ABSTRACT
Lanthanides have unique photoluminescence (PL) emission properties, including very long PL lifetimes. This makes them ideal for biological imaging applications, especially using PL lifetime imaging microscopy (PLIM). PLIM is an inherently multidimensional technique with exceptional advantages for quantitative biological imaging. Unfortunately, due to the required prolonged acquisitions times, photobleaching of lanthanide PL emission currently constitutes one of the main drawbacks of PLIM. In this study, we report a small aqueous-soluble, lanthanide antenna, 8-methoxy-2-oxo-1,2,4,5-tetrahydrocyclopenta[de]quinoline-3-phosphonic acid, PAnt, specifically designed to dynamically interact with lanthanide ions, serving as exchangeable dye aimed at mitigating photobleaching in PLIM microscopy in cellulo. Thus, self-assembled lanthanide complexes that may be photobleached during image acquisition are continuously replenished by intact lanthanide antennas from a large reservoir. Remarkably, our self-assembled lanthanide complex clearly demonstrated a significant reduction of PL photobleaching when compared to well-established lanthanide cryptates, used for bioimaging. This concept of exchangeable lanthanide antennas opens new possibilities for quantitative PLIM bioimaging.
Subject(s)
Lanthanoid Series Elements , Microscopy , Luminescence , PhotobleachingABSTRACT
In Chile, overnutrition continues to increase, especially affecting children. Solving this public health problem requires the development of promotion and prevention strategies that consider the suggestions of the communities, especially those of the children themselves. OBJECTIVE: To know the opinions and suggestions of third and fourth-grade children from schools in the southern area of Santiago, Chile, regarding their eating practices and physical activity, as part of the FONDEF IT 1810016 project. SUBJECTS AND METHOD: Seven School Meetings were held in seven schools using a participatory qualitative methodology, collecting the opinions of 176 children regarding both their food and physical activity habits and preferences. RESULTS: The most consumed and preferred foods are those easy to prepare and highly available, such as bread, pasta, and milk. Foods that require preparation or are less available, such as fish, legumes, fruits, vegetables, and homemade preparations, are less consumed and have less preference. Regarding physical activities, video games and soccer stand out. Students propose increasing the hours of physical education and recesses and improving the availability and access to healthy foods in school environments as a solution strategy. CONCLUSIONS: School Meetings as a participatory strategy contribute to the joint generation of knowledge. The need to include communities as participants in health initiatives recognizes, through their role, children as subjects of rights.
Subject(s)
Diet , Feeding Behavior , Animals , Child , Humans , Schools , Exercise , VegetablesABSTRACT
In recent years, the prevalence of amyloid neurodegenerative diseases such as Alzheimer's disease (AD) has significantly increased in developed countries due to increased life expectancy. This amyloid disease is characterized by the presence of accumulations and deposits of ß-amyloid peptide (Aß) in neuronal tissue, leading to the formation of oligomers, fibers, and plaques. First, oligomeric intermediates that arise during the aggregation process are currently thought to be primarily responsible for cytotoxicity in cells. This work aims to provide further insights into the mechanisms of cytotoxicity by studying the interaction of Aß aggregates with Neuro-2a (N2a) neuronal cells and the effects caused by this interaction. For this purpose, we have exploited the advantages of advanced, multidimensional fluorescence microscopy techniques to determine whether different types of Aß are involved in higher rates of cellular toxicity, and we measured the cellular stress caused by such aggregates by using a fluorogenic intracellular biothiol sensor. Stress provoked by the peptide is evident by N2a cells generating high levels of biothiols as a defense mechanism. In our study, we demonstrate that Aß aggregates act as seeds for aggregate growth upon interacting with the cellular membrane, which results in cell permeability and damage and induces lysis. In parallel, these damaged cells undergo a significant increase in intracellular biothiol levels.
Subject(s)
Amyloid beta-Peptides/metabolism , Cell Membrane/metabolism , Neurons/metabolism , Protein Aggregation, Pathological/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Animals , Cell Line , Cell Membrane/pathology , Cell Membrane Permeability , Mice , Neurons/pathology , Protein Aggregates , Protein Aggregation, Pathological/pathologyABSTRACT
The aberrant aggregation of certain peptides and proteins, forming extracellular plaques of fibrillar material, is one of the hallmarks of amyloid diseases, such as Alzheimer's and Parkinson's. Herein, we have designed a new family of solvatochromic dyes based on the 9-amino-quinolimide moiety capable of reporting during the early stages of amyloid fibrillization. We have rationally improved the photophysical properties of quinolimides by placing diverse amino groups at the 9-position of the quinolimide core, leading to higher solvatochromic and fluorogenic character and higher lifetime dependence on the hydrophobicity of the environment, which represent excellent properties for the sensitive detection of prefibrillar aggregates. Among the different probes prepared, the 9-azetidinyl-quinolimide derivative showed striking performance in the following ß-amyloid peptide (Aß) aggregation in solution in real time and identifying the formation of different types of early oligomers of Aß, the most important species linked to cytotoxicity, using novel, multidimensional fluorescence microscopy, with one- or two-photon excitation. Interestingly, the new dye allowed the visualization of proteinaceous inclusion bodies in a zebrafish model with neuronal damage induced by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Our results support the potential of the novel fluorophores as powerful tools to follow amyloid aggregation using fluorescence microscopy in vivo, revealing heterogeneous populations of different types of aggregates and, more broadly, to study protein interactions.
Subject(s)
Amyloid beta-Peptides , Zebrafish , Amyloidogenic Proteins , Animals , Fluorescent Dyes , Microscopy, FluorescenceABSTRACT
Ferritin, a soluble and highly robust protein with subunits packed into well-defined helices, is a key component of the iron regulatory system in the brain and thus is widely recognized as a crucial protein for iron metabolism, but may also bear possible implications in some neurodegenerative disorders. Here, we present evidence of how human recombinant apoferritin can convert into an unusual structure from its folded native state; that is, amyloid fibrils analogue to those found in pathological disorders such as Alzheimer's and Parkinson's diseases. An extensive combination of advanced microscopy, spectroscopy and scattering techniques concur to reveal that apoferritin fibrils possess a common double stranded twisted ribbon structure which can result in a mesoscopic right-handed chirality. We highlight a direct connection between the chirality and morphology of the resulting amyloid fibrils, and the initial protein subunits composition, advancing our understanding on the possible role of misfolding in some ferritin-related pathologies and posing new bases for the design of chiral 1D functional nanostructures.
Subject(s)
Amyloid/chemistry , Apoferritins/chemistry , Protein Aggregates , Animals , Humans , Models, Molecular , Protein Conformation , StereoisomerismABSTRACT
El neurocitoma o tumor epitelial disembrioplásico (TND) es un tumor infrecuente del sistema nervioso central (SNC) clasificado Grado I, según la OMS, y las series que aparecen en la literatura médica informan de pocos casos. Por considerarse una entidad poco frecuente y por haber asistido en un corto período a 2 pacientes adolescentes uno con recidiva de tumor cerebral que fue reintervenido y donde el diagnóstico patológico inicial se correspondía con un astrocitoma de bajo grado y la otra, llevada a sala de operaciones con el diagnóstico de astrocitoma de alto grado, y donde después de estudios de inmunohistoquímica el diagnóstico final fue de tumor neuroepitelial disembrioplásico extraventricular. Se indicó tratamiento con radiaciones ionizantes. Se decidió revisar la literatura y presentar estos 2 casos
The Neurocytoma or dysembryoplasia epithelial tumor (DET) is an infrequent tumor of the central nervous system (CNS) classified as Degree I according to the WHO and the series appearing in the medical literature report not much cases. It is considered a not much frequent entity and due to the care during a short period to 2 adolescent patients, one of them with relapse of cerebral tumor re-operated on and where the former pathologic diagnosis was in correspondence with a high degree astrocytoma and that after the immunohistochemistry studies the final diagnosis was of a extraventricular dysembryoplasia neuroepithelial tumor. The treatment prescribed was with ionizing radiations. Literature was reviewed and two cases were presented
Subject(s)
Humans , Child , Adolescent , Central Nervous System Neoplasms/pathology , Neurocytoma/radiotherapy , Radiation, IonizingABSTRACT
El neurocitoma o tumor epitelial disembrioplásico (TND) es un tumor infrecuente del sistema nervioso central (SNC) clasificado Grado I, según la OMS, y las series que aparecen en la literatura médica informan de pocos casos. Por considerarse una entidad poco frecuente y por haber asistido en un corto período a 2 pacientes adolescentes uno con recidiva de tumor cerebral que fue reintervenido y donde el diagnóstico patológico inicial se correspondía con un astrocitoma de bajo grado y la otra, llevada a sala de operaciones con el diagnóstico de astrocitoma de alto grado, y donde después de estudios de inmunohistoquímica el diagnóstico final fue de tumor neuroepitelial disembrioplásico extraventricular. Se indicó tratamiento con radiaciones ionizantes. Se decidió revisar la literatura y presentar estos 2 casos(AU)
The Neurocytoma or dysembryoplasia epithelial tumor (DET) is an infrequent tumor of the central nervous system (CNS) classified as Degree I according to the WHO and the series appearing in the medical literature report not much cases. It is considered a not much frequent entity and due to the care during a short period to 2 adolescent patients, one of them with relapse of cerebral tumor re-operated on and where the former pathologic diagnosis was in correspondence with a high degree astrocytoma and that after the immunohistochemistry studies the final diagnosis was of a extraventricular dysembryoplasia neuroepithelial tumor. The treatment prescribed was with ionizing radiations. Literature was reviewed and two cases were presented(AU)
