Implications of dealing with airborne substances and reactive oxygen species: what mammalian lungs, animals, and plants have to say?

A gas-exchange structure interacts with the environment and is constantly challenged by contaminants that may elicit defense responses, thus compromising its primary function. It is also exposed to high concentrations of O2 that can generate reactive oxygen species (ROS). Revisiting the lung of mammals, an integrative picture emerges, indicating that this bronchi-alveolar structure deals with inflammation in a special way, which minimizes compromising the gas-exchange role. Depending on the challenge, pro-inflammatory or antiinflammatory responses are elicited by conserved molecules, such as surfactant proteins A and D. An even broader picture points to the participation of airway sensors, responsive to inflammatory mediators, in a loop linking the immunological and nervous systems and expanding the role played by respiratory organs in functions other than gas-exchange. A byproduct of exposure to high concentration of O2 is the formation of superoxide (), hydrogen peroxide (H2O2), hydroxyl radical (HO•), and other ROS, which are known to be toxic to different types of cells, including the lung epithelium. A balance between antioxidants and oxidants exists; in pulmonary epithelial cells high intracellular and extracellular levels of antioxidants are found. Antioxidant adaptations related to plant and animal life-styles involve a broad range of overlapping strategies based on well-conserved molecules. Glutathione (GSH) is an abundant and ubiquitous thiol-tripeptide antioxidant, also present in lungs, whose role in providing information on the intracellular redox state of animals and plants is well established. In these organisms, GSH influences gene expression associated with stress, maximizing defense responses. Several enzymatic antioxidants, such as glutathione peroxidase (GPx), glutathione reductase, glutathione S-transferase, and glucose 6-phosphate dehydrogenase participate in the redox system; in animals that are stress-tolerant GPx is a key element against oxidative assaults. Most importantly, alternative roles of ROS as signaling molecules have been found in all plants and animals. For example, alveolar macrophages produce that act as second messengers, in addition to having a bactericidal role. The nonradical ROS H2O2 signals inflammation in mammalian lungs, apoptosis in different animal tissues, and is also involved in stomatal closure, root development, gene expression, and defense responses of plants. Antioxidant adaptations in some water-breathing animals involve the excretion of H2O2 by diffusion through gas-exchange structures. The fine balance among a multitude of factors and cells makes the difference between damage and protection in animals and plants. Knowledge about the mechanisms and consequences of these molecular interactions is now starting to be integrate

A novel hybrid nanofibrous strategy to target progenitor cells for cost-effective in situ angiogenesis

Although the impact of composites based on Ti-doped calcium phosphate glasses is low compared with that of bioglass, they have been already shown to possess great potential for bone tissue engineering. Composites made of polylactic acid (PLA) and a microparticle glass of 5TiO(2)-44.5CaO-44.5P(2)O(5)-6Na(2)O (G5) molar ratio have already demonstrated in situ osteo-and angiogenesis-triggering abilities. As many of the hybrid materials currently developed usually promote osteogenesis but still lack the ability to induce vascularization, a G5/PLA combination is a cost-effective option for obtaining new instructive scaffolds. In this study, nanostructured PLA-ORMOGLASS (organically modified glass) fibers were produced by electro-spinning, in order to fabricate extra-cellular matrix (ECM)-like substrates that simultaneously promote bone formation and vascularization. Physical-chemical and surface characterization and tensile tests demonstrated that the obtained scaffolds exhibited homogeneous morphology, higher hydrophilicity and enhanced mechanical properties than pure PLA. In vitro assays with rat mesenchymal stem cells (rMSCs) and rat endothelial progenitor cells (rEPCs) also showed that rMSCs attached and proliferated on the materials influenced by the calcium content in the environment. In vivo assays showed that hybrid composite PLA-ORMOGLASS fibers were able to promote the formation of blood vessels. Thus, these novel fibers are a valid option for the design of functional materials for tissue engineering applications

Implications of dealing with airborne substances and reactive oxygen species: what mammalian lungs, animals and plants have to say?

A gas-exchange structure interacts with the environment and is constantly challenged by contaminants that may elicit defense responses, thus compromising its primary function. It is also exposed to high concentrations of O2 that can generate reactive oxygen species (ROS). Revisiting the lung of mammals, an integrative picture emerges, indicating that this bronchi-alveolar structure deals with inflammation in a special way, which minimizes compromising the gas-exchange role. Depending on the challenge, pro-inflammatory or antiinflammatory responses are elicited by conserved molecules, such as surfactant proteins A and D. An even broader picture points to the participation of airway sensors, responsive to inflammatory mediators, in a loop linking the immunological and nervous systems and expanding the role played by respiratory organs in functions other than gas-exchange. A byproduct of exposure to high concentration of O2 is the formation of superoxide (), hydrogen peroxide (H2O2), hydroxyl radical (HO•), and other ROS, which are known to be toxic to different types of cells, including the lung epithelium. A balance between antioxidants and oxidants exists; in pulmonary epithelial cells high intracellular and extracellular levels of antioxidants are found. Antioxidant adaptations related to plant and animal life-styles involve a broad range of overlapping strategies based on well-conserved molecules. Glutathione (GSH) is an abundant and ubiquitous thiol-tripeptide antioxidant, also present in lungs, whose role in providing information on the intracellular redox state of animals and plants is well established. In these organisms, GSH influences gene expression associated with stress, maximizing defense responses. Several enzymatic antioxidants, such as glutathione peroxidase (GPx), glutathione reductase, glutathione S-transferase, and glucose 6-phosphate dehydrogenase participate in the redox system; in animals that are stress-tolerant GPx is a key element against oxidative assaults. Most importantly, alternative roles of ROS as signaling molecules have been found in all plants and animals. For example, alveolar macrophages produce that act as second messengers, in addition to having a bactericidal role. The nonradical ROS H2O2 signals inflammation in mammalian lungs, apoptosis in different animal tissues, and is also involved in stomatal closure, root development, gene expression, and defense responses of plants. Antioxidant adaptations in some water-breathing animals involve the excretion of H2O2 by diffusion through gas-exchange structures. The fine balance among a multitude of factors and cells makes the difference between damage and protection in animals and plants. Knowledge about the mechanisms and consequences of these molecular interactions is now starting to be integrated

GenSeed-HMM: A tool for progressive assembly using profile HMMs as seeds and its application in Alpavirinae viral discovery from metagenomic data

This work reports the development of GenSeed-HMM, a program that implements seed-driven progressive assembly, an approach to reconstruct specific sequences from unassembled data, starting from short nucleotide or protein seed sequences or profile Hidden Markov Models (HMM). The program can use any one of a number of sequence assemblers. Assembly is performed in multiple steps and relatively few reads are used in each cycle, consequently the program demands low computational resources. As a proof-of-concept and to demonstrate the power of HMM-driven progressive assemblies, GenSeed-HMM was applied to metagenomic datasets in the search for diverse ssDNA bacteriophages from the recently described Alpavirinae subfamily. Profile HMMs were built using Alpavirinae-specific regions from multiple sequence alignments using either the viral protein 1 (VP1) (major capsid protein) or VP4 (genome replication initiation protein). These profile HMMs were used by GenSeed-HMM (running Newbler assembler) as seeds to reconstruct viral genomes from sequencing datasets of human fecal samples. All contigs obtained were annotated and taxonomically classified using similarity searches and phylogenetic analyses. The most specific profile HMM seed enabled the reconstruction of 45 partial or complete Alpavirinae genomic sequences. A comparison with conventional (global) assembly of the same original dataset, using Newbler in a standalone execution, revealed that GenSeed-HMM outperformed global genomic assembly in several metrics employed. This approach is capable of detecting organisms that have not been used in the construction of the profile HMM, which opens up the possibility of diagnosing novel viruses, without previous specific information, constituting a de novo diagnosis. Additional applications include, but are not limited to, the specific assembly of extrachromosomal elements such as plastid and mitochondrial genomes from metagenomic data. Profile HMM seeds can also be used to reconstruct specific protein coding genes for gene diversity studies, and to determine all possible gene variants present in a metagenomic sample. Such surveys could be useful to detect the emergence of drug-resistance variants in sensitive environments such as hospitals and animal production facilities, where antibiotics are regularly used. Finally, GenSeed-HMM can be used as an adjunct for gap closure on assembly finishing projects, by using multiple contig ends as anchored seeds

The importance of primary data for life cycle assessment of construction products in Brazil

This work presents a study of six construction products: sand, gravel, clay block, concrete block, ready-mix concrete and mortar. National LCIs were developed using primary data collected at manufacturers located in the State of São Paulo, and upstream and downstream processes were based on the ecoinvent database. Datasets available in ecoinvent deemed representative of these six construction products were chosen for comparison. Four impact indicators were calculated: Global Warming Potential, Water Depletion, Cumulative Energy Demand and Resource Depletion. The differences between the national and the international impact results range from 10% to 255%, with an overall average difference of 69%. GWP was the indicator with the least average difference (53%); while Water Depletion had the highest (101%). Regarding the products, the differences considering all impact indicators range from 42% (gravel) to 109% (clay block). The results indicate the importance of national LCIs based on primary data in order to ensure reliable construction LCA studies in Brazi

High mobility group box 1 levels in large vessel vasculitis are not associated with disease activity but are influenced by age and statins

Introduction: Takayasu arteritis (TA) and giant cell arteritis (GCA) are large vessel vasculitides (LVV) that usually present as granulomatous inflammation in arterial walls. High mobility group box 1 (HMGB1) is a nuclear protein that acts as an alarmin when released by dying or activated cells. This study aims to evaluate whether serum HMGB1 can be used as a biomarker in LVV. Methods: Twenty-nine consecutive TA patients with 29 healthy controls (HC) were evaluated in a cross-sectional study. Eighteen consecutive GCA patients with 16 HC were evaluated at the onset of disease and some of them during follow-up. Serum HMGB1 levels were measured by enzyme-linked immunosorbent assay. Results: In GCA patients at disease onset mean serum HMGB1 levels did not differ from HC (5.74 +/- 4.19 ng/ml vs. 4.17 +/- 3.14 ng/ml; p = 0.230). No differences in HMGB1 levels were found between GCA patients with and without polymyalgia rheumatica (p = 0.167), ischemic manifestations (p = 0.873), systemic manifestations (p = 0.474) or relapsing disease (p = 0.608). During follow-up, no significant fluctuations on serum HMGB1 levels were observed from baseline to 3 months (n = 13) (p = 0.075), 12 months (n = 6) (p = 0.093) and at the first relapse (n = 4) (p = 0.202). Serum HMGB1 levels did not differ between TA patients and HC [1.19 (0.45-2.10) ng/ml vs. 1.46 (0.89-3.34) ng/ml; p = 0.181] and no difference was found between TA patients with active disease and in remission [1.31 (0.63-2.16) ng/ml vs. 0.75 (0.39-2.05) ng/ml; p = 0.281]. HMGB1 levels were significantly lower in 16 TA patients on statins compared with 13 patients without statins [0.59 (0.29-1.46) ng/ml vs. 1.93 (0.88-3.34) ng/ml; p = 0.019]. Age was independently associated with higher HMGB1 levels regardless of LVV or control status. Conclusions: Patients with TA and GCA present similar serum HMGB1 levels compared with HC. Serum HMGB1 is not useful to discriminate between active disease and remission. In TA, use of statins was associated with lower HMGB1 levels. HMGB1 is not a biomarker for LVV

DWORF Extends Life Span in a PLN-R14del Cardiomyopathy Mouse Model by Reducing Abnormal Sarcoplasmic Reticulum Clusters

BACKGROUND: The p.Arg14del variant of the PLN (phospholamban) gene causes cardiomyopathy, leading to severe heart failure. Calcium handling defects and perinuclear PLN aggregation have both been suggested as pathological drivers of this disease. Dwarf open reading frame (DWORF) has been shown to counteract PLN regulatory calcium handling function in the sarco/endoplasmic reticulum (S/ER). Here, we investigated the potential disease-modulating action of DWORF in this cardiomyopathy and its effects on calcium handling and PLN aggregation. METHODS: We studied a PLN-R14del mouse model, which develops cardiomyopathy with similar characteristics as human patients, and explored whether cardiac DWORF overexpression could delay cardiac deterioration. To this end, R14Δ/Δ (homozygous PLN-R14del) mice carrying the DWORF transgene (R14Δ/ΔDWORFTg [R14Δ/Δ mice carrying the DWORF transgene]) were used. RESULTS: DWORF expression was suppressed in hearts of R14Δ/Δ mice with severe heart failure. Restoration of DWORF expression in R14Δ/Δ mice delayed cardiac fibrosis and heart failure and increased life span &gt;2-fold (from 8 to 18 weeks). DWORF accelerated sarcoplasmic reticulum calcium reuptake and relaxation in isolated cardiomyocytes with wild-type PLN, but in R14Δ/Δ cardiomyocytes, sarcoplasmic reticulum calcium reuptake and relaxation were already enhanced, and no differences were detected between R14Δ/Δ and R14Δ/ΔDWORFTg. Rather, DWORF overexpression delayed the appearance and formation of large pathogenic perinuclear PLN clusters. Careful examination revealed colocalization of sarcoplasmic reticulum markers with these PLN clusters in both R14Δ/Δ mice and human p.Arg14del PLN heart tissue, and hence these previously termed aggregates are comprised of abnormal organized S/ER. This abnormal S/ER organization in PLN-R14del cardiomyopathy contributes to cardiomyocyte cell loss and replacement fibrosis, consequently resulting in cardiac dysfunction. CONCLUSIONS: Disorganized S/ER is a major characteristic of PLN-R14del cardiomyopathy in humans and mice and results in cardiomyocyte death. DWORF overexpression delayed PLN-R14del cardiomyopathy progression and extended life span in R14Δ/Δ mice, by reducing abnormal S/ER clusters.</p

“Quem ensina também aprende” : a formação pela prática de professores primários na província do Paraná

Resumo Segundo a historiografia da educação brasileira, muitas foram as ações relacionadas aos modos de formar professores primários durante o período imperial. Desses estudos, a maioria se centra na formação de professores atrelada à instituição das escolas normais, entretanto, há uma parcela menor de trabalhos que se propõem a discutir outro aspecto da formação de professores ao longo do século XIX, mais especificamente, a forma como sujeitos que não frequentaram esse espaço institucional (a escola normal), constituíram-se docentes primários. O artigo que aqui se apresenta partilha dessa perspectiva, e volta o olhar para os modos de formação pela prática de professores primários no Paraná na segunda metade do século XIX, por compreender que esse tipo de formação marcou um período em que a instrução pública estava se consolidando em meio a ações, deliberações, dificuldades e tensões, na tentativa de melhorias de sua condição. A pesquisa valeu-se da consulta da legislação educacional do período e de documentos advindos dos sujeitos envolvidos com a instrução pública, naquele momento, disponíveis no acervo do Arquivo Público do Paraná. No cotejamento e análise das fontes, é possível afirmar, que a formação pela prática dos professores primários na província do Paraná se deu no decorrer do desenvolvimento do processo de constituição do magistério primário

Potential red-flag identification of colorectal adenomas with wide-field fluorescence molecular endoscopy

Adenoma miss rates in colonoscopy are unacceptably high, especially for sessile serrated adenomas / polyps (SSA/Ps) and in high-risk populations, such as patients with Lynch syndrome. Detection rates may be improved by fluorescence molecular endoscopy (FME), which allows morphological visualization of lesions with high-definition white-light imaging as well as fluorescence-guided identification of lesions with a specific molecular marker. In a clinical proof-of-principal study, we investigated FME for colorectal adenoma detection, using a fluorescently labelled antibody (bevacizumab-800CW) against vascular endothelial growth factor A (VEGFA), which is highly upregulated in colorectal adenomas. Methods: Patients with familial adenomatous polyposis (n = 17), received an intravenous injection with 4.5, 10 or 25 mg of bevacizumab-800CW. Three days later, they received NIR-FME. Results: VEGFA-targeted NIR-FME detected colorectal adenomas at all doses. Best results were achieved in the highest (25 mg) cohort, which even detected small adenomas ( < 3 mm). Spectroscopy analyses of freshly excised specimen demonstrated the highest adenoma-to-normal ratio of 1.84 for the 25 mg cohort, with a calculated median tracer concentration in adenomas of 6.43 nmol/mL. Ex vivo signal analyses demonstrated NIR fluorescence within the dysplastic areas of the adenomas. Conclusion: These results suggest that NIR-FME is clinically feasible as a real-time, red-flag technique for detection of colorectal adenomas