RESUMEN
Tau becomes abnormally hyper-phosphorylated and aggregated in tauopathies like Alzheimers disease (AD). As age is the greatest risk factor for developing AD, it is important to understand how tau protein itself, and the pathways implicated in its turnover, change during aging. We investigated age-related changes in total and phosphorylated tau in brain samples from two cohorts of cognitively normal individuals spanning 19-74 years, without overt neurodegeneration. One cohort utilised resected tissue and the other used post-mortem tissue. Total soluble tau levels declined with age in both cohorts. Phosphorylated tau was undetectable in the post-mortem tissue but was clearly evident in the resected tissue and did not undergo significant age-related change. To ascertain if the decline in soluble tau was correlated with age-related changes in autophagy, three markers of autophagy were tested but only two appeared to increase with age and the third was unchanged. This implies that in individuals who do not develop neurodegeneration, there is an age-related reduction in soluble tau which could potentially be due to age-related changes in autophagy. Thus, to explore how an age-related increase in autophagy might influence tau-mediated dysfunctions in vivo, autophagy was enhanced in a Drosophila model and all age-related tau phenotypes were significantly ameliorated. These data shed light on age-related physiological changes in proteins implicated in AD and highlights the need to study pathways that may be responsible for these changes. It also demonstrates the therapeutic potential of interventions that upregulate turnover of aggregate-prone proteins during aging.
Asunto(s)
Enfermedad de Alzheimer , Tauopatías , Animales , Humanos , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Proteínas tau/metabolismo , Tauopatías/metabolismo , Enfermedad de Alzheimer/metabolismo , Encéfalo/metabolismo , Drosophila/metabolismo , Autofagia/genética , FosforilaciónRESUMEN
Alcohol intoxication is known to affect pitch variability in non-tonal languages. In this study, intoxication's effects on pitch were examined in tonal and non-tonal language speakers, in both their native language (L1; German, Korean, Mandarin) and nonnative language (L2; English). Intoxication significantly increased pitch variability in the German group (in L1 and L2), but not in the Korean or Mandarin groups (in L1 or L2), although there were individual differences. These results support the view that pitch control is related to the functional load of pitch and is an aspect of speech production that can be advantageously transferred across languages, overriding the expected effects of alcohol.
Asunto(s)
Lenguaje , Percepción del Habla , Pueblo Asiatico , Humanos , Individualidad , Minerales , HablaRESUMEN
Although it has been often hypothesized that children learn to produce new sound patterns first in frequently heard words, the available evidence in support of this claim is inconclusive. To re-examine this question, we conducted a survival analysis of word-initial consonant clusters produced by three children in the Providence Corpus (0 ; 11-4 ; 0). The analysis took account of several lexical factors in addition to lexical input frequency, including the age of first production, production frequency, neighborhood density and number of phonemes. The results showed that lexical input frequency was a significant predictor of the age at which the accuracy level of cluster production in each word first reached 80%. The magnitude of the frequency effect differed across cluster types. Our findings indicate that some of the between-word variance found in the development of sound production can indeed be attributed to the frequency of words in the child's ambient language.