Displaying publications 21 - 40 of 149 in total

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  1. Miller V, Jenkins DA, Dehghan M, Srichaikul K, Rangarajan S, Mente A, et al.
    Lancet Diabetes Endocrinol, 2024 May;12(5):330-338.
    PMID: 38588684 DOI: 10.1016/S2213-8587(24)00069-X
    BACKGROUND: The association between the glycaemic index and the glycaemic load with type 2 diabetes incidence is controversial. We aimed to evaluate this association in an international cohort with diverse glycaemic index and glycaemic load diets.

    METHODS: The PURE study is a prospective cohort study of 127 594 adults aged 35-70 years from 20 high-income, middle-income, and low-income countries. Diet was assessed at baseline using country-specific validated food frequency questionnaires. The glycaemic index and the glycaemic load were estimated on the basis of the intake of seven categories of carbohydrate-containing foods. Participants were categorised into quintiles of glycaemic index and glycaemic load. The primary outcome was incident type 2 diabetes. Multivariable Cox Frailty models with random intercepts for study centre were used to calculate hazard ratios (HRs).

    FINDINGS: During a median follow-up of 11·8 years (IQR 9·0-13·0), 7326 (5·7%) incident cases of type 2 diabetes occurred. In multivariable adjusted analyses, a diet with a higher glycaemic index was significantly associated with a higher risk of diabetes (quintile 5 vs quintile 1; HR 1·15 [95% CI 1·03-1·29]). Participants in the highest quintile of the glycaemic load had a higher risk of incident type 2 diabetes compared with those in the lowest quintile (HR 1·21, 95% CI 1·06-1·37). The glycaemic index was more strongly associated with diabetes among individuals with a higher BMI (quintile 5 vs quintile 1; HR 1·23 [95% CI 1·08-1·41]) than those with a lower BMI (quintile 5 vs quintile 1; 1·10 [0·87-1·39]; p interaction=0·030).

    INTERPRETATION: Diets with a high glycaemic index and a high glycaemic load were associated with a higher risk of incident type 2 diabetes in a multinational cohort spanning five continents. Our findings suggest that consuming low glycaemic index and low glycaemic load diets might prevent the development of type 2 diabetes.

    FUNDING: Full funding sources are listed at the end of the Article.

  2. Tan L, Sun W, Li X, Zhao J, Qu Y, Choo YM, et al.
    Biotechnol J, 2015 Jun;10(6):915-25.
    PMID: 25866127 DOI: 10.1002/biot.201400733
    Bisulfite pretreatment is a proven effective method for improving the enzymatic hydrolysis of empty fruit bunch (EFB) from oil palm for bioethanol production. In this study, we set out to determine the changes that occur in the structure and properties of EFB materials and fractions of hemicellulose and lignin during the bisulfite pretreatment process. The results showed that the crystallinity of cellulose in EFB increased after bisulfite pretreatment, whereas the EFB surface was damaged to various degrees. The orderly structure of EFB, which was maintained by hydrogen bonds, was destroyed by bisulfite pretreatment. Bisulfite pretreatment also hydrolyzed the glycosidic bonds of the xylan backbone of hemicellulose, thereby decreasing the molecular weight and shortening the xylan chains. The lignin fractions obtained from EFB and pretreated EFB were typically G-S lignin, and with low content of H units. Meanwhile, de-etherification occurred at the β-O-4 linkage, which was accompanied by polymerization and demethoxylation as a result of bisulfite pretreatment. The adsorption ability of cellulase differed for the various lignin fractions, and the water-soluble lignin fractions had higher adsorption capacity on cellulase than the milled wood lignin. In general, the changes in the structure and properties of EFB provided insight into the benefits of bisulfite pretreatment.
  3. Wang Y, Cheng C, Zhang Z, Wang J, Wang Y, Li X, et al.
    Am J Med Genet B Neuropsychiatr Genet, 2018 12;177(8):709-716.
    PMID: 30350918 DOI: 10.1002/ajmg.b.32675
    No biologically based diagnostic criteria are in clinical use today for obsessive-compulsive disorder (OCD), schizophrenia, and major depressive disorder (MDD), which are defined with reference to Diagnostic and Statistical Manual clinical symptoms alone. However, these disorders cannot always be well distinguished on clinical grounds and may also be comorbid. A biological blood-based dynamic genomic signature that can differentiate among OCD, MDD, and schizophrenia would therefore be of great utility. This study enrolled 77 patients with OCD, 67 controls with no psychiatric illness, 39 patients with MDD, and 40 with schizophrenia. An OCD-specific gene signature was identified using blood gene expression analysis to construct a predictive model of OCD that can differentiate this disorder from healthy controls, MDD, and schizophrenia using a logistic regression algorithm. To verify that the genes selected were not derived as a result of chance, the algorithm was tested twice. First, the algorithm was used to predict the cohort with true disease/control status and second, the algorithm predicted the cohort with disease/control status randomly reassigned (null set). A six-gene panel (COPS7A, FKBP1A, FIBP, TP73-AS1, SDF4, and GOLGA8A) discriminated patients with OCD from healthy controls, MDD, and schizophrenia in the training set (with an area under the receiver-operating-characteristic curve of 0.938; accuracy, 86%; sensitivity, 88%; and specificity, 85%). Our findings indicate that a blood transcriptomic signature can distinguish OCD from healthy controls, MDD, and schizophrenia. This finding further confirms the feasibility of using dynamic blood-based genomic signatures in psychiatric disorders and may provide a useful tool for clinical staff engaged in OCD diagnosis and decision making.
  4. Chai X, Li X, Hii KS, Zhang Q, Deng Q, Wan L, et al.
    Mar Environ Res, 2021 Jul;169:105398.
    PMID: 34171592 DOI: 10.1016/j.marenvres.2021.105398
    Coastal eutrophication is one of the pivotal factors driving occurrence of harmful algal blooms (HABs), whose underlying mechanism remained unclear. To better understand the nutrient regime triggering HABs and their formation process, the phytoplankton composition and its response to varying nitrogen (N) and phosphorus (P), physio-chemical parameters in water and sediment in Johor Strait in March 2019 were analyzed. Surface and sub-surface HABs were observed with the main causative species of Skeletonema, Chaetoceros and Karlodinium. The ecophysiological responses of Skeletonema to the low ambient N/P ratio such as secreting alkaline phosphatase, regulating cell morphology (volume; surface area/volume ratio) might play an important role in dominating the community. Anaerobic sediment iron-bound P release and simultaneous N removal by denitrification and anammox, shaped the stoichiometry of N and P in water column. The decrease of N/P ratio might shift the phytoplankton community into the dominance of HABs causative diatoms and dinoflagellates.
  5. Tay K, Kamarul T, Lok WY, Mansor M, Li X, Wong J, et al.
    Malays Orthop J, 2020 Jul;14(2).
    PMID: 32313613 DOI: 10.5704/MOJ.2007.001
    With the increasing number of COVID-19 cases and related deaths worldwide, we decided to share the development of this condition in Singapore and Malaysia. First few cases were diagnosed in the two countries at the end of January 2020, and the numbers have surged to thousands by end of March 2020. We will focus on strategies adopted by the government and also the Orthopaedic community of the two countries up till the beginning of April 2020. We hope that by sharing of relevant information and knowledge on how we are managing the COVID-19 condition, we can help other communities, and health care workers to more effectively overcome this pandemic.
  6. Hantoko D, Li X, Pariatamby A, Yoshikawa K, Horttanainen M, Yan M
    J Environ Manage, 2021 May 15;286:112140.
    PMID: 33652254 DOI: 10.1016/j.jenvman.2021.112140
    The COVID-19 pandemic has imposed a global emergency and also has raised issues with waste management practices. This study emphasized the challenges of increased waste disposal during the COVID-19 crisis and its response practices. Data obtained from the scientific research papers, publications from the governments and multilateral organizations, and media reports were used to quantify the effect of the pandemic towards waste generation. A huge increase in the amount of used personal protective equipments (facemasks, gloves, and other protective stuffs) and wide distribution of infectious wastes from hospitals, health care facilities, and quarantined households was found. The amount of food and plastic waste also increased during the pandemic. These factors caused waste treatment facilities to be overwhelmed, forcing emergency treatment and disposals (e.g., co-disposal in a municipal solid waste incinerator, cement kilns, industrial furnaces, and deep burial) to ramp up processing capacity. This paper discussed the ways the operation of those facilities must be improved to cope with the challenge of handling medical waste, as well as working around the restrictions imposed due to COVID-19. The study also highlights the need for short, mid, and longer-term responses towards waste management during the pandemic. Furthermore, the practices discussed in this paper may provide an option for alternative approaches and development of sustainable strategies for mitigating similar pandemics in the future.
  7. Gao X, Liu H, Li X, Fu S, Cao L, Shao N, et al.
    Vector Borne Zoonotic Dis, 2019 Jan;19(1):35-44.
    PMID: 30207876 DOI: 10.1089/vbz.2018.2291
    Japanese encephalitis virus (JEV) is a representative virus of the JEV serogroup in genus Flavivirus, family Flaviviridae. JEV is a mosquito-borne virus that causes Japanese encephalitis (JE), one of the most severe viral encephalitis diseases in the world. JEV is divided into five genotypes (G1-G5), and each genotype has its own distribution pattern. However, the distribution of different JEV genotypes has changed markedly in recent years. JEV G1 has replaced G3 as the dominant genotype in the traditional epidemic areas in Asia, while G3 has spread from Asia to Europe and Africa and caused domestic JE cases in Africa. G2 and G5, which were endemic in Malaysia, exhibited great geographical changes as well. G2 migrated southward and led to prevalence of JE in Australia, while G5 emerged in China and South Korea after decades of silence. Along with these changes, JE occurred in some non-traditional epidemic regions as an emerging infectious disease. The regional changes in JEV pose a great threat to human health, leading to huge disease burdens. Therefore, it is of great importance to strengthen the monitoring of JEV as well as virus genotypes, especially in non-traditional epidemic areas.
  8. Wen D, Cheng Z, Li J, Zheng X, Yao W, Dong X, et al.
    J Neurosci Methods, 2021 Nov 01;363:109353.
    PMID: 34492241 DOI: 10.1016/j.jneumeth.2021.109353
    BACKGROUND: The application of deep learning models to electroencephalogram (EEG) signal classification has recently become a popular research topic. Several deep learning models have been proposed to classify EEG signals in patients with various neurological diseases. However, no effective deep learning model for event-related potential (ERP) signal classification is yet available for amnestic mild cognitive impairment (aMCI) with type 2 diabetes mellitus (T2DM).

    METHOD: This study proposed a single-scale multi-input convolutional neural network (SSMICNN) method to classify ERP signals between aMCI patients with T2DM and the control group. Firstly, the 18-electrode ERP signal on alpha, beta, and theta frequency bands was extracted by using the fast Fourier transform, and then the mean, sum of squares, and absolute value feature of each frequency band were calculated. Finally, these three features are converted into multispectral images respectively and used as the input of the SSMICNN network to realize the classification task.

    RESULTS: The results show that the SSMICNN can fuse MSI formed by different features, SSMICNN enriches the feature quantity of the neural network input layer and has excellent robustness, and the errors of SSMICNN can be simultaneously transmitted to the three convolution channels in the back-propagation phase. Comparison with Existing Method(s): SSMICNN could more effectively identify ERP signals from aMCI with T2DM from the control group compared to existing classification methods, including convolution neural network, support vector machine, and logistic regression.

    CONCLUSIONS: The combination of SSMICNN and MSI can be used as an effective biological marker to distinguish aMCI patients with T2DM from the control group.

  9. Li X, Lam SS, Xia C, Zhong H, Sonne C
    Science, 2023 Dec;382(6674):1007.
    PMID: 38033061 DOI: 10.1126/science.adl6721
  10. Li S, Lu BP, Feng J, Zhou JJ, Xie ZZ, Liang C, et al.
    Trop Biomed, 2020 Dec 01;37(4):852-863.
    PMID: 33612738 DOI: 10.47665/tb.37.4.852
    Fructose-1,6-bisphosphate aldolase (FbA), a well characterized glycometabolism enzyme, has been found to participate in other important processes besides the classic catalysis. To understand the important functions of three fructose-1,6-bisphosphate aldolases from Clonorchis sinensis (CsFbAs, CsFbA-1/2/3) in host-parasite interplay, the open reading frames of CsFbAs were cloned into pET30a (+) vector and the resulting recombinant plasmids were transformed into Escherichia coli BL21 (DE3) for expression of the proteins. Purified recombinant CsFbAs proteins (rCsFbAs) were approximately 45.0 kDa on 12% SDS-PAGE and could be probed with each rat anti-rCsFbAs sera by western blotting analysis. ELISA and ligand blot overlay indicated that rCsFbAs of 45.0 kDa as well as native CsFbAs of 39.5 kDa from total worm extracts and excretory-secretory products of Clonorchis sinensis (CsESPs) could bind to human plasminogen, and the binding could be efficiently inhibited by lysine analog ε-aminocaproic acid. Our results suggested that as both the components of CsESPs and the plasminogen binding proteins, three CsFbAs might be involved in preventing the formation of the blood clot so that Clonorchis sinensis could acquire enough nutrients from host tissue for their successful survival and colonization in the host. Our work will provide us with new information about the biological function of three CsFbAs and their roles in hostparasite interplay.
  11. Qiu C, Zhang Z, Li X, Sang S, McClements DJ, Chen L, et al.
    NPJ Sci Food, 2023 Jun 14;7(1):29.
    PMID: 37316567 DOI: 10.1038/s41538-023-00186-2
    In this study, composite nanoparticles consisting of zein and hydroxypropyl beta-cyclodextrin were prepared using a combined antisolvent co-precipitation/electrostatic interaction method. The effects of calcium ion concentration on the stability of the composite nanoparticles containing both curcumin and quercetin were investigated. Moreover, the stability and bioactivity of the quercetin and curcumin were characterized before and after encapsulation. Fluorescence spectroscopy, Fourier Transform infrared spectroscopy, and X-ray diffraction analyses indicated that electrostatic interactions, hydrogen bonding, and hydrophobic interactions were the main driving forces for the formation of the composite nanoparticles. The addition of calcium ions promoted crosslinking of the proteins and affected the stability of the protein-cyclodextrin composite particles through electrostatic screening and binding effects. The addition of calcium ions to the composite particles improved the encapsulation efficiency, antioxidant activity, and stability of the curcumin and quercetin. However, there was an optimum calcium ion concentration (2.0 mM) that provided the best encapsulation and protective effects on the nutraceuticals. The calcium crosslinked composite particles were shown to maintain good stability under different pH and simulated gastrointestinal digestion conditions. These results suggest that zein-cyclodextrin composite nanoparticles may be useful plant-based colloidal delivery systems for hydrophobic bio-active agents.
  12. Yang C, Li X, Li Q, Zhang B, Li H, Lin J
    Neuroreport, 2017 Dec 06;28(17):1180-1185.
    PMID: 28953094 DOI: 10.1097/WNR.0000000000000903
    Chicken embryos are used widely in the fields of developmental biology and neurobiology. The chicken embryo also serves as a model to analyze gene expression and function using in ovo electroporation. Plasmids may be injected into the spinal cord or tectum of the chicken central nervous system by microinjection for electroporation. Here, we developed a novel method that combines in ovo electroporation and neuronal culturing to study gene function in the chicken tectum during embryo development. Our method can be used to study in-vivo and in-vitro exogenous genes' function. In addition, live cell imaging microscopy, immunostaining, and transfection can be used with our method to study neuronal growth, development, neurite growth and retraction, and axonal pathfinding. Our result showed that axons were present in isolated neurons after culturing for 24 h, and cell debris was low after replacing the media at 48 h. Many GFP-expressing neurons were observed in the cultured cells after 48 h. We successfully cultured the neurons for 3 weeks. Together, this method combines in ovo electroporation and neuronal culturing advantages and is more convenient for the gene function analysis.
  13. Chen C, Granados A, Brodie JF, Kays R, Davies TJ, Liu R, et al.
    Conserv Biol, 2023 Nov 08.
    PMID: 37937455 DOI: 10.1111/cobi.14221
    Reliable maps of species distributions are fundamental for biodiversity research and conservation. The International Union for Conservation of Nature (IUCN) range maps are widely recognized as authoritative representations of species' geographic limits, yet they might not always align with actual occurrence data. In recent area of habitat (AOH) maps, areas that are not habitat have been removed from IUCN ranges to reduce commission errors, but their concordance with actual species occurrence also remains untested. We tested concordance between occurrences recorded in camera trap surveys and predicted occurrences from the IUCN and AOH maps for 510 medium- to large-bodied mammalian species in 80 camera trap sampling areas. Across all areas, cameras detected only 39% of species expected to occur based on IUCN ranges and AOH maps; 85% of the IUCN only mismatches occurred within 200 km of range edges. Only 4% of species occurrences were detected by cameras outside IUCN ranges. The probability of mismatches between cameras and the IUCN range was significantly higher for smaller-bodied mammals and habitat specialists in the Neotropics and Indomalaya and in areas with shorter canopy forests. Our findings suggest that range and AOH maps rarely underrepresent areas where species occur, but they may more often overrepresent ranges by including areas where a species may be absent, particularly at range edges. We suggest that combining range maps with data from ground-based biodiversity sensors, such as camera traps, provides a richer knowledge base for conservation mapping and planning.
  14. Yang S, Li X, Jiang Z, Xiao M
    PLoS One, 2023;18(10):e0290126.
    PMID: 37844110 DOI: 10.1371/journal.pone.0290126
    Based on the data of the Chinese A-share listed firms in China Shanghai and Shenzhen Stock Exchange from 2014 to 2021, this article explores the relationship between common institutional investors and the quality of management earnings forecasts. The study used the multiple linear regression model and empirically found that common institutional investors positively impact the precision of earnings forecasts. This article also uses graph neural networks to predict the precision of earnings forecasts. Our findings have shown that common institutional investors form external supervision over restricting management to release a wide width of earnings forecasts, which helps to improve the risk warning function of earnings forecasts and promote the sustainable development of information disclosure from management in the Chinese capital market. One of the marginal contributions of this paper is that it enriches the literature related to the economic consequences of common institutional shareholding. Then, the neural network method used to predict the quality of management forecasts enhances the research method of institutional investors and the behavior of management earnings forecasts. Thirdly, this paper calls for strengthening information sharing and circulation among institutional investors to reduce information asymmetry between investors and management.
  15. Yang X, Ikhwanuddin M, Li X, Lin F, Wu Q, Zhang Y, et al.
    Mar Biotechnol (NY), 2018 Feb;20(1):20-34.
    PMID: 29152671 DOI: 10.1007/s10126-017-9784-2
    The molecular mechanism underlying sex determination and gonadal differentiation of the mud crab (Scylla paramamosain) has received considerable attention, due to the remarkably biological and economic differences between sexes. However, sex-biased genes, especially non-coding genes, which account for these differences, remain elusive in this crustacean species. In this study, the first de novo gonad transcriptome sequencing was performed to identify both differentially expressed genes and long non-coding RNAs (lncRNAs) between male and female S. paramamosain by using Illumina Hiseq2500. A total of 79,282,758 and 79,854,234 reads were generated from ovarian and testicular cDNA libraries, respectively. After filtrating and de novo assembly, 262,688 unigenes were produced from both libraries. Of these unigenes, 41,125 were annotated with known protein sequences in public databases. Homologous genes involved in sex determination and gonadal development pathways (Sxl-Tra/Tra-2-Dsx/Fru, Wnt4, thyroid hormone synthesis pathway, etc.) were identified. Three hundred and sixteen differentially expressed unigenes were further identified between both transcriptomes. Meanwhile, a total of 233,078 putative lncRNAs were predicted. Of these lncRNAs, 147 were differentially expressed between sexes. qRT-PCR results showed that nine lncRNAs negatively regulated the expression of eight genes, suggesting a potential role in sex differentiation. These findings will provide fundamental resources for further investigation on sex differentiation and regulatory mechanism in crustaceans.
  16. Weng Q, Goh SL, Wu J, Persson MSM, Wei J, Sarmanova A, et al.
    Br J Sports Med, 2023 Aug;57(15):990-996.
    PMID: 36593092 DOI: 10.1136/bjsports-2022-105898
    OBJECTIVE: Clinical guidelines recommend exercise as a core treatment for knee or hip osteoarthritis (OA). However, how its analgesic effect compares to analgesics, for example, oral non-steroidal anti-inflammatory drugs (NSAIDs) and paracetamol-the most commonly used analgesics for OA, remains unknown.

    DESIGN: Network meta-analysis.

    DATA SOURCES: PubMed, Embase, Scopus, Cochrane Library and Web of Science from database inception to January 2022.

    ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials (RCTs) comparing exercise therapy with oral NSAIDs and paracetamol directly or indirectly in knee or hip OA.

    RESULTS: A total of n=152 RCTs (17 431 participants) were included. For pain relief, there was no difference between exercise and oral NSAIDs and paracetamol at or nearest to 4 (standardised mean difference (SMD)=-0.12, 95% credibility interval (CrI) -1.74 to 1.50; n=47 RCTs), 8 (SMD=0.22, 95% CrI -0.05 to 0.49; n=2 RCTs) and 24 weeks (SMD=0.17, 95% CrI -0.77 to 1.12; n=9 RCTs). Similarly, there was no difference between exercise and oral NSAIDs and paracetamol in functional improvement at or nearest to 4 (SMD=0.09, 95% CrI -1.69 to 1.85; n=40 RCTs), 8 (SMD=0.06, 95% CrI -0.20 to 0.33; n=2 RCTs) and 24 weeks (SMD=0.05, 95% CrI -1.15 to 1.24; n=9 RCTs).

    CONCLUSIONS: Exercise has similar effects on pain and function to that of oral NSAIDs and paracetamol. Given its excellent safety profile, exercise should be given more prominence in clinical care, especially in older people with comorbidity or at higher risk of adverse events related to NSAIDs and paracetamol.CRD42019135166.

  17. Shi X, Wu X, Song T, Li X
    Nanoscale, 2016 Jul 22.
    PMID: 27444699
    The design of DNA nanotubes is a promising and hot research branch in structural DNA nanotechnology, which is rapidly developing as a versatile method for achieving subtle nanometer scale materials and molecular diagnostic/curative devices. Multifarious methods have been proposed to achieve varied DNA nanotubes, such as using square tiles and single-stranded tiles, but it is still a challenge to develop a bottom-up assembly way to build DNA nanotubes with different diameters and patterns using certain universal DNA nanostructures. This work addresses the challenge by assembling three types of spatial DNA nanotubes with different diameters and patterns from the so-called "basic bricks", i.e., hierarchical DNA sub-tiles. A high processing rate and throughput synthesis of DNA nanotubes are observed and analyzed by atomic force microscopy. Experimental observations and data analysis suggests the stability and controllability of DNA nanotubes assembled by hierarchical DNA sub-tiles.
  18. Yang S, Tan ML, Song Q, He J, Yao N, Li X, et al.
    J Environ Manage, 2023 Mar 15;330:117244.
    PMID: 36621311 DOI: 10.1016/j.jenvman.2023.117244
    Global climate change has led to an increase in both the frequency and magnitude of extreme events around the world, the risk of which is especially imminent in tropical regions. Developing hydrological models with better capabilities to simulate streamflow, especially peak flow, is urgently needed to facilitate water resource planning and management as well as climate change mitigation efforts in the tropics. In view of the need, this paper explores the feasibility of improving streamflow simulation performance in the tropical Kelantan River Basin (KRB) of Peninsular Malaysia through coupling a conceptual process-based hydrological model - Soil and Water Assessment Tool (SWAT) with a deep learning model - Bidirectional Long Short-Term Memory (Bi-LSTM) in two ways. All SWAT parameters were set as their default values in one hybrid model (SWAT-D-LSTM), whereas three most sensitive SWAT parameters were calibrated in the other hybrid model (SWAT-T-LSTM). Comparison of daily streamflow simulation results have shown that SWAT-T-LSTM consistently performs better than SWAT-D-LSTM as well as the stand-alone SWAT and Bi-LSTM model throughout the simulation period. Particularly, SWAT-T-LSTM performs considerably better than the other three models in simulating daily peak flow. Based on the latest projection results of five GCMs from the Sixth Phase of the Coupled Model Intercomparison Project (CMIP6) under three emission scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5), the best-performed SWAT-T-LSTM was run to assess the potential impacts of climate change on streamflow in the KRB. Ensemble assessment results have concluded that both average and extreme streamflow is much likely to increase considerably in the already wet northeast monsoon season from November to January, which has surely raised the alarm for more frequent flood occurrence in the KRB.
  19. Lou Z, Xu Y, Xiang K, Su N, Qin L, Li X, et al.
    FEBS J, 2006 Oct;273(19):4538-47.
    PMID: 16972940
    The Nipah and Hendra viruses are highly pathogenic paramyxoviruses that recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. These characteristics have led to their classification into the new genus Henpavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. The fusion protein, an enveloped glycoprotein essential for viral entry, belongs to the family of class I fusion proteins and is characterized by the presence of two heptad repeat (HR) regions, HR1 and HR2. These two regions associate to form a fusion-active hairpin conformation that juxtaposes the viral and cellular membranes to facilitate membrane fusion and enable subsequent viral entry. The Hendra and Nipah virus fusion core proteins were crystallized and their structures determined to 2.2 A resolution. The Nipah and Hendra fusion core structures are six-helix bundles with three HR2 helices packed against the hydrophobic grooves on the surface of a central coiled coil formed by three parallel HR1 helices in an oblique antiparallel manner. Because of the high level of conservation in core regions, it is proposed that the Nipah and Hendra virus fusion cores can provide a model for membrane fusion in all paramyxoviruses. The relatively deep grooves on the surface of the central coiled coil represent a good target site for drug discovery strategies aimed at inhibiting viral entry by blocking hairpin formation.
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