ORCID Profile
0000-0003-2809-6457
Current Organisations
Sun Yat-Sen University
,
Garvan Institute of Medical Research
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Publisher: EMBO
Date: 15-07-2021
Publisher: Public Library of Science (PLoS)
Date: 05-07-2018
Publisher: Centers for Disease Control and Prevention (CDC)
Date: 07-2007
Publisher: Shared Science Publishers OG
Date: 10-09-2018
Publisher: Oxford University Press (OUP)
Date: 09-10-2020
Abstract: Poor sleep quality can have harmful health consequences. Although many aspects of sleep are heritable, the understandings of genetic factors involved in its physiology remain limited. Here, we performed a genome-wide association study (GWAS) using the Pittsburgh Sleep Quality Index (PSQI) in a multi-ethnic discovery cohort (n = 2868) and found two novel genome-wide loci on chromosomes 2 and 7 associated with global sleep quality. A meta-analysis in 12 independent cohorts (100 000 in iduals) replicated the association on chromosome 7 between NPY and MPP6. While NPY is an important sleep gene, we tested for an independent functional role of MPP6. Expression data showed an association of this locus with both NPY and MPP6 mRNA levels in brain tissues. Moreover, knockdown of an orthologue of MPP6 in Drosophila melanogaster sleep center neurons resulted in decreased sleep duration. With convergent evidence, we describe a new locus impacting human variability in sleep quality through known NPY and novel MPP6 sleep genes.
Publisher: Springer Science and Business Media LLC
Date: 12-2017
DOI: 10.1038/S41598-017-16849-6
Abstract: Water intake is essential for survival and thus under strong regulation. Here, we describe a simple high throughput system to monitor water intake over time in Drosophila . The design of the assay involves dehydrating fly food and then adding water back separately so flies either eat or drink. Water consumption is then evaluated by weighing the water vessel and comparing this back to an evaporation control. Our system is high throughput, does not require animals to be artificially dehydrated, and is simple both in design and implementation. Initial characterisation of homeostatic water consumption shows high reproducibility between biological replicates in a variety of experimental conditions. Water consumption was dependent on ambient temperature and humidity and was equal between sexes when corrected for mass. By combining this system with the Drosophila genetics tools, we could confirm a role for ppk28 and DopR1 in promoting water consumption, and through functional investigation of RNAseq data from dehydrated animals, we found DopR1 expression in the mushroom body was sufficient to drive consumption and enhance water taste sensitivity. Together, we provide a simple high throughput water consumption assay that can be used to dissect the cellular and molecular machinery regulating water homeostasis in Drosophila .
Publisher: MDPI AG
Date: 27-12-2022
DOI: 10.3390/LIFE13010081
Abstract: Many studies show that genetics play a major contribution to the onset of obesity. Human genome-wide association studies (GWASs) have identified hundreds of genes that are associated with obesity. However, the majority of them have not been functionally validated. SEC16B has been identified in multiple obesity GWASs but its physiological role in energy homeostasis remains unknown. Here, we use Drosophila to determine the physiological functions of dSec16 in energy metabolism. Our results showed that global RNAi of dSec16 increased food intake and triglyceride (TAG) levels. Furthermore, this TAG increase was observed in flies with a specific RNAi of dSec16 in insulin-like peptide producing cells (IPCs) with an alteration of endocrine peptides. Together, our study demonstrates that dSec16 acting in IPCs controls energy balance and advances the molecular understanding of obesity.
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.CMET.2017.07.002
Abstract: Despite widespread consumption of non-nutritive sweeteners (NNSs), the impact of manipulating the perceived sweetness of food is unclear. Previously we reported that chronic consumption of the NNSs sucralose or L-glucose led to increased calories consumed post-exposure however, a recent study suggested this effect occurs because NNSs acutely suppress food intake, leading to a caloric debt. Here we show that acute ingestion of sucralose in the context of a low-carbohydrate diet causes a pronounced increase in calories consumed. Moreover, neither sucralose nor L-glucose had a lasting effect on food intake during chronic exposure however, both NNSs enhance food intake post-exposure. Together these data confirm that sucralose and L-glucose promote food intake under a variety of experimental conditions.
Publisher: Springer Science and Business Media LLC
Date: 29-04-2019
Publisher: Elsevier BV
Date: 06-2017
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 2022
Publisher: Springer Science and Business Media LLC
Date: 22-10-2015
DOI: 10.1038/NCOMMS9570
Abstract: Disease incidences increase with age, but the molecular characteristics of ageing that lead to increased disease susceptibility remain inadequately understood. Here we perform a whole-blood gene expression meta-analysis in 14,983 in iduals of European ancestry (including replication) and identify 1,497 genes that are differentially expressed with chronological age. The age-associated genes do not harbor more age-associated CpG-methylation sites than other genes, but are instead enriched for the presence of potentially functional CpG-methylation sites in enhancer and insulator regions that associate with both chronological age and gene expression levels. We further used the gene expression profiles to calculate the ‘transcriptomic age’ of an in idual, and show that differences between transcriptomic age and chronological age are associated with biological features linked to ageing, such as blood pressure, cholesterol levels, fasting glucose, and body mass index. The transcriptomic prediction model adds biological relevance and complements existing epigenetic prediction models, and can be used by others to calculate transcriptomic age in external cohorts.
Publisher: Elsevier BV
Date: 10-2008
Publisher: EMBO
Date: 14-12-2018
Publisher: Springer Science and Business Media LLC
Date: 16-05-2023
DOI: 10.1038/S41467-023-37714-3
Abstract: The “death cap”, Amanita phalloides , is the world’s most poisonous mushroom, responsible for 90% of mushroom-related fatalities. The most fatal component of the death cap is α-amanitin. Despite its lethal effect, the exact mechanisms of how α-amanitin poisons humans remain unclear, leading to no specific antidote available for treatment. Here we show that STT3B is required for α-amanitin toxicity and its inhibitor, indocyanine green (ICG), can be used as a specific antidote. By combining a genome-wide CRISPR screen with an in silico drug screening and in vivo functional validation, we discover that N-glycan biosynthesis pathway and its key component, STT3B, play a crucial role in α-amanitin toxicity and that ICG is a STT3B inhibitor. Furthermore, we demonstrate that ICG is effective in blocking the toxic effect of α-amanitin in cells, liver organoids, and male mice, resulting in an overall increase in animal survival. Together, by combining a genome-wide CRISPR screen for α-amanitin toxicity with an in silico drug screen and functional validation in vivo, our study highlights ICG as a STT3B inhibitor against the mushroom toxin.
Publisher: Elsevier BV
Date: 11-2017
Publisher: American Association for the Advancement of Science (AAAS)
Date: 05-07-2019
Abstract: Nerve injury leads to loss of central inhibition and neuropathic pain in the fruit fly.
Publisher: Elsevier BV
Date: 02-2023
DOI: 10.1016/J.YMTHE.2022.10.012
Abstract: N6-methyladenosine (m
Publisher: Elsevier BV
Date: 03-2023
Publisher: Springer Science and Business Media LLC
Date: 05-07-2012
DOI: 10.1007/S10096-011-1328-5
Abstract: Angiostrongylus cantonensis was first discovered in 1935 and has become an important emerging pathogen causing human angiostrongyliasis. Major outbreaks of human angiostrongyliasis have been reported in endemic regions. Thousands of cases of human angiostrongyliasis have been documented worldwide. A. cantonensis has spread from its traditional endemic regions of the Pacific islands and Southeast Asia to the American continent including the USA, Caribbean islands and Brazil. Humans acquire A. cantonensis by consumption of raw or undercooked intermediate snail hosts or paratenic hosts. The main clinical manifestations of human angiostrongyliasis are eosinophilic meningitis and ocular angiostrongyliasis. The treatment of this disease includes supportive treatment, corticosteroid therapy, and combined therapy with corticosteroids and anthelminthics. The most effective method for prevention is to persuade people not to eat raw or undercooked intermediate and paratenic hosts.
Publisher: Springer Science and Business Media LLC
Date: 02-2019
DOI: 10.1038/S41467-019-08492-8
Abstract: Hundreds of genetic variants have been associated with Body Mass Index (BMI) through genome-wide association studies (GWAS) using observational cohorts. However, the genetic contribution to efficient weight loss in response to dietary intervention remains unknown. We perform a GWAS in two large low-caloric diet intervention cohorts of obese participants. Two loci close to NKX6.3/MIR486 and RBSG4 are identified in the Canadian discovery cohort ( n = 1166) and replicated in the DiOGenes cohort ( n = 789). Modulation of HGTX ( NKX6.3 ortholog) levels in Drosophila melanogaster leads to significantly altered triglyceride levels. Additional tissue-specific experiments demonstrate an action through the oenocytes, fly hepatocyte-like cells that regulate lipid metabolism. Our results identify genetic variants associated with the efficacy of weight loss in obese subjects and identify a role for NKX6.3 in lipid metabolism, and thereby possibly weight control.
Publisher: Public Library of Science (PLoS)
Date: 31-08-2011
Publisher: National Institute for Health and Care Research
Date: 2022
DOI: 10.3310/YOWK7214
Abstract: The impact of parental drug use on children is a major public health problem. However, opioid-dependent fathers have been largely ignored in parenting research. To implement and test the feasibility and acceptability of the Parents under Pressure programme (PuP4Dads) for opioid-dependent fathers and their families, and to determine whether or not a full-scale evaluation could be conducted. A mixed-methods feasibility study. Two non-NHS family support services for parents who use drugs in Scotland. Fathers prescribed opioid substitution therapy ( n = 25), their partners ( n = 17) and children, as well as practitioners, supervisors, service managers and referrers. A home-visiting programme, including an integrated theoretical framework, case formulation, collaborative goal-setting and modules designed to improve parenting, the caregiving environment and child welfare. The programme was delivered flexibly over 6 months by accredited practitioners. Feasibility progression criteria included the recruitment target ( n = 24 fathers), acceptability of PuP4Dads, father engagement in the study (including a minimum of 66% of fathers completing PuP and a minimum of 10 fathers completing baseline and post-treatment research interviews), engagement in qualitative interviews (including a minimum of 10 fathers and 90% practitioner uptake and 80% manager uptake), focus groups (with a minimum of 80% referrer uptake), adequate fidelity and no adverse events. The following researcher-administered validated questionnaires were used: the Brief Child Abuse Potential Inventory, the Parenting Sense of Competence Scale, the Difficulties in Emotion Regulation Scale, the Paternal Antenatal Attachment Scale, the Maternal Antenatal Attachment Scale, the Emotional Availability Scale, the Brief Infant Toddler Social and Emotional Assessment, the Strengths and Difficulties Questionnaire, the Conflict Tactics Scale, Treatment Outcome Profile and the EuroQol-5 Dimensions, five-level version. Other sources included parent-completed service use (an economic measure), social work child protection data, NHS opioid substitution therapy prescription data and practitioner-reported attendance data. We also conducted interviews with fathers ( n = 23), mothers ( n = 14), practitioners ( n = 8), supervisors ( n = 2) and service managers ( n = 7) conducted focus groups with referrers ( n = 28) and held an ‘expert event’ with stakeholders ( n = 39) . The PuP4Dads was successfully delivered within non-NHS settings and was considered acceptable and suitable for the study population. Referrals ( n = 44) resulted in 38 (86%) eligible fathers, of whom 25 (66%) fathers and 17 partners/mothers consented to participate. Most fathers reported no previous parenting support. A total of 248 sessions was delivered to the 20 fathers and 14 mothers who started the intervention. Fourteen fathers (and 10 mothers) completed ≥ 6 sessions and six fathers (and four mothers) completed ≤ 5 sessions. Father and mother attendance rates were equal (mean 71%). Median length of engagement for fathers was 26 weeks and for mothers it was 30 weeks. Twenty-three fathers completed interviews at baseline, 16 fathers completed interviews at follow-up 1 and 13 fathers completed interviews at follow-up 2. Outcome measures were well tolerated however, the suitability of some measures was dependent on family circumstances. The researcher-administered questionnaires had few missing data. The perceived benefits of PuP4Dads reported by parents, practitioners and managers included the following: the therapeutic focus on fathers improved parental emotion regulation, there was improved understanding and responding to child’s needs, there was better multiagency working and the programme was a good fit with practice ‘ethos’ and policy agenda. Learning highlighted the importance of service-wide adoption and implementation support, strategies to improve recruitment and retention of fathers, managing complex needs of both parents concurrently, understanding contextual factors affecting programme delivery and variables affecting intervention engagement and outcomes. Lack of emotional availability and economic (service use) data. A larger evaluation of PuP4Dads is feasible. Further work is required to demonstrate the effectiveness of PuP4Dads and the cost implications. A better understanding is needed of how the intervention works, for whom, under what circumstances and why. Current Controlled Trials ISRCTN43209618. This project was funded by the National Institute for Health Research (NIHR) Public Health Research programme and will be published in full in Public Health Research Vol. 10, No. 3. See the NIHR Journals Library website for further project information.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.CMET.2016.06.010
Abstract: Non-nutritive sweeteners like sucralose are consumed by billions of people. While animal and human studies have demonstrated a link between synthetic sweetener consumption and metabolic dysregulation, the mechanisms responsible remain unknown. Here we use a diet supplemented with sucralose to investigate the long-term effects of sweet/energy imbalance. In flies, chronic sweet/energy imbalance promoted hyperactivity, insomnia, glucose intolerance, enhanced sweet taste perception, and a sustained increase in food and calories consumed, effects that are reversed upon sucralose removal. Mechanistically, this response was mapped to the ancient insulin, catecholamine, and NPF/NPY systems and the energy sensor AMPK, which together comprise a novel neuronal starvation response pathway. Interestingly, chronic sweet/energy imbalance promoted increased food intake in mammals as well, and this also occurs through an NPY-dependent mechanism. Together, our data show that chronic consumption of a sweet/energy imbalanced diet triggers a conserved neuronal fasting response and increases the motivation to eat.
Publisher: Wiley
Date: 25-08-2010
Publisher: Elsevier BV
Date: 11-2018
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.IJPARA.2009.11.009
Abstract: Trypanosoma brucei evansi, a widely distributed species of trypanosome infecting different livestock species in many countries in Africa, Asia and South America, has recently been reported as a pathogen causing a case of human trypanosomiasis in India. To date, there is little information regarding the natural resistance of animal-infective stocks of T. b. evansi to normal human serum (NHS). In this study, we investigated the degree of sensitivity to NHS of 15 stocks of T. b. evansi from different geographical origins and found that 10 of the stocks were completely susceptible to the action of NHS parasites disappeared from the blood of infected mice within a few hours and the mice remained free from infection for more than 1 month. The remaining five stocks were partially resistant to NHS although parasites initially disappeared from the circulation more than 50% of the mice showed relapse infection 10-18 days later. Studies on one stock, T. b. evansi STIB 810, showed that the changes in parasitaemia in the infected mice were correlated with the amount of NHS inoculated (correlation factor -0.584 and P=0.001). When this stock was passaged 25 times in mice in the presence of NHS it was found that the trypanosomes' serum resistance increased compared with the parent stock from which they were derived 40% of the passaged parasites survived after in vitro incubation with 50% NHS for 7h, while only 1% of in idual trypanosomes of the parent stock survived under the same conditions. These findings show, to our knowledge for the first time, that human serum sensitivity varies amongst stocks of T. b. evansi, that some of them naturally display resistance to NHS and that, furthermore, T. b. evansi serum resistance can be increased by sub-passage in the presence of NHS.
Publisher: Mary Ann Liebert Inc
Date: 12-2022
Publisher: Elsevier BV
Date: 04-2023
Publisher: Springer Science and Business Media LLC
Date: 02-12-2019
DOI: 10.1038/S41467-019-13114-4
Abstract: Protein oxidation sits at the intersection of multiple signalling pathways, yet the magnitude and extent of crosstalk between oxidation and other post-translational modifications remains unclear. Here, we delineate global changes in adipocyte signalling networks following acute oxidative stress and reveal considerable crosstalk between cysteine oxidation and phosphorylation-based signalling. Oxidation of key regulatory kinases, including Akt, mTOR and AMPK influences the fidelity rather than their absolute activation state, highlighting an unappreciated interplay between these modifications. Mechanistic analysis of the redox regulation of Akt identified two cysteine residues in the pleckstrin homology domain (C60 and C77) to be reversibly oxidized. Oxidation at these sites affected Akt recruitment to the plasma membrane by stabilizing the PIP 3 binding pocket. Our data provide insights into the interplay between oxidative stress-derived redox signalling and protein phosphorylation networks and serve as a resource for understanding the contribution of cellular oxidation to a range of diseases.
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 05-2019
Publisher: Elsevier BV
Date: 08-2008
DOI: 10.1016/J.ACTATROPICA.2008.05.003
Abstract: Clonorchis sinensis causes the important food-borne zoonosis, clonorchiasis, which is endemic in East Asia, especially in China mainly in Guangdong, Guangxi and Heilongjiang provinces and Korea. Although comparisons on isoenzymes and some molecular profiles of C. sinensis collected from different parts of China and Korea have been studied, few works on the genetic variation among the in iduals from different regions of China has been reported. In the present study, in idual adults of C. sinensis were collected from cats in two geographic locations (Guangdong province in the South and Heilongjiang province in the North) of China and 44 of them were examined by using random lified polymorphic DNA (RAPD)-PCR and mobile genetic elements (MGEs)-PCR techniques to assess the in idual genetic variability within and between the two groups of this parasite. Six arbitrary primers and two pairs of MGE primers were employed in the genomic DNA lification. The molecular patterns showed significant polymorphism among the in iduals. The RAPD data displayed that the similarity coefficient (SC) of the in iduals within Heilongjiang group was much higher than that of the Guangdong group, which was further confirmed by MGE-PCR results. In iduals from Heilongjiang were found genetically closer with lesser polymorphisms than those collected from Guangdong province. These results demonstrated that RAPD and MGE-PCR techniques, particularly RAPD method, could be useful for investigating genetic variations among C. sinensis in iduals. They may also indicate that the genetic variation of C. sinensis occurs in the subtropical region--Guangdong--faster than that in the cold-region--Heilongjiang province--due to more generations (life cycle) occurred.
Publisher: Elsevier BV
Date: 02-2011
DOI: 10.1016/J.ACTATROPICA.2010.11.010
Abstract: The African trypanosome Trypanosoma brucei is the cause of sleeping sickness in humans and Nagana in animals. Here we report that semicarbazide-sensitive amine oxidases (SSAOs), enzymes that are abound in T. brucei mammal hosts, eliminate trypanosomes by oxidation of its substrate in vitro. SSAO and its endogenous substrate methylamine are not toxic to T. brucei, but parasites were killed in the presence of both of them. SSAO inhibitors antagonized the SSAO-methylamine induced toxicity on T. brucei. The trypanocidal activity was mainly associated with formaldehyde generated in the SSAO mediated oxidation of methylamine. This finding suggests that SSAO may play some roles in non-specific defense of trypanosome infection in mammals.
Publisher: Wiley
Date: 14-02-2023
DOI: 10.1002/MCO2.207
Abstract: Anti‐obesity medications act by suppressing energy intake (EI), promoting energy expenditure (EE), or both. Metformin (Met) and mirabegron (Mir) cause weight loss by targeting EI and EE, respectively. However, anti‐obesity effects during concurrent use of both have yet to be explored. In this study, we investigated the anti‐obesity effects, metabolic benefits, and underlying mechanisms of Met/Mir combination therapy in two clinically relevant contexts: the prevention model and the treatment model. In the prevention model, Met/Mir caused further 12% and 14% reductions in body weight (BW) gain induced by a high‐fat diet compared to Met or Mir alone, respectively. In the treatment model, Met/Mir additively promoted 17% BW loss in diet‐induced obese mice, which was 13% and 6% greater than Met and Mir alone, respectively. Additionally, Met/Mir improved glucose tolerance and insulin sensitivity. These benefits of Met/Mir were associated with increased EE, activated brown adipose tissue thermogenesis, and white adipose tissue browning. Significantly, Met/Mir did not cause cardiovascular dysfunction in either model. Together, the combination of Met and Mir could be a promising approach for the prevention and treatment of obesity by targeting both EI and EE simultaneously.
Publisher: Springer Science and Business Media LLC
Date: 30-04-2019
DOI: 10.1038/S41467-019-09681-1
Abstract: The box jellyfish Chironex fleckeri is extremely venomous, and envenoming causes tissue necrosis, extreme pain and death within minutes after severe exposure. Despite rapid and potent venom action, basic mechanistic insight is lacking. Here we perform molecular dissection of a jellyfish venom-induced cell death pathway by screening for host components required for venom exposure-induced cell death using genome-scale lenti-CRISPR mutagenesis. We identify the peripheral membrane protein ATP2B1, a calcium transporting ATPase, as one host factor required for venom cytotoxicity. Targeting ATP2B1 prevents venom action and confers long lasting protection. Informatics analysis of host genes required for venom cytotoxicity reveal pathways not previously implicated in cell death. We also discover a venom antidote that functions up to 15 minutes after exposure and suppresses tissue necrosis and pain in mice. These results highlight the power of whole genome CRISPR screening to investigate venom mechanisms of action and to rapidly identify new medicines.
Publisher: Public Library of Science (PLoS)
Date: 16-10-2018
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.CUB.2017.07.022
Abstract: The gut microbiota affects a wide spectrum of host physiological traits, including development [1-5], germline [6], immunity [7-9], nutrition [4, 10, 11], and longevity [12, 13]. Association with microbes also influences fitness-related behaviors such as mating [14] and social interactions [15, 16]. Although the gut microbiota is evidently important for host wellbeing, how hosts become associated with particular assemblages of microbes from the environment remains unclear. Here, we present evidence that the gut microbiota can modify microbial and nutritional preferences of Drosophila melanogaster. By experimentally manipulating the gut microbiota of flies subjected to behavioral and chemosensory assays, we found that fly-microbe attractions are shaped by the identity of the host microbiota. Conventional flies exhibit preference for their associated Lactobacillus, a behavior also present in axenic flies as adults and marginally as larvae. By contrast, fly preference for Acetobacter is primed by early-life exposure and can override the innate preference. These microbial preferences are largely olfactory guided and have profound impact on host foraging, as flies continuously trade off between acquiring beneficial microbes and balancing nutrients from food. Our study shows a role of animal microbiota in shaping host fitness-related behavior through their chemosensory responses, opening a research theme on the interrelationships between the microbiota, host sensory perception, and behavior.
Publisher: Elsevier BV
Date: 04-2009
Publisher: EMBO
Date: 27-02-2020
Publisher: Elsevier BV
Date: 03-2007
Publisher: Springer Science and Business Media LLC
Date: 11-05-2021
DOI: 10.1038/S41467-021-22925-3
Abstract: Obesity is caused by an imbalance between food intake and energy expenditure (EE). Here we identify a conserved pathway that links signalling through peripheral Y1 receptors (Y1R) to the control of EE. Selective antagonism of peripheral Y1R, via the non-brain penetrable antagonist BIBO3304, leads to a significant reduction in body weight gain due to enhanced EE thereby reducing fat mass. Specifically thermogenesis in brown adipose tissue (BAT) due to elevated UCP1 is enhanced accompanied by extensive browning of white adipose tissue both in mice and humans. Importantly, selective ablation of Y1R from adipocytes protects against diet-induced obesity. Furthermore, peripheral specific Y1R antagonism also improves glucose homeostasis mainly driven by dynamic changes in Akt activity in BAT. Together, these data suggest that selective peripheral only Y1R antagonism via BIBO3304, or a functional analogue, could be developed as a safer and more effective treatment option to mitigate diet-induced obesity.
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Qiao-Ping Wang.