RESUMO
BACKGROUND: Language delay is extremely common in children with autism spectrum disorder (ASD), yet it is unclear whether measurable variation in early language is associated with genetic liability for ASD. Assessment of language development in unaffected siblings of children with ASD can inform whether decreased early language ability aggregates with inherited risk for ASD and serves as an ASD endophenotype. METHODS: We implemented two approaches: (1) a meta-analysis of studies comparing language delay, a categorical indicator of language function, and language scores, a continuous metric, in unaffected toddlers at high and low familial risk for ASD, and (2) a parallel analysis of 350 unaffected 24-month-olds in the Infant Brain Imaging Study (IBIS), a prospective study of infants at high and low familial risk for ASD. An advantage of the former was its detection of group differences from pooled data across unique samples; an advantage of the latter was its sensitivity in quantifying early manifestations of language delay while accounting for covariates within a single large sample. RESULTS: Meta-analysis showed that high-risk siblings without ASD (HR-noASD) were three to four times more likely to exhibit language delay versus low-risk siblings without ASD (LR-noASD) and had lower mean receptive and expressive language scores. Analyses of IBIS data corroborated that language delay, specifically receptive language delay, was more frequent in the HR-noASD (n = 235) versus LR-noASD group (n = 115). IBIS language scores were continuously and unimodally distributed, with a pathological shift towards decreased language function in HR-noASD siblings. The elevated inherited risk for ASD was associated with lower receptive and expressive language scores when controlling for sociodemographic factors. For receptive but not expressive language, the effect of risk group remained significant even when controlling for nonverbal cognition. CONCLUSIONS: Greater frequency of language delay and a lower distribution of language scores in high-risk, unaffected toddler-aged siblings support decreased early language ability as an endophenotype for ASD, with a more pronounced effect for receptive versus expressive language. Further characterization of language development is warranted to refine genetic investigations of ASD and to elucidate factors influencing the progression of core autistic traits and related symptoms.
Assuntos
Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/genética , Endofenótipos , Transtornos do Desenvolvimento da Linguagem/complicações , Transtornos do Desenvolvimento da Linguagem/genética , Irmãos/psicologia , Transtorno do Espectro Autista/fisiopatologia , Transtorno do Espectro Autista/psicologia , Encéfalo/fisiopatologia , Pré-Escolar , Feminino , Predisposição Genética para Doença , Humanos , Lactente , Transtornos do Desenvolvimento da Linguagem/fisiopatologia , Masculino , Estudos ProspectivosRESUMO
The neuropeptide Y (NPY) Y2 receptors and the pancreatic polypeptide Y4 receptors from rabbit kidney cortex are isolated largely as approximately 180 kDa complexes constituted of one receptor dimer and one G-protein heterotrimer, similar to NPY receptors expressed in the Chinese hamster ovary (CHO) cells. As expected, kidney and CHO cell Y2 dimers are converted into monomers by increasing concentrations of a selective agonist. Prevalence of dimeric Y2 receptors in the kidney could be related to low plasma levels of Y2 agonists, and possibly also to a relatively low concentration of Gi alpha subunits.
Assuntos
Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Proteínas de Ligação ao GTP/metabolismo , Córtex Renal/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Células CHO , Cricetinae , Cricetulus , Dimerização , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/genética , Masculino , Ligação Proteica , Coelhos , Receptores de Neuropeptídeo Y/agonistas , SolubilidadeRESUMO
The neuropeptide Y(NPY) Y2 receptors are detected largely as dimers in the clonal expressions in CHO cells and in particulates from rabbit kidney cortex. However, in two areas of the forebrain (rat or rabbit piriform cortex and hypothalamus), these receptors are found mainly as monomers. Evidence is presented that this difference relates to large levels of G proteins containing the Gi alpha -subunit in the forebrain areas. The predominant monomeric status of these Y2 receptors should also be physiologically linked to large synaptic inputs of the agonist NPY. The rabbit kidney and the human CHO cell-expressed Y2 dimers are converted by agonists to monomers in vitro at a similar rate in the presence of divalent cations.
Assuntos
Rim/metabolismo , Prosencéfalo/metabolismo , Receptores de Neuropeptídeo Y/metabolismo , Animais , Células CHO , Cátions Bivalentes/farmacologia , Cricetinae , Cricetulus , Dimerização , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Guanosina 5'-O-(3-Tiotrifosfato)/metabolismo , Humanos , Masculino , Ligação Proteica/efeitos dos fármacos , Coelhos , Ratos , Receptores de Neuropeptídeo Y/agonistas , Transdução de Sinais/efeitos dos fármacos , Frações Subcelulares/efeitos dos fármacos , Frações Subcelulares/metabolismoRESUMO
Peritrich ciliates of the genus Trichodina are internal or external symbionts of invertebrate and vertebrate hosts. We describe here Trichodina ctenophorii n. sp., a symbiont of Mnemiopsis mccraydii and Beroë ovata (Phylum Ctenophora). The morphology of fixed and living specimens is revealed by silver impregnation, scanning electron microscopy, and differential interference microscopy. Distinguishing features of Trichodina ctenophorii include a denticular morphology composed of falcate, blunt-tipped blades, and long, straight thorns, with five pins per denticle. Trichodina ctenophorii is found only on the comb plates of these ctenophores. To the best of our knowledge, this is the first report of a trichodinid from the Gulf of Mexico and the first associated with ctenophores.