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1.  Genome-Wide Transcriptome Profiles of Rice Hybrids and Their Parents 
Heterosis is a widely studied phenomenon in several plant species. However, its genetic basis still remains to be elucidated. In this study, we used RNA-seq data from two rice genotypes and their reciprocal hybrids, and used a combination of transcriptome profiling and allele-specific expression analysis to identify genes that are differentially expressed in the hybrids and their parents or expressed in an allele-specific manner. The differentially expressed genes (DEGs) were identified by a pairwise comparison of the four genotypes. Detailed annotation of DEGs suggested that these genes showed enrichment in some gene ontology categories, and they tend to have tissue-specific expression patterns compared to all genes. A total of 1033 (10.24%) of 10,195 genes with informative single nucleotide polymorphism (SNPs) were identified as ASE genes. These allele-specific expessed (ASE) genes showed a broader expression breadth suggesting that they function in diverse developmental stages. Among 1033 ASE genes, we also identified 45 ASE transcription factors belonging to 17 transcription factor families. These ASE transcription factors may act in trans to regulate gene expression in filial 1 (F1) hybrids. Our analyses provide a comprehensive transcriptome profile of rice hybrids and their parents, and would be a useful resource for the rice research community.
PMCID: PMC4264198  PMID: 25402644
transcriptome profile; hybrid rice; allele-specific expressed genes; differentially-expressed genes
2.  Synaptic mutant huntingtin inhibits synapsin-1 phosphorylation and causes neurological symptoms 
The Journal of Cell Biology  2013;202(7):1123-1138.
Polyglutamine-expanded huntingtin specifically targeted to synapses binds to synapsin-1, inhibits its phosphorylation, and causes defects in neurotransmitter release and age-dependent defects in neurological function.
Many genetic mouse models of Huntington’s disease (HD) have established that mutant huntingtin (htt) accumulates in various subcellular regions to affect a variety of cellular functions, but whether and how synaptic mutant htt directly mediates HD neuropathology remains to be determined. We generated transgenic mice that selectively express mutant htt in the presynaptic terminals. Although it was not overexpressed, synaptic mutant htt caused age-dependent neurological symptoms and early death in mice as well as defects in synaptic neurotransmitter release. Mass spectrometry analysis of synaptic fractions and immunoprecipitation of synapsin-1 from HD CAG150 knockin mouse brains revealed that mutant htt binds to synapsin-1, a protein whose phosphorylation is critical for neurotransmitter release. We found that polyglutamine-expanded exon1 htt binds to the C-terminal region of synapsin-1 to reduce synapsin-1 phosphorylation. Our findings point to a critical role for synaptic htt in the neurological symptoms of HD, providing a new therapeutic target.
PMCID: PMC3787372  PMID: 24081492
3.  Neuronal expression of TATA box-binding protein containing expanded polyglutamine in knock-in mice reduces chaperone protein response by impairing the function of nuclear factor-Y transcription factor 
Brain  2011;134(7):1943-1958.
The polyglutamine diseases consist of nine neurodegenerative disorders including spinocerebellar ataxia type 17 that is caused by a polyglutamine tract expansion in the TATA box-binding protein. In all polyglutamine diseases, polyglutamine-expanded proteins are ubiquitously expressed throughout the body but cause selective neurodegeneration. Understanding the specific effects of polyglutamine-expanded proteins, when expressed at the endogenous levels, in neurons is important for unravelling the pathogenesis of polyglutamine diseases. However, addressing this important issue using mouse models that either overly or ubiquitously express mutant polyglutamine proteins in the brain and body has proved difficult. To investigate the pathogenesis of spinocerebellar ataxia 17, we generated a conditional knock-in mouse model that expresses one copy of the mutant TATA box-binding protein gene, which encodes a 105-glutamine repeat, selectively in neuronal cells at the endogenous level. Neuronal expression of mutant TATA box-binding protein causes age-dependent neurological symptoms in mice and the degeneration of cerebellar Purkinje cells. Mutant TATA box-binding protein binds more tightly to the transcription factor nuclear factor-Y, inhibits its association with the chaperone protein promoter, as well as the promoter activity and reduces the expression of the chaperones Hsp70, Hsp25 and HspA5, and their response to stress. These findings demonstrate how mutant TATA box-binding protein at the endogenous level affects neuronal function, with important implications for the pathogenesis and treatment of polyglutamine diseases.
PMCID: PMC3122377  PMID: 21705419
polyglutamine; transcription factor; neurodegeneration; ataxia; animal models
4.  Tannin extracts from immature fruits of Terminalia chebula Fructus Retz. promote cutaneous wound healing in rats 
Tannins extracted from immature fruits of Terminalia chebula Fructus Retz. are considered as effective components promoting the process of wound healing. The objective of this study is to explore the optimal extraction and purification technology (OEPT) of tannins, while studying the use of this drug in the treatment of a cutaneous wound of rat as well as its antibacterial effects.
The content of tannin extracts was measured by the casein method, and antibacterial ability was studied by the micro-dilution method in vitro. In wound healing experiment, animals in group Ⅰ, Ⅱ and Ⅲ were treated with vaseline ointment, tannin extracts (tannin content: 81%) and erythromycin ointment, respectively (5 mg of ointment were applied on each wound). To evaluate the process of wound healing, selected pharmacological and biochemical parameters were applied.
After optimal extraction and purification, content of tannin extracts was increased to 81%. Tannin extracts showed the inhibition of Staphylococcus aureus and Klebsiella Pneumonia in vitro. After excision of wounds, on days 7 and 10, the percent of wound contraction of group Ⅱ was higher than that of group Ⅰ. After being hurt with wounds, on days 3, 7, and 10, the wound healing quality of group Ⅱ was found to be better than that of group Ⅰ in terms of granulation formation and collagen organization. After wound creation, on day 3, the vascular endothelial growth factor expression of group Ⅱ was higher than that of group Ⅰ.
The results suggest that tannin extracts from dried immature fruits of Terminalia chebula Fructus Retz. can promote cutaneous wound healing in rats, probably resulting from a powerful anti-bacterial and angiogenic activity of the extracts.
PMCID: PMC3198757  PMID: 21982053
5.  The Potential for Low-Temperature Abiotic Hydrogen Generation and a Hydrogen-Driven Deep Biosphere 
Astrobiology  2011;11(7):711-724.
The release and oxidation of ferrous iron during aqueous alteration of the mineral olivine is known to reduce aqueous solutions to such extent that molecular hydrogen, H2, forms. H2 is an efficient energy carrier and is considered basal to the deep subsurface biosphere. Knowledge of the potential for H2 generation is therefore vital to understanding the deep biosphere on Earth and on extraterrestrial bodies.
Here, we provide a review of factors that may reduce the potential for H2 generation with a focus on systems in the core temperature region for thermophilic to hyperthermophilic microbial life. We show that aqueous sulfate may inhibit the formation of H2, whereas redox-sensitive compounds of carbon and nitrogen are unlikely to have significant effect at low temperatures. In addition, we suggest that the rate of H2 generation is proportional to the dissolution rate of olivine and, hence, limited by factors such as reactive surface areas and the access of water to fresh surfaces. We furthermore suggest that the availability of water and pore/fracture space are the most important factors that limit the generation of H2. Our study implies that, because of large heat flows, abundant olivine-bearing rocks, large thermodynamic gradients, and reduced atmospheres, young Earth and Mars probably offered abundant systems where microbial life could possibly have emerged. Key Words: Serpentinization—Olivine—Hydrogen—Deep biosphere—Water—Mars. Astrobiology 11, 711–724.
PMCID: PMC3176347  PMID: 21923409
6.  Inhibiting the ubiquitin–proteasome system leads to preferential accumulation of toxic N-terminal mutant huntingtin fragments 
Human Molecular Genetics  2010;19(12):2445-2455.
An expanded polyglutamine (polyQ) domain in the N-terminal region of huntingtin (htt) causes misfolding and accumulation of htt in neuronal cells and the subsequent neurodegeneration of Huntington's disease (HD). Clearing the misfolded htt is critical for preventing neuropathology, and this process is mediated primarily by both the ubiquitin–proteasome system (UPS) and autophagy. Although overexpression of mutant htt can inhibit UPS activity in cultured cells, mutant htt does not inhibit global UPS activity in the brains of HD transgenic mice. These findings underscore the importance of investigating the function of the UPS and autophagy in the brain when mutant proteins are not overexpressed. When cultured PC12 cells were treated with either UPS or autophagy inhibitors, more N-terminal mutant htt fragments accumulated via inhibition of the UPS. Furthermore, in HD CAG repeat knock-in mouse brain, inhibiting the UPS also resulted in a greater accumulation of N-terminal, but not full-length, mutant htt than inhibiting autophagy did. Our findings suggest that impairment of the UPS may be more important for the accumulation of N-terminal mutant htt and might therefore make an attractive therapeutic target.
PMCID: PMC2876889  PMID: 20354076
7.  Transcriptional dysregulation of TrkA associates with neurodegeneration in spinocerebellar ataxia type 17 
Human Molecular Genetics  2009;18(21):4141-4152.
TATA binding protein (TBP), a universal transcription factor, is broadly required by nuclear RNA polymerases for the initiation of transcription. TBP contains a polymorphic polyglutamine tract in its N-terminal region, and expansion of this tract leads to spinocerebellar ataxia type 17 (SCA17), one of nine dominantly inherited neurodegenerative diseases caused by polyglutamine expansion in the affected proteins. The expanded polyglutamine proteins are ubiquitously expressed, but cause selective and characteristic neurodegeneration in distinct brain regions in each disease. Unlike many other polyglutamine proteins, whose functions are not yet fully understood, TBP is a well-characterized transcription factor that is restricted to the nucleus. Thus, investigating how mutant TBP mediates neuropathology should help elucidate the mechanisms by which transcriptional dysregulation contributes to neuronal dysfunction and/or neurodegeneration in polyglutamine diseases. To this end, we characterized cellular and mouse models expressing polyQ-expanded TBP. The cell model exhibits characteristic features of neuronal dysfunction, including decreased cell viability and defective neurite outgrowth. We found that the high-affinity nerve growth factor receptor, TrkA, is down-regulated by mutant TBP in cells. Down-regulation of TrkA also occurs in the cerebellum of SCA17 transgenic mice prior to Purkinje cell degeneration. Mutant TBP binds more Sp1, reduces its occupancy of the TrkA promoter and inhibits the activity of the TrkA promoter. These findings suggest that the transcriptional down-regulation of TrkA by mutant TBP contributes to SCA17 pathogenesis.
PMCID: PMC2758144  PMID: 19643914

Results 1-7 (7)