Effective Field Theory for Nonstandard Top Quark Couplings

We present an effective-field-theory calculation of the effect of a dimension-six operator involving the top quark on precision electroweak data via a top-quark loop. We demonstrate the renormalizability, in the modern sense, of the effective field theory. We use the oblique parameter U to bound the coefficient of the operator, and compare with the bound derived from top-quark decay.Comment: 10 pages, 3 figure

Effective Field Theory: A Modern Approach to Anomalous Couplings

We advocate an effective field theory approach to anomalous couplings. The effective field theory approach is the natural way to extend the standard model such that the gauge symmetries are respected. It is general enough to capture any physics beyond the standard model, yet also provides guidance as to the most likely place to see the effects of new physics. The effective field theory approach also clarifies that one need not be concerned with the violation of unitarity in scattering processes at high energy. We apply these ideas to pair production of electroweak vector bosons.Comment: 16 pages, 1 figur

7th Drug hypersensitivity meeting: part two

No abstract availabl

A neural crest cell isotropic-to-nematic phase transition in the developing mammalian gut

International audienceAbstract While the colonization of the embryonic gut by neural crest cells has been the subject of intense scrutiny over the past decades, we are only starting to grasp the morphogenetic transformations of the enteric nervous system happening in the fetal stage. Here, we show that enteric neural crest cell transit during fetal development from an isotropic cell network to a square grid comprised of circumferentially-oriented cell bodies and longitudinally-extending interganglionic fibers. We present ex-vivo dynamic time-lapse imaging of this isotropic-to-nematic phase transition and show that it occurs concomitantly with circular smooth muscle differentiation in all regions of the gastrointestinal tract. Using conditional mutant embryos with enteric neural crest cells depleted of β1-integrins, we show that cell-extracellular matrix anchorage is necessary for ganglia to properly reorient. We demonstrate by whole mount second harmonic generation imaging that fibrous, circularly-spun collagen I fibers are in direct contact with neural crest cells during the orientation transition, providing an ideal orientation template. We conclude that smooth-muscle associated extracellular matrix drives a critical reorientation transition of the enteric nervous system in the mammalian fetus

Shifting into high gear: how Interstitial Cells of Cajal change the motility pattern of the developing intestine

International audienceThe first contractile waves in the developing embryonic gut are purely myogenic; they only involve smooth muscle. Here, we provide evidence for a transition from smooth muscle to interstitial cell of Cajal (ICC)-driven contractile waves in the developing chicken gut. In situ hybridization staining for anoctamin-1 (ANO1), a known ICC marker, shows that ICCs are already present throughout the gut, as from embryonic day (E)7. We devised a protocol to reveal ICC oscillatory and propagative calcium activity in embryonic gut whole mount and found that the first steady calcium oscillations in ICCs occur on (E14). We show that the activation of ICCs leads to an increase in contractile wave frequency, regularity, directionality, and velocity between E12 and E14. We finally demonstrate that application of the c-KIT antagonist imatinib mesylate in organ culture specifically depletes the ICC network and inhibits the transition to a regular rhythmic wave pattern. We compare our findings to existing results in the mouse and predict that a similar transition should take place in the human fetus between 12 and 14 wk of development. Together, our results point to an abrupt physiological transition from smooth muscle mesenchyme self-initiating waves to ICC-driven motility in the fetus and clarify the contribution of ICCs to the contractile wave pattern. NEW & NOTEWORTHY We reveal a sharp transition from smooth muscle to interstitial cell of Cajal (ICC)-driven motility in the chicken embryo, leading to higher-frequency, more rhythmic contractile waves. We predict the transition to happen between 12 and 14 embryonic wk in humans. We image for the first time the onset of ICC activity in an embryonic gut by calcium imaging. We show the first KIT and anoctamin-1 (ANO1) in situ hybridization micrographs in the embryonic chicken gut. Copyright © 2020 the American Physiological Societ

Calcium wave dynamics in the embryonic mouse gut mesenchyme: impact on smooth muscle differentiation

International audienceAbstract Intestinal smooth muscle differentiation is a complex physico-biological process involving several different pathways. Here, we investigate the properties of Ca 2+ waves in the developing intestinal mesenchyme using GCamp6f expressing mouse embryos and investigate their relationship with smooth muscle differentiation. We find that Ca 2+ waves are absent in the pre-differentiation mesenchyme and start propagating immediately following α-SMA expression. Ca 2+ waves are abrogated by Ca V 1.2 and gap-junction blockers, but are independent of the Rho pathway. The myosine light-chain kinase inhibitor ML-7 strongly disorganized or abolished Ca 2+ waves, showing that perturbation of the contractile machinery at the myosine level also affected the upstream Ca 2+ handling chain. Inhibiting Ca 2+ waves and contractility with Ca V 1.2 blockers did not perturb circular smooth muscle differentiation at early stages. At later stages, Ca V 1.2 blockers abolished intestinal elongation and differentiation of the longitudinal smooth muscle, leading instead to the emergence of KIT-expressing interstitial cells of Cajal at the gut periphery. Ca V 1.2 blockers also drove apoptosis of already differentiated, Ca V 1.2-expressing smooth muscle and enteric neural cells. We provide fundamental new data on Ca 2+ waves in the developing murine gut and their relation to myogenesis in this organ

Impact of Tacrolimus Daily Dose Limitation in Renal Transplant Recipients Expressing CYP3A5: A Retrospective Study

The pharmacokinetic variability of tacrolimus can be partly explained by CYP3A5 activity. Our objective was to evaluate a tacrolimus sparing policy on renal graft outcome according to CYP3A5 6986A>G genetic polymorphism. This retrospective study included 1114 recipients with a median follow-up of 6.3 years. Genotyping of the 6986A>G allelic variant corresponding to CYP3A5*3 was systematically performed. One year after transplantation, tacrolimus blood trough concentration (C0) target range was 5–7 ng/mL. However, daily dose was capped to 0.10 mg/kg/day regardless of the CYP3A5 genotype. A total 208 CYP3A5*1/- patients were included. Despite a higher daily dose, CYP3A5*1/- recipients exhibited lower C0 during follow-up (p < 0.01). Multivariate analysis did not show any significant influence of CYP3A5*1/- genotype (HR = 0.70, 0.46–1.07, p = 0.10) on patient-graft survival. Glomerular Filtration Rate (GFR) decline was significantly lower for the CYP3A5*1/- group (p = 0.02). The CYP3A5*1/- genotype did not significantly impact the risk of biopsy-proven acute rejection (BPAR) (HR = 1.01, 0.68–1.49, p = 0.97) despite significantly lower C0. Based on our experience, a strategy of tacrolimus capping is associated with a better GFR evolution in CYP3A5*1/- recipients without any significant increase of BPAR incidence. Our study raised some issues about specific therapeutic tacrolimus C0 targets for CYP3A5*1/- patients and suggests to set up randomized control studies in this specific population

Distribution and breeding numbers of a recently split species, the West African Crested Tern Thalasseus albididorsalis

This study investigated the distribution, numbers and conservation threats of the West African Crested Tern, which was recently elevated to full species after it was split from the Royal Tern with an American and African subspecies. In the period 1998–2019, a total of 13 West African coastal islands were identified as breeding localities, stretching from Mauritania to Guinea. All the islands are isolated, usually sandy and subject to erosion. There was great yearly variation in the numbers of breeding pairs within and between sites. A complete census of all breeding locations in 2015 and 2019 resulted in estimates of 79 000 and 77 000 pairs, respectively. The threats identified are predation, human disturbance, nest flooding and loss of breeding habitat as a result of coastal erosion. Predation of eggs and chicks by Sacred Ibises and especially Great White Pelicans may heavily impact on the species’ breeding output. Human disturbance is slight because most of the breeding islands are within protected areas. Flooding of nests has increasingly been observed in recent years, occurring at nine of 11 islands occupied by the terns in 2015. Most islands are subject to erosion, which has resulted in substantial loss of suitable breeding habitat over the 22-year study period. Two important islands have become completely unsuitable. We conclude that West African Crested Terns have an uncertain future. Food shortage resulting from industrial fishing is suspected, and the effects of climate change might negatively impact on habitat suitability and food availability. Monitoring of the total population at three-year intervals is recommended