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Host defense peptides (HDPs) are naturally occurring polypeptide sequences that, in addition to being active against bacteria, fungi, viruses, and other parasites, may stimulate immunomodulatory responses. Cathelicidins, a family of HDPs, are produced by diverse animal species, such as mammals, fish, birds, amphibians, and reptiles, to protect them against pathogen infections. These peptides have variable C-terminal domains responsible for their antimicrobial and immunomodulatory activities and a highly conserved N-terminal pre-pro region homologous to cathelin. Although cathelicidins are the major components of innate immunity, the molecular basis by which they induce an immune response is still unclear. In this review, we will address the role of the LL-37 domain and its SK-24, IV-20, FK-13 and LL-37 fragments in the immunity response. Other cathelicidins also share structural and functional characteristics with the LL-37 domain, suggesting that these fragments may be responsible for interaction between these peptides and receptors in humans. Fragments of the LL-37 domain can give us clues about how homologous cathelicidins, in general, induce an immune response.

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INTRODUCTION: Antimicrobial peptides (AMP) have received particular attention due to their capacity to kill bacteria. Although much is known about them, peptides are currently being further researched. A large number of AMPs have been discovered, but only a few have been approved for topical use, due to their promiscuity and other challenges, which need to be overcome. AREAS COVERED: AMPs are diverse in structure. Consequently, they have varied action mechanisms when targeting microorganisms or eukaryotic cells. Herein, the authors focus on linear peptides, particularly those that are alpha-helical structured, and examine how their charge distribution and hydrophobic amino acids could modulate their biological activity. EXPERT OPINION: The world currently needs urgent solutions to the infective problems caused by resistant pathogens. In order to start the race for antimicrobial development from the charge distribution viewpoint, bioinformatic tools will be necessary. Currently, there is no software available that allows to discriminate charge distribution in AMPs and predicts the biological effects of this event. Furthermore, there is no software available that predicts the side-chain length of residues and its role in biological functions. More specialized software is necessary.

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Background: Fluid regimens in acute respiratory distress syndrome (ARDS) are conflicting. The amount of fluid and positive end-expiratory pressure (PEEP) level may interact leading to ventilator-induced lung injury (VILI). We therefore evaluated restrictive and liberal fluid strategies associated with low and high PEEP levels with regard to lung and kidney damage, as well as cardiorespiratory function in endotoxin-induced ARDS. Methods: Thirty male Wistar rats received an intratracheal instillation of Escherichia coli lipopolysaccharide. After 24 h, the animals were anesthetized, protectively ventilated (VT = 6 ml/kg), and randomized to restrictive (5 ml/kg/h) or liberal (40 ml/kg/h) fluid strategies (Ringer lactate). Both groups were then ventilated with PEEP = 3 cmH2O (PEEP3) and PEEP = 9 cmH2O (PEEP9) for 1 h (n = 6/group). Echocardiography, arterial blood gases, and lung mechanics were evaluated throughout the experiments. Histologic analyses were done on the lungs, and molecular biology was assessed in lungs and kidneys using six non-ventilated animals with no fluid therapy. Results: In lungs, the liberal group showed increased transpulmonary plateau pressure compared with the restrictive group (liberal, 23.5 ± 2.9 cmH2O; restrictive, 18.8 ± 2.3 cmH2O, p = 0.046) under PEEP = 9 cmH2O. Gene expression associated with inflammation (interleukin [IL]-6) was higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.006) and restrictive-PEEP9 (p = 0.012), Regardless of the fluid strategy, lung mechanical power and the heterogeneity index were higher, whereas birefringence for claudin-4 and zonula-ocludens-1 gene expression were lower in the PEEP9 groups. Perivascular edema was higher in liberal groups, regardless of PEEP levels. Markers related to damage to epithelial cells [club cell secreted protein (CC16)] and the extracellular matrix (syndecan) were higher in the liberal-PEEP9 group than the liberal-PEEP3 group (p = 0.010 and p = 0.024, respectively). In kidneys, the expression of IL-6 and neutrophil gelatinase-associated lipocalin was higher in PEEP9 groups, regardless of the fluid strategy. For the liberal strategy, PEEP = 9 cmH2O compared with PEEP = 3 cmH2O reduced the right ventricle systolic volume (37%) and inferior vena cava collapsibility index (45%). Conclusion: The combination of a liberal fluid strategy and high PEEP led to more lung damage. The application of high PEEP, regardless of the fluid strategy, may also be deleterious to kidneys.

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In the last few decades, antimicrobial resistance (AMR) has been a worldwide concern. The excessive use of antibiotics affects animal and human health. In the last few years, livestock production has used antibiotics as food supplementation. This massive use can be considered a principal factor in the accelerated development of genetic modifications in bacteria. These modifications are responsible for AMR and can be widespread to pathogenic and commensal bacteria. In addition, these antibiotic residues can be dispersed by water and sewer water systems, the contamination of soil and, water and plants, in addition, can be stocked in tissues such as muscle, milk, eggs, fat, and others. These residues can be spread to humans by the consumption of water or contaminated food. In addition, studies have demonstrated that antimicrobial resistance may be developed by vertical and horizontal gene transfer, producing a risk to public health. Hence, the World Health Organization in 2000 forbid the use of antibiotics for feed supplementation in livestock. In this context, to obtain safe food production, one of the potential substitutes for traditional antibiotics is the use of antimicrobial peptides (AMPs). In general, AMPs present anti-infective activity, and in some cases immune response. A limited number of AMP-based drugs are now available for use in animals and humans. This use is still not widespread due to a few problems like in-vivo effectiveness, stability, and high cost of production. This review will elucidate the different AMPs applications in animal diets, in an effort to generate safe food and control AMR.

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Host immune responses contribute to dengue's pathogenesis and severity, yet the possibility that failure in endogenous inflammation resolution pathways could characterise the disease has not been contemplated. The pro-resolving protein Annexin A1 (AnxA1) is known to counterbalance overexuberant inflammation and mast cell (MC) activation. We hypothesised that inadequate AnxA1 engagement underlies the cytokine storm and vascular pathologies associated with dengue disease. Levels of AnxA1 were examined in the plasma of dengue patients and infected mice. Immunocompetent, interferon (alpha and beta) receptor one knockout (KO), AnxA1 KO, and formyl peptide receptor 2 (FPR2) KO mice were infected with dengue virus (DENV) and treated with the AnxA1 mimetic peptide Ac2-26 for analysis. In addition, the effect of Ac2-26 on DENV-induced MC degranulation was assessed in vitro and in vivo. We observed that circulating levels of AnxA1 were reduced in dengue patients and DENV-infected mice. Whilst the absence of AnxA1 or its receptor FPR2 aggravated illness in infected mice, treatment with AnxA1 agonistic peptide attenuated disease manifestationsatteanuated the symptoms of the disease. Both clinical outcomes were attributed to modulation of DENV-mediated viral load-independent MC degranulation. We have thereby identified that altered levels of the pro-resolving mediator AnxA1 are of pathological relevance in DENV infection, suggesting FPR2/ALX agonists as a therapeutic target for dengue disease.

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Increases in positive end-expiratory pressure (PEEP) or recruitment maneuvers may increase stress in lung parenchyma, extracellular matrix, and lung vessels; however, adaptative responses may occur. We evaluated the effects of PEEP on lung damage and cardiac function when increased abruptly, gradually, or more gradually in experimental mild/moderate acute respiratory distress syndrome (ARDS) induced by Escherichia coli lipopolysaccharide intratracheally. After 24 h, Wistar rats (n = 48) were randomly assigned to four mechanical ventilation strategies according to PEEP levels: 1) 3 cmH2O for 2 h (control); 2) 3 cmH2O for 1 h followed by an abrupt increase to 9 cmH2O for 1 h (no adaptation time); 3) 3 cmH2O for 30 min followed by a gradual increase to 9 cmH2O over 30 min then kept constant for 1 h (shorter adaptation time); and 4) more gradual increase in PEEP from 3 cmH2O to 9 cmH2O over 1 h and kept constant thereafter (longer adaptation time). At the end of the experiment, oxygenation improved in the shorter and longer adaptation time groups compared with the no-adaptation and control groups. Diffuse alveolar damage and expressions of interleukin-6, club cell protein-16, vascular cell adhesion molecule-1, amphiregulin, decorin, and syndecan were higher in no adaptation time compared with other groups. Pulmonary arterial pressure was lower in longer adaptation time than in no adaptation (P = 0.002) and shorter adaptation time (P = 0.025) groups. In this model, gradually increasing PEEP limited lung damage and release of biomarkers associated with lung epithelial/endothelial cell and extracellular matrix damage, as well as the PEEP-associated increase in pulmonary arterial pressure.NEW & NOTEWORTHY In a rat model of Escherichia coli lipopolysaccharide-induced mild/moderate acute respiratory distress syndrome, a gradual PEEP increase (shorter adaptation time) effectively mitigated histological lung injury and biomarker release associated with lung inflammation, damage to epithelial cells, endothelial cells, and the extracellular matrix compared with an abrupt increase in PEEP. A more gradual PEEP increase (longer adaptation time) decreased lung damage, pulmonary vessel compression, and pulmonary arterial pressure.

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Antibiotic growth promoters (AGPs) have been administered in livestock for decades to improve food digestion in growing animals, while also contributing to the control of microbial pathogens. The long-term and indiscrimate use of AGPs has generated genetic modifications in bacteria, leading to antimicrobial resistance (AMR), which can be disseminated to commensal and pathogenic bacteria. Thus, antimicrobial peptides (AMPs) are used to replaced AGPs. AMPs are found in all domains of life, and their cationic characteristics can establish electrostatic interactions with the bacterial membrane. These molecules used as growth promoters can present benefits for nutrient digestibility, intestinal microbiota, intestinal morphology, and immune function activities. Therefore, this review focuses on the application of AMPs with growth promoting potential in livestock, as an alternative to conventional antibiotic growth promoters, in an attempt to control AMR. KEY POINTS: • The long-term and indiscriminate use of AGPs in animal food can cause AMR. • AMPs can be used as substitute of antibiotics in animal food suplementation. • Animal food suplementated with AMPs can provied economic efficiency and sustainable livestock production.

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RESUMO Com o crescimento da população urbana e consequente alteração do uso e da ocupação do solo nas bacias hidrográficas, as inundações têm ficado cada vez mais frequentes. O presente trabalho teve como objetivo verificar os efeitos do emprego de técnicas compensatórias na sub-bacia hidrográfica Ribeirão do Santa Rita, localizada no município de Fernandópolis, São Paulo, Brasil. Foram analisados a vazão de pico e o tempo de resposta de diversos cenários, com o intuito de verificar o potencial de atenuação das inundações. A metodologia utilizada empregou o Storm Water Management Model (SWMM) para propagar o escoamento, e o software de Sistema de Informação Geográfica (SIG) para obter as características da bacia em estudo e os locais de potencial emprego das técnicas. Foi simulada a instalação de diversas técnicas compensatórias, isoladamente e em conjunto, para a configuração urbana de 2017. Mediante os hidrogramas gerados por cada cenário, constatou-se que os melhores resultados ocorreram em eventos com tempo de retorno menor. A atenuação da vazão de pico chegou a 33,72% utilizando-se trincheiras de infiltração, 31,38% para pavimentos permeáveis, 31,08% empregando jardins de chuva e 12,20% com telhados verdes. O aumento no tempo de resposta foi de até 16 minutos. No cenário com todas as técnicas compensatórias, a redução foi de até 37,29% da vazão de pico e o aumento do tempo de resposta foi de 18 minutos. Portanto, as técnicas compensatórias podem reduzir a vazão de pico e aumentar o tempo de resposta da sub-bacia, mitigando as ocorrências de inundações.

ABSTRACT With the growth of the urban population and the consequent alteration of land use and occupation in the watersheds, floods have become more frequent. This paper aimed to verify the effects of the use of compensatory techniques in the watershed Ribeirão do Santa Rita, located in the city of Fernandópolis, São Paulo, Brazil. Peak flow and response time of various scenarios were analyzed in order to verify the potential for flood mitigation. The methodology used Storm Water Management Model (SWMM) to propagate the flow, with the support of the Geographic Information Systems (GIS) to obtain the characteristics of the studied watersheed and the places of potential use of the techniques. The installation of several compensatory techniques was simulated, separately and together, for the 2017 urban configuration. Upon the hydrographs generated by each scenario, it was found that the best results occurred in events with shorter return time. Peak flow attenuation reached 33.72% using infiltration trenches, 31.38% for pours pavements, 31.08% using rain gardens, and 12.20% with green roofs. The increase in lag time was up to 16 minutes. In the scenario with all compensatory techniques, the reduction in peak flow was up to 37.29% and the response time increased by 18 minutes. Therefore, compensatory techniques can reduce peak flow and increase the response time of the sub-basin, consequently mitigating the occurrences of floods.

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Metagenomic studies revealed the prevalence of Acidobacteria in soils, but the physiological and ecological reasons for their success are not well understood. Many Acidobacteria exhibit carotenoid-related pigments, which may be involved in their tolerance of environmental stress. The aim of this work was to investigate the role of the orange pigments produced by Acidobacteria strain AB23 isolated from a savannah-like soil and to identify putative carotenoid genes in Acidobacteria genomes. Phylogenetic analysis revealed that strain AB23 belongs to the Occallatibacter genus from the class Acidobacteriia (subdivision 1). Strain AB23 produced carotenoids in the presence of light and vitamins; however, the growth rate and biomass decreased when cells were exposed to light. The presence of carotenoids resulted in tolerance to hydrogen peroxide. Comparative genomics revealed that all members of Acidobacteriia with available genomes possess the complete gene cluster for phytoene production. Some Acidobacteriia members have an additional gene cluster that may be involved in the production of colored carotenoids. Both colored and colorless carotenoids are involved in tolerance to oxidative stress. These results show that the presence of carotenoid genes is widespread among Acidobacteriia. Light and atmospheric oxygen stimulate carotenoid synthesis, but there are other natural sources of oxidative stress in soils. Tolerance to environmental oxidative stress provided by carotenoids may offer a competitive advantage for Acidobacteria in soils.

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Infectious diseases are a worldwide concern. They are responsible for increasing the mortality rate and causing economic and social problems. Viral epidemics and pandemics, such as the COVID-19 pandemic, force the scientific community to consider molecules with antiviral activity. A number of viral infections still do not have a vaccine or efficient treatment and it is imperative to search for vaccines to control these infections. In this context, nanotechnology in association with the design of vaccines has presented an option for virus control. Nanovaccines have displayed an impressive immune response using a low dosage. This review aims to describe the advances and update the data in studies using nanovaccines and their immunomodulatory effect against human viruses.

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Obesity is associated with bioenergetic dysfunction of peripheral muscles; however, little is known regarding the impact of obesity on the diaphragm. We hypothesized that obesity would be associated with diaphragm dysfunction attributable to mitochondrial oxygen consumption and structural and ultrastructural changes. Wistar rat litters were culled to 3 pups to induce early postnatal overfeeding and consequent obesity. Control animals were obtained from unculled litters. From postnatal day 150, diaphragm ultrasound, computed tomography, high-resolution respirometry, immunohistochemical, biomolecular, and ultrastructural histological analyses were performed. The diaphragms of obese animals, compared with those of controls, presented changes in morphology as increased thickening fraction, diaphragm excursion, and diaphragm dome height, as well as increased mitochondrial respiratory capacity coupled to ATP synthesis and maximal respiratory capacity. Fatty acid synthase gene expression was also higher in obese animals, suggesting a source of energy for the respiratory chain. Myosin heavy chain-IIA was increased, indicating shift from glycolytic toward oxidative muscle fiber profile. Diaphragm tissue also exhibited ultrastructural changes, such as compact, round, and swollen mitochondria with fainter cristae and more lysosomal bodies. Dynamin-1 expression in the diaphragm was reduced in obese rats, suggesting decreased mitochondrial fission. Furthermore, gene expressions of peroxisome γ proliferator-activated receptor coactivator-1α and superoxide dismutase-2 were lower in obese animals than in controls, which may indicate a predisposition to oxidative injury. In conclusion, in the obesity model used herein, muscle fiber phenotype was altered in a manner likely associated with increased mitochondrial respiratory capability, suggesting respiratory adaptation to increased metabolic demand.NEW & NOTEWORTHY Obesity has been associated with peripheral muscle dysfunction; however, little is known about its impact on the diaphragm. In the current study, we found high oxygen consumption in diaphragm tissue and changes in muscle fiber phenotypes toward a more oxidative profile in experimental obesity.

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The presence of genes for glycosyl hydrolases in many Acidobacteria genomes indicates an important role in the degradation of plant cell wall material. Acidobacteria bacterium AB60 was obtained from Cerrado oligotrophic soil in Brazil, where this phylum is abundant. The 16S rRNA gene analyses showed that AB60 was closely related to the genera Occallatibacter and Telmatobacter. However, AB60 grew on xylan as carbon source, which was not observed in Occallatibacter species; but growth was not detected on medium containing carboxymethyl cellulose, as observed in Telmatobacter. Nevertheless, the genome analysis of AB60 revealed genes for the enzymes involved in cellulose as well as xylan degradation. In addition to enzymes involved in xylan degradation, α-l-rhamnosidase was detected in the cultures of AB60. Functional screening of a small-insert genomic library did not identify any clones capable of carboxymethyl cellulose degradation, but open reading frames coding α-l-arabinofuranosidase and α-l-rhamnosidase were present in clones showing xylan degradation halos. Both enzymes act on the lateral chains of heteropolymers such as pectin and some hemicelluloses. These results indicate that the hydrolysis of α-linked sugars may offer a metabolic niche for slow-growing Acidobacteria, allowing them to co-exist with other plant-degrading microbes that hydrolyze ß-linked sugars from cellulose or hemicellulose backbones.

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INTRODUCTION: The need to develop new drugs for the control of pathogenic microorganisms has redoubled efforts to prospect for antimicrobial peptides (AMPs) from natural sources and to characterize its structure and function. These molecules present a broad spectrum of action against different microorganisms and frequently present promiscuous action, with anticancer and immunomodulatory activities. Furthermore, AMPs can be used as biopharmaceuticals in the treatment of hospital-acquired infections and other serious diseases with relevant social and economic impacts.Areas covered: The low yield and the therefore difficult extraction and purification process in AMPs are problems that limit their industrial application and scientific research. Thus, optimized heterologous expression systems were developed to significantly boost AMP yields, allow high efficiency in purification and structural optimization for the increase of therapeutic activity.Expert opinion: This review provides an update on recent developments in the recombinant production of ribosomal and non-ribosomal synthesis of AMPs and on strategies to increase the expression of genes encoding AMPs at the transcriptional and translational levels and regulation of the post-translational modifications. Moreover, there are detailed reports of AMPs that have already reached marketable status or are in the pipeline under advanced stages of preclinical testing.

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Infections caused by invasive fungal biofilms have been widely associated with high morbidity and mortality rates, mainly due to the advent of antibiotic resistance. Moreover, fungal biofilms impose an additional challenge, leading to multidrug resistance. This fact, along with the contamination of medical devices and the limited number of effective antifungal agents available on the market, demonstrates the importance of finding novel drug candidates targeting pathogenic fungal cells and biofilms. In this context, an alternative strategy is the use of antifungal peptides (AFPs) against fungal biofilms. AFPs are considered a group of bioactive molecules with broad-spectrum activities and multiple mechanisms of action that have been widely used as template molecules for drug design strategies aiming at greater specificity and biological efficacy. Among the AFP classes most studied in the context of fungal biofilms, defensins, cathelicidins and histatins have been described. AFPs can also act by preventing the formation of fungal biofilms and eradicating preformed biofilms through mechanisms associated with cell wall perturbation, inhibition of planktonic fungal cells' adhesion onto surfaces, gene regulation and generation of reactive oxygen species (ROS). Thus, considering the critical scenario imposed by fungal biofilms and associated infections and the application of AFPs as a possible treatment, this review will focus on the most effective AFPs described to date, with a core focus on antibiofilm peptides, as well as their efficacy in vivo, application on surfaces and proposed mechanisms of action.

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In recent decades, cancer and multidrug resistance have become a worldwide problem, resulting in high morbidity and mortality. Some infectious agents like Streptococcus pneumoniae, Stomatococcus mucilaginous, Staphylococcus spp., E. coli. Klebsiella spp., Pseudomonas aeruginosa, Candida spp., Helicobacter pylori, hepatitis B and C, and human papillomaviruses (HPV) have been associated with the development of cancer. Chemotherapy, radiotherapy and antibiotics are the conventional treatment for cancer and infectious disease. This treatment causes damage in healthy cells and tissues, and usually triggers systemic side-effects, as well as drug resistance. Therefore, the search for new treatments is urgent, in order to improve efficacy and also reduce side-effects. Proteins and peptides originating from bacteria can thus be a promising alternative to conventional treatments used nowadays against cancer and infectious disease. These molecules have demonstrated specific activity against cancer cells and bacterial infection; indeed, proteins and peptides can be considered as future antimicrobial and anticancer drugs. In this context, this review will focus on the desirable characteristics of proteins and peptides from bacterial sources that demonstrated activity against microbial infections and cancer, as well as their efficacy in vitro and in vivo.

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Severe mosaic symptoms, accompanied by yellow spots, abnormally small leaves, fruit malformation and cracking, reduced plant growth, and high levels of whitefly (Bemisia tabaci MEAM1) infestation were observed in passionflower (Passiflora edulis) orchards in southwestern Bahia, Brazil. The aim of this work was to identify the species of begomovirus infecting the passionflowers, its prevalence in southwestern Bahia, and the spatial and temporal dynamics of the disease. Leaf samples from symptomatic plants collected at 57 orchards located in ten counties were evaluated by PCR for begomovirus infection. Complete nucleotide sequences of DNA-A for two isolates revealed 97 % identity with Passionfruit severe leaf distortion virus (PSLDV). The occurrence of PSLDV in 57 orchards was evaluated based on the presence of characteristic disease symptoms. Approximately 235,000 visually assessed plants exhibited symptoms characteristic of begomovirus infection. Epidemiological studies, conducted in two orchards in Dom Basílio County, showed that disease progress was relatively slow until 121 days after transplanting (DAT), but more rapid in the following 35 days, reaching 100 % infected plants by 156 DAT. The exponential model was fitted to the temporal dynamic of the disease for both areas. An aggregated pattern of diseased plants was predominant for almost all evaluations. It is possible that the primary and secondary spread of the pathogen occurred concurrently during the epidemic progression in both areas, especially late in the season. Containment measures to prevent the virus and the vector from spreading to other passionfruit producing areas in Brazil should be implemented.(AU)

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Severe mosaic symptoms, accompanied by yellow spots, abnormally small leaves, fruit malformation and cracking, reduced plant growth, and high levels of whitefly (Bemisia tabaci MEAM1) infestation were observed in passionflower (Passiflora edulis) orchards in southwestern Bahia, Brazil. The aim of this work was to identify the species of begomovirus infecting the passionflowers, its prevalence in southwestern Bahia, and the spatial and temporal dynamics of the disease. Leaf samples from symptomatic plants collected at 57 orchards located in ten counties were evaluated by PCR for begomovirus infection. Complete nucleotide sequences of DNA-A for two isolates revealed 97 % identity with Passionfruit severe leaf distortion virus (PSLDV). The occurrence of PSLDV in 57 orchards was evaluated based on the presence of characteristic disease symptoms. Approximately 235,000 visually assessed plants exhibited symptoms characteristic of begomovirus infection. Epidemiological studies, conducted in two orchards in Dom Basílio County, showed that disease progress was relatively slow until 121 days after transplanting (DAT), but more rapid in the following 35 days, reaching 100 % infected plants by 156 DAT. The exponential model was fitted to the temporal dynamic of the disease for both areas. An aggregated pattern of diseased plants was predominant for almost all evaluations. It is possible that the primary and secondary spread of the pathogen occurred concurrently during the epidemic progression in both areas, especially late in the season. Containment measures to prevent the virus and the vector from spreading to other passionfruit producing areas in Brazil should be implemented.

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Yellow fever virus (YFV) is a member of the Flaviviridae family. In Brazil, yellow fever (YF) cases have increased dramatically in sylvatic areas neighboring urban zones in the last few years. Because of the high lethality rates associated with infection and absence of any antiviral treatments, it is essential to identify therapeutic options to respond to YFV outbreaks. Repurposing of clinically approved drugs represents the fastest alternative to discover antivirals for public health emergencies. Other Flaviviruses, such as Zika (ZIKV) and dengue (DENV) viruses, are susceptible to sofosbuvir, a clinically approved drug against hepatitis C virus (HCV). Our data showed that sofosbuvir docks onto YFV RNA polymerase using conserved amino acid residues for nucleotide binding. This drug inhibited the replication of both vaccine and wild-type strains of YFV on human hepatoma cells, with EC50 values around 5 µM. Sofosbuvir protected YFV-infected neonatal Swiss mice and adult type I interferon receptor knockout mice (A129-/-) from mortality and weight loss. Because of its safety profile in humans and significant antiviral effects in vitro and in mice, Sofosbuvir may represent a novel therapeutic option for the treatment of YF. Key-words: Yellow fever virus; Yellow fever, antiviral; sofosbuvir.

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Antimicrobial peptides (AMPs), especially antibacterial peptides, have been widely investigated as potential alternatives to antibiotic-based therapies. Indeed, naturally occurring and synthetic AMPs have shown promising results against a series of clinically relevant bacteria. Even so, this class of antimicrobials has continuously failed clinical trials at some point, highlighting the importance of AMP optimization. In this context, the computer-aided design of AMPs has put together crucial information on chemical parameters and bioactivities in AMP sequences, thus providing modes of prediction to evaluate the antibacterial potential of a candidate sequence before synthesis. Quantitative structure-activity relationship (QSAR) computational models, for instance, have greatly contributed to AMP sequence optimization aimed at improved biological activities. In addition to machine-learning methods, the de novo design, linguistic model, pattern insertion methods, and genetic algorithms, have shown the potential to boost the automated design of AMPs. However, how successful have these approaches been in generating effective antibacterial drug candidates? Bearing this in mind, this review will focus on the main computational strategies that have generated AMPs with promising activities against pathogenic bacteria, as well as anti-infective potential in different animal models, including sepsis and cutaneous infections. Moreover, we will point out recent studies on the computer-aided design of antibiofilm peptides. As expected from automated design strategies, diverse candidate sequences with different structural arrangements have been generated and deposited in databases. We will, therefore, also discuss the structural diversity that has been engendered.