Crosslinking-induced endocytosis of acetylcholine receptors by quantum dots

In a majority of patients with myasthenia gravis (MG), anti-acetylcholine receptor (AChR) antibodies target postsynaptic AChR clusters and thus compromise the membrane integrity of neuromuscular junctions (NMJs) and lead to muscle weakness. Antibody-induced endocytosis of AChRs in the postsynaptic membrane represents the initial step in the pathogenesis of MG; however, the molecular mechanisms underlying AChR endocytosis remain largely unknown. Here, we developed an approach to mimic the pathogenic antibodies for inducing the crosslinking and internalization of AChRs from the postsynaptic membrane. Using biotin-α-bungarotoxin and quantum dot (QD)-streptavidin, cell-surface and internalized AChRs could be readily distinguished by comparing the size, fluorescence intensity, trajectory, and subcellular localization of the QD signals. QD-induced AChR endocytosis was mediated by clathrin-dependent and caveolin-independent mechanisms, and the trafficking of internalized AChRs in the early endosomes required the integrity of microtubule structures. Furthermore, activation of the agrin/MuSK (muscle-specific kinase) signaling pathway strongly suppressed QD-induced internalization of AChRs. Lastly, QD-induced AChR crosslinking potentiated the dispersal of aneural AChR clusters upon synaptic induction. Taken together, our results identify a novel approach to study the mechanisms of AChR trafficking upon receptor crosslinking and endocytosis, and demonstrate that agrin-MuSK signaling pathways protect against crosslinking-induced endocytosis of AChRs. © 2014 Lee et al.published_or_final_versio

Increasing the civil service retirement age in Hong Kong : a study of policy processes and dynamics

published_or_final_versionPolitics and Public AdministrationMasterMaster of Public Administratio

Comparative transcriptomics of multidrug-resistant Acinetobacter baumannii in response to antibiotic treatments

Abstract Multidrug-resistant Acinetobacter baumannii, a major hospital-acquired pathogen, is a serious health threat and poses a great challenge to healthcare providers. Although there have been many genomic studies on the evolution and antibiotic resistance of this species, there have been very limited transcriptome studies on its responses to antibiotics. We conducted a comparative transcriptomic study on 12 strains with different growth rates and antibiotic resistance profiles, including 3 fast-growing pan-drug-resistant strains, under separate treatment with 3 antibiotics, namely amikacin, imipenem, and meropenem. We performed deep sequencing using a strand-specific RNA-sequencing protocol, and used de novo transcriptome assembly to analyze gene expression in the form of polycistronic transcripts. Our results indicated that genes associated with transposable elements generally showed higher levels of expression under antibiotic-treated conditions, and many of these transposon-associated genes have previously been linked to drug resistance. Using co-expressed transposon genes as markers, we further identified and experimentally validated two novel genes of which overexpression conferred significant increases in amikacin resistance. To the best of our knowledge, this study represents the first comparative transcriptomic analysis of multidrug-resistant A. baumannii under different antibiotic treatments, and revealed a new relationship between transposons and antibiotic resistance

Posterolateral Lumbar Spinal Fusion with Autogenous Bone Chips from Laminectomy Extended with OsteoSet®

BackgroundThis study was conducted to evaluate posterolateral lumbar fusion with autogenous corticocancellous bone chips from the laminae and spinous processes extended with OsteoSet® instead of cancellous bone from the iliac crest.MethodsA total of 124 patients who underwent posterior decompression and posterolateral fusion with instrumentation between May 2001 and December 2003 were analyzed retrospectively. The study population comprised 49 males and 75 females with a mean age of 66 ± 9.5 years. In all the patients, corticocancellous bone chips from laminectomy and OsteoSet® were used as the graft material. There was no cancellous bone harvested from the iliac crest. The follow-up period was 28 + 7.1 months.ResultsThe overall union rate was 91%, and the average union time was 3.9 months. There were 3 complications, including 2 patients with dura tear, and 1 with deep infection. At the final follow-up, the good and excellent results were up to 83.9%.ConclusionGraft material from laminae and spinous processes extended with OsteoSet® is reliable and effective enough to replace the graft from the posterior iliac crest

Sleeping mattress determinants and evaluation: a biomechanical review and critique

Background Sleeping mattress parameters significantly influence sleeping comfort and health, as reflected by the extensive investigations of sleeping support biomechanics to prevent sleep-related musculoskeletal problems. Methodology Herein, we review the current trends, research methodologies, and determinants of mattress biomechanics research, summarizing evidence published since 2008. In particular, we scrutinize 18 articles dealing with the development of new designs, recommendation criteria, instruments/methods of spine alignment evaluation, and comparative evaluation of different designs. Results The review demonstrated that mattress designs have strived for customization, regional features, and real-time active control to adapt to the biomechanical features of different body builds and postures. However, the suggested threshold or target values for desirable spine alignment and body pressure distribution during sleep cannot yet be justified in view of the lack of sufficient evidence. Conclusions It is necessary to formulate standard objectives and protocols for carrying out mattress evaluation

Biomechanics and bioengineering of orthopedic and cardiovascular rehabilitation

Musculoskeletal problem, such as traumatic injury, osteoporosis, and osteoarthritis, is one of the leading causes of disability worldwide and is therefore a crucial branch of public health. Biomechanics has been proven to play a critical role in musculoskeletal pathology, treatment, and rehabilitation. Rehabilitation describes specialized healthcare dedicated to improving, maintaining, or restoring physiological strength, cognition, and mobility with maximized results. It helps an individual achieve the highest level of function or greatest independence and quality of life possible after illness, injury, or surgery using physical training, instruments, devices, or other methods. Advances in rehabilitation, including the theory, paradigm, protocol, modality, invention, and engineering, can improve the development of modern medicine and also the quality of life especially for the disabled and elderly people. The main focus of this special issue is on innovative theory and application of biomechanics to understand musculoskeletal pathology and to improve the techniques for the treatment and rehabilitation

Would transcranial direct current stimulation (tDCS) enhance the effects of working memory training in older adults with mild neurocognitive disorder due to Alzheimer’s disease: study protocol for a randomized controlled trial

© 2015 Cheng et al. Background: There has been longstanding interesting in cognitive training for older adults with cognitive impairment. In this study, we will investigate the effects of working memory training, and explore augmentation strategies that could possibly consolidate the effects in older adults with mild neurocognitive disorder. Transcranial direct current stimulation (tDCS) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance. As tDCS may also modulate cognitive function through changes in neuroplastic response, it would be adopted as an augmentation strategy for working memory training in the present study. Methods/Design: This is a 4-week intervention double-blind randomized controlled trial (RCT) of tDCS. Chinese older adults (aged 60 to 90 years) with mild neurocognitive disorder due to Alzheimer 's disease (DSM-5 criteria) would be randomized into a 4-week intervention of either tDCS-working memory (DCS-WM), tDCS-control cognitive training (DCS-CC), and sham tDCS-working memory (WM-CD) groups. The primary outcome would be working memory test - the n-back task performance and the Chinese version of the Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-Cog). Secondary outcomes would be test performance of specific cognitive domains and mood. Intention-to-treat analysis would be carried out. Changes of efficacy indicators with time and intervention would be tested with mixed effect models. Discussion: This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation, working memory training and dual stimulation in older adults at risk of cognitive decline. It would also examine the tolerability, program adherence and adverse effects of this novel intervention. Information would be helpful for further research of dementia prevention studies. Trial registration: ChiCTR-TRC- 14005036Date of registration: 31 July 2014.published_or_final_versio

How students cope with part-time study

This study provides a qualitative test and illustration of a model of how students cope with the demands of part-time study. The model shows that students who are successful in finding the time to complete the requirements of part-time courses do so by adopting three mechanisms; sacrifice, support and the negotiation of arrangements. All three mechanisms operate in four domains, namely work, family, social lives and the self. The mechanisms and domains were related together in a three by four matrix. Data to verify and illuminate the model were gathered by the researchers through an on-line forum discussion on the topic of coping with part-time study. The researchers themselves were studying part-time in a course called Adult Education and Professional Development. Analysis of the data showed that the work domain was very important but little adaptation was possible. The family was seen as the most important domain and all three mechanisms were used. Time was commonly found for part-time study by sacrificing social lives. The self-domain was interpreted as important in establishing motivation and self-determination