Dissecting the Effects of Cephenemyia stimulator on the Olfactory Turbinates and Nasopharynx of Roe Deers (Capreolus capreolus).

Nasopharyngeal myiasis in European roe deer (Capreolus capreolus) is a pathological condition caused by the larval stages of Cephenemyia stimulator, a fly from the Oestridae family. These larvae reside in the host's upper respiratory tract for months, inducing significant tissue damage and clinical symptoms. The lifecycle of Cephenemyia stimulator is complex, involving three larval stages before maturation into adult flies, with each stage contributing to the progressive pathology observed in the host. Despite their prevalence, the histopathological effects of these larvae in the nasal and nasopharyngeal cavities have been understudied. Our study fills this knowledge gap by providing a detailed histopathological analysis of the affected tissues, using various staining techniques to reveal the extent and nature of the damage caused by these parasitic larvae. This histopathological examination reveals significant alterations within the nasopharyngeal mucosa and nasal cavity, including erythematous changes, mucosal metaplasia, fibrosis, and tissue necrosis. Parasitic cysts and eosinophilic infiltration further characterize the impact of the infestation, compromising not only the mucosal integrity but also potentially the olfactory function of the affected animals. This research is crucial for understanding the impact of myiasis on both the health and olfactory capabilities of roe deer populations and could have significant implications for wildlife management and conservation.

Impact of breastfeeding on ICU admissions and need for mechanical ventilation in infants younger than 6 months with RSV+ bronchiolitis. An observational study.

INTRODUCTION: This work aimed to analyze whether breastfeeding is a predictive factor for admission to ICU or needing mechanical ventilation in children under 6 months with RSV+ respiratory infection. METHODS: A retrospective cohort study was performed in three hospitals. Binary and multiple logistic regression analyses were performed to evaluate the association of variables with admission to the ICU or receiving mechanical ventilation. RESULTS: We analyzed 414 admissions, of which 293 (70.8%) had received breastfeeding, 43 (8.1%) were admitted to the ICU, and 26 (5.4%) required mechanical ventilation. Bivariate analysis showed that breastfeeding for at least 15 days and a longer duration of breastfeeding were associated with a lower risk of admission to the ICU and requiring mechanical ventilation. Multivariate analysis showed that not having been breastfed for at least 1 month was predictive of ICU admission; not having been breastfed for at least 2 months was predictive of needing mechanical ventilation. CONCLUSIONS: Breastfeeding for as little as 15-28 days could be associated with a lower risk of ICU admission and requiring mechanical ventilation in infants younger than 6 months admitted for RSV+ bronchiolitis. Since breastfeeding is one of the few protective factors that can be promoted, this finding is relevant for current clinical practice and the development of health promotion programs. Future studies can compare their results to ours.

The vomeronasal system of the wolf (Canis lupus signatus): The singularities of a wild canid.

Wolves, akin to their fellow canids, extensively employ chemical signals for various aspects of communication, including territory maintenance, reproductive synchronisation and social hierarchy signalling. Pheromone-mediated chemical communication operates unconsciously among individuals, serving as an innate sensory modality that regulates both their physiology and behaviour. Despite its crucial role in the life of the wolf, there is a lacuna in comprehensive research on the neuroanatomical and physiological underpinnings of chemical communication within this species. This study investigates the vomeronasal system (VNS) of the Iberian wolf, simultaneously probing potential alterations brought about by dog domestication. Our findings demonstrate the presence of a fully functional VNS, vital for pheromone-mediated communication, in the Iberian wolf. While macroscopic similarities between the VNS of the wolf and the domestic dog are discernible, notable microscopic differences emerge. These distinctions include the presence of neuronal clusters associated with the sensory epithelium of the vomeronasal organ (VNO) and a heightened degree of differentiation of the accessory olfactory bulb (AOB). Immunohistochemical analyses reveal the expression of the two primary families of vomeronasal receptors (V1R and V2R) within the VNO. However, only the V1R family is expressed in the AOB. These findings not only yield profound insights into the VNS of the wolf but also hint at how domestication might have altered neural configurations that underpin species-specific behaviours. This understanding holds implications for the development of innovative strategies, such as the application of semiochemicals for wolf population management, aligning with contemporary conservation goals.

LanDis: the disease landscape explorer.

From a network medicine perspective, a disease is the consequence of perturbations on the interactome. These perturbations tend to appear in a specific neighbourhood on the interactome, the disease module, and modules related to phenotypically similar diseases tend to be located in close-by regions. We present LanDis, a freely available web-based interactive tool ( https://paccanarolab.org/landis ) that allows domain experts, medical doctors and the larger scientific community to graphically navigate the interactome distances between the modules of over 44 million pairs of heritable diseases. The map-like interface provides detailed comparisons between pairs of diseases together with supporting evidence. Every disease in LanDis is linked to relevant entries in OMIM and UniProt, providing a starting point for in-depth analysis and an opportunity for novel insight into the aetiology of diseases as well as differential diagnosis.

Structurally-informed human interactome reveals proteome-wide perturbations by disease mutations.

Human genome sequencing studies have identified numerous loci associated with complex diseases. However, translating human genetic and genomic findings to disease pathobiology and therapeutic discovery remains a major challenge at multiscale interactome network levels. Here, we present a deep-learning-based ensemble framework, termed PIONEER (Protein-protein InteractiOn iNtErfacE pRediction), that accurately predicts protein binding partner-specific interfaces for all known protein interactions in humans and seven other common model organisms, generating comprehensive structurally-informed protein interactomes. We demonstrate that PIONEER outperforms existing state-of-the-art methods. We further systematically validated PIONEER predictions experimentally through generating 2,395 mutations and testing their impact on 6,754 mutation-interaction pairs, confirming the high quality and validity of PIONEER predictions. We show that disease-associated mutations are enriched in PIONEER-predicted protein-protein interfaces after mapping mutations from ~60,000 germline exomes and ~36,000 somatic genomes. We identify 586 significant protein-protein interactions (PPIs) enriched with PIONEER-predicted interface somatic mutations (termed oncoPPIs) from pan-cancer analysis of ~11,000 tumor whole-exomes across 33 cancer types. We show that PIONEER-predicted oncoPPIs are significantly associated with patient survival and drug responses from both cancer cell lines and patient-derived xenograft mouse models. We identify a landscape of PPI-perturbing tumor alleles upon ubiquitination by E3 ligases, and we experimentally validate the tumorigenic KEAP1-NRF2 interface mutation p.Thr80Lys in non-small cell lung cancer. We show that PIONEER-predicted PPI-perturbing alleles alter protein abundance and correlates with drug responses and patient survival in colon and uterine cancers as demonstrated by proteogenomic data from the National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium. PIONEER, implemented as both a web server platform and a software package, identifies functional consequences of disease-associated alleles and offers a deep learning tool for precision medicine at multiscale interactome network levels.

Do fossorial water voles have a functional vomeronasal organ? A histological and immunohistochemical study.

The fossorial water vole, Arvicola scherman, is an herbivorous rodent that causes significant agricultural damages. The application of cairomones and alarm pheromones emerges as a promising sustainable method to improve its integrated management. These chemical signals would induce stress responses that could interfere with the species regular reproductive cycles and induce aversive reactions, steering them away from farmlands and meadows. However, there is a paucity of information regarding the water vole vomeronasal system, both in its morphological foundations and its functionality, making it imperative to understand the same for the application of chemical communication in pest control. This study fills the existing gaps in knowledge through a morphological and immunohistochemical analysis of the fossorial water vole vomeronasal organ. The study is primarily microscopic, employing two approaches: histological, using serial sections stained with various dyes (hematoxylin-eosin, Periodic acid-Schiff, Alcian blue, Nissl), and immunohistochemical, applying various markers that provide morphofunctional and structural information. These procedures have confirmed the presence of a functional vomeronasal system in fossorial water voles, characterized by a high degree of differentiation and a significant expression of cellular markers indicative of active chemical communication in this species.

Immunohistological study of the unexplored vomeronasal organ of an endangered mammal, the dama gazelle (Nanger dama).

Dama gazelle is a threatened and rarely studied species found primarily in northern Africa. Human pressure has depleted the dama gazelle population from tens of thousands to a few hundred individuals. Since 1970, a founder population consisting of the last 17 surviving individuals in Western Sahara has been maintained in captivity, reproducing naturally. In preparation for the future implementation of assisted reproductive technology, certain aspects of dama gazelle reproductive biology have been established. However, the role played by semiochemical-mediated communications in the sexual behavior of dama gazelle remains unknown due partially to a lack of a neuroanatomical or morphofunctional characterization of the dama gazelle vomeronasal organ (VNO), which is the sensory organ responsible for pheromone processing. The present study characterized the dama gazelle VNO, which appears fully equipped to perform neurosensory functions, contributing to current understanding of interspecies VNO variability among ruminants. By employing histological, lectin-histochemical, and immunohistochemical techniques, we conducted a detailed morphofunctional evaluation of the dama gazelle VNO along its entire longitudinal axis. Our findings of significant structural and neurochemical transformation along the entire VNO suggest that future studies of the VNO should take a similar approach. The present study contributes to current understanding of dama gazelle VNO, providing a basis for future studies of semiochemical-mediated communications and reproductive management in this species. RESEARCH HIGHLIGHTS: This exhaustive immunohistological study of the vomeronasal organ (VNO) of the dama gazelle provides the first evidence of notable differences in the expression of neuronal markers along the rostrocaudal axis of the VNO. This provides a morphological basis for the implementation of pheromones in captive populations of dama gazelle.

Chimeric Peptides Derived from Bovine Lactoferricin and Buforin II: Antifungal Activity against Reference Strains and Clinical Isolates of Candida spp.

Antimicrobial peptides (AMPs) are considered to be a valuable source for the identification and/or design of promising candidates for the development of antifungal treatments, since they have advantages such as lower tendency to induce resistance, ease of production, and high purity and safety. Bovine lactoferricin (LfcinB) and buforin II (BFII) are AMPs to which great antimicrobial potential has been attributed. The minimum motives with antimicrobial activity derived from LfcinB and BFII are RRWQWR and RLLR, respectively. Nine chimeras containing the minimum motives of both peptides were synthesized and their antifungal activity against fluconazole (FLC)-sensitive and resistant C. albicans, C. glabrata, and C. auris strains was evaluated. The results showed that peptides C9: (RRWQWR)2K-Ahx-RLLRRRLLR and C6: KKWQWK-Ahx-RLLRRLLR exhibited the greatest antifungal activity against two strains of C. albicans, a FLC-sensitive reference strain and a FLC-resistant clinical isolate; no medically significant results were observed with the other chimeras evaluated (MIC ~200 µg/mL). The chimera C6 was also active against sensitive and resistant strains of C. glabrata and C. auris. The combination of branched polyvalent chimeras together with FLC showed a synergistic effect against C. albicans. In addition to exhibiting antifungal activity against reference strains and clinical isolates of Candida spp., they also showed antibacterial activity against both Gram-positive and Gram-negative bacteria, suggesting that these chimeras exhibit a broad antimicrobial spectrum and can be considered to be promising molecules for therapeutic applications.

Comparative Neuroanatomical Study of the Main Olfactory Bulb in Domestic and Wild Canids: Dog, Wolf and Red Fox.

The sense of smell plays a fundamental role in mammalian survival. There is a considerable amount of information available on the vomeronasal system of both domestic and wild canids. However, much less information is available on the canid main olfactory system, particularly at the level of the main olfactory bulb. Comparative study of the neuroanatomy of wild and domestic canids provides an excellent model for understanding the effects of selection pressure associated with domestication. A comprehensive histological (hematoxylin-eosin, Nissl, Tolivia and Gallego's Trichrome stains), lectin (UEA, LEA) and immunohistochemical (Gαo, Gαi2, calretinin, calbindin, olfactory marker protein, glial fibrillary acidic protein, microtubule-associated protein 2) study of the olfactory bulbs of the dog, fox and wolf was performed. Our study found greater macroscopic development of the olfactory bulb in both the wolf and fox compared to the dog. At the microscopic level, all three species show a well-developed pattern of lamination and cellularity typical of a macrosmatic animal. However, greater development of cellularity in the periglomerular and mitral layers of wild canids is characteristic. Likewise, the immunohistochemical study shows comparable results between the three species, but with a noticeably higher expression of markers in wild canids. These results suggest that the reduction in encephalization experienced in dogs due to domestication also corresponds to a lower degree of morphological and neurochemical differentiation of the olfactory bulb.

Unlike Chloroquine, Mefloquine Inhibits SARS-CoV-2 Infection in Physiologically Relevant Cells.

Despite the development of specific therapies against severe acute respiratory coronavirus 2 (SARS-CoV-2), the continuous investigation of the mechanism of action of clinically approved drugs could provide new information on the druggable steps of virus-host interaction. For example, chloroquine (CQ)/hydroxychloroquine (HCQ) lacks in vitro activity against SARS-CoV-2 in TMPRSS2-expressing cells, such as human pneumocyte cell line Calu-3, and likewise, failed to show clinical benefit in the Solidarity and Recovery clinical trials. Another antimalarial drug, mefloquine, which is not a 4-aminoquinoline like CQ/HCQ, has emerged as a potential anti-SARS-CoV-2 antiviral in vitro and has also been previously repurposed for respiratory diseases. Here, we investigated the anti-SARS-CoV-2 mechanism of action of mefloquine in cells relevant for the physiopathology of COVID-19, such as Calu-3 cells (that recapitulate type II pneumocytes) and monocytes. Molecular pathways modulated by mefloquine were assessed by differential expression analysis, and confirmed by biological assays. A PBPK model was developed to assess mefloquine's optimal doses for achieving therapeutic concentrations. Mefloquine inhibited SARS-CoV-2 replication in Calu-3, with an EC50 of 1.2 µM and EC90 of 5.3 µM. It reduced SARS-CoV-2 RNA levels in monocytes and prevented virus-induced enhancement of IL-6 and TNF-α. Mefloquine reduced SARS-CoV-2 entry and synergized with Remdesivir. Mefloquine's pharmacological parameters are consistent with its plasma exposure in humans and its tissue-to-plasma predicted coefficient points suggesting that mefloquine may accumulate in the lungs. Altogether, our data indicate that mefloquine's chemical structure could represent an orally available host-acting agent to inhibit virus entry.

Machine learning and network medicine approaches for drug repositioning for COVID-19.

We present two machine learning approaches for drug repurposing. While we have developed them for COVID-19, they are disease-agnostic. The two methodologies are complementary, targeting SARS-CoV-2 and host factors, respectively. Our first approach consists of a matrix factorization algorithm to rank broad-spectrum antivirals. Our second approach, based on network medicine, uses graph kernels to rank drugs according to the perturbation they induce on a subnetwork of the human interactome that is crucial for SARS-CoV-2 infection/replication. Our experiments show that our top predicted broad-spectrum antivirals include drugs indicated for compassionate use in COVID-19 patients; and that the ranking obtained by our kernel-based approach aligns with experimental data. Finally, we present the COVID-19 repositioning explorer (CoREx), an interactive online tool to explore the interplay between drugs and SARS-CoV-2 host proteins in the context of biological networks, protein function, drug clinical use, and Connectivity Map. CoREx is freely available at: https://paccanarolab.org/corex/.

Does a third intermediate model for the vomeronasal processing of information exist? Insights from the macropodid neuroanatomy.

The study of the α-subunit of Gi2 and Go proteins in the accessory olfactory bulb (AOB) was crucial for the identification of the two main families of vomeronasal receptors, V1R and V2R. Both families are expressed in the rodent and lagomorph AOBs, according to a segregated model characterized by topographical anteroposterior zonation. Many mammal species have suffered from the deterioration of the Gαo pathway and are categorized as belonging to the uniform model. This scenario has been complicated by characterization of the AOB in the tammar wallaby, Notamacropus eugenii, which appears to follow a third model of vomeronasal organization featuring exclusive Gαo protein expression, referred to as the intermediate model, which has not yet been replicated in any other species. Our morphofunctional study of the vomeronasal system (VNS) in Bennett's wallaby, Notamacropus rufogriseus, provides further information regarding this third model of vomeronasal transduction. A comprehensive histological, lectin, and immunohistochemical study of the Bennett's wallaby VNS was performed. Anti-Gαo and anti-Gαi2 antibodies were particularly useful because they labeled the transduction cascade of V2R and V1R receptors, respectively. Both G proteins showed canonical immunohistochemical labeling in the vomeronasal organ and the AOB, consistent with the anterior-posterior zonation of the segregated model. The lectin Ulex europaeus agglutinin selectively labeled the anterior AOB, providing additional evidence for the segregation of vomeronasal information in the wallaby. Overall, the VNS of the Bennett's wallaby shows a degree of differentiation and histochemical and neurochemical diversity comparable to species with greater VNS development. The existence of the third intermediate type in vomeronasal information processing reported in Notamacropus eugenii is not supported by our lectin-histochemical and immunohistochemical findings in Notamacropus rufogriseus.

Can domestication shape Canidae brain morphology? The accessory olfactory bulb of the red fox as a case in point.

BACKGROUND: The accessory olfactory bulb (AOB) is the first integrative center of the vomeronasal system (VNS), and the general macroscopic, microscopic, and neurochemical organizational patterns of the AOB differ fundamentally among species. Therefore, the low degree of differentiation observed for the dog AOB is surprising. As the artificial selection pressure exerted on domestic dogs has been suggested to play a key role in the involution of the dog VNS, a wild canid, such as the fox, represents a useful model for studying the hypothetical effects of domestication on the AOB morphology. METHODS: A comprehensive histological, lectin-histochemical, and immunohistochemical study of the fox AOB was performed. Anti-Gαo and anti-Gαi2 antibodies were particularly useful, as they label the transduction cascade of the vomeronasal receptor types 1 (V1R) and 2 (V2R), respectively. Other employed antibodies included those against proteins such as microtubule-associated protein 2 (MAP-2), tubulin, glial fibrillary acidic protein, growth-associated protein 43 (GAP-43), olfactory marker protein (OMP), calbindin, and calretinin. RESULTS: The cytoarchitecture of the fox AOB showed a clear lamination, with neatly differentiated layers; a highly developed glomerular layer, rich in periglomerular cells; and large inner cell and granular layers. The immunolabeling of Gαi2, OMP, and GAP-43 delineated the outer layers, whereas Gαo and MAP-2 immunolabeling defined the inner layers. MAP-2 characterized the somas of AOB principal cells and their dendritic trees. Anti-calbindin and anti-calretinin antibodies discriminated neural subpopulations in both the mitral-plexiform layer and the granular cell layer, and the lectin Ulex europeus agglutinin I (UEA-I) showed selectivity for the AOB and the vomeronasal nerves. CONCLUSION: The fox AOB presents unique characteristics and a higher degree of morphological development compared with the dog AOB. The comparatively complex neural basis for semiochemical information processing in the fox compared with that observed in dogs suggests loss of AOB anatomical complexity during the evolutionary history of dogs and opens a new avenue of research for studying the effects of domestication on brain structures.

The olfactory limbus of the red fox (Vulpes vulpes). New insights regarding a noncanonical olfactory bulb pathway.

Introduction: The olfactory system in most mammals is divided into several subsystems based on the anatomical locations of the neuroreceptor cells involved and the receptor families that are expressed. In addition to the main olfactory system and the vomeronasal system, a range of olfactory subsystems converge onto the transition zone located between the main olfactory bulb (MOB) and the accessory olfactory bulb (AOB), which has been termed the olfactory limbus (OL). The OL contains specialized glomeruli that receive noncanonical sensory afferences and which interact with the MOB and AOB. Little is known regarding the olfactory subsystems of mammals other than laboratory rodents. Methods: We have focused on characterizing the OL in the red fox by performing general and specific histological stainings on serial sections, using both single and double immunohistochemical and lectin-histochemical labeling techniques. Results: As a result, we have been able to determine that the OL of the red fox (Vulpes vulpes) displays an uncommonly high degree of development and complexity. Discussion: This makes this species a novel mammalian model, the study of which could improve our understanding of the noncanonical pathways involved in the processing of chemosensory cues.

A comprehensive structural, lectin and immunohistochemical characterization of the zebrafish olfactory system.

Fish chemosensory olfactory receptors allow them to detect a wide range of water-soluble chemicals, that mediate fundamental behaviours. Zebrafish possess a well-developed sense of smell which governs reproduction, appetite, and fear responses. The spatial organization of functional properties within the olfactory epithelium and bulb are comparable to those of mammals, making this species suitable for studies of olfactory differentiation and regeneration and neuronal representation of olfactory information. The advent of genomic techniques has been decisive for the discovery of specific olfactory cell types and the identification of cell populations expressing vomeronasal receptors. These advances have marched ahead of morphological and neurochemical studies. This study aims to fill the existing gap in specific histological, lectin-histochemical and immunohistochemical studies on the olfactory rosette and the olfactory bulb of the zebrafish. Tissue dissection and microdissection techniques were employed, followed by histological staining techniques, lectin-histochemical labelling (UEA, LEA, BSI-B4) and immunohistochemistry using antibodies against G proteins subunits αo and αi2, growth-associated protein-43, calbindin, calretinin, glial-fibrillary-acidic-protein and luteinizing-hormone-releasing-hormone. The results obtained enrich the available information on the neurochemical patterns of the zebrafish olfactory system, pointing to a greater complexity than the one currently considered, especially when taking into account the peculiarities of the nonsensory epithelium.

Neuroanatomical and Immunohistological Study of the Main and Accessory Olfactory Bulbs of the Meerkat (Suricata suricatta).

We approached the study of the main (MOB) and accessory olfactory bulbs (AOB) of the meerkat (Suricata suricatta) aiming to fill important gaps in knowledge regarding the neuroanatomical basis of olfactory and pheromonal signal processing in this iconic species. Microdissection techniques were used to extract the olfactory bulbs. The samples were subjected to hematoxylin-eosin and Nissl stains, histochemical (Ulex europaeus agglutinin, Lycopersicon esculentum agglutinin) and immunohistochemical labelling (Gαo, Gαi2, calretinin, calbindin, olfactory marker protein, glial fibrillary acidic protein, microtubule-associated protein 2, SMI-32, growth-associated protein 43). Microscopically, the meerkat AOB lamination pattern is more defined than the dog's, approaching that described in cats, with well-defined glomeruli and a wide mitral-plexiform layer, with scattered main cells and granular cells organized in clusters. The degree of lamination and development of the meerkat MOB suggests a macrosmatic mammalian species. Calcium-binding proteins allow for the discrimination of atypical glomerular subpopulations in the olfactory limbus between the MOB and AOB. Our observations support AOB functionality in the meerkat, indicating chemosensory specialization for the detection of pheromones, as identified by the characterization of the V1R vomeronasal receptor family and the apparent deterioration of the V2R receptor family.

The vomeronasal system of the newborn capybara: a morphological and immunohistochemical study.

The vomeronasal system (VNS) is responsible for the perception mainly of pheromones and kairomones. Primarily studied in laboratory rodents, it plays a crucial role in their socio-sexual behaviour. As a wild rodent, the capybara offers a more objective and representative perspective to understand the significance of the system in the Rodentia, avoiding the risk of extrapolating from laboratory rodent strains, exposed to high levels of artificial selection pressure. We have studied the main morphological and immunohistochemical features of the capybara vomeronasal organ (VNO) and accessory olfactory bulb (AOB). The study was done in newborn individuals to investigate the maturity of the system at this early stage. We used techniques such as histological stains, lectins-labelling and immunohistochemical characterization of a range of proteins, including G proteins (Gαi2, Gαo) and olfactory marking protein. As a result, we conclude that the VNS of the capybara at birth is capable of establishing the same function as that of the adult, and that it presents unique features as the high degree of differentiation of the AOB and the active cellular migration in the vomeronasal epithelium. All together makes the capybara a promising model for the study of chemical communication in the first days of life.

The vomeronasal organ of wild canids: the fox (Vulpes vulpes) as a model.

The vomeronasal system (VNS) has been extensively studied within specific animal families, such as Rodentia. However, the study of the VNS in other families, such as Canidae, has long been neglected. Among canids, the vomeronasal organ (VNO) has only been studied in detail in the dog, and no studies have examined the morphofunctional or immunohistochemical characteristics of the VNS in wild canids, which is surprising, given the well-known importance of chemical senses for the dog and fox and the likelihood that the VNS plays roles in the socio-reproductive physiology and behaviours of these species. In addition, characterising the fox VNS could contribute to a better understanding of the domestication process that occurred in the dog, as the fox would represent the first wild canid to be studied in depth. Therefore, the aim of this study was to analyze the morphological and immunohistochemical characteristics of the fox VNO. Tissue dissection and microdissection techniques were employed, followed by general and specific histological staining techniques, including with immunohistochemical and lectin-histochemical labelling strategies, using antibodies against olfactory marker protein (OMP), growth-associated protein 43 (GAP-43), calbindin (CB), calretinin (CR), α-tubulin, Gαo, and Gαi2 proteins, to highlight the specific features of the VNO in the fox. This study found significant differences in the VNS between the fox and the dog, particularly concerning the expression of Gαi2 and Gαo proteins, which were associated with the expression of the type 1 vomeronasal receptors (V1R) and type 2 vomeronasal receptors (V2R), respectively, in the vomeronasal epithelium. Both are immunopositive in foxes, as opposed to the dog, which only expresses Gαi2. This finding suggests that the fox possesses a well-developed VNO and supports the hypothesis that a profound transformation in the VNS is associated with domestication in the canid family. Furthermore, the unique features identified in the fox VNO confirm the necessity of studying the VNS system in different species to better comprehend specific phylogenetic aspects of the VNS.

[Ask-Upmark kidney: description of a case and review of the literature]. / Riñón de Ask--Upmark: descripción de un caso y revisión en la literatura.

We present a 15-year-old male patient diagnosed histopathologically as suffering from Ask-Upmark kidney, in the absence of vesicoureteral reflux and with hypertension. The first clinical manifestation was completely atypical: right loin pain, with so many agudisation treated at our emergency serve that justified a thorough study. The pathogenesis of the Ask-Upmark kidney is still unknown; some authors defend the congenital malformation hypothesis, as it was first described in 1929, but there are groups who support the Ask-Upmark kidney as a form of reflux nephropathy. After our description we present a review of the literature.