Circulating miRNAs: Potential Novel Biomarkers for Hepatopathology Progression and Diagnosis of Schistosomiasis Japonica in Two Murine Models

BACKGROUND: Schistosomiasis remains a major public health issue, with an estimated 230 million people infected worldwide. Novel tools for early diagnosis and surveillance of schistosomiasis are currently needed. Elevated levels of circulating microRNAs (miRNAs) are commonly associated with the initiation and progression of human disease pathology. Hence, serum miRNAs are emerging as promising biomarkers for the diagnosis of a variety of human diseases. This study investigated circulating host miRNAs commonly associated with liver diseases and schistosome parasite-derived miRNAs during the progression of hepatic schistosomiasis japonica in two murine models.

METHODOLOGY/PRINCIPAL FINDINGS: Two mouse strains (C57BL/6 and BALB/c) were infected with a low dosage of Schistosoma japonicum cercariae. The dynamic patterns of hepatopathology, the serum levels of liver injury-related enzymes and the serum circulating miRNAs (both host and parasite-derived) levels were then assessed in the progression of schistosomiasis japonica. For the first time, an inverse correlation between the severity of hepatocyte necrosis and the level of liver fibrosis was revealed during S. japonicum infection in BALB/c, but not in C57BL/6 mice. The inconsistent levels of the host circulating miRNAs, miR-122, miR-21 and miR-34a in serum were confirmed in the two murine models during infection, which limits their potential value as individual diagnostic biomarkers for schistosomiasis. However, their serum levels in combination may serve as a novel biomarker to mirror the hepatic immune responses induced in the mammalian host during schistosome infection and the degree of hepatopathology. Further, two circulating parasite-specific miRNAs, sja-miR-277 and sja-miR-3479-3p, were shown to have potential as diagnostic markers for schistosomiasis japonica.

CONCLUSIONS/SIGNIFICANCE: We provide the first evidence for the potential of utilizing circulating host miRNAs to indicate different immune responses and the severity of hepatopathology outcomes induced in two murine strains infected with S. japonicum. This study also establishes a basis for the early and cell-free diagnosis of schistosomiasis by targeting circulating schistosome parasite-derived miRNAs.

Hierarchical Task Network Planning with Common-Sense Reasoning for Multiple-People Behaviour Analysis

Safety on public transport is a major concern for the relevant authorities. We
address this issue by proposing an automated surveillance platform which combines data from video, infrared and pressure sensors. Data homogenisation and integration is achieved by a distributed architecture based on communication middleware that resolves interconnection issues, thereby enabling data modelling. A common-sense knowledge base models and encodes knowledge about public-transport platforms and the actions and activities of passengers. Trajectory data from passengers is modelled as a time-series of human activities. Common-sense knowledge and rules are then applied to detect inconsistencies or errors in the data interpretation. Lastly, the rationality that characterises human behaviour is also captured here through a bottom-up Hierarchical Task Network planner that, along with common-sense, corrects misinterpretations to explain passenger behaviour. The system is validated using a simulated bus saloon scenario as a case-study. Eighteen video sequences were recorded with up to six passengers. Four metrics were used to evaluate performance. The system, with an accuracy greater than 90% for each of the four metrics, was found to outperform a rule-base system and a system containing planning alone.