Estudo de 43 pacientes com atrofia muscular espinhal e seu diagnóstico molecular

Apendice e AnexosOrientadora: Rosana Herminia ScolaDissertaçao(mestrado)- Universidade Federal do Paraná. Setor de Ciencias da Saúde. Departamento de Clínica Médica. Curso de Pós-graduaçao em Medicina InternaInclui bibliografiaResumo: A atrofia muscular espinhal e uma doenca degenerativa das celulas do como anterior da medula, com quatro tipos descritos (I, II, IIIa/b, IV). Somente os tipos I, II, Illa e Illb apresentam comprometimento do cromossomo 5ql3, em que dois genes sao os causadores da doenca: o primeiro codifica a proteina de sobrevivencia do neuronio motor (SMN) e o segundo codifica a proteina inibidora da apoptose neuronal (NAIP). Ha delecao dos exons 7 e 8 em mais de 90% dos casos, ambos envolvidos na codificacao do SMN. A delecao do exon 5, envolvido na codificacao do NAIP, ocorre em 45% a 70% dos pacientes com atrofia muscular espinhal tipo I, e em menos de 20% dos casos tipo II e III. Com o proposito de desenvolver e introduzir o diagnostico molecular nas investigacoes de rotina da atrofia muscular espinhal, selecionaram-se 43 pacientes com diagnostico ja estabelecido de atrofia muscular espinhal, baseando-se no quadro clinico, dosagens enzimaticas, resultados de biopsia muscular e eletromiografia. Pesquisou-se a delecao dos exons envolvidos no DNA extraido de biopsias musculares atraves da analise por reacao em cadeia da polimerase. Relacionaram-se os resultados com os respectivos pacientes, por meio de dados de anamnese, exame fisico, achados de biopsia muscular e eletroneuromiografia. Nove pacientes foram classificados como tendo atrofia muscular espinhal tipo I; quatorze pacientes, como atrofia muscular espinhal tipo II, e 20, como atrofia muscular espinhal tipo III (12 Illa e 8 Illb). Nos pacientes com atrofia muscular espinhal tipo I, houve delecao do NAIP em 5 dos 9 casos (55%); naqueles com o tipo II, houve delecao em 3 dos 14 casos (21,4%). Todos os casos considerados como tipo I e II demonstraram delecao simultanea dos exons 7 e 8. No tipo III, o exon 5 esteve deletado em 5 dos 20 casos (25%), mas com delecao do exon 7 em 18 dos 20 pacientes (90%) e do exon 8 em 19 deles (95%). A delecao do NAIP teve relacao estatisticamente significante com os casos de fraqueza muscular da porcao distai dos membros superiores (p < 0,05) e com o achado de nucleos internos na biopsia muscular (p < 0,05). A delecao do exon 8 foi estatisticamente significante na presenca de fibras angulares atroficas (p < 0,05) e de fibras redondas atroficas dispersas (p < 0,05) na biopsia muscular. A biopsia muscular foi condizente com desinervacao em 80% dos casos, e a eletromiografia em 88,8%, enquanto que a delecao concomitante dos exons 7 e 8 esteve presente em 93% dos casos nos tres tipos de atrofia muscular espinhal. Ha estreita relacao entre o diagnostico clinico e o diagnostico molecular, corroborando os indices de delecao descritos na literatura. A analise pela reacao em cadeia da polimerase, portanto, serve como exame diagnostico tao seguro e preciso quanto a biopsia muscular e a eletromiografia. alem de menos invasiva.Abstract: Spinal muscle atrophy results from degeneration of motor neurons in the anterior horn of the spinal cord. There are four clinical types (I, II, IIIa/b, IV), but only three forms (I, II, Ilia and Illb) were found to be linked to the 5ql3 region o f chromosome 5, where 2 genes were postulated: one was designated as the Survival Motor Neuron (SMN) gene, and the other as the Neuronal Apoptosis Inhibitory Protein (NAIP) gene. Deletion of exons 7 and 8 occurs in over 90% of cases, both related to SMN codification. Deletion of exon 5 (related to NAIP gene) occurs in 45% to 70% of type I spinal muscle atrophy patients, and in less than 20% o f type II and III patients. The purpose o f this study is to develop and to establish molecular research in routine investigation of spinal muscle atrophy. Forty-three patients were included in this study, all o f them with previous diagnosis o f spinal muscle atrophy, according to their clinical features, muscular enzymes levels, electromyography and anatomopathologic results. The DNA was isolated from muscle biopsies. Polimerase chain reaction (PCR) amplification of SMN exons 7 and 8, and NAIP exon 5 was carried out and to clinical history, physical exam, electromyography and anatomopathologic results. A population o f 9 type I, fourteen patients type II and 20 patients type III (12 Ilia and 8 Illb) was enrolled into this study. Type I spinal muscle atrophy patients presented deletion of exon 5 (NAIP gene) in 5 cases (55%), and type II patients presented this deletion in 3 cases (21,4%). Type I and type II patients showed concomitant deletion of exons 7 and 8 in 100% o f cases. In type III patients, exon 5 was deleted in 5 cases (25%), with deletion of exon 7 in 18 patients (90%) and deletion o f exon 8 in 19 (95%) of them. Distal impairment of upper limbs was significantly correlated to the cases of NAIP deletion (p < 0,05), as to the presence of internal nucleus in muscle biopsy {p < 0,05). Deletion o f exon 8 was significantly correlated when associated to atrophic angulated fibers (p < 0,05) as well to the presence o f atrophic dispersed rounded fibers (p < 0,05) in muscle biopsy. Muscle biopsy presented with denervation in 80% of cases, and electromyography with the same pattern in 88,8%. Concomitant deletion of exons 7 and 8 occurred in 93% o f cases, in all three types of spinal muscle atrophy. Precise identification of deletion by PCR in spinal muscle atrophy patients provides an important diagnostic achievement, which may be considered as good as the muscle biopsy and electromyography, but less invasive

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

ATLANTIC EPIPHYTES: a data set of vascular and non-vascular epiphyte plants and lichens from the Atlantic Forest

Epiphytes are hyper-diverse and one of the frequently undervalued life forms in plant surveys and biodiversity inventories. Epiphytes of the Atlantic Forest, one of the most endangered ecosystems in the world, have high endemism and radiated recently in the Pliocene. We aimed to (1) compile an extensive Atlantic Forest data set on vascular, non-vascular plants (including hemiepiphytes), and lichen epiphyte species occurrence and abundance; (2) describe the epiphyte distribution in the Atlantic Forest, in order to indicate future sampling efforts. Our work presents the first epiphyte data set with information on abundance and occurrence of epiphyte phorophyte species. All data compiled here come from three main sources provided by the authors: published sources (comprising peer-reviewed articles, books, and theses), unpublished data, and herbarium data. We compiled a data set composed of 2,095 species, from 89,270 holo/hemiepiphyte records, in the Atlantic Forest of Brazil, Argentina, Paraguay, and Uruguay, recorded from 1824 to early 2018. Most of the records were from qualitative data (occurrence only, 88%), well distributed throughout the Atlantic Forest. For quantitative records, the most common sampling method was individual trees (71%), followed by plot sampling (19%), and transect sampling (10%). Angiosperms (81%) were the most frequently registered group, and Bromeliaceae and Orchidaceae were the families with the greatest number of records (27,272 and 21,945, respectively). Ferns and Lycophytes presented fewer records than Angiosperms, and Polypodiaceae were the most recorded family, and more concentrated in the Southern and Southeastern regions. Data on non-vascular plants and lichens were scarce, with a few disjunct records concentrated in the Northeastern region of the Atlantic Forest. For all non-vascular plant records, Lejeuneaceae, a family of liverworts, was the most recorded family. We hope that our effort to organize scattered epiphyte data help advance the knowledge of epiphyte ecology, as well as our understanding of macroecological and biogeographical patterns in the Atlantic Forest. No copyright restrictions are associated with the data set. Please cite this Ecology Data Paper if the data are used in publication and teaching events. © 2019 The Authors. Ecology © 2019 The Ecological Society of Americ

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Estudo de 43 pacientes com atrofia muscular espinhal e seu diagnóstico molecular

Apendice e AnexosOrientadora: Rosana Herminia ScolaDissertaçao(mestrado)- Universidade Federal do Paraná. Setor de Ciencias da Saúde. Departamento de Clínica Médica. Curso de Pós-graduaçao em Medicina InternaInclui bibliografiaResumo: A atrofia muscular espinhal e uma doenca degenerativa das celulas do como anterior da medula, com quatro tipos descritos (I, II, IIIa/b, IV). Somente os tipos I, II, Illa e Illb apresentam comprometimento do cromossomo 5ql3, em que dois genes sao os causadores da doenca: o primeiro codifica a proteina de sobrevivencia do neuronio motor (SMN) e o segundo codifica a proteina inibidora da apoptose neuronal (NAIP). Ha delecao dos exons 7 e 8 em mais de 90% dos casos, ambos envolvidos na codificacao do SMN. A delecao do exon 5, envolvido na codificacao do NAIP, ocorre em 45% a 70% dos pacientes com atrofia muscular espinhal tipo I, e em menos de 20% dos casos tipo II e III. Com o proposito de desenvolver e introduzir o diagnostico molecular nas investigacoes de rotina da atrofia muscular espinhal, selecionaram-se 43 pacientes com diagnostico ja estabelecido de atrofia muscular espinhal, baseando-se no quadro clinico, dosagens enzimaticas, resultados de biopsia muscular e eletromiografia. Pesquisou-se a delecao dos exons envolvidos no DNA extraido de biopsias musculares atraves da analise por reacao em cadeia da polimerase. Relacionaram-se os resultados com os respectivos pacientes, por meio de dados de anamnese, exame fisico, achados de biopsia muscular e eletroneuromiografia. Nove pacientes foram classificados como tendo atrofia muscular espinhal tipo I; quatorze pacientes, como atrofia muscular espinhal tipo II, e 20, como atrofia muscular espinhal tipo III (12 Illa e 8 Illb). Nos pacientes com atrofia muscular espinhal tipo I, houve delecao do NAIP em 5 dos 9 casos (55%); naqueles com o tipo II, houve delecao em 3 dos 14 casos (21,4%). Todos os casos considerados como tipo I e II demonstraram delecao simultanea dos exons 7 e 8. No tipo III, o exon 5 esteve deletado em 5 dos 20 casos (25%), mas com delecao do exon 7 em 18 dos 20 pacientes (90%) e do exon 8 em 19 deles (95%). A delecao do NAIP teve relacao estatisticamente significante com os casos de fraqueza muscular da porcao distai dos membros superiores (p < 0,05) e com o achado de nucleos internos na biopsia muscular (p < 0,05). A delecao do exon 8 foi estatisticamente significante na presenca de fibras angulares atroficas (p < 0,05) e de fibras redondas atroficas dispersas (p < 0,05) na biopsia muscular. A biopsia muscular foi condizente com desinervacao em 80% dos casos, e a eletromiografia em 88,8%, enquanto que a delecao concomitante dos exons 7 e 8 esteve presente em 93% dos casos nos tres tipos de atrofia muscular espinhal. Ha estreita relacao entre o diagnostico clinico e o diagnostico molecular, corroborando os indices de delecao descritos na literatura. A analise pela reacao em cadeia da polimerase, portanto, serve como exame diagnostico tao seguro e preciso quanto a biopsia muscular e a eletromiografia. alem de menos invasiva.Abstract: Spinal muscle atrophy results from degeneration of motor neurons in the anterior horn of the spinal cord. There are four clinical types (I, II, IIIa/b, IV), but only three forms (I, II, Ilia and Illb) were found to be linked to the 5ql3 region o f chromosome 5, where 2 genes were postulated: one was designated as the Survival Motor Neuron (SMN) gene, and the other as the Neuronal Apoptosis Inhibitory Protein (NAIP) gene. Deletion of exons 7 and 8 occurs in over 90% of cases, both related to SMN codification. Deletion of exon 5 (related to NAIP gene) occurs in 45% to 70% of type I spinal muscle atrophy patients, and in less than 20% o f type II and III patients. The purpose o f this study is to develop and to establish molecular research in routine investigation of spinal muscle atrophy. Forty-three patients were included in this study, all o f them with previous diagnosis o f spinal muscle atrophy, according to their clinical features, muscular enzymes levels, electromyography and anatomopathologic results. The DNA was isolated from muscle biopsies. Polimerase chain reaction (PCR) amplification of SMN exons 7 and 8, and NAIP exon 5 was carried out and to clinical history, physical exam, electromyography and anatomopathologic results. A population o f 9 type I, fourteen patients type II and 20 patients type III (12 Ilia and 8 Illb) was enrolled into this study. Type I spinal muscle atrophy patients presented deletion of exon 5 (NAIP gene) in 5 cases (55%), and type II patients presented this deletion in 3 cases (21,4%). Type I and type II patients showed concomitant deletion of exons 7 and 8 in 100% o f cases. In type III patients, exon 5 was deleted in 5 cases (25%), with deletion of exon 7 in 18 patients (90%) and deletion o f exon 8 in 19 (95%) of them. Distal impairment of upper limbs was significantly correlated to the cases of NAIP deletion (p < 0,05), as to the presence of internal nucleus in muscle biopsy {p < 0,05). Deletion o f exon 8 was significantly correlated when associated to atrophic angulated fibers (p < 0,05) as well to the presence o f atrophic dispersed rounded fibers (p < 0,05) in muscle biopsy. Muscle biopsy presented with denervation in 80% of cases, and electromyography with the same pattern in 88,8%. Concomitant deletion of exons 7 and 8 occurred in 93% o f cases, in all three types of spinal muscle atrophy. Precise identification of deletion by PCR in spinal muscle atrophy patients provides an important diagnostic achievement, which may be considered as good as the muscle biopsy and electromyography, but less invasive

Núcleos de Ensino da Unesp: artigos 2008

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans—anteaters, sloths, and armadillos—have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, 10 anteaters, and 6 sloths. Our data set includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the southern United States, Mexico, and Caribbean countries at the northern portion of the Neotropics, to the austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n = 5,941), and Cyclopes sp. have the fewest (n = 240). The armadillo species with the most data is Dasypus novemcinctus (n = 11,588), and the fewest data are recorded for Calyptophractus retusus (n = 33). With regard to sloth species, Bradypus variegatus has the most records (n = 962), and Bradypus pygmaeus has the fewest (n = 12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other data sets of Neotropical Series that will become available very soon (i.e., Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans data set. Please cite this data paper when using its data in publications. We also request that researchers and teachers inform us of how they are using these data