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BackgroundLeprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells–glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host–pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signaling molecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron–glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae–Schwann cell interaction.MethodsM. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzyme-linked immunosorbent assay.ResultsWe demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB.ConclusionThese findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus.

Abstract The extraction of valuable compounds from dried fruits and vegetables by microwave hydrodiffusion and gravity (MHG) requires previous hydration of the plant material. In this work, ultrasound was used to speed up the hydration of guarana powder before MHG extraction and increase caffeine recovery. The humidification step was speeded up with ultrasound taking only 15 min over 60 min without ultrasound. Water and 50% (v/v) ethanol were evaluated as green solvents for humidification, with a higher concentration of caffeine obtained for the hydroalcoholic solution. Ultrasound pretreatment allowed guarana extracts from MHG with two times more caffeine for both solvents evaluated. Therefore, ultrasound can be used in the hydration step before MHG extraction to reduce time and increase caffeine recovery from guarana powder.

Several technological approaches have been used to develop vaccines against COVID-19, including those based on inactivated viruses, viral vectors, and mRNA. This study aimed to monitor the maintenance of anti-SARS-CoV-2 antibodies in individuals from Brazil according to the primary vaccination regimen, as follows: BNT162b2 (group 1; 22) and ChAdOx1 (group 2; 18). Everyone received BNT162b2 in the first booster while in the second booster CoronaVac, Ad26.COV2.S, or BNT162b2. Blood samples were collected from 2021 to 2023 to analyze specific RBD (ELISA) and neutralizing antibodies (PRNT50). We observed a progressive increase in anti-RBD and neutralizing antibodies in each subsequent dose, remaining at high titers until the end of follow-up. Group 1 had higher anti-RBD antibody titers than group 2 after beginning the primary regimen, with significant differences after the 2nd and 3rd doses. Group 2 showed a more expressive increase after the first booster with BNT162B2 (heterologous booster). Group 2 also presented high levels of neutralizing antibodies against the Gamma and Delta variants until five months after the second booster. In conclusion, the circulating levels of anti-RBD and neutralizing antibodies against the two variants of SARS-CoV-2 were durable even five months after the 4th dose, suggesting that periodic booster vaccinations (homologous or heterologous) induced long-lasting immunity.

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection (‘twinfection’) is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19.

The aim of this study was to evaluate the effect of multilamellar vesicles (MLVs) of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in co-culture with in vitro-produced bovine embryos (IVPEs). The stability of five concentrations of MLVs (1.0, 1.25, 1.5, 1.75, and 2.0 mM) produced using ultrapure water or embryonic culture medium with 24 or 48 h of incubation at 38.5 °C with 5% CO2 was assessed. In addition, the toxicity of MLVs and their modulation of the lipid profile of the plasma membrane of IVPEs were evaluated after 48 h of co-culture. Both media allowed the production of MLVs. Incubation (24 and 48 h) did not impair the MLV structure but affected the average diameter. The rate of blastocyst production was not reduced, demonstrating the nontoxicity of the MLVs even at 2.0 mmol/L. The lipid profile of the embryos was different depending on the MLV concentration. In comparison with control embryos, embryos cultured with MLVs at 2.0 mmol/L had a higher relative abundance of six lipid ions (m/z 720.6, 754.9, 759.0, 779.1, 781.2, and 797.3). This study sheds light on a new culture system in which the MLV concentration could change the lipid profile of the embryonic cell membrane in a dose-dependent manner.

Abstract An ultrasound pretreatment was used to increase anthocyanins content in blackberry juice. Whole fruits were inserted into a glass vessel without contact with any solvent, sonicated in an ultrasonic bath, and then pressed with a manual juicer. The experimental design showed that 7 min at 65% of ultrasound amplitude increased the anthocyanin content in juices from 31 to 56% for BRS Xingu, Guarani, and Xavante cultivars. Two major anthocyanins, cyanidin-3-glucoside and cyanidin-3-rutinoside were found in higher concentrations for sonicated fruits. Therefore, ultrasonic pretreatment of whole fruits increased the anthocyanins in blackberry juices using a simple, fast, and green approach.

ABSTRACT Materials from renewable sources have been increasingly used in construction to assist in sustainable development. Therefore, the use of timber becomes an environmentally advantageous solution, especially if used for long-term purposes, such as in structures. In this sense, this study aimed to evaluate the performance of glued-laminated timber frames reinforced in their main connections. The structures were made using timber from the Araucaria angustifolia species and polyurethane adhesive based on vegetable oils. The frames, on a reduced scale, had a pillar height and free span of 2 m and were reinforced in the connections between the roof beams and pillars. The rupture strength values of the structures averaged 38.02 kN, approximately 5.47 times the design load, and represented a 32% increase in strength compared to non-reinforced structures. The displacements did not reach the normative limit for the design load and presented a linear behavior for strengths higher than three times those of the design. The structures presented satisfactory structural behavior and had an improvement in resistance and rigidity caused by the addition of reinforcements.

Objectives: To describe the differences in clinical presentation and relative disease burden of congenital Zika syndrome (CZS)-associated microcephaly at 2 large hospitals in Salvador, Brazil that serve patients of different socioeconomic status (SES). Methods: Clinical and serologic data were collected prospectively from pregnant women and their infants, who delivered at 2 study centers during the 2015–2016 Zika virus (ZIKV) epidemic in Salvador, Brazil. Results: Pregnant women from Salvador, Brazil delivering in a low SES hospital had 3 times higher ZIKV exposure rate than women at a high SES hospital. However, different SES hospitals had similar prevalence of infants with CZS-associated microcephaly (10% vs 6%, p = 0.16) after controlling for ZIKV exposure in their mothers. Conclusions: Our study supports the positive association between low SES, high maternal ZIKV exposure, and high rates of CZS-associated microcephaly.

Guanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those that showed a high purinoreceptor similarity and were expressed in glioma cells, where GBPs exerted a powerful antiproliferative effect. Of the GPRs chosen, only the silencing of GPR23, also known as lysophosphatidic acid (LPA) 4 receptor, counteracted GBP-induced growth inhibition in U87 cells. Guanine (GUA) was the most potent compound behind the GPR23-mediated effect, acting as the endpoint effector of GBP antiproliferative effects. Accordingly, cells stably expressing GPR23 showed increased sensitivity to GUA. Furthermore, while GPR23 expression was low in a hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)-mutated melanoma cell line showing poor sensitivity to GBPs, and in HGPRT-silenced glioma cells, GPR23-induced expression in both cell types rescued GUA-mediated cell growth inhibition. Finally, binding experiments using [3H]-GUA and U87 cell membranes revealed the existence of a selective GUA binding (KD = 29.44 ± 4.07 nM; Bmax 1.007 ± 0.035 pmol/mg prot) likely to GPR23. Overall, these data suggest GPR23 involvement in modulating responses to GUA in tumor cell lines, although further research needs to verify whether this receptor mediates other GUA effects.

The respiratory system is the main target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 19 (COVID-19) where acute respiratory distress syndrome is considered the leading cause of death. Changes in pulmonary blood vessels, among which an endothelialitis/endotheliitis has been particularly emphasized, have been suggested to play a central role in the development of acute lung injury. Similar vascular changes are also observed in animal models of COVID-19. The present study aimed to determine whether the latter are specific for SARS-CoV-2 infection, investigating the vascular response in the lungs of mice infected with SARS-CoV-2 and other respiratory viruses (influenza A and murine gammaherpesvirus) by in situ approaches (histology, immunohistology, morphometry) combined with RNA sequencing and bioinformatic analysis. Non-selective recruitment of monocytes and T and B cells from larger muscular veins and arteries was observed with all viruses, matched by a comparable transcriptional response. There was no evidence of endothelial cell infection in any of the models. Both the morphological investigation and the transcriptomics approach support the interpretation that the lung vasculature in mice mounts a stereotypic response to alveolar and respiratory epithelial damage. This may have implications for the treatment and management of respiratory disease in humans.

The global demand for minimally processed vegetables (MPVs) has grown, driven by changes in the population’s lifestyle. MPVs are fresh vegetables that undergo several processing steps, resulting in ready-to-eat products, providing convenience for consumers and food companies. Among the processing steps, washing–disinfection plays an important role in reducing the microbial load and eliminating pathogens that may be present. However, poor hygiene practices can jeopardize the microbiological quality and safety of these products, thereby posing potential risks to consumer health. This study provides an overview of minimally processed vegetables (MPVs), with a specific focus on the Brazilian market. It includes information on the pricing of fresh vegetables and MPVs, as well as an examination of the various processing steps involved, and the microbiological aspects associated with MPVs. Data on the occurrence of hygiene indicators and pathogenic microorganisms in these products are presented. The focus of most studies has been on the detection of Escherichia coli, Salmonella spp., and Listeria monocytogenes, with prevalence rates ranging from 0.7% to 100%, 0.6% to 26.7%, and 0.2% to 33.3%, respectively. Foodborne outbreaks associated with the consumption of fresh vegetables in Brazil between 2000 and 2021 were also addressed. Although there is no information about whether these vegetables were consumed as fresh vegetables or MPVs, these data highlight the need for control measures to guarantee products with quality and safety to consumers.

Objective. To establish the risk of microcephaly in neonates born to women infected with ZIKV during pregnancy. Methods. A cohort of laboratory-confirmed ZIKV cases of congenital infections (109 mothers infected during pregnancy and 101 newborns) among 308 suspect cases was followed in Belem, Pará, Brazil, from October 2015 to December 2017. Results. A microcephaly risk of 1.98% (95% CI 0.54-6.93%) was found, or 2 cases among the 101 neonates infected with ZIKV during pregnancy. 72% of the pregnant women had ZIKV infection confirmed by RT-qPCR during gestation. Conclusions. Results showed a low incidence of ZIKV-associated birth defects, stillbirth, and miscarriage, which contrasts with previous studies in other Brazilian regions. Previous exposure to yellow fever vaccine and/or multiserotype DENV infection could be implicated in the protection from ZIKV congenital infection.

Cleomaceae is closely related to Brassicaceae and includes C3, C3–C4, and C4 species. Thus, this family represents an interesting system for studying the evolution of the carbon concentrating mechanism. However, inadequate genetic information on Cleomaceae limits their research applications. Here, we characterized 22 Cleomaceae accessions [3 genera (Cleoserrata, Gynandropsis, and Tarenaya) and 11 species] in terms of genome size; molecular phylogeny; as well as anatomical, biochemical, and photosynthetic traits. We clustered the species into seven groups based on genome size. Interestingly, despite clear differences in genome size (2C, ranging from 0.55 to 1.3 pg) in Tarenaya spp., this variation was not consistent with phylogenetic grouping based on the internal transcribed spacer (ITS) marker, suggesting the occurrence of multiple polyploidy events within this genus. Moreover, only G. gynandra, which possesses a large nuclear genome, exhibited the C4 metabolism. Among the C3-like species, we observed intra- and interspecific variation in nuclear genome size as well as in biochemical, physiological, and anatomical traits. Furthermore, the C3-like species had increased venation density and bundle sheath cell size, compared to C4 species, which likely predisposed the former lineages to C4 photosynthesis. Accordingly, our findings demonstrate the potential of Cleomaceae, mainly members of Tarenaya, in offering novel insights into the evolution of C4 photosynthesis.

Abstract Italy is significantly affected by ever-present flood and landslide risks and has experienced many disasters. Local social awareness and engagement, however, differ and need to be increased by decision makers and citizens through improvements in risk preparedness. With this aim, the #italiasicura web platform was developed by Fondazione Politecnico di Milano and released in 2015 to show country to local level hazard maps and risk reduction projects in Italy. Any stage of the user experience with the platform can be shared via social media. Using this tool, an awareness-oriented web analytics process was structured to develop a set of indicators for the increase of knowledge linked to flood and landslide hazards. In so doing, it is possible to measure community disaster awareness actions and competence in the area of hazard knowledge. This article presents the results obtained by using data from the platform.

Abstract Background Broad copy number aberrations (BCNAs) represent a common form of genome instability in colorectal cancer (CRC). CRCs show large variations in their level of aneuploidy: microsatellite-instable (MSI) tumors are known to have a near-diploid karyotype while microsatellite-stable (MSS) tumors show high level of chromosomal instability. However, MSS tumors have great heterogeneity in the number of BCNAs, with a minor percentage of samples showing an almost normal karyotype. In the present work we subdivided MSS CRCs according to a “BCNA score” and characterized their transcriptome profiles, considered as a proxy to their phenotypic features. Methods Microsatellite testing, genome-wide DNA copy number and whole-transcript expression analysis (HTA) were performed on 33 tumor samples and 25 normal colonic tissue samples from 32 CRC patients. 15.1% of the samples were MSI tumors (n = 5), whereas 84.9% were MSS tumors (n = 28). Gene expression data of 34 additional MSI tumors was retrieved from a public functional genomics data repository. Results Using as a threshold the first quartile of the BCNA score distribution, MSS samples were classified as low-BCNA (LB, n = 7) or high-BCNA (HB, n = 21). LB tumors were enriched for mucinous CRCs and their gene-expression profile resembled that of MSI samples for what concerns a subset of genes involved in secretory processes, mucosal protection, and extracellular matrix remodeling. HB tumors were predominantly non-mucinous adenocarcinomas and showed overexpression of a subset of genes typical of surface colonocytes and EGF signaling. A large percentage of unclassified samples according to the consensus molecular subtypes (CMS) classifier was found in the LB group (43%), whereas 76% HB tumors belonged to CMS2. Conclusions A classification of colorectal tumors based on the number of BCNAs identifies two groups of MSS tumors which differ for histopathology and gene expression profile. Such information can be exploited for its translational relevance in different aspects of CRC clinical management.

Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated.

The COVID-19 pandemic is the biggest public health threat facing the world today. Multiple vaccines have been approved; however, the emergence of viral variants such as the recent Omicron raises the possibility of booster doses to achieve adequate protection. In Brazil, the CoronaVac (Sinovac, Beijing, China) vaccine was used; however, it is important to assess the immune response to this vaccine over time. This study aimed to monitor the anti-SARS-CoV-2 antibody responses in those immunized with CoronaVac and SARS-CoV-2 infected individuals. Samples were collected between August 2020 and August 2021. Within the vaccinated cohort, some individuals had a history of infection by SARS-CoV-2 prior to immunization, while others did not. We analyzed RBD-specific and neutralizing-antibodies. Anti-RBD antibodies were detected in both cohorts, with a peak between 45–90 days post infection or vaccination, followed by a steady decline over time. In those with a previous history of COVID-19, a higher, longer, more persistent response was observed. This trend was mirrored in the neutralization assays, where infection, followed by immunization, resulted in higher, longer lasting responses which were conditioned on the presence of levels of RBD antibodies right before the vaccination. This supports the necessity of booster doses of CoronaVac in due course to prevent serious disease.

The Carajás Mineral Province has one of the largest concentrations of caves in Brazil, and its iron ore is among the country’s main exports. As a result of iron ore intense extraction, new environmental policies have been implemented. In an attempt to balance economic activity and environmental conservation, an inventory and a relevance-based classification of caves were implemented in 2008 as criteria for environmental licensing of mining ventures. This implementation motivated the present study of phosphate speleothems in Carajás’ caves developed in ferriferous rocks. The objectives of this study are to describe the phosphate minerals and their formation processes based on geochemical and petrographic analysis, X-ray powder diffraction (XRD), differential scanning calorimetry coupled with thermogravimetry (DSC-TG), Fourier-transform infrared (FTIR) and scanning electron microscopy (SEM). Eight caves were selected for this study, along the slopes of the plateaus from Carajás. The phosphate speleothems usually present compositional zoning, with strengite-phosphosiderite in the core and leucophosphite-spheniscidite on the edges. This zoning cannot be related to leucophosphite-spheniscidite decomposition, since the DSC-TG curves show that dehydroxylation and loss of NH3 from leucophosphite-spheniscidite require temperatures higher than 250°C. FTIR results allowed us to identify the NH4 functional group, based on absorbance bands at 1,430 and 3,040 cm-1, which associated to other data confirm the presence of spheniscidite. Refined values of the unit cell parameters for spheniscidite (a = 9.803 Å, b = 9.722 Å, c = 9.858 Å, β = 102.78°) obtained using the Rietveld refinement, were slightly lower than those of the ICSD-39654 file. These smaller values are attributed to increasing substitutions of K+ for NH4+, and Al3+ for Fe3+. Based on the geochemical analysis, significant enrichment in P2O5, Zn, Ni, and Rb was detected in phosphate speleothems, and phosphatized laterite, suggesting that bat guano was a potential source of these elements.

Reporter virus neutralization test (RVNT) has been used as an alternative to the more laborious and time-demanding conventional PRNT assay for both DENV and ZIKV. However, few studies have investigated how these techniques would perform in epidemic areas with the circulation of multiple flavivirus. Here, we evaluate the performance of ZIKV and DENV Rluc RVNT and ZIKV mCh RVNT assays in comparison to the conventional PRNT assay against patient sera collected before and during ZIKV outbreak in Brazil. These samples were categorized into groups based on (1) acute and convalescent samples according to the time of disease, and (2) laboratorial diagnostic results (DENV and ZIKV RT-PCR and IgM-capture ELISA). Our results showed that DENV Rluc assay presented 100% and 78.3% sensitivity and specificity, respectively, with 93.3% accuracy, a similar performance to the traditional PRNT. ZIKV RVNT90, on the other hand, showed much better ZIKV antibody detection performance (around nine-fold higher) when compared to PRNT, with 88% clinical sensitivity. Specificity values were on average 76.8%. Even with these results, however, ZIKV RVNT90 alone was not able to reach a final diagnostic conclusion for secondary infection in human samples due to flavivirus cross reaction. As such, in regions where the flavivirus differential diagnosis represents a challenge, we suggest the establishment of a RVNT panel including other flaviviruses circulating in the region, associated with the other serological techniques such as IgM ELISA and the investigation of seroconversion, in order to help define an accurate diagnostic conclusion using serology.

Quantitative data on observed flood ground effects are precious information to assess current risk levels and to improve our capability to forecast future flood damage, with the final aim of defining effective prevention policies and checking their success. This paper presents the first collection and analysis of flood damage claims produced in Italy in the past 7 years since a homogeneous national procedure for damage recognition became available. The database currently contains more than 70,000 claims referring to significant events and shows good homogeneity on the intensity of the related phenomena. We then propose an empirical model, based on observed data, to allow for a quick estimation of direct damage to private assets (i.e., residential buildings), based only on the knowledge of the perimeter of the flooded area. Single model calibration was performed at the multi-regional scale, focused on southern Italy. Model validation shows encouraging performances, considering the considerable natural uncertainty that characterizes this type of estimate. The procedure is of great interest when there is a need to evaluate, however roughly, flood damage in the immediacy of the event to assess the extent of the flood effects and to plan support actions for the affected communities.

Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (SPINK2, TMA7, SPCS2, CDCP1, CAPZA1, FGFR1OP2, MAN1A2, NT5C3A and SRP54. In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.

Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A1R (CPA, CCPA) or A2AR (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective A1R (DPCPX) or A2AR (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [3H]GUO binding became saturable at 100–300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [3H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [3H]GUO binding, but the sum of the two effects was able to displace [3H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by A1R and A2AR agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs.

The problem of levee embankment control during high flows is crucial for flood risk management in floodplains. Levee defense lines are often hundreds of kilometers long and surveys during emergencies are not easy tasks. For these reasons, levees monitored with in situ sensors and a suitable Information Technology (IT) real-time data communication and integration infrastructure, so-called “smart levees”, are gaining increasing interest as a crucial protection technology in floodplains. The paper presents the conceptualization of a prototype of a levee smart revetment, based on the integration of an optical fiber (OF) cable into a steel double-twisted wire mesh. In this paper the feasibility of this kind of revetment is firstly assessed. The flow pattern of overtopping water on the embankment is discussed, thus producing a raw estimation of the shear stress acting on the revetment in the field. A sample case is then analyzed in both numerical and laboratory tests. For this purpose, a numerical Finite Element Model (FEM) to describe the mechanical behavior of a double-twisted wire mesh when loaded along its own plane is presented. Numerical results indicate that the related strain, relatively low as compared to the steel wire yield stress, can be fully detected by the optical fiber continuous Brillouin sensor. This has been validated by the experimental activity performed and a digital twin of the prototype of the smart revetment, suitable for virtually testing the product under any load and constraint conditions and tailoring the production process, has been created.

Mounting evidence suggests that the guanine-based purines stand out as key player in cell metabolism and in several models of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. Guanosine (GUO) and guanine (GUA) are extracellular signaling molecules derived from the breakdown of the correspondent nucleotide, GTP, and their intracellular and extracellular levels are regulated by the fine-tuned activity of two major enzymes, purine nucleoside phosphorylase (PNP) and guanine deaminase (GDA). Noteworthy, GUO and GUA, seem to play opposite roles in the modulation of cognitive functions, such as learning and memory. Indeed GUO, despite exerting neuroprotective, anti-apoptotic and neurotrophic effects, causes a decay of cognitive activities, whereas GUA administration in rats results in working memory improvement (prevented by L-NAME pre-treatment). This study was designed to investigate, in a model of SH-SY5Y neuroblastoma cell line, the signal transduction pathway activated by extracellular GUA. Altogether, our results showed that: (i) in addition to an enhanced phosphorylation of ASK1, p38 and JNK, likely linked to a non-massive and transient ROS production, the PKB/NO/sGC/cGMP/PKG/ERK cascade seems to be the main signaling pathway elicited by extracellular GUA; (ii) the activation of this pathway occurs in a pertussis-toxin sensitive manner, thus suggesting the involvement of a putative G protein coupled receptor; (iii) the GUA-induced NO production, strongly reduced by cell pre-treatment with L-NAME, is negatively modulated by the EPAC-cAMP-CaMKII pathway, which causes the over-expression of GDA that, in turn, reduces the levels of GUA. These molecular mechanisms activated by GUA may be useful to support our previous observation showing that GUA improves learning and memory functions through the stimulation of NO signaling pathway, and underscore the therapeutic potential of oral administration of guanine for treating memory-related disorders.

Genomic location can inform on potential function and recruitment signals for chromatin-associated proteins. High mobility group (Hmg) proteins are of similar size as histones with Hmga1 and Hmga2 being particularly abundant in replicating normal tissues and in cancerous cells. While several roles for Hmga proteins have been proposed we lack a comprehensive description of their genomic location as a function of chromatin, DNA sequence and functional domains. Here we report such a characterization in mouse embryonic stem cells in which we introduce biotin-tagged constructs of wild-type and DNA-binding domain mutants. Comparative analysis of the genome-wide distribution of Hmga proteins reveals pervasive binding, a feature that critically depends on a functional DNA-binding domain and which is shared by both Hmga proteins. Assessment of the underlying queues instructive for this binding modality identifies AT richness, defined as high frequency of A or T bases, as the major criterion for local binding. Additionally, we show that other chromatin states such as those linked to cis-regulatory regions have little impact on Hmga binding both in stem and differentiated cells. As a consequence, Hmga proteins are preferentially found at AT-rich regions such as constitutively heterochromatic regions but are absent from enhancers and promoters arguing for a limited role in regulating individual genes. In line with this model, we show that genetic deletion of Hmga proteins in stem cells causes limited transcriptional effects and that binding is conserved in neuronal progenitors. Overall our comparative study describing the in vivo binding modality of Hmga1 and Hmga2 identifies the proteins' preference for AT-rich DNA genome-wide and argues against a suggested function of Hmga at regulatory regions. Instead we discover pervasive binding with enrichment at regions of higher AT content irrespective of local variation in chromatin modifications.

Pfaffia glomerata contains high levels of β-ecdysone, which has shown a range of beneficial pharmacological effects. The present study demonstrated that inflorescences of P. glomerata contain other important bioactive compounds in addition to β-ecdysone. The identification of compounds from inflorescences using liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was performed for the first time. The eight compounds identified were β-ecdysone, flavonoid glycosides such as quercetin-3-O-glucoside, kaempferol-3-O-glucoside and kaempferol-3-O-(6-p-coumaroyl)-glucoside, oleanane-type triterpenoid saponins such as ginsenoside Ro and chikusetsusaponin IV, in addition to oleanonic acid and gluconic acid. This study provided information on the phytochemicals contained in P. glomerata inflorescences revealing the potential application of this plant part as raw material for the phytotherapeutic and cosmetic industries.

This study aimed to assess the foodborne diseases (FBD) outbreaks reported in Brazil between 2000 and 2018, based on data from the Brazilian Ministry of Health (official data) and from scientific literature. According to official data, 13,163 FBD outbreaks were reported in the country during this period, involving 247,570 cases and 195 deaths. The largest prevalence of FBD outbreaks was observed in the Southeast region of Brazil (45.6%). In most outbreaks it was not possible to determine the food implicated (45.9%) but among those identified, water was the most frequently associated (12.0%). The etiological agent was not identified in most outbreaks (38.0%), while Salmonella (14.4%) was the most frequently reported among those identified. Homes were the main site of FBD occurrence (12.5%). Regarding data obtained from the scientific literature, 57 articles dealing with FBD in the country throughout the same period were selected and analyzed. Based on these articles, mixed foods were the most prevalent in the outbreaks (31.6%), Salmonella spp. was the pathogen most frequently reported (22.8%) and homes were also the main site of FBD occurrence (45.6%). Despite under-notification, the records of FBD outbreaks that have occurred in Brazil in the past recent years show alarming data, requiring attention from health authorities. The notification of outbreaks is essential to facilitate public health actions.

Benzoquinones are usually present in arthropod defence exudates. Here, we describe the chemical profiles of 12 harvestman species belonging to the neotropical family Gonyleptidae. Nine of the studied species produced benzoquinones, while three produced alkyl phenols. Two benzoquinones and one phenol exhibited biological activity against bacteria and fungi. We also studied the biosynthesis of 2-ethyl-1,4-benzoquinone by feeding Magnispina neptunus individuals with 13C-labelled precursors; the benzoquinones were biosynthesised through a polyketide pathway using acetate and propionate building blocks.

This paper aimed to evaluate the initial growth of "mutambo" seedlings in different conditions of light intensity and treatments with gibberellic acid (GA). The seedlings were kept under full sun and 50% of shading. Sixty days after the emergence, seedlings were sprayed with: 1) 100 mg L-1 GA3; 2) 200 mg L-1 GA3; 3) control. At the end of the appraisals, seedlings height under 50% of shading was compared to the height that were growing under full sun with 200 mg L-1 GA. Stem diameter was lower under shading. Leaf area did not vary among the treatments, but the root system growth was higher under full sun and did not vary among GA levels. The number of stomata, trichomes and epidermal cells on adaxial and abaxial sides was higher under full sun. Total dry masses of leaf and root were highe runder full sun and with 200 mg L-1 GA application. "Mutambo" seedlings presented a higher initial growth under full sun, although with a lower height, diameter, and lenght of the largest root and total dry masses of leaf and root were higher. A concentration with 200 mg L-1 promoted a higher growthO objetivo desse trabalho foi avaliar o crescimento inicial das mudas de mutambo em diferentes condições de luminosidade e tratamentos com ácido giberélico (GA). As mudas foram mantidas em sombrite 50% de sombra e a pleno sol e aos 60 dias após a emergência as mudas foram pulverizadas com: 1) ácido giberélico 100 mg L-1; 2) ácido giberélico 200 mg. L-1 e 3) testemunha. Ao final das avaliações a altura sob 50% de sombreamento foi maior comparada com aquelas crescendo a pleno sol com GA 200 mg L-1. O diâmetro de colo foi menor sob sombreamento. A área foliar não variou entre os tratamentos, porém o crescimento do sistema radicular foi maior a pleno sol não variando entre os níveis de GA. O número de estômatos, tricomas e células epidérmicas nas faces adaxial e abaxial foram maiores a pleno sol. As massas secas total, de folha e raiz foi maior a pleno sol e com aplicação deGA 200 mg L-1. As mudas de mutambo apresentaram umcrescimento inicial melhor a pleno sol, embora com menoraltura, o diâmetro, o comprimento da maior raiz e a massaseca total, de folha e de raiz foram maiores. A concentraçãode 200 mg L-1 de GA promoveu maior crescimento

The aim of this work is to evaluate the influence of octene-1 incorporation in the polybutadiene chain on the polymerization reaction and polymer characteristics. Thus, copolymerization of butadiene-1,3 with octene-1 using a Ziegler-Natta ternary catalyst based on neodymium was performed. The weight ratios of butadiene-1,3/α-olefin 100/0, 99/1, 97/3, 95/5, 90/10, 80/20 and 70/30 were evaluated. The copolymers were characterized by size exclusion chromatography (SEC), infrared spectroscopy (FTIR) and thermogravimetric analysis (TG). The results showed that the degradation temperature (Tmax) was not affected by the addition of alpha-olefin, while the thermal behavior has undergone significant changes. The polymer microstructure was not influenced by the increasing of octene-1 content. However, a tendency to molecular mass increase was observed with the increasing of octene-1 content. It was also observed a trend in reduction of the polymerization conversion as the octene-1 content increased.

Misturas de elastômeros vêm sendo largamente utilizadas na indústria de borracha com a finalidade de se conseguir propriedades específicas, sem a necessidade de sintetizar novos polímeros. O polibutadieno puro (BR) não apresenta boas características de processamento e de resistência à tração e ao rasgamento sendo, por essa razão, normalmente utilizado em misturas com outros elastômeros, principalmente NR e SBR. Tais misturas são amplamente utilizadas na indústria de pneus. Neste trabalho o polibutadieno (BR) foi misturado à borracha natural (NR) na proporção de 1:1 em peso. As composições foram preparadas em misturador de cilindros, empregando-se quatro maneiras distintas de incorporação dos aditivos. Após a vulcanização, foram estudadas as propriedades mecânicas (resistência à tração, ao rasgamento e dureza) e a morfologia das composições. Os resultados mostram que, apesar de apresentarem a mesma formulação, as propriedades das misturas são bastante influenciadas pelo modo de preparo.Elastomer Blends have been widely used in the rubber industry with the purpose of reaching specific properties without the need of synthesizing new polymers. Polybutadiene rubber (BR) presents poor stress and tear strengths, which is the main reason why BR is usually blended with NR and SBR. These blends are extensively used in the manufacture of tyres. In this work natural rubber (NR) was mixed to polybutadiene rubber (BR) in a 50:50 w/w ratio. The compositions were prepared in a two-roll mill employing four different modes of introducing the additives. After vulcanization, the mixtures were studied with evaluation of their mechanical (stress and tear strengths and hardness) properties and morphology. The results show that the properties varied even using the same NR/BR formulations due to the different preparation techniques.

A temperatura da água exerce influência sobre o seu consumo pelas aves e sobre a produtividade das mesmas. Entretanto, existe carência de informações comparando a temperatura da água entre os bebedouros mais comumente empregados em aviários de postura no Brasil. Neste trabalho, avaliou-se a variação da temperatura da água para dois tipos de bebedouro: "nipple" e calha. O experimento foi conduzido em uma instalação comercial de postura, localizada na região Oeste do Paraná. Para a determinação da temperatura da água, das 8 às 18 h, foram instalados termômetros de mercúrio com o bulbo inserido no interior da água em bebedouros tipo "nipple" e calha, em dois galpões idênticos. Foi estimado o ITGU do ambiente a partir de dados obtidos de termômetros de globo negro instalados em local próximo ao da coleta de temperatura da água, na região central dos galpões. Os maiores valores de temperatura da água foram observados no sistema "nipple", que atingiu 31 ºC às 16 h, em média, enquanto no sistema calha atingiu 26,4 ºC. Observou-se a existência de relação entre a temperatura da água e os valores de ITGU, sendo o maior coeficiente de correlação encontrado para o sistema "nipple", de R² = 0,9040, enquanto para o sistema de calha foi de R² = 0,8424. Desconsiderando o aspecto sanitário, para as condições em que o trabalho foi desenvolvido, pode-se concluir que o melhor sistema, em termos de temperatura da água de bebida, foi o tipo calha.Animal's water consumption and productivity are influenced by the drinking water temperature. However, there is a lack of information comparing water temperature in nipple and continuous drinker systems, commonly employed in Brazilian layer hens housing. In this research, drinking water temperature variation was evaluated considering two waterier systems: nipple and continuous. The trial was conduced in a laying hens commercial housing, located in the West region of Paraná State, Brazil. For the water temperature recording, thermometers were placed inside the water in the nipple and the continuous drinker systems, in two similar buildings, from 8:00 AM to 6:00 PM. The BGHI (black globe humidity index) was estimated using the obtained data from black globe thermometers placed near the place where water temperature was recorded, in the central area of the building. The highest water temperature values were observed in the nipple system, that reached 31 ºC at 4:00 PM (average values), while in the continuous system it reached 26.4 ºC. A relation between water temperature and environmental BGHI values was calculated. The highest correlation coefficient was found for the nipple system. Without considering the sanitary aspect for the conditions in which the work was developed, it can be concluded that the best system is the continuous waterier, in terms of drinking water temperature.

O potencial do óleo de mamona como um ativador para a vulcanização de composições de borracha natural (NR) contendo sílica foi investigado. Utilizando-se um planejamento de experimentos adequado, manteve-se a concentração de sílica e outros aditivos constantes enquanto as quantidades de ácido esteárico, óleo de mamona e poli(etileno-glicol) foram variadas. A cura foi conduzida em um reômetro de disco oscilatório TI-100 e a variável de controle escolhida foi a resistência à tração. Os resultados demonstraram que o óleo de mamona sozinho não exerce influência considerável sobre o desempenho mecânico da borracha natural em presença de sílica.

O objetivo deste trabalho foi analisar a pele de três espécies de peixes (piavuçu Leporinus macrocephalus, pacu prata Mylossoma sp e piraputanga Brycon hilarii) através de análise histologica e morfometrica e testes de resistência após o curtimento. Amostras de peles da região dorsal foram coletadas, fixadas em Bouin por 24 horas, incluídas em parafina, cortadas em 5 µm de espessura e coradas por Hematoxilina-eosina. Os cortes foram analisados pela microscopia de luz. Foi utilizado o dinamômetro EMIC para a análise físico-mecânica do couro em 10 amostras no sentido longitudinal a partir da região dorsal do peixe de cada espécie. A derme desses peixes possui um padrão estrutural comum aos teleósteos, porém a disposição e distribuição das fibras colágenas apresentaram-se diferentes entre as espécies analisadas. Através da análise morfométrica constatou-se que a espessura da derme da pele diferiu entre as três espécies. Não houve diferença no teste de resistência à tração no couro da piraputanga (16,88 N/mm²) e piavuçu (18,50 N/mm²). Os resultados para os couros destas duas espécies de peixes foram superiores ao pacu (11,83 N/mm²). O valor de alongamento até a ruptura foi superior para piavuçu (52,83%) e piraputanga (60,45%), não diferindo entre eles, porém foi inferior para o pacu (33,83%). O rasgamento progressivo foi maior no couro de pacu (36,51 N/mm). As peles das três espécies analisadas podem ser transformadas em couro para sua aplicação em diversos artefatos.

BackgroundThe state of Pará encompasses 26% of Brazilian Amazon where an enormous diversity of arboviruses has been found. This study aimed to assess the prevalence and distribution of hemagglutination-inhibition antibodies against antigens of six Flavivirus(yellow fever virus, Ilheus virus, Saint Louis encephalitis virus, Cacipacore virus, Bussuquara virus and Rocio virus) in water buffaloes in Pará state, Brazil. The prevalence of antibodies in these farm animals is important to determine the circulating arboviruses.FindingsAll investigated arboviruses were detected in the species studied and our results indicate that water buffaloes are susceptible to Flavivirusinfection. Furthermore, there is solid evidence of active circulation of these viruses in the Brazilian Amazon.ConclusionsWater buffaloes showed higher prevalence of heterotypic antibody reactions and we hypothesized that they can serve as sentinels to detect the movement of such arboviruses in the Brazilian Amazon.

Quantitative bibliographical research, sub-project of a work entitled “Management Model of Nursing Ambulatory Care to the Patient with Hypertension”, aims to raise scientific production concerning Nursing ambulatory care to the patient with Hypertension. Thirty eight national publications located in the Nursing Database (BDENF) have been used, from the 90’s to our current days. Results: in the analyzed period, there has been ample advertising of the theme in respectable Brazilian scientific magazines, most of which having been published between 1996 and 2002 in the Southern region, mainly in the states of São Paulo and Rio de Janeiro. Conclusion: there should be better distribution of the scientific work concerning the theme, by nursing professionals to keep them updated with the techniques used in nursing ambulatory care to the patient with hypertension, focussing on non-hypertension medicated treatment.

Inclusion of students with autism has been a challenge for educators who indicate gaps in professional training, especially regarding interventions in the school context. The international literature shows evidence of the effectiveness of a type of intervention not found in the national literature, called peer-mediated intervention (PMI). This study aims to review the PMI in the education of students with autism and its implications for research and pedagogical practice. The theoretical principles of child development behind this intervention are examined to describe the evolution of different procedures and methodologies historically used. Research shows effectiveness of this intervention for improving social skills of special education students and, more recently, for academic learning of children with autism. The broad use from naturalistic to controlled environments, the low cost, and complexity favor its use as a pedagogical practice by kindergarten teachers in inclusive settings. However, the need of future studies addressing this topic in the Brazilian educational context is identified. [This is an unofficial English translation provided by the authors and has not been peer-reviewed.]

Background: Leprosy is a chronic infectious disease caused by Mycobacterium leprae, which can lead to a disabling neurodegenerative condition. M. leprae preferentially infects skin macrophages and Schwann cells-glial cells of the peripheral nervous system. The infection modifies the host cell lipid metabolism, subverting it in favor of the formation of cholesterol-rich lipid droplets (LD) that are essential for bacterial survival. Although researchers have made progress in understanding leprosy pathogenesis, many aspects of the molecular and cellular mechanisms of host-pathogen interaction still require clarification. The purinergic system utilizes extracellular ATP and adenosine as critical signalingmolecules and plays several roles in pathophysiological processes. Furthermore, nucleoside surface receptors such as the adenosine receptor A2AR involved in neuroimmune response, lipid metabolism, and neuron-glia interaction are targets for the treatment of different diseases. Despite the importance of this system, nothing has been described about its role in leprosy, particularly adenosinergic signaling (AdoS) during M. leprae-Schwann cell interaction. Methods: M. leprae was purified from the hind footpad of athymic nu/nu mice. ST88-14 human cells were infected with M. leprae in the presence or absence of specific agonists or antagonists of AdoS. Enzymatic activity assays, fluorescence microscopy, Western blotting, and RT-qPCR analysis were performed. M. leprae viability was investigated by RT-qPCR, and cytokines were evaluated by enzymelinked immunosorbent assay. Results: We demonstrated that M. leprae-infected Schwann cells upregulated CD73 and ADA and downregulated A2AR expression and the phosphorylation of the transcription factor CREB (p-CREB). On the other hand, activation of A2AR with its selective agonist, CGS21680, resulted in: 1) reduced lipid droplets accumulation and pro-lipogenic gene expression; 2) reduced production of IL-6 and IL-8; 3) reduced intracellular M. leprae viability; 4) increased levels of p-CREB. Conclusion: These findings suggest the involvement of the AdoS in leprosy neuropathogenesis and support the idea that M. leprae, by downmodulating the expression and activity of A2AR in Schwann cells, decreases A2AR downstream signaling, contributing to the maintenance of LD accumulation and intracellular viability of the bacillus. [ABSTRACT FROM AUTHOR]

COVID-19 is a spectrum of clinical symptoms in humans caused by infection with SARS-CoV-2. The coalescence of SARS-CoV-2 with seasonal respiratory viruses, particularly influenza viruses, is a global health concern. To understand this, transgenic mice expressing the human ACE2 receptor (K18-hACE2) were infected with influenza A virus (IAV) followed by SARS-CoV-2 and the host response and effect on virus biology was compared to K18-hACE2 mice infected with IAV or SARS-CoV-2 alone. The sequentially infected mice showed reduced SARS-CoV-2 RNA synthesis, yet exhibited more rapid weight loss, more severe lung damage and a prolongation of the innate response compared to the singly infected or control mice. Sequential infection also exacerbated the extrapulmonary encephalitic manifestations associated with SARS-CoV-2 infection. Conversely, prior infection with a commercially available, multivalent live-attenuated influenza vaccine (Fluenz Tetra) elicited the same reduction in SARS-CoV-2 RNA synthesis, albeit without the associated increase in disease severity. This suggests that the innate immune response stimulated by IAV inhibits SARS-CoV-2. Interestingly, infection with an attenuated, apathogenic influenza vaccine does not result in an aberrant immune response and enhanced disease severity. Taken together, the data suggest coinfection ('twinfection') is deleterious and mitigation steps should be instituted as part of the comprehensive public health and management strategy of COVID-19. [ABSTRACT FROM AUTHOR]