RESUMEN
BACKGROUND: The mechanism underlying autism spectrum disorder (ASD) remains incompletely understood, but researchers have identified over a thousand genes involved in complex interactions within the brain, nervous, and immune systems, particularly during the mechanism of brain development. Various contributory environmental effects including circadian rhythm have also been studied in ASD. Thus, capturing the global picture of the ASD-clock network in combined form is critical. METHODS: We reconstructed the protein-protein interaction network of ASD and circadian rhythm to understand the connection between autism and the circadian clock. A graph theoretical study is undertaken to evaluate whether the network attributes are biologically realistic. The gene ontology enrichment analyses provide information about the most important biological processes. RESULTS: This study takes a fresh look at metabolic mechanisms and the identification of potential key proteins/pathways (ribosome biogenesis, oxidative stress, insulin/IGF pathway, Wnt pathway, and mTOR pathway), as well as the effects of specific conditions (such as maternal stress or disruption of circadian rhythm) on the development of ASD due to environmental factors. CONCLUSION: Understanding the relationship between circadian rhythm and ASD provides insight into the involvement of these essential pathways in the pathogenesis/etiology of ASD, as well as potential early intervention options and chronotherapeutic strategies for treating or preventing the neurodevelopmental disorder.
Asunto(s)
Trastorno del Espectro Autista , Trastorno Autístico , Relojes Circadianos , Trastornos del Neurodesarrollo , Humanos , Trastorno del Espectro Autista/genética , Trastorno Autístico/genética , Ritmo Circadiano/genéticaRESUMEN
Regional agricultural projects based on water resource development have many potential impacts on social and natural environments. In this research, potential long-term environmental problems of the Southeastern Anatolian Project (GAP) related to water resources, land use, land degradation, agricultural pollution and demography are analysed from a systems perspective. The analysis focuses on the totality of environmental, social and economic issues. For this purpose, a system dynamics simulation model (GAPSIM) has been developed as an experimental platform for policy analysis. GAPSIM was validated, first 'structurally', using the tests suggested by the literature and then the model 'behaviour' was tested and calibrated with respect to available data. The reference behaviour of GAPSIM reveals that, as the irrigated lands are developed, GAP faces significant water scarcity because of the increased intensity of cotton, the crop with the highest demands for water. Simulation results also indicate that two key environmental factors, pesticide and fertilizer consumption may reach undesirable levels. Alternative irrigation water release strategies, development rates of irrigated fields and farm rotation practices appear as important policy tools in achieving long-term environmental sustainability. GAPSIM promises to be not only a useful laboratory for policy makers of GAP, but also a useful generic structure applicable to other similar regional development projects.