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1.
Elife ; 82019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31502537

RESUMO

An important computational goal of the visual system is 'representational untangling' (RU): representing increasingly complex features of visual scenes in an easily decodable format. RU is typically assumed to be achieved in high-level visual cortices via several stages of cortical processing. Here we show, using a canonical population coding model, that RU of low-level orientation information is already performed at the first cortical stage of visual processing, but not before that, by a fundamental cellular-level property: the thresholded firing rate nonlinearity of simple cells in the primary visual cortex (V1). We identified specific, experimentally measurable parameters that determined the optimal firing threshold for RU and found that the thresholds of V1 simple cells extracted from in vivo recordings in awake behaving mice were near optimal. These results suggest that information re-formatting, rather than maximisation, may already be a relevant computational goal for the early visual system.


Assuntos
Potenciais de Ação , Neurônios/fisiologia , Orientação Espacial , Córtex Visual/citologia , Córtex Visual/fisiologia , Percepção Visual , Animais , Camundongos , Modelos Neurológicos
2.
Curr Pharm Des ; 19(23): 4155-72, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23170883

RESUMO

The ABC (ATP Binding Cassette) transporter protein superfamily comprises a large number of ubiquitous and functionally versatile proteins conserved from archaea to humans. ABC transporters have a key role in many human diseases and also in the development of multidrug resistance in cancer and in parasites. Although a dramatic progress has been achieved in ABC protein studies in the last decades, we are still far from a detailed understanding of their molecular functions. Several aspects of pharmacological ABC transporter targeting also remain unclear. Here we summarize the conformational and protonation changes of ABC transporters and the potential use of this information in pharmacological design. Network related methods, which recently became useful tools to describe protein structure and dynamics, have not been applied to study allosteric coupling in ABC proteins as yet. A detailed description of the strengths and limitations of these methods is given, and their potential use in describing ABC transporter dynamics is outlined. Finally, we highlight possible future aspects of pharmacological utilization of network methods and outline the future trends of this exciting field.


Assuntos
Transportadores de Cassetes de Ligação de ATP/química , Prótons , Modelos Moleculares , Conformação Proteica
3.
Brief Funct Genomics ; 11(6): 443-56, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23165349

RESUMO

The network approach became a widely used tool to understand the behaviour of complex systems in the last decade. We start from a short description of structural rigidity theory. A detailed account on the combinatorial rigidity analysis of protein structures, as well as local flexibility measures of proteins and their applications in explaining allostery and thermostability is given. We also briefly discuss the network aspects of cytoskeletal tensegrity. Finally, we show the importance of the balance between functional flexibility and rigidity in protein-protein interaction, metabolic, gene regulatory and neuronal networks. Our summary raises the possibility that the concepts of flexibility and rigidity can be generalized to all networks.


Assuntos
Modelos Biológicos , Algoritmos , Modelos Teóricos , Transdução de Sinais
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