The Netrin-4/ Neogenin-1 axis promotes neuroblastoma cell survival and migration

Neogenin-1 (NEO1) is a transmembrane receptor involved in axonal guidance, angiogenesis, neuronal cell migration and cell death, during both embryonic development and adult homeostasis. It has been described as a dependence receptor, because it promotes cell death in the absence of its ligands (Netrin and Repulsive Guidance Molecule (RGM) families) and cell survival when they are present. Although NEO1 and its ligands are involved in tumor progression, their precise role in tumor cell survival and migration remain unclear. Public databases contain extensive information regarding the expression of NEO1 and its ligands Netrin-1 (NTN1) and Netrin-4 (NTN4) in primary neuroblastoma (NB) tumors. Analysis of this data revealed that patients with high expression levels of both NEO1 and NTN4 have a poor survival rate. Accordingly, our analyses in NB cell lines with different genetic backgrounds revealed that knocking-down NEO1 reduces cell migration, whereas silencing of endogenous NTN4 induced cell death. Conversely, overexpression of NEO1 resulted in higher cell migration in the presence of NTN4, and increased apoptosis in the absence of ligand. Increased apoptosis was prevented when utilizing physiological concentrations of exogenous Netrin-4. Likewise, cell death induced after NTN4 knock-down was rescued when NEO1 was transiently silenced, thus revealing an important role for NEO1 in NB cell survival. In vivo analysis, using the chicken embryo chorioallantoic membrane (CAM) model, showed that NEO1 and endogenous NTN4 are involved in tumor extravasation and metastasis. Our data collectively demonstrate that endogenous NTN4/NEO1 maintain NB growth via both pro-survival and pro-migratory molecular signaling.Veronica Palma's work was supported by FONDECYT-1140697. Andrea A. Villanueva, Paulina Falcon and Luis Solano were beneficiaries of CONICYT Fellowships for PhD studies (21130521, AV; 21120358, PF; 21110302, LS).S

High Prevalence of Mycoplasma pneumoniae and Chlamydia pneumoniae in Children with Acute Respiratory Infections from Lima, Peru

Background Mycoplasma pneumoniae and Chlamydia pneumoniae are atypical pathogens responsible for pneumonia and a leading cause of morbidity and mortality in low income countries. The study objective is to determine the prevalence of this pathogens in Peruvian children with acute respiratory infections. Methods A consecutive cross-sectional study was conducted in Lima, Peru from May 2009 to September 2010. A total of 675 children admitted with clinical diagnoses of acute respiratory infections were tested for Mycoplasma pneumoniae and Chlamydia pneumoniae detection by polymerase chain reaction (PCR), and clinical symptoms were registered by the attending physician. Results Mycoplasma pneumonia was detected in 25.19% (170/675) of nasopharyngeal samples and Chlamydia pneumonia in 10.52% (71/675). The most common symptoms in patients with these atypical pathogens were rhinorrhea, cough and fever. A higher prevalence of Mycoplasma pneumoniae cases were registered in summer, between December 2009 and March 2010. Conclusions Mycoplasma pneumoniae and Chlamydia pneumonia are a significant cause of morbidity in Peruvian children with acute respiratory infections (ARI). Further studies should evaluate the use of reliable techniques such as PCR in Peru in order to avoid underdiagnoses of these atypical pathogens

VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad

Acta de congresoLa conmemoración de los cien años de la Reforma Universitaria de 1918 se presentó como una ocasión propicia para debatir el rol de la historia, la teoría y la crítica en la formación y en la práctica profesional de diseñadores, arquitectos y urbanistas. En ese marco el VIII Encuentro de Docentes e Investigadores en Historia del Diseño, la Arquitectura y la Ciudad constituyó un espacio de intercambio y reflexión cuya realización ha sido posible gracias a la colaboración entre Facultades de Arquitectura, Urbanismo y Diseño de la Universidad Nacional y la Facultad de Arquitectura de la Universidad Católica de Córdoba, contando además con la activa participación de mayoría de las Facultades, Centros e Institutos de Historia de la Arquitectura del país y la región. Orientado en su convocatoria tanto a docentes como a estudiantes de Arquitectura y Diseño Industrial de todos los niveles de la FAUD-UNC promovió el debate de ideas a partir de experiencias concretas en instancias tales como mesas temáticas de carácter interdisciplinario, que adoptaron la modalidad de presentación de ponencias, entre otras actividades. En el ámbito de VIII Encuentro, desarrollado en la sede Ciudad Universitaria de Córdoba, se desplegaron numerosas posiciones sobre la enseñanza, la investigación y la formación en historia, teoría y crítica del diseño, la arquitectura y la ciudad; sumándose el aporte realizado a través de sus respectivas conferencias de Ana Clarisa Agüero, Bibiana Cicutti, Fernando Aliata y Alberto Petrina. El conjunto de ponencias que se publican en este Repositorio de la UNC son el resultado de dos intensas jornadas de exposiciones, cuyos contenidos han posibilitado actualizar viejos dilemas y promover nuevos debates. El evento recibió el apoyo de las autoridades de la FAUD-UNC, en especial de la Secretaría de Investigación y de la Biblioteca de nuestra casa, como así también de la Facultad de Arquitectura de la UCC; va para todos ellos un especial agradecimiento

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Distribución y estructura de las comunidades de escarabeidos coprófagos (Coleoptera, Scarabaeoidea) a lo largo de gradientes de altitud

Los rangos de distribución y la fenología de las especies están determinados por diferentes factores que varían a lo largo del tiempo; por ejemplo, por el efecto del cambio climático. Los sistemas montañosos presentan un escenario idóneo para el estudio de los gradientes altitudinales y los cambios de distribución de las especies en un espacio reducido. El objetivo principal de esta tesis fue determinar la distribución y composición de las comunidades de escarabeidos coprófagos (Coleoptera, Scarabaeoidea) en gradientes altitudinales. Para ello, se realizó una monitorización estandarizada entre 775 y 1900 m s.n.m. en la Sierra de Guadarrama (capítulo 2,3 y 4) y un muestreo entre 400 y 2600 m s.n.m. en las estribaciones orientales de la cordillera de los Andes (capítulo 5). Los datos compilados en la Sierra de Guadarrama sirvieron para observar los cambios en los rangos de distribución de los escarabajos coprófagos en un escenario de cambio climático. Se realizó una comparativa de los datos procedentes de bases de datos para cuatro especies, identificándose cambios en su fenología y distribución. Sin embargo, la baja disponibilidad de datos históricos impidió encontrar una evidencia clara de dichas variaciones, pudiendo ser un artefacto creado por la falta de muestreo o por información incompleta en los metadatos (capítulo 2). En la Sierra de Guadarrama se registraron 70 especies de los tres grupos de Scarabaeoidea Paleárticos (39 Scarabaeidae, 26 Aphodiidae y 5 Geotrupidae). Sus respuestas fenológicas presentaron variaciones en abundancia de manera variable a lo largo del gradiente de altitud, en función de variaciones térmicas estacionales. Las respuestas de las especies ante la altitud y la temperatura pueden clasificarse en cuatro tipos básicos, en función de si son generalistas o especialistas para uno o ambos factores (capítulo 3)..

¿Cuál es el alcance de la crisis de la Taxonomía? Conflictos, retos y estrategias para la construcción de una Taxonomía renovada

Peer reviewe

Thermal niche dimensionality could limit species’ responses to temperature changes: Insights from dung beetles

[Aim]: Adequate responses of species to climate changes require that thermal changes remain compatible across different key biological aspects (e.g. reproduction, feeding and development). However, limits of thermal compatibility to such biological aspects are largely unknown in extant ectotherm groups. To fill this gap, we studied the in-traspecific congruence of thermal responses across biological aspects.[Location]: Iberian Peninsula.[Taxon]: Scarabaeidae Dung beetles.[Methods]: We studied the role of temperature in determining the diel, seasonal and geographical occurrences of 16 dung beetle species. We fitted polynomial GLMs of the abundance/occurrence of each species as a function of temperature and alterna-tive predictors for each spatiotemporal scale, using deviance partitioning to explore the relative contribution of temperature. We used the fitted models to estimate real-ized thermal niche attributes at these three spatiotemporal scales, and assessed their intraspecific congruence through the correlation of niche attributes from different scales.[Results]: We found that temperature has relatively low—but not negligible—explanatory capacity at the three spatiotemporal scales, once alternative predictors are taken into account. More importantly, the estimated thermal responses were largely incongru-ent across scales, indicating that these species have multidimensional thermal niches.[Main conclusions]: The multidimensionality of thermal niches entails that species’ adjustments to fulfil temperature requirements for one biological aspect (such as sea-sonal ontogenetic cycles) may result in detrimental effects on other elements (e.g. diel activity). These trade-offs could expose individuals to inadequate temperatures at certain moments, reducing populations’ performance. Paradoxically, the weak effects of temperature we found may have severe consequences for species responses to warming if temperature regulates essential aspects of their biology in divergent ways.Peer reviewe

The Netrin-4/Neogenin-1 axis promotes neuroblastoma cell survival and migration

Neogenin-1 (NEO1) is a transmembrane receptor involved in axonal guidance, angiogenesis, neuronal cell migration and cell death, during both embryonic development and adult homeostasis. It has been described as a dependence receptor, because it promotes cell death in the absence of its ligands (Netrin and Repulsive Guidance Molecule (RGM) families) and cell survival when they are present. Although NEO1 and its ligands are involved in tumor progression, their precise role in tumor cell survival and migration remain unclear. Public databases contain extensive information regarding the expression of NEO1 and its ligands Netrin-1 (NTN1) and Netrin-4 (NTN4) in primary neuroblastoma (NB) tumors. Analysis of this data revealed that patients with high expression levels of both NEO1 and NTN4 have a poor survival rate. Accordingly, our analyses in NB cell lines with different genetic backgrounds revealed that knocking-down NEO1 reduces cell migration, whereas silencing of endogenous NTN4 induce