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1.  Influence of Preferred Orientation on the Electrical Conductivity of Fluorine-Doped Tin Oxide Films 
Scientific Reports  2014;4:3679.
Current development of high-performance transparent conductive oxide (TCO) films is limited with tradeoff between carrier mobility and concentration since none of them can be improved without sacrificing the other. In this study, we prepare fluorine doped tin oxide (FTO) films by chemical vapor deposition with inclusions of different additives and report that the mobility can be varied from 0.65 to 28.5 cm2 V−1 s−1 without reducing the achieved high carrier concentration of 4 × 1020 cm−3. Such an increase in mobility is shown to be clearly associated with the development of (200) preferred orientation (PO) but concurrent degradation of (110) PO in films. Thus, at a constant high carrier concentration, the electrical conductivity can be improved via carrier mobility simply by PO control. Such a one-step approach avoiding conventional post-deposition treatment is suggested for developing next-generation FTO as well as other TCO films with better than ever conductivities.
doi:10.1038/srep03679
PMCID: PMC3890905  PMID: 24419455
2.  Comparison of Cochlear Cell Death Caused by Cisplatin, Alone and in Combination with Furosemide 
Toxicologic pathology  2013;42(2):376-385.
Establishment of appropriate animal models is an important step in exploring the mechanisms of drug-induced ototoxicity. In the present study, using guinea pigs we compared cochlear lesions induced by cisplatin administered in two regimens: consecutive application alone and in combination with furosemide. The effects of furosemide alone were also evaluated; it was found to cause temporary hearing loss and reversible damage to the stria vascularis. Consecutive application of cisplatin alone appeared to be disadvantageous because it resulted in progressive body weight loss and higher mortality compared to the combined regimen, which used a smaller cisplatin dose. The combined regimen resulted in comparable hearing loss and hair cell loss but a markedly lower mortality. However, their coadministration failed to cause similar damage to spiral ganglion neurons (SGN), as seen in animals that received cisplatin alone. This difference suggests that the combined regimen did not mimic the damage to cochlear neuronal innervation caused by the clinical application of cisplatin. The difference also suggests that the SGN lesion is not caused by cisplatin entering the cochlea via the stria vascularis.
doi:10.1177/0192623313483213
PMCID: PMC3977928  PMID: 23548607 CAMSID: cams4248
totoxicity; cisplatin; furosemide; auditory brain-stem response; hair cell; spiral ganglion neuron
3.  Evolutionary Origin of Asymptotically Stable Consensus 
Scientific Reports  2014;4:4590.
Consensus is widely observed in nature as well as in society. Up to now, many works have focused on what kind of (and how) isolated single structures lead to consensus, while the dynamics of consensus in interdependent populations remains unclear, although interactive structures are everywhere. For such consensus in interdependent populations, we refer that the fraction of population adopting a specified strategy is the same across different interactive structures. A two-strategy game as a conflict is adopted to explore how natural selection affects the consensus in such interdependent populations. It is shown that when selection is absent, all the consensus states are stable, but none are evolutionarily stable. In other words, the final consensus state can go back and forth from one to another. When selection is present, there is only a small number of stable consensus state which are evolutionarily stable. Our study highlights the importance of evolution on stabilizing consensus in interdependent populations.
doi:10.1038/srep04590
PMCID: PMC3975236  PMID: 24699444
4.  LipidSeq: a next-generation clinical resequencing panel for monogenic dyslipidemias[S] 
Journal of Lipid Research  2014;55(4):765-772.
We report the design of a targeted resequencing panel for monogenic dyslipidemias, LipidSeq, for the purpose of replacing Sanger sequencing in the clinical detection of dyslipidemia-causing variants. We also evaluate the performance of the LipidSeq approach versus Sanger sequencing in 84 patients with a range of phenotypes including extreme blood lipid concentrations as well as additional dyslipidemias and related metabolic disorders. The panel performs well, with high concordance (95.2%) in samples with known mutations based on Sanger sequencing and a high detection rate (57.9%) of mutations likely to be causative for disease in samples not previously sequenced. Clinical implementation of LipidSeq has the potential to aid in the molecular diagnosis of patients with monogenic dyslipidemias with a high degree of speed and accuracy and at lower cost than either Sanger sequencing or whole exome sequencing. Furthermore, LipidSeq will help to provide a more focused picture of monogenic and polygenic contributors that underlie dyslipidemia while excluding the discovery of incidental pathogenic clinically actionable variants in nonmetabolism-related genes, such as oncogenes, that would otherwise be identified by a whole exome approach, thus minimizing potential ethical issues.
doi:10.1194/jlr.D045963
PMCID: PMC3966710  PMID: 24503134
next generation sequencing; DNA diagnosis; familial dyslipidemia; Sanger sequencing; mutations; genetic risk score; polygenic dyslipidemia
5.  Effectiveness of predicting in-hospital mortality in critically ill children by assessing blood lactate levels at admission 
BMC Pediatrics  2014;14:83.
Background
Hyperlactatemia upon admission is a documented risk factor for mortality in critically ill adult patients. However, the predictive significance of a single lactate measurement at admission for mortality in the general population of critically ill children remains uncertain. This study evaluated the predictive value of blood lactate levels at admission and determined the cut-off values for predicting in-hospital mortality in the critically ill pediatric population.
Methods
We enrolled 1109 critically ill children who were admitted to a pediatric intensive care unit between July 2008 and December 2010. Arterial blood samples were collected in the first 2 hours after admission, and the lactate levels were determined. The Pediatric Risk of Mortality III (PRISM III) scores were calculated during the first 24 hours after admission.
Results
Of the 1109 children admitted, 115 (10.4%) died in the hospital. The median (interquartile range) blood lactate level in critically ill children was 3.2 mmol/l (2.2-4.8). Among the children, 859 (77.5%) had a lactate concentration >2.0 mmol/l. The blood lactate level upon admission was significantly associated with mortality (odds ratio [OR] = 1.38; 95% confidence interval [CI], 1.30-1.46; p <0.001), even after adjustment for age, gender, and illness severity assessed by PRISM III (OR = 1.27; p <0.001). Multivariate regression analysis showed that a high blood lactate level (OR = 1.17; 95% CI, 1.07-1.29; p = 0.001), a high PRISM III score (OR = 1.15; 95% CI, 1.11-1.20; p <0.001), and a low serum albumin (OR =0.92; 95% CI, 0.88-0.96; p <0.001) were independent risk factors for mortality in critically ill children. Blood lactate achieved an area under-the-receiver-operating-characteristic curve (AUC) of 0.79 (p <0.001) for predicting mortality that was similar to that of PRISM III (AUC = 0.82; p <0.001). The p-value for a comparison of both AUCs was 0.318. Blood lactate displayed a sensitivity of 61% and a specificity of 86% in predicting mortality at the optimal cut-off value of 5.55 mmol/l, and the positive and negative likelihood ratios were 4.5 and 0.45, respectively.
Conclusions
A high blood lactate level at admission is independently associated with and predictive of in-hospital mortality in the general population of critically ill children.
doi:10.1186/1471-2431-14-83
PMCID: PMC3976355  PMID: 24673817
Blood lactate; Critically ill children; Cut-off value; In-hospital mortality; Pediatric risk of mortality III (PRISM III); Predictive test
6.  Comparison of Vegetarian Diets and Omnivorous Diets on Plasma Level of HDL-c: A Meta-Analysis 
PLoS ONE  2014;9(3):e92609.
Low plasma level of high density lipoprotein cholesterol (HDL-c) was an independent risk factor for cardio vascular disorder, and associated with poor outcomes in pulmonary arterial hypertension. To compare the effects of vegetarian diets and omnivorous diets on HDL-c in plasma, we identified cross-sectional and cohort studies related to HDL-c listed on PubMed and ISI Web of Knowledge as well as the corresponding references (until Nov, 2013). Twelve studies with a total of 4177 individuals were selected for meta-analysis. This meta-analysis indicates that vegetarian diets did not alter plasma HDL-c concentrations, as it wasn’t initially expected by the authors [Standardized Mean Difference (SMD) = 0.02 mmol/l; 95% confidence interval (CI): −0.19 to 0.22 mmol/l]. In Asia and Latin America countries, no significant differences in HDL-c levels between vegetarians and omnivores were found (SMD = −0.09 mmol/l; 95% CI: −0.43 to 0.25 mmol/l). In Europe and North America countries, the plasma level of HDL-c was also not different between the two diets (SMD = 0.09 mmol/l; 95% CI: −0.19 to 0.36 mmol/l). In light of this meta-analysis, we conclude that there is no evidence that plasma HDL-c levels differs in vegetarians and omnivores, even after adjusting for cultural circumstances.
doi:10.1371/journal.pone.0092609
PMCID: PMC3966789  PMID: 24671216
7.  Association between Tumor necrosis factor-alpha gene polymorphisms and prostate cancer risk: a meta-analysis 
Diagnostic Pathology  2014;9:74.
Background
Tumor necrosis factor-alpha (TNF-α) is an important inflammatory cytokine that may play a role in controlling the progression of prostate cancer. Two common polymorphisms in the TNF-α gene, −308G/A and −238C/T, have been suggested to alter the risk for prostate cancer, but the results have been inconclusive so far. In order to obtain a better understanding of the effects of these two polymorphisms on prostate cancer risk, all available studies were considered in a meta-analysis.
Methods
We conducted a comprehensive literature search in the Cochrane Library, PubMed, EMBASE, Chinese Biomedical Literature database (CBM), and the China National Knowledge Infrastructure (CNKI). The associations were evaluated by calculating the pooled odds ratio (OR) with 95% confidence interval (95% CI).
Results
In this meta-analysis, we included 14 studies with 5,757 patients and 6,137 control subjects for the TNF-α-308G/A polymorphism and 1,967 patients and 2,004 control subjects for the TNF-α-238C/T polymorphism. A significantly increased prostate cancer risk was found to be associated with the TNF-α-308C/T polymorphism in studies with healthy volunteers (AA + AG vs. GG: OR = 1.531, 95% CI = 1.093–2.145; P = 0.013; AG vs. GG: OR = 1.477, 95% CI = 1.047–2.085; P = 0.026). No significant association was found between the TNF-α-238G/A polymorphism and prostate cancer risk in the overall or subgroup analyses. There was no risk of publication bias in this meta-analysis.
Conclusions
Our results suggest that while the TNF-α-238G/A polymorphism may not be associated with prostate cancer the TNF-α-308C/T polymorphism may significantly contribute to prostate cancer susceptibility in healthy volunteers.
Virtual slides
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1629288120116301
doi:10.1186/1746-1596-9-74
PMCID: PMC3977697  PMID: 24666463
Tumor necrosis factor- alpha; Prostate cancer; Meta-analysis; Polymorphism
8.  Carbon nanocages: A new support material for Pt catalyst with remarkably high durability 
Scientific Reports  2014;4:4437.
Low durability is the major challenge hindering the large-scale implementation of proton exchange membrane fuel cell (PEMFC) technology, and corrosion of carbon support materials of current catalysts is the main cause. Here, we describe the finding of remarkably high durability with the use of a novel support material. This material is based on hollow carbon nanocages developed with a high degree of graphitization and concurrent nitrogen doping for oxidation resistance enhancement, uniform deposition of fine Pt particles, and strong Pt-support interaction. Accelerated degradation testing shows that such designed catalyst possesses a superior electrochemical activity and long-term stability for both hydrogen oxidation and oxygen reduction relative to industry benchmarks of current catalysts. Further testing under conditions of practical fuel cell operation reveals almost no degradation over long-term cycling. Such a catalyst of high activity, particularly, high durability, opens the door for the next-generation PEMFC for “real world” application.
doi:10.1038/srep04437
PMCID: PMC3963085  PMID: 24658614
9.  A Disposable Blood Cyanide Sensor 
Analytica chimica acta  2013;768:129-135.
Deaths due to smoke inhalation in fires are often due to poisoning by HCN. Rapid administration of antidotes can result in complete resuscitation of the patient but judicious dosing requires the knowledge of the level of cyanide exposure. Rapid sensitive means for blood cyanide quantitation are needed. Hydroxocyanocobinamide (OH(CN)Cbi) reacts with cyanide rapidly; this is accompanied by a large spectral change. The disposable device consists of a pair of nested petri dish bottoms and a single top that fits the outer bottom dish. The top cover has a diametrically strung porous polypropylene membrane tube filled with aqueous OH(CN)Cbi. One end of the tube terminates in an amber (583 nm) light emitting diode; the other end in a photodiode via an acrylic optical fiber. An aliquot of the blood sample is put in the inner dish, the assembly covered and acid is added through a port in the cover. Evolved HCN diffuses into the OH(CN)Cbi solution and the absorbance in the long path porous membrane tube cell is measured within 160s. The LOD was 0.047, 1.0, 0.15, 5.0 and 2.2 μM, respectively, for water (1 mL), bovine blood (100 μL, 1 mL), and rabbit blood (20μL, 50 μL). RSDs were < 10% in all cases and the linear range extended from 0.5 to 200 μM. The method was validated against a microdiffusion approach and applied to the measurement of cyanide in rabbit and human blood. The disposable device permits field measurement of blood cyanide in < 4 min.
doi:10.1016/j.aca.2013.01.029
PMCID: PMC3596829  PMID: 23473259
Porous membrane; HCN; Cobinamide; Liquid Core Waveguide
10.  Tea polyphenols induced apoptosis of breast cancer cells by suppressing the expression of Survivin 
Scientific Reports  2014;4:4416.
To study the mechanism of tea polyphenols (TP)-induced apoptosis of breast cancer cells. Proliferation of MCF-7 and SK-BR-3 cells was evaluated by MTT assays. Cellular ultrastructure was examined by electron microscopy. Apoptosis was detected by TUNEL. PCNA、 Cyclin D1、 Cyclin E and Survivin expression was measured by Western blot. Cell proliferation was significantly inhibited by TP. Spindle and round cells were loosely distributed with increased particles after TP treatment. Increased cell size, frequent nuclear atypia and a collapse of apoptosis were observed. The nucleus was pushed towards one side, while the cytoplasm was rich in free ribosome. The membrane of mitochondria was thickening, and the cell apoptotic body was observed. TP treated cells experienced significantly enhanced apoptosis compared with 5-Fu treated or control groups. The expression of survivin was downregulated by TP. To conclude, TP can inhibit cell growth and induce apoptosis through downregulating the expression of survivin in breast cancer.
doi:10.1038/srep04416
PMCID: PMC3960584  PMID: 24646833
11.  A New Carbon Allotrope with Six-Fold Helical Chains in all-sp2 Bonding Networks 
Scientific Reports  2014;4:4339.
Using a recently developed approach to constructing covalent network structures from linear carbyne, we identify by ab initio calculations a new carbon allotrope in () symmetry that comprises six-fold helical chains with alternating sp2-type single and double bonds along the chains that are connected via zigzag benzene rings. This 6-fold carbene is characterized as a three-dimensional three-connected chiral crystalline modification of graphite. Phonon and electronic band calculations indicate that this new structure is dynamically stable and is a semiconductor with a band gap of 0.47 eV, in contrast to the semimetallic nature of graphite. Simulated x-ray diffraction patterns of the 6-fold carbene provide an excellent match to the previously unexplained distinct diffraction peak of a new carbon allotrope found in recent detonation experiments. These results establish a new carbon phase and offer insights into its outstanding structural and electronic properties.
doi:10.1038/srep04339
PMCID: PMC3949244  PMID: 24614093
12.  Tumor Vascularity and Glucose Metabolism Correlated in Adenocarcinoma, but Not in Squamous Cell Carcinoma of the Lung 
PLoS ONE  2014;9(3):e91649.
Background/Objectives
To prospectively examine the relation between tumor vascularity and glucose metabolism in adenocarcinoma (AC) and squamous cell carcinoma(SCC) of the lung by using positron emission tomography/computed tomography (PET/CT) and dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).
Materials and Methods
Forty-one consecutive patients with histologically confirmed untreated NSCLC underwent routine diagnostic work-up, including DCE-MRI and PET/CT. PET/CT images were used to derive glucose metabolism (SUVmax and SUVmean), and DCE-MRI images were used to derive tumor vascularity (Ktrans, Kep, Ve and iAUC). Any differences in the DCE-MRI and PET/CT estimations between the NSCLC subtypes were determined by the Wilcoxon rank sum test. Spearman’s rank correlation coefficients were calculated between the DCE-MRI parameter values and the SUV.
Results
SUVmean and SUVmax in AC were significantly lower than in SCC, but Ktrans and Ve in AC were significantly higher than in SCC. Significant correlations between SUV and DCE-MRI parameters were observed for SUVmax and Ve (ρ = −0.357, P = 0.022), SUVmean and Ktrans (ρ = −0.341, P = 0.029), and SUVmean and iAUC (ρ = −0.374, P = 0.016 ) in total; for SUVmax and iAUC (ρ = −0.420, P = 0.037), SUVmean and Ktrans (ρ = −0.411, P = 0.041), SUVmean and Kep (ρ = −0.045, P = 0.026), and SUVmean and iAUC (ρ = −0.512, P = 0.009) in AC; However, for neither in SCC.
Conclusion
AC and SCC showed different patterns in both tumor vascularity and glucose metabolism. Tumor vascularity and glucose metabolism negatively correlated in AC, but not in SCC. These differences may underlie the heterogeneity in clinical aspect of NSCLC subtypes and have implications for their imaging profiling and monitor the treatment response.
doi:10.1371/journal.pone.0091649
PMCID: PMC3948888  PMID: 24614132
13.  Associations between Two Polymorphisms (FokI and BsmI) of Vitamin D Receptor Gene and Type 1 Diabetes Mellitus in Asian Population: A Meta-Analysis 
PLoS ONE  2014;9(3):e89325.
Background
Vitamin D receptor (VDR) gene polymorphisms are possibly involved in the development of type 1 diabetes mellitus (T1DM). However, the results to date have been inconclusive. We performed a meta-analysis to examine the association between 2 polymorphisms (FokI and BsmI) of the VDR gene and T1DM in the Asian population.
Methods
Literature was retrieved from PubMed, Web of Science, CBM, Embase and Chinese databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using a random or fixed effect model.
Results
In total, 20 papers (BsmI: 13 studies; FokI: 13 studies) were included. In contrast to the FokI polymorphism, the BsmI polymorphism was associated with an increased risk of T1DM in the Asian population (OR = 1.47, 95% CI = 1.13–1.91, P = 0.004 for B vs. b). Upon stratification by regional geography, an increased risk of T1DM in association with the BsmI polymorphism was observed in the East Asian population (OR = 1.97, 95% CI = 1.38–2.83, P<0.001 for B vs. b), whereas the FokI polymorphism was associated with an increased risk of T1DM in the West Asian population (OR = 1.45, 95% CI = 1.12–1.88, P = 0.004 for F vs. f).
Conclusions
Our meta-analysis suggests that the BsmI polymorphism may be a risk factor for susceptibility to T1DM in the East Asian population, and the FokI polymorphism is associated with an increased risk of T1DM in the West Asian population. However, because the study size was limited, further studies are essential to confirm our results.
doi:10.1371/journal.pone.0089325
PMCID: PMC3945782  PMID: 24603699
14.  Mutations in LPL, APOC2, APOA5, GPIHBP1 and LMF1 in patients with severe hypertriglyceridaemia 
Journal of internal medicine  2012;272(2):185-196.
Objective
The severe forms of hypertriglyceridaemia (HTG) are caused by mutations in genes that lead to loss of function of lipoprotein lipase (LPL). In most patients with severe HTG (TG >10 mmol/L) it is a challenge to define the underlying cause. We investigated the molecular basis of severe HTG in patients referred to the Lipid Clinic at the Academic Medical Center Amsterdam.
Methods
The coding regions of LPL, APOC2, APOA5 and two novel genes, lipase maturation factor 1 (LMF1) and GPI-anchored HDL-binding protein 1 (GPIHBP1), were sequenced in 86 patients with type 1 and type 5 HTG and 327 controls.
Results
In 46 patients (54%) rare DNA sequence variants were identified, comprising variants in LPL (n=19), APOC2 (n=1), APOA5 (n=2), GPIHBP1 (n=3) and LMF1 (n=8). In 22 patients (26%) only common variants in LPL (p.Asp36Asn, p.Asn318Ser and p.Ser474Ter) and APOA5 (p.Ser19Trp) could be identified, whereas no mutations were found in 18 patients (21%). In vitro validation revealed that the mutations in LMF1 were not associated with compromised LPL function. Consistent with this, five of the eight LMF1 variants were also found in controls and therefore cannot account for the observed phenotype.
Conclusion
The prevalence of mutations in LPL was 34% and mostly restricted to patients with type 1 HTG. Mutations in GPIHBP1 (n=3), APOC2 (n=1) and APOA5 (n=2) were rare but the associated clinical phenotype was severe. Routine sequencing of candidate genes in severe HTG has improved our understanding of the molecular basis of this phenotype associated with acute pancreatitis, and may help to guide future individualized therapeutic strategies.
doi:10.1111/j.1365-2796.2012.02516.x
PMCID: PMC3940136  PMID: 22239554
triglycerides; lipoprotein lipase; APOC2; APOA5; LMF1; GPIHBP1
15.  Crystallization and preliminary X-ray crystallographic analysis of a blue-light-absorbing proteorhodopsin 
A purified blue-light-absorbing proteorhodopsin D97N mutant protein (BPR_D97N) has been crystallized using the vapour-diffusion method.
Proteorhodopsins (PRs), seven-transmembrane chromoproteins with retinal as a chromophore, are light-driven proton pumps. To elucidate the light-driven proton-pumping mechanism of PRs, a pET28a vector containing the blue-light-absorbing proteorhodopsin (BPR) gene was constructed and the protein was overexpressed in Escherichia coli. The protein was purified by immobilized metal-ion affinity chromatography (IMAC). The purified BPR D97N mutant protein (BPR_D97N) was crystallized using the vapour-diffusion method. Preliminary X-ray diffraction data analysis showed that the crystal belonged to the orthorhombic space group P21212, with unit-cell parameters a = 161.6, b = 168.6, c = 64.7 Å. A complete data set was collected to 3.3 Å resolution using synchrotron radiation on beamline X06 of the Swiss Light Source (SLS). Molecular replacement was unsuccessful. To solve the structure of BPR_D97N by experimental phasing, selenomethionine-substituted protein crystals were prepared. These crystals diffracted to 3.0 Å resolution and a complete data set was collected on beamline BL17U of the Shanghai Synchrotron Radiation Facility (SSRF). Heavy-atom substructure determination and phasing by SAD clearly showed that the crystal contained five molecules in the asymmetric unit, with a V M of 3.26 Å3 Da−1 and a solvent content of 62.3%.
doi:10.1107/S1744309111043612
PMCID: PMC3310530  PMID: 22442222
proteorhodopsins; BPR
16.  Propofol increases expression of basic fibroblast growth factor after transient cerebral ischemia in rats 
Neurochemical research  2012;38(3):530-537.
Anesthetics such as propofol can provide neuroprotective effects against cerebral ischemia. However, the underlying mechanism of this beneficial effect is not clear. Therefore, we subjected male Sprague-Dawley rats to 2 h of middle cerebral artery occlusion and investigated how post-ischemic administration of propofol affected neurologic outcome and the expression of basic fibroblast growth factor (bFGF). After 2 h of ischemia, just before reperfusion, the animals were randomly assigned to receive either propofol (20 mg•kg−1•h−1) or vehicle (10% intralipid, 2 ml•kg−1•h−1) intravenously for 4 h. Neurologic scores, infarct volume, and brain water content were measured at different time points after reperfusion. mRNA level of bFGF was measured by real-time PCR, and the protein expression level of bFGF was analyzed by immunohistochemistry and Western blot. At 6 h, 24 h, 72 h, and 7 days of reperfusion, infarct volume was significantly reduced in the propofol-treated group compared to that in the vehicle-treated group (all P<0.05). Propofol post-treatment also attenuated brain water content at 24 and 72 h and reduced neurologic deficit score at 72 h and 7 days of reperfusion (all P<0.05). Additionally, in the peri-infarct area, bFGF mRNA and protein expression were elevated at 6, 24, and 72 h of reperfusion compared to that in the vehicle-treated group (all P<0.05). These results show that post-ischemic administration of propofol provides neural protection from cerebral ischemia-reperfusion injury. This protection may be related to an early increase in the expression of bFGF.
doi:10.1007/s11064-012-0945-4
PMCID: PMC3574197  PMID: 23247820
brain; basic fibroblast growth factor; ischemia-reperfusion; propofol
17.  Sensation seeking genes and physical activity in youth 
Genes, brain, and behavior  2012;12(2):181-188.
Many studies examining genetic influences on physical activity (PA) have evaluated the impact of single nucleotide polymorphisms (SNPs) related to the development of lifestyle-related chronic diseases, under the hypothesis that they would be associated with PA. However, PA is a multi-determined behavior and associated with a multitude of health consequences. Thus, examining a broader range of candidate genes associated with a boarder range of PA correlates may provide new insights into the genetic underpinnings of PA. In this study we focus on one such correlate – sensation seeking behavior. Participants (N=1,130 Mexican origin youth) provided a saliva sample and data on PA and sensation seeking tendencies in 2008–09. Participants were genotyped for 630 functional and tagging variants in the dopamine, serotonin, and cannabinoid pathways. Overall 30% of participants (males – 37.6%; females – 22.0%) reported ≥60 minutes of PA on five out of seven days. After adjusting for gender, age and population stratification, and applying the Bayesian False Discovery Probability approach for assessing noteworthiness, four gene variants were significantly associated with PA. In a multivariable model, being male, having higher sensation seeking tendencies and at least one copy of the minor allele for SNPs in ACE (rs8066276 OR=1.44; p=0.012) and TPH2 (rs11615016 OR=1.73; p=0.021) were associated with increased likelihood of meeting PA recommendations. Participants with at least one copy of the minor allele for SNPs in SNAP25 (rs363035 OR=0.53; p=0.005) and CNR1 (rs6454672 OR=0.62; p=0.022) have decreased likelihood of meeting PA recommendations. Our findings extend current knowledge of the complex relationship between PA and possible genetic underpinnings.
doi:10.1111/gbb.12006
PMCID: PMC3581711  PMID: 23190435
Physical Activity; Genes; Sensation Seeking; Mexican origin youth
18.  Radiological study on disc degeneration of thoracolumbar burst fractures treated by percutaneous pedicle screw fixation 
European Spine Journal  2012;22(3):489-494.
Objective
To examine disc degeneration at levels adjacent and next adjacent to the fractured vertebra and to analyses, if the disc degeneration is determined by the endplate fracture.
Summary of background data
Thoracolumbar burst fracture is one of the most common spinal injuries. The diagnostic (clinical and imaging) approach and treatment of a fractured vertebra is well established; however, some controversy remains. The associated disc degeneration is less well known after 9–12 months of the short segment pedicle screw fixations. There is a major controversy whether spinal trauma with vertebral endplate fractures can result in posttraumatic disc degeneration. No study to date, however, has assessed disc degeneration of the AO type A3 thoracolumbar fractures without neurologic deficits after pedicle screw fixations.
Methods
Twenty-six patients with single-level AO type A3 thoracolumbar fractures and no neurological deficit were treated by using postural reduction and short segment percutaneous pedicle screw fixation. No laminectomy and fusion were performed. Implants were removed 9–12 months after the first operation. The thoracolumbar magnetic resonance imaging (MRI) was used to assess disc degeneration at levels adjacent and next adjacent to the fractured vertebra before the first operation and after the second operation in a retrospective study.
Results
After the instrumentation removal, new disc degeneration was usually found at level adjacent to the cranial endplate of fractured vertebra by MRI examination in 24 patients. The average Pfirrmann grade of degenerative discs adjacent to the cranial fractured endplates deteriorated from 2.1 pre-operatively to 3.4 after the second operation. No change of disc degeneration was seen at the caudal disc space adjacent to the fractured vertebra and the levels next adjacent to the fractured vertebra. The discs next adjacent to the fractured vertebra were showed to be relatively normal without changes of degeneration during the study period.
Conclusions
Disc degeneration usually occurs at level adjacent to the fractured endplate of thoracolumbar burst fractures. Endplate fracture is strongly associated with disc degeneration. No correlation between fixation level and disc degeneration is seen in this study.
doi:10.1007/s00586-012-2462-1
PMCID: PMC3585651  PMID: 22890568
Disc degeneration; Thoracolumbar fracture; Endplate; Pedicle screw fixation; Minimally invasive surgery
19.  Antioxidant Properties and PC12 Cell Protective Effects of a Novel Curcumin Analogue (2E,6E)-2,6-Bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH) 
The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•− quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 μM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63–5.00 μM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.
doi:10.3390/ijms15033970
PMCID: PMC3975378  PMID: 24603537
curcumin analogue; free radical scavenger; hydrogen peroxide; PC12 cells; apoptosis
20.  A Novel Role for GADD45β as a Mediator of MMP-13 Gene Expression during Chondrocyte Terminal Differentiation*S 
The Journal of biological chemistry  2005;280(46):38544-38555.
The growth arrest and DNA damage-inducible 45β (GADD45β) gene product has been implicated in the stress response, cell cycle arrest, and apoptosis. Here we demonstrated the unexpected expression of GADD45β in the embryonic growth plate and uncovered its novel role as an essential mediator of matrix metalloproteinase-13 (MMP-13) expression during terminal chondrocyte differentiation. We identified GADD45β as a prominent early response gene induced by bone morphogenetic protein-2 (BMP-2) through a Smad1/Runx2-dependent pathway. Because this pathway is involved in skeletal development, we examined mouse embryonic growth plates, and we observed expression of Gadd45β mRNA coincident with Runx2 protein in pre-hypertrophic chondrocytes, whereas GADD45β protein was localized prominently in the nucleus in late stage hypertrophic chondrocytes where Mmp-13 mRNA was expressed. In Gadd45β−/− mouse embryos, defective mineralization and decreased bone growth accompanied deficient Mmp-13 and Col10a1 gene expression in the hypertrophic zone. Transduction of small interfering RNA-GADD45β in epiphyseal chondrocytes in vitro blocked terminal differentiation and the associated expression of Mmp-13 and Col10a1 mRNA in vitro. Finally, GADD45β stimulated MMP-13 promoter activity in chondrocytes through the JNK-mediated phosphorylation of JunD, partnered with Fra2, in synergy with Runx2. These observations indicated that GADD45β plays an essential role during chondrocyte terminal differentiation.
doi:10.1074/jbc.M504202200
PMCID: PMC3937966  PMID: 16144844
21.  Association of Meteorological Factors with Pediatric Intussusception in Subtropical China: A 5-Year Analysis 
PLoS ONE  2014;9(2):e90521.
Purpose
The aim of this study was to determine whether climate factors correlate with variations in the rate of pediatric intussusception cases presenting to the Children’s Hospital in Suzhou, China.
Material and Methods
The hospital records of 5,994 pediatric cases of intussusception who had presented between Aug 2006 and Dec 2011 were retrospectively analyzed. Demographic data and air enema reduction data were collected for each case.
Results
The monthly rate of new intussusception cases fluctuated throughout the year generally rising from April to September with a peak from May to July. This annual cycling of intussusception incidence was highly significant over the 5 year observation period. Poisson regression analysis showed that the monthly number of intussusception cases was associated with an increase in mean temperature per month (P = 0.0001), sum of sunshine per month (P<0.0001), precipitation per month (P<0.0001), and was marginally associated with increased mean wind speed per month (P = 0.0709).
Conclusion
The incidence of intussusception in Suzhou was seasonally variable with a peak in cases presenting during hotter, sunnier, and wetter months demonstrating a positive association with certain climatic factors.
doi:10.1371/journal.pone.0090521
PMCID: PMC3938762  PMID: 24587386
22.  Twinning-like lattice reorientation without a crystallographic twinning plane 
Nature Communications  2014;5:3297.
Twinning on the plane is a common mode of plastic deformation for hexagonal-close-packed metals. Here we report, by monitoring the deformation of submicron-sized single-crystal magnesium compressed normal to its prismatic plane with transmission electron microscopy, the reorientation of the parent lattice to a ‘twin’ lattice, producing an orientational relationship akin to that of the conventional twinning, but without a crystallographic mirror plane, and giving plastic strain that is not simple shear. Aberration-corrected transmission electron microscopy observations reveal that the boundary between the parent lattice and the ‘twin’ lattice is composed predominantly of semicoherent basal/prismatic interfaces instead of the twinning plane. The migration of this boundary is dominated by the movement of these interfaces undergoing basal/prismatic transformation via local rearrangements of atoms. This newly discovered deformation mode by boundary motion mimics conventional deformation twinning but is distinct from the latter and, as such, broadens the known mechanisms of plasticity.
Deformation twinning and dislocations are known to govern the plastic behaviour of metals at room temperature. Here the authors demonstrate a new deformation mechanism in single-crystal magnesium characterized by twin-like crystal reorientation and special interfaces.
doi:10.1038/ncomms4297
PMCID: PMC3929781  PMID: 24522756
23.  Elevated Expression of miR-210 Predicts Poor Survival of Cancer Patients: A Systematic Review and Meta-Analysis 
PLoS ONE  2014;9(2):e89223.
Background
MiRNAs are important regulators of different biological processes, including tumorigenesis. MiR-210 is a potential prognostic factor for survival in patients with cancer according to previous clinical researches. We conducted a systematic review and meta-analysis to summarize the significance of increased miR-210 expression in the prognosis of indicated cancers.
Methodology/Principal Findings
The present systematic review and meta-analysis of 16 researches included 1809 patients with 7 different types of cancers from 7 countries, and aimed to explore the association between miR-210 expression and the survival of cancer patients. Over-expression of miR-210 may predict poor overall survival (OS, HR = 1.33, 95% CI: 0.85–2.09, P = 0.210), but the effect was not significant. While the predictive effect on disease-free survival (DFS, HR = 1.89, 95% CI: 1.30–2.74, P = 0.001), progression-free survival (PFS, HR = 1.20, 95% CI: 1.05–1.38, P = 0.007) and relapse-free survival(RFS, HR = 4.42, 95% CI: 2.14–9.15, P = 0.000) for patients with breast cancer, primary head and neck squamous cell carcinoma (HNSCC), renal cancer, soft-tissue sarcoma, pediatric osteosarcoma, bladder cancer or glioblastoma was certain. Subgroup analysis showed the limited predictive effect of over-expressed miR-210 on breast cancer OS (HR = 1.63, 95% CI: 0.47–5.67, P = 0.443), breast cancer DFS (HR = 2.03, 95% CI: 0.90–4.57, P = 0.088), sarcoma OS (HR = 1.24, 95% CI: 0.20–7.89, P = 0.818) and renal cancer OS (HR = 1.16, 95% CI: 0.27–4.94, P = 0.842).
Conclusions/Significance
This systematic review and meta-analysis suggests that miR-210 has a predictive effect on survival of patients with studied cancer types as indexed by disease-free survival, progression-free survival and relapse-free survival. While the predictive effect on overall survival, breast cancer overall survival, breast cancer disease-free survival, sarcoma overall survival and renal cancer overall survival was not statistically significant.
doi:10.1371/journal.pone.0089223
PMCID: PMC3930667  PMID: 24586608
24.  Over-Expressed Testis-Specific Protein Y-Encoded 1 as a Novel Biomarker for Male Hepatocellular Carcinoma 
PLoS ONE  2014;9(2):e89219.
Hepatocellular carcinoma (HCC) is a male-predominant cancer. Previous studies have focused on the sex-related disparity in HCC, but the underlying mechanism remains unclear. Here, we aimed to discover characteristic biomarkers for male HCC. Clinical samples were subjected to iTRAQ labeling followed by 2DLC-ESI-MS/MS analysis. Seventy-three differential proteins containing 16 up-regulated and 57 down-regulated proteins were screened out in the male HCC group compared to that in female HCC group. Testis-specific Protein Y-encoded 1(TSPY1) is characteristically present in male HCC and was chosen for further investigation. The data from the functional effects of TSPY1 indicated that over-expression of TSPY1 could potentiate HCC cell proliferation, increase soft agar colonization, induce higher cell invasive ability and correlate with the metastatic potential of the HCC cell lines. In addition, TSPY1 and androgen receptor (AR) were co-expressed simultaneously in HCC cell lines as well as in HCC tissue. TSPY1 up- or down-regulation could lead to a high or low level expression of AR. These results implied that TSPY1 may be included in the regulation of AR expression involved in male HCC and it may act as a novel biomarker for male HCC.
doi:10.1371/journal.pone.0089219
PMCID: PMC3930679  PMID: 24586606
25.  Measurement of retinal thickness in macular region of high myopic eyes using spectral domain OCT 
AIM
To investigate the changes of retinal thickness in macula of high myopic eyes using spectral domain optical coherence tomography (OCT).
METHODS
Middle-aged and young myopic patients were divided into three groups according to their refractive error/axial length: low and medium myopia group (LMMG), high myopia group (HMG) and super high myopia group (SHMG). Cirrus HD-OCT was used to evaluate total average macular thickness, central subfield thickness, inner/outer macular thickness and macular volume. The differences among experimental groups were analyzed by one-factor analysis of variance. Associations between macular thickness and refractive error/axial length were analyzed by Pearson correlation analysis.
RESULTS
There was no significant difference in age among the three groups (P=0.2789). The mean refraction error in the LMMG, HMG, and SHMG groups was -2.49±1.38D, -8.53±1.95D and -13.88±1.76D, respectively (P<0.001). The central subfield thickness of three groups was 244.56±12.19µm, 254.33±11.61µm and 261.75±11.83µm, respectively, and there were statistically significance between random two groups. The total average macular thickness, inner/outer macular thickness, and macular volume decreased with increased myopia/axial length. Average foveal thickness had negative correlations with refractive error (P<0.001), and positive correlations with axial length. The inferior and temporal inner macular thickness, all the quadrants of outer ring, total average macular thickness and macular volume featured positive correlations with refractive error, and negative correlations with axial length. Average foveal thickness, superior and temporal inner macular thicknesses, and temporal outer macular thickness was lower in females compared to males.
CONCLUSION
With an increase in myopia degree/axial length, the average foveal thickness increased and the inner/outer macular thickness decreased. Females featured thicker average foveal thickness, and thinner macular thickness compared to males.
doi:10.3980/j.issn.2222-3959.2014.01.23
PMCID: PMC3949472  PMID: 24634877
optical coherence tomography; retinal thickness; high myopic eyes

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