The Impact of Overstocking and Negative Energy Balance on Quantitative Measurement of Non-typhoidal Salmonella in Periparturient Dairy Cattle

Stressful conditions in animal production facilities may exacerbate the fecal shedding and foodborne transmission of non-typhoidal Salmonella enterica subsp. enterica. Dairy cows are reservoirs of this zoonotic microorganism, and its prevalence has roughly doubled in the past decade on dairy farms in United States. Dairy cows are commonly overstocked at the feed bunk, and stressors placed on the animal prior to parturition may exacerbate Salmonella shedding. However, no studies have evaluated the impact of overstocking and metabolic stress on fecal concentrations of the pathogen. Therefore, we conducted a field trial with 120 multiparous dairy cows randomized into one of four treatment groups with different stocking densities at the feed bunk during the periparturient period as follows: US, understocked from -60 to -1 DRC; OS, overstocked from -60 to -1 DRC; USOS, understocked from -60 to -26 DRC/overstocked from -25 to -1 DRC; and OSUS, overstocked from -60 to -26 DRC/ understocked from -25 to -1 DRC. Fecal and blood samples were collected at four time points relative to calving. qPCR assays were used to quantify Salmonella invA gene and total bacterial community from fecal samples, and a subset of isolates recovered from fecal bacterial culture were characterized using pulsed field gel electrophoresis and serotyping. Serum non-esterified fatty acids (NEFA) were measured as a metabolic stress indicator using an immunoassay. Multivariable analyses were performed to test if changes in Salmonella concentrations were associated with stocking density, energy balance, or days relative to calving. From fecal isolates, three Salmonella serovars were identified, S. Cerro; Kentucky; Meleagridis. Concentrations of Salmonella increased as cows approached calving. Higher stocking densities at the feed bunk did not impact total bacterial community or NEFA; however, cows in the overstocked groups had higher Salmonella fecal concentrations. Further, cows with higher NEFA concentrations after calving had a higher likelihood of detection of Salmonella. Future farm interventions should aim to reduce environmental and metabolic stress during the periparturient period to decrease the dissemination of Salmonella to cattle, the environment, and humans.Peer reviewe

R-loop formation during S phase is restricted by PrimPol-mediated repriming

During DNA replication conflicts with ongoing transcription are frequent and require careful management to avoid genetic instability. R-loops, three stranded nucleic acid structures comprising a DNA:RNA hybrid and displaced single stranded DNA, are important drivers of damage arising from such conflicts. How R-loops stall replication and the mechanisms that restrain their formation during S phase are incompletely understood. Here we show in vivo how R-loop formation drives a short purine-rich repeat, (GAA)10, to become a replication impediment that engages the repriming activity of the primase-polymerase PrimPol. Further, the absence of PrimPol leads to significantly increased R-loop formation around this repeat during S phase. We extend this observation by showing that PrimPol suppresses R-loop formation in genes harbouring secondary structure-forming sequences, exemplified by G quadruplex and H-DNA motifs, across the genome in both avian and human cells. Thus, R- loops promote the creation of replication blocks at susceptible structure-forming sequences, while PrimPol-dependent repriming limits the extent of unscheduled R-loop formation at these sequences, mitigating their impact on replication

Varicella zoster virus glycoprotein C increases chemokine-mediated leukocyte migration

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZ

Sturgeon osteocalcin shares structural features with matrix gla protein evolutionary relationship and functional implications

Osteocalcin (OC) and matrix Gla protein (MGP) are considered evolutionarily related because they share key structural features, although they have been described to exert different functions. In this work, we report the identification and characterization of both OC and MGP from the Adriatic sturgeon, a ray-finned fish characterized by a slow evolution and the retention of many ancestral features. Sturgeon MGP shows a primary structure, post-translation modifications, and patterns of mRNA/protein distribution and accumulation typical of known MGPs, and it contains seven possible Gla residues that would make the sturgeon protein the most gamma-carboxylated among known MGPs. In contrast, sturgeon OC was found to present a hybrid structure. Indeed, although exhibiting protein domains typical of known OCs, it also contains structural features usually found in MGPs (e. g. a putative phosphorylated propeptide). Moreover, patterns of OC gene expression and protein accumulation overlap with those reported for MGP; OC was detected in bone cells and mineralized structures but also in soft and cartilaginous tissues. We propose that, in a context of a reduced rate of evolution, sturgeon OC has retained structural features of the ancestral protein that emerged millions of years ago from the duplication of an ancient MGP gene and may exhibit intermediate functional features.Portuguese Science and Technology Foundation [POCTI/MAR/57921/2004, SFRH/BD/9077/2002]; Fundo Europeu De Desenvolvimento Regional (FEDER) (Portugal); National Funding; Center of Marine Sciences (CCMAR

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

Measurement of the lepton charge asymmetry in W-boson decays produced in p-pbar collisions

We describe a measurement of the charge asymmetry of leptons from W boson decays in the rapidity range 0 enu, munu events from 110+/-7 pb^{-1}of data collected by the CDF detector during 1992-95. The asymmetry data constrain the ratio of d and u quark momentum distributions in the proton over the x range of 0.006 to 0.34 at Q2 \approx M_W^2. The asymmetry predictions that use parton distribution functions obtained from previously published CDF data in the central rapidity region (0.0<|y_l|<1.1) do not agree with the new data in the large rapidity region (|y_l|>1.1).Comment: 13 pages, 3 tables, 1 figur

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for squarks and gluinos in events with isolated leptons, jets and missing transverse momentum at s√=8 TeV with the ATLAS detector

The results of a search for supersymmetry in final states containing at least one isolated lepton (electron or muon), jets and large missing transverse momentum with the ATLAS detector at the Large Hadron Collider are reported. The search is based on proton-proton collision data at a centre-of-mass energy s√=8 TeV collected in 2012, corresponding to an integrated luminosity of 20 fb−1. No significant excess above the Standard Model expectation is observed. Limits are set on supersymmetric particle masses for various supersymmetric models. Depending on the model, the search excludes gluino masses up to 1.32 TeV and squark masses up to 840 GeV. Limits are also set on the parameters of a minimal universal extra dimension model, excluding a compactification radius of 1/R c = 950 GeV for a cut-off scale times radius (ΛR c) of approximately 30