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Innate immune response against Brucella abortus involves activation of Toll-like receptors (TLRs) and NOD-like receptors (NLRs). Among the NLRs involved in the recognition of B. abortus are NLRP3 and AIM2. Here, we demonstrate that B. abortus triggers non-canonical inflammasome activation dependent on caspase-11 and gasdermin-D (GSDMD). Additionally, we identify that Brucella-LPS is the ligand for caspase-11 activation. Interestingly, we determine that B. abortus is able to trigger pyroptosis leading to pore formation and cell death, and this process is dependent on caspase-11 and GSDMD but independently of caspase-1 protease activity and NLRP3. Mice lacking either caspase-11 or GSDMD were significantly more susceptible to infection with B. abortus than caspase-1 knockout or wild-type animals. Additionally, guanylate-binding proteins (GBPs) present in mouse chromosome 3 participate in the recognition of LPS by caspase-11 contributing to non-canonical inflammasome activation as observed by the response of Gbpchr3-/- BMDMs to bacterial stimulation. We further determined by siRNA knockdown that among the GBPs contained in mouse chromosome 3, GBP5 is the most important for Brucella LPS to be recognized by caspase-11 triggering IL-1β secretion and LDH release. Additionally, we observed a reduction in neutrophil, dendritic cell and macrophage influx in spleens of Casp11-/- and Gsdmd-/- compared to wild-type mice, indicating that caspase-11 and GSDMD are implicated in the recruitment and activation of immune cells during Brucella infection. Finally, depletion of neutrophils renders wild-type mice more susceptible to Brucella infection. Taken together, these data suggest that caspase-11/GSDMD-dependent pyroptosis triggered by B. abortus is important to infection restriction in vivo and contributes to immune cell recruitment and activation.

Excessive adiposity raises blood pressure and accounts for 65–75% of primary hypertension, which is a major driver of cardiovascular and kidney diseases. In obesity, abnormal kidney function and associated increases in tubular sodium reabsorption initiate hypertension, which is often mild before the development of target organ injury. Factors that contribute to increased sodium reabsorption in obesity include kidney compression by visceral, perirenal and renal sinus fat; increased renal sympathetic nerve activity (RSNA); increased levels of anti-natriuretic hormones, such as angiotensin II and aldosterone; and adipokines, particularly leptin. The renal and neurohormonal pathways of obesity and hypertension are intertwined. For example, leptin increases RSNA by stimulating the central nervous system proopiomelanocortin–melanocortin 4 receptor pathway, and kidney compression and RSNA contribute to renin–angiotensin–aldosterone system activation. Glucocorticoids and/or oxidative stress may also contribute to mineralocorticoid receptor activation in obesity. Prolonged obesity and progressive renal injury often lead to the development of treatment-resistant hypertension. Patient management therefore often requires multiple antihypertensive drugs and concurrent treatment of dyslipidaemia, insulin resistance, diabetes and inflammation. If more effective strategies for the prevention and control of obesity are not developed, cardiorenal, metabolic and other obesity-associated diseases could overwhelm health-care systems in the future.Hypertension is one of the most common comorbid conditions that is associated with obesity. Here, the authors discuss the complex interactions between renal, hormonal and nervous system factors that link excess adiposity with elevated blood pressure.

Activation of inflammasomes has been implicated in sensing pathogens. Now Dario Zamboni and colleagues report that the Nlrp3 inflammasome has a key role in restricting replication of Leishmania parasites in macrophages and in mice by triggering interleukin-1A–dependent induction of nitric oxide, a crucial mediator of defense against Leishmania . Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study we show that the Nlrp3 inflammasome is activated in response to Leishmania infection and is important for the restriction of parasite replication both in macrophages and in vivo as demonstrated through the infection of inflammasome-deficient mice with Leishmania amazonensis , Leishmania braziliensis and Leishmania infantum chagasi . Inflammasome-driven interleukin-1β (IL-1β) production facilitated host resistance to infection, as signaling through IL-1 receptor (IL-1R) and MyD88 was necessary and sufficient to trigger inducible nitric oxide synthase (NOS2)-mediated production of NO. In this manuscript we identify a major signaling platform for host resistance to Leishmania spp. infection and describe the molecular mechanisms underlying Leishmania -induced NO production.

This paper presents the results of an opinion poll conducted in Brazil on the perception of social isolation during the COVID-19 pandemic. The questionnaire was prepared on Google Forms, disseminated through social networks, with questions about the socioeconomic profile and factors associated with isolation. A non-probabilistic sample was obtained with 16,440 respondents. Data were analyzed using the Stata 13 software. Social interaction was the most affected aspect among people with higher education and income (45.8%), and financial problems caused a more significant impact (35%) among people with low income and education. Those who practice some physical activity showed lower levels of stress 13%, as well as greater normality in sleep 50.3%. People who reported living in worse habitability conditions reported willingness to remain isolated for less time, 73.9%. Among non-isolated people (10.7% of the total sample), 75.8% believe that social isolation will reduce the number of victims of COVID-19. We conclude, based on this sample, that the perception about social isolation as a pandemic mitigation action varies by income, education, age, and gender. However, most believe that it is the most appropriate control measure and are willing to wait as long as necessary to contribute to the fight against COVID-19.

Leishmania RNA virus (LRV) is an important virulence factor associated with the development of mucocutaneous Leishmaniasis, a severe form of the disease. LRV-mediated disease exacerbation relies on TLR3 activation, but downstream mechanisms remain largely unexplored. Here, we combine human and mouse data to demonstrate that LRV triggers TLR3 and TRIF to induce type I IFN production, which induces autophagy. This process results in ATG5-mediated degradation of NLRP3 and ASC, thereby limiting NLRP3 inflammasome activation in macrophages. Consistent with the known restricting role of NLRP3 for Leishmania replication, the signaling pathway triggered by LRV results in increased parasite survival and disease progression. In support of this data, we find that lesions in patients infected with LRV+ Leishmania are associated with reduced inflammasome activation and the development of mucocutaneous disease. Our findings reveal the mechanisms triggered by LRV that contribute to the development of the debilitating mucocutaneous form of Leishmaniasis. NLRP3 activation by Leishmania parasites is critical to the outcome of the disease. Here the authors show that LRV, a virus infecting Leishmania strains associated with more severe human disease, enables the parasite to suppress the inflammasome by activating type 1 interferon through TLR3, which leads to autophagy-mediated NLRP3 degradation.

In the search for new strategies to control Aedes aegypti Linnaeus (Diptera: Culicidae), several studies have successfully related pyriproxyfen (PPF) tarsal transference to breeding sites (autodissemination), as well as the sterilization potential of females exposed to PPF. Potential PPF autodissemination by mosquito feces after the ingestion of sugar baits has also been proposed. Therefore, the present work evaluated several parameters, e.g., fecal production, residuality under dry and aqueous conditions, PPF excretion affecting emergence inhibition (EI) by fecal deposits of Ae. aegypti fed with attractive toxic sugar baits (ATSBs) containing PPF as well as their reproductive potential. Females were fed with ATSBs offered as droplets and the feces were collected using filter paper and transferred to plastic cups with L3 larvae to evaluate EI. The residual effect of feces in aqueous and dry conditions and PPF excretion on EI was obtained by keeping the feces in water or dried for different time intervals and using feces collected at 24-h intervals, respectively. Females received a bloodmeal after feeding on ATSBs, eggs and larval counting expressed the reproductive potential. The fecal mass was not affected by PPF concentration, but EI increased from 33 to 54% as the PPF concentration increased. The PPF excretion in the feces exceeded 96 h. The residual effect in the EI for feces kept in water was reduced by more than 60% after 30 d but was not affected under dry conditions. The fecundity and fertility of the females were reduced up to 51% and 97%, respectively.

Mosquitoes are insects of medical importance due their role as vectors of different pathogens to humans. There is a lack of information about the evolutionary history and phylogenetic positioning of the majority of mosquito species. Here we characterized the mitogenomes of mosquito species through low-coverage whole genome sequencing and data mining. A total of 37 draft mitogenomes of different species were assembled from which 16 are newly-sequenced species. We datamined additional 49 mosquito mitogenomes, and together with our 37 mitogenomes, we reconstructed the evolutionary history of 86 species including representatives from 15 genera and 7 tribes. Our results showed that most of the species clustered in clades with other members of their own genus with exception of Aedes genus which was paraphyletic. We confirmed the monophyletic status of the Mansoniini tribe including both Coquillettidia and Mansonia genus. The Aedeomyiini and Uranotaeniini were consistently recovered as basal to other tribes in the subfamily Culicinae, although the exact relationships among these tribes differed between analyses. These results demonstrate that low-coverage sequencing is effective to recover mitogenomes, establish phylogenetic knowledge and hence generate basic fundamental information that will help in the understanding of the role of these species as pathogen vectors.

The increasing presence of pharmaceutical products in municipality wastewaters has raised serious environmental concerns. Ozonation is one of the advanced oxidation processes that can degrade these substances, instead of simply transferring them from aqueous to another phase. Treatability studies applying ozonation to degrade benzodiazepine drugs are scarce. The aim of this investigation was to apply design of experiments (DoE) to optimize ozonation processes for removal of bromazepam, clonazepam, and diazepam from two effluents of municipal wastewater treatment plants (WWTP1 and WWTP2) both located in Rio de Janeiro City, Brazil. During a preliminary study using ultrapure water, OHº radicals were more efficient (removal efficiency greater than 99% (< LOQ) at pH = 10, 15 min) than O3 in degrading all psychoactive drugs (removal efficiency from 46 to 85% at pH = 4, 15 min). The optimum values for the tested variables were pH = 8.03; O3 specific dose = 4.8 mgO3.mgDOC−1; and O3 mass flow rate = 22.07 mgO3.min−1. The WWTP1 and WWTP2 effluents were treated under optimized conditions by ozonation in two effluent volumes (5L and 8L). When 8 L effluent was treated, the degradation of all benzodiazepine drugs was improved, due to the higher water column used, which favors the mass transfer of O3 from the gas phase to the liquid phase, promoting greater contact between oxidant and target compounds. Using a specific dose of 1.8 mgO3.mgDOC−1, more than 93% of all anxiolytic drugs were removed from 8 L of WWTP2 effluent, whereas for the WWTP1, more than 90% were removed using 2.7 times higher specific dose (4.8 mgO3.mgDOC−1).

Chiral compounds exist as enantiomers that are non-superimposable mirror images of each other. Owing to the importance of enantiomerically pure chiral compounds 1 —for example, as active pharmaceutical ingredients—separation of racemates (1:1 mixtures of enantiomers) is extensively performed 2 . Frequently, however, only a single enantiomeric form of a chiral compound is required, which raises the question of how a racemate can be selectively converted into a single enantiomer. Such a deracemization 3 process is entropically disfavoured and cannot be performed by a conventional catalyst in solution. Here we show that it is possible to photochemically deracemize chiral compounds with high enantioselectivity using irradiation with visible light (wavelength of 420 nanometres) in the presence of catalytic quantities (2.5 mole per cent) of a chiral sensitizer. We converted an array of 17 chiral racemic allenes into the respective single enantiomers with 89 to 97 per cent enantiomeric excess. The sensitizer is postulated to operate by triplet energy transfer to the allene, with different energy-transfer efficiencies for the two enantiomers. It thus serves as a unidirectional catalyst that converts one enantiomer but not the other, and the decrease in entropy is compensated by light energy. Photochemical deracemization enables the direct formation of enantiopure materials from a racemic mixture of the same compound, providing a novel approach to the challenge of creating asymmetry. Photochemical deracemization through irradiation with visible light in the presence of a chiral sensitizer enables the direct formation of single enantiomers from a racemic mixture of the same compound.

The artisanal fisheries of Ecuador operate within one of the most dynamic and productive marine ecosystems of the world. This study investigates the catch composition of the Ecuadorian artisanal fishery for large pelagic fishes, including aspects of its spatio-temporal dynamics. The analyses of this study are based on the most extensive dataset available to date for this fishery: a total of 106,963 trip-landing inspection records collected at its five principal ports during 2008 ‒ 2012. Ecuadorian artisanal fisheries remove a substantial amount of biomass from the upper trophic-level predatory fish community of the eastern tropical Pacific Ocean. It is estimated that at least 135 thousand metric tons (mt) (about 15.5 million fish) were landed in the five principal ports during the study period. The great novelty of Ecuadorian artisanal fisheries is the \"oceanic-artisanal\" fleet component, which consists of mother-ship (nodriza) boats with their towed fiber-glass skiffs (fibras) operating with pelagic longlines. This fleet has fully expanded into oceanic waters as far offshore as 100°W, west of the Galapagos Archipelago. It is estimated that nodriza operations produce as much as 80% of the total catches of the artisanal fishery. The remainder is produced by independent fibras operating in inshore waters with pelagic longlines and/or surface gillnets. A multivariate regression tree analysis was used to investigate spatio-environmental effects on the nodriza fleet (n = 6,821 trips). The catch species composition of the nodriza fleet is strongly influenced by the northwesterly circulation of the Humboldt Current along the coast of Peru and its associated cold waters masses. The target species and longline gear-type used by nodrizas change seasonally with the incursion of cool waters (< 25°C) from the south and offshore. During this season, dolphinfish (Coryphaena hippurus) dominates the catches. However, in warmer waters, the fishery changes to tuna-billfish-shark longline gear and the catch composition becomes much more diverse.