Selective miRNA Modulation Fails to Activate HIV Replication in In Vitro Latency Models

HIV remains incurable because of viral persistence in latent reservoirs that are inaccessible to antiretroviral therapy. A potential curative strategy is to reactivate viral gene expression in latently infected cells. However, no drug so far has proven to be successful in vivo in reducing the reservoir, and therefore new anti-latency compounds are needed. We explored the role of microRNAs (miRNAs) in latency maintenance and their modulation as a potential anti-latency strategy. Latency models based on treating resting CD4 T cells with chemokine (C-C motif) ligand 19 (CCL19) or interleukin-7 (IL7) before HIV infection and next-generation sequencing were used to identify the miRNAs involved in HIV latency. We detected four upregulated miRNAs (miRNA-98, miRNA-4516, miRNA-4488, and miRNA-7974). Individual or combined inhibition of these miRNAs was performed by transfection into cells latently infected with HIV. Viral replication, assessed 72 h after transfection, did not increase after miRNA modulation, despite miRNA inhibition and lack of toxicity. Furthermore, the combined modulation of five miRNAs previously associated with HIV latency was not effective in these models. Our results do not support the modulation of miRNAs as a useful strategy for the reversal of HIV latency. As shown with other drugs, the potential of miRNA modulation as an HIV reactivation strategy could be dependent on the latency model usedThis work wasfunded by the Spanish Ministry of Economy and Competitiveness(PIE 13/00040) and the Spanish AIDS Research Network (RIS)(RD16/0025/0001) as part of the Plan Estatal I+D+I and co-financedby Instituto de Salud Carlos III (ISCIII)-Subdirección General deEvaluación y Fomento de la Investigación and Fondo Europeo deDesarrollo Regional (FEDER) (European Regional DevelopmentFund). M.R.L-H. was supported by the Spanish Ministry of Economyand Competitiveness with ISCIII-FEDER funding (PIE 13/00040 and RD12/0017/0017). N.M.E. and C.G. were supported bythe Spanish AIDS Research Network (RD12/0017/0017 and RD16/0025/001

Effects of challenge dose and inoculation route of the virulent Neospora caninum Nc-Spain7 isolate in pregnant cattle at mid-gestation

International audienceAbstractParameters such as pathogen dose and inoculation route are paramount in animal models when studying disease pathogenesis. Here, clinical findings, including foetal mortality, parasite transmission rates and lesion severity, and immune responses were evaluated in Asturiana pregnant heifers at day 110 of gestation challenged with a virulent (Nc-Spain7) Neospora caninum isolate. Four different doses of parasite tachyzoites were inoculated intravenously (IV1, 107 parasites, n = 6; IV2, 105, n = 6; IV3, 103, n = 6; and IV4, 102, n = 5), and the subcutaneous (SC) inoculation route was also assessed for the dose of 105 tachyzoites (SC, n = 6). In addition, a control group (n = 4 pregnant heifers) was evaluated. Foetal death was observed in all infected groups from 25 to 62 days post-infection, varying with the dose (IV1:4/6, IV2:3/6; IV4:2/5, IV3:1/6), and was three times less frequently associated with the SC route than IV inoculation (1/6 vs. 3/6). A dose-dependent effect for parasite loads in placental and foetal brain tissues was also detected. After SC challenge, a reduced number of tachyzoites were able to reach foetal brain tissues, and no lesions were observed. In calves, specific IgG responses in precolostral sera were mainly associated with high-dose groups (IV1 [100.0%] and IV2 [66.7%]), and cerebral parasite DNA detection was scarce (3/18). In dams, IFN-γ production and the dynamics of anti-N. caninum IgG antibodies varied with the dose, and the cell-mediated immune response was also found to be route-dependent. Our results confirm the influence of parasite dose and inoculation route on the outcome and dynamics of bovine neosporosis at mid-gestation

Early Neospora caninum infection dynamics in cattle after inoculation at mid-gestation with high (Nc-Spain7)- or low (Nc-Spain1H)-virulence isolates

© The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.[EN] Early Neospora caninum infection dynamics were investigated in pregnant heifers intravenously inoculated with PBS (G-Control) or 107 tachyzoites of high (G-NcSpain7)- or low (G-NcSpain1H)-virulence isolates at 110 days of gestation. Serial culling at 10 and 20 days post-infection (dpi) was performed. Fever was detected at 1 dpi in both infected groups (P < 0.0001), and a second peak was detected at 3 dpi only in G-NcSpain7 (P < 0.0001). At 10 dpi, Nc-Spain7 was detected in placental samples from one animal related to focal necrosis, and Nc-Spain7 transmission was observed, although no foetal lesions were associated with this finding. The presence of Nc-Spain1H in the placenta or foetuses, as well as lesions, were not detected at 10 dpi. At 20 dpi, G-NcSpain7 animals showed almost 100% positive placental tissues and severe focal necrosis as well as 100% transmission. Remarkably, foetal mortality was detected in two G-NcSpain7 heifers. Only one animal from G-NcSpain1H presented positive placental samples. No foetal mortality was detected, and lesions and parasite transmission to the foetus were not observed in this group. Finally, 100% of G-NcSpain7 heifers at 20 dpi presented specific antibodies, while only 60% of G-NcSpain1H animals presented specific antibodies at 20 dpi. In addition, earlier seroconversion in G-Nc-Spain7 was observed. In conclusion, tachyzoites from Nc-Spain7 reached the placenta earlier and multiplied, leading to lesion development, transmission to the foetus and foetal mortality, whereas Nc-Spain1H showed delayed infection of the placenta and no lesional development or transmission during early infection.SIThis work was supported by the Spanish Ministry of Economy and Competi‑ tiveness (AGL2013-44694-R) and the Community of Madrid (PLATESA2-CM P2018/BAA-4370). Laura Jiménez-Pelayo was fnancially supported by a fellowship from the Complutense University of Madrid and Marta GarcíaSánchez was fnancially supported through a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-070723). Patricia Vázquez had a Juan de la Cierva-Formación post-doctoral contract (FJCI-2014-20982) from the Spanish Ministry of Economy and Competitiveness (MINECO). Alicia Román-Trufero was supported by a FPI-INIA fellowship from the Spanish National Institute for Agriculture and Food Research and Technology (INIA). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Authors gratefully acknowledge to: (1) SERIDA (Regional Service of Agri-food Research and Development of Asturias) Institution and Personal for their facilities and personal support. Special thanks to David Iglesias for their clinical assistance; (2) Mountain Livestock Institute (IGM), University of León CSIC-ULE for their histopathological specialist support, especially to Miguel Fernández for his help during the sampling; (3) Saluvet Group members, especially to Ale‑ jandro Jiménez-Meléndez and Roberto Sánchez-Sánchez; (4) Saluvet-innova members, especially to Paula García-Luna

La construcció conjunta d'una guia per a la implementació de la carpeta d'aprenentatge en l'àmbit de l'educació superior

Els autors d'aquesta comunicació formen part del grup GI-CAES 1(Carpetes d'Aprenentatge en l'Educació Superior) emmarcat en l'IDES des de l'any 2004. En l'actualitat el configuren 14 professors i professores de 7 departaments diferents i una professora d'una Escola Normal de Mèxic. Aquest grup s'estructura com una plataforma de recerca sobre les innovacions docents que pot generar la incorporació de les carpetes d'aprenentatge en els processos d'ensenyament /aprenentatge a la formació universitària. Alhora, es promou la difusió dins i fora de la UAB de les experiències, que en el marc del grup, es van generalitzant d'una manera estable. Aquest àmbit d'innovació repensa la metodologia docent i l'avaluació dels aprenentatges a través de la gradual incorporació de les carpetes d'aprenentatge en la formació dels estudiants. Això suposa prendre decisions sobre el què, el com, el quan i el amb què, de l'ús de les CAES. El treball d'actualització permanent permet explorar tant els aspectes teòrics com els operatius del professorat participant i així poder implementar experiències pràctiques a les aules i aportar elements per a la reflexió/revisió d'altres docents.The authors of this communication are members of the GI-CAES (Learning Portfolios in Higher Education) group within IDES (Teaching Innovation Unit in Higher Education) framework since 2004. Nowadays, in GI-CAES there are 14 professors from 7 different departments in this University (UAB) besides from a teacher based in a Mexican school. Our group is structured as a research platform for teaching innovations, which can lead to the implementation of teaching/learning portfolios in University training. At the same time, we also promote (inside and outside UAB) all the experiencies carried out in the group, which appear to generalize steadily. This innovation context implies rethinking teaching methodologies and learning assessment through the continuous implementation of learning portfolios in students' training. This makes us take decisions on what, how, when and in which way should these portfolios be used. Our constant updating work allows us to explore both the theoretical aspects and the intervention of the teaching staff involved in the experimentation. Thus, implementing practical experiences in the classroom and bringing reflective/revising elements to other professors at University

Crosstalk between Neospora caninum and the bovine host at the maternal-foetal interface determines the outcome of infection

© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creat iveco mmons .org/licen ses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creat iveco mmons .org/publi cdoma in/ zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.[EN]Neospora caninum is an apicomplexan cyst-forming parasite that is considered one of the main causes of abortion. The pathogenic mechanisms associated with parasite virulence at the maternal-foetal interface that are responsible for the outcome of infection are largely unknown. Here, utilizing placentomes from cattle experimentally infected with high-virulence (Nc-Spain7) and low-virulence (Nc-Spain1H) isolates, we studied key elements of the innate and adaptive immune responses, as well as components of the extracellular matrix (ECM), at 10 and 20 days post-infection (dpi). The low-virulence isolate elicited a robust immune response characterized by upregulation of genes involved in pathogen recognition, chemokines and pro-inflammatory cytokines, crucial for its adequate control. In addition, Nc-Spain1H triggered the expression of anti-inflammatory cytokines and other mechanisms implicated in the maintenance of ECM integrity to ensure foetal survival. In contrast, local immune responses were initially (10 dpi) impaired by Nc-Spain7, allowing parasite multiplication. Subsequently (20 dpi), a predominantly pro-inflammatory Th1-based response and an increase in leucocyte infiltration were observed. Moreover, Nc-Spain7-infected placentomes from animals carrying non-viable foetuses exhibited higher expression of the IL-8, TNF-α, iNOS and SERP-1 genes and lower expression of the metalloproteases and their inhibitors than Nc-Spain7-infected placentomes from animals carrying viable foetuses. In addition, profound placental damage characterized by an alteration in the ECM organization in necrotic foci, which could contribute to foetal death, was found. Two different host-parasite interaction patterns were observed at the bovine placenta as representative examples of different evolutionary strategies used by this parasite for transmission to offspring.SIThis work was supported by the Spanish Ministry of Economy and Competitiveness (AGL2013-44694-R and AGL2016-75935-C2-1-R) and the Community of Madrid (PLATESA2-CM P2018/BAA-4370). Laura Jiménez-Pelayo was financially supported by a fellowship from the University Complutense of Madrid (including two research stays in 2017 and 2018) and Marta García-Sánchez was financially supported through a grant from the Spanish Ministry of Economy and Competitiveness (BES-2014-070723). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

Understanding the retreat of the Jurassic Cantabrian coast (N. Spain): comprehensive monitoring and 4D evolution model of the Tazones Lighthouse landslide

Forecasting coastal dynamics and sea cliff retreat under different sea level rise scenarios requires a good understanding of the conditioning factors and their relative contribution to cliff stability. The so-called Jurassic Cantabrian Coast extends along 76 km of the coastline of the Asturias region (N Spain) and is well-known worldwide due to its paleontological heritage, in particular the presence of dinosaur remains and footprints. The abundance of stratigraphic, paleontological and tectonic studies contrasts with the scarcity of studies focused on the stability of this rocky coastline where cliffs predominate, sometimes exceeding 120 m in height. In fact, evidence of current and recent instability processes can be observed along the entire coastline. In this regard, continuous monitoring is crucial to understand ongoing instabilities in rocky coastlines, as in these settings some instabilities might initiate as slow movements that induce subtle topographic changes whose detection from either satellite or aerial imagery is problematic due to the spatial and temporal resolutions.This research is part of 1) the “COSINES” Project [CGL2017-83909-R], Call 2017 for RETOS Projects funded by the Spanish Economy, Industry and Competitiveness Ministry-Ministerio de Economía, Industria y Competitividad (MINECO), the Spanish Research Agency-Agencia Estatal de Investigación (AEI) and the European Regional Development Found (FEDER) and 2) the GEOCANCOSTA research group, supported by the Asturian Regional Government (Spain) [grant number GRUPIN-IDI-2018-184]

Parasitología interactiva: Protozoos y afines

Desarrollo de una guía interactiva donde se muestran los ciclos biológicos, imágenes y dibujos de los estadios evolutivos de los principales géneros y especies de parásitos protozoos relevantes en al ámbito veterinario