Helotonio Carvalho | Universidade de Pernambuco - UFPE (Brasil) (original) (raw)
Papers by Helotonio Carvalho
2020 IEEE International Conference on Teaching, Assessment, and Learning for Engineering (TALE), 2020
the pandemic closure brings [4], [5]. This plan was a challenge to K-12 students from Public Scho... more the pandemic closure brings [4], [5]. This plan was a challenge to K-12 students from Public Schools: physical exercises in which the students could learn in a playful and experiential way a concept of Natural Sciences [6]. This challenge focused on building cognitive, socio-emotional, and behavioral skills, and on quality of life through the care of the physical health of educational actors [7]. The chosen concept was the "center of mass" because it is a biometric, dynamic, and contextual variable linked to body movement-kinesiology [8], [9], where students could be experienced in the quarantine period ('lockdown') through physical exercises. Also, there is a significant probabilistic relationship between the more a child is physically active (spontaneous and induced sports practices), the more the child's ability to learn and solve problems (within the zone of proximal development) [10], [11]. An Interactive Model ("Change your Center of Mass!") was built based on a mathematical model with the center of mass as a dependent variable and independent variables: body mass index and vertical jump, in which students and teachers could insert data, and qualify as your center of mass is: from regular (not very active physically) to excellent (in activity with high performance). And this interaction with the Model could be a motivating factor for the student to remain active during and after the pandemic. The center of mass is a hypothetical point where the whole mass converges as if all external forces were being applied at that point. The center of mass can coincide with the center of gravity when a human body is under the influence of a uniform gravitational field [8], [12], [13]. This biophysical variable is important because it is related to the student's biomechanics and biometrics, his body volume has a direct and proportional relationship with his movement, it can be quantified (e.g. body mass index on running speed) and qualified: the perceptual effort used to get out of inertia (e.g. laziness) [14]. Jumping jacks is a physical exercise in which you can study and analyze the center of mass about its induced variation because it is a vertical movement in which, over time, we can verify a variation in the position of the center of mass in student (or athlete), if students are actives and change Abstract-The pandemic caused by Sars-CoV-2 resulted in a period of physical distance and school closures. This motivated us to elaborate on some physical and psychological harm reduction plan for the students. A challenge was proposed to K-12 students from Public Schools of the Recife City: physical exercises in which the students could learn playfully and experientially a concept of Natural Sciences. The chosen concept was the "center of mass" because it is a biometric, dynamic, and contextual variable linked to body movement, which could be experienced in the quarantine period. The objectives of this work were: (i) to propose a challenge through the physical exercise to K-12 students (jumping jacks), which implies the study of "center of mass" (COM) concept, (ii) to quantify the dependent variable COM and to relate with independent variables (e.g. body mass index), (iii) to build a learning object "Interactive Model" from the data obtained, (iv) to evaluate the didactic process. The objectives proposed were successfully implemented. The Interactive Model: "Change your Center of Mass!" was built and evaluated by teachers of Public Schools (Brazil), who highlighted its potential (impact, complexity, applicability, innovation) suggesting the model to the educational system.
The Lancet Planetary Health
The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from ... more The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from WHO Air Quality Reports from 2014, 2016 and 2018, and compares to the previous and the new WHO Air Quality Guidelines. The purpose was to highlight the importance of the revision of the values for these new Air Quality Guidelines as well as the challenge that will mean for many cities/countries to comply with them. Cities were divided in groups of lower and higher air pollution levels. Many of the lower air pollution ones were already above the previous guidelines, while just two of them, Porto and Stockholm, already complied with the new guidelines considering 2018 data. Even in this group of cities, many will need to reduce PM2.5 concentrations between 50% to more than 70% to be under the new WHO guidelines. Among the cities with higher air pollution levels, most of them will need to decrease PM2.5 concentrations more than 90% to meet new WHO guidelines, including Beijing, Riyadh, Karachi, Ulaanbaatar and New Delhi. These new Air Quality Guidelines along with the simultaneous pressure to reduce the use of fossil fuels to mitigate climate change, with many countries stablishing goals for reduction of CO2 emissions to comply to the Paris Agreement, will sure be essential for the transition to a decarbonized world, contributing to save millions of lives.
Teorias e Métodos da Biofísica, 2019
2020 IEEE International Conference on Teaching, Assessment, and Learning for Engineering (TALE), 2020
The pandemic caused by Sars-CoV-2 resulted in a period of physical distance and school closures. ... more The pandemic caused by Sars-CoV-2 resulted in a period of physical distance and school closures. This motivated us to elaborate on some physical and psychological harm reduction plan for the students. A challenge was proposed to K12 students from Public Schools of the Recife City: physical exercises in which the students could learn playfully and experientially a concept of Natural Sciences. The chosen concept was the "center of mass" because it is a biometric, dynamic, and contextual variable linked to body movement, which could be experienced in the quarantine period. The objectives of this work were: (i) to propose a challenge through the physical exercise to K-12 students (jumping jacks), which implies the study of “center of mass” (COM) concept, (ii) to quantify the dependent variable COM and to relate with independent variables (e.g. body mass index), (iii) to build a learning object “Interactive Model” from the data obtained, (iv) to evaluate the didactic process. T...
Exploring DNA damage responses in human cells with recombinant adenoviral vectors
Journal of Global Health, 2021
www.jogh.org • doi: 10.7189/jogh.11.03089 1 2021 • Vol. 11 • 03089 COVID-19 has changed the world... more www.jogh.org • doi: 10.7189/jogh.11.03089 1 2021 • Vol. 11 • 03089 COVID-19 has changed the world since it was first discovered in Wuhan, China in December 2019. Many countries imposed lockdowns to reduce SARS-CoV-2 transmission and minimize the need for hospitalization and/or an ICU. Even though, by the end of June 2021, more than 181 million cases had been registered and more than 3.9 million people had died around in the world [1]. This health emergence gave rise to highly articulated systems of data collection in order to keep track of the advance of the disease in every country. One of the most used and cited of these systems was created and is maintained by Johns Hopkins University [1,2].
Biochimie, 2003
Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and d... more Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing with a variety of helix-distorting lesions, such as the UV-induced photoproducts cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4 PPs). In this review, we describe the main protein players and the different sequential steps of the eukaryotic NER mechanism in human cells, from lesion recognition to damage removal and DNA synthesis. Studies on the dynamics of protein access to the damaged site, and the kinetics of lesion removal contribute to the knowledge of how the cells respond to genetic insult. DNA lesions as well as NER factors themselves are also implicated in changes in cell metabolism, influencing cell cycle progression or arrest, apoptosis and genetic instability. These changes are related to increased mutagenesis and carcinogenesis. Finally, the recent collection of genomic data allows one to recognize the high conservation and the evolution of eukaryotic NER. The distribution of NER orthologues in different organisms, from archaea to the metazoa, displays challenging observations. Some of NER proteins are widespread in nature, probably representing ancient DNA repair proteins, which are candidates to participate in a primitive NER mechanism.
The interplay between cellular iron homeostasis and metabolism of reactive oxidative species is r... more The interplay between cellular iron homeostasis and metabolism of reactive oxidative species is reviewed, mainly from the viewpoint of the possible consequences for DNA damage inflicted by these species. It is shown that genetic manipulation of the iron homeostasis gene repertoire affects directly the response of DNA to the aggression by oxidant species. It is also shown that a condition of oxidative stress alters iron homeostasis, providing the perception that these two events are mutually dependent. The presence of iron in the nucleus is reviewed and new data are discussed ; pointing both to (i) the participation of iron as a ligand of an unknown chromatin component, and to (ii) mechanisms of active transport of iron into the nucleus. The question of which mechanism is more important for DNA strand breaks under oxidative stress, either a calcium-activated nuclease or OH radical generated by the Fenton reaction is discussed. New data are reviewed showing that the chemical nature of...
Cancer chemotherapy …, 2010
Purpose Anthracyclines have been widely used as antitumor agents, playing a crucial role in the s... more Purpose Anthracyclines have been widely used as antitumor agents, playing a crucial role in the successful treatment of many types of cancer, despite some side eVects related to cardiotoxicity. New anthracyclines have been designed and tested, but the Wrst ones discovered, doxorubicin and daunorubicin, continue to be the drugs of choice. Despite their extensive use in chemotherapy, little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines. The anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis, characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene. Methods We assessed the induction of apoptosis (Sub-G 1) by cosmomycin D in nucleotide excision repair-deWcient Wbroblasts (XP-A and XP-C) as well as the levels of DNA damage (alkaline comet assay). Results Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner, with highest apoptosis levels observed 96 h after treatment. The eVects of cosmomycin D were equivalent to those obtained with doxorubicin. The broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells, and DNA damage induced by cosmomycin D was conWrmed by alkaline comet assay. Conclusions Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deWcient Wbroblasts. Despite similar apoptosis levels, cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin. This may be related to diVerences in structure between cosmomycin D and doxorubicin.
Iron is an essential metal for all living organisms. However, iron homeostasis needs to be tightl... more Iron is an essential metal for all living organisms. However, iron homeostasis needs to be tightly controlled since iron can mediate the production of reactive oxygen species, which can damage cell components and compromise the integrity and/or cause DNA mutations, ultimately leading to cancer. In eukaryotes, iron-regulatory protein 1 (IRP1) plays a central role in the control of intracellular iron homeostasis. This occurs by interaction of IRP1 with iron-responsive element regions at 5' of ferritin mRNA and 3' of transferrin mRNA which, respectively, represses translation and increases mRNA stability. We have expressed IRP1 using the plasmid pT7-His-hIRP1, which codifies for human IRP1 attached to an NH 2-terminal 6-His tag. IRP1 was expressed in Escherichia coli using the strategy of co-expressing chaperonins GroES and GroEL, in order to circumvent inclusion body formation and increase the yield of soluble protein. The protein co-expressed with these chaperonins was obtained mostly in the soluble form, which greatly increased the efficiency of protein purification. Metal affinity and FPLC ion exchange chromatography were used in order to obtain highly purified IRP1. Purified protein was biologically active, as assessed by electrophoretic mobility shift assay, and could be converted to the cytoplasmic aconitase form. These results corroborate previous studies, which suggest the use of folding catalysts as a powerful strategy to increase protein solubility when expressing heterologous proteins in E. coli.
Lancet Planetary Health , 2021
The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from ... more The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from WHO Air Quality Reports from 2014, 2016 and 2018, and compares to the previous and the new WHO Air Quality Guidelines. The purpose was to highlight the importance of the revision of the values for these new Air Quality Guidelines as well as the challenge that will mean for many cities/countries to comply with them. Cities were divided in groups of lower and higher air pollution levels. Many of the lower air pollution ones were already above the previous guidelines, while just two of them, Porto and Stockholm, already complied with the new guidelines considering 2018 data. Even in this group of cities, many will need to reduce PM2.5 concentrations between 50% to more than 70% to be under the new WHO guidelines. Among the cities with higher air pollution levels, most of them will need to decrease PM2.5 concentrations more than 90% to meet new WHO guidelines, including Beijing, Riyadh, Karachi, Ulaanbaatar and New Delhi.
These new Air Quality Guidelines along with the simultaneous pressure to reduce the use of fossil fuels to mitigate climate change, with many countries stablishing goals for reduction of CO2 emissions to comply to the Paris Agreement, will sure be essential for the transition to a decarbonized world, contributing to save millions of lives.
Revista Brasileira de Ensino de Ciências e Matemática
A poluição litorânea está na lista dos graves problemas ambientais que prejudicam a sociedade e a... more A poluição litorânea está na lista dos graves problemas ambientais que prejudicam a sociedade e a manutenção dos ecossistemas. Considerando esse cenário e a complexidade que envolve os problemas ambientais é importante que as escolas, não mais de forma ingênua, realizem ações que conversem com os diversos saberes curriculares com uso de ferramentas e estratégias de ensino que sejam potencialmente significativas. Nesse contexto, foi desenvolvida uma Unidade de Ensino Potencialmente Significativa (UEPS) acerca da temática “Água e Poluição na Educação Básica”. A UEPS foi idealizada utilizando uma sequência de ações de ensino de modo interdisciplinar utilizando uma variedade de estratégias e ferramentas e com a avaliação pautada na produção de mapas conceituais, tendo sido aplicada a estudantes do ensino médio de uma escola da rede estadual de Pernambuco. Durante as estratégias didáticas utilizadas foram encontradas evidências de que novos conceitos se ancoraram aos conhecimentos prévio...
Recombinant adenoviral vectors provide efficient means for gene transduction in mammalian cells i... more Recombinant adenoviral vectors provide efficient means for gene transduction in mammalian cells in vitro and in vivo. We are currently using these vectors to transduce DNA repair genes into repair deficient cells, derived from xeroderma pigmentosum (XP) patients. XP is an autosomal syndrome characterized by a high frequency of skin tumors, especially in areas exposed to sunlight, and, occasionally, developmental and neurological abnormalities. XP cells are deficient in nucleotide excision repair (affecting one of the seven known XP genes, xpa to xpg) or in DNA replication of DNA lesions (affecting DNA polymerase eta, xpv). The adenovirus approach allows the investigation of different consequences of DNA lesions in cell genomes. Adenoviral vectors carrying several xp and photolyases genes have been constructed and successfully tested in cell culture systems and in vivo directly in the skin of knockout model mice. This review summarizes these recent data and proposes the use of recombinant adenoviruses as tools to investigate the mechanisms that provide protection against DNA damage in human cells, as well as to better understand the higher predisposition of XP patients to cancer. Human & Experimental Toxicology (2007) 26, 899—906
Blucher Biophysics Proceedings
Journal of Global Health, 2021
Data access has been fundamental during Covid-19 pandemics. All over the world, data on the numbe... more Data access has been fundamental during Covid-19 pandemics. All over the world, data on the number of infections and deaths caused by Sars-Cov-2 have been collected and used by health officials and governments to analyse the need for lockdowns in order to decrease the spread of the virus and save lives. Air pollution has been positively impacted by these measures, since better air quality was observed in many of the cities/countries which adopted them. Unfortunately, access to air pollution data is not always straightforward. There is no single source for ground levels air pollution data that covers most of the countries in detail. Despite some national or regional services, in general detailed data can only be obtained through local authorities. The present article analyses access to air quality data for 23 cities around the world, focusing in PM2.5 data and analysing time frame availability, data search tools, availability of an English webpage and its functions, and data retrieval format. While cities like London and New Delhi have a highly user-friendly and complete website, many cities such as Tokyo, Beijing and Seoul have problems with data accessibility, and many others like Islamabad and Dubai do not grant free access to air quality data. Air pollution causes more than 7 million deaths each year and particulate matter is the component most associated with health problems. Air quality depends on monitoring, data availability, and policies to decrease air pollution levels, which help to reduce health problems and deaths caused by air pollution. The present article expects to bring to light the need for more accessibility/transparency for air quality data.
Cancer Letters, 2011
Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action... more Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. In fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA.
2020 IEEE International Conference on Teaching, Assessment, and Learning for Engineering (TALE), 2020
the pandemic closure brings [4], [5]. This plan was a challenge to K-12 students from Public Scho... more the pandemic closure brings [4], [5]. This plan was a challenge to K-12 students from Public Schools: physical exercises in which the students could learn in a playful and experiential way a concept of Natural Sciences [6]. This challenge focused on building cognitive, socio-emotional, and behavioral skills, and on quality of life through the care of the physical health of educational actors [7]. The chosen concept was the "center of mass" because it is a biometric, dynamic, and contextual variable linked to body movement-kinesiology [8], [9], where students could be experienced in the quarantine period ('lockdown') through physical exercises. Also, there is a significant probabilistic relationship between the more a child is physically active (spontaneous and induced sports practices), the more the child's ability to learn and solve problems (within the zone of proximal development) [10], [11]. An Interactive Model ("Change your Center of Mass!") was built based on a mathematical model with the center of mass as a dependent variable and independent variables: body mass index and vertical jump, in which students and teachers could insert data, and qualify as your center of mass is: from regular (not very active physically) to excellent (in activity with high performance). And this interaction with the Model could be a motivating factor for the student to remain active during and after the pandemic. The center of mass is a hypothetical point where the whole mass converges as if all external forces were being applied at that point. The center of mass can coincide with the center of gravity when a human body is under the influence of a uniform gravitational field [8], [12], [13]. This biophysical variable is important because it is related to the student's biomechanics and biometrics, his body volume has a direct and proportional relationship with his movement, it can be quantified (e.g. body mass index on running speed) and qualified: the perceptual effort used to get out of inertia (e.g. laziness) [14]. Jumping jacks is a physical exercise in which you can study and analyze the center of mass about its induced variation because it is a vertical movement in which, over time, we can verify a variation in the position of the center of mass in student (or athlete), if students are actives and change Abstract-The pandemic caused by Sars-CoV-2 resulted in a period of physical distance and school closures. This motivated us to elaborate on some physical and psychological harm reduction plan for the students. A challenge was proposed to K-12 students from Public Schools of the Recife City: physical exercises in which the students could learn playfully and experientially a concept of Natural Sciences. The chosen concept was the "center of mass" because it is a biometric, dynamic, and contextual variable linked to body movement, which could be experienced in the quarantine period. The objectives of this work were: (i) to propose a challenge through the physical exercise to K-12 students (jumping jacks), which implies the study of "center of mass" (COM) concept, (ii) to quantify the dependent variable COM and to relate with independent variables (e.g. body mass index), (iii) to build a learning object "Interactive Model" from the data obtained, (iv) to evaluate the didactic process. The objectives proposed were successfully implemented. The Interactive Model: "Change your Center of Mass!" was built and evaluated by teachers of Public Schools (Brazil), who highlighted its potential (impact, complexity, applicability, innovation) suggesting the model to the educational system.
The Lancet Planetary Health
The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from ... more The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from WHO Air Quality Reports from 2014, 2016 and 2018, and compares to the previous and the new WHO Air Quality Guidelines. The purpose was to highlight the importance of the revision of the values for these new Air Quality Guidelines as well as the challenge that will mean for many cities/countries to comply with them. Cities were divided in groups of lower and higher air pollution levels. Many of the lower air pollution ones were already above the previous guidelines, while just two of them, Porto and Stockholm, already complied with the new guidelines considering 2018 data. Even in this group of cities, many will need to reduce PM2.5 concentrations between 50% to more than 70% to be under the new WHO guidelines. Among the cities with higher air pollution levels, most of them will need to decrease PM2.5 concentrations more than 90% to meet new WHO guidelines, including Beijing, Riyadh, Karachi, Ulaanbaatar and New Delhi. These new Air Quality Guidelines along with the simultaneous pressure to reduce the use of fossil fuels to mitigate climate change, with many countries stablishing goals for reduction of CO2 emissions to comply to the Paris Agreement, will sure be essential for the transition to a decarbonized world, contributing to save millions of lives.
Teorias e Métodos da Biofísica, 2019
2020 IEEE International Conference on Teaching, Assessment, and Learning for Engineering (TALE), 2020
The pandemic caused by Sars-CoV-2 resulted in a period of physical distance and school closures. ... more The pandemic caused by Sars-CoV-2 resulted in a period of physical distance and school closures. This motivated us to elaborate on some physical and psychological harm reduction plan for the students. A challenge was proposed to K12 students from Public Schools of the Recife City: physical exercises in which the students could learn playfully and experientially a concept of Natural Sciences. The chosen concept was the "center of mass" because it is a biometric, dynamic, and contextual variable linked to body movement, which could be experienced in the quarantine period. The objectives of this work were: (i) to propose a challenge through the physical exercise to K-12 students (jumping jacks), which implies the study of “center of mass” (COM) concept, (ii) to quantify the dependent variable COM and to relate with independent variables (e.g. body mass index), (iii) to build a learning object “Interactive Model” from the data obtained, (iv) to evaluate the didactic process. T...
Exploring DNA damage responses in human cells with recombinant adenoviral vectors
Journal of Global Health, 2021
www.jogh.org • doi: 10.7189/jogh.11.03089 1 2021 • Vol. 11 • 03089 COVID-19 has changed the world... more www.jogh.org • doi: 10.7189/jogh.11.03089 1 2021 • Vol. 11 • 03089 COVID-19 has changed the world since it was first discovered in Wuhan, China in December 2019. Many countries imposed lockdowns to reduce SARS-CoV-2 transmission and minimize the need for hospitalization and/or an ICU. Even though, by the end of June 2021, more than 181 million cases had been registered and more than 3.9 million people had died around in the world [1]. This health emergence gave rise to highly articulated systems of data collection in order to keep track of the advance of the disease in every country. One of the most used and cited of these systems was created and is maintained by Johns Hopkins University [1,2].
Biochimie, 2003
Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and d... more Nucleotide excision repair (NER) is the most versatile mechanism of DNA repair, recognizing and dealing with a variety of helix-distorting lesions, such as the UV-induced photoproducts cyclobutane pyrimidine dimers (CPDs) and pyrimidine 6-4 pyrimidone photoproducts (6-4 PPs). In this review, we describe the main protein players and the different sequential steps of the eukaryotic NER mechanism in human cells, from lesion recognition to damage removal and DNA synthesis. Studies on the dynamics of protein access to the damaged site, and the kinetics of lesion removal contribute to the knowledge of how the cells respond to genetic insult. DNA lesions as well as NER factors themselves are also implicated in changes in cell metabolism, influencing cell cycle progression or arrest, apoptosis and genetic instability. These changes are related to increased mutagenesis and carcinogenesis. Finally, the recent collection of genomic data allows one to recognize the high conservation and the evolution of eukaryotic NER. The distribution of NER orthologues in different organisms, from archaea to the metazoa, displays challenging observations. Some of NER proteins are widespread in nature, probably representing ancient DNA repair proteins, which are candidates to participate in a primitive NER mechanism.
The interplay between cellular iron homeostasis and metabolism of reactive oxidative species is r... more The interplay between cellular iron homeostasis and metabolism of reactive oxidative species is reviewed, mainly from the viewpoint of the possible consequences for DNA damage inflicted by these species. It is shown that genetic manipulation of the iron homeostasis gene repertoire affects directly the response of DNA to the aggression by oxidant species. It is also shown that a condition of oxidative stress alters iron homeostasis, providing the perception that these two events are mutually dependent. The presence of iron in the nucleus is reviewed and new data are discussed ; pointing both to (i) the participation of iron as a ligand of an unknown chromatin component, and to (ii) mechanisms of active transport of iron into the nucleus. The question of which mechanism is more important for DNA strand breaks under oxidative stress, either a calcium-activated nuclease or OH radical generated by the Fenton reaction is discussed. New data are reviewed showing that the chemical nature of...
Cancer chemotherapy …, 2010
Purpose Anthracyclines have been widely used as antitumor agents, playing a crucial role in the s... more Purpose Anthracyclines have been widely used as antitumor agents, playing a crucial role in the successful treatment of many types of cancer, despite some side eVects related to cardiotoxicity. New anthracyclines have been designed and tested, but the Wrst ones discovered, doxorubicin and daunorubicin, continue to be the drugs of choice. Despite their extensive use in chemotherapy, little is known about the DNA repair mechanisms involved in the removal of lesions caused by anthracyclines. The anthracycline cosmomycin D is the main product isolated from Streptomyces olindensis, characterized by a peculiar pattern of glycosylation with two trisaccharide rings attached to the A ring of the tetrahydrotetracene. Methods We assessed the induction of apoptosis (Sub-G 1) by cosmomycin D in nucleotide excision repair-deWcient Wbroblasts (XP-A and XP-C) as well as the levels of DNA damage (alkaline comet assay). Results Treatment of XP-A and XP-C cells with cosmomycin D resulted in apoptosis in a time-dependent manner, with highest apoptosis levels observed 96 h after treatment. The eVects of cosmomycin D were equivalent to those obtained with doxorubicin. The broad caspase inhibitor Z-VAD-FMK strongly inhibited apoptosis in these cells, and DNA damage induced by cosmomycin D was conWrmed by alkaline comet assay. Conclusions Cosmomycin D induced time-dependent apoptosis in nucleotide excision repair-deWcient Wbroblasts. Despite similar apoptosis levels, cosmomycin D caused considerably lower levels of DNA damage compared to doxorubicin. This may be related to diVerences in structure between cosmomycin D and doxorubicin.
Iron is an essential metal for all living organisms. However, iron homeostasis needs to be tightl... more Iron is an essential metal for all living organisms. However, iron homeostasis needs to be tightly controlled since iron can mediate the production of reactive oxygen species, which can damage cell components and compromise the integrity and/or cause DNA mutations, ultimately leading to cancer. In eukaryotes, iron-regulatory protein 1 (IRP1) plays a central role in the control of intracellular iron homeostasis. This occurs by interaction of IRP1 with iron-responsive element regions at 5' of ferritin mRNA and 3' of transferrin mRNA which, respectively, represses translation and increases mRNA stability. We have expressed IRP1 using the plasmid pT7-His-hIRP1, which codifies for human IRP1 attached to an NH 2-terminal 6-His tag. IRP1 was expressed in Escherichia coli using the strategy of co-expressing chaperonins GroES and GroEL, in order to circumvent inclusion body formation and increase the yield of soluble protein. The protein co-expressed with these chaperonins was obtained mostly in the soluble form, which greatly increased the efficiency of protein purification. Metal affinity and FPLC ion exchange chromatography were used in order to obtain highly purified IRP1. Purified protein was biologically active, as assessed by electrophoretic mobility shift assay, and could be converted to the cytoplasmic aconitase form. These results corroborate previous studies, which suggest the use of folding catalysts as a powerful strategy to increase protein solubility when expressing heterologous proteins in E. coli.
Lancet Planetary Health , 2021
The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from ... more The manuscript analyzes the levels of PM2.5 in 47 cities from all over the world using data from WHO Air Quality Reports from 2014, 2016 and 2018, and compares to the previous and the new WHO Air Quality Guidelines. The purpose was to highlight the importance of the revision of the values for these new Air Quality Guidelines as well as the challenge that will mean for many cities/countries to comply with them. Cities were divided in groups of lower and higher air pollution levels. Many of the lower air pollution ones were already above the previous guidelines, while just two of them, Porto and Stockholm, already complied with the new guidelines considering 2018 data. Even in this group of cities, many will need to reduce PM2.5 concentrations between 50% to more than 70% to be under the new WHO guidelines. Among the cities with higher air pollution levels, most of them will need to decrease PM2.5 concentrations more than 90% to meet new WHO guidelines, including Beijing, Riyadh, Karachi, Ulaanbaatar and New Delhi.
These new Air Quality Guidelines along with the simultaneous pressure to reduce the use of fossil fuels to mitigate climate change, with many countries stablishing goals for reduction of CO2 emissions to comply to the Paris Agreement, will sure be essential for the transition to a decarbonized world, contributing to save millions of lives.
Revista Brasileira de Ensino de Ciências e Matemática
A poluição litorânea está na lista dos graves problemas ambientais que prejudicam a sociedade e a... more A poluição litorânea está na lista dos graves problemas ambientais que prejudicam a sociedade e a manutenção dos ecossistemas. Considerando esse cenário e a complexidade que envolve os problemas ambientais é importante que as escolas, não mais de forma ingênua, realizem ações que conversem com os diversos saberes curriculares com uso de ferramentas e estratégias de ensino que sejam potencialmente significativas. Nesse contexto, foi desenvolvida uma Unidade de Ensino Potencialmente Significativa (UEPS) acerca da temática “Água e Poluição na Educação Básica”. A UEPS foi idealizada utilizando uma sequência de ações de ensino de modo interdisciplinar utilizando uma variedade de estratégias e ferramentas e com a avaliação pautada na produção de mapas conceituais, tendo sido aplicada a estudantes do ensino médio de uma escola da rede estadual de Pernambuco. Durante as estratégias didáticas utilizadas foram encontradas evidências de que novos conceitos se ancoraram aos conhecimentos prévio...
Recombinant adenoviral vectors provide efficient means for gene transduction in mammalian cells i... more Recombinant adenoviral vectors provide efficient means for gene transduction in mammalian cells in vitro and in vivo. We are currently using these vectors to transduce DNA repair genes into repair deficient cells, derived from xeroderma pigmentosum (XP) patients. XP is an autosomal syndrome characterized by a high frequency of skin tumors, especially in areas exposed to sunlight, and, occasionally, developmental and neurological abnormalities. XP cells are deficient in nucleotide excision repair (affecting one of the seven known XP genes, xpa to xpg) or in DNA replication of DNA lesions (affecting DNA polymerase eta, xpv). The adenovirus approach allows the investigation of different consequences of DNA lesions in cell genomes. Adenoviral vectors carrying several xp and photolyases genes have been constructed and successfully tested in cell culture systems and in vivo directly in the skin of knockout model mice. This review summarizes these recent data and proposes the use of recombinant adenoviruses as tools to investigate the mechanisms that provide protection against DNA damage in human cells, as well as to better understand the higher predisposition of XP patients to cancer. Human & Experimental Toxicology (2007) 26, 899—906
Blucher Biophysics Proceedings
Journal of Global Health, 2021
Data access has been fundamental during Covid-19 pandemics. All over the world, data on the numbe... more Data access has been fundamental during Covid-19 pandemics. All over the world, data on the number of infections and deaths caused by Sars-Cov-2 have been collected and used by health officials and governments to analyse the need for lockdowns in order to decrease the spread of the virus and save lives. Air pollution has been positively impacted by these measures, since better air quality was observed in many of the cities/countries which adopted them. Unfortunately, access to air pollution data is not always straightforward. There is no single source for ground levels air pollution data that covers most of the countries in detail. Despite some national or regional services, in general detailed data can only be obtained through local authorities. The present article analyses access to air quality data for 23 cities around the world, focusing in PM2.5 data and analysing time frame availability, data search tools, availability of an English webpage and its functions, and data retrieval format. While cities like London and New Delhi have a highly user-friendly and complete website, many cities such as Tokyo, Beijing and Seoul have problems with data accessibility, and many others like Islamabad and Dubai do not grant free access to air quality data. Air pollution causes more than 7 million deaths each year and particulate matter is the component most associated with health problems. Air quality depends on monitoring, data availability, and policies to decrease air pollution levels, which help to reduce health problems and deaths caused by air pollution. The present article expects to bring to light the need for more accessibility/transparency for air quality data.
Cancer Letters, 2011
Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action... more Doxorubicin (DOX) is an important tumor chemotherapeutic agent, acting mainly by genotoxic action. This work focus on cell processes that help cell survival, after DOX-induced DNA damage. In fact, cells deficient for XPA or DNA polymerase eta (pol eta, XPV) proteins (involved in distinct DNA repair pathways) are highly DOX-sensitive. Moreover, LY294002, an inhibitor of PIKK kinases, showed a synergistic killing effect in cells deficient in these proteins, with a strong induction of G2/M cell cycle arrest. Taken together, these results indicate that XPA and pol eta proteins participate in cell resistance to DOX-treatment, and kinase inhibitors can selectively enhance its killing effects, probably reducing the cell ability to recover from breaks induced in DNA.