Staphylococcus aureus Exfoliative Toxin E,Oligomeric State and Flip of P186: Implications for Its Action Mechanism

Staphylococcal exfoliative toxins (ETs) are glutamyl endopeptidases that specifically cleave the Glu381-Gly382 bond in the ectodomains of desmoglein 1 (Dsg1) via complex action mechanisms. To date, four ETs have been identified in different Staphylococcus aureus strains and ETE is the most recently characterized. The unusual properties of ETs have been attributed to a unique structural feature, i.e., the 180° flip of the carbonyl oxygen (O) of the nonconserved residue 192/186 (ETA/ETE numbering), not conducive to the oxyanion hole formation. We report the crystal structure of ETE determined at 1.61 Å resolution, in which P186(O) adopts two conformations displaying a 180° rotation. This finding, together with free energy calculations, supports the existence of a dynamic transition between the conformations under the tested conditions. Moreover, enzymatic assays showed no significant differences in the esterolytic efficiency of ETE and ETE/P186G, a mutant predicted to possess a functional oxyanion hole, thus downplaying the influence of the flip on the activity. Finally, we observed the formation of ETE homodimers in solution and the predicted homodimeric structure revealed the participation of a characteristic nonconserved loop in the interface and the partial occlusion of the protein active site, suggesting that monomerization is required for enzymatic activity.     

A new algorithm for finding faces in wireframes

The problem of identifying the topology implied by wireframe drawings of polyhedral objects requires the identification of face loops, loops of edges which correspond to a face in the object the drawing portrays.In this paper, we survey the advantages and limitations of known approaches, and present and discuss test results which illustrate the successes and failures of a currently popular approach based on Dijkstra’s Algorithm. We conclude that the root cause of many failure cases is that the underlying algorithm assumes that the cost of traversing an edge is fixed.We propose a new polynomial-order algorithm for finding faces in wireframes. This algorithm could be adapted to any graph-theoretical least-cost circuit problem where the cost of traversing an edge is not fixed but context-dependent.     

Early bankruptcy prediction using ENPC

Bankruptcy prediction has long time been an active research field in finance. One of the main approaches to this issue is dealing with it as a classification problem. Among the range of instruments available, we focus our attention on the Evolutionary Nearest Neighbor Classifier (ENPC). In this work we assess the performance of the ENPC comparing it to six alternatives. The results suggest that this algorithm might be considered a good choice.     

Beacon-Less Geographic Routing in Real Wireless Sensor Networks

Geographic Routing(GR)algorithms require nodes to periodically transmit HELLO messages to allow neigh- bors to know their positions(beaconing mechanism).Beacon-less routing algorithms have recently been proposed to reduce the control overheads due to these messages.However,existing beacon-less algorithms have not considered realistic physical layers.Therefore,those algorithms cannot work properly in realistic scenarios.In this paper we present a new beacon- less routing protocol called BOSS.Its design is based on the conclusions of our open-field experiments using Tmote-sky sensors.BOSS is adapted to error-prone networks and incorporates a new mechanism to reduce collisions and duplicate messages produced during the selection of the next forwarder node.We compare BOSS with Beacon-Less Routing(BLR) and Contention-Based Forwarding(CBF)algorithms through extensive simulations.The results show that our scheme is able to achieve almost perfect packet delivery ratio(like BLR)while having a low bandwidth consumption(even lower than CBF).Additionally,we carried out an empirical evaluation in a real testbed that shows the correctness of our simulation results.     

Removal of an Azo Dye from Wastewater through the Use of Two Technologies: Magnetic Cyclodextrin Polymers and Pulsed Light

Water pollution by dyes is a huge environmental problem; there is a necessity to produce new decolorization methods that are effective, cost-attractive, and acceptable in industrial use. Magnetic cyclodextrin polymers offer the advantage of easy separation from the dye solution. In this work, the β-CD-EPI-magnetic (β-cyclodextrin-epichlorohydrin) polymer was synthesized, characterized, and tested for removal of the azo dye Direct Red 83:1 from water, and the fraction of non-adsorbed dye was degraded by an advanced oxidation process. The polymer was characterized in terms of the particle size distribution and surface morphology (FE-SEM), elemental analysis (EA), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), infrared spectrophotometry (IR), and X-ray powder diffraction (XRD). The reported results hint that 0.5 g and pH 5.0 were the best conditions to carry out both kinetic and isotherm models. A 30 min contact time was needed to reach equilibrium with a qmax of 32.0 mg/g. The results indicated that the pseudo-second-order and intraparticle diffusion models were involved in the assembly of Direct Red 83:1 onto the magnetic adsorbent. Regarding the isotherms discussed, the Freundlich model correctly reproduced the experimental data so that adsorption was confirmed to take place onto heterogeneous surfaces. The calculation of the thermodynamic parameters further demonstrates the spontaneous character of the adsorption phenomena (ΔG° = −27,556.9 J/mol) and endothermic phenomena (ΔH° = 8757.1 J/mol) at 25 °C. Furthermore, a good reusability of the polymer was evidenced after six cycles of regeneration, with a negligible decline in the adsorption extent (10%) regarding its initial capacity. Finally, the residual dye in solution after treatment with magnetic adsorbents was degraded by using an advanced oxidation process (AOP) with pulsed light and hydrogen peroxide (343 mg/L); >90% of the dye was degraded after receiving a fluence of 118 J/cm²; the discoloration followed a pseudo first-order kinetics where the degradation rate was 0.0196 cm²/J. The newly synthesized β-CD-EPI-magnetic polymer exhibited good adsorption properties and separability from water which, when complemented with a pulsed light-AOP, may offer a good alternative to remove dyes such as Direct Red 83:1 from water. It allows for the reuse of both the polymer and the dye in the dyeing process.     

Differential Plasma Metabolites between High- and Low-Grade Meningioma Cases

Meningiomas (MGMs) are currently classified into grades I, II, and III. High-grade tumors are correlated with decreased survival rates and increased recurrence rates. The current grading classification is based on histological criteria and determined only after surgical tumor sampling. This study aimed to identify plasma metabolic alterations in meningiomas of different grades, which would aid surgeons in predefining the ideal surgical strategy. Plasma samples were collected from 51 patients with meningioma and classified into low-grade (LG) (grade I; n = 43), and high-grade (HG) samples (grade II, n = 5; grade III, n = 3). An untargeted metabolomic approach was used to analyze plasma metabolites. Statistical analyses were performed to select differential biomarkers among HG and LG groups. Metabolites were identified using tandem mass spectrometry along with database verification. Five and four differential biomarkers were identified for HG and LG meningiomas, respectively. To evaluate the potential of HG MGM metabolites to differentiate between HG and LG tumors, a receiving operating characteristic curve was constructed, which revealed an area under the curve of 95.7%. This indicates that the five HG MGM metabolites represent metabolic alterations that can differentiate between LG and HG meningiomas. These metabolites may indicate tumor grade even before the appearance of histological features.     

GSK3β Inhibition by Phosphorylation at Ser389 Controls Neuroinflammation

The inhibition of Glycogen Synthase Kinase 3 β (GSK3β) by Ser⁹ phosphorylation affects many physiological processes, including the immune response. However, the consequences of GSK3β inhibition by alternative Ser³⁸⁹ phosphorylation remain poorly characterized. Here we have examined neuroinflammation in GSK3β Ser³⁸⁹ knock-in (KI) mice, in which the phosphorylation of Ser³⁸⁹ GSK3β is impaired. The number of activated microglia/infiltrated macrophages, astrocytes, and infiltrated neutrophils was significantly higher in these animals compared to C57BL/6J wild-type (WT) counterparts, which suggests that the failure to inactivate GSK3β by Ser³⁸⁹ phosphorylation results in sustained low-grade neuroinflammation. Moreover, glial cell activation and brain infiltration of immune cells in response to lipopolysaccharide (LPS) failed in GSK3β Ser³⁸⁹ KI mice. Such effects were brain-specific, as peripheral immunity was not similarly affected. Additionally, phosphorylation of the IkB kinase complex (IKK) in response to LPS failed in GSK3β Ser³⁸⁹ KI mice, while STAT3 phosphorylation was fully conserved, suggesting that the NF-κB signaling pathway is specifically affected by this GSK3β regulatory pathway. Overall, our findings indicate that GSK3β inactivation by Ser³⁸⁹ phosphorylation controls the brain inflammatory response, raising the need to evaluate its role in the progression of neuroinflammatory pathologies.     

Finite sample properties of Moran's I test for spatial autocorrelation in tobit models

In this note, we investigate the finite‐sample properties of Moran's I test statistic for spatial autocorrelation in tobit models suggested by Kelejian and Prucha. We fill a void in the theoretical literature by investigating the finite sample properties of this test statistic in a series of Monte Carlo simulations, using data sets ranging from 49 to 15,625 observations. We find that the test is unbiased, has considerable power and approximates the asymptotic normal distribution even for medium‐sized sample sizes, empirically confirming the theoretical results of Kelejian and Prucha. However, some caution is needed, since the statistic turns out to be sensitive to misspecification in the form of heteroscedasticity. In such instances the test over‐rejects the null hypothesis, mistaking heteroscedasticity for spatial autocorrelation.     

Performance of a New Microbial Test for Quinolone Residues in Muscle

Concerns regarding the presence of drug residues in foods include allergic reactions, toxicity, technological problems in fermented products and the development of antibiotic resistance in human pathogens. The analysis of antimicrobial residues in foods is generally carried out, in a first step, through microbiological screening tests. These tests commonly use Geobacillus stearothermophilus as target specie but show a low ability to detect quinolones. The goal of our study was to evaluate the performance of a new microbiological test (Equinox) for detection of quinolone residues in muscle. The kit contains an ampoule with a standardized number of freeze-dried Escherichia coli and must be diluted with a specific detection medium containing a redox indicator. Microbial growth will modify the redox potential of the medium being observed through a colour change (from blue to brown/orange). Equinox limits of detection for most of tested quinolones (enrofloxacin, norfloxacin, sarafloxacin, marbofloxacin, ciprofloxacin, danofloxacin and difloxacin) were below or around maximum residue limit (MRL) UE and CCβ values obtained corresponded with the determined sensitivities. In contrast, flumequine could not be detected at MRL UE levels. Moreover, Equinox displayed a low sensitivity to other antimicrobials. Sensitivity data obtained in vitro were consistent when testing incurred muscle samples. Matrix constituents, test batch and animal species did not affect the performance of the test. Equinox could be easily automated enabling a large numbers of simultaneous analysis, and a photometric reading can be applied for a precise interpretation. The results obtained in this study prove that Equinox is a useful tool when screening for quinolone residues or can be combined with other methods for screening of unknown samples.