'One Health' for the people of Hong Kong and the world

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Adenoviral delivery of RNA decoys restores cellular proapoptotic protein PUMA expression by silencing Epstein-Barr virus-encoded miR-BART5 in nasopharyngeal carcinoma cells

Poster Session 1 - Vaccines and Anti-Viral Therapeutics: no. 3.17Epstein-Barr virus (EBV) encodes 48 mature microRNAs that play important roles in viral maintenance and promote host cell survival by regulating viral transcripts expression, inhibiting apoptosis or facilitating to evade cell immune surveillance. We have previously shown that EBV-encoded miR-BART5 targets and downregulates cellular pro-apoptotic protein p53-upregulated modulator of apoptosis (PUMA) to promote cellular survival of EBV-infected nasopharyngeal carcinoma (NPC) cells. Since compromising miR-BART5 might induce apoptosis of EBV-infected NPC cell, in this study we have established an adenoviral expression system to deliver anti-miR-BART5 decoys to NPC cells. The anti-miR-BART5 decoys comprised 6 tandem repeats of miR-BART5 binding sites and their expression was driven by EBVEBER2 promoter. They were designed to serve as a competitive inhibitor of miR-BART5 to reverse miR-BART5's inhibitory effects on PUMA in EBV-infected NPC cells. The RNA polymerase III-dependent EBER2 promoter is particularly strong in ...postprin

CRTC1 transcriptional coactivator is required for hepatitis B virus gene expression and replication

This journal suppl. entitled: Metabolism, Diet and Disease 2014: Cancer and metabolismConference Theme: Cancer and metabolismPoster Presentation: P31BACKGROUND: Chronic hepatitis B virus (HBV) infection occurs in over 400 million people worldwide, 15-40% of whom will terminally develop severe liver diseases including hepatocellular carcinoma. Although development of HCC is a multi-step process, high HBV DNA level is a major risk factor for disease progression. Transcription of HBV from the cccDNA template is essential for its replication and requires CREB transcription factor, a master regulator of cell metabolism. However, transcriptional coactivators that facilitate CREB-dependent activation of HBV transcription remain to be identified and characterized …published_or_final_versio

Ubiquitination and proteosome-dependent degradation of the activated form of human liver-enriched transcription factor CREB-H regulated by protein kinase A

Poster Presentation - Theme 1: Cell biologyCREB-H is a membrane-bound bZIP transcription factor which is mainly expressed in liver and small intestine. CREB-H plays important roles in the regulation of lipid metabolism, iron metabolism, gluconeogenesis and acute phase response. CREB-H is proteolytically activated by regulated intramembrane proteolysis to generate a C-terminal truncated form known as ...postprin

LKB1 tumor suppressor and salt-inducible kinases negatively regulate human T-cell leukemia virus type 1 transcription

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Clinical and molecular characterization of a novel PLIN1 frameshift mutation identified in patients with familial partial lipodystrophy.

Perilipin 1 is a lipid droplet coat protein predominantly expressed in adipocytes, where it inhibits basal and facilitates stimulated lipolysis. Loss-of-function mutations in the PLIN1 gene were recently reported in patients with a novel subtype of familial partial lipodystrophy, designated as FPLD4. We now report the identification and characterization of a novel heterozygous frameshift mutation affecting the carboxy-terminus (439fs) of perilipin 1 in two unrelated families. The mutation cosegregated with a similar phenotype including partial lipodystrophy, severe insulin resistance and type 2 diabetes, extreme hypertriglyceridemia, and nonalcoholic fatty liver disease in both families. Poor metabolic control despite maximal medical therapy prompted two patients to undergo bariatric surgery, with remarkably beneficial consequences. Functional studies indicated that expression levels of the mutant protein were lower than wild-type protein, and in stably transfected preadipocytes the mutant protein was associated with smaller lipid droplets. Interestingly, unlike the previously reported 398 and 404 frameshift mutants, this variant binds and stabilizes ABHD5 expression but still fails to inhibit basal lipolysis as effectively as wild-type perilipin 1. Collectively, these findings highlight the physiological need for exquisite regulation of neutral lipid storage within adipocyte lipid droplets, as well as the possible metabolic benefits of bariatric surgery in this serious disease.Wellcome TrustThis is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db14-010

UCL E-Learning Evaluation Toolkit

A framework for evaluating the pedagogical effectiveness of e-learning and technology-enhanced learning spaces

Outcomes of SDHB Pathogenic Variant Carriers.

CONTEXT: Carriers of germline pathogenic variants (PVs) in succinate dehydrogenase type B (SDHB) are at increased risk of developing pheochromocytomas and paragangliomas (PPGLs). Understanding their outcomes can guide recommendations for risk assessment and early detection. OBJECTIVE: We performed a systematic review and meta-analysis of the following outcomes in SDHB PV carriers: age-specific risk of developing tumors, metastatic progression, second primary tumor development, and mortality. METHODS: PubMed, MEDLINE, and EMBASE were searched. Sixteen studies met the inclusion criteria and were sorted into 4 outcome categories: age-specific penetrance, metastatic disease, risk of second tumor, and mortality. We assessed heterogeneity and performed a meta-analysis across studies using a random-effects model with the DerSimonian and Laird method. RESULTS: Penetrance of PPGLs for nonproband/nonindex SDHB PV carriers by age 20 was 4% (95% CI, 3%-6%), 11% (95% CI, 8%-15%) by age 40, 24% (95% CI, 19%-31%) by age 60%, and 35% (95% CI, 25%-47%) by age 80. The overall risk of metastatic disease for nonproband/nonindex carriers with PPGLs was 9% (95%, CI 5%-16%) per lifetime. In all affected cases (combining both proband/index and nonproband/nonindex carriers with tumors), the risk of a second tumor was 24% (95% CI, 18%-31%) and all-cause 5-year mortality was 18% (95% CI, 6%-40%). CONCLUSION: Penetrance for PPGLs in SDHB PV carriers increases linearly with age. Affected carriers are at risk of developing and dying of metastatic disease, or of developing second tumors. Lifelong surveillance is appropriate

Factors associated to bed net use in Cameroon: a retrospective study in Mfou health district in the Centre Region

Introduction: Insecticide treated net remains a tool of choice for malaria prevention in Cameroon. However, data suggests that its use by thepopulation, especially vulnerable groups remains low. Moreover, there is a paucity of information about factors influencing its use. We sought outto identify factors associated with net use in Mfou health district, prior to distribution of long lasting insecticides treated nets (LLINs) in households.Methods: A two-stage cluster random sampling was conducted in 4 health areas with an average of 13 villages each. A total of 541 householdswere selected and heads interviewed using a structured household questionnaire. Data collected were entered into a database and multivariate logistic regression analyses of the association between net use and explanatory factors were performed using SPSS.Results: Net possession and use were respectively, 59.7 and 42.6%; thus, 2 out of 5 people who spent the previous night in households, slept under a net. Factors associated with net use included: net density.0.5 (OR=8.88, 95% CI: 6.24-12.64), age.5 years (OR=0.37, 95%CI: 0.28-0.47), secondary education (OR=1.41, 95% CI: 1.11-1.80) compared to primary/no education, parent status (OR=3.32, 95% CI: 2.31-4.76), house  construction (OR=1.37, 95% CI: 1.10-1.71) and environment characteristics (OR=1.46, 95% CI: 1.18-1.80).Conclusion: These data suggest that a universal coverage with one LLIN for two people should be achieved in households. Then, malaria health education should be conducted to re-enforce net use among school-aged children and adolescents, as well as older household members. Moreover, management of environment and improvement in houses construction are necessary.Key words: Malaria, factors, insecticides treated nets, health district, Cameroo

Evaluation of the InDUCKtion project at UCL

Executive summary: There is evidence that a good induction to university life can help with student retention; however, there is also a danger of overwhelming students during the intense period of fresher’s week. Under the auspices of a small grant from the Higher Education Academy’s ‘Changing the Learning Landscape’ funding stream, staff at two universities (University College London and Southampton Solent University) collaborated to produce an innovative and engaging induction project entitled ‘InDUCKtion’, based on the idea of an induction duck being a fun character for students to interact with. At UCL, the InDUCKtion duck existed in the form of a physical plastic duck included in international postgraduate student induction packs, and they were encouraged to take photos of themselves in and around UCL and London as part of a photo challenge using social media. It was anticipated that this would enable students to familiarise themselves with the locale, make friends and have fun at the same time. The InDUCKtion duck was also evident on flyers and posters with QR codes advertising an online tour to enable students to gain an accelerated familiarisation with the campus and its facilities. Within UCL, the project was a collaborative, cross-departmental venture instigated by members of UCL’s E-Learning Environments (ELE) working in partnership with the Centre for the Advancement of Learning and Teaching (CALT) and Student Support and Wellbeing (SSW). The logistics of the project meant that the team members also had to liaise with a number of other individuals and departments around UCL, to help promote and implement the project. Despite a rapid following on Twitter in a relatively short period, a reasonable hit rate on the QR code for the main page of the online tour resource, and some engagement with the photo challenges using social media, participation in the project was lower than anticipated. Lessons learned from an evaluation perspective revealed that adding another activity to an already overwhelming fresher’s week was problematic, despite its innovative and interactive nature. The use of QR codes was problematic for a number of reasons, and the project needed more buy-in from student representatives and academics to provide institutional endorsement. Recommendations for future instances of the project include securing student representation and academic endorsement, integrating the activity with parallel induction activities – particularly with academic departments, replacing QR codes with an alternative technology-enhanced learning approach and optimising the learning design to better motivate students and promote groupwork