The Specification of Dorsal and Lateral Pattern in the <i>Drosophila</i> Embryo

The dorsal-ventral axis of the Drosophila embryo is established through the nuclear gradient expression of the maternal morphogen dorsal, which sets up the dorsal, lateral, and ventral domains along the embryo circumference. The steps from this maternal signal to the onset of patterning and morphogenesis is quite rapid, and although genetic approaches have identified several zygotic genes that are transcriptionally regulated by dorsal, the direct targets of these zygotic genes, as well as other targets of dorsal, are still unknown. A molecular screen was utilized in order to identify genes that are differentially expressed along the dorsal-ventral axis, with a specific focus on dorsal-lateral genes involved in patterning and differentiation. A subtractive cDNA library highly enriched for genes expressed in the dorsal and lateral regions of the embryo was screened twice. From the two screens, 24 non-crosshybridizing clones were obtained, 21 of which appear to be novel genes based on preliminary sequence analysis and in situ hybridization patterns. Two clones turned out to be cDNA fragments of previously identified genes. One clone had an identical sequence to the Drosophila POU domain genes pdm-1 and pdm-2, while the other turned out to be tolloid, one of the dorsal-ventral patterning genes. In conjunction with previously described genes, several clones from the library were then chosen to serve as molecular markers for specific domains along the dorsal-ventral axis. In situ hybridizations were performed on a series of mutant embryos either lacking progressively larger portions of the dorsal part of the embryo (zygotic ventralizing mutants), or lacking the entire mesoderm (twist snail double mutants). The aim of this thesis was to understand how patterning along the dorsal-ventral axis occurs, and to determine whether the current model on how the genes for the zygotic ventralizing mutants interact with one another to pattern the dorsal part of the embryo is correct. Indeed, a number of results show that this model may have to be revised

Mujeres imaginadas : mujeres migrantes, mujeres exiliadas y sexualidades no normativas

Programa Oficial de Doctorado en HumanidadesPresidente: Isabel Carrera Suárez.- Secretario: Julio Enrique Checa Puerta.- Vocal: Rosa Pellicer Domíngue

Complejo industrial fronterizo, sexualidad y género

Me propongo revisar cómo el largo horizonte colonial de género y sexualidad –en el marco de las relaciones coloniales entre América Latina y España reactualizadas mediante la migración, el desplazamiento, el exilio y el destierro– hace parte del funcionamiento del Complejo Industrial Fronterizo. Elaboro este artículo a partir de un trabajo que se extiende por un período de diez años de reflexión e investigación etnográfica multisituada–en Bogotá, Cali, Medellín, Cartagena, Madrid y Barcelona– sobre migraciones, hecha desde una perspectiva interseccional. Mostraré cómo personas con sexualidades e identidades no hegemónicas llegan a hacer parte de la carne de la industria migratoria en medio de la operación de las «tramas transnacionales del cuidado» y en el contexto de la agenda internacional neocolonial «contra la ideología de género»

Control remoto

Se hace un análisis sobre el espectador, y cómo se conforma como individuo, ante lo que la televisión presenta, y como también se establece en una sociedad pues la televisión es un transmisor fundamental de la cultura, tanto a escalas macropolíticas como micropolíticas. Como el individuo se configura en la sociedad por lo que consume, y como este consumo está determinado por los ideales que vende la televisión. El trabajo se cierra con la explicación del producto que materializa las consideraciones que se exponen en los tres primeros capítulos que hablan sobre el funcionamiento de la televisión como agente político y económico fundamental de la vida postmoderna. Se anexan los códigos, el diseño de la camiseta, el programa y las instrucciones para poder ver el producto del que se habla, y que se presentó como fruto de la investigación.Comunicador (a) SocialPregrad

Interseccionalidad y políticas públicas LGBTI en Colombia: usos y desplazamientos de una noción crítica

Este artículo es una aproximación a las experiencias de formación de políticas públicas en Colombia que han hecho uso de la noción de interseccionalidad, específicamente, las políticas dirigidas a los sectores LGBTI en Bogotá, Valle del Cauca y Colombia. Planteamos un ejercicio analítico de estas experiencias de las que hemos sido partícipes, cada una de nosotras en distintos momentos, y que representan el reto de llevar propuestas de los movimientos sociales y la academia, en particular de los feminismos negros y de color, al escenario estatal. Nuestra participación en la formación de dichas políticas y, ahora, la escritura de este artículo nos permiten buscar porosidades y vínculos en y entre distintos escenarios: el estatal, el académico y los movimientos sociales.This article offers an approach to the experiences of public policy formation that have used the concept of intersectionality, in particular, those policies aimed at LGBTI people in Bogota, Valle del Cauca and Colombia in general. We propose an analytical exercise of these experiences, in which we have each participated at different times. These exercises have challenged us in terms of bringing proposals from social movements and academia—such as black feminism and feminisms of color, among other actors—to the realm of the state. Our participation in the formation of these policies, and in writing this article, let us seek strategies that allow for movements among different political arenas and discursive practices, illuminating porosities in and linkages among different scenarios: the state, academia and social movements.Este artigo é uma aproximação às experiências de formação de políticas públicas na Colômbia que têm feito uso da noção de interseccionalidade, especificamente, as políticas dirigidas aos setores LGBTI em Bogotá, Valle del Cauca e Colômbia. Propomos um exercício analítico dessas experiências das quais temos sido partícipes, cada uma de nós em diferentes momentos, e que representam o desafio de levar propostas dos movimentos sociais e da academia, em particular dos feminismos negros e de cor, ao cenário estatal. Nossa participação na formação dessas políticas e, agora, da construção deste artigo, nos permitem buscar porosidades e vínculos em e entre diferentes cenários: o estatal, o acadêmico e os movimentos sociais

Cambios neuropsicológicos asociados a estimulación cerebral profunda en enfermedad de Parkinson: Revisión Teórica

La enfermedad de Parkinson es una patolog&iacute;a neurodegenerativa causada por la p&eacute;rdida de c&eacute;lulas dopaminergicas en la sustancia negra mesencef&aacute;lica. Esto produce una disfunci&oacute;n de los n&uacute;cleos basales que se manifiesta con s&iacute;ntomas motores como temblor, rigidez y bradicinecia entre otros. Con la estimulaci&oacute;n cerebral profunda (ECP) ha resurgido la cirug&iacute;a como opci&oacute;n terap&eacute;utica y es el n&uacute;cleo subtal&aacute;mico el &aacute;rea diana predilecta. Los estudios muestran mejoras significativas en los d&eacute;ficits motores, pero no hay claridad sobre los cambios neuropsicol&oacute;gicos de los pacientes sometidos a ECP. Se hace una revisi&oacute;n de los diferentes estudios que han investigado los cambios cognitivos, emocionales y comportamentales concluyendo que la mayor&iacute;a de habilidades cognitivas se mantienen o mejoran despu&eacute;s de la ECP, pero pueden existir cambios emocionales y comportamentales adversos que est&aacute;n relacionadas con el n&uacute;cleo cerebral donde se implanta el electrodo y con las caracter&iacute;sticas premorbidas de personalidad

Zebrafish Bioassay-guided Microfractionation for the Rapid in vivo Identification of Pharmacologically Active Natural Products

The rapid acquisition of structural and bioactivity information on natural products (NPs) at the sub- milligram scale is key for performing efficient bioactivity-guided isolations. Zebrafish offer the possibility of rapid in vivo bioactivity analysis of small molecules at the microgram scale – an attractive feature when combined with high-resolution fractionation technologies and analytical methods such as UHPLC-TOF-MS and microflow NMR. Numerous biomedically relevant assays are now available in zebrafish, encompassing most indication areas. Zebrafish also provide the possibility to screen bioactive compounds for potential hepato-, cardio-, and neurotoxicities at a very early stage in the drug discovery process. Here we describe two strategies using zebrafish bioassays for the high-resolution in vivo bioactivity profiling of medicinal plants, using either a one-step or a two-step procedure for active compound isolation directly into 96-well plates. The analysis of the microfractions by microflow NMR in combination with UHPLC-TOF-MS of the extract enables the rapid dereplication of compounds and an estimation of their microgram quantities for zebrafish bioassays. Both the one-step and the two-step isolation procedures enable a rapid estimation of the bioactive potential of NPs directly from crude extracts. In summary, we present an in vivo , microgram-scale NP discovery platform combining zebrafish bioassays with microscale analytics to identify, isolate and evaluate pharmacologically active NPs

Perinatal exposure to potential endocrine disrupting chemicals and autism spectrum disorder: From Norwegian birth cohort to zebrafish studies

publishedVersionpublishedVersio

N-Benzyl-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) with hybrid structure as a candidate for a broad-spectrum antiepileptic drug

In our recent studies, we identified compound N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide (AS-1) as a broad-spectrum hybrid anticonvulsant which showed potent protection across the most important animal acute seizure models such as the maximal electroshock (MES) test, the subcutaneous pentylenetetrazole (s.c. PTZ) test, and the 6-Hz (32 mA) test in mice. Therefore, AS-1 may be recognized as a candidate for new anticonvulsant effective in different types of human epilepsy with a favorable safety margin profile determined in the rotarod test in mice. In the aim of further pharmacological evaluation of AS-1, in the current study, we examined its activity in the 6-Hz (44 mA) test, which is known as the model of drug-resistant epilepsy. Furthermore, we determined also the antiseizure activity in the kindling model of epilepsy induced by repeated injection of pentylenetetrazole (PTZ) in mice. As a result, AS-1 revealed relatively potent protection in the 6-Hz (44 mA) test, as well as delayed the progression of kindling induced by repeated injection of PTZ in mice at doses of 15 mg/kg, 30 mg/kg, and 60 mg/kg. Importantly, the isobolographic analysis showed that a combination of AS-1 and valproic acid (VPA) at the fixed ratio of 1:1 displayed a supra-additive (synergistic) interaction against PTZinduced seizures inmice. Thus, AS-1may be potentially used in an add-on therapy with VPA. Moreover, incubation of zebrafish larvae with AS-1 substantially decreased the number, cumulative but not the mean duration of epileptiform-like events in electroencephalographic assay. Finally, the in vitro ADME-Tox studies revealed that AS-1 is characterized by a very good permeability in the parallel artificial membrane permeability assay test, excellent metabolic stability on human liver microsomes (HLMs), no significant influence on CYP3A4/CYP2D6 activity, and moderate inhibition of CYP2C9 in a concentration of 10 $\mu$M, as well as no hepatotoxic properties in HepG2 cells (concentration of 10 $\mu$M)

Discovery of (R)-N-benzyl-2-(2,5-dioxopyrrolidin-1-yl)propanamide [(R)-AS-1], a novel orally bioavailable EAAT2 modulator with drug-like properties and potent antiseizure activity in vivo

[Image: see text] (R)-7 [(R)-AS-1] showed broad-spectrum antiseizure activity across in vivo mouse seizure models: maximal electroshock (MES), 6 Hz (32/44 mA), acute pentylenetetrazol (PTZ), and PTZ-kindling. A remarkable separation between antiseizure activity and CNS-related adverse effects was also observed. In vitro studies with primary glia cultures and COS-7 cells expressing the glutamate transporter EAAT2 showed enhancement of glutamate uptake, revealing a stereoselective positive allosteric modulator (PAM) effect, further supported by molecular docking simulations. (R)-7 [(R)-AS-1] was not active in EAAT1 and EAAT3 assays and did not show significant off-target activity, including interactions with targets reported for marketed antiseizure drugs, indicative of a novel and unprecedented mechanism of action. Both in vivo pharmacokinetic and in vitro absorption, distribution, metabolism, excretion, toxicity (ADME-Tox) profiles confirmed the favorable drug-like potential of the compound. Thus, (R)-7 [(R)-AS-1] may be considered as the first-in-class small-molecule PAM of EAAT2 with potential for further preclinical and clinical development in epilepsy and possibly other CNS disorders