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Find video protocols related to scientific articles indexed in Pubmed.
Outcome of free digital artery perforator flap transfer for reconstruction of fingertip defects.
Indian J Orthop
PUBLISHED: 11-19-2014
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Fingertip defect can be treated with many flaps such as random pattern abdominal flap, retrograde digital artery island flap, V-Y advancement flap, etc. However, swelling in the fingertip, dysfunction of sensation, flexion and extension contracture or injury in the hemi-artery of the finger usually occurs during the recovery phase. Recently, digital artery perforator flaps have been used for fingertip reconstructions. With the development of super microsurgery techniques, free flaps can be more effective for sensory recovery and durability of the fingertip.
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Fosfomycin for the treatment of prostate infection.
Intern. Med.
PUBLISHED: 11-15-2014
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A 69-year-old man with diabetes mellitus was diagnosed with a prostate abscess. Although the pathogen was fluoroquinolone-resistant Escherichia coli and the oral administration of trimethoprim-sulfamethoxazole was initiated, the infection recurred after three months. The antibiotic therapy was subsequently changed to intravenous fosfomycin, and the patient's condition promptly improved. Four weeks of fosfomycin therapy was successfully continued without any adverse events. In the era of antibiotic resistance, revival of forgotten drugs is an important issue for clinicians. Fosfomycin can be applied as an alternative option for prostate infections, considering the remaining susceptibility of multidrug-resistant pathogens to fosfomycin and the good pharmacokinetics of this drug in prostatic tissue.
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Effect of Crystallization of Cu2ZnSnSxSe4-x Counter Electrode on the Performance for Efficient Dye-Sensitized Solar Cells.
ACS Appl Mater Interfaces
PUBLISHED: 11-11-2014
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Cu2ZnSnSxSe4-x (CZTSSe) counter electrodes (CEs) in dye-sensitized solar cells (DSSCs) are commonly developed with porous structure, but their high surface area could also retard electron transport processes owing to the abundant grain boundaries. Herein, we employed a convenient solution method and a rapid heating process to prepare well crystalline CZTSSe CE in DSSCs. The influence of crystallization of CZTSSe film on DSSCs performances was discussed in depth. The thermogravimetric analysis, phase morphology, conductivity and electrochemical characteristics of CZTSSe films were performed. It is found that the rapid heating process is beneficial to the formation of well crystalline film with large-grain. As the porosity and grain boundaries in the bulk film are dramatically reduced with the enhanced crystallization, the charge transport process is gradually improved. Using cyclic voltammogram (CV) and electrochemical impedance spectroscopy (EIS) measurements, we propose that the accelerating charge transport is of great important to the photovoltaic performances of DSSCs due to their superior electrocatalytic activities. As the highest cell efficiency achieved, well crystalline CZTSSe is an efficient CE catalytic material.
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White Spot Syndrome Virus Protein Kinase 1 (PK1) Defeats the Host Cell's Iron Withholding Defense Mechanism by Interacting with Host Ferritin.
J. Virol.
PUBLISHED: 11-08-2014
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Iron is an essential nutrient for nearly all living organisms, including both hosts and invaders. Proteins such as ferritin regulate the iron levels in a cell, and in the event of a pathogenic invasion, the host can use an iron withholding mechanism to restrict the availability of this essential nutrient to the invading pathogens. However, pathogens use various strategies to overcome this host defense. In this study, we demonstrated that white spot syndrome virus (WSSV) protein kinase 1 (PK1) interacted with shrimp ferritin by the yeast two-hybrid system. A pull-down assay and 27-MHz quartz crystal microbalance (QCM) confirmed the interaction between PK1 and both ferritin and apoferritin. PK1 did not promote the release of iron ions from ferritin, but it prevented apoferritin from binding ferrous ions. When PK1 was overexpressed in Sf9 cells, the cellular labile iron pool (LIP) levels were elevated significantly. Immunoprecipitation and atomic absorption spectrophotometry (AAS) further showed that the number of iron ions bound by ferritin decreased significantly at 24 h post-WSSV infection. Taken together, these results suggest that PK1 prevents apoferritin from iron loading and thus stabilizes the cellular LIP levels, and that WSSV uses this novel mechanism to counteract the host cell's iron withholding defense mechanism.
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Methamphetamine induces a rapid increase of intracellular Ca(++) levels in neurons overexpressing GCaMP5.
Addict Biol
PUBLISHED: 11-08-2014
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In this study, methamphetamine (Meth)- and glutamate (Glu)-mediated intracellular Ca(++) (Ca(++) i) signals were examined in real time in primary cortical neurons overexpressing an intracellular Ca(++) probe, GCaMP5, by adeno-associated viral (AAV) serotype 1. Binding of Ca(++) to GCaMP increased green fluorescence intensity in cells. Both Meth and Glu induced a rapid increase in Ca(++) i, which was blocked by MK801, suggesting that Meth enhanced Ca(++) i through Glu receptor in neurons. The Meth-mediated Ca(++) signal was also blocked by Mg(++) , low Ca(++) or the L-type Ca(++) channel inhibitor nifedipine. The ryanodine receptor inhibitor dantrolene did not alter the initial Ca(++) influx but partially reduced the peak of Ca(++) i. These data suggest that Meth enhanced Ca(++) influx through membrane Ca(++) channels, which then triggered the release of Ca(++) from the endoplasmic reticulum in the cytosol. AAV-GCaMP5 was also injected to the parietal cortex of adult rats. Administration of Meth enhanced fluorescence in the ipsilateral cortex. Using immunohistochemistry, Meth-induced green fluorescence was found in the NeuN-containing cells in the cortex, suggesting that Meth increased Ca(++) in neurons in vivo. In conclusion, we have used in vitro and in vivo techniques to demonstrate a rapid increase of Ca(++) i by Meth in cortical neurons through overexpression of GCaMP5. As Meth induces behavioral responses and neurotoxicity through Ca(++) i, modulation of Ca(++) i may be useful to reduce Meth-related reactions.
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[Spatial and temporal characteristics of human brucellosis, from 2004 to 2012 in Shandong province].
Zhonghua Liu Xing Bing Xue Za Zhi
PUBLISHED: 11-08-2014
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To explore the spatial and temporal characteristics of human brucellosis in Shandong province and to provide scientific basis for the development of related regional public health strategies.
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EPR detection of hydroxyl radical generation and oxidative perturbations in lead-exposed earthworms (Eisenia fetida) in the presence of decabromodiphenyl ether.
Ecotoxicology
PUBLISHED: 10-28-2014
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Lead (Pb) and decabromodiphenyl ether (BDE209) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impacts on the oxidative perturbations and hydroxyl radical (·OH) generation in earthworms of exposure to the two chemicals remain almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the effects of Pb in earthworms Eisenia fetida in the presence of BDE209 through the use of several biomarkers in microcosms. The results have demonstrated that the addition of BDE209 (1 or 10 mg kg(-1)) decreased the enzymatic activities [superoxide dismutase, catalase (CAT), peroxidase] and total antioxidant capacity (T-AOC) compared with exposure to BDE209 alone (50, 250 or 500 mg kg(-1)). Electron paramagnetic resonance spectra indicated that ·OH radicals in earthworms were significantly induced by Pb in the presence of BDE209. The changing pattern of malondialdehyde (MDA) contents was accordant with that of ·OH intensity suggested that reactive oxygen species might lead to cellular lipid peroxidation. Furthermore, CAT exhibited more sensitive response to single Pb exposure than the other biomarkers, while T-AOC, ·OH and MDA might be three most sensitive biomarkers in earthworms after simultaneous exposure to Pb and BDE209. The results of these observations suggested that oxidative stress appeared in E. fetida, and it may play an important role in inducing the Pb and BDE209 toxicity to earthworms.
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Enhanced M1/M2 Macrophage Ratio Promotes Orthodontic Root Resorption.
J. Dent. Res.
PUBLISHED: 10-26-2014
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Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-? and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-? were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-? inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio.
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Genomic Analysis Reveals Effect of Actin-like Protein Encoded by Two Bacillus pumilus Phages on Phage Unstable Lysogeny.
Appl. Environ. Microbiol.
PUBLISHED: 10-26-2014
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We characterized two newly isolated myoviruses, Bp8p-C and Bp8p-T, infecting the ginger rhizome rot disease pathogen Bacillus pumilus GR8. The plaque of Bp8p-T exhibited a clear center with a turbid rim, suggesting that Bp8p-T could transform into latent phage. Lysogeny assays showed that both the two phages could form latent states, while Bp8p-T could form latent phage at a higher frequency and stability than Bp8p-C. The genomes of Bp8p-C and Bp8p-T were 151,417 bp and 151,419 bp, respectively; both encoded 212 putative proteins, and only differed by three nucleotides. Moreover, owing to this difference, Bp8p-C encoded a truncated, putative actin-like plasmid segregation protein Gp27-C. Functional analysis of protein Gp27 showed that Gp27-T encoded by Bp8p-T exhibited higher ATPase activity and assembly ability than Gp27-C. The results indicate that the difference in Gp27 affected the phage lysogenic ability. Structural proteome analysis of Bp8p-C virion resulted in the identification of fourteen structural proteins, among which a pectin lyase-like protein, a putative poly-gamma-glutamate hydrolase, and three proteins with unknown function, were firstly identified as components of the phage virion. Both phages exhibited specific lytic ability to the host strain GR8. Bp8p-C showed better control effect on the pathogen in ginger rhizome slices than Bp8p-T, suggesting that Bp8p-C has a potential application in bio-control of ginger rhizome rot disease.
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Selection for Growth on 3-Nitrotoluene by 2-Nitrotoluene-Utilizing Acidovorax sp. Strain JS42 Identifies Nitroarene Dioxygenases with Altered Specificities.
Appl. Environ. Microbiol.
PUBLISHED: 10-26-2014
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Acidovorax sp. strain JS42 uses 2-nitrotoluene as a sole source of carbon and energy. The first enzyme of the degradation pathway, 2-nitrotoluene 2,3-dioxygenase, adds both atoms of molecular oxygen to 2-nitrotoluene, forming nitrite and 3-methylcatechol. All three mononitrotoluene isomers serve as substrates for 2-nitrotoluene dioxygenase, but strain JS42 is unable to grow on 3- or 4-nitrotoluene. Using both long- and short-term selections we obtained spontaneous mutants of strain JS42 that could grow on 3-nitrotoluene. All of the strains obtained by short-term selection had mutations in the gene encoding the ? subunit of 2-nitrotoluene dioxygenase that changed isoleucine 204 at the active site to valine. Those from long-term selections had mutations that changed the same residue to valine, alanine, or threonine or changed the alanine at position 405, which is just outside the active site, to glycine. All of these changes altered the regiospecificity of the enzymes with 3-nitrotoluene such that 4-methylcatechol was the primary product rather than 3-methylcatechol. Kinetic analyses indicated that the evolved enzymes had enhanced affinities for 3-nitrotoluene and were more catalytically efficient with 3-nitrotoluene compared to the wild-type enzyme. In contrast, the corresponding amino acid substitutions in the closely related enzyme nitrobenzene 1,2-dioxygenase were detrimental to enzyme activity. When cloned genes encoding the evolved dioxygenases were introduced into a JS42 mutant lacking a functional dioxygenase, the strains acquired the ability to grow on 3-nitrotoluene, but with significantly longer doubling times than the evolved strains, suggesting that additional beneficial mutations occurred elsewhere in the genome.
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Reduced-intensity FOLFOXIRI in Treating Refractory Metastatic Colorectal Cancer: A Pilot Study.
Am. J. Clin. Oncol.
PUBLISHED: 10-22-2014
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To report on the efficacy and safety of reduced-intensity FOLFOXIRI (RI-FOLFOXIRI) as salvage chemotherapy for patients with refractory metastatic colorectal cancer (mCRC).
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Chlorogenic acid alters the voltage-gated potassium channel currents of trigeminal ganglion neurons.
Int J Oral Sci
PUBLISHED: 10-08-2014
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Chlorogenic acid (5-caffeoylquinic acid, CGA) is a phenolic compound that is found ubiquitously in plants, fruits and vegetables and is formed via the esterification of caffeic acid and quinic acid. In addition to its notable biological functions against cardiovascular diseases, type-2 diabetes and inflammatory conditions, CGA was recently hypothesized to be an alternative for the treatment of neurological diseases such as Alzheimer's disease and neuropathic pain disorders. However, its mechanism of action is unclear. Voltage-gated potassium channel (Kv) is a crucial factor in the electro-physiological processes of sensory neurons. Kv has also been identified as a potential therapeutic target for inflammation and neuropathic pain disorders. In this study, we analysed the effects of CGA on the two main subtypes of Kv in trigeminal ganglion neurons, namely, the IK,A and IK,V channels. Trigeminal ganglion (TRG) neurons were acutely disassociated from the rat TRG, and two different doses of CGA (0.2 and 1?mmol?L(-1)) were applied to the cells. Whole-cell patch-clamp recordings were performed to observe alterations in the activation and inactivation properties of the IK,A and IK,V channels. The results demonstrated that 0.2?mmol?L(-1) CGA decreased the peak current density of IK,A. Both 0.2?mmol?L(-1) and 1?mmol?L(-1) CGA also caused a significant reduction in the activation and inactivation thresholds of IK,A and IK,V. CGA exhibited a strong effect on the activation and inactivation velocities of IK,A and IK,V. These findings provide novel evidence explaining the biological effects of CGA, especially regarding its neurological effects.International Journal of Oral Science (2014) 6, doi:10.1038/ijos.2014.58; published online 14 November 2014.
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Safety and Efficacy of Adalimumab for Patients With Moderate to Severe Crohn's Disease: The Taiwan Society of Inflammatory Bowel Disease (TSIBD) Study.
Intest Res
PUBLISHED: 09-26-2014
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Only moderate to severe Crohn's Disease (CD) patients without a satisfactory conventional therapy effect are eligible to get reimbursement from the National Health Insurance of Taiwan for using adalimumab. These are more stringent criteria than in many Western countries and Japan and Korea. We aim to explore the efficacy of using adalimumab in CD patients under such stringent criteria.
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Force-induced Adrb2 in Periodontal Ligament Cells Promotes Tooth Movement.
J. Dent. Res.
PUBLISHED: 09-24-2014
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The sympathetic nervous system (SNS) regulates bone resorption through ?-2 adrenergic receptor (Adrb2). In orthodontic tooth movement (OTM), mechanical force induces and regulates alveolar bone remodeling. Compressive force-associated osteoclast differentiation and alveolar bone resorption are the rate-limiting steps of tooth movement. However, whether mechanical force can activate Adrb2 and thus contribute to OTM remains unknown. In this study, orthodontic nickel-titanium springs were applied to the upper first molars of rats and Adrb1/2(-/-) mice to confirm the role of SNS and Adrb2 in OTM. The results showed that blockage of SNS activity in the jawbones of rats by means of superior cervical ganglion ectomy reduced OTM distance from 860 to 540 ?m after 14 d of force application. In addition, the injection of nonselective Adrb2 agonist isoproterenol activated the downstream signaling of SNS to accelerate OTM from 300 to 540 ?m after 7 d of force application. Adrb1/2(-/-) mice showed significantly reduced OTM distance (19.5 ?m) compared with the wild-type mice (107.6 ?m) after 7 d of force application. Histopathologic analysis showed that the number of Adrb2-positive cells increased in the compressive region of periodontal ligament after orthodontic force was applied on rats. Mechanistically, mechanical compressive force upregulated Adrb2 expression in primary-cultured human periodontal ligament cells (PDLCs) through the elevation of intracellular Ca(2+) concentration. Activation of Adrb2 in PDLCs increased the RANKL/OPG ratio and promoted the peripheral blood mononuclear cell differentiation to osteoclasts in the cocultured system. Upregulation of Adrb2 in PDLCs promoted osteoclastogenesis, which accelerated OTM through Adrb2-enhanced bone resorption. In summary, this study suggests that mechanical force-induced Adrb2 activation in PDLCs contributes to SNS-regulated OTM.
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Radix Angelicae Sinensis and Radix Hedysari enhance radiosensitivity of 12C6+ radiation in human liver cancer cells by modulating apoptosis protein.
Saudi Med J
PUBLISHED: 09-18-2014
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To investigate the radiosensitizing effects of Radix Angelicae Sinensis-Radix Hedysari (RAS-RH [an ultra-filtration extract]) and its underlying mechanisms in human liver cancer cells H22.
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The novel I?B kinase ? inhibitor IMD-0560 prevents bone invasion by oral squamous cell carcinoma.
Oncotarget
PUBLISHED: 09-16-2014
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Oral squamous cell carcinoma (OSCC) cells display significantly augmented nuclear factor-?B (NF-?B) activity, and inhibiting this activity suppresses malignant tumor characteristics. Thus, we evaluated the effect of IMD-0560, a novel inhibitor of I?B kinase (IKK) ? that is under assessment in a clinical trial of rheumatoid arthritis, on bone invasion by the mouse OSCC cell line SCCVII. We examined the inhibitory effects of IMD-0560 on NF-?B activity and tumor invasion using human OSCC cell lines and SCCVII cells in vitro. Using a mouse model of jaw bone invasion by SCCVII cells, we assessed the inhibitory effect of IMD-0560 on jaw bone invasion, tumor growth, and matrix degradation in vivo. IMD-0560 suppressed the nuclear translocation of NF-?B and the degradation of I?B? in OSCC cells. IMD-0560 also inhibited invasion by suppressing matrix metalloproteinase-9 (MMP-9) production in OSCC cells. IMD-0560 protected against zygoma and mandible destruction by SCCVII cells, reduced the number of osteoclasts by inhibiting receptor activator of NF-?B ligand (RANKL) expression in osteoblastic cells and SCCVII cells, increased SCCVII cell death and suppressed cell proliferation and MMP-9 production in SCCVII cells. Based on these results, IMD-0560 may represent a new therapeutic agent for bone invasion by OSCC cells.
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Effects of the joint exposure of decabromodiphenyl ether and tetrabromobisphenol A on soil bacterial community structure.
Environ Sci Pollut Res Int
PUBLISHED: 08-10-2014
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Decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) are the main contaminants at electronic waste (e-waste) recycling sites (EWRSs), and their potential toxicological effects have received extensive attention. However, the impact on soil microorganism of joint exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the response of soil bacterial community structure in the joint presence of BDE209 and TBBPA for the first time. The results have demonstrated that the soil bacterial diversity generally declined with increasing BDE209 and TBBPA concentrations and moderate and high doses of both chemicals can cause inhibitory effects. PCR-DGGE analysis indicated that the correlations between Shannon-Weaver index and contaminant concentrations could be well represented by a second-order polynomial model. The combined toxicity of the two chemicals was antagonistic during the first 14 days and then synergistic. Pectobacterium carotovorum, Sinorhizobium fredii HH103, and Stenotrophomonas maltophilia were highly tolerant to joint exposure during the entire incubation period. Moreover, some Staphylococcus strains were enriched after 90 days exposed to TBBPA or low concentrations of BDE209, indicating that they might degrade the two chemicals effectively. The results of these observations have provided some basic understanding of potential ecological effects of joint exposure to BDE209 and TBBPA on soil microorganism at EWRSs.
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Lean Big Data integration in systems biology and systems pharmacology.
Trends Pharmacol. Sci.
PUBLISHED: 08-07-2014
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Data sets from recent large-scale projects can be integrated into one unified puzzle that can provide new insights into how drugs and genetic perturbations applied to human cells are linked to whole-organism phenotypes. Data that report how drugs affect the phenotype of human cell lines and how drugs induce changes in gene and protein expression in human cell lines can be combined with knowledge about human disease, side effects induced by drugs, and mouse phenotypes. Such data integration efforts can be achieved through the conversion of data from the various resources into single-node-type networks, gene-set libraries, or multipartite graphs. This approach can lead us to the identification of more relationships between genes, drugs, and phenotypes as well as benchmark computational and experimental methods. Overall, this lean 'Big Data' integration strategy will bring us closer toward the goal of realizing personalized medicine.
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Health-related quality of life and cost comparison of adjuvant capecitabine versus 5-fluorouracil/leucovorin in stage III colorectal cancer patients.
Qual Life Res
PUBLISHED: 07-28-2014
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The purpose of this study was to compare health-related quality of life (HRQoL) and costs associated with 2 adjuvant chemotherapy regimens [capecitabine-based therapy versus 5-fluorouracil/leucovorin (5-FU/LV)-based therapy] in stage III colorectal cancer patients.
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[The role of interleukin-2 pathway in pathogenesis of nasal polyps].
Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi
PUBLISHED: 07-11-2014
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To study the expression of Interleukin2 (IL-2) signaling pathway related factors and Treg cell in nasal tissue of nasal polyps, so that to investigate the possible mechanism of IL-2 signaling pathway in the progress of nasal polyps and the correlation between IL-2 pathway and Treg cell.
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Bismuth oxide nanotubes-graphene fiber-based flexible supercapacitors.
Nanoscale
PUBLISHED: 07-01-2014
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Graphene-bismuth oxide nanotube fiber as electrode material for constituting flexible supercapacitors using a PVA/H3PO4 gel electrolyte is reported with a high specific capacitance (Ca) of 69.3 mF cm(-2) (for a single electrode) and 17.3 mF cm(-2) (for the whole device) at 0.1 mA cm(-2), respectively. Our approach opens the door to metal oxide-graphene hybrid fibers and high-performance flexible electronics.
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The role of adjuvant chemotherapy in stage II colorectal cancer patients.
Int J Colorectal Dis
PUBLISHED: 06-22-2014
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Adjuvant chemotherapy use in stage II colorectal cancer (CRC) is debated. We evaluated the prognostic significance of clinicopathological features recommended by most guidelines for identifying high-risk stage II CRC and adjuvant chemotherapeutic response.
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Toxic effects of the joint exposure of decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) on soil microorganism and enzyme activity.
Environ. Toxicol. Pharmacol.
PUBLISHED: 05-29-2014
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Decabromodiphenyl ether (BDE209) and tetrabromobisphenol A (TBBPA) are the main contaminants at e-waste recycling sites, and their potential toxicological effects have received extensive attention. However, the impact on soil culturable microbial population and enzyme activity of joint exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the eco-toxicological response in the joint presence of BDE209 and TBBPA for the first time. The results have demonstrated some notable toxic effects due to long-term exposure to either or both contaminants. The inhibition ratios of microbial populations increased with incubation time and increasing concentrations of BDE209 or TBBPA following certain dose-response relationships and time-effect trends. The response sensitivity sequence was fungi>bacteria>actinomycete. The influence of the two chemicals on soil enzymes reached peak values on day 7, and highly significant differences (P<0.01) were observed compared to the controls. Urease was more susceptive to the two chemicals than catalase and saccharase activities. Generally, the joint toxicity of both contaminants on soil microbes, catalase or saccharase activities indicated antagonistic effects, while, as for urease activity, addition role was dominant. Such observations have provided the useful information of potential ecological effects of brominated flame retardants contamination in the environment.
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Admission hyperglycemia predicts poorer short- and long-term outcomes after primary percutaneous coronary intervention for ST-elevation myocardial infarction.
J Diabetes Investig
PUBLISHED: 05-21-2014
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Admission hyperglycemia is associated with poor outcome in patients with myocardial infarction. The present study evaluated the relationship between admission glucose level and other clinical variables in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).
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Synaptic, transcriptional and chromatin genes disrupted in autism.
Silvia De Rubeis, Xin He, Arthur P Goldberg, Christopher S Poultney, Kaitlin Samocha, A Ercument Cicek, Yan Kou, Li Liu, Menachem Fromer, Susan Walker, Tarjinder Singh, Lambertus Klei, Jack Kosmicki, Shih-Chen Fu, Branko Aleksic, Monica Biscaldi, Patrick F Bolton, Jessica M Brownfeld, Jinlu Cai, Nicholas G Campbell, Angel Carracedo, Maria H Chahrour, Andreas G Chiocchetti, Hilary Coon, Emily L Crawford, Lucy Crooks, Sarah R Curran, Geraldine Dawson, Eftichia Duketis, Bridget A Fernandez, Louise Gallagher, Evan Geller, Stephen J Guter, R Sean Hill, Iuliana Ionita-Laza, Patricia Jimenez Gonzalez, Helena Kilpinen, Sabine M Klauck, Alexander Kolevzon, Irene Lee, Jing Lei, Terho Lehtimäki, Chiao-Feng Lin, Avi Ma'ayan, Christian R Marshall, Alison L McInnes, Benjamin Neale, Michael J Owen, Norio Ozaki, Mara Parellada, Jeremy R Parr, Shaun Purcell, Kaija Puura, Deepthi Rajagopalan, Karola Rehnström, Abraham Reichenberg, Aniko Sabo, Michael Sachse, Stephan J Sanders, Chad Schafer, Martin Schulte-Rüther, David Skuse, Christine Stevens, Peter Szatmari, Kristiina Tammimies, Otto Valladares, Annette Voran, Li-San Wang, Lauren A Weiss, A Jeremy Willsey, Timothy W Yu, Ryan K C Yuen, , Edwin H Cook, Christine M Freitag, Michael Gill, Christina M Hultman, Thomas Lehner, Aarno Palotie, Gerard D Schellenberg, Pamela Sklar, Matthew W State, James S Sutcliffe, Christopher A Walsh, Stephen W Scherer, Michael E Zwick, Jeffrey C Barrett, David J Cutler, Kathryn Roeder, Bernie Devlin, Mark J Daly, Joseph D Buxbaum.
Nature
PUBLISHED: 05-18-2014
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The genetic architecture of autism spectrum disorder involves the interplay of common and rare variants and their impact on hundreds of genes. Using exome sequencing, here we show that analysis of rare coding variation in 3,871 autism cases and 9,937 ancestry-matched or parental controls implicates 22 autosomal genes at a false discovery rate (FDR) < 0.05, plus a set of 107 autosomal genes strongly enriched for those likely to affect risk (FDR < 0.30). These 107 genes, which show unusual evolutionary constraint against mutations, incur de novo loss-of-function mutations in over 5% of autistic subjects. Many of the genes implicated encode proteins for synaptic formation, transcriptional regulation and chromatin-remodelling pathways. These include voltage-gated ion channels regulating the propagation of action potentials, pacemaking and excitability-transcription coupling, as well as histone-modifying enzymes and chromatin remodellers-most prominently those that mediate post-translational lysine methylation/demethylation modifications of histones.
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A multi-biomarker risk assessment of the impact of brominated flame retardant-decabromodiphenyl ether (BDE209) on the antioxidant system of earthworm Eisenia fetida.
Environ. Toxicol. Pharmacol.
PUBLISHED: 05-09-2014
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Decabromodiphenyl ether (BDE209) is the major contaminant at e-waste recycling sites (EWRSs), and its potential toxicological effects on terrestrial organisms have received extensive attention. However, the impacts of BDE209 on the antioxidant defense system in terrestrial organisms remain vague. Therefore, indoor incubation tests were performed systematically on control and contaminated soil samples to determine the effects of BDE209 on the antioxidant system of earthworm Eisenia fetida. The results showed that compared to the controls, superoxide dismutase (SOD) activities in all treated groups were elevated significantly after 21 and 28 days exposure; catalase (CAT) activities were much higher in all tests during the entire exposure period; peroxidase (POD) and glutathione-s-transferase (GST) activities generally decreased and indicated contrary response trend; the total antioxidant capacity (T-AOC) after exposure to low level of BDE209 (1 mg kg(-1)) was induced, whereas at 10 and 100 mg kg(-1) concentrations it showed suppression status; electron paramagnetic resonance (EPR) spectra suggested that hydroxyl radicals (OH) in earthworms were significantly induced by BDE209; the changes in malondialdehyde (MDA) contents suggested that reactive oxygen species (ROS) might lead to cellular lipid peroxidation in earthworms. The results of these observations suggested that severe oxidative stress occurred in E. fetida, and it may play an important role in inducing the BDE209 toxicity to earthworms.
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Andrographolide suppresses IL-6/Stat3 signaling in peripheral blood mononuclear cells from patients with chronic rhinosinusitis with nasal polyps.
Inflammation
PUBLISHED: 05-08-2014
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The mechanisms underlying the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) remain largely unknown. CRSwNP has garnered considerable public health concern owing to its high incidence and unsatisfactory treatment outcomes. Herbal remedies are promising candidates for the treatment of CRSwNP. We examined the utility of andrographolide, a diterpenoid lactone extracted from the Chinese herb Andrographis paniculata, an anti-inflammatory agent for CRSwNP treatment by evaluating interleukin (IL)-6 and IL-17 production and monitoring T helper 17 (Th17) differentiation of peripheral blood mononuclear cells (PBMCs) isolated from 20 Chinese CRSwNP patients and 11 control subjects. All CRSwNP patients exhibited clinical features of CRSwNP. Andrographolide significantly inhibited IL-6 and IL-17 production, suppressed p-Stat3 expression, and inhibited Th17 differentiation of PBMCs in vitro. These findings suggested that andrographolide has useful anti-inflammatory properties and could be used for the treatment of CRSwNP.
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Meta-analysis of tumor necrosis factor alpha -308 polymorphism and knee osteoarthritis risk.
BMC Musculoskelet Disord
PUBLISHED: 04-20-2014
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Several case-control studies have been conducted to clarify the association between the tumor necrosis factor alpha (TNF-alpha) -G308A polymorphism and risk of osteoarthritis (OA); however, the results are inconsistent. This meta-analysis was performed to clarify this issue using all the available evidence.
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Effects of moderate static magnetic fields on the voltage-gated sodium and calcium channel currents in trigeminal ganglion neurons.
Electromagn Biol Med
PUBLISHED: 04-10-2014
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Abstract Aim: To study the effects of static magnetic fields (SMF) on the electrophysiological properties of voltage-gated sodium and calcium channels on trigeminal ganglion (TRG) neurons. Methods: Acutely dissociated TRG neurons of neonatal SD rats were exposed to 125-mT and 12.5-mT SMF in exposure devices and whole-cell patch-clamp recordings were carried out to observe the changes of voltage-gated sodium channels (VGSC) and calcium channels (VGCC) currents, while laser scanning confocal microscopy was used to detect intracellular free Ca(2+) concentration in TRG neurons, respectively. Results: (1) No obvious change of current-voltage (I-V) relationship and the peak current densities of VGSC and VGCC currents were found when TRG neurons were exposed to 125-mT and 12.5-mT SMF. However, the activation threshold, inactivation threshold and velocity of the channel currents above were significantly altered by 125-mT and 12.5-mT SMF. (2) The fluctuation of intracellular free Ca(2+) concentration within TRG neurons were slowed by 125-mT and 12.5-mT SMF. When SMF was removed, the Ca(2+) concentration level showed partial recovery in the TRG neurons previously exposed by 125-mT SMF, while there was a full recovery found in 12.5-mT-SMF-exposed neurons. Conclusions: Moderate-intensity SMF could affect the electrophysiological characteristics of VGCS and VGCC by altering their activation and inactivation threshold and velocity. The fluctuations of intracellular free Ca(2+) caused by SMF exposure were not permanent in TRG neurons.
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The prognostic role of microsatellite instability, codon-specific KRAS, and BRAF mutations in colon cancer.
J Surg Oncol
PUBLISHED: 04-07-2014
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This study aimed to establish a correlation between MSI, KRAS mutations, and BRAF(V600E) in colon cancer and to investigate the prognostic effect.
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Clinical relevance of alterations in quantity and quality of plasma DNA in colorectal cancer patients: based on the mutation spectra detected in primary tumors.
Ann. Surg. Oncol.
PUBLISHED: 03-29-2014
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While circulating plasma DNA (cpDNA) likely originates in tumors, its utility is limited without knowledge of tumor mutations. This study assessed mutational spectra in primary tumors and clarified the utility of quantitative and qualitative cpDNA alterations in colorectal cancer (CRC) patients.
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Coaxial wet-spun yarn supercapacitors for high-energy density and safe wearable electronics.
Nat Commun
PUBLISHED: 03-28-2014
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Yarn supercapacitors have great potential in future portable and wearable electronics because of their tiny volume, flexibility and weavability. However, low-energy density limits their development in the area of wearable high-energy density devices. How to enhance their energy densities while retaining their high-power densities is a critical challenge for yarn supercapacitor development. Here we propose a coaxial wet-spinning assembly approach to continuously spin polyelectrolyte-wrapped graphene/carbon nanotube core-sheath fibres, which are used directly as safe electrodes to assembly two-ply yarn supercapacitors. The yarn supercapacitors using liquid and solid electrolytes show ultra-high capacitances of 269 and 177 mF cm(-2) and energy densities of 5.91 and 3.84 ?Wh cm(-2), respectively. A cloth supercapacitor superior to commercial capacitor is further interwoven from two individual 40-cm-long coaxial fibres. The combination of scalable coaxial wet-spinning technology and excellent performance of yarn supercapacitors paves the way to wearable and safe electronics.
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Polyelectrolyte-stabilized graphene oxide liquid crystals against salt, pH, and serum.
Langmuir
PUBLISHED: 03-28-2014
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Stabilization of colloids is of great significance in nanoscience for their fundamental research and practical applications. Electrostatic repulsion-stabilized anisotropic colloids, such as graphene oxide (GO), can form stable liquid crystals (LCs). However, the electrostatic field would be screened by ions. To stabilize colloidal LCs against electrolyte is an unsolved challenge. Here, an effective strategy is proposed to stabilize GO LCs under harsh conditions by association of polyelectrolytes onto GO sheets. Using sodium poly(styrene sulfonate) (PSS) and poly[2-(methacryloyloxy)ethyl]dimethyl-(3-sulfopropyl)ammonium hydroxide (PMEDSAH), a kind of polyzwitterion, GO LCs were well-maintained in the presence of NaCl (from 0 M to saturated), extreme pH (from 1 to 13), and serum. Moreover, PSS- or PMEDSAH-coated chemically reduced GO (rGO) also showed stability against electrolyte.
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Interleukin-17A modulates circulating tumor cells in tumor draining vein of colorectal cancers and affects metastases.
Clin. Cancer Res.
PUBLISHED: 03-27-2014
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Metastasis is the major cause of death in patients with colorectal cancer (CRC). Circulating tumor cells (CTC) are believed to cause metastasis and serve as a prognostic marker for mortality in clinical stage IV patients. However, most studies are conducted in late-stage cases when distant metastases have already occurred; thus, such results provide limited clinical use. This study focused on whether CTCs can predict the risk of metastasis after treatment of the primary tumor in early-stage patients with CRC.
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Histone H3.3 and its proteolytically processed form drive a cellular senescence programme.
Nat Commun
PUBLISHED: 03-21-2014
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The process of cellular senescence generates a repressive chromatin environment, however, the role of histone variants and histone proteolytic cleavage in senescence remains unclear. Here, using models of oncogene-induced and replicative senescence, we report novel histone H3 tail cleavage events mediated by the protease Cathepsin L. We find that cleaved forms of H3 are nucleosomal and the histone variant H3.3 is the preferred cleaved form of H3. Ectopic expression of H3.3 and its cleavage product (H3.3cs1), which lacks the first 21 amino acids of the H3 tail, is sufficient to induce senescence. Further, H3.3cs1 chromatin incorporation is mediated by the HUCA histone chaperone complex. Genome-wide transcriptional profiling revealed that H3.3cs1 facilitates transcriptional silencing of cell cycle regulators including RB/E2F target genes, likely via the permanent removal of H3K4me3. Collectively, our study identifies histone H3.3 and its proteolytically processed forms as key regulators of cellular senescence.
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Two novel ail-positive biotype 1A strains of Yersinia enterocolitica isolated in China with unequal adhesion and invasion properties.
Infect. Genet. Evol.
PUBLISHED: 03-19-2014
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Yersinia enterocolitica is an enteric pathogen having six biotypes: 1A, 1B, 2, 3, 4, and 5. Different bioserotypes have been associated with varying pathogenicity, and the strains of biotype 1A lack the virulence-associated pYV-bearing genes and were once considered to be avirulent. However, there is growing epidemiological, clinical, and experimental evidence to suggest some biotype 1A isolates are virulent and can cause gastrointestinal disease. Here, we describe two biotype 1A strains discovered from 3807 isolates that carry the ail (attachment and invasion locus) gene. The two strains showed unique PFGE patterns compared to all other isolates in the Chinese Y. enterocolitica isolate PFGE database. Strain SDWL-003 isolated from a sheep shared ail sequence identical to A1 pattern, and the foxA (ferrioxamine receptor) sequence was identical to the pathogenic F5 pattern, besides, the PFGE patterns of SDWL-003 was also cluster to pathogenic branch; however it does not attach to or invade Hep-2 cells. The ail sequence of strain 2006RAT isolated from a Microtus fortis showed several mutations compared to other published genomes, and therefore formed an entirely new pathogenic pattern. Though it clustered to non-pathogenic block with foxA sequence polymorphism analysis or PFGE assay, the strain 2006RAT showed adhesion properties. The data here bring new insights into the molecular genetics of Y. enterocolitica biotype 1A, show some isolates of 1A biotype gaining potential pathogenicity using the function of the virulence gene - ail, and indicate the lateral gene transfer of ail virulence genes proceeded between pathogenic and nonpathogenic Y. enterocolitica.
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Comparison of cetuximab to bevacizumab as the first-line bio-chemotherapy for patients with metastatic colorectal cancer: Superior progression-free survival is restricted to patients with measurable tumors and objective tumor response-a retrospective study.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 03-18-2014
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We aimed to compare the treatment efficacy of cetuximab versus bevacizumab in combination with either irinotecan-based or oxaliplatin-based regimens (targeted triplet) as the first-line treatment for patients with metastatic colorectal cancer.
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The genome and occlusion bodies of marine Penaeus monodon nudivirus (PmNV, also known as MBV and PemoNPV) suggest that it should be assigned to a new nudivirus genus that is distinct from the terrestrial nudiviruses.
BMC Genomics
PUBLISHED: 03-17-2014
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Penaeus monodon nudivirus (PmNV) is the causative agent of spherical baculovirosis in shrimp (Penaeus monodon). This disease causes significant mortalities at the larval stage and early postlarval (PL) stage and may suppress growth and reduce survival and production in aquaculture. The nomenclature and classification status of PmNV has been changed several times due to morphological observation and phylogenetic analysis of its partial genome sequence. In this study, we therefore completed the genome sequence and constructed phylogenetic trees to clarify PmNV's taxonomic position. To better understand the characteristics of the occlusion bodies formed by this marine occluded virus, we also compared the chemical properties of the polyhedrin produced by PmNV and the baculovirus AcMNPV (Autographa californica nucleopolyhedrovirus).
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Association study between interleukin-12 receptor ?1/?2 genes and allergic rhinitis in the Chinese Han population.
Eur Arch Otorhinolaryngol
PUBLISHED: 03-12-2014
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Interleukin-12 (IL-12) plays a key role in the protection against allergic reaction induced by allergen as well as the differentiation of T helper 1 cells in patients with allergic rhinitis (AR), exerting its biological effects through binding to specific IL-12 receptors (IL-12Rs) termed IL-12R?1 and IL-12R?2. In this study, we investigated the relationship between polymorphisms in the IL-12R gene and AR in the Chinese Han population. A total of 543 patients with AR and 749 normal controls were genotyped for IL-12R?1/rs438421, IL-12R?2/rs3790565, rs3790567, and rs6679356 using a PCR restriction fragment length polymorphism analysis. The association study of each polymorphism of the IL-12R?1 and IL-12R?2 gene and AR showed that a significantly increased prevalence of the homozygous rs438421 GG genotype and G allele appeared in the AR patients compared with healthy controls. A significantly decreased prevalence of AG in rs438421 in AR patients is compared with healthy controls. Our research demonstrated an important association between polymorphisms in IL-12R?1 and AR in the Chinese Han population. A strong association between rs438421 in a single nucleotide polymorphism of IL-12R?1 and AR was identified.
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A roadmap for natural product discovery based on large-scale genomics and metabolomics.
Nat. Chem. Biol.
PUBLISHED: 03-11-2014
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Actinobacteria encode a wealth of natural product biosynthetic gene clusters, whose systematic study is complicated by numerous repetitive motifs. By combining several metrics, we developed a method for the global classification of these gene clusters into families (GCFs) and analyzed the biosynthetic capacity of Actinobacteria in 830 genome sequences, including 344 obtained for this project. The GCF network, comprising 11,422 gene clusters grouped into 4,122 GCFs, was validated in hundreds of strains by correlating confident mass spectrometric detection of known small molecules with the presence or absence of their established biosynthetic gene clusters. The method also linked previously unassigned GCFs to known natural products, an approach that will enable de novo, bioassay-free discovery of new natural products using large data sets. Extrapolation from the 830-genome data set reveals that Actinobacteria encode hundreds of thousands of future drug leads, and the strong correlation between phylogeny and GCFs frames a roadmap to efficiently access them.
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The characteristic direction: a geometrical approach to identify differentially expressed genes.
BMC Bioinformatics
PUBLISHED: 03-11-2014
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Identifying differentially expressed genes (DEG) is a fundamental step in studies that perform genome wide expression profiling. Typically, DEG are identified by univariate approaches such as Significance Analysis of Microarrays (SAM) or Linear Models for Microarray Data (LIMMA) for processing cDNA microarrays, and differential gene expression analysis based on the negative binomial distribution (DESeq) or Empirical analysis of Digital Gene Expression data in R (edgeR) for RNA-seq profiling.
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Collision tumor of low-grade B-cell lymphoma and adenocarcinoma with tuberculosis in the colon: a case report and literature review.
World J Surg Oncol
PUBLISHED: 03-08-2014
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This report presents a case of collision tumors of low-grade B-cell lymphoma and adenocarcinoma in the sigmoid colon of an 81-year-old man. All surgically resected regional mesenteric lymph nodes were found to be occupied by low-grade B-cell lymphoma, and one lymph node showed the presence of adenocarcinoma. Low-grade B-cell lymphoma was also observed in the resected spleen. Moreover, concurrent tuberculosis infection in the resected colon was proven by the presence of positive results obtained with polymerase chain reaction analysis of the mycobacterial DNA. Systemic chemotherapy was administered for advanced colon cancer with lung metastasis, and anti-tuberculosis treatment was also prescribed. The occurrence of synchronous lymphoma and adenocarcinoma of the colorectal region is rare. Furthermore, collisions of these different entities are also extremely unusual. The accurate clinical determination of the dominant tumor and a timely follow-up are required for the proper treatment of these cases.
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AR-14-0079R3 accept for first look The distinct distributions of immunocompetent cells in rat dentin pulp after pulpotomy.
Anat Rec (Hoboken)
PUBLISHED: 03-06-2014
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Pulpotomy involves the removal of the coronal portion of pulp, including the diseased tissue, with the intent of maintaining the vitality of the remaining pulpal tissue via a therapeutic dressing. Once odontoblasts suffer injuries, the differentiation of mesenchymal cells is induced from the precursor cell population in the dental pulp, and these cells are recruited to the injured site to differentiate into odontoblasts. However, the involvement of immunocompetent cells during pulpal regeneration remains unclear. Thus, the purpose of this study was to investigate the properties of macrophages that infiltrated wound healing sites in rats between 1 and 28 days after pulpotomy (dap). During the inflammatory phase, ED1(+) (CD68(+) ) macrophages significantly increased throughout root pulp, especially apical to the demarcation zone, and this population persisted until 3 dap before decreasing gradually until 28 dap. OX6(+) macrophages expressing class II MHC also increased in the apical pulp at 1 dap and declined thereafter. However, OX6(+) cells appeared prior to dentin bridge formation at 3 dap and appeared again apical to the dentin bridge during the healing stage at 14 dap. The shift from ED1(+) cells in the inflammation phase to OX6(+) cells during dentin bridge formation might contribute to wound healing. Anat Rec, 2014. © 2014 Wiley Periodicals, Inc.
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One family cluster of avian influenza A(H7N9) virus infection in Shandong, China.
BMC Infect. Dis.
PUBLISHED: 02-12-2014
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The first case of human infection with avian influenza A (H7N9) virus was identified in March, 2013 and the new H7N9 virus infected 134 patients and killed 45 people in China as of September 30, 2013. Family clusters with confirmed or suspected the new H7N9 virus infection were previously reported, but the family cluster of H7N9 virus infection in Shandong Province was first reported.
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An aryl hydrocarbon receptor ligand acts on dendritic cells and T cells to suppress the Th17 response in allergic rhinitis patients.
Lab. Invest.
PUBLISHED: 02-10-2014
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A predominant Th17 population is a marker of allergic rhinitis (AR). The aryl hydrocarbon receptor (AhR) exhibits strong immunomodulation potential via regulation of the differentiation of T lymphocytes and dendritic cells (DCs) after activation by its ligand, such as 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE). The aim of this study was to analyze the effect of AhR on Th17 differentiation by investigating the action of ITE on DCs and CD4(+) T cells from patients with AR. In all, 26 AR patients and 12 healthy controls were included in this study. The expression of interleukin (IL)-1?, IL-6, IL-10, and IL-17 in the culture supernatant and the presence of Th17 cells in CD4(+) T cells and DC-CD4(+) T-cell co-culture system were measured before and after treatment with ITE. We show that ITE significantly induced cell secretion of IL-10 and inhibited IL-1? and IL-6 production in DCs, and promoted IL-10 production and suppressed IL-17 expression in CD4(+) T cells in vitro. It also suppressed the expansion of Th17 cells in vitro. Our work demonstrates that ITE acts on DCs and CD4(+) T cells to inhibit the Th17 response that suppresses AR; the AhR-DC-Th17 axis may be an important pathway in the treatment of AR. ITE, a nontoxic AhR ligand, attenuated the Th17 response; thus, it appears to be a promising therapeutic candidate for suppressing the inflammatory responses associated with AR.
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DAWN: a framework to identify autism genes and subnetworks using gene expression and genetics.
Mol Autism
PUBLISHED: 02-03-2014
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De novo loss-of-function (dnLoF) mutations are found twofold more often in autism spectrum disorder (ASD) probands than their unaffected siblings. Multiple independent dnLoF mutations in the same gene implicate the gene in risk and hence provide a systematic, albeit arduous, path forward for ASD genetics. It is likely that using additional non-genetic data will enhance the ability to identify ASD genes.
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Bioaccumulation of decabromodiphenyl ether (BDE209) in earthworms in the presence of lead (Pb).
Chemosphere
PUBLISHED: 01-22-2014
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BDE209 (decabromodiphenyl ether) and lead (Pb) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impact on earthworms of exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the uptake and transformation of BDE209 in the presence of Pb for the first time. The results have demonstrated that Pb addition can affect BDE209 bioaccumulation efficiency compared with exposure to BDE209 alone. For a low BDE209 concentration (1mgkg(-1)), Pb addition barely affected the uptake of BDE209, whereas for a high BDE209 concentration (100mgkg(-1)), Pb addition elicited a complex response. Scanning electron microscope (SEM) observation indicated that a higher level of Pb (250 and 500mgkg(-1)) facilitated the uptake of BDE209 through the skin. Gas chromatography/mass spectrometry (GC/MS) analysis showed that the peak of BDE209 accumulation usually appeared in the joint exposure groups involving 10 or 100mgkg(-1) BDE209 and 250mgkg(-1) Pb, and the average bioaccumulation factor (BAF) was 0.53, which is more than 1.2 times that of single exposure to BDE209 (average=0.44). Also, the earthworms eliminated more BDE209 after 21d, and the biodegradation products were mainly BDE206 and BDE208. Furthermore, Pb addition can affect the transformation efficiency of BDE209 in earthworms, and several lower bromodiphenyl ethers can be detected. The results of these observations have provided a basic understanding of the potential ecotoxicological effects of joint PBDE and heavy metal exposure on terrestrial invertebrates.
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Temsirolimus enhances the efficacy of cetuximab in colon cancer through a CIP2A-dependent mechanism.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 01-20-2014
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A dozen clinical trials examining a combination of temsirolimus and cetuximab in treating metastatic colon cancer are currently underway. We investigated the role of cancerous inhibitor of protein phosphatase 2A (CIP2A) in the synergism between temsirolimus and cetuximab in colon cancer.
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Cyanohydrin phosphonate natural product from Streptomyces regensis.
J. Nat. Prod.
PUBLISHED: 01-17-2014
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Streptomyces regensis strain WC-3744 was identified as a potential phosphonic acid producer in a large-scale screen of microorganisms for the presence of the pepM gene, which encodes the key phosphonate biosynthetic enzyme phosphoenolpyruvate phosphonomutase. (31)P NMR revealed the presence of several unidentified phosphonates in spent medium after growth of S. regensis. These compounds were purified and structurally characterized via extensive 1D and 2D NMR spectroscopic and mass spectrometric analyses. Three new phosphonic acid metabolites, whose structures were confirmed by comparison to chemically synthesized standards, were observed: (2-acetamidoethyl)phosphonic acid (1), (2-acetamido-1-hydroxyethyl)phosphonic (3), and a novel cyanohydrin-containing phosphonate, (cyano(hydroxy)methyl)phosphonic acid (4). The gene cluster responsible for synthesis of these molecules was also identified from the draft genome sequence of S. regensis, laying the groundwork for future investigations into the metabolic pathway leading to this unusual natural product.
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Assessment of the value of carcinoembryonic antigen reduction ratio as a prognosis factor in rectal cancer.
Am. J. Surg.
PUBLISHED: 01-16-2014
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Carcinoembryonic antigen (CEA) is the most widely used tumor marker for colorectal cancer. This study aimed to investigate the role of CEA reduction ratio after preoperative chemoradiotherapy (CRT).
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Genetic variations are associated with lymph node metastasis in colorectal cancer patients.
J Surg Oncol
PUBLISHED: 01-15-2014
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Regional lymph nodes (LNs) are believed to be a first-line barrier against tumor metastasis. However, it remains unclear whether underlying genetic factors exist and affect LN metastasis risk. We therefore evaluated inherited risk variants using single nucleotide polymorphisms (SNPs) in pathological T3 colorectal cancer patients in the absence or presence of LN metastasis.
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Toward synthesis of third-generation spin-labeled podophyllotoxin derivatives using isocyanide multicomponent reactions.
Eur J Med Chem
PUBLISHED: 01-15-2014
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Spin-labeled podophyllotoxins have elicited widespread interest due to their far superior antitumor activity compared to podophyllotoxin. To extend our prior studies in this research area, we synthesized a new generation of spin-labeled podophyllotoxin analogs via isocyanide multicomponent reactions and evaluated their cytotoxicity against four human cancer cell lines (A-549, DU-145, KB and KBvin). Most of the compounds exhibited potent cytotoxic activity against all four cell lines, notably against the drug resistant KBvin cancer cell line. Among the new analogs, compounds 12e (IC50: 0.60-0.75 ?M) and 12h (IC50: 1.12-2.03 ?M) showed superior potency to etoposide (IC50: 2.03 to >20 ?M), a clinically available anticancer drug. With a concise efficient synthesis and potent cytotoxic profiles, compounds 12e and 12h merit further development as a new generation of epipodophyllotoxin-derived antitumor clinical trial candidates.
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The phenotype and tissue-specific nature of multipotent cells derived from human mature adipocytes.
Biochem. Biophys. Res. Commun.
PUBLISHED: 01-14-2014
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Dedifferentiated fat (DFAT) cells derived from mature adipocytes have been considered to be a homogeneous group of multipotent cells, which present to be an alternative source of adult stem cells for regenerative medicine. However, many aspects of the cellular nature about DFAT cells remained unclarified. This study aimed to elucidate the basic characteristics of DFAT cells underlying their functions and differentiation potentials. By modified ceiling culture technique, DFAT cells were converted from human mature adipocytes from the human buccal fat pads. Flow cytometry analysis revealed that those derived cells were a homogeneous population of CD13(+) CD29(+) CD105(+) CD44(+) CD31(-) CD34(-) CD309(-) ?-SMA(-) cells. DFAT cells in this study demonstrated tissue-specific differentiation properties with strong adipogenic but much weaker osteogenic capacity. Neither did they express endothelial markers under angiogenic induction.
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[Expressions and clinical significances of iASPP and caspase-9 in esophageal cancer].
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi
PUBLISHED: 01-11-2014
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To investigate the expressions of inhibitory member of the apoptosis stimulating protein of p53 family (iASPP) and caspase-9 in the esophageal cancer (EC) tissues and their correlations with clinical pathological parameters.
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Two Metallothionein Genes in Oxya chinensis: Molecular Characteristics, Expression Patterns and Roles in Heavy Metal Stress.
PLoS ONE
PUBLISHED: 01-01-2014
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Metallothioneins (MTs) are small, cysteine-rich, heavy metal-binding proteins involved in metal homeostasis and detoxification in living organisms. In the present study, we cloned two MT genes (OcMT1 and OcMT2) from Oxya chinensis, analyzed the expression patterns of the OcMT transcripts in different tissues and at varying developmental stages using real-time quantitative PCR (RT-qPCR), evaluated the functions of these two MTs using RNAi and recombinant proteins in an E. coli expression system. The full-length cDNAs of OcMT1 and OcMT2 encoded 40 and 64 amino acid residues, respectively. We found Cys-Cys, Cys-X-Cys and Cys-X-Y-Z-Cys motifs in OcMT1 and OcMT2. These motifs might serve as primary chelating sites, as in other organisms. These characteristics suggest that OcMT1 and OcMT2 may be involved in heavy metal detoxification by capturing the metals. Two OcMT were expressed at all developmental stages, and the highest levels were found in the eggs. Both transcripts were expressed in all eleven tissues examined, with the highest levels observed in the brain and optic lobes, followed by the fat body. The expression of OcMT2 was also relatively high in the ovaries. The functions of OcMT1 and OcMT2 were explored using RNA interference (RNAi) and different concentrations and treatment times for the three heavy metals. Our results indicated that mortality increased significantly from 8.5% to 16.7%, and this increase was both time- and dose-dependent. To evaluate the abilities of these two MT proteins to confer heavy metal tolerance to E. coli, the bacterial cells were transformed with pET-28a plasmids containing the OcMT genes. The optical densities of both the MT-expressing and control cells decreased with increasing concentrations of CdCl2. Nevertheless, the survival rates of the MT-overexpressing cells were higher than those of the controls. Our results suggest that these two genes play important roles in heavy metal detoxification in O. chinensis.
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A promising gene delivery system developed from PEGylated MoS2 nanosheets for gene therapy.
Nanoscale Res Lett
PUBLISHED: 01-01-2014
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A new class of two-dimensional (2D) nanomaterial, transition metal dichalcogenides (TMDCs) such as MoS2, MoSe2, WS2, and WSe2 which have fantastic physical and chemical properties, has drawn tremendous attention in different fields recently. Herein, we for the first time take advantage of the great potential of MoS2 with well-engineered surface as a novel type of 2D nanocarriers for gene delivery and therapy of cancer. In our system, positively charged MoS2-PEG-PEI is synthesized with lipoic acid-modified polyethylene glycol (LA-PEG) and branched polyethylenimine (PEI). The amino end of positively charged nanomaterials can bind to the negatively charged small interfering RNA (siRNA). After detection of physical and chemical characteristics of the nanomaterial, cell toxicity was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Polo-like kinase 1 (PLK1) was investigated as a well-known oncogene, which was a critical regulator of cell cycle transmission at multiple levels. Through knockdown of PLK1 with siRNA carried by novel nanovector, qPCR and Western blot were used to measure the interfering efficiency; apoptosis assay was used to detect the transfection effect of PLK1. All results showed that the novel nanocarrier revealed good biocompatibility, reduced cytotoxicity, as well as high gene-carrying ability without serum interference, thus would have great potential for gene delivery and therapy.
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Fine Epitope Mapping of the Central Immunodominant Region of Nucleoprotein from Crimean-Congo Hemorrhagic Fever Virus (CCHFV).
PLoS ONE
PUBLISHED: 01-01-2014
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Crimean-Congo hemorrhagic fever (CCHF), a severe viral disease known to have occurred in over 30 countries and distinct regions, is caused by the tick-borne CCHF virus (CCHFV). Nucleocapsid protein (NP), which is encoded by the S gene, is the primary antigen detectable in infected cells. The goal of the present study was to map the minimal motifs of B-cell epitopes (BCEs) on NP. Five precise BCEs (E1, 247FDEAKK252; E2a, 254VEAL257; E2b, 258NGYLNKH264; E3, 267EVDKA271; and E4, 274DSMITN279) identified through the use of rabbit antiserum, and one BCE (E5, 258NGYL261) recognized using a mouse monoclonal antibody, were confirmed to be within the central region of NP and were partially represented among the predicted epitopes. Notably, the five BCEs identified using the rabbit sera were able to react with positive serum mixtures from five sheep which had been infected naturally with CCHFV. The multiple sequence alignment (MSA) revealed high conservation of the identified BCEs among ten CCHFV strains from different areas. Interestingly, the identified BCEs with only one residue variation can apparently be recognized by the positive sera of sheep naturally infected with CCHFV. Computer-generated three-dimensional structural models indicated that all the antigenic motifs are located on the surface of the NP stalk domain. This report represents the first identification and mapping of the minimal BCEs of CCHFV-NP along with an analysis of their primary and structural properties. Our identification of the minimal linear BCEs of CCHFV-NP may provide fundamental data for developing rapid diagnostic reagents and illuminating the pathogenic mechanism of CCHFV.
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Use of CHADS2 and CHA2DS2-VASc Scores to Predict Subsequent Myocardial Infarction, Stroke, and Death in Patients with Acute Coronary Syndrome: Data from Taiwan Acute Coronary Syndrome Full Spectrum Registry.
PLoS ONE
PUBLISHED: 01-01-2014
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Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS2 and CHA2DS2-VASc scores were useful tools to assess the risk for adverse events among ACS patients.
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Single nucleotide polymorphisms associated with colorectal cancer susceptibility and loss of heterozygosity in a Taiwanese population.
PLoS ONE
PUBLISHED: 01-01-2014
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Given the significant racial and ethnic diversity in genetic variation, we are intrigued to find out whether the single nucleotide polymorphisms (SNPs) identified in genome-wide association studies of colorectal cancer (CRC) susceptibility in East Asian populations are also relevant to the population of Taiwan. Moreover, loss of heterozygosity (LOH) may provide insight into how variants alter CRC risk and how regulatory elements control gene expression. To investigate the racial and ethnic diversity of CRC-susceptibility genetic variants and their relevance to the Taiwanese population, we genotyped 705 CRC cases and 1,802 healthy controls (Taiwan Biobank) for fifteen previously reported East Asian CRC-susceptibility SNPs and four novel genetic variants identified by whole-exome sequencing. We found that rs10795668 in FLJ3802842 and rs4631962 in CCND2 were significantly associated with CRC risk in the Taiwanese population. The previously unreported rs1338565 was associated with a significant increased risk of CRC. In addition, we also genotyped tumor tissue and paired adjacent normal tissues of these 705 CRC cases to search for LOH, as well as risk-associated and protective alleles. LOH analysis revealed preferential retention of three SNPs, rs12657484, rs3802842, and rs4444235, in tumor tissues. rs4444235 has been recently reported to be a cis-acting regulator of BMP4 gene; in this study, the C allele was preferentially retained in tumor tissues (p?=?0.0023). rs4631962 and rs10795668 contribute to CRC risk in the Taiwanese and East Asian populations, and the newly identified rs1338565 was specifically associated with CRC, supporting the ethnic diversity of CRC-susceptibility SNPs. LOH analysis suggested that the three CRC risk variants, rs12657484, rs3802842, and rs4444235, exhibited somatic allele-specific imbalance and might be critical during neoplastic progression.
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Multifactorial comparative proteomic study of cytochrome P450 2E1 function in chronic alcohol administration.
PLoS ONE
PUBLISHED: 01-01-2014
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With the use of iTRAQ technique, a multifactorial comparative proteomic study can be performed. In this study, to obtain an overview of ethanol, CYP2E1 and gender effects on liver injury and gain more insight into the underlying molecular mechanism, mouse liver proteomes were quantitatively analyzed using iTRAQ under eight conditions including mice of different genders, wild type versus CYP2E1 knockout, and normal versus alcohol diet. A series of statistical and bioinformatic analyses were explored to simplify and clarify multifactorial comparative proteomic data. First, with the Principle Component analysis, six proteins, CYP2E1, FAM25, CA3, BHMT, HIBADH and ECHS1, involved in oxidation reduction, energy and lipid metabolism and amino acid metabolism, were identified as the most differentially expressed gene products across all of the experimental conditions of our chronic alcoholism model. Second, hierarchical clustering analysis showed CYP2E1 knockout played a primary role in the overall differential protein expression compared with ethanol and gender factors. Furthermore, pair-wise multiple comparisons have revealed that the only significant expression difference lied in wild-type and CYP2E1 knockout mice both treated with ethanol. Third, K-mean clustering analysis indicated that the CYP2E1 knockout had the reverse effect on ethanol induced oxidative stress and lipid oxidation. More importantly, IPA analysis of proteomic data inferred that the gene expressions of two upstream regulators, NRF2 and PPAR?, regulated by chronic alcohol feeding and CYP2E1 knockout, are involved in ethanol induced oxidative stress and lipid oxidation. The present study provides an effectively comprehensive data analysis strategy to compare multiple biological factors, contributing to biochemical effects of alcohol on the liver. The mass spectrometry proteomics data have been deposited to the ProteomeXchange with data set identifier of PXD000635.
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Characterization and interactome study of white spot syndrome virus envelope protein VP11.
PLoS ONE
PUBLISHED: 01-01-2014
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White spot syndrome virus (WSSV) is a large enveloped virus. The WSSV viral particle consists of three structural layers that surround its core DNA: an outer envelope, a tegument and a nucleocapsid. Here we characterize the WSSV structural protein VP11 (WSSV394, GenBank accession number AF440570), and use an interactome approach to analyze the possible associations between this protein and an array of other WSSV and host proteins. Temporal transcription analysis showed that vp11 is an early gene. Western blot hybridization of the intact viral particles and fractionation of the viral components, and immunoelectron microscopy showed that VP11 is an envelope protein. Membrane topology software predicted VP11 to be a type of transmembrane protein with a highly hydrophobic transmembrane domain at its N-terminal. Based on an immunofluorescence assay performed on VP11-transfected Sf9 cells and a trypsin digestion analysis of the virion, we conclude that, contrary to topology software prediction, the C-terminal of this protein is in fact inside the virion. Yeast two-hybrid screening combined with co-immunoprecipitation assays found that VP11 directly interacted with at least 12 other WSSV structural proteins as well as itself. An oligomerization assay further showed that VP11 could form dimers. VP11 is also the first reported WSSV structural protein to interact with the major nucleocapsid protein VP664.
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[Autoimmune hemolytic anemia with a paroxysmal nocturnal hemoglobinuria-like defect: report of one case].
Nan Fang Yi Ke Da Xue Xue Bao
PUBLISHED: 12-27-2013
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Both autoimmune hemolytic anemia and paroxysmal nocturnal hemoglobinuria are common hemolytic diseases. The former causes hemolysis because of immune disorder, and the latter is an acquired clonal hematologic disorder of stem cells. The two entities are often separate diseases, but can also occur concomitantly or secondary to each other. paroxysmal nocturnal haemoglobinuria-like defect-like defect is a special type of autoimmune haemolytic anaemia and should be distinguished from typical paroxysmal nocturnal haemoglobinuria-like defect.
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The DNA Virus White Spot Syndrome Virus Uses an Internal Ribosome Entry Site for Translation of the Highly Expressed Nonstructural Protein ICP35.
J. Virol.
PUBLISHED: 10-02-2013
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Although shrimp white spot syndrome virus (WSSV) is a large double-stranded DNA virus (?300 kbp), it expresses many polycistronic mRNAs that are likely to use internal ribosome entry site (IRES) elements for translation. A polycistronic mRNA encodes the gene of the highly expressed nonstructural protein ICP35, and here we use a dual-luciferase assay to demonstrate that this protein is translated cap independently by an IRES element located in the 5 untranslated region of icp35. A deletion analysis of this region showed that IRES activity was due to stem-loops VII and VIII. A promoterless assay, a reverse transcription-PCR together with quantitative real-time PCR analysis, and a stable stem-loop insertion upstream of the Renilla luciferase open reading frame were used, respectively, to rule out the possibility that cryptic promoter activity, abnormal splicing, or read-through was contributing to the IRES activity. In addition, a Northern blot analysis was used to confirm that only a single bicistronic mRNA was expressed. The importance of ICP35 to viral replication was demonstrated in a double-stranded RNA (dsRNA) interference knockdown experiment in which the mortality of the icp35 dsRNA group was significantly reduced. Tunicamycin was used to show that the ? subunit of eukaryotic initiation factor 2 is required for icp35 IRES activity. We also found that the intercalating drug quinacrine significantly inhibited icp35 IRES activity in vitro and reduced the mortality rate and viral copy number in WSSV-challenged shrimp. Lastly, in Sf9 insect cells, we found that knockdown of the gene for the Spodoptera frugiperda 40S ribosomal protein RPS10 decreased icp35 IRES-regulated firefly luciferase activity but had no effect on cap-dependent translation.
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Genomics-enabled discovery of phosphonate natural products and their biosynthetic pathways.
J. Ind. Microbiol. Biotechnol.
PUBLISHED: 09-27-2013
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Phosphonate natural products have proven to be a rich source of useful pharmaceutical, agricultural, and biotechnology products, whereas study of their biosynthetic pathways has revealed numerous intriguing enzymes that catalyze unprecedented biochemistry. Here we review the history of phosphonate natural product discovery, highlighting technological advances that have played a key role in the recent advances in their discovery. Central to these developments has been the application of genomics, which allowed discovery and development of a global phosphonate metabolic framework to guide research efforts. This framework suggests that the future of phosphonate natural products remains bright, with many new compounds and pathways yet to be discovered.
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Use of a Phosphonate Methyltransferase in the Identification of the Fosfazinomycin Biosynthetic Gene Cluster.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 09-24-2013
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Natural product discovery has been boosted by genome mining approaches, but compound purification is often still challenging. We report an enzymatic strategy for "stable isotope labeling of phosphonates in extract" (SILPE) that facilitates their purification. We used the phosphonate methyltransferase DhpI involved in dehydrophos biosynthesis to methylate a variety of phosphonate natural products in crude spent medium with a mixture of labeled and unlabeled S-adenosyl methionine. Mass-guided fractionation then allowed straightforward purification. We illustrate its utility by purifying a phosphonate that led to the identification of the fosfazinomycin biosynthetic gene cluster. This unusual natural product contains a hydrazide linker between a carboxylic acid and a phosphonic acid. Bioinformatic analysis of the gene cluster provides insights into how such a structure might be assembled.
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Sphincter-preserving surgery for rectal cancer: a population-based study in Taiwan.
Hepatogastroenterology
PUBLISHED: 09-19-2013
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Sphincter-preserving surgery (SPS) has been considered a surrogate for surgical quality for rectal cancer. This study aims to assess its rate for rectal cancer between centers and over time in Taiwan.
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Lead accumulations and toxic effects in earthworms (Eisenia fetida) in the presence of decabromodiphenyl ether.
Environ Sci Pollut Res Int
PUBLISHED: 09-17-2013
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Lead (Pb) and decabromodiphenyl ether (BDE209) are the main contaminants at e-waste recycling sites, and their potential toxicological effects on terrestrial organisms have received extensive attention. However, the impact on earthworms of exposure to the two chemicals remains almost unknown. Therefore, indoor incubation tests were performed on control and contaminated soil samples to determine the Pb accumulations and toxic effects by earthworms in the presence of BDE209 for the first time. The results have demonstrated that BDE209 presence can affect Pb bioaccumulation efficiency compared with exposure to Pb alone. The Pb contents in earthworms had a highly positive correlation with the Pb concentrations in soils. For different Pb doses, almost contrary response trends were found for Pb uptake examined separately on day 7 or 28, and dose-effect relationships were clearly observed in the presence of BDE209. After 7 days of exposure, the earthworm bodies receiving 1-mg kg(-1) BDE209 dose showed significantly lower Pb contents (average?=?175.85 mg kg(-1)) and bioaccumulation factor (average?=?0.574) than those receiving non-BDE209 treatments (217.39 mg kg(-1) and 1.209, respectively). As the incubation time extended, the influence of BDE209 presence on Pb uptake gradually declined. Additionally, either single or combined exposure to both chemicals can affect the protein synthesis in earthworms (p?
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Changes of salivary functions in experimental periodontitis model rats.
Arch. Oral Biol.
PUBLISHED: 07-23-2013
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This study was designed to investigate the mechanism of salivary dysfunction in an experimental periodontitis rat model and to examine the improvements in salivary secretion following treatment of the experimental periodontitis.
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Identification of small exonic CNV from whole-exome sequence data and application to autism spectrum disorder.
Am. J. Hum. Genet.
PUBLISHED: 07-17-2013
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Copy number variation (CNV) is an important determinant of human diversity and plays important roles in susceptibility to disease. Most studies of CNV carried out to date have made use of chromosome microarray and have had a lower size limit for detection of about 30 kilobases (kb). With the emergence of whole-exome sequencing studies, we asked whether such data could be used to reliably call rare exonic CNV in the size range of 1-30 kilobases (kb), making use of the eXome Hidden Markov Model (XHMM) program. By using both transmission information and validation by molecular methods, we confirmed that small CNV encompassing as few as three exons can be reliably called from whole-exome data. We applied this approach to an autism case-control sample (n = 811, mean per-target read depth = 161) and observed a significant increase in the burden of rare (MAF ?1%) 1-30 kb CNV, 1-30 kb deletions, and 1-10 kb deletions in ASD. CNV in the 1-30 kb range frequently hit just a single gene, and we were therefore able to carry out enrichment and pathway analyses, where we observed enrichment for disruption of genes in cytoskeletal and autophagy pathways in ASD. In summary, our results showed that XHMM provided an effective means to assess small exonic CNV from whole-exome data, indicated that rare 1-30 kb exonic deletions could contribute to risk in up to 7% of individuals with ASD, and implicated a candidate pathway in developmental delay syndromes.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.