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1.  Chemical Constituents from the Stems of Manihot esculenta 
Abstract
Two new compounds, maniesculentins A (1) and B (6), together with four known ones were isolated from the stems of Manihot esculenta Crantz. The structures of the new compounds were elucidated by extensive spectroscopic methods including NMR spectroscopy and mass spectrometry. The two new compounds (1, 6) were assayed for antibacterial activity against four tested bacteria lines.
Graphical Abstract
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-015-0052-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-015-0052-8
PMCID: PMC4328001  PMID: 25673419
Euphorbiaceae; Manihot esculenta; Chemical constituents; Diterpenoids
2.  Chemical Constituents from the Stems of Manihot esculenta 
Abstract
Two new compounds, maniesculentins A (1) and B (6), together with four known ones were isolated from the stems of Manihot esculenta Crantz. The structures of the new compounds were elucidated by extensive spectroscopic methods including NMR spectroscopy and mass spectrometry. The two new compounds (1, 6) were assayed for antibacterial activity against four tested bacteria lines.
Graphical Abstract
Electronic supplementary material
The online version of this article (doi:10.1007/s13659-015-0052-8) contains supplementary material, which is available to authorized users.
doi:10.1007/s13659-015-0052-8
PMCID: PMC4328001  PMID: 25673419
Euphorbiaceae; Manihot esculenta; Chemical constituents; Diterpenoids
3.  X-linked myotubular myopathy in Rottweiler dogs is caused by a missense mutation in Exon 11 of the MTM1 gene 
Skeletal Muscle  2015;5(1):1.
Background
Congenital and inherited myopathies in dogs are faithful models of human muscle diseases and are being recognized with increasing frequency. In fact, canine models of dystrophin deficient muscular dystrophy and X-linked myotubular myopathy are of tremendous value in the translation of new and promising therapies for the treatment of these diseases. We have recently identified a family of Australian Rottweilers in which male puppies were clinically affected with severe muscle weakness and atrophy that resulted in early euthanasia or death. X-linked myotubular myopathy was suspected based on the early and severe clinical presentation and histopathological changes within muscle biopsies. The aim of this study was to determine the genetic basis for myopathy in these dogs and compare and contrast the clinical presentation, histopathology, ultrastructure, and mutation in this family of Rottweiler dogs with the previously described myotubular myopathy in Labrador retrievers.
Results
Histopathology, histochemistry, and ultrastructural examination of muscle biopsies from affected Rottweiler puppies were consistent with an X-linked myotubular myopathy. An unusual finding that differed from the previously reported Labradors and similar human cases was the presence of excessive autophagy and prominent autophagic vacuoles. Molecular investigations confirmed a missense mutation in exon 11 of MTM1 that was predicted to result in a non-functional phosphatase activity. Although the clinical presentations and histopathology were similar, the MTM1 p.(Q384P) mutation is different from the p.(N155K) mutation in exon 7 affecting Labrador retrievers with X-linked myotubular myopathy.
Conclusions
Here we describe a second pathogenic mutation in MTM1 causing X-linked myotubular myopathy in dogs. Our findings suggest a variety of MTM1 mutations in dogs as seen in human patients. The number of MTM1 mutations resulting in similar severe and progressive clinical myopathy and histopathological changes are likely to increase as canine myopathies are further characterized.
doi:10.1186/s13395-014-0025-3
PMCID: PMC4320619  PMID: 25664165
Congenital myopathy; Myotubularin; Canine myopathy; Animal model
4.  Loss of FHL1 induces an age-dependent skeletal muscle myopathy associated with myofibrillar and intermyofibrillar disorganization in mice 
Human Molecular Genetics  2013;23(1):209-225.
Recent human genetic studies have provided evidences that sporadic or inherited missense mutations in four-and-a-half LIM domain protein 1 (FHL1), resulting in alterations in FHL1 protein expression, are associated with rare congenital myopathies, including reducing body myopathy and Emery–Dreifuss muscular dystrophy. However, it remains to be clarified whether mutations in FHL1 cause skeletal muscle remodeling owing to gain- or loss of FHL1 function. In this study, we used FHL1-null mice lacking global FHL1 expression to evaluate loss-of-function effects on skeletal muscle homeostasis. Histological and functional analyses of soleus, tibialis anterior and sternohyoideus muscles demonstrated that FHL1-null mice develop an age-dependent myopathy associated with myofibrillar and intermyofibrillar (mitochondrial and sarcoplasmic reticulum) disorganization, impaired muscle oxidative capacity and increased autophagic activity. A longitudinal study established decreased survival rates in FHL1-null mice, associated with age-dependent impairment of muscle contractile function and a significantly lower exercise capacity. Analysis of primary myoblasts isolated from FHL1-null muscles demonstrated early muscle fiber differentiation and maturation defects, which could be rescued by re-expression of the FHL1A isoform, highlighting that FHL1A is necessary for proper muscle fiber differentiation and maturation in vitro. Overall, our data show that loss of FHL1 function leads to myopathy in vivo and suggest that loss of function of FHL1 may be one of the mechanisms underlying muscle dystrophy in patients with FHL1 mutations.
doi:10.1093/hmg/ddt412
PMCID: PMC3916749  PMID: 23975679
5.  The impact of smoking on the clinical outcome of locoregionally advanced nasopharyngeal carcinoma after chemoradiotherapy 
Background
Cigarette smoking is a common risk factor for developing nasopharyngeal carcinoma. However, the relationship between smoking and clinical outcomes remains uncertain.
Methods
The patients who participated in this study were drawn from a randomized clinical trial, for which the purpose was to compare the efficacy of induction chemotherapy plus concurrent chemoradiotherapy with that of induction chemotherapy plus radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. The patients who ever smoked were divided into the following categories of cumulative smoking exposure based on the duration of smoking and the quantity of cigarettes smoked: light, short-term smokers; light, long-term smokers; heavy, short-term smokers; and heavy, long-term smokers. A log-rank test and Cox models were used to assess the association between smoking and the clinical outcomes of overall survival (OS), failure-free survival (FFS), locoregional recurrence failure-free survival (LRFFS) and distant failure-free survival (DFFS).
Results
We found that ever-smokers experienced significantly shorter LRFFS times than never-smokers (5-year LRFFS rates: 85.8% vs. 88.5%, P = 0.022). The amount of smoking was significantly associated with FFS (P = 0.046) and LRFFS (P = 0.001) in the different ever-smoker groups. The amount of smoking was associated with LRFFS [P = 0.002, HR = 2.069 (95% confident interval (CI), 1.298-3.299)] even after a multivariable adjustment.
Conclusions
Smoking increases the risk of locoregional recurrence. Furthermore, the amount of smoking influences the prognosis of smokers, and these effects are dose-dependent.
doi:10.1186/s13014-014-0246-y
PMCID: PMC4251838  PMID: 25424191
Nasopharyngeal carcinoma; Prognostic factor; Radiotherapy; Smoking
6.  Platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the cyclooxygenase 1 signaling pathway 
Nature communications  2013;4:2657.
While it has been long known that patients with sepsis often have thrombocytopenia and that septic patients with severe thrombocytopenia have a poor prognosis and higher mortality, the role of platelets in the pathogenesis of sepsis is poorly understood. Here we report a protective role of platelets in septic shock. We show that experimental thrombocytopenia by intraperitoneal injection of an anti-glycoprotein Ibα monoclonal antibody increases mortality and aggravates organ failure whereas transfusion of platelets reduces mortality in Lipopolysaccharide-induced endotoxemia and a bacterial infusion mouse sepsis model. Plasma concentrations of proinflammatory cytokines TNF-α and IL-6 are elevated by thrombocytopenia and decreased by platelet transfusion in septic mice. Furthermore, we identify that platelets protect from septic shock by inhibiting macrophage-dependent inflammation via the COX1/PGE2/EP4 dependent pathway. Thus, these findings demonstrate a previously unappreciated role for platelets in septic shock and suggest that platelet transfusion may be effective in treating severe septic patients.
doi:10.1038/ncomms3657
PMCID: PMC4217311  PMID: 24150174
7.  A Novel Mutation in CLCN1 Associated with Feline Myotonia Congenita 
PLoS ONE  2014;9(10):e109926.
Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1∶100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a ‘swarm of bees’. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine β-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.
doi:10.1371/journal.pone.0109926
PMCID: PMC4214686  PMID: 25356766
8.  Epigenetic changes of mesenchymal stem cells in three-dimensional (3D) spheroids 
Mesenchymal stem cells (MSCs) hold profound promise in tissue repair/regeneration. However, MSCs undergo remarkable spontaneous differentiation and aging during monolayer culture expansion. In this study, we found that 2–3 days of three-dimensional (3D) spheroid culture of human MSCs (hMSCs) that had been expanded in monolayer for six passages increased their clonogenicity and differentiation potency to neuronal cells. Moreover, in accordance with these changes, the expression levels of miRNA which were involved in stem cell potency were changed and levels of histone H3 acetylation in K9 in promoter regions of Oct4, Sox2 and Nanog were elevated. Our results indicate that spheroid culture increases their multi-potency and changes the epigenetic status of pluripotent genes in hMSCs.
doi:10.1111/jcmm.12336
PMCID: PMC4244016  PMID: 25090911
mesenchymal stem cells; miRNA; histone acetylation; 3D culture; multi-potency
9.  Dihydroartemisinin inhibits vascular endothelial growth factor-induced endothelial cell migration by a p38 mitogen-activated protein kinase-independent pathway 
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, has been demonstrated to possess a strong antiangiogenic activity. However, the molecular mechanisms underlying this effect remain unclear. Endothelial cell (EC) migration is an essential component of angiogenesis, and the p38 mitogen-activated protein kinase (MAPK) signaling pathway plays a key role in the regulation of migration induced by vascular endothelial growth factor (VEGF). The aim of the present study was to investigate the effects of DHA on EC migration and the p38 MAPK signaling pathway. Human umbilical vein ECs (HUVECs) were treated with DHA and VEGF-induced migration was analyzed. The activation of p38 MAPK was detected by western blot analysis, and the migration assays were performed with a p38-specific inhibitor, SB203850. It was revealed that 20 μM DHA significantly reduced EC migration in the transwell migration assay, wound healing assay and electrical cell-substrate impedance sensing real-time analysis. However, DHA did not affect p38 MAPK phosphorylation or expression. In the absence or presence of SB203850, DHA induced a similar proportional reduction of EC migration in the three migration assays. Therefore, the present study demonstrated that DHA inhibits VEGF-induced EC migration via a p38 MAPK-independent pathway.
doi:10.3892/etm.2014.1997
PMCID: PMC4217775  PMID: 25371719
dihydroartemisinin; migration; p38 mitogen-activated protein kinase; endothelial cell; angiogenesis
10.  Association of p53 expression with prognosis in patients with esophageal squamous cell carcinoma 
It has been well accepted that p53 overexpression is associated with advanced stages of cancer. However, the prognostic role of p53 overexpression in esophageal squamous cell carcinoma (ESCC) remains unclear. To investigate the prognostic role of p53 overexpression in patients with ESCC, a retrospective cohort study of 136 ESCC patients was carried out. The expression of p53 protein in tumor tissues was investigated immunohistochemically. Positive expression of p53 protein was detected in 57 ESCC patients (41.9%). The p53 overexpression was associated with smoking (P < 0.001), tumor differentiation (P < 0.001), and tumor size (P < 0.001). In the Kaplan-Meier analysis, patients with p53 overexpression had significantly shorter overall survival than those patients with negative p53 expression (log-rank P < 0.001). Multivariable analysis by Cox regression model further showed that p53 overexpression was a significantly independent predictor of poorer overall survival (hazard ratio [HR] = 1.91; 95% confidence interval [95% CI] 1.03-3.54, P = 0.04). Thus, p53 overexpression is associated with poor prognosis in patients with early stage esophageal squamous cell carcinoma, and it’s a significantly independent predictor of poorer overall survival.
PMCID: PMC4230131  PMID: 25400812
Esophageal squamous cell carcinoma; p53; survival
11.  Efficient Open Fermentative Production of Polymer-Grade L-Lactate from Sugarcane Bagasse Hydrolysate by Thermotolerant Bacillus sp. Strain P38 
PLoS ONE  2014;9(9):e107143.
Lactic acid is one of the top 30 potential building-block chemicals from biomass, of which the most extensive use is in the polymerization of lactic acid to poly-lactic-acid (PLA). To reduce the cost of PLA, the search for cheap raw materials and low-cost process for lactic acid production is highly desired. In this study, the final titer of produced L-lactic acid reached a concentration of 185 g·L−1 with a volumetric productivity of 1.93 g·L−1·h−1 by using sugarcane bagasse hydrolysate as the sole carbon source simultaneously with cottonseed meal as cheap nitrogen sources under the open fed-batch fermentation process. Furthermore, a lactic acid yield of 0.99 g per g of total reducing sugars was obtained, which is very close to the theoretical value (1.0 g g−1). No D-isomer of lactic acid was detected in the broth, and thereafter resulted in an optical purity of 100%, which exceeds the requirement of lactate polymerization process. To our knowledge, this is the best performance of fermentation on polymer-grade L-lactic acid production totally using lignocellulosic sources. The high levels of optically pure l-lactic acid produced, combined with the ease of handling and low costs associated with the open fermentation strategy, indicated the thermotolerant Bacillus sp. P38 could be an excellent candidate strain with great industrial potential for polymer-grade L-lactic acid production from various cellulosic biomasses.
doi:10.1371/journal.pone.0107143
PMCID: PMC4156441  PMID: 25192451
12.  A COLQ Missense Mutation in Labrador Retrievers Having Congenital Myasthenic Syndrome 
PLoS ONE  2014;9(8):e106425.
Congenital myasthenic syndromes (CMSs) are heterogeneous neuromuscular disorders characterized by skeletal muscle weakness caused by disruption of signal transmission across the neuromuscular junction (NMJ). CMSs are rarely encountered in veterinary medicine, and causative mutations have only been identified in Old Danish Pointing Dogs and Brahman cattle to date. Herein, we characterize a novel CMS in 2 Labrador Retriever littermates with an early onset of marked generalized muscle weakness. Because the sire and dam share 2 recent common ancestors, CMS is likely the result of recessive alleles inherited identical by descent (IBD). Genome-wide SNP profiles generated from the Illumina HD array for 9 nuclear family members were used to determine genomic inheritance patterns in chromosomal regions encompassing 18 functional candidate genes. SNP haplotypes spanning 3 genes were consistent with autosomal recessive transmission, and microsatellite data showed that only the segment encompassing COLQ was inherited IBD. COLQ encodes the collagenous tail of acetylcholinesterase, the enzyme responsible for termination of signal transduction in the NMJ. Sequences from COLQ revealed a variant in exon 14 (c.1010T>C) that results in the substitution of a conserved amino acid (I337T) within the C-terminal domain. Both affected puppies were homozygous for this variant, and 16 relatives were heterozygous, while 288 unrelated Labrador Retrievers and 112 dogs of other breeds were wild-type. A recent study in which 2 human CMS patients were found to be homozygous for an identical COLQ mutation (c.1010T>C; I337T) provides further evidence that this mutation is pathogenic. This report describes the first COLQ mutation in canine CMS and demonstrates the utility of SNP profiles from nuclear family members for the identification of private mutations.
doi:10.1371/journal.pone.0106425
PMCID: PMC4148433  PMID: 25166616
13.  Transducin β-like 1 X-linked receptor 1 suppresses cisplatin sensitivity in Nasopharyngeal Carcinoma via activation of NF-κB pathway 
Molecular Cancer  2014;13(1):195.
Background
Transducin β-like 1 X-linked receptor 1 (TBL1XR1) is an important transcriptional cofactor involved in the regulation of many signaling pathways, and is associated with carcinogenesis and tumor progression. However, the precise role of TBL1XR1 in these processes is not well understood.
Methods
We detected the expression of TBL1XR1 protein and mRNA in nasopharyngeal carcinoma (NPC) cell lines and biopsies by western blotting, real-time PCR and immunohistochemical staining (IHC). Overexpression of TBL1XR1 in NPC enhanced chemoresistance to cisplatin using two NPC cell lines in vitro and in vivo.
Results
TBL1XR1 was upregulated in NPC cell lines and clinical samples. The expression of TBL1XR1 was correlated with several clinicopathological factors including clinical stage, T classification, N classification and patient survival. Univariate and multivariate analysis revealed that TBL1XR1 was an independent prognostic factor for patient survival. In vitro and in vivo studies demonstrated that TBL1XR1 high expression induced resistance to cisplatin-induced apoptosis in NPC cells. Furthermore, we found that TBL1XR1 activated the NF-κB pathway and promoted transcription of genes downstream of NF-κB, especially anti-apoptotic genes.
Conclusions
Upregulation of TBL1XR1 induces NPC cells resistance to cisplatin by activating the NF-κB pathway, and correlates with poor overall survival of NPC patients. TBL1XR1 has a pivotal role in NPC and could be a valuable prognostic factor as well as a novel biomarker for tailoring appropriate therapeutic regimes.
Electronic supplementary material
The online version of this article (doi:10.1186/1476-4598-13-195) contains supplementary material, which is available to authorized users.
doi:10.1186/1476-4598-13-195
PMCID: PMC4158072  PMID: 25145705
TBL1XR1; Nasopharyngeal carcinoma; Cisplatin; Chemotherapy; Anti-Apoptotic; NF-κB signalling
14.  Free Energy of Binding of Coiled-Coil Complexes with Different Electrostatic Environments: The Influence of Force Field Polarisation and Capping 
Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) simulations using the MM/GBSA method have been used to predict the free energy of interaction of these proteins. The influence of force field polarisation and capping on the predicted free energy of binding of complexes with different electrostatic environments (net charge) were investigated. Although both force field polarisation and peptide capping are important for the prediction of the absolute free energy of binding, peptide capping has the largest influence on the predicted free energy of binding. Polarisable simulations appear better suited to determine structural properties of the complexes of these proteins while non-polarisable simulations seem to give better predictions of the associated free energies of binding.
doi:10.1007/s13659-014-0036-0
PMCID: PMC4199946  PMID: 25159896
Free energy of binding; c-Fos; c-Jun; Leucine zipper; Molecular dynamics; MM/GBSA; Coiled-coil
15.  Free Energy of Binding of Coiled-Coil Complexes with Different Electrostatic Environments: The Influence of Force Field Polarisation and Capping 
Coiled-coils are well known protein–protein interaction motifs, with the leucine zipper region of activator protein-1 (AP-1) consisting of the c-Jun and c-Fos proteins being a typical example. Molecular dynamics (MD) simulations using the MM/GBSA method have been used to predict the free energy of interaction of these proteins. The influence of force field polarisation and capping on the predicted free energy of binding of complexes with different electrostatic environments (net charge) were investigated. Although both force field polarisation and peptide capping are important for the prediction of the absolute free energy of binding, peptide capping has the largest influence on the predicted free energy of binding. Polarisable simulations appear better suited to determine structural properties of the complexes of these proteins while non-polarisable simulations seem to give better predictions of the associated free energies of binding.
doi:10.1007/s13659-014-0036-0
PMCID: PMC4199946  PMID: 25159896
Free energy of binding; c-Fos; c-Jun; Leucine zipper; Molecular dynamics; MM/GBSA; Coiled-coil
16.  Differentially expressed microRNAs and affected biological pathways revealed by modulated modularity clustering (MMC) analysis of human preeclamptic and IUGR placentas 
Placenta  2013;34(7):599-605.
Introduction
This study focuses on the implementation of modulated modularity clustering (MMC) a new cluster algorithm for the identification of molecular signatures of preeclampsia and intrauterine growth restriction (IUGR), and the identification of affected microRNAs
Methods
Eighty-six human placentas from normal (40), growth-restricted (27), and preeclamptic (19) term pregnancies were profiled using Illumina Human-6 Beadarrays. MMC was utilized to generate modules based on similarities in placental transcriptome. Gene Set Enrichment Analysis (GSEA) was used to predict affected microRNAs. Expression levels of these candidate microRNAs were investigated in seventy-one human term placentas as follows: control (29); IUGR (26); and preeclampsia (16).
Results
MMC identified two modules, one representing IUGR placentas and one representing preeclamptic placentas. 326 differentially expressed genes in the module representing IUGR and 889 differentially expressed genes in a module representing preeclampsia were identified. Functional analysis of molecular signatures associated with IUGR identified P13K/AKT, mTOR, p70S6K, apoptosis and IGF-1 signaling as being affected. Analysis of variance of GSEA-predicted microRNAs indicated that miR-194 was significantly down-regulated both in preeclampsia (p=0.0001) and IUGR (p=0.0304), and miR-149 was significantly down-regulated in preeclampsia (p=0.0168).
Discussion
Implementation of MMC, allowed identification of genes disregulated in IUGR and preeclampsia. The reliability of MMC was validated by comparing to previous linear modeling analysis of preeclamptic placentas.
Conclusion
MMC allowed the elucidation of a molecular signature associated with preeclampsia and a subset of IUGR samples. This allowed the identification of genes, pathways, and microRNAs affected in these diseases.
doi:10.1016/j.placenta.2013.04.007
PMCID: PMC3677766  PMID: 23639576
Placenta; preeclampsia; IUGR; miR-194; miR-149
17.  Primary chondrosarcoma presenting as an intrathoracic mass: A report of three cases 
Oncology Letters  2014;8(3):1151-1154.
Primary intrathoracic chondrosarcomas are rare tumors. The present study reports three cases of primary intrathoracic chondrosarcomas in two males and one female aged between 45 and 64 years. Clinically, one case presented with cough and blood sputum, while the other two cases of primary intrathoracic chondrosarcoma were found incidently during a routine health examination. Radiologically, the chondrosarcomas presented as large masses with intratumoral calcification. Chondrosarcoma should be distinguished from other calcified pulmonary lesions. In this study, all three cases underwent surgical treatment, and in one case, the surgery was accompanied by radiotherapy. To date, all patients have been followed up for between two and three years and are alive.
doi:10.3892/ol.2014.2275
PMCID: PMC4114614  PMID: 25120676
chondrosarcoma; imaging; computed tomography; roentgenogram; magnetic resonance imaging
18.  miR-365 Promotes Cutaneous Squamous Cell Carcinoma (CSCC) through Targeting Nuclear Factor I/B (NFIB) 
PLoS ONE  2014;9(6):e100620.
Aberrant expression of microRNAs plays vital roles in tumor development and progression. As transcription factors (TFs) are the critical components of signaling cascades, specific targeting effects of microRNAs to specific TFs may determine the role of microRNAs in different cancers. In this study, we identified Nuclear Factor I/B (NFIB) as one of the targets of miR-365 which was previously verified as an onco-miR in cutaneous squamous cell carcinoma (CSCC). Down-regulation of NFIB was a general feature in both CSCC cell lines and tumors from patients which show drastically up-regulated miR-365 expression levels. The siRNA-based knockdown of NFIB mimic the carcinogenic transformation of normal cells by ectopically expression of miR-365 which indicates depletion of NFIB is necessary for miR-365 to exert its pro-carcinogenic function. NFIB may represent a functional barrier targeted by miR-365 to the development of CSCC. Further studies also discovered a conserved feedback regulatory circuitry formed by NFIB and miR-365 in CSCC development which may be potentially utilized as therapeutic target to improve the clinical CSCC treatment.
doi:10.1371/journal.pone.0100620
PMCID: PMC4065106  PMID: 24949940
19.  Transcriptomes and Proteomes Define Gene Expression Progression in Pre-meiotic Maize Anthers 
G3: Genes|Genomes|Genetics  2014;4(6):993-1010.
Plants lack a germ line; consequently, during reproduction adult somatic cells within flowers must switch from mitotic proliferation to meiosis. In maize (Zea mays L.) anthers, hypoxic conditions in the developing tassel trigger pre-meiotic competence in the column of pluripotent progenitor cells in the center of anther lobes, and within 24 hr these newly specified germinal cells have patterned their surrounding neighbors to differentiate as the first somatic niche cells. Transcriptomes were analyzed by microarray hybridization in carefully staged whole anthers during initial specification events, after the separation of germinal and somatic lineages, during the subsequent rapid mitotic proliferation phase, and during final pre-meiotic germinal and somatic cell differentiation. Maize anthers exhibit a highly complex transcriptome constituting nearly three-quarters of annotated maize genes, and expression patterns are dynamic. Laser microdissection was applied to begin assigning transcripts to tissue and cell types and for comparison to transcriptomes of mutants defective in cell fate specification. Whole anther proteomes were analyzed at three developmental stages by mass spectrometric peptide sequencing using size-fractionated proteins to evaluate the timing of protein accumulation relative to transcript abundance. New insights include early and sustained expression of meiosis-associated genes (77.5% of well-annotated meiosis genes are constitutively active in 0.15 mm anthers), an extremely large change in transcript abundances and types a few days before meiosis (including a class of 1340 transcripts absent specifically at 0.4 mm), and the relative disparity between transcript abundance and protein abundance at any one developmental stage (based on 1303 protein-to-transcript comparisons).
doi:10.1534/g3.113.009738
PMCID: PMC4065268  PMID: 24939185
archesporial cell; cell fate specification; Multiple archesporial cells 1; mac1; pre-meiotic development; genetics of sex
20.  Comparative study of MALDI-TOF MS and VITEK 2 in bacteria identification 
Journal of Thoracic Disease  2014;6(5):534-538.
Background
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has recently been introduced in diagnostic microbiology laboratories for the identification of bacterial and yeast strains isolated from clinical samples. This study aimed to evaluate the accuracy of MALDI-TOF MS in clinical microbiology diagnosis by comparing it with commonly-used VITEK 2 or gene sequencing.
Methods
The performances of MALDI-TOF MS and VITEK 2 were compared retrospectively for identifying routine isolates. Discrepancies were analyzed by gene sequencing analysis of the 16S genes.
Results
For 1,025 isolates, classified as 55 species of 25 genera, 1,021 (99.60%) isolates were accurately identified at the genus level, and 957 (93.37%) isolates at the species level by using MALDI-TOF MS. A total of 949 (92.59%) isolates were completely matched by both methods. Both methods found 76 unmatched isolates among which one strain had no definite identification by MALDI-TOF MS and VITEK 2 respectively. However, MALDI-TOF MS made no errors at the genus level while VITEK 2 made 6 (0.58%) errors at the genus level. At the species level, the identification error rates for MALDI-TOF MS and VITEK 2 were 5.56% and 6.24%, respectively.
Conclusions
With a lower identification error rate, MALDI-TOF MS has better performance than VITEK 2 in identifying bacteria found routinely in the clinical laboratory. It is a quick and cost-effective technique, and has the potential to replace conventional phenotype methods in identifying common bacterial isolates in clinical microbiology laboratories.
doi:10.3978/j.issn.2072-1439.2014.02.18
PMCID: PMC4015025  PMID: 24822115
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS); VITEK2; bacteria identification
21.  Acquisition of Tense Marking in English-Speaking Children with Cochlear Implants: A Longitudinal Study 
This study investigated the development of tense markers (e.g., past tense –ed) in children with cochlear implants (CIs) over a 3-year span. Nine children who received CIs before 30 months of age participated in this study at three, four, and five years postimplantation. Nine typical 3-, 4-, and 5-year- olds served as control groups. All children participated in a story-retell task. Percent correct of tense marking in the task was computed. Within the groups, percent correct of tense marking changed significantly in children with CIs and in typical children who had more hearing experience. Across the groups, children with CIs were significantly less accurate in tense marking than typical children at four and five years postimplantation. In addition, the performance of tense marking in children with CIs was correlated with their speech perception skills at earlier time points. Errors of tense marking tended to be omission rather than commission errors in typical children as well as in children with CIs. The findings suggested that despite the perceptual and processing constraints, children who received CIs may learn tense marking albeit with a delayed pattern.
doi:10.1093/deafed/ens069
PMCID: PMC3697805  PMID: 23288713
22.  Endoscope-Guided Interstitial Intensity-Modulated Brachytherapy and Intracavitary Brachytherapy as Boost Radiation for Primary Early T Stage Nasopharyngeal Carcinoma 
PLoS ONE  2014;9(3):e90048.
Background
Intracavitary brachytherapy (ICBT) is usually applied as boost radiotherapy for superficial residual of nasopharyngeal carcinoma (NPC) after primary extern-beam radiptherapy (ERT). Here, we evaluated the outcome of endoscope-guided interstitial intensity-modulated brachytherapy (IMBT) boost radiation for deep-seated residual NPC.
Methodology/Principal Findings
Two hundred and thirteen patients with residual NPC who were salvaged with brachytherapy boost radiation during 2005–2009 were analyzed retrospectively. Among these patients, 171 patients had superficial residual NPC (≤1 cm below the nasopharyngeal epithelium) were treated with ICBT boost radiation, and interstitial IMBT boost radiation was delivered to 42 patients with deep-seated residual NPC (>1 cm below the nasopharyngeal epithelium). We found that IMBT boost subgroup had a higher ratio of T2b (81.0% VS 34.5%, P<0.001) and stage II (90.5% VS 61.4%, P = 0.001) than that of ICBT boost subgroup. The dosage of external-beam radiotherapy in the nasopharyngeal (63.0±3.8 VS 62.6±4.3 Gray (Gy), P = 0.67) and regional lymph nodes (55.8±5.0 VS 57.5±5.7 Gy, P = 0.11) was comparable in both groups. For brachytherapy, IMBT subgroup had a lower boost radiation dosage than ICBT subgroup (11.0±2.9 VS 14.8±3.2 Gy, P<0.01). Though the IMBT group had deeper residual tumors and received lower boost radiation dosages, both subgroups had the similar 5-year actuarial overall survival rate (IMBT VS ICBT group: 96.8% VS 93.6%, P = 0.87), progression-free survival rate (92.4% VS 86.5%, P = 0.41) and distant metastasis-free survival rate (94.9% VS 92.7%, P = 0.64). Moreover, IMBT boost radiation subgroup had a similar local (97.4% VS 94.4%, P = 0.57) and regional (95.0% VS 97.2%, P = 0.34) control to ICBT subgroup. The acute and late toxicities rates were comparable between the both subgroups.
Conclusions/Significance
IMBT boost radiation may be a promising therapeutic selection for deep-seated residual NPC.
doi:10.1371/journal.pone.0090048
PMCID: PMC3940723  PMID: 24595299
23.  NDM-1–producing Strains, Family Enterobacteriaceae, in Hospital, Beijing, China 
Emerging Infectious Diseases  2014;20(2):340-342.
doi:10.3201/eid2002.121263
PMCID: PMC3901461  PMID: 24456600
NDM-1; Enterobacteriaceae; Providencia rettgeri; Raoultella ornithinolytica; bacteria; China; New Delhi metallo-β-lactamase-1–producing strains
24.  Consonant Development in Pediatric Cochlear Implant Users Who Were Implanted Before 30 Months of Age 
This study provided a yearly record of consonant development for the initial 4 years of cochlear implant (CI) use and established a precedent for using a standardized articulation test, the Goldman–Fristoe Test of Articulation—2 (Goldman, R., & Fristoe, M. [2000]. Goldman–Fristoe Test of Articulation—2. Circle Pines, MN: American Guidance Services). The study used CI age as a referent for 32 children who received their CI before 30 months of age. Consonants produced by 70% of the children were listed, as were the most common error types, which were consonant omissions and substitutions. Using consonant repertoire lists and standard scores, the study revealed that children with CIs had acquisition patterns that were similar to their peers when the duration of CI experience was similar to the chronological age norms of typically developing children. The results revealed that CI users need time to coordinate their articulatory organizing principles with the input they receive from their CI. It is appropriate to use length of CI use as a proxy for chronological age during the first 4 years when comparing articulation development with hearing peers.
doi:10.1093/deafed/ens038
PMCID: PMC3521776  PMID: 23143855
25.  Seroprevalence of Toxoplasma gondii infection in Liaoning cashmere goat from northeastern China 
Parasite  2014;21:22.
In the present study, serum samples from 650 goats were collected from five counties between May and June 2012 and antibodies to Toxoplasma gondii were detected by indirect haemagglutination assay; 58 (9%) had antibodies to T. gondii with antibody titres of 1:64 to 1:1024. Seropositive samples were distributed in all five counties: seroprevalences in Kuandian county (15%, 21/139, 95% confidence interval [CI] 9–21%) were statistically different from the four other counties (Gaizhou, Huanren, Xiuyan and Liaoyang), and the seroprevalence difference between Xiuyan county (12%, 15/127, 95% CI 6–17%) and two other counties (Huanren, Liaoyang) was significantly different (P < 0.05). To our knowledge, this is the first report of the seroprevalence of T. gondii exposure in Liaoning cashmere goat in China. Our results indicated that Liaoning cashmere goat could be a potential reservoir for the transmission of T. gondii in Liaoning Province.
doi:10.1051/parasite/2014023
PMCID: PMC4027814  PMID: 24845552
Toxoplasma gondii; seroprevalence; Liaoning cashmere goat; indirect haemagglutination assay

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