RESUMO
Latin America (LatAm) has a rich and historically significant role in delineating both novel and well-documented genetic disorders. However, the ongoing advancements in the field of human genetics pose challenges to the relatively slow adaption of LatAm in the field. Here, we describe past and present contributions of LatAm to the discovery of novel genetic disorders, often referred as novel gene-disease associations (NGDA). We also describe the current methodologies for discovery of NGDA, taking into account the latest developments in genomics. We provide an overview of opportunities and challenges for NGDA research in LatAm considering the steps currently performed to identify and validate such associations. Given the multiple and diverse needs of populations and countries in LatAm, it is imperative to foster collaborations amongst patients, indigenous people, clinicians and scientists. Such collaborative effort is essential for sustaining and enhancing the LatAm´s contributions to the field of NGDA.
RESUMO
The feeding behavior in fish is a complex activity that relies on the ability of the brain to integrate multiple signals to produce appropriate responses in terms of food intake, energy expenditure, and metabolic activity. Upon stress cues including viral infection or mediators such as the proinflammatory cytokines, prostaglandins, and cortisol, both Pomc and Npy/Agrp neurons from the hypothalamus are stimulated, thus triggering a response that controls both energy storage and expenditure. However, how appetite modulators or neuro-immune cues link pathogenesis and energy homeostasis in fish remains poorly understood. Here, we provide the first evidence of a molecular linkage between inflammation and food intake in Salmon salar. We show that in vivo viral challenge with infectious pancreatic necrosis virus (IPNV) impacts food consumption by activating anorexic genes such as mc4r, crf, and pomcb and 5-HT in the brain of S. salar. At the molecular level, viral infection induces an overall reduction in lipid content in the liver, favoring the production of AA and EPA associated with the increment of elovl2 gene. In addition, infection upregulates leptin signaling and inhibits insulin signaling. These changes are accompanied by a robust inflammatory response represented by the increment of Il-1b, Il-6, Tnfa, and Pge2 as well as an increased cortisol level in vivo. Thus, we propose a model in which hypothalamic neurons respond to inflammatory cytokines and stress-related molecules and interact with appetite induction/inhibition. These findings provide evidence of crosstalk between pathogenesis-driven inflammation and hypothalamic-pituitary-adrenocortical axes in stress-induced food intake behavior in fish.
Assuntos
Infecções por Birnaviridae , Comportamento Alimentar , Hipotálamo/metabolismo , Inflamação , Metabolismo dos Lipídeos , Salmo salar/fisiologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Hipotálamo/fisiologia , Vírus da Necrose Pancreática Infecciosa , Insulina/metabolismo , Leptina/metabolismo , Salmo salar/metabolismo , Salmo salar/virologia , Transdução de SinaisRESUMO
During tissue morphogenesis and differentiation, cells must self-renew while contemporaneously generating daughters that contribute to the growing tissue. How tissues achieve this precise balance between proliferation and differentiation is, in most instances, poorly understood. This is in part due to the difficulties in dissociating the mechanisms that underlie tissue patterning from those that regulate proliferation. In the migrating posterior lateral line primordium (PLLP), proliferation is predominantly localised to the leading zone. As cells emerge from this zone, they periodically organise into rosettes that subsequently dissociate from the primordium and differentiate as neuromasts. Despite this reiterative loss of cells, the primordium maintains its size through regenerative cell proliferation until it reaches the tail. In this study, we identify a null mutation in the Wnt-pathway transcription factor Lef1 and show that its activity is required to maintain proliferation in the progenitor pool of cells that sustains the PLLP as it undergoes migration, morphogenesis and differentiation. In absence of Lef1, the leading zone becomes depleted of cells during its migration leading to the collapse of the primordium into a couple of terminal neuromasts. We show that this behaviour resembles the process by which the PLLP normally ends its migration, suggesting that suppression of Wnt signalling is required for termination of neuromast production in the tail. Our data support a model in which Lef1 sustains proliferation of leading zone progenitors, maintaining the primordium size and defining neuromast deposition rate.