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54. Yeast genome-wide telomere screens and insights into cancer

Author

Pedro Rodrigues, Joana Cristina

Subjects
572.8
Abstract

Telomeres are the very ends of linear eukaryotic chromosomes and when too short or dysfunctional they can trigger senescence (ageing). If the cell can bypass senescence, it can lead to genetic instability or cancer. Telomere capping proteins such as the CST (Cdc13, Stn1 and Ten1) complex and Yku70 are essential for the telomeres not to be recognised as double strand breaks. In this thesis I have used published yeast genome-wide screens to identify genes that are relevant to cancer and telomere biology. Overall 14 out of 19 genetic interactions identified by genome-wide screens could be confirmed by small scale experiments. This work mainly focuses on the telomeric roles of VPS74 and the PAF1 complex. Here, I show that the Golgi gene VPS74, whose human orthologue, GOLPH3, is an oncogene, genetically interacts with telomere capping genes and DNA damage response genes. I demonstrate that Vps74 is important for cell fitness of yku70Δ cells and that the low fitness of Vps74 depleted cells is dependent on the presence of DNA damage checkpoint proteins. I have also systematically investigated the roles of PAF1 complex (Cdc73, Paf1, Ctr9, Leo1 and Rtf1, in yeast) components on telomere biology. The conserved PAF1 complex affects RNA abundance in eukaryotes. I demonstrate that individual PAF1 complex components perform different functions at telomeres. I show that loss of Cdc73 improves fitness of telomere defective yeast cells, while loss of other PAF1 components has the opposite effect. Moreover, I show that Paf1 and Ctr9 strongly reduce telomeric repeat-containing non-coding RNA (TERRA), while Cdc73, Leo1 and Rtf1 have little effect. Paf1 and Ctr9 function independently of Sir4 to regulate TERRA and this is because they stimulate TERRA decay, as well as decay of other RNAs. Additionally, I found that Paf1 and Ctr9 decrease TEN1 and STN1 mRNA levels. I suggest that the PAF1 complex plays a specialized role at telomeres, with Paf1 and Ctr9 maintaining telomere integrity and Cdc73 decreasing the fitness of telomere defective cells.

Published
2017

55. Keeping in reserve : rethinking Earth crises through acts and architectures of reservation

Author

Rodrigues, Joana Trigueiros Rafael Sampaio

Subjects
720
Abstract

This thesis concerns architecture and engages with redefining architecture in terms of its relation to acts and structures of reservation, both posited as causes of, and as solutions to Earth crises – i.e crises related to human-induced threats to, or arising from, the planetary environment. Here, what is meant by “reservation” is the production of (and the) arrangements to secure and keep apart – i.e. in reserve/s – things perceived as threatening to humanity or vital to its survival. In addition, the term here refers to another aspect of reservation - the expression of doubt regarding the efficacy of such arrangements. This thesis contends that, despite being intended to act as architectural solutions, agents or safeguards for the future and safety of (human) life on the planet, by failing to respect the inescapably interconnected nature of the environment and the reciprocity of its processes - their extensive, cumulative and temporal qualities – reserve arrangements exacerbate rather than lessen the problems they set out to address. These assimilate the very structure and pattern of crises they attempt to resolve, and keep morphologically reproducing the ill effects of threats - thus, not only exposing architecture and the reserve fragile limits but, ultimately, cementing them as fictions. This argument is made in relation to attempts to guard and defend against three categories of threat from Earth crises: destruction and danger; depletion of natural and artificial resources; contamination and pollution. These are read through ‘voiced reservations’ from the fields of Arts, critical theory, Earth (and social) sciences, radical ecology, speculative philosophy, cultural studies, architectural theory and even science fiction, which offer theoretical means to reflect on general laws of acting upon the planet and in relation to the future. Problematising the construction of the planet through the logic of the reserve, this thesis calls for new methodological engagements.

Published
2017
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61. CD163+macrophages in mantle cell lymphoma induce activation of prosurvival pathways and immune suppression

Author

de Matos Rodrigues, Joana, Lokhande, Lavanya, Olsson, Lina M., Hassan, May, Johansson, Angelica, Janská, Anna, Kumar, Darshan, Schmidt, Lina, Nikkarinen, Anna, Hollander, Peter, Glimelius, Ingrid, Porwit, Anna, Gerdtsson, Anna Sandstrom, Jerkeman, Mats, and Ek, Sara

Abstract

•MCL and infiltrating T cells show enhanced MAPK in the presence of CD163+macrophages.•CD163+macrophages promote immune suppression in regions proximal to the tumor.

Published
2024
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64. Good practices in the pre-analytical phase of blood cultures: a quasi-experimental study in an emergency department

Author

Baptista, Tânia, Sousa Rodrigues, Joana, Baptista, Tânia, and Sousa Rodrigues, Joana

Abstract

Introduction: Blood culture unequivocally identifies the microorganism responsible for bloodstream infections. The diagnostic value of blood culture depends on the quality of each moment of the pre-analytical phase, with full compliance with recommended best practices being essential. The nurse must implement the most current evidence-based recommendations to avoid external contamination of the sample and to obtain a contamination rate of less than 3%. Objective: To analyse the impact of a training intervention on nurses' knowledge and practice of the pre-analytical phase of blood cultures. Methods: This study follows a quasi-experimental, prospective and longitudinal methodology, through the application of a knowledge assessment questionnaire, based on a narrative search of the literature, the elaboration of a training plan and the construction of a Specific Procedure. The knowledge assessment questionnaire was administered to nurses in two stages - before and after training. Results: Sixty percent of the nurses in an Emergency Department of a hospital in central Portugal participated in the study, constituting a convenience non-probabilistic sample. Participants answered 60.4% of questions correctly before the intervention, increasing to 78.3% two months after. A positive change was observed in all questions, with 67.4% of the sample showing increased knowledge. The blood culture contamination rate reached 12.1% two months before the intervention, with no reduction after the intervention. Conclusion: Nurses' knowledge improved after in-service training and the implementation of a specific procedure (p<0.001). However, there was no reduction in the contamination rate, indicating resistance to changes in behaviour. It is necessary to maintain educational intervention and add other strategies appropriate to the team's characteristics to reduce the blood culture contamination rate effectively.

Published
2024

65. dsRNAi-mediated silencing of PIAS2beta specifically kills anaplastic carcinomas by mitotic catastrophe

Author

Universidad de Sevilla. Departamento de Biología Celular, Agencia Estatal de Investigación. España, Instituto de Salud Carlos III, Rodrigues, Joana S., Chenlo, Miguel, Bravo, Susana B., Pérez Romero, Sihara, Suárez Fariña, María, Sobrino, Tomás, Sanz Pamplona, Rebeca, González Prieto, Román, Álvarez, Clara V., Universidad de Sevilla. Departamento de Biología Celular, Agencia Estatal de Investigación. España, Instituto de Salud Carlos III, Rodrigues, Joana S., Chenlo, Miguel, Bravo, Susana B., Pérez Romero, Sihara, Suárez Fariña, María, Sobrino, Tomás, Sanz Pamplona, Rebeca, González Prieto, Román, and Álvarez, Clara V.

Abstract

The E3 SUMO ligase PIAS2 is expressed at high levels in differentiated papillary thyroid carcinomas but at low levels in anaplastic thyroid carcinomas (ATC), an undifferentiated cancer with high mortality. We show here that depletion of the PIAS2 beta isoform with a transcribed double-stranded RNA–directed RNA interference (PIAS2b-dsRNAi) specifically inhibits growth of ATC cell lines and patient primary cultures in vitro and of orthotopic patient-derived xenografts (oPDX) in vivo. Critically, PIAS2b-dsRNAi does not affect growth of normal or non-anaplastic thyroid tumor cultures (differentiated carcinoma, benign lesions) or cell lines. PIAS2b-dsRNAi also has an anti-cancer effect on other anaplastic human cancers (pancreas, lung, and gastric). Mechanistically, PIAS2b is required for proper mitotic spindle and centrosome assembly, and it is a dosage-sensitive protein in ATC. PIAS2b depletion promotes mitotic catastrophe at prophase. High-throughput proteomics reveals the proteasome (PSMC5) and spindle cytoskeleton (TUBB3) to be direct targets of PIAS2b SUMOylation at mitotic initiation. These results identify PIAS2b-dsRNAi as a promising therapy for ATC and other aggressive anaplastic carcinomas.

Published
2024

66. MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 - a Nordic Lymphoma Group study

Author

Rodrigues, Joana M., Hollander, Peter, Schmidt, Lina, Gkika, Eirinaios, Razmara, Masoud, Kumar, Darshan, Geisler, Christian, Grønbæk, Kirsten, Eskelund, Christian W., Räty, Riikka, Kolstad, Arne, Sundström, Christer, Glimelius, Ingrid, Porwit, Anna, Jerkeman, Mats, Ek, Sara, Rodrigues, Joana M., Hollander, Peter, Schmidt, Lina, Gkika, Eirinaios, Razmara, Masoud, Kumar, Darshan, Geisler, Christian, Grønbæk, Kirsten, Eskelund, Christian W., Räty, Riikka, Kolstad, Arne, Sundström, Christer, Glimelius, Ingrid, Porwit, Anna, Jerkeman, Mats, and Ek, Sara

Abstract

The transcription factor MYC is a well-described oncogene with an important role in lymphomagenesis, but its significance for clinical outcome in mantle cell lymphoma (MCL) remains to be determined. We performed an investigation of the expression of MYC protein in a cohort of 251 MCL patients complemented by analyses of structural aberrations and mRNA, in a sub-cohort of patients. Fourteen percent (n=35) of patients showed high MYC protein expression with >20% positive cells (MYChigh), among whom only one translocation was identified, and 86% (n=216) of patients showed low MYC protein expression. Low copy number gains of MYC were detected in ten patients, but with no correlation to MYC protein levels. However, MYC mRNA levels correlated significantly to MYC protein levels with a R2 value of 0.76. Patients with a MYChigh tumor had both an independent inferior overall survival and an inferior progression-free survival (hazard ratio [HR]=2.03, 95% confidence interval [95% CI]: 1.2-3.4 and HR=2.2, 95% CI: 1.04-4.6, respectively) when adjusted for additional high-risk features. Patients with MYChigh tumors also tended to have additional high-risk features and to be older at diagnosis. A subgroup of 13 patients had concomitant MYChigh expression and TP53/p53 alterations and a substantially increased risk of progression (HR=16.9, 95% CI: 7.4-38.3) and death (HR=7.8, 95% CI: 4.4-14.1) with an average overall survival of only 0.9 years. In summary, we found that at diagnosis a subset of MCL patients (14%) overexpressed MYC protein, and had a poor prognosis but that MYC rearrangements were rare. Tumors with concurrent MYC overexpression and TP53/p53 alterations pinpointed MCL patients with a dismal prognosis with a median overall survival of less than 3 years. We propose that MYC needs to be assessed beyond the current high-risk factors in MCL in order to identify cases in need of alternative treatment.

Published
2024

67. The National Student Survey: Validation in Portuguese Medical Students

Author

Martins, Maria João, Reis Marques, Tiago, Laíns, Inês, Leal, Inês, Pessanha, Inês, Brochado, Bruno, Oliveira Santos, Manuel, Pinto Teixeira, Pedro, Fernandes, Diogo Hipólito, Silva, João Carlos, Sampaio, Filipa Almeida, Brandão, Mariana, Morais, Inês, Laranjinha, Inês, Teixeira, Nelson, Fernandes, Tiago, Carneiro, Diogo, Calvão, Joana, Pratas, Miguel, Palmela, Carolina, Lima, António, Pires, Guilherme, Reis, Joel, Raimundo, Miguel, Afonso, Raquel Rocha, Costa e Silva, Miguel, Quintas, Catarina, Rodrigues, Tiago M., Coelho, Nuno Henriques, Ramos, Sónia Afonso, Policiano, Catarina, Rato, Catarina, Faria, Daniel Candeias, Lopes, Alice, Rodrigues, Joana Ramos, Ferreira, Afonso Nunes, Costeira, Filipa de Sousa, Marques, Renata, Cordeiro, Hugo, and Richardson, John T. E.

Abstract

The UK National Student Survey (NSS) is a sound and widely used instrument for assessing students' academic experiences. We aimed to translate the NSS for Portuguese students and to validate the instrument in a sample of medical undergraduates. The research team translated and adapted the NSS for Portuguese students (NSS-P). The survey was administered on an online platform to 1,256 final-year students at eight Portuguese medical schools. A total of 329 medical students (69.9% female) replied to the NSS-P, a response rate of 26.2%. Confirmatory factor analysis showed that the original six-factor structure had an adequate fit to the data. Adequate internal consistency was observed for all the subscales. Medium to large correlations were found among all the subscale scores and between the subscale scores and the students' overall satisfaction. Multiple regression showed that the scores on the Teaching, Organization and Management and Personal Development subscales significantly predicted the students' overall satisfaction. Approximately 64% of the students reported being satisfied with the quality of their courses. Significant differences among the medical schools in their NSS-P scores were found. The NSS-P is a valid and reliable measure for assessing medical students' perceptions of academic quality.

Published
2019
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68. I Congresso Brasileiro Sobre Doenças Raras - I CONBRASDRA

Author

Lima, Lucas Santos, primary, Miranzi, Mário Alfredo Silveira, additional, Vieira, Larissa Fernanda Medeiros, additional, Gonçalves, Isabela de Souza, additional, Lima, Matheus Santos, additional, Reis Filho, Lupércio Rocha, additional, Andrade, Gustavo Medeiros, additional, Silva Filho, Antônio José Magalhães, additional, Estácio, Rayssa Carolinne Costa Mota, additional, Silva, Décio Fragata da, additional, Silveira, Danilo José de Andrade Santos, additional, Andrade, Thiago Vaz de, additional, Lima, Yvnna Santos, additional, Duarte, Meyling Eng de Almeida, additional, Chagas, Arthur Matos Bitencourt, additional, Vasconcelos, Fernanda de Castro de, additional, Araujo, Ângelo Marcel Santana Duarte, additional, Santana, José Vinícius Lima, additional, Sobral Neto, José Monteiro, additional, Barboza, Jully Cristina Vilar, additional, Mellara, Gabriel Guimarães, additional, Vieira, Arthur Sobral, additional, VALADARES, FABIANA TORRES, additional, Bomfim Neto, Raul, additional, Galindo, Renata Feitosa, additional, Diniz, Sophia Rezende, additional, MONTE, KAHENA MONTEIRO ALMEIDA, additional, Barros, Pablo da Cruz, additional, Goes, Vinicius, additional, Gomes, Melissa Vieira, additional, Gomes, José Natthanael de Aquino, additional, Pachêco, Bruna de Lima, additional, Melo, Josevaldo Araújo de, additional, Ferreira, Emanuela Altmann, additional, Moraes, Thiago Henrique da Silva, additional, Sá, Maria Hélida Alves Callou de, additional, Silvestre, Zenilda Gueiros, additional, Silva, Millena Nayara da, additional, Campagnolo, Ângela Quatrin, additional, Barreto, D'Angelis dos Anjos, additional, Costa, Maria Vitória Pinheiro da, additional, Ferreira, Sara Alves, additional, Melo, Janaína de Oliveira, additional, Castro, Amanda Miranda, additional, Lima, Kelen Cristina Sant'Anna de, additional, Nunes, Ana Paula Nogueira, additional, Alves, Paula Aryane Brito, additional, Starling, Ana Lúcia Pimenta, additional, Miranda, Arícia Gomes, additional, Faustino, Luciana Rocha, additional, Cunha, Sofia Carneiro da, additional, Pereira, Breno Serafim, additional, Silva, Kleyciane Kévilin Pereira da, additional, Melo, Ricardo Eugenio Varela Ayres de, additional, Paiva, Patrícia Sthefânia Mulatinho, additional, Silva, Alana Milena Honorato, additional, Queiroz, José Thomas Azevedo de, additional, Salvador, Viviane de Albuquerque Azevedo, additional, Santos, Luana Maria de Moura, additional, Andrade, Ana Carolina Soares de, additional, Rocha, Bruna Thaís Santos da, additional, Fernandes, Marcela Côrte Real, additional, Melo, Ricardo Eugênio Varela Ayres de, additional, Gontijo, Maria Clara de Araújo, additional, Gama, Henrique Valladão Pires, additional, CAMPOS, EDUARDA MEDEIROS, additional, Mariante, Luiza Thomopoulos, additional, Avelar, Marcos Salomão Staut, additional, Lemos, Maria Eduarda Ferreira, additional, Feitosa, Polyana Santos, additional, Viana, Thiago José Magalhães Silva, additional, Dantas, Cley Gabriel Lima Carvalho, additional, Dantas, Vanessa Silva, additional, Santana, Kathllen Corrêa, additional, Andrade, José Vinícius Rezende de, additional, Dinísio, Társilla de Menezes, additional, Jesus, Aryel Andrade de, additional, Santana, Maria Eduarda Oliveira, additional, Lima, Liliane Santos, additional, Souza, Danilo Santos, additional, Nascimento Filho, Vital Menezes do, additional, Perígolo, Lavínia Barbosa da Terra, additional, Souza, Ana Cláudia de, additional, Assunção, Cláudia Gomes, additional, Pacciulli, Letícia Pinheiro Maia, additional, Barreto, Yesly Marinho da Rocha, additional, Silva, Hozana Fernanda da, additional, Arruda, Maria Dhescyca Ingrid Silva, additional, Bezerra, Maria Eduarda Lopes de Macedo, additional, Gabriel, Isabella Gonçalves, additional, Andrade, Carlos Eugênico Fernandez de, additional, Mancini, Camila dos Santos, additional, Abbamonti, Giulia Afonso, additional, Ferreyra, Heloisa Correia de Morais, additional, Neves, Nathalia Meneses, additional, Jordao, Nicole Oliveira, additional, Mauro, Athene Maria de Marco França, additional, Godoi, Lorena Fontinele, additional, Nunes, Jomar Diogo Costa, additional, Silva, Vitória Regina Vidal Sabá e, additional, Nascimento, Antonia Amanda Cortez do, additional, Cortêz, Thayná Huet Carneiro, additional, Leite Neto, Felipe, additional, Nascimento, Antônia Amanda Cortez do, additional, Chemello, Raissa Massaia Londero, additional, Silva, Millena Nayara Da, additional, Barreto, Dangelis dos Anjos, additional, Farias, Raquel Viégas Martins, additional, Santos, João Paulo Velloso Medrado, additional, Almeida, Camille Teles Ferreira de, additional, Ramos, Dandara Rocha, additional, Aguiar, Manuela Santana, additional, Almeida, Elielton de Jesus, additional, Alves, Yorrane Kelly Gomes, additional, Santos, Igor Luiz Vieira de Lima, additional, Silva, Maria Eduarda Wanderley de Barros, additional, Araújo, Tainá Oliveira de, additional, Cruz, Ellen Karolaine Lucena da, additional, Souza, Juliana Araujo de, additional, França, Beatriz Paulina Santos, additional, Oliveira, Maria Luiza Farias, additional, Santos, Quézia Ellen da Silva, additional, Rodrigues, Anne Wirginne de Lima, additional, Ferreira, Jayana Gabrielle Sobral, additional, Silva, Nephtys Verissimo da, additional, Barros, Mateus Silva de, additional, Araújo, Amanda Geovana Pereira de, additional, Feitosa, Paula Yhasmym de Oliveira, additional, Melo, Josevaldo Araujo de, additional, Silvestre, Zenila Gueiros, additional, Rodrigues, Joana Rosa, additional, Barbisan, Fernanda, additional, Ferreira, Wellington Claudino, additional, PINTO, GUSTAVO DOMINGOS MELO, additional, Santos, Jordan Ramos, additional, Dias, Simone Braga, additional, Silva, Wanusa Belarmino da, additional, Rodrigues, Geicy Bianca Martins, additional, Batalha, Murilo Fialho, additional, Ferrante, Igor Mello, additional, Santos, Mariana da Silva, additional, Wojciechovski, Júlia, additional, Pereira, Mariana Schenato Araujo, additional, Traub, Anna Clara, additional, Mendes, Carolina Dusi, additional, Correa, Giovana Luiza, additional, Pereira, Mariana Araujo Schenato, additional, Silva, Decio Fragata Da, additional, Estacio, Rayssa Carolinne Costa Mota, additional, Araujo, Angelo Marcel Santana Duarte, additional, Bonfim Neto, Raul, additional, Limav, Yvnna Santos, additional, Barboza, Jully Cristina Villar, additional, Vasconcelos, Fernanda de Castro, additional, Santos, Áleff Edrei Gomes, additional, Ferraro, Halley Oliveira, additional, Silveira, Danilo Jose de Andrade Santos, additional, COUTO, LETÍCIA MACHADO, additional, Silva, Yuri Cássio de Lima, additional, Aguiar, Camila Siqueira, additional, Melo, Rodrigo Henrique Melo Varela Ayres de, additional, Rhoden, Deise Louise Bohn, additional, Melo, Milena Melo Varela Ayres de, additional, Melo, Victor Leonardo Melo Varela Ayres de, additional, Melo Júnior, Frederico Márcio Varela Ayres de, additional, Melo, Bruna Heloísa Costa Varela Ayres de, additional, Beck, Júlia Souza, additional, Lira, Luiz Henrique Campello, additional, Seixas, Zélia de Albuquerque, additional, Freitas, Nela Dulce Varela de Melo Costa, additional, Melo, Jussara Diana Varela Ayres de, additional, Sousa, Douglas Monteiro de, additional, Silva, Luísa Margareth Carneiro da, additional, Cabral, Ananda Leticia Silva, additional, Gonçalves, Elielson Felix, additional, Arruda, Isabela Tatiana Sales de, additional, Paiva, Wemerson Sousa, additional, Xavier, Barbara Julia Rodrigues, additional, Alvarenga, Pedro Victor Santana, additional, Matias, Tamires de Alexandria, additional, oliveira, Halley ferraro, additional, Chagas, Arthur Matos Bittencourt, additional, Silveira, Danilo José Andrade dos Santos, additional, Santana, José Vinicius Lima, additional, Duarte, Ângelo Marcel Santana, additional, Duarte, Meylling Eng de Almeida, additional, Ferreira Filho, Ecliê Santos, additional, Campos, Ana Helena Prado Santana, additional, Santana, Letícia Brandão, additional, Souza, Anelise Marques Feitosa de, additional, Cordeiro, Maria Eduarda Santana, additional, Rosa, Heloísa, additional, Marinheiro, Juliana Cristina, additional, Martins Neto, José da Silva, additional, Carmo, Monique Santos do, additional, Neves, Julia Alim Maluf, additional, Sousa Junior, Paulo Ferreira de, additional, Alves, Yorrane kelly Gomes, additional, Oliveira, Halley Ferraro, additional, Alves, Matheus Porto, additional, Carvalho, Letícia Gonçalves, additional, Paoliello, Adriana Balbina, additional, Fogari, Letícia Raiane, additional, Caparroz, Maria Eduarda Leati, additional, Sousa, Daniela Heitzmann Amaral Valentim de, additional, Alves, Yorrane kelly gomes, additional, Bomfim, Vitória Vilas Boas da Silva, additional, Diniz, Samara Dantas de Medeiros, additional, Galvão, Natallie Cecília dos Santos, additional, Vieira, Walisson da Silva, additional, Fernandes, Nathalia Emmanuele Pereira, additional, Oliveira, Bianca Diniz, additional, RIBEIRO, Ricardo de Souza, additional, Duarte, Henrique Maciel, additional, Araújo Junior, José Geraldo, additional, BRAGA, Maria Gabriella Borges, additional, Oliveira, Vinícius Carvalho de, additional, Ribeiro, Ricardo de Souza, additional, Dias, Sylvia Carriel, additional, Freire, Márcia Helena de Souza, additional, Saganski, Gabrielle Freitas, additional, Lima, Lohana Maylane Aquino Correia de, additional, Aguiar, Camilla Siqueira de, additional, Melo, Victor Leonardo Mello Varela Ayres de, additional, Melo Junior, Frederico Marcio Varela Ayres de, additional, Beck, Júlia de Souza, additional, Melo, Rodrigo Henrique Mello Varela Ayres de, additional, Pinheiro, Milena Mello Varela Ayres de Melo, additional, Freitas, Nely Dulce Varela de Melo Costa, additional, Nascimento, Antonia Amanda Cortêz do, additional, Araújo, Iara Medeiros de, additional, Alavrenga, Pedro Victor Santana, additional, Assis, Bruno Mouallem de, additional, Pinto, Gustavo Domingos Melo, additional, Temponi, Bárbara Vilaça, additional, Chaves, Ana Luisa Rogana, additional, Faria, Arthur Pereira Barbosa de, additional, Costa, Carolina Siqueira Florentino, additional, Pimenta, Pedro Pires Costa, additional, Paiva, Patricia Sthefânia Mulatinho, additional, Pereira, Ayane Paula Mendonça, additional, Dellalibera, Edileine, additional, Sousa, Laila Eliza Teixeira de, additional, Paula, Ana Karolina Nascimento, additional, Alves, Even Herlany Pereira, additional, Oliveira, Pedro Henrique Sales de, additional, Pontes, Vitória de Melo, additional, Silva, Diego dos Santos, additional, Leite, Igor José Paiva, additional, Martins, Willian Silva, additional, Gomes, Alanna Carvalho, additional, chagas, arthur matos bitencourt, additional, ferreira, isabella lisboa, additional, lima, yvnna santos, additional, ferreira filho, eclie santos, additional, campos, ana helena prado, additional, silveira, danilo jose de andrade santos, additional, Tenório Neto, José Alves, additional, Albuquerque, Amanda Oliveira Bernardino Cavalcanti de, additional, marques, Rebeca Ribeiro, additional, Santos, Dayane Priscila dos, additional, Hessmann, Giovanna, additional, and Pinto, Luanna, additional

Published
2021
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71. Quantification and Profiling of Early and Late Differentiation Stage T Cells in Mantle Cell Lymphoma Reveals Immunotherapeutic Targets in Subsets of Patients.

Author

Lokhande, Lavanya, Nilsson, Daniel, de Matos Rodrigues, Joana, Hassan, May, Olsson, Lina M., Pyl, Paul-Theodor, Vasquez, Louella, Porwit, Anna, Gerdtsson, Anna Sandström, Jerkeman, Mats, and Ek, Sara

Subjects
NON-Hodgkin's lymphoma, T cells, RESEARCH funding, CANCER patients, DESCRIPTIVE statistics, GENE expression, DEEP learning, PROTEOMICS, TUMOR classification, CELL differentiation, T helper cells, CELL receptors, IMMUNOSUPPRESSION
Abstract

Simple Summary: In our study, we investigated immune regulation in a subtype of lymphoma called mantle cell lymphoma (MCL). Our goal was to understand how different types of immune cells, specifically T cells, behave in MCL. To do this, we combined image analysis and a technology called digital spatial profiling. We looked at tumor tissue from 102 MCL patients and analyzed different T-cell subsets. Interestingly, we found that late-stage differentiated T cells (CD57+) were more common in tumor-rich areas. These T cells also showed an increased expression of immune suppressive markers. We identified potential targets for treatment, such as CD47, IDO1, and CTLA-4. Additionally, we found that patients with sparse T-cell infiltration had an increased amount of GITR, which tentatively can be therapeutically targeted. Our findings shed light on previously unknown features of T-cell behavior in MCL. With the aim to advance the understanding of immune regulation in MCL and to identify targetable T-cell subsets, we set out to combine image analysis and spatial omic technology focused on both early and late differentiation stages of T cells. MCL patient tissue (n = 102) was explored using image analysis and GeoMx spatial omics profiling of 69 proteins and 1812 mRNAs. Tumor cells, T helper (TH) cells and cytotoxic (TC) cells of early (CD57−) and late (CD57+) differentiation stage were analyzed. An image analysis workflow was developed based on fine-tuned Cellpose models for cell segmentation and classification. TC and CD57+ subsets of T cells were enriched in tumor-rich compared to tumor-sparse regions. Tumor-sparse regions had a higher expression of several key immune suppressive proteins, tentatively controlling T-cell expansion in regions close to the tumor. We revealed that T cells in late differentiation stages (CD57+) are enriched among MCL infiltrating T cells and are predictive of an increased expression of immune suppressive markers. CD47, IDO1 and CTLA-4 were identified as potential targets for patients with T-cell-rich MCL TIME, while GITR might be a feasible target for MCL patients with sparse T-cell infiltration. In subgroups of patients with a high degree of CD57+ TC-cell infiltration, several immune checkpoint inhibitors, including TIGIT, PD-L1 and LAG3 were increased, emphasizing the immune-suppressive features of this highly differentiated T-cell subset not previously described in MCL. [ABSTRACT FROM AUTHOR]

Published
2024
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72. A Fortran-Python Interface for Integrating Machine Learning Parameterization into Earth System Models.

Author

Zhang, Tao, Morcrette, Cyril, Zhang, Meng, Lin, Wuyin, Xie, Shaocheng, Liu, Ye, Weverberg, Kwinten Van, and Rodrigues, Joana

Subjects
MACHINE learning, PARAMETERIZATION, CLIMATOLOGY, COMPUTER software reusability, PROBLEM solving, FORTRAN
Abstract

Parameterizations in Earth System Models (ESMs) are subject to biases and uncertainties arising from subjective empirical assumptions and incomplete understanding of the underlying physical processes. Recently, the growing representational capability of machine learning (ML) in solving complex problems has spawned immense interests in climate science applications. Specifically, ML-based parameterizations have been developed to represent convection, radiation and microphysics processes in ESMs by learning from observations or high-resolution simulations, which have the potential to improve the accuracies and alleviate the uncertainties. Previous works have developed some surrogate models for these processes using ML. These surrogate models need to be coupled with the dynamical core of ESMs to investigate the effectiveness and their performance in a coupled system. In this study, we present a novel Fortran-Python interface designed to seamlessly integrate ML parameterizations into ESMs. This interface showcases high versatility by supporting popular ML frameworks like PyTorch, TensorFlow, and Scikit-learn. We demonstrate the interface's modularity and reusability through two cases: a ML trigger function for convection parameterization and a ML wildfire model. We conduct a comprehensive evaluation of memory usage and computational overhead resulting from the integration of Python codes into the Fortran ESMs. By leveraging this flexible interface, ML parameterizations can be effectively developed, tested, and integrated into ESMs. [ABSTRACT FROM AUTHOR]

Published
2024
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74. Hands-On Data Publishing with Researchers: Five Experiments with Metadata in Multiple Domains

Author

Rodrigues, Joana, Castro, João Aguiar, da Silva, João Rocha, Ribeiro, Cristina, Barbosa, Simone Diniz Junqueira, Series Editor, Filipe, Joaquim, Series Editor, Kotenko, Igor, Series Editor, Sivalingam, Krishna M., Series Editor, Washio, Takashi, Series Editor, Yuan, Junsong, Series Editor, Zhou, Lizhu, Series Editor, Ghosh, Ashish, Series Editor, Manghi, Paolo, editor, Candela, Leonardo, editor, and Silvello, Gianmaria, editor

Published
2019
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75. Economic and Clinical Impact of Ventilator-Associated Pneumonia in Intensive Care Units of a University Hospital Center

Author

Rodrigues, Joana, Sousa, Paulo, Kacprzyk, Janusz, Series Editor, Pal, Nikhil R., Advisory Editor, Bello Perez, Rafael, Advisory Editor, Corchado, Emilio S., Advisory Editor, Hagras, Hani, Advisory Editor, Kóczy, László T., Advisory Editor, Kreinovich, Vladik, Advisory Editor, Lin, Chin-Teng, Advisory Editor, Lu, Jie, Advisory Editor, Melin, Patricia, Advisory Editor, Nedjah, Nadia, Advisory Editor, Nguyen, Ngoc Thanh, Advisory Editor, Wang, Jun, Advisory Editor, Cotrim, Teresa Patrone, editor, Serranheira, Florentino, editor, Sousa, Paulo, editor, Hignett, Sue, editor, Albolino, Sara, editor, and Tartaglia, Riccardo, editor

Published
2019
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83. Cross-sectional epidemiological study to understand the approach to treatment in the routine care of patients with hemophilia B in Spain and Portugal

Author

Álvarez-Román, María T., primary, Carvalho, Manuela, additional, Benítez-Hidalgo, Olga, additional, Catarino, Cristina, additional, García-Frade, Luis J., additional, Rodríguez-López, Manuel, additional, Antunes, Margarida, additional, Fernández-Mosteirín, Nuria, additional, Kjöllerström, Paula, additional, Morais, Sara, additional, Galmes, Bernat, additional, López-Fernández, María F., additional, Riera-Sans, Lluis, additional, Rodrigues, Joana F., additional, Jiménez-Yuste, Víctor, additional, and Salvado, Ramón, additional

Published
2023
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86. Profilin 1 delivery tunes cytoskeletal dynamics toward CNS axon regeneration

Author

Pinto-Costa, Rita, Sousa, Sara C., Leite, Sergio C., Nogueira-Rodrigues, Joana, da Silva, Tiago Ferreira, Machado, Diana, Marques, Joana, Costa, Ana Catarina, Liz, Marcia A., Bartolini, Francesca, Brites, Pedro, Costell, Mercedes, Fassler, Reinhard, and Sousa, Monica M.

Subjects
Thermo Fisher Scientific Inc., Actin -- Analysis, Scientific equipment industry -- Analysis, Rodents, Health care industry
Abstract

After trauma, regeneration of adult CNS axons is abortive, causing devastating neurologic deficits. Despite progress in rehabilitative care, there is no effective treatment that stimulates axonal growth following injury. Using models with different regenerative capacities, followed by gain- and loss-of-function analysis, we identified profilin 1 (Pfn1) as a coordinator of actin and microtubules (MTs), powering axonal growth and regeneration. In growth cones, Pfn1 increased actin retrograde flow, MT growth speed, and invasion of filopodia by MTs, orchestrating cytoskeletal dynamics toward axonal growth. In vitro, active Pfn1 promoted MT growth in a formin-dependent manner, whereas localization of MTs to growth cone filopodia was facilitated by direct MT binding and interaction with formins. In vivo, Pfn1 ablation limited regeneration of growth- competent axons after sciatic nerve and spinal cord injury. Adeno-associated viral (AAV) delivery of constitutively active Pfn1 to rodents promoted axonal regeneration, neuromuscular junction maturation, and functional recovery of injured sciatic nerves, and increased the ability of regenerating axons to penetrate the inhibitory spinal cord glial scar. Thus, we identify Pfn1 as an important regulator of axonal regeneration and suggest that AAV-mediated delivery of constitutively active Pfn1, together with the identification of modulators of Pfn1 activity, should be considered to treat the injured nervous system., Introduction In the adult CNS, developmental axonal growth capacity declines such that regeneration after injury is abortive. This derives from the highly inhibitory environment formed at the injury site, and [...]

Published
2020
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88. Ensaios toxicológicos do noni (Morinda citrifolia)

Author

Bezerra Santos, Elvis, primary, Siqueira de Góis Rodrigues, Joana, additional, RAFAELLE DE ARAÚJO SILVA, ELAINE, additional, Libanio de Lima, Maksuelly, additional, Francieli da Silva, Nabuêr, additional, and ESTEVAO ALVES FALCAO, ROSANGELA, additional

Published
2021
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91. Strengthening geoscience communication and public relations through geo-cartoons / geo-emojis: a digital option or …?

Author

Frey, Marie-Luise, Ciobanu, Cristian, Rodrigues, Joana, and Toma, Cristina

Abstract

People in different societies, including adults, young people, and children, are usually confronted with explanations and/or drawings by geoscientists on topics presented in museums, visitor centres and in the field when it comes to communicating geoscientific topics. In formal education, the focus is usually on conveying scientific concepts, research findings, and results. With the emergence of geopaths/-trails in Germany since the 1970s and later geoparks since 1992, the interest of citizens aged 3 to 100 years has been awakened with information panels, adventure boards and/or brochures in the broadest sense, encouraging the discovery of nature, landscape and their geoscientific phenomena and processes, including a wide range of earth sciences. Since then, geological trails, geo-hiking trails, geo-routes, mountain bike trails as well as brochures and teaching resources for various age groups have been created to communicate geoscientific topics. With the changes in life and society, the emergence of generations X, Y, Z and Alpha has established new target groups. This shift has created a new dynamic and changed the preferences of contemporary culture, which requires a paradigm shift and innovative approaches in communication strategies. Independently of the poem by the German poet Joseph Victor Scheffel (1826–1886) “Der Ichthyosaurus”, which initially inspired geoscientists, geo-cartoons were created and used by Global Geoparks. Since the early 1990s, they have probably been published for the first time in Germany and France, others have followed, e. g. in the Republic of Ireland, Portugal, Romania, Hong Kong (PR China) and are used as “mascots” especially in Global Geoparks. Together with storytelling, their popularity has increased and their use has also expanded significantly in terms of digitalisation. This article addresses the target audiences, gives aspects of the interpretation of geoscientific topics, presents examples of geo-cartoons and concepts and builds a bridge to the use of cartoons to communicate geoscience to adults and the necessary professional partners, including their use in digital communication.

Published
2024
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95. An Intermediate-mass Black Hole of Over 500 Solar Masses in the Galaxy ESO 243-49

Author

Farrell, Sean, Webb, Natalie, Barret, Didier, Godet, Olivier, and Rodrigues, Joana

Subjects
Astrophysics - High Energy Astrophysical Phenomena, Astrophysics - Cosmology and Extragalactic Astrophysics
Abstract

Ultra-luminous X-ray sources are extragalactic objects located outside the nucleus of the host galaxy with bolometric luminosities >10^39 erg s^-1. These extreme luminosities - if the emission is isotropic and below the theoretical (i.e. Eddington) limit, where the radiation pressure is balanced by the gravitational pressure - imply the presence of an accreting black hole with a mass of ~10^2-10^5 times that of the Sun. The existence of such intermediate mass black holes is in dispute, and though many candidates have been proposed, none are widely accepted as definitive. Here we report the detection of a variable X-ray source with a maximum 0.2-10 keV luminosity of up to 1.2 x 10^42 erg s^-1 in the edge-on spiral galaxy ESO 243-49, with an implied conservative lower limit of the mass of the black hole of ~500 Msun. This finding presents the strongest observational evidence to date for the existence of intermediate mass black holes, providing the long sought after missing link between the stellar mass and super-massive black hole populations., Comment: 5 pages, 2 figures, 1 table, published in Nature

Published
2010
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99. MYC protein is a high-risk factor in mantle cell lymphoma and identifies cases beyond morphology, proliferation and TP53/p53 – a Nordic Lymphoma Group study

Author

Rodrigues, Joana M., primary, Hollander, Peter, additional, Schmidt, Lina, additional, Gkika, Eirinaios, additional, Razmara, Masoud, additional, Kumar, Darshan, additional, Geisler, Christian, additional, Grønbæk, Kirsten, additional, Eskelund, Christian W., additional, Räty, Riikka, additional, Kolstad, Arne, additional, Sundström, Christer, additional, Glimelius, Ingrid, additional, Porwit, Anna, additional, Jerkeman, Mats, additional, and Ek, Sara, additional

Published
2023
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