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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: 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 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.

Zika virus (ZIKV) causes microcephaly by killing neural precursor cells (NPCs) and other brain cells. ZIKV also displays therapeutic oncolytic activity against glioblastoma (GBM) stem cells (GSCs). Here we demonstrate that ZIKV preferentially infected and killed GSCs and stem-like cells in medulloblastoma and ependymoma in a SOX2-dependent manner. Targeting SOX2 severely attenuated ZIKV infection, in contrast to AXL. As mechanisms of SOX2-mediated ZIKV infection, we identified inverse expression of antiviral interferon response genes (ISGs) and positive correlation with integrin αv (ITGAV). ZIKV infection was disrupted by genetic targeting of ITGAV or its binding partner ITGB5 and by an antibody specific for integrin αvβ5. ZIKV selectively eliminated GSCs from species-matched human mature cerebral organoids and GBM surgical specimens, which was reversed by integrin αvβ5 inhibition. Collectively, our studies identify integrin αvβ5 as a functional cancer stem cell marker essential for GBM maintenance and ZIKV infection, providing potential brain tumor therapy.

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.

Seeding rate recommendations for wheat (Triticum aestivum L.) are often 150–450 seeds m−2. However, we hypothesize that wheat grown with high resource availability (i.e., fertility and moisture) can maximize yield under considerably lower rates. Our objectives were to explore winter wheat response to low populations under high resource availability using yield‐contest fields as a case study. A factorial experiment evaluated four wheat varieties (i.e., Joe, WB‐Grainfield, Langin, and LCS Revere) exposed to five seeding rates (50, 100, 150, 200, and 250 seeds m−2) during five seasons in commercial wheat fields managed by yield‐contest winning producers near Leoti, KS. Fields were silt‐loam soils with high available water‐holding capacity, long‐term history of manure application with non‐limiting fertility, and adopted a sorghum [Sorghum bicolor (L.) Moench]–fallow–wheat rotation. Plant density ranged from 26 to 341 plants m−2 and yield ranged from 3.2 to 6.8 Mg ha−1. Water use efficiency of 19.5 kg ha−1 mm−1 suggested no management limitations to yield. Quadratic models portrayed the grain yield–plant density relation well, with 95% of the maximum yield reached at 68 to 91 plants m−2 for crops sown at the optimum date (4 out of 5 years), and at 312 plants m−2 for a late‐sown crop. Greater fall temperature accumulation reduced the relative yield between the maximum and minimum seeding rates. There was no variety × plant density interaction and Langin was the most consistent yielding variety across environments. Optimum plant density for winter wheat in environments with high resource availability may be considerably lower than current recommendations. Core Ideas: Winter wheat response to plant density depends on resource availability.Under high resource (fertility and moisture), winter wheat response to density relied on fall temperature.Note that 68–91 plants m−2 reached 95% maximum yield in four out of five seasons under optimum sowing time.Note that 312 plants m−2 reached 95% maximum yield in one out of five seasons with late sowing.Current seeding rate recommendations could be lowered for intensively managed fields. [ABSTRACT FROM AUTHOR]

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., Introduction COVID-19 is the major acute global public health issue in this century. Patients with severe COVID-19 develop acute respiratory distress syndrome (ARDS), which may progress to organ dysfunction and [...]

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.

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.