129 research outputs found

    Evolutionary Dynamics in Gene Networks and Inference Algorithms

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    Dynamical interactions among sets of genes (and their products) regulate developmental processes and some dynamical diseases, like cancer. Gene regulatory networks (GRNs) are directed networks that define interactions (links) among different genes/proteins involved in such processes. Genetic regulation can be modified during the time course of the process, which may imply changes in the nodes activity that leads the system from a specific state to a different one at a later time (dynamics). How the GRN modifies its topology, to properly drive a developmental process, and how this regulation was acquired across evolution are questions that the evolutionary dynamics of gene networks tackles. In the present work we review important methodology in the field and highlight the combination of these methods with evolutionary algorithms. In recent years, this combination has become a powerful tool to fit models with the increasingly available experimental data.Junta de Andalucía FQM-12

    Core regulatory network motif underlies the ocellar complex patterning in Drosophila melanogaster

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    During organogenesis, developmental programs governed by Gene Regulatory Networks (GRN) define the functionality, size and shape of the different constituents of living organisms. Robustness, thus, is an essential characteristic that GRNs need to fulfill in order to maintain viability and reproducibility in a species. In the present work we analyze the robustness of the patterning for the ocellar complex formation in Drosophila melanogaster fly. We have systematically pruned the GRN that drives the development of this visual system to obtain the minimum pathway able to satisfy this pattern. We found that the mechanism underlying the patterning obeys to the dynamics of a 3-nodes network motif with a double negative feedback loop fed by a morphogenetic gradient that triggers the inhibition in a French flag problem fashion. A Boolean modeling of the GRN confirms robustness in the patterning mechanism showing the same result for different network complexity levels. Interestingly, the network provides a steady state solution in the interocellar part of the patterning and an oscillatory regime in the ocelli. This theoretical result predicts that the ocellar pattern may underlie oscillatory dynamics in its genetic regulation.Junta de Andalucía FQM-122España, Ministerio de Ciencia e Innovación MICINN / MINECOFondos Federales BFU2012-34324Consolider Ingenio-2010 CSD 2007-00

    A Hh-driven gene network controls specification, pattern and size of the Drosophila simple eyes

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    During development, extracellular signaling molecules interact with intracellular gene networks to control the specification, pattern and size of organs. One such signaling molecule is Hedgehog (Hh). Hh is known to act as a morphogen, instructing different fates depending on the distance to its source. However, how Hh, when signaling across a cell field, impacts organ-specific transcriptional networks is still poorly understood. Here, we investigate this issue during the development of the Drosophila ocellar complex. The development of this sensory structure, which is composed of three simple eyes (or ocelli) located at the vertices of a triangular patch of cuticle on the dorsal head, depends on Hh signaling and on the definition of three domains: two areas of eya and so expression - the prospective anterior and posterior ocelli - and the intervening interocellar domain. Our results highlight the role of the homeodomain transcription factor engrailed (en) both as a target and as a transcriptional repressor of hh signaling in the prospective interocellar region. Furthermore, we identify a requirement for the Notch pathway in the establishment of en maintenance in a Hh-independent manner. Therefore, hh signals transiently during the specification of the interocellar domain, with en being required here for hh signaling attenuation. Computational analysis further suggests that this network design confers robustness to signaling noise and constrains phenotypic variation. In summary, using genetics and modeling we have expanded the ocellar gene network to explain how the interaction between the Hh gradient and this gene network results in the generation of stable mutually exclusive gene expression domains. In addition, we discuss some general implications our model may have in some Hh-driven gene networks.Ministerio de Ciencias e Innovacion BFU2009-07044 FIS2008-04120Junta de Andalucía CVI 265

    Bartonella Endocarditis in Spain: Case Reports of 21 Cases

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    Endocarditis por Bartonella; Endocarditis infecciosaBartonella endocarditis; Infective endocarditisEndocarditis per Bartonella; Endocarditis infecciosaBlood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella IE from the “Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)”cohort. Here we presented 21 cases of Bartonella IE. This represents 0.3% of a total of 5590 cases and 2% of the BCNE from the GAMES cohort. 62% were due to Bartonella henselae and 38% to Bartonella quintana. Cardiac failure was the main presenting form (61.5% in B. hensalae, 87.5% in B. quintana IE) and the aortic valve was affected in 85% of the cases (76% in B. henselae, 100% in B. quintana IE). Typical signs such as fever were recorded in less than 40% of patients. Echocardiography showed vegetations in 92% and 100% of the patients with B. henselae and B. quintana, respectively. Culture was positive only in one patient and the remaining were diagnosed by serology and PCR. PCR was the most useful tool allowing for diagnosis in 16 patients (100% of the studied valves). Serology, at titers recommended by guidelines, only coincided with PCR in 52.4%. Antimicrobial therapy, in different combinations, was used in all cases. Surgery was performed in 76% of the patients. No in-hospital mortality was observed. One-year mortality was 9.4%. This article remarks the importance for investigating the presence of Bartonella infection as causative agent in all BCNE since the diagnosis needs specific microbiological tools and patients could benefit of a specific treatment

    La inteligencia artificial fue poco utilizada pero relevante en las revisiones sistemáticas sobre el COVID-19: un estudio metodológico

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    Este trabajo de investigación fue presentado como Trabajo Fin de Grado en la Facultad de Medicina de nuestra Universidad (convocatoria ordinaria, curso 2021/2022) el 13 de junio de 2022.Objective: A rapidly developing scenario like a pandemic requires the prompt production of high-quality systematic reviews, which can be automated using artificial intelligence (AI) techniques. We evaluated the application of AI tools in COVID–19 evidence syntheses. Study design: After prospective registration of the review protocol, we automated the download of all open-access COVID–19 systematic reviews in the COVID–19 Living Overview of Evidence database, indexed them for AI-related keywords, and located those that used AI tools. We compared their journals’ JCR Impact Factor, citations per month, screening workloads, completion times (from pre-registration to preprint or submission to a journal) and AMSTAR–2 methodology assessments (maximum score 13 points) with a set of publication date matched control reviews without AI. Results: Of the 3 999 COVID–19 reviews, 28 (0.7 %, 95 % CI 0.47-1.03 %) made use of AI. On average, compared to controls (n = 64), AI reviews were published in journals with higher Impact Factors (median 8.9 vs. 3.5, P<0.001), and screened more abstracts per author (302.2 vs. 140.3, P=0.009) and per included study (189.0 vs. 365.8, P<0.001) while inspecting less full texts per author (5.3 vs. 14.0, P=0.005). No differences were found in citation counts (0.5 vs. 0.6, P=0.600), inspected full texts per included study (3.8 vs. 3.4, P=0.481), completion times (74.0 vs. 123.0, P=0.205) or AMSTAR–2 (7.5 vs. 6.3, P=0.119). Conclusion: AI was an underutilized tool in COVID–19 systematic reviews. Its usage, compared to reviews without AI, was associated with more efficient screening of literature and higher publication impact. There is scope for the application of AI in automating systematic reviews.Objetivo: Un escenario dinámico como una pandemia requiere la rápida producción de revisiones sistemáticas de calidad, que pueden automatizarse utilizando inteligencia artificial (IA). Se evaluó el uso de herramientas de IA en las revisiones sistemáticas sobre COVID–19. Diseño del estudio: Tras el registro prospectivo del protocolo del estudio, automatizamos la descarga de todas las revisiones sistemáticas open-access sobre COVID–19 en la base de datos COVID–19 Living Overview of Evidence, las indexamos en busca de palabras clave relacionadas con la IA y localizamos aquellas que utilizaban herramientas de IA. Comparamos el factor de impacto de sus revistas, las citas por mes recibidas, las cargas de trabajo en screening, el tiempo de elaboración (días desde el registro del protocolo hasta el primer preprint o envío a una revista) y la evaluación metodológica AMSTAR–2 (máximo, 13 puntos) con un grupo control de revisiones sistemáticas que no usaron IA emparejadas por fecha de publicación. Resultados: De las 3999 revisiones sobre COVID–19, 28 (0,7%, IC al 95%: 0,471,03 %) hicieron uso de IA. De media, en comparación con los controles (n = 64), las revisiones con IA se publicaron en revistas con mayor factor de impacto (mediana 8,9 vs. 3,5, P<0,001), y examinaron más abstracts por autor (302,2 vs. 140,3, P=0,009) y por estudio incluido (189,0 vs. 365,8, P<0,001), a la vez que inspeccionaron menos full texts por autor (5,3 vs. 14,0, P=0,005). No se encontraron diferencias en las citas recibidas (0,5 vs. 0,6, P=0,600), en full texts inspeccionados por estudio incluido (3,8 vs. 3,4, P=0,481), en los tiempos de elaboración (74 frente a 123, P=0,205) ni en puntuación AMSTAR–2 (7,5 frente a 6,3, P=0,119). Conclusión: La IA fue una herramienta infrautilizada en las revisiones sistemáticas sobre COVID–19. Su uso, en comparación con las revisiones sin IA, se asoció con una selección más eficiente de la literatura y un mayor impacto de publicación. Hay cabida para la aplicación de la IA en la automatización de las revisiones sistemáticas.La elaboración de este estudio fue becada con una “Beca de Iniciación a la Investigación para Estudiantes de Grado” del Plan Propio de Investigación 2021 de la UGR. El coste de la publicación open-access fue financiado por la Universidad de Granada y el Consorcio de Bibliotecas Universitarias de Andalucía (CBUA)

    La farmacovigilancia, un determinante en el uso racional de los medicamentos

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    Resumen: La OMS define Farmacovigilancia como: “La ciencia y las actividades relacionadas con la detección, evaluación, entendimiento y prevención de efectos adversos o algún otro posible Problema Relacionado con Medicamentos”. Es un conjunto de métodos, observaciones y registros obtenidos durante el uso de un medicamento en la etapa de su comercialización con el fin de establecer una relación de causalidad entre la administración del medicamento y la aparición de un efecto nocivo, como también el de promover el uso seguro y racional de los medicamentos. La farmacovigilancia estudia posibles interacciones y que gravedad puede tener una persona al consumir medicamentos con otros mismos medicamentos, también con alimentos, bebidas e incluso hasta con productos naturales. en muchos departamentos de Antioquia como a nivel mundial existe una problemática bastante compleja de salud pública y por la cual lucha esta gran rama de la farmacovigilancia con contrarrestar más daños en la salud de las personas, y es sobre el mal uso que se les da a los medicamentos La labor que cumple un regente de farmacia es de gran importancia en la sociedad por que mediante las numerosas funciones que este realiza, le brinda a la comunidad un servicio oportuno y eficaz en la distribución, preparación, dispensación, control y utilización adecuada de los medicamentos y otros productos El desarrollo de un fármaco es fundamental para la efectividad y seguridad en un tratamiento farmacológico, ya que un medicamento puede tener muchos beneficios pero puede llegar a ser perjudicial en muchos casos.Abstract The WHO defines Pharmacovigilance as: "The science and activities related to the detection, evaluation, understanding and prevention of adverse effects or any other possible Drug Related Problem". It is a set of methods, observations and records obtained during the use of a drug at the stage of its commercialization in order to establish a causal relationship between the administration of the drug and the appearance of a harmful effect, as well as promoting safe and rational use of medications. Pharmacovigilance studies what possible interactions and how serious a person can be when consuming drugs with other drugs, also with food, drinks and even even natural products. In many departments of Antioquia, as well as at a general level, there is a fairly complex public health problem and for which this great branch of pharmacovigilance is fighting to counteract more damage to people's health, and it is about the misuse that is given to medicines The work performed by a pharmacy manager is of great importance in society because, through the numerous functions it performs, it provides the community with a timely and effective service in the distribution, preparation, dispensing, control and proper use of drugs and other products The development of a drug is essential for the effectiveness and safety of a pharmacological treatment, since a drug can have many benefits but can be harmful in many cases
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