Biology subjects

Guo, X.

Publications and source records attributed to Guo, X..

23 records · Page 2Linked to original sources

bioRxiv2017

Uterine progesterone signaling is a target for metformin therapy in polycystic ovary syndrome

Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.

physiology↗

bioRxiv2017

High-throughput creation and functional profiling of eukaryotic DNA sequence variant libraries using CRISPR/Cas9

Construction of genetic variant libraries with phenotypic measurement is central to advancing todays functional genomics, and remains a grand challenge. Here, we introduce a Cas9-based approach for generating pools of mutants with defined genetic alterations (deletions, substitutions and insertions), along with methods for tracking their fitness en masse. We demonstrate the utility of our approach in performing focused analysis of hundreds of mutants of a single protein and in investigating the biological function of an entire family of poorly characterized genetic elements. Our platform allows fundamental biology questions to be investigated in a quick, easy and affordable manner.

bioengineering↗

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

A novel k-mer set memory (KSM) motif representation improves regulatory variant prediction

The representation and discovery of transcription factor (TF) sequence binding specificities is critical for understanding gene regulatory networks and interpreting the impact of disease-associated non-coding genetic variants. We present a novel TF binding motif representation, the K-mer Set Memory (KSM), which consists of a set of aligned k-mers that are over-represented at TF binding sites, and a new method called KMAC for de novo discovery of KSMs. We find that KSMs more accurately predict in vivo binding sites than position weight matrix models (PWMs) and other more complex motif models across a large set of ChIP-seq experiments. KMAC also identifies correct motifs in more experiments than four state-of-the-art motif discovery methods. In addition, KSM derived features outperform both PWM and deep learning model derived sequence features in predicting differential regulatory activities of expression quantitative trait loci (eQTL) alleles. Finally, we have applied KMAC to 1488 ENCODE TF ChIP-seq datasets and created a public resource of KSM and PWM motifs. We expect that the KSM representation and KMAC method will be valuable in characterizing TF binding specificities and in interpreting the effects of non-coding genetic variations.

genomics↗

bioRxiv2017

A Cassava Drought Inducible CC-Type Glutaredoxin, MeGRX232, Negatively Regulates Drought Tolerance In Arabidopsis By Inhibition Of ABA-Dependent Stoma

CC-type glutaredoxins (GRXs) are a land plant-specific GRX subgroup that evolved from CGFS GRXs, and participate in organ development and stress responses through the regulation of transcription factors. Here, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (MeGRX058, 232, 360, 496, 785, and 892) were induced by drought and ABA stress in cassava leaves. Furthermore, we found that overexpression of MeGRX232 results in drought hypersensitivity in soil-grown plants, with a higher water loss rate, but with increased tolerance of mannitol and ABA in Arabidopsis on the sealed agar plates. The ABA induced stomatal closure is impaired in MeGRX232-OE Arabidopsis. Further analysis reveals that the overexpression of MeGRX232 leads to more ROS accumulation in guard cells. MeGRX232 can interact with TGA5 from Arabidopsis and MeTGA074 from cassava in vitro and in vivo. The results of microarray assays show that MeGRX232-OE affected the expression of a set of drought and oxidative stress related genes. Taken together, we demonstrated that CC-type GRXs involved in ABA signal transduction and play roles in response to drought through regulating stomatal closure.\n\nNovelty statementWe found that drought and ABA stress induced the transcription of CC-type glutaredoxins (GRXs) in cassava leaves. Ectopic expression of one of them, MeGRX232 in Arabidopsis affected the sensitivity to abscisic acid (ABA) and mannitol, and caused drought hypersensitivity by impairment of ABA-dependent stomatal closure.

molecular biology↗