BackgroundArthropod-borne diseases are some of the most rapidly spreading diseases. Reducing the vector population is currently the only effective way to reduce case numbers. Central metabolic pathways are potential targets to control vector populations, but have not been well explored to this aim. The information available on energy metabolism, as a way to control lifespan and dispersion through flight of dipteran vectors, is inadequate.MethodsPhosphofructokinase (PFK) activity was measured in the presence of both of its substrates, fructose-6-phosphate (F6P) and ATP, as well as some allosteric effectors: Fructose- 2,6 – bisphosphate (F2, 6BP), citrate and AMP. Aedes aegypti phosphofructokinase sequence (AaPFK) was aligned with many other insects and also vertebrate sequences. A 3D AaPFK model was produced and docking experiments were performed with AMP and citrate.ResultsThe kinetic parameters of AaPFK were determined for both substrates: F6P (V = 4.47 ± 0.15 μmol of F1, 6BP/min, K0.5 = 1.48 ± 0.22 mM) and ATP (V = 4.73 ± 0.57 μmol of F1, 6BP/min, K0.5 = 0.43 ± 0.10 mM). F2,6P was a powerful activator of AaPFK, even at low ATP concentrations. AaPFK inhibition by ATP was not enhanced by citrate, consistent with observations in other insects. After examining the sequence alignment of insect and non-insect PFKs, the hypothesis is that a modification of the citrate binding site is responsible for this unique behavior. AMP, a well-known positive effector of PFK, was not capable of reverting ATP inhibition. Aedes, Anopheles and Culex are dengue, malaria and filariasis vectors, respectively, and are shown to have this distinct characteristic in phosphofructokinase control. The alignment of several insect PFKs suggested a difference in the AMP binding site and a significant change in local charges, which introduces a highly negative charge in this part of the protein, making the binding of AMP unlikely. This hypothesis was supported by 3D modeling of PFK with AMP docking, which suggested that the AMP molecule binds in a reverse orientation due to the electrostatic environment. The present findings imply a potential new way to control PFK activity and are a unique feature of these Diptera.ConclusionsThe present findings provide the first molecular explanation for citrate insensitivity in insect PFKs, as well as demonstrating for the first time AMP insensitivity in dipterans. It also identified a potential target for novel insecticides for the control of arthropod-borne diseases.Electronic supplementary materialThe online version of this article (doi:10.1186/s13071-016-1391-y) contains supplementary material, which is available to authorized users.
Resumo O presente artigo trata da descrição do Sistema Composicional Intermarkoviano, resultado de uma convergência entre a teoria da intertextualidade e das cadeias de Markov, com o objetivo de estabelecer diretrizes pré-composicionais. Tais diretrizes se originam, no caso específico deste trabalho, das partições texturais rítmicas e dos contornos melódicos de uma obra musical original: o segundo movimento dos Cinco Movimentos para Quarteto de Cordas, Op. 5 de Webern. A operacionalidade do sistema é facilitada através de um aplicativo computacional denominado Markov Model, desenvolvido durante a pesquisa. Como resultado composicional, foi planejada e composta uma nova obra, cujas relações profundas de interdependência textural e contorno melódico se aproximam da obra original.
A common defect found when reproducing old vinyl and gramophone recordings with mechanical devices are the long pulses with significant low-frequency content caused by the interaction of the arm-needle system with deep scratches or even breakages on the media surface. Previous approaches to their suppression on digital counterparts of the recordings depend on a prior estimation of the pulse location, usually performed via heuristic methods. This paper proposes a novel Bayesian approach capable of jointly estimating the pulse location; interpolating the almost annihilated signal underlying the strong discontinuity that initiates the pulse; and also estimating the long pulse tail by a simple Gaussian Process, allowing its suppression from the corrupted signal. The posterior distribution for the model parameters as well for the pulse is explored via Markov-Chain Monte Carlo (MCMC) algorithms. Controlled experiments indicate that the proposed method, while requiring significantly less user intervention, achieves perceptual results similar to those of previous approaches and performs well when dealing with naturally degraded signals.
In audio signal processing there are several tools employed to perform time-frequency analysis, being the spectrogram one of the most widely used. In a nutshell, it can be understood as a visual representation of the frequency content of an audio signal as it varies with time. Here we propose a probabilistic alternative to the spectrogram, which can be roughly interpreted as the most likely frequency to be present within an audio signal, also along time. This will be achieved by computing a specific posterior distribution in a Bayesian context. Preliminary experiments indicating the suitability of this object are presented, and potential applications to audio signal processing are outlined.
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