FGF signaling controls caudal hindbrain specification through Ras-ERK1/2 pathway

<p>Abstract</p> <p>Background</p> <p>During early steps of embryonic development the hindbrain undergoes a regionalization process along the anterior-posterior (AP) axis that leads to a metameric organization in a series of rhombomeres (r). Refinement of the AP identities within the hindbrain requires the establishment of local signaling centers, which emit signals that pattern territories in their vicinity. Previous results demonstrated that the transcription factor <it>vHnf1 </it>confers caudal identity to the hindbrain inducing <it>Krox20 </it>in r5 and <it>MafB/Kreisler </it>in r5 and r6, through FGF signaling <abbrgrp><abbr bid="B1">1</abbr></abbrgrp>.</p> <p>Results</p> <p>We show that in the chick hindbrain, <it>Fgf3 </it>is transcriptionally activated as early as 30 min after <it>mvHnf1 </it>electroporation, suggesting that it is a direct target of this transcription factor. We also analyzed the expression profiles of FGF activity readouts, such as <it>MKP3 </it>and <it>Pea3</it>, and showed that both are expressed within the hindbrain at early stages of embryonic development. In addition, <it>MKP3 </it>is induced upon overexpression of <it>mFgf3 </it>or <it>mvHnf1 </it>in the hindbrain, confirming <it>vHnf1 </it>is upstream FGF signaling. Finally, we addressed the question of which of the FGF-responding intracellular pathways were active and involved in the regulation of <it>Krox20 </it>and <it>MafB </it>in the hindbrain. While Ras-ERK1/2 activity is necessary for <it>MKP3, Krox20 and MafB </it>induction, PI3K-Akt is not involved in that process.</p> <p>Conclusion</p> <p>Based on these observations we propose that <it>vHnf1 </it>acts directly through FGF3, and promotes caudal hindbrain identity by activating <it>MafB </it>and <it>Krox20 </it>via the Ras-ERK1/2 intracellular pathway.</p

La Formació del cervell dels vertebrats, una telenovel·la?

El cervell dels vertebrats és tan complex que traçar-ne els orígens evolutius és problemàtic. Els estudis dels parents més propers als vertebrats, els ascidis i l'amfiox, mostraven que les proteïnes necessàries per formar aquest cervell eren exclusives dels vertebrats; ara bé, un nou article exposa que les bases gèniques d'aquesta estructura ja eren presents en branques més llunyanes de l'arbre evolutiu

Transient Exposure to Ethanol during Zebrafish Embryogenesis Results in Defects in Neuronal Differentiation : An Alternative Model System to Study FASD

The exposure of the human embryo to ethanol results in a spectrum of disorders involving multiple organ systems, including the impairment of the development of the central nervous system (CNS). In spite of the importance for human health, the molecular basis of prenatal ethanol exposure remains poorly understood, mainly to the difficulty of sample collection. Zebrafish is now emerging as a powerful organism for the modeling and the study of human diseases. In this work, we have assessed the sensitivity of specific subsets of neurons to ethanol exposure during embryogenesis and we have visualized the sensitive embryonic developmental periods for specific neuronal groups by the use of different transgenic zebrafish lines. In order to evaluate the teratogenic effects of acute ethanol exposure, we exposed zebrafish embryos to ethanol in a given time window and analyzed the effects in neurogenesis, neuronal differentiation and brain patterning. Zebrafish larvae exposed to ethanol displayed small eyes and/or a reduction of the body length, phenotypical features similar to the observed in children with prenatal exposure to ethanol. When neuronal populations were analyzed, we observed a clear reduction in the number of differentiated neurons in the spinal cord upon ethanol exposure. There was a decrease in the population of sensory neurons mainly due to a decrease in cell proliferation and subsequent apoptosis during neuronal differentiation, with no effect in motoneuron specification. Our investigation highlights that transient exposure to ethanol during early embryonic development affects neuronal differentiation although does not result in defects in early neurogenesis. These results establish the use of zebrafish embryos as an alternative research model to elucidate the molecular mechanism(s) of ethanol-induced developmental toxicity at very early stages of embryonic development

Community-based screening of Chagas disease among Latin American migrants in a non-endemic country: an observational study

Background: Chagas disease is a parasitic disease endemic to Latin America, but it has become a disease of global concern due to migration flows. Asymptomatic carriers may host the parasite for years, without knowing they are infected. The aim of this study is to assess prevalence of Chagas disease and evaluate the participants' level of knowledge between Latin American migrants attending a community-based screening campaign. Methods: Three community-based campaigns were performed in Alicante (Spain) in 2016, 2017 and 2018, including educational chats and blood tests for Trypanosoma cruzi serology. Participants completed a questionnaire assessing knowledge about the mechanisms of transmission, disease presentation, diagnosis, and treatment. People seropositive for T. cruzi underwent diagnostic confirmation by two different tests. Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios (aORs), adjusting for age, sex, and time in Spain. Results: A total of 596 participants were included in the study; 17% were aged under 18 years. Prevalence in adults was 11% [54/496; 95% confidence interval (CI): 8.3-14.5%] versus 0% among children. All but one case were in Bolivians. Diagnosis was independently associated with having been born in Bolivia (aOR: 102, 95% CI: 13-781) and a primary school-level education (aOR: 2.40, 95% CI: 1.14-5.06). Of 54 people diagnosed with Chagas disease (most of whom were asymptomatic), 42 (77.7%) returned to the clinic at least once, and 24 (44.4%) received treatment. Multivariable analysis showed that coming from Argentina (aOR: 13, 95% CI: 1.61-1188) or Bolivia (aOR: 1.90, 95% CI: 1.19-3.39) and having received information about Chagas disease in Spain (aOR: 4.63, 95% CI: 2.54-8.97) were associated with a good level of knowledge on the disease. Having primary level studies (aOR: 0.59, 95% CI: 0.34-0.98) and coming from Ecuador (aOR: 4.63, 95% CI: 2.52-847) were independently associated with a lower level of knowledge. Conclusions: Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected, asymptomatic individuals.This study was partially supported by the third call for research grants (J-M.R.-R.) from the Institute of Health and Biomedical Research of Alicante (ISABIAL)/FISABIO Foundation (III convocatoria de ayudas a proyectos de investigación del Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) – Fundación FISABIO) (UGP-16-158); and by the collaborative agreement between ISABIAL/Fundación FISABIO and Fundación Mundo Sano-Spain, in accordance with the Sponsorship Law. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Asymptomatic Strongyloidiasis among Latin American Migrants in Spain: A Community-Based Approach

Strongyloides stercoralis infection is frequently underdiagnosed since many infections remain asymptomatic. Aim: To estimate the prevalence and characteristics of asymptomatic S. stercoralis infection in Latin American migrants attending a community-based screening program for Chagas disease in Spain. Methodology: Three community-based Chagas disease screening campaigns were performed in Alicante (Spain) in 2016, 2017, and 2018. Serological testing for S. stercoralis infection was performed using a non-automatized IVD-ELISA detecting IgG (DRG Instruments GmbH, Marburg, Germany). Results: Of the 616 migrants from Central and South America who were screened, 601 were included in the study: 100 children and adolescents (<18 years of age) and 501 adults. Among the younger group, 6 participants tested positive (prevalence 6%, 95% confidence interval [CI] 2.5% to 13.1%), while 60 adults did so (prevalence 12%, 95% CI 9.3% to 15.3%). S. stercoralis infection was more common in men than in women (odds ratio adjusted [ORa] 2.28, 95% CI 1.289 to 4.03) and in those from Bolivia (ORa 2.03, 95% CI 1.15 to 3.59). Prevalence increased with age (ORa 1.02, 95% CI 0.99 to 1.05). In contrast, a university education had a protective effect (ORa 0.29, 95% CI 0.31 to 0.88). Forty-one (41/66; 62.1%) of the total cases of S. stercoralis infection were treated at the health care center. Positive stool samples were observed in 19.5% of the followed-up positive cases. Conclusion: Incorporating serological screening for S. stercoralis into community-based screening for Chagas disease is a useful intervention to detect asymptomatic S. stercoralis infection in Central and South American migrants and an opportunity to tackle neglected tropical diseases in a transversal way. The remaining challenge is to achieve patients' adherence to the medical follow-up.This study was partially supported by the 3rd call for research project grants for the Institute of Health and Biometric Research of Alicante (ISABIAL)/FISABIO Foundation (UGP-16-158), and by the collaboration agreement regulated under the Law of Patronage between ISABIAL/FISABIO and the Foundation Mundo Sano, Spain.S

Transcriptome Fingerprinting Analysis: An Approach to Explore Gene Expression Patterns in Marine Microbial Communities

Microbial transcriptomics are providing new insights into the functional processes of microbial communities. However, analysis of each sample is still expensive and time consuming. A rapid and low cost method that would allow the identification of the most interesting samples for posterior in-depth metatranscriptomics analysis would be extremely useful. Here we present Transcriptome Fingerprinting Analysis (TFA) as an approach to fulfill this objective in microbial ecology studies. We have adapted the differential display technique for mRNA fingerprinting based on the PCR amplification of expressed transcripts to interrogate natural microbial eukaryotic communities. Unlike other techniques, TFA does not require prior knowledge of the mRNA sequences to be detected. We have used a set of arbitrary primers coupled with a fluorescence labeled primer targeting the poly(A) tail of the eukaryotic mRNA, with further detection of the resulting labeled cDNA products in an automated genetic analyzer. The output represented by electropherogram peak patterns allowed the comparison of a set of genes expressed at the time of sampling. TFA has been optimized by testing the sensitivity of the method for different initial RNA amounts, and the repeatability of the gene expression patterns with increasing time after sampling both with cultures and environmental samples. Results show that TFA is a promising approach to explore the dynamics of gene expression patterns in microbial communities

Some thoughts about open ccience: a few challenges and a great opportunity for science

Open Science focuses on spreading knowledge generated by scientific research as soon as it is available using digital and collaborative technology. The aim is to make science more accessible, inclusive, and equitable for the benefit of all. In this article, I will discuss some of the challenges and opportunities of this approach to the scientific process towards a comprehensive, effective open science from my perspective as a scientist in biology and health sciences. My aim is to share this with the academic community, since as Vice-Rector for Research and as scientist, I think this is one opportunity that we do not want to miss