2,869 research outputs found

    Fluorescence imaging for the anterior segment of the eye

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    Diagnostic technologies for the anterior segment of the eye, especially for hard-to-diagnose diseases such as microbial keratitis, are still lacking. Although in vivo confocal microscopy and optical coherence tomography are becoming more widely applicable to a variety of conditions, they are often prohibitively expensive, require specialized training and equipment, and are intrinsically insensitive to chemical changes. Here, ultraviolet-fluorescence imaging is proposed as a new technique to aid in investigation of the anterior segment. In this work, a novel two-color line-of-sight fluorescence imaging technique is described for imaging of the anterior segment. The technique is applied to seven ex vivo porcine eyes to illustrate the utility of the technique. The image data was used to estimate an effective fluorescence quantum yield of each eye at 370 nm. The eyes were then inoculated with bacteria to simulate microbial keratitis, a common sight-threatening infection, and the measurement was repeated. A simplified fluorescence-extinction model was developed to describe and analyze the relative intensities of the eye and biofilm fluorescence. Overall, the technique appears to have utility in clinical practice and with proper development may be suitable for detecting chemical changes in the eye, or the presence of foreign matter; however, further investigation is needed to develop the technique and analysis procedures into a quantitative diagnostic tool

    Optical mapping and optogenetics in cardiac electrophysiology research and therapy:a state-of-the-art review

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    State-of-the-art innovations in optical cardiac electrophysiology are significantly enhancing cardiac research. A potential leap into patient care is now on the horizon. Optical mapping, using fluorescent probes and high-speed cameras, offers detailed insights into cardiac activity and arrhythmias by analysing electrical signals, calcium dynamics, and metabolism. Optogenetics utilizes light-sensitive ion channels and pumps to realize contactless, cell-selective cardiac actuation for modelling arrhythmia, restoring sinus rhythm, and probing complex cell‚Äďcell interactions. The merging of optogenetics and optical mapping techniques for ‚Äėall-optical‚Äô electrophysiology marks a significant step forward. This combination allows for the contactless actuation and sensing of cardiac electrophysiology, offering unprecedented spatial‚Äďtemporal resolution and control. Recent studies have performed all-optical imaging ex vivo and achieved reliable optogenetic pacing in vivo, narrowing the gap for clinical use. Progress in optical electrophysiology continues at pace. Advances in motion tracking methods are removing the necessity of motion uncoupling, a key limitation of optical mapping. Innovations in optoelectronics, including miniaturized, biocompatible illumination and circuitry, are enabling the creation of implantable cardiac pacemakers and defibrillators with optoelectrical closed-loop systems. Computational modelling and machine learning are emerging as pivotal tools in enhancing optical techniques, offering new avenues for analysing complex data and optimizing therapeutic strategies. However, key challenges remain including opsin delivery, real-time data processing, longevity, and chronic effects of optoelectronic devices. This review provides a comprehensive overview of recent advances in optical mapping and optogenetics and outlines the promising future of optics in reshaping cardiac electrophysiology and therapeutic strategies

    Single-cell time-series analysis of metabolic rhythms in yeast

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    The yeast metabolic cycle (YMC) is a biological rhythm in budding yeast (Saccharomyces cerevisiae). It entails oscillations in the concentrations and redox states of intracellular metabolites, oscillations in transcript levels, temporal partitioning of biosynthesis, and, in chemostats, oscillations in oxygen consumption. Most studies on the YMC have been based on chemostat experiments, and it is unclear whether YMCs arise from interactions between cells or are generated independently by each cell. This thesis aims at characterising the YMC in single cells and its response to nutrient and genetic perturbations. Specifically, I use microfluidics to trap and separate yeast cells, then record the time-dependent intensity of flavin autofluorescence, which is a component of the YMC. Single-cell microfluidics produces a large amount of time series data. Noisy and short time series produced from biological experiments restrict the computational tools that are useful for analysis. I developed a method to filter time series, a machine learning model to classify whether time series are oscillatory, and an autocorrelation method to examine the periodicity of time series data. My experimental results show that yeast cells show oscillations in the fluorescence of flavins. Specifically, I show that in high glucose conditions, cells generate flavin oscillations asynchronously within a population, and these flavin oscillations couple with the cell division cycle. I show that cells can individually reset the phase of their flavin oscillations in response to abrupt nutrient changes, independently of the cell division cycle. I also show that deletion strains generate flavin oscillations that exhibit different behaviour from dissolved oxygen oscillations from chemostat conditions. Finally, I use flux balance analysis to address whether proteomic constraints in cellular metabolism mean that temporal partitioning of biosynthesis is advantageous for the yeast cell, and whether such partitioning explains the timing of the metabolic cycle. My results show that under proteomic constraints, it is advantageous for the cell to sequentially synthesise biomass components because doing so shortens the timescale of biomass synthesis. However, the degree of advantage of sequential over parallel biosynthesis is lower when both carbon and nitrogen sources are limiting. This thesis thus confirms autonomous generation of flavin oscillations, and suggests a model in which the YMC responds to nutrient conditions and subsequently entrains the cell division cycle. It also emphasises the possibility that subpopulations in the culture explain chemostat-based observations of the YMC. Furthermore, this thesis paves the way for using computational methods to analyse large datasets of oscillatory time series, which is useful for various fields of study beyond the YMC

    CANCER TREATMENT BY TARGETING HDAC4 TRANSLOCATION INDUCED BY MICROSECOND PULSED ELECTRIC FIELD EXPOSURE: MECHANISTIC INSIGHTS THROUGH KINASES AND PHOSPHATASES

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    Epigenetic modifications, arising from sub-cellular shifts in histone deacetylase (HDAC) activity and localization, present promising strategies for diverse cancer treatments. HDACs, enzymes responsible for post-translational histone modifications, induce these epigenetic changes by removing acetyl groups from őĶ-N-acetyl-lysine residues on histones, thereby suppressing gene transcription. Within the HDAC group, class IIa HDACs are notable for their responsiveness to extracellular signals, bridging the gap between external stimuli, plasma membrane, and genome through nuclear-cytoplasmic translocation. This localization offers two significant mechanisms for cancer treatment: nuclear accumulation of HDACs represses oncogenic transcription factors, such as myocyte-specific enhancer factor 2C (MEF2C), triggering various cell death pathways. Conversely, cytoplasmic HDAC accumulation acts similarly to HDAC inhibitors by silencing genes. My dissertation introduces an innovative approach for glioblastoma and breast cancer treatment by investigating the application of microsecond pulsed electric fields. It particularly focuses on HDAC4, a class IIa HDAC overexpressed in these cancers. Beyond demonstrating HDAC4 translocation, my research delves into the intricate roles of kinases and phosphatases, shedding light on the underlying factors governing HDAC4 translocation

    Characterisation of peroxisomes in the fission Yeast Schizosaccharomyces pombe and slime mold Dictyostelium discoideum

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    Peroxisome is a compartment that is found in most eukaryotic organisms' cells. It has several crucial roles, such as fatty acid beta (ő≤) oxidation and hydrogen peroxide (H2O2) detoxification. It contains many essential enzymes, including oxidase and catalase, and has several metabolic and non-metabolic pathways, depending on the environment and the organisms within its cells. This study investigates the role of peroxisomes in two organisms, S. pombe and D. discoideum. Although S. pombe is a well-studied yeast, there is only one study of this yeast that has focused on peroxisomes. This study offers a few crucial observations, including that S. pombe contains peroxisomes, that GFP containing a well-characterized PTS1 (SKL) is efficiently imported, and that peroxisome numbers increase in cells grown on a fatty acid as the sole carbon source, suggesting a role for peroxisomes in fatty acid degradation. The starting point in my research was initially a bioinformatics screen. This screening recognized the enzymes imported into peroxisomes based on the presence of a potential peroxisomal targeting signal. A few proteins were found. However, the low number of proteins with a classical PTS might be the result of different targeting signals that are not recognized by our bioinformatics parameters. Indeed, in other organisms, there are proteins without PTS1 that still use Pex5 for import. The first example is S. cerevisiae Acyl-CoA oxidase. In a global yeast two-hybrid screen, S. pombe Pex5 was found to bind S. pombe Str3 and Lys3. Consequently, we think that there is conserved targeting of a peroxisomal protein lacking a PTS1 and PTS2 imported into the peroxisome by Pex5. One of these is the Str3 case. Interestingly, proteins involved in peroxisomal fatty acid ő≤ -oxidation are absent from the S. pombe genome, casting doubt on the conclusions from the previous study and explaining the low number of potential peroxisomal enzymes. In D. discoideum, this study investigates the dynamic regulation of peroxisome numbers in response to growth conditions and identifies peroxisomal import and contents through a proximity labeling approach (BioID). Overall, this study sheds light on the roles and regulation of peroxisomes in these two organisms

    Two-photon excitation fluorescence in ophthalmology: safety and improved imaging for functional diagnostics

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    Two-photon excitation fluorescence (TPEF) is emerging as a powerful imaging technique with superior penetration power in scattering media, allowing for functional imaging of biological tissues at a subcellular level. TPEF is commonly used in cancer diagnostics, as it enables the direct observation of metabolism within living cells. The technique is now widely used in various medical fields, including ophthalmology. The eye is a complex and delicate organ with multiple layers of different cell types and tissues. Although this structure is ideal for visual perception, it generates aberrations in TPEF eye imaging. However, adaptive optics can now compensate for these aberrations, allowing for improved imaging of the eyes of animal models for human diseases. The eye is naturally built to filter out harmful wavelengths, but these wavelengths can be mimicked and thereby utilized in diagnostics via two-photon (2Ph) excitation. Recent advances in laser-source manufacturing have made it possible to minimize the exposure of in vivo measurements within safety, while achieving sufficient signals to detect for functional images, making TPEF a viable option for human application. This review explores recent advances in wavefront-distortion correction in animal models and the safety of use of TPEF on human subjects, both of which make TPEF a potentially powerful tool for ophthalmological diagnostics

    Investigation of the metabolism of rare nucleotides in plants

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    Nucleotides are metabolites involved in primary metabolism, and specialized metabolism and have a regulatory role in various biochemical reactions in all forms of life. While in other organisms, the nucleotide metabolome was characterized extensively, comparatively little is known about the cellular concentrations of nucleotides in plants. The aim of this dissertation was to investigate the nucleotide metabolome and enzymes influencing the composition and quantities of nucleotides in plants. For this purpose, a method for the analysis of nucleotides and nucleosides in plants and algae was developed (Chapter 2.1), which comprises efficient quenching of enzymatic activity, liquid-liquid extraction and solid phase extraction employing a weak-anionexchange resin. This method allowed the analysis of the nucleotide metabolome of plants in great depth including the quantification of low abundant deoxyribonucleotides and deoxyribonucleosides. The details of the method were summarized in an article, serving as a laboratory protocol (Chapter 2.2). Furthermore, we contributed a review article (Chapter 2.3) that summarizes the literature about nucleotide analysis and recent technological advances with a focus on plants and factors influencing and hindering the analysis of nucleotides in plants, i.e., a complex metabolic matrix, highly stable phosphatases and physicochemical properties of nucleotides. To analyze the sub-cellular concentrations of metabolites, a protocol for the rapid isolation of highly pure mitochondria utilizing affinity chromatography was developed (Chapter 2.4). The method for the purification of nucleotides furthermore contributed to the comprehensive analysis of the nucleotide metabolome in germinating seeds and in establishing seedlings of A. thaliana, with a focus on genes involved in the synthesis of thymidilates (Chapter 2.5) and the characterization of a novel enzyme of purine nucleotide degradation, the XANTHOSINE MONOPHOSPHATE PHOSPHATASE (Chapter 2.6). Protein homology analysis comparing A. thaliana, S. cerevisiae, and H. sapiens led to the identification and characterization of an enzyme involved in the metabolite damage repair system of plants, the INOSINE TRIPHOSPHATE PYROPHOSPHATASE (Chapter 2.7). It was shown that this enzyme dephosphorylates deaminated purine nucleotide triphosphates and thus prevents their incorporation into nucleic acids. Lossof-function mutants senesce early and have a constitutively increased content of salicylic acid. Also, the source of deaminated purine nucleotides in plants was investigated and it was shown that abiotic factors contribute to nucleotide damage.Nukleotide sind Metaboliten, die am Prim√§rstoffwechsel und an spezialisierten Stoffwechselvorg√§ngen beteiligt sind und eine regulierende Rolle bei verschiedenen biochemischen Reaktionen in allen Lebensformen spielen. W√§hrend bei anderen Organismen das Nukleotidmetabolom umfassend charakterisiert wurde, ist in Pflanzen vergleichsweise wenig √ľber die zellul√§ren Konzentrationen von Nukleotiden bekannt. Ziel dieser Dissertation war es, das Nukleotidmetabolom und die Enzyme zu untersuchen, die die Zusammensetzung und Menge der Nukleotide in Pflanzen beeinflussen. Zu diesem Zweck wurde eine Methode zur Analyse von Nukleotiden und Nukleosiden in Pflanzen und Algen entwickelt (Kapitel 2.1), die ein effizientes Stoppen enzymatischer Aktivit√§t, eine Fl√ľssig-Fl√ľssig-Extraktion und eine Festphasenextraktion unter Verwendung eines schwachen Ionenaustauschers umfasst. Mit dieser Methode konnte das Nukleotidmetabolom von Pflanzen eingehend analysiert werden, einschlie√ülich der Quantifizierung von Desoxyribonukleotiden und Desoxyribonukleosiden mit geringer Abundanz. Die Einzelheiten der Methode wurden in einem Artikel zusammengefasst, der als Laborprotokoll dient (Kapitel 2.2). Dar√ľber hinaus wurde ein √úbersichtsartikel (Kapitel 2.3) verfasst, der die Literatur √ľber die Analyse von Nukleotiden und die j√ľngsten technologischen Fortschritte zusammenfasst. Der Schwerpunkt lag hierbei auf Pflanzen und Faktoren, die die Analyse von Nukleotiden in Pflanzen beeinflussen oder behindern, d. h. eine komplexe Matrix, hochstabile Phosphatasen und physikalisch-chemische Eigenschaften von Nukleotiden. Um die subzellul√§ren Konzentrationen von Metaboliten zu analysieren, wurde ein Protokoll f√ľr die schnelle Isolierung hochreiner Mitochondrien unter Verwendung einer Affinit√§tschromatographie entwickelt (Kapitel 2.4). Die Methode zur Analyse von Nukleotiden trug au√üerdem zu einer umfassenden Analyse des Nukleotidmetaboloms in keimenden Samen und in sich etablierenden Keimlingen von A. thaliana bei, wobei der Schwerpunkt auf Genen lag, die an der Synthese von Thymidilaten beteiligt sind (Kapitel 2.5), sowie zu der Charakterisierung eines neuen Enzyms des Purinnukleotidabbaus, der XANTHOSINE MONOPHOSPHATE PHOSPHATASE (Kapitel 2.6). Eine Proteinhomologieanalyse, die A. thaliana, S. cerevisiae und H. sapiens miteinander verglich f√ľhrte zur Identifizierung und Charakterisierung eines Enzyms, das an der Reparatur von gesch√§digten Metaboliten in Pflanzen beteiligt ist, der INOSINE TRIPHOSPHATE PYROPHOSPHATASE (Kapitel 2.7). Es konnte gezeigt werden, dass dieses Enzym desaminierte Purinnukleotidtriphosphate dephosphoryliert und so deren Einbau in Nukleins√§uren verhindert. Funktionsverlustmutanten altern fr√ľh und weisen einen konstitutiv erh√∂hten Gehalt an Salicyls√§ure auf. Au√üerdem wurde die Quelle der desaminierten Purinnukleotide in Pflanzen untersucht, und es wurde gezeigt, dass abiotische Faktoren zur Nukleotidsch√§digung beitragen

    Cytotoxicity and Cell Viability Assessment of Biomaterials

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    Biocompatibility testing is essential for medical devices and pharmaceutical agents, regardless of their mechanical, physical, and chemical properties. These tests assess cytotoxic effects and acute systemic toxicity to ensure safety and effectiveness before clinical use. Cell viability, indicating the number of healthy cells in a sample, is determined through various assays that measure live-to-dead cell ratios. Cytotoxicity measures a substance’s potential for cell damage or death, and is evaluated through numerous assay methods based on different cell functions. Ensuring biocompatibility is crucial for the successful integration of medical devices and pharmaceuticals into clinical practice. As part of the evaluation process, researchers utilize a range of cell viability assays and cytotoxicity tests to assess the potential impact of these products on living cells. The results of these tests inform the optimization of cell culture conditions and drug candidates, as well as guide the development of safer, more effective medical devices. By thoroughly examining the interactions between devices, drugs, and biological systems, researchers aim to minimize the risk of adverse reactions and improve patient outcomes

    Lanthanide-doped upconversion nanoparticles (UCNPs) for biomedical applications

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    This thesis examines the need for new antibacterial materials to treat small colony variants (SCVs) of Staphylococcus (S.) aureus bacteria and their parental strains. While ZnO-based nanoparticles (NPs) activated by ultraviolet (UV) and short wavelength visible light have been researched for their antibacterial properties, the potential benefits of incorporating UCNPs to allow activation by near-infrared (NIR) light have been overlooked. This study aims to fill this research gap by comprehensively investigating the synthesis and performance of ZnO-coated lanthanide-doped upconversion nanoparticle (UCNP) composites activated by NIR light against S. aureus SCVs and parental strains. Furthermore, this research addresses the limited understanding of the potential risks associated with UV emission from UCNPs used as fluorescent probes in super-resolution microscopy (SRM). Despite extensive research on the usage of UCNPs as fluorescent probes for SRMs, the potential cytotoxic effects of UV emission from UCNPs have not been thoroughly studied. To advance cellular imaging techniques and ensure cellular viability, a comprehensive investigation of UV emission from UCNPs is necessary. This thesis aims to identify and quantify UV emission by UCNPs used in SRM and develop strategies to minimise UV emission and mitigate potential cytotoxic effects. These two main aims are addressed in three results chapters. The first aim, the focus of chapters 2 and 3, focuses on the synthesis UCNP@ZnO composites that can be activated by NIR light for antimicrobial photodynamic therapy (aPDT) applications against S. aureus SCVs and parental strains. Chapter 2 reports the synthesis and performance of these composites, showing these materials to be effective antibacterial therapies against S. aureus SCVs, while chapter 3 improves upon the performance of these composites by careful tuning of the UCNP core and provides enhancements to the ZnO shell composition to improve reactive oxygen species generation and add a second mode of action in the form of silver nanoparticles. The second aim of this research is covered in chapter 4, which reports an investigation into the UV emission from UCNPs used as fluorescent probes in SRM. The work posits the need to understand the UV emission properties of these UCNPs as knowledge of these and the potential for cytotoxic effects are crucial for optimizing cellular imaging experiments and ensuring accurate and reliable results. Chapter 4 identifies design features and compositions that can limit UV emission, thereby minimizing the risk of phototoxicity and advancing the field of cellular imaging. Overall, the findings from this research have the potential to contribute to the development of safer and more effective targeted antibacterial therapies and enhance the understanding of UV emissions in cellular imaging techniques.Thesis (Ph.D.) -- University of Adelaide, School of Chemical Engineering, 202

    Use of omic tools for environmental risk assessment of emerging contaminants in marine species of commercial interest

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    La presente tesis doctoral busca evaluar los posibles efectos toxicol√≥gicos que pueden tener los contaminantes ‚Äėemergentes‚Äô (CE) en los organismos marinos expuestos a ellos. En concreto, se han evaluado dos filtros solares, un repelente de insectos y un biocida, todos ellos presentes en productos de cuidado personal (PCP). Estas sustancias llegan a los sistemas marinos a trav√©s de los vertidos de aguas residuales, as√≠ como las entradas directas procedentes de actividades recreativas, tales como la nataci√≥n y el ba√Īo. La exposici√≥n a estos contaminantes se hace a muy bajas concentraciones y de forma cr√≥nica, por tanto, evaluar sus posibles efectos a nivel molecular resulta un paso clave para determinar su toxicidad. Las tecnolog√≠as ‚Äú√≥micas‚ÄĚ permiten el estudio global de los diferentes niveles biol√≥gicos (transcriptoma, proteoma, metaboloma‚Ķ) desde un punto de vista hol√≠stico e integrado. La integraci√≥n de datos √≥micos, junto con la fusi√≥n de datos de bioconcentraci√≥n y toxicocin√©tica, es un m√©todo extremadamente √ļtil para dilucidar el modo de acci√≥n (MoA) de los contaminantes. De este modo, en la presente tesis doctoral se ha implementado el uso y la integraci√≥n de herramientas √≥micas (metabol√≥mica y transcript√≥mica) para evaluar el efecto toxicol√≥gico de dos filtros solares (4-metilbencilideno alcanfor (4-MBC) y sulisobenzona (BP-4)), un repelente de insectos (N,N-Dietil-meta-toluamida (DEET)) y un biocida (triclos√°n (TCS)) en dos especies marinas de inter√©s comercial, la dorada (Sparus aurata) y la almeja japonesa (Ruditapes philippinarum). Adicionalmente se realizaron estudios de bioconcentraci√≥n y toxicocin√©tica. Primero, se realizaron siete experimentos de exposici√≥n con los contaminantes y organismos anteriormente mencionados usando un flujo continuo para reproducir escenarios de exposici√≥n ambiental bajo condiciones controladas de laboratorio. Tras la aplicaci√≥n de t√©cnicas anal√≠ticas y de alto rendimiento, se observ√≥ que la bioacumulaci√≥n de los contaminantes es superior en la almeja que en los peces. Esto evidencia la importancia de tener en cuenta organismos de distintos niveles tr√≥ficos para evaluar el potencial de bioacumulaci√≥n de los contaminantes ambientales. Adem√°s, se observ√≥ que el filtro solar 4-MBC present√≥ el factor de bioacumulaci√≥n (BCF) m√°s alto (368 565 L Kg -1) y la tasa de eliminaci√≥n m√°s baja (61.65%) que, junto con la persistencia de este compuesto en el medio, son probablemente indicativos de un riesgo potencial para el medio acu√°tico marino que puede llegar a magnificarse a trav√©s de la red alimentaria. Tambi√©n se observ√≥ que este compuesto sufr√≠a varias biotransformaciones (reducci√≥n, oxidaci√≥n, hidroxilaci√≥n‚Ķ) con el fin de ser excretado, afectando al metabolismo de las drogas y xenobi√≥ticos y al del glutati√≥n, llegando a producir estr√©s oxidativo. Por otro lado, se observ√≥ que, aunque el TCS y BP-4 ten√≠an altos BCF en la almeja (1309 y 850 L Kg -1 respectivamente), sus tasas de eliminaci√≥n tambi√©n eran altas (97.12 y 99.99%). Sin embargo, la exposici√≥n a estos contaminantes produjo, entre otros, alteraciones en el metabolismo de los l√≠pidos lo que puede deberse a su capacidad como disruptores endocrinos. El DEET present√≥ el BCF m√°s bajo en la almeja (9.9 L Kg -1) y una alta tasa de eliminaci√≥n (98.85%). El principal impacto de la exposici√≥n de este compuesto a nivel transcript√≥mico se observ√≥ en el metabolismo de biodegradaci√≥n de xenobi√≥ticos y en el de los carbohidratos, lo que sugiere que se estaba realizando un gran consumo energ√©tico para poder llevar a cabo la excreci√≥n del compuesto. En el m√ļsculo de la dorada se observ√≥ que tanto el DEET como la BP-4 presentaban bajos BCF (2.6 y 0.7 L Kg -1 respectivamente) mientras que el TCS presentaba un BCF de 113 L Kg -1. Sin embargo, los an√°lisis transcript√≥micos en el h√≠gado de las doradas revelaron que tras la exposici√≥n a DEET y BP-4, se expresaron 250 y 371 genes diferencialmente, mientras que no se encontraron genes diferencialmente expresados en la dorada tras la exposici√≥n a TCS. Tras la integraci√≥n con los datos metabol√≥micos realizados en las mismas muestras, se determin√≥ que el DEET causaba en la dorada agotamiento energ√©tico a trav√©s de la alteraci√≥n de los metabolismos de carbohidratos y amino√°cidos, estr√©s oxidativo que daba lugar a da√Īos en el ADN, peroxidaci√≥n lip√≠dica y da√Īos en la membrana celular y apoptosis. Tambi√©n se observ√≥ la activaci√≥n del metabolismo de los xenobi√≥ticos, as√≠ como una reacci√≥n inmune-inflamatoria. Finalmente, la integraci√≥n de datos multi√≥micos revel√≥ que la BP-4 causaba en la dorada impacto en el metabolismo energ√©tico y oxidaci√≥n lip√≠dica, as√≠ como, impacto en la bios√≠ntesis de las hormonas esteroideas y tiroideas y en el metabolismo de los nucle√≥tidos. En conclusi√≥n, esta tesis muestra la utilidad de integrar datos a distintos niveles biol√≥gicos y demuestra que el enfoque multi√≥mico desarrollado y aplicado supone una gran ventaja para dilucidar modos de acci√≥n de los compuestos estudiados que, con enfoques diferentes, como el uso de una sola herramienta √≥mica, podr√≠an haberse pasado por alto
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