Biology subjects

Hong, S.-T.

Publications and source records attributed to Hong, S.-T..

3 recordsLinked to original sources

bioRxiv2021

Phodopus roborovskii SH101 as a systemic infection model of SARS-CoV-2

Severe acute respiratory syndrome CoV-2 (SARS-CoV-2) is currently causing a worldwide threat with its unusually high transmission rates and rapid evolution into diverse strains. Unlike typical respiratory viruses, SARS-CoV-2 frequently causes systemic infection by breaking the boundaries of the respiratory systems. The development of animal models recapitulating the clinical manifestations of COVID-19 is of utmost importance not only for the development of vaccines and antivirals but also for understanding the pathogenesis. However, there has not been developed an animal model for systemic infection of SARS-CoV-2 representing most aspects of the clinical manifestations of COVID-19 with systemic symptoms. Here we report that a hamster strain of Phodopus roborovskii SH101, a laboratory inbred hamster strain of P. roborovskii, displayed most symptoms of systemic infection upon SARS-CoV-2 infection as in the case of the human counterpart, unlike current COVID-19 animal models. P. roborovskii SH101 post-infection of SARS-CoV-2 represented most clinical symptoms of COVID-19 such as snuffling, dyspnea, cough, labored breathing, hunched posture, progressive weight loss, and ruffled fur, in addition to high fever following shaking chills. Histological examinations also revealed a serious right-predominated pneumonia as well as slight organ damages in the brain and liver, manifesting systemic COVID-19 cases. Considering the merit of a small animal as well as its clinical manifestations of SARS-CoV-2 infection in human, this hamster model seems to provide an ideal tool to investigate COVID-19. Author summaryAlthough the current animal models supported SARS-CoV-2 replication and displayed varying degrees of illness after SARS-CoV-2 infection, the infections of SARS-CoV-2 were mainly limited to the respiratory systems of these animals, including hACE2 transgenic mice, hamsters, ferrets, fruit bats, guinea pigs, African green monkey, Rhesus macaques, and Cynomolgus macaques. While these animal models can be a modest model for the respiratory infection, there is a clear limit for use them in the study of COVID-19 that also displays multiple systemic symptoms. Therefore, the development of an animal model recapitulating COVID-19-specific symptoms such as the right-predominated pneumonia would be the utmost need to overcome the imminent threat posed by COVID-19. We identified a very interesting hamster strain, Phodopus roborovskii SH101, which mimics almost all aspects of the clinical manifestations of COVID-19 upon SARS-CoV-2 infection. Unlike the current animal models, SARS-CoV-2-infected P. roborovskii SH101 not only displayed the symptoms of respiratory infection but also clinical manifestations specific to human COVID-19 such as high fever following shaking chills, serious right-predominated pneumonia, and minor organ damages in the brain and liver.

microbiology↗

bioRxiv2019

Cost implications of a nationwide survey of schistosomiasis and other intestinal helminthiases in Sudan

BackgroundIt is vital to share details of concrete experiences of conducting a nationwide survey, so that the global health community could adapt it to expand geographic mapping programs, eventually contributing to the development of control and elimination strategies with limited resources. A nationwide survey of schistosomiasis and nine other intestinal helminthiases was conducted from December 2016 to March 2017 in Sudan. ObjectivesWe aimed to describe details of the key activities and components required for the nationwide survey of schistosomiasis and other intestinal helminthiases and to analyze its costs. MethodsWe estimated financial and economic costs from the providers perspective. Cash expenditures incurred to implement the survey were defined as financial costs. We took into account all of the resources invested in the survey for economic costs, including the components that were not paid for, such as vehicles and survey equipment provided by the Ministry of Health, Sudan and the opportunity costs of primary school teachers time spent on the survey. We ran one-way sensitivity and probabilistic analyses using Monte-Carlo methods with 10,000 draws to examine the robustness of the primary analysis results. ResultsA total of USD 1,465,902 and USD 1,516,238 was incurred for the financial and economic costs, respectively. The key cost drivers of the nationwide survey were personnel and transportation, for both financial and economic costs. Personnel and transportation accounted for around 64% and 18% of financial costs, respectively. ConclusionsThe cost is expected to vary depending on the quantity and quality of existing laboratory facilities, equipment, and consumables, and the capability of laboratory technicians and sample collectors. Establishing central-level and independent supervision mechanisms to ensure the quality of the survey is equally important. We expect the global health community to draw on this study when developing nationwide surveys of schistosomiasis and other intestinal helminthiases. Author SummaryAlthough large-scale mapping of schistosomiasis and other intestinal helminthiases has been conducted in some countries, little is known about the details of nationwide surveys, such as the necessary scale of the workforce, logistics, and the cost of conducting a nationwide survey. A nationwide survey of schistosomiasis and nine other intestinal helminthiases was conducted from December 2016 to March 2017 in Sudan. A total of 105,167 students participated in the survey from 1,772 primary schools in 183 districts of all 18 states of Sudan. Herein, we present the activities that were necessary to prepare and conduct a nationwide neglected tropical disease survey, along with details on the types and amounts of personnel, survey equipment, and consumables that are required. In addition, through an analysis of the costs of the nationwide survey, we generated average costs at the district and sub-district level. The key cost drivers were personnel and transportation, both of which were recurrent costs. Establishing a steering committee to develop and reach consensus on a survey protocol, assessing the capacities of potential staff (particularly laboratory technicians), and training laboratory technicians and data collectors were key components required to prepare a nationwide survey. If a government finds a way to mobilize existing government officials with no additional payment using the health system already in place, the cost of a nationwide survey would be remarkably lower. We expect the global health community to draw on this study to develop nationwide surveys for schistosomiasis and other intestinal helminthiases.

microbiology↗

bioRxiv2018

Oligomeric α-synuclein-specific degradation by HtrA2/Omi to bestow a neuroprotective function

Although the malfunction of HtrA2/Omi leads to Parkinsons disease (PD), the underlying mechanism has remained unknown. Here, we showed that HtrA2/Omi specifically removed oligomeric -Syn but not monomeric -Syn to protect oligomeric -Syn-induced neurodegeneration. Experiments using mnd2 mice indicated that HtrA2/Omi degraded oligomeric -Syn specifically without affecting monomers. Transgenic Drosophila melanogaster experiments of the co-expression -Syn and HtrA2/Omi and expression of genes individually also confirmed that pan-neuronal expression of HtrA2/Omi completely rescued Parkinsonism in the -Syn-induced PD Drosophila model by specifically removing oligomeric -Syn. HtrA2/Omi maintained the health and integrity of the brain and extended the life span of transgenic flies. Because HtrA2/Omi specifically degraded oligomeric -Syn, co-expression of HtrA2/Omi and -Syn in Drosophila eye maintained a healthy retina, while the expression of -Syn induced retinal degeneration. This work showed that the bacterial function of HtrA to degrade toxic misfolded proteins is evolutionarily conserved in mammalian brains as HtrA2/Omi.

neuroscience↗