Identification and characterization of early photoreceptor cis-regulatory elements and their relation to Onecut1

Background: Cone and rod photoreceptors are two of the primary cell types affected in human retinal disease. Potential strategies to combat these diseases are the use of gene therapy to rescue compromised photoreceptors or to generate new functional photoreceptors to replace those lost in the diseased retina. Cis-regulatory elements specific to cones, rods, or both types of photoreceptors are critical components of successful implementation of these two strategies. The purpose of this study was to identify and characterize the cell type specificity and activity of cis-regulatory elements active in developing photoreceptors. Methods: Cis-regulatory elements were introduced into the developing chicken and mouse retina by electroporation. Characterization of reporter activity in relation with cell type markers was determined using confocal microscopy. In addition, two high-throughput flow cytometry assay were developed to assess whether these elements were downstream of Onecut1 in the photoreceptor specification network. Results: The majority of cis-regulatory elements were active in both cone and rod photoreceptors and were largely uninfluenced by a Onecut1 dominant-negative construct. Elements associated with the Thrb, Nr2e3, and Rhodopsin genes showed highly enriched activity in cones or rods, and were affected by interference in Onecut1 signaling. Rhodopsin promoter activity was the most highly influenced by Onecut1 activity and its induction could be modulated by the Maf family transcription factor L-Maf. Nr2e3 elements were observed to have activity in cone photoreceptors and Nr2e3 protein was expressed in developing cone photoreceptors, suggesting a role for this predominant rod gene in cone photoreceptor development. Conclusions: The analysis presented here provides an experimental framework to determine the specificity and strength of photoreceptor elements within specific genetic networks during development. The Onecut1 transcription factor is one such factor that influences the gene regulatory networks specific to cones and rods, but not those that are common to both

Efectos de sustancias psicoactivas en la salud humana y sus consecuencias en el bienestar físico-mental

The use of psychoactive substances is a global problem of concern, especially among adolescents, with significant consequences for physical and mental health. This study focuses on identifying the effects of these substances on human health and their impact on physical-mental well-being. The main objective of this research is to determine the effects of psychoactive substances on human health and their consequences on physical-mental well-being. The aim is to understand the main substances consumed, the risk factors and the short and long term implications. To address this objective, a descriptive approach was used based on a systematic review of the scientific literature. Primary research and relevant sources from the last 5 to 10 years were collected and analyzed, using tools such as Google Scholar, Scielo, UNODC, Pan American Health Organization and WHO. Various psychoactive substances were identified, such as alcohol, tobacco, cannabis, cocaine, among others, with negative impacts on physical and mental health. The stages of consumption, risk factors and adverse consequences were described, ranging from neurochemical imbalances to cardiovascular problems, psychological disorders and death. Addressing the consumption of psychoactive substances requires effective policies and strategies supported by scientific evidence. Despite the efforts made, the lack of exhaustive studies makes it difficult to fully understand its impact on health. It is crucial to continue research to develop more effective interventions and prevent negative impacts on the physical and mental health of people who use these substances.El consumo de sustancias psicoactivas es un problema global de preocupación, especialmente entre los adolescentes, con consecuencias significativas para la salud física y mental. Este estudio se centra en identificar los efectos de estas sustancias en la salud humana y su impacto en el bienestar físico-mental. El objetivo principal de esta investigación es determinar los efectos de las sustancias psicoactivas en la salud humana y sus consecuencias en el bienestar físico-mental. Se busca comprender las principales sustancias consumidas, los factores de riesgo y las implicaciones a corto y largo plazo. Para abordar este objetivo, se empleó un enfoque descriptivo basado en una revisión sistemática de la literatura científica. Se recopilaron y analizaron investigaciones primarias y fuentes relevantes de los últimos 5 a 10 años, utilizando herramientas como Google Scholar, Scielo, UNODC, Organización Panamericana de la Salud y la OMS. Se identificaron diversas sustancias psicoactivas, como el alcohol, tabaco, cannabis, cocaína, entre otras, con impactos negativos en la salud física y mental. Se describieron las etapas del consumo, factores de riesgo y las consecuencias adversas, que van desde desajustes neuroquímicos hasta problemas cardiovasculares, trastornos psicológicos y muerte. El abordaje del consumo de sustancias psicoactivas requiere políticas y estrategias eficaces respaldadas por evidencia científica. A pesar de los esfuerzos realizados, la falta de estudios exhaustivos dificulta la comprensión completa de sus repercusiones en la salud. Es crucial continuar investigando para desarrollar intervenciones más efectivas y prevenir los impactos negativos en la salud física y mental de las personas que consumen estas sustancias

Increasing Maternal or Post-Weaning Folic Acid Alters Gene Expression and Moderately Changes Behavior in the Offspring

Background Studies have indicated that altered maternal micronutrients and vitamins influence the development of newborns and altered nutrient exposure throughout the lifetime may have potential health effects and increased susceptibility to chronic diseases. In recent years, folic acid (FA) exposure has significantly increased as a result of mandatory FA fortification and supplementation during pregnancy. Since FA modulates DNA methylation and affects gene expression, we investigated whether the amount of FA ingested during gestation alters gene expression in the newborn cerebral hemisphere, and if the increased exposure to FA during gestation and throughout the lifetime alters behavior in C57BL/6J mice. Methods Dams were fed FA either at 0.4 mg or 4 mg/kg diet throughout the pregnancy and the resulting pups were maintained on the diet throughout experimentation. Newborn pups brain cerebral hemispheres were used for microarray analysis. To confirm alteration of several genes, quantitative RT-PCR (qRT-PCR) and Western blot analyses were performed. In addition, various behavior assessments were conducted on neonatal and adult offspring. Results Results from microarray analysis suggest that the higher dose of FA supplementation during gestation alters the expression of a number of genes in the newborns’ cerebral hemispheres, including many involved in development. QRT-PCR confirmed alterations of nine genes including down-regulation of Cpn2, Htr4, Zfp353, Vgll2 and up-regulation of Xist, Nkx6-3, Leprel1, Nfix, Slc17a7. The alterations in the expression of Slc17a7 and Vgll2 were confirmed at the protein level. Pups exposed to the higher dose of FA exhibited increased ultrasonic vocalizations, greater anxiety-like behavior and hyperactivity. These findings suggest that although FA plays a significant role in mammalian cellular machinery, there may be a loss of benefit from higher amounts of FA. Unregulated high FA supplementation during pregnancy and throughout the life course may have lasting effects, with alterations in brain development resulting in changes in behavior