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Abstract Background Sarcoptic mange is an emerging and neglected contagious skin disease caused by the mite Sarcoptes scabiei, affecting humans, domestic animals, and wildlife. Mange is the main disease and a major concern for the management and conservation of populations of Iberian ibex (Capra pyrenaica), a medium-sized mountain ungulate endemic to the Iberian Peninsula and Northern Pyrenees. Differences in host-parasite interaction and host immune response determine mange clinical outcome, but little is known about the related differences in gene expression. This study determined blood and skin gene expressions in S. scabiei-experimentally infested Iberian ibexes. Results Infestation with S. scabiei promoted immune and inflammatory genomic responses both in skin and blood, with two different clinical outcomes: either severe infestation or recovery. Sarcoptes scabiei induced local skin immunosuppression to favour its multiplication and establishment of the infestation in the host. Skin gene expression was mostly inflammatory and inefficient to control mange in the severely infected ibexes. Conversely, the immune skin response of the recovered ibexes effectively recognised S. scabiei and activated T-cells, limiting the infestation. Consequently, inflammation-related genes were more expressed in the blood of the severely infested ibexes than in those that recovered. Conclusions The results demonstrate that skin local cellular immune response is key to control sarcoptic mange and prevent the systemic spread of the disease and the associated inflammatory response. These results will be useful to understand the pathogenesis and drivers of the differential outcome of mange at individual scale, and the population and ecological consequences of such variability in Iberian ibex, as well as in other wildlife species, domestic animals, and humans.

Although the idea of conserving parasites as part of biodiversity is not new, these in general and lice in particular, are not included in the threatened list of invertebrate fauna. Assuming that the conservation status of a lice species is similar to that of its host, the number of threatened lice within the Spanish entomofauna was estimated based on the known host-lice assemblages. The lice parasitizing many of the Spanish birds and mammals are unknown. Overall, I found 6 extinct (EX) species; 4 critically endangered (CR); 15 endangered (EN), 7 vulnerable (VU) and 1 species near threatened (NT), at regional level. Since the status of hosts varies through time and space, it, (together with those of their lice, must be periodically updated. In addition to a number of reasons that justify the conservation of parasites, lice deserve being conserved, particularly, because of their scientific value.

Abstract Background Sarcoptic mange is one of the main parasitic diseases affecting the Iberian ibex Capra pyrenaica. Scabietic animals suffer a decline in body condition and reproductive fitness and in severe cases may die. Although several previous studies of the pathology of this disease and the physiological changes it produces in ibex have been carried out in recent years, our knowledge of the relationship between Sarcoptes scabiei and other ectoparasites of this host is still limited. Methods We analysed 430 Iberian ibex skin samples. Ectoparasites were removed, counted and identified. Mite (S. scabiei) numbers were obtained after digesting the skin samples in a 5% KOH solution. We modelled mite numbers in terms of host sex and age, site, year, season and the presence of other ectoparasites such as ticks and lice using generalized linear mixed models (GLMMs) and ectoparasite co-occurrence patterns using two different models: the probabilistic model species co-occurrence and the generalized linear latent variable model (GLLVM). Results The ectoparasite community was mainly composed of S. scabiei, six ticks (Haemaphysalis sulcata, Haemaphysalis punctata, Rhipicephalus bursa, Rhipicephalus turanicus, Dermacentor marginatus and Ixodes ricinus) and two lice (Bovicola crassipes and Linognathus stenopsis). Adult male ibex harboured more mites than females. Mite numbers varied greatly spatially and seasonally and increased with the presence of other parasites. Some positive co-occurrence relationships between pairs of different ectoparasites were observed, particularly between ticks. The presence of S. scabiei negatively affected lice and H. sulcata numbers. Conclusions Sarcoptic mange has spread above all in ibex populations in and around the Mediterranean Basin, where it is now found in almost a third of its host’s range. Mite numbers varied seasonally and spatially and were higher in male hosts. The presence of S. scabiei had a negative effect on lice numbers but favoured the presence of ticks. Graphical Abstract

Abstract Habitat loss is one of the main threats to species survival and, in the case of parasites, it is their hosts that provide their habitat. Therefore, extinction even at local scale of host taxa also implies the extinction of their parasites in a process known as co-extinction. This is the case of the bearded vulture (Gypaetus barbatus), which almost became extinct at the beginning of the twentieth century. After several attempts, this species was successfully reintroduced into the Alps at the end of the twentieth century. We collected 25 lice specimens from an electrocuted bearded vulture from Susa (Italian Alps) that were morphologically identified as Degeeriella punctifer. Six individuals were studied by scanning electron microscopy, with particular emphasis on their cephalic sensorial structures, while four further specimens were characterized at molecular level by amplifying partial regions of the 12SrRNA, COX1 and elongation factor 1 alpha (EF-1) genes. From a morphological perspective, the number, type and arrangement of the sensillae on the two distal antennal segments is quite similar to that of other species of the family Philopteridae (Phthiraptera: Ischnocera). The mandibles and tarsal claws allow lice to cling firmly to their host’s feathers. Phylogenetic analyses help unravel the paraphyletic nature of the genus Degeeriella and demonstrate the clear differentiation between lice parasitizing Accipitriformes and Falconiformes, as well as the close relationship between D. punctifer, D. fulva, D. nisus and Capraiella sp. that, along with other genera, parasitize rollers (Aves: Coraciiformes).

Trichinellosis is a notifiable zoonotic disease caused by parasitic nematode larvae belonging to the genus Trichinella. Domestic pig and wild boar are important hosts within the natural cycle of T. spiralis, the last one being an animal whose populations have experienced an important growth. Therefore, this paper studies the prevalence of Trichinella infection in wild boar in Spain, as well as its relation with hunting and its impact on public health during the period 2006–2019. For this purpose, different sources of information were consulted and analyzed depending on the autonomous communities of Spain and years. During the fourteen years of study, the number of wild boars hunted and the number of cases of Trichinella infection in them increased (from 172 cases in 2006 to 421 in 2019), although prevalence values remained low as the number of animals analyzed also increased. On the other hand, trichinellosis in humans tended to decrease (from a peak of 107 cases in 2007 to 11 cases in 2019). Nevertheless, the numbers of both wild boars and humans infected with Trichinella in Spain are among the highest in Europe, and this emphasizes the importance of food safety, sanitary controls of game meat and citizen awareness campaigns, which prevent the spread of Trichinella through the human population.

IntroductionSarcoptic 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.MethodsFourteen 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.ResultsAn 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.DiscussionThe 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.

Summary: Background: Glioblastoma is one of the most devastating and incurable cancers due to its aggressive behaviour and lack of available therapies, being its overall-survival from diagnosis ∼14-months. Thus, identification of new therapeutic tools is urgently needed. Interestingly, metabolism-related drugs (e.g., metformin/statins) are emerging as efficient antitumour agents for several cancers. Herein, we evaluated the in vitro/in vivo effects of metformin and/or statins on key clinical/functional/molecular/signalling parameters in glioblastoma patients/cells. Methods: An exploratory-observational-randomized retrospective glioblastoma patient cohort (n = 85), human glioblastoma/non-tumour brain human cells (cell lines/patient-derived cell cultures), mouse astrocytes progenitor cell cultures, and a preclinical xenograft glioblastoma mouse model were used to measure key functional parameters, signalling-pathways and/or antitumour progression in response to metformin and/or simvastatin. Findings: Metformin and simvastatin exerted strong antitumour actions in glioblastoma cell cultures (i.e., proliferation/migration/tumoursphere/colony-formation/VEGF-secretion inhibition and apoptosis/senescence induction). Notably, their combination additively altered these functional parameters vs. individual treatments. These actions were mediated by the modulation of key oncogenic signalling-pathways (i.e., AKT/JAK-STAT/NF-κB/TGFβ-pathways). Interestingly, an enrichment analysis uncovered a TGFβ-pathway activation, together with AKT inactivation, in response to metformin + simvastatin combination, which might be linked to an induction of the senescence-state, the associated secretory-phenotype, and to the dysregulation of spliceosome components. Remarkably, the antitumour actions of metformin + simvastatin combination were also observed in vivo [i.e., association with longer overall-survival in human, and reduction in tumour-progression in a mouse model (reduced tumour-size/weight/mitosis-number, and increased apoptosis)]. Interpretation: Altogether, metformin and simvastatin reduce aggressiveness features in glioblastomas, being this effect significantly more effective (in vitro/in vivo) when both drugs are combined, offering a clinically relevant opportunity that should be tested for their use in humans. Funding: Spanish Ministry of Science, Innovation and Universities; Junta de Andalucía; CIBERobn (CIBER is an initiative of Instituto de Salud Carlos III, Spanish Ministry of Health, Social Services and Equality).

Prostate-specific antigen (PSA) is the gold-standard marker to screen prostate cancer (PCa) nowadays. Unfortunately, its lack of specificity and sensitivity makes the identification of novel tools to diagnose PCa an urgent medical need. In this context, microRNAs (miRNAs) have emerged as potential sources of non-invasive diagnostic biomarkers in several pathologies. Therefore, this study was aimed at assessing for the first time the dysregulation of the whole plasma miRNome in PCa patients and its putative implication in PCa from a personalized perspective (i.e., obesity condition). Plasma miRNome from a discovery cohort (18 controls and 19 PCa patients) was determined using an Affymetrix-miRNA array, showing that the expression of 104 miRNAs was significantly altered, wherein six exhibited a significant receiver operating characteristic (ROC) curve to distinguish between control and PCa patients (area under the curve [AUC] = 1). Then, a systematic validation using an independent cohort (135 controls and 160 PCa patients) demonstrated that miR-107 was the most profoundly altered miRNA in PCa (AUC = 0.75). Moreover, miR-107 levels significantly outperformed the ability of PSA to distinguish between control and PCa patients and correlated with relevant clinical parameters (i.e., PSA). These differences were more pronounced when considering only obese patients (BMI > 30). Interestingly, miR-107 levels were reduced in PCa tissues versus non-tumor tissues (n = 84) and in PCa cell lines versus non-tumor cells. In vitro miR-107 overexpression altered key aggressiveness features in PCa cells (i.e., proliferation, migration, and tumorospheres formation) and modulated the expression of important genes involved in PCa pathophysiology (i.e., lipid metabolism [i.e., FASN] and splicing process). Altogether, miR-107 might represent a novel and useful personalized diagnostic and prognostic biomarker and a potential therapeutic tool in PCa, especially in obese patients.

Abstract Background Glioblastoma is one of the most devastating cancer worldwide based on its locally aggressive behavior and because it cannot be cured by current therapies. Defects in alternative splicing process are frequent in cancer. Recently, we demonstrated that dysregulation of the spliceosome is directly associated with glioma development, progression, and aggressiveness. Methods Different human cohorts and a dataset from different glioma mouse models were analyzed to determine the mutation frequency as well as the gene and protein expression levels between tumor and control samples of the splicing-factor-3B-subunit-1 (SF3B1), an essential and druggable spliceosome component. SF3B1 expression was also explored at the single-cell level across all cell subpopulations and transcriptomic programs. The association of SF3B1 expression with relevant clinical data (e.g., overall survival) in different human cohorts was also analyzed. Different functional (proliferation/migration/tumorspheres and colonies formation/VEGF secretion/apoptosis) and mechanistic (gene expression/signaling pathways) assays were performed in three different glioblastomas cell models (human primary cultures and cell lines) in response to SF3B1 blockade (using pladienolide B treatment). Moreover, tumor progression and formation were monitored in response to SF3B1 blockade in two preclinical xenograft glioblastoma mouse models. Results Our data provide novel evidence demonstrating that the splicing-factor-3B-subunit-1 (SF3B1, an essential and druggable spliceosome component) is low-frequency mutated in human gliomas (~ 1 %) but widely overexpressed in glioblastoma compared with control samples from the different human cohorts and mouse models included in the present study, wherein SF3B1 levels are associated with key molecular and clinical features (e.g., overall survival, poor prognosis and/or drug resistance). Remarkably, in vitro and in vivo blockade of SF3B1 activity with pladienolide B drastically altered multiple glioblastoma pathophysiological processes (i.e., reduction in proliferation, migration, tumorspheres formation, VEGF secretion, tumor initiation and increased apoptosis) likely by suppressing AKT/mTOR/ß-catenin pathways, and an imbalance of BCL2L1 splicing. Conclusions Together, we highlight SF3B1 as a potential diagnostic and prognostic biomarker and an efficient pharmacological target in glioblastoma, offering a clinically relevant opportunity worth to be explored in humans.

Nasopharyngeal myiasis in red deer has never been studied in Portugal. For this reason, from December 2015 to February 2016 a study was derived on hunted red deer in Idanha-a-Nova county to evaluate the Diptera larvae presence. During the initial examination on the spot, the larvae was analysed at the nasopharynx. When present, larvae were collected for further species identification. The infestation prevalence was 50.6 ± 7.61% (CI 95%), and the mean parasitism intensity was 11.38 larvae per affected host. Two larvae species were found, Pharyngomyia picta and Cephenemyia auribarbis, both on single or concomitant infection, with the first species having a higher prevalence and mean infestation intensity than the second. The larvae’s prevalence was significantly higher (X2 = 4.35; p = 0.0370) in males (62.16 ± 11.05%) than in females (41.30 ± 10.06%). Within age groups, younger animals showed a higher prevalence. This study shows the presence of P. picta and C. auribarbis larvae in the wild red deer population in Portugal for the first time. The high parasitic prevalence and mean intensity highlight the importance of this parasitosis in this wild species. For this reason, more scientific research is required to accurately assess its prevalence in other geographic areas, and evaluate the risk factors as well effects of this parasitosis on the deer population.

Urbanization creates new ecological conditions that can affect biodiversity at all levels, including the diversity and prevalence of parasites of species that may occupy these environments. However, few studies have compared bird–ectoparasite interactions between urban and rural individuals. Here, we analyze the ectoparasite community and co-infection patterns of urban and rural burrowing owls, Athene cunicularia, to assess the influence of host traits (i.e., sex, age, and weight), and environmental factors (i.e., number of conspecifics per nest, habitat type and aridity) on its composition. Ectoparasites of burrowing owls included two lice, one flea, and one mite. The overall prevalence for mites, lice and fleas was 1.75%, 8.76% and 3.50%, respectively. A clear pattern of co-infection was detected between mites and fleas and, to less extent, between mites and lice. Adult owls harbored fewer ectoparasites than nestlings, and adult females harbored more lice than males. Our results also show that mite and flea numbers were higher when more conspecifics cohabited the same burrow, while lice showed the opposite pattern. Rural individuals showed higher flea parasitism and lower mite parasitism than urban birds. Moreover, mite numbers were negatively correlated with aridity and host weight. Although the ectoparasitic load of burrowing owls appears to be influenced by individual age, sex, number of conspecifics per nest, and habitat characteristics, the pattern of co-infection found among ectoparasites could also be mediated by unexplored factors such as host immune response, which deserves further research.