Mus musculus populations in Western Australia lack VKORC1 mutations conferring resistance to first generation anticoagulant rodenticides: Implications for conservation and biosecurity

Background Humans routinely attempt to manage pest rodent populations with anticoagulant rodenticides (ARs). We require information on resistance to ARs within rodent populations to have effective eradication programs that minimise exposure in non-target species. Mutations to the VKORC1 gene have been shown to confer resistance in rodents with high proportions of resistance in mice found in all European populations tested. We screened mutations in Mus musculus within Western Australia, by sampling populations from the capital city (Perth) and a remote island (Browse Island). These are the first Australian mouse populations screened for resistance using this method. Additionally, the mitochondrial D-loop of house mice was sequenced to explore population genetic structure, identify the origin of Western Australian mice, and to elucidate whether resistance was linked to certain haplotypes. Results No resistance-related VKORC1 mutations were detected in either house mouse population. A genetic introgression in the intronic sequence of the VKORC1 gene of Browse Island house mouse was detected which is thought to have originated through hybridisation with the Algerian mouse (Mus spretus). Analysis of the mitochondrial D-loop reported two haplotypes in the house mouse population of Perth, and two haplotypes in the population of Browse Island. Conclusions Both house mouse populations exhibited no genetic resistance to ARs, in spite of free use of ARs in Western Australia. Therefore weaker anticoagulant rodenticides can be employed in pest control and eradication attempts, which will result in reduced negative impacts on non-target species. Biosecurity measures must be in place to avoid introduction of resistant house mice, and new house mouse subspecies to Western Australia

UEG's prospects for the future Strategic plan 2023-2026

Cellular mechanisms in basic and clinical gastroenterology and hepatolog

Effect of Angiogenesis-Related Cytokines on Rotator Cuff Disease: The Search for Sensitive Biomarkers of Early Tendon Degeneration

Background Hallmarks of the pathogenesis of rotator cuff disease (RCD) include an abnormal immune response, angiogenesis, and altered variables of vascularity. Degenerative changes enhance production of pro-inflammatory, anti-inflammatory, and vascular angiogenesis-related cytokines (ARC) that play a pivotal role in the immune response to arthroscopic surgery and participate in the pathogenesis of RCD. The purpose of this study was to evaluate the ARC profile, ie, interleukin (IL): IL-1β, IL-6, IL-8, IL-10, vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and angiogenin (ANG), in human peripheral blood serum and correlate this with early degenerative changes in patients with RCD. Methods Blood specimens were obtained from 200 patients with RCD and 200 patients seen in the orthopedic clinic for nonrotator cuff disorders. Angiogenesis imaging assays was performed using power Doppler ultrasound to evaluate variables of vascularity in the rotator cuff tendons. Expression of ARC was measured by commercial Bio-Plex Precision Pro Human Cytokine Assays. Results Baseline concentrations of IL-1β, IL-8, and VEGF was significantly higher in RCD patients than in controls. Significantly higher serum VEGF levels were found in 85% of patients with RCD, and correlated with advanced stage of disease (r = 0.75; P < 0.0005), average microvascular density (r = 0.68, P < 0.005), and visual analog score (r = 0.75, P < 0.0002) in RCD patients. ANG and IL-10 levels were significantly lower in RCD patients versus controls. IL-1β and ANG levels were significantly correlated with degenerative tendon grade in RCD patients. No difference in IL-6 and bFGF levels was observed between RCD patients and controls. Patients with degenerative changes had markedly lower ANG levels compared with controls. Power Doppler ultrasound showed high blood vessel density in patients with tendon rupture. Conclusion The pathogenesis of RCD is associated with an imbalance between pro-inflammatory, anti-inflammatory, and vascular ARC

Molecular Mimicry of Human Cytochrome P450 by Hepatitis C Virus at the Level of Cytotoxic T Cell Recognition

Hepatitis C virus (HCV) is thought to be involved in the pathogenesis of autoimmune hepatitis (AIH) type 2, which is defined by the presence of type I antiliver kidney microsome autoantibodies directed mainly against cytochrome P450 (CYP)2D6 and by autoreactive liver infiltrating T cells. Virus-specific CD8+ cytotoxic T lymphocytes (CTLs) that recognize infected cells and contribute to viral clearance and tissue injury during HCV infection could be involved in the induction of AIH. To explore whether the antiviral cellular immunity may turn against self-antigens, we characterized the primary CTL response against an HLA-A*0201–restricted HCV-derived epitope, i.e., HCV core 178–187, which shows sequence homology with human CYP2A6 and CYP2A7 8–17. To determine the relevance of these homologies for the pathogenesis of HCV-associated AIH, we used synthetic peptides to induce primary CTL responses in peripheral blood mononuclear cells of healthy blood donors and patients with chronic HCV infection. We found that the naive CTL repertoire of both groups contains cross-reactive CTLs inducible by the HCV peptide recognizing both CYP2A6 and CYP2A7 peptides as well as endogenously processed CYP2A6 protein. Importantly, we failed to induce CTLs with the CYP-derived peptides that showed a lower capacity to form stable complexes with the HLA-A2 molecule. These findings demonstrate the potential of HCV to induce autoreactive CD8+ CTLs by molecular mimicry, possibly contributing to virus-associated autoimmunity

A Pragmatic Assessment of Government Support for Organic Agriculture in Ireland

Drawing on a pragmatic approach, this paper provides an analysis of governmental support for organic farming in Ireland. There are varying levels of encouragement and programmes provided to farmers in their conversion from conventional to organic production, and in their maintenance of organic production. Support policies vary across regions and are linked to European Union legislation, thus it is challenging to document the many types of support in place. This research investigates relevant technical, financial, and policy support available to organic farmers in Ireland. This exploratory study develops an assessment of Ireland within eight key categories of organic agricultural support: leadership, policy, research, technical support, financial support, marketing and promotion, education and information, and future developments. Information and data from the Irish Department of Agriculture, Fisheries and Food (DAFF), the Irish Agriculture and Food Development Authority (Teagasc), and other governmental and semi-governmental agencies were utilized to assess the level of support in each category. Following the pragmatic approach, this assessment provides key findings which allow policymakers, organizations and citizens to better understand the current situation and set a path for the future development of organic farming in Ireland

Search for lepton-flavor violation at HERA

A search for lepton-flavor-violating interactions $e p \to \mu X$ and $e p\to \tau X$ has been performed with the ZEUS detector using the entire HERA I data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data were taken at center-of-mass energies, $\sqrt{s}$, of 300 and 318 GeV. No evidence of lepton-flavor violation was found, and constraints were derived on leptoquarks (LQs) that could mediate such interactions. For LQ masses below $\sqrt{s}$, limits were set on $\lambda_{eq_1} \sqrt{\beta_{\ell q}}$, where $\lambda_{eq_1}$ is the coupling of the LQ to an electron and a first-generation quark $q_1$, and $\beta_{\ell q}$ is the branching ratio of the LQ to the final-state lepton $\ell$ ($\mu$ or $\tau$) and a quark $q$. For LQ masses much larger than $\sqrt{s}$, limits were set on the four-fermion interaction term $\lambda_{e q_\alpha} \lambda_{\ell q_\beta} / M_{\mathrm{LQ}}^2$ for LQs that couple to an electron and a quark $q_\alpha$ and to a lepton $\ell$ and a quark $q_\beta$, where $\alpha$ and $\beta$ are quark generation indices. Some of the limits are also applicable to lepton-flavor-violating processes mediated by squarks in $R$-Parity-violating supersymmetric models. In some cases, especially when a higher-generation quark is involved and for the process $e p\to \tau X$, the ZEUS limits are the most stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig. 6) adde

Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s

Multijet production rates in neutral current deep inelastic scattering have been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2. The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s) = 318 GeV using the ZEUS detector and correspond to an integrated luminosity of 82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster algorithm in the longitudinally invariant inclusive mode. Measurements of differential dijet and trijet cross sections are presented as functions of jet transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD calculations describe the data well. The value of the strong coupling constant alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections, is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.) {+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure

Measurement of charm fragmentation ratios and fractions in photoproduction at HERA

The production of D^*+, D^0, D^+, D_s^+ and Lambda_c^+ charm hadrons and their antiparticles in ep scattering at HERA was measured with the ZEUS detector using an integrated luminosity of 79 pb^-1. The measurement has been performed in the photoproduction regime with the exchanged-photon virtuality Q^2 < 1 GeV^2 and for photon-proton centre-of-mass energies in the range 130 < W < 300 GeV. The charm hadrons were reconstructed in the range of transverse momentum p_T(D, Lambda_c) > 3.8 GeV and pseudorapidity |eta(D, Lambda_c)| < 1.6. The production cross sections were used to determine the ratio of neutral and charged D-meson production rates, R_u/d, the strangeness-suppression factor, gamma_s, and the fraction of charged D mesons produced in a vector state, P_v^d. The measured R_u/d and gamma_s values agree with those obtained in deep inelastic scattering and in e^+e^- annihilations. The measured P_v^d value is smaller than, but consistent with, the previous measurements. The fractions of c quarks hadronising as a particular charm hadron, f(c -> D, Lambda_c), were derived in the given kinematic range. The measured open-charm fragmentation fractions are consistent with previous results, although the measured f(c -> D^*+) is smaller and f(c -> Lambda_c^+) is larger than those obtained in e^+e^- annihilations. These results generally support the hypothesis that fragmentation proceeds independently of the hard sub-process.Comment: 29 pages, 5 figures, 6 tables; minor text revision

Can parasites adapt to pollutants? A multigenerational experiment with a Daphnia x Metschnikowia model system exposed to the fungicide tebuconazole

There is increasing evidence about negative effects of fungicides on non-target organisms, including parasitic species, which are key elements in food webs. Previous experiments showed that environmentally relevant concentrations of fungicide tebuconazole are toxic to the microparasite Metschnikowia bicuspidata, a yeast species that infects the planktonic crustacean Daphnia spp. However, due to their short-term nature, this and other experimental studies were not able to test if parasites could potentially adapt to these contaminants. Here, we tested if M. bicuspidata parasite can adapt to tebuconazole selective pressure. Infected D. magna lineages were reared under control conditions (no tebuconazole) and environmentally realistic tebuconazole concentrations, for four generations, and their performance was compared in a follow-up reciprocal assay. Additionally, we assessed whether the observed effects were transient (phenotypic) or permanent (genetic), by reassessing parasite fitness after the removal of selective pressure. Parasite fitness was negatively affected throughout the multigenerational exposure to the fungicide: prevalence of infection and spore load decreased, whereas host longevity increased, in comparison to control (naive) parasite lineages. In a follow-up reciprocal assay, tebuconazole-conditioned (TEB) lineages performed worse than naive parasite lineages, both in treatments without and with tebuconazole, confirming the cumulative negative effect of tebuconazole. The underperformance of TEB lineages was rapidly reversed after removing the influence of the selective pressure (tebuconazole), demonstrating that the costs of prolonged exposure to tebuconazole were phenotypic and transient. The microparasitic yeast M. bicuspidata did not reveal potential for rapid evolution to an anthropogenic selective pressure; instead, the long-term exposure to tebuconazole was hazardous to this non-target species. These findings highlight the potential environmental risks of azole fungicides on non-target parasit- This work was supported by the European Regional Development Fund (programmes COMPETE2020 and PT2020) and by National Funds (Portuguese Science Foundation - FCT, I.P.), through the strategic programmes UID/AMB/50017/2013 and UID/BIA/04050/2019 (POCI-01-0145-FEDER-007569), as well as by the research projects FunG-Eye (POCI-01-0145-FEDER-029505) and EcoAgriFood (NORTE-01-0145-FEDER-000009). Part of the work presented here was developed during the PhD of Ana P. Cuco, who was supported by FCT (PhD grant SFRH/BD/81661/2011). JW was supported by Beethoven Life-1 grant from the German Science Foundation and Polish National Science Center (WO 1587/9-1). Nelson Abrantes is the recipient of an individual postdoctoral research contract (CEECIND/01653/2017)

The <i>Ectocarpus</i> genome and the independent evolution of multicellularity in brown algae

Brown algae (Phaeophyceae) are complex photosynthetic organisms with a very different evolutionary history to green plants, to which they are only distantly related1. These seaweeds are the dominant species in rocky coastal ecosystems and they exhibit many interesting adaptations to these, often harsh, environments. Brown algae are also one of only a small number of eukaryotic lineages that have evolved complex multicellularity (Fig. 1).We report the 214 million base pair (Mbp) genome sequence of the filamentous seaweed Ectocarpus siliculosus (Dillwyn) Lyngbye, a model organism for brown algae, closely related to the kelps (Fig. 1). Genome features such as the presence of an extended set of light-harvesting and pigment biosynthesis genes and new metabolic processes such as halide metabolism help explain the ability of this organism to cope with the highly variable tidal environment. The evolution of multicellularity in this lineage is correlated with the presence of a rich array of signal transduction genes. Of particular interest is the presence of a family of receptor kinases, as the independent evolution of related molecules has been linked with the emergence of multicellularity in both the animal and green plant lineages. The Ectocarpus genome sequence represents an important step towards developing this organism as a model species, providing the possibility to combine genomic and genetic2 approaches to explore these and other aspects of brown algal biology further