Dll1 haploinsufficiency causes brain abnormalities with functional relevance

IntroductionThe Notch pathway is fundamental for the generation of neurons during development. We previously reported that adult mice heterozygous for the null allele of the gene encoding the Delta-like ligand 1 for Notch (Dll1lacZ) have a reduced neuronal density in the substantia nigra pars compacta. The aim of the present work was to evaluate whether this alteration extends to other brain structures and the behavioral consequences of affected subjects.MethodsBrains of Dll1+/lacZ embryos and mice at different ages were phenotypically compared against their wild type (WT) counterpart. Afterwards, brain histological analyses were performed followed by determinations of neural cell markers in tissue slices. Neurological deficits were diagnosed by applying different behavioral tests to Dll1+/lacZ and WT mice.ResultsBrain weight and size of Dll1+/lacZ mice was significantly decreased compared with WT littermates (i.e., microcephaly), a phenotype detected early after birth. Interestingly, enlarged ventricles (i.e., hydrocephalus) was a common characteristic of brains of Dll1 haploinsufficient mice since early ages. At the cell level, general cell density and number of neurons in several brain regions, including the cortex and hippocampus, of Dll1+/lacZ mice were reduced as compared with those regions of WT mice. Also, fewer neural stem cells were particularly found in the adult dentate gyrus of Dll1+/lacZ mice but not in the subventricular zone. High myelination levels detected at early postnatal ages (P7–P24) were an additional penetrant phenotype in Dll1+/lacZ mice, observation that was consistent with premature oligodendrocyte differentiation. After applying a set of behavioral tests, mild neurological alterations were detected that caused changes in motor behaviors and a deficit in object categorization.DiscussionOur observations suggest that Dll1 haploinsufficiency limits Notch signaling during brain development which, on one hand, leads to reduced brain cell density and causes microcephaly and hydrocephalus phenotypes and, on the other, alters the myelination process after birth. The severity of these defects could reach levels that affect normal brain function. Therefore, Dll1 haploinsufficiency is a risk factor that predisposes the brain to develop abnormalities with functional consequences

Enfermedades crónicas

Adherencia al tratamiento farmacológico y relación con el control metabólico en pacientes con DM2Aluminio en pacientes con terapia de reemplazo renal crónico con hemodiálisis en Bogotá, ColombiaAmputación de extremidades inferiores: ¿están aumentando las tasas?Consumo de edulcorantes artificiales en jóvenes universitariosCómo crecen niños normales de 2 años que son sobrepeso a los 7 añosDiagnóstico con enfoque territorial de salud cardiovascular en la Región MetropolitanaEfecto a corto plazo de una intervención con ejercicio físico, en niños con sobrepesoEfectos de la cirugía bariátrica en pacientes con síndrome metabólico e IMC < 35 KG/M2Encuesta mundial de tabaquismo en estudiantes de profesiones de saludEnfermedades crónicas no transmisibles: Consecuencias sociales-sanitarias de comunidades rurales en ChileEpidemiología de las muertes hospitalarias por patologías relacionadas a muerte encefálica, Chile 2003-2007Estado nutricional y conductas alimentarias en adolescentes de 4º medio de la Región de CoquimboEstudio de calidad de vida en una muestra del plan piloto para hepatitis CEvaluación del proceso asistencial y de resultados de salud del GES de diabetes mellitus 2Factores de riesgo cardiovascular en población universitaria de la Facsal, universidad de TarapacáImplicancias psicosociales en la génesis, evolución y tratamiento de pacientes con hipertensión arterial esencialInfarto agudo al miocardio (IAM): Realidad en el Hospital de Puerto Natales, 2009-2010Introducción de nuevas TIC y mejoría de la asistencia a un programa de saludNiños obesos atendidos en el Cesfam de Puerto Natales y su entorno familiarPerfil de la mortalidad por cáncer de cuello uterino en Río de JaneiroPerfil del paciente primo-consultante del Programa de Salud Cardiovascular, Consultorio Cordillera Andina, Los AndesPrevalencia de automedicación en mujeres beneficiarias del Hospital Comunitario de Til-TiPrevalencia de caries en población preescolar y su relación con malnutrición por excesoPrevalencia de retinopatía diabética en comunas dependientes del Servicio de Salud Metropolitano Occidente (SSMOC)Problemas de adherencia farmacológica antihipertensiva en población mapuche: Un estudio cualitativoRol biológico de los antioxidantes innatos en pacientes portadores de VIH/SidaSobrepeso en empleados de un restaurante de una universidad pública del estado de São Paul

Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

Regulation of differentiation flux by Notch signalling influences the number of dopaminergic neurons in the adult brain

Notch signalling is a well-established pathway that regulates neurogenesis. However, little is known about the role of Notch signalling in specific neuronal differentiation. Using Dll1 null mice, we found that Notch signalling has no function in the specification of mesencephalic dopaminergic neural precursor cells (NPCs), but plays an important role in regulating their expansion and differentiation into neurons. Premature neuronal differentiation was observed in mesencephalons of Dll1-deficient mice or after treatment with a Notch signalling inhibitor. Coupling between neurogenesis and dopaminergic differentiation was indicated from the coincident emergence of neuronal and dopaminergic markers. Early in differentiation, decreasing Notch signalling caused a reduction in NPCs and an increase in dopaminergic neurons in association with dynamic changes in the proportion of sequentially-linked dopaminergic NPCs (Msx1/2+, Ngn2+, Nurr1+). These effects in differentiation caused a significant reduction in the number of dopaminergic neurons produced. Accordingly, Dll1 haploinsufficient adult mice, in comparison with their wild-type littermates, have a consistent reduction in neuronal density that was particularly evident in the substantia nigra pars compacta. Our results are in agreement with a mathematical model based on a Dll1-mediated regulatory feedback loop between early progenitors and their dividing precursors that controls the emergence and number of dopaminergic neurons

. 11-12 Año 6 (2017) enero-agosto. CR. Conservación y restauración

- Editorial por Manuel Alejandro González Gutiérrez y Magdalena Rojas Vences. -Proyecto de atención del acervo documental de Ixcamilpa de Guerrero por Patricia de la Garza Cabrera, Marie Vander Meeren, Laura Olivia Ibarra Carmona, Nora A. Pérez Castellanos, Carlos Orejel Delgadillo, Silvia Yocelin Pérez Ramírez, Débora Y. Ontiveros Ramírez, Denisse Ochoa Gutiérrez, Hugo Arriaga González y Gerardo Gutiérrez. - Haciendo frente a los embates medioambientales: conservación integral del sitio rupestre Cuevas Pintas,Baja California Sur por Sandra Cruz Flores, Alejandra Bourillón Moreno, Anacaren Morales Ortiz, Rodrigo Ruiz Herrera y María Fernanda López-Armenta. - Estrategia para la accesibilidad e inclusión de las personas con discapacidad a zonas arqueológicas “El pasado es de todos” por Daniela Tovar Ortiz y Luis Antonio Huitrón Santoyo. - Atención a grupos sociales. Sistematización de actividades por Manuel González Gutiérrez y Denisse Ochoa Gutiérrez. - Tañendo campanas: trabajando en equipo. Intervención de las campanas robadas en la capilla de Nuestra Señora de la Concepción, Escobedo, Nuevo León por Gabriela Peñuelas Guerrero, Carlos I. Cañete Ibáñez, Claudia Sánchez Gándara, Jannen Contreras Vargas e Ingrid K. Jiménez Cosme. - La apropiación del patrimonio cultural de El Ocote. Una aportación etnográfica para la sostenibilidad por Hugo Arriaga González. - Churubusco. 50 años en la memoria. Una muestra conmemorativa de la conservación en el INAH por Mónica Badillo Leal, Gabriela Gómez Llorente y Mariana Pascual Cáceres. - Los órganos y su conservación en la CNCPC por Norma Cristina Peña Peláez, Sandra María Álvarez Jacinto, José Luis Acevedo Guzmán y Fanny Magaña Nieto. - Conservación de cestería en espiral proveniente de la Cueva de la Candelaria, Torreón, Coahuila: criterios, tratamientos y líneas de investigación por Gloria Martha Sánchez Valenzuela, Miriam Elizabeth Castro Rodríguez y Adriana Reyes García. - Evaluación de recubrimientos de protección para metales. Caso de estudio: Imagen de México, relieve escultórico del Museo Nacional de Antropología. Primera etapa por Aline Moreno Núñez, Arturo A. Egea Salas, Gilda E. Salgado Manzanares, Mauricio B. Jiménez Ramírez, Armando Arciniega Corona y Nora A. Pérez Castellanos. - Patrimonio arqueológico digital. Uso de las tecnologías de la información y la comunicación para la divulgación del patrimonio arqueológico por Eduardo Andrés Escalante Carrillo y Luis Antonio Huitrón Santoyo. - El laboratorio de documentación y análisis tridimensional de la CNCPC. Resultados a un año de operación María Fernanda López-Armenta, Gilberto García Quintana y Celedonio Rodríguez Vidal. - La conservación-restauración de los bienes culturales en el Museo Regional de Querétaro: retos y perspectivas por María del Rosario Bravo Aguilar Conocer y reconocer a los actores sociales en la conservación de los bienes patrimoniales por Mitzi Vania García Toribio y Fanny Magaña Nieto. - Foro Anual de Trabajo. Una historia sin historia en el archivo de la CNCPC por Débora Y. Ontiveros Ramírez. - Expediente de incidentes en el tiempo. El Ehécatl-Quetzalcóatl de Coyoacán y cómo su caso puede ser usado para difundir la conservación en museos por Roberto Velasco Alonso. - Conservación en la vida cotidiana por María Bertha Peña Tenorio. - La Mediateca del INAH por Thalía E. Velasco Castelán. - Finaliza CNCPC la recuperación de sillares simulados originales en la bóveda del templo franciscano de Huaquechula, Puebla por Oscar Adrián Gutiérrez Vargas. - San Francisco de Asís en Huejotzingo, Puebla María Eugenia Rivera Pérez. - Investiga INAH factores de deterioro en la pirámide de la Serpiente Emplumada por Oscar Adrián Gutiérrez Vargas. - Lo que querías saber y no te atrevías a preguntar sobre el INAH en El Ocote por Oscar Adrián Gutiérrez Vargas. - Para saber más de El Caballito por Oscar Adrián Gutiérrez Vargas