Impact of Truncated O-glycans in Gastric-Cancer-Associated CD44v9 Detection

CD44 variant isoforms are often upregulated in cancer and associated with increased aggressive tumor phenotypes. The CD44v9 is one of the major protein splice variant isoforms expressed in human gastrointestinal cancer cells. Immunodetection of CD44 isoforms like CD44v9 in tumor tissue is almost exclusively performed by using specific monoclonal antibodies. However, the structural variability conferred by both the alternative splicing and CD44 protein glycosylation is disregarded. In the present work, we have evaluated the role of O-glycosylation using glycoengineered gastric cancer models in the detection of CD44v9 by monoclonal antibodies. We demonstrated, using different technical approaches, that the presence of immature O-glycan structures, such as Tn and STn, enhance CD44v9 protein detection. These findings can have significant implications in clinical applications mainly at the detection and targeting of this cancer-related CD44v9 isoform and highlight the utmost importance of considering glycan structures in cancer biomarker detection and in therapy targeting.This work was funded by FEDER funds through the Operational Programme for Competitiveness Factors-COMPETE, grant numbers POCI-01-0145-FEDER-016585; POCI-01-0145-FEDER-007274; OCI-01-0145-FEDER-031028; and national funds through the Foundation for Science and Technology (FCT), grant numbers PTDC/BBB-EBI/0567/2014 (to CAR), UID/BIM/04293/2013, and PTDC/MED-QUI/29780/2017; and the project NORTE-01-0145-FEDER-000029, supported by Norte Portugal Regional Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). F. Pinto received a fellowship from FCT (SFRH/BPD/115730/2016)

Aurora A triggers Lgl cortical release during symmetric division to control planar spindle orientation

Mitotic spindle orientation is essential to control cell-fate specification and epithelial architecture. The tumor suppressor Lgl localizes to the basolateral cortex of epithelial cells, where it acts together with Dlg and Scrib to organize apicobasal polarity. Dlg and Scrib also control planar spindle orientation, but how the organization of polarity complexes is adjusted to control symmetric division is largely unknown. Here, we show that the Dlg complex is remodeled during Drosophila follicular epithelium cell division, when Lgl is released to the cytoplasm. Lgl redistribution during epithelial mitosis is reminiscent of asymmetric cell division, where it is proposed that Aurora A promotes aPKC activation to control the localization of Lgl and cell-fate determinants. We show that Aurora A controls Lgl localization directly, triggering its cortical release at early prophase in both epithelial and S2 cells. This relies on double phosphorylation within the putative aPKC phosphorylation site, which is required and sufficient for Lgl cortical release during mitosis and can be achieved by a combination of aPKC and Aurora A activities. Cortical retention of Lgl disrupts planar spindle orientation, but only when Lgl mutants that can bind Dlg are expressed. Hence, our work reveals that Lgl mitotic cortical release is not specifically linked to the asymmetric segregation of fate determinants, and we propose that Aurora A activation breaks the Dlg/Lgl interaction to allow planar spindle orientation during symmetric division via the Pins (LGN)/Dlg pathway.We thank J. Knoblich, D. St Johnston, D. Bilder, D. Glover, S. Brogna, R. Martinho, H. Maiato, D. Bergstralh, and the Bloomington Stock Center for fly stocks and reagents. This work was funded by FEDER funds through the Operational Competitiveness Programme COMPETE and by National Funds through FCT (Fundação para a Ciência e a Tecnologia) under the project FCOMP-01-0124-FEDER-019738 (PTDC/BIA-BCM/120132/2010), which also supported fellowships to C.C. and S.M. E.M. was funded by a Marie Curie-IEF and currently holds a FCT Investigator position

Comparativo de personajes de la historia de la enfermería brasileña

Este artículo es una reflexión sobre la historia de los profesionales que se destacaron en la enfermería. Para ello, la búsqueda se llevó a cabo en algunos personajes que hicieron mucho para la enfermería y la salud en el país. El análisis de las historias de estas enfermeras puesto de manifiesto en hechos común como: la ruptura de paradigmas relacionado con el matrimonio, la formación en instituciones de renombre, la ocupación en puestos de gran importancia, la participación en asociaciones profesionales expresiva, a si como una relación con la formación de calidad. A través de sus biografías, se puede ver que a pesar del contexto político de la época han favorecido la formación de esas enfermeras, mucho esfuerzo y dedicación fueron necesarios para esas trayectorias de éxito, que cooperaron en la consolidación de la enfermería brasileña.This article presents a reflection about the story of outstanding nursing professionals. For this purpose, a survey was conducted among some people who contributed a lot to nursing and health in Brazil. The analysis of these nurses' stories unveiled facts in common: breaking of paradigms relating to marriage, education at renowned institutions, holding of very important jobs, significant membership in professional associations, and quality education. The bios of these nurses reveal that, while the political scenario then existing contributed to their education, unswerving dedication and diligence, were the key for their successful careers and helped consolidate nursing in Brazil.Este artigo trata de uma reflexão sobre a história de profissionais que se destacaram na Enfermagem. Para isso, foi realizada uma pesquisa sobre algumas personagens que muito realizaram pela Enfermagem e pela saúde no país. A análise das histórias dessas enfermeiras revelou fatos em comum, como: o rompimento de paradigmas relacionados ao casamento; a formação em instituições renomadas; a ocupação em cargos de grande importância; a participação expressiva em entidades de classe, assim como uma relação com a formação de qualidade. Através de suas biografias, percebe-se que, apesar de o contexto político da época ter favorecido na formação dessas enfermeiras, muito esforço e dedicação foram necessários para essas trajetórias de sucesso, que colaboraram para a consolidação da Enfermagem brasileira.UNIFESPUNIFESPSciEL

Experimental and theoretical study of demagnetization fields in superconducting samples of orthorhombic shape

In this work we present a model for the calculation of the magnetic properties of superconductors of orthorhombic shape in the perfect shielding state when an external uniform magnetic field is applied in the direction of one of the principal axes of the sample. Our model accounts for demagnetization effects and it is free of fitting parameters and boundary value conditions. We consider planar linear circuits that lie perpendicular to the direction of the applied field. Calculation of the value of the currents is based on magnetic energy minimization. The model is proved to be accurate enough to reproduce experimental results as long as the dimension along the applied field is not much lower than the other dimensions. Calculations of surface currents, as well as measurements and calculations of magnetization and initial susceptibility, are reported. We also present an empirical formula that provides a good fit to the initial susceptibility of a general sample of orthorhombic shape. Demagnetization effects observed on the experimental results are explained in terms of the induced currents in the superconductor. (C) 2004 American Institute of Physics.96148649

In vitro and in vivo performance of methacrylated gellan gum hydrogel formulations for cartilage repair

Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions

Levels of Angiopoietin 2 Are Predictive for Mortality in Patients Infected With Yellow Fever Virus

In 2018 there was a large yellow fever outbreak in São Paulo, Brazil, with a high fatality rate. Yellow fever virus can cause, among other symptoms, hemorrhage and disseminated intravascular coagulation, indicating a role for endothelial cells in disease pathogenesis. Here, we conducted a case-control study and measured markers related to endothelial damage in plasma and its association with mortality. We found that angiopoietin 2 is strongly associated with a fatal outcome and could serve as a predictive marker for mortality. This could be used to monitor severe cases and provide care to improve disease outcome

A comprehensive characterization of chronic norovirus infection in immunodeficient hosts.

Letter to the edito

Comparative cytogenetics among populations of Astyanax altiparanae (Characiformes, Characidae, Incertae sedis)

Cytogenetic data are presented for Astyanax altiparanae populations from three Brazilian hydrographic systems. The chromosomal data obtained in A. altiparanae support the hypothesis of diploid number conservation. However, small differences in the karyotype formula and number of nucleolar organizer regions were observed in these populations. The apparent karyotypical similarity among the studied populations strongly suggests a close relationship among them with some chromosomal divergences due to gene flow restriction