The use of insecticides has become increasingly frequent, and studies indicate that these compounds are involved in the intoxication of bees. Imidacloprid is a widely used neonicotinoid; thus, we ...have highlighted the importance of assessing its oral toxicity to Africanized bees and used transmission electron microscopy to investigate the sublethal effects in the brain, the target organ, and the midgut, responsible for the digestion/absorption of food. In addition, the distribution of proteins involved in important biological processes in the brain were evaluated on the 1st day of exposure by MALDI-imaging analysis. Bioassays were performed to determine the Median Lethal Concentration (LC
50
) of imidacloprid to bees, and the value obtained was 1.4651 ng imidacloprid/μL diet. Based on this result, the sublethal concentration to be administered at 1, 4 and 8 days was established as a hundredth (1/100) of the LC
50
. The results obtained from the ultrastructural analysis showed alterations in the midgut cells of bees as nuclear and mitochondrial damage and an increase of vacuoles. The insecticide caused spacing among the Kenyon cells in the mushroom bodies, chromatin condensation and loss of mitochondrial cristae. The MALDI-imaging analysis showed an increase in the expression of such proteins as vascular endothelial growth factor receptor, amyloid protein precursor and protein kinase C, which are related to oxygen supply, neuronal degeneration and memory/learning, and a decrease in the expression of the nicotinic acetylcholine receptor alpha 1, which is fundamental to the synapses. These alterations demonstrated that imidacloprid could compromise the viability of the midgut epithelium, as well as inhibiting important cognitive processes in individuals, and may be reflected in losses of the colony.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The proboscis extension response (PER) reflex may be used to condition the pairing of an odor with sucrose, which is applied to the antennae, in experiments to induce learning, where the odor ...represents a conditioned stimulus, while sucrose represents an unconditioned stimulus. A series of studies have been conducted on honeybees, relating learning and memory acquisition/retrieval using the PER as a strategy for accessing their ability to exhibit an unconditioned stimulus; however, the major metabolic processes involved in the PER are not well known. Thus, the aim of this investigation is profiling the metabolome of the honeybee brain involved in the PER. In this study, a semiquantitative approach of matrix-assisted laser desorption ionization (MALDI) mass spectral imaging (MSI) was used to profile the most abundant metabolites of the honeybee brain that support the PER. It was reported that execution of the PER requires the metabolic transformations of arginine, ornithine, and lysine as substrates for the production of putrescine, cadaverine, spermine, spermidine, 1,3-diaminopropane, and γ-aminobutyric acid (GABA). Considering the global metabolome of the brain of honeybee workers, the PER requires the consumption of large amounts of cadaverine and 1,3-diaminopropane, in parallel with the biosynthesis of high amounts of spermine, spermidine, and ornithine. To exhibit the PER, the brain of honeybee workers processes the conversion of l-arginine and l-lysine through the polyamine pathway, with different regional metabolomic profiles at the individual neuropil level. The outcomes of this study using this metabolic route as a reference are indicating that the antennal lobes and the calices (medial and lateral) were the most active brain regions for supporting the PER.
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The yellow fever virus (YFV) caused a severe outbreak in Brazil in 2016-2018 that rapidly spread across the Atlantic Forest in its most populated region without viral circulation for almost 80 years. ...A comprehensive entomological survey combining analysis of distribution, abundance and YFV natural infection in mosquitoes captured before and during the outbreak was conducted in 44 municipalities of five Brazilian states. In total, 17,662 mosquitoes of 89 species were collected. Before evidence of virus circulation, mosquitoes were tested negative but traditional vectors were alarmingly detected in 82% of municipalities, revealing high receptivity to sylvatic transmission. During the outbreak, five species were found positive in 42% of municipalities. Haemagogus janthinomys and Hg. leucocelaenus are considered the primary vectors due to their large distribution combined with high abundance and natural infection rates, concurring together for the rapid spread and severity of this outbreak. Aedes taeniorhynchus was found infected for the first time, but like Sabethes chloropterus and Aedes scapularis, it appears to have a potential local or secondary role because of their low abundance, distribution and infection rates. There was no evidence of YFV transmission by Aedes albopictus and Aedes aegypti, although the former was the most widespread species across affected municipalities, presenting an important overlap between the niches of the sylvatic vectors and the anthropic ones. The definition of receptive areas, expansion of vaccination in the most affected age group and exposed populations and the adoption of universal vaccination to the entire Brazilian population need to be urgently implemented.
HIV-infected patients are at particular risk for invasive pneumococcal disease (IPD).We describe cases of IPD in people living with HIV/AIDS (PLWHA) and find associated risk factors for infection and ...death. Methods: A retrospective case-control study, nested in a cohort, including PLWHAwith and without IPD, conducted in Brazil, 2005-2020. Controls were of the same gender/age and seen at the same time/place as cases. Results: We identified 55 episodes of IPD (cases) in 45 patients and 108 controls. The incidence of IPD was 964/100,000 person-years. A total of 42 of 55 (76.4%) IPD episodes presented with pneumonia and 11 (20%) with bacteremia without a focus and 38/45 (84.4%) were hospitalized. Blood cultures were positive in 54/55 (98.2%). Liver cirrhosis and COPD were the only factors associated with IPD in PLWHA in univariate analysis, although no associated factors were found in multivariate analysis. Penicillin resistance was found in 4/45 (8.9%). Regarding antiretroviral therapy (ART), 40/45 (88.9%) cases vs. 80/102 controls (74.1%) were in use ('p' = 0.07). Patients with HIV and IPD had a higher CD4 count of 267 cells/mm3 compared with the control group, in which it was 140 cells/mm3 ('p' = 0.027). Pneumococcal vaccination was documented in 19%. Alcoholism (p = 0.018), hepatic cirrhosis ('p' = 0.003), and lower nadir CD4 count ('p' = 0.033) were associated with the risk of death in patients with IPD. In-hospital mortality among PLWHA and IPD was 21.1%, and it was associated with thrombocytopenia and hypoalbuminemia, elevated band forms, creatinine, and aspartate aminotransferase (AST). Conclusions: The incidence of IPD in PLWHA remained high despite ART. The vaccination rate was low. Liver cirrhosis was associated with IPD and death.
In the present study, we provide a retrospective genomic epidemiology analysis of the SARS-CoV-2 pandemic in the state of Rio de Janeiro, Brazil. We gathered publicly available data from GISAID and ...sequenced 1927 new genomes sampled periodically from March 2021 to June 2021 from 91 out of the 92 cities of the state. Our results showed that the pandemic was characterized by three different phases driven by a successive replacement of lineages. Interestingly, we noticed that viral supercarriers accounted for the overwhelming majority of the circulating virus (>90%) among symptomatic individuals in the state. Moreover, SARS-CoV-2 genomic surveillance also revealed the emergence and spread of two new variants (P.5 and P.1.2), firstly reported in this study. Our findings provided important lessons learned from the different epidemiological aspects of the SARS-CoV-2 dynamic in Rio de Janeiro. Altogether, this might have a strong potential to shape future decisions aiming to improve public health management and understanding mechanisms underlying virus dispersion.
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The occurrence and spatial distribution of the neuropeptides AmTRP-5 and AST-1 in the honeybee brain were monitored via MALDI spectral imaging according to the ontogeny of Africanized Apis mellifera. ...The levels of these peptides increased in the brains of 0–15 day old honeybees, and this increase was accompanied by an increase in the number of in-hive activities performed by the nurse bees, followed by a decrease in the period from 15 to 25 days of age, in which the workers began to perform activities outside the nest (guarding and foraging). The results obtained in the present investigation suggest that AmTRP-5 acts in the upper region of both pedunculi of young workers, possibly regulating the cell cleaning and brood capping activities. Meanwhile, the localized occurrence of AmTRP-5 and AST-1 in the antennal lobes, subesophageal ganglion, upper region of the medulla, both lobula, and α- and β-lobes of both brain hemispheres in 20 to 25 day old workers suggest that the action of both neuropeptides in these regions may be related to their localized actions in these regions, regulating foraging and guarding activities. Thus, these neuropeptides appear to have some functions in the honeybee brain that are specifically related to the age-related division of labor.
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Hepatocellular Carcinoma (HCC) is a primary neoplasm derived from hepatocytes with low responsiveness and recurrent chemoresistance. Melatonin is an alternative agent that may be helpful in treating ...HCC. We aimed to study in HuH 7.5 cells whether melatonin treatment exerts antitumor effects and, if so, what cellular responses are induced and involved.
We evaluated the effects of melatonin on cell cytotoxicity and proliferation, colony formation, morphological and immunohistochemical aspects, and on glucose consumption and lactate release.
Melatonin reduced cell motility and caused lamellar breakdown, membrane damage, and reduction in microvillus. Immunofluorescence analysis revealed that melatonin reduced TGF and N-cadherin expression, which was further associated with inhibition of epithelial-mesenchymal transition process. In relation to the Warburg-type metabolism, melatonin reduced glucose uptake and lactate production by modulating intracellular lactate dehydrogenase activity.
Our results indicate that melatonin can act upon pyruvate/lactate metabolism, preventing the Warburg effect, which may reflect in the cell architecture. We demonstrated the direct cytotoxic and antiproliferative effect of melatonin on the HuH 7.5 cell line, and suggest that melatonin is a promising candidate to be further tested as an adjuvant to antitumor drugs for HCC treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PurposeAgile methods are increasingly being applied in the contexts of innovation beyond traditional information technology (IT) and physical product development projects, such as when process ...improvements are being implemented. Nevertheless, this phenomenon is still recent and little addressed in the literature, with few descriptions of empirical cases. This study aims to address this gap.Design/methodology/approachThis multiple case study aims to present and discuss the application of Agile practices embedded in large companies’ innovation value chains, focusing on improvements of business processes. The following research question is pursued: How are large companies applying elements of Agile methods to their innovation processes when implementing incremental improvements in their operational processes? Based on the idea that the Agile-Stage-Gate model is an alternative to this challenge, this study investigates the application of this hybrid model in two large Brazilian companies by presenting their idiosyncrasies, lessons learned, adaptations, challenges and benefits.FindingsOverall, it was observed that the experience with the application of the Agile-Stage-Gate model is positive for these companies, with better customer engagement, easier project control and increased productivity of the project team.Originality/valueFor those aiming to implement the Agile-Stage-Gate model, this paper identifies the main adaptations made in order to combine the purist approaches and critical success factors for its implementation.
Background/objectiveThere is evidence that metabolic profile changes after Roux-Y gastric bypass (RYGB), especially due to modifications in the gastrointestinal tract. In addition, previous studies ...have suggested that probiotics can modify the microbiome and produce metabolites important for metabolic health maintenance. In this sense, the aim of this study was to verify the influence of probiotic supplementation on the plasma metabolite profile after RYGB.MethodsThis was a randomized, double-blind, placebo-controlled clinical trial conducted with 31 patients subjected to RYGB surgery, randomized in probiotic group that was supplemented with a probiotic supplement (FloraVantage®) for 3 months after surgery or a placebo group. Plasma metabonomics was performed using nuclear magnetic resonance (NMR) at the preoperative period (T0) and at 45–50 days (T1) and 90–95 days (T2) during the postoperative period/intervention.ResultsReductions in trimethylamine-N-oxide (TMAO) and alanine were observed in both groups, however this reduction was greater in the probiotic group (TMAO 13.82%, p = 0.01 and alanine 14.03%, p = 0.03) at T2. Additionally, β-hydroxybutyrate (BHB) levels increased 10.77% in the probiotic group (p = 0.03) compared to the placebo group at T2.ConclusionSupplementation with Lactobacillus acidophilus NCFM and Bifidobacterium lactis Bi-07 was able to associate with significant differences in relevant plasma metabolites associated with improved metabolic health.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Intrahost genetic diversity is thought to facilitate arbovirus adaptation to changing environments and hosts, and it might also be linked to viral pathogenesis. Dengue virus serotype 2 (DENV-2) has ...circulated in Brazil since 1990 and is associated with severe disease and explosive outbreaks. Intending to shed light on the viral determinants for severe dengue pathogenesis, we sought to analyze the DENV-2 intrahost genetic diversity in 68 patient cases clinically classified as dengue fever (
= 31), dengue with warning signs (
= 19), and severe dengue (
= 18). Unlike previous DENV intrahost diversity studies whose approaches employed PCR, here we performed viral whole-genome deep sequencing from clinical samples with an amplicon-free approach, representing the real intrahost diversity scenario. Striking differences were detected in the viral population structure between the three clinical categories, which appear to be driven mainly by different infection times and selection pressures, rather than being linked with the clinical outcome itself. Diversity in the NS2B gene, however, showed to be constrained, irrespective of clinical outcome and infection time. Finally, 385 non-synonymous intrahost single-nucleotide variants located along the viral polyprotein, plus variants located in the untranslated regions, were consistently identified among the samples. Of them, 124 were exclusively or highly detected among cases with warning signs and among severe cases. However, there was no variant that by itself appeared to characterize the cases of greater severity, either due to its low intrahost frequency or the conservative effect on amino acid substitution. Although further studies are necessary to determine their real effect on viral proteins, this heightens the possibility of epistatic interactions. The present analysis represents an initial effort to correlate DENV-2 genetic diversity to its pathogenic potential and thus contribute to understanding the virus's dynamics within its human host.
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