294 research outputs found
Bioline Publications : How its evolution has mirrored the growth of the Internet
No full textBioline was set up in 1993 as a result of an increasingly loud rumble of dissatisfaction among scientists about the way research information was (or was not) distributed. The rumble reached a crescendo at a biotechnology/ bioinformatics conference in Trieste, Italy at which Professor Joshua Lederberg (winner of the 1958 Noble Prize in Medicine) deplored the growing gap between the cost of learned journals and the budgets of libraries to purchase them (Branin and Case, 1998). This problem was recognised as being particularly pronounced for research institutions in developing countries (Ginsparg, 1996). At the same time, the appearance of a possible means of using information technology and communications (ICT) set the research community thinking that there may, just possibly, be a low cost solution in sight. Some of us had been collaborating as working scientists on online databases and had some experience in the use of electronic communication. We had skills in database development, in software development and in serving on editorial boards of various biological journals during the normal course of our academic careers. We had contacts in the international scientific community and in the publishing world. As scientists, we also knew what scientists wanted. Perhaps we had enough collective knowledge to do something constructive to test the electronic publishing water. On the negative side, we had little experience of the likely impact of the new technologies on the distribution of scientific research; we knew little about the likely response from the scientific community to a novel method of accessing research information. We also had no idea of the consequences of e-publishing on the economics of journal publishing. Would we become millionaires or debtors? We decided to test the water. This article describes the progress of Bioline Publications from birth to the present time and draws some conclusions from our experience
The role of AIM2 inflammasome in systemic lupus erythematosus
No full textSystemic lupus erythematosus (SLE) is a prototypic autoimmune disease with heterogeneous clinical manifestations, disease course and prognosis. Whilst lupus is originally considered to be a B and T cell-mediated disease, growing evidence highlights the critical involvement of dysregulated innate immune responses in SLE aethiopathogenesis. The inflammasomes are multiprotein complexes which oligomerise in the cytosol of monocytes/macrophages to trigger innate inflammatory responses against pathogenic ligands or endogenous stressors. An inflammasome comprises of a pattern recognition receptor (PRR), an adaptor protein named apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC), and a caspase-1 (CASP1) effector which cleaves and activates two potent proinflammatory cytokines, interleukin (IL)-1β and IL-18. Notably, elevated levels of IL-1β and IL-18 have been detected in the skin, kidneys and sera of SLE patients. Absent in Melanoma 2 (AIM2), which uniquely senses double-stranded DNA (dsDNA), is one of the few known PRRs that induces the assembly of inflammasomes. Although the accumulation of endogenous dsDNA (SLE autoantigen) is well documented in SLE, the role of AIM2 inflammasome remains controversial in murine SLE, and is poorly understood in human SLE. Therefore, current study aimed to characterise the functional role of AIM2 inflammasome in SLE patients.
Firstly, gene expression of AIM2, ASC and CASP1 were found significantly higher in SLE monocytes than healthy control (HC) monocytes. Secondly, SLE monocytes were found to exhibit augmented production of IL-1β and IL-18 by AIM2 inflammasome. Together, current study revealed an anomalous state of the AIM2 inflammasome in SLE patients. Additionally, dysregulated expression of the AIM2 inflammasome components were associated with lower platelet count, haemoglobin level and the use of hydroxychloroquine in SLE patients. Next, I showed that SLE serum could upregulate both mRNA and protein levels of AIM2 in healthy monocytes, and correspondingly, mediate higher AIM2 inflammasome activity. Type I IFNs was later delineated to be the pathogenic factor which could potentiate AIM2 inflammasome response in human monocytes through upregulating AIM2 expression. Transcriptional profiling further revealed elevated expression of signal transducer and activator of transcription (STAT) 1 and STAT2, in SLE monocytes, which might in turn regulate AIM2 expression. Using chromatin immunoprecipitation assay, I confirmed that type I IFNs could increase the binding of these two transcription factors to an ISRE (interferon-stimulated regulatory element)-like site in AIM2 promoter to mediate higher gene expression.
This study demonstrates that the dysregulation of AIM2 inflammasome in SLE patients is mediated by elevated levels of type I IFNs. Additionally, these findings further support the pathogenic role of type I IFNs in SLE development through a novel mechanism by which AIM2 inflammasome response is amplified via the STAT1/STAT2/AIM2 axis in monocytes. Hitherto, there is no cure for lupus and patients are mainly managed using corticosteroids and immunosuppressants. Hence, novel inhibitors targeting AIM2 and its upstream TFs (STAT1/2) or type I IFNs might constitute an alternate strategy to help dampen chronic inflammation and damage in SLE patients, especially those with high levels of IL-1β and IL-18.published_or_final_versionMedicineDoctoralDoctor of Philosoph
Cellular and molecular dysregulations of neutrophils in systemic lupus erythematosus
No full textSystemic lupus erythematosus (SLE) is a female-biased chronic autoimmune disorder presenting a broad spectrum of clinical manifestations in multiple organ systems. As the most abundant immune cells in innate immunity, neutrophils are actively involved in the regulation of inflammation and immune responses in SLE. However, the molecular and cellular dysfunctions of neutrophils in lupus remain ambiguous. The aim of this study was to investigate the expression and functional significance of two molecular targets, namely interleukin-18 receptor accessory protein (IL18RAP) and peptidylarginine deiminase 4 (PADI4), in neutrophils of SLE patients.
IL18RAP is an indispensable subunit for the IL-18 receptor (IL-18R) complex’s ability to mediate high-affinity IL-18 binding and signaling transduction. Research in IL-18 in SLE has been mostly focused on its role as a type 1 T helper cell-driving cytokine. The functional significance of IL18RAP in mediating the IL-18-driven response in myeloid cells in SLE remains largely unexplored. Elevated IL18RAP expression in association with neutrophil activation network was initially identified in a pilot transcriptome profile analysis of SLE leukocytes. In a larger patient cohort, an increased expression of IL18RAP was observed in neutrophils from SLE patients, particularly those with a history of nephritis. IL18RAP expression was positively correlated with SLE disease activity. The increased IL18RAP expression in SLE neutrophils could be attributed to the elevated type I interferon level in sera. Functionally, neutrophils from SLE patients showed higher IL-18-mediated enhancement in reactive oxygen species (ROS) generation, which showed positive correlation with IL18RAP expression and could be neutralized by anti-IL18RAP blocking antibodies. The findings suggest that IL-18 could contribute to SLE pathogenesis through mediation of neutrophil dysfunction via the upregulation of IL18RAP expression.
PADI4 is a calcium dependent enzyme that catalyzes the conversion of positively charged arginine into neutrally charged citrulline. PADI4 is mainly expressed in neutrophils, is responsible for histones citrullination and was shown to correlate with chromatin decondensation during neutrophil extracellular traps (NETs) formation. However, the effects of PADI4 on lupus progression were contradictory in different lupus mouse models. In this study, elevated expressions of PADI4 were observed in neutrophils of SLE patients. Functionally, SLE neutrophils were prone to form NETs. Significantly decreased NETs formation was exhibited in PADI4 specific inhibitor GSK484-treated neutrophils and PADI4-knockdown neutrophil-like HL-60 cells (dHL-60). Neutrophils from SLE patients produced more ROS upon stimulation and expressed higher levels of the NADPH oxidase complex subunits. Furthermore, PADI4-deficient dHL-60 cells showed reduced chromatin accessibility in gene regions of NADPH subunits, which could account for their suppressed expression and led to reduced ROS induction. Hence, dysregulated PADI4 expression in SLE neutrophils could mediate enhanced NETs formation and ROS induction, thereby contributing to SLE pathogenesis through providing excessive autoantigens and facilitating oxidative damage.
Taken together, these findings reveal the overactivity of IL18RAP and PADI4 in SLE neutrophils and provide expression and functional bases for their use as potential therapeutic targets or biomarkers for lupus.published_or_final_versionMedicineDoctoralDoctor of Philosoph
Dissecting the physiological role of the novel lupus-associated C-type lectin-like protein CLEC16A
No full textThe CLEC16A locus has been identified as a susceptibility gene for multiple autoimmune diseases, including multiple sclerosis, type-I diabetes and systemic lupus erythematosus (SLE), in genome-wide association studies. CLEC16A encodes a novel C-type lectin-like protein, by virtue of a predicted C-type lectinlike domain (CTLD), with unclear function. Studies on the disease-associated SNPs have suggested that CLEC16A polymorphisms affect the expression of neighboring genes, while the effect on its own expression is unclear. Several functional studies have interrogated the physiological role(s) of CLEC16A in disparate directions. The Drosophila ortholog of CLEC16A, Ema, has been reported to regulate endosomal protein trafficking and the autophagic process, while CLEC16A has been found to participate in LPS-induced inflammatory cytokine response in rat astrocytes. Since there is not a consenting role ascribed to CLEC16A, this study was undertaken to investigate the functional involvement(s) of CLEC16A in mammalian cells and the expression of CLEC16A in lupus patients, with the attempt to comprehend the association between CLEC16A and SLE.
By overexpressing in non-immune epithelial cells, CLEC16A was revealed to be an intracellular protein of ~130 kDa in size. CLEC16A displayed a punctated expression pattern, which did not co-localize with endosomes, lysosomes, autophagosomes or endoplasmic reticulum in steady state. When treated with rapamycin or serum-starved, CLEC16A-overexpressing cells exhibited a reduced autophagic response, suggesting that CLEC16A may have an inhibitory role in autophagy. Besides the predicted CTLD, motif prediction has also implicated an immunomodulatory role for CLEC16A. Due to the observed inhibition on autophagy, coupled with recent findings linking autophagy and inflammasome activation, the involvement of CLEC16A in NLRP3 inflammasome was investigated. By knocking down CLEC16A in the human macrophage-like THP-1 cells, CLEC16A was found to potentially regulate NLRP3 inflammasome activation via inhibiting the LPS-induced pro-IL-1aasynthesis. Finally, the expressions of the long and short isoforms, CLEC16A_V1 and CLEC16A_V2 of CLEC16A in PBMCs were compared between healthy controls and SLE patients. A higher CLEC16A_V1 expression was observed in SLE patients, whereas the reverse was found for CLEC16A_V2. The expressions of the isoforms, however, were not correlated with the disease severity and clinical manifestations.
The finding that CLEC16A may inhibit autophagy is in contrast with the reported function of Ema in supporting autophagy, and such discrepancy could be because of the different cell systems used. The finding that CLEC16A may downregulate NLRP3 inflammasome activation has not been previously reported, and the mechanism(s) of such regulation warrant(s) future studies. The molecular basis of how CLEC16A regulates autophagy and inflammasome waits to be delineated. Such knowledge, together with information of where endogenous CLEC16A is expressed, shall incite better understanding of the contribution of CLEC16A to SLE development.published_or_final_versionMedicineDoctoralDoctor of Philosoph
Search for Key Performance Indicators (KPIs) for target cost contracts in Hong Kong
No full textDepartment of Building and Real EstateRefereed conference pape
Defective dendritic cells and mesenchymal stromal cells in systemic lupus erythematosus and the potential of mesenchymal stromal cells ascell-therapy
No full textpublished_or_final_versionMedicineDoctoralDoctor of Philosoph
USING WAVE-COEFFICIENTS AS FEATURE VECTORS TO IDENTIFY AEROSPACE TARGETS
No full textAn original target identification method using Wave-Coefficients (WCs) as feature vector is proposed. The scattering fields of arbitrary shaped targets are expressed as a sum of spherical waves and the distinctive coefficients are exploited as the target feature. Decision rule based on correlation coefficient is established, and some analyses on the properties of the WCs are conducted. Numerical simulations of four targets are carried out and the recognition performances without and with noise are provided and discussed.Engineering, Electrical & ElectronicPhysics, AppliedTelecommunicationsSCI(E)EI0ARTICLE465-48013
Systemic Lupus Erythematosus And Immunodeficiency
No full textSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease caused by a combination of genetic, epigenetic, and environmental factors. Recent advances in genetic analysis coupled with better understanding of different immune regulatory and signaling pathways have revealed the complex relationship between autoimmunity, including SLE, and immunodeficiency. Furthermore, the expanding therapeutic armamentarium has led to the increasing awareness of secondary immunodeficiency in these patients. This article serves to update the current understanding of SLE and immunodeficiency by discussing the shared genetic factors and immunobiology. We also summarize the effects of immunosuppressive therapies with a focus on secondary antibody deficiency (SAD) after B-cell targeted therapies
The effect of a childbirth psychoeducation program on postnatal depression
No full textOBJECTIVES: 1. To evaluate the effect of a childbirth psychoeducation program (CPP) on learned resourcefulness and postnatal depression in Chinese mothers; 2. To examine the strengths and weaknesses of the CPP from participants’ perspectives. METHODS: This study used a mixed method design. A pretestposttest, control group quasi-experimental design was used to evaluate the effectiveness of CPP in reducing postnatal depression at 6 weeks postpartum. The intervention was based on the concept of learned resourcefulness which focused on cognitive restructuring, problem-solving and efficacy enhancement. The experimental group (n = 92) received the CPP which was incorporated into the routine childbirth education in the experimental hospital. The comparison group (n = 92) received the routine childbirth education alone in the comparison hospital. Outcomes were measured by the Self-Control Schedule and Edinburgh Postnatal Depression Scale. A purposive sample of 16 mothers who had participated in the CPP was interviewed at 6 weeks postpartum to identify the strengths and limitations of the program. RESULTS: Women receiving the CPP had significant improvement in learned resourcefulness (p < 0.001) and depressive symptoms from baseline to 6 weeks postpartum (p < 0.05) compared to the comparison group. Participants perceived the CPP to be helpful in enhancing their emotional control, fostering the development of learned resourcefulness skills, and increasing their confidence in taking up the maternal role. CONCLUSIONS: The CPP appears to be a very promising intervention for promoting learned resourcefulness and minimizing the risk of postnatal depression in the Chinese society.The 3rd World Congress of Asian Psychiatry (WCAP 2011), Melbourne, Australia, 31 July-4 August 2011. In Asian Journal of Psychiatry, 2011, v. 4, suppl. 1, p. S69-S70, abstract no. 106The 3rd World Congress of Asian Psychiatry (WCAP 2011), Melbourne, Australia, 31 July-4 August 2011. In Asian Journal of Psychiatry, 2011, v. 4, suppl. 1, p. S69-S70, abstract no. 10
Comparing the stretching technique and the wavelet cross-spectrum technique for measuring stress-induced wave-velocity changes in concrete
No full textCoda wave interferometry (CWI) holds promise as a technique for concrete stress monitoring. This is because the coda, which consists of multiply scattered arrivals, is the result of propagation through the medium over large distances. As such, it is sensitive to both minute structural changes and small velocity changes in that medium. Previous studies focusing on concrete have predominantly utilized the time-domain-based stretching technique to measure travel-time changes. There is, however, a lack of consensus on how to quantify these changes effectively. In this study, we conduct a systematic comparison between two techniques, namely the stretching technique and the wavelet cross-spectrum (WCS) technique, for measuring stress-induced velocity changes in a cylindrical concrete sample. Our comparison focuses on two key aspects: (i) stability against cycle skipping and (ii) consistency in retrieving velocity changes. Experimental results reveal that both the WCS technique and the stretching technique yield consistent velocity changes. In terms of stability, it is challenging to determine which technique performs better, due to differences in the mechanisms triggering cycle skipping. However, when considering waves with frequencies ranging from 50 kHz to 80 kHz, both techniques exhibit comparable performance. Based on our findings, we offer the following recommendations for utilizing these CWI techniques in concrete stress monitoring: For the stretching technique, selecting the time window length based on the wave frequency and the expected magnitude of velocity change. For the WCS technique, operating it in the frequency band where spectral decomposition shows sufficiently high energy in the signal and can accommodate the expected magnitude of velocity change.Concrete StructuresApplied Geophysics and Petrophysic
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