The local skin cellular immune response determines the clinical outcome of sarcoptic mange in Iberian ibex (Capra pyrenaica)

Sarcoptic mange, caused by Sarcoptes scabiei, is a disease with implications for wildlife conservation and management. Its severity depends on the host's local skin immune response, which is largely unknown in Iberian ibex (Capra pyrenaica), a mountain ungulate dramatically affected by mange. In this species, the clinical outcome of sarcoptic mange varies among individuals, and the local immune response could be key to controlling the infestation. This study aims to characterize the local cellular immune response and its relationship with the clinical outcome. Fourteen Iberian ibexes were experimentally infested with S. scabiei and six more served as controls. Clinical signs were monitored, and skin biopsies were collected from the withers at 26, 46, and 103 days post-infection (dpi). The presence and distribution of macrophages (including M1 and M2 phenotypes), T lymphocytes, B lymphocytes, plasma cells, and interleukine 10 were quantitatively evaluated using immunohistochemical techniques. An inflammatory infiltrate that decreased significantly from 26 to 103 dpi was observed in all the infested ibexes. The predominant inflammatory cell population in the skin of the mangy ibexes was formed by macrophages (mainly the M2 phenotype) followed by T lymphocytes, with lower numbers of B lymphocytes and plasma cells. Three clinical courses were identified: total recovery, partial recovery, and terminal stage. The inflammatory infiltrates were less pronounced in the fully recovered ibexes than in those that progressed to the terminal stage throughout the study. The results suggest an exacerbated but effective Th1-type cellular immune response controlling mange in Iberian ibex. Furthermore, the local immune response appears to determine the variability of the clinical responses to S. scabiei infestation in this species. This first report on the progression of local skin immune cells is relevant not only for individuals but also for population management and conservation

Ivermectin Plasma Concentration in Iberian Ibex (Capra pyrenaica) Following Oral Administration: A Pilot Study

Copyright © 2022 Moroni, Granados Torres, López-Olvera, Espinosa Cerrato, Ráez Bravo, Mentaberre, Fandos, Pazzi, Romagnoli, Gardini, Rossi, Valldeperes, Serrano, Ramos and Odore. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, 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. No use, distribution or reproduction is permitted which does not comply with these terms.[EN] Sarcoptic mange is considered the main driver of demographic declines occurred in the last decades in Iberian ibex (Capra pyrenaica) populations. Mass treatment campaigns by administration of in-feed acaricides are used as a measure to mitigate the impact of mange in the affected populations. However, there are no data on ivermectin (IVM) pharmacokinetics in this wild caprine, and the treatment through medicated feed is not endorsed by evidence on its effectiveness. The aim of this study is to determine the pharmacokinetic profile of IVM in plasma samples of ibexes after the experimental oral administration of IVM, using high performance liquid chromatography (HPLC) with automated solid phase extraction and fluorescence detection. A dose of 500 μg of IVM per body weight was orally administered in a feed bolus to nine healthy adult ibexes (seven males and two females). Blood samples were collected by jugular venipuncture into heparin-coated tubes at day 1, 2, 3, 4, 7, 10, 15, and 45 post-administration (dpa). The highest plasma concentration of IVM (Cmax = 3.4 ng/ml) was detected 24 h after the oral administration (T1), followed by a rapid decrease during the first week post-administration. Our results reveal that plasma IVM concentration drops drastically within 5 days of ingestion, questioning the effectiveness of a single in-feed dose of this drug to control sarcoptic mange. To the best of our knowledge, this is the first study on plasma availability of oral IVM in ibexes and in any wild ungulate species.SIThis project was funded by the Consejería de Medio Ambiente de la Junta de Andalucía (project 173/2009/M/00; 03/15/M/00; 861_11_M_00 and 2016/00014/M), and by the Spanish Ministerio de Economía y Competitividad (projects CGL2012-40043-C02-01, CGL2012-40043-C02- 02, and CGL2016-80543-P). The authors’ research activities are partially supported by the Plan Andaluz de Investigación (RNM118 group). MV is supported by a FI-GENCAT Fellowship (2020_FI_B2_00049, co-financiated by Agència de Gestió d’Ajuts Universitaris i de Recerca and European Social Fund) and ES by the Spanish Ministerio de Ciencia Innovación y Universidades (MICINN) through a Ramon y Cajal agreement (RYC-2016-21120). GM is a Serra Húnter Fellow.We are grateful to all the people involved in the experiment. Special thanks goes also to the park wardens and fieldworkers in the SNNS and, in particular, to José López, Isidro Puga, Apolo Sánchez, and Antonio Rodríguez for their professional and personal involvement in the study

Diseases of Iberian ibex (Capra pyrenaica)

Iberian ibex (Capra pyrenaica) is an ecologically and economically relevant medium-sized emblematic mountain ungulate. Diseases participate in the population dynamics of the species as a regulating agent, but can also threaten the conservation and viability of vulnerable population units. Moreover, Iberian ibex can also be a carrier or even a reservoir of pathogens shared with domestic animals and/or humans, being therefore a concern for livestock and public health. The objective of this review is to compile the currently available knowledge on (1) diseases of Iberian ibex, presented according to their relevance on the health and demography of free-ranging populations; (2) diseases subjected to heath surveillance plans; (3) other diseases reported in the species; and (4) diseases with particular relevance in captive Iberian ibex populations. The systematic review of all the information on diseases affecting the species unveils unpublished reports, scientific communications in meetings, and scientific articles, allowing the first comprehensive compilation of Iberian ibex diseases. This review identifies the gaps in knowledge regarding pathogenesis, immune response, diagnostic methods, treatment, and management of diseases in Iberian ibex, providing a base for future research. Moreover, this challenges wildlife and livestock disease and wildlife population managers to assess the priorities and policies currently implemented in Iberian ibex health surveillance and monitoring and disease management

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Wildlife-Livestock Host Community Maintains Simultaneous Epidemiologic Cycles of Mycoplasma conjunctivae in a Mountain Ecosystem

Altres ajuts: Plan Andaluz de Investigación RNM-118Infectious keratoconjunctivitis is an eye disease caused by Mycoplasma conjunctivae that affects domestic and wild caprines, including Iberian ibex (Capra pyrenaica) and domestic sheep and goats. This study assessed M. conjunctivae in the host community of the Natural Space of Sierra Nevada (NSSN), a mountain habitat in southern Spain. Mycoplasma conjunctivae strains circulated endemically without causing clinical signs in Iberian ibex and livestock, either shared or maintained independently by each host species. In Iberian ibex, endemic infection was maintained by naïve subadults, with an epizootic outbreak when the infection spread to adults. Goat was at least as important as sheep in maintaining M. conjunctivae. The results suggest that the epidemiological role of wild ungulates should be considered in mountain ecosystems, as their mobility may contribute to the spread of IKC and other shared pathogens among spatially segregated livestock flocks. Infectious keratoconjunctivitis (IKC) is an eye disease caused by Mycoplasma conjunctivae that affects domestic and wild caprines, including Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate. However, its role in IKC dynamics in multi-host communities has been poorly studied. This study assessed M. conjunctivae in Iberian ibex and seasonally sympatric domestic small ruminants in the Natural Space of Sierra Nevada (NSSN), a mountain habitat in southern Spain. From 2015 to 2017, eye swabs were collected from 147 ibexes (46 subadults, 101 adults) and 169 adult domestic small ruminants (101 sheep, 68 goats). Mycoplasma conjunctivae was investigated through real-time qPCR and statistically assessed according to species, sex, age category, year, period, and area. The lppS gene of M. conjunctivae was sequenced and phylogenetically analysed. Mycoplasma conjunctivae was endemic and asymptomatic in the host community of the NSSN. Three genetic clusters were shared by ibex and livestock, and one was identified only in sheep, although each host species could maintain the infection independently. Naïve subadults maintained endemic infection in Iberian ibex, with an epizootic outbreak in 2017 when the infection spread to adults. Wild ungulates are epidemiologically key in maintaining and spreading IKC and other shared diseases among spatially segregated livestock flocks

Ivermectin Plasma Concentration in Iberian Ibex (Capra pyrenaica) Following Oral Administration : A Pilot Study

Sarcoptic mange is considered the main driver of demographic declines occurred in the last decades in Iberian ibex (Capra pyrenaica) populations. Mass treatment campaigns by administration of in-feed acaricides are used as a measure to mitigate the impact of mange in the affected populations. However, there are no data on ivermectin (IVM) pharmacokinetics in this wild caprine, and the treatment through medicated feed is not endorsed by evidence on its effectiveness. The aim of this study is to determine the pharmacokinetic profile of IVM in plasma samples of ibexes after the experimental oral administration of IVM, using high performance liquid chromatography (HPLC) with automated solid phase extraction and fluorescence detection. A dose of 500 μg of IVM per body weight was orally administered in a feed bolus to nine healthy adult ibexes (seven males and two females). Blood samples were collected by jugular venipuncture into heparin-coated tubes at day 1, 2, 3, 4, 7, 10, 15, and 45 post-administration (dpa). The highest plasma concentration of IVM (Cmax = 3.4 ng/ml) was detected 24 h after the oral administration (T1), followed by a rapid decrease during the first week post-administration. Our results reveal that plasma IVM concentration drops drastically within 5 days of ingestion, questioning the effectiveness of a single in-feed dose of this drug to control sarcoptic mange. To the best of our knowledge, this is the first study on plasma availability of oral IVM in ibexes and in any wild ungulate species

Assessing the levels of intraspecific admixture and interspecific hybridization in Iberian wild goats (Capra pyrenaica)

Iberian wild goats (Capra pyrenaica, also known as Iberian ibex, Spanish ibex, and Spanish wild goat) underwent strong genetic bottlenecks during the 19th and 20th centuries due to overhunting and habitat destruction. From the 1970s to 1990s, augmentation translocations were frequently carried out to restock Iberian wild goat populations (very often with hunting purposes), but they were not systematically planned or recorded. On the other hand, recent data suggest the occurrence of hybridization events between Iberian wild goats and domestic goats (Capra hircus). Augmentation translocations and interspecific hybridization might have contributed to increase the diversity of Iberian wild goats. With the aim of investigating this issue, we have genotyped 118 Iberian wild goats from Tortosa-Beceite, Sierra Nevada, Muela de Cortes, Gredos, Batuecas, and Ordesa and Monte Perdido by using the Goat SNP50 BeadChip (Illumina). The analysis of genotypic data indicated that Iberian wild goat populations are strongly differentiated and display low diversity. Only three Iberian wild goats out from 118 show genomic signatures of mixed ancestry, a result consistent with a scenario in which past augmentation translocations have had a limited impact on the diversity of Iberian wild goats. Besides, we have detected eight Iberian wild goats from Tortosa-Beceite with signs of domestic goat introgression. Although rare, hybridization with domestic goats could become a potential threat to the genetic integrity of Iberian wild goats; hence, measures should be taken to avoid the presence of uncontrolled herds of domestic or feral goats in mountainous areas inhabited by this iconic wild ungulate.This research was funded by the European Regional Development Fund (FEDER)/Ministerio de Ciencia e Innovaci?n?Agencia Estatal de Investigaci?n/Project Reference grant: PID2019-105805RB-I00 and by the CERCA Programme/Generalitat de Catalunya. We acknowledge the support of the Spanish Ministry of Economy and Competitiveness for the Center of Excellence Severo Ochoa 2020?2023 (CEX2019-000902-S) grant awarded to the Centre for Research in Agricultural Genomics (CRAG). We also acknowledge Jos? Folch, of the Centro de Investigaci?n y Tecnolog?a Agroalimentaria de Arag?n for his help in the development of his research. MGLS was funded with a FPI Ph.D. grant from the Spanish Ministry of Education (BES-C-2017-079079). TFC was funded with a fellowship from the CAPES Foundation-Coordination of Improvement of Higher Education, Ministry of Education of the Federal Government of Brazil. EMS was funded with a FPU Ph.D. grant from the Spanish Ministry of Education (FPU15/01733). GM is a Serra H?nter fellow (professor) of the Generalitat de Catalunya. Thanks also to the CERCA Programme of the Generalitat de Catalunya for their support. Sample collection benefitted from the research grants CGL2012-40043-C02-01, CGL2012-40043-C02-02, and CGL2016-80543-P, also from the Spanish Ministry of Economy and Competitiveness. Many thanks to Laura Botigu? for her help and assistance in carrying out the f3 tests of admixture

5p and 3p Strands of miR-34 Family Members Have Differential Effects in Cell Proliferation, Migration, and Invasion in Cervical Cancer Cells

The micro RNA (miR)-34 family is composed of 5p and 3p strands of miR-34a, miR-34b, and miR-34c. The 5p strand’s expression and function is studied in cervical cancer. The 3p strand’s function and regulation remain to be elucidated. To study the function of the passenger strands of miR-34 family members, we overexpressed 5p and 3p strands using a synthetic miRNA in cervical cell lines. Cell proliferation was evaluated using crystal violet. Migration and invasion were tested using transwell assays, Western blot, and zymography. Possible specific targets and cell signaling were investigated for each strand. We found that miR-34a-5p inhibited proliferation, migration, and cell invasion accompanied by matrix metalloproteinase 9 (MMP9) activity and microtubule-associated protein 2 (MAP2) protein reduction. We also found that miR-34b-5p and miR-34c-5p inhibit proliferation and migration, but not invasion. In contrast, miR-34c-5p inhibits MMP9 activity and MAP2 protein, while miR-34b-5p has no effect on these genes. Furthermore, miR-34a-3p and miR-34b-3p inhibit proliferation and migration, but not invasion, despite the later reducing MMP2 activity, while miR-34c-3p inhibit proliferation, migration, and cell invasion accompanied by MMP9 activity and MAP2 protein inhibition. The difference in cellular processes, MMP2 and MMP9 activity, and MAP2 protein inhibition by miR-34 family members suggests the participation of other regulated genes. This study provides insights into the roles of passenger strands (strand*) of the miR-34 family in cervical cancer

Assessing the levels of intraspecific admixture and interspecific hybridization in Iberian wild goats (Capra pyrenaica)

Iberian wild goats (Capra pyrenaica, also known as Iberian ibex, Spanish ibex, and Spanish wild goat) underwent strong genetic bottlenecks during the 19 th and 20 th centuries due to overhunting and habitat destruction. From the 1970s to 1990s, augmentation translocations were frequently carried out to restock Iberian wild goat populations (very often with hunting purposes), but they were not systematically planned or recorded. On the other hand, recent data suggest the occurrence of hybridization events between Iberian wild goats and domestic goats (Capra hircus). Augmentation translocations and interspecific hybridization might have contributed to increase the diversity of Iberian wild goats. With the aim of investigating this issue, we have genotyped 118 Iberian wild goats from Tortosa-Beceite, Sierra Nevada, Muela de Cortes, Gredos, Batuecas, and Ordesa and Monte Perdido by using the Goat SNP50 BeadChip (Illumina). The analysis of genotypic data indicated that Iberian wild goat populations are strongly differentiated and display low diversity. Only three Iberian wild goats out from 118 show genomic signatures of mixed ancestry, a result consistent with a scenario in which past augmentation translocations have had a limited impact on the diversity of Iberian wild goats. Besides, we have detected eight Iberian wild goats from Tortosa-Beceite with signs of domestic goat introgression. Although rare, hybridization with domestic goats could become a potential threat to the genetic integrity of Iberian wild goats; hence, measures should be taken to avoid the presence of uncontrolled herds of domestic or feral goats in mountainous areas inhabited by this iconic wild ungulate

Inherited BCL10 deficiency impairs hematopoietic and nonhematopoietic immunity

Heterotrimers composed of B cell CLL/lymphoma 10 (BCL10), mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1), and caspase recruitment domain–containing (CARD) family adaptors play a role in NF-κB activation and have been shown to be involved in both the innate and the adaptive arms of immunity in murine models. Moreover, individuals with inherited defects of MALT1, CARD9, and CARD11 present with immunological and clinical phenotypes. Here, we characterized a case of autosomal-recessive, complete BCL10 deficiency in a child with a broad immunodeficiency, including defects of both hematopoietic and nonhematopoietic immunity. The patient died at 3 years of age and was homozygous for a loss-of-expression, loss-of function BCL10 mutation. The effect of BCL10 deficiency was dependent on the signaling pathway, and, for some pathways, the cell type affected. Despite the noted similarities to BCL10 deficiency in mice, including a deficient adaptive immune response, human BCL10 deficiency in this patient resulted in a number of specific features within cell populations. Treatment of the patient’s myeloid cells with a variety of pathogen-associated molecular pattern molecules (PAMPs) elicited a normal response; however, NF-κB–mediated fibroblast functions were dramatically impaired. The results of this study indicate that inherited BCL10 deficiency should be considered in patients with combined immunodeficiency with B cell, T cell, and fibroblast defects