The advances in molecular biology have increased the production of enormous amount of genetic information in a small period of time. This capacity of data production motivated the researchers to increase the rhythm of their researches. This necessity demands the use of efficient softwares in order to manage these data. Besides this, it also demands the development of good softwares in order to assist the researchers in the task of analyzing the data and giving them a biological meaning in a brief space of time. This work proposes a software model that will support the study of Forensic DNA, whose main repository is the autossomic DNA. This software intends to support the researchers in the identification of condemned persons or persons that are suspected of a crime. It also intends to assist the researchers in the study of paternity and the search for disappeared persons. The results of this work will be applied in the Forensic DNA Laboratory of UFAL. The software modeled here has four modules study of paternity , criminal , disappeared people and the bank of populational frequencies . The modules were modeled independently from each other, considering the specifications related to the analysis of genetic links. The software was developed using the JAVA programming language together with PostgreSQL database. Both are free software and have an excellent relationship between cost and benefit usage / Fundação de Amparo a Pesquisa do Estado de Alagoas / Os avanços da biologia molecular vêm favorecendo a geração de uma enorme quantidade de informações genéticas em um tempo cada vez menor. Essa capacidade de geração de dados permite que os pesquisadores acelerem o ritmo de suas pesquisas, exigindo a utilização de ferramentas eficientes para o gerenciamento desses dados. Outra necessidade está relacionada com o desenvolvimento de ferramentas computacionais com capacidade de auxiliar na tarefa de análisar e dar um significado biológico a estes dados em um breve espaço de tempo para os pesquisadores. Este trabalho propõe a modelagem de um ambiente de apoio à análise e ao estudo do DNA Forense, cujo principal repositório seja o DNA autossômico. Este ambiente visa dar suporte a identificação de pessoas condenadas ou suspeitas de ter realizado algum tipo de crime contra a sociedade, bem como auxiliar no estudo de paternidade e na busca de pessoas desaparecidas. Este ambiente irá atender ao Laboratório de DNA Forense, da UFAL, que vêm realizando estas atividades. O modelo do ambiente aqui proposto, possui quatro módulos, estudo de paternidade , criminal , desaparecido e o banco de freqüência das populações . Os módulos foram modelados de forma que funcionem independentemente, atendendo as especificações inerentes à análise sobre vínculo genético. O sistema foi desenvolvido na linguagem de programação JAVA com banco de dados PostgreSQL. Ambas as ferramentas possuem característica de software aberto e uma relação custo/benefício excelentes

Ce projet de recherche porte sur l’étude de la régulation des systèmes cannabinoïdes et vanilloïdes chez Caenorhabditis elegans (C. elegans), dans le but d’évaluer les effets antinociceptifs du tétrahydrocannabinol (THC) et du cannabidiol (CBD). C. elegans est un modèle largement utilisé pour étudier la nociception, visant principalement à caractériser les réponses nociceptives induites par le THC et le CBD, ainsi qu’à identifier les mécanismes et les cibles moléculaires impliqués. Les résultats des études sur l’utilisation du cannabis dans le traitement de la douleur chronique chez les mammifères sont controversés. Cette recherche vise à étudier l’effet du CBD et du THC sur la réponse nociceptive chez C. elegans et à approfondir la compréhension des mécanismes pharmacologiques sous-jacents. La méthodologie consiste à quantifier l’effet antinociceptif du CBD et du THC chez C. elegans par la méthode de la thermotaxie. Les nématodes sauvages (N2) étaient exposés à des concentrations croissantes de phytocannabinoïdes pour évaluer la relation concentration-effet. D’autres tests étaient effectués sur des souches mutantes exprimant des récepteurs cannabinoïdes et vanilloïdes afin d’identifier préalablement leurs cibles. Enfin, les analyses protéomiques et bioinformatiques seront effectuées pour identifier les voies de signalisation et les processus biologiques induits par l’interaction entre les phytocannabinoïdes et leurs cibles. Cette étude démontre l’activité antinociceptive du CBD et du THC chez C. elegans avec des effets rémanents pour THC, en ciblant respectivement le vanilloïde pour le CBD et le cannabinoïde pour les systèmes THC. Les analyses protéomiques et bio-informatiques mettent en évidence des différences significatives dans leurs voies de signalisation et leurs processus biologiques. / The objective of this research project was to focus on studying the regulation of cannabinoid and vanilloid systems in Caenorhabditis elegans (C. elegans) to evaluate the anti-nociceptive effects of tetrahydrocannabinol (THC) and cannabidiol (CBD). C. elegans is a widely used model for studying nociception, with the main objective being to characterize nociceptive responses induced by THC and CBD, as well as identify the underlying molecular mechanisms and targets involved. Recent studies on the use of cannabis for the treatment of chronic pain in mammals have shown controversial results. This research aims to investigate the effect of CBD and THC on the nociceptive response in C. elegans and understand the underlying pharmacological mechanisms. The methodology consisted in quantifying the antinociceptive effect of CBD and THC in C. elegans using the thermotaxis method. WT(N2) were exposed to decreasing concentrations of phytocannabinoids to evaluate the dose and effect relationship. Further tests performed on mutant expressing cannabinoid and vanilloid receptors allowed preliminarily identification of their targets. Finally, proteomic and bioinformatics analyses were used to identify the signaling pathways and biological processes induced by these phytocannabinoids. The result of this study confirmed the antinociceptive effect of CBD and THC in C. elegans, with a remanent effect of THC. This effect is mediated by the vanilloid system for CBD and the cannabinoid system for THC, respectively. Also, proteomics and bioinformatics analyses revealed significant differences in signaling pathways and biological processes.

<p>Neutrophils are the first cells recruited to an immune stimulus stemming from infection or sterile injuries via a mixture of chemoattractant cues. In addition to eliminating pathogens, neutrophils coordinate the overall inflammation by activating and producing inflammatory signals in the tissue while modulating the activation of other immune cells which in some cases leads to adverse tissue damage. Over amplified or chronic neutrophil recruitment directly leads to autoimmune diseases including rheumatic arthritis, diabetes, neurodegenerative diseases, and cancer. Dampening neutrophil recruitment is a strategy to intervene in neutrophil-orchestrated chronic inflammation. Despite intensive research over the past several decades, clinical studies targeting neutrophil migration have been largely unsuccessful, possibly due to the prominent redundancy of adhesion receptors and chemokines. Additional challenges lie in the balance of dampening detrimental inflammation while preserving immunity. Neutrophils are terminally differentiated cells that are hard to study in cell culture. Mouse models are often used to study hematopoiesis, migration, and chemotaxis of neutrophils but is very labor intensive. To discover novel therapeutic targets that modulate neutrophil migration, we performed a neutrophil-specific microRNA (miRNA) overexpression screen in zebrafish and identified eight miRNAs as potent suppressors of neutrophil migration. We have generated transgenic zebrafish lines that overexpresses these candidate miRNAs where we recapitulated the mitigation in neutrophil motility and chemotaxis to tissue injury or infection. Among those we further characterized two miRNAs which have not been reported to regulate neutrophil migration, namely miR-722 and miR-199.</p> <p> </p> <p>MiR-722 downregulates the transcript level of <i>rac2</i> through binding to the <i>rac2</i> 3'UTR. Furthermore, miR-722-overexpressing larvae display improved outcomes in both sterile and bacterial systemic models, which correlates with a robust upregulation of the anti-inflammatory cytokines in the whole larvae and isolated neutrophils. miR-722 protects zebrafish from lethal lipopolysaccharide challenge. In addition, overexpression of mir-722 reduced chemotaxis of human neutrophil like cells, indicating that miR-722 is a potential agent to reduce inflammation in humans. </p> <p>MiR-199<i>,</i> decreases neutrophil chemotaxis in zebrafish and human neutrophil-like cells. Intriguingly, in terminally differentiated neutrophils, miR-199 alters the cell cycle-related pathways and directly suppresses cyclin-dependent kinase 2 (<i>cdk2</i>), whose known activity is restricted to cell cycle progression and cell differentiation. Inhibiting Cdk2, but not DNA replication, disrupts cell polarity and chemotaxis of zebrafish neutrophils without inducing cell death. Human neutrophil-like cells deficient in CDK2 fail to polarize and display altered signaling downstream of the formyl peptide receptor. Chemotaxis of primary human neutrophils is also reduced upon CDK2 inhibition. Furthermore, miR-199 overexpression or CDK2 inhibition significantly improves the outcome of lethal systemic inflammation challenges in zebrafish. </p> <p> </p> <p>In summary, our results reveal previously unknown functions of these miRNAs, and provide potential avenues to modulate neutrophil migration as well as lead to discoveries of novel factors which can regulate this process. We have also discovered a non-classical role of CDK2 in regulating neutrophil migration which provides directions for alleviating systemic inflammation and a better understanding of neutrophil biology. </p>

<p dir="ltr">The genetic perturbations caused by spaceflight on biological systems tend to have a system-wide effect which is often difficult to deconvolute into individual signals with specific points of origin. Single cell multi-omic data can provide a profile of the perturbational effects but does not necessarily indicate the initial point of interference within a network. The objective of this project is to take advantage of large scale and genome-wide perturbational or Perturb-Seq datasets by using them to pre-train a generalist machine learning model that is capable of predicting the effects of unseen perturbations in new data. Perturb-Seq datasets are large libraries of single cell RNA sequencing data collected from CRISPR knock out screens in cell culture. The advent of generative machine learning algorithms, particularly transformers, make it an ideal time to re-assess large scale data libraries in order to grasp cell and even organism-wide genomic expression motifs. By tailoring an algorithm to learn the downstream effects of the genetic perturbations, we present a pre-trained generalist model capable of predicting the effects of multiple perturbations in combination, locating points of origin for perturbation in new datasets, predicting the effects of known perturbations in new datasets, and annotation of large-scale network motifs. We demonstrate the utility of this model by identifying key perturbational signatures in RNA sequencing data from spaceflown biological samples from the NASA Open Science Data Repository.</p>