Examinando por Autor "Bloch Morel, Natasha Ivonne"
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Publicación Acceso abierto Análisis de desequilibrio de transmisión de variantes comunes en el Trastorno del Espectro Autista en familias colombianas(Universidad de los Andes, 2025-12-03) Lozano Martínez, Angélica Lizeth; Lattig Matiz, María Claudia; Bloch Morel, Natasha Ivonne; Celis Ramírez, Adriana Marcela; Facultad de Ciencias::Servicios Integrales en Genética Humana (Sigen); Centro de investigaciones en genética humana CIGENEl Trastorno del Espectro Autista (TEA) es un trastorno del neurodesarrollo, el cual se caracteriza por su heterogeneidad a nivel clínico y genético. La arquitectura genética está compuesta tanto por variantes raras con alto impacto funcional como por variantes comunes de bajo efecto a lo largo de todo el genoma. Sin embargo, la mayoría de estudios genéticos se han realizado en poblaciones de origen europeo, lo que limita la comprensión del componente genético del TEA en poblaciones latinoamericanas con ancestría admixta. Por este motivo, el presente estudio tuvo como objetivo el análisis de las variantes comunes en el TEA en familias en trío de una cohorte colombiana, utilizando el Test de Desequilibrio de Transmisión (TDT). El estudio se realizó a partir de datos de SNP array, sometidos a control de calidad, filtrado, imputación genómica y aplicación del TDT, seguido de análisis de desequilibrio de ligamiento y anotación funcional regulatoria de las variantes sobretransmitidas. Se identificaron en total 11 variantes sugestivas (p≤1x10-5), presentes en los cromosomas 7, 12, 13 y 17. Las variantes presentes en los cromosomas 7 y 12 se hallaron cercanas a los genes THSD7A y CHST11 respectivamente, pero se consideraron outliers debido a su expresión en tejidos no neuronales. Por otra parte, las variantes ubicadas en los cromosomas 13 y 17 tuvieron mayor relevancia biológica al encontrarse en regiones regulatorias cerca a los genes DACH1 y RGS9. La evidencia funcional previa en estos genes sugiere expresión en ganglios basales del cerebro en vías dopaminérgicas y GABAérgicas importantes para procesos conductuales, alterados en la condición del TEA.Publicación Acceso abierto Análisis de patrones de expresión espaciotemporal del gen nlgn3 en el cerebro de peces hembra de la especie Poecilia reticulata tras la exposición a diversos contextos sociales(Universidad de los Andes, 2023-12-18) Aparicio Martínez, Nicolás; Bloch Morel, Natasha Ivonne; Bernal Giraldo, Adriana Jimena; 52863778; 52644215El presente estudio muestra la relación que existe entre la expresión del gen nlgn3 en el cerebro de las hembras de la especie Poecilia reticulata al momento de ser expuestas a diferentes contextos: contexto social y contexto de apareamiento, mostrando así la importancia de este gen en la toma de decisiones sociales.Publicación Acceso abierto Aptamer-based biosensing of bioactive compounds: towards the rational screening of metagenomic libraries(Universidad de los Andes, 2021) Ocasión Martínez, Camila; Reyes Barrios, Luis Humberto; Cruz Jiménez, Juan Carlos; Bloch Morel, Natasha Ivonne; González Barrios, Andrés FernandoLos estudios de metagenómica han sido prometedores porque han conducido al descubrimiento de nuevos bioproductos como enzimas y metabolitos. Sin embargo, este proceso es ineficiente debido a las bajas tasas de transcripción, traducción y la dificultad para detectar los productos de interés. Estos problemas se han estudiado individualmente utilizando soluciones como transposones a modo de promotores, cepas con codones no nativos y biosensores con genes reporteros, respectivamente. Sin embargo, estas estrategias no han mostrado más que resultados parciales y ninguna mejora integrada para cribado de bibliotecas metagenómicas. Este proyecto propone una solución integrada que consiste en una metodología robusta metodología que permite el cribado funcional de bibliotecas metagenómicas utilizando biosensores. Con este propósito, se llevó a cabo un diseño in-silico y la validación de biosensores utilizando el paquete Vienna RNA, Rosetta, AutoDock Vina y GROMACS. La biblioteca de riboswitchs obtenida se clonó en Escherichia coli y tras un cribado, se obtuvieron biosensores para la detección de narigenina. Se demostró que la metodología de diseño y validación in silico e in vitro funciona, se obtuvo una librería de riboswitches para el ligando de interés y el cribado SELEX permitió la identificación de dos potenciales biosensores capaces de detectarlo a bajas concentraciones. Esta metodología integrada demostró ser robusta y eficiente para el diseño y desarrollo de biosensores, que podrían ser integrados en una biblioteca metagenómica para facilitar su cribado funcional.Publicación Restringido Buforin II-Escherichia coli's DNA interactome: Routes to elucidate the molecular mechanisms of its antimicrobial activity(Universidad de los Andes, 2021) Rubio Olaya, Daniela; Cruz Jiménez, Juan Carlos; Bloch Morel, Natasha Ivonne; González Barrios, Andrés FernandoThe increase of multi-resistant bacteria in the last decade has become a global health issue that requires the development of alternative treatments. Antimicrobial peptides are of great interest due to their high effectiveness and differential mechanisms.Buforin II (BUFII) is a 21 amino acid antibacterial peptide that is thought to kill bacteria by entering across the membrane and interacting with intracellular molecules that are possibly involved in vital mechanisms. However, these specific interactions are still unknown, and thus far no reports are available in targeted regions or DNA sequences associated with bacterial death. Here, we proposed a study of the interaction between BUFII and the DNA of Escherichia coli using molecular, spectroscopic and microscopic techniques, complemented with whole genome sequencing. We developed an in vitro method to identify the Escherichia coli DNA interactome with BUFII using the BUFII-magnetite nanobioconjugates. This approach allows taking advantage of the strong magnetic response of the conjugates to isolate the interacting moieties. The complete biophysical study conducted here allowed us to put forward the notion that BUFII interacts with DNA very strongly most likely due to electrostatic interactions. As a result, the BUFII-DNA pair can form spherical supramolecular complexes with nanoscale dimensions where DNA is likely supercoiled. The pull-down approach introduced here along with the complementary biophysical techniques might be helpful to improve the rational peptide design and discovery by providing a more robust set of recommendations regarding the targeted interactions with bacterial components responsible for resistance.Publicación Acceso abierto Cell penetrating and antibacterial nanobioconjugates based on immobilized BUF-II on polyetheramine (PEA)-modified magnetite nanoparticles(Uniandes, 2019) Pérez Pineda, Jessica Giovanna; Cruz Jiménez, Juan Carlos; González Barrios, Andrés Fernando; Bloch Morel, Natasha IvonneEn la actualidad uno de los mayores retos en el área de farmacología es el desarrollo de sistemas de entrega de medicamentos a partir de moléculas terapéuticas de manera controlada y localizada sin causar daño a los tejidos o células circundantes. Adicionalmente, uno de los objetivos de estos vehículos es la de mejorar la eficiencia de entrada a las células blanco. Los sistemas utilizados actualmente son poco específicos y presentan bajas tasas de liberación debido a que no son capaces de cruzar las membranas celulares. Por esta razón, se busca mejorar los vehículos de liberación utilizando moléculas con capacidad de traslocación e inmovilizados junto con el componente activo o medicamento, como una forma de mejorar los problemas anteriormente mencionados. Una de estas moléculas translocantes Buforina II (BUF-II), el cual en estudios recientes por nuestro Grupo de investigación GINIB se ha encontrado que tiene la capacidad de atravesar la membrana de las células mamíferas. Por esta razón, BUF-II se inmovilizó en nanoparticulas de magnetita preparadas por el método de coprecipitación de cloruros de hierro; para preservar la actividad translocante del nanoconjugado, se realizó un recubrimiento superficial con PEG oxidado utilizando KMnO4. BUF-II fue conjugada con ayuda de EDC y NHS en la superficie de las nanopartículas y para validar eficiencia de conjugación se realizaron pruebas de termogravimetría utilizando el TGA y espectroscópicas vía FTIR. Además de realizar análisis microscópicos con TEM y SEM y de dispersión de tamaño de partícula DLS. Al mismo tiempo se evaluó la biocompatibilidad, habilidad de translocación y de formación de endosomas intracelulares de los nanoconjugados en células de mamífero utilizando microscopía confocal y ensayos de viabilidad celular. Los resultados de biocompatibilidad mostraron una viabilidad celular mayor al 75%, y un porcentaje de hemolisis inferior al 10%.Publicación Acceso abierto Completing spatial transcriptomics data for gene expression prediction benchmarking(Universidad de los Andes, 2025-08-01) Ruiz López, Daniela Andrea; Arbeláez Escalante, Pablo Andrés; Bloch Morel, Natasha Ivonne; Mejía Sepúlveda, Gabriel Mateo; Facultad de IngenieríaSpatial Transcriptomics is a groundbreaking technology that integrates histology images with spatially resolved gene expression profiles. Among the various Spatial Transcriptomics techniques available, Visium has emerged as the most widely adopted. However, its accessibility is limited by high costs, the need for specialized expertise, and slow clinical integration. Additionally, gene capture inefficiencies lead to significant dropout, corrupting acquired data. To address these challenges, the deep learning community has explored the gene expression prediction task directly from histology images. Yet, inconsistencies in datasets, preprocessing, and training protocols hinder fair comparisons between models. To bridge this gap, we introduce SpaRED, a systematically curated database comprising 26 public datasets, providing a standardized resource for model evaluation. We further propose SpaCKLE, a state-of-the-art transformerbased gene expression completion model that reduces mean squared error by over 82.5% compared to existing approaches. Finally, we establish the SpaRED benchmark, evaluating eight state-of-the-art prediction models on both raw and SpaCKLEcompleted data, demonstrating SpaCKLE substantially improves the results across all the gene expression prediction models. Altogether, our contributions constitute the most comprehensive benchmark of gene expression prediction from histology images to date and a stepping stone for future research on Spatial TranscriptomicsPublicación Acceso abierto Coupling genetic and epidemiological dynamics to unravel parasite structure in transmission gradients(Universidad de los Andes, 2023-06-05) Suárez Salazar, Carlos David; Santos Vega, Oscar Mauricio; 80874246; Bloch Morel, Natasha Ivonne; Grupo de Investigación de Biología Matemática y Computacional (BIOMACUnderstanding the genetic structure of Plasmodium falciparum populations, the parasite responsible for malaria, is crucial for developing effective disease control and eradication strategies. In this study, we aimed to investigate how populations, epidemiological conditions, and transmission patterns define the evolutionary trajectories of these parasites. To address this question, we developed a stochastic agent-based model that combines disease transmission's genetic and epidemiological dynamics. This allows us to assess how population genetic structure is shaped by varying initial genetic diversity and biting rates. In addition, we discovered that the initial genetic diversity of the population had a modulating effect on the genetic response of the populations, serving as a factor that either maintains or reduces population genetic distance, as well as generating diversity within the population. Our findings highlight the importance of these dual analyses that incorporate genetic dynamics into the disease transmission process, aiming to establish a platform where sequenced parasite genomes can be used to understand these populations' evolutionary status and genetic exchange.Publicación Acceso abierto Detection of pathogens causing fever of unknown origin and co-circulating with SARS CoV 2 using a portable and lowcost device(Universidad de los Andes, 2022-07-28) Gómez León, Laura Andrea; Restrepo Restrepo, Silvia; González Rosas, Camila; Cordovez Álvarez, Juan Manuel; 39784728; 52393017; 80505711; Bernal Giraldo, Adriana Jimena; Bloch Morel, Natasha IvonneInfectious diseases are caused by bacteria, viruses, parasites, and fungi. These diseases can be transmitted, directly or indirectly, from one person to another. In Colombia, there are around 150 infectious diseases under surveillance according to the Ministry of Health and the National Institute of Health. These diseases can be diagnosed using multiple laboratory techniques, including culture, antigen detection methods, nucleic acid detection, and serology. However, many of these traditional diagnostic techniques, especially culture, are time-consuming, expensive, and often require sophisticated equipment, trained personnel, and specific conditions to perform. Therefore, this project aimed to standardize a low-cost and time-saving technique for detecting parasites and viruses that cause different infectious diseases. For this purpose, using the PLUM device, LAMP and ELISA techniques were implemented for the detection of nucleic acids and antibodies in nasopharyngeal swab samples and serum from different regions of the country to evaluate the presence of Leishmaniasis, Zika, Dengue, and Chikungunya, highly prevalent diseases in Colombia. From the tests, it was possible to verify that these techniques through a portable device can be implemented in rural areas, with low resources and/or far from diagnostic centers. It also has several advantages over currently existing techniques, reducing processing times from three hours to one hour and reducing costs from $150 a molecular test to around $2, representing an advantage for monitoring and treatment. timing of infectious diseases.Publicación Restringido Development of a non-viral delivery nanoplatform for genomic therapy based on iron oxide nanoparticles and recombinant Cas9 for potential use in genetic heterozygous orphan diseases(Universidad de los Andes, 2022-01-31) Ellis-Aguilar, Laura Daniela; Cabrera Pérez, Rodrigo; Muñoz Camargo, Carolina; 52715720; Bloch Morel, Natasha Ivonne; Reyes Barrios, Luis Humberto; Grupo de Investigación Ingeniería Celular y Nanobiomateriales - GIINIBSince it was first described, the CRISPR/Cas9 technology has opened new possibilities in the molecular biology fields. CRISPR/Cas9 has become one of the favorite tools for researchers from cell culture improvement to design of therapies for rare diseases. However, its clinical application has been hindered by the dearth of safe and efficient delivery systems. Here, we develop and characterized a magnetite-based nanoplatform to potentially deliver, both recombinant Cas9 and single guide RNA (sgRNA) targeting a pathogenic COL3A1 mutation in a cell culture model of hereditary Thoracic Aortic Aneurism. Specifically, we designed and synthesized several sgRNAs to test their activity through an allele specific DNA digestion assay. For this, we amplified the affected region using genomic DNA from a patient carrying the mutation and evaluated the cleavage efficiency of different Cas9-sgRNA ribonucleoproteins. Once the optimal conditions were obtained, we carried out DiGenome-Seq analysis to identify potential off-target effects. In parallel, we synthesized Magnetite Nanoparticles (MNPs), functionalized the particles by adding a polymer spacer (polyethylene glycol PEG) and conjugated the cell-penetrating peptide (CPP) Buforin II (BUFII) for membrane translocation alongside recombinant Cas9. We successfully characterized the MNP-PEG-BUFII-Cas9 conjugates by transmission electron microscopy (TEM) and dynamic light scattering (DLS), finding an average particle size of 15 nm and a hydrodynamic diameter from 120 to 250 nm. Fourier transform infrared spectroscopy (FTIR) lead us to corroborate correct functionalization in each step and find N-H stretch peaks at 3180 cm ¹ and 3500 cm ¹ which corresponded to the Cas9. And thermogravimetric analysis (TGA) displayed rising weight losses (6.97%, 7.77%, 10.41%) in each step of the synthesis. We also conducted a biocompatibility battery test that includes lactate dehydrogenase (LDH) cytotoxicity assay, platelet aggregation, hemolytic activity, and the Ames test for mutagenicity (Salmonella Tiphimurium TA98 strain). We demonstrated in vitro biocompatibility and highlight a platelet aggregation behavior (p > 0.001) of MNP-PEG-BUFII-Cas9. Finally, we performed a proof-of-principle of our MNP-PEG-BUFII-Cas9 nanoplatform, evaluating cell (HDFa and HaCat) internalization and endosomal escape of the MNP-PEG-BUFII-Cas9 without the sgRNA by confocal microscope image analysis. Overall, here we demonstrate the efficacy of MNP-PEG-BUFII-Cas9 nanoplatform as safe and promising non-viral delivery vehicles for CRISPR/Cas9 localized gene editing attempting to treat heterozygous mutations.Publicación Acceso abierto Development of an intracranial injection system of nanostructured vehicles for gene editing and drug delivery in the brain of the Guppy Fish (P. reticulata)(Universidad de los Andes, 2024-04-03) Vergara Ramírez, Miguel Augusto; Bloch Morel, Natasha Ivonne; Cruz Jiménez, Juan Carlos; 52863778; 79949732; Osma Cruz, Johann Faccelo; Akle Álvarez, Verónica; Facultad de Ingeniería::Grupo de Ingenieria BiomédicaMedical treatments using CRISPR-Cas are currently being widely studied, as they represent an alternative that counteracts genetic disorders by deletion or edition of the mutations that generate them. Due to its complexity and limited treatment options, gene therapy represents an alternative of enormous potential for neurological and neuropsychiatric disorders. However, the correct administration of this type of treatment represents limitations for genome editing, Magnetite (Fe3O4) nanoparticles (MNPs) have shown good potential as transport vectors for efficient intracellular delivery of gene editing machinery, overcoming several of the challenges of this process such as degradation by nucleases, membrane translocation and endosomal escape. In the present study, in vivo validation of the administration of magnetite nanoparticles in the brain is performed by analyzing behavior, nanoparticle biodistribution and cell viability, using a model of guppy fish (Poecilia reticulata). This species has central nervous system homology with humans and has also served as an excellent study model to analyze social behavior dynamics, allowing the development of a study system for the administration of CRISPR/Cas in the brain in vivo and the investigation of genes responsible for neurological and neurodegenerative disorders. We found that cell viability levels in different brain regions were maintained over 80% after administrations of MNPs, biodistribution showed important accumulation in the liver, but also increased levels of iron in the brain, and finally we found diminished locomotor activity of injected guppy fish but no major affection in their zonal preference. These results suggest that MNPs might be a suitable nanocarrier for gene editing in the brain using the ICV injection delivery system.Publicación Acceso abierto Diseño y construcción de sistemas CRISPRa y CRISPRi para el desarrollo de una terapia génica para el Parkinson(Universidad de los Andes, 2020) Bittar Yepes, Amaury Fernando; Bloch Morel, Natasha Ivonne; Reyes Barrios, Luis Humberto; Bernal Giraldo, Adriana JimenaParkinson's disease is the second most common neurodegenerative disease in the world. It affects 170 people per 100,000 inhabitants and is currently a relevant public health problem in older adults. Despite this, the usual treatments for this disease only treat the symptoms without impeding it's progress, which causes patients to deteriorate over time. Therefore, current approaches seek the development of new treatments based on neuronal proliferation and survival. Within these approaches, gene therapy is one of the most promising because it tries to provide the body with the ability to constantly generate the proteins necessary for treatment. Therefore, this work proposes the development of plasmids that contain CRISPRa and CRISPRi systems to alter gene expression and generate a disease-modifying treatment model. With this objective, the computational design and the initial steps of the molecular assembly were carried out for a therapy focused on the GDNF, PINK1 and PRKN genes.--Taken from the Degree Document Format.Publicación Acceso abierto Dopaminergic neuroimmune co-culture systems model Parkinsons Disease microenvironments in vitro(Universidad de los Andes, 2022-06-08) Rueda Gensini, Laura; Muñoz Camargo, Carolina; Cruz Jiménez, Juan Carlos; 52715720; 79949732; Bloch Morel, Natasha Ivonne; Reyes Barrios, Luis Humberto; Grupo de Investigación en Nanobiomateriales, Ingeniería Celular y BioimpresiónParkinsons disease (PD) is a complex and multifaceted neurodegenerative disorder that depends on multiple environmental factors and multicellular interactions. Although several PD neuropathologies have been identified and described, the thorough understanding of PD pathophysiology and research has been largely limited by the absence of reliable in vitro models that truly recapitulate PD microenvironments. Here, we propose the development of neuroimmune co-culture systems that integrate relevant multicellular interactions within brain-mimicking environments for the modeling PD neuropathologies. Specifically, we simultaneously develop (i) a 3D bioprinted neuronal core composed of mature dopaminergic (DA) neurons grown on extracellular matrix-derived bioinks doped with electroconductive graphene oxide-based nanostructures, and (ii) a 2D direct co-culture of astrocytes and differentiated monocytes. Finally, we elicit PD-mimicking pathologies through the transwell-based co-culture of these two compartments and simultaneous exposure to A53T a-synuclein, which stimulates both the development of neurotoxic responses in DA neurons and neuroinflammatory responses from co-cultured immune cells. For this, we differentiate neural progenitor cells into DA neurons within these biomimetic constructs and demonstrate the appearance of functional and mature dopaminergic 3D networks, as evidenced by the expression of neuronal (e.g., Tuj1), dopaminergic (e.g., TH, DAT, KCNJ6) and synaptic (e.g., Syn I) markers in comparable or superior values to those obtained through their widely described 2D differentiation. Moreover, we define optimal monocyte differentiation schemes for the appearance of monocyte-derived macrophages and dendritic cell phenotypes, as well as optimal co-culture ratios with astrocytes that maximize inflammatory responses upon A53T a-synuclein stimulation. In this regard, we show that the defined co-culture parameters allow the significant upregulation of pro-inflammatory surface markers (e.g., CCR7 and GFAP) in both astrocytes and differentiated monocytes, and increase the secretion of 10 proinflammatory cytokines (e.g., IL-1b, TNF-a, IL-6, MCP-1, IL-12p70, IFN-g, IFN-a2, IL-8, IL-18, IL-23) with key roles in neurodegenerative diseases. This neuroinflammatory environment, added to the independent uptake of A53T a-synuclein by DA neurons, stimulated the formation of intracellular a-synuclein aggregates, induced progressive mitochondrial dysfunction and ROS production, downregulated the expression of synaptic, dopaminergic and mitophagy-related genes, and promoted the initiation of apoptotic processes. Most importantly, these intracellular pathologies were comparable or superior to those generated with a rotenone-stimulated 2D control that represents the current standard for in vitro PD models, and showed increased resilience towards these neurotoxic insults, allowing the study of disease progression through longer time periods than current models. These results position the proposed model as a superior alternative to current 2D models for generating PD-related pathologies in vitro.Publicación Acceso abierto Efecto de la exposición a estrés crónico en la expresión de genes asociados al comportamiento ansiogénico sam2 y nlgn1 en pez cebra (Danio rerio)(Universidad de los Andes, 2021) Ávila Matallana, Laura Catalina; Bloch Morel, Natasha Ivonne; Bernal Giraldo, Adriana Jimena; Akle Alvarez, VerónicaLa salud mental se ha considerado un componente integral y esencial, que se ha visto fuertemente afectado por una amplia variedad de cambios y estímulos en la vida cotidiana. Condiciones como estrés, se han relacionado como factores de riesgo a enfermedades y representan una complicación adicional en los procesos de tratamiento y recuperación. Se destaca la necesidad de ampliar conocimiento en relación con la conexión entre el estrés y su repercusión en los individuos, de manera que se evidencien los factores fisiológicos, moleculares y comportamentales. Este estudio, se centra en entender que cambios moleculares pueden estar asociados con los cambios en comportamiento y el proceso de regeneración derivados de la exposición de los individuos a condiciones de estrés crónico teniendo en cuenta el pez cebra (Danio rerio) como modelo animal. Lo anterior, evaluando la existencia de diferencias en los niveles de expresión génica de dos genes sam2 y ngln1 que se han relacionado en estudios previos con comportamiento ansiogénico. Se observó, que hay una diferencia significativa entre los niveles de expresión para sam2 entre los grupos experimentales, en donde, se identificaron mayores niveles de expresión en los individuos del grupo estrés en comparación con el grupo control. No se identificaron diferencias significativas en los niveles de expresión para nlgn1. La exploración de los cambios moleculares que ocurren luego de la exposición de los individuos a estrés permite entender los mecanismos a través de los cuales se da la relación entre el estrés el comportamiento y la capacidad de regeneración en los individuos, en donde el eje hipotalámico-pituitario-interrenal (HPI) podría ser el principal protagonista.Publicación Acceso abierto Effects of chronic stress exposure on the anxiogenic behavior and regenerative capacity of zebrafish (Danio rerio)(Universidad de los Andes, 2021) Henríquez Martínez, Angie; Bloch Morel, Natasha Ivonne; Akle Álvarez, VerónicaEnvironmental stimuli such as daily routine, dietary habits and stress are strongly related to the physiology of our body. However, we still do not know entirely how this relationship occurs. The zebrafish has been used as a promising model in behavior, stress, anxiety and neuroscience research, thanks to its homology with vertebrates like rodents and mammals. Here in this study, we report preliminary results about the effect of chronic stress on the regeneration of the caudal fin in zebrafish (Danio rerio). We exposed fish to a UCS protocol to stimulated chronic stress conditions and performed behavioral tests (open field and light/dark preference) to evaluated anxiety-like behavior. Then we cut the lower part of the caudal fin to evaluated the effect of the stress on tissue regeneration.Publicación Embargo Evaluación de la viabilidad, perfil de diferenciación y expresión génica de progenitores hematopoyéticos de sangre de cordón umbilical cultivados en constructos de PLA/COL/HA/células estromales mesenquimales como estrategia de expansión in vitro(Universidad de los Andes, 2022-06-06) Medina Solano, Martha Lliliana; Silva Cote, Ingrid Zulay; Cordovez Álvarez, Juan Manuel; 80505711; 60394352; Salguero, Gustavo; Bloch Morel, Natasha Ivonne; Cárdenas Parra, Luis FernandoPublicación Acceso abierto Evaluation of Plastic Brain Response to Long-Term Exposure to Varying Habitat Complexities in Guppies (Poecilia reticulata)(Universidad de los Andes, 2024-07-30) Sierra Peña, Paula Natalia; Bloch Morel, Natasha Ivonne; Molina Escobar, Jorge AlbertoUnderstanding how environmental complexity influences neuroanatomy and brain function is key in elucidating the adaptive mechanisms of organisms. Here, we investigate the plastic brain response of guppies (Poecilia reticulata) to long-term exposure (8 months) to varying habitat complexities. Guppies were housed in habitats with increasing spatial complexities: low (empty tank), medium (gravel and one artificial plant), and high (gravel with multiple artificial plants). After the exposure period, fish underwent spatial cognition tests to evaluate their spatial abilities and were euthanized to carry out neuroanatomical analyses. Additionally, immunohistochemistry was performed to quantify neuronal densities and understand mechanisms underlying brain plasticity. We found differences between males and females, suggesting sex-specific responses to the challenges presented by varying environmental complexities. Similarly, neuroanatomical analyses exhibited significant differences between sexes for all complexity levels, notably in males. Our findings underscore the dynamic interplay between environmental complexity and brain plasticity in guppies. By systematically assessing various aspects of brain morphology and function, we provide valuable insights into how guppy brains respond to long-term environmental complexity.Publicación Acceso abierto Exploring the impact of spatial complexity on guppies brain plasticity and the implications of a bigger brain(Universidad de los Andes, 2024-01-11) Peñuela Romero, María Fernanda; Bloch Morel, Natasha Ivonne; 52863778; Akle Álvarez, Verónica; Giraldo Trujillo, Luis FelipeFish are believed to rely on the spatial information around them to find food, mates and hide from predators. In fish, brain size and morphology can vary greatly in a plastic manner due to the demands of the environment. Thus, recent studies have suggested that environmental complexity can generate changes in brain size; however, the direction in which the size changes is not always consistent. Likewise, mechanisms that produce the plastic response to the complexity still need to be fully understood. It is also essential to understand the parameters driving brain evolution and the conditions necessary for plastic changes to remain over time. In fish, a larger brain has been associated with cognitive improvements that can help in various situations. However, it also has a higher energy cost that affects several physiological variables and can reduce reproductive success. Here, we aim to study the impact that spatial complexity can have on brain size and morphology and evaluate whether these plastic changes are associated with variations in neuronal density. We also aim to evaluate whether a large brain is better than a small one for fish, considering both the cognitive benefits and the physiological cost that a larger brain implies. We expose juvenile and adult guppy fish to tanks with three different levels of spatial complexity. At the end of the exposure period, we measured their brain size and the volume of brain regions. We estimated their neuronal density to better understand the mechanisms behind plasticity in the brain. In addition, we developed an agent-based model to simulate the costs and benefits that a larger brain entails to observe after several generations if large-brained fish prevail over small-brained ones. Spatial complexity did not generate significant differences in neuronal density or brain size. It only had a sex-specific effect on the volume of the optic tectum in adults. These results do not allow us to affirm that this factor can stimulate evident plastic changes in the brain. The model showed that the cognitive benefits outweigh the energetic costs and favor the selection of large-brained fish. The results of our model also highlight the importance of studying plastic changes in the brain as something that must be justifiable and beneficial outside of an experimental environment.Publicación Acceso abierto Exploring the Potential Implications of Variation in Optical Density for the Coevolution of Avian Visual Systems and Color Signals(Universidad de los Andes, 2022) Meneses Giorgi, María Alejandra; Cadena Ordónez, Carlos Daniel; Bloch Morel, Natasha IvonneColor vision enables visually oriented animals to sense their environments and successfully perform most of their vital activities. Several studies have demonstrated that natural and sexual selection may shape the evolution of vision, but it has seldom been considered that because selection may act differently on males and females, certain characteristics of visual systems may differ between the sexes. Few examples of sexual dimorphism in vision have been described in vertebrates, and whether males and females differentially perceive the world based on vision remains widely unanswered probably because of the difficulties involved in studying visual systems in depth. Here, I assessed the effects of optical density, an unexplored possible axis of variation of avian vision, on color perception and asked whether optical density may mediate differences between males and females in color vision. Using mathematical modeling I found that variation in optical density can alter the sensitivity spectra of retinal cones in birds. Furthermore, changes in optical density modeled under physiologically realistic scenarios informed by data from New World warblers (Parulidae) may result in subtle differences in the color discrimination abilities of males and females. Moreover, comparisons among species indicate that sexual dichromatism in plumage coloration is associated with sexual differences in color discrimination abilities. My work, along with physiological and behavioral evidence from diverse animal species, suggests that broader evidence for the exciting idea that color signals and visual systems coevolve can be found if we fully characterize visual systems and evaluate differences using visual models.Publicación Acceso abierto Exploring the role of the nlgn1 gene in the response to stress through a CRISPR Cas9-mediated nlgn1 zebrafish knockout(Universidad de los Andes, 2023-12-11) Ávila Matallana, Laura Catalina; Bloch Morel, Natasha Ivonne; Akle Álvarez, Verónica; 52863778; 52699074; Lattig Matiz, María Claudia; Muñoz Camargo, Carolina; Facultad de Medicina::Neurociencia Traslacional; Facultad de Ingeniería::Grupo de Ingenieria BiomédicaNeuroligin 1 (Nlgn1) is a neuronal cell membrane protein that plays a critical role in synapse formation and remodeling processes. Previous studies have suggested that neuroligin 1 (nlgn1) mutations could contribute to the development of post-traumatic stress disorder (PTSD), a neuropsychiatric condition with an unclear genetic and molecular basis. Here, we aim to generate a nlgn1 zebrafish knockout line (KO) using CRISPR-Cas9genomeeditingandinvestigate the functional consequences of silencing nlgn1, in zebrafish. Knocking-out nlgn1 in one-cell embryos produces a strong neurological phenotype, that significantly decreases survival. We successfully crossed surviving KO individuals to generate an F1 and an F2 generation of the nlgn1 KO line. We performed behavioral test to evaluate the effect of silencing nlgn1 on stress behavior. We observed significant changes in the behavior of F1 generation individuals after the application of a chronic stress protocol. These results suggest thatnlgn1 has a role mediating stress response in zebrafish. By unraveling the role of nlgn1 in stress-related disorders, we aim to shed light on the molecular pathways involved in PTSD development and contribute to a better understanding of the underlying factors influencing the risk of developing PTSD.Publicación Acceso abierto Functional evaluation of the activation of pink1 gene using a CRISPRa system in the parkinson's disease context(Universidad de los Andes, 2024-01-20) Sotelo Montero, Sebastián; Bloch Morel, Natasha Ivonne; Reyes Barrios, Luis Humberto; Cruz Jiménez, Juan Carlos; Muñoz Camargo, Carolina; 52863778; 91161254; 79949732; 52715720; Sutachán Rubio, Jhon Jairo; Briceño Triana, Juan Carlos; Facultad de Ingeniería::Grupo de Ingenieria BiomédicaParkinson’s Disease (PD) is a neurodegenerative disorder that causes motor symptoms due to the progressive degeneration of dopaminergic neurons. Currently, there is no cure for PD, and the treatment is based on the treatment of the symptoms. The use of nanostructured vehicles as an innovative form of delivering genetic material into the cells has been recently presented, and gene therapy is a promising tool to treat genetic PD. An approximation to treat PD is related to dysfunction in astrocytes, which has been associated with an increase in oxidative stress in the brain. More specifically, malfunction in the pink1 gene is related to spoilage in the mitochondrial function and generating neuroinflammation. This project aims to evaluate a gene therapy consisting of the overexpression of the pink1 gene through a CRISPRa system and its effects on the MAO-B activation, ROS production, and changes in the mitochondrial membrane potential. The results are in the expected direction, with a reduction in the MAO-B activation, ROS production, and an increase in the mitochondrial membrane potential. However, the vehicle used had unexpected failures, so it is necessary to repeat the experiments to ensure the results.