Vinícius Santana Nunes

Instituto de Desenvolvimento Sustentável Mamirauá

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Nilmar Silvio Moretti

Universidade Federal de São Paulo

Sérgio Schenkman

Universidade Federal de São Paulo

Luíz Ricardo Orsini Tosi

Universidade de São Paulo

Marcelo S. da Silva

Universidade de São Paulo

Marcela Segatto

Faculdade Brasil

Maria Isabel Nogueira Cano

Universidade Estadual Paulista (Unesp)

Jeziel D. Damasceno

University of Glasgow

Remo H.M. Furtado

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Eduardo Ramacciotti

Loyola University Medical Center

Lucas Tramujas

Hospital do Coração

Cooperative Institutions

Universidade de São Paulo

Universidade Federal de São Paulo

Faculdade Brasil

Universidade Federal de Minas Gerais

Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Universidade Estadual Paulista (Unesp)

Beneficência Portuguesa de São Paulo

Hospital São Paulo

Universidade Estadual de Campinas (UNICAMP)

Fundação Oswaldo Cruz

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Turner-Kieser Syndrome or Iliac Horn Syndrome, a Challenge for the Anesthesiologist: A Case Report and a Literature Review

Open Journal of Anesthesiology (2022)

Erika Amorim Melo Moreira Kelly Ribeiro Moura Barboza Suellen Leal Pagano Michelle Magnago Ribeiro Vinícius Santana Nunes

Turner-Kieser syndrome is a rare genetic disorder, autosomal dominant, which is related to variable gene expression and high penetrance, due to mutations in the LMX1B gene that affects connective tissue. The clinic has characteristics with alterations in nails, knees, elbows, and presence of iliac horns that makes the anesthetic difficult. However, data in the literature needs more research on this area. The present report is a cesarean section under general intravenous anesthesia performed on a 32-week pregnant woman due to the maternal risk of full-term evolution and aims to contribute to the anesthetic management of patients with this syndrome as there are few descriptions in the literature regarding the anesthetic management in Turner-Kieser syndrome. Even being a case report, the syndrome is rare and it is important to be reported to all anesthesiologists becoming aware of its management and to choose the best technique and anticipate possible complications. During general anesthesia, the technique chosen for the case reported here, we emphasize the risks of possible difficulty in intubating and positioning the patient, as well as renal impairment caused by changes in the cardiovascular autonomic response due to the choice of some drugs. Therefore, in the present report, our option was intravenous general anesthesia because of maternal complications, where fast acting drugs without renal metabolism or excretion were selected, resulting in an uneventful anesthetic procedure.

Penetrance

Iliac fossa

Variable Expression

10.4236/ojanes.2022.123009

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Nuclear subcompartments: an overview

Cell Biology International (2016)

Vinícius Santana Nunes Nilmar Silvio Moretti

Abstract The advance in biochemical and microscopy techniques has revealed the complexity and intricate nucleoplasm structure. Several subcompartments were identified in nucleus and the importance of these subcompartments in processes crucial for normal nuclear activity has been demonstrated. In this mini‐review, we will give an overview about the composition, function, and importance of the major nuclear subcompartments. Also, we will show the impact that perturbing these structures can cause in normal nuclear activity, and how these can contribute to the development of some human diseases.

Nucleoplasm

10.1002/cbin.10703

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Citations (17)

The Putative Leishmania Telomerase RNA (LeishTER) Undergoes Trans-Splicing and Contains a Conserved Template Sequence

PLoS ONE (2014)

Elton J. R. Vasconcelos Vinícius Santana Nunes Marcelo S. da Silva Marcela Segatto Peter J. Myler

Telomerase RNAs (TERs) are highly divergent between species, varying in size and sequence composition. Here, we identify a candidate for the telomerase RNA component of Leishmania genus, which includes species that cause leishmaniasis, a neglected tropical disease. Merging a thorough computational screening combined with RNA-seq evidence, we mapped a non-coding RNA gene localized in a syntenic locus on chromosome 25 of five Leishmania species that shares partial synteny with both Trypanosoma brucei TER locus and a putative TER candidate-containing locus of Crithidia fasciculata. Using target-driven molecular biology approaches, we detected a ∼2,100 nt transcript (LeishTER) that contains a 5′ spliced leader (SL) cap, a putative 3′ polyA tail and a predicted C/D box snoRNA domain. LeishTER is expressed at similar levels in the logarithmic and stationary growth phases of promastigote forms. A 5′SL capped LeishTER co-immunoprecipitated and co-localized with the telomerase protein component (TERT) in a cell cycle-dependent manner. Prediction of its secondary structure strongly suggests the existence of a bona fide single-stranded template sequence and a conserved C[U/C]GUCA motif-containing helix II, representing the template boundary element. This study paves the way for further investigations on the biogenesis of parasite TERT ribonucleoproteins (RNPs) and its role in parasite telomere biology.

Crithidia fasciculata

Synteny

Conserved sequence

10.1371/journal.pone.0112061

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Predictors of bleeding and thrombotic events among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomized clinical trial

Journal of Thrombosis and Thrombolysis (2024)

Pedro Gabriel Melo de Barros e Silva Remo H.M. Furtado Mariana Silveira de Alcântara Chaud Ariane Vieira Scarlatelli Macedo Bruna Bronhara

Hematology

D-dimer

2019-20 coronavirus outbreak

10.1007/s11239-024-02995-y

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Variables associated with bleeding and thrombotic outcomes among patients admitted to the hospital with COVID-19 and elevated D-dimer: insights from the ACTION randomised clinical trial

European Heart Journal (2022)

P G Barros E Silva Renato D. Lópes Remo H.M. Furtado A V S Macedo B Bronhara

Abstract Background In the ACTION trial, therapeutic anticoagulation did not show benefit on mortality, days of hospitalization and oxygens therapy at 30 days among patients with COVID19. However, this strategy was associated with higher rate of bleeding and a potential reduction in the rate of clinical thrombotic events. The current analysis evaluated which variables were independently associated with both outcomes in order to help the identification of the risk for thrombotic and hemorrhagic events among patients with COVID19. Methods A total of 615 patients hospitalized with COVID-19 and elevated D-dimer levels were randomly assigned to prophylactic anticoagulation (mainly in-hospital heparin) or a therapeutic strategy that used in-hospital rivaroxaban 20 mg daily for stable patients, or enoxaparin 1 mg/kg twice daily for unstable patients, followed by rivaroxaban through 30 days. One patient withdrew consent and was not included in the analysis. The current analysis tested baseline clinical characteristics and laboratorial exams one by one with independent logistic regressions for the composite of bleeding (major bleeding and clinically relevant nonmajor bleeding) and thrombotic events (venous thromboembolism, myocardial infarction, stroke, systemic embolism, and major adverse limb events). Significant variables (p<0.05) were selected to adjust several multiple logistic models. Final models were chosen based on Akaike information criterion and therapeutic anticoagulation was included in the final model based on the primary results of the trial. Results The model for bleeding events showed an accuracy of area under the curve (AUC) of 0.635 (table 1) while the model for thrombotic events had an AUC of 0.725 (table 2). Level of respiratory support (especially invasive ventilation) was associated with both outcomes in the multivariable analysis (tables 1 and 2). Beyond respiratory support, level of creatinine and history of coronary disease were also independently associated to the risk of thrombotic events. When the utilization of therapeutic anticoagulation (mainly with rivaroxaban) was included in the multivariable analysis, this variable was strongly associated with higher risk of bleeding (model AUC of 0.718) but was not associated with lower rate of thrombotic events (Tables 1 and 2). Conclusion Since the variables associated with higher risk of thrombotic events are similar to the variables associated to bleeding complications, the selection of patients with better balance of risk vs. benefit to use therapeutic anticoagulation in COVID-19 still a challenging decision. Coronary disease and creatine may help to identify patients at higher risk of thrombotic complications while the use of therapeutic dose of direct oral anticoagulant increased the risk of bleeding in almost 4 times among patients hospitalized due to COVID19. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Investigator initiated research with financial support of Bayer

Stroke

10.1093/eurheartj/ehac544.1492

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Estudo sobre a percepção dos acadêmicos em formação médica frente à morte e ao morrer

Brazilian Journal of Health Review (2020)

Ludmila Oliveira Athayde Arleu Amanda Viguini Tolentino Correa Bruna Giovenardi Morgana Caliman Rocha Raquel Jackobsen Coelho Panceri

10.34119/bjhrv3n4-228

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The natural absence of RPA1N domain did not impair Leishmania amazonensis RPA-1 participation in DNA damage response and telomere protection

Parasitology (2013)

Rita de Cássia Viveiros da Silveira Marcelo S. da Silva Vinícius Santana Nunes Arina Marina Perez Maria Isabel Nogueira Cano

SUMMARY We have previously shown that the subunit 1 of Leishmania amazonensis RPA (LaRPA-1) alone binds the G-rich telomeric strand and is structurally different from other RPA-1. It is analogous to telomere end-binding proteins described in model eukaryotes whose homologues were not identified in the protozoan´s genome. Here we show that LaRPA-1 is involved with damage response and telomere protection although it lacks the RPA1N domain involved with the binding with multiple checkpoint proteins. We induced DNA double-strand breaks (DSBs) in Leishmania using phleomycin. Damage was confirmed by TUNEL-positive nuclei and triggered a G1/S cell cycle arrest that was accompanied by nuclear accumulation of LaRPA-1 and RAD51 in the S phase of hydroxyurea-synchronized parasites. DSBs also increased the levels of RAD51 in non-synchronized parasites and of LaRPA-1 and RAD51 in the S phase of synchronized cells. More LaRPA-1 appeared immunoprecipitating telomeres in vivo and associated in a complex containing RAD51, although this interaction needs more investigation. RAD51 apparently co-localized with few telomeric clusters but it did not immunoprecipitate telomeric DNA. These findings suggest that LaRPA-1 and RAD51 work together in response to DNA DSBs and at telomeres, upon damage, LaRPA-1 works probably to prevent loss of single-stranded DNA and to assume a capping function.

Telomere-binding protein

10.1017/s0031182012002028

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Citations (21)

Caracterização do gene LmHUS1 e de sua participação no fenômeno de amplificação gênica em Leishmania spp.

Vinícius Santana Nunes

L. braziliensisleishmania braziliensis PIKfosfo-inositol quinase ATMproteína ataxia telangiectasia mutada ATRataxia telangiectasia and Rad3-related protein CHKquinase checkpoint BRCA

10.11606/t.17.2011.tde-18102011-151410

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LmHus1 is required for the DNA damage response in Leishmania major and forms a complex with an unusual Rad9 homologue

Molecular Microbiology (2013)

Jeziel D. Damasceno Vinícius Santana Nunes Luíz Ricardo Orsini Tosi

Genotoxic stress activates checkpoint-signalling pathways leading to cell cycle arrest and DNA repair. In many eukaryotes, the Rad9-Hus1-Rad1 (9-1-1) checkpoint complex participates in the early steps of the DNA damage response to replicative stress and is a pivotal contributor to genome homeostasis. The remarkable genome plasticity of the protozoan Leishmania hints at a peculiar DNA metabolism in these ancient eukaryotes. Therefore, we set out to investigate the existence of homologues of the 9-1-1 components in Leishmania major and found that LmHus1 and LmRad9 are phylogenetically related to the 9-1-1 complex subunits from other eukaryotes. Altered levels of LmHus1 and LmRad9 affected the parasite ability to manage genotoxic stress and LmHus1-defficent cells were defective in controlling cell cycle progression in response to genotoxic stress. Upon DNA damage, LmHus1 was recruited to the chromatin and colocalized with the single-stranded DNA-binding protein LmRpa1. Also, LmHus1 interacted with LmRad9 to form a DNA damage responsive complex in vivo. Altogether, our data strongly indicate the participation of LmHus1, LmRad9 and LmRpa1 in the L. major DNA damage response and suggest their involvement in genome maintenance mechanisms.

CHEK1

10.1111/mmi.12418

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Citations (19)

Leishmania amazonensis Promastigotes Present Two Distinct Modes of Nucleus and Kinetoplast Segregation during Cell Cycle

PLoS ONE (2013)

Marcelo S. da Silva J. P. Monteiro Vinícius Santana Nunes Elton J. R. Vasconcelos Arina Marina Perez

Here, we show the morphological events associated with organelle segregation and their timing in the cell cycle of a reference strain of Leishmania (L.) amazonensis promastigotes, the main causative agent of Tegumentary leishmaniasis in the Americas. We show evidences that during the cell cycle, L. amazonensis promastigotes present two distinct modes of nucleus and kinetoplast segregation, which occur in different temporal order in different proportions of cells. We used DAPI-staining and EdU-labeling to monitor the segregation of DNA-containing organelles and DNA replication in wild-type parasites. The emergence of a new flagellum was observed using a specific monoclonal antibody. The results show that L. amazonensis cell cycle division is peculiar, with 65% of the dividing cells duplicating the kinetoplast before the nucleus, and the remaining 35% doing the opposite or duplicating both organelles concomitantly. In both cases, the new flagellum appeared during S to G2 phase in 1N1K cells and thus before the segregation of both DNA-containing organelles; however, we could not determine the exact timing of flagellar synthesis. Most of these results were confirmed by the synchronization of parasites using hydroxyurea. Altogether, our data show that during the cell cycle of L. amazonensis promastigotes, similarly to L. donovani, the segregation of nucleus and kinetoplast do not follow a specific order, especially when compared to other trypanosomatids, reinforcing the idea that this characteristic seems to be species-specific and may represent differences in cellular biology among members of the Leishmania genus.

Kinetoplast

Organelle

Minicircle

10.1371/journal.pone.0081397

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Citations (123)