Biology subjects

Tong, Y.

Publications and source records attributed to Tong, Y..

5 recordsLinked to original sources

bioRxiv2018

Transection of the ventral hippocampal commissure impairs spatial but not contextual memory in split-brain mice

Plasticity is a neural phenomenon in which experience induces long-lasting changes to neuronal circuits and is at the center of most neurobiological theories of learning and memory. However, too much plasticity is maladaptive and must be balanced with substrate stability. Area CA3 of the hippocampus is lateralized with the left hemisphere dominant in plasticity and the right specialized for stability. Left and right CA3 project bilaterally to CA1; however, it is not known whether this downstream merging of lateralized plasticity and stability is functional. We hypothesized that interhemispheric integration of input from these pathways is essential for integrating spatial memory stored in the left CA3 with spatial working memory facilitated by the right CA3. To test this, we severed interhemispheric connections between the left and right hippocampi in mice and assessed learning and memory. Despite damage to this major hippocampal fiber tract, hippocampus-dependent spatial working memory and short- and long-term memory were both spared. However, tasks that required the integration of information retrieved from memory with ongoing spatial working memory and navigation were impaired. We propose that one function of interhemispheric communication in the mouse hippocampus is to integrate lateralized processing of plastic and stable circuits to facilitate memory-guided spatial navigation.

neuroscience↗

bioRxiv2018

Drug target identification and virtual screening in pursuit of phytochemical intervention of Mycobacterium chelonae

Mycobacterium chelonae is a rapidly growing mycobacterium present in the environment. It is associated with skin and soft tissue infections including abscess, cellulitis and osteomyelitis. Other infections by this bacterium are post-operative/transplant-associated, catheter, prostheses and even concomitant to haemodialytic procedures. In this study, we employ a subtractive genomics approach to predict the potential therapeutic candidates, intended for experimental research against this bacterium. A computational workflow was devised and executed to procure core proteome targets essential to the pathogen but with no similarity to the human host. Initially, essential Mycobacterium chelonae proteins were predicted through homology searching of core proteome content from 19 different bacteria. Druggable proteins were then identified and N-acetylglucosamine-1-phosphate uridyltransferase (GlmU) was chosen as a case study from identified therapeutic targets, based on its important bifunctional role. Structure modeling was followed by virtual screening of phytochemicals (N > 10,000) against it. 4,4-[(1E)-5-hydroxy-4-(methoxymethyl)-1-pentene-1,5-diyl]diphenol, apigenin-7-O-beta-gluconopyranoside and methyl rosmarinate were screened as compounds having best potential for binding GlmU. Phytotherapy helps curb the menace of antibiotic resistance so treatment of Mycobacterium chelonae infection through this method is recommended.

bioinformatics↗

bioRxiv2017

Epidemic Potential for Human Infection with Influenza A (H7N9) Virus in China through Web Search Behaviors: A Data-Driven Study

Since the beginning of September 2016, a steep upsurge of the human cases of avian influenza A (H7N9) virus has been reported in China, which are alarming public concern for the pandemic potential of the H7N9 virus. In this study, we collected the data from H7N9 epidemics and H7N9-related Baidu Search Index (BSI) in China between September 2013 and June 2017. And we observed a strong correlation between the numbers of Influenza A (H7N9) cases and H7N9-related BSI in Guangdong province and Shanghai municipality (p<0.001). Autoregressive integrated moving average (ARIMA) models were constructed for the dynamic estimation of seasonal H7N9 outbreaks in 2016-2017 and the online search data acted as an external regressor with the historical H7N9 epidemic data in the forecasting model to improve the quality of predictions. Predictions by the models closely matched the actual numbers of reported cases during current H7N9 epidemic season. Especially, the estimated numbers of reported cases sharply increased to reach 49.88 (95% CI: 0-194.05) in Guangdong and 9.05 (95% CI: 0-37.43) in Shanghai from December 2016 to June 2017. Moreover, this accessible and flexible dynamic forecast model could be used in the monitoring of H7N9 virus to provide advanced warning of future emerging infection diseases.\n\nAuthor summaryAs the availability and popularity of the internet has greatly increased in recent years, an increasing number of cyber users, including patients and their family members, search online for health information on personal computers (PCs) and mobile phones (MPs) before seeking medical attention, making it possible to investigate the influenza prevalence by monitoring changes in frequencies of uses of particular search terms. In this study, we collected the data from H7N9 epidemics and H7N9-related Baidu Search Index (BSI) in China between September 2013 and June 2017. And then, we showed a strong correlation between the numbers of Influenza A (H7N9) cases and H7N9-related BSI in Guangdong province and Shanghai municipality (p<0.001). Furthermore, we reconstructed an improved dynamic forecasting method for outbreaks of H7N9 influenza using Autoregressive integrated moving average (ARIMA) models to predict future patterns of H7N9 transmission and the online search data acted as an external regressor with the historical H7N9 epidemic data in the forecasting model to improve the quality of predictions. Our results suggest that data from the Baidu search engine, combed with data from a traditional disease surveillance system, may be considered for early detection of H7N9 influenza outbreaks in mainland China.

epidemiology↗

bioRxiv2017

Intestinal cell kinase regulates chondrocyte proliferation and maturation during skeletal development

An autosomal recessive loss-of-function mutation R272Q in human ICK (intestinal cell kinase) gene causes profound multiplex developmental defects in human ECO (endocrine-cerebro-osteodysplasia) syndrome. ECO patients exhibit a wide variety of skeletal abnormalities, yet the underlying cellular and molecular mechanisms by which ICK regulates skeletal development remain largely unknown. The goal of this study is to understand the structural and mechanistic basis underlying skeletal anomalies caused by ICK dysfunction. Ick R272Q knock in transgenic mouse model not only recapitulated major ECO skeletal defects such as short limbs and polydactyly but also revealed a deformed spine with deficient intervertebral disc. Loss of ICK functions markedly reduces mineralization in the spinal column, ribs, and long bones. Ick mutants show a significant decrease in the number of proliferating chondrocytes and type X collagen-expressing hypertrophic chondrocytes in the spinal column and the growth plate of long bones. Our results demonstrate that ICK plays an important role in bone and intervertebral disc development by promoting chondrocyte proliferation and maturation, and thus provide novel mechanistic insights into the skeletal phenotypes of human ECO syndrome.

developmental biology↗

bioRxiv2017

Gαq Mediates Clozapine Effects in Caenorhabditis elegans

Clozapine binds and has significant effects on multiple neurotransmitter receptors, notably including some dopamine receptors. Downstream of these receptors, clozapine affects the balance of Gi- and Gq-dependent second-messenger signaling. We used Caenorhabiditis elegans as a genetic model to study further how clozapine affects both dopamine receptors and downstream Gq mediated signaling. Four of six worm dopamine receptor orthologs, dop-1, dop-2, dop-4, and dop-5 produced resistance to clozapine induced developmental delay when mutated, suggesting that both type I and type II dopamine receptors mediate the behavioral effects of clozapine in C. elegans. Beyond these receptors, reduction of function of one of the G proteins, egl-30 (Gq), produced greatly increased susceptibility to clozapine. Gq has multiple known downstream effects. Among these is the control of acetylcholine release, which is in balance with monoamines in the human brain and is another target of clozapine and other antipsychotic drugs. We tested for downstream effects on acetylcholine at the neuromuscular junction upon clozapine treatment but found no evidence for effects of clozapine. In contrast, modulation of Gq upstream leads to worms that are either more resistant or more susceptible to clozapine, emphasizing the importance of Gq proteins in mediating effects of clozapine. A genetic screen for suppressors of egl-30 recovered eight mutants. By characterizing the behavioral effects of these mutants, we found that clozapine exerts its function on development by affecting Gq signaling through control of the pharyngeal pumping rate. A whole-genome sequencing technique was utilized and identified a list of candidate genes for these suppressor mutations. Further characterization of these mutants promises the discovery of novel components participating in Gq signaling and a better understanding of the mechanisms of action of clozapine.

genetics↗