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This study introduces a pioneering framework for modeling students' cognitive processes in mathematics education through Fuzzy Cognitive Maps (FCMs). By integrating key educational theories-Duval's Semiotic Representation Theory, Niss's Mathematical Competencies, Marton's Variation Theory, and the broad Engagement, Motivation, and Participation framework- the model offers a comprehensive and holistic understanding of students' cognitive landscapes. This research underscores the necessity of a multidimensional approach to capturing the intricate interplay of cognitive, affective, and behavioral factors in students' mathematical learning experiences. The novelty lies in its methodological innovation, employing FCMs to transcend traditional qualitative analyzes and facilitate quantitative insights into students' cognitive processes. This approach is particularly relevant in the current era dominated by digital learning environments and artificial intelligence, where real-time, automated analysis of student interactions is increasingly vital. The proposed FCM has been developed over the years with a data-driven approach; the concepts and relationships in it have been derived from the literature and refined by the author's experience in the field. Illustrated through case studies, the framework's utility is demonstrated in diverse contexts, highlighting how the quantitative data obtained are confirmed by qualitative approach: analyzing the impact of remote learning during the Covid-19 pandemic on student engagement and exploring Augmented Reality's role in enhancing mathematical conceptualization. These applications show the framework's adaptability and its potential to integrate new technologies in educational practices. However, the transition from qualitative to quantitative methodologies poses a challenge, given the prevalent use of qualitative approaches in mathematics education research. Additionally, the technological implementation of the FCM model in educational software presents practical hurdles, necessitating further development to ensure ease of integration and use in real-time educational settings. Future work will focus on bridging these methodological gaps and overcoming technological challenges to broaden the FCM model's applicability and enhance its contribution to advancing mathematics education.
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Hyperpolarization of 13C by dissolution dynamic nuclear polarization (dDNP) boosts the sensitivity of magnetic resonance spectroscopy (MRS), making possible the monitoring in vivo and in real time of the biochemical reactions of exogenously infused 13C-labeled metabolic tracers. The preparation of a hyperpolarized substrate requires the use of free radicals as polarizing agents. Although added at very low doses, these radicals are not biologically inert. Here, we demonstrate that the presence of the nitroxyl radical TEMPOL influences significantly the cerebral metabolic readouts of a hyperpolarized [1-13C] lactate bolus injection in a mouse model of ischemic stroke with reperfusion. Thus, the choice of the polarizing agent in the design of dDNP hyperpolarized MRS experiments is of great importance and should be taken into account to prevent or to consider significant effects that could act as confounding factors.
Assuntos
Fenômenos Bioquímicos , AVC Isquêmico , Animais , Camundongos , 2-NaftilaminaRESUMO
Type C hepatic encephalopathy (HE) is a complex neuropsychiatric disorder occurring as a consequence of chronic liver disease. Alterations in energy metabolism have been suggested in type C HE, but in vivo studies on this matter remain sparse and have reported conflicting results. Here, we propose a novel preclinical 18F-FDG PET methodology to compute quantitative 3D maps of the regional cerebral metabolic rate of glucose (CMRglc) from a labelling steady-state PET image of the brain and an image-derived input function. This quantitative approach shows its strength when comparing groups of animals with divergent physiology, such as HE animals. PET CMRglc maps were registered to an atlas and the mean CMRglc from the hippocampus and the cerebellum were associated to the corresponding localized 1H MR spectroscopy acquisitions. This study provides for the first time local and quantitative information on both brain glucose uptake and neurometabolic profile alterations in a rat model of type C HE. A 2-fold lower brain glucose uptake, concomitant with an increase in brain glutamine and a decrease in the main osmolytes, was observed in the hippocampus and in the cerebellum. These novel findings are an important step towards new insights into energy metabolism in the pathophysiology of HE.
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Encefalopatia Hepática , Animais , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Glucose/metabolismo , Glutamina/metabolismo , Encefalopatia Hepática/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , RatosRESUMO
The invasive behavior of glioblastoma, the most aggressive primary brain tumor, is considered highly relevant for tumor recurrence. However, the invasion zone is difficult to visualize by Magnetic Resonance Imaging (MRI) and is protected by the blood brain barrier, posing a particular challenge for treatment. We report biological features of invasive growth accompanying tumor progression and invasion based on associated metabolic and transcriptomic changes observed in patient derived orthotopic xenografts (PDOX) in the mouse and the corresponding patients' tumors. The evolution of metabolic changes, followed in vivo longitudinally by 1H Magnetic Resonance Spectroscopy (1H MRS) at ultra-high field, reflected growth and the invasive properties of the human glioblastoma transplanted into the brains of mice (PDOX). Comparison of MRS derived metabolite signatures, reflecting temporal changes of tumor development and invasion in PDOX, revealed high similarity to spatial metabolite signatures of combined multi-voxel MRS analyses sampled across different areas of the patients' tumors. Pathway analyses of the transcriptome associated with the metabolite profiles of the PDOX, identified molecular signatures of invasion, comprising extracellular matrix degradation and reorganization, growth factor binding, and vascular remodeling. Specific analysis of expression signatures from the invaded mouse brain, revealed extent of invasion dependent induction of immune response, recapitulating respective signatures observed in glioblastoma. Integrating metabolic profiles and gene expression of highly invasive PDOX provided insights into progression and invasion associated mechanisms of extracellular matrix remodeling that is essential for cell-cell communication and regulation of cellular processes. Structural changes and biochemical properties of the extracellular matrix are of importance for the biological behavior of tumors and may be druggable. Ultra-high field MRS reveals to be suitable for in vivo monitoring of progression in the non-enhancing infiltration zone of glioblastoma.
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Neoplasias Encefálicas/genética , Glioblastoma/genética , Adulto , Idoso , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Feminino , Glioblastoma/diagnóstico por imagem , Glioblastoma/metabolismo , Glioblastoma/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Metaboloma , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Transplante de Neoplasias , Espectroscopia de Prótons por Ressonância Magnética , TranscriptomaRESUMO
Sertraline, a selective serotonin reuptake inhibitor, is commonly prescribed for the treatment of moderate-to-severe depression. We report a case of a 36-year-old male taking sertraline for 7 weeks prior to developing a dry cough, pleuritic chest pain, hypoxia and diffuse ground-glass attenuation with mediastinal lymphadenopathy on imaging. No infectious aetiology was identified and multiple causes of pneumonitis excluded. Sertraline-induced interstitial lung disease was subsequently diagnosed. Sertraline was discontinued and treatment commenced with a weaning course of oral dexamethasone, leading to a rapid reduction in oxygen requirement and successful discharge. Given the increasing prevalence of selective serotonin reuptake inhibitor use, it is vital that medical professionals can recognize sertraline as a rare, albeit potentially life-threatening, cause of interstitial lung disease-allowing for the rapid diagnosis and appropriate management of this condition.
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Glucose utilization increases in tumors, a metabolic process that is observed clinically by 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET). However, is increased glucose uptake important for tumor cells, and which transporters are implicated in vivo? In a genetically-engineered mouse model of lung adenocarcinoma, we show that the deletion of only one highly expressed glucose transporter, Glut1 or Glut3, in cancer cells does not impair tumor growth, whereas their combined loss diminishes tumor development. 18F-FDG-PET analyses of tumors demonstrate that Glut1 and Glut3 loss decreases glucose uptake, which is mainly dependent on Glut1. Using 13C-glucose tracing with correlated nanoscale secondary ion mass spectrometry (NanoSIMS) and electron microscopy, we also report the presence of lamellar body-like organelles in tumor cells accumulating glucose-derived biomass, depending partially on Glut1. Our results demonstrate the requirement for two glucose transporters in lung adenocarcinoma, the dual blockade of which could reach therapeutic responses not achieved by individual targeting.
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Adenocarcinoma de Pulmão/fisiopatologia , Deleção de Genes , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 2/genética , Glucose/metabolismo , Animais , Linhagem Celular Tumoral , Feminino , Fluordesoxiglucose F18/química , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 2/metabolismo , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Tomografia por Emissão de Pósitrons , Espectrometria de Massa de Íon SecundárioRESUMO
Cerebral metabolism, which can be monitored by magnetic resonance spectroscopy (MRS), changes rapidly after brain ischaemic injury. Hyperpolarisation techniques boost 13C MRS sensitivity by several orders of magnitude, thereby enabling in vivo monitoring of biochemical transformations of hyperpolarised (HP) 13C-labelled precursors with a time resolution of seconds. The exogenous administration of the metabolite L-lactate was shown to decrease lesion size and ameliorate neurological outcome in preclinical studies in rodent stroke models, as well as influencing brain metabolism in clinical pilot studies of acute brain injury patients. The aim of this study was to demonstrate the feasibility of measuring HP [1-13C] L-lactate metabolism in real-time in the mouse brain after ischaemic stroke when administered after reperfusion at a therapeutic dose. We showed a rapid, time-after-reperfusion-dependent conversion of [1-13C] L-lactate to [1-13C] pyruvate and [13C] bicarbonate that brings new insights into the neuroprotection mechanism of L-lactate. Moreover, this study paves the way for the use of HP [1-13C] L-lactate as a sensitive molecular-imaging biosensor in ischaemic stroke patients after endovascular clot removal.
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Isquemia Encefálica/metabolismo , Ácido Láctico/metabolismo , Fármacos Neuroprotetores/metabolismo , Acidente Vascular Cerebral/metabolismo , Animais , Bicarbonatos/metabolismo , Técnicas Biossensoriais/métodos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Isótopos de Carbono , Sistemas Computacionais , Modelos Animais de Doenças , Estudos de Viabilidade , Humanos , Imuno-Histoquímica , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/terapia , Ácido Láctico/administração & dosagem , Espectroscopia de Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Imagem Molecular/métodos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Ácido Pirúvico/metabolismo , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapiaRESUMO
Despite the improving imaging techniques, it remains challenging to produce magnetic resonance (MR) imaging fingerprints depicting severity of acute ischemia. The aim of this study was to evaluate the potential of the overall high-field 1 H MR Spectroscopy (1 H-MRS) neurochemical profile as a metabolic signature for acute ischemia severity in rodent brains. We modeled global ischemia with one-stage 4-vessel-occlusion (4VO) in rats. Vascular structures were assessed immediately by magnetic resonance angiography. The neurochemical responses in the bilateral cortex were measured 1 h after stroke onset by 1 H-MRS. Then we used Partial-Least-Squares discriminant analysis on the overall neurochemical profiles to seek metabolic signatures for ischemic severity subgroups. This approach was further tested on neurochemical profiles of mouse striatum 1 h after permanent middle cerebral artery occlusion, where vascular blood flow was monitored by laser Doppler. Magnetic resonance angiography identified successful 4VO from controls and incomplete global ischemia (e.g., 3VO). 1 H-MR spectra of rat cortex after 4VO showed a specific metabolic pattern, distinct from that of respective controls and rats with 3VO. Partial-Least-Squares discriminant analysis on the overall neurochemical profiles revealed metabolic signatures of acute ischemia that may be extended to mice after permanent middle cerebral artery occlusion. Fingerprinting severity of acute ischemia using neurochemical information may improve MR diagnosis in stroke patients.
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Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Mapeamento de Peptídeos/métodos , Índice de Gravidade de Doença , Animais , Masculino , Camundongos , Camundongos Endogâmicos ICR , Prótons , Ratos , Ratos WistarRESUMO
With the increasing development of transgenic mouse models of neurodegenerative diseases allowing improved understanding of the underlying mechanisms of these disorders, robust quantitative mapping techniques are also needed in rodents. MP2RAGE has shown great potential for structural imaging in humans at high fields. In the present work, MP2RAGE was successfully implemented at 9.4T and 14.1T. Following fractionated injections of MnCl2, MP2RAGE images were acquired allowing simultaneous depiction and T1 mapping of structures in the mouse brain at both fields. In addition, T1 maps demonstrated significant T1 shortenings in different structures of the mouse brain (p < 0.0008 at 9.4T, p < 0.000001 at 14.1T). T1 values recovered to the levels of saline-injected animals 1 month after the last injection except in the pituitary gland. We believe that MP2RAGE represents an important prospective translational tool for further structural MRI.
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Mapeamento Encefálico/métodos , Encéfalo/anatomia & histologia , Imageamento por Ressonância Magnética/métodos , Manganês/administração & dosagem , Animais , Cloretos , Meios de Contraste , Aumento da Imagem , Processamento de Imagem Assistida por Computador , Compostos de Manganês , Camundongos , Camundongos Endogâmicos C57BL , Razão Sinal-RuídoAssuntos
Nutrição Enteral/métodos , Gastroscopia/métodos , Gastrostomia/métodos , Seleção de Pacientes , Complicações Pós-Operatórias/prevenção & controle , Obstrução do Cateter , Celulite (Flegmão)/prevenção & controle , Celulite (Flegmão)/terapia , Obstrução da Saída Gástrica/prevenção & controle , Obstrução da Saída Gástrica/terapia , Humanos , Perfuração Intestinal/prevenção & controle , Perfuração Intestinal/terapia , Peritonite/prevenção & controle , Peritonite/terapia , Complicações Pós-Operatórias/terapia , Hemorragia Pós-Operatória/prevenção & controle , Hemorragia Pós-Operatória/terapia , Cuidados Pré-Operatórios/métodos , Aspiração Respiratória de Conteúdos Gástricos/prevenção & controle , Aspiração Respiratória de Conteúdos Gástricos/terapiaRESUMO
The ability of Mn(2+) to follow Ca(2+) pathways upon stimulation transform them into remarkable surrogate markers of neuronal activity using activity-induced manganese-dependent MRI (AIM-MRI). In the present study, a precise follow-up of physiological parameters during MnCl2 and mannitol infusions improved the reproducibility of AIM-MRI allowing in-depth evaluation of the technique. Pixel-by-pixel T1 data were investigated using histogram distributions in the barrel cortex (BC) and the thalamus before and after Mn(2+) infusion, after blood brain barrier opening and after BC activation. Mean BC T1 values dropped significantly upon trigeminal nerve (TGN) stimulation (-38 %, P = 0.02) in accordance with previous literature findings. T1 histogram distributions showed that 34 % of T1s in the range 600-1500 ms after Mn(2+ )+ mannitol infusions shifted to 50-350 ms after TGN stimulation corresponding to a twofold increase of the percentage of pixels with the lowest T1s in BC. Moreover, T1 changes in response to stimulation increased significantly from superficial cortical layers (I-III) to deeper layers (V-VI). Cortical cytoarchitecture detection during a functional paradigm was performed extending the potential of AIM-MRI. Quantitative AIM-MRI could thus offer a means to interpret local neural activity across cortical layers while identification of the role of calcium dynamics in vivo during brain activation could play a key role in resolving neurovascular coupling mechanisms.
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Mapeamento Encefálico/métodos , Cloretos/administração & dosagem , Meios de Contraste/administração & dosagem , Imageamento por Ressonância Magnética/métodos , Compostos de Manganês/administração & dosagem , Córtex Somatossensorial/diagnóstico por imagem , Animais , Barreira Hematoencefálica/metabolismo , Encéfalo/anatomia & histologia , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismo , Cloretos/química , Cloretos/farmacocinética , Meios de Contraste/química , Meios de Contraste/farmacocinética , Masculino , Compostos de Manganês/química , Compostos de Manganês/farmacocinética , Ratos , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Córtex Somatossensorial/anatomia & histologia , Córtex Somatossensorial/metabolismoAssuntos
Abstinência de Álcool , Antibacterianos/uso terapêutico , Ascite/terapia , Diuréticos/uso terapêutico , Cirrose Hepática/terapia , Transplante de Fígado , Paracentese , Peritonite/tratamento farmacológico , Derivação Portossistêmica Transjugular Intra-Hepática , Ascite/etiologia , Dieta Hipossódica , Gerenciamento Clínico , Humanos , Cirrose Hepática/complicações , Peritonite/etiologiaRESUMO
AIMS: In the adult heart, Notch signalling regulates the response to injury. Notch inhibition leads to increased cardiomyocyte apoptosis, and exacerbates the development of cardiac hypertrophy and fibrosis. The role of Notch in the mesenchymal stromal cell fraction, which contains cardiac fibroblasts and cardiac precursor cells, is, however, largely unknown. In the present study, we evaluate, therefore, whether forced activation of the Notch pathway in mesenchymal stromal cells regulates pathological cardiac remodelling. METHODS AND RESULTS: We generated transgenic mice overexpressing the Notch ligand Jagged1 on the surface of cardiomyocytes to activate Notch signalling in adjacent myocyte and non-myocyte cells. In neonatal transgenic mice, activated Notch sustained cardiac precursor and myocyte proliferation after birth, and led to increased numbers of cardiac myocytes in adult mice. In the adult heart under pressure overload, Notch inhibited the development of cardiomyocyte hypertrophy and transforming growth factor-ß/connective tissue growth factor-mediated cardiac fibrosis. Most importantly, Notch activation in the stressed adult heart reduced the proliferation of myofibroblasts and stimulated the expansion of stem cell antigen-1-positive cells, and in particular of Nkx2.5-positive cardiac precursor cells. CONCLUSIONS: We conclude that Notch is pivotal in the healing process of the injured heart. Specifically, Notch regulates key cellular mechanisms in the mesenchymal stromal cell population, and thereby controls the balance between fibrotic and regenerative repair in the adult heart. Altogether, these findings indicate that Notch represents a unique therapeutic target for inducing regeneration in the adult heart via mobilization of cardiac precursor cells.
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Receptores Notch/fisiologia , Transdução de Sinais/fisiologia , Remodelação Ventricular/fisiologia , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Cardiomegalia/fisiopatologia , Cardiomegalia/terapia , Proliferação de Células/fisiologia , Tamanho Celular , Constrição , Fibrose/metabolismo , Coração/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Proteína Jagged-1 , Proteínas de Membrana/metabolismo , Camundongos Transgênicos , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Regeneração , Proteínas Serrate-Jagged , Serina-Treonina Quinases TOR/metabolismo , Fatores de Crescimento Transformadores/metabolismoRESUMO
Glucose metabolism is difficult to image with cellular resolution in mammalian brain tissue, particularly with (18) fluorodeoxy-D-glucose (FDG) positron emission tomography (PET). To this end, we explored the potential of synchrotron-based low-energy X-ray fluorescence (LEXRF) to image the stable isotope of fluorine (F) in phosphorylated FDG (DG-6P) at 1 µm(2) spatial resolution in 3-µm-thick brain slices. The excitation-dependent fluorescence F signal at 676 eV varied linearly with FDG concentration between 0.5 and 10 mM, whereas the endogenous background F signal was undetectable in brain. To validate LEXRF mapping of fluorine, FDG was administered in vitro and in vivo, and the fluorine LEXRF signal from intracellular trapped FDG-6P over selected brain areas rich in radial glia was spectrally quantitated at 1 µm(2) resolution. The subsequent generation of spatial LEXRF maps of F reproduced the expected localization and gradients of glucose metabolism in retinal Müller glia. In addition, FDG uptake was localized to periventricular hypothalamic tanycytes, whose morphological features were imaged simultaneously by X-ray absorption. We conclude that the high specificity of photon emission from F and its spatial mapping at ≤1 µm resolution demonstrates the ability to identify glucose uptake at subcellular resolution and holds remarkable potential for imaging glucose metabolism in biological tissue.
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Mapeamento Encefálico/métodos , Córtex Cerebral/diagnóstico por imagem , Fluordesoxiglucose F18 , Glucose/metabolismo , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos , Animais , Córtex Cerebral/metabolismo , Metabolismo Energético/fisiologia , Estudos de Viabilidade , Fluorescência , Ratos , Ratos Sprague-Dawley , Raios XRESUMO
In the damaged heart, cardiac adaptation relies primarily on cardiomyocyte hypertrophy. The recent discovery of cardiac stem cells in the postnatal heart, however, suggests that these cells could participate in the response to stress via their capacity to regenerate cardiac tissues. Using models of cardiac hypertrophy and failure, we demonstrate that components of the Notch pathway are up-regulated in the hypertrophic heart. The Notch pathway is an evolutionarily conserved cell-to-cell communication system, which is crucial in many developmental processes. Notch also plays key roles in the regenerative capacity of self-renewing organs. In the heart, Notch1 signaling takes place in cardiomyocytes and in mesenchymal cardiac precursors and is activated secondary to stimulated Jagged1 expression on the surface of cardiomyocytes. Using mice lacking Notch1 expression specifically in the heart, we show that the Notch1 pathway controls pathophysiological cardiac remodeling. In the absence of Notch1, cardiac hypertrophy is exacerbated, fibrosis develops, function is altered, and the mortality rate increases. Therefore, in cardiomyocytes, Notch controls maturation, limits the extent of the hypertrophic response, and may thereby contribute to cell survival. In cardiac precursors, Notch prevents cardiogenic differentiation, favors proliferation, and may facilitate the expansion of a transient amplifying cell compartment.
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Coração/fisiologia , Miocárdio , Miócitos Cardíacos/fisiologia , Receptor Notch1/metabolismo , Transdução de Sinais/fisiologia , Estresse Fisiológico , Alanina/análogos & derivados , Alanina/metabolismo , Secretases da Proteína Precursora do Amiloide/antagonistas & inibidores , Animais , Apoptose/fisiologia , Azepinas/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Regulação da Expressão Gênica , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Miocárdio/metabolismo , Miocárdio/patologia , Miócitos Cardíacos/citologia , Análise de Sequência com Séries de Oligonucleotídeos , Receptor Notch1/genética , Células-Tronco/citologia , Células-Tronco/metabolismoRESUMO
PURPOSE: Despite ubiquitous expression of the keratoepithelin (KE) protein encoded by the transforming growth factor beta induced/beta induced gene human clone 3 (TGFBI/BIGH3) gene, corneal dystrophies are restricted to the cornea, and no other tissues are affected. We investigated the role of TGFBI/BIGH3 in Groenouw corneal dystrophies by generating transgenic mice overexpressing TGFBI/BIGH3 containing the R555W mutation. METHODS: Transgenic animals expressing the Groenouw mutation of human TGFBI/BIGH3 were generated using lentiviral vectors. The line expressed TGFBI/BIGH3 containing the R555W mutation under the control of the phosphoglycerate kinase (PGK) promoter. Expression of the transgene was monitored by Southern and western blotting and by RT-PCR. Electroretinogram analysis was performed and four mice were subjected to complete necroscopy. RESULTS: Transgene expression was observed in different organs although without specific expression in the cornea. The overall morphology of the transgenic animals was not severely affected by KE overexpression. However, we observed an age-dependent retinal degeneration both functionally and histologically. Female-specific follicular hyperplasia in the spleen and increased levels of lipofuscin in the adrenal gland were also seen in transgenic animals. CONCLUSIONS: Cellular degeneration in the retina of transgenic animals suggest that perturbation of the transforming growth factor beta (TGFbeta) family regulation may affect photoreceptor survival and may induce possible accelerated aging in several tissues. No corneal phenotype could be observed, probably due to the lack of transgene expression in this tissue.
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Proteínas da Matriz Extracelular/metabolismo , Proteínas Mutantes/metabolismo , Degeneração Retiniana/patologia , Fator de Crescimento Transformador beta/metabolismo , Animais , Southern Blotting , Western Blotting , Eletrorretinografia , Proteínas da Matriz Extracelular/genética , Feminino , Regulação da Expressão Gênica , Humanos , Hiperplasia , Lentivirus , Masculino , Camundongos , Camundongos Transgênicos , Tamanho do Órgão , Especificidade de Órgãos , Fosfoglicerato Quinase/genética , Regiões Promotoras Genéticas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reprodutibilidade dos Testes , Degeneração Retiniana/enzimologia , Baço/patologia , Fator de Crescimento Transformador beta/genética , Integração ViralRESUMO
Recent evidence suggests that the heart possesses a greater regeneration capacity than previously thought. In the present study, we isolated undifferentiated precursors from the cardiac nonmyocyte cell population of neonatal hearts, expanded them in culture, and induced them to differentiate into functional cardiomyocytes. These cardiac precursors appear to express stem cell antigen-1 and demonstrate characteristics of multipotent precursors of mesodermal origin. Following infusion into normal recipients, these cells home to the heart and participate in physiological and pathophysiological cardiac remodeling. Cardiogenic differentiation in vitro and in vivo depends on FGF-2. Interestingly, this factor does not control the number of precursors but regulates the differentiation process. These findings suggest that, besides its angiogenic actions, FGF-2 could be used in vivo to facilitate the mobilization and differentiation of resident cardiac precursors in the treatment of cardiac diseases.