Notch/neurogenin 3 signalling is involved in the neuritogenic actions of oestradiol in developing hippocampal neurones

10 pages. - PMID: 21251092 [PubMed - in process]The ovarian hormone oestradiol promotes neuritic outgrowth in different neuronal types, by mechanisms that remain elusive. Recent studies have shown that the Notch-regulated transcription factor neurogenin 3 controls neuritogenesis. In the present study, we assessed whether oestradiol regulates neurogenin 3 in primary hippocampal neurones. As expected, neuritogenesis was increased in the cultures treated with oestradiol. However, the neuritogenic action of oestradiol was not prevented by ICI 182,780, an antagonist of classical oestrogen receptors (ERs). Oestradiol decreased the expression of Hairy and Enhancer of Split-1, a Notch-regulated gene that negatively controls the expression on neurogenin 3. Furthermore, oestradiol increased the expression of neurogenin 3 and regulated its distribution between the neuronal cell nucleus and the cytoplasm. The effect of oestradiol on neurogenin 3 expression was not blocked by antagonists of classical nuclear ER-mediated transcription and was not imitated by selective agonists of nuclear ERs. By contrast, G1, a ligand of G protein receptor 30/G protein-coupled ER, fully reproduced the effect of oestradiol on neuritogenesis, neurogenin 3 expression and neurogenin 3 subcellular localisation. Moreover, knockdown of neurogenin 3 in neurones by transfection with small interference RNA for neurogenin 3 completely abrogated the neuritogenic actions of oestradiol and G1. These results suggest that oestradiol regulates neurogenin 3 in primary hippocampal neurones by a nonclassical steroid signalling mechanism, which involves the down-regulation of Notch activity and the activation of G protein receptor 30/G protein-coupled ER or of other unknown G1 targets. In addition, our findings indicate that neurogenin 3 participates in the neuritogenic mechanisms of oestradiol in hippocampal neurones.Peer reviewe

Approach to the Lower Pliocene marine-continental correlation from southern Spain. The micrommamal site of Alhaurín el Grande-1 (Málaga Basin, Betic Cordillera, Spain)

A new micromammal site at Alhaurín el Grande (Málaga, southern Spain) located above early Pliocene marine deposits allows an approach to the marine-continental correlation for this age. The early Pliocene marine filling throughout the Málaga Basin is developed in three transgressive-regressive sequences (Pl-1, Pl-2, and Pl-3 units) bounded by discontinuities. At the top of the intermediate sequence Pl-2, peaty sediments have yielded fossils of Rodentia, Lagomorpha, Insectivora, and Crocodylia. The presence of Cricetus barrieri Mein & Michaux, 1970 in combination with murids, both of primitive morphology, such as Apodemus gudrunae Van de Weerd, 1976, and more advanced forms (i.e. Occitanomys brailloni Michaux, 1969 and Stephanomys donnezani cordii Ruiz Bustos, 1986), points to an early Ruscinian age (MN 14 biozone). Based on the planktonic foraminifers, the biostratigraphic data indicate that marine sediments just below the micromammal beds belong to the MPl-2 biozone of the early Zanclean. Available paleomagnetic data from the marine sediments show that the micromammal bed must be located between the normal geomagnetic subchron C3n3n (4.89-4.80 Ma) and the subchron C3n2n (4.63-4.49 Ma), limiting the age of this site to the late part of the early Zanclean

Diagnostic accuracy of first-trimester combined screening for early-onset and preterm pre-eclampsia at 8-10 compared with 11-13 weeks' gestation

To compare the ability of first-trimester combined screening for pre-eclampsia (PE) to predict early-onset and preterm PE when pregnancy-associated plasma protein-A (PAPP-A) and placental growth factor (PlGF) were assessed before vs after 11 weeks' gestation. This was a secondary analysis of a prospective cohort study of singleton pregnancies undergoing routine first-trimester screening conducted at Vall d'Hebron University Hospital, Barcelona, Spain, between October 2015 and September 2017. Demographic characteristics, obstetric history, maternal history and biophysical markers (mean uterine artery pulsatility index and mean arterial blood pressure (MAP)) were recorded at the first-trimester scan (at 11 + 0 to 13 + 6 weeks' gestation). Maternal serum concentrations of PAPP-A and PlGF were assessed from the routine first-trimester blood test (at 8 + 0 to 13 + 6 weeks). Women were classified into two groups depending on whether serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks or at 11 + 0 to 13 + 6 weeks. Probability scores for early-onset and preterm PE were calculated by using two different algorithms: the multivariate Gaussian-distribution model and The Fetal Medicine Foundation (FMF) competing-risks model. Receiver-operating-characteristics (ROC) curves were produced and detection rates at fixed 5% and 10% false-positive rates were computed to compare the performance of these algorithms when PAPP-A and PlGF were assessed before vs after 11 weeks. Of the 2641 women included, serum biomarkers were assessed before 11 weeks in 1675 (63.4%) and at or after 11 weeks in 966 (36.6%). Of these, 90 (3.4%) women developed PE, including 11 (0.4%) cases of early-onset PE and 30 (1.1%) of preterm PE. Five (45.5%) cases of early-onset and 16 (53.3%) of preterm PE were identified in the group in which serum biomarkers were assessed at 8 + 0 to 10 + 6 weeks and six (54.5%) cases of early-onset and 14 (46.7%) of preterm PE in the group in which serum biomarkers were assessed at 11 + 0 to 13 + 6 weeks. In the prediction of early-onset and preterm PE using the Gaussian algorithm, no differences were observed between the areas under the ROC curves (AUCs) when PAPP-A and PlGF were measured before or after 11 weeks. In the prediction of early-onset and preterm PE using the FMF algorithm, no differences were observed between AUCs for any of the combinations used for risk calculation when the serum biomarkers were obtained before vs after 11 weeks, except for the combination of PAPP-A and MAP, which showed a greater AUC for the prediction of early-onset PE when PAPP-A was measured at or after 11 weeks. The prediction of early-onset and preterm PE is similar when serum biomarkers are measured before or after 11 weeks. This allows the use of a two-step approach for PE risk assessment that permits immediate risk calculation at the time of the first-trimester scan. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology

BÚSQUEDA DE PRINCIPIOS ACTIVOS ANTIPARASITARIOS EN PLANTAS DE USO TRADICIONAL DE LA AMAZONIA PERUANA. ESPECIAL ENFASIS EN ALCALOIDES INDOLICOS

A fin de evaluar el potencial antimalárico de remedios tradicionales utilizadas en el Perú por las poblaciones indígenas y mestizas del río Nanay en Loreto, fueron entrevistados sobre el uso medicina tradicional para el tratamiento de la malaria. La encuesta se llevó a cabo en seis pueblos y llevaron a la recolección de 59 plantas. 35 extracciones hidro-alcohólico se realizaron en las 21 plantas más citadas. A continuación se ensayaron los extractos para la actividad antiplasmodial in vitro sobre cepa resistente a la cloroquina de Plasmodium falciparum (FCR-3), y también se realizó la prueba de inhibición de ferriprotoporfirina con el fin de asumir propiedades farmacológicas. Los extractos de 9 plantas, en veintiún evaluados, mostraron una actividad antiplasmodial interesante (IC50 <10 µg/ml) y 16 extractos resultaron activos en la prueba de inhibición de la ferriprotoporfirina. Cinco alcaloides oxindólicos y dos alcaloides de tipo plumerano subtipo haplophitina, fueron aislados de plantas medicinales: Aspidosperma rigidum y A. schultesii. Uno de estos compuestos se identificó como un confórmero rotámero transoide de la 18-Oxo-O-metilaspidoalbina que no se describió anteriormente, también fueron determinada la actividad antiparasitaria de los compuestos contra Trypanosoma cruzi y Leishmania infantum

Síndrome de Joubert. Reporte de un caso

El síndrome de Joubert es una ciliopatía que se hereda en forma autosómica recesiva, estimaciones de la prevalencia oscilan entre 1/80.000 y 1/100.000 nacidos vivos. La enfermedad se presenta clínicamente con hipotonía de las extremidades, deterioro cognitivo, ataxia, taquipnea episódica, movimientos anormales del ojo, y agenesia del vermis cerebeloso. Esta última característica, junto mencionados, dan el diagnóstico para el síndrome de Joubert. Actualmente no se cuenta con un tratamiento curativo. Tiene un alto riesgo de recurrencia del 25% por lo cual se emplean métodos de detección prenatal en parejas que han tenido antecedentes de hijos con la enfermedad

Diversidad genética de Dioscorea trifida “sachapapa” de cinco cuencas hidrográficas de la amazonía peruana

Dioscorea trifida “sachapapa” es una de las especies promisorias amazónicas que podemos considerarla huérfana de la ciencia, por las escasas investigaciones que hay sobre esta especie. El objetivo de esta investigación fue determinar la diversidad genética intra e interpoblacional de D. trifida de cinco cuencas hidrográficas de la amazonía peruana. Las hojas fueron colectadas de una colección de germoplasma y purificó el ADN con métodos estándares. El polimorfismo genético se evaluó con la técnica RAPD y los parámetros de genética poblacional fueron estimados con el programa POPGENE. Los análisis espectrofotométrico (A260/A280=1,7±0,1) y electroforético (bandas de ADN íntegras) mostraron que el ADN purificado fue de alta calidad. Asimismo, la cantidad obtenida fue apropiada para estudios de diversidad genética (rendimiento promedio = 582±248 mg ADN/mg hojas). La diversidad genética intrapoblacional más alta se encontró en la cuenca del Itaya (h = 0,24±0,11) y la más baja en la cuenca del Marañón (h = 0,10±0,04). Adicionalmente, la diversidad genética interpoblacional más alta se registró entre las poblaciones de Itaya vs Ucayali (GST = 1,00), mientras que la más baja entre las poblaciones de Nanay vs Tapiche (GST = 0,07). En conclusión, D. trifida muestra variación en su diversidad genética intra e interpoblacional en las cinco cuencas hidrográficas de la amazonía peruana, siendo la cuenca del Itaya la que presenta mayor diversidad genética intrapoblacional y las poblaciones de Itaya vs Ucayali las que presentan mayor diversidad genética interpoblacional, que en parte se atribuyen al flujo de genes diferencial entre las poblaciones analizadas

Brote de Alta Mortalidad en Terneros Lecheros por Diarrea Neonatal Producida por Cryptosporidium sp Asociado a Bacteriemia en un Establo Lechero de Lima

This paper presents and discusses the clinical and pathological findings of an outbreak of neonatal diarrhea that caused a high mortality in a dairy farm in Lima, Peru. The diarrheas did not respond to antibiotics and occurred in calves less than one month old. The animals showed signs of dehydration, fluid feces, fever and marked depression of sensory. They were negative for coronavirus and rotavirus but were positive for Criptosporidium sp. In the post mortem study, a severe diffuse acute mucohemorrhagic enterocolitis was found and the histopathological diagnosis corroborated that it was a severe acute diffuse catarrhal enteritis associated with Cryptosporidium sp and bacterial nests. In the barn was found deficiencies in the management of colostrum and hygiene of the containers in which the milk was offered to the calves. The problem was solved introducing a series of good practices in calf handling.En el presente trabajo se presenta y discute los hallazgos clínicos y patológicos de un brote de diarrea neonatal que causó una alta mortalidad en un establo lechero de Lima, Perú. Los cuadros de diarrea no respondían a la antibioterapia y se presentaron en terneros menores de un mes de edad. Los animales presentaban signos de deshidratación, heces líquidas, fiebre y marcada depresión de sensorio. Fueron negativos a coronavirus y rotavirus, pero fueron positivos a Criptosporidium sp. Al estudio posmortem se encontró una severa enterocolitis mucohemorrágica difusa aguda y al diagnóstico histopatológico se corroboró que se trataba de una severa enteritis catarral difusa aguda asociada a Cryptosporidium sp y nidos bacterianos. En el establo se encontró deficiencias en el manejo del calostro e higiene de los recipientes en los que se ofrecía la leche a los terneros. El problema fue solucionado introduciendo una serie de buenas prácticas de manejo del terneraje

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART) : study protocol

Altres ajuts: RETICS funded by the PN 2018-2021 (Spain).Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD. , on 4th December 2016 (retrospectively registered)

Multicenter prospective clinical study to evaluate children short-term neurodevelopmental outcome in congenital heart disease (children NEURO-HEART): study protocol.

BACKGROUND: Congenital heart disease (CHD) is the most prevalent congenital malformation affecting 1 in 100 newborns. While advances in early diagnosis and postnatal management have increased survival in CHD children, worrying long-term outcomes, particularly neurodevelopmental disability, have emerged as a key prognostic factor in the counseling of these pregnancies. METHODS: Eligible participants are women presenting at 20 to < 37 weeks of gestation carrying a fetus with CHD. Maternal/neonatal recordings are performed at regular intervals, from the fetal period to 24 months of age, and include: placental and fetal hemodynamics, fetal brain magnetic resonance imaging (MRI), functional echocardiography, cerebral oxymetry, electroencephalography and serum neurological and cardiac biomarkers. Neurodevelopmental assessment is planned at 12 months of age using the ages and stages questionnaire (ASQ) and at 24 months of age with the Bayley-III test. Target recruitment is at least 150 cases classified in three groups according to three main severe CHD groups: transposition of great arteries (TGA), Tetralogy of Fallot (TOF) and Left Ventricular Outflow Tract Obstruction (LVOTO). DISCUSSION: The results of NEURO-HEART study will provide the most comprehensive knowledge until date of children's neurologic prognosis in CHD and will have the potential for developing future clinical decisive tools and improving preventive strategies in CHD