Quantitative genetic analyses have been increasingly used to estimate the genetic basis of life-history traits in natural populations. Imperfect detection of individuals is inherent to studies that ...monitor populations in the wild, yet it is seldom accounted for by quantitative genetic studies, perhaps leading to flawed inference. To facilitate the inclusion of imperfect detection of individuals in such studies, we develop a method to estimate additive genetic variance and assess heritability for binary traits such as survival, using capture-recapture (CR) data. Our approach combines mixed-effects CR models with a threshold model to incorporate discrete data in a standard 'animal model' approach. We employ Markov chain Monte Carlo sampling in a Bayesian framework to estimate model parameters. We illustrate our approach using data from a wild population of blue tits (Cyanistes caeruleus) and present the first estimate of heritability of adult survival in the wild. In agreement with the prediction that selection should deplete additive genetic variance in fitness, we found that survival had low heritability. Because the detection process is incorporated, capture-recapture animal models (CRAM) provide unbiased quantitative genetics analyses of longitudinal data collected in the wild.
Using cre/loxP gene targeting, transgenic mice with muscle-specific inactivation of the GLUT4 gene (muscle GLUT4 KO) were generated and shown to develop a diabetes phenotype. To determine the ...mechanism, we examined insulin-stimulated glucose uptake and metabolism during hyperinsulinemic-euglycemic clamp in control and muscle GLUT4 KO mice before and after development of diabetes. Insulin-stimulated whole body glucose uptake was decreased by 55% in muscle GLUT4 KO mice, an effect that could be attributed to a 92% decrease in insulin-stimulated muscle glucose uptake. Surprisingly, insulin's ability to stimulate adipose tissue glucose uptake and suppress hepatic glucose production was significantly impaired in muscle GLUT4 KO mice. To address whether these latter changes were caused by glucose toxicity, we treated muscle GLUT4 KO mice with phloridzin to prevent hyperglycemia and found that insulin-stimulated whole body and skeletal muscle glucose uptake were decreased substantially, whereas insulin-stimulated glucose uptake in adipose tissue and suppression of hepatic glucose production were normal after phloridzin treatment. In conclusion, these findings demonstrate that a primary defect in muscle glucose transport can lead to secondary defects in insulin action in adipose tissue and liver due to glucose toxicity. These secondary defects contribute to insulin resistance and to the development of diabetes.
New strategies allowing the transfer of molecules, especially peptides, through the blood‐brain barriers are a major pharmacological challenge for the treatment of brain diseases. The present study ...aims at evaluating in vivo the cerebral bioavailability of carrier systems, based on small and functionalizable 2,5‐diketopiperazine (DKP) motifs. We studied 2 different cyclo(Lys‐Lys) DKP scaffolds alone and a cyclo(Lys‐Gly) DKP carrier bearing as peptide model, the tau protein hexapeptide VQIVYK sequence.
The different carrier systems were synthesized and radiolabeled using one of the free domains. The stability, biodistribution, and ability to cross blood‐brain barrier were investigated in vivo in mice for 99mTc‐DKP scaffolds, 99mTc‐HVQIVYK peptide alone, and 99mTc‐DKP‐VQIVYK. 125I‐labelled bovine serum albumin was used as negative control for brain uptake.
Both radiolabeled DKPs scaffolds and 99mTc‐DKP‐VQIVYK showed a high stability, while peptide 99mTc‐HVQIVYK alone was quickly degraded in vivo. The presence of 99mTc‐DKPs scaffolds and 99mTc‐DKP‐VQIVYK was observed in the ventricular and subarachnoid spaces and to a lower extent in the brain parenchyma up to 45 minutes post‐injection in mice.
This work highlights the potentiality of DKP scaffolds as vectors to transport peptides into the brain by limiting proteolysis and favoring cerebral bioavailability.
We evaluated the cerebral bioavailability of 99mTc‐diketopiperazine (DKP) carriers. The DKPs scaffolds and a DKP derivative bearing the VQIVYK sequence were evaluated. Radiolabeled DKPs scaffolds and DKP‐VQIVYK showed a high stability in vivo. The radiolabeled peptide HVQIVYK alone was quickly degraded after injection in mice. A retention of DKPs scaffolds and DKP‐VQIVYK was observed in vivo into the brain.
Abstract
Conventional, hadronic matter consists of baryons and mesons made of three quarks and a quark–antiquark pair, respectively
1,2
. Here, we report the observation of a hadronic state ...containing four quarks in the Large Hadron Collider beauty experiment. This so-called tetraquark contains two charm quarks, a
$$\overline{{{u}}}$$
u
¯
and a
$$\overline{{{d}}}$$
d
¯
quark. This exotic state has a mass of approximately 3,875 MeV and manifests as a narrow peak in the mass spectrum of
D
0
D
0
π
+
mesons just below the
D
*+
D
0
mass threshold. The near-threshold mass together with the narrow width reveals the resonance nature of the state.
1. Identifying how selection shapes life-history traits by causally relating environment to phenotype, performance and fitness has often proven elusive due to limitations of classical analysis ...methods, which only identify covariance in traits, and to the difficulties in experimentally manipulating environment to expose cause and effect in wild populations. 2. In an approach resembling the experimental method common to all modern research, structural equation modelling can not only identify covariance in traits, but also test hypotheses of direct and indirect causal paths that tie environment to phenotypes and fitness through natural selection. Here, we use novel confirmatory path analyses and a long-term study of Corsican blue tits to analyse the interactions between environmental variables (prey abundance and ectoparasite load), phenotypic traits (mass and haematocrit), physiological performance (aerobic capacity) and nestling recruitment. 3. Our analyses show that an antagonistic interaction between ectoparasites and food abundance sets tissue development and oxygen carrying capacity of blood at fledging, and that identical paths link these variables to physiological performance and recruitment. 4. This study suggests that metabolic capacity at fledging may be important in determining subsequent recruitment and unmasks subtle fitness costs of an ectoparasite.
Abstract
The standard model of particle physics currently provides our best description of fundamental particles and their interactions. The theory predicts that the different charged leptons, the ...electron, muon and tau, have identical electroweak interaction strengths. Previous measurements have shown that a wide range of particle decays are consistent with this principle of lepton universality. This article presents evidence for the breaking of lepton universality in beauty-quark decays, with a significance of 3.1 standard deviations, based on proton–proton collision data collected with the LHCb detector at CERN’s Large Hadron Collider. The measurements are of processes in which a beauty meson transforms into a strange meson with the emission of either an electron and a positron, or a muon and an antimuon. If confirmed by future measurements, this violation of lepton universality would imply physics beyond the standard model, such as a new fundamental interaction between quarks and leptons.
The waxy surfaces of three carnivorous plants,
Nepenthes ventrata (Nepenthaceae),
Brocchinia reducta and
Catopsis berteroniana (Bromeliaceae), were compared using scanning electron microscopy (SEM). ...Their effects on attachment and locomotion of the fly
Calliphora vomitoria were studied. The waxy surface of
N. ventrata is comprised of a heterogeneous layer from which only platelet-shaped crystalloids could be detached by brushing. In the two bromeliads, the crystalloids are thread-shaped and form a homogenous dense network, which was entirely removable from the epidermis. Experimental data showed that none of the flies was able to walk across any of the waxy surfaces and only a few were able to take off from those surfaces. Both the absence of sites for claw anchorage, especially in
N. ventrata, and the wax itself were shown to contribute to the trapping ability of the plants. Only half of the flies quickly recovered their locomotion ability on a glass surface after 20 min of being tested on waxy plant surfaces. SEM observations revealed that the wax of
C. berteroniana formed a powder of broken crystals on the tenent setae of the flies' pulvilli. In contrast, the waxes of
B. reducta and
N. ventrata appeared to have lost their crystal structure in contact with the tenent setae and formed an amorphous substance that adhered setae together. We hypothesize that wax interacts with adhesive fluids secreted by the fly pad and thereby prevents the tenent setae from functioning effectively.
The branching fraction ratio R(D^{*})≡B(Bover ¯^{0}→D^{*+}τ^{-}νover ¯_{τ})/B(Bover ¯^{0}→D^{*+}μ^{-}νover ¯_{μ}) is measured 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 τ^{-}→μ^{-}νover ¯_{μ}ν_{τ}. The semitauonic decay is sensitive to contributions from non-standard-model particles that preferentially couple to the third generation of fermions, in particular, Higgs-like charged scalars. A multidimensional fit to kinematic distributions of the candidate Bover ¯^{0} decays gives R(D^{*})=0.336±0.027(stat)±0.030(syst). This result, which is the first measurement of this quantity at a hadron collider, is 2.1 standard deviations larger than the value expected from lepton universality in the standard model.
Study of the doubly charmed tetraquark Tcc Abdelmotteleb, A. S. W; Ajaltouni, Z; Andreianov, A ...
Nature communications,
12/2022, Letnik:
13, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Quantum chromodynamics, the theory of the strong force, describes interactions of coloured quarks and gluons and the formation of hadronic matter. Conventional hadronic matter consists of baryons and ...mesons made of three quarks and quark-antiquark pairs, respectively. Particles with an alternative quark content are known as exotic states. Here a study is reported of an exotic narrow state in the D0D0π+ mass spectrum just below the D*+D0 mass threshold produced in proton-proton collisions collected with the LHCb detector at the Large Hadron Collider. The state is consistent with the ground isoscalar Tcc+ tetraquark with a quark content of ccu¯d¯ and spin-parity quantum numbers JP = 1+. Study of the DD mass spectra disfavours interpretation of the resonance as the isovector state. The decay structure via intermediate off-shell D*+ mesons is consistent with the observed D0π+ mass distribution. To analyse the mass of the resonance and its coupling to the D*D system, a dedicated model is developed under the assumption of an isoscalar axial-vector Tcc+ state decaying to the D*D channel. Using this model, resonance parameters including the pole position, scattering length, effective range and compositeness are determined to reveal important information about the nature of the Tcc+ state. In addition, an unexpected dependence of the production rate on track multiplicity is observed.The existence and properties of tetraquark states with two heavy quarks and two light antiquarks have been widely debated. Here, the authors use a unitarized model to study the properties of an exotic narrow state compatible with a doubly charmed tetraquark.