The Pro-Oncogenic Sphingolipid-Metabolizing Enzyme β-Galactosylceramidase Modulates the Proteomic Landscape in BRAF(V600E)-Mutated Human Melanoma Cells

beta-Galactosylceramidase (GALC) is a lysosomal enzyme involved in sphingolipidmetabolismby removing beta-galactosyl moieties from fi-galactosylceramide and beta-galactosylsphingosine. Previous observations have shown that GALC may exert pro-oncogenic functions in melanoma and Galc silencing, leading to decreased oncogenic activity in murine B16 melanoma cells. The tumor-driving BRAF(V600E) mutation is present in approximately 50% of human melanomas and represents a major therapeutic target. However, such mutation is missing in melanoma B16 cells. Thus, to assess the impact of GALC in human melanoma in a more relevant BRAF-mutated background, we investigated the effect of GALC overexpression on the proteomic landscape of A2058 and A375 human melanoma cells harboring the BRAF(V600E) mutation. The results obtained by liquid chromatography-tandem mass spectrometry (LC-MS/MS) demonstrate that significant differences exist in the protein landscape expressed under identical cell culture conditions by A2058 and A375 human melanoma cells, both harboring the same BRAF(V600E)-activating mutation. GALC overexpression resulted in a stronger impact on the proteomic profile of A375 cells when compared to A2058 cells (261 upregulated and 184 downregulated proteins versus 36 and 14 proteins for the two cell types, respectively). Among them, 25 proteins appeared to be upregulated in both A2058-upGALC and A375-upGALC cells, whereas two proteins were significantly downregulated in both GALC-overexpressing cell types. These proteins appear to be involved in melanoma biology, tumor invasion and metastatic dissemination, tumor immune escape, mitochondrial antioxidant activity, endoplasmic reticulum stress responses, autophagy, and/or apoptosis. Notably, analysis of the expression of the corresponding genes in human skin cutaneous melanoma samples (TCGA, Firehose Legacy) using the cBioPortal for Cancer Genomics platform demonstrated a positive correlation between GALC expression and the expression levels of 14 out of the 27 genes investigated, thus supporting the proteomic findings. Overall, these data indicate for the first time that the expression of the lysosomal sphingolipid-metabolizing enzyme GALC may exert a pro-oncogenic impact on the proteomic landscape in BRAF-mutated human melanoma

Marteletes desgastados afetam negativamente as características operacionais da moagem e físicas do milho processado em moinho do tipo martelo

Foi conduzido um trabalho para avaliar os efeitos dos níveis de desgaste de marteletes de moinho tipo martelo, sobre características físicas do milho e operacionais de moagem. Foram utilizados quatro diferentes lotes de milho, um moinho martelo com motor de 3.500 RPM, cinco conjuntos de marteletes com diferentes níveis de desgaste do vértice (0, 20, 43, 57 e 63%) e quatro diferentes peneiras com diâmetros de furos de 1, 3, 5 e 12 mm sob um esquema fatorial 5x4, com quatro repetições em um total de 80 unidades experimentais. O aumento no diâmetro dos furos das peneiras influenciou (P<0,05) com aumento na produção, nos decibéis, no diâmetro geométrico médio (DGM), no desvio padrão geométrico (DPG), na densidade e com redução no consumo de energia elétrica e no ângulo de repouso (AR). O maior desgaste do martelo aumentou (P<0,05) o consumo de energia elétrica, DGM, DPG, AR e com redução (P<0,05) na produtividade e densidade. A análise de Linear response plateau (LRP) indicou piora na produtividade do equipamento a partir dos 55,1% de desgaste. Neste contexto, o desgaste dos marteletes influenciou negativamente as características operacionais do equipamento e físicas do milho. Para favorecer as características físicas do milho moído e evitar perdas na produtividade do equipamento recomenda-se a moagem com martelos isentos de desgaste

Molecular Interaction Studies of HIV-1 Matrix Protein p17 and Heparin: IDENTIFICATION OF THE HEPARIN-BINDING MOTIF OF p17 AS A TARGET FOR THE DEVELOPMENT OF MULTITARGET ANTAGONISTS

Once released by HIV cells, p17 binds heparan sulfate proteoglycans (HSPGs) and CXCR1 on leukocytes causing their dysfunction. By exploiting an approach integrating computational modeling, site-directed mutagenesis of p17, chemical desulfation of heparin, and surface plasmon resonance, we characterized the interaction of p17 with heparin, a HSPG structural analog, and CXCR1. p17 binds to heparin with an affinity (Kd 190 nM) that is similar to those of other heparin-binding viral proteins. Two stretches of basic amino acids (basic motifs) are present in p17 N and C termini. Neutralization (Arg3Ala substitution) of the N-terminal, but not of the C-terminal basic motif, causes the loss of p17 heparin-binding capacity. The N-terminal heparin-binding motif of p17 partially overlaps the CXCR1-binding domain. Accordingly, its neutralization prevents also p17 binding to the chemochine receptor. Competition experiments demonstrated that free heparin and heparan sulfate (HS), but not selectively 2-O-, 6-O-, and N-O desulfated heparins, prevent p17 binding to substrate-immobilized heparin, indicating that the sulfate groups of the glycosaminoglycan mediate p17 interaction. Evaluation of the p17 antagonist activity of a panel of biotechnological heparins derived by chemical sulfation of the Escherichia coli K5 polysaccharide revealed that the highlyN,O-sulfated derivative prevents the binding of p17 to both heparin and CXCR1, thus inhibiting p17-driven chemotactic migration of human monocytes with an efficiency that is higher than those of heparin and HS. Here, we characterized at a molecular level the interaction of p17 with its cellular receptors, laying the basis for the development of heparin-mimicking p17 antagonists

Pessoas com deficiência visual: esporte e lazer como fator de inclusão

El desafío de este proyecto es vivenciar prácticas de actividades físicas y de ocio en el ambiente de la Universidad, involucrando a personas con discapacidad visual de la APACE / Passo Fundo, en el sentido de repensar nuestras prácticas con miras a contribuir en el proceso de inclusión social. Elementos de lectura de realidad/diagnóstico: El deporte y el ocio en las diversas modalidades posibilitan espacios para diferentes edades, intereses y condiciones. La actuación con portadores de deficiencia visual es un desafío en virtud de las pocas vivencias, informaciones, materiales, desconocimiento en adaptar actividades y la poca motivación de las personas hacia las prácticas, teniendo en cuenta que muchos todavía permanecen en la oscuridad de la sociedad, sea por falta de divulgación o la resistencia a las experimentaciones. Aparentemente existe interés y anhelo e incluso insistencia para involucrarse, pero acaban chocando con el sentimiento de inferioridad, olvidándose de sus capacidades y potencialidades. La sede de APACE es el punto de encuentro de los asociados, todos portadores de alguna deficiencia visual, que revelan anhelos, voluntades y deseos, unidos en un solo propósito, la búsqueda de hacer su vida lo más integrada posible. El espacio no es adecuado para las actividades prácticas, por lo que todas son realizadas en la Universidad. Se percibe que la discapacidad no los hace menos capaces de usufructuar y conducir sus vidas, en el área del deporte y del ocio, no retirando la capacidad de construir su autonomía y su historia. Pero todavía está muy presente signos de inseguridad para enfrentar las situaciones de lo cotidiano. El proyecto viene sirve de oportunidad para la convivencia con videntes mediante las actividades, reafirmando la posibilidad de transformación en el modo de pensar, actuar y sentir, en un proceso que se construye en las relaciones e interrelaciones.The challenge of this project is to experience practices of physical and leisure activities in the University environment, involving people with visual disabilities of the APACE / Passo Fundo, in the sense of rethinking our practices with a view to contributing to the social inclusion process. Elements of reality/diagnosis reading: Sport and leisure in the different modalities allow spaces for different ages, interests and conditions. The performance with carriers of visual impairment is a challenge because of the few experiences, information, materials, ignorance in adapting activities and the low motivation of people towards the practices, taking into account that many still remain in the darkness of society, either for lack of disclosure or resistance to experimentation. Apparently there is interest and longing and even insistence to get involved, but they end up colliding with the feeling of inferiority, forgetting their capabilities and potential. The headquarters of APACE is the meeting point of the associates, all bearers of some visual deficiency, which reveal longings, wills and desires, united in a single purpose, the search to make their life as integrated as possible. The space is not suitable for practical activities, so all are done at the University. It is perceived that disability does not make them less able to enjoy and lead their lives, in the area of sports and leisure, not removing the ability to build their autonomy and their history. But signs of insecurity are still very present to face situations of everyday life. The project is an opportunity for coexistence with seers through activities, reaffirming the possibility of transformation in the way of thinking, acting and feeling, in a process that is built on relationships and interrelationships.O desafio deste Projeto é vivenciar práticas de atividades físicas e de lazer no ambiente da Universidade envolvendo pessoas com deficiência visual da APACE / Passo Fundo no sentido de repensar nossas práticas numa perspectiva de contribuir no processo de inclusão social. Elementos de leitura de realidade/diagnóstico: O esporte e o lazer nas variadas modalidades possibilitam espaços para diferentes idades, interesses e condições. Atuar com portadores de deficiência visual é desafiador em virtude de poucas vivências, informações, materiais, desconhecimento em adaptar atividades e a pouca motivação das pessoas para as práticas, tendo em vista, que muitos ainda permanecem na escuridão da sociedade, seja por falta de divulgação ou ainda a resistência às experimentações. Aparentemente existe interesse e anseio e até insistência para se envolver, mas acabam esbarrando no sentimento de inferioridade, esquecendo-se de suas capacidades e potencialidades. A sede da APACE é o ponto de encontro dos associados, todos portadores de alguma deficiência visual, que revelam anseios, vontades e desejos, unidos em um só propósito, a busca de tornar sua vida a mais integrada possível. O espaço não é adequado para as atividades práticas, por este motivo todas são realizadas na Universidade. Percebe-se que a deficiência não os torna menos capazes de usufruir e conduzir suas vidas, na área do esporte e do Lazer, não retirando a capacidade de construir sua autonomia e sua história. Porém ainda está muito presente sinais de insegurança para enfrentar as situações do cotidiano. O projeto vem para oportunizar o convívio com videntes pelas atividades reafirmando a possibilidade de transformação no modo de pensar, agir e sentir, num processo que se constrói nas relações e inter-relações.peerReviewe

Effects of a brief mindfulness-based intervention on emotional regulation and levels of mindfulness in senior students

Mindfulness-based interventions have been applied in diverse populations and achieved mental health benefits. This study examined the effects of a brief mindfulness program for emotional regulation and levels of mindfulness on senior students in Brazil. The intervention consisted of six weekly meetings attended by 30 participants. It is a pre-experimental research, with pre- and post-test comparative and correlation measurements. The preliminary results, which relied on parametrical and non-parametrical tests, revealed a reduction in total emotional regulation difficulties (p = 0.0001; r = − 0.55). Also, there was an increase in the levels of mindfulness in the subtests for both dimensions under evaluation: “Awareness” (p = 0.0001; d = 0.77) and “Acceptance” (p = 0.048; d = 0.37). By associating the amount of meditative practices performed by students with the variables, a significant positive correlation was found with the mindfulness dimension “Awareness” (rP = 0.422; p = 0.020), and there was a significant negative correlation with Difficulties in emotion regulation (rS = − 0.478; p = 0.008) and with its respective subscales “Non-acceptance” (rS = − 0.654; p = 0.0001) and “Clarity” (rS = − 0.463; p = 0.010). In conclusion, the application of a brief mindfulness-based intervention is promising in Brazilian university contexts; moreover, it can bring benefits to students, e.g., an increase in emotion regulation as well as in levels of mindfulness. We suggest that further research should use an experimental design and follow-up.info:eu-repo/semantics/publishedVersio

Projeto Bioeste Florestas: desenvolvimento de tecnologias para florestas energéticas no oeste do Paraná.

A região da Bacia do Paraná 3 apresenta grande produção de grãos, associada a um grande consumo de biomassa fl orestal para secagem de grãose outras atividades doagronegócio que demandam energia térmica. Para trabalhar essa questão, o projeto Bioeste Florestas foi desenhado através de uma parceria da Itaipu, CIBiogase Embrapa Florestas, objetivando aumentara competitividadeda cadeia produtiva fl orestal no oeste do Paraná através do teste e da validação de tecnologias, com o intuito de garantir a oferta de biomassa florestal necessária as demandas regionais

Does conversion to reduced tillage really increase soil organic carbon stocks in organic arable farming?

Aggravation of weather extremes increases awareness of climate change consequences. Mitigation options are in demand that aim to reduce the atmospheric concentration of greenhouse gases. Amongst others, the conversion from ploughing to reduced tillage is argued to increase soil organic carbon (SOC) stocks as an accumulation of SOC in topsoil layers is commonly reported. Yet, reviews and meta-analyses describe various results from significant increases to just a redistribution of SOC in the soil profile. Reasons can be found in different sampling depths, SOC and bulk density measurement procedure, and stock calculation (equivalent soil mass vs. equal sampling depth). Furthermore, few studies evaluated the impact of organic farming systems. In nine long-term experiments on tillage systems in temperate Europe (France, Germany, Netherlands, and Switzerland), a common soil sampling campaign took place in spring and autumn 2017, and spring 2018. All trials represent common mixed organic farming systems of the respective region and contain plots with conventional and reduced tillage practices. While climatic conditions are similar, soil types vary from sandy to clayey soils. We took three undisturbed soil cores with driving hammer probes (8 cm in diameter) in each plot (minimum 3 plots per treatment) to a maximum depth of 100 cm and divided the cores in the increments 0-30, 30-50, 50-70, and 70-100 cm. The topsoil (0-30 cm) was further divided into the different tillage depths of the respective trial. We determined bulk density and organic carbon concentration as main variables and soil texture and pH as co-variates for each sample and collected C-inputs for each plot in all trails on a yearly basis. Multivariate statistics will enable the comprehensive evaluation of tillage effects on SOC stocks up to a depth of 100 cm in organic long-term trials. Texture, trial age, and the co-variate C-input will be decisive for the development of SOC stocks and enable the evaluation of carbon sequestration potentials of agricultural soils through improved tillage practices

Negotiating colonial violence: spaces of precarisation in Palestine

This paper examines the ways in which colonial violence is transformed and spatialised into negotiated precarities at the occupied Palestine. The notion of “negotiated precarity” is developed herein, to refer to two aspects in particular. First, to spatial compartmentalisation, which shows how the settler colonial power operates by creating precarious administrative zones, where the life of the colonised becomes prone to several flexible, negotiated uses of power. Second, negotiated precarity is used to refer to the conduct of the colonised that counters, transforms, redirects, cancels or hampers the colonial spatialisations of power. By focusing on the “negotiated precarities” in a singular West Bank village, I exemplify how the colonial governing is entwined with spatial compartments that enable several informal, indirect and ad hoc techniques of colonial violence, but also how the colonial governing is constantly mobilised, negotiated, countered and redirected in/through the everyday Palestinian spaces.publishedVersionPeer reviewe