Citrus leprosis virus C infection results in hypersensitive-like response, suppression of the JA/ET plant defense pathway and promotion of the colonization of its mite vector

Leprosis is a serious disease of citrus caused by Citrus leprosis virus C (CiLV-C, genus Cilevirus) whose transmission is mediated by false spider mites of the genus Brevipalpus. CiLV-C infection does not systemically spread in any of its known host plants, thus remaining restricted to local lesions around the feeding sites of viruliferous mites. To get insight into this unusual pathosystem, we evaluated the expression profiles of genes involved in defense mechanisms of Arabidopsis thaliana and Citrus sinensis upon infestation with non-viruliferous and viruliferous mites by using reverse-transcription qPCR. These results were analyzed together with the production of reactive oxygen species (ROS) and the appearance of dead cells as assessed by histochemical assays. After interaction with non-viruliferous mites, plants locally accumulated ROS and triggered the salicylic acid (SA) and jasmonate/ethylene (JA/ET) pathways. ERE branch of the JA/ET pathways was highly activated. In contrast, JA pathway genes were markedly suppressed upon the CiLV-C infection mediated by viruliferous mites. Viral infection also intensified the ROS burst and cell death, and enhanced the expression of genes involved in the RNA silencing mechanism and SA pathway. After 13 days of infestation of two sets of Arabidopsis plants with non-viruliferous and viruliferous mites, the number of mites in the CiLV-C infected Arabidopsis plants was significantly higher than in those infested with the non-viruliferous ones. Oviposition of the viruliferous mites occurred preferentially in the CiLV-C infected leaves. Based on these results, we postulated the first model of plant/Brevipalpus mite/cilevirus interaction in which cells surrounding the feeding sites of viruliferous mites typify the outcome of a hypersensitive-like response, whereas viral infection induces changes in the behavior of its vector7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP573848/08-4; 375843/2012-42012/18771- 0; 2014/00366-8; 2008/57909-2; 2014/08458-

Correction: optimized labeling of bone marrow mesenchymal cells with superparamagnetic iron oxide nanoparticles and in vivo visualization by magnetic resonance imaging

Abstract Background Stem cell therapy has emerged as a promising addition to traditional treatments for a number of diseases. However, harnessing the therapeutic potential of stem cells requires an understanding of their fate in vivo. Non-invasive cell tracking can provide knowledge about mechanisms responsible for functional improvement of host tissue. Superparamagnetic iron oxide nanoparticles (SPIONs) have been used to label and visualize various cell types with magnetic resonance imaging (MRI). In this study we performed experiments designed to investigate the biological properties, including proliferation, viability and differentiation capacity of mesenchymal cells (MSCs) labeled with clinically approved SPIONs. Results Rat and mouse MSCs were isolated, cultured, and incubated with dextran-covered SPIONs (ferumoxide) alone or with poly-L-lysine (PLL) or protamine chlorhydrate for 4 or 24 hrs. Labeling efficiency was evaluated by dextran immunocytochemistry and MRI. Cell proliferation and viability were evaluated in vitro with Ki67 immunocytochemistry and live/dead assays. Ferumoxide-labeled MSCs could be induced to differentiate to adipocytes, osteocytes and chondrocytes. We analyzed ferumoxide retention in MSCs with or without mitomycin C pretreatment. Approximately 95% MSCs were labeled when incubated with ferumoxide for 4 or 24 hrs in the presence of PLL or protamine, whereas labeling of MSCs incubated with ferumoxide alone was poor. Proliferative capacity was maintained in MSCs incubated with ferumoxide and PLL for 4 hrs, however, after 24 hrs it was reduced. MSCs incubated with ferumoxide and protamine were efficiently visualized by MRI; they maintained proliferation and viability for up to 7 days and remained competent to differentiate. After 21 days MSCs pretreated with mitomycin C still showed a large number of ferumoxide-labeled cells. Conclusions The efficient and long lasting uptake and retention of SPIONs by MSCs using a protocol employing ferumoxide and protamine may be applicable to patients, since both ferumoxides and protamine are approved for human use.</p

Genome-wide signatures of complex introgression and adaptive evolution in the big cats.

The great cats of the genus Panthera comprise a recent radiation whose evolutionary history is poorly understood. Their rapid diversification poses challenges to resolving their phylogeny while offering opportunities to investigate the historical dynamics of adaptive divergence. We report the sequence, de novo assembly, and annotation of the jaguar (Panthera onca) genome, a novel genome sequence for the leopard (Panthera pardus), and comparative analyses encompassing all living Panthera species. Demographic reconstructions indicated that all of these species have experienced variable episodes of population decline during the Pleistocene, ultimately leading to small effective sizes in present-day genomes. We observed pervasive genealogical discordance across Panthera genomes, caused by both incomplete lineage sorting and complex patterns of historical interspecific hybridization. We identified multiple signatures of species-specific positive selection, affecting genes involved in craniofacial and limb development, protein metabolism, hypoxia, reproduction, pigmentation, and sensory perception. There was remarkable concordance in pathways enriched in genomic segments implicated in interspecies introgression and in positive selection, suggesting that these processes were connected. We tested this hypothesis by developing exome capture probes targeting ~19,000 Panthera genes and applying them to 30 wild-caught jaguars. We found at least two genes (DOCK3 and COL4A5, both related to optic nerve development) bearing significant signatures of interspecies introgression and within-species positive selection. These findings indicate that post-speciation admixture has contributed genetic material that facilitated the adaptive evolution of big cat lineages

Collagen-Based Films Containing Liposome-Loaded Usnic Acid as Dressing for Dermal Burn Healing

The aim of this study was assess the effect of collagen-based films containing usnic acid as a wound dressing for dermal burn healing. Second-degree burn wounds were performed in forty-five Wistar rats, assigned into nine groups: COL—animals treated with collagen-based films; PHO—animals treated with collagen films containing empty liposomes; UAL—animals treated with collagen-based films containing usnic acid incorporated into liposomes. After 7, 14, and 21 days the animals were euthanized. On 7th day there was a moderate infiltration of neutrophils, in UAL, distributed throughout the burn wounds, whereas in COL and PHO, the severity of the reaction was slighter and still limited to the margins of the burn wounds. On the 14th day, the inflammatory reaction was less intense in UAL, with remarkable plasma cells infiltration. On the 21st day, there was reduction of the inflammation, which was predominantly composed of plasma cells in all groups, particularly in UAL. The use of the usnic acid provided more rapid substitution of type-III for type-I collagen on the 14th day, and improved the collagenization density on the 21st day. It was concluded that the use of reconstituted bovine type-I collagen-based films containing usnic acid improved burn healing process in rats

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space. While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes, vast areas of the tropics remain understudied. In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity, but it remains among the least known forests in America and is often underrepresented in biodiversity databases. To worsen this situation, human-induced modifications may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge, it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Chemical composition similarity between the essential oils isolated from male and female specimens of each five Baccharis species

In the few studies published on essential oils from female and male specimens of Baccharis species, strong differences between the compositions of both samples were always found. The experiments conducted in this study make use of strategies to minimize the interference from genetic and environmental factors. Essential oils from leaves of female and male specimens of five Baccharis species were investigated by gas chromatography-mass spectrometry plus flame ionization detector (GC-MS-FID): B. caprariaefolia and B. dracunculifolia, which have been previously studied with similar aims; and B. coridifolia, B. semiserrata var. elaegnoides and B. pentaptera, the latter two not yet mentioned in the literature. The results were followed by hierarchical cluster analysis, verifying the formation of groups indicative of the great similarity of essential oils from male and female specimens of all five species. The study reinforces the value of field observation in natural product research and points genetic and ecological factors as main responsible for differences in the secondary metabolites of the studied plants._________________________________________________________________________________________ RESUMO: Nos poucos estudos publicados comparando óleos essenciais de espécimes femininos e masculinos de espécies Baccharis, fortes diferenças entre as composições de ambas as amostras foram sempre encontradas. Os experimentos realizados nesta pesquisa utilizam estratégias para minimizar a interferência de fatores genéticos e ecológicos. Os óleos essenciais das folhas de espécimes femininos e masculinos de cinco espécies Baccharis foram pesquisados com uso de um cromatógrafo gasoso acoplado a um espectrômetro de massas e a um detector de ionização de chama (CG-EM-DIC): B. caprariaefolia e B. dracunculifolia, já pesquisadas anteriormente com objetivos similares; e B. coridifolia, B. semiserrata var. elaegnoides e B. pentaptera, as duas últimas ainda não mencionadas na literatura química. Os resultados foram acompanhados por análise hierárquica de grupos, verificando-se a formação de grupos indicativos da grande similaridade entre óleos essenciais dos espécimes masculinos e femininos de todas as cinco espécies. O estudo reafirma o valor das observações de campo na pesquisa de produtos naturais, e aponta fatores genéticos e ecológicos como principais responsáveis por diferenças no metabolismo secundário das plantas estudadas

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

A cross-sectional study of quality of life among Brazilian adults with type 1 diabetes treated with insulin glargine : findings and implications

We conducted a cross-sectional study with 401 patients of type 1 diabetes mellitus treated with insulin glargine in Minas Gerais, Brazil. Health-related quality of life (HRQoL) was assessed using EQ-5D-3L and the Diabetes Quality of Life Measure. Our findings showed that a worse HRQoL was associated with a low level of education, self-perceived health reported as poor/very poor, being bedridden and not physically exercised, had seen a doctor more than four times in the past year before the interview, and had reported comorbidities and episodes of hypoglycemia

Construindo a participação social no SUS: um constante repensar em busca de equidade e transformação

Trata-se de um ensaio que expõe reflexões sobre a busca e o exercício da participação social no Sistema Único de Saúde (SUS), compreendendo seu conceito como as diferentes ações dos grupos sociais que influenciam a formulação, execução, fiscalização e avaliação das políticas públicas. Por isso o fato de a comunidade participar no sistema de saúde é visto como condição fundamental para o exercício pleno da saúde, capaz de promover equidade e de transformar a atenção à saúde. As ações de construir a cidadania e formar sujeitos coletivos são tomadas como fundamentos para a conquista de espaços democráticos e de direitos sociais. Mapeou-se a normatização atual referente à participação popular, considerando seus avanços, mas explicitando também suas fragilidades, principalmente no que tange aos conselhos e conferências de saúde. No ambiente dos espaços institucionais de participação, foram destacados elementos necessários para consolidar e efetivar a participação popular, como a relação entre os atores e a comunicação para a socializar as informações e conhecimentos em saúde. Busca-se também problematizar o assunto, trazendo à tona alguns dos obstáculos e críticas relativos à participação social. Pretende-se, com este ensaio, colaborar para a democratização dos diferentes espaços de escuta da sociedade civil, tornando-os locais cada vez mais apropriados para as tomadas de decisão sobre a construção de políticas e serviços de saúde, dos quais a população se apropria coletivamente, superando a simples obrigatoriedade burocrática da participação e contribuindo para a saúde e qualidade de vida.It concerns an essay that presents reflections on the search and the practice of the social participation in the Brazilian Unified Health System (SUS), including the understanding of its concept as to how the different actions of the social groups influence the formularization, execution, fiscalization and evaluation of the public policies. Therefore the participation of the community in the health system is considered an essential condition for the full exercise of the health, capable of promoting fairness and to transforming the health attention. The building of citizenship and the formation of collective citizens are taken as beddings for the conquest of democratic spaces and social rights. The current normalization of the public participation has been mapped considering its advances, but also stating its fragilities, mainly those that concerning the participation out of health councils and conferences. In the institutional environment, some elements where pointed as necessary to consolidate and effect the communitarian participation, like the relation between the actors and the communication for the socialization of health information and knowledge. Questions of the subject are also sought by bringing to attention some of the critical obstacles in relation to the social participation. This essay is intended to collaborate in behalf of the real democratization of the different spaces where the civil society can be heard, transforming these places in more appropriate locations to make decisions concerning the construction of health policies and services. The population can benefit from these spaces collectively surpassing the simple bureaucratic obligatoriness of the participation and contributing for the health and quality of life