Physical and functional interaction between the dopamine transporter and the synaptic vesicle protein synaptogyrin-3.

Uptake through the dopamine transporter (DAT) represents the primary mechanism used to terminate dopaminergic transmission in brain. Although it is well known that dopamine (DA) taken up by the transporter is used to replenish synaptic vesicle stores for subsequent release, the molecular details of this mechanism are not completely understood. Here, we identified the synaptic vesicle protein synaptogyrin-3 as a DAT interacting protein using the split ubiquitin system. This interaction was confirmed through coimmunoprecipitation experiments using heterologous cell lines and mouse brain. DAT and synaptogyrin-3 colocalized at presynaptic terminals from mouse striatum. Using fluorescence resonance energy transfer microscopy, we show that both proteins interact in live neurons. Pull-down assays with GST (glutathione S-transferase) proteins revealed that the cytoplasmic N termini of both DAT and synaptogyrin-3 are sufficient for this interaction. Furthermore, the N terminus of DAT is capable of binding purified synaptic vesicles from brain tissue. Functional assays revealed that synaptogyrin-3 expression correlated with DAT activity in PC12 and MN9D cells, but not in the non-neuronal HEK-293 cells. These changes were not attributed to changes in transporter cell surface levels or to direct effect of the protein-protein interaction. Instead, the synaptogyrin-3 effect on DAT activity was abolished in the presence of the vesicular monoamine transporter-2 (VMAT2) inhibitor reserpine, suggesting a dependence on the vesicular DA storage system. Finally, we provide evidence for a biochemical complex involving DAT, synaptogyrin-3, and VMAT2. Collectively, our data identify a novel interaction between DAT and synaptogyrin-3 and suggest a physical and functional link between DAT and the vesicular DA system

Long-term surveillance of the feline leukemia virus in the endangered Iberian lynx (Lynx pardinus) in Andalusia, Spain (2008-2021)

Feline leukemia virus (FeLV) infection is considered one of the most serious disease threats for the endangered Iberian lynx (Lynx pardinus) Over 14 years (2008-2021), we investigated FeLV infection using point-of-care antigen test and quantitative real-time TaqMan qPCR for provirus detection in blood and tissues in lynxes from Andalusia (Southern Spain). A total of 776 samples from 586 individuals were included in this study. The overall prevalence for FeLV antigen in blood/serum samples was 1.4% (5/360) (95% CI: 0.2-2.6), FeLV proviral DNA prevalence in blood samples was 6.2% (31/503) (95% CI: 4.1-8.6), and FeLV proviral DNA in tissues samples was 10.2% (34/333) (95% CI: 7-13.5). From a subset of 129 longitudinally sampled individuals, 9.3% (12/129) PCR-converted during the study period. Our results suggest that FeLV infection in the Andalusian population is enzootic, with circulation of the virus at low levels in almost all the sampling years. Moreover, since only one viremic individual succumbed to the infection, this study suggests that lynxes may therefore control the infection decreasing the possibility of developing a more aggressive outcome. Although our results indicate that the FeLV infection in the Iberian lynx from Andalusia tends to stay within the regressive stage, continuous FeLV surveillance is paramount to predict potential outbreaks and ensure the survival of this population

Implantación de un registro específico de reacciones adversas a ferroterapia endovenosa ambulatoria en un hospital de tercer nivel

Poster [PC-118] Introducción: La Agencia Española de medicamentos y productos sanitarios (AEMPS) estableció en 2013 nuevas recomendaciones para la administración intravenosa de preparados de hierro tras la notificación de reacciones de hipersensibilidad. Aunque estos preparados mantienen un balance beneficio-riesgo favorable se deben establecer medidas específicas para la identificación temprana y el tratamiento inmediato de las reacciones alérgicas. Pacientes y Métodos: Implantación de medidas de seguridad en la vigilancia de la administración intravenosa de preparados de hierro cumpliendo los tiempos de observación recomendados por la AEMPS. Elaboración de un formulario de reacciones adversas específico para la administración de ferroterapia endovenosa, de fácil cumplimentación por el personal de Enfermería del hospital de Día de Hematología del Hospital Universitario Miguel Servet. Análisis de la incidencia de reacciones adversas en relación con la ferroterapia prescrita desde la consulta de Eritropatología a pacientes con anemia ferropénica. Estudio descriptivo y prospectivo realizado en un periodo de 4 meses (Enero 2018 – Mayo 2018). Análisis de las reacciones adversas detectadas en relación al tratamiento con hierro endovenoso disponible en nuestro centro en diferentes posologías: hierro-sacarosa (Venofer®) 200 mg, hierro-carboximaltosa (Ferinject®) 500 mg y 1 gr. Resultados: Se han estudiado 77 pacientes. 52 hombres y 25 mujeres. La mediana de edad fue 68 años. 21 (27, 27%) pacientes tenían alergias o intolerancias conocidas previamente. 53 (68, 83%) recibieron tratamiento con hierro sacarosa (200mg) y 24 (31, 17%) con hierro carboximaltosa [20 (83, 83%) 500mg, 4 (16, 67%) 1g]. Todos los pacientes cumplieron los tiempos de vigilancia recomendados por la AEMPS. Únicamente dos pacientes presentaron reacciones adversas al hierro y ambos con dosis de 200mg de hierro sacarosa. Los dos presentaron reacciones gastrointestinales leves de duración autolimitada de unos 15 minutos, sin repercusión orgánica y sin precisar medicación para su resolución. Conclusiones: Las reacciones graves de hipersensibilidad al hierro endovenoso son, como en nuestra serie de casos, efectos adversos muy poco frecuentes. A diferencia de los casos descritos de reacciones graves anafilácticas, en nuestro centro no hemos detectado ninguna gravedad en todos los tratamientos administrados. Tampoco hemos podido relacionar las dos reacciones leves detectadas con predisposición previa de los pacientes al desarrollo de alergias medicamentosas u otras intolerancias, ni tampoco con la dosis de hierro o preparado administrado. Dada la alerta de la AEMPS, nuestro registro específico de reacciones adversas a ferroterapia endovenosa nos permite estar alerta y constatar de manera objetiva la existencia o no de dichas reacciones así como su gravedad

Elective Cancer Surgery in COVID-19-Free Surgical Pathways During the SARS-CoV-2 Pandemic: An International, Multicenter, Comparative Cohort Study.

PURPOSE: As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19-free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS: This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19-free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS: Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19-free surgical pathways. Patients who underwent surgery within COVID-19-free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19-free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score-matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19-free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION: Within available resources, dedicated COVID-19-free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Elective cancer surgery in COVID-19-free surgical pathways during the SARS-CoV-2 pandemic: An international, multicenter, comparative cohort study

PURPOSE As cancer surgery restarts after the first COVID-19 wave, health care providers urgently require data to determine where elective surgery is best performed. This study aimed to determine whether COVID-19–free surgical pathways were associated with lower postoperative pulmonary complication rates compared with hospitals with no defined pathway. PATIENTS AND METHODS This international, multicenter cohort study included patients who underwent elective surgery for 10 solid cancer types without preoperative suspicion of SARS-CoV-2. Participating hospitals included patients from local emergence of SARS-CoV-2 until April 19, 2020. At the time of surgery, hospitals were defined as having a COVID-19–free surgical pathway (complete segregation of the operating theater, critical care, and inpatient ward areas) or no defined pathway (incomplete or no segregation, areas shared with patients with COVID-19). The primary outcome was 30-day postoperative pulmonary complications (pneumonia, acute respiratory distress syndrome, unexpected ventilation). RESULTS Of 9,171 patients from 447 hospitals in 55 countries, 2,481 were operated on in COVID-19–free surgical pathways. Patients who underwent surgery within COVID-19–free surgical pathways were younger with fewer comorbidities than those in hospitals with no defined pathway but with similar proportions of major surgery. After adjustment, pulmonary complication rates were lower with COVID-19–free surgical pathways (2.2% v 4.9%; adjusted odds ratio [aOR], 0.62; 95% CI, 0.44 to 0.86). This was consistent in sensitivity analyses for low-risk patients (American Society of Anesthesiologists grade 1/2), propensity score–matched models, and patients with negative SARS-CoV-2 preoperative tests. The postoperative SARS-CoV-2 infection rate was also lower in COVID-19–free surgical pathways (2.1% v 3.6%; aOR, 0.53; 95% CI, 0.36 to 0.76). CONCLUSION Within available resources, dedicated COVID-19–free surgical pathways should be established to provide safe elective cancer surgery during current and before future SARS-CoV-2 outbreaks

Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Expediciones Humboldt: Honda-Méndez, Tolima

Este informe presenta los resultados de la caracterización biológica de uno de los bosques secos con mejor estado de conservación en el departamento del Tolima, ubicado entre los municipio de Honda, Méndez y Armero-Guayabal. Estos bosques se encuentran en una matriz de ganadería y producción agropecuaria, donde las coberturas boscosas son conservadas por los propietarios, conscientes de la importancia de este ecosistema para la provisión de bienes y servicios ecosistémicos. Esperamos que esta información producto de la capacidad científica del Instituto Humboldt, sea relevante y útil en las decisiones de planificación estratégica tanto en el ordenamiento territorial de los municipios de Honda, Méndez y Armero-Guayabal, como para las decisiones de conservación que se tomen en la regiónBogotáCiencias Básicas de la Biodiversida

Cuentos del Olivar

En este apasionante viaje tenemos las puertas abiertas para todo aquel que se quiera sumar, ya sea trabajando en pos de la difusión de la cultura ligada al olivo o disfrutando de lecturas como las que se recogen en este libro, que seguro les depara un sabroso disfrute y les descubre una cultura del olivar que tiene a sus espaldas varios milenios de historia. Les deseo que paladeen cada uno de estos relatos, que conforman un excelente aperitivo literario.Área de Historia del Art

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types