References of "Wang, Kai"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailThe extracellular RNA complement of Escherichia coli
Ghosal, Anubrata UL; Upadhyaya, Bimal Babu UL; Fritz, Joëlle UL et al

in MicrobiologyOpen (2015)

he secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but ... [more ▼]

he secretion of biomolecules into the extracellular milieu is a common and well-conserved phenomenon in biology. In bacteria, secreted biomolecules are not only involved in intra-species communication but they also play roles in inter-kingdom exchanges and pathogenicity. To date, released products, such as small molecules, DNA, peptides, and proteins, have been well studied in bacte- ria. However, the bacterial extracellular RNA complement has so far not been comprehensively characterized. Here, we have analyzed, using a combination of physical characterization and high-throughput sequencing, the extracellular RNA complement of both outer membrane vesicle (OMV)-associated and OMV-free RNA of the enteric Gram-negative model bacterium Escherichia coli K-12 substrain MG1655 and have compared it to its intracellular RNA comple- ment. Our results demonstrate that a large part of the extracellular RNA com- plement is in the size range between 15 and 40 nucleotides and is derived from specific intracellular RNAs. Furthermore, RNA is associated with OMVs and the relative abundances of RNA biotypes in the intracellular, OMV and OMV- free fractions are distinct. Apart from rRNA fragments, a significant portion of the extracellular RNA complement is composed of specific cleavage products of functionally important structural noncoding RNAs, including tRNAs, 4.5S RNA, 6S RNA, and tmRNA. In addition, the extracellular RNA pool includes RNA biotypes from cryptic prophages, intergenic, and coding regions, of which some are so far uncharacterised, for example, transcripts mapping to the fimA- fimL and ves-spy intergenic regions. Our study provides the first detailed char- acterization of the extracellular RNA complement of the enteric model bacte- rium E. coli. Analogous to findings in eukaryotes, our results suggest the selective export of specific RNA biotypes by E. coli, which in turn indicates a potential role for extracellular bacterial RNAs in intercellular communication. [less ▲]

Detailed reference viewed: 215 (15 UL)
Full Text
Peer Reviewed
See detailSystems genomics evaluation of the SH-SY5Y neuroblastoma cell line as a model for Parkinson’s disease
Krishna, Abhimanyu UL; Biryukov, Maria UL; Trefois, Christophe UL et al

in BMC Genomics (2014), 15(1154),

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often ... [more ▼]

Background: The human neuroblastoma cell line, SH-SY5Y, is a commonly used cell line in studies related to neurotoxicity, oxidative stress, and neurodegenerative diseases. Although this cell line is often used as a cellular model for Parkinson’s disease, the relevance of this cellular model in the context of Parkinson’s disease (PD) and other neurodegenerative diseases has not yet been systematically evaluated. Results: We have used a systems genomics approach to characterize the SH-SY5Y cell line using whole-genome sequencing to determine the genetic content of the cell line and used transcriptomics and proteomics data to determine molecular correlations. Further, we integrated genomic variants using a network analysis approach to evaluate the suitability of the SH-SY5Y cell line for perturbation experiments in the context of neurodegenerative diseases, including PD. Conclusions: The systems genomics approach showed consistency across different biological levels (DNA, RNA and protein concentrations). Most of the genes belonging to the major Parkinson’s disease pathways and modules were intact in the SH-SY5Y genome. Specifically, each analysed gene related to PD has at least one intact copy in SH-SY5Y. The disease-specific network analysis approach ranked the genetic integrity of SH-SY5Y as higher for PD than for Alzheimer’s disease but lower than for Huntington’s disease and Amyotrophic Lateral Sclerosis for loss of function perturbation experiments. [less ▲]

Detailed reference viewed: 240 (25 UL)
Full Text
Peer Reviewed
See detailRNA in circulation: sources and functions of extracellular exogenous RNA in blood
Galas, David J. UL; Wilmes, Paul UL; Wang, Kai

in Nelson, Karen (Ed.) Encyclopedia of Metagenomics (2014)

Molecules of many kinds are abundant in circulating blood and play a wide range of important roles, both known and unknown. These include macromolecules like proteins and nucleic acids and a wide range of ... [more ▼]

Molecules of many kinds are abundant in circulating blood and play a wide range of important roles, both known and unknown. These include macromolecules like proteins and nucleic acids and a wide range of smaller molecules. A number of questions are raised by recent findings of stable RNA molecules in plasma that is circulating RNA outside of cells. Among the issues that need to be addressed are: what are the origins of these RNA molecules; what are the mechanisms by which they enter and are stabilized in the blood; what are their possible biological functions; and finally, what are the potential applications of these extracellular RNA molecules in diagnostic and therapeutic medicine? While the precise biological functions remain to be pinned down, extracellular RNA has been proposed as a vehicle for a previously unknown cell-cell communication system. Recent reports of the detection of foreign, exogenous sources of some of the extracellular RNA have thus intensified the need to investigate and understand these processes. This overview summarizes the findings, some recent developments, and the current state of research in the circulating RNA field, and some of the key open questions in the field are specifically addressed. [less ▲]

Detailed reference viewed: 279 (17 UL)
Full Text
Peer Reviewed
See detailThe spectrum of circulating RNA: A window into systems toxicology
Wang, Kai; Yuan, Yue; Cho, Ji-Hoon et al

in Toxicological Sciences (2013), 132(2), 478492

Adverse effects caused by therapeutic drugs are a serious and costly health concern. Despite the body’s systemic responses to therapeutics, the liver is often the focus of damage and is usually the focus ... [more ▼]

Adverse effects caused by therapeutic drugs are a serious and costly health concern. Despite the body’s systemic responses to therapeutics, the liver is often the focus of damage and is usually the focus of studies of toxic effects due to its active roles in the metabolism of xenobiotics. It is extremely difficult, however, to assess systemic responses with currently available methods. Comprehensive cataloging of cell-free circulating RNAs using next-generation sequencing technology may open a window to assess drug-associated adverse effects at the systems level. To explore this potential, we conducted an RNA profiling study using the well-characterized acetaminophen overdose mouse model on liver and plasma with microarray and next-generation sequencing platforms, respectively. After drug treatment, the levels of a number of transcripts, both endogenous and exogenous RNAs, showed significant changes in plasma, reflecting not only the classical liver injury induced by acetaminophen overdose but also damage in tissues other than the liver. The changes in exogenous RNAs also reflect alteration on dieting behavior after acetaminophen overdose. Besides reporting an extensive list of circulating RNAbased biomarker candidates, this study illustrates the possibility of using circulating RNAs to assess global effects of therapeutics. This could also lead to a new approach for a more comprehensive assessment of the efficacy and safety of therapeutics. [less ▲]

Detailed reference viewed: 67 (0 UL)
Full Text
Peer Reviewed
See detailRNASEQR—a streamlined and accurate RNA-seq sequence analysis program
Chen, Leslie Y.; Wei, Kuo-Chen; Huang, Abner C.-Y. et al

in Nucleic Acids Research (2012), 40(6), 42-

Next-generation sequencing (NGS) technologiesbased transcriptomic profiling method often called RNA-seq has been widely used to study global gene expression, alternative exon usage, new exon discovery ... [more ▼]

Next-generation sequencing (NGS) technologiesbased transcriptomic profiling method often called RNA-seq has been widely used to study global gene expression, alternative exon usage, new exon discovery, novel transcriptional isoforms and genomic sequence variations. However, this technique also poses many biological and informatics challenges to extracting meaningful biological information. The RNA-seq data analysis is built on the foundation of high quality initial genome localization and alignment information for RNA-seq sequences. Toward this goal, we have developed RNASEQR to accurately and effectively map millions of RNA-seq sequences. We have systematically compared RNASEQR with four of the most widely used tools using a simulated data set created from the Consensus CDS project and two experimental RNA-seq data sets generated from a human glioblastoma patient. Our results showed that RNASEQR yields more accurate estimates for gene expression, complete gene structures and new transcript isoforms, as well as more accurate detection of single nucleotide variants (SNVs). RNASEQR analyzes raw data from RNA-seq experiments effectively and outputs results in a manner that is compatible with a wide variety of specialized downstream analyses on desktop computers. [less ▲]

Detailed reference viewed: 77 (0 UL)
Full Text
Peer Reviewed
See detailMicroRNA as biomarkers and regulators in B-cell chronic lymphocytic leukemia
Moussay, Etienne; Wang, Kai; Cho, Ji-Hoon et al

in Proceedings of the National Academy of Sciences of the United States of America (2011), 108(16), 6573-6578

Early cancer detection and disease stratification or classification are critical to successful treatment. Accessible, reliable, and informative cancer biomarkers can be medically valuable and can provide ... [more ▼]

Early cancer detection and disease stratification or classification are critical to successful treatment. Accessible, reliable, and informative cancer biomarkers can be medically valuable and can provide some relevant insights into cancer biology. Recent studies have suggested improvements in detecting malignancies by the use of specific extracellular microRNAs (miRNAs) in plasma. In chronic lymphocytic leukemia (CLL), an incurable hematologic disorder, sensitive, early, and noninvasive diagnosis and better disease classification would be very useful for more effective therapies. We show here that circulating miRNAs can be sensitive biomarkers for CLL, because certain extracellular miRNAs are present in CLL patient plasma at levels significantly different from healthy controls and from patients affected by other hematologic malignancies. The levels of several of these circulating miRNAs also displayed significant differences between zeta-associated protein 70 (ZAP-70)(+) and ZAP-70(-) CLL. We also determined that the level of circulating miR-20a correlates reliably with diagnosis-to-treatment time. Network analysis of our data, suggests a regulatory network associated with BCL2 and ZAP-70 expression in CLL. This hypothesis suggests the possibility of using the levels of specific miRNAs in plasma to detect CLL and to determine the ZAP-70 status. [less ▲]

Detailed reference viewed: 97 (1 UL)