RESUMO
INTRODUCTION: CAD (MIM*114010) encodes a large multifunctional protein with the enzymatic activity of the first three enzymes initiating and controlling the de novo pyrimidine biosynthesis pathway. Biallelic pathogenic variants in CAD cause the autosomal recessive developmental and epileptic encephalopathy 50 (MIM #616457) or CAD deficiency presenting with epilepsy, status epilepticus (SE), neurological deterioration and anemia with anisopoikilocytosis. Mortality is around 9% of patients, mainly related to the no use of its specific treatment with uridine. Majority of reported cases have an early onset during infancy, with some few starting later in childhood. CASE REPORT: Here we report a deceased female patient with CAD deficiency whose epilepsy started at 14 years. She showed a rapid neurologic deterioration including cognitive decline, electroencephalographic background slowing which later evolved to a fatal refractory SE and supra and infratentorial atrophy on neuroimaging. Anemia developed after SE onset. METHODS AND RESULTS: her post-mortem whole exome sequencing identified biallelic missense variants in CAD (NM_004341.5): c.[2944G > A];[5366G > A] p.[(Asp982Asn)];[(Arg1789Gln)]. Our review of twenty-eight reported cases (2015-2023) revealed an epilepsy age onset from neonatal period to 7 years and the SE prevalence of 46 %. DISCUSSION: With our case, we highlight the relevance of suspecting this treatable condition in older patients and in SE with no evident etiology.
Assuntos
Epilepsia , Humanos , Feminino , Epilepsia/genética , Adolescente , Di-Hidro-Orotase/genética , Mutação de Sentido Incorreto , Estado Epiléptico/genética , Disfunção Cognitiva/genética , Idade de Início , Aspartato Carbamoiltransferase , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)RESUMO
Army ant colonies host a diverse community of arthropod symbionts. Among the best-studied symbiont communities are those of Neotropical army ants of the genus Eciton. It is clear, however, that even in these comparatively well studied systems, a large proportion of symbiont biodiversity remains unknown. Even more striking is our lack of knowledge regarding the nature and specificity of these host-symbiont interactions. Here we surveyed the diversity and host specificity of rove beetles of the genus Tetradonia Wasmann, 1894 (Staphylinidae: Aleocharinae). Systematic community sampling of 58 colonies of the six local Eciton species at La Selva Biological Station, Costa Rica, combined with an integrative taxonomic approach, allowed us to uncover species diversity, host specificity, and co-occurrence patterns of symbionts in unprecedented detail. We used an integrative taxonomic approach combining morphological and genetic analyses, to delineate species boundaries. Mitochondrial DNA barcodes were analyzed for 362 Tetradonia specimens, and additional nuclear markers for a subset of 88 specimens. All analyses supported the presence of five Tetradonia species, including two species new to science. Host specificity is highly variable across species, ranging from generalists such as T. laticeps, which parasitizes all six local Eciton species, to specialists such as T. lizonae, which primarily parasitizes a single species, E. hamatum. Here we provide a dichotomous key along with diagnostic molecular characters for identification of Tetradonia species at La Selva Biological Station. By reliably assessing biodiversity and providing tools for species identification, we hope to set the baseline for future studies of the ecological and evolutionary dynamics in these species-rich host-symbiont networks.
Assuntos
Formigas/parasitologia , Biodiversidade , Besouros/fisiologia , Simbiose , Animais , Formigas/classificação , Aspartato Carbamoiltransferase/classificação , Aspartato Carbamoiltransferase/genética , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/classificação , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/genética , Besouros/classificação , Besouros/genética , Costa Rica , Código de Barras de DNA Taxonômico/métodos , DNA Mitocondrial/química , DNA Mitocondrial/genética , Di-Hidro-Orotase/classificação , Di-Hidro-Orotase/genética , Complexo IV da Cadeia de Transporte de Elétrons/classificação , Complexo IV da Cadeia de Transporte de Elétrons/genética , Especificidade de Hospedeiro , Proteínas de Insetos/classificação , Proteínas de Insetos/genética , Filogenia , Especificidade da EspécieRESUMO
Anopheles darlingi is a widely distributed and important malaria vector in Colombia. Biogeographical and ecological heterogeneity across the Colombian distribution led to the hypothesis of behavioral and genetic differentiation among A. darlingi populations. A total of 2017 A. darlingi specimens were collected during 222 h of sampling. This vector was the most abundant anopheline species in most of the localities sampled. Subdivision between samples collected west and east of the Andes was indicated by 1) mitochondrial COI and nuclear CAD sequences from NW-W and CE-S populations (COI ΦST=0.48761-0.81974, CAD FST=0.11319-0.21321), 2) a COI haplotype network, and 3) SAMOVA. Endo- and exophagy were detected in populations west of the Andes, whereas exophagy was evident in PTG, a locality east of the Andes. Isolation by resistance was significant for COI and explained 26% of the genetic differentiation. We suggest that at a macrogeographic scale, the Andes influence the differentiation of A. darlingi in Colombia and may drive divergence, and, at a microgeographic scale, ecological differences have a significant impact on structure. These data could constitute a baseline for the design of effective vector interventions, locality-specific for the east and similar for panmictic populations west of the Andes.
Assuntos
Anopheles/classificação , Anopheles/genética , Aspartato Carbamoiltransferase/genética , Evolução Biológica , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/genética , Di-Hidro-Orotase/genética , Complexo IV da Cadeia de Transporte de Elétrons/genética , Animais , Anopheles/fisiologia , Colômbia , Deriva Genética , Variação Genética , Haplótipos , Proteínas de Insetos/genética , Filogeografia , Densidade DemográficaRESUMO
Due to the lack of a complete urea cycle, uricotelic species, such as broilers, are not able to synthesize de novo arginine (Arg), thus depending exclusively on dietary Arg. High levels of dietary lysine (Lys) increase the demand for Arg because of the antagonistic relationship between these amino acids. The Arg-Lys antagonism promotes an expressive increase in the renal Arg activity and consequently induces the degradation of Arg and the decrease in the activity of glycine amidinotransferase, an enzyme that uses Arg in the synthesis of muscle creatin. Arg is considered an important modulator of immunological and physiological processes. The degradation of Arg produces ornithine, a precursor of polyamines that are key to cell division, DNA synthesis, and cell cycle regulation. Arg participates in the synthesis of nitric oxide (NO), a highly reactive free radical in cells and membranes and participates in several cell processes, including in neurotransmission and immune response. Arg is also considered a potent secretagogue of insulin, growth hormone, and IGF-I in the blood stream. Exclusively vegetarian diets may not provide an adequate supply of Arg, which is required for maximum production and for the immune system of current broiler lineages.
Devido à falta de um completo ciclo da uréia, espécies uricotélicas como os frangos de corte são incapazes de sintetizar arginina (Arg) de novo, por isso dependem exclusivamente da Arg dietética. Níveis elevados de lisina (Lys) dietética aumentam a exigência de Arg devido à relação antagônica entre estes aminoácidos. O antagonismo entre Arg e Lys promove expressiva elevação da atividade da arginase renal e conseqüentemente induz à degradação da Arg e leva à diminuição da atividade da glicina amidinotransferase, enzima que utiliza Arg na síntese de creatina muscular. Arg é considerada importante modulador da imunidade e de processos fisiológicos. A degradação de Arg gera ornitina, precursor das poliaminas que têm papel-chave na divisão celular, síntese de DNA e regulação do ciclo celular. A Arg é utilizada na síntese de óxido nítrico (NO), um radical livre altamente reativo, permeável às células e membranas que participa de vários processos celulares, incluindo a neurotransmissão e a imunidade. A Arg é também considerada um potente secretagogo da insulina, hormônio do crescimento e IGF-I. Dietas exclusivamente vegetais podem ser limitantes no fornecimento adequado de Arg para a maximização produtiva e do sistema imune das atuais linhagens de frangos de corte.
Assuntos
Animais , Arginina/deficiência , Arginina/imunologia , Arginina/metabolismo , Carbamoil Fosfato Sintase (Glutamina-Hidrolizante)/metabolismo , Creatina/metabolismo , Poliaminas/metabolismo , Óxido Nítrico/metabolismo , Arginina/administração & dosagem , Arginina/efeitos adversos , Ureia/efeitos adversos , Ureia/metabolismoRESUMO
Due to the lack of a complete urea cycle, uricotelic species, such as broilers, are not able to synthesize de novo arginine (Arg), thus depending exclusively on dietary Arg. High levels of dietary lysine (Lys) increase the demand for Arg because of the antagonistic relationship between these amino acids. The Arg-Lys antagonism promotes an expressive increase in the renal Arg activity and consequently induces the degradation of Arg and the decrease in the activity of glycine amidinotransferase, an enzyme that uses Arg in the synthesis of muscle creatin. Arg is considered an important modulator of immunological and physiological processes. The degradation of Arg produces ornithine, a precursor of polyamines that are key to cell division, DNA synthesis, and cell cycle regulation. Arg participates in the synthesis of nitric oxide (NO), a highly reactive free radical in cells and membranes and participates in several cell processes, including in neurotransmission and immune response. Arg is also considered a potent secretagogue of insulin, growth hormone, and IGF-I in the blood stream. Exclusively vegetarian diets may not provide an adequate supply of Arg, which is required for maximum production and for the immune system of current broiler lineages.(AU)
Devido à falta de um completo ciclo da uréia, espécies uricotélicas como os frangos de corte são incapazes de sintetizar arginina (Arg) de novo, por isso dependem exclusivamente da Arg dietética. Níveis elevados de lisina (Lys) dietética aumentam a exigência de Arg devido à relação antagônica entre estes aminoácidos. O antagonismo entre Arg e Lys promove expressiva elevação da atividade da arginase renal e conseqüentemente induz à degradação da Arg e leva à diminuição da atividade da glicina amidinotransferase, enzima que utiliza Arg na síntese de creatina muscular. Arg é considerada importante modulador da imunidade e de processos fisiológicos. A degradação de Arg gera ornitina, precursor das poliaminas que têm papel-chave na divisão celular, síntese de DNA e regulação do ciclo celular. A Arg é utilizada na síntese de óxido nítrico (NO), um radical livre altamente reativo, permeável às células e membranas que participa de vários processos celulares, incluindo a neurotransmissão e a imunidade. A Arg é também considerada um potente secretagogo da insulina, hormônio do crescimento e IGF-I. Dietas exclusivamente vegetais podem ser limitantes no fornecimento adequado de Arg para a maximização produtiva e do sistema imune das atuais linhagens de frangos de corte.(AU)