Identification and characterization of long-range SOX9 enhancers in limb development

The transcription factor Sox9 is a master regulator of skeletogenesis. Heterozygous mutations of human SOX9 result in Campomelic Dysplasia (CD), in which affected individuals display distinct abnormalities in limbs and other skeletal assemblies. Recently, chromosomal translocations and deletions at >1Mb from SOX9 have been detected in some CD patients, suggesting the requirement of long‐range regulatory elements in mediating both spatiotemporal and dosage of Sox9 during limb development. To this end, we exploited several published ChIP‐Seq data, and identified nine, evolutionarily conserved, putative limb enhancers of SOX9, namely E1Sox9 to E9Sox9. Transgenic mouse embryos carrying E1Sox9‐driven LacZ reporter showed discrete transgene expression at the pre‐scapular domain where endogenous Sox9 is also expressed. Bioinformatic analyses on our candidate enhancers result in the identification of several signaling effector binding motifs, and indeed, we revealed that BMP‐Smad and Shh‐Gli pathways are possible upstream regulatory networks that govern the spatiotemporal and dosage of limb Sox9 expression via our predicted enhancers, respectively. Our results unveil the underlying molecular control in governing the complex patterning of Sox9 expression in the developing limb, and provide new molecular insight to the etiology of CD syndrome.postprin

Clinical and molecular epidemiology of human bocavirus in respiratory and fecal samples from children in Hong Kong

Background. Human bocavirus (HBoV) is a recently discovered parvovirus associated with respiratory tract infections in children. We conducted the first systematic prospective clinical and molecular study using nasopharyngeal aspirates (NPAs) and fecal samples. Methods. NPAs negative for influenza virus, parainfluenza virus, respiratory syncytial virus, adenovirus, and coronavirus and fecal samples from patients with acute gastroenteritis were included. On the basis of results from a pilot study using 400 NPAs from all age groups, a prospective 12-month study was conducted to detect HBoV in 1200 NPAs and 1435 fecal samples from patients <18 years old by polymerase chain reaction. The complete genome sequences of HBoVs from 12 NPAs and 12 fecal samples were determined. Results. Of the 400 NPAs collected in the pilot study, 20 (5.0%) were found to contain HBoV, all from children <5 years old. In the subsequent prospective study of pediatric patients, HBoV was detected in 83 (6.9%) of 1200 NPAs. Upper and lower respiratory tract infections were equally common. HBoV was detected in 30 (2.1%) of 1435 fecal samples. Fever and watery diarrhea were the most common symptoms. The seasonality of HBoV in NPAs and fecal samples was similar. Codetection with other pathogens occurred in 33% and 56% of NPAs and fecal samples, respectively, from patients with HBoV infection. Genomes of HBoVs from NPAs and fecal samples displayed minimal sequence variations. Conclusions. HBoV was detected in fecal specimens in children with acute gastroenteritis. A single lineage of HBoV was associated with both respiratory tract and enteric infections. © 2007 by the Infectious Diseases Society of America. All rights reserved.published_or_final_versio

Validation of the Drug Abuse Screening Test (Dast-10): A Study on Illicit Drug Use among Chinese Pregnant Women

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Investigating molecular pathogenesis of Campomelic Dysplasia

Student Stage Presentation Session 1: no. T01Two decades after the discovery that sequence alterations within and around SOX9 cause Campomelic Dysplasia (CD) - a rare skeletal malformation syndrome characterized by severe bowing of long bones (campomelia), the underlying molecular pathogenesis leading to bone dysmorphism remains unclear ...postprin

New life courses and social risks. Implications for social policy in East Asia

Social policy in modern industrialised societies is increasingly challenged by new social risks. These include insecure employment resulting from ever more volatile labour markets, new family and gender relationships resulting from the growing participation of women in the labour market, and the many problems resulting from very much longer human life expectancy. Whereas once social policy had to be in step with a standardised, relatively stable and predictable life course, it now has to cope with non-standardised individual preferences, life courses and families, and the consequent increased risks and uncertainties. This book examines these new life courses and their impact on social policy across a range of East Asian societies. It shows how governments and social welfare institutions have been slow to respond to the new challenges. In response, we propose a life-course sensitised policy as an approach to manage these risks. Overall, the book provides many new insights which will assist advance social policy in East Asia

Succinate Dehydrogenase Subunit B (SDHB) Gene Mutations In Paediatric Metastatic Paraganglioma: A Report Of Two Cases

Poster PresentationBackground: Paragangliomas and pheochromocytomas are catecholamine-releasing neuroendocrine tumors that occur rarely in the paediatric population. Mutations in cancer susceptibility genes can be identified in up to 40% of paediatric cases. Germline mutations in the succinate dehydrogenase subunit B (SDHB) gene in particular, are associated with extra-adrenal paraganglioma with high rate of metastasis and young age at presentation. Methods: Patients with metastatic paraganglioma diagnosed below the age of 18 years were identified from the Hong Kong Paediatric Haematology and Oncology Study Group database. With informed consent, peripheral blood was obtained from the subjects for extraction of DNA, PCR and direct DNA sequencing of all the 8 exons and splice sites of the SDHB were performed to test for germline mutation. Results: Two patients were identified and recruited for testing. Patient 1 was a 12-year-old boy diagnosed with subhepatic paraganglioma. The patient underwent adjuvant chemotherapy (gemcitabine, docetaxol, avastin) followed by en-bloc tumour resection. At the age of 15, MIBG-avid metastatic lesions at the L3-4 vertebrae were detected in surveillance scan and subtotal spondylectomy was performed. Urine HVA/VMA were normal all along. Family history was unremarkable. Further immunohistochemistry demonstrated loss of SDHB staining in the tumour cells. Sequencing of the SDHB gene revealed a novel heterozygous mutation, c.415C>T (p.Leu139Phe) that was not present in 150 normal controls. Sequencing of SDHC, SDHD, and VHL genes showed wild-type sequence. Patient 2 was a 13 year-old girl with negative family history who suffered from subhepatic paraganglioma and right adrenal phaeochromocytoma with metastasis to the right scapula and skull bone. Debulking surgery was performed for the abdominal primaries and curettage to the right shoulder metastasis. Three courses of 131-I-MIBG therapy were given with response. The patient subsequently developed left adrenal phaeochromocytoma and was treated surgically. Nevertheless, she relapsed at the age of 22 with metastasis at the intraabdominal nodes as well as lumbar vertebrae and was then managed with palliation. Sequencing of the SDHB gene confirmed the presence of a known pathogenic heterozygous mutation, c.572G>A (p.Cys191Tyr)

Identification and characterization of long-range SOX9 enhancers in limb development

Conference Theme: From Embryology to Disease MechanismsSymposium in Honor of Patrick Tam FRS "60 Years & Still Gastrulating

A home-based dyadic music-with-movement intervention for people with dementia and caregivers : a hybrid type 2 cluster-randomized effectiveness-implementation design

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Identification and characterization of long-range SOX9 enhancers in limb development

Conference Theme: From Embryology to Disease MechanismsSymposium in Honor of Patrick Tam FRS "60 Years & Still Gastrulating

Identification and characterization of long-range SOX9 enhancers in limb development

Poster Presentation - Theme 1: Genetics & Development, Translational & Regenerative Medicine: no. 1.3