Multifaceted CK2 in malignant and healthy T cells

Copyright © Ribeiro et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and re-production in any medium, provided the original author and source are credited.Among kinases that support the survival and turnover of tumor cells, the serine/threonine protein kinase CK2 has been shown to be frequently overexpressed or hyperactivated in solid and hematological malignancies. Our previous work on T-cell acute lymphoblastic leukemia (T-ALL) showed that CK2 maintains leukemia cell viability by phosphorylating and thereby inactivating the tumor suppressor PTEN, which results in hyperactivation of PI3K/AKT signaling. We also demonstrated the potential of using the clinical-grade CK2-specific chemical inhibitor, CX-4945 (Silmitasertib), against primary T-ALL cells. We have now extended these findings to the rare (<10% of all cases) form of T-ALL that derives from the transformation of thymocytes belonging to the γδ T-cell lineage.info:eu-repo/semantics/publishedVersio

Five layers of receptor signaling in γδ T-Cell differentiation and activation

Copyright: © 2015 Ribeiro, Ribot and Silva-Santos. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.The contributions of γδ T-cells to immunity to infection or tumors critically depend on their activation and differentiation into effectors capable of secreting cytokines and killing infected or transformed cells. These processes are molecularly controlled by surface receptors that capture key extracellular cues and convey downstream intracellular signals that regulate γδ T-cell physiology. The understanding of how environmental signals are integrated by γδ T-cells is critical for their manipulation in clinical settings. Here, we discuss how different classes of surface receptors impact on human and murine γδ T-cell differentiation, activation, and expansion. In particular, we review the role of five receptor types: the T-cell receptor (TCR), costimulatory receptors, cytokine receptors, NK receptors, and inhibitory receptors. Some of the key players are the costimulatory receptors CD27 and CD28, which differentially impact on pro-inflammatory subsets of γδ T-cells; the cytokine receptors IL-2R, IL-7R, and IL-15R, which drive functional differentiation and expansion of γδ T-cells; the NK receptor NKG2D and its contribution to γδ T-cell cytotoxicity; and the inhibitory receptors PD-1 and BTLA that control γδ T-cell homeostasis. We discuss these and other receptors in the context of a five-step model of receptor signaling in γδ T-cell differentiation and activation, and discuss its implications for the manipulation of γδ T-cells in immunotherapy.Our work is supported by Fundação para a Ciência e Tecnologia (SFRH/BD/84123/2012 to Sérgio T. Ribeiro; SFRH/BPD/78135/2011 and EXPL/IMI-IMU/0170/2013 to Julie C. Ribot) and European Research Council (StG_260352 to Bruno Silva-Santos).info:eu-repo/semantics/publishedVersio

Geochronology and isotope geochemistry of granitoids and metasediments of São Pedro das Águias area (Tabuaço W project)

As litologias identificadas na área da Quinta de São Pedro das Águias correspondem a: xistos biotíticos, xistos negros, mármores, rochas calcossilicatadas s.s. e skarns da sequência metassedimentar da Formação de Bateiras, pertencente ao Grupo do Douro do CXG;granito de Paredes da Beira-Tabuaço; vários corpos aplíticos e pegmatíticos. Para as litologias granitoides, foi obtida uma isócrona Rb-Sr de 311±7 Ma (MSWD=1,7; 87Sr/86Sr inicial = 0,7146), a qual é aqui interpretada como datando a sua instalação durante uma etapa tardia da D3 varisca. O granito revela caraterísticas do tipo S, nomeadamente por ser moscovítico e peraluminoso (A/CNK médio = 1,28), e ter assinatura isotópica claramente compatível com crosta metassedimentar (-8,9≤εNd311≤-7,8; +129≤εSr311≤+192). A sobreposição da assinatura isotópica do granito com a dos metapelitos encaixantes indica que o magma parental foi provavelmente gerado por anatexia de metassedimentos do Grupo do Douro. Os metapelitos estudados são, do ponto de vista isotópico, em particular por apresentarem valores mais baixos de εNd311, claramente distintos dos metassedimentos do CXG do Grupo das Beiras, assemelhando-se, em contrapartida, a outras unidades metassedimentares do Maciço Ibérico.In the area of Quinta de São Pedro das Águias, the following lithologies were identified: biotite-zone “normal” and black phyllites, marbles, calcsilicate (s.s.) rocks and skarns, belonging to the Bateiras Formation, of the Douro Group of the CXG; Paredes da Beira-Tabuaço granite; several aplitic and pegmatitic bodies. Rb-Sr isotope analyses provided a 311±7 Ma whole-rock isochron (MSWD=1.7; initial 87Sr/86Sr = 0,7146) for the granitoids. This date is interpreted here as the emplacement age of the granitoid magmas, during a late stage of the Variscan D3. The granite revealed a S-type nature, namely because it is a muscovite granite, it shows a peraluminous composition (average A/CNK = 1.28), and the Sr and Nd isotope fingerprints (-8.9≤εNd311≤-7.8; +129≤εSr311≤+192) fit into the composition of metasedimentary crust. The isotope signatures, at 311 Ma, of the granite and of the studied metapelites overlap each other, suggesting that the parental magma was generated by anatexis of Grupo do Douro metasediments. Isotopically, especially due to their lower εNd311, the studied metapelites are clearly distinct from the Grupo das Beiras metasediments (the other major division of the CXG), and, instead, they resemble other metasedimentary units of the Iberian Massif

Geochronology and geochemistry of lithologies of the Tabuaço W-prospect area (Northern Portugal)

This work is focussed on lithologies occurring at Quinta de São Pedro das Águias, which is located in the Tabuaço prospect (an area of 45 km2 where exploration for W-skarn deposits is taking place, in northern Portugal, close to the Douro valley). At Quinta de São Pedro das Águias several lithologies are recognized: “normal” phyllites, black phyllites (graphite-bearing), marbles, calcsilicate (s.s.) rocks and skarns (sometimes, scheelite-bearing), belonging to the Bateiras Formation, of the Douro Group (one of the two major subdivisions of the Neoproterozoic-Cambrian Dúrico-Beirão Supergroup); Paredes da Beira-Tabuaço granite; several aplitic and pegmatitic bodies. The studied area belongs to the Central Iberian Zone, a geotectonic unit of the Iberian Variscan Chain. Rb-Sr isotope analyses done in the scope of this work, provided a 316 ± 7 Ma whole-rock isochron (MSWD = 1.7; initial 87Sr/86Sr = 0.7146) for the granitoids, using the 87Rb decay constant recently recommended by IUPAC-IUGS (Villa et al., 2015). This date is interpreted here as the emplacement age of those rocks, during a late stage of the Variscan D3. The granite revealed a S-type nature, namely because it is a muscovite granite, it shows a peraluminous composition (average A/CNK = 1.28), and the Sr and Nd isotope fingerprints (-8.9 ≤ εNd316 ≤ -7.8; +0.7105 ≤ [87Sr/86Sr]316 ≤ 0.7182) fit into the composition of metasedimentary crust. The analysed phyllites show the following isotopic compositions: -9.7 ≤ εNd316 ≤ -8.2; +0.7148 ≤ [87Sr/86Sr]316 ≤ 0.7188. Therefore, the isotope signatures, at 316 Ma, of the granite and of the studied metapelites overlap, suggesting that the parental magma was generated by anatexis of Grupo do Douro metasediments. According to their petrographic, geochemical and isotopic features, aplites and pegmatites are viewed as extreme differentiates from the granite. São Pedro das Águias metapelites show biotite zone parageneses. Geochemically, their REE normalized patterns are very similar to those displayed by NIBAS and by other upper crustal reference compositions. Isotopically, especially due to their lower εNd316, the studied metapelites are clearly distinct from the Grupo das Beiras metasediments (the other major division of the Dúrico-Beirão Supergroup), and, instead, they resemble other metasedimentary units of the Iberian Massif. Several lines of evidence, namely the isotope data (-8.1 ≤ εNd316 ≤ -6.4; +0.7090 ≤ [87Sr/86Sr]316 ≤ 0.7102) and the occurrence of fine intercalations of sub-mm layers enriched in phyllosilicates, suggest that calcsilicate (s.l.) rocks owe their composition not only to metasomatism that accompanied the granite intrusion, but also to an inheritance from their protoliths, which should have resulted from mixed sedimentation, both chemical and terrigenous

The combined effect of pressure and temperature on kefir production - a case study of food fermentation in unconventional conditions

Food fermentation under pressure has been studied in recent years as a way to produce foods with novel properties. The purpose of this work was to study kefir production under pressure (7–50 MPa) at different temperatures (17–32 °C), as a case study of unconventional food fermentation. The fermentation time to produce kefir was similar at all temperatures (17, 25, and 32 °C) up to 15 MPa, compared to atmospheric pressure. At 50 MPa, the fermentation rate was slower, but the difference was reduced as temperature increased. During fermentation, lactic and acetic acid concentration increased while citric acid decreased. The positive activation volumes (Va) obtained indicate that pressure decreased the fermentation rate, while the temperature rise led to the attenuation of the pressure effect (lower Va). On the other hand, higher activation energies (Ea) were observed with pressure increase, indicating that fermentation became more sensitive to temperature. The condition that resulted in a faster fermentation, higher titratable acidity, and higher concentration of lactic acid was 15 MPa/32 °C. As the authors are aware, this is the second work in the literature to study the combined effect of pressure and temperature on a fermentative process.info:eu-repo/semantics/publishedVersio

A pilot study combining ultrafiltration with ozonation for the treatment of secondary urban wastewater: organic micropollutants, microbial load and biological effects

Ozonation followed by ultrafiltration (O3 + UF) was employed at pilot scale for the treatment of secondary urban wastewater, envisaging its safe reuse for crop irrigation. Chemical contaminants of emerging concern (CECs) and priority substances (PSs), microbial load, estrogenic activity, cell viability and cellular metabolic activity were measured before and immediately after O3 + UF treatment. The microbial load was also evaluated after one-week storage of the treated water to assess potential bacteria regrowth. Among the organic micropollutants detected, only citalopram and isoproturon were not removed below the limit of quantification. The treatment was also effective in the reduction in the bacterial loads considering current legislation in water quality for irrigation (i.e., in terms of enterobacteria and nematode eggs). However, after seven days of storage, total heterotrophs regrew to levels close to the initial, with the concomitant increase in the genes 16S rRNA and intI1. The assessment of biological effects revealed similar water quality before and after treatment, meaning that O3 + UF did not produce detectable toxic by-products. Thus, the findings of this study indicate that the wastewater treated with this technology comply with the water quality standards for irrigation, even when stored up to one week, although improvements must be made to minimise microbial overgrowth.info:eu-repo/semantics/publishedVersio

Magnetoliposomes incorporated in peptide-based hydrogels: towards development of magnetolipogels

A major problem with magnetogels is the encapsulation of hydrophobic drugs. Magnetoliposomes not only provide these domains but also improve drug stability and avert the aggregation of the magnetic nanoparticles. In this work, two magnetoliposome architectures, solid and aqueous, were combined with supramolecular peptide-based hydrogels, which are of biomedical interest owing to their biocompatibility, easy tunability, and wide array of applications. This proof-of-concept was carried out through combination of magnetoliposomes (loaded with the model drug curcumin and the lipid probe Nile Red) with the hydrogels prior to pH triggered gelation, and fluorescence spectroscopy was used to assess the dynamics of the encapsulated molecules. These systems allow for the encapsulation of a wider array of drugs. Further, the local environment of the encapsulated molecules after gelation is unaffected by the used magnetoliposome architecture. This system design is promising for future developments on drug delivery as it provides a means to independently modify the components and adapt and optimize the design according to the required conditions.FCT -Fundação para a Ciência e a Tecnologia(UIDB/00686/2020

A Orla de Atalaia em Aracaju/SE e seus equipamentos de esporte e lazer como problemática de pesquisa: levantamento e discussão dos dados

O presente estudo analisou a infraestrutura de esporte e lazer da Orla da praia de Atalaia em Aracaju/SE, entre maio e dezembro/2010, no qual se identificou as condições de manutenção, acesso e uso dos equipamentos de esporte e lazer desse espaço. Os dados indicam a predominância de equipamentos esportivos de lazer, em detrimento dos infantis e culturais; um processo gradativo de privatização de alguns equipamentos públicos; a ausência de projetos e políticas públicas de incentivo ao pleno acesso da população aos equipamentos; estrutura diversificada de suporte ao lazer, mas com deficiências em relação aos banheiros e transporte públicos e segurança no local. As conclusões indicam a necessidade do estado de Sergipe e do município de Aracaju reavaliarem e ampliarem as políticas públicas de esporte e lazer neste espaço, para garantir o pleno acesso da população local, e não apenas aos turistas e às classes mais abastadas