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RESUMO Após uma introdução sobre a importância do voto no nível municipal para habitantes que vivem numa democracia, enfocamos as eleições municipais e passamos a discutir um perfil para o “eleitor ideal”, que é aquele que investiga as candidaturas de forma multifacetada e não somente por um único critério. Colocamos 10 pontos que podem ser usados como guia para que o eleitor avalie candidaturas e sugerimos uma forma de comparar candidatos usando um ranqueamento numérico (notas de zero a dez) com a média sendo um critério para avaliar os candidatos que merecem votos. Em seguida, descrevemos um perfil para o que seriam os “candidatos ideais” para os cargos executivo e legislativo nas cidades. Ancorados em trabalho que realizamos na USP no âmbito do Instituto de Estudos Avançados e do Programa Eixos Temáticos da USP, descrevemos sete pontos que consideramos essenciais para quaisquer candidaturas em cidades brasileiras. Um dos argumentos principais é que, para que a democracia funcione, o eleitor precisa se ocupar com análises mais profundas dos candidatos, evitando que eles sejam eleitos por um processo que, em muitos casos, é quase aleatório.

Abstract The β-glucosidase gene from Aspergillus nidulans FGSC A4 was cloned and overexpressed in the A. nidulans A773. The resulting purified β-glucosidase, named AnGH3, is a monomeric enzyme with a molecular weight of approximately 80 kDa, as confirmed by SDS-PAGE. Circular dichroism further validated its unique canonical barrel fold (β/α), a feature also observed in the 3D homology model of AnGH3. The most striking aspect of this recombinant enzyme is its robustness, as it retained 100% activity after 24 h of incubation at 45 and 50 ºC and pH 6.0. Even at 55 °C, it maintained 72% of its enzymatic activity after 6 h of incubation at the same pH. The kinetic parameters Vmax, KM, and Kcat/KM for ρ-nitrophenyl-β-D-glucopyranoside (ρNPG) and cellobiose were also determined. Using ρNPG, the enzyme demonstrated a Vmax of 212 U mg − 1, KM of 0.0607 mmol L − 1, and Kcat/KM of 4521 mmol L − 1 s − 1 when incubated at pH 6.0 and 65 °C. The KM, Vmax, and Kcat/KM using cellobiose were 2.7 mmol L − 1, 57 U mg − 1, and 27 mmol –1 s − 1, respectively. AnGH3 activity was significantly enhanced by xylose and ethanol at concentrations up to 1.5 mol L − 1 and 25%, respectively. Even in challenging conditions, at 65 °C and pH 6.0, the enzyme maintained its activity, retaining 100% and 70% of its initial activity in the presence of 200 mmol L − 1 furfural and 5-hydroxymethylfurfural (HMF), respectively. The potential of this enzyme was further demonstrated by its application in the saccharification of the forage grass Panicum maximum, where it led to a 48% increase in glucose release after 24 h. These unique characteristics, including high catalytic performance, good thermal stability in hydrolysis temperature, and tolerance to elevated concentrations of ethanol, D-xylose, furfural, and HMF, position this recombinant enzyme as a promising tool in the hydrolysis of lignocellulosic biomass as part of an efficient multi-enzyme cocktail, thereby opening new avenues in the field of biotechnology and enzymology.

Abstract Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L’s important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L-/- peritoneal cells from mice subjected to medium-grade CLP exhibit a heightened pro-inflammatory transcriptional profile, reflecting a loss of control of the immune response to the infection. Intravenous administration of recombinant CD5L (rCD5L) in immunocompetent C57BL/6 wild-type (WT) mice significantly ameliorates measures of disease in the setting of high-grade CLP-induced sepsis. Furthermore, rCD5L lowers endotoxin and damage-associated molecular pattern (DAMP) levels, and protects WT mice from LPS-induced endotoxic shock. These findings warrant the investigation of rCD5L as a possible treatment for sepsis in humans.

A broadband and compact planar UHF antenna is presented for use in MIMO Digital TV indoor applications. The choice of the element and its physical implementation is oriented towards a low-profile, low-cost, and single-layer deployment. Since it is intended to be used in a 2 × 1 MIMO array, two antennas were constructed and tested to minimize their coupling to provide larger MIMO gains. Regarding the excitation, two different structures were evaluated to observe their impact on the final impedance profile. The option of an infinite balun provided a 62% fractional bandwidth (394 MHz to 747 MHz), covering the desired band and with good isolation levels when analyzed in the array. Results regarding MIMO parameters are provided herein, such as Envelope Correlation Coefficient and Total Active Reflection Coefficient, proving the potential of the proposed antenna array to be used in MIMO Digital TV applications in covering the UHF band.

Performing exercise in hot environmental conditions presents athletes with potential negative physiological and perceptual implications. Key constituents, such as fluid and electrolytes, are lost during sweating through the process of cooling the human body. The loss of electrolytes impairs exercise performance. Heat training is one strategy to combat sweat electrolyte loss, with decreased sweat electrolyte concentration being a main sudomotor adaptation. To measure sweat electrolyte concentration, two common assessment methods are typically utilized: whole-body washdown and regional sweat patch measurements. The effects of physiological adaptations and sweat electrolyte assessment methodology have been investigated; however, the importance of methodological differences between sweat electrolyte measurements following heat training has yet to be explored. This review explores the differences between sweat electrolyte measurement techniques following adaptations incurred with heat training. Future research directions are also provided.

This paper addresses the estimation of critical loads in FFF (Fused Filament Fabrication) printed polymers and composites containing notches. Particularly, the analysis is focused on the fracture load estimations of 39 PLA (polylactic acid) and 39 graphene reinforced PLA (PLA-Gr) printed plates containing two different types of notches (U- and V-notches) and combining different plate thicknesses and defect length to plate width (a/W) ratios. The addition of graphene (1 wt.%) increases both the yield stress and the ultimate tensile strength, also reducing the strain at rupture and, thus, generating a material whose behavior is closer to linear elasticity. Among the different assessment tools that may be used to estimate critical loads, this work applies the well-known Averaged Strain Energy Density (ASED) criterion, which compares the averaged strain energy over a certain control volume at the notch tip with the corresponding critical value, the latter being a material property. This approach has a linear-elastic nature, so its application to non-fully linear materials may require the use of specific corrections or calibrations. For the two materials analyzed here, PLA and PLA-Gr, it has been observed that the ordinary linear-elastic ASED criterion provides good estimations for the PLA-Gr material, whereas the pristine PLA, with more evident non-linear behavior, the obtainment of accurate results requires a previous specific calibration of the ASED material parameters

The scaled water-cooled Reactor Cavity Cooling System (RCCS) experimental facility reproduces a passive safety feature to be implemented in Generation IV nuclear reactors. It keeps the reactor cavity and other internal structures in operational conditions by removing heat leakage from the reactor pressure vessel. The present work uses Flownex one-dimensional thermal-fluid code to model the facility and predict the experimental thermal-hydraulic behavior. Two representative steady-state cases defined by the bulk volumetric flow rate are simulated (Re = 2,409 and Re = 11,524). Results of the cavity outlet temperature, risers' temperature profile, and volumetric flow split in the cooling panel are also compared with the experimental data and RELAP system code simulations. The comparisons are in reasonable agreement with the previous studies, demonstrating the ability of Flownex to simulate the RCCS behavior. It is found that the low Re case of 2,409, temperature and flow split are evenly distributed across the risers. On the contrary, there's an asymmetry trend in both temperature and flow split distributions for the high Re case of 11,524.

Bast fibers are defined as those obtained from the outer cell layers of the bast of various plant families. They are finding use in textile applications and are widely used as reinforcements for green composites, as bast fibers are perceived as “sustainable”. There is a growing demand for bast fibers across the world due to their renewable and biodegradable nature. The bast fibers are mainly composed of cellulose, which potentially considers the growing techniques, harvesting and extraction processes of bast fibers most used to produce fibers with appropriate quality to apply in the daily lives of modern men and women in contemporary society. This review paper looks at many aspects of natural fibers, with a focus on plant bast fibers, including their impact on prehistoric and historical society. This review shows that bast fibers are competitive compared to man-made fibers in many applications, but variability in mechanical properties and low tenacity may limit their use in high-strengthh composites and extend to, particularly in aerospace, automotive, packaging, building industries, insulation, E-composites (Eco composites), geotextiles and many other applications are currently being explored. Considering, important characteristics of bast fibers include physical, mechanical, and chemical properties. This makes bast fibers one of the most important classes of plant fibers to use as reinforcing agents in thermosetting/thermoplastic polymer matrices. And the effect of bast fibers as reinforcement in the properties of ECO-composites, GREEN-composites, BIO-composites, lightweight composites. Bast fibers play an important role in sustainability, the preservation of the health of the environment, the well-being of the next generation, and even the daily lives of men and women in the contemporary world.

This study introduces an innovative approach to the layered model, emphasizing the physical–chemical characterization of miscible liquid systems through ultrasonic techniques, with a specific focus on the water–ethanol system used in pharmaceutical formulations. Traditional characterization methods, while effective, face challenges due to the complex nature of solutions, such as the need for large pressure variations and strict temperature control. The proposed approach integrates partial molar volumes and partial propagation velocity functions into the layered model, enabling a nuanced understanding of miscibility and interactions. Ultrasonic techniques are used to calculate the isentropic compressibility coefficient for each component of the mixture as well as the total value using an additive mixing rule. Unlike conventional methods, this technique uses tabulated and experimental data to estimate the propagation velocity in the mixture, leading to a more precise computation of the isentropic compressibility coefficient. The results indicate a significant improvement in predicting the behavior of the water–ethanol system compared to the classical layered model. The methodology demonstrates the potential to provide new physicochemical insights that can be applied to other miscible systems beyond water–ethanol. This research has implications for improving the efficiency and accuracy of liquid medication formulations in the pharmaceutical industry.

Most deleterious variants are recessive and segregate at relatively low frequency. Therefore, high sample sizes are required to identify these variants. In this study we report a large-scale sequence based genome-wide association study (GWAS) in pigs, with a total of 120,000 Large White and 80,000 Synthetic breed animals imputed to sequence using a reference population of approximately 1,100 whole genome sequenced pigs. We imputed over 20 million variants with high accuracies (R2>0.9) even for low frequency variants (1-5% minor allele frequency). This sequence-based analysis revealed a total of 14 additive and 9 non-additive significant quantitative trait loci (QTLs) for growth rate and backfat thickness. With the non-additive (recessive) model, we identified a deleterious missense SNP in the CDHR2 gene reducing growth rate and backfat in homozygous Large White animals. For the Synthetic breed, we revealed a QTL on chromosome 15 with a frameshift variant in the OBSL1 gene. This QTL has a major impact on both growth rate and backfat, resembling human 3M-syndrome 2 which is related to the same gene. With the additive model, we confirmed known QTLs on chromosomes 1 and 5 for both breeds, including variants in the MC4R and CCND2 genes. On chromosome 1, we disentangled a complex QTL region with multiple variants affecting both traits, harboring 4 independent QTLs in the span of 5 Mb. Together we present a large scale sequence-based association study that provides a key resource to scan for novel variants at high resolution for breeding and to further reduce the frequency of deleterious alleles at an early stage in the breeding program.

Abstract The present study aimed was to evaluate the spatial variability of weed species by means of phytosociological parameters and their correlations with the physical-chemical soil properties, under semiarid climate conditions. Weed phytosociology and soil characterization were carried out in two areas one newly deforested area covering 8.86 ha, and one experimental agricultural area covering 24.7 ha; both in the semi-arid region of Brazil. Weed and soil were sampled by following georeferenced grids in each area. Biomass and the total number of weed individuals, as well as soil properties, were mapped by the ordinary Kriging method. The predominant herbaceous plants in the newly deforested area were Hexasepalum teres and Digitaria insularis. The weed species that predominated in the agricultural area were Cyperus rotundus L., Euphorbia heterophylla L. and Herissantia Crispa (L.) Brizicky; the latter species outstanding for dry biomass (873.5g). Spatial dependence was observed for the predominant species, except for Digitaria insularis. The spatial distribution of these weeds was conditioned by soil K+ contents in both areas, and by sand content for the experimental agricultural area. Therefore, these two soil attributes resulted key factors for weed infestation in this semi-arid region.

Abstract Background The genetic correlation between purebred (PB) and crossbred (CB) performances ( $${r}_{pc}$$ r pc ) partially determines the response in CB when selection is on PB performance in the parental lines. An earlier study has derived expressions for an upper and lower bound of $${r}_{pc}$$ r pc , using the variance components of the parental purebred lines, including e.g. the additive genetic variance in the sire line for the trait expressed in one of the dam lines. How to estimate these variance components is not obvious, because animals from one parental line do not have phenotypes for the trait expressed in the other line. Thus, the aim of this study was to propose and compare three methods for approximating the required variance components. The first two methods are based on (co)variances of genomic estimated breeding values (GEBV) in the line of interest, either accounting for shrinkage (VCGEBV-S) or not (VCGEBV). The third method uses restricted maximum likelihood (REML) estimates directly from univariate and bivariate analyses (VCREML) by ignoring that the variance components should refer to the line of interest, rather than to the line in which the trait is expressed. We validated these methods by comparing the resulting predicted bounds of $${r}_{pc}$$ r pc with the $${r}_{pc}$$ r pc estimated from PB and CB data for five traits in a three-way cross in pigs. Results With both VCGEBV and VCREML, the estimated $${r}_{pc}$$ r pc (plus or minus one standard error) was between the upper and lower bounds in 14 out of 15 cases. However, the range between the bounds was much smaller with VCREML (0.15–0.22) than with VCGEBV (0.44–0.57). With VCGEBV-S, the estimated $${r}_{pc}$$ r pc was between the upper and lower bounds in only six out of 15 cases, with the bounds ranging from 0.21 to 0.44. Conclusions We conclude that using REML estimates of variance components within and between parental lines to predict the bounds of $${r}_{pc}$$ r pc resulted in better predictions than methods based on GEBV. Thus, we recommend that the studies that estimate $${r}_{pc}$$ r pc with genotype data also report estimated genetic variance components within and between the parental lines.

Network Slicing (NS) is an essential technique extensively used in 5G networks computing strategies, mobile edge computing, mobile cloud computing, and verticals like the Internet of Vehicles and industrial IoT, among others. NS is foreseen as one of the leading enablers for 6G futuristic and highly demanding applications since it allows the optimization and customization of scarce and disputed resources among dynamic, demanding clients with highly distinct application requirements. Various standardization organizations, like 3GPP’s proposal for new generation networks and state-of-the-art 5G/6G research projects, are proposing new NS architectures. However, new NS architectures have to deal with an extensive range of requirements that inherently result in having NS architecture proposals typically fulfilling the needs of specific sets of domains with commonalities. The Slicing Future Internet Infrastructures (SFI2) architecture proposal explores the gap resulting from the diversity of NS architectures target domains by proposing a new NS reference architecture with a defined focus on integrating experimental networks and enhancing the NS architecture with Machine Learning (ML) native optimizations, energy-efficient slicing, and slicing-tailored security functionalities. The SFI2 architectural main contribution includes the utilization of the slice-as-a-service paradigm for end-to-end orchestration of resources across multi-domains and multi-technology experimental networks. In addition, the SFI2 reference architecture instantiations will enhance the multi-domain and multi-technology integrated experimental network deployment with native ML optimization, energy-efficient aware slicing, and slicing-tailored security functionalities for the practical domain.

Abstract Fraud, corruption, and collusion are the most common types of crime in public procurement processes; they produce significant monetary losses, inefficiency, and misuse of the public treasury. However, empirical research in this area to detect these crimes is still insufficient. This article presents a systematic literature review focusing on the most contemporary data-driven techniques applied to crime detection in public procurement. The preferred reporting items for systematic reviews and meta-analyses (PRISMA) methodology was adopted to identify typical elements that lead to crimes in public contracting. We collected scientific papers and analyzed the selected research using the Scopus repository. We evaluated and summarized findings related to crime detection techniques based mainly on machine learning and network science, as well as studies using fraud risk indices. Some methodologies presented promising results in identifying crimes, especially those using labeled data and machine learning techniques. However, due to the frequent unavailability of pre-labeled data on past cases, analysis through network science tools has become more evident and relevant in exploratory research.

Pectic polysaccharides containing apiose, xylose, and uronic acids are excellent candidates for boron fixation. Duckweeds are the fastest-growing angiosperms that can absorb diverse metals and contaminants from water and have high pectin content in their cell walls. Therefore, these plants can be considered excellent boron (B) accumulators. This work aimed to investigate the relationship between B assimilation capacity with apiose content in the cell wall of Spirodela polyrhiza subjected to different boric acid concentrations. Plants were grown for 7 and 10 days in ½ Schenck-Hildebrandt media supplemented with 0 to 56 mg B.L-1, the non-structural and structural carbohydrates, and related genes were evaluated. The results showed that B altered the morphology and carbohydrate composition of this species during plant development. The optimum B concentration (1.8 mg B.L-1) led to the highest relative growth and biomass accumulation, reduced starch, and high pectin and apiose contents, together with increased expression of UDP-apiose/UDP-xylose synthase (AXS) and 1,4-α-galacturonosyltransferase (GAUT). The toxic state (28 and 56 mg B.L-1) increased the hexose contents in the cell wall with a concomitant reduction of pectins, apiose, and growth. The pectin content of S. polyrhiza was strongly associated with its growth capacity and regulation of B content within the cells, which have AXS as an important regulator. These findings suggest that duckweeds are suitable for B remediation, and their biomass can be used for bioenergy production.

IntroductionDuring infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Mycobacterium tuberculosis may colonize the BM, studies using the mouse model of infection and the laboratory reference strain M. tuberculosis H37Rv have demonstrated limited emergency myelopoiesis and trained immunity.MethodsTo further address this issue, we aerosol- infected C57BL/6 mice with high doses of the hypervirulent M. tuberculosis isolate HN878 and monitored alterations to the BM. This experimental model better resembles the human blood immune signature of TB.Results and discussionWe found increased frequencies of lineage-Sca-1+cKit+ (LSK) cells and the granulocyte/macrophage progenitor (GMP) population. At the mature cell level, we observed an increase of monocytes and neutrophils in the blood and lung, likely reflecting the increased BM myeloid output. Monocytes or monocyte-derived macrophages recovered from the BM of M. tuberculosis HN878-infected mice did not show signs of trained immunity, suggesting an uncoupling of emergency myelopoiesis and trained immunity in the BM. Surprisingly, M. tuberculosis HN878-induced emergency myelopoiesis was not fully dependent on IFNγ, as mice lacking this cytokine and infected under the same conditions as wild-type mice still presented BM alterations. These data expand our understanding of the immune response to M. tuberculosis and raise awareness of pathogen strain-imposed differences to host responses.

This paper explores implementation of self-weight and inertial loading in topology optimization (TO) employing the Simulated Annealing (SA) algorithm as a non-gradient-based technique. This method can be applied to find optimum design of structures with no need for gradient information. To enhance the convergence of the SA algorithm, a novel approach incorporating the crystallization factor is introduced. The method is applied in a benchmark problem of a cantilever beam. The study systematically examines multiple scenarios, including cases with and without self-weight effects, as well as varying point loads. Compliance values are calculated and compared to those reported in existing literature to validate the accuracy of the optimization results. The findings highlight the versatility and effectiveness of the SA-based TO methodology in addressing complex design challenges with considerable self-weight or inertial effect. This work can contribute to structural design of systems where only the objective value is available with no gradient information to use sensitivity-based algorithms.

The popping expansion is a characteristic that is positively related with the quality of popcorn. A positive correlation between the volume of expansion and the thickness of the pericarp, and between the proportion of the opaque/shiny endosperm and the grain weight and volume, were postulated. However, there are no reports in the literature that address the importance of cell wall components in the popping expansion. Here, we investigate the biochemical composition of the pericarp cell walls of three inbred lines of popcorn with different popping expansion. Inbred lines GP12 (expansion volume >40 mL g−1), P11 (expansion volume 30 mL g−1) and P16 (expansion volume 14 mL g−1) were used for the analysis and quantification of monosaccharides by HPAEC-PAD, and ferulic and p-coumaric acids and lignin by HPLC. Our hypothesis is that the biochemical composition of the pericarp cell walls may be related to greater or lesser popping expansion. Our data suggest that the lignin content and composition contribute to popping expansion. The highest concentration of lignin (129.74 μg mg−1; 12.97%) was detected in the pericarp cell wall of the GP12 inbred line with extremely high popping expansion, and the lowest concentration (113.52 μg mg−1; 11.35%) was observed in the P16 inbred line with low popping expansion. These findings may contribute to indicating the quantitative trait locus for breeding programs and to developing other methods to improve the popping expansion of popcorn.

Abstract The optimization of three-dimensional device has widely been explored and designated as computational challenge in photonic device design. In this context, this work presents a novel multi-symmetric level (MSL) optimization procedure based on Genetic Algorithm (GA) to decrease the computational requirements in a three-dimensional photonic coupler device optimization. The proposed procedure divides the device optimization into many local regions by dimensional symmetric aspects, being based on divide- to-conquer strategies. As the optimization converges to acceptance values, the number of symmetric areas are decreasing until a unique local area that modeled the total 3D photonic device. This procedure was validated by the minimization of a photonic coupler modeled to interconnect optical waveguides with different height, width and refractive indices.

Abstract Fraud in public funding can have deleterious consequences for societies’ economic, social, and political well-being. Fraudulent activity associated with public procurement contracts accounts for losses of billions of euros every year. Thus, it is of utmost relevance to explore analytical frameworks that can help public authorities identify agents that are more susceptible to irregular activities. Here, we use standard network science methods to study the co-bidding relationships between firms that participate in public tenders issued by the 184 municipalities of the State of Ceará (Brazil) between 2015 and 2019. We identify 22 groups/communities of firms with similar patterns of procurement activity, defined by their geographic and activity scopes. The profiling of the communities allows us to highlight organizations that are more susceptible to market manipulation and irregular activities. Our work reinforces the potential application of network analysis in policy to unfold the complex nature of relationships between market agents in a scenario of scarce data.

ABSTRACT The growing demand for clean energy aimed at reducing greenhouse gas emissions associated with the oil crises has encouraged the search for biofuels, among which biodiesel has stood out in the gradual replacement of diesel. This study aimed to evaluate the performance of an agricultural tractor fueled with four types of biodiesels (peanut, sunflower, soybean, and waste frying oil) added to diesel at five proportions (0, 25, 50, 75, and 100% biodiesel, that is, B0, B25, B50, B75, and B100, respectively). The experiment was carried out at the Laboratory of Biofuel and Machinery Testing at FCAV–UNESP. A Valtra BM100 4×2 FWD tractor with a power of 74 kW (100 hp) was used. The drawbar pull force (DF), displacement velocity (V), drawbar power (DP), volumetric fuel consumption (VC), weight fuel consumption (WC), and specific fuel consumption (SC) were studied. The factors did not influence DF, V, and DP. The proportion factor influenced (p

Xyloglucans are polysaccharides found in plant cell walls. Here, the authors describe the xyloglucan depolymerization machinery of phytopathogenic Xanthomonas bacteria, and show that sugars released by this system induce the expression of key virulence factors driving pathogenesis.

Backfat is an important trait in pork production, and it has been included in the breeding objectives of genetic companies for decades. Although adipose tissue is a good energy storage, excessive fat results in reduced efficiency and economical losses. A large QTL for backfat thickness on chromosome 5 is still segregating in different commercial pig breeds. We fine mapped this QTL region using a genome-wide association analysis (GWAS) with 133,358 genotyped animals from five commercial populations (Landrace, Pietrain, Large White, Synthetic, and Duroc) imputed to the porcine 660K SNP chip. The lead SNP was located at 5:66103958 (G/A) within the third intron of the CCND2 gene, with the G allele associated with more backfat, while the A allele is associated with less backfat. We further phased the QTL region to discover a core haplotype of five SNPs associated with low backfat across three breeds. Linkage disequilibrium analysis using whole-genome sequence data revealed three candidate causal variants within intronic regions and downstream of the CCND2 gene, including the lead SNP. We evaluated the association of the lead SNP with the expression of the genes in the QTL region (including CCND2) in a large cohort of 100 crossbred samples, sequenced in four different tissues (lung, spleen, liver, muscle). Results show that the A allele increases the expression of CCND2 in an additive way in three out of four tissues. Our findings indicate that the causal variant for this QTL region is a regulatory variant within the third intron of the CCND2 gene affecting the expression of CCND2.

This investigative work was carry out through a factorial planning, using Design of Experiment (DoE) in order to evaluate the impact performance properties of Kevlar® woven structure impregnated with Non-Newtonian Fluids (NNF). Pull out and drop tower tests were performed. The pull out test showed that Kevlar® strength values with NNF composition 3 were better (10.55 N) when compared to others (1 and 2). The drop tower test showed that woven samples with highest concentration of NNF nanoparticles (3OR) exhibited the best behavior with respect to the penetration depth for P1 (19.5%) and S1 (48.0%) knife blade geometries. Thus, evidencing best residual energy dissipation when compared to the others. Results also showed that the composition (1, 2 and 3) of NNF as well as the orientation of the woven layers can be used to improve impact performance properties. Therefore, the impact protection performance depends on the friction between the yarns (pull out), the knife blade geometry and mainly the composition of the NNF which, in turn, is directly related to the nanoparticle and agent content of silane coupling present in the composition of the Non-Newtonian Fluid. Finally, this study also demonstrates that the use of statistical analysis promoted the improvement for obtaining and effectiveness of the behavior of lightweight impact protection textile structures.

This work presents results of the first study of the variation by exposure to high temperatures from two stay-in-place polyvinyl chloride (SIP-PVC) formwork concrete exposed to the ISO 834 fire curve. A systematic sampling based on the proximity of the fire and the spalling of the concrete was carried out and microstructural, thermal, crystallographic and spectroscopic changes were studied according to the degree of affectation by fire using SEM, TGA-DTA, XRD and FTIR. The response to high temperature exposure of the microstructure of SIP-PVC formwork concrete after fire was established using the experimental results. Results show a relationship between the microstructure of concrete paste and exposure temperature, as well as, the relationship between exposure temperature and dehydration of calcium hydrates, CSH gel and Portlandite and decarbonation of Calcite. These reactions can be considered as tracers of the degree of exposure to high temperatures from stay-in-place PVC formwork concrete.

Abstract Background Fluid overload (FO) assessed by bioimpedance spectroscopy (BIS) is associated with higher mortality risk in maintenance haemodialysis (HD). The aim was to assess if a better management of FO through short daily haemodialysis (SDHD) could improve survival. Methods Retrospective analysis of patients who were on HD 3 sessions/week for at least 3 months and shifted to in-centre SDHD (5 or 6 sessions/week, 2 to 3 h/session) between July 2012 and June 2016 at 23 dialysis units in Brazil. The 12-month risk of death was analysed according to the predialysis hydration status measured before and 6 months after initiation of SDHD. Predialysis hydration status was considered adequate when FO ≤15% of extracellular volume. Results A total of 297 patients on SDHD were included in the analysis. Their median age was 57 (IQR 45–67) years, 62% were males, 44% diabetics, 57% on 6 dialysis sessions/week, with a median session duration of 130 (IQR 120–150) minutes. BIS assessment at initiation of the SDHD regimen was performed in 220 patients and FO > 15% was found in 46.4%. Twelve-month survival rates for those with FO ≤15 and > 15% before initiating SDHD were 87.4 and 88.0%, respectively (P = 0.92). BIS analysis when completing 6 months on SDHD were available for 229 patients, 26.6% with FO > 15%. The survival rates for the next 12 months (from the 6th to the 18th month of follow-up) for those with FO ≤15 and > 15% were 91.0 and 72.0%, respectively (P = 0.0006). In a Cox regression model, after adjustment for demographic, clinical and laboratory variables, FO ≤ 15% persisted associated with a lower mortality risk (hazard ratio 0.34, 95%CI 0.13–0.87). Conclusions Moving from conventional HD to SDHD was associated with better control of excessive extracellular volume. Patients who reached or maintained predialysis fluid overload ≤15% after initiating SDHD presented a lower risk of death.

The Cayenne tick, Amblyomma cajennense (Fabricius, 1787) (Ixodida: Ixodidae), parasitizes a range of vertebrate hosts, including humans, accidentally. Infestation by this species has important implications for public health, given that these ticks habitually bite humans and may act as the vectors of several pathogens. Here, we present a detailed case of human parasitism by A. cajennense and provide the first record of the occurrence of the species in the state of Acre, Brazil.

Arboviruses such as Dengue, yellow fever, West Nile, and Zika are flaviviruses vector-borne RNA viruses transmitted biologically among vertebrate hosts by blood-taking vectors. Many flaviviruses are associated with neurological, viscerotropic, and hemorrhagic diseases, posing significant health and socioeconomic concerns as they adapt to new environments. Licensed drugs against them are currently unavailable, so searching for effective antiviral molecules is still necessary. Epigallocatechin molecules, a green tea polyphenol, have shown great virucidal potential against flaviviruses, including DENV, WNV, and ZIKV. The interaction of EGCG with the viral envelope protein and viral protease, mainly identified by computational studies, describes the interaction of these molecules with viral proteins; however, how the viral NS2B/NS3 protease interacts with epigallocatechin molecules is not yet fully deciphered. Consequently, we tested the antiviral potential of two epigallocatechin molecules (EGC and EGCG) and their derivative (AcEGCG) against DENV, YFV, WNV, and ZIKV NS2B/NS3 protease. Thus, we assayed the effect of the molecules and found that a mixture of the molecules EGC (competitive) and EGCG (noncompetitive) inhibited the virus protease of YFV, WNV, and ZIKV more effectively with IC50 values of 1.17 ± 0.2 µM, 0.58 ± 0.07 µM, and 0.57 ± 0.05 µM, respectively. As these molecules fundamentally differ in their inhibitory mode and chemical structure, our finding may open a new line for developing more effective allosteric/active site inhibitors to combat flaviviruses infection.

Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial infections, many other families of pattern recognition receptors (PRRs) have been described. One of such receptor clusters is composed by, if not all, at least several members of the scavenger receptor cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane receptors of immune cells; however, a small subset consists of secreted receptors that are therefore in circulation. We here describe the first characterization of biological and functional roles of the circulating human protein SSC4D, one of the least scrutinized members of the family. Within leukocyte populations, SSC4D was found to be expressed by monocytes/macrophages, neutrophils, and B cells, but its production was particularly evident in epithelial cells of several organs and tissues, namely, in the kidney, thyroid, lung, placenta, intestinal tract, and liver. Similar to other SRCR proteins, SSC4D shows the capacity of physically binding to different species of bacteria, and this opsonization can increase the phagocytic capacity of monocytes. Importantly, we have uncovered the capacity of SSC4D of binding to several protozoan parasites, a singular feature seldom described for PRRs in general and here demonstrated for the first time for an SRCR family member. Overall, our study is pioneer in assigning a PRR role to SSC4D.

OBJECTIVES: To prospectively evaluate demographic, anthropometric and health-related quality of life (HRQoL) in pediatric patients with laboratory-confirmed coronavirus disease 2019 (COVID-19) METHODS: This was a longitudinal observational study of surviving pediatric post-COVID-19 patients (n=53) and pediatric subjects without laboratory-confirmed COVID-19 included as controls (n=52) was performed. RESULTS: The median duration between COVID-19 diagnosis (n=53) and follow-up was 4.4 months (0.8-10.7). Twenty-three of 53 (43%) patients reported at least one persistent symptom at the longitudinal follow-up visit and 12/53 (23%) had long COVID-19, with at least one symptom lasting for >12 weeks. The most frequently reported symptoms at the longitudinal follow-up visit were headache (19%), severe recurrent headache (9%), tiredness (9%), dyspnea (8%), and concentration difficulty (4%). At the longitudinal follow-up visit, the frequencies of anemia (11% versus 0%, p=0.030), lymphopenia (42% versus 18%, p=0.020), C-reactive protein level of >30 mg/L (35% versus 0%, p=0.0001), and D-dimer level of >1000 ng/mL (43% versus 6%, p=0.0004) significantly reduced compared with baseline values. Chest X-ray abnormalities (11% versus 2%, p=0.178) and cardiac alterations on echocardiogram (33% versus 22%, p=0.462) were similar at both visits. Comparison of characteristic data between patients with COVID-19 at the longitudinal follow-up visit and controls showed similar age (p=0.962), proportion of male sex (p=0.907), ethnicity (p=0.566), family minimum monthly wage (p=0.664), body mass index (p=0.601), and pediatric pre-existing chronic conditions (p=1.000). The Pediatric Quality of Live Inventory 4.0 scores, median physical score (69 [0-100] versus 81 [34-100], p=0.012), and school score (60 [15-100] versus 70 [15-95], p=0.028) were significantly lower in pediatric patients with COVID-19 at the longitudinal follow-up visit than in controls. CONCLUSIONS: Pediatric patients with COVID-19 showed a longitudinal impact on HRQoL parameters, particularly in physical/school domains, reinforcing the need for a prospective multidisciplinary approach for these patients. These data highlight the importance of closer monitoring of children and adolescents by the clinical team after COVID-19.

This study evaluated the effects of dietary macauba pulp on the growth performance, carcass, and pork traits of growing-finishing pigs; and whether differences in residual feed intake breeding values could influence the pigs’ growth responses to macauba pulp inclusion in the diet. A total of 282 (34.8 ± 4.40 kg) pigs (barrows and females), progeny of sires with high (HRFI) or low (LRFI) breeding value for residual feed intake, were pair-housed on the basis of sex, breeding value, and initial BW. Diets with (macauba) or without (control) of 50 g/kg of macauba pulp inclusion were randomly assigned to the experimental pens. There were eight treatment groups: HRFI barrows were fed the control diet; HRFI barrows were fed the macauba diet; LRFI barrows were fed the control diet; LRFI barrows were fed the macauba diet; HRFI female pigs were fed the control diet; HRFI female pigs were fed the macauba diet; LRFI female pigs were fed the control diet; and LRFI female pigs were fed the macauba diet. The trial lasted 90 days and was divided into four phases: growing phase 1 (G1) and 2 (G2); and finishing phases 1 (F1) and 2 (F2). There was no interaction between sex, breeding value, and diet for performance, carcass, and pork traits. Barrows had higher feed intake (ADFI), daily gain (ADG), feed conversion rate (FCR), and final body weight than female pigs. The breeding value had no effect on performance measurements. The inclusion of macauba pulp in the pigs’ diets did not affect any growth parameter during G1, G2 and F1 phases. However, reduced ADFI and improved FCR were observed in F2. Female pigs had lower backfat thickness (BF) and higher loin eye area (LEA) than barrows. HRFI pigs had higher hot carcass weight and LEA, and lower BF than LRFI pigs. There was no effect of macauba pulp inclusion on carcass traits. Pork from barrows presented lower Warner–Bratzler shear force and higher fat content than pork from the females. There was no effect of breeding value on pork traits. Pork from pigs fed the macauba diet showed lower moisture content and water-holding capacity. In conclusion, macauba pulp can partially replace corn without reducing the performance of pigs. Regardless of sex and breeding value for RFI, pigs responded similarly to macauba pulp inclusion in diets.

Two simple, precise, accurate and robust UV zero and first derivative orders spectrophometric methods have been developed and validated for the simultaneous determination of oxytetracycline (OTC) associated either with diclofenac sodium (DICLO) or with piroxicam (PIRO) in veterinary pharmaceuticals, without prior separation of the drugs. These proposed methods are also suitable for individual estimation of each drug in pharmaceutical products for human use. The first method is a zero order spectrophotometry for estimation of OTC at 360 nm in the association with DICLO. The second one employs a first derivative at 339 nm, using a zero-crossing technique to measure the OTC content in the association with PIRO. Both nonsteroidal anti-inflammatory drugs (DICLO and PIRO) were analyzed by first derivative spectrophometric at 298.5 nm (OTC zero-crossing point) in their respective associations. All measurements were carried out in acetronitrile:water (50:50, v/v; pH 2.5) and at room temperature (25 ± 2 °C). Analytical curves were linear (r > 0.9996) in the concentration range of 10.0–80.0 μg mL−1 for OTC, 1.5–25.0 μg mL−1 for DICLO and 2.5–30.0 μg mL−1 for PIRO. The limits of quantification were lower than 1.50 μg mL−1 and the mean of recoveries were within the acceptable limits of 98–102% for all three drugs. The developed methods can be successfully applied in the quality control routine for the simultaneous or individual determination of OTC, DICLO and PIRO in pharmaceutical dosage forms. Keywords: Zero order and derivative spectrophotometry, Veterinary pharmaceuticals, Quality control, Validation

En nuestro país, por lo general, las aulas han sido construidas sin considerar criterios acústicos, generando ambientes inadecuados para el proceso de enseñanza-aprendizaje. Ésta situación, interfiere tanto en el desempeño académico de los alumnos, como en la salud de los docentes. En este trabajo se analizan los principales factores acústicos intervinientes en dicho proceso, tales como: geometría y materiales del recinto, ruido de fondo, tiempos de reverberación y relación señal/ruido. Los resultados evidencian que una cantidad significativa de aulas utilizadas en el dictado de carreras de grado no presentan condiciones adecuadas para el desarrollo del proceso de enseñanza-aprendizaje. Los resultados presentados se obtuvieron en el marco del PID UTN 1658: “Estudio de características principales del campo sonoro en aulas y auditorios.

Laboratories and industries that handle chemicals are ubiquitously prone to leakages. These may occur in storage rooms, cabinets or even in temporary locations, such as workbenches and shelves. A relevant number of these chemicals are corrosive, thus commercial products already exist to prevent material damage and injuries. One strategy consists of the use of absorbing mats, where few display neutralizing properties, and even less a controlled neutralization. Nevertheless, to the authors’ knowledge, the commercially available neutralizing mats are solely dedicated to neutralizing acid or alkali solutions, never both. Therefore, this work describes the development and proof of a completely novel concept, where a dual component active mat (DCAM) is able to perform a controlled simultaneous neutralization of acid and alkali leakages by using microencapsulated active components. Moreover, its active components comprise food-grade ingredients, embedded in nonwoven polypropylene. The acid neutralizing mats contain sodium carbonate (Na2CO3) encapsulated in sodium alginate microcapsules (MC-ASC). Alkali neutralizing mats possess commercial encapsulated citric acid in hydrogenated palm oil (MIRCAP CT 85-H). A DCAM encompasses both MC-ASC and MIRCAP CT 85-H and was able to neutralize solutions up to 10% (v/v) of hydrochloric acid (HCl) and sodium hydroxide (NaOH). The efficacy of the neutralization was assessed by direct titration and using pH strip measurement tests to simulate the leakages. Due to the complexity of neutralization efficacy evaluation based solely on pH value, a thorough conductivity study was performed. DCAM reduced the conductivity of HCl and NaOH (1% and 2% (v/v)) in over 70%. The composites were characterized by scanning electron microscopy (SEM), differential calorimetry (DSC) and thermogravimetric analysis (TGA). The size of MC-ASC microcapsules ranged from 2 μm to 8 μm. Finally, all mat components displayed thermal stability above 150 °C.

Cellulosic ethanol is an alternative for increasing the amount of bioethanol production in the world. In Brazil, sugarcane leads the bioethanol production, and to improve its yield, besides bagasse, sugarcane straw is a possible feedstock. However, the process that leads to cell wall disassembly under field conditions is unknown, and understanding how this happens can improve sugarcane biorefinery and soil quality. In the present work, we aimed at studying how sugarcane straw is degraded in the field after 3, 6, 9, and 12 months. Non-structural and structural carbohydrates, lignin content, ash, and cellulose crystallinity were analyzed. The cell wall composition was determined by cell wall fractionation and determination of monosaccharide composition. Non-structural carbohydrates degraded quickly during the first 3 months in the field. Pectins and lignin remained in the plant waste for up to 12 months, while the hemicelluloses and cellulose decreased 7.4 and 12.4%, respectively. Changes in monosaccharide compositions indicated solubilization of arabinoxylan (xylose and arabinose) and β-glucans (β-1,3 1,4 glucan; after 3 months) followed by degradation of cellulose (after 6 months). Despite cellulose reduction, the xylose:glucose ratio increased, suggesting that glucose is consumed faster than xylose. The degradation and solubilization of the cell wall polysaccharides concomitantly increased the level of compounds related to recalcitrance, which led to a reduction in saccharification and an increase in minerals and ash contents. Cellulose crystallinity changed little, with evidence of silica at the latter stages, indicating mineralization of the material. Our data suggest that for better soil mineralization, sugarcane straw must stay in the field for over 1 year. Alternatively, for bioenergy purposes, straw should be used in less than 3 months.

IntroductionChildhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA.MethodsThis was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention vs. standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [18F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life.ResultsThirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response (P=0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients (P ≤ 0.05).ConclusionsExercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA.Clinical Trial Registrationhttps://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.

β-Glucosidases are a limiting factor in the conversion of cellulose to glucose for the subsequent ethanol production. Here, β-glucosidase production by Malbranchea pulchella was optimized using Composite Central Designs and Response Surface Methodologies from a medium designed. The coefficient of determination (R2) was 0.9960, F-value was very high, and the lack of fit was found to be non-significant. This indicates a statistic valid and predictive result. M. pulchella enzymatic extract was successfully tested as an enzymatic cocktail in a mixture design using sugarcane bagasse, soybean hull and barley bagasse. We proved that the optimization of the β-glucosidase production and the application in hydrolysis using unexpansive biomass and agricultural wastes can be accomplished by means of statistical methodologies. The strategy presented here can be useful for the improvement of enzyme production and the hydrolysis process, arising as an alternative for bioeconomy.

Several neurotropic viruses are members of the flavivirus and alphavirus families. Infections caused by these viruses may cause long-term neurological sequelae in humans. The continuous emergence of infections caused by viruses around the world, such as the chikungunya virus (CHIKV) (Alphavirus genus), the zika virus (ZIKV) and the yellow fever virus (YFV) (both of the Flavivirus genus), warrants the development of new strategies to combat them. Our study demonstrates the inhibitory potential of the water-soluble vitamin riboflavin against NS2B/NS3pro of ZIKV and YFV and nsP2pro of CHIKV. Riboflavin presents a competitive inhibition mode with IC50 values in the medium µM range of 79.4 ± 5.0 µM for ZIKV NS2B/NS3pro and 45.7 ± 2.9 μM for YFV NS2B/NS3pro. Against CHIKV nsP2pro, the vitamin showed a very strong effect (93 ± 5.7 nM). The determined dissociation constants (KD) are significantly below the threshold value of 30 µM. The ligand binding increases the thermal stability between 4 °C and 8 °C. Unexpectedly, riboflavin showed inhibiting activity against another viral protein; the molecule was also able to inhibit the viral entry of CHIKV. Molecular dynamics simulations indicated great stability of riboflavin in the protease active site, which validates the repurposing of riboflavin as a promising molecule in drug development against the viruses presented here.

The respiratory epithelium is highly complex, and its composition varies along the conducting airways and alveoli. In addition to their primary function in maintaining the respiratory barrier and lung homeostasis for gas exchange, epithelial cells interact with inhaled pathogens, which can manipulate cell signaling pathways, promoting adhesion to these cells or hosting tissue invasion. Moreover, pathogens (or their products) can induce the secretion of chemokines and cytokines by epithelial cells, and in this way, these host cells communicate with the immune system, modulating host defenses and inflammatory outcomes. This review will focus on the response of respiratory epithelial cells to two human fungal pathogens that cause systemic mycoses: Aspergillus and Paracoccidioides. Some of the host epithelial cell receptors and signaling pathways, in addition to fungal adhesins or other molecules that are responsible for fungal adhesion, invasion, or induction of cytokine secretion will be addressed in this review.

The potential outcome of flavivirus and alphavirus co-infections is worrisome due to the development of severe diseases. Hundreds of millions of people worldwide live under the risk of infections caused by viruses like chikungunya virus (CHIKV, genus Alphavirus), dengue virus (DENV, genus Flavivirus), and zika virus (ZIKV, genus Flavivirus). So far, neither any drug exists against the infection by a single virus, nor against co-infection. The results described in our study demonstrate the inhibitory potential of two flavonoids derived from citrus plants: Hesperetin (HST) against NS2B/NS3pro of ZIKV and nsP2pro of CHIKV and, Hesperidin (HSD) against nsP2pro of CHIKV. The flavonoids are noncompetitive inhibitors and the determined IC50 values are in low µM range for HST against ZIKV NS2B/NS3pro (12.6 ± 1.3 µM) and against CHIKV nsP2pro (2.5 ± 0.4 µM). The IC50 for HSD against CHIKV nsP2pro was 7.1 ± 1.1 µM. The calculated ligand efficiencies for HST were > 0.3, which reflect its potential to be used as a lead compound. Docking and molecular dynamics simulations display the effect of HST and HSD on the protease 3D models of CHIKV and ZIKV. Conformational changes after ligand binding and their effect on the substrate-binding pocket of the proteases were investigated. Additionally, MTT assays demonstrated a very low cytotoxicity of both the molecules. Based on our results, we assume that HST comprise a chemical structure that serves as a starting point molecule to develop a potent inhibitor to combat CHIKV and ZIKV co-infections by inhibiting the virus proteases.

Abstract Background Use of whole-genome sequence data (WGS) is expected to improve identification of quantitative trait loci (QTL). However, this requires imputation to WGS, often with a limited number of sequenced animals for the target population. The objective of this study was to investigate imputation to WGS in two pig lines using a multi-line reference population and, subsequently, to investigate the effect of using these imputed WGS (iWGS) for GWAS. Methods Phenotypes and genotypes were available on 12,184 Large White pigs (LW-line) and 4943 Dutch Landrace pigs (DL-line). Imputed 660 K and 80 K genotypes for the LW-line and DL-line, respectively, were imputed to iWGS using Beagle v.4.1. Since only 32 LW-line and 12 DL-line boars were sequenced, 142 animals from eight commercial lines were added. GWAS were performed for each line using the 80 K and 660 K SNPs, the genotype scores of iWGS SNPs that had an imputation accuracy (Beagle R2) higher than 0.6, and the dosage scores of all iWGS SNPs. Results For the DL-line (LW-line), imputation of 80 K genotypes to iWGS resulted in an average Beagle R2 of 0.39 (0.49). After quality control, 2.5 × 106 (3.5 × 106) SNPs had a Beagle R2 higher than 0.6, resulting in an average Beagle R2 of 0.83 (0.93). Compared to the 80 K and 660 K genotypes, using iWGS led to the identification of 48.9 and 64.4% more QTL regions, for the DL-line and LW-line, respectively, and the most significant SNPs in the QTL regions explained a higher proportion of phenotypic variance. Using dosage instead of genotype scores improved the identification of QTL, because the model accounted for uncertainty of imputation, and all SNPs were used in the analysis. Conclusions Imputation to WGS using the multi-line reference population resulted in relatively poor imputation, especially when imputing from 80 K (DL-line). In spite of the poor imputation accuracies, using iWGS instead of a lower density SNP chip increased the number of detected QTL and the estimated proportion of phenotypic variance explained by these QTL, especially when dosage scores were used instead of genotype scores. Thus, iWGS, even with poor imputation accuracy, can be used to identify possible interesting regions for fine mapping.

Gastropod Molluscs rely exclusively on the innate immune system to protect from pathogens, defending their embryos through maternally transferred effectors. In this regard, Pomacea snail eggs, in addition to immune defenses, have evolved the perivitellin-2 or PV2 combining two immune proteins into a neurotoxin: a lectin and a pore-forming protein from the Membrane Attack Complex/Perforin (MACPF) family. This binary structure resembles AB-toxins, a group of toxins otherwise restricted to bacteria and plants. Many of these are enterotoxins, leading us to explore this activity in PV2. Enterotoxins found in bacteria and plants act mainly as pore-forming toxins and toxic lectins, respectively. In animals, although both pore-forming proteins and lectins are ubiquitous, no enterotoxins have been reported. Considering that Pomacea snail eggs ingestion induce morpho-physiological changes in the intestinal mucosa of rodents and is cytotoxic to intestinal cells in culture, we seek for the factor causing these effects and identified PmPV2 from Pomacea maculata eggs. We characterized the enterotoxic activity of PmPV2 through in vitro and in vivo assays. We determined that it withstands the gastrointestinal environment and resisted a wide pH range and enzymatic proteolysis. After binding to Caco-2 cells it promoted changes in surface morphology and an increase in membrane roughness. It was also cytotoxic to both epithelial and immune cells from the digestive system of mammals. It induced enterocyte death by a lytic mechanism and disrupted enterocyte monolayers in a dose-dependent manner. Further, after oral administration to mice PmPV2 attached to enterocytes and induced large dose-dependent morphological changes on their small intestine mucosa, reducing the absorptive surface. Additionally, PmPV2 was detected in the Peyer's patches where it activated lymphoid follicles and triggered apoptosis. We also provide evidence that the toxin can traverse the intestinal barrier and induce oral adaptive immunity with evidence of circulating antibody response. As a whole, these results indicate that PmPV2 is a true enterotoxin, a role that has never been reported to lectins or perforin in animals. This extends by convergent evolution the presence of plant- and bacteria-like enterotoxins to animals, thus expanding the diversity of functions of MACPF proteins in nature.

The C30 endopeptidase (3C-like protease; 3CLpro) is essential for the life cycle of SARS-CoV-2 (severe acute respiratory syndrome-coronavirus-2) since it plays a pivotal role in viral replication and transcription and, hence, is a promising drug target. Molecules isolated from animals, insects, plants, or microorganisms can serve as a scaffold for the design of novel biopharmaceutical products. Crotamine, a small cationic peptide from the venom of the rattlesnake Crotalus durissus terrificus, has been the focus of many studies since it exhibits activities such as analgesic, in vitro antibacterial, and hemolytic activities. The crotamine derivative L-peptides (L-CDP) that inhibit the 3CL protease in the low µM range were examined since they are susceptible to proteolytic degradation; we explored the utility of their D-enantiomers form. Comparative uptake inhibition analysis showed D-CDP as a promising prototype for a D-peptide-based drug. We also found that the D-peptides can impair SARS-CoV-2 replication in vivo, probably targeting the viral protease 3CLpro.

A linear electromagnetic energy harvesting device for underwater applications, fabricated with a simple manufacturing process, was developed to operate with movement frequencies from 0.1 to 0.4 Hz. The generator has two coils, and the effect of the combination of the two coils was investigated. The experimental study has shown that the energy capture system was able to supply energy to several ocean sensors, producing 7.77 mJ per second with wave movements at 0.4 Hz. This study shows that this energy is enough to restore the energy used by the battery or the capacitor and continue supplying energy to the sensors used in the experimental work. For an ocean wave frequency of 0.4 Hz, the generator can supply power to 8 sensors or 48 sensors, depending on the energy consumed and its optimization.

Objective: To assess the efficacy of the Baby's Mouth early dental care prevention and promotion program in preventing oral diseases (caries, gingivitis, or malocclusions) in children attended since 2010. Methods: This was a cross‐sectional and cohort study that assessed 252 children between 36 and 60 months of age in both sexes. The children were divided into three groups: G1: effective participants of the program from birth; G2: children who have stopped participating for more than 24 months, and G3: children who have never attended a prevention program. The evaluation was carried out in two stages: first, an interview with the mothers and, afterwards, a clinical children examination to assess the presence of caries, gingivitis, and malocclusion. The chi‐squared test was used for statistical analysis between groups (p

Abstract Background In recent years, there has been increased interest in the study of the molecular processes that affect semen traits. In this study, our aim was to identify quantitative trait loci (QTL) regions associated with four semen traits (motility, progressive motility, number of sperm cells per ejaculate and total morphological defects) in two commercial pig lines (L1: Large White type and L2: Landrace type). Since the number of animals with both phenotypes and genotypes was relatively small in our dataset, we conducted a weighted single-step genome-wide association study, which also allows unequal variances for single nucleotide polymorphisms. In addition, our aim was also to identify candidate genes within QTL regions that explained the highest proportions of genetic variance. Subsequently, we performed gene network analyses to investigate the biological processes shared by genes that were identified for the same semen traits across lines. Results We identified QTL regions that explained up to 10.8% of the genetic variance of the semen traits on 12 chromosomes in L1 and 11 chromosomes in L2. Sixteen QTL regions in L1 and six QTL regions in L2 were associated with two or more traits within the population. Candidate genes SCN8A, PTGS2, PLA2G4A, DNAI2, IQCG and LOC102167830 were identified in L1 and NME5, AZIN2, SPATA7, METTL3 and HPGDS in L2. No regions overlapped between these two lines. However, the gene network analysis for progressive motility revealed two genes in L1 (PLA2G4A and PTGS2) and one gene in L2 (HPGDS) that were involved in two biological processes i.e. eicosanoid biosynthesis and arachidonic acid metabolism. PTGS2 and HPGDS were also involved in the cyclooxygenase pathway. Conclusions We identified several QTL regions associated with semen traits in two pig lines, which confirms the assumption of a complex genetic determinism for these traits. A large part of the genetic variance of the semen traits under study was explained by different genes in the two evaluated lines. Nevertheless, the gene network analysis revealed candidate genes that are involved in shared biological pathways that occur in mammalian testes, in both lines.

This paper represents how typical advanced engineering design can be structured using a set of parameters and objective functions corresponding to the nature of the problem. The set of parameters can be in different types, including integer, real, cyclic, combinatorial, interval, etc. Similarly, the objective function can be presented in various types including integer (discrete), float, and interval. The simulated annealing with crystallization heuristic can deal with all these combinations of parameters and objective functions when the crystallization heuristic presents a sensibility for real parameters. Herein, simulated annealing with the crystallization heuristic is enhanced by combining Bates and Gaussian distributions and by incorporating feedback strategies to emphasize exploration or refinement, or a combination of the two. The problems that are studied include solving an electrical impedance tomography problem with float parameters and a partially evaluated objective function represented by an interval requiring the solution of 32 sparse linear systems defined by the finite element method, as well as an airplane design problem with several parameters and constraints used to reduce the explored domain. The combination of the proposed feedback strategies and simulated annealing with the crystallization heuristic is compared with existing simulated annealing algorithms and their benchmark results are shown. The enhanced simulated annealing approach proposed herein showed better results for the majority of the studied cases.