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A major outbreak of yellow fever (YF) occurred in Brazil during 2016-2018. Epizootics in New World nonhuman primates are sentinel events for YF virus circulation. However, genus-specific susceptibilities and suitability for YF surveillance remain poorly understood. We obtained and compared epidemiologic, histopathologic, immunohistochemical, and molecular results from 93 human and 1,752 primate cases submitted during the recent YF outbreak in Brazil (2017), with the support of the Brazilian National YF Surveillance Program. We detected heterogeneous YF-associated profiles among the various genera of primates we analyzed. Alouatta primates were the most reliable sentinel; Sapajus and Callicebus primates had higher viral loads but lower proportional mortality rates. Callithrix primates were the least sensitive, showing lower viral loads, lower proportional mortality rates, and no demonstrable YF virus antigen or extensive lesions in liver, despite detectable viral RNA. These differences in susceptibility, viral load, and mortality rates should be considered in strategic surveillance of epizootics and control measures for YF.

The Zika Virus (ZIKV) is an emerging arbovirus of great public health concern, particularly in the Americas after its last outbreak in 2015. There are still major challenges regarding disease control, and there is no ZIKV vaccine currently approved for human use. Among many different vaccine platforms currently under study, the recombinant envelope protein from Zika Virus (rEZIKV) constitutes an alternative option for vaccine development and has great potential for monitoring ZIKV infection and antibody response. This study describes a method to obtain a bioactive and functional rEZIKV using an E. coli expression system, with the aid of a 5-L airlift bioreactor and following an automated fast protein liquid chromatography (FPLC) protocol, capable of obtaining high yields of approximately 20 mg of recombinant protein per liter of bacterium cultures. The purified rEZIKV presented preserved antigenicity and immunogenicity. Our results show that the use of an airlift bioreactor for the production of rEZIKV is ideal for establishing protocols and further research on ZIKV vaccines bioprocess, representing a promising system for the production of a ZIKV envelope recombinant protein-based vaccine candidate.

São Paulo (SP), a densely inhabited state in southeast Brazil that contains the fourth most populated city in the world, recently experienced its largest yellow fever virus (YFV) outbreak in decades. YFV does not normally circulate extensively in SP, so most people were unvaccinated when the outbreak began. Surveillance in non-human primates (NHPs) is important for determining the magnitude and geographic extent of an epizootic, thereby helping to evaluate the risk of YFV spillover to humans. Data from infected NHPs can give more accurate insights into YFV spread than when using data from human cases alone. To contextualise human cases, identify epizootic foci and uncover the rate and direction of YFV spread in SP, we generated and analysed virus genomic data and epizootic case data from NHP in SP. We report the occurrence of three spatiotemporally distinct phases of the outbreak in SP prior to February 2018. We generated 51 new virus genomes from YFV positive cases identified in 23 different municipalities in SP, mostly sampled from non-human primates between October 2016 and January 2018. Although we observe substantial heterogeneity in lineage dispersal velocities between phylogenetic branches, continuous phylogeographic analyses of generated YFV genomes suggest that YFV lineages spread in SP state at a mean rate of approximately 1km per day during all phases of the outbreak. Viral lineages from the first epizootic phase in northern SP subsequently dispersed towards the south of the state to cause the second and third epizootic phases there. This alters our understanding of how YFV was introduced into the densely populated south of SP state. Our results shed light on the sylvatic transmission of yellow fever in highly fragmented forested regions in SP state and highlight the importance of continued surveillance of zoonotic pathogens in sentinel species. Competing Interest Statement The authors have declared no competing interest.

The use of media by children in early childhood is increasingly common, and it is necessary to investigate the determinants of screen time, which is understood as the total child screen exposure time, including television and interactive media. This is a descriptive, exploratory, and cross-sectional study conducted with 180 children between 24 and 42 months of age, allocated in Group 1, less than two hours daily screen exposure time; Group 2, daily screen exposure time equal to or more than two hours. Bivariate and binary logistic regression analyses were performed. Screen time determining factors studied were family environment, evaluated with the Family Environment Resource Inventory; socioeconomic factors; nutritional status and child development status, evaluated with the Bayley III test. As a result, 63% of children had daily screen time exceeding two hours, and television still is the main culprit for children screen exposure. We observed that screen time exposure was positively associated with family resources, economic level, and language development. However, only the last two factors explained the longer screen time.

Muscular dystrophies (MD) are a group of hereditary diseases marked by progressive muscle loss, leading to weakness and degeneration of skeletal muscles. These conditions often result from structural defects in the Dystrophin–Glycoprotein Complex (DGC), as seen in Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Since MDs currently have no cure, research has focused on identifying potential therapeutic targets to improve patients’ quality of life. In this study, skeletal muscle tissue samples from DMD and BMD patients, as well as non-dystrophic controls, were analyzed using label-free mass spectrometry (MS/MS) to characterize the proteomic profile of these conditions and identify biomarkers for differential diagnosis. In-silico analysis revealed that dystrophic muscle tissues are linked to biological processes related to cellular energy metabolism, including oxidation of organic compounds, energy production, and cellular respiration. Enrichment of functions associated with cell structure and RNA binding was also observed, including cytoskeletal protein binding and RNA binding. The human phenotypes most related to the proteomic signature were abnormal circulating metabolites, muscle physiology, and weakness. Quantitative analysis identified significant changes in proteins associated with sarcomere organization and protein ubiquitination, such as myomesin, myozenin, and E3 ubiquitin-protein ligase rififylin, suggesting these as potential therapeutic targets.

Yellow Fever (YF) is a severe disease caused by Yellow Fever Virus (YFV), endemic in some parts of Africa and America. In Brazil, YFV is maintained by a sylvatic transmission cycle involving non-human primates (NHP) and forest canopy-dwelling mosquitoes, mainly Haemagogus -spp and Sabethes- spp. Beginning in 2016, Brazil faced one of the largest Yellow Fever (YF) outbreaks in recent decades, mainly in the southeastern region. In São Paulo city, YFV was detected in October 2017 in Aloutta monkeys in an Atlantic Forest area. From 542 NHP, a total of 162 NHP were YFV positive by RT-qPCR and/or immunohistochemistry, being 22 Callithrix- spp. most from urban areas. Entomological collections executed did not detect the presence of strictly sylvatic mosquitoes. Three mosquito pools were positive for YFV, 2 Haemagogus leucocelaenus , and 1 Aedes scapularis . In summary, YFV in the São Paulo urban area was detected mainly in resident marmosets, and synanthropic mosquitoes were likely involved in viral transmission.

Dengue virus (DENV) is spread through most tropical and subtropical areas of the world and represents a serious public health problem. At present, the control of dengue disease is mainly hampered by the absence of antivirals or a vaccine, which results in an estimated half worldwide population at risk of infection. The immune response against DENV is not yet fully understood and a better knowledge of it is now recognized as one of the main challenge for vaccine development. In previous studies, we reported that a DNA vaccine containing the signal peptide sequence from the human tissue plasminogen activator (t-PA) fused to the DENV2 NS1 gene (pcTPANS1) induced protection against dengue in mice. In the present work, we aimed to elucidate the contribution of cellular and humoral responses elicited by this vaccine candidate for protective immunity. We observed that pcTPANS1 exerts a robust protection against dengue, inducing considerable levels of anti-NS1 antibodies and T cell responses. Passive immunization with anti-NS1 antibodies conferred partial protection in mice infected with low virus load (4 LD50), which was abrogated with the increase of viral dose (40 LD50). The pcTPANS1 also induced activation of CD4+ and CD8+ T cells. We detected production of IFN-γ and a cytotoxic activity by CD8+ T lymphocytes induced by this vaccine, although its contribution in the protection was not so evident when compared to CD4+ cells. Depletion of CD4+ cells in immunized mice completely abolished protection. Furthermore, transfer experiments revealed that animals receiving CD4+ T cells combined with anti-NS1 antiserum, both obtained from vaccinated mice, survived virus infection with survival rates not significantly different from pcTPANS1-immunized animals. Taken together, results showed that the protective immune response induced by the expression of NS1 antigen mediated by the pcTPANS1 requires a cooperation between CD4+ T cells and the humoral immunity.

Meningiomas are among the most common primary tumors of the central nervous system (CNS) and originate from the arachnoid or meningothelial cells of the meninges. Surgery is the first option of treatment, but depending on the location and invasion patterns, complete removal of the tumor is not always feasible. Reports indicate many differences in meningiomas from male versus female patients; for example, incidence is higher in females, whereas males usually develop the malignant and more aggressive type. With this as motivation, we used shotgun proteomics to compare the proteomic profile of grade I meningioma biopsies of male and female patients. Our results listed several differentially abundant proteins between the two groups; some examples are S100-A4 and proteins involved in RNA splicing events. For males, we identified enriched pathways for cell-matrix organization and for females, pathways related to RNA transporting and processing. We believe our findings contribute to the understanding of the molecular differences between grade I meningiomas of female and male patients.

Plant growth-promoting bacteria (PGPB) represent an eco-friendly alternative to reduce the use of chemical products while increasing the productivity of economically important crops. The emission of small gaseous signaling molecules from PGPB named volatile organic compounds (VOCs) has emerged as a promising biotechnological tool to promote biomass accumulation in model plants (especially Arabidopsis thaliana ) and a few crops, such as tomato, lettuce, and cucumber. Rice ( Oryza sativa ) is the most essential food crop for more than half of the world’s population. However, the use of VOCs to improve this crop performance has not yet been investigated. Here, we evaluated the composition and effects of bacterial VOCs on the growth and metabolism of rice. First, we selected bacterial isolates (IAT P4F9 and E.1b) that increased rice dry shoot biomass by up to 83% in co-cultivation assays performed with different durations of time (7 and 12 days). Metabolic profiles of the plants co-cultivated with these isolates and controls (without bacteria and non-promoter bacteria—1003-S-C1) were investigated via 1 H nuclear magnetic resonance. The analysis identified metabolites (e.g., amino acids, sugars, and others) with differential abundance between treatments that might play a role in metabolic pathways, such as protein synthesis, signaling, photosynthesis, energy metabolism, and nitrogen assimilation, involved in rice growth promotion. Interestingly, VOCs from IAT P4F9 displayed a more consistent promotion activity and were also able to increase rice dry shoot biomass in vivo . Molecular identification by sequencing the 16S rRNA gene of the isolates IAT P4F9 and E.1b showed a higher identity with Serratia and Achromobacter species, respectively. Lastly, volatilomes of these and two other non-promoter bacteria (1003-S-C1 and Escherichia coli DH5α) were evaluated through headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry. Compounds belonging to different chemical classes, such as benzenoids, ketones, alcohols, sulfide, alkanes, and pyrazines, were identified. One of these VOCs, nonan-2-one, was validated in vitro as a bioactive compound capable of promoting rice growth. Although further analyses are necessary to properly elucidate the molecular mechanisms, our results suggest that these two bacterial isolates are potential candidates as sources for bioproducts, contributing to a more sustainable agriculture.

Butantan-Dengue Vaccine (Butantan-DV) is an investigational, single-dose, live, attenuated, tetravalent vaccine against dengue disease, but data on its overall efficacy are needed. In an ongoing phase 3, double-blind trial in Brazil, we randomly assigned participants to receive Butantan-DV or placebo, with stratification according to age (2 to 6 years, 7 to 17 years, and 18 to 59 years); 5 years of follow-up is planned. The objectives of the trial were to evaluate overall vaccine efficacy against symptomatic, virologically confirmed dengue of any serotype occurring more than 28 days after vaccination (the primary efficacy end point), regardless of serostatus at baseline, and to describe safety up to day 21 (the primary safety end point). Here, vaccine efficacy was assessed on the basis of 2 years of follow-up for each participant, and safety as solicited vaccine-related adverse events reported up to day 21 after injection. Key secondary objectives were to assess vaccine efficacy among participants according to dengue serostatus at baseline and according to the dengue viral serotype; efficacy according to age was also assessed. Over a 3-year enrollment period, 16,235 participants received either Butantan-DV (10,259 participants) or placebo (5976 participants). The overall 2-year vaccine efficacy was 79.6% (95% confidence interval [CI], 70.0 to 86.3) - 73.6% (95% CI, 57.6 to 83.7) among participants with no evidence of previous dengue exposure and 89.2% (95% CI, 77.6 to 95.6) among those with a history of exposure. Vaccine efficacy was 80.1% (95% CI, 66.0 to 88.4) among participants 2 to 6 years of age, 77.8% (95% CI, 55.6 to 89.6) among those 7 to 17 years of age, and 90.0% (95% CI, 68.2 to 97.5) among those 18 to 59 years of age. Efficacy against DENV-1 was 89.5% (95% CI, 78.7 to 95.0) and against DENV-2 was 69.6% (95% CI, 50.8 to 81.5). DENV-3 and DENV-4 were not detected during the follow-up period. Solicited systemic vaccine- or placebo-related adverse events within 21 days after injection were more common with Butantan-DV than with placebo (58.3% of participants, vs. 45.6%). A single dose of Butantan-DV prevented symptomatic DENV-1 and DENV-2, regardless of dengue serostatus at baseline, through 2 years of follow-up. (Funded by Instituto Butantan and others; DEN-03-IB ClinicalTrials.gov number, NCT02406729, and WHO ICTRP number, U1111-1168-8679.).