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Abstract Fat accumulation, de novo lipogenesis, and glycolysis are key drivers of hepatocyte reprogramming and the consequent metabolic dysfunction-associated steatotic liver disease (MASLD). Here we report that obesity leads to dysregulated expression of hepatic protein-tyrosine phosphatases (PTPs). PTPRK was found to be increased in steatotic hepatocytes in both humans and mice, and correlates positively with PPARγ-induced lipogenic signaling. High-fat-fed PTPRK knockout male and female mice have lower weight gain and reduced hepatic fat accumulation. Phosphoproteomic analysis in primary hepatocytes and hepatic metabolomics identified fructose-1,6-bisphosphatase 1 and glycolysis as PTPRK targets in metabolic reprogramming. Mechanistically, PTPRK-induced glycolysis enhances PPARγ and lipogenesis in hepatocytes. Silencing PTPRK in liver cancer cell lines reduces colony-forming capacity and high-fat-fed PTPRK knockout mice exposed to a hepatic carcinogen develop smaller tumours. Our study defines the role of PTPRK in the regulation of hepatic glycolysis, lipid metabolism, and tumour development in obesity.

Abstract Background The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or ‘endozepine’) increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer. Methods We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing. Results Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers. Conclusion These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance.

Acyl CoA binding protein (ACBP, which is encoded by diazepam binding inhibitor, DBI) acts on the gamma-amino butyric acid (GABA) receptor type A via a specific binding site that is shared by diazepam and other benzodiazepines. Both ACBP/DBI and benzodiazepines act as positive allosteric modulators, hence increasing GABA effects on this receptor. Recently, we found that ACBP/DBI acts as an endogenous immunosuppressor, meaning that its antibody-mediated neutralization has immunostimulatory effects and enhances the efficacy of immunotherapy and chemoimmunotherapy in mouse models. Driven by these considerations, we investigated whether diazepam administration in mice would reverse the beneficial effects of ACBP/DBI neutralization on cancer chemoimmunotherapy. Indeed, diazepam abolished the therapeutic of anti-ACBP/DBI antibodies, supporting the idea that diazepam exerts immunosuppressive properties. Of note, treatment with benzodiazepines was associated with poor clinical responses to chemoimmunotherapy in patients with non-small cell lung cancer (NSCLC) as compared to individuals not receiving any psychotropic drugs. Medication with other psychotropic drugs than benzodiazepines did not compromise the outcome of chemoimmunotherapy, indicating that this immunosuppressive effect was benzodiazepine specific. We conclude that benzodiazepines may confer systemic immunosuppression. This hypothesis requires further epidemiological and clinical confirmation.

Abstract Acyl-CoA binding protein (ACBP) encoded by diazepam binding inhibitor (DBI) is an extracellular inhibitor of autophagy acting on the gamma-aminobutyric acid A receptor (GABAAR) γ2 subunit (GABAARγ2). Here, we show that lipoanabolic diets cause an upregulation of GABAARγ2 protein in liver hepatocytes but not in other major organs. ACBP/DBI inhibition by systemically injected antibodies has been demonstrated to mediate anorexigenic and organ-protective, autophagy-dependent effects. Here, we set out to develop a new strategy for developing ACBP/DBI antagonists. For this, we built a molecular model of the interaction of ACBP/DBI with peptides derived from GABAARγ2. We then validated the interaction between recombinant and native ACBP/DBI protein and a GABAARγ2-derived eicosapeptide (but not its F77I mutant) by pull down experiments or surface plasmon resonance. The GABAARγ2-derived eicosapeptide inhibited the metabolic activation of hepatocytes by recombinant ACBP/DBI protein in vitro. Moreover, the GABAARγ2-derived eicosapeptide (but not its F77I-mutated control) blocked appetite stimulation by recombinant ACBP/DBI in vivo, induced autophagy in the liver, and protected mice against the hepatotoxin concanavalin A. We conclude that peptidomimetics disrupting the interaction between ACBP/DBI and GABAARγ2 might be used as ACBP/DBI antagonists. This strategy might lead to the future development of clinically relevant small molecules of the ACBP/DBI system.

We reviewed information about mammals naturally infected by highly pathogenic avian influenza A virus subtype H5N1 during 2 periods: the current panzootic (2020–2023) and previous waves of infection (2003–2019). In the current panzootic, 26 countries have reported >48 mammal species infected by H5N1 virus; in some cases, the virus has affected thousands of individual animals. The geographic area and the number of species affected by the current event are considerably larger than in previous waves of infection. The most plausible source of mammal infection in both periods appears to be close contact with infected birds, including their ingestion. Some studies, especially in the current panzootic, suggest that mammal-to-mammal transmission might be responsible for some infections; some mutations found could help this avian pathogen replicate in mammals. H5N1 virus may be changing and adapting to infect mammals. Continuous surveillance is essential to mitigate the risk for a global pandemic.

IntroductionSchistosomiasis (SM) is a parasitic disease caused by Schistosoma mansoni. SM causes chronic inflammation induced by parasitic eggs, with collagen/fibrosis deposition in the granuloma process in the liver, spleen, central nervous system, kidneys, and lungs. Pulmonary arterial hypertension (PAH) is a clinical manifestation characterized by high pressure in the pulmonary circulation and right ventricular overload. This study investigated the production of functional autoantibodies (fAABs) against the second loop of the G-protein-coupled receptor (GPCR) in the presence of hepatic and PAH forms of human SM.MethodsUninfected and infected individuals presenting acute and chronic manifestations (e.g., hepatointestinal, hepato-splenic without PAH, and hepato-splenic with PAH) of SM were clinically evaluated and their blood was collected to identify fAABs/GPCRs capable of recognizing endothelin 1, angiotensin II, and a-1 adrenergic receptor. Human serum was analyzed in rat cardiomyocytes cultured in the presence of the receptor antagonists urapidil, losartan, and BQ123.ResultsThe fAABs/GPCRs from chronic hepatic and PAH SM individuals, but not from acute SM individuals, recognized the three receptors. In the presence of the antagonists, there was a reduction in beating rate changes in cultured cardiomyocytes. In addition, binding sites on the extracellular domain functionality of fAABs were identified, and IgG1 and/or IgG3 antibodies were found to be related to fAABs.ConclusionOur data suggest that fAABs against GPCR play an essential role in vascular activity in chronic SM (hepatic and PAH) and might be involved in the development of hypertensive forms of SM.

Summary: The ecosystem services framework is essential for biodiversity conservation, emphasizing the role of nature in achieving sustainable development goals (SDGs). This study offers a global view on vulture-associated ecosystem services and their SDG contributions, based on insights from 206 experts. The findings reveal global consensus on the importance of vultures in regulation and maintenance services, such as waste recycling and disease control. Cultural services attributed to vultures are moderate and vary regionally. Provisioning services are consistently rated low across all regions. Experts’ views on vultures' key ecosystem roles are often biased toward well-known services and may not align with all scientific evidence. The study emphasizes vultures’ role in achieving SDGs, particularly impacting life on land and health, and calls for reevaluating their contribution to sustainable practices. It stresses the need to customize conservation to regional values and perceptions, recognizing vultures’ critical role in ecological balance, public health, and sustainable development.

We describe the evolution of the outbreak of Highly Pathogenic Avian Influenza (HPAI) A(H5N1) in sea lions (Otaria flavescens) of South America. At least 24,000 sea lions died in Peru, Chile, Argentina, Uruguay, and Brazil between January–October 2023. The most plausible route of infection is cohabiting with or foraging on infected birds. However, we urge a detailed evaluation of the sea lions actual source of infection given that the concomitant massive wild bird mortalities registered in the Pacific Ocean did not occur in the Atlantic Ocean.

We report a massive mortality of 5,224 sea lions (Otaria flavescens) in Peru that seemed to be associated with highly pathogenic avian influenza A(H5N1) virus infection. The transmission pathway may have been through the close contact of sea lions with infected wild birds. We recommend evaluating potential virus transmission among sea lions.

Abstract Protein regulator of cytokinesis 1 (PRC1) is involved in cytokinesis. Growing evidence suggests the association of PRC1 with multiple cancers. Here, we unveil that, in 28 cancer types, PRC1 is higher expressed in tumor tissues than in non-malignant tissues. Overexpression of PRC1 indicates unfavorable prognostic value, especially in ACC, LGG, KIRP, LICH, LUAD, MESO, PAAD, SARC and UCEC, while methylation of the PRC1 gene at sites associated with its inactivation has a favorable prognostic value in ACC, KIRP, LUAD, MESO, KIRP and LGG. Differentially expressed genes (DEGs) associated with high (> median) PRC1 expression contribute to key signaling pathways related with cell cycle, DNA damage and repair, EMT, cell migration, invasion and cell proliferation in most cancer types. More specifically, the DEGs involved in RAS/RAF/MAPK, PI3K/AKT, WNT, NOTCH, TGF-β, integrin, EMT process, focal adhesion, RHO GTPase-related pathway or microtubule cytoskeleton regulation are upregulated when PRC1 expression is above median, as confirmed for most cancers. Most importantly, high expression of PRC1 appears to be associated with an overabundance of poor-prognosis TH2 cells. Furthermore, positive correlations of PRC1 and some immune checkpoint genes (CD274, CTLA4, HAVCR2, LAG3, PDCD1, PDCD1LG2, TIGIT, and CD86) were observed in several cancers, especially BLCA, BRCA, KIRC, LUAD, LIHC, PRAD and THCA. These findings plead in favor of further studies validating the diagnostic and prognostic impact of PRC1 as well as the elaboration of pharmacological strategies for targeting PRC1.

Abstract While natural protected areas are conceived for nature conservation, humans and their activities must also be considered. Conflict between the public and managers of protected areas can be minimized by regulations that clearly communicate which activities are allowed. Domestic dogs (Canis lupus familiaris) affect threatened species and impact numerous protected areas. In this study we evaluate: (1) the accessibility and clarity of regulations regarding dog access to protected areas in Argentina, (2) the public’s knowledge of these regulations, (3) the public’s expectations of the regulations (4) which institutions people consider should act when dog aggression occurs, and (5) measures suggested by people when dog aggression occurs. Poor accessibility and clarity of regulations were associated with poor public knowledge of them; there was also an association between visited protected areas that did not mention regulations and respondents who reported not knowing whether dogs were allowed or thinking dogs were allowed. In general, the respondents supported measures to regulate dog access to protected areas and the control of problematic dogs. We discuss several aspects that lead to a lack of clarity on dog regulations in protected areas and suggest approaches that could be used to overcome this conservation problem.

Protein kinase CK1δ (CK1δ) is a serine-threonine/kinase that modulates different physiological processes, including the cell cycle, DNA repair, and apoptosis. CK1δ overexpression, and the consequent hyperphosphorylation of specific proteins, can lead to sleep disorders, cancer, and neurodegenerative diseases. CK1δ inhibitors showed anticancer properties as well as neuroprotective effects in cellular and animal models of Parkinson’s and Alzheimer’s diseases and amyotrophic lateral sclerosis. To obtain new ATP-competitive CK1δ inhibitors, three sets of benzimidazole-2-amino derivatives were synthesized (1–32), bearing different substituents on the fused benzo ring (R) and diverse pyrazole-containing acyl moieties on the 2-amino group. The best-performing derivatives were those featuring the (1H-pyrazol-3-yl)-acetyl moiety on the benzimidazol-2-amino scaffold (13–32), which showed CK1δ inhibitor activity in the low micromolar range. Among the R substituents, 5-cyano was the most advantageous, leading to a compound endowed with nanomolar potency (23, IC50 = 98.6 nM). Molecular docking and dynamics studies were performed to point out the inhibitor–kinase interactions.

En el presente artículo analizamos las representaciones históricas y presentes del topónimo “Valcheta”, nombre actual de la localidad ubicada en la provincia de Río Negro, Argentina. Como objetivo se pretende examinar su discusión toponímica vinculada a dos lenguas indígenas, el mapuzungun y günün a iajüch, con el fin de comprender las disputas de clasificación históricas y actuales. A través de consultas de documentos históricos, principalmente cartografías del siglo xix y xx, en el Archivo del Museo Provincial “María Inés Kopp”, ubicado en la localidad de Valcheta, como en el Archivo Histórico de Río Negro de Viedma, y consultas virtuales en la Biblioteca Nacional Mariano Moreno de Buenos Aires, analizamos esta discusión. Asimismo, mediante el trabajo etnográfico en Valcheta con una comunidad indígena mapuche-tehuelche, indagamos en los discursos vinculados a las transformaciones toponímicas. Como resultado, este trabajo permitió identificar cómo el topónimo Valcheta, referenciado en distintas fuentes, ha cambiado a lo largo del tiempo en lo que refiere a los avances soberanos del Estado Nacional Argentino. Además, al entender que es un proceso de larga duración, atravesado por una lucha de clasificaciones que continúa en el presente, se habilita la comprensión de los sentidos indígenas locales. Finalmente, como conclusión, este análisis histórico y antropológico brinda la oportunidad de reflexionar sobre un problema mayor: la extranjerización del pueblo mapuche.

Power lines endanger birds around the world, as a large number of them are killed every year through electrocutions and collisions. This problem can have severe consequences at population level, particularly for threatened species. While this threat has been widely studied in different parts of the world, information from South America is scarce. Here, we review information from scientific and grey literature on the collision and electrocution of birds on power lines from this sub-continent. We complement this information with novel data provided by a citizen science project, electrical companies and field monitoring records. Our results show that although in South America scientific and anecdotal information on this topic is scarce, data suggests that this threat is present in many areas of this sub-continent and affects several species, some of which are seriously threatened. However, information on the most affected species, the number of individuals impacted, the most dangerous geographical areas and the effectiveness of mitigation action is scarce and mainly anecdotal. This is worrying, because South America is a hot spot of biodiversity with many threatened and endemic bird species. We urge conservationists to evaluate this problem in more detail, define areas where it is important to avoid power line installation and establish priority areas for implementation of effective mitigation actions. Scientific evidence shows that dangerous power lines require retrofitting, but this knowledge should also be applied to the new energy facilities and the establishment of national regulations, which would undoubtedly reduce the impact of this infrastructure on wildlife.

Abstract The metabolic syndrome (MetS) is a clinical manifestation strongly associated with cardiovascular disease, the main cause of death worldwide. In view of this scenario, many therapeutic proposals have appeared in order to optimize the treatment of individuals with MetS, including the practice of exercise training (ET) and the consumption of okra (O). The aim of the present study was to evaluate the effect of O consumption and/or ET in animals with MetS. In all, 32 male Zucker rats (fa/fa) at 10 weeks old were randomly distributed into four groups of 8 animals each: MetS, MetS+O, MetS+ET and MetS+ET+O, and 8 lean Zucker rats (fa/ +) comprised the control group. Okra was administered by orogastric gavage 2x/day (morning and night, 100 mg/kg), 5 days/week, for 6 weeks. The ET was performed on a treadmill 1x/day (afternoon), 5 days/week, 60 min/day, in an intensity of 70% of maximal capacity, for the same days of O treatment. It was found that, O consumption alone was able to promote improved insulin sensitivity (MetS 93.93 ± 8.54 mg/dL vs. MetS+O 69.95 ± 18.7 mg/dL, p ≤ 0.05, d = 1.65, CI = 50.32 −89.58, triglyceride reduction (MetS 492.9 ± 97.8 mg/dL vs. MetS+O 334.9 ± 98.0 mg/dL, p ≤ 0.05, d = 1.61, CI = 193.2–398.7). In addition, it promoted a reduction in systolic blood pressure (MetS 149.0 ± 9.3 mmHg vs. MetS+O 132.0 ± 11.4 mmHg, p ≤ 0.05, d = 1.63, CI = 120–140), prevented an increase in cardiac collagen (MetS 12.60 ± 2.08% vs. MetS+O 7.52 ± 0.77%, p ≤ 0.05, d = 3.24, CI = 6.56–8.49). When associated with ET, the results were similar. Thus, we conclude that O consumption combined or not with aerobic ET can have a protective effect on the cardiac tissue of rats with MetS.

Purpose: This study aimed to evaluate whether supplementation with L-arginine alone or in combination with physical exercise training can modulate rats' lipid and inflammatory profiles after a single intense exercise session. Methods: Male Wistar rats were divided into four different groups: control (C), trained (T), supplemented with L-arginine (C + A) and trained and supplemented (T + A). Animals from supplemented groups (C + A and T + A groups) received 300 mg/kg animal body weight L-arginine diluted in 30 mL of drinking water for 8 weeks. Exercise training protocol (moderate intensity--70% achieved in the maximum effort test) was held 5 days/week for 8 weeks. Results: Exercise training induced a decrease in the amount of plasma, cholesterol and triglyceride totals, and skeletal muscle VEGF and CINC. Supplementation alone showed a benefit by reducing LDL levels. Conclusion: Training combined with supplementation showed a pronounced reduction in skeletal muscle VEGF and CINC amount. L-arginine supplementation, especially when associated with the regular aerobic physical exercise at moderate intensity was able to improve not only plasma lipid profile but also the inflammatory response of skeletal muscle immediately after an exhaustive physical exercise session.

Abstract Acyl-coenzyme-A-binding protein (ACBP), also known as a diazepam-binding inhibitor (DBI), is a potent stimulator of appetite and lipogenesis. Bioinformatic analyses combined with systematic screens revealed that peroxisome proliferator-activated receptor gamma (PPARγ) is the transcription factor that best explains the ACBP/DBI upregulation in metabolically active organs including the liver and adipose tissue. The PPARγ agonist rosiglitazone-induced ACBP/DBI upregulation, as well as weight gain, that could be prevented by knockout of Acbp/Dbi in mice. Moreover, liver-specific knockdown of Pparg prevented the high-fat diet (HFD)-induced upregulation of circulating ACBP/DBI levels and reduced body weight gain. Conversely, knockout of Acbp/Dbi prevented the HFD-induced upregulation of PPARγ. Notably, a single amino acid substitution (F77I) in the γ2 subunit of gamma-aminobutyric acid A receptor (GABAAR), which abolishes ACBP/DBI binding to this receptor, prevented the HFD-induced weight gain, as well as the HFD-induced upregulation of ACBP/DBI, GABAAR γ2, and PPARγ. Based on these results, we postulate the existence of an obesogenic feedforward loop relying on ACBP/DBI, GABAAR, and PPARγ. Interruption of this vicious cycle, at any level, indistinguishably mitigates HFD-induced weight gain, hepatosteatosis, and hyperglycemia.

Background: Chronic Obstructive Pulmonary Disease is a high prevalence disease, characterized by a diffuse chronic lung inflammation and alveolar destruction. Aim: The purpose of this study is to evaluate the therapeutic effects of eugenol and its dimmer biseugenol, both isolated from Brazilian plant Nectandra leucantha (Lauraceae) on pulmonary alterations in a model of experimental emphysema that was induced by porcine pancreatic elastase (PPE). Material and Methods: First, we evaluated the anti-oxidative potential of both substances in silico. Posteriorly, C57BL/6 mice received 50 µl of PPE solution (intranasal instillation) for emphysema induction. Eugenol and biseugenol (20 mg/kg, i.p) was given for 8 days consecutively beginning 21 days after PPE instillation. Animals were euthanized on day 28, and lungs removed for histological analysis. Results: Biseugenol showed higher antioxidant potential. In vivo, both compounds reduced alveolar destruction measured by mean alveolar diameter (Lm) and the inflammatory cells in bone marrow, in bronchoalveolar lavage fluid (BALF) and in lung tissue that was induced by PPE. These treatments also reduced positive cells to IL-1β, IL-6, IL-17, NF-kB, MMP-9, and iNOS in lung tissue. Only eugenol reduced the expression of TIMP-1 and Nrf2 in lung tissue. No effects of both compounds were observed in collagen deposition and in SOD-1 and 2 positive expressions in lung tissue. Conclusion: These data indicate that eugenol and biseugenol were effective in controlling emphysema and lung inflammation. These effects can be due to controlling MMP-9 and TIMP-1 and by reduction of iNOS. Both compounds may be effective tools, combined or not with conventional medication, to be considered in emphysema treatment.

Abstract The evolution of large vultures linked to mountainous habitats was accompanied by extreme physiological and behavioral specializations for energetically efficient flights. However, little is known on the genetic traits associated with the evolution of these obligate soaring scavengers. Mitochondrial DNA plays a vital role in regulating oxidative stress and energy production, and hence may be an important target of selection for flight performance. Herein, we characterized the first mitogenomes of the Andean and California condors, the world’s heaviest flying birds and the only living representatives of the Vultur and Gymnogyps genus. We reconstructed the phylogenetic relationships and evaluated possible footprints of convergent evolution associated to the life-history traits and distributional range of vultures. Our phylogenomic analyses supported the independent evolution of vultures, with the origin of Cathartidae in the early Paleogene (~ 61 Mya), and estimated the radiation of extant condors during the late Miocene (~ 11 Mya). Selection analyses indicated that vultures exhibit signals of relaxation of purifying selection relative to other accipitrimorph raptors, possibly indicating the degeneration of flapping flight ability. Overall, our results suggest that the extreme specialization of vultures for efficient soaring flight has compensated the evolution of large body sizes mitigating the selection pressure on mtDNA.

El objetivo del estudio fue indagar si las prácticas de enseñanza desarrolladas en tiempos de aislamiento social preventivo obligatorio en Argentina favorecen la inclusión, los aprendizajes y la autonomía de los/as estudiantes con discapacidad intelectual, en opinión de sus profesionales de apoyo a la inclusión y de sus familias. Se realizó un diseño exploratorio-descriptivo, con un muestreo intencional. Se aplicó un cuestionario semiestructurado a 75 profesionales de apoyo a la inclusión y a 40 familias de niños/as y adolescentes con discapacidad intelectual incluidos en escuelas comunes de gestión estatal y privada de Córdoba (mayoritariamente) y otras provincias argentinas. Como resultado el Estado no ha logrado garantizar el acceso de sus estudiantes con discapacidad intelectual, en igualdad de condiciones, a la enseñanza remota de emergencia no solo por no asegurar la tecnología necesaria y la conectividad. La tarea docente se centró en planificaciones homogéneas dejando a los/as profesionales de apoyo externos las adaptaciones curriculares, la atención directa con el/la estudiante con discapacidad y el asesoramiento a las familias. El vínculo del docente con el/la estudiante con discapacidad intelectual muestra escasa comunicación, escucha y relación positiva. Como consecuencia muchos/as estudiantes no han alcanzado los objetivos de aprendizaje propuestos ni la autonomía esperada.

Abstract Content published on social media may affect user’s attitudes toward wildlife species. We evaluated viewers’ responses to videos published on a popular social medium, focusing particularly on how the content was framed (i.e., the way an issue is conveyed to transmit a certain meaning). We analyzed videos posted on YouTube that showed vultures interacting with livestock. The videos were negatively or positively framed, and we evaluated viewers’ opinions of these birds through the comments posted. We also analyzed negatively framed videos of mammalian predators interacting with livestock, to evaluate whether comments on this content were similar to those on vultures. We found that the framing of the information influenced the tone of the comments. Videos showing farmers talking about their livestock losses were more likely to provoke negative comments than videos not including farmer testimonies. The probability of negative comments being posted on videos about vultures was higher than for mammalian predators. Finally, negatively framed videos on vultures had more views over time than positive ones. Our results call for caution in the presentation of wildlife species online, and highlight the need for regulations to prevent the spread of misinformed videos that could magnify existing human-wildlife conflicts.

Currently, the number of patients with neurodegenerative pathologies is estimated at over one million, with consequences also on the economic level. Several factors contribute to their development, including overexpression of A2A adenosine receptors (A2AAR) in microglial cells and up-regulation and post-translational alterations of some casein kinases (CK), among them, CK-1δ. The aim of the work was to study the activity of A2AAR and CK1δ in neurodegeneration using in-house synthesized A2A/CK1δ dual anta-inhibitors and to evaluate their intestinal absorption. Experiments were performed on N13 microglial cells, which were treated with a proinflammatory CK cocktail to simulate an inflammatory state typical of neurodegenerative diseases. Results showed that the dual anta-inhibitors have the ability to counteract the inflammatory state, even if compound 2 is more active than compound 1. In addition, compound 2 displayed an important antioxidant effect similar to the reference compound ZM241385. Since many known kinase inhibitors are very often unable to cross lipid bilayer membranes, the ability of A2A/CK1δ double anta-inhibitors to cross the intestinal barrier was investigated by an everted gut sac assay. HPLC analysis revealed that both compounds are able to cross the intestinal barrier, making them promising candidates for oral therapy.

Immature individuals move from their natal area to the area where they settle and reproduce, and this may take several years. This process is essential for long-lived species such as vultures and condors, which spend long periods as immature and move extensively. We studied the movement behavior of 26 GPS-tagged immature Andean condors (Vultur gryphus) from northwestern Patagonia throughout the immature stage, analyzing whether these patterns differed according to age, sex and season. We found that season and age influenced home range size and flight distances, the warm season being when immature condors move most; movement patterns were greater in sub-adults than in juveniles. The age effect was associated with the sex of individuals, with males increasing their home range more than females. Our results provide the first description of how immature Andean condor movement patterns are affected by internal and external factors. This information could be key to understanding condor responses to environmental change and threats at different stages during their immature phase. Until now, condor conservation efforts have not considered the areas used by dispersing individuals. Our results increase our understanding of ranging behavior during the immature stage of this threatened bird, enabling us to improve the conservation policies and management strategies designed to protect them.

Neste artigo, procuramos rastrear nos textos de juventude de Marx os nexos que tornam possível Marx fundar uma ontologia do ser social a partir de duas críticas a Hegel, e de sua crítica a Feuerbach. Argumentamos que Marx visualiza na realidade histórico-concreta alemã, e no seu contato posterior com a economia política clássica via Engels o fundamento de uma reorientação radical da filosofia. Momento em que Marx terá como necessidade inverter o sentido de sua crítica em relação à Hegel sem renunciar as suas descobertas fundamentais, isto é, a prioridade descoberta na sociedade civil como chave heurística. A partir dessa crítica Marx irá fundamentar uma estrutura abrangente de sistematização que tem como pressuposto uma reorientação radical da filosofia em um sentido realmente universal, fundamentando ao mesmo tempo uma ciência positiva.

Human-wildlife interactions can be negative when the needs and behavior of wildlife negatively influence human goals, or vice-versa, and management of these interactions may lead to conflict. Here, we review information on negative interactions between humans and wildlife in South America contained in 136 scientific publications, focusing on terrestrial mammalian predators and raptors. We found that most studies were conducted in Brazil, Argentina, Chile and Colombia. The methodology most commonly used to investigate negative interactions was interviews with rural inhabitants. Studies were performed mainly on interactions involving large felids such as Panthera onca and Puma concolor, and —to a lesser extent— on other mammalian predators and raptors such as eagles or scavenger birds. The main drivers of negative interactions involved perceived or actual impacts on human economy (material) (e.g., livestock or crop losses) or were based on non-material (intangible) aspects (e.g., fear, myths, and religious beliefs). The studies showed that negative attitudes and perceptions toward terrestrial mammalian predators and raptors are widespread in South America. Although non-lethal strategies for mitigation of negative interactions have been proposed, most are not widely used and lethal controls are still very common. A multidisciplinary approach is required, based on multiple actions (e.g., improving livestock practices, running educational programs, increasing stakeholder involvement, providing farmers with solutions), which would minimize negative interactions and promote coexistence between humans and wildlife. This is key to maintaining threatened species, ecological interactions and healthy environments in the anthropized landscapes of biodiverse South America.

Predators relying on a particular prey as their main food resource are especially susceptible to fluctuation in prey availability. When prey abundance decreases they show a functional response by adjusting their diet. After this, predators may suffer a numerical response. These responses have been poorly studied in presence of alien invasive preys. The black-chested buzzard-eagle (Geranoaetus melanoleucus) is a large raptor inhabiting open areas of South America. Here we present the first long-term study on this eagle population tendency, analyzing functional and numerical responses associated with changes in the abundance of the exotic European hare (Lepus europaeus). We measured breeding performance and studied eagles’ diet during the breeding seasons of 1991, 1992, 2006, 2011 and 2012. We also estimated the relative abundance of hares in those years. Eagles diets changed over the years with a decrease in hare consumption. The number of eagles decreased from 1992 to less than half in 2012. Forty one percent of the total eagles observed in 1991/92, and 27% in 2006 were immature, while in 2011 and 2012 no immature were observed. We found similar tendencies of decrease in the abundance of hares which suggest that the decrease in eagles population may be related with the decreasing tendency of hares. No other factor that may have affected immature eagles abundance was evident in the area during this period. Our data suggest that changes in the abundance of an exotic lagomorph may lead numerical and functional responses in a top predator by affecting its diet, age structure, and ultimately abundance. Keywords: Numerical response, Functional response, Alien species, Top predator, Black-chested buzzard-eagle, European hare

The mass rapid transit hubs are adopted increasingly as significant public places of contemporary urban space, often charging of meanings and values superior to the mere functional sphere. The search for these places of beauty and relationship with heritage are making them a space for spatial experimentation that implies an increasingly active role for art and historical-archaeological heritage. The article aims to highlight possible frontiers for museum statutes outside the Museum and the potential of the infrastructure as a museum disseminated all under the city as a sort of City Wide Web Museum, thanks to the overcoming of the merely decorative dimension and the involvement of both artistic operations and archaeological finds.

Abstract Background Global positioning systems (GPS) and altimeters are increasingly used to monitor vertical space use by aerial species, a key aspect of their ecological niche, that we need to know to manage our own use of the airspace, and to protect those species. However, there are various sources of error in flight height data (“height” above ground, as opposed to “altitude” above a reference like the sea level). First the altitude is measured with a vertical error from the devices themselves. Then there is error in the ground elevation below the tracked animals, which translates into error in flight height computed as the difference between altitude and ground elevation. Finally, there is error in the horizontal position of the animals, which translates into error in the predicted ground elevation below the animals. We used controlled field trials, simulations, and the reanalysis of raptor case studies with state-space models to illustrate the effect of improper error management. Results Errors of a magnitude of 20 m appear in benign conditions for barometric altimeters and GPS vertical positioning (expected to be larger in more challenging context). These errors distort the shape of the distribution of flight heights, inflate the variance in flight height, bias behavioural state assignments, correlations with environmental covariates, and airspace management recommendations. Improper data filters such as removing all negative flight height records introduce several biases in the remaining dataset, and preclude the opportunity to leverage unambiguous errors to help with model fitting. Analyses that ignore the variance around the mean flight height, e.g., those based on linear models of flight height, and those that ignore the variance inflation caused by telemetry errors, lead to incorrect inferences. Conclusion The state-space modelling framework, now in widespread use by ecologists and increasingly often automatically implemented within on-board GPS data processing algorithms, makes it possible to fit flight models directly to the output of GPS devices, with minimal data pre-selection, and to analyse the full distribution of flight heights, not just the mean. In addition to basic research about aerial niches, behaviour quantification, and environmental interactions, we highlight the applied relevance of our recommendations for airspace management and the conservation of aerial wildlife.

The complications of Metabolic Syndrome (MetS) include kidney disease, and most dialysis patients are diagnosed with MetS. The benefit of exercise training (ET) for MetS treatment is already well defined in the literature, but the antidiabetic and antihyperlipidemic benefits of okra (O) have been discovered only recently. The aim of this study was to evaluate the effects of O and/or ET supplementation on renal function and histology; serum urea and creatinine value; inflammation (IL-6, IL-10, TNF-α) and oxidative stress in renal tissue. For this, 32 Zucker rats (fa/fa) were randomly separated into four groups of 8 animals each: Metabolic Syndrome (MetS), MetS + Okra (MetS + O), MetS + Exercise Training (MetS + ET), and MetS + Exercise Training and Okra (MetS + ET + O), and 8 Zucker lean (fa/+) rats comprised the Control group (CTL). Okra was administered by orogastric gavage 2x/day (morning and night, 100 mg/kg) and ET performed on the treadmill, at moderate intensity, 1h/day, 5x/week for 6 weeks. Although the renal function was not altered, the animals with MetS showed greater fibrotic deposition accompanied by a worse stage of renal injury, in addition to increased kidney weight. Although all interventions were beneficial in reducing fibrosis, only ET combined with O was able to improve the degree of renal tissue impairment. ET improved the anti-inflammatory status and reduced nitrite levels, but the combination of ET and O was more beneficial as regards catalase activity. Okra consumption alone did not promote changes in inflammatory cytokines and oxidative stress in the kidney. In conclusion, ET combined or not with O seems to be beneficial in preventing the progression of renal disease when renal function is not yet altered.

Based on a screening of a chemical library of A2A adenosine receptor (AR) antagonists, a series of di- and tri-substituted adenine derivatives were synthesized and tested for their ability to inhibit the activity of the enzyme casein kinase 1 delta (CK1δ) and to bind adenosine receptors (ARs). Some derivatives, here called “dual anta-inhibitors”, demonstrated good CK1δ inhibitory activity combined with a high binding affinity, especially for the A2AAR. The N6-methyl-(2-benzimidazolyl)-2-dimethyamino-9-cyclopentyladenine (17, IC50 = 0.59 μM and KiA2A = 0.076 μM) showed the best balance of A2AAR affinity and CK1δ inhibitory activity. Computational studies were performed to simulate, at the molecular level, the protein–ligand interactions involving the compounds of our series. Hence, the dual anta-inhibitor 17 could be considered the lead compound of new therapeutic agents endowed with synergistic effects for the treatment of chronic neurodegenerative and cancer diseases.