Analysis of Thyroid Response Element Activity during Retinal Development

Thyroid hormone (TH) signaling components are expressed during retinal development in dynamic spatial and temporal patterns. To probe the competence of retinal cells to mount a transcriptional response to TH, reporters that included thyroid response elements (TREs) were introduced into developing retinal tissue. The TREs were placed upstream of a minimal TATA-box and two reporter genes, green fluorescent protein (GFP) and human placental alkaline phosphatase (PLAP). Six of the seven tested TREs were first tested in vitro where they were shown to drive TH-dependent expression. However, when introduced into the developing retina, the TREs reported in different cell types in both a TH-dependent and TH-independent manner, as well as revealed specific spatial patterns in their expression. The role of the known thyroid receptors (TR), TRα and TRβ, was probed using shRNAs, which were co-electroporated into the retina with the TREs. Some TREs were positively activated by TR+TH in the developing outer nuclear layer (ONL), where photoreceptors reside, as well as in the outer neuroblastic layer (ONBL) where cycling progenitor cells are located. Other TREs were actively repressed by TR+TH in cells of the ONBL. These data demonstrate that non-TRs can activate some TREs in a spatially regulated manner, whereas other TREs respond only to the known TRs, which also read out activity in a spatially regulated manner. The transcriptional response to even simple TREs provides a starting point for understanding the regulation of genes by TH, and highlights the complexity of transcriptional regulation within developing tissue

Efficacy of Major Plant Extracts/Molecules on Field Insect Pests

Insect pests are considered the major hurdle in enhancing the production and productivity of any farming system. The use of conventional synthetic pesticides has led to the emergence of pesticide-resistant insects, environmental pollution, and negative effects on natural enemies, which have caused an ecological imbalance of the predator-prey ratio and human health hazards; therefore, eco-friendly alternative strategies are required. The plant kingdom, a rich repertoire of secondary metabolites, can be tapped as an alternative for insect pest management strategies. A number of plants have been documented to have insecticidal properties against various orders of insects in vitro by acting as antifeedants, repellents, sterilant and oviposition deterrents, etc. However, only a few plant compounds are applicable at the field level or presently commercialised. Here, we have provided an overview of the broad-spectrum insecticidal activity of plant compounds from neem, Annona, Pongamia, and Jatropha. Additionally, the impact of medicinal plants, herbs, spices, and essential oils has been reviewed briefl

Caminho das letras: educação, formação e perspectivas

ial que se apresenta com o tema “Caminho das letras: Educação, Formação e Perspectivas”, partindo da vida escolar como aluno, chegando a atuação como professora, caracteriza-se também por uma reflexão teórica acerca do papel que as escolas cumprem na sociedade - será que servem como redutoras, ou apenas como indutoras da desigualdade social? A igualdade já deve começar em relação aos conhecimentos, conteúdos, de forma que contemplem suas aspirações, capacidades e possibilidades dos educandos, uma vez que o poder do capital refletiu também no sistema educacional, pois esta ficou com a tarefa de preparar mão-de-obra para a indústria, se preocupando apenas em atender ao mercado de trabalho, educando-se para seguir modelos, regras, se disciplinar e especializar. Deste modo, com base em textos trabalhados durante as aulas, vou teorizar minhas memórias, muitas não tão distantes. Neste trabalho, procuro relatar como compreendi o sentido da escola, se o seu papel é de formar ou apenas informar. Fiz-me esta questão, uma vez que Educação e instrução caminham juntas, completando o intelectual e o social, e assim a Gestão Escolar, há de ter representatividade, não ser meramente funcional. Dessa forma, uma Gestão Escolar com representatividade é democrática e autônoma, que envolve os diferentes atores da Educação (alunos, pais, professores, coordenação e direção). Deve garantir um ensino não fragmentado, proporcionar um intercâmbio entre as matérias, para que o aluno tenha uma visão unificada dos conhecimentos. Por fim, cheguei à conclusão entendendo que, o aluno não aprende por discursos, e sim pela vivência, muitos aprendizados são adquiridos com base nos relacionamentos, ou seja, nas interações e conflitos com o outro

Thyroid Hormone Economy in the Perinatal Mouse Brain: Implications for Cerebral Cortex Development.

Thyroid hormones (THs, T4 and the transcriptionally active hormone T3) play an essential role in neurodevelopment; however, the mechanisms underlying T3 brain delivery during mice fetal development are not well known. This work has explored the sources of brain T3 during mice fetal development using biochemical, anatomical, and molecular approaches. The findings revealed that during late gestation, a large amount of fetal brain T4 is of maternal origin. Also, in the developing mouse brain, fetal T3 content is regulated through the conversion of T4 into T3 by type-2 deiodinase (D2) activity, which is present from earlier prenatal stages. Additionally, D2 activity was found to be essential to mediate expression of T3-dependent genes in the cerebral cortex, and also necessary to generate the transient cerebral cortex hyperthyroidism present in mice lacking the TH transporter Monocarboxylate transporter 8. Notably, the gene encoding for D2 (Dio2) was mainly expressed at the blood-cerebrospinal fluid barrier (BCSFB). Overall, these data signify that T4 deiodinated by D2 may be the only source of T3 during neocortical development. We therefore propose that D2 activity at the BCSFB converts the T4 transported across the choroid plexus into T3, thus supplying the brain with active hormone to maintain TH homeostasis.This work was supported by the Spanish Ministry of Economy and Competitiveness (grant numbers SAF2011-25608, SAF2012-32491, and SAF2014-54919-R), the Center for Biomedical Research on Rare Diseases (CIBERER) of Instituto de Salud Carlos III under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases (project acronym THYRONERVE) and by Comunidad de Madrid (CAM; grant number S2010/BMD-2423). S.B.-L. is a recipient of a predoctoral fellowship and contract from the FPI program of the Plan Nacional de I+D+i. The cost of this publication has been paid in part by FEDER funds.Peer reviewe

The basal ganglia: a new possible therapeutic target in the Allan-Herndon-Dudley Syndrome

Resumen del póster presentado al 3rd Symposium on Biomedical Research: "Advances and Perspectives in Neuroscience", celebrado en la Universidad Autónoma de Madrid el 22 de abril de 2016.The Allan-Herndon-Dudley syndrome (AHDS) is a rare disease caused by mutations in the gene SLC16A2, which codifies for the monocarboxylate transporter 8 (MCT8), the solely cell-membrane transporter that specifically transports thyroid hormones. The altered expression of the mutated MCT8 causes peripheral hyperthyroidism and brain hypothyroidism, which is thought to be the cause of the neurological phenotype in AHDS patients that includes mental and developmental retardation, hypotonia and in most of the cases epilepsy. These clinical features start early in the infancy and develop in the adulthood to spastic tetraplegia and paroxysmal dyskinesia. The mechanisms underlying the disease are unknown so far and there is not an effective treatment. In this study, we have focused our work on the basal ganglia, as they are part of the motor voluntary movement controlling system. We have analyzed human paraffin-embedded brain sections of the basal ganglia taken from necropsies of AHDS patients and controls by immunohistochemistry for detection of MCT8, some of the characteristic markers of striatal neural populations (enkephalin and choline acetyltransferase) and other markers of synapsis (synaptophysin) or damage. We have observed an alteration of the basal ganglia circuitry based on the abnormal expression pattern of enkephalin and choline acetyltransferase in the striatum of the AHDS patients. We have also observed alterations in the synaptophysin staining in patients versus control basal ganglia. These results indicate that the basal ganglia are severely affected by mutations in MCT8 and that structural and functional alterations in this region could be the cause of some clinical features found in AHDS patients, which suggests that those areas could be considered therapeutic targets in AHDS.Supported by grants from the Spanish Ministry of Economy and Competitiveness (MINECO) SAF2014-54919-R.Peer Reviewe

MCT8-D2 knock-out mice present hyperactivity and deep alterations in their metabolic rates during the dark phase

Trabajo presentado en el FENS Regional Meeting, celebrado en Belgrado (Serbia) del 10 al 13 de julio de 2019