pm 0.009 \, \mathrm{ps}^{-1}$, where the first uncertainty is statistical and the second systematic.Comment: All figures and tables, along with machine-readable versions and any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-025.htm