The allosteric transition of glucosamine-6-phosphate deaminase: the structure of the T state at 2.3 Å resolution

AbstractBackground: The allosteric hexameric enzyme glucosamine-6-phosphate deaminase from Escherichia coli catalyses the regulatory step of N-acetylglucosamine catabolism, which consists of the isomerisation and deamination of glucosamine 6-phosphate (GlcN6P) to form fructose 6-phosphate (Fru6P) and ammonia. The reversibility of the catalysis and its rapid-equilibrium random kinetic mechanism, among other properties, make this enzyme a good model for studying allosteric processes.Results: Here we present the structure of P6322 crystals, obtained in sodium acetate, of GlcN6P deaminase in its ligand-free T state. These crystals are very sensitive to X-ray radiation and have a high (78%) solvent content. The active-site lid (residues 162–185) is highly disordered in the T conformer; this may contribute significantly to the free-energy change of the whole allosteric transition. Comparison of the structure with the crystallographic coordinates of the R conformer (Brookhaven Protein Data Bank entry 1dea) allows us to describe the geometrical changes associated with the allosteric transition as the movement of two rigid entities within each monomer. The active site, located in a deep cleft between these two rigid entities, presents a more open geometry in the T conformer than in the R conformer.Conclusions: The differences in active-site geometry are related to alterations in the substrate-binding properties associated with the allosteric transition. The rigid nature of the two mobile structural units of each monomer seems to be essential in order to explain the observed kinetics of the deaminase hexamer. The triggers for both the homotropic and heterotropic allosteric transitions are discussed and particular residues are assigned to these functions. A structural basis for an entropic term in the allosteric transition is an interesting new feature that emerges from this study

INDEPENDENT COMPONENT ANALYSIS AND DISCRETE WAVELET TRANSFORM FOR ARTIFACT REMOVAL IN BIOMEDICAL SIGNAL PROCESSING

Recent works have shown that artifact removal in bi omedical signals can be performed by using Discrete Wavelet Transform (DWT) or Independent Component Analysis (ICA). It results often very difficult to remove some artifacts because they could be superimposed on the recordings and they could corrupt the signals in the frequency domain. The two conditions could compromise the performance of both DWT and ICA methods. In this study we show that if the two methods are jointly implemented, it is possible to improve the performances for the artifact rejection procedure. We discuss in detail the new method and we also show how this method provides advantages with respect to DWT of ICA procedure. Finally, we tested the new approach on real data

A Spatial Calculus of Wrapped Compartments

The Calculus of Wrapped Compartments (CWC) is a recently proposed modelling language for the representation and simulation of biological systems behaviour. Although CWC has no explicit structure modelling a spatial geometry, its compartment labelling feature can be exploited to model various examples of spatial interactions in a natural way. However, specifying large networks of compartments may require a long modelling phase. In this work we present a surface language for CWC that provides basic constructs for modelling spatial interactions. These constructs can be compiled away to obtain a standard CWC model, thus exploiting the existing CWC simulation tool. A case study concerning the modelling of Arbuscular Mychorrizal fungi growth is discussed.Comment: Presented at MeCBIC 201

The INSEAN E779a Propeller Test Case: a Database For CFD Validation

In the last few years, remarkable improvements in numerical modeling of viscous flows around marine propellers have been obtained. In particular, Reynolds Averaged Navier-Stokes (RANS) equation solvers start to be widely used to analyze viscosity effects on propulsors at model-scale Reynolds number, in the case of uniform inflow and non-cavitating conditions. The development of such advanced computational tools is required, especially in modern propeller design, where for reducing propeller-induced hull vibrations, efficiency decay and noise generation due to cavitation, there is a continuous trend towards an increased complexity of the blade geometry, primarily due to the low aspect ratio and to the skew of marine propellers, which cause strong three-dimensional effects. This complexity requires a better knowledge of the wake characteristics in terms of the mean field and turbulent quantities. Therefore, there is a rising interest on detailed data of the velocity flow field around the blades and in the wake, supporting the flow modeling and the validation of the computational tools. Starting since 1997 at INSEAN started a project aimed to obtain high quality data for CFD validation. Measurements of velocity fields, radiated pressure fields cavitation patterns were performed. The chosen propeller was the INSEAN E779a, propeller which was already investigated in the 80\u27s by adopting phase sampling LDV technique

Path Loss Prediction Using Fuzzy Inference System and Ellipsoidal Rules

It is well known as the prediction of radio wave path loss in urban environment plays a key role in order to correctly plan wireless systems and mobile communication networks. To obtain more flexible prediction models able to give accurate results, in recent years Soft computing Techniques has been exploited. In this study, a novel approach based on ellipsoidal fuzzy inference system EFIS is investigated. Results compared with those provided by the Okumura Hata model and the standard Fuzzy Inference System approach (FIS) show superior performances of the EFIS approach

Interrelationship between TP53 gene deletion, protein expression and chromosome 17 aneusomy in gastric adenocarcinoma

Background: This study evaluates the existence of numerical alterations of chromosome 17 and TP53 gene deletion in gastric adenocarcinoma. the p53 protein expression was also evaluated, as well as, possible associations with clinicopathological characteristics.Methods: Dual-color fluorescence in situ hybridization and immunostaining were performed in twenty gastric cancer samples of individuals from Northern Brazil.Results: Deletion of TP53 was found in all samples. TP53 was inactivated mainly by single allelic deletion, varying to 7-39% of cells/case. Aneusomy of chromosome 17 was observed in 85% of cases. Chromosome 17 monosomy and gain were both observed in about half of cases. Cells with gain of chromosome 17 frequently presented TP53 deletion. the frequency of cells with two chr17 and one TP53 signals observed was higher in diffuse than in intestinal-type GC. Immunoreactivity of p53 was found only in intestinal-type samples. the frequency of cells with two chr17 and two TP53 signals found was higher in samples with positive p53 expression than in negative cases in intestinal-type GC.Conclusion: We suggest that TP53 deletion and chromosome 17 aneusomy is a common event in GC and other TP53 alterations, as mutation, may be implicated in the distinct carcinogenesis process of diffuse and intestinal types.Financiadora de Estudos e Projetos (FINEP CT-INFRA/FADESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Fed Univ Para, Inst Biol Sci, Humans Cytogenet Lab, BR-66075900 Belem, Para, BrazilUniv Fed Piaui, Dept Biol, Campus Minist Reis Velloso Parnaiba, Teresina, PI, BrazilUniversidade Federal de São Paulo, Dept Morphol, Div Genet, São Paulo, BrazilUniv Fed Ceara, Sch Med, Dept Pathol, Mol Genet Lab, Fortaleza, Ceara, BrazilFed Univ Para, Joao de Barros Barreto Univ Hosp, BR-66075900 Belem, Para, BrazilUniversidade Federal de São Paulo, Dept Morphol, Div Genet, São Paulo, BrazilFinanciadora de Estudos e Projetos (FINEP CT-INFRA/FADESP): 0927-03. RRBWeb of Scienc

Physical Exercise in Major Depression: Reducing the Mortality Gap While Improving Clinical Outcomes

Major depression shortens life while the effectiveness of frontline treatments remains modest. Exercise has been shown to be effective both in reducing mortality and in treating symptoms of major depression, but it is still underutilized in clinical practice, possibly due to prevalent misperceptions. For instance, a common misperception is that exercise is beneficial for depression mostly because of its positive effects on the body (“from the neck down”), whereas its effectiveness in treating core features of depression (“from the neck up”) is underappreciated. Other long-held misperceptions are that patients suffering from depression will not engage in exercise even if physicians prescribe it, and that only vigorous exercise is effective. Lastly, a false assumption is that exercise may be more harmful than beneficial in old age, and therefore should only be recommended to younger patients. This narrative review summarizes relevant literature to address the aforementioned misperceptions and to provide practical recommendations for prescribing exercise to individuals with major depression