Remoção de auto-anticorpos de amostras sericass de pacientes com doenças auto-imunes empregando filtração em membranas de afinidade

Orientadores: Sonia Maria Alves Bueno, Ricardo de Lima ZollnerDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Engenharia QuimicaResumo: As doenças auto-imunes caracterizam-se pelo desenvolvimento de auto-anticorpos devido a um reconhecimento de certos componentes celulares do próprio organismo como antígenos. Essas doenças são normalmente tratadas com a administração de medicamentos que, em geral estabilizam a doença, mas não a eliminam, O tratamento extracorpóreo de pacientes com doenças auto-imunes tem sido investigado e pode ser por troca de plasma ou adsorção seletiva do auto-anticorpo. A troca de plasma possui um custo elevado além de expor o paciente ao risco de infecções. Devido a esses inconvenientes, a terapia de adsorção seletiva de auto-anticorpos tem sido a mais indicada. Como alternativa aos suportes existentes para o tratamento extracorpóreo de doenças auto-imunes utilizou-se histidina imobilizada em membranas de fibras ocas de álcool poli etileno vinílico. A fim de se determinar as melhores condições de retenção de IgG no módulo de filtração, estudou-se a influência das variáveis QF (vazão do filtrado)/QI (vazão de alimentação) e da concentração de IgG na alimentação na retenção de IgG no suporte através de um planejamento experimental. A variável QF/QI não apresentou efeito significativo na retenção de IgG e a capacidade de retenção de IgG aumentou de acordo com a concentração de IgG na alimentação. Testou-se a influência da variável QF/QI, mantendo-se a concentração de IgG na alimentação (5 mg/ml) constante, para plasma humano sadio e verificou-se também que QF/QI não apresentou um efeito relevante na retenção de IgG do suporte. Definiu-se QF/QI igual a 0,86, valor tradicionalmente usado em circulação extracorpórea, para os experimentos de filtração in vitro com soro de pacientes com doenças auto-imunes e investigou-se a retenção e adsorção dos auto-anticorpos anti-dsDNA, anti-SS-A/Ro, anti-Sm, anti-Sm/RNP e anti-cardiolipina em presença de tampão Hepes e Tris-HCl. Como resultado, houve adsorção de todos os auto-anticorpos testados em ambos tampões e para anti-SS-A/Ro, as maiores quantidades adsorvidas e retidas foram obtidas em presença de tampão Tris-HClAbstract: Among the pathogenic consequences related to autoimmune diseases is the expression of autoantibodies directed against a series of cellular components from the own organism. The utilization of corticosteroid and imunosupressive drugs are effective in relieving symptoms in most cases, however some patients respond poorly to prolonged imunosupression. As an alternative, the extracorporeal treatment for patients with autoimmune diseases has been suggested, which can be done by plasma exchange or selective adsorption of autoantibodies. Plasma exchange presents a high cost beside exposing the patient to the risk of infections. Due to these inconveniences, the autoantibodies selective adsorption therapy has been indicated. As an alternative to the already existing supports for the extracorporeal treatment of autoimmune diseases, L-histide was immobilized onto poly (ethylene vinyl alcohol) hollow-fiber membranes. In order to verify the better conditions for autoantibody removal, an experimental design was made to study the influence of QFfiltrate flow rate)/QI(inlet flow rate) based on the initial IgG concentration. The results showed that QF/QI did not have statistical influence for IgG retention in this affinity membrane and the IgG retaining capacity increased according to the IgG concentration in the feedstream. The influence of QF/QI based on the IgG concentration in the feedstream (5 mg/ml) was also verified in human plasma and the same result as before was obtained. Thus, for the filtration in vitro experiments, the ratio QF/QI was kept constant at 0.86, classical value used in extracorporeal circuits, and the removal and adsorption of anti-dsDNA, anti-SS-A/Ro, anti-Sm, anti-Sm/RNP and anti-cardiolipin autoantibodies present in serum of patients with autoimmune diseases were investigated when Hepes and Tris-HCl buffer are utilized. As a result, these membranes were able to remove these autoantibodies if Hepes or Tris-HCl are used and specifically for the removal and adsorption of anti-SS-A/Ro, the better results were obtained with buffer Tris-HClMestradoMestre em Engenharia Químic

Developmental peculiarities in placentae of ovine uniparental conceptuses

Genomic imprinting is an epigenetic phenomenon regulating mono-allelic expression of genes depending on their parental origin. Defective genomic imprinting is involved in several placental disorders, such as intrauterine growth restriction and pre-eclampsia. Uniparental embryos, having maternal-only or paternal-only genomes (parthenogenotes [PAR] and androgenotes [AND], respectively), are useful models to study placentation. The aim of this work was to reveal the effect of parental genome (maternal and paternal) on placentation. To do this, uniparental (AND and PAR) and biparental (CTR) in vitro produced sheep embryos transferred to recipient females were collected at day 20 of pregnancy and their placentae were analyzed. qPCR analysis showed that imprinted genes (H19, IGF2R and DLK1) were expressed accordingly to their parental origin while the expression f DNA methyltransferases () was disregulated, especially in PAR (P < 0.05). AND placentae were significantly hypomethylated compared to both PAR and CTR (P = 0.023). Chorion-allantoid of AND showed impaired development of vessels and reduced mRNA expression of vasculogenetic factors (ANG2 P = 0.05; VEGFR2 P< 0.001; TIE2 P < 0.001). Morphologically, PAR placentae were characterized by abnormal structure of the trophoectodermal epithelium and reduced total number (P<0.03) of Trophoblastic Binucleate Cells. A reduced implantation rate of both classes of uniparental embryos (P<0.03) was also noted. Our results provide new insights into the characterization of uniparental embryos and demonstrate the complementary role of parental genomes for the correct establishment of pregnancy. Thus, our findings may suggest new targets to improve our understanding of the origin of imprinting-related placental dysfunction

Transient Analysis of Photovoltaic Module Integrated with Phase Change Material (PCM)

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Numerical Simulations of a PV Module with Phase Change Material (PV-PCM) under Variable Weather Conditions

The electrical efficiency of photovoltaic (PV) modules can be improved through the cooling of the PV. Among the passive cooling strategy, one of the most promising concerns the use of phase change materials (PCMs) to decrease the operative temperature of a PV panel. This paper investigates the performances of a conventional PV panel in which two organic PCMs are added (PV-PCM) to reduce the temperature rise of PV cells and consequently to increase the electrical performances. With this aim, unsteady numerical simulations have been carried with Ansys Fluent software using a two-dimensional simplified geometry for the PV modules with the PCM is incorporated (PV-PCM), as well as for the benchmark PV module. The numerical simulations have allowed evaluating the PV cell temperatures, the power production, as well the PCM thermal behavior. As regards this latter aspect the dynamic analysis has evidenced the need to extend the time of simulation at least for two days in such way to take into account of the degree of solidification achieved during the night by the PCM materials. PCM with low melting temperature cannot complete solidifying during the night and so the heat stored during the day will be lesser than the theoretical one. The results of this study pointed out that the PV-PCM units allow achieving higher performances in comparison with a conventional PV module, especially during the hottest months. An increase in the peak power of 10% and of 3.5% of the energy produced all year round is attained

NFE2L2 and STAT3 converge on common targets to promote survival of primary lymphoma cells

NFE2L2 and STAT3 are key pro-survival molecules, and thus, their targeting may represent a promising anti-cancer strategy. In this study, we found that a positive feedback loop occurred between them and provided evidence that their concomitant inhibition efficiently impaired the survival of PEL cells, a rare, aggressive B cell lymphoma associated with the gammaherpesvirus KSHV and often also EBV. At the molecular level, we found that NFE2L2 and STAT3 converged in the regulation of several pro-survival molecules and in the activation of processes essential for the adaption of lymphoma cells to stress. Among those, STAT3 and NFE2L2 promoted the activation of pathways such as MAPK3/1 and MTOR that positively regulate protein synthesis, sustained the antioxidant response, expression of molecules such as MYC, BIRC5, CCND1, and HSP, and allowed DDR execution. The findings of this study suggest that the concomitant inhibition of NFE2L2 and STAT3 may be considered a therapeutic option for the treatment of this lymphoma that poorly responds to chemotherapies

Exploring Consumer's Propensity to Consume Insect-Based Foods. Empirical Evidence from a Study in Southern Italy

While admitting that neophobia and sociocultural factors negatively affect consumers' propensity to consume insect-based foods, other aspects related to food values that consumers attach to these foods could have an influence on consuming decision. In order to identify the motivations and determinants that influence the propensity to consume insects and then to explore the drivers behind consumers' willingness to consume insect-based foods, the data collected through the questionnaire were processed. After a descriptive analysis of the data, ANOVA was performed. Moreover, Student's t test and pairwise correlation indices were estimated in order to determine statistically significant correlation. Our findings show that information about edible insects brought about an increase in food neophobia and appearance affected the expected liking levels. In addition, we have shown that respondents' propensity to consume insect-based foods also depends on consumers' subjective beliefs about food values such as healthiness, naturalness and environmental impact. We also found that respondents' beliefs about food values associated with insect-based foods do not depend on the degree of information provided but are probably due to pre-existing prejudices about them

High Light Intensity from Blue-Red LEDs Enhance Photosynthetic Performance, Plant Growth, and Optical Properties of Red Lettuce in Controlled Environment

Plant factories using artificial light to produce vegetables have high energy costs due to the high demand for electricity for lighting. Compared to conventional light sources, light-emitting diodes (LEDs) offer the possibility of tailoring the light spectrum and regulating light intensity and are more energy-efficient in terms of energy conversion regardless of the levels of lighting intensity. Optimal light intensity and daily light integral (DLI) requirements are key factors for plant growth; however, their values vary among species and varieties. Our experiment aimed to identify the best light intensity to produce lettuce plants in controlled environment. Lettuce plants of the type Batavia cv ‘Blackhawk’ were grown in plastic pots filled with perlite and peat (20:80 v/v) for 33 days in a growth chamber under blue (B, 20%) and red (R, 80%) LED light at a photosynthetic flux density of 130 µmol m −2 s −1 (BR 130, DLI 7.49 mol m −2 d −1 ), 259 µmol m −2 s −1 (BR 259, DLI 14.92 mol m −2 d −1 ), and 389 µmol m −2 s −1 (BR 389, DLI 22.41 mol m −2 d −1 ). Our results showed that increasing light intensity and DLI promotes net photosynthesis, sustains the electron transport rate (ETR), and stimulates the synthesis of anthocyanins and carotenoids, with positive results for plant photoprotection. Furthermore, the decreases in vegetation indexes (photochemical reflectance index (PRI), greenness, and modified chlorophyll absorption in reflectance index (MCARI1)) also indicate changes in photosynthetic pigment content in response to plant acclimation to different DLIs. Among the three light intensities, 389 µmol m −2 s −1 (DLI 22.41 mol m −2 d −1 ) gave the best results for growing Batavia red lettuce cv ‘Blackhawk’, since it enhances both production and qualitative traits. These results highlight the importance of a proper light intensity to promote plant growth and qualitative traits and to reach high production targets. Hence, preliminary screening of plant performance under different light treatments is recommended to optimise plant response to artificial lighting

The inhibition of IRE1alpha/XBP1 axis prevents EBV-driven lymphomagenesis in NSG mice

Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous diseases originating in conditions of immune deficiency, whose main driver is considered to be Epstein-Barr virus (EBV). Here, we explored the role of IRE1alpha/XBP1s axis in EBV-driven lymphomagenesis in an NOD SCID gamma mouse model, as these animals develop malignancies that closely resemble PTLD when engrafted with EBV-positive peripheral blood momonuclear cells (PBMC). This study evidences for the first time that 4μ8C IRE1 alpha endoribonuclease inhibitor prevented lymphomagenesis in vivo and B-cell immortalization in vitro driven by the virus. At the molecular level, 4μ8C reduced the expression of EBV antigens such as ZEBRA and LMP1, downregulated c-Myc and cyclin D1, and prevented the activation of STAT3, molecules known to be involved in viral lymphomagenesis. The results obtained in this study suggest that the inhibition of IRE1 alpha endoribonuclease may represent a promising therapeutic strategy to prevent EBV-associated PTLD that arise in immune-deficient patients.IMPORTANCEThe novelty of this study lies in the fact that it shows that IRE1 alpha endoribonuclease inhibition by 4μ8C was able to counteract Epstein-Barr virus-driven lymphomagenesis in NOD SCID gamma mice and prevent B-cell immortalization in vitro, unveiling that this drug may be a promising therapeutic approach to reduce the risk of post-transplant lymphoproliferative disorders (PTLD) onset in immune-deficient patients. This hypothesis is further supported by the fact that 4μ8C impaired the survival of PTLD-like cells derived from mice, meaning that it could be helpful also in the case in which there is the possibility that these malignancies have begun to arise

Modulation of Antioxidant Compounds in Fruits of Citrus reticulata Blanco Using Postharvest LED Irradiation

Phlegrean mandarin fruits are already known for health-promoting properties due to the high concentration of phytochemicals in peel, pulp, and seed. Biotic and abiotic factors, including light, may modulate their biosynthesis, metabolism, and accumulation. In this context, light-emitting diodes (LED) have recently been applied to control nutritional traits, ripening process, senescence, fruit shelf-life, and pathogenic microbial spoilage of fruits. This study investigated the effect of the seven-day exposure of Phlegrean mandarin fruits to two LED regimes, white (W) and red–blue (RB), to test the possibility that the storage under specific light wavelengths may be used as green preservation technology that enhances fruit phytochemical properties. To pursue this aim, the antioxidant activity and polyphenolic profile of the pulp and peel of mandarins under W and RB light regimes were evaluated and compared with Control fruits not exposed to LED treatment. Our results indicated that storage under W and RB treatments modulates the antioxidant content in pulp and peel differently. Compared to W, the RB regime increases the ascorbic acid, flavonoid, anthocyanin, and carotenoid concentrations, while the polyphenol profile analysis reveals that the number of important phytochemicals, i.e., quercetin rutinoside, chlorogenic acid, sinensetin, and rutin, are higher under W. The overall data demonstrated that postharvest LED irradiation is a valid tool for modifying fruit phytochemical properties, which also boosts specific bioactive compounds

CONTRADIÇÕES DA GARANTIA DO EMPREGO: UMA ANÁLISE SOBRE AS RELAÇÕES DE GÊNERO ESTABELECIDAS ENTRE MULHERES E SEU TRABALHO NA ENFERMAGEM

This study investigated the conceptions of female nurses about the imbrications between gender attributions and aspects of the organization of their work, in the context of the precariousness of the global work and employment relationships.&nbsp; This study was conducted at a public maternity hospital located in São Paulo – Brazil and was based on a qualitative approach. Data was gathered by ethnography and 10 in-depth interviews. The data collection was organized into two kinds of databases: ‘Field Journals’ and ‘Interviews Database’, which were analyzed by&nbsp; ‘Triangulation Method’ according to the conceptual framework of hermeneutical referential. Female nurses were in charge to provide financially for the family since they had the ‘stable job’ at the house (being public servants) whereas their partners worked under contract. Those women had to conciliate the shift work with housework and motherhood. Their resting time was reduced, mainly the night workers and they complained about social loss related to the shift schedule. Thus, despite having the guarantee of employment, the burden of the precarious global labor market that subjugates their partners fell on these women's shoulders&nbsp; and&nbsp; had negative impacts on their physical and mental health.Neste estudo investigaram-se as concepções de trabalhadoras da enfermagem de uma maternidade pública paulistana sobre as consequências dos imbricamentos entre atribuições de gênero e a precarização das relações de trabalho. Foi utilizada metodologia qualitativa, com observações etnográficas e entrevistas em profundidade, produzindo ‘Diários de Campo’ e ‘Banco de Narrativas’, analisados pela técnica de triangulação de métodos, sob referencial hermenêutico-filosófico. As trabalhadoras explicitaram ocupar a posição de ‘chefe de família’, com responsabilidade de provimento do lar. Elas eram detentoras do vínculo de trabalho seguro (funcionárias públicas) e ganhavam mais que seus parceiros: eles eram celetistas ou tinham contrato informal de trabalho. Elas relataram a necessidade de conciliação dos turnos de trabalho com tarefas domésticas e cuidado dos filhos. O tempo para descanso era reduzido, principalmente para as do turno noturno, e todas referiram perdas sociais por causa dos plantões. Apesar de possuírem a garantia do emprego, o ônus das relações precarizadas do mercado de trabalho brasileiro a que estavam submetidos seus parceiros recaiam sobre essas mulheres, com impactos negativos para sua saúde física e mental