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Aplicações translacionais de Drosophila melanogaster em neurociência: mecanismos moleculares, modelos de doenças e investigação terapêutica

Fri, 20 Feb 2026 00:00:00 GMT

Title: Aplicações translacionais de Drosophila melanogaster em neurociência: mecanismos moleculares, modelos de doenças e investigação terapêutica Abstract: This thesis investigated the translational applications of Drosophila melanogaster in neuroscience through studies focused on neurodegeneration and nociception. In the first study, metabolic and peptide fractions derived from kefir were evaluated in amyloidogenic models of Alzheimer’s disease in D. melanogaster and in cell culture. The biomolecules were investigated using biochemical, in vitro, and in vivo approaches. The results demonstrated the neuroprotective potential of the kefir-derived fractions, including attenuation of neurodegenerative phenotypes, improvement of oxidative parameters, and reduction of neurodegeneration-associated alterations in the experimental models. In the second study, a voltage-gated sodium channel mutant model in D. melanogaster was validated as an experimental tool for investigating mechanisms related to nociception and chronic pain. Using this model, the modulatory potential of cannabidiol (CBD) on nociceptive parameters and conserved neural pathways associated with pain signaling was evaluated. Collectively, the findings reinforce the translational relevance of D. melanogaster as a model organism in neuroscience, highlighting its applicability in the investigation of conserved molecular mechanisms, the experimental modeling of neurological diseases, and the prospecting of therapeutic strategies with neuroprotective and analgesic potential.

Produtos Naturais como Fontes de Compostos Biotecnológicos e Terapêuticos

Thu, 26 Feb 2026 00:00:00 GMT

Title: Produtos Naturais como Fontes de Compostos Biotecnológicos e Terapêuticos Abstract: This thesis investigated natural products as sources of biotechnological and therapeutic innovation in two studies. In the first study, the total water-soluble fraction of kefir (WSF) and its <10 kDa fraction were used for the green synthesis of silver nanoparticles (AgNPs). The WSF-AgNPs exhibited an absorbance peak at 470 nm, a negative zeta potential (-30 mV), and a broad hydrodynamic size distribution (500-1000 nm). AgNPs derived from the <10 kDa fraction showed predominantly smaller particles (50-200 nm), although with lower stability. The WSF-AgNPs inhibited multidrug-resistant bacteria, with MIC values of 25 μg/mL for Acinetobacter baumannii and 50 μg/mL for Klebsiella pneumoniae, showing bactericidal activity at the minimum inhibitory concentrations. In Drosophila melanogaster, larval exposure to 100 μg/mL impaired developmental parameters, whereas no robust changes in 15-day adult survival were observed, despite subtle signs of redox imbalance, suggesting a dose- and stage-dependent safety window. In the second study, ethanolic and acetonic extracts of Saskatoon berry (Amelanchier alnifolia) were characterized by LC-MS/MS and in silico analyses, indicating solvent-dependent composition and potential interactions with targets associated with Alzheimer’s disease. The acetonic extract showed higher total phenolic content and strong antioxidant performance. In cellular models, it exhibited low cytotoxicity and a neuroprotective effect under beta-amyloid peptide challenge. In D. melanogaster, supplementation with both extracts increased longevity in healthy flies and, in the AD-like model driven by GMR-GAL4, the acetonic extract reduced beta-amyloid burden and preserved retinal thickness and structure, with a tendency toward dose- and sex-dependent responses. Together, these findings support the potential of fermented matrices and polyphenol-rich fruits as promising sources of candidates for antimicrobial and neuroprotective applications.

Avaliação dos efeitos de dendropsofina 1, um peptídeo natural antimicrobiano, e de dois peptídeos análogos sobre a inflamação crônica induzida por implante de esponja sintética em camundongos

Fri, 27 Feb 2026 00:00:00 GMT

Title: Avaliação dos efeitos de dendropsofina 1, um peptídeo natural antimicrobiano, e de dois peptídeos análogos sobre a inflamação crônica induzida por implante de esponja sintética em camundongos Abstract: Inflammation is a biological process aimed at restoring homeostasis after harmful stimuli. Through these events, the immune system removes injury-causing agents and promotes tissue repair. Although inflammatory events are essential for life, failure in their resolution may result in the development of chronic-degenerative diseases. Chronic inflammation is present in many disorders, such as diabetes mellitus, rheumatoid arthritis, cancer, and hard-to-heal wounds. In fact, many of the leading causes of death and major burdens on healthcare systems are diseases in which a persistent inflammatory state is present. Under these conditions, there is exacerbated activity of one or more components of chronic inflammation, namely inflammatory mediators, fibrogenesis, and/or angiogenesis. Continuous tissue damage and unsuccessful attempts at repair coexist in chronic inflammation. Thus, cytokines produced at the inflammatory site influence angiogenesis and extracellular matrix (ECM) deposition. Consequently, fibrosis may develop and local tissue function may be lost. Given this scenario, there is a clear need to search for biologically active compounds capable of keeping inflammation under control without completely silencing it; compounds that enable the return to homeostasis while minimizing functional loss. Antimicrobial peptides (AMPs) are a diverse group of bioactive proteins that constitute the first line of defense of various organisms against pathogens. Amphibian skin, for example, is an important reservoir of AMPs. In addition to exerting direct antimicrobial activity, these peptides may inhibit the expression of pro-inflammatory cytokines and chemokines, act as chemotactic molecules, activate immune cells, and modulate fibrogenic and vascular components of inflammation. The present study highlights the activity of a peptide isolated from the skin secretion of Dendropsophus columbianus, a tree frog endemic to Colombia, and two of its synthetic analogs. In 2018, the native peptide, named dendropsophin 1 (Dc1), was isolated, and subsequently the analogs Dc1.2 and Dc1.2.2 were synthesized. These peptides have documented antimicrobial activity; however, since their in vivo immunomodulatory action had not yet been elucidated, we evaluated the effects of their daily administration in a mouse model of chronic inflammation induced by polyester-polyurethane sponge implants. The sponge matrices induce a chronic foreign body-type inflammatory response and form fibrovascular tissue. Therefore, this model makes it possible to simultaneously evaluate inflammatory markers, angiogenesis, and fibrogenesis in vivo. To date, this is the first study to analyze the effects of dendropsophin 1 and its analogs in this context, and it demonstrates the therapeutic potential of this peptide for the treatment of conditions that require tissue repair and inflammatory control.

Evaluating Advanced Strategies in Plant Breeding using Simulation: Genomic Selection with Rapid-cycling, Speed Breeding and Gene Editing

Tue, 15 Apr 2025 00:00:00 GMT

Title: Evaluating Advanced Strategies in Plant Breeding using Simulation: Genomic Selection with Rapid-cycling, Speed Breeding and Gene Editing Abstract: This review summarizes findings from simulation studies on quantitative traits in plant breeding and translates these insights into practical schemes. As agricultural productivity faces growing challenges, plant breeding is central to addressing these issues. Simulations use mathematical models to replicate biological conditions, bridging theory and practice by validating hypotheses early and optimizing genetic gain and resource use. While strategies can improve trait value, they reduce genetic diversity, making a combination of approaches essential. Studies emphasize the importance of aligning strategy with trait heritability and selection timing and maintaining genetic diversity while considering genotype-environment interactions to avoid biases in early selection. Using markers accelerates breeding cycles when marker placement is precise, foreground and background selection are balanced, and QTL are effectively managed. Genomic selection increases genetic gains by shortening breeding cycles and improving parent selection, especially for low heritability traits and complex genetic architectures. Regular updates of training sets are critical, regardless of genetic architecture. Bayesian methods perform well with fewer genes and in early breeding cycles, while BLUP is more robust for traits with many QTL, and RR-BLUP proves flexible across different conditions. Larger populations lead to greater gains when clear objectives and adequate germplasm are available. Accuracy declines over generations, influenced by genetic architecture and population size. For low heritability traits, multi-trait analysis improves accuracy, especially when correlated with high heritability traits. Updates including top-performing candidates, but conserving variability enhances gains and accuracy. Low-density genotyping and imputation offer cost-effective alternatives to high-density genotyping, achieving comparable results. Targeting populations optimizes genetic relationships, further improving accuracy and breeding outcomes. Evaluating genomic selection reveals a balance between short-term gains and long-term potential and rapid-cycling genomic programs excel. Diverse approaches preserve rare alleles, achieve significant gains, and maintain diversity, highlighting the trade-offs in optimizing breeding success.