CBR - Contribuições em Revistas Científicas / Contribution to Journals
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- Reemergence of yellow fever virus in forest and periurban settings in BrazilPublication . Andrade, Valnete das Graças Dantas; Adelino, Talita Émile Ribeiro; Fonseca, Vagner; Moreno, Keldenn Melo Farias; Tomé, Luiz Marcelo Ribeiro; Pereira, Luiz Augusto; La-Roque, Debora Glenda Lima de; Filippis, Ana Maria Bispo de; Ramos, Daniel Garkauskas; Ramalho, Dario Brock; Furtado, Kátia Cristina de Lima; Borges, Gleissy Adriane Lima; Martins, Livia Caricio; Frutuoso, Livia C. V.; Lamounier, Ludmila Oliveira; Guimarães, Natália Rocha; Barros, Patrícia Miriam Sayuri Sato; Almeida, Priscila Souza de; Silva, Paulo Eduardo de Souza da; Pinheiro, Rodrigo Giesbrecht; Stabeli, Rodrigo Guerino; Chagas, Shirley Moreira da Silva; Pedroso, Sílvia Helena Sousa Pietra; Kashima, Simone; Penante, Solange Gonçalves; Oliveira, Marília Santini de; Silva, Vinicius Lemes da; Voorhis, Wesley C. Van; Holmes, Edward C.; Lourenço, José; Iani, Felipe Campos de Melo; Júnior, Alberto Simões Jorge; Giovanetti, Marta; Alcantara, Luiz Carlos JuniorBackground: Yellow fever virus remains a major public health threat in Brazil, where recent resurgence risks affecting both forest and periurban populations. Understanding viral movement across ecological settings is critical to support early detection and prevent outbreaks. Methods: We performed genomic surveillance in two Brazilian states, a northern Amazon region and a southeastern region, between 2023 and 2025. Human and non-human primate samples were collected across forest, rural, and urban environments. Viral genomes were generated and analyzed using phylogenetic, phylogeographic, and temporal approaches to reconstruct viral transmission patterns. Results: Here, we show evidence of continued yellow fever virus circulation and diversification in distinct ecological settings. We generate 25 genomes from humans and non-human primates, including the first human-derived genomes from the Amazon region. All genomes fall within the South American lineage. We identify one cluster in the Amazon region consistent with undetected viral persistence and reemergence, and a second cluster in the southeast associated with reintroduction followed by sustained local transmission. Conclusions: These findings demonstrate ongoing yellow fever virus activity in Brazil, with forest regions serving as reservoirs for reemergence and periurban areas supporting continued spread. Strengthened genomic and epizootic surveillance is required to detect viral expansion early and inform targeted prevention strategies across Brazil and the Americas.
- Mechanisms of parasite-mediated disruption of brain vesselsPublication . Loira, Leonor; Arroz-Madeira, Sílvia; Franco, Cláudio A.; Pereira, Sara SilvaThe brain vasculature is a critical barrier to maintain central nervous system (CNS) homeostasis. Parasitic infections can profoundly disrupt the brain vasculature, with consequences ranging from subtle neurological alterations to severe, life-threatening pathologies. In this review, we explore the diverse mechanisms by which endoparasites interact with, modulate and breach CNS blood and lymphatic vessels. We highlight how these pathogens manipulate endothelial function, alter barrier permeability and exploit vascular surface molecules to access or influence the brain. These interactions often trigger local inflammation, endothelial activation and blood–brain barrier breakdown, with significant implications for parasite survival and host pathology. Here, we review the molecular and cellular mechanisms underlying these processes, providing an integrative view of parasite-vascular crosstalk in the brain and identifying emerging research areas. Understanding these interactions offers new insights into brain vascular disease pathogenesis and may inform future strategies for intervention.
- Targeted CRISPR-Cas9 screening identifies core transcription factors controlling murine haemato-endothelial fate commitmentPublication . Teske, Michael; Wertheimer, Tobias; Butz, Stefan; Zwicky, Pascale; Mallona, Izaskun; Nopper, Svenja L.; Münz, Christian; Elling, Ulrich; Lancrin, Christophe; Becher, Burkhard; Grosso, Ana Rita; Baubec, Tuncay; Schmolka, NinaDuring development, blood generation begins in the yolk sac with the differentiation of haemato-endothelial mesoderm forming haematopoietic progenitors. This study aims to identify the crucial molecular regulators of haemato-endothelial mesoderm formation and to extend our knowledge of the process in an unbiased way. We employ a murine embryonic stem cell model that recapitulates embryonic blood development, and perform targeted CRISPR-Cas9 knock out screens focusing on transcription factors and chromatin regulators. We identify the transcription factors ETV2, LDB1, SMAD1, SIX4 and ZBTB7b as regulators of haemato-endothelial mesoderm commitment. Embryonic stem cells lacking these regulators give rise to mesodermal subsets with a defined lineage differentiation bias, while transcriptome analysis of these cells uncovers the precise impact of each factor on gene expression in the developing mesoderm. Our study reveals molecular pathways governing mesodermal development crucial to allow endothelial and haematopoietic lineage specification and paves the way for future advances in haematopoietic stem cell applications.
- Shifting dynamics of Dengue virus serotype 2 and emergence of cosmopolitan genotype, Costa Rica, 2024Publication . González-Elizondo, Mauricio; Soto, Dihala Picado; Laurent, Estela Cordero; Martínez, Francisco Duarte; Alcantara, Luiz Carlos Junior; Fonseca, Vagner; Rico, Jairo Andrés Méndez; Lourenço, José; Franco, Leticia; Giovanetti, Marta; Garita, Claudio SotoDengue remains a major public health challenge. In Costa Rica, we implemented nationwide genomic surveillance to track dengue virus serotype 2 cosmopolitan genotype emergence. Phylogenetic and eco-epidemiologic analyses revealed early detection, climate-driven spread, and spatial heterogeneity. Our findings underscore the need for integrated surveillance to guide adaptive responses to emerging arboviral threats.
- Chikungunya in Brazil: vaccination strategies informed by mathematical modellingPublication . Lourenço, José; Giovanetti, Marta
- Visualizing influenza A virus assembly by in situ cryo-electron tomographyPublication . Wachsmuth-Melm, Moritz; Peterl, Sarah; O’Riain, Aidan; Makroczyová, Jana; Fischer, Konstantin; Krischuns, Tim; Vale-Costa, Sílvia; Amorim, Maria João; Chlanda, PetrInfluenza A virus (IAV) forms pleomorphic particles that package eight ribonucleoprotein complexes (vRNPs), each carrying a distinct RNA genome segment. vRNPs assemble in the nucleus and undergo selective sorting during Rab11a-mediated trafficking to the plasma membrane. Virion assembly is orchestrated by matrix protein 1 (M1), which forms a layer beneath the viral envelope containing hemagglutinin (HA) and neuraminidase (NA). However, molecular details of vRNP distribution, cytosolic trafficking, and coordination of IAV assembly remains unclear. Using in situ cryo-ET, we reveal that HA-containing membranes provide Rab11a-dependent platforms for membrane-assisted vRNP clustering, reducing inter-vRNP distances. In the absence of HA, vRNPs cluster on NA-containing membranes and virus assembly remains intact, indicating that vRNP clustering and trafficking is membrane-assisted but HA independent. The characteristic 7 + 1 vRNP bundle forms concomitantly with budding and is orchestrated by M1 layer assembly that precedes plasma membrane attachment. We further reveal that intracellular M1 forms multilayered helical assemblies of antiparallel dimers, structurally distinct from the M1 layer in virions. These assemblies are compact in the nucleus but partially dissociate in the cytoplasm, likely serving as a reservoir for budding. Together, our findings uncover membrane-assisted vRNP clustering and molecular details of M1 coordinated influenza virus assembly.
- CANA v1.0.0: efficient quantification of canalization in automata networksPublication . Marcus, Austin M.; Rozum, Jordan; Sizek, Herbert; Rocha, Luis M.The biomolecular networks underpinning cell function exhibit canalization, or the buffering of fluctuations required to function in a noisy environment. We present a new major release of CANA, v1.0.0, an open-source Python package for understanding canalization in automata network models, discrete dynamical systems in which activation of biomolecular entities (e.g. transcription of genes) is modeled as the activity of coupled automata. One understudied putative mechanism for canalization is the functional equivalence of biomolecular regulators (e.g. among the transcription factors for a gene). We study this mechanism using the theory of symmetry in discrete functions. We present a new exact method, schematodes, for finding maximal symmetry groups among the inputs to discrete functions, and integrate it into CANA. The schematodes method substantially outperforms the inexact method of previous CANA versions both in speed and accuracy. We apply CANA v1.0.0 to study symmetry in 74 experimentally supported automata network models from the Cell Collective (CC) repository. The symmetry distribution is significantly different in the CC than in random automata with the same in-degree (connectivity) and bias (average output) (Kolmogorov-Smirnov test, P???.001). Its spread is much wider than in a null model (IQR 0.31 versus IQR 0.20 with equal medians), demonstrating that the CC is enriched in functions with extreme symmetry or asymmetry.
- Ecchordosis physaliphora: a rare and challenging clinical entity in a patient with acromegalyPublication . Marques, Pedro; Neto, Lia; Tortosa, Francisco; Sagarribay, Amets
- Outcomes of transcatheter aortic valve replacement in younger low-risk patients: a comprehensive meta-analysis of efficacy and safetyPublication . Almeida, António Rocha de; Lima, Maria Rita; Gomes, Daniel A.; Almeida, Manuel de Sousa; Fernandes, Renato; Oliveira, Eduardo Infante; Gonçalves, Pedro Araújo; Teles, Rui Campante; Patrício, LinoBackground and aims: Severe aortic stenosis (AS) was traditionally managed with surgical aortic valve replacement (SAVR). Transcatheter aortic valve implantation (TAVI) emerged as a less invasive alternative, initially for high-risk patients. This meta-analysis evaluates the outcomes of TAVI in younger, low-risk patients, in whom SAVR is currently the gold standard. Methods: Following PRISMA guidelines, we systematically searched randomized controlled trials (RCTs) comparing TAVI with SAVR in younger (mean age <75 years) low-risk patients (STS score <4%) with severe AS. The primary endpoint was a composite of death or disabling stroke. Secondary endpoints included all-cause mortality, disabling stroke, atrial fibrillation (AF), permanent pacemaker implantation (PPI), bleeding, functional class (NYHA), and quality-of-life (KCCQ score) improvements. Results: Four RCTs were included with 4,252 patients (2,125 TAVI and 2,127 SAVR). At a mean follow-up of 16 ± 5 months, TAVI showed a non-significant reduction in the composite of death or disabling stroke [2.8% vs. 5.1% risk ratio (RR) 0.98, 95% confidence interval (CI) (0.96–1.00), p = 0.11] and all-cause mortality [2.1% vs. 3.7%, RR 0.99, 95% CI (0.97–1.00), p = 0.15]. The incidence of disabling stroke was significantly lower in TAVI [0.9 vs. 2.1 RR 0.99, 95% CI (0.98–1.00), p < 0.01]. Hospital readmission [7.1% vs. 9.5% RR 0.97, 95% CI (0.96–0.99), p < 0.01] and bleeding rates [4.7% vs. 16%, RR 0.87, 95% CI (0.82–0.93), p < 0.01] were significantly lower in the TAVI group. Conversely, TAVI had a higher PPI rate [14% vs. 6%, RR 1.08, 95% CI (1.02–1.14), p < 0.01]. Faster symptomatic and quality-of-life improvements were sustained in the TAVI group. Conclusions: TAVI is a viable option for younger low-risk patients with severe AS, being non-inferior to SAVR in short-term outcomes. The benefits of TAVI include a lower risk of disabling stroke, hospital readmission, and bleeding, as well as quicker improvements in symptoms and quality of life. However, higher PPI rates require careful patient selection. The results support a tailored approach to TAVI in younger patients, with ongoing evaluation of long-term outcomes. Systematic Review Registration: https: www.crd.york.ac.uk/PROSPERO/view/CRD42024559473, PROSPERO (CRD42024559473).
- Quantifying edge relevance for epidemic spreading via the semi-metric topology of complex networksPublication . Soriano-Paños, David; Costa, Felipe Xavier; Rocha, Luis M.Sparsification aims at extracting a reduced core of associations that best preserves both the dynamics and topology of networks while reducing the computational cost of simulations. We show that the semi-metric topology of complex networks yields a natural and algebraically-principled sparsification that outperforms existing methods on those goals. Weighted graphs whose edges represent distances between nodes are \textit{semi-metric} when at least one edge breaks the triangle inequality (transitivity). We first confirm with new experiments that the \textit{metric backbone}—a unique subgraph of all edges that obey the triangle inequality and thus preserve all shortest paths—recovers Susceptible-Infected dynamics over the original non-sparsified graph. This recovery is improved when we remove only those edges that break the triangle inequality significantly, i.e., edges with large semi-metric distortion. Based on these results, we propose the new \textit{semi-metric distortion sparsification} method to progressively sparsify networks in decreasing order of semi-metric distortion. Our method recovers the macro- and micro-level dynamics of epidemic outbreaks better than other methods while also yielding sparser yet connected subgraphs that preserve all shortest paths. Overall, we show that semi-metric distortion overcomes the limitations of edge betweenness in ranking the dynamical relevance of edges not participating in any shortest path, as it quantifies the existence and strength of alternative transmission pathways.