Advancing 21st Century Competencies in Hong Kong

This paper is one of five case studies that accompany the Asia Society reportpublished_or_final_versio

Transcriptome-wide analysis reveals different categories of response to a standardised immune challenge in a wild rodent

Individuals vary in their immune response and, as a result, some are more susceptible to infectious disease than others. Little is known about the nature of this individual variation in natural populations, or which components of immune pathways are most responsible, but defining this underlying landscape of variation is an essential first step to understanding the drivers of this variation and, ultimately, predicting the outcome of infection. We describe transcriptome-wide variation in response to a standardised immune challenge in wild field voles. We find that markers can be categorised into a limited number of types. For the majority of markers, the response of an individual is dependent on its baseline expression level, with significant enrichment in this category for conventional immune pathways. Another, moderately sized, category contains markers for which the responses of different individuals are also variable but independent of their baseline expression levels. This category lacks any enrichment for conventional immune pathways. We further identify markers which display particularly high individual variability in response, and could be used as markers of immune response in larger studies. Our work shows how a standardised challenge performed on a natural population can reveal the patterns of natural variation in immune response

Photochemical studies of cis-[Ru(bpy)2(4-bzpy)(CO)](PF6)2 and cis-[Ru(bpy)2(4-bzpy)(Cl)](PF6): Blue light-induced nucleobase binding.

The ruthenium(II) compounds cis-[Ru(bpy)2(4-bzpy)(CO)](PF6)2 (I) and cis-[Ru(bpy)2(4-bzpy)(Cl)](PF6) (II) (4-bzpy=4-benzoylpyridine, bpy=2,2'-bipyridine) were synthesized and characterized by spectroscopic and electrochemical techniques. The crystal structure of II was determined by X-ray diffraction. The photochemical behavior of I in aqueous solution shows that irradiation with ultraviolet light (365nm) releases both CO and 4-bzpy leading to the formation of the cis-[Ru(bpy)2(H2O)2]2+ ion as identified by NMR and electronic spectroscopy. Carbon monoxide release was confirmed with the myoglobin method and by gas chromatographic analysis of the headspace. CO release was not observed when aqueous I was irradiated with blue light (453nm). Changes in the electronic and 1H NMR spectra indicate that I undergoes photoaquation of 4-bzpy to form cis-[Ru(bpy)2(CO)(H2O)]2+. Blue light irradiation of aqueous II released the coordinated 4-bzpy to give the cis-[Ru(bpy)2(H2O)(Cl)]2+ ion. When the latter reaction was carried out in the presence of the nucleobase guanine, Ru-guanine adducts were formed, indicating that the metal containing photoproduct may also participate in biologically relevant reactions. The photochemical behavior of I indicates that it can release either CO or 4-bzpy depending on the wavelength chosen, a feature that may have therapeutic application

A candidate tolerance gene identified in a natural population of field voles (Microtus agrestis)

The animal immune response has hitherto been viewed primarily in the context of resistance only. However, individuals, can also employ a tolerance strategy to maintain good health in the face of on-going infection. To shed light on the genetic and physiological basis of tolerance, we use a natural population of field voles, Microtus agrestis, to search for an association between the expression of the transcription factor Gata3, previously identified as a marker of tolerance in this system, and polymorphism in 84 immune and non-immune genes. Our results show clear evidence for an association between Gata3 expression and polymorphism in the Fcer1a gene, with the explanatory power of this polymorphism being comparable to that of other non-genetic variables previously identified as important predictors of Gata3 expression. We also uncover the possible mechanism behind this association using an existing protein-protein interaction network for the mouse model rodent, Mus musculus, which we validate using our own expression network for M. agrestis. Our results suggest that the polymorphism in question may be working at the transcriptional level, leading to changes in the expression of the Th2-related genes, Tyrosine-protein kinase BTK and Tyrosine-protein kinase TXK, and hence potentially altering the strength of the Th2 response, of which Gata3 is a mediator. We believe our work has implications for both treatment and control of infectious disease

Screen for DNA-damage-responsive histone modifications identifies H3K9Ac and H3K56Ac in human cells

Recognition and repair of damaged DNA occurs within the context of chromatin. The key protein components of chromatin are histones, whose post-translational modifications control diverse chromatin functions. Here, we report our findings from a large-scale screen for DNA-damage-responsive histone modifications in human cells. We have identified specific phosphorylations and acetylations on histone H3 that decrease in response to DNA damage. Significantly, we find that DNA-damage-induced changes in H3S10p, H3S28p and H3.3S31p are a consequence of cell-cycle re-positioning rather than DNA damage per se. In contrast, H3K9Ac and H3K56Ac, a mark previously uncharacterized in human cells, are rapidly and reversibly reduced in response to DNA damage. Finally, we show that the histone acetyl-transferase GCN5/KAT2A acetylates H3K56 in vitro and in vivo. Collectively, our data indicate that though most histone modifications do not change appreciably after genotoxic stress, H3K9Ac and H3K56Ac are reduced in response to DNA damage in human cells

A randomised controlled trial of a theory-based intervention to improve sun protective behaviour in adolescents ('you can still be HOT in the shade'): study protocol

Background: Most skin cancers are preventable by encouraging consistent use of sun protective behaviour. In Australia, adolescents have high levels of knowledge and awareness of the risks of skin cancer but exhibit significantly lower sun protection behaviours than adults. There is limited research aimed at understanding why people do or do not engage in sun protective behaviour, and an associated absence of theory-based interventions to improve sun safe behaviour. This paper presents the study protocol for a school-based intervention which aims to improve the sun safe behaviour of adolescents. Methods/design: Approximately 400 adolescents (aged 12-17 years) will be recruited through Queensland, Australia public and private schools and randomized to the intervention (n = 200) or 'wait-list' control group (n = 200). The intervention focuses on encouraging supportive sun protective attitudes and beliefs, fostering perceptions of normative support for sun protection behaviour, and increasing perceptions of control/self-efficacy over using sun protection. It will be delivered during three × one hour sessions over a three week period from a trained facilitator during class time. Data will be collected one week pre-intervention (Time 1), and at one week (Time 2) and four weeks (Time 3) post-intervention. Primary outcomes are intentions to sun protect and sun protection behaviour. Secondary outcomes include attitudes toward performing sun protective behaviours (i.e., attitudes), perceptions of normative support to sun protect (i.e., subjective norms, group norms, and image norms), and perceived control over performing sun protective behaviours (i.e., perceived behavioural control). Discussion: The study will provide valuable information about the effectiveness of the intervention in improving the sun protective behaviour of adolescents

Importance of the Public Service in Achieving the UN SDGs

Public service is the engine of effective governance delivery in the world economy; governments across the world cannot function well without the enabling structures of public administration to deliver on their mandate as set out mostly in (political) manifestos, while also making sure the core mandate for meeting citizens’ basic welfare needs are made available through an efficient market system. The operation of such a market system must enable entities or agents to act in the best interest of delivering high services, which would have already been set as dictated through regulation of the legal system – this should also facilitate the presence of information symmetry for agents to operate (Jackson and Jabbie, 2019; Winston, 2006; Weiner and Vining, 2004)

Schistosomiasis and Urinary Bladder Cancer in North Western Tanzania: A Retrospective Review of 185 Patients.

Worldwide, cancers of the urinary bladder are well known to be associated with environmental chemical carcinogens such as smoking and occupational exposure to polycyclic aromatic hydrocarbons. These cancers are typically transitional cell carcinoma (urothelial carcinoma). In areas where schistosomiasis is endemic there is a high incidence of squamous cell carcinoma of the urinary bladder. Schistosomiasis causes chronic granulomatous cystitis leading to squamous metaplasia of transitional epithelium, and subsequently development of squamous cell carcinoma. The western part of Tanzania on the shores of Lake Victoria is such an endemic area. This study was done to document the burden of urinary bladder cancer associated with schistosomiasis in this region. This was a descriptive retrospective study of histologically confirmed cases of urinary bladder cancer seen at the Department of Pathology Bugando Medical Centre (BMC) over a period of 10 years. Data were retrieved from the records of the Departments of Pathology, Medical Records and Surgery. Data were analyzed by the use of contingency tables. A total of 185 patients were diagnosed with cancer of the urinary bladder during the study period, where as 90 (48.6%) were males and 95 (51.4) were females. The mean age at diagnosis was 54.3 years. Squamous cell carcinoma was the most frequent histological type (55.1%), followed by conventional transitional cell carcinoma (40.5%). Eighty three of all cancer cases (44.9%) were found to have schistosomal eggs. Schistosomiasis was commonly associated with squamous cancers compared to non squamous cancers. Most of the cancers associated with schistosomiasis had invaded the muscularis propria of the urinary bladder at the time of diagnosis (p<0.001) and such cancers were frequent below 50 years of age with a significant statistical difference (p<0.001). Poorly differentiated tumors were more frequent in females than males with a significant statistical difference (p=0.006). The majority of urinary bladder cancers seen in the Lake Region were squamous cell carcinoma associated with schistosomiasis. These cancers showed an aggressive behavior and were commonly seen in the younger age groups. Effective control of schistosomiasis in this region should significantly reduce the burden of urinary bladder cancer

Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 $\beta$-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the $\beta$-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn$^{143}$, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200