Synthetic mixed-signal computation in living cells

Living cells implement complex computations on the continuous environmental signals that they encounter. These computations involve both analogue- and digital-like processing of signals to give rise to complex developmental programs, context-dependent behaviours and homeostatic activities. In contrast to natural biological systems, synthetic biological systems have largely focused on either digital or analogue computation separately. Here we integrate analogue and digital computation to implement complex hybrid synthetic genetic programs in living cells. We present a framework for building comparator gene circuits to digitize analogue inputs based on different thresholds. We then demonstrate that comparators can be predictably composed together to build band-pass filters, ternary logic systems and multi-level analogue-to-digital converters. In addition, we interface these analogue-to-digital circuits with other digital gene circuits to enable concentration-dependent logic. We expect that this hybrid computational paradigm will enable new industrial, diagnostic and therapeutic applications with engineered cells.Fundacao para a Ciencia e a Tecnologia (Fellowship SFRH/BD/51576/2011)National Science Foundation (U.S.) (1350625)National Science Foundation (U.S.) (1124247)United States. Office of Naval Research (N000141310424)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008435)National Centers for Systems Biology (U.S.) (1P50GM098792

Proceedings of the Association for Research in Vision and Ophthalmology and Champalimaud Foundation Ocular Oncogenesis and Oncology Conference

Ophthalmic researc

I Diretrizes do Grupo de Estudos em Cardiogeriatria da Sociedade Brasileira de Cardiologia

O idoso apresenta características próprias na manifestação das doenças, na resposta à terapêutica e no efeito colateral dos medicamentos. Constitui um grupo de maior risco para o aparecimento das doenças degenerativas, em geral, e cardiovasculares, em particular, além de apresentar maior número de comorbidades

Gene networks that compensate for crosstalk with crosstalk

Crosstalk is a major challenge to engineering sophisticated synthetic gene networks. A common approach is to insulate signal-transduction pathways by minimizing molecular-level crosstalk between endogenous and synthetic genetic components, but this strategy can be difficult to apply in the context of complex, natural gene networks and unknown interactions. Here, we show that synthetic gene networks can be engineered to compensate for crosstalk by integrating pathway signals, rather than by pathway insulation. We demonstrate this principle using reactive oxygen species (ROS)-responsive gene circuits in Escherichia coli that exhibit concentration-dependent crosstalk with non-cognate ROS. We quantitatively map the degree of crosstalk and design gene circuits that introduce compensatory crosstalk at the gene network level. The resulting gene network exhibits reduced crosstalk in the sensing of the two different ROS. Our results suggest that simple network motifs that compensate for pathway crosstalk can be used by biological networks to accurately interpret environmental signals.National Science Foundation (U.S.) (Grant 1350625)National Science Foundation (U.S.) (Grant 1124247)United States. Office of Naval Research (Grant N000141310424)National Institutes of Health (U.S.) (New Innovator Award 1DP2OD008435)National Institutes of Health (U.S.). National Centers for Systems Biology (Grant 1P50GM098792

Vision Status in Older Adults: The Brazilian Amazon Region Eye Survey

Older adults living in remote areas with limited access to health services are at higher risk to develop visual impairment and blindness. We conducted a population-based survey to determine the vision status in subjects 45 years of age and older from urban and rural areas of Parintins city, Brazilian Amazon Region. Participants underwent ophthalmic examination, including uncorrected (UCVA), presenting (PVA) and best-corrected visual acuity (BCVA). Vision status was described as lines of visual acuity (VA) impairment and lines of VA improvement from UCVA to BCVA and from PVA to BCVA in the better-seeing eye. A total of 2384 subjects were enumerated, 2041 (85.6%) were examined, with reliable VA measurements obtained from 2025 participants. Vision status in lines of VA impairment was (mean +/- standard deviation): 3.44 +/- 3.53 for UCVA, 2.85 +/- 3.52 for PVA and 1.50 +/- 3.51 for BCVA. Female gender, older age and lower education were associated with >= 6 lines of UCVA impairment. Lines of improvement >= 3 was found in 626 (30.9%) participants and associated with female gender and rural residency. In conclusion, a third of participants could have at least three lines of VA improvement with proper refraction. Strategies to improve access to eye care and affordable glasses are needed.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico - CNPq, Brasilia, Brasil, Programa Ciencia sem FronteirasFundacao de Amparo a Pesquisa do Estado de Sao Paulo, FAPESP, Sao Paulo, BrasilSightFirst Program - Lions Club International FoundationUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Oftalmol & Ciencias Visuais, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med Ribeirao Preto, Dept Oftalmol Otorrinolaringol & Cirurgia Cabeca, Ribeirao Preto, SP, BrazilUniv La Frontera, Dept Salud Publ, Temuco, ChileUniv Fed UFPA, Fac Med, Belem, PA, BrazilUniv Fed Minas Gerais, Fac Med, Dept Oftalmol & Otorrinolaringol, Belo Horizonte, MG, BrazilUniv Fed Amazonas UFAM, Fac Med, Dept Cirurgia, Div Oftalmol, Manaus, Amazonas, BrazilUniv Fed Sao Paulo UNIFESP, Escola Paulista Med, Dept Oftalmol & Ciencias Visuais, Sao Paulo, SP, BrazilCNPq: 402120/2012-4FAPESP: 2013/16397-7Lions Club International Foundation: 1758Web of Scienc