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Search Results: 1 - 10 of 33707 matches for " Cheng-Ting Chien "
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The Proto-Oncogene Int6 Is Essential for Neddylation of Cul1 and Cul3 in Drosophila
Sigal Rencus-Lazar, Yaniv Amir, Junetai Wu, Cheng-Ting Chien, Daniel A. Chamovitz, Daniel Segal
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002239
Abstract: Int6 is a proto-oncogene implicated in various types of cancer, but the mechanisms underlying its activity are not clear. Int6 encodes a subunit of the eukaryotic translation initiation factor 3, and interacts with two related complexes, the proteasome, whose activity is regulated by Int6 in S. pombe, and the COP9 signalosome. The COP9 signalosome regulates the activity of Cullin-Ring Ubiquitin Ligases via deneddylation of their cullin subunit. We report here the generation and analysis of two Drosophila mutants in Int6. The mutants are lethal demonstrating that Int6 is an essential gene. The mutant larvae accumulate high levels of non-neddylated Cul1, suggesting that Int6 is a positive regulator of cullin neddylation. Overexpression in Int6 in cell culture leads to accumulation of neddylated cullins, further supporting a positive role for Int6 in regulating neddylation. Thus Int6 and the COP9 signalosome play opposing roles in regulation of cullin neddylation.
The COP9 Signalosome Converts Temporal Hormone Signaling to Spatial Restriction on Neural Competence
Yi-Chun Huang,Yu-Nung Lu,June-Tai Wu,Cheng-Ting Chien ,Haiwei Pi
PLOS Genetics , 2014, DOI: doi/10.1371/journal.pgen.1004760
Abstract: During development, neural competence is conferred and maintained by integrating spatial and temporal regulations. The Drosophila sensory bristles that detect mechanical and chemical stimulations are arranged in stereotypical positions. The anterior wing margin (AWM) is arrayed with neuron-innervated sensory bristles, while posterior wing margin (PWM) bristles are non-innervated. We found that the COP9 signalosome (CSN) suppresses the neural competence of non-innervated bristles at the PWM. In CSN mutants, PWM bristles are transformed into neuron-innervated, which is attributed to sustained expression of the neural-determining factor Senseless (Sens). The CSN suppresses Sens through repression of the ecdysone signaling target gene broad (br) that encodes the BR-Z1 transcription factor to activate sens expression. Strikingly, CSN suppression of BR-Z1 is initiated at the prepupa-to-pupa transition, leading to Sens downregulation, and termination of the neural competence of PWM bristles. The role of ecdysone signaling to repress br after the prepupa-to-pupa transition is distinct from its conventional role in activation, and requires CSN deneddylating activity and multiple cullins, the major substrates of deneddylation. Several CSN subunits physically associate with ecdysone receptors to represses br at the transcriptional level. We propose a model in which nuclear hormone receptors cooperate with the deneddylation machinery to temporally shutdown downstream target gene expression, conferring a spatial restriction on neural competence at the PWM.
Fak56 functions downstream of integrin alphaPS3betanu and suppresses MAPK activation in neuromuscular junction growth
Pei-I Tsai, Hsiu-Hua Kao, Caroline Grabbe, Yu-Tao Lee, Aurnab Ghose, Tzu-Ting Lai, Kuan-Po Peng, David Van Vactor, Ruth H Palmer, Ruey-Hwa Chen, Shih-Rung Yeh, Cheng-Ting Chien
Neural Development , 2008, DOI: 10.1186/1749-8104-3-26
Abstract: We have generated mutants for the Drosophila FAK gene, Fak56. Null Fak56 mutants display overgrowth of larval neuromuscular junctions (NMJs). Localization of phospho-FAK and rescue experiments suggest that Fak56 is required in presynapses to restrict NMJ growth. Genetic analyses imply that FAK mediates the signaling pathway of the integrin αPS3βν heterodimer and functions redundantly with Src. At NMJs, Fak56 downregulates ERK activity, as shown by diphospho-ERK accumulation in Fak56 mutants, and suppression of Fak56 mutant NMJ phenotypes by reducing ERK activity.We conclude that Fak56 is required to restrict NMJ growth during NMJ development. Fak56 mediates an extracellular signal through the integrin receptor. Unlike its conventional role in activating MAPK/ERK, Fak56 suppresses ERK activation in this process. These results suggest that Fak56 mediates a specific neuronal signaling pathway distinct from that in other cellular processes.Formation and stabilization of neuronal synapses demands communication between pre- and post-synaptic partners, as well as signals from the extracellular matrix (ECM). These signals can reorganize local cytoskeletal structures or be transduced into the nucleus to regulate transcription, thereby modulating neuronal plasticity [1-3]. One major receptor family for ECM signals comprises the transmembrane protein integrins, which have been shown to play critical roles in sequential steps of neuronal wiring, such as in neurite outgrowth, axon guidance, and synaptic formation and maturation [4-7]. In Drosophila, various integrin subunits have been shown to function in motor axon pathfinding and target recognition, and synaptic morphogenesis at neuromuscular junctions (NMJs) [8-10]. Mutant analyses for the integrin subunits αPS3 and βPS indicate that integrin signaling is involved in synaptic growth and arborization of larval NMJs [8-10]. Although specific ECM signals for these integrin receptors are not clear, dynamic NMJ growth is regulated
Gene Mapping via Bulked Segregant RNA-Seq (BSR-Seq)
Sanzhen Liu, Cheng-Ting Yeh, Ho Man Tang, Dan Nettleton, Patrick S. Schnable
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0036406
Abstract: Bulked segregant analysis (BSA) is an efficient method to rapidly and efficiently map genes responsible for mutant phenotypes. BSA requires access to quantitative genetic markers that are polymorphic in the mapping population. We have developed a modification of BSA (BSR-Seq) that makes use of RNA-Seq reads to efficiently map genes even in populations for which no polymorphic markers have been previously identified. Because of the digital nature of next-generation sequencing (NGS) data, it is possible to conduct de novo SNP discovery and quantitatively genotype BSA samples by analyzing the same RNA-Seq data using an empirical Bayesian approach. In addition, analysis of the RNA-Seq data provides information on the effects of the mutant on global patterns of gene expression at no extra cost. In combination these results greatly simplify gene cloning experiments. To demonstrate the utility of this strategy BSR-Seq was used to clone the glossy3 (gl3) gene of maize. Mutants of the glossy loci exhibit altered accumulation of epicuticular waxes on juvenile leaves. By subjecting the reference allele of gl3 to BSR-Seq, we were able to map the gl3 locus to an ~2 Mb interval. The single gene located in the ~2 Mb mapping interval whose expression was down-regulated in the mutant pool was subsequently demonstrated to be the gl3 gene via the analysis of multiple independent transposon induced mutant alleles. The gl3 gene encodes a putative myb transcription factor, which directly or indirectly affects the expression of a number of genes involved in the biosynthesis of very-long-chain fatty acids.
Dental and Skeletal Changes Following Surgically Assisted Rapid Maxillary Anteriorposterior Expansion
Cheng-Ting Ho,Lun-Jou Lo,Eric JW Liou,Chiung Shing Huang
Chang Gung Medical Journal , 2008,
Abstract: Background: Lengthening the maxillary dental arch as a treatment approach for patientswith maxillary deficiency and dental crowding is seldom reported. The purposeof this study was to assess dental and skeletal changes in the maxilla inthe correction of maxillary deficiency associated with a retruded maxillaryarch using a surgically assisted rapid maxillary anterior-posterior expansionappliance.Methods: Predistraction and postraction lateral cephalometric and periapical radiographsand maxillary dental casts of six young adolescents (four boys, twogirls, mean age 11 years, 2 months) were examined. These patients receiveda maxillary anterior segmental osteotomy and distraction osteogenesis withan anteroposteriorly oriented Hyrax expansion appliance based on the biologicalprinciples of bone distraction.Results: The retruded dental arch and dental crowding were successfully corrected.Significant forward movement of the point anterior nasal spine, point A, centralincisors and first premolars was noted. The maxillary dental arch depthincreased an average of 4.2 mm while the arch width remained unchanged.In total, 11.5 mm of dental space was created in the maxillary arch whichwas sufficient to resolve dental crowding. New bone formation along the distractionsite was observed three months after distraction.Conclusions: The use of maxillary anterior segmental osteotomy combined with a Hyraxexpansion distraction appliance was effective in arch lengthening and creationof dental space. An overcorrection in this interdental distraction osteogenesiscould be a good treatment option for children with maxillary deficiencycombined with crowded maxillary dentition.
The microbiological profile and presence of bloodstream infection influence mortality rates in necrotizing fasciitis
I-Chuan Chen, Wen-Cheng Li, Yu-Cheng Hong, Shian-Sen Shie, Wen-Chih Fann, Cheng-Ting Hsiao
Critical Care , 2011, DOI: 10.1186/cc10278
Abstract: In this retrospective study, we analyzed 323 patients who presented with necrotizing fasciitis at two different institutions. Bloodstream infection (BSI) was defined as a positive blood culture result. The patients were categorized as survivors and non-survivors. Eleven clinically important variables which were statistically significant by univariate analysis were selected for multivariate regression analysis and a stepwise logistic regression model was developed to determine the association between BSI and mortality.Univariate logistic regression analysis showed that patients with hypotension, heart disease, liver disease, presence of Vibrio spp. in wound cultures, presence of fungus in wound cultures, and presence of Streptococcus group A, Aeromonas spp. or Vibrio spp. in blood cultures, had a significantly higher risk of in-hospital mortality. Our multivariate logistic regression analysis showed a higher risk of mortality in patients with pre-existing conditions like hypotension, heart disease, and liver disease. Multivariate logistic regression analysis also showed that presence of Vibrio spp in wound cultures, and presence of Streptococcus Group A in blood cultures were associated with a high risk of mortality while debridement > = 3 was associated with improved survival.Mortality in patients with necrotizing fasciitis was significantly associated with the presence of Vibrio in wound cultures and Streptococcus group A in blood cultures.Understanding the mechanisms underlying the pathophysiology of an infectious disease and characterization of the causative organism are key to providing better medical or surgical care, preventing complications and initiating early, appropriate antimicrobial treatment. Necrotizing fasciitis (NF), a life-threatening infectious disease with mortality rate ranging from 17% to 34% [1-6] actually refers to a spectrum of diseases where necrosis of deeper soft tissue is driven by an infective microorganism [7]. NF primarily involves the
A Novel Method of Estimating Dose Responses for Polymer Gels Using Texture Analysis of Scanning Electron Microscopy Images
Cheng-Ting Shih, Jui-Ting Hsu, Rou-Ping Han, Bor-Tsung Hsieh, Shu-Jun Chang, Jay Wu
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0067281
Abstract: Polymer gels are regarded as a potential dosimeter for independent validation of absorbed doses in clinical radiotherapy. Several imaging modalities have been used to convert radiation-induced polymerization to absorbed doses from a macro-scale viewpoint. This study developed a novel dose conversion mechanism by texture analysis of scanning electron microscopy (SEM) images. The modified N-isopropyl-acrylamide (NIPAM) gels were prepared under normoxic conditions, and were administered radiation doses from 5 to 20 Gy. After freeze drying, the gel samples were sliced for SEM scanning with 50×, 500×, and 3500× magnifications. Four texture indices were calculated based on the gray level co-occurrence matrix (GLCM). The results showed that entropy and homogeneity were more suitable than contrast and energy as dose indices for higher linearity and sensitivity of the dose response curves. After parameter optimization, an R2 value of 0.993 can be achieved for homogeneity using 500× magnified SEM images with 27 pixel offsets and no outlier exclusion. For dose verification, the percentage errors between the prescribed dose and the measured dose for 5, 10, 15, and 20 Gy were ?7.60%, 5.80%, 2.53%, and ?0.95%, respectively. We conclude that texture analysis can be applied to the SEM images of gel dosimeters to accurately convert micro-scale structural features to absorbed doses. The proposed method may extend the feasibility of applying gel dosimeters in the fields of diagnostic radiology and radiation protection.
Mu Transposon Insertion Sites and Meiotic Recombination Events Co-Localize with Epigenetic Marks for Open Chromatin across the Maize Genome
Sanzhen Liu,Cheng-Ting Yeh,Tieming Ji,Kai Ying,Haiyan Wu,Ho Man Tang,Yan Fu,Dan Nettleton,Patrick S. Schnable
PLOS Genetics , 2009, DOI: 10.1371/journal.pgen.1000733
Abstract: The Mu transposon system of maize is highly active, with each of the ~50–100 copies transposing on average once each generation. The approximately one dozen distinct Mu transposons contain highly similar ~215 bp terminal inverted repeats (TIRs) and generate 9-bp target site duplications (TSDs) upon insertion. Using a novel genome walking strategy that uses these conserved TIRs as primer binding sites, Mu insertion sites were amplified from Mu stocks and sequenced via 454 technology. 94% of ~965,000 reads carried Mu TIRs, demonstrating the specificity of this strategy. Among these TIRs, 21 novel Mu TIRs were discovered, revealing additional complexity of the Mu transposon system. The distribution of >40,000 non-redundant Mu insertion sites was strikingly non-uniform, such that rates increased in proportion to distance from the centromere. An identified putative Mu transposase binding consensus site does not explain this non-uniformity. An integrated genetic map containing more than 10,000 genetic markers was constructed and aligned to the sequence of the maize reference genome. Recombination rates (cM/Mb) are also strikingly non-uniform, with rates increasing in proportion to distance from the centromere. Mu insertion site frequencies are strongly correlated with recombination rates. Gene density does not fully explain the chromosomal distribution of Mu insertion and recombination sites, because pronounced preferences for the distal portion of chromosome are still observed even after accounting for gene density. The similarity of the distributions of Mu insertions and meiotic recombination sites suggests that common features, such as chromatin structure, are involved in site selection for both Mu insertion and meiotic recombination. The finding that Mu insertions and meiotic recombination sites both concentrate in genomic regions marked with epigenetic marks of open chromatin provides support for the hypothesis that open chromatin enhances rates of both Mu insertion and meiotic recombination.
High-Resolution Genotyping via Whole Genome Hybridizations to Microarrays Containing Long Oligonucleotide Probes
Yan Fu,Nathan M. Springer,Kai Ying,Cheng-Ting Yeh,A. Leonardo Iniguez,Todd Richmond,Wei Wu,Brad Barbazuk,Dan Nettleton,Jeff Jeddeloh,Patrick S. Schnable
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014178
Abstract: To date, microarray-based genotyping of large, complex plant genomes has been complicated by the need to perform genome complexity reduction to obtain sufficiently strong hybridization signals. Genome complexity reduction techniques are, however, tedious and can introduce unwanted variables into genotyping assays. Here, we report a microarray-based genotyping technology for complex genomes (such as the 2.3 GB maize genome) that does not require genome complexity reduction prior to hybridization. Approximately 200,000 long oligonucleotide probes were identified as being polymorphic between the inbred parents of a mapping population and used to genotype two recombinant inbred lines. While multiple hybridization replicates provided ~97% accuracy, even a single replicate provided ~95% accuracy. Genotyping accuracy was further increased to >99% by utilizing information from adjacent probes. This microarray-based method provides a simple, high-density genotyping approach for large, complex genomes.
Synthesis and Anticancer Activity of Glucosylated Podophyllotoxin Derivatives Linked via 4β-Triazole Rings
Cheng-Ting Zi,Feng-Qing Xu,Gen-Tao Li,Yan Li,Zhong-Tao Ding,Jun Zhou,Zi-Hua Jiang,Jiang-Miao Hu
Molecules , 2013, DOI: 10.3390/molecules181113992
Abstract: A series of 4 β-triazole-linked glucose podophyllotoxin conjugates have been designed and synthesized by employing a click chemistry approach. All the compounds were evaluated for their anticancer activity against a panel of five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480) using MTT assays. Most of these triazole derivatives have good anticancer activity. Among them, compound 35 showed the highest potency against all five cancer cell lines tested, with IC 50 values ranging from 0.59 to 2.90 μM, which is significantly more active than the drug etoposide currently in clinical use. Structure-activity relationship analysis reveals that the acyl substitution on the glucose residue, the length of oligoethylene glycol linker, and the 4'-demethylation of podophyllotoxin scaffold can significantly affect the potency of the anticancer activity. Most notably, derivatives with a perbutyrylated glucose residue show much higher activity than their counterparts with either a free glucose or a peracetylated glucose residue.
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