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1.
Genes Brain Behav ; 14(2): 158-66, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25640316

RESUMO

Aerobic glycolysis involves increased glycolysis and decreased oxidative catabolism of glucose even in the presence of an ample oxygen supply. Aerobic glycolysis, a common metabolic pattern in cancer cells, was recently discovered in both the healthy and diseased human brain, but its functional significance is not understood. This metabolic pattern in the brain is surprising because it results in decreased efficiency of adenosine triphosphate (ATP) production in a tissue with high energetic demands. We report that highly aggressive honey bees (Apis mellifera) show a brain transcriptomic and metabolic state consistent with aerobic glycolysis, i.e. increased glycolysis in combination with decreased oxidative phosphorylation. Furthermore, exposure to alarm pheromone, which provokes aggression, causes a metabolic shift to aerobic glycolysis in the bee brain. We hypothesize that this metabolic state, which is associated with altered neurotransmitter levels, increased glycolytically derived ATP and a reduced cellular redox state, may lead to increased neuronal excitability and oxidative stress in the brain. Our analysis provides evidence for a robust, distinct and persistent brain metabolic response to aggression-inducing social cues. This finding for the first time associates aerobic glycolysis with naturally occurring behavioral plasticity, which has important implications for understanding both healthy and diseased brain function.


Assuntos
Agressão/fisiologia , Comportamento Animal , Encéfalo/metabolismo , Glicólise/fisiologia , Trifosfato de Adenosina/metabolismo , Animais , Abelhas , Glucose/metabolismo , Análise em Microsséries/métodos , Feromônios
2.
J Intern Med ; 271(2): 111-21, 2012 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22142401

RESUMO

A grand challenge impeding optimal treatment outcomes for patients with cancer arises from the complex nature of the disease: the cellular heterogeneity, the myriad of dysfunctional molecular and genetic networks as results of genetic (somatic) and environmental perturbations. Systems biology, with its holistic approach to understanding fundamental principles in biology, and the empowering technologies in genomics, proteomics, single-cell analysis, microfluidics and computational strategies, enables a comprehensive approach to medicine, which strives to unveil the pathogenic mechanisms of diseases, identify disease biomarkers and begin thinking about new strategies for drug target discovery. The integration of multidimensional high-throughput 'omics' measurements from tumour tissues and corresponding blood specimens, together with new systems strategies for diagnostics, enables the identification of cancer biomarkers that will enable presymptomatic diagnosis, stratification of disease, assessment of disease progression, evaluation of patient response to therapy and the identification of reoccurrences. Whilst some aspects of systems medicine are being adopted in clinical oncology practice through companion molecular diagnostics for personalized therapy, the mounting influx of global quantitative data from both wellness and diseases is shaping up a transformational paradigm in medicine we termed 'predictive', 'preventive', 'personalized', and 'participatory' (P4) medicine, which requires new strategies, both scientific and organizational, to enable bringing this revolution in medicine to patients and to the healthcare system. P4 medicine will have a profound impact on society - transforming the healthcare system, turning around the ever escalating costs of healthcare, digitizing the practice of medicine and creating enormous economic opportunities for those organizations and nations that embrace this revolution.


Assuntos
Oncologia/métodos , Neoplasias/diagnóstico , Medicina de Precisão/métodos , Biologia de Sistemas , Biomarcadores Tumorais/sangue , Perfilação da Expressão Gênica/métodos , Genoma Humano/genética , Genômica/métodos , Humanos , Mutação/genética , Neoplasias/genética , Neoplasias/prevenção & controle , Proteômica/métodos , Análise de Célula Única/métodos
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