187 research outputs found

    Genetic landscape of autism spectrum disorder in Vietnamese children

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    Autism spectrum disorder (ASD) is a complex disorder with an unclear aetiology and an estimated global prevalence of 1%. However, studies of ASD in the Vietnamese population are limited. Here, we first conducted whole exome sequencing (WES) of 100 children with ASD and their unaffected parents. Our stringent analysis pipeline was able to detect 18 unique variants (8 de novo and 10 ×-linked, all validated), including 12 newly discovered variants. Interestingly, a notable number of X-linked variants were detected (56%), and all of them were found in affected males but not in affected females. We uncovered 17 genes from our ASD cohort in which CHD8, DYRK1A, GRIN2B, SCN2A, OFD1 and MDB5 have been previously identified as ASD risk genes, suggesting the universal aetiology of ASD for these genes. In addition, we identified six genes that have not been previously reported in any autism database: CHM, ENPP1, IGF1, LAS1L, SYP and TBX22. Gene ontology and phenotype-genotype analysis suggested that variants in IGF1, SYP and LAS1L could plausibly confer risk for ASD. Taken together, this study adds to the genetic heterogeneity of ASD and is the first report elucidating the genetic landscape of ASD in Vietnamese children

    Influenza B viruses in swine: virus tropism in swine respiratory organ explant cultures

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    Poster Session: Virology and Viral ReceptorsBackground: Swine has been considered an animal reservoir of pandemic influenza A virus (IAV), for example, the 2009 H1N1 pandemic virus, swine is acting as a “mixing vessel” for the reassortment of swine, human and avian IAVs. Certain influenza B virus (IBV) strains were also found to be readily infecting piglets as early as in 1969. However, tissue tropism of IBV in swine is understudied, at least in 2000s, mainly due to the misconception that IBV causes milder disease than IAV. IBV has in fact circulated in many parts of the world causing regular seasonal epidemics in humans with mortality rates sometimes higher than that in IAV seasons. Here, our research group hypothesizes that swine could be a neglected host of IBV, apart from human and seal, due to the previous infectivity of IBV in this animal, as well as the fact that swine has close contact with human and possesses a similar sialic acid (influenza virus receptor) distribution profile as the human respiratory tract. We aim to examine the characteristics of IBV tissue tropism using swine tracheal and lung explant models, and risk assess swine susceptibility to a panel of IBV strains from both Yamagata and Victoria lineages of different years. Materials and Methods: The tracheal and lung explants were prepared from fresh swine respiratory organs from approximately 6-month-old pigs, and cultured with maximal similarity to the in vivo conditions. A panel of IBV strains, from both Yamagata and Victoria lineages and from different years, were used to infect the tissue explants at 37oC or 39oC according to the original physiological temperature of the tissue. The virus replication efficiencies were evaluated through viral titration and immunohistochemistry of the collected supernatant and formalin-fixed tissue explants respectively at 1, 24, 48 and 72 h postinfection. Seasonal IAVs (H1N1 - A/OK/447/08 and H3N2 - A/OK/370/05) were used as controls. Results: Most of the tested IBVs showed productive replication in the swine lung explants. Swine tracheal explants, on the other hand, supported the replication of limited IBV strains. Most of these IBVs belong to the Victoria lineage, which spread across the years from 2005 to 2011. IBVs that could replicate in swine lung explants reached their maxima at 48 hpi or sometimes later. This is comparatively slower than the replication rates of seasonal IAVs (H1N1 & H3N2) used in the study, which usually showed significant increase at 24 hpi with still increasing virus yields at 48 hpi in some cases. However, the overall increase in titres between the IBVs and seasonal IAVs were similar. In swine tracheal explants, both IBVs and seasonal IAVs showed limited replications with similar trends of having maxima being reached at 24 hpi. Conclusions: The successful replication of IBVs in swine explants cultures indicates the possible susceptibility of swine to IBV and provides the essential basis for further investigation on the likelihood for swine to be an animal reservoir of the virus, as well as the threat it may pose to humans. Continuous studies on the replication kinetics of a greater number of IBVs in swine explant cultures across a wider range of years, countries and lineages will probably be our future target.published_or_final_versio

    Evaluation of the human adaptation of influenza A/H7N9 virus in PB2 protein using human and swine respiratory tract explant cultures

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    Novel avian H7N9 virus emerged in China in 2013 resulting in a case fatality rate of around 39% and continues to pose zoonotic and pandemic risk. Amino acid substitutions in PB2 protein were shown to influence the pathogenicity and transmissibility of H7N9 following experimental infection of ferrets and mice. In this study, we evaluated the role of amino acid substitution PB2-627K or compensatory changes at PB2-591K and PB2-701N, on the tropism and replication competence of H7N9 viruses for human and swine respiratory tracts using ex vivo organ explant cultures. Recombinant viruses of A/Shanghai/2/2013 (rgH7N9) and its mutants with PB2-K627E, PB2-K627E + Q591K and PB2-K627E + D701N were generated by plasmid-based reverse genetics. PB2-E627K was essential for efficient replication of rgH7N9 in ex vivo cultures of human and swine respiratory tracts. Mutant rgPB2-K627E + D701N replicated better than rgPB2-K627E in human lung but not as well as rgH7N9 virus. The rgPB2-K627E mutant failed to replicate in human type I-like pneumocytes (ATI) and peripheral blood monocyte-derived macrophages (PMϕ) at 37 °C while the compensatory mutant rgPB2-K627E + Q591K and rgPB2-K627E + D701N had partly restored replication competence in PMϕ. Our results demonstrate that PB2-E627K was important for efficient replication of influenza H7N9 in both human and swine respiratory tracts.published_or_final_versio

    The asymmetric effect of all-inclusive holiday service quality attributes on tourist satisfaction

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    All-inclusive holidays have regained popularity among budget-conscious holidaymakers amidst inflation and living cost crisis. Following the pandemic, tourists are now staying at the hotel more and venture out less, which further makes all-inclusive holidays more popular than ever. With the increasing popularity of all-inclusive holidays, knowledge expansion of this tourism segment is necessary. This study extends the under-developed all-inclusive holiday literature by exploring service quality attributes of all-inclusive holidays and evaluating their asymmetric effect on tourist satisfaction. Suggestions on prioritizing service quality attributes for improvement are expected to support industry practitioners in managing service quality and satisfaction strategically

    Proof by Earnestness (PoE) to determine the authenticity of subjective information in blockchains - application in supply chain risk management

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    Blockchain is being used in various global supply chains with its ever-increasing maturity and popularity. However, in the presence of subjective information that does not have a digital footprint, blockchain application is a grey area. This is due to the difficulty in confirming the authenticity or legitimacy of information before achieving consensus on it using existing mechanisms such as Proof of Work (PoW), Proof of Authority (PoA) or Proof of Stake (PoS). In this paper, we attempt to address this issue. Specifically, we propose the Proof by Earnestness (PoE) consensus mechanism that determines the subjective information's truthfulness before further processing and formalising in blockchains. We consider supply chain risk management (SCRM) as our application area due to the vast amount of available subjective information

    SIAEF/PoE: Accountability of Earnestness for encoding subjective information in Blockchain

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    Blockchain technology has the potential to be applied widely in supply chain operations. One such area is proactive supply chain risk management (SCRM). In this area, existing researchers have highlighted the fraudulent behaviour of supply chain partners who do not disclose information on the risks that impact their operations. Blockchain can address this problem by encoding each partner's commitment to SCRM and achieve consensus. However, before this can be achieved, a key challenge to address is the inability of existing consensus mechanisms such as Proof of Work (PoW), Proof of Authority (PoA) and Proof of Stake (PoS) to deal with information that does not have a digital footprint. In this paper, we address this gap by proposing the Proof by Earnestness (PoE) consensus mechanism which accounts for the authenticity, legitimacy and trustworthiness of information that does not have a digital footprint. We also propose the Subjective Information Authenticity Earnestness Framework (SIAEF) as the overarching framework that assists PoE in achieving its aim. We test the applicability of SIAEF and PoE in a real-world blockchain environment by deploying it as a decentralized application (Dapp) and applying it in BscScan Testnet which is an official test blockchain network

    SIAEF/PoE: Accountability of Earnestness for encoding subjective information in Blockchain

    Get PDF
    Blockchain technology has the potential to be applied widely in supply chain operations. One such area is proactive supply chain risk management (SCRM). In this area, existing researchers have highlighted the fraudulent behaviour of supply chain partners who do not disclose information on the risks that impact their operations. Blockchain can address this problem by encoding each partner's commitment to SCRM and achieve consensus. However, before this can be achieved, a key challenge to address is the inability of existing consensus mechanisms such as Proof of Work (PoW), Proof of Authority (PoA) and Proof of Stake (PoS) to deal with information that does not have a digital footprint. In this paper, we address this gap by proposing the Proof by Earnestness (PoE) consensus mechanism which accounts for the authenticity, legitimacy and trustworthiness of information that does not have a digital footprint. We also propose the Subjective Information Authenticity Earnestness Framework (SIAEF) as the overarching framework that assists PoE in achieving its aim. We test the applicability of SIAEF and PoE in a real-world blockchain environment by deploying it as a decentralized application (Dapp) and applying it in BscScan Testnet which is an official test blockchain network

    Aerobic co-composting degradation of highly PCDD/F-contaminated field soil. A study of bacterial community

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    © 2018 Elsevier B.V. This study investigated bacterial communities during aerobic food waste co-composting degradation of highly PCDD/F-contaminated field soil. The total initial toxic equivalent quantity (TEQ) of the soil was 16,004 ng-TEQ kg −1 dry weight. After 42-day composting and bioactivity-enhanced monitored natural attenuation (MNA), the final compost product's TEQ reduced to 1916 ng-TEQ kg −1 dry weight (approximately 75% degradation) with a degradation rate of 136.33 ng-TEQ kg −1 day −1 . Variations in bacterial communities and PCDD/F degraders were identified by next-generation sequencing (NGS). Thermophilic conditions of the co-composting process resulted in fewer observed bacteria and PCDD/F concentrations. Numerous organic compound degraders were identified by NGS, supporting the conclusion that PCDD/Fs were degraded during food waste co-composting. Bacterial communities of the composting process were defined by four phyla (Proteobacteria, Actinobacteria, Bacteroidetes and Firmicutes). At the genus level, Bacillus (Firmicutes) emerged as the most dominant phylotype. Further studies on specific roles of these bacterial strains are needed, especially for the thermophiles which contributed to the high degradation rate of the co-co-composting treatment's first 14 days

    Synaptic dysfunction, memory deficits and hippocampal atrophy due to ablation of mitochondrial fission in adult forebrain neurons

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    Well-balanced mitochondrial fission and fusion processes are essential for nervous system development. Loss of function of the main mitochondrial fission mediator, dynamin-related protein 1 (Drp1), is lethal early during embryonic development or around birth, but the role of mitochondrial fission in adult neurons remains unclear. Here we show that inducible Drp1 ablation in neurons of the adult mouse forebrain results in progressive, neuronal subtype-specific alterations of mitochondrial morphology in the hippocampus that are marginally responsive to antioxidant treatment. Furthermore, DRP1 loss affects synaptic transmission and memory function. Although these changes culminate in hippocampal atrophy, they are not sufficient to cause neuronal cell death within 10 weeks of genetic Drp1 ablation. Collectively, our in vivo observations clarify the role of mitochondrial fission in neurons, demonstrating that Drp1 ablation in adult forebrain neurons compromises critical neuronal functions without causing overt neurodegeneration
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