The effects of male social environment on sperm phenotype and genome integrity

Sperm function and quality are primary determinants of male reproductive performance and hence fitness. The presence of rival males has been shown to affect ejaculate and sperm traits in a wide range of taxa. However, male physiological conditions may not only affect sperm phenotypic traits but also their genetic and epigenetic signatures, affecting the fitness of the resulting offspring. We investigated the effects of male-male competition on sperm quality using TUNEL assays and geometric morphometrics in the zebrafish, Danio rerio. We found that the sperm produced by males exposed to high male-male competition had smaller heads but larger midpiece and flagellum than sperm produced by males under low competition. Head and flagella also appeared less sensitive to the osmotic stress induced by activation with water. In addition, more sperm showed signals of DNA damage in ejaculates of males under high competition. These findings suggest that the presence of a rival male may have positive effects on phenotypic traits but negative effects on DNA integrity. Overall, males facing the presence of rival males may produce faster swimming and more competitive sperm but this may come at a cost for the next generation. This article is protected by copyright. All rights reserved

Enhanced interferon regulatory factor 3 binding to the interleukin-23p19 promoter correlates with enhanced interleukin-23 expression in systemic lupus erythematosus.

OBJECTIVE: To examine the role of interferon regulatory factor 3 (IRF-3) in the regulation of interleukin-23 (IL-23) production in patients with systemic lupus erythematosus (SLE). METHODS: Bone marrow-derived macrophages were isolated from both wild-type and IRF3(-/-) C57BL/6 mice. These cells were stimulated with the Toll-like receptor 3 (TLR-3) agonist poly(I-C), and IL-23p19 cytokine levels were analyzed by enzyme-linked immunosorbent assay. IRF-3 binding to the IL-23p19 gene promoter region in monocytes from patients with SLE and healthy control subjects was analyzed by chromatin immunoprecipitation (ChIP) assay. Luciferase reporter gene assays were performed to identify key drivers of IL-23p19 promoter activity. TANK-binding kinase 1 (TBK-1) protein levels were determined by Western blotting. RESULTS: ChIP assays demonstrated that IRF-3 was stably bound to the human IL-23p19 promoter in monocytes; this association increased following TLR-3 stimulation. Patients with SLE demonstrated increased levels of IRF-3 bound to the IL-23p19 promoter compared with control subjects, which correlated with enhanced IL-23p19 production in monocytes from patients with SLE. Investigations of the TLR-3-driven responses in monocytes from patients with SLE revealed that TBK-1, which is critical for regulating IRF-3 activity, was hyperactivated in both resting and TLR-3-stimulated cells. CONCLUSION: Our results demonstrate for the first time that patients with SLE display enhanced IL-23p19 expression as a result of hyperactivation of TBK-1, resulting in increased binding of IRF-3 to the promoter. These findings provide novel insights into the molecular pathogenesis of SLE and the potential role for TLR-3 in driving this response

Loss of the Lupus Autoantigen Ro52/Trim21 Induces Tissue Inflammation and Systemic Autoimmunity by Disregulating the IL-23–Th17 Pathway

Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren's syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 may promote development of systemic autoimmune diseases has not been explored. To address this issue, we generated Ro52-null mice ($Ro52^{−/−}$), which appear phenotypically normal if left unmanipulated. However, $Ro52^{−/−}$ mice develop severe dermatitis extending from the site of tissue injury induced by ear tags. The affected mice further develop several signs of systemic lupus with hypergammaglobulinemia, autoantibodies to DNA, proteinuria, and kidney pathology. Ro52, which was recently identified as an E3 ligase, mediates ubiquitination of several members of the interferon regulatory factor (IRF) family, and the Ro52-deficient mice have an enhanced production of proinflammatory cytokines that are regulated by the IRF transcription factors, including cytokines involved in the Th17 pathway (interleukin [IL] 6, IL-12/IL-23p40, and IL-17). Loss of IL-23/IL-17 by genetic deletion of IL-23/p19 in the $Ro52^{−/−}$ mice conferred protection from skin disease and systemic autoimmunity. These data reveal that the lupus-associated Ro52 protein is an important negative regulator of proinflammatory cytokine production, and they provide a mechanism by which a defective Ro52 function can lead to tissue inflammation and systemic autoimmunity through the IL-23–Th17 pathway

Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23-Th17 pathway.

Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren\u27s syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 may promote development of systemic autoimmune diseases has not been explored. To address this issue, we generated Ro52-null mice (Ro52(-/-)), which appear phenotypically normal if left unmanipulated. However, Ro52(-/-) mice develop severe dermatitis extending from the site of tissue injury induced by ear tags. The affected mice further develop several signs of systemic lupus with hypergammaglobulinemia, autoantibodies to DNA, proteinuria, and kidney pathology. Ro52, which was recently identified as an E3 ligase, mediates ubiquitination of several members of the interferon regulatory factor (IRF) family, and the Ro52-deficient mice have an enhanced production of proinflammatory cytokines that are regulated by the IRF transcription factors, including cytokines involved in the Th17 pathway (interleukin [IL] 6, IL-12/IL-23p40, and IL-17). Loss of IL-23/IL-17 by genetic deletion of IL-23/p19 in the Ro52(-/-) mice conferred protection from skin disease and systemic autoimmunity. These data reveal that the lupus-associated Ro52 protein is an important negative regulator of proinflammatory cytokine production, and they provide a mechanism by which a defective Ro52 function can lead to tissue inflammation and systemic autoimmunity through the IL-23-Th17 pathway

Transgenic Mice Expressing Porcine Prion Protein Resistant to Classical Scrapie but Susceptible to Sheep Bovine Spongiform Encephalopathy and Atypical Scrapie

Atypical scrapie strain phenotypes may shift when transmitted to a new host

Measurements of the pp → ZZ production cross section and the Z → 4ℓ branching fraction, and constraints on anomalous triple gauge couplings at √s = 13 TeV

Four-lepton production in proton-proton collisions, pp -> (Z/gamma*)(Z/gamma*) -> 4l, where l = e or mu, is studied at a center-of-mass energy of 13 TeV with the CMS detector at the LHC. The data sample corresponds to an integrated luminosity of 35.9 fb(-1). The ZZ production cross section, sigma(pp -> ZZ) = 17.2 +/- 0.5 (stat) +/- 0.7 (syst) +/- 0.4 (theo) +/- 0.4 (lumi) pb, measured using events with two opposite-sign, same-flavor lepton pairs produced in the mass region 60 4l) = 4.83(-0.22)(+0.23) (stat)(-0.29)(+0.32) (syst) +/- 0.08 (theo) +/- 0.12(lumi) x 10(-6) for events with a four-lepton invariant mass in the range 80 4GeV for all opposite-sign, same-flavor lepton pairs. The results agree with standard model predictions. The invariant mass distribution of the four-lepton system is used to set limits on anomalous ZZZ and ZZ. couplings at 95% confidence level: -0.0012 < f(4)(Z) < 0.0010, -0.0010 < f(5)(Z) < 0.0013, -0.0012 < f(4)(gamma) < 0.0013, -0.0012 < f(5)(gamma) < 0.0013

Evaluation of the plasmatic level of mepivacaine in different anatomical regions

To evaluate the serum level of the local anesthetic mepivacaine 3% without vasoconstrictor in patients who underwent procedures performed in the anterior and posterior maxilla, through a method of possible extraction to quantify it in human plasma by high performance liquid chromatography (HPLC). This was a hybrid study consisting of 18 patients (7 females and 11 males) classified as ASA I, adults and with normal body mass index, submitted to procedures in the anterior region (group I) and posterior region of the maxilla (group II). For 40 minutes, five 6 ml blood samples were collected every 10 minutes after infiltrative injection in each region of the maxilla. Serum levels of the drug were obtained through HPLC. Blood pressure (BP) and heart rate (HR) were measured throughout the procedure. When compared to the general average of the concentrations of each group, significant values (p<0.05) with greater absorption were observed for the anterior region of the maxilla (group I). There was no significant difference when comparing blood pressure (BP) and heart rate (HR) values. The concentrations found are safe for infiltrative anesthesia in the analyzed patients, there was a higher plasma level of the local anesthetic in the anterior region of the maxilla and there was no change in HR and BP in relation to the anesthetized area

Population structure and gene flow of Geoffroy's cat (Leopardus geoffroyi) in the Uruguayan Savanna ecoregion

Felids are among the species most threatened by habitat fragmentation resulting from land-use change. In the Uruguayan Savanna ecoregion, about 30% of natural habitats have been lost, large felids have been eradicated from most of the region, and the impact of anthropogenic threats over the smaller species that remain is unknown. To develop management strategies, it is important to enhance knowledge about species population structure and landscape connectivity, particularly when land-use change will continue and intensify in the next years. In this study, we evaluate the population structure and gene flow of Geoffroy's cat in the Uruguayan Savanna ecoregion. We generated a matrix of 11 microsatellite loci for 70 individuals. Based on Bayesian approaches we found that within the Uruguayan Savanna, Geoffroy's cat shows high levels of genetic variability and no population structure. However, we observed genetic differences between individuals from the Uruguayan Savanna and those from the contiguous ecoregion, the Argentinian Humid Pampa. Four first-generation migrants from Humid Pampa were identified in the Uruguayan Savanna, suggesting a stronger gene flow in the west-east direction. We detected a past bottleneck followed by a subsequent recovery in Geoffroy's cat populations in both ecoregions. These results lay the groundwork to understand the population dynamics and conservation status of Geoffroy's cat in the Uruguayan Savanna ecoregion, and provide baseline data to establish population monitoring.Fil: Bou, Nadia. Ministerio de Educacion y Cultura.; UruguayFil: Soutullo, Álvaro. Universidad de la Republica; UruguayFil: Hernández, Daniel. Laboratorio de Control Ambiental; UruguayFil: Mannise, Natalia. Ministerio de Educacion y Cultura.; UruguayFil: González, Susana. Ministerio de Educacion y Cultura.; UruguayFil: Bartesaghi, Lucía. Ministerio de Educacion y Cultura.; UruguayFil: Pereira, Javier Adolfo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; ArgentinaFil: Merino, Mariano Lisandro. Universidad Nacional del Noroeste de la Provincia de Buenos Aires. Centro de Bioinvestigaciones (Sede Junín); ArgentinaFil: Espinosa, Caroline. Universidade Federal do Rio Grande do Sul; BrasilFil: Trigo, Tatiane C.. Museu de Ciencias Naturais; ArgentinaFil: Cosse, Mariana. Ministerio de Educacion y Cultura.; Urugua

Reducing self-stigma in psychosis: a systematic review and meta-analysis of psychological interventions

The burden of self-stigma in psychosis has been widely studied, leading to the development and implementation of self-stigma reduction programmes to ameliorate its impact. In order to successfully improve self-stigma in psychosis, we must evaluate the effect of available interventions to help clinicians select the most appropriate approach for their patients. This systematic review and meta-analysis aimed to evaluate the effect of self-stigma reduction interventions in people with psychosis while considering the interventions’ characteristics as an important moderator of their effect. The results from this systematic review suggest that interventions involving more than one component, particularly those combining psychoeducation, social skills training and cognitive approaches, were most effective at reducing self-stigma in people with psychosis. Additionally, shorter interventions were found best reduced self-stigma at post-treatment evaluation. A meta-analysis mirrored these results, finding an overall favourable effect of interventions but high heterogeneity in the sample. Subgroup analyses found larger self-stigma reductions following multi-component interventions compared to single-component interventions. An analysis of risk of bias revealed a trend suggesting studies with lower risk of bias produced smaller effects. The results of this review can inform practitioners select and develop interventions to reduce self-stigma in psychosis."This review was carried out under the PERMEPSY project. The PERMEPSY project was supported under the frame of ERA PerMed by: Instituto de Salud Carlos III (ISCIII), Spain; German Federal Ministry of Education and Research (BMBF), Germany; Agence Nationale de la Recherche (ANR), France; National Centre for Research and Development (NCBR), Poland; Agencia Nacional de Investigación y Desarrollo (ANID), Chile"Peer ReviewedPostprint (published version