Bruno Bueno De Jesus - Academia.edu (original) (raw)
Papers by Bruno Bueno De Jesus
Metabolites
Heart disease is the leading cause of mortality in developed countries. The associated pathology ... more Heart disease is the leading cause of mortality in developed countries. The associated pathology is characterized by a loss of cardiomyocytes that leads, eventually, to heart failure. In this context, several cardiac regenerative strategies have been developed, but they still lack clinical effectiveness. The mammalian neonatal heart is capable of substantial regeneration following injury, but this capacity is lost at postnatal stages when cardiomyocytes become terminally differentiated and transit to the fetal metabolic switch. Cardiomyocytes are metabolically versatile cells capable of using an array of fuel sources, and the metabolism of cardiomyocytes suffers extended reprogramming after injury. Apart from energetic sources, metabolites are emerging regulators of epigenetic programs driving cell pluripotency and differentiation. Thus, understanding the metabolic determinants that regulate cardiomyocyte maturation and function is key for unlocking future metabolic interventions fo...
Cancers, 2020
Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunot... more Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer treatment. Despite their potential success, current approaches depend on efficient tumor antigen presentation which are often inaccessible, and most tumors turn refractory to current immunotherapy. Patient-derived induced pluripotent stem cells (iPSCs) have been shown to share several characteristics with cancer (stem) cells (CSCs), eliciting a specific anti-tumoral response when injected in rodent cancer models. Indeed, artificial cellular reprogramming has...
Frontiers in Physiology, 2021
Heart disease is the leading cause of mortality in developed countries. The associated pathology ... more Heart disease is the leading cause of mortality in developed countries. The associated pathology is typically characterized by the loss of cardiomyocytes that leads, eventually, to heart failure. Although conventional treatments exist, novel regenerative procedures are warranted for improving cardiac regeneration and patients well fare. Whereas following injury the capacity for regeneration of adult mammalian heart is limited, the neonatal heart is capable of substantial regeneration but this capacity is lost at postnatal stages. Interestingly, this is accompanied by a shift in the metabolic pathways and energetic fuels preferentially used by cardiomyocytes from embryonic glucose-driven anaerobic glycolysis to adult oxidation of substrates in the mitochondria. Apart from energetic sources, metabolites are emerging as key regulators of gene expression and epigenetic programs which could impact cardiac regeneration. Long non-coding RNAs (lncRNAs) are known master regulators of cellula...
Frontiers in Physiology, 2021
Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangem... more Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangement of the cardiac structure and function and to a subsequent increased risk of heart failure. An intricate network of distinct pathways contributes to age-related alterations during healthy heart aging and account for a higher susceptibility of heart disease. Our understanding of the systemic aging process has already led to the design of anti-aging strategies or to the adoption of protective interventions. Nevertheless, our understanding of the molecular determinants operating during cardiac aging or repair remains limited. Here, we will summarize the molecular and physiological alterations that occur during aging of the heart, highlighting the potential role for long non-coding RNAs (lncRNAs) as novel and valuable targets in cardiac regeneration/repair.
BMC Cancer, 2019
Background: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcrip... more Background: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcriptome. LncRNAs present a very stringent cell-type/tissue specificity being potential candidates for therapeutical applications during aging and disease. As example, targeting of MALAT1, a highly conserved lncRNA originally identified in metastatic non-small cell lung cancer, has shown promising results in cancer regression. Nevertheless, the regulation and specificity of MALAT1 have not been directly addressed. Interestingly, MALAT1 locus is spanned by an antisense transcript named TALAM1. Methods: Here using a collection of breast cancer cells and in vitro and in vivo migration assays we characterized the dynamics of expression and demonstrated that TALAM1 regulates and synergizes with MALAT1 during tumorigenesis. Results: Down-regulation of TALAM1 was shown to greatly impact on the capacity of breast cancer cells to migrate in vitro or to populate the lungs of immunocompromised mice. Additionally, we demonstrated that TALAM1 cooperates with MALAT1 in the regulation of the properties guiding breast cancer aggressiveness and malignancy. Conclusions: By characterizing this sense/anti-sense pair we uncovered the complexity of MALAT1 locus regulation, describing new potential candidates for cancer targeting.
International Journal of Molecular Sciences, 2019
Epithelial–mesenchymal transition (EMT) is a cellular process by which differentiated epithelial ... more Epithelial–mesenchymal transition (EMT) is a cellular process by which differentiated epithelial cells undergo a phenotypic conversion to a mesenchymal nature. The EMT has been increasingly recognized as an essential process for tissue fibrogenesis during disease and normal aging. Higher levels of EMT proteins in aged tissues support the involvement of EMT as a possible cause and/or consequence of the aging process. Here, we will highlight the existing understanding of EMT supporting the phenotypical alterations that occur during normal aging or pathogenesis, covering the impact of EMT deregulation in tissue homeostasis and stem cell function.
Aging Cell, 2018
One of the most outstanding observations from next-generation sequencing approaches was that only... more One of the most outstanding observations from next-generation sequencing approaches was that only 1.5% of our genes code for proteins. The biggest part is transcribed but give rise to different families of RNAs without coding potential. The functional relevance of these abundant transcripts remains far from elucidated. Among them are the long non-coding RNAs (lncRNAs), a relatively large and heterogeneous group of RNAs shown to be highly tissue-specific, indicating a prominent role in processes controlling cellular identity. In particular, lncRNAs have been linked to both stemness properties and detrimental pathways regulating the aging process, being novel players in the intricate network guiding tissue homeostasis. Here, we summarize the up-to-date information on the role of lncRNAs that affect stemness and hence impact upon aging, highlighting the likelihood that lncRNAs may represent an unexploited reservoir of potential therapeutic targets for reprogramming applications and aging-related diseases.
Nature communications, Jan 8, 2018
Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here,... more Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here, we report that fibroblasts from old mice express higher levels of Zeb2, a transcription factor that activates epithelial-to-mesenchymal transition. Synthesis of Zeb2 protein is controlled by a natural antisense transcript named Zeb2-NAT. We show that transfection of adult fibroblasts with specific LNA Gapmers induces a robust downregulation of Zeb2-NAT transcripts and Zeb2 protein and enhances the reprogramming of old fibroblasts into pluripotent cells. We further demonstrate that Zeb2-NAT expression is precociously activated by differentiation stimuli in embryonic stem (ES) cells. By knocking down Zeb2-NAT, we were able to maintain ES cells challenged with commitment signals in the ground state of pluripotency. In conclusion, our study identifies a long noncoding RNA that is overlapping and antisense to the Zeb2 locus as a target for rejuvenation strategies.
Revista Cientifica Integrada, Jun 30, 2014
Revista Cientifica Integrada, Jun 30, 2014
Revista Cientifica Integrada, Jun 30, 2014
Revista Cientifica Integrada, Jun 30, 2014
Http Www Theses Fr, 2008
Afin de preserver l'integrite du genome des differentes lesions de l'ADN, plusieurs mecan... more Afin de preserver l'integrite du genome des differentes lesions de l'ADN, plusieurs mecanismes de reparation ont ete mis en place dans les cellules de mammiferes. La persistance des dommages de l'ADN dans le genome peut potentiellement porter atteinte a l'integrite cellulaire et a l'homeostasie, mais peut aussi conduire a l'apoptose de la cellule, a la senescence ou au cancer. Les mecanismes de reparation de l'ADN sont generalement divises en quatre grandes voies en fonction de la lesion portee par l'ADN : BER (reparation par excision de base), NER (reparation par excision de nucleotides), DSBR (reparation des cassures double brins), et MMR (reparation des mesappariements). NER est une voie de reparation de l'ADN qui traite une grande variete de lesions volumineuses (telles que les dommages a l'ADN formes par le rayonnement UV ou induits par les produits chimiques). Ce mecanisme pourrait etre divise en deux sous-voies: TCR (reparation couplee a la transcription) ou GGR (reparation globale du genome). BER est la voie responsable de la reparation des lesions qui distordent moins l’ADN, comme les modifications de bases, telle que celle produite par le stress oxydatif ou par la desamination. Dans la GGR, le complexe XPC-HR23B est responsable de l’etape de reconnaissance de la lesion, illustrant ainsi in vivo la premiere association entre des proteines de reparation et l’ADN endommage. En plus de l’activite d’ouverture a proximite du dommage, XPC pourrait aider a la reparation de des dommages oxydatifs de l'ADN. Des mutations dans la voie de NER pourraient conduire a trois maladies genetiques: Xeroderma pigmentosum (XP), le syndrome de Cockayne (CS) et la trichothiodystrophie (TTD). XP est caracterise par une extreme sensibilite a la lumiere du soleil, une predisposition au cancer de la peau et, dans certains cas, des de��ficiences neurologiques. Les differentes manifestations pathologiques observees chez les patients XP nous ont guide pour etudier la correlation possible entre le phenotype et le genotype de ces patients. Les resultats obtenus avec des patients XP-C ont contribue a une meilleure comprehension de l’etape de reconnaissance du dommage pendant la reparation par NER. Dans le meme temps, nous avons montre comment des mutations observees chez des patients XP-C peuvent abolir certains processus biologiques, et que la proteine XPC mutee dans les differents processus biologiques pourrait contribuer au phenotype du patient. Dans un second temps, nous avons egalement ete interesses par le role de XPA dans la voie de NER. De recents resultats ont demontre que XPA verifiait la bonne conformation de l’ADN, illustrant un possible «checkpoint» au cours de la reaction de reparation. En effet, les mutations dans XPA conduisent la reaction de reparation vers une impasse, etat qui pourrait contribuer a certains des phenotypes observes chez certains patients XP. Nos resultats avec les proteines XPC (impliquees dans la reconnaissance de la lesion) et XPA (impliquees dans la verification de la lesion) ont contribue a dessiner une image plus precise de la premiere etape de la NER. Dans le meme temps, nous avons elucide certaines proprietes biochimiques qui pourraient etre a l’origine des phenotypes observes chez les patients XP, en aidant a une meilleure caracterisation de la pathologie XP.
Revista Cientifica Integrada, May 12, 2013
Revista Cientifica Integrada, Jun 30, 2014
ABSTRACT O objetivo do presente estudo foi avaliar a aptidão física relacionada à saúde de homens... more ABSTRACT O objetivo do presente estudo foi avaliar a aptidão física relacionada à saúde de homens e mu-lheres, estudantes do curso de Educação Física/Esporte. Para tanto, 257 voluntários do curso de Educação Física/Esporte de ambos os sexos (132 mulheres e 125 homens), de 17 a 26 anos, foram submetidos a medidas antropométricas e os seguintes testes motores: sentar e alcançar (SA), abdominal modificado (ABD) e corrida/caminhada de 12 minutos (12min). Os resultados demonstraram diferenças significantes (p<0,05) entre homens e mulheres para o teste de 12min (homens = 2479 ± 333 vs. mulheres = 1899 ± 230 m), ABD (homens = 45 ± 9 vs. mulheres = 34 ± 10 repetições) e SA (homens = 31 ± 8 vs. mulheres = 33 ± 7 cm). Os homens apresentaram uma maior taxa de atendimento aos critérios estabelecidos no teste de 12min (homens = 62% vs. mulheres = 11%; p<0,05) e ABD (homens = 95% vs. mulheres = 85%; p<0,05), sem diferença significante entre os sexos no SA (homens = 93% vs. mulheres = 96%; p>0,05).A grande maioria dos sujeitos investigados atenderam os critérios estabelecidos para dois ou três testes analisados (92% dos homens e 85% das mulheres). Assim, os resultados sugerem que estudantes do curso de graduação em Educação Física/Esporte tendem a apresentar elevados níveis de resistência de força abdominal e flexibilidade, independente do sexo, embora grande parte deles apresente níveis de aptidão cardiorrespiratória insatisfatórios.
Revista Brasileira de Atividade Física & Saúde, 2013
This study aimed to evaluate health-related physical fitness in male and female undergraduate stu... more This study aimed to evaluate health-related physical fitness in male and female undergraduate students of Physical Education and Sports. Two hundred and fifty-seven 257 volunteer students aged 17 to 26 years (132 females and 125 males) underwent an antrhopometric assessment and motor fitness tests including sit-and-reach test (SRT), a modified abdominal fitness test (ABDT), and 12-minute run-walk test (12MRW). The results showed significant gender differences (p<0.05) in the 12MRW (males = 2,479 ± 333 vs. females = 1,899 ± 230 m), ABDT (males = 45 ± 9 vs. females = 34 ± 10 repetitions) and SRT (males = 31 ± 8 vs. females = 33 ± 7 cm). A higher proportion of males met the criteria in the 12MRW (males = 62% vs. females = 11%) and ABDT (males = 95% vs. females = 85%). Most subjects met the criteria in two or three tests (92% males and 85% females). These findings suggest that undergraduate students of Physical Education and Sports, either males or females, tend to have higher levels of abdominal strength and endurance and flexibility despite a low level of cardiorespiratory fitness.
Nature Communications, 2014
Coronary heart disease is one of the main causes of death in the developed world, and treatment s... more Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI.
Cell Reports, 2012
Aberrantly short telomeres result in decreased longevity in both humans and mice with defective t... more Aberrantly short telomeres result in decreased longevity in both humans and mice with defective telomere maintenance. Normal populations of humans and mice present high interindividual variation in telomere length, but it is unknown whether this is associated with their lifespan potential. To address this issue, we performed a longitudinal telomere length study along the lifespan of wild-type and transgenic telomerase reverse transcriptase mice. We found that mouse telomeres shorten $100 times faster than human telomeres. Importantly, the rate of increase in the percentage of short telomeres, rather than the rate of telomere shortening per month, was a significant predictor of lifespan in both mouse cohorts, and those individuals who showed a higher rate of increase in the percentage of short telomeres were also the ones with a shorter lifespan. These findings demonstrate that short telomeres have a direct impact on longevity in mammals, and they highlight the importance of performing longitudinal telomere studies to predict longevity.
Metabolites
Heart disease is the leading cause of mortality in developed countries. The associated pathology ... more Heart disease is the leading cause of mortality in developed countries. The associated pathology is characterized by a loss of cardiomyocytes that leads, eventually, to heart failure. In this context, several cardiac regenerative strategies have been developed, but they still lack clinical effectiveness. The mammalian neonatal heart is capable of substantial regeneration following injury, but this capacity is lost at postnatal stages when cardiomyocytes become terminally differentiated and transit to the fetal metabolic switch. Cardiomyocytes are metabolically versatile cells capable of using an array of fuel sources, and the metabolism of cardiomyocytes suffers extended reprogramming after injury. Apart from energetic sources, metabolites are emerging regulators of epigenetic programs driving cell pluripotency and differentiation. Thus, understanding the metabolic determinants that regulate cardiomyocyte maturation and function is key for unlocking future metabolic interventions fo...
Cancers, 2020
Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunot... more Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer treatment. Despite their potential success, current approaches depend on efficient tumor antigen presentation which are often inaccessible, and most tumors turn refractory to current immunotherapy. Patient-derived induced pluripotent stem cells (iPSCs) have been shown to share several characteristics with cancer (stem) cells (CSCs), eliciting a specific anti-tumoral response when injected in rodent cancer models. Indeed, artificial cellular reprogramming has...
Frontiers in Physiology, 2021
Heart disease is the leading cause of mortality in developed countries. The associated pathology ... more Heart disease is the leading cause of mortality in developed countries. The associated pathology is typically characterized by the loss of cardiomyocytes that leads, eventually, to heart failure. Although conventional treatments exist, novel regenerative procedures are warranted for improving cardiac regeneration and patients well fare. Whereas following injury the capacity for regeneration of adult mammalian heart is limited, the neonatal heart is capable of substantial regeneration but this capacity is lost at postnatal stages. Interestingly, this is accompanied by a shift in the metabolic pathways and energetic fuels preferentially used by cardiomyocytes from embryonic glucose-driven anaerobic glycolysis to adult oxidation of substrates in the mitochondria. Apart from energetic sources, metabolites are emerging as key regulators of gene expression and epigenetic programs which could impact cardiac regeneration. Long non-coding RNAs (lncRNAs) are known master regulators of cellula...
Frontiers in Physiology, 2021
Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangem... more Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangement of the cardiac structure and function and to a subsequent increased risk of heart failure. An intricate network of distinct pathways contributes to age-related alterations during healthy heart aging and account for a higher susceptibility of heart disease. Our understanding of the systemic aging process has already led to the design of anti-aging strategies or to the adoption of protective interventions. Nevertheless, our understanding of the molecular determinants operating during cardiac aging or repair remains limited. Here, we will summarize the molecular and physiological alterations that occur during aging of the heart, highlighting the potential role for long non-coding RNAs (lncRNAs) as novel and valuable targets in cardiac regeneration/repair.
BMC Cancer, 2019
Background: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcrip... more Background: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcriptome. LncRNAs present a very stringent cell-type/tissue specificity being potential candidates for therapeutical applications during aging and disease. As example, targeting of MALAT1, a highly conserved lncRNA originally identified in metastatic non-small cell lung cancer, has shown promising results in cancer regression. Nevertheless, the regulation and specificity of MALAT1 have not been directly addressed. Interestingly, MALAT1 locus is spanned by an antisense transcript named TALAM1. Methods: Here using a collection of breast cancer cells and in vitro and in vivo migration assays we characterized the dynamics of expression and demonstrated that TALAM1 regulates and synergizes with MALAT1 during tumorigenesis. Results: Down-regulation of TALAM1 was shown to greatly impact on the capacity of breast cancer cells to migrate in vitro or to populate the lungs of immunocompromised mice. Additionally, we demonstrated that TALAM1 cooperates with MALAT1 in the regulation of the properties guiding breast cancer aggressiveness and malignancy. Conclusions: By characterizing this sense/anti-sense pair we uncovered the complexity of MALAT1 locus regulation, describing new potential candidates for cancer targeting.
International Journal of Molecular Sciences, 2019
Epithelial–mesenchymal transition (EMT) is a cellular process by which differentiated epithelial ... more Epithelial–mesenchymal transition (EMT) is a cellular process by which differentiated epithelial cells undergo a phenotypic conversion to a mesenchymal nature. The EMT has been increasingly recognized as an essential process for tissue fibrogenesis during disease and normal aging. Higher levels of EMT proteins in aged tissues support the involvement of EMT as a possible cause and/or consequence of the aging process. Here, we will highlight the existing understanding of EMT supporting the phenotypical alterations that occur during normal aging or pathogenesis, covering the impact of EMT deregulation in tissue homeostasis and stem cell function.
Aging Cell, 2018
One of the most outstanding observations from next-generation sequencing approaches was that only... more One of the most outstanding observations from next-generation sequencing approaches was that only 1.5% of our genes code for proteins. The biggest part is transcribed but give rise to different families of RNAs without coding potential. The functional relevance of these abundant transcripts remains far from elucidated. Among them are the long non-coding RNAs (lncRNAs), a relatively large and heterogeneous group of RNAs shown to be highly tissue-specific, indicating a prominent role in processes controlling cellular identity. In particular, lncRNAs have been linked to both stemness properties and detrimental pathways regulating the aging process, being novel players in the intricate network guiding tissue homeostasis. Here, we summarize the up-to-date information on the role of lncRNAs that affect stemness and hence impact upon aging, highlighting the likelihood that lncRNAs may represent an unexploited reservoir of potential therapeutic targets for reprogramming applications and aging-related diseases.
Nature communications, Jan 8, 2018
Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here,... more Aging imposes a barrier to somatic cell reprogramming through poorly understood mechanisms. Here, we report that fibroblasts from old mice express higher levels of Zeb2, a transcription factor that activates epithelial-to-mesenchymal transition. Synthesis of Zeb2 protein is controlled by a natural antisense transcript named Zeb2-NAT. We show that transfection of adult fibroblasts with specific LNA Gapmers induces a robust downregulation of Zeb2-NAT transcripts and Zeb2 protein and enhances the reprogramming of old fibroblasts into pluripotent cells. We further demonstrate that Zeb2-NAT expression is precociously activated by differentiation stimuli in embryonic stem (ES) cells. By knocking down Zeb2-NAT, we were able to maintain ES cells challenged with commitment signals in the ground state of pluripotency. In conclusion, our study identifies a long noncoding RNA that is overlapping and antisense to the Zeb2 locus as a target for rejuvenation strategies.
Revista Cientifica Integrada, Jun 30, 2014
Revista Cientifica Integrada, Jun 30, 2014
Revista Cientifica Integrada, Jun 30, 2014
Revista Cientifica Integrada, Jun 30, 2014
Http Www Theses Fr, 2008
Afin de preserver l'integrite du genome des differentes lesions de l'ADN, plusieurs mecan... more Afin de preserver l'integrite du genome des differentes lesions de l'ADN, plusieurs mecanismes de reparation ont ete mis en place dans les cellules de mammiferes. La persistance des dommages de l'ADN dans le genome peut potentiellement porter atteinte a l'integrite cellulaire et a l'homeostasie, mais peut aussi conduire a l'apoptose de la cellule, a la senescence ou au cancer. Les mecanismes de reparation de l'ADN sont generalement divises en quatre grandes voies en fonction de la lesion portee par l'ADN : BER (reparation par excision de base), NER (reparation par excision de nucleotides), DSBR (reparation des cassures double brins), et MMR (reparation des mesappariements). NER est une voie de reparation de l'ADN qui traite une grande variete de lesions volumineuses (telles que les dommages a l'ADN formes par le rayonnement UV ou induits par les produits chimiques). Ce mecanisme pourrait etre divise en deux sous-voies: TCR (reparation couplee a la transcription) ou GGR (reparation globale du genome). BER est la voie responsable de la reparation des lesions qui distordent moins l’ADN, comme les modifications de bases, telle que celle produite par le stress oxydatif ou par la desamination. Dans la GGR, le complexe XPC-HR23B est responsable de l’etape de reconnaissance de la lesion, illustrant ainsi in vivo la premiere association entre des proteines de reparation et l’ADN endommage. En plus de l’activite d’ouverture a proximite du dommage, XPC pourrait aider a la reparation de des dommages oxydatifs de l'ADN. Des mutations dans la voie de NER pourraient conduire a trois maladies genetiques: Xeroderma pigmentosum (XP), le syndrome de Cockayne (CS) et la trichothiodystrophie (TTD). XP est caracterise par une extreme sensibilite a la lumiere du soleil, une predisposition au cancer de la peau et, dans certains cas, des de��ficiences neurologiques. Les differentes manifestations pathologiques observees chez les patients XP nous ont guide pour etudier la correlation possible entre le phenotype et le genotype de ces patients. Les resultats obtenus avec des patients XP-C ont contribue a une meilleure comprehension de l’etape de reconnaissance du dommage pendant la reparation par NER. Dans le meme temps, nous avons montre comment des mutations observees chez des patients XP-C peuvent abolir certains processus biologiques, et que la proteine XPC mutee dans les differents processus biologiques pourrait contribuer au phenotype du patient. Dans un second temps, nous avons egalement ete interesses par le role de XPA dans la voie de NER. De recents resultats ont demontre que XPA verifiait la bonne conformation de l’ADN, illustrant un possible «checkpoint» au cours de la reaction de reparation. En effet, les mutations dans XPA conduisent la reaction de reparation vers une impasse, etat qui pourrait contribuer a certains des phenotypes observes chez certains patients XP. Nos resultats avec les proteines XPC (impliquees dans la reconnaissance de la lesion) et XPA (impliquees dans la verification de la lesion) ont contribue a dessiner une image plus precise de la premiere etape de la NER. Dans le meme temps, nous avons elucide certaines proprietes biochimiques qui pourraient etre a l’origine des phenotypes observes chez les patients XP, en aidant a une meilleure caracterisation de la pathologie XP.
Revista Cientifica Integrada, May 12, 2013
Revista Cientifica Integrada, Jun 30, 2014
ABSTRACT O objetivo do presente estudo foi avaliar a aptidão física relacionada à saúde de homens... more ABSTRACT O objetivo do presente estudo foi avaliar a aptidão física relacionada à saúde de homens e mu-lheres, estudantes do curso de Educação Física/Esporte. Para tanto, 257 voluntários do curso de Educação Física/Esporte de ambos os sexos (132 mulheres e 125 homens), de 17 a 26 anos, foram submetidos a medidas antropométricas e os seguintes testes motores: sentar e alcançar (SA), abdominal modificado (ABD) e corrida/caminhada de 12 minutos (12min). Os resultados demonstraram diferenças significantes (p<0,05) entre homens e mulheres para o teste de 12min (homens = 2479 ± 333 vs. mulheres = 1899 ± 230 m), ABD (homens = 45 ± 9 vs. mulheres = 34 ± 10 repetições) e SA (homens = 31 ± 8 vs. mulheres = 33 ± 7 cm). Os homens apresentaram uma maior taxa de atendimento aos critérios estabelecidos no teste de 12min (homens = 62% vs. mulheres = 11%; p<0,05) e ABD (homens = 95% vs. mulheres = 85%; p<0,05), sem diferença significante entre os sexos no SA (homens = 93% vs. mulheres = 96%; p>0,05).A grande maioria dos sujeitos investigados atenderam os critérios estabelecidos para dois ou três testes analisados (92% dos homens e 85% das mulheres). Assim, os resultados sugerem que estudantes do curso de graduação em Educação Física/Esporte tendem a apresentar elevados níveis de resistência de força abdominal e flexibilidade, independente do sexo, embora grande parte deles apresente níveis de aptidão cardiorrespiratória insatisfatórios.
Revista Brasileira de Atividade Física & Saúde, 2013
This study aimed to evaluate health-related physical fitness in male and female undergraduate stu... more This study aimed to evaluate health-related physical fitness in male and female undergraduate students of Physical Education and Sports. Two hundred and fifty-seven 257 volunteer students aged 17 to 26 years (132 females and 125 males) underwent an antrhopometric assessment and motor fitness tests including sit-and-reach test (SRT), a modified abdominal fitness test (ABDT), and 12-minute run-walk test (12MRW). The results showed significant gender differences (p<0.05) in the 12MRW (males = 2,479 ± 333 vs. females = 1,899 ± 230 m), ABDT (males = 45 ± 9 vs. females = 34 ± 10 repetitions) and SRT (males = 31 ± 8 vs. females = 33 ± 7 cm). A higher proportion of males met the criteria in the 12MRW (males = 62% vs. females = 11%) and ABDT (males = 95% vs. females = 85%). Most subjects met the criteria in two or three tests (92% males and 85% females). These findings suggest that undergraduate students of Physical Education and Sports, either males or females, tend to have higher levels of abdominal strength and endurance and flexibility despite a low level of cardiorespiratory fitness.
Nature Communications, 2014
Coronary heart disease is one of the main causes of death in the developed world, and treatment s... more Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI.
Cell Reports, 2012
Aberrantly short telomeres result in decreased longevity in both humans and mice with defective t... more Aberrantly short telomeres result in decreased longevity in both humans and mice with defective telomere maintenance. Normal populations of humans and mice present high interindividual variation in telomere length, but it is unknown whether this is associated with their lifespan potential. To address this issue, we performed a longitudinal telomere length study along the lifespan of wild-type and transgenic telomerase reverse transcriptase mice. We found that mouse telomeres shorten $100 times faster than human telomeres. Importantly, the rate of increase in the percentage of short telomeres, rather than the rate of telomere shortening per month, was a significant predictor of lifespan in both mouse cohorts, and those individuals who showed a higher rate of increase in the percentage of short telomeres were also the ones with a shorter lifespan. These findings demonstrate that short telomeres have a direct impact on longevity in mammals, and they highlight the importance of performing longitudinal telomere studies to predict longevity.