Flavio de Souza - Academia.edu (original) (raw)
Papers by Flavio de Souza
Colecao Meira Mattos Revista Das Ciencias Militares, Aug 26, 2014
Fitopatologia Brasileira, 2006
Proceedings of the Ifip Tc13 Third Interational Conference on Human Computer Interaction, 1990
This paper reports a case study of the evaluation of the effectiveness of a draft standard contai... more This paper reports a case study of the evaluation of the effectiveness of a draft standard containing human factors guidelines for menu interface design. Three designers were given a week to study the guidelines, before spending a day using the guidelines to redesign a menu interface. They were asked to justify their design in terms of the guidelines. The designers made errors or had difficulties with 91% of the guidelines. The cause of the errors and difficulties was analysed, which enabled recommendations for improvements to be made. Despite the difficulties with interpretation of the guidelines, the resulting interfaces only violated an average of 11% of the guidelines which could be assessed. It is concluded that it was difficult for the designers to integrate detailed design guidelines with their existing experience.
International journal of biological macromolecules, Jan 15, 2015
A novel GH1 β-glucosidase (EaBgl1A) from a bacterium isolated from Antarctica soil samples was re... more A novel GH1 β-glucosidase (EaBgl1A) from a bacterium isolated from Antarctica soil samples was recombinantly overexpressed in Escherichia coli cells and characterized. The enzyme showed unusual pH dependence with maximum activity at neutral pH and retention of high catalytic activity in the pH range 6 to 9, indicating a catalytic machinery compatible with alkaline conditions. EaBgl1A is also a cold-adapted enzyme, exhibiting activity in the temperature range from 10 to 40°C with optimal activity at 30°C, which allows its application in industrial processes using low temperatures. Kinetic characterization revealed an enzymatic turnover (Kcat) of 6.92s(-1) (cellobiose) and 32.98s(-1) (pNPG) and a high tolerance for product inhibition, which is an extremely desirable feature for biotechnological purposes. Interestingly, the enzyme was stimulated by up to 200mM glucose, whereas the commercial cocktails tested were found fully inhibited at this concentration. These properties indicate Ea...
Abakós, 2015
A sepse representa um evento mórbido de extrema importância do ponto de vista clínico e de saúde ... more A sepse representa um evento mórbido de extrema importância do ponto de vista clínico e de saúde pública, atingindo milhares de pessoas anualmente, no mundo. De uma perspectiva imunológica, os macrófagos são células extremamente importantes na interação Homo sapiens sapiens/ bactérias, ainda que muitos aspectos da atuação dessas células permaneçam aguardando elucidação. O presente artigo apresenta os requerimentos para a simulação computacional do macrófago no sistema AutoSimmune, permitindo o desenvolvimento de estudos sobre o papel dessa célula na sepse.
Proceedings of the National Academy of Sciences, 2015
Food intake and body weight regulation depend on proper expression of the proopiomelanocortin gen... more Food intake and body weight regulation depend on proper expression of the proopiomelanocortin gene (Pomc) in a group of neurons located in the mediobasal hypothalamus of all vertebrates. These neurons release POMC-encoded melanocortins, which are potent anorexigenic neuropeptides, and their absence from mice or humans leads to hyperphagia and severe obesity. Although the pathophysiology of hypothalamic POMC neurons is well understood, the genetic program that establishes the neuronal melanocortinergic phenotype and maintains a fully functional neuronal POMC phenotype throughout adulthood remains unknown. Here, we report that the early expression of the LIM-homeodomain transcription factor Islet 1 (ISL1) in the developing hypothalamus promotes the terminal differentiation of melanocortinergic neurons and is essential for hypothalamic Pomc expression since its initial onset and throughout the entire lifetime. We detected ISL1 in the prospective hypothalamus just before the onset of Pomc expression and, from then on, Pomc and Isl1 coexpress. ISL1 binds in vitro and in vivo to critical homeodomain binding DNA motifs present in the neuronal Pomc enhancers nPE1 and nPE2, and mutations of these sites completely disrupt the ability of these enhancers to drive reporter gene expression to hypothalamic POMC neurons in transgenic mice and zebrafish. ISL1 is necessary for hypothalamic Pomc expression during mouse and zebrafish embryogenesis. Furthermore, conditional Isl1 inactivation from POMC neurons impairs Pomc expression, leading to hyperphagia and obesity. Our results demonstrate that ISL1 specifies the identity of hypothalamic melanocortin neurons and is required for melanocortin-induced satiety and normal adiposity throughout the entire lifespan. hypothalamus | melanocortin | obesity | Isl1 | pomc
PLoS genetics, 2015
Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual en... more Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual enhancer controlling a particular expression domain. In contrast, multiple enhancers drive similar expression patterns of some genes involved in embryonic development, suggesting regulatory redundancy. Work in Drosophila has indicated that functionally overlapping enhancers canalize development by buffering gene expression against environmental and genetic disturbances. However, little is known about regulatory redundancy in vertebrates and in genes mainly expressed during adulthood. Here we study nPE1 and nPE2, two phylogenetically conserved mammalian enhancers that drive expression of the proopiomelanocortin gene (Pomc) to the same set of hypothalamic neurons. The simultaneous deletion of both enhancers abolished Pomc expression at all ages and induced a profound metabolic dysfunction including early-onset extreme obesity. Targeted inactivation of either nPE1 or nPE2 led to very low leve...
Mobile genetic elements, 2012
The proopiomelanocortin (Pomc) gene encodes a prepropeptide with essential functions in the respo... more The proopiomelanocortin (Pomc) gene encodes a prepropeptide with essential functions in the response to stress and energy balance, which is expressed in the pituitary and hypothalamus of vertebrate animals. Neuronal expression of Pomc is controlled by two distal enhancers named nPE1 and nPE2. Using transgenic mice, we observed that both enhancers drive identical expression patterns in the mammalian hypothalamus, starting at embryonic day 10.5, when endogenous Pomc expression commences. This overlapping enhancer activity is maintained throughout hypothalamic development and into adulthood. We also found that nPE1 and nPE2 were exapted as neuronal enhancers into the POMC locus after the sequential insertion of two unrelated retroposons. Thus, nPE1 and nPE2 are functional analogs and represent an authentic first example of convergent molecular evolution of cell-specific transcriptional enhancers. In this Commentary we discuss the following questions that remain unanswered: (1) how does...
Results in Mathematics, 2009
... [16] RS Pina, K. Tenenblat ... Flávio Raimundo de Souza Instituto Federal de Educaçao, Ciênc... more ... [16] RS Pina, K. Tenenblat ... Flávio Raimundo de Souza Instituto Federal de Educaçao, Ciência e Tecnologia de Goiás Campus Goiânia 74055-110 Goiânia, GO Brazil e-mail: matfrs@yahoo. com.br Keti Tenenblat Departamento de Matemática Universidade de Brasılia 70910 ...
Plant Systematics and Evolution, 2014
Molecular Biology and Evolution, 2005
The proopiomelanocortin gene (POMC) encodes several bioactive peptides, including adrenocorticotr... more The proopiomelanocortin gene (POMC) encodes several bioactive peptides, including adrenocorticotropin hormone, a-, b-, and c-melanocyte-stimulating hormone, and the opioid peptide b-endorphin, which play key roles in vertebrate physiology. In the human, mouse, and chicken genomes, there is only one POMC gene. By searching public genome projects, we have found that Tetraodon (Tetraodon nigroviridis), Fugu (Takifugu rubripes), and zebrafish (Danio rerio) possess two POMC genes, which we called POMCa and POMCb, and we present phylogenetic and mapping evidence that these paralogue genes originated in the whole-genome duplication specific to the teleost lineage over 300 MYA. In addition, we present evidence for two types of subfunction partitioning between the paralogues. First, in situ hybridization experiments indicate that the expression domains of the ancestral POMC gene have been subfunctionalized in Tetraodon, with POMCa expressed in the nucleus lateralis tuberis of the hypothalamus, as well as in the rostral pars distalis and pars intermedia (PI) of the pituitary, whereas POMCb is expressed in the preoptic area of the brain and weakly in the pituitary PI. Second, POMCb genes have a b-endorphin segment that lacks the consensus opioid signal and seems to be under neutral evolution in tetraodontids, whereas POMCa genes possess well-conserved peptide regions. Thus, POMC paralogues have experienced subfunctionalization of both expression and peptide domains during teleost evolution. The study of regulatory regions of fish POMC genes might shed light on the mechanisms of enhancer partitioning between duplicate genes, as well as the roles of POMC-derived peptides in fish physiology.
Molecular and Cellular Biology, 2005
The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypo... more The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-offunction mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions containing these enhancers are able to direct reporter gene expression to POMC hypothalamic neurons, but not the pituitary of transgenic mice. Conversely, deletion of nPE1 and nPE2 in the context of the entire transcriptional unit of POMC abolishes transgene expression in the hypothalamus without affecting pituitary expression. Our results indicate that the nPEs are necessary and sufficient for hypothalamic POMC expression and that POMC expression in the brain and pituitary is controlled by independent sets of enhancers. Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity.
Law & Social Inquiry, 2011
... in collaboration with Flavio de Souza, Associate Professor at the Federal University of Perna... more ... in collaboration with Flavio de Souza, Associate Professor at the Federal University of Pernambuco, Brazil, (survey analysis); Cecilia Giusti, Assistant ... work effectively and that this applies in developed countries as well as in developing countries (Linn 1983; de Soto 2000; Cole ...
International Planning Studies, 2000
PNAS, 2011
We are sorry, but NCBI web applications do not support your browser, and may not function properl... more We are sorry, but NCBI web applications do not support your browser, and may not function properly. More information here... ...
IEEE Transactions on Systems, Man and Cybernetics, Part C (Applications and Reviews), 2000
Page 1. 236 IEEE TRANSACTIONS ON SYSTEMS, MAN, AND CYBERNETICSPART C: APPLICATIONS AND REVIEWS, ... more Page 1. 236 IEEE TRANSACTIONS ON SYSTEMS, MAN, AND CYBERNETICSPART C: APPLICATIONS AND REVIEWS, VOL. 36, NO. 2, MARCH 2006 Inverted Hierarchical Neuro-Fuzzy BSP System: A Novel Neuro-Fuzzy Model for Pattern Classification and Rule ...
Arquivos Brasileiros de Cardiologia, 1999
Colecao Meira Mattos Revista Das Ciencias Militares, Aug 26, 2014
Fitopatologia Brasileira, 2006
Proceedings of the Ifip Tc13 Third Interational Conference on Human Computer Interaction, 1990
This paper reports a case study of the evaluation of the effectiveness of a draft standard contai... more This paper reports a case study of the evaluation of the effectiveness of a draft standard containing human factors guidelines for menu interface design. Three designers were given a week to study the guidelines, before spending a day using the guidelines to redesign a menu interface. They were asked to justify their design in terms of the guidelines. The designers made errors or had difficulties with 91% of the guidelines. The cause of the errors and difficulties was analysed, which enabled recommendations for improvements to be made. Despite the difficulties with interpretation of the guidelines, the resulting interfaces only violated an average of 11% of the guidelines which could be assessed. It is concluded that it was difficult for the designers to integrate detailed design guidelines with their existing experience.
International journal of biological macromolecules, Jan 15, 2015
A novel GH1 β-glucosidase (EaBgl1A) from a bacterium isolated from Antarctica soil samples was re... more A novel GH1 β-glucosidase (EaBgl1A) from a bacterium isolated from Antarctica soil samples was recombinantly overexpressed in Escherichia coli cells and characterized. The enzyme showed unusual pH dependence with maximum activity at neutral pH and retention of high catalytic activity in the pH range 6 to 9, indicating a catalytic machinery compatible with alkaline conditions. EaBgl1A is also a cold-adapted enzyme, exhibiting activity in the temperature range from 10 to 40°C with optimal activity at 30°C, which allows its application in industrial processes using low temperatures. Kinetic characterization revealed an enzymatic turnover (Kcat) of 6.92s(-1) (cellobiose) and 32.98s(-1) (pNPG) and a high tolerance for product inhibition, which is an extremely desirable feature for biotechnological purposes. Interestingly, the enzyme was stimulated by up to 200mM glucose, whereas the commercial cocktails tested were found fully inhibited at this concentration. These properties indicate Ea...
Abakós, 2015
A sepse representa um evento mórbido de extrema importância do ponto de vista clínico e de saúde ... more A sepse representa um evento mórbido de extrema importância do ponto de vista clínico e de saúde pública, atingindo milhares de pessoas anualmente, no mundo. De uma perspectiva imunológica, os macrófagos são células extremamente importantes na interação Homo sapiens sapiens/ bactérias, ainda que muitos aspectos da atuação dessas células permaneçam aguardando elucidação. O presente artigo apresenta os requerimentos para a simulação computacional do macrófago no sistema AutoSimmune, permitindo o desenvolvimento de estudos sobre o papel dessa célula na sepse.
Proceedings of the National Academy of Sciences, 2015
Food intake and body weight regulation depend on proper expression of the proopiomelanocortin gen... more Food intake and body weight regulation depend on proper expression of the proopiomelanocortin gene (Pomc) in a group of neurons located in the mediobasal hypothalamus of all vertebrates. These neurons release POMC-encoded melanocortins, which are potent anorexigenic neuropeptides, and their absence from mice or humans leads to hyperphagia and severe obesity. Although the pathophysiology of hypothalamic POMC neurons is well understood, the genetic program that establishes the neuronal melanocortinergic phenotype and maintains a fully functional neuronal POMC phenotype throughout adulthood remains unknown. Here, we report that the early expression of the LIM-homeodomain transcription factor Islet 1 (ISL1) in the developing hypothalamus promotes the terminal differentiation of melanocortinergic neurons and is essential for hypothalamic Pomc expression since its initial onset and throughout the entire lifetime. We detected ISL1 in the prospective hypothalamus just before the onset of Pomc expression and, from then on, Pomc and Isl1 coexpress. ISL1 binds in vitro and in vivo to critical homeodomain binding DNA motifs present in the neuronal Pomc enhancers nPE1 and nPE2, and mutations of these sites completely disrupt the ability of these enhancers to drive reporter gene expression to hypothalamic POMC neurons in transgenic mice and zebrafish. ISL1 is necessary for hypothalamic Pomc expression during mouse and zebrafish embryogenesis. Furthermore, conditional Isl1 inactivation from POMC neurons impairs Pomc expression, leading to hyperphagia and obesity. Our results demonstrate that ISL1 specifies the identity of hypothalamic melanocortin neurons and is required for melanocortin-induced satiety and normal adiposity throughout the entire lifespan. hypothalamus | melanocortin | obesity | Isl1 | pomc
PLoS genetics, 2015
Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual en... more Cell-specific expression of many genes is conveyed by multiple enhancers, with each individual enhancer controlling a particular expression domain. In contrast, multiple enhancers drive similar expression patterns of some genes involved in embryonic development, suggesting regulatory redundancy. Work in Drosophila has indicated that functionally overlapping enhancers canalize development by buffering gene expression against environmental and genetic disturbances. However, little is known about regulatory redundancy in vertebrates and in genes mainly expressed during adulthood. Here we study nPE1 and nPE2, two phylogenetically conserved mammalian enhancers that drive expression of the proopiomelanocortin gene (Pomc) to the same set of hypothalamic neurons. The simultaneous deletion of both enhancers abolished Pomc expression at all ages and induced a profound metabolic dysfunction including early-onset extreme obesity. Targeted inactivation of either nPE1 or nPE2 led to very low leve...
Mobile genetic elements, 2012
The proopiomelanocortin (Pomc) gene encodes a prepropeptide with essential functions in the respo... more The proopiomelanocortin (Pomc) gene encodes a prepropeptide with essential functions in the response to stress and energy balance, which is expressed in the pituitary and hypothalamus of vertebrate animals. Neuronal expression of Pomc is controlled by two distal enhancers named nPE1 and nPE2. Using transgenic mice, we observed that both enhancers drive identical expression patterns in the mammalian hypothalamus, starting at embryonic day 10.5, when endogenous Pomc expression commences. This overlapping enhancer activity is maintained throughout hypothalamic development and into adulthood. We also found that nPE1 and nPE2 were exapted as neuronal enhancers into the POMC locus after the sequential insertion of two unrelated retroposons. Thus, nPE1 and nPE2 are functional analogs and represent an authentic first example of convergent molecular evolution of cell-specific transcriptional enhancers. In this Commentary we discuss the following questions that remain unanswered: (1) how does...
Results in Mathematics, 2009
... [16] RS Pina, K. Tenenblat ... Flávio Raimundo de Souza Instituto Federal de Educaçao, Ciênc... more ... [16] RS Pina, K. Tenenblat ... Flávio Raimundo de Souza Instituto Federal de Educaçao, Ciência e Tecnologia de Goiás Campus Goiânia 74055-110 Goiânia, GO Brazil e-mail: matfrs@yahoo. com.br Keti Tenenblat Departamento de Matemática Universidade de Brasılia 70910 ...
Plant Systematics and Evolution, 2014
Molecular Biology and Evolution, 2005
The proopiomelanocortin gene (POMC) encodes several bioactive peptides, including adrenocorticotr... more The proopiomelanocortin gene (POMC) encodes several bioactive peptides, including adrenocorticotropin hormone, a-, b-, and c-melanocyte-stimulating hormone, and the opioid peptide b-endorphin, which play key roles in vertebrate physiology. In the human, mouse, and chicken genomes, there is only one POMC gene. By searching public genome projects, we have found that Tetraodon (Tetraodon nigroviridis), Fugu (Takifugu rubripes), and zebrafish (Danio rerio) possess two POMC genes, which we called POMCa and POMCb, and we present phylogenetic and mapping evidence that these paralogue genes originated in the whole-genome duplication specific to the teleost lineage over 300 MYA. In addition, we present evidence for two types of subfunction partitioning between the paralogues. First, in situ hybridization experiments indicate that the expression domains of the ancestral POMC gene have been subfunctionalized in Tetraodon, with POMCa expressed in the nucleus lateralis tuberis of the hypothalamus, as well as in the rostral pars distalis and pars intermedia (PI) of the pituitary, whereas POMCb is expressed in the preoptic area of the brain and weakly in the pituitary PI. Second, POMCb genes have a b-endorphin segment that lacks the consensus opioid signal and seems to be under neutral evolution in tetraodontids, whereas POMCa genes possess well-conserved peptide regions. Thus, POMC paralogues have experienced subfunctionalization of both expression and peptide domains during teleost evolution. The study of regulatory regions of fish POMC genes might shed light on the mechanisms of enhancer partitioning between duplicate genes, as well as the roles of POMC-derived peptides in fish physiology.
Molecular and Cellular Biology, 2005
The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypo... more The proopiomelanocortin (POMC) gene is expressed in the pituitary and arcuate neurons of the hypothalamus. POMC arcuate neurons play a central role in the control of energy homeostasis, and rare loss-offunction mutations in POMC cause obesity. Moreover, POMC is the prime candidate gene within a highly significant quantitative trait locus on chromosome 2 associated with obesity traits in several human populations. Here, we identify two phylogenetically conserved neuronal POMC enhancers designated nPE1 (600 bp) and nPE2 (150 bp) located approximately 10 to 12 kb upstream of mammalian POMC transcriptional units. We show that mouse or human genomic regions containing these enhancers are able to direct reporter gene expression to POMC hypothalamic neurons, but not the pituitary of transgenic mice. Conversely, deletion of nPE1 and nPE2 in the context of the entire transcriptional unit of POMC abolishes transgene expression in the hypothalamus without affecting pituitary expression. Our results indicate that the nPEs are necessary and sufficient for hypothalamic POMC expression and that POMC expression in the brain and pituitary is controlled by independent sets of enhancers. Our study advances the understanding of the molecular nature of hypothalamic POMC neurons and will be useful to determine whether polymorphisms in POMC regulatory regions play a role in the predisposition to obesity.
Law & Social Inquiry, 2011
... in collaboration with Flavio de Souza, Associate Professor at the Federal University of Perna... more ... in collaboration with Flavio de Souza, Associate Professor at the Federal University of Pernambuco, Brazil, (survey analysis); Cecilia Giusti, Assistant ... work effectively and that this applies in developed countries as well as in developing countries (Linn 1983; de Soto 2000; Cole ...
International Planning Studies, 2000
PNAS, 2011
We are sorry, but NCBI web applications do not support your browser, and may not function properl... more We are sorry, but NCBI web applications do not support your browser, and may not function properly. More information here... ...
IEEE Transactions on Systems, Man and Cybernetics, Part C (Applications and Reviews), 2000
Page 1. 236 IEEE TRANSACTIONS ON SYSTEMS, MAN, AND CYBERNETICSPART C: APPLICATIONS AND REVIEWS, ... more Page 1. 236 IEEE TRANSACTIONS ON SYSTEMS, MAN, AND CYBERNETICSPART C: APPLICATIONS AND REVIEWS, VOL. 36, NO. 2, MARCH 2006 Inverted Hierarchical Neuro-Fuzzy BSP System: A Novel Neuro-Fuzzy Model for Pattern Classification and Rule ...
Arquivos Brasileiros de Cardiologia, 1999