Gene Regulation by the transcription factor ZEB1 in Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is the most prevalent type of glioma, bearing the highest incidence rate of brain and Central Nervous System (CNS) malignant tumors and the lowest survival rate. GBMs distinguish themselves from lower grade glial tumors by the presence of certain hallmark histological features such as the presence of central necrosis in the tumor mass, marginal proliferation of endothelial cells and the presence of palisading cells around the area of necrosis. Several hallmark features contribute to the poor responsiveness that GBM tumors have to treatment including their high inter- and intratumoral heterogeneity at a phenotypic, cellular, genetic and epigenetic level. Most importantly, the existence of cancer stem cell (CSC) populations within GBM tumors is crucial for driving invasive tumor growth due to their potential to proliferate in vascular conditions, while becoming highly invasive in hypoxic conditions. Moreover, the ability of GBM CSCs to infiltrate surrounding brain parenchyma means that even the smallest number of such cells left after surgery will cause tumor recurrence.(...

Artrite reumatóide e exercícios propriocetivos atividade da doença, capacidade funcional, composição corporal e biomecânica da marcha

Orientação : João Manuel Cunha da Silva AbrantesObjetivos – Avaliar os efeitos dos exercícios propriocetivos sobre mulheres pós menopáusicas com artrite reumatóide (MPAR). Especificamente, examinar a atividade da doença, capacidade funcional, composição corporal e biomecânica da marcha. Métodos – 27 MPAR colocadas no grupo de exercício (GE; n=15) ou no grupo de exercício placebo (GEP; n=12). GE: exercícios propriocetivos; 12 semanas; 3 sessões individualizadas/semana; 30 minutos/sessão. GEP: exercícios de alongamento para tronco e membros superiores; 12 semanas; 1 sessão quinzenal individualizada; 30 minutos/sessão. Disease Activity Score-28 joints (DAS-28) avaliou atividade da doença. Health Assessment Questionnaire (HAQ) avaliou a capacidade funcional. Composição corporal avaliada por bioimpedância. Marcha examinada por análise tridimensional do movimento (200Hz) sincronizado com uma plataforma de forças (1000Hz). Resultados – GE: menor HAQ score (p<0.001); maior velocidade da marcha (p<0.05); maior comprimento da passada (p<0.05); menor percentagem da fase de duplo apoio (p<0.05); maior velocidade do centro de massa (p<0.05); maior pico máximo da potência articular do tornozelo (p<0.05); não foram encontradas diferenças no DAS-28, composição corporal e rigidez dinâmica articular do tornozelo. GEP: não foram encontradas diferenças. Conclusões – Exercícios propriocetivos em MPAR parecem ser seguros; verificaram-se, como resultado destes exercícios, evidências da melhoria da capacidade funcional e da aproximação aos valores normativos das variáveis biomecânicas da marcha.Objectives – Assess the effects of proprioceptive exercises on rheumatoid arthritis postmenopausal women (RAPW). Specifically, to assess disease activity, functional capacity, body composition, and gait biomechanics. Methods – Twenty-seven RAPW assigned to exercise group (EG; n=15) or to placebo exercise group (PEG; n=12). EG performed a 12-week proprioceptive exercises individualized program (3 sessions/week; 30 minutes/session) and PEG performed a 12-week individualized program of stretching exercises for trunk and upper limbs (1 session every two weeks; 30 minutes/session). Disease Activity Score-28 joints (DAS-28) assessed disease activity. Health Assessment Questionnaire (HAQ) assessed functional capacity. Body composition assessed by a bioelectrical impedance analysis. Gait assessed by a threedimensional motion analysis (200Hz) synchronized with a force plate (1000Hz). Results – After program, EG showed: lower HAQ score (p<0.001), higher gait speed (p<0.05), higher stride length (p<0.05), lower percentage of double support phase (p<0.05), higher centre of mass velocity (p<0.05), and higher ankle power peak (p<0.001); no differences in DAS-28, body composition, and DJSankle. After program, PEG showed no differences. Conclusions – Proprioceptive exercises seem to be safe in RAPW; were verified, as a result of these exercises, evidence of improvement of the functional capacity and evidence of approximation to the normative values of the gait biomechanical variables

Residências artísticas em Sines : Torre de escritores

A vertente prática da unidade curricular de Projeto Final de Arquitetura, correspondente ao ano letivo de 2015/2016, consistiu numa intervenção projetual em Sines, no âmbito do Concurso Universidades Trienal de Lisboa Millennium bcp, segundo o tema Sines-Indústria e Estrutura Portuária. A cidade de Sines situa-se no litoral sudoeste de Portugal, a cerca de 150 quilómetros de Lisboa, caraterizando-se por uma forte presença industrial, com a existência de um porto de pesca, porto comercial, refinaria e central termoelétrica. É neste âmbito que surge o desafio lançado pela Trienal, propondo um “debate sobre o valor sociopolítico da indústria e sobre a capacidade da Arquitetura de ativar esse potencial” e incentivando uma reflexão sobre o “aproveitamento dos recursos existentes, do potencial programático do lugar e das relações e contextos que superam a escala do próprio território”, pretextos para fazer arquitetura

Acute HIV-1 and SARS-CoV-2 infections Share Slan+ Monocyte Depletion - evidence from an hyperacute HIV-1 case report

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Monocytes are key modulators in acute viral infections, determining both inflammation and development of specific B- and T-cell responses. Recently, these cells were shown to be associated to different SARS-CoV-2 infection outcome. However, their role in acute HIV-1 infection remains unclear. We had the opportunity to evaluate the mononuclear cell compartment in an early hyper-acute HIV-1 patient in comparison with an untreated chronic HIV-1 and a cohort of SARS-CoV-2 infected patients, by high dimensional flow cytometry using an unsupervised approach. A distinct polarization of the monocyte phenotype was observed in the two viral infections, with maintenance of pro-inflammatory M1-like profile in HIV-1, in contrast to the M2-like immunosuppressive shift in SARS-CoV-2. Noticeably, both acute infections had reduced CD14low/-CD16+ non-classical monocytes, with depletion of the population expressing Slan (6-sulfo LacNac), which is thought to contribute to immune surveillance through pro-inflammatory properties. This depletion indicates a potential role of these cells in acute viral infection, which has not previously been explored. The inflammatory state accompanied by the depletion of Slan+ monocytes may provide new insights on the critical events that determine the rate of viral set-point in acute HIV-1 infection and subsequent impact on transmission and reservoir establishment.This work was funded by the following grants from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through “Apoio Especial Research4COVID-19”, project numbers 125 to S.M.F. and 803 to A.C.T. Fellowships funded by FCT (Doctorates4COVID-19, 2020.10202.BD), and Janssen-Cilag Farmacêutica were received by A.M.C.G. and G.B.F., respectively.info:eu-repo/semantics/publishedVersio

Severe COVID-19 recovery is associated with timely acquisition of a myeloid cell immune-regulatory phenotype

Copyright © 2021 Trombetta, Farias, Gomes, Godinho-Santos, Rosmaninho, Conceição, Laia, Santos, Almeida, Mota, Gomes, Serrano, Veldhoen, Sousa and Fernandes. 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) and the copyright owner(s) 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.After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an urgent need for understanding the underlying pathogenic mechanisms to guide therapeutic interventions. This study was designed to assess myeloid cell activation and phenotype leading to recovery in patients surviving severe COVID-19. We evaluated longitudinally patients with COVID-19 related respiratory insufficiency, stratified according to the need of intensive care unit admission (ICU, n = 11, and No-ICU, n = 9), and age and sex matched healthy controls (HCs, n = 11), by flow cytometry and a wide array of serum inflammatory/immune-regulatory mediators. All patients featured systemic immune-regulatory myeloid cell phenotype as assessed by both unsupervised and supervised analysis of circulating monocyte and dendritic cell subsets. Specifically, we observed a reduction of CD14lowCD16+ monocytes, and reduced expression of CD80, CD86, and Slan. Moreover, mDCs, pDCs, and basophils were significantly reduced, in comparison to healthy subjects. Contemporaneously, both monocytes and DCs showed increased expression of CD163, CD204, CD206, and PD-L1 immune-regulatory markers. The expansion of M2-like monocytes was significantly higher at admission in patients featuring detectable SARS-CoV-2 plasma viral load and it was positively correlated with the levels of specific antibodies. In No-ICU patients, we observed a peak of the alterations at admission and a progressive regression to a phenotype similar to HCs at discharge. Interestingly, in ICU patients, the expression of immuno-suppressive markers progressively increased until discharge. Notably, an increase of M2-like HLA-DRhighPD-L1+ cells in CD14++CD16- monocytes and in dendritic cell subsets was observed at ICU discharge. Furthermore, IFN-γ and IL-12p40 showed a decline over time in ICU patients, while high values of IL1RA and IL-10 were maintained. In conclusion, these results support that timely acquisition of a myeloid cell immune-regulatory phenotype might contribute to recovery in severe systemic SARS-CoV-2 infection and suggest that therapeutic agents favoring an innate immune system regulatory shift may represent the best strategy to be implemented at this stage.The Research was funded by Fundação para a Ciência e Tecnologia (FCT), “APOIO ESPECIAL RESEARCH 4COVID-19” projects 803, 125, 231_596873172, and 729. AMCG and GF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD), and JANSSEN- CILAG FARMACÊUTICA, respectively. The funder was not involved in the study design, collection, analysis, interpretation of data, writing of the article or decision to submit it for publication. MV was supported by the European Union H2020 ERA project (No 667824 – EXCELLtoINNOV). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 667824.info:eu-repo/semantics/publishedVersio

Monozygotic twins concordant for common variable immunodeficiency : strikingly similar clinical and immune profile associated with a polygenic burden

Copyright © 2019 Silva, Fonseca, Pereira, Silva, Barbosa, Serra-Caetano, Blanco, Rosmaninho, Pérez-Andrés, Sousa, Raposo, Gama-Carvalho, Victorino, Hammarstrom and Sousa. 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) and the copyright owner(s) 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.Monozygotic twins provide a unique opportunity to better understand complex genetic diseases and the relative contribution of heritable factors in shaping the immune system throughout life. Common Variable Immunodeficiency Disorders (CVID) are primary antibody defects displaying wide phenotypic and genetic heterogeneity, with monogenic transmission accounting for only a minority of the cases. Here, we report a pair of monozygotic twins concordant for CVID without a family history of primary immunodeficiency. They featured a remarkably similar profile of clinical manifestations and immunological alterations at diagnosis (established at age 37) and along the subsequent 15 years of follow-up. Interestingly, whole-exome sequencing failed to identify a monogenic cause for CVID, but unraveled a combination of heterozygous variants, with a predicted deleterious impact. These variants were found in genes involved in relevant immunological pathways, such as JUN, PTPRC, TLR1, ICAM1, and JAK3. The potential for combinatorial effects translating into the observed disease phenotype is inferred from their roles in immune pathways, namely in T and B cell activation. The combination of these genetic variants is also likely to impose a significant constraint on environmental influences, resulting in a similar immunological phenotype in both twins, despite exposure to different living conditions. Overall, these cases stress the importance of integrating NGS data with clinical and immunological phenotypes at the single-cell level, as provided by multi-dimensional flow-cytometry, in order to understand the complex genetic landscape underlying the vast majority of patients with CVID, as well as those with other immunodeficiencies.This work received funding from PAC - PRECISE - LISBOA-01-0145-FEDER-016394, co-funded by FEDER through POR Lisboa 2020 - Programa Operacional Regional de Lisboa PORTUGAL 2020 and Fundação para a Ciência e a Tecnologia; and UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado. Work in MG-C lab is supported by UID/MULTI/04046/2019 Research Unit grant from FCT, Portugal (to BioISI) and FCT research grant PTDC/BIA-CEL/29257/2017.info:eu-repo/semantics/publishedVersio

SARS‐CoV2 pneumonia recovery is linked to expansion of innate lymphoid cells type 2 expressing CCR10

© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.Accelerate lung repair in SARS-CoV-2 pneumonia is essential for pandemic handling. Innate lymphoid cells (ILCs) are likely players, given their role in mucosal protection and tissue homeostasis. We studied ILC subpopulations at two time points in a cohort of patients admitted in the hospital due to SARS-CoV-2 infection. COVID-19 patients with moderate/severe respiratory failure featured profound depletion of circulating ILCs at hospital admission, in agreement with overall lymphocyte depletion. However, ILCs recovered in direct correlation with lung function improvement as measured by oxygenation index and in negative association with inflammatory and lung/endothelial damage markers like RAGE. While both ILC1 and ILC2 expanded, ILC2 showed the most striking phenotype changes, with CCR10 upregulation in strong correlation with these parameters. Overall, CCR10+ ILC2 emerge as relevant contributors to SARS-CoV-2 pneumonia recovery.This work was funded by the following grants from Fundação para a Ciência e a Tecnologia (FCT), Portugal, through “APOIO ESPECIAL RESEARCH4COVID-19,” project numbers 125 to SMF and 803 to ACT. AMCG and GBF received fellowships funded by FCT (DOCTORATES4COVID-19, 2020.10202.BD) and JANSSEN- CILAG FARMACÊUTICA, respectively.info:eu-repo/semantics/publishedVersio

A dataset of ITS-G5 and cellular vehicular connectivity in urban environment

Connecting vehicles to the Internet is an emerging challenge of wireless networks. There are two competing methods for achieving this. First, the wireless local area network (WLAN) approach is based on the IEEE 802.11p standard (in its European version called ETSI ITS-G5) created for Cooperative-Intelligent Transportation System applications. Second, the cellular network approach is based on LTE/5G technologies which have been exploited in recent years to support vehicular applications. Advantages such as high bandwidth, high coverage and high reliability make cellular networks a great option for the vehicular environment.This article describes two datasets that support the analysis of WLAN (ETSI ITS-G5) and Cellular (LTE/5G) technologies in a real vehicular and road environment. The two datasets summarize the results obtained in a collection of network performance tests performed in the city of Aveiro, Portugal. In these tests, a set of vehicles (8 On-Board Units) moved randomly around the city, passing near a group of stationary nodes (11 Road-Side Units) uploading data to a server. In the WLAN dataset, data was sent using the ETSI ITS-G5 technology, whereas, in the Cellular dataset, data was sent using LTE/5G technologies. While testing, location, signal quality, and network performance data (achieved throughput, jitter, etc.) were collected.This dataset can support a realistic analysis of WLAN and Cellular performance in an environment that is not only vehicular but also urban, with obstacles and interference

On the performance of 5G for cloud- and edge-based emergency services in smart cities

The deployment of emergency services in a city scenario, such as the ones for users’ safety in the roads, require the support of fast network technologies and efficient network architectures. Moreover, these services need to be available city-wide, so a flexible approach is needed to deploy high-speed technology to the overall city.This paper addresses the performance of 5G technology and its architecture to deploy emergency services with strict requirements, when compared to the use of fiber throughout the city. It considers the location of demanding services, in this specific case the people detection in the road through video cameras, both in the edge and the cloud, and with both fiber and real 5G connection between the edge and the cloud. We evaluate this architecture in a real scenario with real users and vehicles in the area. The obtained results show that 5G with an edge-based approach can provide similar services to fiber-based connections to the cloud.info:eu-repo/semantics/publishedVersio

The dysfunctional immune system in common variable immunodeficiency increases the susceptibility to gastric cancer

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p < 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.This article is a result of the projects DOCnet (NORTE-01-0145-FEDER-000003/000029), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). This research was funded by FCT-Foundation for Science and Technology/Ministério da Ciência, Tecnologia e Inovação, grantnumber PTDC/MED-PAT/32462/2017 and PTDC/BIM-MEC/2834/2014.This work is funded by grant PAC-PRECISE-LISBOA-01-0145-FEDER-016394, co-funded by FEDER through POR Lisboa 2020—Programa Operacional Regional de Lisboa PORTUGAL 2020 and FCT, and UID/BIM/50005/2019 funded by FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estadoinfo:eu-repo/semantics/publishedVersio