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1.  Non-alcoholic steatohepatitis-related liver cirrhosis is increasing in China: A ten-year retrospective study 
Clinics  2015;70(8):563-568.
Little is known about metabolic factors in cirrhotic patients in China. Therefore, we aimed to quantify the prevalence of both metabolic factors and non-alcoholic steatohepatitis-related liver cirrhosis in China.
The medical records of 1,582 patients diagnosed with liver cirrhosis from June 2003 to July 2013 at Daping Hospital (Chongqing, China) were retrospectively reviewed through a computer-generated search.
Serum hepatitis B virus surface antigen was present in 1,083 (68.5%) patients, and hepatitis B was found to be the only etiological factor in 938 (59.3%) of all patients. Obesity, diabetes mellitus, and arterial hypertension were observed in 229 (14.5%), 159 (10.1%), and 129 (8.2%) patients, respectively. From 2012-2013, the proportion of non-alcoholic steatohepatitis-related liver cirrhosis increased to 3.2%, whereas the average proportion of non-alcoholic steatohepatitis-related liver cirrhosis in the previous ten years was 1.9%. The incidence of hepatocellular carcinoma was much higher in males than in females (6.3% vs. 3.7%, respectively, p=0.036). Obesity and diabetes mellitus did not significantly increase the incidence of hepatocellular carcinoma in the whole cirrhotic group. The presence of hepatitis B virus was the only risk factor for hepatocellular carcinoma in cirrhotic patients (p<0.001).
Although hepatitis B virus remains the main etiology of liver cirrhosis in China, steatohepatitis-related liver cirrhosis is increasing in frequency. Hepatitis B virus was the sole significant risk factor for hepatocellular carcinoma in the whole cirrhotic group in the present study, in contrast to obesity and diabetes mellitus, for which only a trend of increased hepatocellular carcinoma was found.
PMCID: PMC4518765  PMID: 26247669
Non-Alcoholic Steatohepatitis; Non-Alcoholic Fatty Liver Disease; Liver Cirrhosis; Obesity; Metabolism
2.  Marked methylation changes in intestinal genes during the perinatal period of preterm neonates 
BMC Genomics  2014;15(1):716.
The serious feeding- and microbiota-associated intestinal disease, necrotizing enterocolitis (NEC), occurs mainly in infants born prematurely (5-10% of all newborns) and most frequently after formula-feeding. We hypothesized that changes in gene methylation is involved in the prenatal maturation of the intestine and its response to the first days of formula feeding, potentially leading to NEC in preterm pigs used as models for preterm infants.
Reduced Representation Bisulfite Sequencing (RRBS) was used to assess if changes in intestinal DNA methylation are associated with formula-induced NEC outbreak and advancing age from 10 days before birth to 4 days after birth. Selected key genes with differentially methylated gene regions (DMRs) between groups were further validated by HiSeq-based bisulfite sequencing PCR and RT-qPCR to assess methylation and expression levels. Consistent with the maturation of many intestinal functions in the perinatal period, methylation level of most genes decreased with advancing pre- and postnatal age. The highest number of DMRs was identified between the newborn and 4 d-old preterm pigs. There were few intestinal DMR differences between unaffected pigs and pigs with initial evidence of NEC. In the 4 d-old formula-fed preterm pigs, four genes associated with intestinal metabolism (CYP2W1, GPR146, TOP1MT, CEND1) showed significant hyper-methylation in their promoter CGIs, and thus, down-regulated transcription. Methylation-driven down-regulation of such genes may predispose the immature intestine to later metabolic dysfunctions and severe NEC lesions.
Pre- and postnatal changes in intestinal DNA methylation may contribute to high NEC sensitivity in preterm neonates. Optimizing gene methylation changes via environmental stimuli (e.g. diet, nutrition, gut microbiota), may help to make immature newborn infants more resistant to gut dysfunctions, both short and long term.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2164-15-716) contains supplementary material, which is available to authorized users.
PMCID: PMC4153944  PMID: 25163507
DNA methylation; Preterm neonates; Necrotizing enterocolitis
3.  MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes 
Genome Biology  2014;15(7):419.
We propose a statistical algorithm MethylPurify that uses regions with bisulfite reads showing discordant methylation levels to infer tumor purity from tumor samples alone. MethylPurify can identify differentially methylated regions (DMRs) from individual tumor methylome samples, without genomic variation information or prior knowledge from other datasets. In simulations with mixed bisulfite reads from cancer and normal cell lines, MethylPurify correctly inferred tumor purity and identified over 96% of the DMRs. From patient data, MethylPurify gave satisfactory DMR calls from tumor methylome samples alone, and revealed potential missed DMRs by tumor to normal comparison due to tumor heterogeneity.
Electronic supplementary material
The online version of this article (doi:10.1186/s13059-014-0419-x) contains supplementary material, which is available to authorized users.
PMCID: PMC4165374  PMID: 25103624
4.  Obligate mutualism within a host drives the extreme specialization of a fig wasp genome 
Genome Biology  2013;14(12):R141.
Fig pollinating wasps form obligate symbioses with their fig hosts. This mutualism arose approximately 75 million years ago. Unlike many other intimate symbioses, which involve vertical transmission of symbionts to host offspring, female fig wasps fly great distances to transfer horizontally between hosts. In contrast, male wasps are wingless and cannot disperse. Symbionts that keep intimate contact with their hosts often show genome reduction, but it is not clear if the wide dispersal of female fig wasps will counteract this general tendency. We sequenced the genome of the fig wasp Ceratosolen solmsi to address this question.
The genome size of the fig wasp C. solmsi is typical of insects, but has undergone dramatic reductions of gene families involved in environmental sensing and detoxification. The streamlined chemosensory ability reflects the overwhelming importance of females finding trees of their only host species, Ficus hispida, during their fleeting adult lives. Despite long-distance dispersal, little need exists for detoxification or environmental protection because fig wasps spend nearly all of their lives inside a largely benign host. Analyses of transcriptomes in females and males at four key life stages reveal that the extreme anatomical sexual dimorphism of fig wasps may result from a strong bias in sex-differential gene expression.
Our comparison of the C. solmsi genome with other insects provides new insights into the evolution of obligate mutualism. The draft genome of the fig wasp, and transcriptomic comparisons between both sexes at four different life stages, provide insights into the molecular basis for the extreme anatomical sexual dimorphism of this species.
PMCID: PMC4053974  PMID: 24359812
5.  Molecular footprints of domestication and improvement in soybean revealed by whole genome re-sequencing 
BMC Genomics  2013;14:579.
Artificial selection played an important role in the origin of modern Glycine max cultivars from the wild soybean Glycine soja. To elucidate the consequences of artificial selection accompanying the domestication and modern improvement of soybean, 25 new and 30 published whole-genome re-sequencing accessions, which represent wild, domesticated landrace, and Chinese elite soybean populations were analyzed.
A total of 5,102,244 single nucleotide polymorphisms (SNPs) and 707,969 insertion/deletions were identified. Among the SNPs detected, 25.5% were not described previously. We found that artificial selection during domestication led to more pronounced reduction in the genetic diversity of soybean than the switch from landraces to elite cultivars. Only a small proportion (2.99%) of the whole genomic regions appear to be affected by artificial selection for preferred agricultural traits. The selection regions were not distributed randomly or uniformly throughout the genome. Instead, clusters of selection hotspots in certain genomic regions were observed. Moreover, a set of candidate genes (4.38% of the total annotated genes) significantly affected by selection underlying soybean domestication and genetic improvement were identified.
Given the uniqueness of the soybean germplasm sequenced, this study drew a clear picture of human-mediated evolution of the soybean genomes. The genomic resources and information provided by this study would also facilitate the discovery of genes/loci underlying agronomically important traits.
PMCID: PMC3844514  PMID: 23984715
Artificial selection; Evolution; Genetic diversity; Population genomics; Soybean
6.  A rare Von Hippel–Lindau disease that mimics acute myelitis: case report and review of the literature 
Neurological Sciences  2010;32(2):305-307.
Von Hippel–Lindau disease (VHL) comprises a series of complicated clinical manifestations. We hereby report one unique case of VHL with a natural history that mimics acute myelitis. MRI and biopsy in this patient showed multiple solid hemangioblastomas of the central nervous system and kidney. This study further confirmed that VHL is of highly clinical, imaging, and pathological heterogeneity. Diagnosis for VHL should be based on combination of clinical, radiological, pathological, and genetic data.
PMCID: PMC3056988  PMID: 20927563
Von Hippel–Lindau disease; Hemangioblastoma; Clinical manifestation; Magnetic resonance image; Histopathology
7.  Alcohol Elicits Functional and Structural Plasticity Selectively in Dopamine D1 Receptor-Expressing Neurons of the Dorsomedial Striatum 
The Journal of Neuroscience  2015;35(33):11634-11643.
Addiction is thought to be a maladaptive form of learning and memory caused by drug-evoked aberrant synaptic plasticity. We previously showed that alcohol facilitates synaptic plasticity in the dorsomedial striatum (DMS), a brain region that drives goal-directed behaviors. The majority of DMS cells are medium spiny neurons (MSNs) that express dopamine D1 receptors (D1Rs) or D2 receptors (D2Rs), which drive “Go” or “No-Go” behaviors, respectively. Here, we report that alcohol induces cell type-specific synaptic and structural plasticity in the DMS. Using mice that express a fluorescence marker to visualize D1R or D2R MSNs, we show that repeated cycles of systemic administration of alcohol or alcohol consumption induces a long-lasting increase in AMPAR activity specifically in DMS D1R but not in D2R MSNs. Importantly, we report that alcohol consumption increases the complexity of dendritic branching and the density of mature mushroom-shaped spines selectively in DMS D1R MSNs. Finally, we found that blockade of D1R but not D2R activity in the DMS attenuates alcohol consumption. Together, these data suggest that alcohol intake produces profound functional and structural plasticity events in a subpopulation of neurons in the DMS that control reinforcement-related learning.
SIGNIFICANCE STATEMENT Alcohol addiction is considered maladaptive learning and memory processes. Here we unraveled a long-lasting cellular mechanism that may contribute to the memory of alcohol-seeking behaviors. Specifically, we found that alcohol consumption produces a long-lasting enhancement of channel activity and persistent alterations of neuronal morphology in a part of the brain (DMS) that controls alcohol-drinking behaviors. Furthermore, we show that these alterations occur only in a subpopulation of neurons that positively control reward and reinforcement of drugs of abuse. Finally, we report that blocking the activity of this neuronal population reduces alcohol intake. As such synaptic and structural changes are the cellular hallmarks of learning and memory, and these neuroadaptations may drive the development of pathological heavy alcohol consumption.
PMCID: PMC4540799  PMID: 26290240
addiction; alcohol; dendritic spines; dorsal striatum; ethanol; synaptic plasticity
8.  Kavalactone content and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of kavalactones using different solvents 
The South Pacific islanders have consumed kava beverage for thousands of years. The quality of kava and kava beverage is evaluated through determination of the content of six major kavalactones including methysticin, dihydromethysticin, kavain, dihydrokavain, yangonin and desmethoxyyangonin. In this study, we determined contents of kavalactones in and chemotype of kava beverages prepared from roots and rhizomes of Isa and Mahakea varieties and extraction efficiency of five different solvents including hexane, acetone, methanol, ethanol and ethyl acetate. The six major kavalactones were detected in all kava beverages with these five solvents. Different solvents had different extraction efficiencies for kavalactones from the lyophilized kava preparations. The contents of kavalactones in the extracts with acetone, ethanol, and methanol did not differ significantly. Ethanol had the highest extraction efficiency for the six major kavalactones whereas hexane gave the lowest extraction efficiency.
PMCID: PMC4325077  PMID: 25694734
Piper methysticum; Kava; Kavalactone; Chemotype; Extraction efficiency
9.  Methicillin-resistant Staphylococcal periprosthetic joint infections can be effectively controlled by systemic and local daptomycin 
Methicillin-resistant Staphylococcus remains a serious problem in the treatment of periprosthetic joint infection (PJI). Higher failure rates were reported when vancomycin was used in 2-stage exchange arthroplasty. Therefore a better therapeutic drug is needed to treat PJI caused by methicillin-resistant organisms. The purpose of the study was to evaluate the safety and efficacy of daptomycin when administered in bone cement combined with systemic use for methicillin-resistant Staphylococci PJI.
We conducted a retrospective study from January 2010 to December 2012. Twenty-two patients (10 knees and 12 hips) with PJI caused by methicillin-resistant Staphylococcus species underwent 2-stage revision arthroplasty. In the first stage, 10 % daptomycin (weight daptomycin per weight bone cement) was incorporated into polymethylmethacrylate bone cement, and systemic daptomycin (6 mg/kg) was administered postoperatively for 14 days. In the second stage, 2.5 % w/w daptomycin was used in the bone cement. The minimum follow-up was 2 years or until recurrence of infection.
The infecting organisms included methicillin-resistant Staphylococcus aureus in 10 patients, methicillin-resistant Staphylococcus epidermidis in 8 patients and methicillin-resistant coagulase-negative Staphylococci in 4 patients. The mean follow-up duration was 33.7 months (range, 24–51 months). The treatment success rate was 100 %. Only one patient developed asymptomatic transient elevation of the creatine phosphokinase level. No patient experienced any adverse effects related to daptomycin such as myositis, rhabdomyolysis, peripheral neuropathy, derangement of liver function, or eosinophilic pneumonia.
In this series, no serious adverse events occurred. Our protocol, using daptomycin-impregnated cement combined with short duration of systemic daptomycin, appears to be an effective and safe treatment for methicillin-resistant Staphylococcus PJI.
PMCID: PMC4735949  PMID: 26830838
Daptomycin; Periprosthetic joint infection; Cement; Staphylococcus
10.  Articulatory Distinctiveness of Vowels and Consonants: A Data-Driven Approach 
The goal of this project was to quantify the articulatory distinctiveness of eight major English vowels and eleven English consonants based on tongue and lip movement time series data using a data-driven approach.
Tongue and lip movements of eight vowels and eleven consonants from ten healthy talkers were collected. First, classification accuracies were obtained using two complementary approaches: Procrustes analysis and support vector machine. Procrustes distance was then used to measure the articulatory distinctiveness among vowels and consonants. Finally, the distance (distinctiveness) matrices of different vowel pairs and consonant pairs were used to derive articulatory vowel and consonant spaces using multi-dimensional scaling.
Vowel classification accuracies of 91.67% and 89.05% and consonant classification accuracies of 91.37% and 88.94% were obtained using Procrustes analysis and support vector machine, respectively. Articulatory vowel and consonant spaces were derived based on the pairwise Procrustes distances.
The articulatory vowel space derived in this study resembled the long-standing descriptive articulatory vowel space defined by tongue height and advancement. The articulatory consonant space was consistent with feature-based classification of English consonants. The derived articulatory vowel and consonant spaces may have clinical implications including serving as an objective measure of the severity of articulatory impairment.
PMCID: PMC4727744  PMID: 23838988
speech production; speech kinematics; articulatory vowel space; articulatory consonant space; Procrustes analysis; support vector machine; multi-dimensional scaling
11.  Analysis of bacterial diversity in two oil blocks from two low-permeability reservoirs with high salinities 
Scientific Reports  2016;6:19600.
The community diversities of two oil reservoirs with low permeability of 1.81 × 10−3 and 2.29 × 10−3 μm2 in Changqing, China, were investigated using a high throughput sequencing technique to analyze the influence of biostimulation with a nutrient activator on the bacterial communities. These two blocks differed significantly in salinity (average 17,500 vs 40,900 mg/L). A core simulation test was used to evaluate the effectiveness of indigenous microbial-enhanced oil recovery (MEOR). The results indicated that in the two high salinity oil reservoirs, one reservoir having relatively lower salinity level and a narrow salinity range had higher bacterial and phylogenetic diversity. The addition of the nutrient activator increased the diversity of the bacterial community structure and the diversity differences between the two blocks. The results of the core simulation test showed that the bacterial community in the reservoir with a salinity level of 17,500 mg/L did not show significant higher MEOR efficiency compared with the reservoir with 40,900 mg/L i.e. MEOR efficiency of 8.12% vs 6.56% (test p = 0.291 > 0.05). Therefore, salinity levels affected the bacterial diversities in the two low permeability oil blocks remarkably. But the influence of salinity for the MEOR recovery was slightly.
PMCID: PMC4726302  PMID: 26786765
12.  Enhanced energy transport owing to nonlinear interface interaction 
Scientific Reports  2016;6:19628.
It is generally expected that the interface coupling leads to the suppression of thermal transport through coupled nanostructures due to the additional interface phonon-phonon scattering. However, recent experiments demonstrated that the interface van der Waals interactions can significantly enhance the thermal transfer of bonding boron nanoribbons compared to a single freestanding nanoribbon. To obtain a more in-depth understanding on the important role of the nonlinear interface coupling in the heat transports, in the present paper, we explore the effect of nonlinearity in the interface interaction on the phonon transport by studying the coupled one-dimensional (1D) Frenkel-Kontorova lattices. It is found that the thermal conductivity increases with increasing interface nonlinear intensity for weak inter-chain nonlinearity. By developing the effective phonon theory of coupled systems, we calculate the dependence of heat conductivity on interfacial nonlinearity in weak inter-chain couplings regime which is qualitatively in good agreement with the result obtained from molecular dynamics simulations. Moreover, we demonstrate that, with increasing interface nonlinear intensity, the system dimensionless nonlinearity strength is reduced, which in turn gives rise to the enhancement of thermal conductivity. Our results pave the way for manipulating the energy transport through coupled nanostructures for future emerging applications.
PMCID: PMC4726369  PMID: 26787363
13.  Three-dimensional printing as an aid to airway evaluation after tracheotomy in a patient with laryngeal carcinoma 
BMC Anesthesiology  2016;16:6.
Difficult airway may result in significant morbidity and mortality. Proficient airway evaluation, therefore, is one of the key elements in the safe conduct of anesthesia. A three-dimensional (3D) printing model was recently introduced for medical application. 3D printing is a fast, convenient, and relatively affordable technique. We present a case in which a 3D-printed airway model was successfully used for airway evaluation.
Case presentation
A 77-year-old man who had previously undergone total laryngectomy was scheduled for resection of a pelvic mass. The condition of his airway, however, complicated the procedure. Routine methods to evaluate his airway were not suitable. Therefore, the patient’s computed tomography imaging data were used to generate stereolithography files and then to print out 3D models of his trachea. These 3D models enhanced our understanding of his tracheal morphology. They helped us devise a preanesthesia plan and effectively execute it without complications.
3D printing models allow better understanding of morphological changes in the airway and aid preanesthesia planning. The successful outcome of our case suggests 3D printing is a potent tool for evaluating difficult and more widespread use is encouraged.
PMCID: PMC4717551  PMID: 26781803
3D printing; Anesthesia; Difficult airway
14.  Coupling of soil prokaryotic diversity and plant diversity across latitudinal forest ecosystems 
Scientific Reports  2016;6:19561.
The belowground soil prokaryotic community plays a cardinal role in sustaining the stability and functions of forest ecosystems. Yet, the nature of how soil prokaryotic diversity co-varies with aboveground plant diversity along a latitudinal gradient remains elusive. By establishing three hundred 400-m2 quadrats from tropical rainforest to boreal forest in a large-scale parallel study on both belowground soil prokaryote and aboveground tree and herb communities, we found that soil prokaryotic diversity couples with the diversity of herbs rather than trees. The diversity of prokaryotes and herbs responds similarly to environmental factors along the latitudinal gradient. These findings revealed that herbs provide a good predictor of belowground biodiversity in forest ecosystems, and provide new perspective on the aboveground and belowground interactions in forest ecosystems.
PMCID: PMC4726043  PMID: 26781165
15.  Analysis of a four generation family reveals the widespread sequence-dependent maintenance of allelic DNA methylation in somatic and germ cells 
Scientific Reports  2016;6:19260.
Differential methylation of the homologous chromosomes, a well-known mechanism leading to genomic imprinting and X-chromosome inactivation, is widely reported at the non-imprinted regions on autosomes. To evaluate the transgenerational DNA methylation patterns in human, we analyzed the DNA methylomes of somatic and germ cells in a four-generation family. We found that allelic asymmetry of DNA methylation was pervasive at the non-imprinted loci and was likely regulated by cis-acting genetic variants. We also observed that the allelic methylation patterns for the vast majority of the cis-regulated loci were shared between the somatic and germ cells from the same individual. These results demonstrated the interaction between genetic and epigenetic variations and suggested the possibility of widespread sequence-dependent transmission of DNA methylation during spermatogenesis.
PMCID: PMC4713049  PMID: 26758766
16.  A graphene oxide/amidoxime hydrogel for enhanced uranium capture 
Scientific Reports  2016;6:19367.
The efficient development of selective materials for the recovery of uranium from nuclear waste and seawater is necessary for their potential application in nuclear fuel and the mitigation of nuclear pollution. In this work, a graphene oxide/amidoxime hydrogel (AGH) exhibits a promising adsorption performance for uranium from various aqueous solutions, including simulated seawater. We show high adsorption capacities (Qm = 398.4 mg g−1) and high % removals at ppm or ppb levels in aqueous solutions for uranium species. In the presence of high concentrations of competitive ions such as Mg2+, Ca2+, Ba2+ and Sr2+, AGH displays an enhanced selectivity for uranium. For low uranium concentrations in simulated seawater, AGH binds uranium efficiently and selectively. The results presented here reveal that the AGH is a potential adsorbent for remediating nuclear industrial effluent and adsorbing uranium from seawater.
PMCID: PMC4725816  PMID: 26758649
17.  An Improved Cuckoo Search Optimization Algorithm for the Problem of Chaotic Systems Parameter Estimation 
This paper proposes an improved cuckoo search (ICS) algorithm to establish the parameters of chaotic systems. In order to improve the optimization capability of the basic cuckoo search (CS) algorithm, the orthogonal design and simulated annealing operation are incorporated in the CS algorithm to enhance the exploitation search ability. Then the proposed algorithm is used to establish parameters of the Lorenz chaotic system and Chen chaotic system under the noiseless and noise condition, respectively. The numerical results demonstrate that the algorithm can estimate parameters with high accuracy and reliability. Finally, the results are compared with the CS algorithm, genetic algorithm, and particle swarm optimization algorithm, and the compared results demonstrate the method is energy-efficient and superior.
PMCID: PMC4737452  PMID: 26880874
18.  Altered expression of mRNA profiles in blood of early-onset schizophrenia 
Scientific Reports  2016;6:16767.
To identify gene expression abnormalities in schizophrenia (SZ), we generated whole-genome gene expression profiles using microarrays on peripheral blood mononuclear cells (PBMCs) from 18 early-onset SZ cases and 12 controls. We detected 84 transcripts differentially expressed by diagnostic status, with 82 genes being upregulated and 2 downregulated. We identified two SZ associated gene coexpression modules (green and red), including 446 genes . The green module is positively correlated with SZ, encompassing predominantly up-regulated genes in SZ; while the red module was negatively correlated with disease status, involving mostly nominally down-regulated genes in SZ. The olfactory transduction pathway was the most enriched pathways for the genes within the two modules. The expression levels of several hub genes, including AKT1, BRCA1, CCDC134, UBD, and ZIC2 were validated using real-time quantitative PCR. Our findings indicate that mRNA coexpression abnormalities may serve as a promising mechanism underlying the development of SZ.
PMCID: PMC4702094  PMID: 26733343
19.  The Sinocyclocheilus cavefish genome provides insights into cave adaptation 
BMC Biology  2016;14:1.
An emerging cavefish model, the cyprinid genus Sinocyclocheilus, is endemic to the massive southwestern karst area adjacent to the Qinghai-Tibetan Plateau of China. In order to understand whether orogeny influenced the evolution of these species, and how genomes change under isolation, especially in subterranean habitats, we performed whole-genome sequencing and comparative analyses of three species in this genus, S. grahami, S. rhinocerous and S. anshuiensis. These species are surface-dwelling, semi-cave-dwelling and cave-restricted, respectively.
The assembled genome sizes of S. grahami, S. rhinocerous and S. anshuiensis are 1.75 Gb, 1.73 Gb and 1.68 Gb, respectively. Divergence time and population history analyses of these species reveal that their speciation and population dynamics are correlated with the different stages of uplifting of the Qinghai-Tibetan Plateau. We carried out comparative analyses of these genomes and found that many genetic changes, such as gene loss (e.g. opsin genes), pseudogenes (e.g. crystallin genes), mutations (e.g. melanogenesis-related genes), deletions (e.g. scale-related genes) and down-regulation (e.g. circadian rhythm pathway genes), are possibly associated with the regressive features (such as eye degeneration, albinism, rudimentary scales and lack of circadian rhythms), and that some gene expansion (e.g. taste-related transcription factor gene) may point to the constructive features (such as enhanced taste buds) which evolved in these cave fishes.
As the first report on cavefish genomes among distinct species in Sinocyclocheilus, our work provides not only insights into genetic mechanisms of cave adaptation, but also represents a fundamental resource for a better understanding of cavefish biology.
Electronic supplementary material
The online version of this article (doi:10.1186/s12915-015-0223-4) contains supplementary material, which is available to authorized users.
PMCID: PMC4698820  PMID: 26728391
Cavefish; Genome; Adaptation; Evolution; Qinghai-Tibetan Plateau; Sinocyclocheilus
20.  Supramolecular polymerization of a prebiotic nucleoside provides insights into the creation of sequence-controlled polymers 
Scientific Reports  2016;6:18891.
Self-assembly of a nucleoside on Au(111) was studied to ascertain whether polymerization on well-defined substrates constitutes a promising approach for making sequence-controlled polymers. Scanning tunneling microscopy and density functional theory were used to investigate the self-assembly on Au(111) of (RS)-N9-(2,3-dihydroxypropyl)adenine (DHPA), a plausibly prebiotic nucleoside analog of adenosine. It is found that DHPA molecules self-assemble into a hydrogen-bonded polymer that grows almost exclusively along the herringbone reconstruction pattern, has a two component sequence that is repeated over hundreds of nanometers, and is erasable with electron-induced excitation. Although the sequence is simple, more complicated ones are envisioned if two or more nucleoside types are combined. Because polymerization occurs on a substrate in a dry environment, the success of each combination can be gauged with high-resolution imaging and accurate modeling techniques. These characteristics make nucleoside self-assembly on a substrate an attractive approach for designing sequence-controlled polymers. Further, by choosing plausibly prebiotic nucleosides, insights may be provided into how nature created the first sequence-controlled polymers capable of storing information. Such insights, in turn, can inspire new ways of synthesizing sequence-controlled polymers.
PMCID: PMC4698751  PMID: 26725380
21.  Gastrointestinal Adverse Events of Glucagon-Like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis 
Introduction: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are a new class of drugs used in the treatment of type 2 diabetes mellitus (T2DM). Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs for GLP-1 RAs. We aim to evaluate the effect of GLP-1 RAs on the incidence of GI AEs of T2DM.
Materials and Methods: The overview of the GI events of GLP-1 RAs has been performed on relevant publications through the literature search, such as MEDLINE, EMBASE, Cochrane Library, and The manufacturer was contacted regarding unpublished data. We analyzed direct and indirect comparisons of different treatments using Bayesian network meta-analysis.
Results: Taspoglutide 30 mg once weekly (TAS30QW) and lixisenatide 30 μg twice daily (LIX30BID) were ranked the top two drugs in terms of GI AEs versus placebo. The odds ratios of nausea and vomiting for TAS30QW were 11.8 (95% confidence interval [CI], 2.89, 46.9) and 51.7 (95% CI, 7.07, 415), respectively, and that of diarrhea was 4.93 (95% CI, 1.75, 14.7) for LIX30BID.
Conclusions: Our study found all GLP-1 RA dose regimens significantly increased the incidence of GI AEs, compared with placebo or conventional treatment. The occurrence of GI AEs was different with diverse dose regimens of GLP-1 RAs. TAS30QW had the maximum probability to occur nausea and vomiting, whereas LIX30BID had the maximum probability to cause development of diarrhea versus other treatments.
PMCID: PMC4290796  PMID: 25375397
22.  Second malignancies in patients with primary central nervous system lymphoma 
Neuro-Oncology  2014;17(1):129-135.
Primary central nervous system lymphoma (PCNSL) is a rare extranodal lymphoma with distinctive biological behaviors. The evolving treatment of PCNSL has greatly improved the outcome for patients with this disease and has stimulated interest in second malignancies (SMs) in patients diagnosed with PCNSL.
The records of 129 cases of PCNSL at Mayo Clinic, diagnosed between January 1, 1988, and November 26, 2012, were reviewed. Data on clinical characteristics, laboratory parameters, treatments, outcomes, and SMs were collected. The mean follow-up time was 44.8 months (range, 0.5–240 months; median, 28.0 months).
Altogether, 28 cases with 30 (23.26%) SMs were identified. Twenty (15.50%) patients had prior or synchronous SM. Ten (7.76%) patients developed a subsequent primary cancer after PCNSL. The most common sites of prior or synchronous SMs were prostate (4/20), skin (4/20), and gastrointestinal (3/20). The most common site of the subsequent SM was skin (4/10). Two cases were identified with both prior SM and subsequent SM.
Second malignancies in cases with PCNSL were not uncommon and occurred in nearly a quarter of our cohort. Nonmelanoma skin cancers were frequently seen. Therefore, screening for SMs should also be considered in long-term follow-up of patients with PCNSL. In addition, the high incidence of subsequent cancer, synchronous cancer, and frequently seen nonmelanoma skin cancers may all indicate an immunosuppressed state in patients with PCNSL.
PMCID: PMC4483043  PMID: 24948826
primary central nervous lymphoma; second malignancies
23.  Replication of GWAS Coding SNPs Implicates MMEL1 as a Potential Susceptibility Locus among Saudi Arabian Celiac Disease Patients 
Disease Markers  2015;2015:351673.
Celiac disease (CD), a gluten intolerance disorder, was implicated to have 57 genetic susceptibility loci for Europeans but not for culturally and geographically distinct ethnic populations like Saudi Arabian CD patients. Therefore, we genotyped Saudi CD patients and healthy controls for three polymorphisms, that is, Phe196Ser in IRAK1, Trp262Arg in SH2B3, and Met518Thr in MMEL1 genes. Single locus analysis identified that carriers of the 518 Thr/Thr (MMEL1) genotype conferred a 1.6-fold increased disease risk compared to the noncarriers (OR = 2.6; 95% CI: 1.22–5.54; P < 0.01). This significance persisted even under allelic (OR = 1.55; 95% CI: 1.05–2.28; P = 0.02) and additive (OR = 0.35; 95% CI: 0.17–0.71; P = 0.03) genetic models. However, frequencies for Trp262Arg (SH2B3) and Phe196Ser (IRAK1) polymorphisms were not significantly different between patients and controls. The overall best MDR model included Met518Thr and Trp262Arg polymorphisms, with a maximal testing accuracy of 64.1% and a maximal cross-validation consistency of 10 out of 10 (P = 0.0156). Allelic distribution of the 518 Thr/Thr polymorphism in MMEL1 primarily suggests its independent and synergistic contribution towards CD susceptibility among Saudi patients. Lack of significant association of IRAK and SH2B3 gene polymorphisms in Saudi patients but their association in European groups suggests the genetic heterogeneity of CD.
PMCID: PMC4710944  PMID: 26843707
24.  Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas 
Nature Communications  2015;6:10131.
The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.
Despite lung adenocarcinoma having a high global mortality, the genetic mutations present in Asian patients are uncharacterized. Here the authors use genomic and transcriptomic analysis to identify thirteen significantly affected genes, including RHPN2, GLI3, MRC2, TP53 and IQGAP3.
PMCID: PMC4682110  PMID: 26647728
25.  Biochemical toxicity and DNA damage of imidazolium-based ionic liquid with different anions in soil on Vicia faba seedlings 
Scientific Reports  2015;5:18444.
In the present study, the toxic effects of 1-octyl-3-methylimidazolium chloride ([Omim]Cl), 1-octyl-3-methylimidazolium bromide ([Omim]Br) and 1-octyl-3-methylimidazolium tetrafluoroborate ([Omim]BF4) in soil on Vicia faba (V. faba) seedlings at 0, 100, 200, 400, 600 and 800 mg kg−1 were assessed for the first time at the cellular and molecular level. Moreover, the toxicity of these three ionic liquids (ILs) was evaluated, and the influence of anions on the toxicity of the ILs was assessed. The results showed that even at 100 mg kg−1, the growth of V. faba seedlings was inhibited after exposure to the three ILs, and the inhibitory effect was enhanced with increasing concentrations of the three ILs. The level of reactive oxygen species (ROS) was increased after exposure to the three ILs, which resulted in lipid peroxidation, DNA damage and oxidative damage in the cells of the V. faba seedlings. In addition, the anion structure could influence the toxicity of ILs, and toxicity of the three tested ILs decreased in the following order: [Omim]BF4 > [Omim]Br > [Omim]Cl. Moreover, oxidative damage is the primary mechanism by which ILs exert toxic effects on crops, and ILs could reduce the agricultural productivity.
PMCID: PMC4682074  PMID: 26675424

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