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2.
J Med Virol ; 96(2): e29416, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38285457

RESUMO

The raising of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants led to the use of COVID-19 bivalent vaccines, which include antigens of the wild-type (WT) virus, and of the Omicron strain. In this study, we aimed to evaluate the impact of bivalent vaccination on the neutralizing antibody (NAb) response. We enrolled 93 volunteers who had received three or four doses of monovalent vaccines based on the original virus (n = 61), or a booster shot with the bivalent vaccine (n = 32). Serum samples collected from volunteers were subjected to neutralization assays using the WT SARS-CoV-2, and Omicron subvariants. In addition, immunoinformatics to quantify and localize highly conserved NAb epitopes were performed. As main result, we observed that the neutralization titers of samples from individuals vaccinated with the bivalent vaccine were higher for the original virus, in comparison to their capacity of neutralizing the Omicron variant and its subvariants. NAb that recognize epitopes mostly conserved in the WT SARS-CoV-2 were boosted, while those that recognize epitopes mostly present in the Omicron variant, and subvariants were primed. These results indicate that formulation of future vaccines shall consider to target present viruses, and not viruses that no longer circulate.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2/genética , Vacinação , Imunização Secundária , Anticorpos Neutralizantes , Epitopos/genética , Vacinas Combinadas
3.
Microbiol Spectr ; 11(6): e0285723, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37909777

RESUMO

IMPORTANCE: Several additional COVID-19 vaccine doses were administered in the Brazilian population to prevent the disease caused by the B.1.1.529 (Omicron) variant. The efficacy of a third dose as a booster is already well described. However, it is important to clarify the humoral immune response gain induced by a fourth dose. In this study, we evaluate the effect of the fourth COVID-19 vaccine dose in a diverse Brazilian population, considering a real-life context. Our study reveals that the fourth dose of the COVID-19 vaccine increased the neutralizing antibody response against SARS-CoV-2 Omicron and significantly contributed in the reduction of the disease caused by this variant.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , SARS-CoV-2/genética , Brasil , COVID-19/prevenção & controle , Anticorpos Neutralizantes , Anticorpos Antivirais
4.
Microbiol Spectr ; 11(6): e0289223, 2023 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-37966210

RESUMO

IMPORTANCE: The emergence of SARS-CoV-2 had a major impact across the world. It is true that the collaboration of scientists from all over the world resulted in a rapid response against COVID-19, mainly with the development of vaccines against the disease. However, many viral genetic variants that threaten vaccines have emerged. Our study reveals highly conserved antigenic regions in the vaccines have emerged. Our study reveals highly conserved antigenic regions in the spike protein in all variants of concern (Alpha, Beta, Gamma, Delta, and Omicron) as well as in the wild-type virus. Such immune targets can be used to fight future SARS-CoV-2 variants.


Assuntos
COVID-19 , Médicos , Vacinas , Humanos , SARS-CoV-2/genética
5.
Front Microbiol ; 14: 1240860, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37680530

RESUMO

Chikungunya, mayaro, dengue, zika, and yellow fever are mosquito-borne viral diseases caused, respectively, by Chikungunya virus, Mayaro virus (CHIKV and MAYV, respectively: Togaviridae: Alphavirus), Dengue virus, Zika virus, and Yellow fever virus (DENV, ZIKV, and YFV, respectively: Flaviviridae: Flavivirus). These viruses have an important epidemiological impact worldwide, especially in Brazil. Western Bahia is one of the less studied regions in that country regarding the circulation of these pathogens. In this study, we aimed to apply molecular biology assays to better know the mosquito-borne viruses circulating in Barreiras and Luís Eduardo Magalhães, two main cities of Western Bahia. From March to June 2021, we enrolled 98 patients with the clinical diagnosis of dengue. Personal information (gender and age) were retrieved at the moment of enrollment. Serum samples were obtained from volunteers and used in molecular detection of CHIKV, MAYV, DENV, ZIKV, and YFV by reverse transcription followed by real-time polymerase chain reaction as well as in genome sequencing aiming phylogenetic analysis. As the main result, we found that from the 98 patients 45 were infected by CHIKV, 32 were infected by serotype 1 of DENV (DENV-1) and six were infected by ZIKV, while 15 were negative for all arboviruses tested. In addition, phylogenetic analysis revealed that all CHIKV-positive samples were of the East/Central/South African (ECSA) genotype, while all DENV-1-positive samples were of the V genotype. These results clearly show that epidemiological surveillance cannot be based only on clinical evaluations. Laboratory diagnosis is important in arbovirus infection that are prevalent in a particular area. These findings also demonstrate the co-circulation of many arboviruses in Western Bahia in 2021.

6.
Soc Sci Med ; 320: 115712, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36753995

RESUMO

RATIONALE: From the earliest days of the COVID-19 pandemic, public health officials and news organizations reported pervasive racial disparities in the infection, morbidity, and mortality of the virus. In both the U.S. and Brazil, Black, Native, and mixed-race individuals were more negatively impacted by COVID-19 than White people. Simultaneously, significant social factions downplayed the threat and insisted on living "normally". We examined how these two factors coexisted. OBJECTIVE: We sought to establish whether Whites' anti-Black attitudes predicted their concern about the pandemic and tendency to behave in ways that exacerbated the pandemic. METHODS: and Results: In five studies, conducted in two countries (total N = 3425), we found that anti-Black attitudes (above and beyond political orientation, White racial identification, and perceptions of racial disparities) were associated with less concern about COVID-19, lower adoption of health and social distancing behaviors, and greater interest in returning to normalcy. DISCUSSION: We discuss how efforts to combat anti-Blackness may improve the health of the general population.


Assuntos
COVID-19 , Pandemias , Racismo , Humanos , Brasil/epidemiologia , COVID-19/psicologia , Pandemias/prevenção & controle , Estados Unidos/epidemiologia , Brancos , População Branca , Racismo/psicologia
7.
J Med Virol ; 95(2): e28481, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36609686

RESUMO

The main coronavirus disease 2019 (COVID-19) vaccine formulations used today are mainly based on the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein as an antigen. However, new virus variants capable of escaping neutralization activity of serum antibodies elicited in vaccinated individuals have emerged. The Omicron (B.1.1.529) variant caused epidemics in regions of the world in which most of the population has been vaccinated. In this study, we aimed to understand what determines individual's susceptibility to Omicron in a scenario of extensive vaccination. For that purpose, we collected nasopharynx swab (n = 286) and blood samples (n = 239) from flu-like symptomatic patients, as well as their vaccination history against COVID-19. We computed the data regarding vaccine history, COVID-19 diagnosis, COVID-19 serology, and viral genome sequencing to evaluate their impact on the number of infections. As main results, we showed that vaccination in general did not reduce the number of individuals infected by Omicron, even with an increased immune response found among vaccinated, noninfected individuals. Nonetheless, we found that individuals who received the third vaccine dose showed significantly reduced susceptibility to Omicron infections. A relevant evidence that support this finding was the higher virus neutralization capacity of serum samples of most patients who received the third vaccine dose. In summary, this study shows that boosting immune responses after a third vaccine dose reduces susceptibility to COVID-19 caused by the Omicron variant. Results presented in this study are useful for future formulations of COVID-19 vaccination policies.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus
8.
Curr Psychol ; 42(3): 2500-2513, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-34539156

RESUMO

Understanding tourist behavior during and after major tourism crises is essential to help destinations recover. The COVID-19 pandemic - a period of uncertainty and risk - makes it relevant to assess factors that influence travel intentions. There has been little research on tourist behavior during health crises and, in particular, on perceived health risk and uncertainty effects on travel intentions. This study was carried out at the beginning of the pandemic in Brazil and aims to investigate the role of health risk perception and intolerance of uncertainty on travel intentions for 2020 and 2021. We applied an online survey to 1150 Brazilian participants from April to May 2020. Our findings indicate that perceived COVID-19 severity, perceived probability of infection, and expected duration of the pandemic are significant predictors of travel intentions for both years. This paper contributes to a deeper understanding of crisis-resistant tourists' characteristics and provides insights for destinations' recovery.

9.
Curr Psychol ; 42(1): 209-219, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-33551627

RESUMO

Conspiracy theories thrive in moments of crises because they provide straightforward answers that assist individuals in coping with threats. The COVID-19 outbreak is such a crisis and is boosted by the political turmoil related to the politicization of the pandemic in some countries. To assess the role of political partisanship, intolerance of uncertainty (IU), and conspiracy beliefs in our two criterion variables (support for COVID-19 prevention measures and compliance with social distancing), we applied an online questionnaire to 662 participants. Our results indicate direct effects of political partisanship on support for COVID-19 prevention measures and non-compliance with social distancing while IU has not directly affected any of them. We have also found a significant effect of political partisanship on conspiracy theory dimensions involving personal wellbeing (PW) and control of information (CI) but not government malfeasance (GM) ones. Moreover, beliefs in CI theories predicted non-compliance with social distancing. Intolerance of uncertainty, on its turn, predicted the three dimensions of conspiracy beliefs. As to interaction effects, belief in GM, PW, and CI conspiracy theories moderated the effect of political partisanship on support for COVID-19 prevention measures whereas only belief in GM and PW theories moderated the effect of IU on past non-compliance with social distancing. Overall, our results suggest the relevance of diminishing politicization around the virus, providing basic scientific knowledge to the general population, and assisting individuals in coping with uncertainty. Besides, these findings provide insights into developing information campaigns to instruct the population to cope with the pandemic, producing behavioral change at societal and individual levels.

10.
Viruses ; 14(10)2022 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-36298869

RESUMO

BACKGROUND: The correct understanding of the epidemiological dynamics of COVID-19, caused by the SARS-CoV-2, is essential for formulating public policies of disease containment. METHODS: In this study, we constructed a picture of the epidemiological dynamics of COVID-19 in a Brazilian population of almost 17000 patients in 15 months. We specifically studied the fluctuations of COVID-19 cases and deaths due to COVID-19 over time according to host gender, age, viral load, and genetic variants. RESULTS: As the main results, we observed that the numbers of COVID-19 cases and deaths due to COVID-19 fluctuated over time and that men were the most affected by deaths, as well as those of 60 or more years old. We also observed that individuals between 30- and 44-years old were the most affected by COVID-19 cases. In addition, the viral loads in the patients' nasopharynx were higher in the early symptomatic period. We found that early pandemic SARS-CoV-2 lineages were replaced by the variant of concern (VOC) P.1 (Gamma) in the second half of the study period, which led to a significant increase in the number of deaths. CONCLUSIONS: The results presented in this study are helpful for future formulations of efficient public policies of COVID-19 containment.


Assuntos
COVID-19 , SARS-CoV-2 , Masculino , Humanos , Pessoa de Meia-Idade , Adulto , SARS-CoV-2/genética , Pandemias , Brasil/epidemiologia , COVID-19/epidemiologia , Nasofaringe
11.
Rev Soc Bras Med Trop ; 55: e0671, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35674563

RESUMO

BACKGROUND: This research addresses two questions: (1) how El Niño Southern Oscillation (ENSO) affects climate variability and how it influences dengue transmission in the Metropolitan Region of Recife (MRR), and (2) whether the epidemic in MRR municipalities has any connection and synchronicity. METHODS: Wavelet analysis and cross-correlation were applied to characterize seasonality, multiyear cycles, and relative delays between the series. This study was developed into two distinct periods. Initially, we performed periodic dengue incidence and intercity epidemic synchronism analyses from 2001 to 2017. We then defined the period from 2001 to 2016 to analyze the periodicity of climatic variables and their coherence with dengue incidence. RESULTS: Our results showed systematic cycles of 3-4 years with a recent shortening trend of 2-3 years. Climatic variability, such as positive anomalous temperatures and reduced rainfall due to changes in sea surface temperature (SST), is partially linked to the changing epidemiology of the disease, as this condition provides suitable environments for the Aedes aegypti lifecycle. CONCLUSION: ENSO may have influenced the dengue temporal patterns in the MRR, transiently reducing its main way of multiyear variability (3-4 years) to 2-3 years. Furthermore, when the epidemic coincided with El Niño years, it spread regionally and was highly synchronized.


Assuntos
Aedes , Dengue , Animais , Brasil/epidemiologia , Dengue/epidemiologia , El Niño Oscilação Sul , Temperatura
12.
Virol J ; 19(1): 93, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35619142

RESUMO

BACKGROUND: Phylogenetic studies indicate bats as original hosts of SARS-CoV-2. However, it remains unclear whether other animals, including pets, are crucial in the spread and maintenance of COVID-19 worldwide. METHODS: In this study, we analyzed the first fatal case of a SARS-CoV-2 and FeLV co-infection in an eight-year-old male cat. We carried out a clinical evaluation and several laboratory analyses. RESULTS: As main results, we observed an animal presenting severe acute respiratory syndrome and lesions in several organs, which led to the animal's death. RT-qPCR analysis showed a SARS-CoV-2 as the causative agent. The virus was detected in several organs, indicating a multisystemic infection. The virus was found in a high load in the trachea, suggesting that the animal may have contribute to the transmission of the virus. The whole-genome sequencing revealed an infection by SARS-CoV-2 Gamma VOC (P.1), and any mutations indicating host adaptation were observed. CONCLUSION: Our data show that FeLV-positive cats are susceptible to SARS-CoV-2 infection and raise questions about the potential of immunocompromised FeLV-positive cats to act as a reservoir for SARS-CoV-2 new variants.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Humanos , Vírus da Leucemia Felina , Masculino , Filogenia , SARS-CoV-2/genética
13.
J Virol ; 96(8): e0017722, 2022 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-35389263

RESUMO

A third vaccine dose against COVID-19 is already a reality in some countries around the world. In this study, we aimed to evaluate the effectiveness of the Brazilian immunization policy for COVID-19, which involves a booster shot. Participants (n = 210) provided serum samples, which were subjected to enzyme-linked immunosorbent assay (ELISA). Immunological profiles were defined as individuals with or without previous SARS-CoV-2 infection who received at least one vaccine dose in the immunization regimens of AstraZeneca, CoronaVac, or CoronaVac plus a booster shot with Pfizer. In addition, nonvaccinated/infected individuals were also included. As main results, we observed that the numbers of infected individuals were significantly reduced among those who were vaccinated, even with one dose. This result indicates that vaccines are highly protective against COVID-19. However, we observed a significant tendency of serum level decreases of specific antibodies over the time after the second dose. In contrast, the booster shot with the Pfizer vaccine after a CoronaVac immunization regimen showed a significant increase in the specific SARS-CoV-2 IgG serum levels. Moreover, we found that vaccination induced a significantly higher humoral immunological status than only the natural infection with SARS-CoV-2. Collectively, results presented here indicate that vaccines are necessary to induce a robust immunological status, which is maintained, restored, or even improved by booster shots. IMPORTANCE COVID-19 continues to spread around the world despite significant progress in vaccine distribution and population immunity. The dynamics of the antiviral antibody response postvaccination is critical to evaluate vaccine effectiveness across different vaccine platforms and over time. In this study, we evaluate the serum levels of antiviral antibodies in patients from Brazil that received either the CoronaVac or the AstraZeneca vaccine. We found that antibody levels wane over time, vaccines induce protective immunity, and humoral immunity is enhanced with a third vaccine dose. This study reveals that the COVID-19 humoral immunological status induced by vaccines significantly benefits from a booster shot.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Anticorpos Antivirais/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/normas , Humanos , SARS-CoV-2/imunologia
14.
Soc Sci Med ; 301: 114912, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35354105

RESUMO

RATIONALE: Belief in COVID-19 conspiracy theories can have severe consequences; it is therefore crucial to understand this phenomenon, in its similarities with general conspiracy belief, but also in how it is context-dependent. OBJECTIVE: The aim of this systematic review is to provide a comprehensive overview of the available research on COVID-19 conspiracy beliefs and to synthesise this research to make it widely accessible. METHODS: We present a synthesis of COVID-19 conspiracy belief research from 85 international articles, identified and appraised through a systematic review, in line with contemporary protocols and guidelines for systematic reviews. RESULTS: We identify a number of potential antecedents of COVID-19 conspiracy beliefs (individual differences, personality traits, demographic variables, attitudes, thinking styles and biases, group identity, trust in authorities, and social media use), their consequences (protective behaviours, self-centred and misguided behaviours such as hoarding and pseudoscientific health practices, vaccination intentions, psychological wellbeing, and other negative social consequences such as discrimination and violence), and the effect sizes of their relations with the conspiracy beliefs. CONCLUSIONS: We conclude that understanding both the potential antecedents and consequences of conspiracy beliefs and how they are context-dependent is highly important to tackle them, whether in the COVID-19 pandemic or future threats, such as that of climate change.


Assuntos
COVID-19 , COVID-19/epidemiologia , Humanos , Pandemias , SARS-CoV-2 , Vacinação/psicologia
15.
Rev. Soc. Bras. Med. Trop ; 55: e0671, 2022. graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1387545

RESUMO

ABSTRACT Background: This research addresses two questions: (1) how El Niño Southern Oscillation (ENSO) affects climate variability and how it influences dengue transmission in the Metropolitan Region of Recife (MRR), and (2) whether the epidemic in MRR municipalities has any connection and synchronicity. Methods: Wavelet analysis and cross-correlation were applied to characterize seasonality, multiyear cycles, and relative delays between the series. This study was developed into two distinct periods. Initially, we performed periodic dengue incidence and intercity epidemic synchronism analyses from 2001 to 2017. We then defined the period from 2001 to 2016 to analyze the periodicity of climatic variables and their coherence with dengue incidence. Results: Our results showed systematic cycles of 3-4 years with a recent shortening trend of 2-3 years. Climatic variability, such as positive anomalous temperatures and reduced rainfall due to changes in sea surface temperature (SST), is partially linked to the changing epidemiology of the disease, as this condition provides suitable environments for the Aedes aegypti lifecycle. Conclusion: ENSO may have influenced the dengue temporal patterns in the MRR, transiently reducing its main way of multiyear variability (3-4 years) to 2-3 years. Furthermore, when the epidemic coincided with El Niño years, it spread regionally and was highly synchronized.

16.
Psico USF ; 26(2): 345-356, Apr.-June 2021. tab, graf
Artigo em Inglês | LILACS, Index Psicologia - Periódicos | ID: biblio-1287601

RESUMO

This research aimed at investigating whether watching Brazilian advertising pieces that portray a sociocultural behavioral pattern called Brazilian jeitinho would influence participant's subsequent behavior. One carried out an experiment in which 200 subjects watched and assessed three advertisement pieces. Upon recruitment, participants were informed that they would be taking part in a raffle for a gift card. The number of tickets received per participant was defined by a die-under-cup task. The more tickets they obtained, the higher the chance to receive the prize, providing an incentive to cheat. Afterwards, respondents took part in a task that defined the number of tickets that each would receive to participate in the raffle. Independent variables consisted in the manipulation of priming of jeitinho (video content: jeitinho or neutral) and privacy of the task (with or without privacy). On the other hand, the dependent variable consisted in the result obtained when participants rolled the dices that defined the number of tickets. One found a significant difference between the groups in which privacy was manipulated, indicating that the groups that performed the task aimed at measuring dishonesty with privacy actually tended to report lower values than the ones actually obtained, entailing an effect of contrast. This finding suggests that the implementation of public policies that utilize propaganda that portrays Brazilian jeitinho could reduce engagement in dishonest behavior among Brazilians. (AU)


Esta pesquisa objetivou investigar se assistir a peças publicitárias nacionais representativas de um padrão de comportamento sociocultural do Brasil, o jeitinho brasileiro, influenciaria o comportamento subsequente dos participantes. Realizou-se um experimento no qual 200 participantes assistiram e avaliariam três anúncios publicitários. Ao serem recrutados, os participantes foram informados de que estariam concorrendo a um sorteio de um vale-presente. O número de tickets do sorteio foi definido por uma tarefa que consistiu em jogar um dado dentro de um copo. Quanto mais tickets obtivessem, maior a chance de ganhar o prêmio, criando-se um incentivo para trapacear. As variáveis independentes constituíram a manipulação da pré-ativação (priming) de jeitinho (conteúdo das peças: jeitinho ou neutro) e da privacidade da tarefa (com ou sem privacidade). Já a variável dependente consistiu no resultado obtido ao jogar dados para definir o número de tickets. Encontrou-se diferença significativa entre os grupos para manipulação de privacidade, indicando que os participantes que realizaram a tarefa de mensuração de desonestidade com privacidade tenderam a reportar valores menores do que os que realmente obtiveram no sorteio, ocasionando um efeito de contraste. Esse achado sugere que a implementação de políticas públicas utilizando propagandas que retratem o jeitinho brasileiro podem reduzir o engajamento em comportamento desonesto entre os brasileiros. (AU)


Este estudio tuvo como objetivo investigar si ver anuncios publicitarios brasileños que retratan a un patrón de comportamiento sociocultural denominado jeitinho brasileño influiría en el comportamiento posterior de los participantes. Se realizó un experimento donde 200 individuos vieron y evaluaron tres anuncios publicitarios. Al ser reclutados, se les informó a los participantes que se realizaría un sorteo de una tarjeta de regalo. El número de boletos de cada participante fue definido mediante una tarea que consistía en lanzar un dado a una taza. Cuantos más boletos obtuvieron, mayor fue la posibilidad de recibir el premio, lo que ofreció un incentivo para hacer posibles trampas. Posteriormente, los encuestados participaron en una tarea que definió la cantidad de boletos que cada uno recibiría para participar en el sorteo del premio. Las variables independientes consistieron en la manipulación de la preactivación (priming) de jeitinho (contenido de los videos: jeitinho o neutro) y de la privacidad de la tarea (con o sin privacidad). Por otro lado, la variable dependiente consistió en el resultado obtenido cuando los participantes lanzaron los dados que definían el número de boletos. Se encontró una diferencia significativa entre los grupos en los que se manipuló la privacidad, lo que indica que en los grupos que realizaron la tarea dirigida a medir la deshonestidad con privacidad, en realidad tendían a informar valores más bajos que los que realmente obtuvieron, lo que conlleva un efecto de contraste. Este resultado sugiere que la implementación de políticas públicas utilizando propaganda que retrata al jeitinho brasileño podría reducir la participación en conductas deshonestas entre los brasileños. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Publicidade , Características Culturais , Normas Sociais , Princípios Morais , Análise de Variância
17.
DNA Repair (Amst) ; 100: 103070, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33618126

RESUMO

The classical small Rho GTPase (Rho, Rac, and Cdc42) protein family is mainly responsible for regulating cell motility and polarity, membrane trafficking, cell cycle control, and gene transcription. Cumulative recent evidence supports important roles for these proteins in the maintenance of genomic stability. Indeed, DNA damage response (DDR) and repair mechanisms are some of the prime biological processes that underlie several disease phenotypes, including genetic disorders, cancer, senescence, and premature aging. Many reports guided by different experimental approaches and molecular hypotheses have demonstrated that, to some extent, direct modulation of Rho GTPase activity, their downstream effectors, or actin cytoskeleton regulation contribute to these cellular events. Although much attention has been paid to this family in the context of canonical actin cytoskeleton remodeling, here we provide a contextualized review of the interplay between Rho GTPase signaling pathways and the DDR and DNA repair signaling components. Interesting questions yet to be addressed relate to the spatiotemporal dynamics of this collective response and whether it correlates with different subcellular pools of Rho GTPases. We highlight the direct and indirect targets, some of which still lack experimental validation data, likely associated with Rho GTPase activation that provides compelling evidence for further investigation in DNA damage-associated events and with potential therapeutic applications in translational medicine.


Assuntos
Citoesqueleto de Actina/metabolismo , Dano ao DNA , Reparo do DNA , Instabilidade Genômica , Transdução de Sinais , Proteínas rho de Ligação ao GTP/metabolismo , Animais , Humanos
18.
Cell Cycle ; 19(12): 1545-1561, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32380926

RESUMO

The DUSP3 phosphatase regulates cell cycle, proliferation, apoptosis and senescence of different cell types, lately shown as a mediator of DNA repair processes. This work evaluated the impact of DUSP3 loss of function (lof) on DNA repair-proficient fibroblasts (MRC-5), NER-deficient cell lines (XPA and XPC) and translesion DNA synthesis (TLS)-deficient cells (XPV), after UV-radiation stress. The levels of DNA strand breaks, CPDs and 6-4-PPs have accumulated over time in all cells under DUSP3 lof, with a significant increase in NER-deficient lines. The inefficient repair of these lesions increased sub-G1 population of XPA and XPC cells 24 hours after UV treatment, notably marked by DUSP3 lof, which is associated with a reduced cell population in G1, S and G2/M phases. It was also detected an increase in S and G2/M populations of XPV and MRC-5 cells after UV-radiation exposure, which was slightly attenuated by DUSP3 lof due to a discrete increase in sub-G1 cells. The cell cycle progression was accompanied by changes in the levels of the main Cyclins (A1, B1, D1 or E1), CDKs (1, 2, 4 or 6), and the p21 Cip1 inhibitor, in a DUSP3-dependent manner. DUSP3 lof affected the proliferation of MRC-5 and XPA cells, with marked worsening of the XP phenotype after UV radiation. This work highlights the roles of DUSP3 in DNA repair fitness and in the fine control of regulatory proteins of cell cycle, essential mechanisms to maintenance of genomic stability.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Reparo do DNA/genética , Fosfatase 3 de Especificidade Dupla/metabolismo , Instabilidade Genômica , Ciclo Celular/efeitos da radiação , Proliferação de Células/genética , Proliferação de Células/efeitos da radiação , Dano ao DNA , Reparo do DNA/efeitos da radiação , Inativação Gênica/efeitos da radiação , Instabilidade Genômica/efeitos da radiação , Humanos , Dímeros de Pirimidina/metabolismo , Estresse Fisiológico/efeitos da radiação , Raios Ultravioleta
19.
Int J Psychol ; 55(4): 674-683, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31745980

RESUMO

Research on scientific integrity is growing in psychology, and questionable research practices (QRPs) have received more attention due to its harmful effect on science. By replicating the procedures of previous research, the present study aimed at describing the use of QRPs among Brazilian psychological researchers and to make an international comparison with previous studies in other countries-the US and Italy. Two hundred and thirty-two Brazilian researchers in the field of psychology answered questions related to 10 different QRPs. Brazilian researchers indicated a lower tendency to engage in two QRPs (failing to report all of a study's dependent measures; deciding whether to collect more data after looking to see whether the results were significant) when compared to their Italian and North American counterparts, but indicated a higher tendency to engage in two other QRPs (selectively reporting studies that "worked"; not reporting all of a study's conditions). Most of the sample did not admit integrity conflicts in their own research but indicated that others have integrity problems, as observed in previous studies. Those discrepancies could be attributed to contextual and systemic factors regarding different publication demands among the different nations. Further studies should focus on identifying the antecedents of QRPs.


Assuntos
Pesquisadores/psicologia , Adulto , Brasil , Humanos , Projetos de Pesquisa
20.
Artigo em Inglês | MEDLINE | ID: mdl-30069819

RESUMO

Protein tyrosine kinases (PTK), discovered in the 1970s, have been considered master regulators of biological processes with high clinical significance as targets for human diseases. Their actions are countered by protein tyrosine phosphatases (PTP), enzymes yet underrepresented as drug targets because of the high homology of their catalytic domains and high charge of their catalytic pocket. This scenario is still worse for some PTP subclasses, for example, for the atypical dual-specificity phosphatases (ADUSPs), whose biological functions are not even completely known. In this sense, the present work focuses on the dual-specificity phosphatase 3 (DUSP3), also known as VH1-related phosphatase (VHR), an uncommon regulator of mitogen-activated protein kinase (MAPK) phosphorylation. DUSP3 expression and activities are suggestive of a tumor suppressor or tumor-promoting enzyme in different types of human cancers. Furthermore, DUSP3 has other biological functions involving immune response mediation, thrombosis, hemostasis, angiogenesis, and genomic stability that occur through either MAPK-dependent or MAPK-independent mechanisms. This broad spectrum of actions is likely due to the large substrate diversity and molecular mechanisms that are still under scrutiny. The growing advances in characterizing new DUSP3 substrates will allow the development of pharmacological inhibitors relevant for possible future clinical trials. This review covers all aspects of DUSP3, since its gene cloning and crystallographic structure resolution, in addition to its classical and novel substrates and the biological processes involved, followed by an update of what is currently known about the DUSP3/VHR-inhibiting compounds that might be considered potential drugs to treat human diseases.


Assuntos
Fosfatase 3 de Especificidade Dupla/genética , Fosfatase 3 de Especificidade Dupla/fisiologia , Fosfatase 3 de Especificidade Dupla/antagonistas & inibidores , Humanos , Proteínas Quinases Ativadas por Mitógeno , Neoplasias/enzimologia , Neovascularização Patológica , Fosforilação , Proteínas Tirosina Fosfatases , Proteínas Tirosina Quinases
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