Juan Francisco Martel and Teresa Palacios have ignored the prosecutor’s request and released the three youths from Tafalla The prosecution demanded a two-year prison sentence nine years of disqualification and a fine of 4,800 euros His acquittals state that the testimony of the Civil Guard alone to confirm the participation of these three people in the brindism is not enough The dates displayed for an article provide information on when various publication milestones were reached at the journal that has published the article activities on preceding journals at which the article was previously under consideration are not shown (for instance submission All content on this site: Copyright © 2025 Elsevier B.V. This website is using a security service to protect itself from online attacks The action you just performed triggered the security solution There are several actions that could trigger this block including submitting a certain word or phrase You can email the site owner to let them know you were blocked Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page Home › Comics › British Comics › In Memoriam: Masters of the Universe and The Phantom artist We’re sorry to report the passing of Spanish comic artist Jose María Ortiz Tafalla perhaps best known for his work on Masters of the Universe for London Editions Not be confused with José Ortiz, Jose María Ortiz Tafalla, aka Jaimie Ortiz and J.M Ortiz, hailed from Valencia, his comic career beginning in the 1950s, Lambiek noting he drew “Roy Clark” in Comandos (Ed and contributed to Fanvencia collections like Aventuras de Guerra and Historias de Guerra Working with writer Pedro Muñoz, he contributed to the Grafidea collections Cuatro Capitanes and Jarko el Temible, and, as an agency artist, worked on French series such as Cinq As, Marino (in Zembla), Scotland Yard, Tenax a superhero strip published in France and Spain he’s also known for the globe-spanning adventure strip commissioned through the agency Interpubli He worked on London Editions Masters of the Universe comic from the very first issue his work still fondly remembered today by fans He is also credited as the artist on some “Battle Complete Stories” for Battle Action (1978) one of the artists on Starblazer, as Jaimie Ortiz, which were reprinted in Spain a “Future Shocks” for 2000AD Prog 386 “A great and prolific artist from the golden age of the Masters of the Universe in Spain now resides in the great pantheon of artists in the history of comics,” the team from the Spanish Mundo Masters site commented in a short tribute on their Masters of the Universe group Our commiserations and condolences to the family and friends • Masters of the Universe UK Comics – London Editions MOTU Comics | Main Site • Chronicle Chamber (Phantom Site): Items featuring José María Ortiz Tafalla • Tebesfera: José Maria Ortiz Tafalla • Lambiek: José Maria Ortiz Tafalla • Historietistas Españoles de la A, a la Z: José María Ortiz Tafalla Gallery • Peter Mennigen on José Maria Ortiz Tafalla (via Facebook) John  is the founder of downthetubes, launched in 1998. He is a comics and magazine editor, writer, and Press Officer for the Lakes International Comic Art Festival. He also runs Crucible Comic Press He’s the writer of  comics such as Pilgrim: Secrets and Lies for B7 Comics; “Crucible”, a creator-owned project with 2000AD artist Smuzz; and “Death Duty” and “Skow Dogs”, with Dave Hailwood. • British and Irish Comic Conventions and SigningsLast Updated: 5th May 2025 • British and Irish Current Comic-Related ExhibitionsLast Updated: 5th May 2025 • 2000AD, Treasury of British Collections and Specials – 2025Last Updated: 20th February 2025 If you have subscribed to the site through our Wordpress "Pop Up" Please support us through a PayPal donation – thank you! we’re proud winners of awards from ComicScene SFX and Tripwire down the years and we’re keen to keep running for you Please note - some interviews and feature items from older versions of the web site are archived. We continue to add these as time permits. The Internet Archive "Wayback" has archived downthetubes since its inception Subscribe now to keep reading and get access to the full archive causing flash floods in the Navarre region on 08 July the town of Guetádar recorded 158.9 mm of rain in 24 hours on 08 July The rain caused the Cidacos (Zidacos) river to break its banks flooding areas around the towns of Tafalla The municipality of Tafalla has been declared catastrophic zone Civil Protection said that levels of the Cidacos river at Olite jumped from 0.18 metres to 5.75 metres this is possibly a record high level for the river in Olite The regional government said that the material damage caused by the flooding was far-reaching sports areas and the N-121 road between Pamplona and Tudela The government of Navarre said would take 1 to 2 months to repair the damages on the national N-121 road Images on Social Media showed car being dragged along streets by flood water they were continuing to find abandoned cars trapped in flood waters One fatality was reported as a result of the floods after a man drowned in his vehicle in the municipality of Ezprogui #Tafalla RT @Armeteo INUNDACIONES TAFALLA | 100 l/m2 en unas pocas horas han caído en #Tafalla. Una situación histórica. Seguiremos informando… pic.twitter.com/cEJZ9V8TLl — P. Civil Tolosa (@PCTolosa) July 8, 2019 Impacta ver la fuerza del #agua. Estado de la N121 en #Pueyo pic.twitter.com/co4vpgpoOT — Policía Foral-Foruzaingoa (@policiaforal_na) July 8, 2019 Impresionante inundación en Tafalla https://t.co/gwMcG1f7Nx pic.twitter.com/XmHsRtXH7E — Diario de Noticias (@NoticiasNavarra) July 8, 2019 https://twitter.com/policiaforal_na/status/1148496124568899584 Cookies | Privacy | Contacts © Copyright 2025 FloodList Metrics details As B cells are singularly equipped with a B cell receptor (BCR) and a range of innate receptors they are able to integrate both antigen-specific and innate signals with the latter being essential to reach an adequate level of activation Whether teleost B cells sense pathogens through innate mechanisms has not yet been explored despite the fact that fish B cells display a wider array of innate receptors than many mammalian B cell subsets we have investigated the effects of inactivated Aeromonas salmonicida on trout splenic IgM+ B cells in vitro in the presence or absence of different inhibitors of Toll-like receptor (TLR) signalling to establish to what degree innate signals are contributing to the activation of B cells in teleosts Our results demonstrate that most of the effects that A salmonicida exerts on trout IgM+ B cells are significantly blocked in the presence of inhibitors of MyD88 and TRIF TLR signalling is essential for the activation of IgM+ B cells These results will be useful for the future optimization of novel vaccines and adjuvants highlighting the great potential of TLR ligands as adjuvants Although commercial vaccines are able to induce long-term protection furunculosis outbreaks are still frequent in several fresh and marine aquacultured species which provide novel information regarding the mechanisms through which fish B cells recognize bacteria and become activated will surely be valuable for the future optimization of novel prevention strategies against this and other pathogenic bacteria salmonicida previously labelled with Syto BC Green at a 1:2 cell:bacteria ratio cells were stained with anti-IgM (shown as red) and plated onto poly-L-lysine coated glass slides Samples were then analysed by confocal fluorescence microscopy Representative confocal microscopy images include a large field (top images) and a higher magnification (lower images) showing both an IgM+ B cell and an IgM- cell phagocyting A 10 µm on the large fields and 2 µm on the higher magnifications) Splenic leukocytes were incubated with MyD88 inhibitor peptide (100 µM) the same volume of DMSO or media alone for 1 h Controls without bacteria were also included cells were stained with anti-trout IgM-APC and analysed by flow cytometry Representative dot plot from one individual fish is shown (b) along with the quantification of the percentage of phagocytic IgM+ B cells (cells in the upper right quadrant) among total IgM+ cells (cells in upper quadrants) after each treatment (mean + SD; n = 7 individual fish) (c Asterisks denote significant differences between groups as indicated (*P ≤ 0.05) A. salmonicida increases IgM+ B cell survival and has lymphoproliferative effects. Splenocytes were incubated with the different inhibitors or left unstimulated as described in the legend of Fig. 1 salmonicida at a ratio 1:2 (cell:bacteria) cells were labelled with anti-trout IgM-APC and the percentage of IgM+ B cells in the cultures determined by flow cytometry together with a quantification of the percentage of IgM+ B cells in cultures (mean + SD; n = 12) (b,c) salmonicida on B cells were determined in parallel cells were pre-treated with the inhibitors and then stimulated with the bacteria as described above splenic leukocytes were incubated with EdU for an additional 24 h cells were labelled with anti-trout IgM-APC and the percentage of proliferating cells determined as described in the Materials and Methods section together with a quantification of the percentage of proliferating IgM+ B cells (mean + SD; n = 9) (e,f) Asterisks denote significant differences between groups as indicated (*P ≤ 0.05; ***P ≤ 0.005) A. salmonicida increases the expression of surface MHC II on IgM+ B cells. Splenocytes were incubated with the different inhibitors or left unstimulated as described in the legend of Fig. 1 cells were labelled with anti-trout IgM-FITC and anti-trout MHC II-APC and analysed by flow cytometry Representative dot plots (a) and histograms (b) showing MHC II expression levels in IgM+ B cells from one representative fish are included along with the quantification of MHC II mean fluorescence intensity (MFI) values in IgM+ B cells (c) and IgM- cells (d) (mean + SD; n = 12) Asterisks denote significant differences between groups as indicated (*P ≤ 0.05; **P ≤ 0.01) A. salmonicida differentiates B cells to IgM-secreting plasmablasts. Splenocytes were incubated with inhibitors or left unstimulated as described in the legend of Fig. 1 cells were plated into ELISPOT plates previously coated with anti-trout IgM and incubated for a further 24 h cells were washed and a biotinylated anti-trout IgM used to detect number of spot forming cells Images from a representative fish are shown (a) together with a quantification of the number of IgM-secreting cells (mean + SD; n = 12) (b) Splenocytes pre-treated with the inhibitors salmonicida were also analysed by flow cytometry after 72 h of incubation with the bacteria IgM+ B cells were gated and the MFI of their forward scatter (FSC) Representative histograms are shown (c) along with a quantification of FSC MFI values in IgM+ B cells (mean + SD; n = 12) (d) splenocyte cultures were stimulated with A IgM+ B cells were isolated by flow cytometry RNA extracted and the levels of transcription of Blimp-1 and Pax5 determined by real time PCR as described in the Materials and Methods section Expression relative to the endogenous control EF-1α was calculated for each sample Asterisks denote significant differences between groups as indicated (*P ≤ 0.05; **P ≤ 0.01; ***P ≤ 0.005) salmonicida or an amount of LPS that corresponded to that same number of bacterial cells for 3 days at 20 ºC cells were labelled anti-trout IgM-APC and analysed by flow cytometry to estimate the percentage of IgM+ B cells (a) Representative dot plots are shown together with a quantification of average IgM+ B cells in cultures (mean + SD; n = 12) (b) At the same time the lymphoproliferative effect was measured after incubating the splenocytes with EdU for a further 24 h cells were labelled with anti-trout IgM-APC and number of proliferating cells determined as described in Materials and Methods Representative dot plots are shown (c) together with a quantification of proliferative IgM+ B cells (mean + SD; n = 9) (d) The expression of MHC II on the surface of IgM+ B cells was also measured after the incubation with A Representative plots and histogram are shown (e) together with a quantification of the mean intensity fluorescence of MHC II on the surface of IgM+ B cells (mean + SD; n = 12) (f) we thought of great interest to establish to what degree TLR signalling was contributing to the activation of B cells in this species an important rainbow trout pathogen that continues to cause mass mortalities in salmonid aquaculture worldwide To rule out any possible bacteria-mediated effects This might explain why most of the reversions of A salmonicida-induced activation of B cells were much stronger in the case of resveratrol than in response to the MyD88 inhibitor it should be noted that the precise effects of the two inhibitors used in this study in downstream TLR signalling has never been established in teleost fish due to a lack of specific reagents although the work presented in this paper represents sufficient evidence of how both inhibitors are capable of blocking inflammatory responses also in fish it might be possible that these inhibitors are not 100% efficacious in fish or that they have effects slightly different to those reported for mammalian cells the receptor that is mediating these effects in B cells is still unknown and is an issue that should be addressed in future studies only resveratrol and not the MyD88 inhibitor was capable of significantly reverting this effect Whether this is a consequence of surface MHC II expression up-regulation requiring the internalization of the bacteria or because this effect is mediated through a TRIF-dependent mechanism is still undetermined and deserves further investigation we found that the bacterial LPS on its own was capable of inducing higher levels of surface MHC II expression in IgM+ B cells than those observed in response to the intact bacteria these results suggests that an internalization of the bacteria is not required to induce surface MHC II expression it seems plausible to hypothesize that TLR engagement plays a quite prominent role in teleost B cells This hypothesis seems confirmed by the fact that the degree of reversion exerted by the TLR inhibitors on the effects provoked by A salmonicida on trout IgM+ B cells was quite high we have demonstrated that upon recognition of inactivated A rainbow trout IgM+ B cells increase in number increase surface MHC II expression and differentiate towards IgM-secreting cells the MyD88 inhibitor significantly reverted the increased IgM+ B cell survival and the up-regulated IgM secretion whereas resveratrol significantly reverted the higher surface MHC II levels and the increased IgM secretion These results highlight a large contribution of TLR signalling in the activation of B cells by the bacteria salmonicida LPS by itself has stronger effects on MHC II surface expression than the complete bacteria while having lower lymphoproliferative effects Understanding how fish B cells sense antigens is essential for the development of effective vaccines and adjuvants therefore our work will hopefully contribute to the design of a more effective A fish were maintained at the Animal Health Research Centre (CISA-INIA) laboratory at 16 ºC with a re-circulating water system and 12:12 h light:dark photoperiod Fish were fed twice a day with a commercial diet (Skretting fish were acclimatized to laboratory conditions for 2 weeks and during this period no clinical signs were ever observed The experiments described comply with the Guidelines of the European Union Council (2010/63/EU) for the use of laboratory animals and were previously approved by the Ethics committee from the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (INIA; Code CEEA PROEX002/17) Invitrogen) supplemented with 100 I.U./ml penicillin and 100 µg/ml streptomycin (P/S 10 units/ml heparin (Sigma) and 5% foetal calf serum (FCS Cell suspensions were placed onto 30/51% discontinuous Percoll (GE Healthcare) density gradients and centrifuged at 500 × g for 30 min at 4 ºC The interface cells were washed twice in L-15 with 2% FCS and cells were resuspended in L-15 with 5% FCS The viable cell concentration was determined by Trypan blue (Sigma-Aldrich) exclusion adjusting the concentration to 2 × 106 cells/ml salmonicida CECT4237 was aerobically grown in Tryptone Soya Broth (Oxoid) at 25 ˚C To stimulate the rainbow trout splenocytes salmonicida grown in broth overnight to exponential phase was heat-inactivated at 65 °C for 1 h salmonicida was used to stimulate the cells LPS was isolated using a commercial extraction kit (iNtRON Biotechnology) following the manufacturer’s protocol The absence of DNA and protein contamination was confirmed by SDS-PAGE and agarose electrophoresis A MyD88 inhibitor peptide was purchased from Novusbio and used at a concentration of 100 µM A control peptide was used as a control at the same concentration was diluted in DMSO and was used in cells at a final concentration of 50 µM the same volume of DMSO was added to cell cultures as a negative control Flow cytometry analysis was performed with FlowJo 10 (TreeStar) cells labelled with anti-trout IgM-APC (5 µg/ml) were washed with serum-free L-15 medium Laser scanning confocal microscopy images (0.3 μm thickness) were acquired with an inverted Zeiss Axiovert LSM 880 microscope Images were analysed with Zen 2.0 (Carl Zeiss) and Fiji (NIH) software packages splenocytes at a concentration of 2 × 106 cells per ml were incubated for 1 h with the different TLR inhibitors their controls or media alone as described above The cells were then stimulated with inactivated A salmonicida for 3 days at 20 ºC as described above or left unstimulated EdU (1 µM) was added to the cultures and the cells were incubated for an additional 24 h cells were collected and stained with anti-trout IgM-APC (0.5 μg/ml) cells were then fixed and permeabilised with Cytofix/Cytoperm buffer for 15 min at room temperature (RT) the incorporation of EdU to the DNA was detected following the manufacturer´s instructions and then analysed by flow cytometry on a FACS Celesta flow cytometer Splenocytes (2 × 106 cells/ml) were incubated with the different TLR inhibitors salmonicida as described above for 48 h at 20 ºC Cells (5 × 104 cells per well) were then transferred to ELISPOT plates pre-coated with anti-trout IgM (2 µg/ml) cells were washed away 5 times with PBS and plates were blocked with 2% BSA in PBS for 1 h at RT biotinylated anti-trout IgM was added to the plates and incubated at 1 µg/ml for 1 h at RT Following additional washing steps (5 times in PBS) the plates were developed using streptavidin-HRP at 100 ng/ml (Thermo Fischer Scientific) at RT for 1 h washed again with PBS and incubated with 3-amino 9-ethylcarbazole (Sigma-Aldrich) for 30 min at RT in the dark Substrate reaction was stopped by washing the plates with tap water the number of spots in each well was determined using an AID iSpot Reader System (Autoimmun Diagnostika GmbH) IgM+ B cells populations were isolated by flow cytometry in a BD FACSAria III cell sorter (BD Biosciences) after staining spleen leukocytes with anti-trout IgM-APC as described above using their FSC/SSC and fluorescence characteristics In this case 7-AAD (BD Biosciences) at 2.5 µg/ml was used to check the cell viability Each sample was measured in duplicate under the following conditions: 10 min at 95 ºC followed by 40 amplification cycles (15 s at 95 ºC and 1 min at 60 ºC) A melting curve for each primer set was obtained by reading fluorescence every degree between 60 ºC and 95 ºC to ensure only a single product had been amplified The expression of individual genes was normalized to the relative expression of trout housekeeping gene elongation factor 1α (EF-1α) and the expression levels were calculated using the 2-ΔCt method where ΔCt is determined by subtracting the EF-1α value from the target Ct No template negative controls and minus reverse transcriptase controls were included in all the experiments Statistical analyses were performed using the Graphpad prism version 6 (Graphpad software) All values were verified to be normally distributed one-way ANOVA followed by Tukey’s test as a post-hoc was performed The differences between the mean values were considered significant on different degrees Pattern recognition receptors in innate immunity TLR signaling in B-cell development and activation The role of pattern-recognition receptors in innate immunity: Update on Toll-like receptors Toll-like receptors–sentries in the B-cell response LPS stimulates IgM production in vivo without help from non-B cells Differential regulation of TLR4 expression in human B cells and monocytes A role for Toll-like receptors in acquired immunity: Up-regulation of TLR9 by BCR triggering in naive B cells and constitutive expression in memory B cells The establishment of early B cell tolerance in humans: Lessons from primary immunodeficiency diseases Toll-like receptor 7 controls the anti-retroviral germinal center response Selective utilization of Toll-like receptor and MyD88 signaling in B cells for enhancement of the antiviral germinal center response Toll-like receptor recognition of bacteria in fish: ligand specificity and signal pathways Ligand specificities of Toll-like receptors in fish: Indications from infection studies Transcriptional heterogeneity of IgM(+) cells in rainbow trout (Oncorhynchus mykiss) tissues Distinct differentiation programs triggered by IL-6 and LPS in teleost IgM(+) B cells in the absence of germinal centers Profiling Atlantic salmon B cell populations: CpG-mediated TLR-ligation enhances IgM secretion and modulates immune gene expression CpG oligodeoxynucleotides modulate innate and adaptive functions of IgM(+) B cells in rainbow trout Aeromonas salmonicida: Updates on an old acquaintance Resveratrol modulates phagocytosis of bacteria through an NF-kappaB-dependent gene program Blimp-1 orchestrates plasma cell differentiation by extinguishing the mature B cell gene expression program B cell-activating factor regulates different aspects of B cell functionality and is produced by a subset of splenic B cells in teleost fish Regulation of IgM(+) B cell activities by rainbow trout APRIL reveals specific effects of this cytokine in lower vertebrates TLR agonists selectively promote terminal plasma cell differentiation of B cell subsets specialized in thymus-independent responses Identification of the first teleost CD5 molecule: Additional evidence on phenotypical and functional similarities between fish IgM(+) B cells and mammalian B1 cells B lymphocytes from early vertebrates have potent phagocytic and microbicidal abilities Different IgM(+) B cell subpopulations residing within the peritoneal cavity of vaccinated rainbow trout are differently regulated by BAFF Control of B-cell responses by Toll-like receptors Adjuvant-enhanced antibody responses in the absence of toll-like receptor signaling Toll-like receptors and innate immunity in B-cell activation and antibody responses Phylogeny of lower vertebrates and their immunological structures Identification of teleost skin CD8alpha+ dendritic-like cells representing a potential common ancestor for mammalian cross-presenting dendritic cells Download references This work was supported by the European Research Council (ERC Consolidator Grant 2016 725061 TEMUBLYM) Innovation and Universities (project AGL2017-85494-C2-1-R) and by the Comunidad de Madrid (grant 2016-T1/BIO-1672) The authors want to acknowledge Lucía González and Diana Martín for technical support Patricia Díaz-Rosales & Carolina Tafalla that also interpreted the results with help from P.D.R The authors declare no competing interests Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-020-73999-w Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science The park that was once a centerpiece of Dallas' Little Mexico turns 100 this year Although it hardly resembles the cultural gathering place it once was Today the neighborhood around Pike Park is called Uptown still calls it “El Barrio,” or Little Mexico “Little Mexico to me was my town," Gonzales said Thousands of Mexicans moved to Dallas in the early 20th century. New homes and Mexican markets sprang up in what used to be the Polish-Jewish neighborhood. By 1920, El Barrio grew to more than 10,000 people. Even though Mexican kids had few places to play besides the dirt streets, they were allowed into what was then called Summit Park – but only at specific times Families would gather to hear Mexican singers who settled in Dallas, like Belen Ortega the city established rules for the joint use of Pike Park for whites and Mexican Americans That was when the Fiestas Patrias – celebrations of Cinco de Mayo and Mexican Independence Day – really took off Nellie Tafalla lived in the Little Mexico housing projects with her eight siblings for more than a decade a place for her to play baseball and softball “We had everything here available for my community here," Tafalla said Tafalla said she hardly recognizes the four-acre space today The main basketball court and swimming pool are gone This used to be a place to just sit and look at the city of Dallas “There’s no reason why it couldn’t be revived just to serve as a small little rec center," Tafalla said We’re growing so fast and we’re covering up the past so fast and we’re not preserving these little green spots.” Tafalla and Gonzales want to be able to show off the park “Because this park belongs not just to the history of the Mexican people and the Jewish," Gonzales said More: Watch the KERA TV documentary, Little Mexico: El Barrio Volume 12 - 2021 | https://doi.org/10.3389/fimmu.2021.778085 Type I Interferon Regulates the Survival and Functionality of B Cells in Rainbow Trout A Corrigendum onType I Interferon Regulates the Survival and Functionality of B Cells in Rainbow Trout By Benedicenti O, Wang T, Morel E, Secombes CJ, Soleto I, Díaz-Rosales P and Tafalla C (2020). Front. Immunol. 11:1494. doi: 10.3389/fimmu.2020.01494 In the original article, there was a mistake in Figure 1 as published. Although the numbers were correct, all dot plots in Figure 1A were the same. The corrected Figure 1 appears below Figure 1 Survival of blood IgM+IgD+ B cells in response to type I and type II IFNs 20 ng/ml rIFNg or media alone (control) and cultured at 20°C for 72 h Leukocytes were then labeled with specific monoclonal antibodies against trout IgM and IgD and analyzed by flow cytometry Cells were gated on the basis of their FSC and SSC and percentages of IgM+IgD+ cells determined on singlet and live (DAPI negative) cells Representative dot plots from one individual fish are shown (A) along with mean percentages and total number of cells detected for IgM+IgD+ B cells (B) and IgM−IgD− cells (C) (mean + SEM; n = 9) B cells were sorted from blood leukocytes using a biotinyilated Fab fragment of anti-IgM 1.14 and then incubated with the rIFNs as described above the percentage of live IgM+IgD+ B cells and the total number of live IgM+IgD+ B cells determined by flow cytometry as described in the Materials and Methods section (mean + SEM; n = 7) (D) Asterisks denote significant differences between samples treated with rIFNs and control samples (*P ≤ 0.05 The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Díaz-Rosales P and Tafalla C (2021) Corrigendum: Type I Interferon Regulates the Survival and Functionality of B Cells in Rainbow Trout Received: 16 September 2021; Accepted: 29 September 2021;Published: 18 October 2021 Copyright © 2021 Benedicenti, Wang, Morel, Secombes, Soleto, Díaz-Rosales and Tafalla. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: Carolina Tafalla, dGFmYWxsYUBpbmlhLmVz Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish All content on this site: Copyright © 2025 Elsevier B.V., its licensors, and contributors. All rights are reserved, including those for text and data mining, AI training, and similar technologies. For all open access content, the relevant licensing terms apply. Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish. Volume 11 - 2020 | https://doi.org/10.3389/fimmu.2020.01093 Proliferative kidney disease (PKD) caused by the myxozoan parasite Tetracapsuloides bryosalmonae is one of the most serious infectious diseases negatively impacting farmed and wild salmonids throughout Europe and North America PKD pathogenesis results in a massive B cell proliferation and dysregulation with aberrant immunoglobulin production and plasma cell differentiation along with a decrease in myeloid cells and inhibition of innate pathways Despite the huge immunopathological reaction in the kidney during infection fish can survive and return to full fitness Fish are unique in this ability to recover renal structure and functionality from extensive tissue damage in contrast to mammals only limited knowledge exists regarding the host immune response coinciding with PKD recovery almost no studies of the immune response during disease recovery exist in fish bryosalmonae system as an immunological model of disease recovery Our results demonstrated that recovery is preceded by an intense immune response at the transcript level and an increased degree of kidney inflammation the immune response transpired with a significant decrease in lymphocytes and an increase in myeloid cells These lymphocytes populations contained lower levels of B cells comparative to the control in the anterior and posterior kidney there was downregulation of several transcripts used as markers for plasma cells (blimp1 The decrease in these T cell transcripts significantly correlated with decreasing parasite intensity there was strong upregulation of pax-5 and igt mem This suggests a change in B cell processes during the recovery phase relative to clinical PKD may be necessary for the host to re-establish homeostasis in terms of an arrest in the dominant antibody like response transitioning to a transcriptional profile associated with resting B cells The knowledge generated here in combination with earlier studies illuminates the full power of analyzing the entire trajectory of disease from the normal healthy state to recovery enabling the measurement of an immune response to pinpoint a specific disease stage Whether a specific Ig response is mounted during the recovery phase is still unknown bryosalmonae parasite system as a model of disease recovery from a chronic immunopathology Our aims were to (1) identify when the host transitioned from the plateau of parasite burden to the parasite clearance phase (2) to temporally examine the histopathological and immune response in the anterior kidney and posterior kidney correlating with this alteration in disease stage we used a combination of FACS to identify leukocyte populations and subgroups and immune gene expression analysis of transcripts associated with different cellular lineages and functional pathways We investigated the immune response in both the anterior and posterior kidney Fish specimens and parasite exposure procedures are identical as those reported earlier (8) were sourced from a commercial hatchery in western Switzerland (L'Isle Fish were transported and acclimated for 2 weeks in the aquarium at the Centre for Fish and Wildlife Health and a control and infection group and a replicate of each were established Experiments used 130 l flow-through glass tanks supplied with tap-water (~1.l/m) constant aeration and artificial light (12 h light to 12 h dark) Freshwater bryozoa (Fredericella sultana), the invertebrate host of T. bryosalmonae, were collected from Swiss rivers known to be endemic for the parasite, transported to the FIWI and screened for infective parasite sacs by dissection of the bryozoan zooids under a binocular as per previous studies performed in our lab (8, 16, 19) bryozoan zooid tissue was disrupted by grinding and the homogenate was kept for 24 h in fresh tap water at room temperature DNA was isolated from the homogenate from two 100 ml replicate samples and qPCR was performed to confirm presence of the parasite DNA in the homogenate for infection Equal volumes of the parasite homogenate were then distributed to the infection replicates and after 1.5 h the flow through was restarted Procedures were performed simultaneously for controls without the addition of parasites bryosalmonae in infected fish was also confirmed by qPCR in the posterior kidney as fish at week 20 P.E had for the majority cleared the parasite we did not investigate the immune response in these fish as there was only a limited number of fish to analyze per parameter fish were euthanized by immersion into a solution of MS-222 (100 μg/l buffered 3-aminobenzoic acid ethyl ester (MS 222® the entire kidney was removed and sectioned into anterior kidney (AK- the kidney tissue located cranially) and posterior kidney (PK- the kidney tissue located past the narrow site below the neck until the caudal end) The PK weight was used to calculate the PK somatic index [PKSI = posterior kidney weights (g)/body weights (g) ×100] The AK and PK were sampled for all molecular and FACS procedures while only the PK was used for histology/immunohistochemistry procedures A DNA sample was taken from the PK of all fish to determine infection intensity The extracted tissues for DNA/RNA isolation were placed on RNase and DNase free Petri dishes and sliced using scapula and forceps into smaller pieces before being transferred to RNAlater (Qiagen Switzerland) on ice for 24 h before storage at −20°C until use FACS was carried out on the day of sampling Histology samples were fixed in Histochoice (Amresco Switzerland) for 3 h at room temperature (RT) and subsequently transferred to graded ethanol (EtOH) (≥99.8–70%) All procedures were carried out according to the Swiss legislation for animal experimentation guidelines and approval for animal experiments was obtained from the cantonal veterinary office (Bern Switzerland) (Authorization number BE60/14) DNA extracted from control fish was analyzed at every time point which always tested negative for T bryosalmonae in addition to non-target controls (water) within the qPCR that never showed any amplification Following routine processing and paraffin embedding PK sections of 3–5 μm thickness were prepared on SuperFrost® Plus positively charged glass slides After deparaffinization in Histo-Clear (Agar Scientific Ltd UK) and rehydration in a graded series EtOH concentrations (≥99.8–50%) the slides were stained with H&E (hematoxylin and eosin) for routine histology Preparation of AK and PK leukocytes was carried out as described earlier (8) the AK and PK was removed from fish and put through a 250 μm mesh filter with Leibovitz's (L-15) medium (Thermofisher Cell suspensions were then layered onto an isotonic Ficoll gradient (Biochrom AG Germany) (r = 1.077 g/ml) and spun at 1,300 RPM for 40 min at 4°C Cells at the Ficoll/medium interphase were then collected washed in L-15 medium and resuspended in 1 ml of medium Red blood cells were then lysed using 9 ml cold distilled water and the cell suspension centrifuged at 1,300 RPM for 1 min at 4°C Cells were then resuspended in 1 ml L-15 medium supplemented 5% FBS (fetal bovine serum) and kept on ice Approximately 25 mg of tissue was used for RNA extraction RNA was extracted from the AK and PK using a Direct-zol™ RNA MiniPrep w/TRI-Reagent® kit following the manufacturer's instructions (Zymo Potential traces of genomic DNA contamination were removed with an on column DNAse treatment provided by the kit manufacturers cDNA was synthesized using The GoScript™ Reverse Transcription System following the manufacturer's instructions (Promega The total volume of the cDNA syntheses was 20 μl which was diluted 1:10 with Nuclease-Free water (Promega USA) and stored at −20°C until analysis No template negative controls and minus reverse transcriptase controls were included in all assays The differences between the control and infection group at each time point in the AK and PK were tested for significant differences using the two-tailed Student t-test The differences between infected fish sampled at the different time points were tested for using a one-way ANOVA and significant differences revealed with the Dunnett's post-hoc test Data failing normality tests and displaying heterogeneity of variance were tested statistically applying the non-parametric Kruskal–Wallis ANOVA on ranks and Dunn's non-parametric multiple comparison tests to reveal differences Gene expression data was tested statistically at the ΔCt stage before the log transformation and immune gene expression (using log transformed data) were assessed by calculating the Pearson correlation coefficient (r) in the T Data were statistically evaluated with SigmaPlot 12.0 (Systat Software CA) and graphically presented with GraphPad Prism 5 (GraphPad Software Significance was set at p ≤ 0.05 and p-values below < 0.005 and < 0.001 were indicated as such in the data presentation At week 8 P.E, T. bryosalmonae intensity in the PK began declining in comparison to week 7 P.E. which was the plateau of parasite intensity when the parasite had appeared to reach its maximum burden within the fish host (Figure 1A) tested after week 7 P.E there was a decline in parasite intensity in contrast to this week P.E Although we did not include week 7 P.E in the immune gene analysis reported here we included the parasite intensity data and also cellular data in this manuscript for the reader to understand our experimental design focusing our study from the start of parasite clearing (week 8 P.E) At week 14 and 20 P.E there were significant decreases in parasite intensity relative to week 7 and week 8 P.E (A) Declining parasite intensity (Arithmetic Mean ± SE) and (B) infection prevalence (mean percentage of infected fish sampled per time point) during recovery in Tetracapsuloides bryosalmonae infected rainbow trout starting at peak of parasite burden [week 7 P.E (post-exposure)] Parasite intensity was expressed as 18S rRNA gene copies of Tetracapsuloides bryosalmonae in rainbow trout posterior kidney sampled at week P.E Numbers above time points in (A) indicate at which week P.E the time point was significantly decreased in comparison to (week 7 P.E) (ANOVA) Number of asterisks indicates level of significance (*p < 0.05 and ***p < 0.001) relative to infected fish sampled at the specific time point N = 12 per time point unless fish were uninfected in which there was no burden i.e. Presence of the parasite was no longer detectable in some fish and subsequent reduction in infection prevalence occurred (mean percent of infected fish sampled per time point). Initially all rainbow trout sampled at week 8 P.E, and week 10 P.E tested positive for T. bryosalmonae infection (12/12 fish sampled) as per earlier time points (Figure 1B) at week 14 P.E the first fish tested negative for presence of the parasite while at week 20 P.E infection prevalence had declined to <50% (5/12 fish sampled) It must also be noted that this prevalence at late time points might be even lower as it could be possible fish with low parasite loads have in fact no viable parasites and that our qPCR method is in fact detecting dead or decayed T it is not possible for us to distinguish between live and dead parasites Collectively histological changes in infected fish showed a steady regression in parasite presence and tissue proliferation becoming displaced with fibrosis tissue, tubuloneogenesis and re-emergence of melanomacrophage centres. However, these changes were often patchy in form occurring in gradients throughout the sections and not systemic, increasing slowly over time starting at week 8 P.E (Figure 2) fish at week 8 and 10 P.E still had histology consistent with advanced PKD and large areas were observed with a complete deterioration of renal tubules While even at week 14 P.E on occasion the presence of parasites was visible although sometimes these were degenerative in form characterized by hypereosinophilia and fragmentation of parasite cells and nuclei Chronicling of rainbow trout recovery from T bryosalmonae infection in the posterior kidney (A–H) (A,B) Posterior kidney section of healthy uninfected fish showing intact tubules and abundant melanomacrophages (C,D) Infected fish at week 8 P.E with strong tissue proliferation deposits of fibrosis tissue and scattered parasites (E,F) Infected fish sampled at week 10 P.E exhibiting increased signs of tissue recovery including tubuloneogenesis and infrequent patches of melanomacrophage there is still some presence of parasites but this is greatly reduced compared to (C,D) (G,H) Infected fish sampled at week 14 P.E showing advanced regeneration and resolution of tubules and abundant melanomacrophages in tissue but not yet completely similar to healthy uninfected fish in (A,B) H&E stain; bars 50 μm (A,C,E,G) and 25 μm (B,D,F,H) The PKSI of infected fish was significantly greater at every time point in comparison to the control although there were no significant differences when comparing infected fish at different time points (Figure 3) and 14 P.E the PKSI even increased relative to week 7 P.E as the parasite burden was declining indicating an increase in inflammation before beginning to decrease slightly at week 14 after week 10 P.E The increase in PKSI was possibly a by-product of the initial alteration in tissue composition caused by the onset of fibrosis as observed from the histology Posterior kidney somatic index of Tetracapsuloides bryosalmonae infected rainbow trout and unexposed control fish (Scatter dot plots with Median ± SE at week post exposure) (P.E) Letter above data plots indicate significant increase to controls (A) the number of asterisks indicates level of significance (*p < 0.05 and ***p < 0.001) and 14 P.E there was a significantly greater number of lymphocytes relative to the control But at weeks 10 and 14 P.E there was a significant decrease in lymphocytes in comparison to infected fish at weeks 7 and 8 P.E In the PK there were also a significantly greater number of lymphocytes at each time point (week 7 between the infected fish there was a significant decrease in lymphocytes over time (week 8 FACS analysis of AK (anterior kidney) and PK (posterior kidney) leukocytes in T Representative FSC (size) and SSC (granularity) dot plots showing the gating strategy in the AK of uninfected (A) or infected (B) fish and in the PK of uninfected (D) and infected (E) fish at week 14 P.E Bar charts showing percent of leukocytes in infected fish in the AK (C) and PK (F) of 104 gated events (Arithmetic Mean ± SE) Letters above data plots indicate significant increase to controls (A) or significant decrease to the controls (B) (t-test) The number of asterisks indicates level of significance (*p < 0.05 Numbers above time points in which values were significantly increased in comparison to infected fish from other time points (ANOVA) Regarding the assessment of myeloid cells in the AK and PK at every time point there were significantly less myeloid cells found in these tissues in infected fish (at weeks 7 the population of myeloid cells in both the AK and PK significantly increased over time in the infection groups as at week 10 and 14 P.E there were significant increases relative to week 7 and 8 P.E and 14 P.E there was a massive decline in the B cells levels of infected fish in comparison to uninfected fish and to infected fish sampled at week 7 P.E While concerning CD8α+ T cells detected using FACS there was a significantly lower amount of these cells detected in the AK at week 10 P.E in comparison to the control but there were no significant differences between the infected fish in either the AK or PK at any time points (data not shown) FACS analysis of rainbow trout AK (anterior kidney) and PK (posterior kidney) leukocytes using monoclonal antibodies staining B cells in Tetracapsuloides bryosalmonae infected rainbow trout Representative dot plots of isotypes in the AK (A) and PK (E) and the levels of B cells measured in the AK of uninfected fish (B) and in the AK of infected fish (C) and in the PK of uninfected fish (F) and in the PK of infected fish (G) all at week 14 P.E Bar charts showing percent of B cells as percentage of control in infected fish at week post exposure (P.E) (Arithmetic Mean ± SE) in the AK (D) and PK (H) The number of asterisks indicates level of significance (*P < 0.05 and ***P < 0.001) Numbers above time points indicate which time point was significantly increased in comparison to in infected fish (ANOVA) —mcsf [fold change (fc): 61.42] and mcsf-r (fc: 12.40) were significantly upregulated in the AK relative to the control as well in comparison to infected fish at week 10 and 14 P.E mcsf was significantly upregulated in the PK at week 8 P.E in comparison to the control at week 10 and 14 P.E there was a drastic shift in the expression profiles of these transcripts in the AK as mcsf and mcsf-r were (fc: 0.14 and 0.16 respectively) significantly downregulated relative to the control mcsf was strongly downregulated at these time points in the PK as was mcsf-r at week 10 P.E relative to their respective controls Such intense fluctuations did not occur in the expression level of il-1β as there was only a small significant decrease in the mRNA levels of this gene at 10 P.E relative to the control in the AK whereas there were no significant differences concerning other time points in the AK or in the regulation of this gene in PK Regulation of innate immune gene transcripts Relative fold change of (A) mcsf ; (B) mcsf-r; and (C) il-1β; measured in the AK and PK of T bryosalmonae infected fish at different weeks post exposure (P.E) (Arithmetic Mean ± SE) Relative fold change was normalized to rainbow trout reference gene ef-1α and subsequently expressed as fold change relative to expression levels of control fish Asterisks indicate differences relative to the control (t-test) Numbers above time points indicate which time point was significantly increased in comparison to other infected time points (ANOVA) In the present study we composed a panel of B cell markers consisting of the secreted and membrane forms of the three fish Igs (igm sec, igd sec, igt sec, igm mem, igd mem, igt mem) and of blimp1, cd38, baff, and pax-5 (Figure 7) the mRNA levels of these B cell markers decreased over time as parasite intensity reduced in infective fish at week 8 P.E regarding blimp1 in the AK of infected fish the mRNA levels of this gene were strongly significantly elevated (fc: 2078.4) relative to the control and in infected fish sampled at week 10 and 14 P.E While blimp1 was still significantly upregulated in the AK at week 10 P.E expression levels were severely decreased (fc: 12.6) before becoming downregulated at week 14 P.E The same expression pattern was followed in the PK for blimp1 declining temporally from week 8 P.E (fc: 177.4) to week 14 P.E (fc: 0.2) in which the gene was significantly downregulated in comparison to the control Relative fold change of (A) blimp-1; (B) igt sec; (C) igt mem; (D) igm sec; (E) igm mem; (F) igd sec; (G) igd mem; (H) cd38; (I) baff; and (J) pax-5 measured in the anterior and posterior kidney of T bryosalmonae infected fish at week post exposure (P.E) (Arithmetic Mean ± SE) Asterisk indicates differences relative to the control (t-test) Number of asterisks indicates level of significant (*p < 0.05 Numbers above time points indicate which time point was significantly increased in comparison to (ANOVA) Concerning the genes measured encoding for the different fish Igs; igt sec was significantly upregulated in the AK and PK at week 8 P.E relative to the control at week 10 and 14 P.E in the AK the mRNA levels of igt sec decreased significantly in contrast to the control and to infected fish sampled at 8 weeks P.E Regarding igt mem the expression of this transcript was significantly stronger expressed at week 8 P.E in both the AK and PK relative to the control fish and infected fish sampled at week 14 P.E in both organs in the PK this transcript was significantly upregulated at week 10 P.E in comparison to the control and T bryosalmonae infected fish sampled at week 14 P.E It must also be stated here that despite mRNA levels decreasing somewhat over time this was the only Ig transcript membrane bound or secreted that remained moderately upregulated in both tissues even at week 14 P.E igm sec was significantly upregulated in AK at week 8 P.E but significantly downregulated at week 10 and 14 P.E and also at week 14 P.E in the PK relative to the control igm mem was significantly elevated in AK at week 8 P.E but downregulated at week 14 P.E in the AK and PK relative to the control the expression levels of igm mem were significantly downregulated in the AK and PK in infected fish at week 10 and 14 P.E in comparison to infected fish at week 8 P.E the expression level of this gene was significantly upregulated in the AK at week 8 P.E and strongly significantly elevated at week 8 P.E in the PK before becoming downregulated in both the AK and PK at week 10 and 14 P.E While igd mem transcripts were significantly elevated in the AK at week 8 P.E in contrast to the respective control and to infected fish sampled at week 10 and 14 P.E Additionally, included in the panel of B cell markers was cd38, which in mammals is suggested to be consistently expressed on terminally differentiated plasma cells (26) At week 8 P.E there were significantly greater mRNA levels of this gene measured in the AK and PK of infected fish in comparison to infected fish sampled at week 10 and 14 P.E the mRNA levels of cd38 significantly declined in the AK and PK of infected fish at week 10 and 14 P.E with the transcript being downregulated in comparison to the control Regarding the expression levels of baff the B cell activation factor in the AK and PK the expression levels of this gene also declined drastically temporally this gene was significantly upregulated in the AK at week 8 P.E in comparison to uninfected control fish and infected fish sampled at week 10 and 14 P.E There were no significant differences concerning the expression of this gene in the PK Additionally, we measured pax-5, which in humans encodes the B cell lineage specific activator protein (Bsap) that is suggested to be expressed at early, but not late stages of B cell differentiation (27) The expression of this gene in infected fish was significantly stronger expressed in the AK at week 8 P.E (fc: 128.4) in relation to the uninfected control fish and to infected fish sampled at week 10 and 14 P.E pax-5 still remained upregulated at week 14 P.E in both organs and it was one of the only genes (along with il-10) to be significantly upregulated at week 14 P.E in both the AK and PK in contrast to the controls The regulation of T cell signature molecules (cd4, cd8α, cd8β, and tcrβ) were evaluated (Figure 8). Preceding PKD pathogenesis transcriptional studies have thus far only indicated a moderate involvement of these generalist T cell genes in contrast to B cell transcripts (8, 10) while cd4 was significantly upregulated in the AK at week 8 P.E the mRNA levels of cd4 eventually decreased at week 10 and 14 P.E as the transcript became significantly downregulated relative to the control in both the AK and PK While cd8α was only moderately expressed or downregulated in both organs throughout the study with expression levels being significantly downregulated at week 10 P.E in comparison to the control The expression signatures of cd8β and tcrβ followed a similar pattern with cd8β expression being significantly greater in the AK and PK of infected fish at week 8 vs 10 and 14 P.E and tcrβ expression levels being upregulated in the AK at week 8 in comparison to the control and infected fish at week 14 P.E prior to a significant decline in both of these transcripts cd8β became significantly downregulated in the AK and PK at week 10 and 14 P.E vs control and tcrβ in the AK at the same time and at week 10 P.E in the PK vs Relative fold change of (A) cd4; (B) cd8α; (C) cd8β; and (D) tcrβ measured in the anterior and posterior kidney of Tetracapsuloides bryosalmonae infected fish at week post exposure (P.E) (Arithmetic Mean ± SE) il-10 is an immunoregulatory cytokine that has been shown to be hyper upregulated in earlier transcriptional studies during PKD pathogenesis (8, 10, 28). In the present study, the mRNA levels of il-10 were also very strongly expressed. As a case in point, in the AK at week 8 P.E (fc: 865.7) and PK (fc: 77.4) at week 8 P.E (Figure 9) The mRNA levels measured at this time point in the AK and PK as well as at week 10 P.E were significantly higher than the controls and to infected fish sampled at week 14 P.E the gene was significantly upregulated at week 14 P.E in the PK relative to the control fish sampled at this time point Regulation of immunoregulatory checkpoint molecules and master transcription factors Relative fold change of (A) il-10; (B) cd137; (C) foxp3a; (D) t-bet; and (E) gata3 measured in the anterior and posterior kidney of T Asterisk indicates differences relative to the control (t-Test) Furthermore, we evaluated the expression of cd137 a reported co-stimulatory immune checkpoint molecule. Accordingly, CD137 modulates not only the activation state of T cells but activation, proliferation, survival, apoptosis, and differentiation of many immune and non-immune cells and the course of immune response (29) (Figure 9) The transcription levels of this gene were significantly upregulated in AK at week 8 P.E relative to the controls and in comparison to infected fish sampled at week 14 P.E while the gene was moderately upregulated in PK and at week 8 and 10 P.E The mRNA levels of cd137 decreased at week 14 P.E in both organs becoming significantly downregulated in the AK and PK in comparison to the control We also assessed foxp3a transcription, this gene functions as a master transcription factor of the regulatory pathway in the development and function of regulatory T cells which are suggested to generally turn the immune response down (30). foxp3a was strongly expressed at week 8 P.E in the AK before becoming downregulated (week 10 P.E) and moderately expressed (week 14 P.E) (Figure 9) in contrast to most of the mRNA data generated in this study the levels of foxp3a did not strongly fluctuate and were somewhat comparable (upregulated at week 8 fc: 21.7 During PKD pathogenesis an imbalanced Th-1 and Th-2 like profile has been described (8, 10). To see if recovery correlated with a skewing to either of these phenotypes, we examined the master transcription factors of each of these functional pathways t-bet (Th-1 like) and gata3 (Th-2 like) (Figure 9) t-bet was significantly elevated at week 8 P.E in the AK in comparison to the controls and relative to infected fish sampled at week 10 and 14 P.E before becoming significantly downregulated at week 10 P.E in the same organ in comparison to the controls While in the PK this molecule was significantly elevated at week 8 P.E in comparison to infected fish sampled at week 14 P.E and in the same organ significantly downregulated relative to the controls at week 10 P.E the Th-2-like master transcription factor was significantly upregulated at week 8 P.E in AK relative to the controls and infected fish at week 10 and 14 P.E One transcript in the AK (pax-5) and nine (mcsf , mcsf-r, igd sec, cd38, cd4, cd8α, cd8β, tcrβ, and foxp3a) in the PK had a significant positive correlation with parasite intensity, indicating that the expression of these genes significantly decreased with the decline of the parasite burden (Table 1) All the T cell signature molecules we measured correlated in the PK positively with parasite intensity no genes investigated in this study were positively correlated with PKSI An explanation for this is that the parasite intensity significantly decreased when comparing burdens at different post exposure time points but the PKSI only had significant differences relative to the control and not between infected fish sampled at different time points Summary of significant correlations between parasite intensity and immune gene expression in the anterior and posterior kidney of Tetracapsuloides bryosalmonae infected rainbow trout assessed by calculating the Pearson correlation coefficient (r) both temporally and correlating with parasite clearance had not yet been fully elucidated in rainbow trout Our results demonstrated that recovery from PKD in young-of-the-year rainbow trout is preceded by an initial intense immune response in both the anterior and posterior kidney at least on the transcript level but an increased degree of kidney inflammation involved in tissue regeneration This expression profile indicated a change in B cell processes during recovery in terms of an arrest in the strong antibody response transitioning to a profile associated with resting B cells Taking the above into account and given the pax-5 expression profile observed here it might be possible to say that this transcript plays a role in restoring B cell homeostasis through reestablishing lineage identity after aberrant plasma cell production the decrease in expression patterns associated with plasma cells and decline of B cells when the parasite burden was decreasing could function in two dimensions: (1) to provide space for new naïve B cells and/or (2) in terms of immunological investment be unnecessary after removal or deterioration of the parasite Still further research during PKD pathogenesis is needed concerning the role of T cells particularly at the functional level that goes beyond what we reported on here and in previous studies the expression of mcsf occurred when almost every measured gene was upregulated before the molecule was downregulated at week 10 P.E at which time many transcripts were also downregulated thus the regulation of this gene may be more indicative of a global transcriptional shift in immune response linked to the parasite despite strong upregulation of mcsf no change in myeloid cells occurred in the AK at week 8 P.E the biological consequences of this mRNA elevation or the mRNA levels of myeloid associated markers at any time point is difficult to disentangle from our data and does not directly correlate with pattern seen in levels of myeloid cells A possible reason being the choice of genes measured bryosalmonae infected fish but did report on the regulation of many genes involved in tissue resolution and apoptosis While gaps still exist concerning the full trajectory in the immune response of rainbow trout infected with T bryosalmonae particularly those which occur immediately after the host encounters the parasite The knowledge generated here can be used to pinpoint if a fish is in recovery this could be particularly important for studying an infected population in which no information is known about the initial infection timing or for investigating the impact of immunotherapies on the disease trajectory Especially as tissue inflammation remains for a long period even after parasite clearance its usefulness as a proxy of recovery is not always informative enough compared to knowledge generated at the protein or cellular level our approach of focusing on disease recovery as an alternative to disease development illuminate's novel information on the pathways that contribute to the re-establishment of host homeostasis after chronic infection by a myxozoan parasite Future studies could also consider comparing these recovery processes to that in brown trout which is not a dead-end host of the parasite The raw datasets supporting the conclusions of this article will be made available by the authors on request The animal study was reviewed and approved by Cantonal veterinary office (Bern analyzed the data under the supervision of CT CB and CT wrote the main body of the manuscript CB was funded by SNF Post Doc Mobility Fellowship number P400PB_183824 the work was partially supported by the European Commission under the Horizon H2020 Research and Innovation Programme (Grant H2020-634429 ParaFishControl) The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest The authors wish to thank Maricruz Guevara for her support collecting the samples used in the experiments we thank Bernd Köllner and Uwe Fischer for kindly providing the antibodies used in this 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Christyn Bailey, Y2hyaXN0eW4uYmFpbGV5QG91dGxvb2suY29t the inhabitants of Tafalla will receive a special welcome Every year people will take the main square The programme has announced a wide range of initiatives the organizers have added another slogan to the slogan “No sexist attacks!” Many generations gather in front of the square of the Casa del Pueblo and the organizers want to transmit the cry to all the people said during the presentation of the Day: “Most of the resources for the promotion of culture and language have been obtained by us We tend to be institutional watchers to get to know them and build projects In order to prevent the clamor from falling into the empty slogan the organizers want to promote the molds of avoiding sexist attacks throughout the year on the occasion of this holiday they want to launch a series of concrete initiatives the Baigorrians “want to help bring this sorrowful subject out of the shadows.” the Baigorrians try to show that they “take pleasure in this work”: “We’re working on that mission.” The social movements promoted in the last months have given the main motto a sense of breeze in the town of Ortzaize in the same region a debate was held to reflect on the involvement of civil society with the aim of giving meaning to the part of “building the people” of the whole motto Begoña Island (Welcome refugees) and Dominique Amestoy (ELB-Lurzaindia) took part in the round table In Ebiakoitza – on Saturday, the artists of the region will meet in the church of Baigor at 21:00. Several musicians want to put an end to the initiative launched during the Sinfo Niko evening in the last two years The classical repertoire will be accompanied by the symphony orchestra in the program there are offers of all tastes A variety of musical styles will be heard in Baigorri which has a special place for the citizens of the city that is related to Baigorri on Navarre Day Death of 55-year-old attacked in Onda is first such fatality since events resumed after Covid hiatus A man has died after he was gored at a bull-running festival in eastern Spain the first such fatality in the country since events resumed after Covid-19 curbs were relaxed during the summer was repeatedly attacked by a bull at a festival in Onda Other participants tried to entice the animal away but their efforts failed A wound to the man’s left thigh perforated an artery and he died in hospital in the nearby town of Villarreal Onda council cancelled all further bull running planned at the festival A public debate over whether bull-running festivals should be abolished has become more heated in recent years and only a small number have taken place since Covid restrictions were lifted The animals let loose for the runs are generally used in bullfights later the same day found 46% of Spaniards were in favour of banning bullfighting 34% were not in favour but did not back a legal ban Associated Press Writer MADRID (AP) – A bull leapt into the packed grandstands of a Spanish bullring and … Home / News MADRID (AP) - A bull leapt into the packed grandstands of a Spanish bullring and ran amok charging and trampling spectators and leaving 40 people injured Video showed the bull jumping several meters (yards) high out of the ring clearing two barriers before landing in the stands and raising a panic as he lurched through the screaming crowd The 500-kilogram (1,100-pound) animal was brought under control by experienced bull handlers after several minutes and later killed The incident occurred Wednesday at the Tafalla arena in the northern region of Navarra during an event attended by about 3,500 spectators in which mostly young people try to get a bull to charge at them so they can dodge it The bull had already attempted to jump into the stands twice he was about to be returned to the corral and replaced with another bull when he tried a third time and succeeded The regional government said in a statement Thursday that three people remained in hospitals in the regional capital of Pamplona best known for its annual San Fermin running of the bulls festival The injured included a 10-year-old boy who was in intensive care after the bull reportedly fell on him Another man was gored in the back and was said to be in stable condition "What could have been a tragedy ended up as a big fright," Tafalla mayor Cristina Sota was cited as saying in the main regional newspaper told the paper: "The bull caught me and hurled me against the (concrete) seating Also lightly injured was 16-year-old Eneko Goyena Sesma "I was with my friends when the bull jumped over and everyone began to run Somebody must have pushed me and I fell to the ground The regional government said the crowd was made up largely of young people and most were able to get away from the bull quickly The Gazette has been informing Iowans with in-depth local news coverage and insightful analysis for over 140 years independent journalism with a subscription today © 2025 The Gazette | All Rights Reserved Igor Vinokurov is the new president of the Torrevieja Tennis Club after Antonio Tafalla decided not to stand for re-election Igor Vinokurov moves up from Board of Directors on which he has served for a number of years and runs a successful business on the Costa Blanca Antonio Tafalla has decided to step down after sixteen years in various committee positions at the Torrevieja Club During his period at the helm he has taken the Club to the highest competitive levels as well as overseeing the renovation and modernisation renovating the restaurant and embellishing its main entrances Log in to leave a comment © 2021 The Leader Digital {{gallery.imageDetails.images.0.description}} Three teenage boys were surrendered to the police by their respective families after they allegedly stabbed and killed their two schoolmates following an altercation in a school comfort room in Las Piñas City on Friday identified the victims as alias “Rye Enzo,” 15 and a Grade 10 student – will be turned over to Bahay Pag-asa in Las Piñas City Tafalla said the victims were walking outside the school when they were attacked at 7:00 p.m He said Enzo suffered a lone stab wound in the left side of the neck and died while undergoing treatment at the Las Piñas Doctors Hospital while Joshua was pronounced dead on arrival at the Las Piñas General Hospital one of the victims and the 15-year-old Grade 9 student engaged in an argument inside the school comfort room A witness told police that one of the victims reportedly played with the lights in the comfort room by turning them off and on The police said the victims were on their way home when attacked by the three suspects Tafalla said the suspects will be charged with homicide or murder depending on the outcome of the investigation © 2025 JNews - 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