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1.  High Genetic Diversity and Novelty in Eukaryotic Plankton Assemblages Inhabiting Saline Lakes in the Qaidam Basin 
PLoS ONE  2014;9(11):e112812.
Saline lakes are intriguing ecosystems harboring extremely productive microbial communities in spite of their extreme environmental conditions. We performed a comprehensive analysis of the genetic diversity (18S rRNA gene) of the planktonic microbial eukaryotes (nano- and picoeukaryotes) in six different inland saline lakes located in the Qaidam Basin. The novelty level are high, with about 11.23% of the whole dataset showing <90% identity to any previously reported sequence in GenBank. At least 4 operational taxonomic units (OTUs) in mesosaline lakes, while up to eighteen OTUs in hypersaline lakes show very low CCM and CEM scores, indicating that these sequences are highly distantly related to any existing sequence. Most of the 18S rRNA gene sequence reads obtained in investigated mesosaline lakes is closely related to Holozoa group (48.13%), whereas Stramenopiles (26.65%) and Alveolates (10.84%) are the next most common groups. Hypersaline lakes in the Qaidam Basin are also dominated by Holozoa group, accounting for 26.65% of the total number of sequence reads. Notably, Chlorophyta group are only found in high abundance in Lake Gasikule (28.00%), whereas less represented in other hypersaline lakes such as Gahai (0.50%) and Xiaochaidan (1.15%). Further analysis show that the compositions of planktonic eukaryotic assemblages are also most variable between different sampling sites in the same lake. Out of the parameters, four show significant correlation to this CCA: altitude, calcium, sodium and potassium concentrations. Overall, this study shows important gaps in the current knowledge about planktonic microbial eukaryotes inhabiting Qaidam Basin (hyper) saline water bodies. The identified diversity and novelty patterns among eukaryotic plankton assemblages in saline lake are of great importance for understanding and interpreting their ecology and evolution.
doi:10.1371/journal.pone.0112812
PMCID: PMC4234628  PMID: 25401703
2.  Dax1 and Nanog act in parallel to stabilize mouse embryonic stem cells and induced pluripotency 
Nature Communications  2014;5:5042.
Nanog expression is heterogeneous and dynamic in embryonic stem cells (ESCs). However, the mechanism for stabilizing pluripotency during the transitions between Nanoghigh and Nanoglow states is not well understood. Here we report that Dax1 acts in parallel with Nanog to regulate mouse ESC (mESCs) identity. Dax1 stable knockdown mESCs are predisposed towards differentiation but do not lose pluripotency, whereas Dax1 overexpression supports LIF-independent self-renewal. Although partially complementary, Dax1 and Nanog function independently and cannot replace one another. They are both required for full reprogramming to induce pluripotency. Importantly, Dax1 is indispensable for self-renewal of Nanoglow mESCs. Moreover, we report that Dax1 prevents extra-embryonic endoderm (ExEn) commitment by directly repressing Gata6 transcription. Dax1 may also mediate inhibition of trophectoderm differentiation independent or as a downstream effector of Oct4. These findings establish a basal role of Dax1 in maintaining pluripotency during the state transition of mESCs and somatic cell reprogramming.
The transcription factor Dax1 is often used as an embryonic stem cell (ESC) marker. Here the authors show that Dax1 acts in parallel to the pluripotency transcription factor Nanog in the maintenance of mouse ESC pluripotency and is required for full somatic cell reprogramming.
doi:10.1038/ncomms6042
PMCID: PMC4205889  PMID: 25284313
3.  Construction of Monitoring Model and Algorithm Design on Passenger Security during Shipping Based on Improved Bayesian Network 
The Scientific World Journal  2014;2014:158652.
A large number of data is needed by the computation of the objective Bayesian network, but the data is hard to get in actual computation. The calculation method of Bayesian network was improved in this paper, and the fuzzy-precise Bayesian network was obtained. Then, the fuzzy-precise Bayesian network was used to reason Bayesian network model when the data is limited. The security of passengers during shipping is affected by various factors, and it is hard to predict and control. The index system that has the impact on the passenger safety during shipping was established on basis of the multifield coupling theory in this paper. Meanwhile, the fuzzy-precise Bayesian network was applied to monitor the security of passengers in the shipping process. The model was applied to monitor the passenger safety during shipping of a shipping company in Hainan, and the effectiveness of this model was examined. This research work provides guidance for guaranteeing security of passengers during shipping.
doi:10.1155/2014/158652
PMCID: PMC4164846  PMID: 25254227
4.  Fabrication of mAb G250-SPIO Molecular Magnetic Resonance Imaging Nanoprobe for the Specific Detection of Renal Cell Carcinoma In Vitro 
PLoS ONE  2014;9(7):e101898.
Molecular magnetic resonance imaging (mMRI) has been paid more and more attention for early diagnosis of cancer. A sensitive and specific mMRI probe plays the most important role in this technique. In this study, superparamagnetic iron oxide (SPIO) nanoparticles and mAb G250 were conjugated as mMRI probe for the detection of clear cell renal cell carcinoma (ccRCC) using 3.0-Tesla MRI in vitro. mAb G250 could specifically recognize carbonic anhydrase IX (CAIX) antigen overexpressed in ccRCC and the SPIO nanoparticles as MRI contrast agent presented excellent MRI response and good biocompatibility. The successful assembly of this nanoprobe was confirmed by UV-vis spectrum, FT-IR spectroscopy and DLS analysis. In vitro MRI study on ccRCC cells and control cells indicated that our fabricated mAb G250-SPIO nanoprobe could be used in the specific labeling of clear cell renal carcinoma cells successfully.
doi:10.1371/journal.pone.0101898
PMCID: PMC4084989  PMID: 24999987
5.  Hepatitis reactivation in patients with rheumatic diseases after immunosuppressive therapy—a report of long-term follow-up of serial cases and literature review 
Clinical Rheumatology  2013;33(4):577-586.
The aims of this paper are to report hepatitis B virus reactivation in 12 patients with rheumatic disease undergoing immunosuppressive therapy and to evaluate whether pre-emptive antiviral therapy is necessary in patients receiving disease-modifying anti-rheumatic drugs. From January 2008 to March 2012, a total of 12 HBV-infected patients with rheumatic diseases were consecutively enrolled in the long-term follow-up. Liver function, HBV DNA, and serum aminotransferase level were tested during the follow-up. We also reviewed the published reports and summarized the clinical characteristics of HBV reactivation during immunosuppressive therapy in patients with rheumatic diseases. The medium duration of follow-up was 41 months (range 16–48). Patients were treated with prednisone, disease-modifying anti-rheumatic drugs (DMARDs) or tumor necrosis factor-alpha-blocking agents (TNFBA). HBV reactivation was only documented in two patients treated with prednisone without pre-emptive antiviral therapy. One hundred patients from literature review were identified as having HBV reactivation; 20.8 % of the patients receiving prednisone experienced HBV reactivation compared to only 4.46 and 9.52 % of patients treated with DMARDs or TNFBA, respectively. This long-term follow-up of serial cases suggests that pre-emptive antiviral therapy should be administered in patients receiving prednisone therapy for rheumatic disease. In contrast, DMARDs and TNFBA are relatively safe to HBV-infected patients with rheumatic diseases. Close monitoring of HBV DNA and ALT levels is necessary in the management of HBV reactivation.
doi:10.1007/s10067-013-2450-9
PMCID: PMC3962582  PMID: 24343455
Disease-modifying anti-rheumatic drugs; Hepatitis B; Rheumatic disease; Steroid; Tumor necrosis factor-alpha-blocking agent
6.  HuPSON: the human physiology simulation ontology 
Background
Large biomedical simulation initiatives, such as the Virtual Physiological Human (VPH), are substantially dependent on controlled vocabularies to facilitate the exchange of information, of data and of models. Hindering these initiatives is a lack of a comprehensive ontology that covers the essential concepts of the simulation domain.
Results
We propose a first version of a newly constructed ontology, HuPSON, as a basis for shared semantics and interoperability of simulations, of models, of algorithms and of other resources in this domain. The ontology is based on the Basic Formal Ontology, and adheres to the MIREOT principles; the constructed ontology has been evaluated via structural features, competency questions and use case scenarios.
The ontology is freely available at: http://www.scai.fraunhofer.de/en/business-research-areas/bioinformatics/downloads.html (owl files) and http://bishop.scai.fraunhofer.de/scaiview/ (browser).
Conclusions
HuPSON provides a framework for a) annotating simulation experiments, b) retrieving relevant information that are required for modelling, c) enabling interoperability of algorithmic approaches used in biomedical simulation, d) comparing simulation results and e) linking knowledge-based approaches to simulation-based approaches. It is meant to foster a more rapid uptake of semantic technologies in the modelling and simulation domain, with particular focus on the VPH domain.
doi:10.1186/2041-1480-4-35
PMCID: PMC4177144  PMID: 24267822
Simulation; Algorithm; Interoperability; Ontology; Semantics; Text mining
7.  ApoE and the role of very low density lipoproteins in adipose tissue inflammation Wang: ApoE and adipose tissue inflammation 
Atherosclerosis  2012;223(2):342-349.
Objective
To identify the role of triglyceride-rich lipoproteins (TGRLs) and apoE, a major apolipoprotein in TGRLs, in adipose tissue inflammation with high-fat diet (HFD)–induced obesity.
Methods
Male apoE−/− and C57BL/6J wild-type (WT) mice fed HFD for 12 weeks were assessed for metabolic and inflammatory parameters. ApoE−/− and WT mice were orally gavaged with [3H]palmitic acid to examine the role of apoE in fat delivery to adipose tissue. VLDL from obese apoE−/− mice were intravenously injected into lean WT or apoE−/− mice to test potential contribution of TGRLs-derived fat delivery to inflammation in adipose tissue and the role of apoE.
Results
ApoE−/− mice gained less body weight, and had less fat mass and lower triglyceride levels in skeletal muscle than WT. ApoE−/− mice on HFD had better insulin sensitivity than WT even when comparing body weight–matched mice. Compared to WT mice, apoE−/− mice on HFD had lower levels of inflammatory cytokines/chemokines and CD11c in adipose tissue, and lower levels of inflammatory markers in skeletal muscle. At 6 hours after oral gavage with [3H]palmitic acid, incorporation of [3H]palmitic acid into adipose tissue and skeletal muscle was lower in apoE−/− mice. After repeated daily injection for 3 days, VLDL from obese apoE−/− mice induced inflammation in adipose tissue of recipient WT but not apoE−/− mice.
Conclusion
In HFD-induced obesity, apoE plays an important role in inflammation in adipose tissue and skeletal muscle, likely by mediating TGRL-derived fat delivery to these tissues.
doi:10.1016/j.atherosclerosis.2012.06.003
PMCID: PMC3411924  PMID: 22770993
adipose tissue; inflammation; insulin resistance; obesity; lipoproteins; apolipoprotein E
8.  Avian Influenza A(H7N9) Virus Infections, Shanghai, China 
Emerging Infectious Diseases  2013;19(7):1179-1181.
doi:10.3201/eid1907.130523
PMCID: PMC3713995  PMID: 23769147
avian influenza virus; viruses; H7N9; influenza; infections; outbreak; Shanghai; China
11.  Methylenetetrahydrofolate Reductase Polymorphisms and Risk of Acute Lymphoblastic Leukemia-Evidence from an updated meta-analysis including 35 studies 
BMC Medical Genetics  2012;13:77.
Background
5,10-methylenetetrahydrofolate reductase (MTHFR) variants, C677T and A1298C, have been reported to be associated with decreased risk of acute lymphoblastic leukemia (ALL). However, results derived from individually underpowered studies are conflicting. We carried out an updated meta-analysis on the association between MTHFR polymorphisms and ALL risk.
Methods
Relevant publications were searched through PUBMED and EMBASE databases. The associations between MTHFR C677T and A1298C polymorphisms and the risk of ALL were evaluated by odds ratios (ORs). The heterogeneity and publication bias were estimated. Meta-regression analysis was performed to evaluate the potential sources of heterogeneity.
Results
C677T polymorphism was associated with a reduced risk of ALL (allele contrast: ORRE = 0.91, 95% CI: 0.83-0.99). Subgroup analysis showed MTHFR C677T variant was associated with decreased susceptibility to ALL in children and Caucasians. Meta-regression showed the logOR for the association between T allele and ALL increased as sex ratio (M/F) in the case group increased (P = 0.01). Regarding A1298C polymorphism, no significant association was observed (allele contrast: ORRE = 1.01, 95% CI: 0.91-1.11). There was no publication bias for C677T or A1298C polymorphism.
Conclusions
The present meta-analysis suggests that the C677T polymorphism, not A1298C, in MTHFR gene is associated with a decreased risk of ALL, particularly among children and Caucasians subjects. Our findings suggest that the influence of the C677T polymorphism on ALL susceptibility is modified by sex ratio in cases (M/F). Since folate intake may be a possible confounding factor, including this factor in future prospective studies is warranted. Further meta-analysis studies should be at least stratified for folate levels and gender to give more powerful and informative results.
doi:10.1186/1471-2350-13-77
PMCID: PMC3459788  PMID: 22943282
Acute lymphoblastic leukemia; Polymorphism; Meta-analysis; 5,10-methylenetetrahydrofolate reductase; Update
12.  ‘Old Drugs for New Applications’: Can Orthopedic Research Benefit from This Strategy? 
New drug exploration is difficult in a clinical setting and the development of new drugs may be costly and time consuming. With further research into the pathological mechanisms and etiology of diseases as well as the rapid development of biological techniques, many ‘old drugs’ that have been applied in clinics may have new therapeutic functions which may shed light on clinical management. Based on this, we have investigated the ‘old drugs for new applications’ strategy in pharmacology which may be less expensive and more efficient in the clinical setting. In this paper we have explored and illustrated the potential applications of ‘old drugs’ for the treatment of orthopedic diseases, especially in arthritis and osteoporosis therapy.
doi:10.1177/1759720X11408487
PMCID: PMC3382676  PMID: 22870479
cholinergic anti-inflammatory pathway; cholinergic antinociceptive pathway; old drugs for new applications; orthopedic research; rheumatoid arthritis
13.  Variability of Gene Expression After Polyhaploidization in Wheat (Triticum aestivum L.) 
G3: Genes|Genomes|Genetics  2011;1(1):27-33.
Interspecific hybridization has a much greater effect than chromosome doubling on gene expression; however, the associations between homeologous gene expression changes and polyhaploidization had rarely been addressed. In this study, cDNA–single strand conformation polymorphism analysis was applied to measure the expression of 30 homeologous transcripts in naturally occurring haploid (ABD, 2n = 21) and its polyploid maternal parent Yumai 21A (AABBDD, 2n = 42) in wheat. Only one gene (TC251989) showed preferentially silenced homoeoalleles in haploids. Further analyses of 24 single-copy genes known to be silenced in the root and/or leaf also found no evidence of homeologous silencing in 1-month-old haploids and two ESTs (BF484100 and BF473379) exhibit different expression patterns between 4-month-old haploids and hexaploids. Global analysis of the gene expression patterns using the Affymetrix GeneChip showed that of the 55,052 genes probed, only about 0.11% in the shoots and 0.25% in the roots were activated by polyhaploidization. The results demonstrate that activation and silencing of homoeoalleles were not widespread in haploid seedlings.
doi:10.1534/g3.111.000091
PMCID: PMC3276123  PMID: 22384315
14.  Inhibition of Aldehyde Dehydrogenase 2 by Oxidative Stress Is Associated with Cardiac Dysfunction in Diabetic Rats 
Molecular Medicine  2010;17(3-4):172-179.
Left ventricular (LV) dysfunction is a common comorbidity in diabetic patients, although the molecular mechanisms underlying this cardiomyopathic feature are not completely understood. Aldehyde dehydrogenase 2 (ALDH2) has been considered a key cardioprotective enzyme susceptible to oxidative inactivation. We hypothesized that hyperglycemia-induced oxidative stress would influence ALDH2 activity, and ALDH2 inhibition would lead to cardiac functional alterations in diabetic rats. Diabetes was induced by intraperitoneal (i.p.) injection of 60 mg/kg streptozotocin. Rats were divided randomly into four groups: control, untreated diabetic, diabetic treated with N-acetylcysteine (NAC) and diabetic treated with α-lipoic acid (α-LA). Cardiac contractile function, oxidative stress markers and reactive oxygen species (ROS) levels were assessed. ALDH2 activity and expression also were determined. The role of ALDH2 activity in change in hyperglycemia-induced mitochondrial membrane potential (Δψ) was tested in cultured neonatal cardiomyocytes. Myocardial MDA content and ROS were significantly higher in diabetic rats than in controls, whereas GSH content and Mn-SOD activity were decreased in diabetic rats. Compared with controls, diabetic rats exhibited significant reduction in LV ejection fraction and fractional shortening, accompanied by decreases in ALDH2 activity and expression. NAC and α-LA attenuated these changes. Mitochondrial Δψ was decreased greatly with hyperglycemia treatment, and high glucose combined with ALDH2 inhibition with daidzin further decreased Δψ. The ALDH2 activity can be regulated by oxidative stress in the diabetic rat heart. ALDH2 inhibition may be associated with LV reduced contractility, and mitochondrial impairment aggravated by ALDH2 inhibition might reflect an underlying mechanism which causes cardiac dysfunction in diabetic rats.
doi:10.2119/molmed.2010.00114
PMCID: PMC3060979  PMID: 20957334
15.  Identification of a biochemical link between energy intake and energy expenditure 
The Journal of Clinical Investigation  2002;109(12):1599-1605.
Obesity is the result of an imbalance between energy intake and energy expenditure. Using high-density DNA microarrays and Northern analyses, we demonstrated that the activation of a nutrient-sensing pathway, the hexosamine biosynthesis pathway (HBP), rapidly decreased the expression of a cluster of nuclear-encoded mitochondrial genes involved in skeletal muscle oxidative phosphorylation. Conversely, the expression of uncoupling protein-1 and of the same mitochondrial genes was increased in brown adipose tissue. Most important, these transcriptional changes were accompanied by a marked decrease in whole-body energy expenditure. Short-term overfeeding replicated this transcriptional pattern, suggesting that this adaptation to nutrient abundance occurs under physiological conditions. Thus, the activation of the HBP by nutrients represents a biochemical link between nutrient availability, mitochondrial proteins, and energy expenditure, and it is likely to play an important role in the regulation of energy balance.
doi:10.1172/JCI15258
PMCID: PMC151013  PMID: 12070307

Results 1-15 (15)