Papers by Beatriz santos 9394
Representative FACS density plots showing the gate strategy for the identification of IL-1β withi... more Representative FACS density plots showing the gate strategy for the identification of IL-1β within CD11c+MHCIIhigh gated on live CD45+ leucocytes in the trigeminal ganglia (a) and spleen (b) from a single HSV1-infected WT mouse. A minimum of 100,000 events was acquired for analysis. (PPTX 386 kb)
PLOS Genetics, 2021
During meiosis, defects in critical events trigger checkpoint activation and restrict cell cycle ... more During meiosis, defects in critical events trigger checkpoint activation and restrict cell cycle progression. The budding yeast Pch2 AAA+ ATPase orchestrates the checkpoint response launched by synapsis deficiency; deletion of PCH2 or mutation of the ATPase catalytic sites suppress the meiotic block of the zip1Δ mutant lacking the central region of the synaptonemal complex. Pch2 action enables adequate levels of phosphorylation of the Hop1 axial component at threonine 318, which in turn promotes activation of the Mek1 effector kinase and the ensuing checkpoint response. In zip1Δ chromosomes, Pch2 is exclusively associated to the rDNA region, but this nucleolar fraction is not required for checkpoint activation, implying that another yet uncharacterized Pch2 population must be responsible for this function. Here, we have artificially redirected Pch2 to different subcellular compartments by adding ectopic Nuclear Export (NES) or Nuclear Localization (NLS) sequences, or by trapping Pch...
The meiotic recombination checkpoint blocks meiotic cell cycle progression in response to synapsi... more The meiotic recombination checkpoint blocks meiotic cell cycle progression in response to synapsis and/or recombination defects to prevent aberrant chromosome segregation. The evolutionarily-conserved budding yeast Pch2TRIP13 AAA+ ATPase participates in this pathway by supporting phosphorylation of the Hop1HORMAD adaptor at T318. In the wild type, Pch2 localizes to synapsed chromosomes and to the unsynapsed rDNA region (nucleolus), excluding Hop1. In contrast, in synaptonemal complex (SC)-defective zip1 mutants, which undergo checkpoint activation, Pch2 is detected only on the nucleolus. Alterations in some epigenetic marks that lead to Pch2 dispersion from the nucleolus suppress zip1-induced checkpoint arrest. These observations have led to the notion that Pch2 nucleolar localization could be important for the meiotic recombination checkpoint. Here we investigate how Pch2 chromosomal distribution impacts on checkpoint function. We have generated and characterized several mutations ...
Trends in psychiatry and psychotherapy
To describe a rare case of a patient who developed psychotic symptoms after a right stroke that d... more To describe a rare case of a patient who developed psychotic symptoms after a right stroke that disappeared with antipsychotic treatment, but appears to need low-dose maintenance antipsychotic therapy. A 65-year-old man presented at the psychiatric emergency service with a history of persistent delusional jealousy, visual illusions and agitation with onset about 1 month after a right posterior cerebral artery ischemic stroke. These symptoms only disappeared with therapeutic dosages of an antipsychotic drug (3 mg/day of risperidone). At 2-year follow-up, he no longer had delusional activity and the antipsychotic treatment was gradually discontinued over the following year. However, 1 week after full cessation, the patient once more became agitated and suspicious and was put back on risperidone at 0.25 mg/day, resulting in rapid clinical remission. One year after the return to low-dose risperidone, the patient's psychopathology is still under control and he is free from psychotic ...
International Journal of Cardiology, 2016
Percutaneous coronary intervention (PCI) is currently considered the gold-standard treatment of a... more Percutaneous coronary intervention (PCI) is currently considered the gold-standard treatment of acute coronary syndromes with ST-segment elevation (STEMI). However, this is not the reality of many European centers, where thrombolysis is performed as primary therapy. To determine, in a STEMI population that performed successful fibrinolytic treatment, if the performance of coronary angiography after the first 24h was associated with more hospital complications, including higher mortality, compared with its performance in the recommended time. Retrospective study, including 1065 patients with STEMI, who performed successful thrombolysis. The population was divided in three groups: A, patients who didn't undergo coronary angiography after successful thrombolysis (n=278; 26.1%); B, patients who underwent coronary angiography in the first 24h after successful thrombolysis (n=127; 11.9%); and C, patients who underwent angiography after the first 24h (n=660; 62.0%). Groups were compared regarding their characteristics and in-hospital complications. Groups B and C had more male patients and had younger patients than group A. Group A presented higher Killip classes at admission, more severe left ventricle dysfunction and a higher number of complications during hospitalization. Logistic regression revealed that: 1) the non-performance of coronary angiography after thrombolysis was an independent predictor of in-hospital mortality; and 2) the performance of angiography after the recommended time wasn't associated with higher mortality. Coronary angiography after thrombolysis constitutes an important strategy, whose non-performance carries worse prognosis. The time interval currently recommended of 24h seems clinically acceptable; however, its realization outside the recommended time doesn't seem to lead to higher mortality.
Revista Portuguesa de Cardiologia, 2015
Linfoma primário do coração; Neoplasia renal; Ecocardiografia; Biópsia cardíaca; Derrame pericárd... more Linfoma primário do coração; Neoplasia renal; Ecocardiografia; Biópsia cardíaca; Derrame pericárdico Resumo O linfoma primário do coração é definido como um linfoma não Hodgkin que envolve o coração e/ou o pericárdio. Trata-se de uma neoplasia rara que envolve principalmente as cavidades direitas e, em especial, a aurícula direita. Por sua vez, o carcinoma das células renais é uma neoplasia relativamente comum que, em situações mais raras, pode metastizar para o coração. Atualmente, é conhecida uma associação entre a ocorrência de linfomas não Hodgkin e de carcinomas das células renais, apesar dos mecanismos a ela subjacentes não serem claramente conhecidos. Com este artigo, os autores apresentam um caso de um linfoma não Hodgkin primário do coração num doente com uma neoplasia renal síncrona e exploram as bases admitidas para esta associação.
Microbiology (Reading, England), Jan 27, 2015
Rho GTPases are small proteins present in all eukaryotic cells, from yeast to mammals, with a fun... more Rho GTPases are small proteins present in all eukaryotic cells, from yeast to mammals, with a function in actin organization and morphogenetic processes. Schizosaccharomyces pombe Rho4 is not essential but it displays a role during cell separation at high temperature. In fact, Rho4 is involved in the secretion of the hydrolytic enzymes that are required for cell septum degradation during this process. In rho4Δ cells, vesicles accumulate in the septum area and the glucanases Eng1 and Agn1 are not secreted to the culture medium. The localization of Eng1 and Agn1 depends on the exocyst and the septins. The exocyst is a conserved multiprotein complex important for the targeting and fusion of Golgi-derived vesicles with the plasma membrane. Septins are a family of GTP-binding proteins conserved in eukaryotes that function during cytokinesis. Here we show that Rho4 is required for the proper localization of the exocyst and septins at high temperature. Moreover, pull-down experiments demon...
Traffic, 2011
Fission yeast Cdc42 regulates polarized growth and is involved in For3 formin activation and acti... more Fission yeast Cdc42 regulates polarized growth and is involved in For3 formin activation and actin cable assembly. We show here that a thermosensitive strain carrying the cdc42L160S allele has membrane traffic defects independent of the actin cable defects. This strain has decreased acid phosphatase (AP) secretion, intracellular accumulation of vesicles and fragmentation of vacuoles. In addition, the exocyst is not localized to the tips of these cells. Overproduction of the scaffold protein Pob1 suppressed cdc42L160S thermosensitive growth and restored exocyst localization and AP secretion. The GTPase Rho3 also suppressed cdc42L160S thermosensitivity, restored exocyst localization and AP secretion. However, Rho3 did not restore the actin cables in these cells as Pob1 does. Similarly, overexpression of psy1(+) , coding a syntaxin (t-SNARE) homolog, or of ypt2(+) , coding an SEC4 homolog in fission yeast, rescued growth at high temperature but did not restore actin cables, nor the exocyst-polarized localization. cdc42L160S cells also have defects in vacuole formation that were rescued by Pob1, Rho3 and Psy1. All together, we propose that Cdc42 and the scaffold Pob1 are required for membrane trafficking and fusion, contributing to polarized secretion, endosome recycling, vacuole formation and growth.
Eukaryotic Cell, 2003
The Rho family of GTPases is present in all eukaryotic cells from yeast to mammals; they are regu... more The Rho family of GTPases is present in all eukaryotic cells from yeast to mammals; they are regulators in signaling pathways that control actin organization and morphogenetic processes. In yeast, Rho GTPases are implicated in cell polarity processes and cell wall biosynthesis. It is known that Rho1 and Rho2 are key proteins in the construction of the cell wall, an essential structure that in Schizosaccharomyces pombe is composed of β-glucan, α-glucan, and mannoproteins. Rho1 regulates the synthesis of 1,3-β- d -glucan by activation of the 1,3-β- d -glucan synthase, and Rho2 regulates the synthesis of α-glucan by the 1,3-α- d -glucan synthase Mok1. Here we describe the characterization of another Rho GTPase in fission yeast, Rho4. rho4 Δ cells are viable but display cell separation defects at high temperature. In agreement with this observation, Rho4 localizes to the septum. Overexpression of rho4 + causes lysis and morphological defects. Several lines of evidence indicate that both...
Molecular Microbiology, 2008
Schizosaccharomyces pombe Rho2 GTPase regulates aD -glucan synthesis and acts upstream of Pck2 to... more Schizosaccharomyces pombe Rho2 GTPase regulates aD -glucan synthesis and acts upstream of Pck2 to activate the MAP kinase pathway for cell integrity. However, little is known about its regulation. Here we describe Rga2 as a Rho2 GTPase-activating protein (GAP) that regulates cell morphology. rga2 + gene is not essential for growth but its deletion causes longer and thinner cells whereas rga2 + overexpression causes shorter and broader cells. rga2 + overexpression also causes abnormal accumulation of Calcofluor-stained material and cell lysis, suggesting that it also participates in cell wall integrity. Rga2 localizes to growth tips and septum region. The N-terminal region of the protein is required for its correct localization whereas the PH domain is necessary exclusively for Rga2 localization to the division area. Also, Rga2 localization depends on polarity markers and on actin polymerization. Rga2 interacts with Rho2 and possesses in vitro and in vivo GAP activity for this GTPase. Accordingly, rga2D cells contain more aD -glucan and therefore partially suppress the thermosensitivity of mok1-664 cells, which have a defective aD -glucan synthase. Additionally, genetic interactions and biochemical analysis suggest that Rga2 regulates Rho2-Pck2 interaction and might participate in the regulation of the MAPK cell integrity pathway.
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Papers by Beatriz santos 9394