8 results on '"Filipa S. Carvalho"'
Search Results
2. From Forensics to Clinical Research: Expanding the Variant Calling Pipeline for the Precision ID mtDNA Whole Genome Panel
- Author
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Filipe Cortes-Figueiredo, Filipa S. Carvalho, Ana Catarina Fonseca, Friedemann Paul, José M. Ferro, Sebastian Schönherr, Hansi Weissensteiner, and Vanessa A. Morais
- Subjects
mitochondrial DNA ,next-generation sequencing ,massively parallel sequencing ,whole genome sequencing ,Precision ID ,Thermo Fisher Scientific ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Despite a multitude of methods for the sample preparation, sequencing, and data analysis of mitochondrial DNA (mtDNA), the demand for innovation remains, particularly in comparison with nuclear DNA (nDNA) research. The Applied Biosystems™ Precision ID mtDNA Whole Genome Panel (Thermo Fisher Scientific, USA) is an innovative library preparation kit suitable for degraded samples and low DNA input. However, its bioinformatic processing occurs in the enterprise Ion Torrent Suite™ Software (TSS), yielding BAM files aligned to an unorthodox version of the revised Cambridge Reference Sequence (rCRS), with a heteroplasmy threshold level of 10%. Here, we present an alternative customizable pipeline, the PrecisionCallerPipeline (PCP), for processing samples with the correct rCRS output after Ion Torrent sequencing with the Precision ID library kit. Using 18 samples (3 original samples and 15 mixtures) derived from the 1000 Genomes Project, we achieved overall improved performance metrics in comparison with the proprietary TSS, with optimal performance at a 2.5% heteroplasmy threshold. We further validated our findings with 50 samples from an ongoing independent cohort of stroke patients, with PCP finding 98.31% of TSS’s variants (TSS found 57.92% of PCP’s variants), with a significant correlation between the variant levels of variants found with both pipelines.
- Published
- 2021
- Full Text
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3. Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration
- Author
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Sandrina Nóbrega-Pereira, Francisco Santos, Miguel Oliveira Santos, Teresa L. Serafim, Ana Patrícia Lopes, Diogo Coutinho, Filipa S. Carvalho, Rosário M. Domingues, Pedro Domingues, Bruno Bernardes de Jesus, Vanessa A. Morais, and Sérgio Dias
- Abstract
Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer. Significance: LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.
- Published
- 2023
4. Supplementary Figure S1 from Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration
- Author
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Sérgio Dias, Vanessa A Morais, Bruno Bernardes de Jesus, Pedro Domingues, Rosário M. Domingues, Filipa S. Carvalho, Diogo Coutinho, Ana Patrícia Lopes, Teresa L. Serafim, Miguel Oliveira Santos, Francisco Santos, and Sandrina Nóbrega-Pereira
- Abstract
LDL-exposed breast cancer cells show differential invasion potential and metastatic tropism to distant sites in xenotransplanted zebrafish larvae at 4dpi (6dpf). Related to Fig. 1.
- Published
- 2023
5. Supplementary Table S1 from Mitochondrial Metabolism Drives Low-density Lipoprotein-induced Breast Cancer Cell Migration
- Author
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Sérgio Dias, Vanessa A Morais, Bruno Bernardes de Jesus, Pedro Domingues, Rosário M. Domingues, Filipa S. Carvalho, Diogo Coutinho, Ana Patrícia Lopes, Teresa L. Serafim, Miguel Oliveira Santos, Francisco Santos, and Sandrina Nóbrega-Pereira
- Abstract
List of primers used for measurements of gene expression levels and mtDNA content by quantitative real-time PCR.
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- 2023
6. Data from Mitochondrial metabolism drives low-density lipoprotein-induced breast cancer cell migration
- Author
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Sérgio Dias, Vanessa A Morais, Bruno Bernardes de Jesus, Pedro Domingues, Rosário M. Domingues, Filipa S. Carvalho, Diogo Coutinho, Ana Patrícia Lopes, Teresa L. Serafim, Miguel Oliveira Santos, Francisco Santos, and Sandrina Nóbrega-Pereira
- Abstract
Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer.Significance:LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.
- Published
- 2023
7. Dynamic interactions and Ca2+-binding modulate the holdase-type chaperone activity of S100B preventing tau aggregation and seeding
- Author
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Urmi Sengupta, Guilherme G. Moreira, Ana P. Carapeto, Filipa S. Carvalho, Andrea Quezada, Mário Rodrigues, Isabel Cardoso, Guenter Fritz, Nicha Puangmalai, Isabelle Landrieu, Federico Herrera, Rakez Kayed, Cláudio M. Gomes, Joana S. Cristóvão, François Xavier Cantrelle, Universidade de Lisboa = University of Lisbon (ULISBOA), Biologie Structurale Intégrative (ERL 9002 - BSI ), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), The University of Texas Medical Branch (UTMB), Universidade do Porto = University of Porto, Instituto de Ciências Biomédicas de Abel Salazar (ICBAS), University of Hohenheim, This work was funded by Fundação para a Ciência e Tecnologia (Portugal) through research grants PTDC/NEU-NMC/2138/2014 (to C.M.G.), PTDC/BIA-BQM/29963/2017 (F.S.C.), PTDC/MED-NEU/31417/2017 (to F.H.), and POCI-01-0145-FEDER-007274 (to I.C.), investigator grants CEECIND/00031/2017 (to A.P.C.) and IF/00094/2013/CP1173/CT0005 (to F.H.), PhD fellowship SFRH/BD/101171/2014 (to J.S.C.) and DFA/BD/6443/2020 (to G.G.M.), and center grants UIDB/04046/2020 and UID/MULTI/04046/2020 (to BioISI) and Norte-01-0145-FEDER-000008 (to IBMC/I3S)., Landrieu, Isabelle, Universidade de Lisboa (ULISBOA), and Universidade do Porto
- Subjects
[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Science ,Tau protein ,General Physics and Astronomy ,tau Proteins ,S100 Calcium Binding Protein beta Subunit ,Protein Aggregation, Pathological ,Article ,Biophysical Phenomena ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Microtubule ,Biophysical chemistry ,Calcium-binding protein ,mental disorders ,Humans ,Protein folding ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,Nuclear Magnetic Resonance, Biomolecular ,[SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM] ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,biology ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,Chemistry ,Neurodegenerative Diseases ,General Chemistry ,Kinetics ,Proteostasis ,Structural biology ,Chaperone (protein) ,biology.protein ,Biophysics ,Protein Structural Elements ,030217 neurology & neurosurgery ,Molecular Chaperones ,Protein Binding ,Binding domain - Abstract
The microtubule-associated protein tau is implicated in the formation of oligomers and fibrillar aggregates that evade proteostasis control and spread from cell-to-cell. Tau pathology is accompanied by sustained neuroinflammation and, while the release of alarmin mediators aggravates disease at late stages, early inflammatory responses encompass protective functions. This is the case of the Ca2+-binding S100B protein, an astrocytic alarmin which is augmented in AD and which has been recently implicated as a proteostasis regulator, acting over amyloid β aggregation. Here we report the activity of S100B as a suppressor of tau aggregation and seeding, operating at sub-stoichiometric conditions. We show that S100B interacts with tau in living cells even in microtubule-destabilizing conditions. Structural analysis revealed that tau undergoes dynamic interactions with S100B, in a Ca2+-dependent manner, notably with the aggregation prone repeat segments at the microtubule binding regions. This interaction involves contacts of tau with a cleft formed at the interface of the S100B dimer. Kinetic and mechanistic analysis revealed that S100B inhibits the aggregation of both full-length tau and of the microtubule binding domain, and that this proceeds through effects over primary and secondary nucleation, as confirmed by seeding assays and direct observation of S100B binding to tau oligomers and fibrils. In agreement with a role as an extracellular chaperone and its accumulation near tau positive inclusions, we show that S100B blocks proteopathic tau seeding. Together, our findings establish tau as a client of the S100B chaperone, providing evidence for neuro-protective functions of this inflammatory mediator across different tauopathies., The calcium binding protein S100B is an abundantly expressed protein in the brain and has neuro-protective functions by inhibiting Aβ aggregation and metal ion toxicity. Here, the authors combine cell biology and biochemical experiments with chemical kinetics and NMR measurements and show that S100B protein is an extracellular Tau chaperone and further characterize the interactions between S100B and Tau.
- Published
- 2021
8. Doxorubicin-induced cardiotoxicity: from bioenergetic failure and cell death to cardiomyopathy
- Author
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Filipa S, Carvalho, Ana, Burgeiro, Rita, Garcia, António J, Moreno, Rui A, Carvalho, and Paulo J, Oliveira
- Subjects
Doxorubicin ,Animals ,Humans ,Antineoplastic Agents ,Cardiomyopathies ,Energy Metabolism ,Mitochondria, Heart ,Rats - Abstract
Doxorubicin (DOX) is an anticancer anthracycline that presents a dose-dependent and cumulative cardiotoxicity as one of the most serious side effects. Several hypotheses have been advanced to explain DOX cardiac side effects, which culminate in the development of life-threatening cardiomyopathy. One of the most studied mechanisms involves the activation of DOX molecule into a more reactive semiquinone by mitochondrial Complex I, resulting in increased oxidative stress. The present review describes and critically discusses what is known about some of the potential mechanisms of DOX-induced cardiotoxicity including mitochondrial oxidative damage and loss of cardiomyocytes. We also discuss alterations of mitochondrial metabolism and the unique characteristics of DOX delayed toxicity, which can also interfere on how the cardiac muscle handles a "second-hit stress." We also present pharmaceutical and nonpharmaceutical approaches that may decrease DOX cardiac alterations in animal models and humans and discuss the limitations of each strategy.
- Published
- 2013
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