Genomic characterisation of Alzheimer’s disease risk genes using long-read sequencing

Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterised by progressive intracellular accumulation of hyperphosphorylated tau and extracellular deposition of beta-amyloid. It affects over 50 million people worldwide with numbers expecting to triple by 2050. Despite recent success in identifying genetic risk factors for AD, the mechanisms underpinning disease progression remain unknown. There is increasing evidence for altered transcriptional regulation and RNA splicing in the development of AD pathology. However, current studies exploring isoform diversity in the AD brain are constrained by the inherent limitations of standard short-read RNA-sequencing approaches, which fail to capture full-length transcripts critical for transcriptome assembly. The primary aim of this thesis was to utilise two long-read sequencing approaches, Pacific Biosciences isoform sequencing and Oxford Nanopore Technologies nanopore cDNA sequencing, to examine isoform diversity and transcript usage in the cortex, and identify alternative splicing events associated with AD pathology in a transgenic model of tau pathology (rTg4510). By generating long reads that span full-length transcripts, our studies revealed widespread RNA isoform diversity with unprecedented detection of novel transcripts not present in existing genome annotations. We further performed ultra-deep targeted long-read sequencing of 20 AD-risk genes, identifying robust expression changes at the transcript level associated with tau accumulation in the cortex. Our analyses provide a systematic evaluation of transcript usage, even in the absence of gene-level expression alterations, and highlight the importance of alternative RNA splicing as a mechanism underpinning gene regulation in the development of tau pathology. Finally, this thesis presents a laboratory and bioinformatics pipeline for the systematic characterisation of isoform diversity and alternative splicing using long-read sequencing. The data generated as part of this research have implications for our understanding of the mechanisms driving the development of tau pathology, and represent a valuable resource to the wider research community

Cervical cancer screening: knowledge, health perception and attendance rate among Hong Kong Chinese women

Sharron SK Leung1, Ivy Leung21School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong; 2Quality Healthcare Medical Services, Hong KongPurpose: Cervical cancer screening has been consistently shown to be effective in reducing the incidence rate and mortality from cervical cancer. However, cervical screening attendance rates are still far from satisfactory in many countries. Strategies, health promotion and education programs need to be developed with clear evidence of the causes and factors relating to the low attendance rate. The study aims to assess the prediction of cervical screening attendance rate by Chinese women’s knowledge about cervical cancer and cervical screening as well as their perception of health.Patients and methods: A survey with self-reported questionnaires was conducted on 385 Chinese women recruited from a community clinic in Hong Kong. Participants were Chinese women, Hong Kong residents, aged 18–65 years, able to read Chinese or English, and were not pregnant.Results: Women aged 37 years or less, with at least tertiary education, who perceived having control over their own health and had better knowledge on risk factors, were more likely to attend cervical cancer screening. Many participants had adequate general knowledge but were unable to identify correct answers on the risk factors.Conclusion: Health promotion efforts need to focus on increasing women’s knowledge on risk factors and enhancing their perceived health control by providing more information on the link between screening and early detection with lower incidence rates and mortality from cervical cancer.Keywords: cervical screening attendance, cervical cancer, health perception and knowledge, perceived health control, Chines

Metal-catalyzed cyclopropanation on the 8-oxabicyclo[3.2.1]oct-6-ene template

Cyclopropanations of an 8-oxabicyclo[3.2.1]octene substrate using diazocarbonyl compounds provided exo, exo-cyclopropanated products as the sole or major diastereomeric oxatricyclic products. Reductive cleavage of a meso-oxatricyclic ketone by samarium iodide resulted in desymmetrization without concomitant oxygen bridge cleavage. © 2005 Elsevier Ltd. All rights reserved.postprin

Neurocutaneous melanosis and negative fluorodeoxyglucose positron emission tomography

Neurocutaneous melanosis is a rare condition characterized by cutaneous melanocytic naevi and the presence of melanocytes in the leptomeninges. It is commonly associated with malignant melanoma formation in the central nervous system (CNS) with poor prognosis. Herewe report a 13-year-old boy with neurocutaneous melanosis who presented with seizure with diffuse CNS malignant melanoma, as demonstrated by magnetic resonance imaging (MRI). 18F-fluorodeoxyglucose positron emission tomography (PET) was carried out, but was unable to detect the CNS involvement. So far, this is the first report involving the use of PET in neurocutaneous melanosis and we suggest that MRI is more sensitive than PET with 18F-fluorodeoxyglucose in such conditions. © 2010 The Authors. Journal compilation © 2010 College of Surgeons of Hong Kong.postprin

Arsenic trioxide suppresses tumour growth in squamous cell lung carcinoma

This journal suppl. entitled: 20th Medical Research Conference; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong KongINTRODUCTION: Squamous cell lung carcinoma (SCC) belongs to the second most common subtype in non–small-cell lung carcinoma. Recently, doublet chemotherapy regimens remain the cornerstone of first-line systemic treatment. Therefore, new therapeutic approach is urgently needed. Arsenic trioxide (ATO) is a traditional Chinese medicine which has multiple anti-cancer mechanisms including apoptosis. ATO has been used clinically in acute promyelocytic leukaemia. ATO has been shown to induce apoptosis in lung adenocarcinoma …published_or_final_versio

The acquisition of Cantonese classifiers by preschool children in Hong Kong

The Cantonese language has a complex classifier system and young learners need to pay attention to both the semantics and syntax of classifiers. This study investigated the repertoire of classifiers produced by 492 Cantonese-speaking preschoolers in three age groups (3 ;0, 4 ;0 and 5 ;0). Spontaneous utterances produced in 30-mmute toy-play contexts were collected and transcribed. Analyses identified a productive repertoire of 73 classifiers in the utterances, which could be appropriately classified into the typology proposed in the present study. An age-related increase in the number of classifier types per child as well as the repertoire size of each group was found. g03 (CL) was widely used as the general classifier by the young children. It was also discovered that the three-year-olds were already showing signs of grasping the basic syntax of classifiers. Cognitive, linguistic and contextual influences presumed to shape the evidence are discussed. © 2007 Cambridge University Press.published_or_final_versio

Massive degradation in FGFR/Akt/Erk signaling by arsenic trioxide and FGFR inhibitor PD173074 in squamous cell lung carcinoma SK-MES-1

This journal suppl. entitled: 20th Medical Research Conference; Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong KongINTRODUCTION: Lung cancer is the top cancer killer. Squamous cell carcinoma (SCC) represents the second most common histological subtype of lung cancer. Arsenic trioxide (ATO) has been demonstrated to inhibit tumour growth in lung adenocarcinoma and initiate apoptosis in acute promyelocytic leukaemia. Fibroblast growth factor (FGF) receptor (FGFR) amplification is shown in some SCC. FGFR inhibitor (eg PD173074) has been …published_or_final_versio

How does mandibular advancement with or without maxillary procedures affect pharyngeal airways? An overview of systematic reviews

published_or_final_versio

Low cost DIY solar energy hot water system

Author name used in this publication: N. C. CheungRefereed conference paper2004-2005 > Academic research: refereed > Refereed conference paperVersion of RecordPublishe

Inviscid two dimensional vortex dynamics and a soliton expansion of the sinh-Poisson equation

The dynamics of inviscid, steady, two dimensional flows is examined for the case of a hyperbolic sine functional relation between the vorticity and the stream function. The 2-soliton solution of the sinh-Poisson equation with complex wavenumbers will reproduce the Mallier-Maslowe pattern, a row of counter-rotating vortices. A special 4-soliton solution is derived and the corresponding flow configuration is studied. By choosing special wavenumbers complex flows bounded by two rigid walls can result. A conjecture regarding the number of recirculation regions and the wavenumber of the soliton expansion is offered. The validity of the new solution is verified independently by direct differentiation with a computer algebra software. The circulation and the vorticity of these novel flow patterns are finite and are expressed in terms of well defined integrals. The questions of the linear stability and the nonlinear evolution of a finite amplitude disturbance of these steady vortices are left for future studies. © 1998 American Institute of Physics.published_or_final_versio