Streptococcus agalactiae clones infecting humans were selected and fixed through the extensive use of tetracycline

Streptococcus agalactiae (Group B Streptococcus, GBS) is a commensal of the digestive and genitourinary tracts of humans that emerged as the leading cause of bacterial neonatal infections in Europe and North America during the 1960s. Due to the lack of epidemiological and genomic data, the reasons for this emergence are unknown. Here we show by comparative genome analysis and phylogenetic reconstruction of 229 isolates that the rise of human GBS infections corresponds to the selection and worldwide dissemination of only a few clones. The parallel expansion of the clones is preceded by the insertion of integrative and conjugative elements conferring tetracycline resistance (TcR). Thus, we propose that the use of tetracycline from 1948 onwards led in humans to the complete replacement of a diverse GBS population by only few TcR clones particularly well adapted to their host, causing the observed emergence of GBS diseases in neonates. \ua9 2014 Macmillan Publishers Limited. All rights reserved

LTP-triggered cholesterol redistribution activates Cdc42 and drives AMPA receptor synaptic delivery

Neurotransmitter receptor trafficking during synaptic plasticity requires the concerted action of multiple signaling pathways and the protein transport machinery. However, little is known about the contribution of lipid metabolism during these processes. In this paper, we addressed the question of the role of cholesterol in synaptic changes during long-term potentiation (LTP). We found that N-methyl-d-aspartate-type glutamate receptor (NMDAR) activation during LTP induction leads to a rapid and sustained loss or redistribution of intracellular cholesterol in the neuron. A reduction in cholesterol, in turn, leads to the activation of Cdc42 and the mobilization of GluA1-containing α-amino-3-hydroxy-5- methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) from Rab11-recycling endosomes into the synaptic membrane, leading to synaptic potentiation. This process is accompanied by an increase of NMDAR function and an enhancement of LTP. These results imply that cholesterol acts as a sensor of NMDAR activation and as a trigger of downstream signaling to engage small GTPase (guanosine triphosphatase) activation and AMPAR synaptic delivery during LTP.Peer Reviewe

A comprehensive review on the colorless carotenoids phytoene and phytofluene

Carotenoids and their derivatives are versatile isoprenoids involved in many varied actions, hence their importance in the agri-food industry, nutrition, health and other fields. All carotenoids are derived from the colorless carotenes phytoene and phytofluene, which are oddities among carotenoids due to their distinct chemical structure. They occur together with lycopene in tomato and other lycopene-containing foods. Furthermore, they are also present in frequently consumed products like oranges and carrots, among others. The intake of phytoene plus phytofluene has been shown to be higher than that of lycopene and other carotenoids in Luxembourg. This is likely to be common in other countries. However, they are not included in food carotenoid databases, hence they have not been linked to health benefits in epidemiological studies. Interestingly, there are evidences in vitro, animal models and humans indicating that they may provide health benefits. In this sense, the study of these colorless carotenes in the context of food science, nutrition and health should be further encouraged. In this work, we review much of the existing knowledge concerning their chemical characteristics, physico-chemical properties, analysis, distribution in foods, bioavailability and likely biological activities

The interplay between gonadal steroids and immune defence in affecting a carotenoid-dependent trait

The hypothesis that sexual ornaments are honest signals of quality because their expression is dependent on hormones with immune-depressive effects has received ambiguous support. The hypothesis might be correct for those signals that are carotenoid-dependent because the required carotenoid deposition in the signal, stimulated by testosterone, might lower the carotenoid-dependent immune defence of the organism. Two pathways underlying this androgen-dependent honest signaling have been suggested. Firstly, androgens that are needed for ornament expression may suppress immune defence, a cost that only high-quality animals can afford. Alternatively, immune activation may downregulate the production of androgens in low-quality individuals. Which of these alternatives is correct, and to what extent these effects are mediated by the different metabolites of androgens, remain open questions. To provide answers to these questions, we manipulated the levels of testosterone (T), 5α-dihydrotestosterone (DHT), and 17-β-estradiol (E2) in diamond doves Geopelia cuneata, a species in which both sexes exhibit a carotenoid-dependent, androgen-regulated red–orange periorbital ring of bare skin. On the first day of the experiment (day 0), we inserted steroid-releasing implants into groups of birds and on day 14, we subjected half of the birds to an immunological challenge by immunizing them with sheep red blood cells (SRBC). In females, but not in males, androgen but not estradiol treatments reduced antibody production to SRBC. In addition, the immunological challenge reduced redness and size of the trait as well as androgens levels in both sexes and in all treatments. This indicates that an immunological challenge can lower circulating T at the cost of the trait expression. These findings are in accordance with both pathways postulated in the immunocompetence-handicap hypothesis, but do not entirely support the idea that the immunosuppressive effect of androgens yields honest signaling since both T and DHT were not immunosuppressive in males, for which sexual signaling is supposed to be especially important

Low exposure long-baseline neutrino oscillation sensitivity of the DUNE experiment

The Deep Underground Neutrino Experiment (DUNE) will produce world-leading neutrino oscillation measurements over the lifetime of the experiment. In this work, we explore DUNE's sensitivity to observe charge-parity violation (CPV) in the neutrino sector, and to resolve the mass ordering, for exposures of up to 100 kiloton-megawatt-years (kt-MW-yr). The analysis includes detailed uncertainties on the flux prediction, the neutrino interaction model, and detector effects. We demonstrate that DUNE will be able to unambiguously resolve the neutrino mass ordering at a 3$\sigma$ (5$\sigma$) level, with a 66 (100) kt-MW-yr far detector exposure, and has the ability to make strong statements at significantly shorter exposures depending on the true value of other oscillation parameters. We also show that DUNE has the potential to make a robust measurement of CPV at a 3$\sigma$ level with a 100 kt-MW-yr exposure for the maximally CP-violating values \delta_{\rm CP}} = \pm\pi/2. Additionally, the dependence of DUNE's sensitivity on the exposure taken in neutrino-enhanced and antineutrino-enhanced running is discussed. An equal fraction of exposure taken in each beam mode is found to be close to optimal when considered over the entire space of interest

Identification and reconstruction of low-energy electrons in the ProtoDUNE-SP detector

Measurements of electrons from $\nu_e$ interactions are crucial for the Deep Underground Neutrino Experiment (DUNE) neutrino oscillation program, as well as searches for physics beyond the standard model, supernova neutrino detection, and solar neutrino measurements. This article describes the selection and reconstruction of low-energy (Michel) electrons in the ProtoDUNE-SP detector. ProtoDUNE-SP is one of the prototypes for the DUNE far detector, built and operated at CERN as a charged particle test beam experiment. A sample of low-energy electrons produced by the decay of cosmic muons is selected with a purity of 95%. This sample is used to calibrate the low-energy electron energy scale with two techniques. An electron energy calibration based on a cosmic ray muon sample uses calibration constants derived from measured and simulated cosmic ray muon events. Another calibration technique makes use of the theoretically well-understood Michel electron energy spectrum to convert reconstructed charge to electron energy. In addition, the effects of detector response to low-energy electron energy scale and its resolution including readout electronics threshold effects are quantified. Finally, the relation between the theoretical and reconstructed low-energy electron energy spectrum is derived and the energy resolution is characterized. The low-energy electron selection presented here accounts for about 75% of the total electron deposited energy. After the addition of lost energy using a Monte Carlo simulation, the energy resolution improves from about 40% to 25% at 50~MeV. These results are used to validate the expected capabilities of the DUNE far detector to reconstruct low-energy electrons.Comment: 19 pages, 10 figure

Snowmass Neutrino Frontier: DUNE Physics Summary

The Deep Underground Neutrino Experiment (DUNE) is a next-generation long-baseline neutrino oscillation experiment with a primary physics goal of observing neutrino and antineutrino oscillation patterns to precisely measure the parameters governing long-baseline neutrino oscillation in a single experiment, and to test the three-flavor paradigm. DUNE's design has been developed by a large, international collaboration of scientists and engineers to have unique capability to measure neutrino oscillation as a function of energy in a broadband beam, to resolve degeneracy among oscillation parameters, and to control systematic uncertainty using the exquisite imaging capability of massive LArTPC far detector modules and an argon-based near detector. DUNE's neutrino oscillation measurements will unambiguously resolve the neutrino mass ordering and provide the sensitivity to discover CP violation in neutrinos for a wide range of possible values of δCP. DUNE is also uniquely sensitive to electron neutrinos from a galactic supernova burst, and to a broad range of physics beyond the Standard Model (BSM), including nucleon decays. DUNE is anticipated to begin collecting physics data with Phase I, an initial experiment configuration consisting of two far detector modules and a minimal suite of near detector components, with a 1.2 MW proton beam. To realize its extensive, world-leading physics potential requires the full scope of DUNE be completed in Phase II. The three Phase II upgrades are all necessary to achieve DUNE's physics goals: (1) addition of far detector modules three and four for a total FD fiducial mass of at least 40 kt, (2) upgrade of the proton beam power from 1.2 MW to 2.4 MW, and (3) replacement of the near detector's temporary muon spectrometer with a magnetized, high-pressure gaseous argon TPC and calorimeter

A Gaseous Argon-Based Near Detector to Enhance the Physics Capabilities of DUNE

This document presents the concept and physics case for a magnetized gaseous argon-based detector system (ND-GAr) for the Deep Underground Neutrino Experiment (DUNE) Near Detector. This detector system is required in order for DUNE to reach its full physics potential in the measurement of CP violation and in delivering precision measurements of oscillation parameters. In addition to its critical role in the long-baseline oscillation program, ND-GAr will extend the overall physics program of DUNE. The LBNF high-intensity proton beam will provide a large flux of neutrinos that is sampled by ND-GAr, enabling DUNE to discover new particles and search for new interactions and symmetries beyond those predicted in the Standard Model