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author:("Wang, yumai")
1.  Genetic analysis of Upland cotton dynamic heterosis for boll number per plant at multiple developmental stages 
Scientific Reports  2016;6:35515.
Yield is an important breeding target. As important yield components, boll number per plant (BNP) shows dynamic character and strong heterosis in Upland cotton. However, the genetic basis underlying the dynamic heterosis is poorly understood. In this study, we conducted dynamic quantitative trait loci (QTL) analysis for BNP and heterosis at multiple developmental stages and environments using two recombinant inbred lines (RILs) and two corresponding backcross populations. By the single-locus analysis, 23 QTLs were identified at final maturity, while 99 QTLs were identified across other three developmental stages. A total of 48 conditional QTLs for BNP were identified for the adjacent stages. QTLs detected at later stage mainly existed in the partial dominance to dominance range and QTLs identified at early stage mostly showed effects with the dominance to overdominance range during plant development. By two-locus analysis, we observe that epistasis played an important role not only in the variation of the performance of the RIL population but also in the expression of heterosis in backcross population. Taken together, the present study reveals that the genetic basis of heterosis is dynamic and complicated, and it is involved in dynamic dominance effect, epistasis and QTL by environmental interactions.
PMCID: PMC5066282  PMID: 27748451
2.  Deletion of Adenosine A2A Receptors from Astrocytes Disrupts Glutamate Homeostasis Leading to Psychomotor and Cognitive Impairment: Relevance to Schizophrenia 
Biological psychiatry  2015;78(11):763-774.
Adenosine A2A receptors (A2AR) modulate dopamine and glutamate signaling and thereby may influence some of the psychomotor and cognitive processes associated with schizophrenia. Because astroglial A2AR regulate the availability of glutamate, we hypothesized that they might play an unprecedented role in some of the processes leading to the development of schizophrenia, which we investigated using a mouse line with a selective deletion of A2AR in astrocytes (Gfa2-A2AR knockout [KO] mice].
We examined Gfa2-A2AR KO mice for behaviors thought to recapitulate some features of schizophrenia, namely enhanced MK-801 psychomotor response (positive symptoms) and decreased working memory (cognitive symptoms). In addition, we probed for neurochemical alterations in the glutamatergic circuitry, evaluating glutamate uptake and release and the levels of key proteins defining glutamatergic signaling (glutamate transporter-I [GLT-I], N-methyl-D-aspartate receptors [NMDA-R] and α-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors [AMPA-R]) to provide a mechanistic understanding of the phenotype encountered.
We show that Gfa2-A2AR KO mice exhibited enhanced MK-801 psychomotor response and decreased working memory; this was accompanied by a disruption of glutamate homeostasis characterized by aberrant GLT-I activity, increased presynaptic glutamate release, NMDA-R 2B subunit upregulation, and increased internalization of AMPA-R. Accordingly, selective GLT-I inhibition or blockade of GluR1/2 endocytosis prevented the psychomotor and cognitive phenotypes in Gfa2-A2AR KO mice, namely in the nucleus accumbens.
These results show that the dysfunction of astrocytic A2AR, by controlling GLT-I activity, triggers an astrocyte-to-neuron wave of communication resulting in disrupted glutamate homeostasis, thought to underlie several endophenotypes relevant to schizophrenia.
PMCID: PMC4714966  PMID: 25869810
Adenosine; Astrocytes; A2AR; GLT-I; NMDA-R; Schizophrenia
3.  Sodium Butyrate Promotes Reassembly of Tight Junctions in Caco-2 Monolayers Involving Inhibition of MLCK/MLC2 Pathway and Phosphorylation of PKCβ2 
As a physiological small molecular product from the microbial fermentation of dietary fibers, butyrate plays an important role in maintaining intestinal health. Our previous works have proved that the effect of sodium butyrate (NaB) on the intestinal barrier function is mediated by activation of AMP-activated protein kinase (AMPK). However, the detailed pathway involved remains unknown. Using the calcium switch assay in the Caco-2 cell monolayer model, we found here that NaB activated AMPK mainly by increasing the calcium level, but not the ATP concentration, via promoting store-operated calcium entry (SOCE). Upon the activation of AMPK, NaB promoted the reassembly of tight junctions (TJs) based on reducing the phosphorylation of myosin II regulatory light chain (MLC2) at Ser19 and increasing phosphorylation of protein kinase C β2 (PKCβ2) at Ser660. Inhibiting (protein kinase C β) PKCβ blocked the reassembly of TJs induced by NaB in the barrier monolayer model. These results indicated that NaB could activate the calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ) pathway to mediate AMPK phosphorylating, which then inhibited the phosphorylation of MLC2 and promoted the phosphorylation of PKCβ2, respectively, so that the downstream molecules of AMPK coordinately contributed to the reassembly of TJs in the Caco-2 barrier model. These results suggested a potential mechanism of butyrate for intestine homeostasis and protection.
PMCID: PMC5085728  PMID: 27735862
butyrate; tight junction; Caco-2; myosin light chain kinase (MLCK); myosin II regulatory light chain (MLC2); (protein kinase C β) PKCβ
4.  Main Effect QTL with Dominance Determines Heterosis for Dynamic Plant Height in Upland Cotton 
G3: Genes|Genomes|Genetics  2016;6(10):3373-3379.
Plant height, which shows dynamic development and heterosis, is a major trait affecting plant architecture and has an indirect influence on economic yield related to biological yield in cotton. In the present study, we carried out dynamic analysis for plant height and its heterosis by quantitative trait loci (QTL) mapping at multiple developmental stages using two recombinant inbred lines (RILs) and their backcross progeny. At the single-locus level, 47 QTL were identified at five developmental stages in two hybrids. In backcross populations, QTL identified at an early stage mainly showed partial effects and QTL detected at a later stage mostly displayed overdominance effects. At the two-locus level, we found that main effect QTL played a more important role than epistatic QTL in the expression of heterosis in backcross populations. Therefore, this study implies that the genetic basis of plant height heterosis shows dynamic character and main effect QTL with dominance determines heterosis for plant height in Upland cotton.
PMCID: PMC5068956  PMID: 27565885
Upland cotton; plant height; QTL; heterosis; backcross population
5.  Genetic Analysis and QTL Detection on Fiber Traits Using Two Recombinant Inbred Lines and Their Backcross Populations in Upland Cotton 
G3: Genes|Genomes|Genetics  2016;6(9):2717-2724.
Cotton fiber, a raw natural fiber material, is widely used in the textile industry. Understanding the genetic mechanism of fiber traits is helpful for fiber quality improvement. In the present study, the genetic basis of fiber quality traits was explored using two recombinant inbred lines (RILs) and corresponding backcross (BC) populations under multiple environments in Upland cotton based on marker analysis. In backcross populations, no significant correlation was observed between marker heterozygosity and fiber quality performance and it suggested that heterozygosity was not always necessarily advantageous for the high fiber quality. In two hybrids, 111 quantitative trait loci (QTL) for fiber quality were detected using composite interval mapping, in which 62 new stable QTL were simultaneously identified in more than one environment or population. QTL detected at the single-locus level mainly showed additive effect. In addition, a total of 286 digenic interactions (E-QTL) and their environmental interactions [QTL × environment interactions (QEs)] were detected for fiber quality traits by inclusive composite interval mapping. QE effects should be considered in molecular marker-assisted selection breeding. On average, the E-QTL explained a larger proportion of the phenotypic variation than the main-effect QTL did. It is concluded that the additive effect of single-locus and epistasis with few detectable main effects play an important role in controlling fiber quality traits in Upland cotton.
PMCID: PMC5015930  PMID: 27342735
fiber quality; QTL; recombinant inbred line; backcross population; Upland cotton
6.  Chloroplast DNA Structural Variation, Phylogeny, and Age of Divergence among Diploid Cotton Species 
PLoS ONE  2016;11(6):e0157183.
The cotton genus (Gossypium spp.) contains 8 monophyletic diploid genome groups (A, B, C, D, E, F, G, K) and a single allotetraploid clade (AD). To gain insight into the phylogeny of Gossypium and molecular evolution of the chloroplast genome in this group, we performed a comparative analysis of 19 Gossypium chloroplast genomes, six reported here for the first time. Nucleotide distance in non-coding regions was about three times that of coding regions. As expected, distances were smaller within than among genome groups. Phylogenetic topologies based on nucleotide and indel data support for the resolution of the 8 genome groups into 6 clades. Phylogenetic analysis of indel distribution among the 19 genomes demonstrates contrasting evolutionary dynamics in different clades, with a parallel genome downsizing in two genome groups and a biased accumulation of insertions in the clade containing the cultivated cottons leading to large (for Gossypium) chloroplast genomes. Divergence time estimates derived from the cpDNA sequence suggest that the major diploid clades had diverged approximately 10 to 11 million years ago. The complete nucleotide sequences of 6 cpDNA genomes are provided, offering a resource for cytonuclear studies in Gossypium.
PMCID: PMC4911064  PMID: 27309527
7.  Correlation Analysis between Polysomnography Diagnostic Indices and Heart Rate Variability Parameters among Patients with Obstructive Sleep Apnea Hypopnea Syndrome 
PLoS ONE  2016;11(6):e0156628.
Heart rate variability (HRV) can reflect the changes in the autonomic nervous system (ANS) that are affected by apnea or hypopnea events among patients with obstructive sleep apnea hypopnea syndrome (OSAHS). To evaluate the possibility of using HRV to screen for OSAHS, we investigated the relationship between HRV and polysomnography (PSG) diagnostic indices using electrocardiography (ECG) and PSG data from 25 patients with OSAHS and 27 healthy participants. We evaluated the relationship between various PSG diagnostic indices (including the apnea hypopnea index [AHI], micro-arousal index [MI], oxygen desaturation index [ODI]) and heart rate variability (HRV) parameters using Spearman’s correlation analysis. Moreover, we used multiple linear regression analyses to construct linear models for the AHI, MI, and ODI. In our analysis, the AHI was significantly associated with relative powers of very low frequency (VLF [%]) (r = 0.641, P = 0.001), relative powers of high frequency (HF [%]) (r = -0.586, P = 0.002), ratio between low frequency and high frequency powers (LF/HF) (r = 0.545, P = 0.049), normalized powers of low frequency (LF [n.u.]) (r = 0.506, P = 0.004), and normalized powers of high frequency (HF [n.u.]) (r = -0.506, P = 0.010) among patients with OSAHS. The MI was significantly related to standard deviation of RR intervals (SDNN) (r = 0.550, P = 0.031), VLF [%] (r = 0.626, P = 0.001), HF [%] (r = -0.632, P = 0.001), LF/HF (r = 0.591, P = 0.011), LF [n.u.] (r = 0.553, P = 0.004), HF [n.u.] (r = -0.553, P = 0.004), and absolute powers of very low frequency (VLF [abs]) (r = 0.525, P = 0.007) among patients with OSAHS. The ODI was significantly correlated with VLF [%] (r = 0.617, P = 0.001), HF [%] (r = -0.574, P = 0.003), LF [n.u.] (r = 0.510, P = 0.012), and HF [n.u.] (r = -0.510, P = 0.012) among patients with OSAHS. The linear models for the PSG diagnostic indices were AHI = -38.357+1.318VLF [%], MI = -13.389+11.297LF/HF+0.266SDNN, and ODI = -55.588+1.715VLF [%]. However, the PSG diagnostic indices were not related to the HRV parameters among healthy participants. Our analysis suggests that HRV parameters are powerful tools to screen for OSAHS patients in place of PSG monitoring.
PMCID: PMC4890801  PMID: 27253187
8.  Optogenetic activation of intracellular adenosine A2A receptor signaling in hippocampus is sufficient to trigger CREB phosphorylation and impair memory 
Molecular psychiatry  2015;20(11):1339-1349.
Human and animal studies have converged to suggest that caffeine consumption prevents memory deficits in aging and Alzheimer’s disease through the antagonism of adenosine A2A receptors (A2AR). To test if A2AR activation in hippocampus is actually sufficient to impair memory function and to begin elucidating the intracellular pathways operated by A2AR, we have developed a chimeric rhodopsin-A2AR protein (optoA2AR), which retains the extracellular and transmembrane domains of rhodopsin (conferring light responsiveness and eliminating adenosine binding pockets) fused to the intracellular loop of A2AR to confer specific A2AR signaling. The specificity of the optoA2AR signaling was confirmed by light-induced selective enhancement of cAMP and phospho-MAPK (but not cGMP) levels in HEK293 cells, which was abolished by a point mutation at the C-terminal of A2AR. Supporting its physiological relevance, optoA2AR activation and the A2AR agonist CGS21680 produced similar activation of cAMP and phospho-MAPK signaling in HEK293 cells, of pMAPK in nucleus accumbens, of c-Fos/pCREB in hippocampus and similarly enhanced long-term potentiation in hippocampus. Remarkably, optoA2AR activation triggered a preferential phospho-CREB signaling in hippocampus and impaired spatial memory performance while optoA2AR activation in the nucleus accumbens triggered MAPK signaling and modulated locomotor activity. This shows that the recruitment of intracellular A2AR signaling in hippocampus is sufficient to trigger memory dysfunction. Furthermore, the demonstration that the biased A2AR signaling and functions depend on intracellular A2AR loops, prompts the possibility of targeting the intracellular A2AR interacting partners to selectively control different neuropsychiatric behaviors.
PMCID: PMC4539301  PMID: 25687775
adenosine A2A receptor; hippocampus; memory; optogenetics; CREB; biased signalling; MAPK; intracellular domain of A2A receptor; striatum
9.  Epigenetic dysregulation of hairy and enhancer of split 4 (HES4) is associated with striatal degeneration in postmortem Huntington brains 
Human Molecular Genetics  2014;24(5):1441-1456.
To investigate epigenetic contributions to Huntington's disease (HD) pathogenesis, we carried out genome-wide mapping of the transcriptional mark, trimethyl-histone H3-lysine 4 (H3K4me3) in neuronal nuclei extracted from prefrontal cortex of HD cases and controls using chromatin immunoprecipitation followed by deep-sequencing. Neuron-specific mapping of the genome-wide distribution of H3K4me3 revealed 136 differentially enriched loci associated with genes implicated in neuronal development and neurodegeneration, including GPR3, TMEM106B, PDIA6 and the Notch signaling genes hairy and enhancer of split 4 (HES4) and JAGGED2, supporting the view that the neuronal epigenome is affected in HD. Importantly, loss of H3K4me3 at CpG-rich sequences on the HES4 promoter was associated with excessive DNA methylation, reduced binding of nuclear proteins to the methylated region and altered expression of HES4 and HES4 targeted genes MASH1 and P21 involved in striatal development. Moreover, hypermethylation of HES4 promoter sequences was strikingly correlated with measures of striatal degeneration and age-of-onset in a cohort of 25 HD brains (r = 0.56, P = 0.006). Lastly, shRNA knockdown of HES4 in human neuroblastoma cells altered MASH1 and P21 mRNA expression and markedly increased mutated HTT-induced aggregates and cell death. These findings, taken together, suggest that epigenetic dysregulation of HES4 could play a critical role in modifying HD disease pathogenesis and severity.
PMCID: PMC4321450  PMID: 25480889
10.  Multi-scale processes of beech wood disintegration and pretreatment with 1-ethyl-3-methylimidazolium acetate/water mixtures 
The valorization of biomass for chemicals and fuels requires efficient pretreatment. One effective strategy involves the pretreatment with ionic liquids which enables enzymatic saccharification of wood within a few hours under mild conditions. This pretreatment strategy is, however, limited by water and the ionic liquids are rather expensive. The scarce understanding of the involved effects, however, challenges the design of alternative pretreatment concepts. This work investigates the multi length-scale effects of pretreatment of wood in 1-ethyl-3-methylimidazolium acetate (EMIMAc) in mixtures with water using spectroscopy, X-ray and neutron scattering.
The structure of beech wood is disintegrated in EMIMAc/water mixtures with a water content up to 8.6 wt%. Above 10.7 wt%, the pretreated wood is not disintegrated, but still much better digested enzymatically compared to native wood. In both regimes, component analysis of the solid after pretreatment shows an extraction of few percent of lignin and hemicellulose. In concentrated EMIMAc, xylan is extracted more efficiently and lignin is defunctionalized. Corresponding to the disintegration at macroscopic scale, SANS and XRD show isotropy and a loss of crystallinity in the pretreated wood, but without distinct reflections of type II cellulose. Hence, the microfibril assembly is decrystallized into rather amorphous cellulose within the cell wall.
The molecular and structural changes elucidate the processes of wood pretreatment in EMIMAc/water mixtures. In the aqueous regime with >10.7 wt% water in EMIMAc, xyloglucan and lignin moieties are extracted, which leads to coalescence of fibrillary cellulose structures. Dilute EMIMAc/water mixtures thus resemble established aqueous pretreatment concepts. In concentrated EMIMAc, the swelling due to decrystallinization of cellulose, dissolution of cross-linking xylan, and defunctionalization of lignin releases the mechanical stress to result in macroscopic disintegration of cells. The remaining cell wall constituents of lignin and hemicellulose, however, limit a recrystallization of the solvated cellulose. These pretreatment mechanisms are beyond common pretreatment concepts and pave the way for a formulation of mechanistic requirements of pretreatment with simpler pretreatment liquors.
Electronic supplementary material
The online version of this article (doi:10.1186/s13068-015-0422-9) contains supplementary material, which is available to authorized users.
PMCID: PMC4706671  PMID: 26752999
Ionic liquid; Lignocellulose; EMIMAc; XRD; SANS; Pretreatment; Crystallinity; Disintegration; Microfibrils
11.  Meta-Analysis on the Correlation Between APOM rs805296 Polymorphism and Risk of Coronary Artery Disease 
The present meta-analysis aimed to summarize the inconsistent findings on the association of apolipoprotein M gene (ApoM) rs805296 polymorphism with the risk of coronary artery disease (CAD), and to obtain a more authentic result about this topic.
A total of 7 available articles were identified through electronic databases – PubMed, EMBASE, and Chinese National Knowledge Infrastructure (CNKI) – and their useful data were carefully extracted. The relationship between ApoM rs805296 polymorphism and CAD risk was assessed by odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs), which were calculated using the fixed- or random-effects model, according to the degree of heterogeneity. Hardy-Weinberg equilibrium test, sensitivity test, and publication bias examination were also performed in this meta-analysis.
According to the pooled results, ApoM rs805296 polymorphism conferred an increased risk of CAD under all the genetic contrasts: CC versus TT, CC + TC versus TT, CC versus TT+TC, C versus T, and TC versus TT (OR=2.13, 95% CI=1.16–3.91; OR=1.80, 95% CI=1.50–2.17; OR=1.91, 95% CI=1.04–3.51; OR=1.72, 95% CI=1.45–2.04; OR=1.78, 95% CI=1.47–2.15).
ApoM rs805296 polymorphism may be a risk factor for developing CAD.
PMCID: PMC4702609  PMID: 26723879
Apolipoproteins; Coronary Artery Disease; Polymorphism, Genetic; Risk Factors
12.  Partial Dominance, Overdominance, Epistasis and QTL by Environment Interactions Contribute to Heterosis in Two Upland Cotton Hybrids 
G3: Genes|Genomes|Genetics  2015;6(3):499-507.
Based on two recombinant inbred line (RIL) populations, two corresponding backcross (BC) populations were constructed to elucidate the genetic basis of heterosis in Upland cotton (Gossypium hirsutum L.). The yield, and yield components, of these populations were evaluated in three environments. At the single-locus level, 78 and 66 quantitative trait loci (QTL) were detected using composite interval mapping in RIL and BC populations, respectively, and 29 QTL were identified based on mid-parental heterosis (MPH) data of two hybrids. Considering all traits together, a total of 50 (64.9%) QTL with partial dominance effect, and 27 (35.1%) QTL for overdominance effect were identified in two BC populations. At the two-locus level, 120 and 88 QTL with main effects (M-QTL), and 335 and 99 QTL involved in digenic interactions (E-QTL), were detected by inclusive composite interval mapping in RIL and BC populations, respectively. A large number of QTL by environment interactions (QEs) for M-QTL and E-QTL were detected in three environments. For most traits, average E-QTL explained a larger proportion of phenotypic variation than did M-QTL in two RIL populations and two BC populations. It was concluded that partial dominance, overdominance, epistasis, and QEs all contribute to heterosis in Upland cotton, and that partial dominance resulting from single loci and epistasis play a relatively more important role than other genetic effects in heterosis in Upland cotton.
PMCID: PMC4777113  PMID: 26715091
QTLs; heterosis; partial dominance; overdominace; epistasis; Upland cotton
13.  Partial Dominance, Overdominance and Epistasis as the Genetic Basis of Heterosis in Upland Cotton (Gossypium hirsutum L.) 
PLoS ONE  2015;10(11):e0143548.
Determination of genetic basis of heterosis may promote hybrid production in Upland cotton (Gossypium hirsutum L.). This study was designed to explore the genetic mechanism of heterosis for yield and yield components in F2: 3 and F2: 4 populations derived from a hybrid ‘Xinza No. 1’. Replicated yield field trials of the progenies were conducted in 2008 and 2009. Phenotypic data analyses indicated overdominance in F1 for yield and yield components. Additive and dominance effects at single-locus level and digenic epistatic interactions at two-locus level were analyzed by 421 marker loci spanning 3814 cM of the genome. A total of 38 and 49 QTLs controlling yield and yield components were identified in F2: 3 and F2: 4 populations, respectively. Analyses of these QTLs indicated that the effects of partial dominance and overdominance contributed to heterosis in Upland cotton simultaneously. Most of the QTLs showed partial dominance whereas 13 QTLs showing overdominance in F2:3 population, and 19 QTLs showed overdominance in F2:4. Among them, 21 QTLs were common in both F2: 3 and F2: 4 populations. A large number of two-locus interactions for yield and yield components were detected in both generations. AA (additive × additive) epistasis accounted for majority portion of epistatic effects. Thirty three complementary two-locus homozygotes (11/22 and 22/11) were the best genotypes for AA interactions in terms of bolls per plant. Genotypes of double homozygotes, 11/22, 22/11 and 22/22, performed best for AD/DA interactions, while genotype of 11/12 performed best for DD interactions. These results indicated that (1) partial dominance and overdominance effects at single-locus level and (2) epistasis at two-locus level elucidated the genetic basis of heterosis in Upland cotton.
PMCID: PMC4664285  PMID: 26618635
14.  Long-term effect of early-life stress from earthquake exposure on working memory in adulthood 
The present study aimed to investigate the long-term effect of 1976 Tangshan earthquake exposure in early life on performance of working memory in adulthood.
A total of 907 study subjects born and raised in Tangshan were enrolled in this study. They were divided into three groups according to the dates of birth: infant exposure (3–12 months, n=274), prenatal exposure (n=269), and no exposure (born at least 1 year after the earthquake, n=364). The prenatal group was further divided into first, second, and third trimester subgroups based on the timing of exposure during pregnancy. Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised (BVMT-R) were used to measure the performance of working memory. Unconditional logistic regression analysis was used to analyze the influential factors for impaired working memory.
The Hopkins Verbal Learning Test-Revised scores did not show significant difference across the three groups. Compared with no exposure group, the BVMT-R scores were slightly lower in the prenatal exposure group and markedly decreased in the infant exposure group. When the BVMT-R scores were analyzed in three subgroups, the results showed that the subjects whose mothers were exposed to earthquake in the second and third trimesters of pregnancy had significantly lower BVMT-R scores compared with those in the first trimester. Education level and early-life earthquake exposure were identified as independent risk factors for reduced performance of visuospatial memory indicated by lower BVMT-R scores.
Infant exposure to earthquake-related stress impairs visuospatial memory in adulthood. Fetuses in the middle and late stages of development are more vulnerable to stress-induced damage that consequently results in impaired visuospatial memory. Education and early-life trauma can also influence the performance of working memory in adulthood.
PMCID: PMC4664544  PMID: 26648728
Tangshan earthquake; early life stress; working memory; chronic effect
15.  Serum MicroRNA-370 as a potential diagnostic and prognostic biomarker for pediatric acute myeloid leukemia 
Background: Controversial data on the expression pattern of microRNA-370 (miR-370) in acute myeloid leukemia (AML) were previously reported. Objective: To clarify the expression pattern of miR-370 and its clinical implications in pediatric AML patients. Methods: Real-time quantitative PCR was performed to detect the expression of miR-370 in both bone marrow mononuclear cells and sera obtained from pediatric AML patients and healthy controls. Results: Compared with healthy controls, the expression levels of miR-370 in the bone marrow and sera of pediatric AML patients were both decreased significantly (both P=0.001). Importantly, serum miR-370 level could efficiently screen pediatric AML patients from healthy controls (Area under receiver operating characteristic curve, AUC =0.993). Then, low serum miR-370 level was significantly associated with French-American-British (FAB) classification subtype M7 subtype (P=0.02) and unfavorable karyotype (P=0.01). Moreover, pediatric AML patients with low serum miR-370 level had shorter relapse-free and overall survivals than those with high serum miR-370 level (both P=0.001). Multivariate analysis further identified serum miR-370 level as an independent prognostic factor for both relapse-free and overall survivals. Interestingly, the prognostic relevance of serum miR-370 level was more obvious in the subgroup of patients with intermediate-risk cytogenetics. Conclusions: MiR-370 expression may be markedly and consistently decreased in pediatric AML patients and in turn contributes to aggressive progression of this malignancy. Serum miR-370 may serve as a potential non-invasive diagnostic/prognostic marker for pediatric AML patients.
PMCID: PMC4713575  PMID: 26823789
Pediatric acute myeloid leukemia; microRNA-370; serum; real-time quantitative PCR; prognosis
16.  Rapid evolutionary divergence of Gossypium barbadense and G. hirsutum mitochondrial genomes 
BMC Genomics  2015;16:770.
The mitochondrial genome from upland cotton, G. hirsutum, was previously sequenced. To elucidate the evolution of mitochondrial genomic diversity within a single genus, we sequenced the mitochondrial genome from Sea Island cotton (Gossypium barbadense L.).
Mitochondrial DNA from week-old etiolated seedlings was extracted from isolated organelles using discontinuous sucrose density gradient method. Mitochondrial genome was sequenced with Solexa using paired-end, 90 bp read. The clean reads were assembled into contigs using ABySS and finished via additional fosmid and BAC sequencing. Finally, the genome was annotated and analyzed using different softwares.
The G. barbadense (Sea Island cotton) mitochondrial genome was fully sequenced (677,434-bp) and compared to the mitogenome of upland cotton. The G. barbadense mitochondrial DNA contains seven more genes than that of upland cotton, with a total of 40 protein coding genes (excluding possible pseudogenes), 6 rRNA genes, and 29 tRNA genes. Of these 75 genes, atp1, mttB, nad4, nad9, rrn5, rrn18, and trnD(GTC)-cp were each represented by two identical copies. A single 64 kb repeat was largely responsible for the 9 % difference in genome size between the two mtDNAs. Comparison of genome structures between the two mitochondrial genomes revealed 8 rearranged syntenic regions and several large repeats. The largest repeat was missing from the master chromosome in G. hirsutum. Both mitochondrial genomes contain a duplicated copy of rps3 (rps3-2) in conjunction with a duplication of repeated sequences. Phylogenetic and divergence considerations suggest that a 544-bp fragment of rps3 was transferred to the nuclear genome shortly after divergence of the A- and D- genome diploid cottons.
These results highlight the insights to the evolution of structural variation between Sea Island and upland cotton mitochondrial genomes.
Electronic supplementary material
The online version of this article (doi:10.1186/s12864-015-1988-0) contains supplementary material, which is available to authorized users.
PMCID: PMC4603758  PMID: 26459858
Mitochondrial genome; Comparative genomics; DNA rearrangement; Duplicated copy; Sequence transfer
17.  The STAT3 HIES mutation is a gain-of-function mutation that activates genes via AGG-element carrying promoters 
Nucleic Acids Research  2015;43(18):8898-8912.
Cytokine or growth factor activated STAT3 undergoes multiple post-translational modifications, dimerization and translocation into nuclei, where it binds to serum-inducible element (SIE, ‘TTC(N3)GAA’)-bearing promoters to activate transcription. The STAT3 DNA binding domain (DBD, 320–494) mutation in hyper immunoglobulin E syndrome (HIES), called the HIES mutation (R382Q, R382W or V463Δ), which elevates IgE synthesis, inhibits SIE binding activity and sensitizes genes such as TNF-α for expression. However, the mechanism by which the HIES mutation sensitizes STAT3 in gene induction remains elusive. Here, we report that STAT3 binds directly to the AGG-element with the consensus sequence ‘AGG(N3)AGG’. Surprisingly, the helical N-terminal region (1–355), rather than the canonical STAT3 DBD, is responsible for AGG-element binding. The HIES mutation markedly enhances STAT3 AGG-element binding and AGG-promoter activation activity. Thus, STAT3 is a dual specificity transcription factor that promotes gene expression not only via SIE- but also AGG-promoter activity.
PMCID: PMC4605325  PMID: 26384563
18.  Impact of Soil Composition and Electrochemistry on Corrosion of Rock-cut Slope Nets along Railway Lines in China 
Scientific Reports  2015;5:14939.
Taking the slope of Suiyu Railway to study, the research separately studied soil resistivity, soil electrochemistry (corrosion potential, oxidization reduction potential, electric potential gradient and pH), soil anions (total soluble salt, Cl−, SO42− and ), and soil nutrition (moisture content, organic matter, total nitrogen, alkali-hydrolysable nitrogen, available phosphorus, and available potassium) at different slope levels, and conducted corrosion grade evaluation on artificial soil according to its single index and comprehensive indexes. Compared with other factors, water has the biggest impact on the corrosion of slope protection net, followed by anion content. Total soluble salt has the moderate impact on the corrosion of slope protection net, and stray current has the moderate impact on the corrosion of mid-slope protection net. Comprehensive evaluation on the corrosive degree of soil samples indicates that the corrosion of upper slope is moderate, and the corrosion of mid-slope and lower slope is strong. Organic matter in soil is remarkably relevant to electric potential gradient. Available nitrogen, available potassium and available phosphorus are remarkably relevant to anions. The distribution of soil nutrient is indirectly relevant to slope type.
PMCID: PMC4598838  PMID: 26450811
19.  Polymorphisms in the DNA Repair Gene ERCC2/XPD and Breast Cancer Risk: A HapMap-Based Case–Control Study Among Han Women in a Chinese Less-Developed Area 
Aims: Genetic variations in DNA repair genes may impact repair functions, DNA damage, and breast cancer risk. This study is aimed to assess the associations of genetic polymorphisms in excision repair cross-complementing group 2 (ERCC2) with the risk of developing breast cancer. Materials and Methods: In total, 101 histopathologically confirmed breast cancer cases and 101 age/region-matched healthy controls were genotyped for rs3916840, rs1799793, and rs238416 in ERCC2 by polymerase chain reaction–restriction fragment length polymorphism. Results: The rs238416 heterozygous GA genotype combined with the rs238416 genotypes (GA+AA) showed a significant association with breast cancer susceptibility (corrected p<0.01, odds ratio [OR]=0.29, 95% confidence interval [CI]=0.15–0.54; corrected p<0.01, OR=0.31, 95% CI=0.17–0.56, respectively). The rs238416 GA genotype carriers had a decreased risk of breast cancer. However, we observed no significant association between the rs3916840 and rs1799793 polymorphisms in ERCC2 and breast cancer risk. Moreover, haplotype analysis showed that the ACG haplotype was associated with a significantly decreased risk of breast cancer, whereas the GCG haplotype was associated with a significantly increased risk of breast cancer (corrected p=0.004 and p=0.002, respectively). Multifactor dimensionality reduction analysis demonstrated that the interactions between rs3916840 and rs238416 were significantly synergistic. Conclusion: To the best of our knowledge, this study is the first to demonstrate that the rs238416 heterozygous genotype likely has a higher DNA repair capacity and, thus, can be protective against breast cancer in Chinese Han women.
PMCID: PMC4183918  PMID: 25117088
20.  Brain Natriuretic Peptide as the long-term cause of mortality in patients with cardiovascular disease: a retrospective cohort study 
Objective: To explore the influence of BNP (Brain Natriuretic Peptide) in plasma on the long-term cause of mortality and prognosis of patients with cardiovascular disease (CVD). Method: We performed a retrospective cohort study of 276 inpatients that enrolled in our hospital from March 2003 to December 2004 and had a history of heart disease and received a BNP test. Kaplan-Meier survival curves with Log-Rank test were used to compare the survival rates among different levels of BNP (<100 ng/L, 101~1000 ng/L, 1001~5000 ng/L and >5000 ng/L). Cox proportional hazards regression models were used to estimate HRs and 95% CIs with adjustments for other covariance’s. Result: After a median follow-up of 7 years, a total of 91 patients died of whom fifty were cardiogenic deaths and 41 were non-cardiogenic. The survival rates were of statistical significance (P=0.0000) between the different levels of BNP in the 4 groups, and the mortality rate increased gradually with the increase in BNP concentration. Multivariable Cox regression analysis showed that BNP levels were inversely associated with the survival rate in CVD patients (HR=0.24, 95% CI: 0.13~0.42). In addition, age and left ventricular ejection fraction values were also of statistical significance in the Cox regression model. Conclusion: Our findings suggested that high Plasma BNP levels may have an adverse effect on the prognosis of patients with cardiovascular disease.
PMCID: PMC4659046  PMID: 26629158
Brain natriuretic peptide; cardiovascular disease
21.  An Efficient Biometric-Based Algorithm Using Heart Rate Variability for Securing Body Sensor Networks 
Sensors (Basel, Switzerland)  2015;15(7):15067-15089.
Body Sensor Network (BSN) is a network of several associated sensor nodes on, inside or around the human body to monitor vital signals, such as, Electroencephalogram (EEG), Photoplethysmography (PPG), Electrocardiogram (ECG), etc. Each sensor node in BSN delivers major information; therefore, it is very significant to provide data confidentiality and security. All existing approaches to secure BSN are based on complex cryptographic key generation procedures, which not only demands high resource utilization and computation time, but also consumes large amount of energy, power and memory during data transmission. However, it is indispensable to put forward energy efficient and computationally less complex authentication technique for BSN. In this paper, a novel biometric-based algorithm is proposed, which utilizes Heart Rate Variability (HRV) for simple key generation process to secure BSN. Our proposed algorithm is compared with three data authentication techniques, namely Physiological Signal based Key Agreement (PSKA), Data Encryption Standard (DES) and Rivest Shamir Adleman (RSA). Simulation is performed in Matlab and results suggest that proposed algorithm is quite efficient in terms of transmission time utilization, average remaining energy and total power consumption.
PMCID: PMC4541821  PMID: 26131666
Body Sensor Network (BSN); biometric; efficiency; Electrocardiogram (ECG); Heart Rate Variability (HRV); security
22.  Mild Cognitive Impairment: Vascular Risk Factors in Community Elderly in Four Cities of Hebei Province, China 
PLoS ONE  2015;10(5):e0124566.
Evidence has demonstrated that vascular risk factors (VRFs) contribute to mild cognitive impairment (MCI) in the elderly population. Because of the race and different diagnosis standard, there is still no definitive conclusions.
To estimate the VRFs and potential protective factors for MCI in elderly population living in the community in North China.
A total of 3136 participants entered the study. They were screened for hypertension, coronary heart disease (CHD), and cerebrovascular disease (CVD). Cognitive function was assessed with Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The diagnosis of MCI was made according to Petersen’s criteria. We investigated the relationship between vascular risk factors, potential protective factors and MCI.
A total of 2511 (80%) participant belonged to normal group and 625 (20%) participants showed MCI. Multiple logistic regression analysis demonstrated that stroke and diabetes, but not hypertension or CHD was associated with MCI. Besides, exercise habit could lower the risk of MCI.
Vascular Risk Factors, including stroke and diabetes, rather than hypertension and CHD are independent risk factors of MCI. Involvement in physical activities seems to reduce the risk of MCI.
PMCID: PMC4427494  PMID: 25962184
23.  Urinary Angiopoietin-2 Is Associated with Albuminuria in Patients with Type 2 Diabetes Mellitus 
Aims. To evaluate the levels of angiopoietin-1 (Ang-1), Ang-2, and vascular endothelial growth factor (VEGF) in serum and urine, and their association with albuminuria in patients with type 2 diabetes mellitus. Methods. In 113 type 2 diabetic patients with normoalbuminuria, microalbuminuria, and macroalbuminuria and 30 healthy controls, the levels of Ang-1, Ang-2, and VEGF in serum and urine were measured by enzyme-linked immunosorbent assay (ELISA). Results. Urinary and serum levels of Ang-2 were significantly higher in diabetic patients with normoalbuminuria than in healthy controls. Increased urinary Ang-2 level was positively associated with the degree of albuminuria. Urinary Ang-1 levels were significantly higher in normoalbuminuria patients and lower in macroalbuminuria patients than in controls. The levels of urinary VEGF increased in the albuminuria subgroup, though serum levels of Ang-1 and VEGF did not change. Urinary Ang-2 levels were correlated positively with albuminuria and negatively with glomerular filtration rate (GFR). Stepwise multiple regression analysis identified albuminuria (P < 0.001) and GFR (P = 0.001) as significant predictors of urinary Ang-2. Conclusions. Our data suggest that urinary Ang-2 is stepwise increased with renal damage in patients with type 2 diabetes mellitus and is associated with albuminuria.
PMCID: PMC4383519  PMID: 25873946
24.  Using Regional Homogeneity to Reveal Altered Spontaneous Activity in Patients with Mild Cognitive Impairment 
BioMed Research International  2015;2015:807093.
Most patients with mild cognitive impairment (MCI) are thought to be in an early stage of Alzheimer's disease (AD). Resting-state functional magnetic resonance imaging reflects spontaneous brain activity and/or the endogenous/background neurophysiological process of the human brain. Regional homogeneity (ReHo) rapidly maps regional brain activity across the whole brain. In the present study, we used the ReHo index to explore whole brain spontaneous activity pattern in MCI. Our results showed that MCI subjects displayed an increased ReHo index in the paracentral lobe, precuneus, and postcentral and a decreased ReHo index in the medial temporal gyrus and hippocampus. Impairments in the medial temporal gyrus and hippocampus may serve as important markers distinguishing MCI from healthy aging. Moreover, the increased ReHo index observed in the postcentral and paracentral lobes might indicate compensation for the cognitive function losses in individuals with MCI.
PMCID: PMC4337114  PMID: 25738156
25.  Overexpression of interleukin-18 protein reduces viability and induces apoptosis of tongue squamous cell carcinoma cells by activation of glycogen synthase kinase-3β signaling 
Oncology Reports  2015;33(3):1049-1056.
The aim of this study was to investigate the effects of interleukin-18 (IL-18) expression on regulating the viability and apoptosis of tongue squamous cell carcinoma (TSCC) cells in vitro and examine the underlying molecular events. Human IL-18 cDNA was cloned into the vector pcDNA3.1 (+) and transfected into CRL-1623™ cells. Quantitative reverse transcription-PCR (RT-qPCR), western blot analysis, immunofluorescence, cell viability MTT assay, flow cytometric Annexin V/propidium iodide (PI), Giemsa staining, and caspase-3 activity assay were performed. The data showed that overexpression of IL-18 protein reduced TSCC cell viability by inducing apoptosis. Compared with cells transfected with the control vector, IL-18 expression activated caspase-3, -7, and -9 by inducing their cleavage and increased the expression of interferon (IFN)-γ and cytochrome c mRNA, but reduced cyclin D1 and A1 expression in TSCC cells. IL-18 expression upregulated the expression and phosphorylation of glycogen synthase kinase (GSK)-3β protein in CRL1623 cells, whereas the selective GSK-3β inhibitor kenpaullone antagonized the effects of IL-18 protein on TSCC cells in vitro. The results indicated that IL-18 played an important role in the inhibition of TSCC cell growth and may be further investigated as a novel therapeutic target against TSCC.
PMCID: PMC4324481  PMID: 25591548
interleukin-18; tongue squamous cell carcinoma; gene expression; apoptosis; GSK-3β

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