RESUMEN
INTRODUCTION: Research suggests an association between global cognition and postural instability/gait disturbance (PIGD) in Parkinson disease (PD), but the relationship between specific cognitive domains and PIGD symptoms is not clear. This study examined the association of cognition (global and specific cognitive domains) with PIGD symptoms in a large, well-characterized sample of individuals with PD. METHODS: Cognitive function was measured with a detailed neuropsychological assessment, including global cognition, executive function, memory, visuospatial function, and language. PIGD symptoms were measured using the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, Motor Examination subscale. Multiple linear regression analyses were performed to assess the relationship between cognition and PIGD symptoms with models adjusting for age, sex, education, enrollment site, disease duration, and motor symptom severity. RESULTS: The analysis included 783 participants, with mean (standard deviation) age of 67.3 (9.7) years and median (interquartile range) MDS-UPDRS Motor Subscale score of 26 (17, 35). Deficits in global cognition, executive function, memory, and phonemic fluency were associated with more severe PIGD symptoms. Deficits in executive function were associated with impairments in gait, freezing, and postural stability, while visuospatial impairments were associated only with more severe freezing, and poorer memory function was associated only with greater postural instability. DISCUSSION: While impairments in global cognition and aspects of executive functioning were associated with more severe PIGD symptoms, specific cognitive domains were differentially related to distinct PIGD components, suggesting the presence of multiple neural pathways contributing to associations between cognition and PIGD symptoms in persons with PD.
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Trastornos del Conocimiento/diagnóstico , Trastornos del Conocimiento/psicología , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/psicología , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/psicología , Equilibrio Postural , Anciano , Cognición/fisiología , Estudios Transversales , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Equilibrio Postural/fisiologíaRESUMEN
The telomerase enzyme lengthens telomeres, an activity essential for chromosome stability in most eukaryotes. The enzyme is composed of a specialized reverse transcriptase and a template RNA. In Saccharomyces cerevisiae, overexpression of TLC1, the telomerase RNA gene, disrupts telomeric structure. The result is both shortened telomere length and loss of a special chromatin structure that normally silences telomere-proximal genes. Because telomerase function is not required for telomeric silencing, we postulated that the dominant-negative effect caused by overexpression of TLC1 RNA originates in a normal interaction between the RNA and an unknown telomeric factor important for silencing; the overexpressed RNA presumably continues to bind the factor and compromises its function. Here we show that a 48-nt stem-loop structure within the 1.3-kb TLC1 RNA is necessary and sufficient for disrupting telomeric silencing and shortening telomeres. Moreover, this short RNA sequence appears to function through an interaction with the conserved DNA end-binding protein Ku. We propose that, in addition to its roles in telomeric silencing, homologous recombination and non-homologous end-joining (NHEJ), S. cerevisiae Ku also helps to recruit or activate telomerase at the telomere through an interaction with this stem-loop of TLC1 RNA.
Asunto(s)
Antígenos Nucleares , ADN Helicasas , Reparación del ADN , Proteínas de Unión al ADN/metabolismo , Proteínas Nucleares/metabolismo , Conformación de Ácido Nucleico , ARN Catalítico/química , ARN Catalítico/metabolismo , Proteínas de Saccharomyces cerevisiae , Telomerasa/genética , Emparejamiento Base , Cromosomas Fúngicos/genética , Cromosomas Fúngicos/metabolismo , Proteínas de Unión al ADN/genética , Regulación Fúngica de la Expresión Génica , Silenciador del Gen , Autoantígeno Ku , Mutación/genética , Proteínas Nucleares/genética , Fenotipo , ARN Catalítico/genética , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Transducción de Señal , Telomerasa/metabolismo , Telómero/genética , Telómero/metabolismoRESUMEN
The nutritive value of wet potato processing waste for dairy cattle was determined in two experiments. In Experiment 1, rations contained, on a dry matter basis, 0, 10, 15, and 20% potato waste and were substituted for high moisture corn in diets for 32 lactating Holstein cows for 12 wk. Substituting potato waste for corn did not significantly affect milk yield, milk composition, milk production persistency, or dry matter intake. Cows fed 20% potato waste tended to decrease in milk fat percent and to shift molar proportions of rumen volatile fatty acids toward a decrease in acetate: propionate ratio. In Experiment 2, six steers were used in a 3 X 3 Latin square design to test digestibility and nitrogen utilization of potato waste substituted for high moisture corn at 0, 10, and 20% of the ration dry matter. A second group of four steers with rumen fistulas were used in a 4 X 4 Latin square to test rumen fermentation parameters. Diets contained 0, 10, 20, and 30% potato wastes and were similar to Experiment 1. Potato waste did not significantly affect digestibility of crude protein or dry matter, but at 20% substitution digestibility of acid detergent fiber decreased. Rumen ammonia, acetate, acetate to propionate ratios, and total volatile fatty acids were lower at high intakes of potato waste and pH was increased. The shift in rumen fermentation when large amounts of potatoes were fed explains the depressed butter fat on these rations.