RESUMO
An important goal in animal breeding is to improve longitudinal traits; that is, traits recorded multiple times during an individual's lifetime or physiological cycle. Longitudinal traits were first genetically evaluated based on accumulated phenotypic expression, phenotypic expression at specific time points, or repeatability models. Until now, the genetic evaluation of longitudinal traits has mainly focused on using random regression models (RRM). Random regression models enable fitting random genetic and environmental effects over time, which results in higher accuracy of estimated breeding values compared with other statistical approaches. In addition, RRM provide insights about temporal variation of biological processes and the physiological implications underlying the studied traits. Despite the fact that genomic information has substantially contributed to increase the rates of genetic progress for a variety of economically important traits in several livestock species, less attention has been given to longitudinal traits in recent years. However, including genomic information to evaluate longitudinal traits using RRM is a feasible alternative to yield more accurate selection and culling decisions, because selection of young animals may be based on the complete pattern of the production curve with higher accuracy compared with the use of traditional parent average (i.e., without genomic information). Moreover, RRM can be used to estimate SNP effects over time in genome-wide association studies. Thus, by analyzing marker associations over time, regions with higher effects at specific points in time are more likely to be identified. Despite the advances in applications of RRM in genetic evaluations, more research is needed to successfully combine RRM and genomic information. Future research should provide a better understanding of the temporal variation of biological processes and their physiological implications underlying the longitudinal traits.
Assuntos
Cruzamento/métodos , Genômica , Característica Quantitativa Herdável , Animais , Lactação/genética , Gado/genética , Modelos Genéticos , Fenótipo , Polimorfismo de Nucleotídeo Único/genética , Análise de RegressãoRESUMO
When the environment on which the animals are raised is very diverse, selecting the best sires for different environments may require the use of models that account for genotype by environment interaction (G × E). The main objective of this study was to evaluate the existence of G × E for yearling weight (YW) in Nellore cattle using reaction norm models with only pedigree and pedigree combined with genomic relationships. Additionally, genomic regions associated with each environment gradient were identified. A total of 67,996 YW records were used in reaction norm models to calculate EBV and genomic EBV. The method of choice for genomic evaluations was single-step genomic BLUP (ssGBLUP). Traditional and genomic models were tested on the ability to predict future animal performance. Genetic parameters for YW were obtained with the average information restricted maximum likelihood method, with and without adding genomic information for 5,091 animals. Additive genetic variances explained by windows of 200 adjacent SNP were used to identify genomic regions associated with the environmental gradient. Estimated variance components for the intercept and the slope in traditional and genomic models were similar. In both models, the observed changes in heritabilities and genetic correlations for YW across environments indicate the occurrence of genotype by environment interactions. Both traditional and genomic models were capable of identifying the genotype by environment interaction; however, the inclusion of genomic information in reaction norm models improved the ability to predict animals' future performance by 7.9% on average. The proportion of genetic variance explained by the top SNP window was 0.77% for the regression intercept (BTA5) and 0.82% for the slope (BTA14). Single-step GBLUP seems to be a suitable model to predict genetic values for YW in different production environments.
Assuntos
Bovinos/genética , Interação Gene-Ambiente , Variação Genética , Genômica , Modelos Genéticos , Animais , Peso Corporal/genética , Cruzamento , Bovinos/crescimento & desenvolvimento , Feminino , Genótipo , Masculino , Linhagem , FenótipoRESUMO
Animal feeding is the most important economic component of beef production systems. Selection for feed efficiency has not been effective mainly due to difficult and high costs to obtain the phenotypes. The application of genomic selection using SNP can decrease the cost of animal evaluation as well as the generation interval. The objective of this study was to compare methods for genomic evaluation of feed efficiency traits using different cross-validation layouts in an experimental beef cattle population genotyped for a high-density SNP panel (BovineHD BeadChip assay 700k, Illumina Inc., San Diego, CA). After quality control, a total of 437,197 SNP genotypes were available for 761 Nelore animals from the Institute of Animal Science, Sertãozinho, São Paulo, Brazil. The studied traits were residual feed intake, feed conversion ratio, ADG, and DMI. Methods of analysis were traditional BLUP, single-step genomic BLUP (ssGBLUP), genomic BLUP (GBLUP), and a Bayesian regression method (BayesCπ). Direct genomic values (DGV) from the last 2 methods were compared directly or in an index that combines DGV with parent average. Three cross-validation approaches were used to validate the models: 1) YOUNG, in which the partition into training and testing sets was based on year of birth and testing animals were born after 2010; 2) UNREL, in which the data set was split into 3 less related subsets and the validation was done in each subset a time; and 3) RANDOM, in which the data set was randomly divided into 4 subsets (considering the contemporary groups) and the validation was done in each subset at a time. On average, the RANDOM design provided the most accurate predictions. Average accuracies ranged from 0.10 to 0.58 using BLUP, from 0.09 to 0.48 using GBLUP, from 0.06 to 0.49 using BayesCπ, and from 0.22 to 0.49 using ssGBLUP. The most accurate and consistent predictions were obtained using ssGBLUP for all analyzed traits. The ssGBLUP seems to be more suitable to obtain genomic predictions for feed efficiency traits on an experimental population of genotyped animals.
Assuntos
Bovinos/genética , Genômica/métodos , Modelos Genéticos , Polimorfismo de Nucleotídeo Único , Ração Animal , Animais , Teorema de Bayes , Brasil , Cruzamento , Bovinos/metabolismo , Ingestão de Alimentos/genética , Ingestão de Alimentos/fisiologia , Genoma , Genótipo , Masculino , SoftwareRESUMO
Leprosy is a contagious and chronic systemic granulomatous disease caused by the bacillus Mycobacterium leprae. To our knowledge, no case of leprosy in a childhood-onset systemic lupus erythematosus (c-SLE) patient has been reported. For a period of 31 years, 312 c-SLE patients were followed at the Pediatric Rheumatology Unit of our University Hospital. One of them (0.3%) had tuberculoid leprosy skin lesions during the disease course and is here reported. A 10-year-old boy from Northwest of Brazil was diagnosed with c-SLE based on malar rash, photosensitivity, oral ulcers, lymphopenia, proteinuria, positive antinuclear antibodies, anti-double-stranded DNA, anti-Sm and anti-Ro/SSA autoantibodies. He was treated with prednisone, hydroxychloroquine and intravenous cyclophosphamide, followed by mycophenolate mofetil. At 12-years-old, he presented asymmetric skin lesions characterized by erythematous plaques with elevated external borders and hypochromic center with sensory loss. Peripheral nerve involvement was not evidenced. No history of familial cases of leprosy was reported, although the region where the patient resides is considered to be endemic for leprosy. Skin biopsy revealed a well-defined tuberculoid form. A marked thickening of nerves was observed, often destroyed by granulomas, without evidence of Mycobacterium leprae bacilli. At that time, the SLEDAI-2K score was 4 and he had been receiving prednisone 15 mg/day, hydroxychloroquine 200 mg/day and mycophenolate mofetil 3 g/day. Paucibacillary treatment for leprosy with dapsone and rifampicine was also introduced. In conclusion, we have reported a rare case of leprosy in the course of c-SLE. Leprosy should always be considered in children and adolescents with lupus who present skin abnormalities, particularly with hypoesthesic or anesthesic cutaneous lesions.
Assuntos
Hanseníase Paucibacilar/diagnóstico , Hanseníase Paucibacilar/microbiologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/microbiologia , Adolescente , Autoanticorpos/análise , Criança , Dapsona/uso terapêutico , Humanos , Hansenostáticos/uso terapêutico , Hanseníase Paucibacilar/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Masculino , Mycobacterium leprae/isolamento & purificação , Doenças Raras , Rifampina/uso terapêuticoRESUMO
Os objetivos deste trabalho foram estimar componentes de variância genética aditiva, fenotípica e residual e a herdabilidade para características relacionadas com a produção de mel e com a estrutura do ninho de abelhas Melipona quadrifasciata anthidioides. Sessenta colônias de diferentes regiões da Bahia foram transladadas para caixas padronizadas modelo INPA e divididas, originando as gerações parentais G1 e G2. Foram medidas as características: estimativa da produção de mel; número, largura, volume e altura dos potes de mel; número, altura e diâmetro dos potes de pólen; peso; número, largura e diâmetro dos discos de cria e estimativa da população da colônia. As medidas foram corrigidas para o efeito fixo de mês de mensuração. Os componentes de variância e herdabilidade foram estimados por meio do método de semelhança entre parentes, utilizando-se abordagem Bayesiana. As médias e os desvios padrão variaram de 2,01±0,70cm para diâmetro de potes de pólen a 2.333,0±384,1kg para o peso das caixas. Houve indicação de convergência para todas as cadeias obtidas. As estimativas de variância genética aditiva variaram de 0,02cm para as características largura dos potes de mel a 38.587,72kg para o peso. Para as estimativas de variâncias fenotípicas, os valores variaram de 0,05 para a altura dos potes de pólen a 95.136,43kg para o peso; e para as variâncias residuais, os valores encontrados variaram de 0,02 para a variável largura dos potes de mel a 56.548,71kg para o peso. As estimativas de herdabilidade variaram de 0,35 a 0,53. Os resultados demonstraram que as características avaliadas possuem variação genética aditiva que garante boa resposta à seleção.
The aim of this study was to estimate components of genetic variance, phenotypic and residual and heritability for traits related to the production of honey and the nest structure of bee Melipona quadrifasciata anthidioides. Sixty colonies from different regions of Bahia were transferred to standard INPA model boxes and divided, creating the parental generations G1 and G2. The following characteristics were measured: estimated production of honey, number, width, height and volume of the honey pots, number, height and diameter of pollen storage pots, weight, number, length and diameter of the brood combs and estimate the population of the colony. The measurements were corrected for the fixed effects of month of measurement. The variance components and heritability were estimated by the method of similarity between relatives using the Bayesian approach. The mean and standard deviations ranged from 2.01±0.70cm diameter pots for pollen to 2333.0±384.1kg to the weight of the boxes. There was indication of convergence for all the chains obtained. Estimates of the additive genetic variance ranged from 0.02cm to the width characteristics of honey pots to 38587.72kg for weight. For the estimates of phenotypic variance the values ranged from 0.05 for the height of the pollen pots to 95136.43kg for weight; and the residual variance the values varied from 0.02 for the variable width of the honey pots to 56548.71kg for weight. The results showed that the characteristics assessed have additive genetic variation that ensures good response to selection.
Assuntos
Animais , Abelhas/genética , Hereditariedade/genética , Análise de Variância , Teorema de Bayes , Mel/análise , Melhoramento Genético/métodos , FenótipoRESUMO
Os objetivos deste trabalho foram estimar componentes de variância genética aditiva, fenotípica e residual e a herdabilidade para características relacionadas com a produção de mel e com a estrutura do ninho de abelhas Melipona quadrifasciata anthidioides. Sessenta colônias de diferentes regiões da Bahia foram transladadas para caixas padronizadas modelo INPA e divididas, originando as gerações parentais G1 e G2. Foram medidas as características: estimativa da produção de mel; número, largura, volume e altura dos potes de mel; número, altura e diâmetro dos potes de pólen; peso; número, largura e diâmetro dos discos de cria e estimativa da população da colônia. As medidas foram corrigidas para o efeito fixo de mês de mensuração. Os componentes de variância e herdabilidade foram estimados por meio do método de semelhança entre parentes, utilizando-se abordagem Bayesiana. As médias e os desvios padrão variaram de 2,01±0,70cm para diâmetro de potes de pólen a 2.333,0±384,1kg para o peso das caixas. Houve indicação de convergência para todas as cadeias obtidas. As estimativas de variância genética aditiva variaram de 0,02cm para as características largura dos potes de mel a 38.587,72kg para o peso. Para as estimativas de variâncias fenotípicas, os valores variaram de 0,05 para a altura dos potes de pólen a 95.136,43kg para o peso; e para as variâncias residuais, os valores encontrados variaram de 0,02 para a variável largura dos potes de mel a 56.548,71kg para o peso. As estimativas de herdabilidade variaram de 0,35 a 0,53. Os resultados demonstraram que as características avaliadas possuem variação genética aditiva que garante boa resposta à seleção(AU)
The aim of this study was to estimate components of genetic variance, phenotypic and residual and heritability for traits related to the production of honey and the nest structure of bee Melipona quadrifasciata anthidioides. Sixty colonies from different regions of Bahia were transferred to standard INPA model boxes and divided, creating the parental generations G1 and G2. The following characteristics were measured: estimated production of honey, number, width, height and volume of the honey pots, number, height and diameter of pollen storage pots, weight, number, length and diameter of the brood combs and estimate the population of the colony. The measurements were corrected for the fixed effects of month of measurement. The variance components and heritability were estimated by the method of similarity between relatives using the Bayesian approach. The mean and standard deviations ranged from 2.01±0.70cm diameter pots for pollen to 2333.0±384.1kg to the weight of the boxes. There was indication of convergence for all the chains obtained. Estimates of the additive genetic variance ranged from 0.02cm to the width characteristics of honey pots to 38587.72kg for weight. For the estimates of phenotypic variance the values ranged from 0.05 for the height of the pollen pots to 95136.43kg for weight; and the residual variance the values varied from 0.02 for the variable width of the honey pots to 56548.71kg for weight. The results showed that the characteristics assessed have additive genetic variation that ensures good response to selection(AU)
Assuntos
Animais , Abelhas/genética , Hereditariedade/genética , Teorema de Bayes , Análise de Variância , Mel/análise , Fenótipo , Melhoramento Genético/métodosRESUMO
This study was conducted to evaluate the effect of inclusion of propolis extraction residue in the feed of broilers from 1 to 21 d of age on phagocytic activity of macrophages, cutaneous basophil hypersensitivity response to phytohemagglutinin, antibody production against Newcastle disease, lymphoid organ weight and hematological profile and to determine the optimal level of inclusion. 120 chicks, reared in metabolism cages until 21 days of age, were distributed in a completely randomized design, with five treatments (0%, 1%, 2%, 3%, and 4% of propolis residue) and six replications. The relative weight of thymus and monocyte percentage were affected by propolis residue, with a quadratic response (p<0.05) and lowest values estimated at 2.38% and 2.49%, respectively. Changes in relative weight of cloacal bursa and spleen, percentage of lymphocyte, heterophil, basophil, eosinophil, and heterophil:lymphocyte ratio, antibody production against Newcastle disease, phagocytic activity of macrophages and the average number of phagocytosed erythrocytes were not observed. The nitric oxide production with regard to positive control (macrophages+erythrocytes) decreased linearly (p<0.05) with increased doses of propolis residue. The remaining variables of nitric oxide production (negative control - macrophages, and difference between the controls) were not affected by propolis residue. The cutaneous basophil hypersensitivity response to phytohemagglutinin as determined by the increase in interdigital skin thickness exhibited a quadratic response (p<0.05), which predicted a lower reaction response at a dose of 2.60% of propolis residue and highest reaction response after 43.05 hours of phytohemagglutinin injection. The inclusion of 1% to 4% of propolis extraction residue in broiler diets from 1 to 21 days of age was not able to improve the immune parameters, despite the modest changes in the relative weight in thymus, blood monocyte percentage, nitric oxide concentration, and interdigital reaction to phytohemagglutinin.
RESUMO
Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childrens Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30-60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14-24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations.
Assuntos
Vesícula/patologia , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/patologia , Vesícula/etiologia , Brasil/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulinas/análise , Lúpus Eritematoso Sistêmico/complicações , Masculino , PrevalênciaRESUMO
The histomorphometric and proliferative characteristics of the collared peccary (Tayassu tajacu) placenta and uterus were analyzed. The material was examined by standard histological techniques and histochemistry (PAS, Perls and Alcian Blue pH 0.5 and 2.5%) and the cellular proliferation by AgNORs and flow cytometry. All the analyzed morphometric variables differed between pregnant and non-pregnant uteri in the luteal phase using the Dunnet test. Height and gland diameter of uterine glands increased linearly during pregnancy, with an intense positive PAS and Perls reaction in all stages. The cells with more than seven AgNORs per nuclei and the cells in the G2M cell cycle phase in the maternal tissue also increased after 70 days of pregnancy. The uteroplacental ridges had a linear increase in size with two distinct areas, base and top, with uterine epithelium and trophoblastic cells changing their morphology following the placental ridge development. Flow cytometry analysis showed the percentage of cells in each cell cycle phase with a quadratic behavior for stages G2/M in the maternal tissue, suggesting an increase in proliferative capacity of maternal tissue after 65 days of pregnancy. The same quadratic effect was observed in the G0/G1 phase in both maternal and fetal tissues. Cells in apoptosis showed cubic behavior in both tissues. The morphometric and cellular dynamic aspects observed in this study have not been previously described and they extend our knowledge of functions relating to maternal-fetal dynamics in this species.
Assuntos
Ciclo Celular , Proliferação de Células , Placenta/citologia , Útero/citologia , Animais , Antígenos Nucleares/metabolismo , Apoptose , Artiodáctilos , Feminino , Citometria de Fluxo , Idade Gestacional , Placenta/metabolismo , Gravidez , Coloração e Rotulagem/métodos , Útero/metabolismoRESUMO
Extreme myocardial degeneration leading to advanced stages of cardiomyopathy with extensive atrophy is rarely observed before patients die. However, heterotopic transplantation is a special situation wherein this phenomenon can be observed. The greater part of the failed heart shows recuperation after receiving circulatory assistance by reduction of myocardial work. Herein we have reported an unusual behavior of degenerative cardiomyopathy associated with intense myocardial apoptosis resulting in extreme ventricular atrophy after heterotopic heart transplantation. An 11-year-old girl with end-stage heart failure due to dilated cardiomyopathy of undetermined etiology without pulmonary hypertension underwent heterotopic cardiac transplantation with an undersized (by weight mismatch) donor heart. After 9 years heart failure reappeared due to native heart enlargement leading to allograft compression. The patient underwent native heart replacement leaving her with 2 donor hearts. Despite normal hemodynamic recuperation, the patient experienced massive arterial microemboli which led to death. Pathological studies showed exuberant myocardial degeneration in the native heart with intense atrophy of the muscle and gigantic ventricular enlargement. The left ventricle wall was extremely thin with rarefaction of cardiomyocytes and replacement by fibrosis. The right ventricle showed old extensive thrombosis. In conclusion, this report is not usual as it is not frequent to observe cardiomyopathy with an intense degree of myocardial degeneration and atrophy, because the patient dies earlier. In special situations it is possible that a recipient may have 2 donor hearts with normal hemodynamics. Heterotopic heart transplantation is a surgical alternative in a priority situation offering excellent outcomes; however, the native heart must be removed when there is compromise of the function of the heterotopic allograft.
Assuntos
Cardiomiopatia Dilatada/cirurgia , Transplante de Coração/métodos , Miocárdio/patologia , Transplante Heterotópico/métodos , Adulto , Atrofia , Criança , Evolução Fatal , Feminino , Seguimentos , Coração/anatomia & histologia , Transplante de Coração/efeitos adversos , Humanos , Tamanho do Órgão , Reoperação , Transplante Heterotópico/efeitos adversos , Transplante Homólogo/efeitos adversosRESUMO
Schistosomiasis mansoni is a non-cirrhotic liver disease. In cirrhosis patients with portal hypertension, a decreased number of reticulated platelets associated with increased thrombopoietin serum levels were reported. We previously reported a 120/nl platelet cutoff level as a marker of clinically significant portal hypertension in schistosomiasis patients. To evaluate reticulated platelet counts and thrombopoietin serum levels (TPO) in schistosomiasis patients and correlate them with portal hypertension markers. Thirty-three schistosomiasis patients without co-morbidities were endoscopically classified as those with (n = 19) or without (n = 14) clinically significant portal hypertension. Flow cytometric determination of reticulated platelets was performed using CD41 antibody and thiazol orange. Ultrasonographic examinations were performed according to the Niamey protocol. TPO and hyaluronic acid serum levels were determined in duplicate using ELISA methods. The platelet number of 120/nl discriminates the two groups with 100% accuracy and 100% positive and negative predictive values, and correlates with spleen length and portal and splenic vein diameters. Differences in reticulated platelets and hyaluronic acid serum levels between both groups were significant (P = 0.025 and 0.012, respectively), but thrombopoietin serum levels were not (P = 0.769). Schistosomiasis patients with portal hypertension have increased reticulated platelets associated with normal TPO serum levels.
Assuntos
Plaquetas/citologia , Esquistossomose/sangue , Trombopoetina/sangue , Plaquetas/metabolismo , Citometria de Fluxo , Humanos , Ácido Hialurônico/sangue , Padrões de Referência , Esquistossomose/diagnóstico por imagem , UltrassonografiaRESUMO
OBJECTIVE: Only few large families with multiple endocrine neoplasia type 1 (MEN1) have been documented. Here, we aimed to investigate the clinical features of a seven-generation Brazilian pedigree, which included 715 at-risk family members. DESIGN: Genealogical and geographic analysis was used to identify the MEN1 pedigree. Clinical and genetic approach was applied to characterize the phenotypic and genotypic features of the family members. RESULTS: Our genetic data indicated that a founding mutation in the MEN1 gene has occurred in this extended Brazilian family. Fifty family members were diagnosed with MEN1. Very high frequencies of functioning and non-functioning MEN1-related tumors were documented and the prevalence of prolactinoma (29.6%) was similar to that previously described in prolactinoma-variant Burin (32%). In addition, bone mineral density analysis revealed severe osteoporosis (T, -2.87+/-0.32) of compact bone (distal radius) in hyperparathyroidism (HPT)/MEN1 patients, while marked bone mineral loss in the lumbar spine (T, -1.95+/-0.39), with most cancellous bone, and femoral neck (mixed composition; T, -1.48+/-0.27) were also present. CONCLUSIONS: In this study, we described clinically and genetically the fifth largest MEN1 family in the literature. Our data confirm previous findings suggesting that prevalence of MEN1-related tumors in large families may differ from reports combining cumulative data of small families. Furthermore, we were able to evaluate the bone status in HPT/MEN1 cases, a subject that has been incompletely approached in the literature. We discussed the bone loss pattern found in our MEN1 patients comparing with that of patients with sporadic primary HPT.
Assuntos
Densidade Óssea , Efeito Fundador , Neoplasia Endócrina Múltipla Tipo 1/genética , Neoplasia Endócrina Múltipla Tipo 1/fisiopatologia , Proteínas Proto-Oncogênicas/genética , Adolescente , Adulto , Densidade Óssea/genética , Brasil , Análise Mutacional de DNA , Família , Feminino , Geografia , Mutação em Linhagem Germinativa/fisiologia , Haplótipos , Humanos , Hipertireoidismo/complicações , Hipertireoidismo/genética , Masculino , Pessoa de Meia-Idade , Neoplasia Endócrina Múltipla Tipo 1/complicações , Neoplasia Endócrina Múltipla Tipo 1/diagnóstico , LinhagemRESUMO
The actin cytoskeleton controls pivotal cellular processes such as motility and cytokinesis, as well as cell-cell and cell-substrate interactions. Assembly and spatial organization of actin filaments are dynamic events regulated by a large repertoire of actin-binding proteins. This report presents the first detailed characterization of the Trypanosoma cruzi actin (TcActin). Protein sequence analysis and homology modelling revealed that the overall structure of T. cruzi actin is conserved and that the majority of amino-acid changes are concentrated on the monomer surface. Immunofluorescence assays using specific polyclonal antibody against TcActin revealed numerous rounded and punctated structures spread all over the parasitic body. No pattern differences could be found between epimastigotes and trypomastigotes or amastigotes. Moreover, in detergent extracts, TcActin was localized only in the soluble fraction, indicating its presence in the G-actin form or in short filaments dissociated from the microtubule cytoskeleton. The trypanosomatid genome was prospected to identify actin-binding and actin-related conserved proteins. The main proteins responsible for actin nucleation and treadmilling in higher eukaryotes are conserved in T. cruzi.
Assuntos
Actinas/metabolismo , Evolução Molecular , Proteínas dos Microfilamentos/química , Proteínas dos Microfilamentos/genética , Trypanosoma cruzi/metabolismo , Actinas/análise , Actinas/química , Actinas/imunologia , Animais , Anticorpos Antiprotozoários , Especificidade de Anticorpos , Sequência Conservada , Humanos , Espaço Intracelular , Dados de Sequência Molecular , Estrutura Terciária de Proteína , Trypanosoma cruzi/genética , Trypanosoma cruzi/imunologiaRESUMO
Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60 percent being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8 percent) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8 percent) and the heterozygous form 677TC was observed in 18 patients (34 percent, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, ß-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Anemia Falciforme/genética , Fator V/genética , /genética , Polimorfismo Genético , Doenças Vasculares Periféricas/etiologia , Protrombina/genética , Alelos , Anemia Falciforme/complicações , Marcadores Genéticos , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
Sickle cell disease (SCD) is one of the most common inherited diseases in the world and the patients present notorious clinical heterogeneity. It is known that patients with SCD present activation of the blood coagulation and fibrinolytic systems, especially during vaso-occlusive crises, but also during the steady state of the disease. We determined if the presence of the factor V gene G1691A mutation (factor V Leiden), the prothrombin gene G20210A variant, and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism may be risk factors for vascular complications in individuals with SCD. We studied 53 patients with SCD (60% being women), 29 with SS (sickle cell anemia; 28 years, range: 13-52 years) and 24 with SC (sickle-hemoglobin C disease; 38.5 years, range: 17-72 years) hemoglobinopathy. Factor V Leiden, MTHFR C677T polymorphism, and prothrombin G20210A variant were identified by PCR followed by further digestion of the PCR product with specific endonucleases. The following vascular complications were recorded: stroke, retinopathy, acute thoracic syndrome, and X-ray-documented avascular necrosis. Only one patient was heterozygous for factor V Leiden (1.8%) and there was no prothrombin G20210A variant. MTHFR 677TT polymorphism was detected in 1 patient (1.8%) and the heterozygous form 677TC was observed in 18 patients (34%, 9 with SS and 9 with SC disease), a prevalence similar to that reported by others. No association was detected between the presence of the MTHFR 677T allele and other genetic modulation factors, such as alpha-thalassemia, beta-globin gene haplotype and fetal hemoglobin. The presence of the MTHFR 677T allele was associated with the occurrence of vascular complications in SCD, although this association was not significant when each complication was considered separately. In conclusion, MTHFR C677T polymorphism might be a risk factor for vascular complications in SCD.
Assuntos
Anemia Falciforme/genética , Fator V/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Doenças Vasculares Periféricas/etiologia , Polimorfismo Genético , Protrombina/genética , Adolescente , Adulto , Idoso , Alelos , Anemia Falciforme/complicações , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Reação em Cadeia da Polimerase , Fatores de RiscoRESUMO
Several infectious etiologies are related to cerebral venous thrombosis (CVT), but a review of literature showed only few cases related to tuberculosis (TB), and only one with neurological manifestations.We report an unusual case of CVT related to TB and mutation in prothrombin gene. A 38-man black presented abrupt right hemiparestesis, and hemiparesis. Investigations revealed CVT. Cerebral spinal fluid (CSF) examination evidenced an infection by Mycobacterium. He was heterozygous for G20210A prothrombin mutation. Probably, hypercoagulability mechanisms of TB, added to mutation of prothrombin gene increase the risk of CVT.
As mais variadas etiologias infecciosas estão relacionadas a trombose venosa cerebral (TVC), mas revisando-se a literatura há apenas poucos relatos de casos que se devem à tuberculose (TB), sendo que em apenas um deles havia manifestações no sistema nervoso central.Relatamos um caso de TVC associado a TB e a mutação do gene da protrombina. Homem 38 anos, negro, apresentou hemiparestesia de instalação súbita à direita, evoluindo com hemiparesia homolateral. Durante a internação, foi coletado líquor que evidenciou infecção por micobactéria. A pesquisa de trombofilias mostrou positividade somente para mutação do gene da protrombina(G20210A). Provavelmente os mecanismos de hipercoagulabilidade intrínsecos à tuberculose somados à mutação do gene da protrombina, potencializam o risco de TVC.
Assuntos
Adulto , Humanos , Masculino , Trombose Intracraniana/microbiologia , Trombose Venosa/microbiologia , Tuberculose do Sistema Nervoso Central/complicações , Imageamento por Ressonância Magnética , Mutação Puntual , Protrombina/genéticaAssuntos
Trombose Intracraniana/genética , Mutação Puntual , Protrombina/genética , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Fator V , Feminino , Humanos , Trombose Intracraniana/epidemiologia , Trombose Intracraniana/etiologia , Masculino , Epidemiologia Molecular , Fatores de Risco , Trombose Venosa/epidemiologia , Trombose Venosa/etiologia , Trombose Venosa/genéticaRESUMO
Fasting total homocysteine (tHcy) and the methylenetetrahydrofolate reductase (MTHFR) C677T mutation were evaluated in 91 patients with venous thromboembolism and without acquired thrombophilia, and in 91 age-matched and sex-matched controls. Hyperhomocysteinemia was detected in 11 patients (12.1%) and in two controls (2.2%), yielding an odds ratio (OR) for venous thrombosis of 6.1 [95% confidence interval (CI), 1.3-28.4]. After excluding 21 patients and four controls with other known genetic risk factors for venous thrombosis, the OR was not substantially changed (7.0; 95% CI, 1.5-33.1). The prevalence of the MTHFR 677TT genotype was not significantly different in patients (9.9%) and in controls (5.5%), with an OR for venous thrombosis of 1.8 (95% CI, 0.6-5.8). Subjects with the MTHFR 677TT genotype showed higher levels of tHcy compared with the 677CC genotype in patients (P = 0.010) and in controls (P = 0.030). In conclusion, we found that fasting hyperhomocysteinemia is a risk factor for venous thrombosis in patients without known acquired thrombophilia and other genetic risk factors for venous thrombosis. Although tHcy levels are significantly higher in those homozygous for the MTHFR C677T mutation, this genotype does not increase the thrombotic risk in our study population.
Assuntos
Substituição de Aminoácidos , Hiper-Homocisteinemia/epidemiologia , Mutação de Sentido Incorreto , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Mutação Puntual , Trombofilia/epidemiologia , Trombose Venosa/epidemiologia , Regiões 3' não Traduzidas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Criança , Jejum/sangue , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2) , Pessoa de Meia-Idade , Razão de Chances , Polimorfismo Genético , Regiões Promotoras Genéticas/genética , Protrombina/genética , Fatores de Risco , Trombofilia/sangue , Trombofilia/genética , Trombose Venosa/etiologiaRESUMO
BACKGROUND AND OBJECTIVES: Thrombin activatable fibrinolysis inhibitor (TAFI) plays an important role in hemostasis, functioning as a potent fibrinolysis inhibitor. TAFI gene variations may contribute to plasma TAFI levels and thrombotic risk. DESIGN AND METHODS: We sequenced a 2083-bp region of the 5'-regulatory region of the TAFI gene in 127 healthy subjects searching for variations, and correlated identified polymorphisms with plasma TAFI levels. TAFI polymorphisms were examined as risk factors for venous thrombosis by determining their prevalence in 388 patients with deep venous thrombosis (DVT) and in 388 controls. RESULTS: Seven novel polymorphisms were identified: -152 A/G, -438 A/G, -530 C/T, -1053 T/C, -1102 T/G, -1690 G/A, and -1925 T/C. -152 A/G, -530 C/T and -1925 T/C were found to be in strong linkage disequilibrium, as were the -438 A/G, -1053 T/C, -1102 T/G and -1690 G/A. Plasma TAFI levels were higher in -438GG/-1053CC/-1102GG/-1690AA homozygotes than in -438AG/-1053TC/-1102TG/-1690GA heterozygotes, and -438AA/-1053TT/-1102TT/-1690GG homozygotes had the lowest TAFI levels (p=0.0003). TAFI concentrations in -152AA/-530CC/-1925TT homozygotes were somewhat higher but not significantly different from levels observed for -152AG/-530CT/-1925TC heterozygotes. Taken in combination, -438AG/-1053TC/-1102TG/-1690GA and -438AA/-1053TT/-1102TT/-1690GG yielded an OR for DVT of 0.8 (95%CI: 0.6-1). In subjects aged <35 years the OR was 0.7 (95%CI: 0.5-1.1). The OR for -152AG/-530CT/-1925TC was 1 (95%CI: 0.5-2.2) in the whole group of patients and controls, whereas in subjects aged <35 years the OR was 0.1 (95%CI: 0.02-0.9). INTERPRETATION AND CONCLUSIONS: Polymorphisms in the TAFI promoter determine plasma antigen levels and may influence the risk of venous thrombophilia.
Assuntos
Regiões 5' não Traduzidas/genética , Carboxipeptidase B2/genética , Trombose Venosa/genética , Adolescente , Adulto , Idoso , Brasil/epidemiologia , Carboxipeptidase B2/efeitos adversos , Carboxipeptidase B2/sangue , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Fatores de Risco , Análise de Sequência de DNA , Trombose Venosa/epidemiologia , Trombose Venosa/etiologiaRESUMO
Severe consumption coagulopathy has been detected in rats after Lopap (a prothrombin activator from Lonomia obliqua caterpillar bristles) infusion and in humans after accidental contact with L. obliqua bristles. However, platelet count and antithrombin (AT) levels were only modestly affected, suggesting that a different form of blood coagulation activation may be involved in this hemorrhagic syndrome. Here we describe that Lopap had no effect on aggregation of washed human platelets induced by several agonists, suggesting that it might not impair platelet function in vivo. AT was able to inhibit the amidolytic activity of thrombin generated by incubation of Lopap with prothrombin in a purified system, which may be different from that generated by the prothrombinase complex in vivo. The surface expression of both ICAM-1 and E-selectin but not of VCAM-1 was upregulated by Lopap in cultured HUVEC, suggesting that it may behave differently from other mediators, such as thrombin and tumor necrosis factor-alpha.