Beta gamma-subunit activation of G-protein-regulated phospholipase C

The availability of purified G alpha 11 and the G-protein-regulated phospholipase C from turkey erythrocytes has allowed an examination of the direct effects of G-protein beta gamma-subunit on the components of the inositol lipid signaling system. Reconstitution of purified turkey erythrocyte or bovine brain beta gamma-subunit into phospholipid vesicles containing G alpha 11 inhibited AlF4- induced activation of phospholipase C. However, beta gamma-subunit at higher concentrations increased phospholipase C activity. This stimulatory effect of beta gamma-subunit on phospholipase C did not require the presence of the alpha-subunit. G alpha o had no effect on the catalytic activity of phospholipase C. However, coreconstitution of G alpha o and beta gamma-subunit shifted to the right the concentration-effect curve for beta gamma-subunit-promoted activation of phospholipase C. As was observed with G alpha 11, the increase in activity observed in the presence of beta gamma-subunit occurred as an increase in the maximal activity and with no change in the apparent affinity for Ca2+ for phospholipase C activation. The concentration dependence of G alpha 11 for activation of turkey erythrocyte phospholipase C and bovine brain phospholipase C-beta, as well as the concentration dependence of the two enzymes for activation by G alpha 11, were very similar. In contrast, beta gamma-subunit was a much less effective activator of bovine brain phospholipase C-beta than the turkey erythrocyte enzyme. The observation of direct effects of free beta gamma-subunit on phospholipase C extend the possibilities for receptor-mediated regulation of this signaling pathway

Sleep characteristics and health-related quality of life in 9- to 11-year-old children from 12 countries

Introduction: Previous studies have linked short sleep duration, poor sleep quality, and late sleep timing with lower health-related quality of life (HRQoL) in children. However, almost all studies relied solely on self-reported sleep information, and most studies were conducted in high-income countries. To address these gaps, we studied both device-measured and self-reported sleep characteristics in relation to HRQoL in a sample of children from 12 countries that vary widely in terms of economic and human development. Methods: The study sample included 6,626 children aged 9-11 years from Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom, and the United States. Waist-worn actigraphy was used to measure total sleep time, bedtime, wake-up time, and sleep efficiency on both weekdays and weekends. Children also reported ratings of sleep quantity and quality. HRQoL was measured by the KIDSCREEN-10 survey. Multilevel regression models were used to determine the relationships between sleep characteristics and HRQoL. Results: Results showed considerable variation in sleep characteristics, particularly duration and timing, across study sites. Overall, we found no association between device-measured total sleep time, sleep timing or sleep efficiency, and HRQoL. In contrast, self-reported ratings of poor sleep quantity and quality were associated with HRQoL. Conclusions: Self-reported, rather than device-based, measures of sleep are related to HRQoL in children. The discrepancy related to sleep assessment methods highlights the importance of considering both device-measured and self-reported measures of sleep in understanding its health effects

Proportion of children meeting recommendations for 24-hour movement guidelines and associations with adiposity in a 12-country study

Background: The Canadian 24-h movement guidelines were developed with the hope of improving health and future health outcomes in children and youth. The purpose of this study was to evaluate adherence to the 3 recommendations most strongly associated with health outcomes in new 24-h movement guidelines and their relationship with adiposity (obesity and body mass index z-score) across countries participating in the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE). Methods: Cross-sectional results were based on 6128 children aged 9-11years from the 12 countries of ISCOLE. Sleep duration and moderate-to-vigorous physical activity (MVPA) were assessed using accelerometry. Screen time was measured through self-report. Body weight and height were measured. Body mass index (BMI, kgm2) was calculated, and BMI z-scores were computed using age- and sex-specific reference data from the World Health Organization. Obesity was defined as a BMI z-score>+2 SD. Meeting the overall 24-h movement guidelines was defined as: 9 to 11h/night of sleep, ≤2h/day of screen time, and at least 60min/day of MVPA. Age, sex, highest parental education and unhealthy diet pattern score were included as covariates in statistical models. Associations between meeting vs. not meeting each single recommendation (and combinations) with obesity were assessed with odds ratios calculated using generalized linear mixed models. A linear mixed model was used to examine the differences in BMI z-scores between children meeting vs. not meeting the different combinations of recommendations. Results: The global prevalence of children meeting the overall recommendations (all three behaviors) was 7%, with children from Australia and Canada showing the highest adherence (15%). Children meeting the three recommendations had lower odds ratios for obesity compared to those meeting none of the recommendations (OR=0.28, 95% CI 0.18-0.45). Compared to not meeting the 24-h movement recommendations either independently or combined, meeting them was significantly associated with a lower BMI z-score. Whenever the MVPA recommendation was included in the analysis the odds ratios for obesity were lower. Conclusions: For ISCOLE participants meeting these 3 healthy movement recommendations the odds ratios of being obese or having high BMI z-scores were lower. However, only a small percentage of children met all recommendations. Future efforts should aim to find promising ways to increase daily physical activity, reduce screen time, and ensure an adequate night's sleep in children. Trial registration: The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) was registered at ClinicalTrials.gov (Identifier NCT01722500) (October 29, 2012)

Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials

Background Patients with chronic obstructive pulmonary disease (COPD) have few options for treatment. The efficacy and safety of the phosphodiesterase-4 inhibitor roflumilast have been investigated in studies of patients with moderate-to-severe COPD, but not in those concomitantly treated with longacting inhaled bronchodilators. The effect of roflumilast on lung function in patients with COPD that is moderate to severe who are already being treated with salmeterol or tiotropium was investigated. Methods In two double-blind, multicentre studies done in an outpatient setting, after a 4-week run-in, patients older than 40 years with moderate-to-severe COPD were randomly assigned to oral roflumilast 500 mu g or placebo once a day for 24 weeks, in addition to salmeterol (M2-127 study) or tiotropium (M2-128 study). The primary endpoint was change in prebronchodilator forced expiratory volume in 1s (FEV(1)). Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, number NCT00313209 for M2-127, and NCT00424268 for M2-128. Findings In the salmeterol plus roflumilast trial, 466 patients were assigned to and treated with roflumilast and 467 with placebo; in the tiotropium plus roflumilast trial, 371 patients were assigned to and treated with roflumilast and 372 with placebo. Compared with placebo, roflumilast consistently improved mean prebronchodilator FEV(1) by 49 mL (p<0.0001) in patients treated with salmeterol, and 80 mL (p<0.0001) in those treated with tiotropium. Similar improvement in postbronchodilator FEV(1) was noted in both groups. Furthermore, roflumilast had beneficial effects on other lung function measurements and on selected patient-reported outcomes in both groups. Nausea, diarrhoea, weight loss, and, to a lesser extent, headache were more frequent in patients in the roflumilast groups. These adverse events were associated with increased patient withdrawal. Interpretation Roflumilast improves lung function in patients with COPD treated with salmeterol or tiotropium, and could become an important treatment for these patients

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

Multidifferential study of identified charged hadron distributions in ZZ-tagged jets in proton-proton collisions at s=\sqrt{s}=13 TeV

Jet fragmentation functions are measured for the first time in proton-proton collisions for charged pions, kaons, and protons within jets recoiling against a $Z$ boson. The charged-hadron distributions are studied longitudinally and transversely to the jet direction for jets with transverse momentum 20 $< p_{\textrm{T}} < 100$ GeV and in the pseudorapidity range $2.5 < \eta < 4$. The data sample was collected with the LHCb experiment at a center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 1.64 fb$^{-1}$. Triple differential distributions as a function of the hadron longitudinal momentum fraction, hadron transverse momentum, and jet transverse momentum are also measured for the first time. This helps constrain transverse-momentum-dependent fragmentation functions. Differences in the shapes and magnitudes of the measured distributions for the different hadron species provide insights into the hadronization process for jets predominantly initiated by light quarks.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-2022-013.html (LHCb public pages

Study of the B−→Λc+Λˉc−K−B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-} decay

The decay $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ is studied in proton-proton collisions at a center-of-mass energy of $\sqrt{s}=13$ TeV using data corresponding to an integrated luminosity of 5 $\mathrm{fb}^{-1}$ collected by the LHCb experiment. In the $\Lambda_{c}^+ K^{-}$ system, the $\Xi_{c}(2930)^{0}$ state observed at the BaBar and Belle experiments is resolved into two narrower states, $\Xi_{c}(2923)^{0}$ and $\Xi_{c}(2939)^{0}$, whose masses and widths are measured to be $$m(\Xi_{c}(2923)^{0}) = 2924.5 \pm 0.4 \pm 1.1 \,\mathrm{MeV}, \\ m(\Xi_{c}(2939)^{0}) = 2938.5 \pm 0.9 \pm 2.3 \,\mathrm{MeV}, \\ \Gamma(\Xi_{c}(2923)^{0}) = \phantom{000}4.8 \pm 0.9 \pm 1.5 \,\mathrm{MeV},\\ \Gamma(\Xi_{c}(2939)^{0}) = \phantom{00}11.0 \pm 1.9 \pm 7.5 \,\mathrm{MeV},$$ where the first uncertainties are statistical and the second systematic. The results are consistent with a previous LHCb measurement using a prompt $\Lambda_{c}^{+} K^{-}$ sample. Evidence of a new $\Xi_{c}(2880)^{0}$ state is found with a local significance of $3.8\,\sigma$, whose mass and width are measured to be $2881.8 \pm 3.1 \pm 8.5\,\mathrm{MeV}$ and $12.4 \pm 5.3 \pm 5.8 \,\mathrm{MeV}$, respectively. In addition, evidence of a new decay mode $\Xi_{c}(2790)^{0} \to \Lambda_{c}^{+} K^{-}$ is found with a significance of $3.7\,\sigma$. The relative branching fraction of $B^{-} \to \Lambda_{c}^{+} \bar{\Lambda}_{c}^{-} K^{-}$ with respect to the $B^{-} \to D^{+} D^{-} K^{-}$ decay is measured to be $2.36 \pm 0.11 \pm 0.22 \pm 0.25$, where the first uncertainty is statistical, the second systematic and the third originates from the branching fractions of charm hadron decays.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-028.html (LHCb public pages

Measurement of the ratios of branching fractions R(D∗)\mathcal{R}(D^{*}) and R(D0)\mathcal{R}(D^{0})

The ratios of branching fractions $\mathcal{R}(D^{*})\equiv\mathcal{B}(\bar{B}\to D^{*}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(\bar{B}\to D^{*}\mu^{-}\bar{\nu}_{\mu})$ and $\mathcal{R}(D^{0})\equiv\mathcal{B}(B^{-}\to D^{0}\tau^{-}\bar{\nu}_{\tau})/\mathcal{B}(B^{-}\to D^{0}\mu^{-}\bar{\nu}_{\mu})$ are measured, assuming isospin symmetry, using a sample of proton-proton collision data corresponding to 3.0 fb${ }^{-1}$ of integrated luminosity recorded by the LHCb experiment during 2011 and 2012. The tau lepton is identified in the decay mode $\tau^{-}\to\mu^{-}\nu_{\tau}\bar{\nu}_{\mu}$. The measured values are $\mathcal{R}(D^{*})=0.281\pm0.018\pm0.024$ and $\mathcal{R}(D^{0})=0.441\pm0.060\pm0.066$, where the first uncertainty is statistical and the second is systematic. The correlation between these measurements is $\rho=-0.43$. Results are consistent with the current average of these quantities and are at a combined 1.9 standard deviations from the predictions based on lepton flavor universality in the Standard Model.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-039.html (LHCb public pages

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals &lt;1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data