Complex evolutionary dynamics have produced extensive variation in brain anatomy in the animal world. In guppies, Poecilia reticulata , brain size and anatomy have been extensively studied in the laboratory contributing to our understanding of brain evolution and the cognitive advantages that arise with brain anatomical variation. However, it is unclear whether these laboratory results can be translated to natural populations. Here, we study brain neuroanatomy and its relationship with sexual traits across 18 wild guppy populations in diverse environments. We found extensive variation in female and male relative brain size and brain region volumes across populations in different environment types and with varying degrees of predation risk. In contrast with laboratory studies, we found differences in allometric scaling of brain regions, leading to variation in brain region proportions across populations. Finally, we found an association between sexual traits, mainly the area of black patches and tail length, and brain size. Our results suggest differences in ecological conditions and sexual traits are associated with differences in brain size and brain regions volumes in the wild, as well as sexual dimorphisms in the brain's neuroanatomy.
CRISPR is a simple and cost-efficient gene-editing technique that has become increasingly popular over the last decades. Various CRISPR/Cas-based applications have been developed to introduce changes in the genome and alter gene expression in diverse systems and tissues. These novel gene-editing techniques are particularly promising for investigating and treating neurodegenerative diseases, including Parkinson’s disease, for which we currently lack efficient disease-modifying treatment options. Gene therapy could thus provide treatment alternatives, revolutionizing our ability to treat this disease. Here, we review our current knowledge on the genetic basis of Parkinson’s disease to highlight the main biological pathways that become disrupted in Parkinson’s disease and their potential as gene therapy targets. Next, we perform a comprehensive review of novel delivery vehicles available for gene-editing applications, critical for their successful application in both innovative research and potential therapies. Finally, we review the latest developments in CRISPR-based applications and gene therapies to understand and treat Parkinson’s disease. We carefully examine their advantages and shortcomings for diverse gene-editing applications in the brain, highlighting promising avenues for future research.
Gene delivery has emerged as a promising alternative to conventional treatment approaches, allowing for the manipulation of gene expression through gene insertion, deletion, or alteration. However, the susceptibility of gene delivery components to degradation and challenges associated with cell penetration necessitate the use of delivery vehicles for effective functional gene delivery. Nanostructured vehicles, such as iron oxide nanoparticles (IONs) including magnetite nanoparticles (MNPs), have demonstrated significant potential for gene delivery applications due to their chemical versatility, biocompatibility, and strong magnetization. In this study, we developed an ION-based delivery vehicle capable of releasing linearized nucleic acids (tDNA) under reducing conditions in various cell cultures. As a proof of concept, we immobilized a CRISPR activation (CRISPRa) sequence to overexpress the pink1 gene on MNPs functionalized with polyethylene glycol (PEG), 3-[(2-aminoethyl)dithio]propionic acid (AEDP), and a translocating protein (OmpA). The nucleic sequence (tDNA) was modified to include a terminal thiol group and was conjugated to AEDP’s terminal thiol via a disulfide exchange reaction. Leveraging the natural sensitivity of the disulfide bridge, the cargo was released under reducing conditions. Physicochemical characterizations, including thermogravimetric analysis (TGA) and Fourier-transform infrared (FTIR) spectroscopy, confirmed the correct synthesis and functionalization of the MNP-based delivery carriers. The developed nanocarriers exhibited remarkable biocompatibility, as demonstrated by the hemocompatibility, platelet aggregation, and cytocompatibility assays using primary human astrocytes, rodent astrocytes, and human fibroblast cells. Furthermore, the nanocarriers enabled efficient cargo penetration, uptake, and endosomal escape, with minimal nucleofection. A preliminary functionality test using RT-qPCR revealed that the vehicle facilitated the timely release of CRISPRa vectors, resulting in a remarkable 130-fold overexpression of pink1. We demonstrate the potential of the developed ION-based nanocarrier as a versatile and promising gene delivery vehicle with potential applications in gene therapy. The developed nanocarrier is capable of delivering any nucleic sequence (up to 8.2 kb) once it is thiolated using the methodology explained in this study. To our knowledge, this represents the first MNP-based nanocarrier capable of delivering nucleic sequences under specific reducing conditions while preserving functionality.
Se presentan dos casos de dengue hemorrágico durante el embarazo, manejados en el Hospital Universitario Metropolitano, el primero con 35 semanas y el segundo con 21 semanas. Comprobándose el diagnóstico de ambos no sólo por el cuadro clínico, sino también por la prueba del torniquete y la positividad de las inmunoglobulinas.Anotamos que no encontramos documentación sobre pacientes con dengue hemorrágico y embarazo sin otra complicación, por lo tanto presentamos y sugerimos el manejo que realizamos, pues fue satisfactorio en las dos pacientes.Consideramos de suma importancia la divulgación de estos casos, ya que son muy escasos los reportes en la literatura sobre dengue y embarazo, y no existe un manejo estipulado para estas pacientes, a pesar de haber revisado las normas de la Organización Panamericana de la Salud (OPS).
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