ABSTRACT
Huntington's disease (HD) is an inherited neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene (HTT). Disease progression is characterized by the loss of vulnerable neuronal populations within the striatum. A consistent phenotype across HD models is disruption of nucleocytoplasmic transport and nuclear pore complex (NPC) function. Here we demonstrate that high content imaging is a suitable method for detecting mislocalization of lamin-B1, RAN and RANGAP1 in striatal neuronal cultures thus allowing a robust, unbiased, highly powered approach to assay nuclear pore deficits. Furthermore, nuclear pore deficits extended to the selectively vulnerable DARPP32 + subpopulation neurons, but not to astrocytes. Striatal neuron cultures are further affected by changes in gene and protein expression of RAN, RANGAP1 and lamin-B1. Lowering total HTT using HTT-targeted anti-sense oligonucleotides partially restored gene expression, as well as subtly reducing mislocalization of proteins involved in nucleocytoplasmic transport. This suggests that mislocalization of RAN, RANGAP1 and lamin-B1 cannot be normalized by simply reducing expression of CAG-expanded HTT in the absence of healthy HTT protein.
ABSTRACT
OBJECTIVE: To determine the factors associated with sleep deprivation and their impact on academic performance of students living in a hostel setting. METHODS: It was a correlational study conducted from January to June, 2018 in Rawalpindi and Islamabad, Pakistan, and comprised university students of either sex aged 18-25 years who were studying at different universities of the twin cities. A semi-structured questionnaire was used along with Pittsburgh Sleep Quality Index to collect data which was analysed using SPSS 21. RESULTS: Of the 850 students, 450(50%) each were males and females. The overall mean age was 21.10±1.84 years. There was academic stress in 672(79%) students which disturbed the normal sleep cycle. Other factors affecting students; sleep were financial issues 632(74%), uncomfortable bed mattresses 671(79%), environmental noise 468 (53%), poor ventilation 666 (78%), hostel near commercial places 233(27%), and the habit of playing mobile games 545(65%). Female students had more sleep problems than males (p<0.05). Bivariate correlation showed no association of these factors and cumulative grade point average (p>0.05). CONCLUSION: The most common factors found to be influencing hostelites' sleep were stress, financial issues, uncomfortable mattresses, environmental noise and playing games on mobile before sleep. Disturbed sleep did not affect academic performance.
