Pyrosequencing-based analysis reveals a novel capsular gene cluster in a KPC-producing Klebsiella pneumoniae clinical isolate identified in Brazil

Background: An important virulence factor of Klebsiella pneumoniae is the production of capsular polysaccharide (CPS), a thick mucus layer that allows for evasion of the host's defense and creates a barrier against antibacterial peptides. CPS production is driven mostly by the expression of genes located in a locus called cps, and the resulting structure is used to distinguish between different serotypes (K types). in this study, we report the unique genetic organization of the cps cluster from K. pneumoniae Kp13, a clinical isolate recovered during a large outbreak of nosocomial infections that occurred in a Brazilian teaching hospital.Results: A pyrosequencing-based approach showed that the cps region of Kp13 (cps(Kp13)) is 26.4 kbp in length and contains genes common, although not universal, to other strains, such as the rm/BADC operon that codes for L-rhamnose synthesis. cpsKp13 also presents some unique features, like the inversion of the wzy gene and a unique repertoire of glycosyltransferases. in silico comparison of cps(Kp13) RFLP pattern with 102 previously published cps PCR-RFLP patterns showed that cpsKp13 is distinct from the C patterns of all other K serotypes. Furthermore, in vitro serotyping showed only a weak reaction with capsular types K9 and K34. We confirm that K9 cps shares common genes with cps(Kp13) such as the rm/BADC operon, but lacks features like uge and Kp13-specific glycosyltransferases, while K34 capsules contain three of the five sugars that potentially form the Kp13 CPS.Conclusions: We report the first description of a cps cluster from a Brazilian clinical isolate of a KPC-producing K. pneumoniae. the gathered data including K-serotyping support that Kp13's K-antigen belongs to a novel capsular serotype. the CPS of Kp13 probably includes L-rhamnose and D-galacturonate in its structure, among other residues. Because genes involved in L-rhamnose biosynthesis are absent in humans, this pathway may represent potential targets for the development of antimicrobial agents. Studying the capsular serotypes of clinical isolates is of great importance for further development of vaccines and/or novel therapeutic agents. the distribution of K-types among multidrug-resistant isolates is unknown, but our findings may encourage scientists to perform K-antigen typing of KPC-producing strains worldwide.LNCC, Rio de Janeiro, BrazilUniv Fed Rio de Janeiro, Inst Microbiol Paulo de Goes, Rio de Janeiro, BrazilUniv Estadual Londrina, Dept Patol Clin Anal Clin & Toxicol, Londrina, BrazilUniversidade Federal de São Paulo, Lab ALERTA, Div Doencas Infecciosas, São Paulo, BrazilUniversidade Federal de São Paulo, Lab ALERTA, Div Doencas Infecciosas, São Paulo, BrazilWeb of Scienc

A selective p53 activator and anticancer agent to improve colorectal cancer therapy

Impairment of the p53 pathway is a critical event in cancer. Therefore, reestablishing p53 activity has become one of the most appealing anticancer therapeutic strategies. Here, we disclose the p53-activating anticancer drug (3S)-6,7-bis(hydroxymethyl)-5-methyl-3-phenyl-1H,3H-pyrrolo[1,2-c]thiazole (MANIO). MANIO demonstrates a notable selectivity to the p53 pathway, activating wild-type (WT)p53 and restoring WT-like function to mutant (mut)p53 in human cancer cells. MANIO directly binds to the WT/mutp53 DNA-binding domain, enhancing the protein thermal stability, DNA-binding ability, and transcriptional activity. The high efficacy of MANIO as an anticancer agent toward cancers harboring WT/mutp53 is further demonstrated in patient-derived cells and xenograft mouse models of colorectal cancer (CRC), with no signs of undesirable side effects. MANIO synergizes with conventional chemotherapeutic drugs, and in vitro and in vivo studies predict its adequate drug-likeness and pharmacokinetic properties for a clinical candidate. As a single agent or in combination, MANIO will advance anticancer-targeted therapy, particularly benefiting CRC patients harboring distinct p53 status.We thank PT national funds (FCT/MCTES, Fundação para a Ciência e a Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) through grants UIDB/50006/2020, UID/BIO/04469/2019, UIDB/04539/2020, and UIDP/04539/2020 (CIBB); BioTecNorte operation (NORTE-01-0145-FEDER000004) and Porto Neurosciences and Neurologic Disease Research Initiative at I3S (Norte-01-0145-FEDER-000008) funded by the European Regional Development Fund under the scope of Norte2020 - Programa Operacional Regional do Norte; Masaryk University (Project MUNI/A/1127/2019) and Ministry of Education, Youth and Sports of the Czech Republic (project nos. LQ1605 and LM2018125); FCT financial support through the fellowships SFRH/BD/119144/2016 (H.R.) and SFRH/BD/117949/2016 (L.R.); Fondazione AIRC (IG#18985, A.I.); and the Programa Operacional Potencial Humano (POCH), specifically the BiotechHealth Programme (Doctoral Programme on Cellular and Molecular Biotechnology Applied to Health Sciences, PD/00016/2012). We thank Dario Rizzotto for assistance in preparing the libraries for RNA sequencing. Funding: This work was supported by PT National Funds (FCT/MCTES, Fundação para a Ciência e Tecnologia, and Ministério da Ciência, Tecnologia e Ensino Superior) via the projects UIDB/50006/2020 (LAQV/REQUIMTE), UIDB/00313/2020, and UIDP/00313/2020, co-funded by COMPETE2020-UE.info:eu-repo/semantics/publishedVersio

Decoding the internesting movements of marine turtles using a fine-scale behavioral state approach

IntroductionAn understanding of animal behavior is critical to determine their ecological role and to inform conservation efforts. However, observing hidden behaviors can be challenging, especially for animals that spend most of their time underwater. Animal-borne devices are valuable tools to estimate hidden behavioral states.MethodsWe investigated the fine-scale behavior of internesting hawksbill turtles using the mixed-membership method for movement (M4) which integrated dive variables with spatial components and estimated latent behavioral states.ResultsFive latent behavioral states were identified: 1) pre-nesting, 2) transit, 3) quiescence, and 4) area restricted search within and 5) near the residence of turtles. The last three states associated with a residency period, showed lower activity levels. Notably, when compared to other behaviors the pre-nesting exhibited shallower and remarkably long dives of up to 292 minutes. We noted high fidelity to residence core areas and nesting beaches, within and between nesting seasons, with residence areas decreasing within a season.DiscussionThe latent behaviors identified provide the most detailed breakdown of turtle movement behaviors during the internesting period to date, providing valuable insights into their ecology and behavior. This information can inform marine turtle conservation and management efforts since utilization distributions of individual behavioral states can be used to determine spatially-explicit susceptibility of turtles to various threats based on their behavior. The analyses of utilization distribution revealed a minimal overlap with existing marine protected areas (0.4%), and we show how a new proposal would expand protection to 30%. In short, this study provides valuable guidance for conservation and management of internesting marine turtles at a fine spatiotemporal resolution and can be used to enhance national action plans for endangered species, including the expansion of existing Marine Protected Areas. By flexibly incorporating biologically informative parameters, this approach can be used to study behavior outside of the hawksbill breeding season or even beyond this species

Dynamics of the Leaf-Litter Arthropod Fauna Following Fire in a Neotropical Woodland Savanna

Fire is an important agent of disturbance in tropical savannas, but relatively few studies have analyzed how soil-and-litter dwelling arthropods respond to fire disturbance despite the critical role these organisms play in nutrient cycling and other biogeochemical processes. Following the incursion of a fire into a woodland savanna ecological reserve in Central Brazil, we monitored the dynamics of litter-arthropod populations for nearly two years in one burned and one unburned area of the reserve. We also performed a reciprocal transplant experiment to determine the effects of fire and litter type on the dynamics of litter colonization by arthropods. Overall arthropod abundance, the abundance of individual taxa, the richness of taxonomic groups, and the species richness of individual taxa (Formiciade) were lower in the burned site. However, both the ordinal-level composition of the litter arthropod fauna and the species-level composition of the litter ant fauna were not dramatically different in the burned and unburned sites. There is evidence that seasonality of rainfall interacts with fire, as differences in arthropod abundance and diversity were more pronounced in the dry than in the wet season. For many taxa the differences in abundance between burned and unburned sites were maintained even when controlling for litter availability and quality. In contrast, differences in abundance for Collembola, Formicidae, and Thysanoptera were only detected in the unmanipulated samples, which had a lower amount of litter in the burned than in the unburned site throughout most of our study period. Together these results suggest that arthropod density declines in fire-disturbed areas as a result of direct mortality, diminished resources (i.e., reduced litter cover) and less favorable microclimate (i.e., increased litter desiccation due to reduction in tree cover). Although these effects were transitory, there is evidence that the increasingly prevalent fire return interval of only 1–2 years may jeopardize the long-term conservation of litter arthropod communities

Ageing and dementia in low and middle income countries - Using research to engage with public and policy makers

Abstract While two thirds of the 24 million people with dementia worldwide live in low and middle income countries, very little research has been conducted to support policy making in these regions. Among the non-communicable diseases, dementia (in common with other chronic NCDs linked more to long-term disability than to mortality) has been relatively under-prioritized. International agreements, plans and policy guidelines have called for an end to ageist discrimination and a focus upon reducing disadvantage arising from poverty and the consequences of ill health. Social protection, access to good quality age-appropriate healthcare and addressing the problem of disability are all key issues. However, as yet, little progress has been made in addressing these concerns. In this review we outline the current international policy agenda for older individuals, and its specific relevance to those with dementia and other disabling non-communicable diseases. We consider the potential for epidemiological research to raise awareness, refine the policy agenda, and promote action, using the example of the dissemination strategy developed by the 10/66 Dementia Research Group

A perspetiva dos professores de educação especial sobre a importância da expressão dramática como técnica psicopedagógica no desenvolvimento da comunicação da criança com perturbação de Asperger

Os princípios pelos quais a escola inclusiva se rege defendem que os alunos não devem apenas estar juntos, mas acima de tudo, devem aprender juntos, de forma a perceberem que a escola é de todos e para todos, ainda que dentro das suas diferenças. Terá o professor capacidades, conhecimentos e estratégias suficientes para abraçar este desafio? Numa tentativa de aprofundarmos o nosso conhecimento acerca da Perturbação de Asperger propomo-nos a desenvolver um trabalho que defina a doença, dentro do já então conhecido, e evidencie tanto as “fragilidades” como as “capacidades” dos portadores, carinhosamente apelidados de “Aspies”. Trata-se de uma tentativa de reunir os conhecimentos necessários para começar a entender a essência dos Asperger. Porque é que na opinião do psicólogo clínico Tony Attwood, especialista mundial nesta Perturbação, precisamos de pessoas com Asperger, sugerindo que estes indivíduos possam ser, de alguma forma, especiais e capazes de grandes feitos. Neste sentido, surge este estudo para tentar perceber a perspetiva dos professores de Educação Especial sobre a importância da Expressão Dramática como técnica psicopedagógica no desenvolvimento da comunicação da criança com Perturbação de Asperger. Pretendemos perceber a influência que a utilização desta técnica pode ter no desenvolvimento comunicacional da criança com Perturbação de Asperger, pois talvez seja relevante sugerir a elaboração de um programa de treino de competências comunicacionais que utilize a Expressão Dramática. A Expressão Dramática vai além do seu papel de ferramenta lúdica e de distração, daí a importância de se conhecer as vantagens da sua utilização nesta área e tentar perceber se pode contribuir ou não para o sucesso de uma criança com esta problemática

Modelling climate change adaptation in European agriculture: Definitions and Current Modelling

Confidential content, in preparation for a peer-reviewed publication