196 research outputs found

    Selective Breeding for a Behavioral Trait Changes Digit Ratio

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    The ratio of the length of the second digit (index finger) divided by the fourth digit (ring finger) tends to be lower in men than in women. This 2D∶4D digit ratio is often used as a proxy for prenatal androgen exposure in studies of human health and behavior. For example, 2D∶4D ratio is lower (i.e. more “masculinized”) in both men and women of greater physical fitness and/or sporting ability. Lab mice have also shown variation in 2D∶4D as a function of uterine environment, and mouse digit ratios seem also to correlate with behavioral traits, including daily activity levels. Selective breeding for increased rates of voluntary exercise (wheel running) in four lines of mice has caused correlated increases in aerobic exercise capacity, circulating corticosterone level, and predatory aggression. Here, we show that this selection regime has also increased 2D∶4D. This apparent “feminization” in mice is opposite to the relationship seen between 2D∶4D and physical fitness in human beings. The present results are difficult to reconcile with the notion that 2D∶4D is an effective proxy for prenatal androgen exposure; instead, it may more accurately reflect effects of glucocorticoids, or other factors that regulate any of many genes

    A practical and catalyst-free trifluoroethylation reaction of amines using trifluoroacetic acid

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    Amines are a fundamentally important class of biologically active compounds and the ability to manipulate their physicochemical properties through the introduction of fluorine is of paramount importance in medicinal chemistry. Current synthesis methods for the construction of fluorinated amines rely on air and moisture sensitive reagents that require special handling or harsh reductants that limit functionality. Here we report practical, catalyst-free, reductive trifluoroethylation reactions of free amines exhibiting remarkable functional group tolerance. The reactions proceed in conventional glassware without rigorous exclusion of either moisture or oxygen, and use trifluoroacetic acid as a stable and inexpensive fluorine source. The new methods provide access to a wide range of medicinally-relevant functionalized tertiary beta-fluoroalkylamine cores, either through direct trifluoroethylation of secondary amines or via a three-component coupling of primary amines, aldehydes and trifluoroacetic acid. A reduction of in situ-generated silyl ester species is proposed to account for the reductive selectivity observed

    The Postpartum Specific Anxiety Scale: development and preliminary validation

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    Perinatal symptoms of anxiety are increasingly recognised due to their high prevalence and impact. Studies using pregnancy-specific anxiety measures have found that they may predict perinatal outcomes more effectively than general measures. However, no such measure exists to assess anxieties specific to the postpartum. This study aimed to develop and validate a measure (Postpartum Specific Anxiety Scale; PSAS) that accurately represents the specific anxieties faced by postpartum women, using a four-stage methodology: (1) 51 items were generated from interviews conducted with a group of 19 postpartum women at two time points, (2) the scale was reviewed and refined by a diverse expert panel, (3) an online pilot study (n = 146) was conducted to assess comprehensibility and acceptability and (4) an online sample of 1282 mothers of infants up to 6 months old completed the PSAS against a battery of convergent measures. A subsample (n = 262) repeated the PSAS 2 weeks later. The PSAS possessed good face and content validity and was comprehensible and acceptable to postpartum women. PSAS scores were significantly correlated with other measures indicating good convergent validity. Principal component analyses (PCA) revealed a simple four-factor structure. Reliability of the overall scale and individual PSAS factors proved to be good to excellent. A preliminary receiver operating characteristic (ROC) analysis also suggested that the PSAS may be a useful screening tool. The psychometric evidence suggests that the PSAS is an acceptable, valid, and reliable research tool to assess anxieties, which are specific to the postpartum period. Next steps in the iterative validation process are considered for both research and screening purposes

    Control of Centrin Stability by Aurora A

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    Aurora A is an oncogenic serine/threonine kinase which can cause cell transformation and centrosome amplification when over-expressed. Human breast tumors show excess Aurora A and phospho-centrin in amplified centrosomes. Here, we show that Aurora A mediates the phosphorylation of and localizes with centrin at the centrosome, with both proteins reaching maximum abundance from prophase through metaphase, followed by their precipitous loss in late stages of mitosis. Over-expression of Aurora A results in excess phospho-centrin and centrosome amplification. In contrast, centrosome amplification is not seen in cells over-expressing Aurora A in the presence of a recombinant centrin mutant lacking the serine phosphorylation site at residue 170. Expression of a kinase dead Aurora A results in a decrease in mitotic index and abrogation of centrin phosphorylation. Finally, a recombinant centrin mutation that mimics centrin phosphorylation increases centrin's stability against APC/C-mediated proteasomal degradation. Taken together, these results suggest that the stability of centrin is regulated in part by Aurora A, and that excess phosphorylated centrin may promote centrosome amplification in cancer

    Relationship between Exercise Capacity and Brain Size in Mammals

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    A great deal of experimental research supports strong associations between exercise, cognition, neurogenesis and neuroprotection in mammals. Much of this work has focused on neurogenesis in individual subjects in a limited number of species. However, no study to date has examined the relationship between exercise and neurobiology across a wide range of mammalian taxa. It is possible that exercise and neurobiology are related across evolutionary time. To test this hypothesis, this study examines the association between exercise and brain size across a wide range of mammals.Controlling for associations with body size, we examined the correlation between brain size and a proxy for exercise frequency and capacity, maximum metabolic rate (MMR; ml O(2) min(-1)). We collected brain sizes and MMRs from the literature and calculated residuals from the least-squares regression line describing the relationship between body mass and each variable of interest. We then analyzed the correlation between residual brain size and residual MMR both before and after controlling for phylogeny using phylogenetic independent contrasts. We found a significant positive correlation between maximum metabolic rate and brain size across a wide range of taxa.These results suggest a novel hypothesis that links brain size to the evolution of locomotor behaviors in a wide variety of mammalian species. In the end, we suggest that some portion of brain size in nonhuman mammals may have evolved in conjunction with increases in exercise capacity rather than solely in response to selection related to cognitive abilities

    Factors associated with spontaneous stone passage in a contemporary cohort of patients presenting with acute ureteric colic. Results from the MIMIC Study (A Multi-centre cohort study evaluating the role of Inflammatory Markers in patients presenting with acute ureteric Colic)

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    Objectives There is conflicting data on the role of white blood cell count (WBC) and other inflammatory markers in spontaneous stone passage in patients with acute ureteric colic. The aim of the study was to assess the relationship of WBC and other routinely collected inflammatory and clinical markers including stone size, stone position and Medically Expulsive Therapy use (MET) with spontaneous stone passage (SSP) in a large contemporary cohort of patients with acute ureteric colic. Subjects and Methods Multi‐centre retrospective cohort study coordinated by the British Urology Researchers in Surgical Training (BURST) Research Collaborative at 71 secondary care hospitals across 4 countries (United Kingdom, Republic of Ireland, Australia and New Zealand). 4170 patients presented with acute ureteric colic and a computer tomography confirmed single ureteric stone. Our primary outcome measure was SSP as defined by the absence of need for intervention to assist stone passage. Multivariable mixed effects logistic regression was used to explore the relationship between key patient factors and SSP. Results 2518 patients were discharged with conservative management and had further follow up with a SSP rate of 74% (n = 1874/2518). Sepsis after discharge with conservative management was reported in 0.6% (n = 16/2518). On multivariable analysis neither WBC, Neutrophils or CRP were seen to predict SSP, with an adjusted OR of 0.97 [95% CI 0.91 to 1.04, p = 0.38], 1.06 [95% CI 0.99 to 1.13, p = 0.1] and 1.00 [95% CI 0.99 to 1.00, p = 0.17], respectively. Medical expulsive therapy (MET) also did not predict SSP [adjusted OR 1.11 [95% CI 0.76 to 1.61]). However, stone size and stone position were significant predictors. SSP for stones 7mm. For stones in the upper ureter the SSP rate was 52% [95% CI 48 to 56], middle ureter was 70% [95% CI 64 to 76], and lower ureter was 83% [95% CI 81 to 85]. Conclusion In contrast to the previously published literature, we found that in patients with acute ureteric colic who are discharged with initial conservative management, neither WBC, Neutrophil count or CRP help determine the likelihood of spontaneous stone passage. We also found no overall benefit from the use of MET. Stone size and position are important predictors and our findings represent the most comprehensive stone passage rates for each mm increase in stone size from a large contemporary cohort adjusting for key potential confounders. We anticipate that these data will aid clinicians managing patients with acute ureteric colic and help guide management decisions and the need for intervention

    Test of lepton universality in b→sℓ+ℓ−b \rightarrow s \ell^+ \ell^- decays

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    The first simultaneous test of muon-electron universality using B+→K+ℓ+ℓ−B^{+}\rightarrow K^{+}\ell^{+}\ell^{-} and B0→K∗0ℓ+ℓ−B^{0}\rightarrow K^{*0}\ell^{+}\ell^{-} decays is performed, in two ranges of the dilepton invariant-mass squared, q2q^{2}. The analysis uses beauty mesons produced in proton-proton collisions collected with the LHCb detector between 2011 and 2018, corresponding to an integrated luminosity of 9 fb−1\mathrm{fb}^{-1}. Each of the four lepton universality measurements reported is either the first in the given q2q^{2} interval or supersedes previous LHCb measurements. The results are compatible with the predictions of 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-2022-046.html (LHCb public pages

    Precision measurement of CP\it{CP} violation in the penguin-mediated decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi

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    A flavor-tagged time-dependent angular analysis of the decay Bs0→ϕϕB_s^{0}\rightarrow\phi\phi is performed using pppp collision data collected by the LHCb experiment at % at s=13\sqrt{s}=13 TeV, the center-of-mass energy of 13 TeV, corresponding to an integrated luminosity of 6 fb^{-1}. The CP\it{CP}-violating phase and direct CP\it{CP}-violation parameter are measured to be ϕssˉs=−0.042±0.075±0.009\phi_{s\bar{s}s} = -0.042 \pm 0.075 \pm 0.009 rad and ∣λ∣=1.004±0.030±0.009|\lambda|=1.004\pm 0.030 \pm 0.009 , respectively, assuming the same values for all polarization states of the ϕϕ\phi\phi system. In these results, the first uncertainties are statistical and the second systematic. These parameters are also determined separately for each polarization state, showing no evidence for polarization dependence. The results are combined with previous LHCb measurements using pppp collisions at center-of-mass energies of 7 and 8 TeV, yielding ϕssˉs=−0.074±0.069\phi_{s\bar{s}s} = -0.074 \pm 0.069 rad and ∣lambda∣=1.009±0.030|lambda|=1.009 \pm 0.030. This is the most precise study of time-dependent CP\it{CP} violation in a penguin-dominated BB meson decay. The results are consistent with CP\it{CP} symmetry and with the Standard Model predictions.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2023-001.html (LHCb public pages

    First observation of a doubly charged tetraquark and its neutral partner

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    A combined amplitude analysis is performed for the decays B0→D‟0Ds+π−B^0 \rightarrow \overline{D}^0 D^+_s\pi^- and B+→D−Ds+π+B^+\rightarrow D^- D^+_s\pi^+, which are related by isospin symmetry. The analysis is based on data collected by the LHCb detector in proton-proton collisions at center-of-mass energies of 7, 8 and 13 TeV\,\rm{TeV}. The full data sample corresponds to an integrated luminosity of 9 fb−1\,\rm{fb^{-1}}. Two new resonant states with masses of 2.908±0.011±0.020 GeV2.908\pm0.011\pm0.020\,\rm{GeV} and widths of 0.136±0.023±0.011 GeV0.136\pm0.023\pm0.011\,\rm{GeV} are observed, which decay to Ds+π+D^+_s\pi^+ and Ds+π−D^+_s\pi^- respectively. The former state indicates the first observation of a doubly charged open-charm tetraquark state with minimal quark content [csˉudˉ][c\bar{s}u\bar{d}], and the latter state is a neutral tetraquark composed of [csˉuˉd][c\bar{s}\bar{u}d] quarks. Both states are found to have spin-parity 0+0^+, and their resonant parameters are consistent with each other, which suggests that they belong to an isospin triplet.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-026.html (LHCb public pages

    Observation of a resonant structure near the Ds+Ds−D_s^+ D_s^- threshold in the B+→Ds+Ds−K+B^+\to D_s^+ D_s^- K^+ decay

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    An amplitude analysis of the B+→Ds+Ds−K+B^+\to D_s^+ D_s^- K^+ decay is carried out to study for the first time its intermediate resonant contributions, using proton-proton collision data collected with the LHCb detector at centre-of-mass energies of 7, 8 and 13 TeV. A near-threshold peaking structure, referred to as X(3960)X(3960), is observed in the Ds+Ds−D_s^+ D_s^- invariant-mass spectrum with significance greater than 12 standard deviations. The mass, width and the quantum numbers of the structure are measured to be 3956±5±103956\pm5\pm10 MeV, 43±13±843\pm13\pm8 MeV and JPC=0++J^{PC}=0^{++}, respectively, where the first uncertainties are statistical and the second systematic. The properties of the new structure are consistent with recent theoretical predictions for a state composed of ccˉssˉc\bar{c}s\bar{s} quarks. Evidence for an additional structure is found around 4140 MeV in the Ds+Ds−D_s^+ D_s^- invariant mass, which might be caused either by a new resonance with the 0++0^{++} assignment or by a J/ψϕ↔Ds+Ds−J/\psi \phi\leftrightarrow D_s^+ D_s^- coupled-channel effect.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2022-018.html (LHCb public pages
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