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ABSTRACT: The potential use of carbon-based methodologies for drug delivery and reproductive biology in cows raises concerns about residues in milk and food safety. This study aimed to assess the potential of Fourier transform Raman spectroscopy and discriminant analysis using partial least squares (PLS-DA) to detect functionalized multiwalled carbon nanotubes (MWCNT) in bovine raw milk. Oxidized MWCNT were diluted in milk at different concentrations from 25.00 to 0.01 µg/mL. Raman spectroscopy measurements and PLS-DA were performed to identify low concentrations of MWCNT in milk samples. The PLS-DA model was characterized by the analysis of the variable importance in projection (VIP) scores. All the training samples were correctly classified by the model, resulting in no false-positive or false-negative classifications. For test samples, only one false-negative result was observed, for 0.01 µg/mL MWCNT dilution. The association between Raman spectroscopy and PLS-DA was able to identify MWCNT diluted in milk samples up to 0.1 µg/mL. The PLS-DA model was built and validated using a set of test samples and spectrally interpreted based on the highest VIP scores. This allowed the identification of the vibrational modes associated with the D and G bands of MWCNT, as well as the milk bands, which were the most important variables in this analysis.

Abstract Colorectal cancers (CRCs) are highly heterogeneous and show a hierarchical organization, with cancer stem cells (CSCs) responsible for tumor development, maintenance, and drug resistance. Our previous studies showed the importance of thyroid hormone-dependent signaling on intestinal tumor development and progression through action on stem cells. These results have a translational value, given that the thyroid hormone nuclear receptor TRα1 is upregulated in human CRCs, including in the molecular subtypes associated with CSC features. We used an established spheroid model generated from the human colon adenocarcinoma cell line Caco2 to study the effects of T3 and TRα1 on spheroid formation, growth, and response to conventional chemotherapies. Our results show that T3 treatment and/or increased TRα1 expression in spheroids impaired the response to FOLFIRI and conferred a survival advantage. This was achieved by stimulating drug detoxification pathways and increasing ALDH1A1-expressing cells, including CSCs, within spheroids. These results suggest that clinical evaluation of the thyroid axis and assessing TRα1 levels in CRCs could help to select optimal therapeutic regimens for patients with CRC. Proposed mechanism of action of T3/TRα1 in colon cancer spheroids. In the control condition, TRα1 participates in maintaining homeostatic cell conditions. The presence of T3 in the culture medium activates TRα1 action on target genes, including the drug efflux pumps ABCG2 and ABCB1. In the case of chemotherapy FOLFIRI, the increased expression of ABC transcripts and proteins induced by T3 treatment is responsible for the augmented efflux of 5-FU and Irinotecan from the cancer cells. Taken together, these mechanisms contribute to the decreased efficacy of the chemotherapy and allow cells to escape the treatment. Created with BioRender.com .

Abstract Polyvinylidene fluoride (PVDF) is a versatile and low-cost polymer with high biocompatibility, mechanical strength, chemical resistance, thermal stability, and ferroelectricity. This material has been widely used in many applications, ranging from membranes to electronic devices. In this study, self-supporting, flexible, and lightweight PVDF films were prepared by an evaporation route using a low-toxicity solvent (dimethyl sulfoxide – DMSO). Graphene oxide (GO) and anatase titania (TiO2) were incorporated into the PVDF after preparing DMSO-based suspensions of these materials. The prepared materials were examined in terms of their structural, electrical, and wetting properties before and after exposure to near ultraviolet (UV-A) light. Substantial structural changes took place after incorporating GO and TiO2 into PVDF. Such modifications were accompanied by dramatic changes in the wetting and electrical properties of the PVDF. UV-A light caused the formation of surface defects on PVDF and GO films. In addition, it promoted the photoreduction of GO into reduced graphene oxide (rGO). Composites containing TiO2 showed high resistance to UV-A light, probably because titania particles absorb the incoming photons and shield the polymer matrix. This study provides new insights into the synthesis and characterization of PVDF/TiO2/GO composite films, which may be useful for many applications, including flexible electronics, solar cells, and biomedical devices.

Este artigo contextualiza saberes da NdC mediante a exploração do conteúdo da história conceitual da ciência, buscando enfrentar a problemática fomentada pela ideia de “visão consensual” de aspectos, características e/ou princípios da NdC, que devem informar o currículo escolar e o processo de ensino-aprendizagem em sala de aula da educação científica. Teórico-metodologicamente, este artigo está fundamentado na epistemologia da solução de problemas de Laudan; em uma extensa investigação acadêmico-científica; e nos aspectos metodológicos da moderna historiografia da ciência. Como resultados, são contextualizados mais seis vínculos epistemológicos, de vinte e um saberes da NdC, que reforçam o caráter da não neutralidade da ciência, em seus respectivos contextos de desenvolvimento. Como considerações complementares, ampliam-se as discussões sobre: (i) a superação do ensino de simples afirmações declarativas dos saberes da NdC em sala de aula; (ii) a proposição da validade epistemológica de saberes da NdC, através da contextualização histórico-filosófica; (iii) a ideia de evitar distorções desses saberes, evidenciando sua natureza contextual; e (iv) a demonstração do potencial que a visão de ciência de Laudan tem fornecido para as investigações no ensino de e sobre as ciências.

RESUMO: A temática em torno de descobertas científicas é bastante negligenciada no âmbito de e sobre ciências, principalmente no que concerne em compreendê-la histórica e epistemologicamente. Inclusive, muitas vezes, descobertas são tratadas como uma simples informação de datas, locais e pessoas. Este trabalho apresenta algumas discussões centradas em episódios históricos ligados a elementos químicos e à Lei periódica, a partir de ponderações de Thomas Kuhn e Norwood Hanson, visando evidenciar e contextualizar a estrutura conceitual e epistemológica de certas descobertas científicas. Dessa forma, resgatam-se questões acerca da inseparabilidade dos contextos da descoberta e da justificativa, as complexas estruturas intrínsecas à gênese do conhecimento científico e distintos tipos e categorias de descobertas na ciência.

Frente à problemática sobre a visão consensual de aspectos, características e princípios que devem informar a educação científica, este artigo apresenta uma nova perspectiva denominada vínculos epistemológicos entre saberes da NdC e o conteúdo da história conceitual da ciência, mediados pela contextualização histórico-filosófica de perguntas da ciência responsáveis pelo seu desenvolvimento cognitivo. Este trabalho está fundamentado na epistemologia da solução de problemas de Laudan e em uma extensa investigação acadêmico-científica. Metodologicamente, essa perspectiva é forjada por uma ampla contextualização de perguntas da ciência que fomentaram o progresso da astronomia, cosmologia e física, da Grécia antiga ao nascimento da ciência moderna nos séculos XVI e XVII. Por essa razão, são apresentados apenas oito de vinte e um saberes da NdC, ficando os demais para mais dois trabalhos complementares. Somando-se às diferentes propostas existentes, a ideia de vínculos epistemológicos pode contribuir para: (i) superar o ensino de simples afirmações declarativas de saberes da NdC em sala de aula; (ii) proporcionar uma substantiva validade epistemológica aos saberes da NdC, mediante contextualização histórico-filosófica de perguntas da ciência; (iii) evitar as distorções desses saberes, por evidenciar sua natureza contextual; e (iv) demonstrar potenciais que a visão de ciência de Laudan tem fornecido para enfrentar problemáticas inerentes ao ensino de e sobre as ciências.

Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS) that may progress to cytokine storm syndrome, organ dysfunction, and death. Considering that complement component 5a (C5a), through its cellular receptor C5aR1, has potent proinflammatory actions and plays immunopathological roles in inflammatory diseases, we investigated whether the C5a/C5aR1 pathway could be involved in COVID-19 pathophysiology. C5a/C5aR1 signaling increased locally in the lung, especially in neutrophils of critically ill patients with COVID-19 compared with patients with influenza infection, as well as in the lung tissue of K18-hACE2 Tg mice (Tg mice) infected with SARS-CoV-2. Genetic and pharmacological inhibition of C5aR1 signaling ameliorated lung immunopathology in Tg-infected mice. Mechanistically, we found that C5aR1 signaling drives neutrophil extracellular traps-dependent (NETs-dependent) immunopathology. These data confirm the immunopathological role of C5a/C5aR1 signaling in COVID-19 and indicate that antagonists of C5aR1 could be useful for COVID-19 treatment.

No contribuir de um (re)humanizar da área educativa e científica, visa-se elaborar uma proposta didática, art(sci)culada e direcionada particularmente (mas não só) a licenciandos(as) e bacharelandos(as) do campo da física. Atividade, esta, mobilizada pelo referencial educacional de Carl R. Rogers — alinhado à proposta das artes expressivas de Natalie Rogers — e pela epistemologia de Paul K. Feyerabend. A temática envolvida — presente em uma história em quadrinhos e nos textos a ela associados — abarca discussões sobre as transformações do pensar e do fazer ciência-física registradas de modo pictórico por alguns povos e em certos momentos históricos. Na ‘Expo(r)-(po)sição Art(sci)culada’ se propõe o desenvolvimento de (mini)projetos artísticos relacionados aos debates históricos-filosóficos supracitados. Por fim, apresentam-se cenários passíveis e viáveis de implementação da atividade — evidenciando que ela é praticável em condições factuais, sobretudo, de Institutos e de Universidades.

Em fevereiro de 1968, a então estudante de pós-graduação Jocelyn Bell, seu orientador Antony Hewish e demais integrantes do grupo de radioastrônomos da Universidade de Cambridge publicaram um artigo na Revista Nature sobre incomuns sinais pulsados em ondas de rádio, identificados inicialmente em meados de agosto de 1967, gerando um amplo movimento da comunidade científica para entendimento deste suposto novo objeto astronômico: os pulsares. Neste artigo, objetivamos discutir aspectos históricos envolvidos no processo de compreensão conceitual dos pulsares, tendo como base artigos científicos publicados à época, comentários sobre o episódio elaborados por Jocelyn Bell Burnell e Antony Hewish, além de estudos secundários sobre a história dos pulsares. A partir de reflexões de Ludwik Fleck e Thomas Kuhn, as discussões de Natureza da Ciência evidenciadas consistem, por exemplo, na extensão temporal e na construção coletiva de uma descoberta científica e no processo complexo de circulação de teorias e de observações sobre um fenômeno entre astrônomos.

The detection of neutron stars is one of the most unique scientific events in the field of Astronomy. This discovery, led by astronomer Jocelyn Bell Burnell, enabled the identification of the first signs that would later be recognized as pulsars, which allows a better understanding of the process of evolution of the stars. However, there is a lack of knowledge by teachers and students about the process of stellar evolution. In this article, we developed a bibliographic research in order to investigate how the history of discovery of pulsars and the performance of Jocelyn Bell Burnell in this episode is manifested in research published in the last decades in the field of Physics and Astronomy Teaching, as well as academic research in these areas. It was selected 35 researches, among papers published in journals and events, in addition to dissertations and theses. The development of the analysis was based on primary and secondary sources that deal with historical elements about the discovery of pulsars. It was observed that specific works carry out a historical discussion about these celestial objects, mainly academic productions in the field of Physics and Astronomy, while research in the field of teaching concentrates discussions in a conceptual scope. Also, this episode presents potential for studies about the nature of science and about the visibility of women in science.

Partindo-se do pressuposto de que relações da arteciência podem auxiliar na compreensão da construção histórica e cultural do conhecimento científico, apresentam-se os resultados da implementação de um módulo de ensino – constituído por uma história em quadrinhos e por seus textos associados – com intuito de se discutir a não neutralidade na observação e o papel dos experimentos no empreendimento científico através de pinturas. O módulo foi aplicado em uma disciplina de história da ciência de um curso de física. A partir dele objetivou-se analisar, com base na teoria fundamentada construtivista de Kathy Charmaz, em que medida o mesmo fornece subsídios para que os(as) alunos(as) possam refletir sobre a prática pedagógica e científica de modo mais crítico e diversificado. Verificou-se que o módulo de ensino apresenta potencialidade para se pensar a ciência com a arte e as pluralidades na educação científica.

Abstract Glioblastoma (GBM) displays marked cellular and metabolic heterogeneity that varies among cellular microenvironments within a tumor. Metabolic targeting has long been advocated as a therapy against many tumors including GBM, but how lipid metabolism is altered to suit different microenvironmental conditions and whether cancer stem cells (CSCs) have altered lipid metabolism are outstanding questions in the field. We interrogated gene expression in separate microenvironments of GBM organoid models that mimic the transition between nutrient-rich and nutrient-poor pseudopalisading/perinecrotic tumor zones using spatial-capture RNA-sequencing. We revealed a striking difference in lipid processing gene expression and total lipid content between diverse cell populations from the same patient, with lipid enrichment in hypoxic organoid cores and also in perinecrotic and pseudopalisading regions of primary patient tumors. This was accompanied by regionally restricted upregulation of hypoxia-inducible lipid droplet-associated (HILPDA) gene expression in organoid cores and pseudopalisading regions of clinical GBM specimens, but not lower-grade brain tumors. CSCs have low lipid droplet accumulation compared to non-CSCs in organoid models and xenograft tumors, and prospectively sorted lipid-low GBM cells are functionally enriched for stem cell activity. Targeted lipidomic analysis of multiple patient-derived models revealed a significant shift in lipid metabolism between GBM CSCs and non-CSCs, suggesting that lipid levels may not be simply a product of the microenvironment but also may be a reflection of cellular state. CSCs had decreased levels of major classes of neutral lipids compared to non-CSCs, but had significantly increased polyunsaturated fatty acid production due to high fatty acid desaturase (FADS1/2) expression which was essential to maintain CSC viability and self-renewal. Our data demonstrate spatially and hierarchically distinct lipid metabolism phenotypes occur clinically in the majority of patients, can be recapitulated in laboratory models, and may represent therapeutic targets for GBM.

One of the objectives of scientific education, at the present time, at any level of education is to provide an understanding of the nature of science compatible with contemporary philosophical reflections. However, implicit discussions about science in teaching materials are not enough to promote meaningful and current learning of the subject. The literature shows that it is necessary to develop strategies that make explicit certain propositions, or questions. In general, decontextualized and declarative principles of succinct and ambiguous statements present in lists that combine theoretically consensual aspects about the nature of science are often distorted and misunderstood by students and teachers. In this sense, this article presents a series of 18 commented statements, which explain overlaps and convergences, as well as divergences, as a potentially useful alternative to approach various aspects of the nature of science and scientific work in teaching. In addition, it contextualizes the genesis of these propositions, initially developed to be articulated to a set of texts on the history of science / physics, but which are equally useful for a link and contrast with historical productions of science in general, epistemological analyzes of films , series / videos, hypermedia, historical documents and narratives and other actions aimed at a better understanding and deepening of this theme in the universe of students, professors and researchers in formation.

Abstract Background RNA-binding proteins (RBPs) function as master regulators of gene expression. Alterations in RBP expression and function are often observed in cancer and influence critical pathways implicated in tumor initiation and growth. Identification and characterization of oncogenic RBPs and their regulatory networks provide new opportunities for targeted therapy. Results We identify the RNA-binding protein SERBP1 as a novel regulator of glioblastoma (GBM) development. High SERBP1 expression is prevalent in GBMs and correlates with poor patient survival and poor response to chemo- and radiotherapy. SERBP1 knockdown causes delay in tumor growth and impacts cancer-relevant phenotypes in GBM and glioma stem cell lines. RNAcompete identifies a GC-rich region as SERBP1-binding motif; subsequent genomic and functional analyses establish SERBP1 regulation role in metabolic routes preferentially used by cancer cells. An important consequence of these functions is SERBP1 impact on methionine production. SERBP1 knockdown decreases methionine levels causing a subsequent reduction in histone methylation as shown for H3K27me3 and upregulation of genes associated with neurogenesis, neuronal differentiation, and function. Further analysis demonstrates that several of these genes are downregulated in GBM, potentially through epigenetic silencing as indicated by the presence of H3K27me3 sites. Conclusions SERBP1 is the first example of an RNA-binding protein functioning as a central regulator of cancer metabolism and indirect modulator of epigenetic regulation in GBM. By bridging these two processes, SERBP1 enhances glioma stem cell phenotypes and contributes to GBM poorly differentiated state.

Abstract High-dose radiation is the main component of glioblastoma therapy. Unfortunately, radio-resistance is a common problem and a major contributor to tumor relapse. Understanding the molecular mechanisms driving response to radiation is critical for identifying regulatory routes that could be targeted to improve treatment response. We conducted an integrated analysis in the U251 and U343 glioblastoma cell lines to map early alterations in the expression of genes at three levels: transcription, splicing, and translation in response to ionizing radiation. Changes at the transcriptional level were the most prevalent response. Downregulated genes are strongly associated with cell cycle and DNA replication and linked to a coordinated module of expression. Alterations in this group are likely driven by decreased expression of the transcription factor FOXM1 and members of the E2F family. Genes involved in RNA regulatory mechanisms were affected at the mRNA, splicing, and translation levels, highlighting their importance in radiation-response. We identified a number of oncogenic factors, with an increased expression upon radiation exposure, including BCL6, RRM2B, IDO1, FTH1, APIP, and LRIG2 and lncRNAs NEAT1 and FTX. Several of these targets have been previously implicated in radio-resistance. Therefore, antagonizing their effects post-radiation could increase therapeutic efficacy. Our integrated analysis provides a comprehensive view of early response to radiation in glioblastoma. We identify new biological processes involved in altered expression of various oncogenic factors and suggest new target options to increase radiation sensitivity and prevent relapse.

Uncoupling protein-1 (UCP1) plays a central role in energy dissipation in brown adipose tissue. Here the authors show that FGF6 and FGF9 induce UCP1 expression in adipocytes and preadipocytes, via modulation of a transcriptional network that is dissociated from brown adipogenesis.

Examina-se a relação de conhecimentos – sobre a natureza e o mundo – de povos originários (e.g., mesopotâmica, egípcia e chinesa) em um período antecedente à escrita e à inquisição investigativa grega do século VI AEC. Como subsídio para a discussão, utilizam-se retratações artísticas de eventos que ocuparam a atenção pública em certos momentos históricos e que se façam expressas sob a forma de representações pictóricas bidimensionais, tais como aquelas adornadas em cavernas, tumbas, ornamentos cilíndricos ou ilustradas em papiros. Para a avaliação das imagens usa-se a análise iconográfica de Erwin Panofsky. Do exame das informações postas, averígua-se a predominância da temática cosmológica-astronômica nas obras supracitadas; construídas sob um viés mítico e desprendidas de interesses e de procedimentos analíticos. Entretanto, também, se identifica uma forma preliminar e rudimentar da base científica – utilitária que coloca em prática aquilo que cotidianamente se observava e pictoricamente se registrava.

No ano de 1967, a então estudante de pós-graduação Jocelyn Bell identificou sinais pulsados de ondas de rádio, que posteriormente puderam corroborar observacionalmente a existência das estrelas de nêutrons. Neste trabalho, desenvolvemos um estudo histórico-epistemológico sobre o episódio de detecção dos pulsares a partir de relatos elaborados por Jocelyn Bell Burnell e por seu orientador, Antony Hewish, e de pesquisas que se debruçaram sobre este tema. Na análise epistemológica, consideramos, predominantemente, aspectos da filosofia da ciência de Thomas Kuhn e Norwood Hanson. Os resultados chamam atenção para o papel da serendipidade em uma descoberta científica e para a importância do trabalho coletivo em um período de ciência normal, que neste caso propiciaram novos estudos teóricos e observacionais para a compreensão deste novo objeto astronômico. Ressaltamos que a discussão da serendipidade e do acaso no contexto de ensino de ciências pode contribuir para desmistificar ideias equivocadas sobre este conceito, favorecendo uma melhor compreensão da natureza do conhecimento científico. O trabalho também possibilita evidenciar o protagonismo de uma mulher cientista em um importante episódio científico.

Abstract Studies of risk perception and risk communication concerning the nuclear area are quite common in scientific literature. However, though numerous studies on this topic point to the importance of scientific and technological knowledge in facilitating the reduction of perceived risks, there are few papers that effectively discuss the role of education in risk communication on the subject, particularly in Brazil. The objective of the present work was to reflect on this problem by analyzing the results obtained from two case studies on the implementation of the Brazilian Multipurpose Reactor, in the city of Iperó, in the state of São Paulo, Brazil. As was verified in the investigation, most participants of the study had high perception of risk with respect to the implementation of the reactor. Nevertheless, although important in the project of the reactor implementation, it was verified that the state, municipal and community schools of the city of Iperó had not participated, in the public hearings nor had they discussed the issue inside the school community, until the moment of the research.

RESUMO: Visa-se a colaborar para a humanização da formação de professores(as) e de cientistas, bem como da própria ciência, ao se investigar perspectivas da correspondência entre alguns aspectos da teoria da aprendizagem significante de Carl R. Rogers e da epistemologia de Paul K. Feyerabend. Das convergências entre o referencial educacional e o epistemológico, averíguam-se potencialidades de correlação do (i) aprender a aprender do sujeito em processo de aprendizagem com a compreensão de um saber científico em constante desenvolvimento; e (ii) do pluralismo metodológico com o uso de práticas diversificadas tanto para o âmbito pedagógico quanto para o científico. Também são apresentadas sugestões de implementação das interlocuções entre os aportes teóricos supracitados; evidenciando que as discussões são praticáveis em condições factuais de universidades.

RNA binding proteins (RBPs) are essential for critical biological processes such as translation regulation and mRNA processing, and misfunctions of these proteins are associated with diseases such as cancer and neurodegeneration. SERBP1 (SERPINE1 mRNA Binding Protein 1) is an RBP that comprises two RG/RGG repeat regions yet lacks other recognizable RNA-binding motifs. It is involved in mRNA maturation, and translational regulation. It was initially identified as a hyaluronic acid binding protein, but recent studies have identified central roles for SERBP1 in brain function and development, especially neurogenesis and synaptogenesis. SERBP1 regulates One-carbon metabolism and epigenetic modification of histones, and increased SERBP1 expression in cancers such as leukemia, ovarian, prostate, liver and glioblastoma is correlated with poor patient outcomes. Despite these important regulatory roles for SERBP1, little is known about its structural and dynamic properties, nor about the molecular mechanisms governing its interaction with mRNA. Here, we define SERBP1 as an intrinsically disordered protein, containing highly conserved elements that were shown to be functionally important. The RNA binding activity of SERBP1 was explored using solution NMR and other biophysical techniques. The outcome of these experiments revealed that SERBP1 preferentially samples compact conformations including a central, stable α-helix and show that SERBP1 recognizes G-rich RNA sequences at the C-terminus involving the RGG box and neighboring residues. Despite the role in RNA recognition, the RGG boxes do not seem to stabilize the central helix and the central helix does not participate in RNA binding. Further, SERBP1 undergoes liquid-liquid phase separation, mediated by salt and RNA, and both RGG boxes are necessary for the efficient formation of condensed phases. Together, these results provide a foundation for understanding the molecular mechanisms of SERBP1 functions in physiological and pathological processes.

Objective To evaluate whether the addition of colchicine to standard treatment for COVID-19 results in better outcomes.Design We present the results of a randomised, double-blinded, placebo-controlled clinical trial of colchicine for the treatment of moderate to severe COVID-19, with 75 patients allocated 1:1 from 11 April to 30 August 2020. Colchicine regimen was 0.5 mg thrice daily for 5 days, then 0.5 mg twice daily for 5 days. The primary endpoints were the need for supplemental oxygen, time of hospitalisation, need for admission and length of stay in intensive care unit and death rate.Results Seventy-two patients (36 for placebo and 36 for colchicine) completed the study. Median (and IQR) time of need for supplemental oxygen was 4.0 (2.0–6.0) days for the colchicine group and 6.5 (4.0–9.0) days for the placebo group (p

A low-cost and disposable graphene polylactic (G-PLA) 3D-printed electrode modified with gold particles (AuPs) was explored to detect the cDNA of SARS-CoV-2 and creatinine, a potential biomarker for COVID-19. For that, a simple, non-enzymatic electrochemical sensor, based on a Au-modified G-PLA platform was applied. The AuPs deposited on the electrode were involved in a complexation reaction with creatinine, resulting in a decrease in the analytical response, and thus providing a fast and simple electroanalytical device. Physicochemical characterizations were performed by SEM, EIS, FTIR, and cyclic voltammetry. Square wave voltammetry was employed for the creatinine detection, and the sensor presented a linear response with a detection limit of 0.016 mmol L−1. Finally, a biosensor for the detection of SARS-CoV-2 was developed based on the immobilization of a capture sequence of the viral cDNA upon the Au-modified 3D-printed electrode. The concentration, immobilization time, and hybridization time were evaluated in presence of the DNA target, resulting in a biosensor with rapid and low-cost analysis, capable of sensing the cDNA of the virus with a good limit of detection (0.30 µmol L−1), and high sensitivity (0.583 µA µmol−1 L). Reproducible results were obtained (RSD = 1.14%, n = 3), attesting to the potentiality of 3D-printed platforms for the production of biosensors.

A novel flexible supercapacitor device was developed from a polyethylene terephthalate substrate, reused from beverage bottles, and a conductive ink based on carbon black (CB) and cellulose acetate (CA). The weight composition of the conductive ink was evaluated to determine the best mass percentage ratio between CB and CA in terms of capacitive behavior. The evaluation was performed by using different electrochemical techniques: cyclic voltammetry, obtaining the highest capacitance value for the device with the 66.7/33.3 wt% CB/CA in a basic H2SO4 solution, reaching 135.64 F g−1. The device was applied in potentiostatic charge/discharge measurements, achieving values of 2.45 Wh kg−1 for specific energy and around 1000 W kg−1 for specific power. Therefore, corroborated with electrochemical impedance spectroscopy assays, the relatively low-price proposed device presented a suitable performance for application as supercapacitors, being manufactured from reused materials, contributing to the energy storage field enhancement.

Summary: Thermogenic fat expends energy during cold for temperature homeostasis, and its activity regulates nutrient metabolism and insulin sensitivity. We measured cold-activated lipid landscapes in circulation and in adipose tissue by MS/MSALL shotgun lipidomics. We created an interactive online viewer to visualize the changes of specific lipid species in response to cold. In adipose tissue, among the approximately 1,600 lipid species profiled, we identified the biosynthetic pathway of the mitochondrial phospholipid cardiolipin as coordinately activated in brown and beige fat by cold in wild-type and transgenic mice with enhanced browning of white fat. Together, these data provide a comprehensive lipid bio-signature of thermogenic fat activation in circulation and tissue and suggest pathways regulated by cold exposure. : In this resource, Lynes et al. use a sensitive MS/MSALL technique to profile over 1,000 lipid species in the blood and adipose tissue of humans and mice exposed to cold. Using the online viewer they created to view these data, pathways activated by cold exposure can be identified. Keywords: brown adipose tissue, white adipose tissue, lipidomics, thermogenesis, cardiolipin

Francis Bacon is sometimes referred to as the first experimental philosopher, and his philosophy is usually tied to the common empirical-inductive idea. In order to show a new Baconian image, this article analyzes parts of his main work, the Novum Organum, and presents his concept of experientia literata, little known. In addition, it explicit counterpoints between some considerations presented by Bacon, particularly about the literata experientia, and certain conceptions of the "new experimentalism", especially in light of the concept of exploratory experimentation outlined by Steinle. Finally, it approaches some implications of these reflections for science teaching.

This work deals with a transmission-reception ultrasonic technique for the real-time estimation of the water content in water-in-crude oil emulsions. The working principle is the measurement of the propagation velocity, using two in-house manufactured transducers designed for water coupling, with a central frequency of about 3 MHz. Water-in-crude oil emulsions with a water volume concentration from 0% to 40% were generated by mechanical emulsification. Tests were carried out at three temperatures. The results showed that the propagation velocity is a sensitive parameter that is able to determine the water content, allowing for differentiating the concentrations of up to 40% of water. The main motivation is the development of techniques for non-invasive and real-time monitoring of the water content of emulsions in petrochemical processes.

Medulloblastoma is the most common malignant brain tumor in children. Treatment with surgery, irradiation, and chemotherapy has improved survival in recent years, but patients are frequently left with devastating neurocognitive and other sequelae. Patients in molecular subgroups 3 and 4 still experience a high mortality rate. To identify new pathways contributing to medulloblastoma development and create new routes for therapy, we have been studying oncogenic RNA-binding proteins. We defined Musashi1 (Msi1) as one of the main drivers of medulloblastoma development. The high expression of Msi1 is prevalent in Group 4 and correlates with poor prognosis while its knockdown disrupted cancer-relevant phenotypes. Genomic analyses (RNA-seq and RIP-seq) indicated that cell cycle and division are the main biological categories regulated by Msi1 in Group 4 medulloblastoma. The most prominent Msi1 targets include CDK2, CDK6, CCND1, CDKN2A, and CCNA1. The inhibition of Msi1 with luteolin affected the growth of CHLA-01 and CHLA-01R Group 4 medulloblastoma cells and a synergistic effect was observed when luteolin and the mitosis inhibitor, vincristine, were combined. These findings indicate that a combined therapeutic strategy (Msi1 + cell cycle/division inhibitors) could work as an alternative to treat Group 4 medulloblastoma.

Abstract Background Dengue is the most prevalent arthropod-borne viral disease in the world. In this article we present results on the development, characterization and immunogenic evaluation of an alternative vaccine candidate against Dengue. Methods The MWNT-DENV3E nanoconjugate was developed by covalent functionalization of carboxylated multi-walled carbon nanotubes (MWNT) with recombinant dengue envelope (DENV3E) proteins. The recombinant antigens were bound to the MWNT using a diimide-activated amidation process and the immunogen was characterized by TEM, AFM and Raman Spectroscopy. Furthermore, the immunogenicity of this vaccine candidate was evaluated in a murine model. Results Immunization with MWNT-DENV3E induced comparable IgG responses in relation to the immunization with non-conjugated proteins; however, the inoculation of the nanoconjugate into mice generated higher titers of neutralizing antibodies. Cell-mediated responses were also evaluated, and higher dengue-specific splenocyte proliferation was observed in cell cultures derived from mice immunized with MWNT-DENV3E when compared to animals immunized with the non-conjugated DENV3E. Conclusions Despite the recent licensure of the CYD-TDV dengue vaccine in some countries, results from the vaccine’s phase III trial have cast doubts about its overall efficacy and global applicability. While questions about the effectiveness of the CYD-TDV vaccine still lingers, it is wise to keep at hand an array of vaccine candidates, including alternative non-classical approaches like the one presented here.

Opsin3 (Opn3) is a transmembrane heptahelical G protein-coupled receptor (GPCR) with the potential to produce a nonvisual photoreceptive effect. Interestingly, anatomical profiling of GPCRs reveals that Opn3 mRNA is highly expressed in adipose tissue. The photosensitive functions of Opn3 in mammals are poorly understood, and whether Opn3 has a role in fat is entirely unknown. In this study, we found that Opn3-knockout (Opn3-KO) mice were prone to diet-induced obesity and insulin resistance. At the cellular level, Opn3-KO brown adipocytes cultured in darkness had decreased glucose uptake and lower nutrient-induced mitochondrial respiration than wild-type (WT) cells. Light exposure promoted mitochondrial activity and glucose uptake in WT adipocytes but not in Opn3-KO cells. Brown adipocytes carrying a defective mutation in Opn3's putative G protein-binding domain also exhibited a reduction in glucose uptake and mitochondrial respiration in darkness. Using RNA-sequencing, we identified several novel light-sensitive and Opn3-dependent molecular signatures in brown adipocytes. Importantly, direct exposure of brown adipose tissue (BAT) to light in living mice significantly enhanced thermogenic capacity of BAT, and this effect was diminished in Opn3-KO animals. These results uncover a previously unrecognized cell-autonomous, light-sensing mechanism in brown adipocytes via Opn3-GPCR signaling that can regulate fuel metabolism and mitochondrial respiration. Our work also provides a molecular basis for developing light-based treatments for obesity and its related metabolic disorders.

O século XVIII valoriza a experimentação na pesquisa científica. Os estudos de Stephen Gray exemplificam a relação existente entre as convicções teóricas do pesquisador e a experimentação que desenvolve. Nessa perspectiva, explicitam as diferentes funções que podem ter o experimento na atividade científica e a pluralidade metodológica existente nesse processo. Contextualiza-se, nesse artigo, o caminho histórico de algumas descobertas realizadas por esse estudioso, pouco conhecido na literatura nacional, como a conceitualização dos corpos isolantes e condutores e a condução elétrica. Ressalta-se, ainda, a importância de se analisar o contexto da descoberta no âmbito de um ensino não apenas de ciência, mas sobre a ciência.

Ilustra-se um aspecto da natureza da ciência (ndc) por meio de um episódio histórico da ciência retratado em imagens, com intuito de ressaltar que, tanto questões teóricas quanto técnicas exercem influência no modo de produção do conhecimento. Em um primeiro momento, enfatiza-se a não neutralidade da observação ao se evidenciar a influência que teorias e técnicas artísticas relativas à perspectiva e ao chiaroscuro exerceram sob a maneira como Thomas Harriot, Galileo Galilei e Lodovico Cardi representaram a superfície lunar. Por fim, pondera-se sobre a potencialidade dessa análise para incrementar a educação científica ao se destacar a importância das imagens na compreensão e na construção histórica do conhecimento

RESUMO: A sociedade contemporânea é marcada por mudanças drásticas e rápidas, e assim uma educação pautada em transmitir verdade, certezas, dicotomias, entidades isoladas vem perdendo o sentido. A escola poderá ser mais útil se preparar os alunos para não serem subjugados aos poderes dominantes presentes na sociedade em que vivemos. Em especial, a educação em ciências pode ter um papel importante nesta nova forma de ver a educação. Este trabalho relata uma pesquisa de caráter teórico e empírico que procurou explorar como as obras de Neil Postman, Paul Feyerabend e Marco Antonio Moreira podem contribuir para evidenciar como a educação científica pode ser útil no século XXI. A articulação desses referenciais para uma educação científica por meio de história da ciência tem o objetivo de formar pessoas questionadoras, flexíveis, criativas, inovadoras, tolerantes e progressistas; que segundo Postman e Moreira, são as que menos se subjugam aos poderes constituídos na sociedade contemporânea.

Researchers in science teaching have advocated concomitant education about and of science. To approach the nature and history of science in basic education is necessary to have an epistemological approach that can go between of rationalism of Bunge and relativism of Feyerabend. In this paper, it is argued that Feyerabend's epistemological stance is that more can help promote meaningful learning critical, so as to form inquiring, flexible, creative, innovative, tolerant and liberal people. In addition, the suggestions Feyerabend's epistemology also complement the Theory of Meaningful Learning Critical to propose a curriculum and a context for the principles of the theory are in science classrooms.

This paper examines the results obtained with the implementation of a teaching module in a discipline of History of Science. Data were collected through a questionnaire which demanded the students a historical and philosophical analysis of a specific period of electricity and a critical assessment of the implemented module in the discipline. In general terms, the proposed module was effective promoting a satisfactory articulation between the historical content and specific aspects of the philosophy of science

Many of the objections to Feyerabend's epistemology arise from misinterpretations of ideas by this author. Terms and expressions as epistemological anarchism, irrationality, control of science and anything goes can give the false impression that the author's arguments are chaotic and unsustainable. This paper discusses these concepts, opposing the misconceptions about them. In initial and continuing teacher education, this reflection can be useful both for the deconstruction of certain misleading images about the nature of science and for the upbringing of critical citizens acquaintated to the concepts of modern philosophy of science.

Charles Du Fay, un filósofo natural del inicio del siglo XVIII, se entregó a una intensa búsqueda por encontrar mecanismos que pudieran explicar ciertos fenómenos eléctricos todavía no comprendidos en su época. Realizando inúmeros experimentos en constante diálogo con las hipótesis desarrolladas, él enuncia dos principios y “descubre” la repulsión como algo legítimo de las interacciones eléctricas. Bajo esta perspectiva, este artículo resalta, además del recorrido histórico de este estudioso, la relevancia del análisis del contexto de la descubierta para que se puedan comprender, con más propiedad, la no neutralidad del estudioso, los errores que impulsan a los éxitos y los distintos métodos de construcción del conocimiento. Además, se resalta la importancia de consideraciones históricas y filosóficas para la enseñanza que pretende discutir, además de conceptos físicos, concepciones relativas a la naturaleza de la ciencia.

RESUMO: Neste trabalho, descreve-se uma revisão bibliográfica em dissertações de mestrados e teses de doutorado no último decênio, que tecem considerações acerca da abordagem didática de história e filosofia da ciência na educação científica. A análise procurou, em um primeiro momento, identificar as referências filosóficas e pedagógicas declaradas pelos autores. A seguir, a investigação buscou os objetivos manifestados pelos autores para o uso didático da história e filosofia da ciência, também se e como eles articulam os referenciais adotados com a abordagem na educação científica de história e filosofia da ciência. Os resultados mostram que, com frequência, um aporte teórico, filosófico e metodológico está ausente. Bem como, quando existe tal fundamentação, há regularmente ausência da articulação e coerência entre elas. Como possíveis conclusões, os resultados podem e devem causar uma reflexão em relação ao desenvolvimento e credibilidade da própria área de pesquisa em educação científica.

ABCA1 is a major regulator of cellular cholesterol efflux and plasma HDL biogenesis. Even though the transcriptional activation of ABCA1 is well established, the posttranscriptional regulation of ABCA1 expression is poorly understood. Here, we investigate the potential contribution of the RNA binding protein (RBP) human antigen R (HuR) on the posttranscriptional regulation of ABCA1 expression. RNA immunoprecipitation assays demonstrate a direct interaction between HuR and ABCA1 mRNA. We found that HuR binds to the 3′ untranslated region of ABCA1 and increases ABCA1 translation, while HuR silencing reduces ABCA1 expression and cholesterol efflux to ApoA1 in human hepatic (Huh-7) and monocytic (THP-1) cells. Interestingly, cellular cholesterol levels regulate the expression, intracellular localization, and interaction between HuR and ABCA1 mRNA. Finally, we found that HuR expression was significantly increased in macrophages from human atherosclerotic plaques, suggesting an important role for this RBP in controlling macrophage cholesterol metabolism in vivo. In summary, we have identified HuR as a novel posttranscriptional regulator of ABCA1 expression and cellular cholesterol homeostasis, thereby opening new avenues for increasing cholesterol efflux from atherosclerotic foam macrophages and raising circulat­ing HDL cholesterol levels.

Parte das investigações físicas e químicas dos núcleos ganharam novas perspectivas com as descobertas do nêutron, em 1932, e da radioatividade artificial, em 1933. Irradiando diversos elementos com nêutrons, Enrico Fermi e seus colaboradores pensaram ter produzido os primeiros transurânicos. Entretanto, com o passar dos anos, essa concepção fez surgir muitas anomalias. Somente em 1939, Otto Hahn e Fritz Strassmann observaram que a irradiação do urânio com nêutrons produzia, na realidade, elementos muito mais leves, como o bário, e Lise Meitner e Otto Frisch identificaram o fenômeno como a fissão nuclear. Este trabalho enfatiza que a característica interdisciplinar das investigações nucleares exerceu papel duplo, evitando que sua descoberta fosse feita em 1934, mas também oferecendo paulatinamente as metodologias e novas possibilidades teóricas nos anos que se seguiram, até 1939, facilitando tal descoberta. Por fim, são analisadas algumas perspectivas para a educação científica, especialmente no que concerne o ensino de certos aspectos da natureza da ciência.

The impacts of forest fragmentation on both reproductive biology and genetic diversity of native plant species is hardly understood, despite some studies have analyzed this current worldwide problem. Since this constitutes one of the main threats to seasonal semi-deciduous forests in Southeastern Brazil, we investigated the reproductive success and the genetic diversity of a distylous, understory shrub (Psychotria hastisepala) within this context of forest fragmentation. For this study, a set of seven forest fragments of sizes ranging from 4.1 to 168.7 hectares were chosen. The intervenient matrix comprised pastures (25-50%), monocultures (33-50%) and rural roads and buildings (14-28.5%). Overall, 91 plants (54 for the short-styled morph and 37 for the long-styled morph; mean of 6.5 plants per fragment) were investigated. To evaluate reproductive success, we quantified fruit and seed production under natural pollination; to evaluate genetic diversity and population structure, we employed ISSR markers on genomic DNA. Plants with the short-styled morph exhibited a significantly higher reproductive success than those with the long-styled morph; there was no association between seed production and size of the forest fragment. Levels of genetic diversity were positively associated with the number of plants per fragment; but they were not related to flower morph. AMOVA showed that about 65% of the overall genetic variation was attributed to the differences between plants within fragments. The results suggested that populations of P. hastisepala were susceptible to decline owing to forest fragmentation. Rev. Biol. Trop. 62 (1): 309-319. Epub 2014 March 01.

Este artigo busca explicitar a estrutura conceitual e epistemológica de uma descoberta científica de modo a contrapor a dicotomia entre os contextos da descoberta e da justificativa, perpetuada por muito tempo na esfera científica. Para tanto, apresenta as ponderações de Hanson, Kipnis e Kuhn sobre esse tema. No ensino de ciências, discussões acerca do processo de uma descoberta ainda são raramente existentes. Desta forma, normalmente, são disseminadas várias imagens inadequadas sobre a ciência. Uma análise da terminologia descoberta nos livros didáticos aprovados no PNLD/2012 evidencia as concepções de ciência que se pode transmitir no ensino quando se utiliza, de maneira ampla e inadvertidamente, esse termo. Por fim, procura argumentar que o contexto da descoberta possui elementos complexos e lógicos, e está, de forma intrínseca, relacionado ao contexto da justificação.

Em filosofia, diz-se que teorias são subdeterminadas pelas evidências, isto é, que não há um conjunto de evidências capaz de determinar uma escolha teórica. Essa questão fica clara no estudo de caso histórico da descoberta da fissão nuclear. Os caminhos tortuosos trilhados por físicos e químicos nucleares mostram as complexidades inerentes ao trabalho científico e os juízos de valor necessários para se guiar a prática científica e resolver anomalias teóricas, metodológicas e mesmo axiológicas. Com o auxílio das visões de ciência de Larry Laudan e Helen Longino, especialmente profícuas para esse episódio, este trabalho busca mostrar que, apesar disso, não se caiu em um abismo ilógico ou irracional nesse período. Uma abordagem educacional desse episódio, centrada nos problemas, na coletividade e na intersubjetividade, tem grande potencialidade para a educação científica.

Discussões sobre a natureza da ciência ainda são bastante incipientes em sala de aula, embora a literatura especializada aponte para a relevância da inserção de questões históricas e epistemológicas na formação do estudante, em geral. Neste trabalho, analisam-se algumas perspectivas educacionais de um material composto por cinco animações potencialmente significativas, desenvolvidas para uma disciplina sobre a história da física de um curso de física na modalidade de Educação a Distância. As animações articulam-se aos textos usados nesta disciplina, que abordam um amplo espectro de conteúdos sobre a história da física à luz da moderna filosofia da ciência, e a outros segmentos típicos de uma disciplina não presencial.

Abstract A new study investigates how microRNAs affect the binding of proteins to RNA.

Abstract Transcription, mRNA decay, translation and protein degradation are essential processes during eukaryotic gene expression, but their relative global contributions to steady‐state protein concentrations in multi‐cellular eukaryotes are largely unknown. Using measurements of absolute protein and mRNA abundances in cellular lysate from the human Daoy medulloblastoma cell line, we quantitatively evaluate the impact of mRNA concentration and sequence features implicated in translation and protein degradation on protein expression. Sequence features related to translation and protein degradation have an impact similar to that of mRNA abundance, and their combined contribution explains two‐thirds of protein abundance variation. mRNA sequence lengths, amino‐acid properties, upstream open reading frames and secondary structures in the 5′ untranslated region (UTR) were the strongest individual correlates of protein concentrations. In a combined model, characteristics of the coding region and the 3′UTR explained a larger proportion of protein abundance variation than characteristics of the 5′UTR. The absolute protein and mRNA concentration measurements for >1000 human genes described here represent one of the largest datasets currently available, and reveal both general trends and specific examples of post‐transcriptional regulation.

Polyurethane/multi-walled carbon nanotube (MWCNT) nanocomposites have been prepared with nanotube concentrations between 0.01 wt% and 1 wt%. MWCNT as-synthesized samples with ~74 nm diameter and ~7 μm length were introduced by solution processing in the polyurethane matrix. Scanning electron microscopy (SEM) images demonstrated good dispersion and adhesion of the CNTs to the polymeric matrix. The C=O stretching band showed evidence of perturbation of the hydrogen interaction between urethanic moieties in the nanocomposites as compared to pure TPU. Differential scanning calorimetry and positron anihilation lifetime spectroscopy measurements allowed the detection of glass transition displacement with carbon nanotube addition. Furthermore, the electrical conductivity of the nanocomposites was significantly increased with the addition of CNT.

Phakopsora pachyrhizi has dispersed globally and brought severe economic losses to soybean growers. The fungus has been established in Brazil since 2002 and is found nationwide. To gather information on the temporal and spatial patterns of genetic variation in P. pachyrhizi , we sequenced the nuclear internal transcribed spacer regions (ITS1 and ITS2). Total genomic DNA was extracted using either lyophilized urediniospores or lesions removed from infected leaves sampled from 26 soybean fields in Brazil and one field in South Africa. Cloning prior to sequencing was necessary because direct sequencing of PCR amplicons gave partially unreadable electrophoretograms with peak displacements suggestive of multiple sequences with length polymorphism. Sequences were determined from four clones per field. ITS sequences from African or Asian isolates available from the GenBank were included in the analyses. Independent sequence alignments of the ITS1 and ITS2 datasets identified 27 and 19 ribotypes, respectively. Molecular phylogeographic analyses revealed that ribotypes of widespread distribution in Brazil displayed characteristics of ancestrality and were shared with Africa and Asia, while ribotypes of rare occurrence in Brazil were indigenous. The results suggest P. pachyrhizi found in Brazil as originating from multiple, independent long-distance dispersal events.

Neste ensaio discute-se o diálogo entre hipótese e experimentação na construção do conhecimento científico, explicitando as novas preocupações epistêmicas que se teve com o experimento, sobretudo no início dos anos 80. Apresenta-se, sucintamente, concepções da experimentação normalmente disseminadas no ensino de ciências. Através do conceito de experimentação exploratória, delineado por Steinle, discorre-se sobre a distinção explicitada por Reichenbach entre os contextos da descoberta e da justificativa evidenciando, por meio de uma revisão bibliográfica, pertinentes objeções a essa dicotomia à luz da moderna filosofia da ciência.