Fighting methicillin-resistant staphylococcus aureus with targeted nanoparticles

Antimicrobial resistance (AMR) is considered one of the greatest threats to global health. Methicillin-resistant Staphylococcus aureus (MRSA) remains at the core of this threat, accounting for about 90% of S. aureus infections widespread in the community and hospital settings. In recent years, the use of nanoparticles (NPs) has emerged as a promising strategy to treat MRSA infections. NPs can act directly as antibacterial agents via antibiotic-independent activity and/or serve as drug delivery systems (DDSs), releasing loaded antibiotics. Nonetheless, directing NPs to the infection site is fundamental for effective MRSA treatment so that highly concentrated therapeutic agents are delivered to the infection site while directly reducing the toxicity to healthy human cells. This leads to decreased AMR emergence and less disturbance of the individual’s healthy microbiota. Hence, this review compiles and discusses the scientific evidence related to targeted NPs developed for MRSA treatment.info:eu-repo/semantics/publishedVersio

The brain decade in debate: II. Panic or anxiety? From animal models to a neurobiological basis

This article is a transcription of an electronic symposium sponsored by the Brazilian Society of Neuroscience and Behavior (SBNeC). Invited researchers from the European Union, North America and Brazil discussed two issues on anxiety, namely whether panic is a very intense anxiety or something else, and what aspects of clinical anxiety are reproduced by animal models. Concerning the first issue, most participants agreed that generalized anxiety and panic disorder are different on the basis of clinical manifestations, drug response and animal models. Also, underlying brain structures, neurotransmitter modulation and hormonal changes seem to involve important differences. It is also common knowledge that existing animal models generate different types of fear/anxiety. A challenge for future research is to establish a good correlation between animal models and nosological classification.Universidade Federal do Paraná Departamento de Farmacologia Laboratório de Fisiologia e Farmacologia do Sistema Nervoso CentralUniversity of Hawaii Department of NeurobiologyUniversity of Hawaii Department of PsychologyUniversidade de São Paulo Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Departamento de PsicobiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de FisiologiaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Departamento de NeuropsiquiatriaUniversidade Federal de Santa Catarina Departamento de FarmacologiaCentral Nervous System Research Department Sanofi SynthelaboAston University Institute of Pharmaceutical SciencesHoffmann-La Roche Ltd.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PsicologiaUniversity of Leeds Department of Psychology Ethopharmacology LaboratoryUniversidade Federal do Espírito Santo Centro de Biomedicina Departamento de Ciências FisiológicasUNIFESP, EPM, Depto. de PsicologiaSciEL

Anthropophilic activity of Aedes aegypti and of Aedes albopictus in area under control and surveillance

OBJECTIVE: To describe the hematophagous activity of Ae. aegypti and Ae. albopictus in an area under control and surveillance. METHODS: The study was conducted during 18 months, from April, 1993 to October, 1994, in Cosmópolis, São Paulo state, Brazil. Human baits were used to collect mosquitoes. The number of females captured is presented monthly by area of the city and local in the household. The rainfall was measured and indices are presented without model adjustment. RESULTS: The presence of females of both species was observed in 83% (Ae albopictus) and 61% (Ae. aegypti) of the period studied. The months of January, February and March presented the highest rates of activity for females of both species, with Ae. albopictus being more frequently captured than Ae. aegypti. Both species were captured in central and peripheral areas of the city, during the day from 9 to 12 am and from 4 to 7 pm. By a Poisson regression, it was observed that Ae. albopictus females were more frequently captured in the peri-housed area, in an independent way considering the area of the city. CONCLUSIONS: It has been identified difference on the hematophagous activity only for Ae. albopictus, being of importance the outside area of the house.OBJETIVO: Descrever a atividade de hematofagia de Aedes aegypti e Aedes albopictus em área submetida ao controle e à vigilância entomológica. MÉTODOS: O estudo foi realizado de abril de 1993 a setembro de 1994, na cidade de Cosmópolis, Estado de São Paulo. Utilizou-se isca humana para coleta dos exemplares. Calculou-se o número médio mensal de fêmeas capturadas por domicílio segundo as áreas central e periférica do município e os locais intra e peridomiciliar. Apresenta-se o índice pluviométrico mensal sem ajuste de modelo. RESULTADOS: Observou-se a presença de fêmeas das espécies em 83% (Ae. albopictus) e 61% (Ae. aegypti) do período estudado. Os meses de janeiro, fevereiro e março apresentaram maior atividade de fêmeas para as duas espécies, com maior presença de Ae. albopictus do que de Ae. aegypti. Os exemplares foram capturados na área central e periférica da cidade, nos períodos matutino, das 9:00 às 12:00 e crepuscular vespertino, das 16:00 às 19:00. Com utilização de modelo de regressão de Poisson, observou-se que fêmeas de Ae. albopictus foram mais capturadas no peridomicílio, independente se área central ou periférica. CONCLUSÕES: Foi detectada diferença no perfil de atividade da hematofagia somente para o Ae. albopictus, sendo de relevância o peridomicílio

An empirical evaluation of camera trap study design: How many, how long and when?

Abstract Camera traps deployed in grids or stratified random designs are a well‐established survey tool for wildlife but there has been little evaluation of study design parameters. We used an empirical subsampling approach involving 2,225 camera deployments run at 41 study areas around the world to evaluate three aspects of camera trap study design (number of sites, duration and season of sampling) and their influence on the estimation of three ecological metrics (species richness, occupancy and detection rate) for mammals. We found that 25–35 camera sites were needed for precise estimates of species richness, depending on scale of the study. The precision of species‐level estimates of occupancy (ψ) was highly sensitive to occupancy level, with 0.75) species, but more than 150 camera sites likely needed for rare (ψ < 0.25) species. Species detection rates were more difficult to estimate precisely at the grid level due to spatial heterogeneity, presumably driven by unaccounted habitat variability factors within the study area. Running a camera at a site for 2 weeks was most efficient for detecting new species, but 3–4 weeks were needed for precise estimates of local detection rate, with no gains in precision observed after 1 month. Metrics for all mammal communities were sensitive to seasonality, with 37%–50% of the species at the sites we examined fluctuating significantly in their occupancy or detection rates over the year. This effect was more pronounced in temperate sites, where seasonally sensitive species varied in relative abundance by an average factor of 4–5, and some species were completely absent in one season due to hibernation or migration. We recommend the following guidelines to efficiently obtain precise estimates of species richness, occupancy and detection rates with camera trap arrays: run each camera for 3–5 weeks across 40–60 sites per array. We recommend comparisons of detection rates be model based and include local covariates to help account for small‐scale variation. Furthermore, comparisons across study areas or times must account for seasonality, which could have strong impacts on mammal communities in both tropical and temperate sites

The Structure of the Oligomerization Domain of Lsr2 from Mycobacterium tuberculosis Reveals a Mechanism for Chromosome Organization and Protection

Lsr2 is a small DNA-binding protein present in mycobacteria and related actinobacteria that regulates gene expression and influences the organization of bacterial chromatin. Lsr2 is a dimer that binds to AT-rich regions of chromosomal DNA and physically protects DNA from damage by reactive oxygen intermediates (ROI). A recent structure of the C-terminal DNA-binding domain of Lsr2 provides a rationale for its interaction with the minor groove of DNA, its preference for AT-rich tracts, and its similarity to other bacterial nucleoid-associated DNA-binding domains. In contrast, the details of Lsr2 dimerization (and oligomerization) via its N-terminal domain, and the mechanism of Lsr2-mediated chromosomal cross-linking and protection is unknown. We have solved the structure of the N-terminal domain of Lsr2 (N-Lsr2) at 1.73 Å resolution using crystallographic ab initio approaches. The structure shows an intimate dimer of two ß–ß–a motifs with no close homologues in the structural databases. The organization of individual N-Lsr2 dimers in the crystal also reveals a mechanism for oligomerization. Proteolytic removal of three N-terminal residues from Lsr2 results in the formation of an anti-parallel β-sheet between neighboring molecules and the formation of linear chains of N-Lsr2. Oligomerization can be artificially induced using low concentrations of trypsin and the arrangement of N-Lsr2 into long chains is observed in both monoclinic and hexagonal crystallographic space groups. In solution, oligomerization of N-Lsr2 is also observed following treatment with trypsin. A change in chromosomal topology after the addition of trypsin to full-length Lsr2-DNA complexes and protection of DNA towards DNAse digestion can be observed using electron microscopy and electrophoresis. These results suggest a mechanism for oligomerization of Lsr2 via protease-activation leading to chromosome compaction and protection, and concomitant down-regulation of large numbers of genes. This mechanism is likely to be relevant under conditions of stress where cellular proteases are known to be upregulated