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The necropsy made to two adult individuals of red deer shot in Sierra Nevada National Park revealed infestation by second- and third-instar larvae of the oestrid Pharyngomyia picta (Meigen 1824). The animals were shot in Dehesa de las Hoyas, about 2000 m above sea level. This is the first record of this parasite in Sierra Nevada National Park. Furthermore, the occurrence of adult P. picta at this altitude could indicate significant changes of the climatic conditions, now matching better the environmental requirements of this bot fly. Its monitoring may, therefore, be of great help for detecting global change signs.

Somatostatin (SST), cortistatin (CORT), and their receptors (SSTR1-5/sst5TMD4-TMD5) comprise a multifactorial hormonal system involved in the regulation of numerous pathophysiological processes. Certain components of this system are dysregulated and play critical roles in the development/progression of different endocrine-related cancers. However, the presence and therapeutic role of this regulatory system in prostate cancer (PCa) remain poorly explored. Accordingly, we performed functional (proliferation/migration/colonies-formation) and mechanistic (Western-blot/qPCR/microfluidic-based qPCR-array) assays in response to SST and CORT treatments and CORT-silencing (using specific siRNA) in different PCa cell models [androgen-dependent (AD): LNCaP; androgen-independent (AI)/castration-resistant PCa (CRPC): 22Rv1 and PC-3], and/or in the normal-like prostate cell-line RWPE-1. Moreover, the expression of SST/CORT system components was analyzed in PCa samples from two different patient cohorts [internal (n = 69); external (Grasso, n = 88)]. SST and CORT treatment inhibited key functional/aggressiveness parameters only in AI-PCa cells. Mechanistically, antitumor capacity of SST/CORT was associated with the modulation of oncogenic signaling pathways (AKT/JNK), and with the significant down-regulation of critical genes involved in proliferation/migration and PCa-aggressiveness (e.g., MKI67/MMP9/EGF). Interestingly, CORT was highly expressed, while SST was not detected, in all prostate cell-lines analyzed. Consistently, endogenous CORT was overexpressed in PCa samples (compared with benign-prostatic-hyperplasia) and correlated with key clinical (i.e., metastasis) and molecular (i.e., SSTR2/SSTR5 expression) parameters. Remarkably, CORT-silencing drastically enhanced proliferation rate and blunted the antitumor activity of SST-analogues (octreotide/pasireotide) in AI-PCa cells. Altogether, we provide evidence that SST/CORT system and SST-analogues could represent a potential therapeutic option for PCa, especially for CRPC, and that endogenous CORT could act as an autocrine/paracrine regulator of PCa progression.

Bladder cancer is the most common malignancy of the urinary tract worldwide. The therapeutic options to tackle this disease comprise surgery, intravesical or systemic chemotherapy, and immunotherapy. Unfortunately, a wide number of patients ultimately become resistant to these treatments and develop aggressive metastatic disease, presenting a poor prognosis. Therefore, the identification of novel therapeutic approaches to tackle this devastating pathology is urgently needed. However, a significant limitation is that the progression and drug response of bladder cancer is strongly associated with its intrinsic molecular heterogeneity. In this sense, RNA splicing is recently gaining importance as a critical hallmark of cancer since can have a significant clinical value. In fact, a profound dysregulation of the splicing process has been reported in bladder cancer, especially in the expression of certain key splicing variants and circular RNAs with a potential clinical value as diagnostic/prognostic biomarkers or therapeutic targets in this pathology. Indeed, some authors have already evidenced a profound antitumor effect by targeting some splicing factors (e.g., PTBP1), mRNA splicing variants (e.g., PKM2, HYAL4-v1), and circular RNAs (e.g., circITCH, circMYLK), which illustrates new possibilities to significantly improve the management of this pathology. This review represents the first detailed overview of the splicing process and its alterations in bladder cancer, and highlights opportunities for the development of novel diagnostic/prognostic biomarkers and their clinical potential for the treatment of this devastating cancer type. This article is categorized under: RNA ProcessingSplicing Regulation/Alternative Splicing RNA in Disease and DevelopmentRNA in Disease.

Inflammasomes are multiprotein intracellular complexes composed of innate immune system receptors and sensors; they activate the inflammatory cascade in response to infectious microbes and/or molecules derived from host proteins. Because of cytokine secretion, inflammasomes can induce amplified systemic responses, its dysregulation can exacerbate symptoms in infectious diseases, and it has been related to the development of autoimmune diseases, inflammatory disorders, and even cancer. Obesity is associated with a chronic low-grade inflammation, in which circulating proinflammatory cytokines are elevated. Some publications describe changes in inflammation markers as a consequence of obesity, but others suggest that chronic inflammation might cause obesity (e.g., C-reactive protein): these assumptions reflect the difficulty of identifying the appropriate role of inflammation as cause or consequence of obesity and its related complications. Obesity is recognized as a clinical risk factor for developing cardiovascular diseases including atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. Changes in the expression of inflammasomes are described in some of these obesity-related complications, and moreover, its modulation might exert a beneficial effect in some cases. Despite some contradictory results, most publications suggest a promising clinical effect based on in vitro and in vivo experiments. In this review, we summarized recent publications about inflammasome dysregulation in humans and its relationship with obesity-related comorbidities.

We analysed the diversity of the cytochrome b gene in Iberian ibex (Capra pyrenaica) populations in the southern Iberian Peninsula by sequencing a fragment (987 bp) of this gene in 347 ibex from 10 population nuclei in Andalusia. We found 25 different haplotypes, which account for 64.10% of all haplotypes thus far described for the species (n = 39). All ibex populations other than those from Sierra de Loja shared haplotype EU081020, which was also the most frequent. Twenty haplotypes (80%) were present exclusively in just one population. Of the studied populations, ibex from the Sierra Nevada Natural Space had the greatest genetic diversity in this marker, which was found to harbour 17 cyt b haplotypes. Phylogenetic analyses based on the cytochrome b marker do not support the subspecific classification of this taxon proposed at the beginning of the twentieth century, although three distinct management units can be distinguished. Finally, we discuss the implications of our results on the management of this species. Although the results presented do not describe the structure of the population or the gene flow, it gives an accurate picture of the diversity of this mitochondrial marker, which can be considered a reflection of the historical processes that these populations have undergone.

Trichinellosis is a notifiable zoonotic disease caused by parasitic nematode larvae belonging to the genus

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

Glioblastoma (GBM) is the most malignant and lethal brain tumor. Current standard treatment consists of surgery followed by radiotherapy/chemotherapy; however, this is only a palliative approach with a mean post-operative survival of scarcely ~12–15 months. Thus, the identification of novel therapeutic targets to treat this devastating pathology is urgently needed. In this context, the truncated splicing variant of the somatostatin receptor subtype 5 (sst5TMD4), which is produced by aberrant alternative splicing, has been demonstrated to be overexpressed and associated with increased aggressiveness features in several tumors. However, the presence, functional role, and associated molecular mechanisms of sst5TMD4 in GBM have not been yet explored. Therefore, we performed a comprehensive analysis to characterize the expression and pathophysiological role of sst5TMD4 in human GBM. sst5TMD4 was significantly overexpressed (at mRNA and protein levels) in human GBM tissue compared to non-tumor (control) brain tissue. Remarkably, sst5TMD4 expression was significantly associated with poor overall survival and recurrent tumors in GBM patients. Moreover, in vitro sst5TMD4 overexpression (by specific plasmid) increased, whereas sst5TMD4 silencing (by specific siRNA) decreased, key malignant features (i.e., proliferation and migration capacity) of GBM cells (U-87 MG/U-118 MG models). Furthermore, sst5TMD4 overexpression in GBM cells altered the activity of multiple key signaling pathways associated with tumor aggressiveness/progression (AKT/JAK-STAT/NF-κB/TGF-β), and its silencing sensitized GBM cells to the antitumor effect of pasireotide (a somatostatin analog). Altogether, these results demonstrate that sst5TMD4 is overexpressed and associated with enhanced malignancy features in human GBMs and reveal its potential utility as a novel diagnostic/prognostic biomarker and putative therapeutic target in GBMs.

Malnutrition in patients with head and neck cancer is frequent, multifactorial and widely associated with clinical evolution and prognosis. Accurate nutritional assessments allow for early identification of patients at risk of malnutrition in order to start nutritional support and prevent sarcopenia. We aimed to perform a novel morphofunctional nutritional evaluation and explore changes in inflammasome-machinery components in 45 patients with head and neck cancer who are undergoing systemic treatment. To this aim, an epidemiological/clinical/anthropometric/biochemical evaluation was performed. Serum RCP, IL6 and molecular expression of inflammasome-components and inflammatory-associated factors (NOD-like-receptors, inflammasome-activation-components, cytokines and inflammation/apoptosis-related components, cell-cycle and DNA-damage regulators) were evaluated in peripheral-blood mononuclear-cells (PBMCs). Clinical-molecular correlations/associations were analyzed. Coherent and complementary information was obtained in the morphofunctional nutritional assessment of the patients when bioimpedance, anthropometric and ultrasound data were analyzed. These factors were also correlated with different biochemical and molecular parameters, revealing the complementary aspect of the whole evaluation. Serum reactive C protein (RCP) and IL6 were the most reliable parameters for determining patients with decreased standardized phase angle, which is associated with increased mortality in patients with solid malignancies. Several inflammasome-components were dysregulated in patients with malnutrition, decreased phase angle and dependency grade or increased circulating inflammation markers. A molecular fingerprint based on gene-expression of certain inflammasome factors (p27/CCL2/ASC) in PBMCs accurately differentiated patients with and without malnutrition. In conclusion, malnutrition induces a profound alteration in the gene-expression pattern of inflammasome-machinery components in PBMCs. A comprehensive nutritional assessment including novel morphofunctional techniques and molecular markers allows a broad characterization of the nutritional status in cancer patients. Profile of certain inflammasome-components should be further studied as potential targets for nutrition-focused treatment strategies in cancer patients.

Glioblastoma (GBM) is the most malignant and lethal brain tumor. Current standard treatment consists of surgery followed by radiotherapy/chemotherapy; however, this is only a palliative approach with a mean post-operative survival of scarcely ~12-15 months. Thus, the identification of novel therapeutic targets to treat this devastating pathology is urgently needed. In this context, the truncated splicing variant of the somatostatin receptor subtype 5 (sst5TMD4), which is produced by aberrant alternative splicing, has been demonstrated to be overexpressed and associated with increased aggressiveness features in several tumors. However, the presence, functional role, and associated molecular mechanisms of sst5TMD4 in GBM have not been yet explored. Therefore, we performed a comprehensive analysis to characterize the expression and pathophysiological role of sst5TMD4 in human GBM. sst5TMD4 was significantly overexpressed (at mRNA and protein levels) in human GBM tissue compared to non-tumor (control) brain tissue. Remarkably

Population estimates of male Western Capercaillies Tetrao urogallus were carried out during the mating season using two methods: counts of singing males and non-invasive genetic analysis. Estimates...

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.

The necropsy made to two adult individuals of red deer shot in Sierra Nevada National Park revealed infestation by second- and third-instar larvae of the oestrid Pharyngomyia picta (Meigen 1824). The animals were shot in Dehesa de las Hoyas, about 2000 m above sea level. This is the first record of this parasite in Sierra Nevada National Park. Furthermore, the occurrence of adult P. picta at this altitude could indicate significant changes of the climatic conditions, now matching better the environmental requirements of this bot fly. Its monitoring may, therefore, be of great help for detecting global change signs.

© Wildlife Disease Association 2015. Our study focuses on the Iberian ibex (Capra pyrenaica) from the Sierra Nevada Natural Space (southern Spain), where sarcoptic mange is an endemic disease and animals are affected by a highly seasonal environment. Our aim was to distinguish between disease and environmental influences on seasonal variation in body weight, hematology, and serum biochemistry in Iberian ibex. We sampled 136 chemically immobilized male ibexes. The single effect of mange influenced hemoglobin, hematocrit, mean corpuscular volume, leukocytes, band neutrophils, monocytes, cholesterol, urea, creatine, and aspartate aminotransferase. Both mange and the period of the year also affected values of mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration, neutrophils, glucose, and serum proteins. Scabietic animals showed a marked reduction in body weight (21.4 kg on average), which was more pronounced in winter. These results reveal that 1) infested animals are anemic, 2) secondary infections likely occur, and 3) sarcoptic mange is catabolic.

Reconstructing the demographic history of endangered taxa is paramount to predict future fluctuations and disentangle the contributing factors. Extinct taxa or populations might also provide key insights in this respect by means of the DNA extracted from museum specimens. Nevertheless, the degraded status of biological material and the limited number of records may pose some constraints. For this reason, identifying all available sources, including private and public biological collections, is a crucial step forward. In this study, we reconstructed the demographic history based on cytochrome-b sequence data of the Pyrenean ibex (Capra pyrenaica pyrenaica), a charismatic taxon of the European wildlife that became extinct in the year 2000. Moreover, we built a database of the museum specimens available in public biological collections worldwide and genotyped a privately owned 140-year-old trophy from the Spanish Pyrenees to confirm its origin. We found that the population of the Pyrenean ibex underwent a recent expansion approximately 20,000 years ago, after which trophy hunting and epizootics triggered a relentless population decline. Our interpretations, based on the genetic information currently available in public repositories, provide a solid basis for more exhaustive analyses relying on all the new sources identified. In particular, the adoption of a genome-wide approach appears a fundamental prerequisite to disentangle the multiple contributing factors associated with low genetic diversity, including inbreeding depression, acting as extinction drivers.

In most unisexual species, the numbers of male and female individuals are approximately equal. The adult sex ratio (ASR) is a key demographic parameter for the conservation and management of wild species. However, in the case of monomorphic birds such as the Rock Ptarmigan Lagopus muta, estimating the sex ratio is difficult. To test if the sex ratio is balanced, we analysed the adult sex ratio of this tetraonid with two different methods, using microsatellite individualisation of non-invasive samples (faeces) and the hunting bag data of birds hunted in the French Alps and Pyrenees. The results of our non-invasive study revealed a balanced ASR in spring, whereas hunted specimens had a strongly male-biased ratio for adults but an approximately balanced sex ratio for juveniles (< 1 year old). The sex ratio estimated from hunting data may be biased for the adult population and, as occurs in other species, is not representative of the overall sex ratio. Our results suggest that, assuming our sampling strategy was adequate, non-invasive sampling is a good method to estimate ASR.—Aleix-Mata, G., Perez, J.M., Adrados, B., Boos, M., Marty, E., Mourieres, P., Lauer, E., Zimmermann, S., Mossoll-Torres, M. & Sanchez, A. (2021). Sex ratio of Alpine and Pyrenean Rock Ptarmigans Lagopus muta estimated by a non-invasive method (faecal DNA analysis) and from hunting bag data. Ardeola, 68: 201-212.

The rock ptarmigan (Lagopus muta) has a wide Holarctic geographical range, within which its status changes locally from threatened to abundant. For the correct management of populations under differing scenarios, accurate and precise estimates of bird abundances and/or densities are required. We used geolocated datasets from 56 counts of singing males carried out in 2003–2017 to estimate the density of Pyrenean rock ptarmigans (Lagopus muta pyrenaica). We analysed these datasets using two methodologies: (1) a plot sampling (PS) approach with two effective detection ranges (EDR) of 250 m and 350 m and (2) a conventional distance sampling (DS) approach. Our results showed that the density estimates obtained by DS were more precise and 30–87% higher than those obtained by PS using 250 m and 350 m EDR. Monitoring with PS underestimates populations and is less precise than DS; this bias is magnified when high EDR values are used. The monitoring of the Pyrenean rock ptarmigan could be significantly improved with greater use of the DS method.

This dataset provides long-term information on the presence of the Iberian ibex (Capra pyrenaica hispanica Schimper, 1848) in Sierra Nevada (SE Iberian Peninsula). Data on the abundance and demographic structure of the Iberian ibex population were compiled over the last three decades. Transects were laid out to record different variables such as the number of individuals sighted, the perpendicular distance of each group of Iberian ibex to the transect line and sex as well as age of individuals in the case of males. These data enabled the calculation of population parameters such as density, sex ratio, birth rate, and age structure. These parameters are key for Iberian ibex conservation and management, given that Sierra Nevada harbours the largest population of this species in the Iberian Peninsula. The data set we present is structured using the Darwin Core biological standard, which contains 3,091 events (582 transect walk events and 2,509 group sighting events), 5,396 occurrences, and 2,502 measurements. The occurrences include the sightings of 11,436 individuals (grouped by sex and age) from 1993 to 2018 in a total of 88 transects distributed along Sierra Nevada, of which 33 have been continuously sampled since 2008., Projects "LIFE-ADAPTAMED: Protection of key ecosystem services by adaptive management of Climate Change endangered Mediterranean socioecosystems" LIFE14 CCA/ES/000612, H2020 project "ECOPOTENTIAL: Improving future ecosystem benefits through earth observations" - European Union's Horizon 2020 research and innovation programme 641762, Elter H2020 project "European Long-Term Ecosystem and Socio-Ecological Research Infrastructure" - European Union's Horizon 2020 programme 654359, 10010003, 10050010, 10040016, 676/2006/A/00, 1571/2007/M/00, 173/2009/M/00, 861/11/M/00, 03/15/M/00, 2016 _00014_M, 2017-00189M

Taking into account that most of the known living organisms are parasites and that they exert a strong influence on the functioning of ecosystems, we can consider parasitism as a successful strategy for life. Because of the harm that parasites can inflict on man and domesticated animals, which can be expressed as economic loss, many parasites become pests. In natural ecosystems, parasites contribute to the prevention of continuous exponential growth of populations and, therefore, they also need to be conserved. The exotic pet trade may result in translocation of exotic species together with their microparasites and macroparasites, potentiating a risk of transmission of exotic diseases to native fauna and to humans. Within this context we need to increase our knowledge of parasites and parasitic diseases of wildlife. Prevention seems to be the choice for managing parasite exposure. This may be achieved through educational programs that refocused on discouraging people to import exotic pets, together with stronger legislative measures to control wildlife trade.