Evolutionary action and structural basis of the allosteric switch controlling β(2)AR functional selectivity

Functional selectivity of G-protein-coupled receptors is believed to originate from ligand-specific conformations that activate only subsets of signaling effectors. In this study, to identify molecular motifs playing important roles in transducing ligand binding into distinct signaling responses, we combined in silico evolutionary lineage analysis and structure-guided site-directed mutagenesis with large-scale functional signaling characterization and non-negative matrix factorization clustering of signaling profiles. Clustering based on the signaling profiles of 28 variants of the β(2)-adrenergic receptor reveals three clearly distinct phenotypical clusters, showing selective impairments of either the Gi or βarrestin/endocytosis pathways with no effect on Gs activation. Robustness of the results is confirmed using simulation-based error propagation. The structural changes resulting from functionally biasing mutations centered around the DRY, NPxxY, and PIF motifs, selectively linking these micro-switches to unique signaling profiles. Our data identify different receptor regions that are important for the stabilization of distinct conformations underlying functional selectivity

Male frequent attenders of general practice and their help seeking preferences

Background: Low rates of health service usage by men are commonly linked to masculine values and traditional male gender roles. However, not all men conform to these stereotypical notions of masculinity, with some men choosing to attend health services on a frequent basis, for a variety of different reasons. This study draws upon the accounts of male frequent attenders of the General Practitioner's (GP) surgery, examining their help-seeking preferences and their reasons for choosing services within general practice over other sources of support. Methods: The study extends thematic analysis of interview data from the Self Care in Primary Care study (SCinPC), a large scale multi-method evaluation study of a self care programme delivered to frequent attenders of general practice. Data were collected from 34 semi-structured interviews conducted with men prior to their exposure to the intervention. Results: The ages of interviewed men ranged from 16 to 72 years, and 91% of the sample (n= 31) stated that they had a current health condition. The thematic analysis exposed diverse perspectives within male help-seeking preferences and the decision-making behind men's choice of services. The study also draws attention to the large variation in men's knowledge of available health services, particularly alternatives to general practice. Furthermore, the data revealed some men's lack of confidence in existing alternatives to general practice. Conclusions: The study highlights the complex nature of male help-seeking preferences, and provides evidence that there should be no 'one size fits all' approach to male service provision. It also provides impetus for conducting further studies into this under researched area of interest. © 2011 WPMH GmbH

Galaxy And Mass Assembly (GAMA): the galaxy stellar mass function to z = 0.1 from the r-band selected equatorial regions

We derive the low-redshift galaxy stellar mass function (GSMF), inclusive of dust corrections, for the equatorial Galaxy And Mass Assembly (GAMA) data set covering 180 deg2. We construct the mass function using a density-corrected maximum volume method, using masses corrected for the impact of optically thick and thin dust. We explore the galactic bivariate brightness plane (M⋆–μ), demonstrating that surface brightness effects do not systematically bias our mass function measurement above 107.5 M⊙. The galaxy distribution in the M–μ plane appears well bounded, indicating that no substantial population of massive but diffuse or highly compact galaxies are systematically missed due to the GAMA selection criteria. The GSMF is fitted with a double Schechter function, with M⋆=1010.78±0.01±0.20M⊙ M⋆=1010.78±0.01±0.20M⊙ , ϕ⋆1=(2.93±0.40)×10−3h370 ϕ1⋆=(2.93±0.40)×10−3h703 Mpc−3, α1 = −0.62 ± 0.03 ± 0.15, ϕ⋆2=(0.63±0.10)×10−3h370 ϕ2⋆=(0.63±0.10)×10−3h703 Mpc−3 and α2 = −1.50 ± 0.01 ± 0.15. We find the equivalent faint end slope as previously estimated using the GAMA-I sample, although we find a higher value of M⋆ M⋆ . Using the full GAMA-II sample, we are able to fit the mass function to masses as low as 107.5  M⊙, and assess limits to 106.5  M⊙. Combining GAMA-II with data from G10-COSMOS, we are able to comment qualitatively on the shape of the GSMF down to masses as low as 106 M⊙. Beyond the well-known upturn seen in the GSMF at 109.5, the distribution appears to maintain a single power-law slope from 109 to 106.5. We calculate the stellar mass density parameter given our best-estimate GSMF, finding Ω⋆=1.66+0.24−0.23±0.97h−170×10−3 Ω⋆=1.66−0.23+0.24±0.97h70−1×10−3 , inclusive of random and systematic uncertainties

Like-minded sources on Facebook are prevalent but not polarizing

Many critics raise concerns about the prevalence of ‘echo chambers’ on social media and their potential role in increasing political polarization. However, the lack of available data and the challenges of conducting large-scale field experiments have made it difficult to assess the scope of the problem 1,2. Here we present data from 2020 for the entire population of active adult Facebook users in the USA showing that content from ‘like-minded’ sources constitutes the majority of what people see on the platform, although political information and news represent only a small fraction of these exposures. To evaluate a potential response to concerns about the effects of echo chambers, we conducted a multi-wave field experiment on Facebook among 23,377 users for whom we reduced exposure to content from like-minded sources during the 2020 US presidential election by about one-third. We found that the intervention increased their exposure to content from cross-cutting sources and decreased exposure to uncivil language, but had no measurable effects on eight preregistered attitudinal measures such as affective polarization, ideological extremity, candidate evaluations and belief in false claims. These precisely estimated results suggest that although exposure to content from like-minded sources on social media is common, reducing its prevalence during the 2020 US presidential election did not correspondingly reduce polarization in beliefs or attitudes

Velocity and angular distributions of evaporation residues from induced32 reactions

Velocity distributions of mass-resolved evaporation residues from reactions of S32 with C12, Mg24, Al27, Si28, and Ca40 have been measured at bombarding energies of 194, 239, and 278 MeV using time-of-flight techniques. In all cases, the observed shifts in the velocity centroids relative to the values expected for complete fusion are consistent with a previously reported parametrization of a threshold for onset of incomplete fusion. Angular distributions were measured and total cross sections extracted for the Mg32 system at all three energies. A comparison with existing results for Mg32 at lower energies, and with other systems leading to the Ni56 compound nucleus, suggests two different types of compound-nuclear limitations to complete fusion at higher energies

El Apego Va a Juicio: Problemas de Custodia y Protección Infantil1

Attachment theory and research are drawn upon in many applied settings, including family courts, but misunderstandings are widespread and sometimes result in misapplications. The aim of this consensus statement is, therefore, to enhance understanding, counter misinformation, and steer family-court utilisation of attachment theory in a supportive, evidence-based direction, especially with regard to child protection and child custody decision-making. This article is divided into two parts. In the first part, we address problems related to the use of attachment theory and research in family courts, and discuss reasons for these problems. To this end, we examine family court applications of attachment theory in the current context of the best-interest-of-the-child standard, discuss misunderstandings regarding attachment theory, and identify factors that have hindered accurate implementation. In the second part, we provide recommendations for the application of attachment theory and research. To this end, we set out three attachment principles: the child’s need for familiar, non-abusive caregivers; the value of continuity of good-enough care; and the benefits of networks of attachment relationships. We also discuss the suitability of assessments of attachment quality and caregiving behaviour to inform family court decision-making. We conclude that assessments of caregiver behaviour should take center stage. Although there is dissensus among us regarding the use of assessments of attachment quality to inform child custody and child-protection decisions, such assessments are currently most suitable for targeting and directing supportive interventions. Finally, we provide directions to guide future interdisciplinary research collaboration

Combination of searches for Higgs boson pairs in pp collisions at \sqrts = 13 TeV with the ATLAS detector

This letter presents a combination of searches for Higgs boson pair production using up to 36.1 fb(-1) of proton-proton collision data at a centre-of-mass energy root s = 13 TeV recorded with the ATLAS detector at the LHC. The combination is performed using six analyses searching for Higgs boson pairs decaying into the b (b) over barb (b) over bar, b (b) over barW(+)W(-), b (b) over bar tau(+)tau(-), W+W-W+W-, b (b) over bar gamma gamma and W+W-gamma gamma final states. Results are presented for non-resonant and resonant Higgs boson pair production modes. No statistically significant excess in data above the Standard Model predictions is found. The combined observed (expected) limit at 95% confidence level on the non-resonant Higgs boson pair production cross-section is 6.9 (10) times the predicted Standard Model cross-section. Limits are also set on the ratio (kappa(lambda)) of the Higgs boson self-coupling to its Standard Model value. This ratio is constrained at 95% confidence level in observation (expectation) to -5.0 &lt; kappa(lambda) &lt; 12.0 (-5.8 &lt; kappa(lambda) &lt; 12.0). In addition, limits are set on the production of narrow scalar resonances and spin-2 Kaluza-Klein Randall-Sundrum gravitons. Exclusion regions are also provided in the parameter space of the habemus Minimal Supersymmetric Standard Model and the Electroweak Singlet Model. For complete list of authors see http://dx.doi.org/10.1016/j.physletb.2019.135103</p

Searches for lepton-flavour-violating decays of the Higgs boson in s=13\sqrt{s}=13 TeV pp\mathit{pp} collisions with the ATLAS detector

This Letter presents direct searches for lepton flavour violation in Higgs boson decays, H → eτ and H → μτ , performed with the ATLAS detector at the LHC. The searches are based on a data sample of proton–proton collisions at a centre-of-mass energy √s = 13 TeV, corresponding to an integrated luminosity of 36.1 fb−1. No significant excess is observed above the expected background from Standard Model processes. The observed (median expected) 95% confidence-level upper limits on the leptonflavour-violating branching ratios are 0.47% (0.34+0.13−0.10%) and 0.28% (0.37+0.14−0.10%) for H → eτ and H → μτ , respectively.publishedVersio