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Find video protocols related to scientific articles indexed in Pubmed.
Role of Neurotoxin Associated Proteins in the Low pH Induced Structural Changes in the Botulinum Neurotoxin Complex.
Protein J.
PUBLISHED: 11-20-2014
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Botulinum Neurotoxin (BoNT) produced by the bacterium Clostridium botulinum as a complex with NAPs causes botulism. It has been known that the NAPs protect the toxin from both extremes of pHs and proteases of the GI tract. In an attempt to emulate the physiological conditions encountered by the toxin, we examined BoNT/A, BoNT/A complex, and NAPs under different pH conditions and monitored their structural characteristics by far-UV CD and thermal denaturation analysis. BoNT/A complex showed the maximum CD signal with a mean residue weight ellipticity of -1.8 × 10(5)° cm(2)/dmol at 222 nm at both acidic and neutral pHs. Thermal denaturation analysis revealed NAPs to be the most stable amongst the three protein samples examined. Interestingly and quite uniquely, at pH 2.5, there was an increase in CD signal for BoNT complex as a function of temperature, which correlated with the NAPs profile, indicating a shielding effect of NAPs on BoNT complex at low pH. Calculation of the weighted mean of the ellipticities at the Tm for thermal unfolding of toxin and NAPs at neutral and acidic pHs showed variation with that of BoNT complex, suggesting structural reorganization in BoNT complex upon the association of NAPs and BoNT. In conclusion, this study reveals the structural behavior of BoNT complex and NAPs with pH changes substantially, which could be quite relevant for BoNT survival under extreme pH conditions in vivo.
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Simian Hemorrhagic Fever Virus Cell Entry is Dependent on CD163 and Uses a Clathrin-mediated Endocytosis-like Pathway.
J. Virol.
PUBLISHED: 10-31-2014
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Simian hemorrhagic fever virus (SHFV) causes a severe and almost uniformly fatal viral hemorrhagic fever in Asian macaques, but is thought to be nonpathogenic for humans. To date, the SHFV lifecycle is almost completely uncharacterized on the molecular level. Here we describe the first steps of the SHFV lifecycle. Our experiments indicate that SHFV enters target cells by low pH-dependent endocytosis. Dynamin inhibitors, chlorpromazine, methyl-?-cyclodextrin, chloroquine, and concanamycin A dramatically reduced SHFV entry efficiency, whereas the macropinocytosis inhibitors EIPA, blebbistatin, and wortmannin, and the caveolin-mediated endocytosis inhibitors nystatin and filipin III had no effect. Furthermore, overexpression and knock-out study and electron-microscopy results indicate that SHFV entry occurs by a dynamin-dependent clathrin-mediated endocytosis-like pathway. Experiments utilizing latrunculin B, cytochalasin B, and cytochalasin D indicate that SHFV does not hijack the actin polymerization pathway. Treatment of target cells with proteases (proteinase K, papain, ?-chymotrypsin, trypsin) abrogated entry, indicating that the SHFV cell-surface receptor is a protein. Phospholipases A2 and D had no effect on SHFV entry. Finally, treatment of cells with antibodies targeting CD163, a cell surface molecule identified as an entry factor for the SHFV-related porcine reproductive and respiratory syndrome virus, diminished SHFV replication, identifying CD163 as an important SHFV entry component.
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Trans-Golgi Network-Located AP1 Gamma Adaptins Mediate Dileucine Motif-Directed Vacuolar Targeting in Arabidopsis.
Plant Cell
PUBLISHED: 10-30-2014
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Membrane proteins on the tonoplast are indispensible for vacuolar functions in plants. However, how these proteins are transported to the vacuole and how they become separated from plasma membrane proteins remain largely unknown. In this study, we used Arabidopsis thaliana vacuolar ion transporter1 (VIT1) as a reporter to study the mechanisms of tonoplast targeting. We showed that VIT1 reached the tonoplast through a pathway involving the endoplasmic reticulum (ER), Golgi, trans-Golgi network (TGN), prevacuolar compartment, and tonoplast. VIT1 contains a putative N-terminal dihydrophobic type ER export signal, and its N terminus has a conserved dileucine motif (EKQTLL), which is responsible for tonoplast targeting. In vitro peptide binding assays with synthetic VIT1 N terminus identified adaptor protein complex-1 (AP1) subunits that interacted with the dileucine motif. A deficiency of AP1 gamma adaptins in Arabidopsis cells caused relocation of tonoplast proteins containing the dileucine motif, such as VIT1 and inositol transporter1, to the plasma membrane. The dileucine motif also effectively rerouted the plasma membrane protein SCAMP1 to the tonoplast. Together with subcellular localization studies showing that AP1 gamma adaptins localize to the TGN, we propose that the AP1 complex on the TGN mediates tonoplast targeting of membrane proteins with the dileucine motif.
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HLA-DQA1 and PLCG2 Are Candidate Risk Loci for Childhood-Onset Steroid-Sensitive Nephrotic Syndrome.
J. Am. Soc. Nephrol.
PUBLISHED: 10-29-2014
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Steroid-sensitive nephrotic syndrome (SSNS) accounts for >80% of cases of nephrotic syndrome in childhood. However, the etiology and pathogenesis of SSNS remain obscure. Hypothesizing that coding variation may underlie SSNS risk, we conducted an exome array association study of SSNS. We enrolled a discovery set of 363 persons (214 South Asian children with SSNS and 149 controls) and genotyped them using the Illumina HumanExome Beadchip. Four common single nucleotide polymorphisms (SNPs) in HLA-DQA1 and HLA-DQB1 (rs1129740, rs9273349, rs1071630, and rs1140343) were significantly associated with SSNS at or near the Bonferroni-adjusted P value for the number of single variants that were tested (odds ratio, 2.11; 95% confidence interval, 1.56 to 2.86; P=1.68×10(-6) (Fisher exact test). Two of these SNPs-the missense variants C34Y (rs1129740) and F41S (rs1071630) in HLA-DQA1-were replicated in an independent cohort of children of white European ancestry with SSNS (100 cases and ?589 controls; P=1.42×10(-17)). In the rare variant gene set-based analysis, the best signal was found in PLCG2 (P=7.825×10(-5)). In conclusion, this exome array study identified HLA-DQA1 and PLCG2 missense coding variants as candidate loci for SSNS. The finding of a MHC class II locus underlying SSNS risk suggests a major role for immune response in the pathogenesis of SSNS.
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Unfavorable effect of small tumor size on cause-specific survival in stage IIA colon cancer, a SEER-based study.
Int J Colorectal Dis
PUBLISHED: 10-25-2014
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We sought to determine the prognostic role of tumor size on cause-specific survival (CSS) of patients with stage IIA colon cancer.
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Genome Sequences of Simian Hemorrhagic Fever Virus Variant NIH LVR42-0/M6941 Isolates (Arteriviridae: Arterivirus).
Genome Announc
PUBLISHED: 10-11-2014
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Simian hemorrhagic fever virus (SHFV) variant NIH LVR42-0/M6941 is the only remaining SHFV in culture, and only a single genome sequence record exists in GenBank/RefSeq. We compared the genomic sequence of NIH LVR42-0/M6941 acquired from the ATCC in 2011 to NIH LVR42-0/M6941 genomes sequenced directly from nonhuman primates experimentally infected in 1989.
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IP-10 and MIG are compartmentalized at the site of disease during pleural and meningeal tuberculosis and are decreased after anti-tuberculosis treatment.
Clin. Vaccine Immunol.
PUBLISHED: 10-03-2014
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The diagnosis of active tuberculosis (TB) disease remains a challenge especially in high-burden settings. Cytokines and chemokines are important in the pathogenesis of TB. Here, we investigate the usefulness of circulating and compartmentalized cytokines/chemokines for diagnosis of TB. The levels of multiple cytokines/chemokines in plasma, pleural fluid (PF) and cerebrospinal fluid (CSF) were determined by Luminex liquid array-based multiplexed immunoassays. Three of 26 cytokines/chemokines in plasma were significantly different between TB and latent tuberculosis infection (LTBI). Among them, IP-10 and MIG had the highest diagnostic values, with an area under the receiver operating characteristic curve (ROC AUC) of 0.92 for IP-10 and 0.86 for MIG to distinguish TB from LTBI. However, IP-10 and MIG in plasma were not different between TB and non-TB lung disease. In contrast, compartmentalized IP-10 and MIG in the PF and CSF showed promising diagnostic values in discriminating TB and non-TB pleural effusion (AUC=0.87 for IP-10, AUC=0.93 for MIG), as well as TB meningitis and non-TB meningitis (AUC=0.9 for IP-10, AUC=0.95 for MIG). A longitudinal study showed that the plasma levels of IP-10, MIG, G-CSF and IFN-Y decreased, while the levels of MCP-1/CCL2 and Eotaxin-1/CCL11 increased, after successful treatment of TB. Our findings provided a practical methodology for discriminating active TB from LTBI by sequential IGRAs and plasma IP-10 test, while increased IP-10 and MIG at the site of infection (PF or CSF) can be used a marker for distinguishing pleural effusion and meningitis caused by TB from those by non-TB.
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Prognostic nomograms for predicting survival and distant metastases in locally advanced rectal cancers.
PLoS ONE
PUBLISHED: 08-29-2014
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To develop prognostic nomograms for predicting outcomes in patients with locally advanced rectal cancers who do not receive preoperative treatment.
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Influenza A Virus Polymerase Is a Site for Adaptive Changes during Experimental Evolution in Bat Cells.
J. Virol.
PUBLISHED: 08-20-2014
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The recent identification of highly divergent influenza A viruses in bats revealed a new, geographically dispersed viral reservoir. To investigate the molecular mechanisms of host-restricted viral tropism and the potential for transmission of viruses between humans and bats, we exposed a panel of cell lines from bats of diverse species to a prototypical human-origin influenza A virus. All of the tested bat cell lines were susceptible to influenza A virus infection. Experimental evolution of human and avian-like viruses in bat cells resulted in efficient replication and created highly cytopathic variants. Deep sequencing of adapted human influenza A virus revealed a mutation in the PA polymerase subunit not previously described, M285K. Recombinant virus with the PA M285K mutation completely phenocopied the adapted virus. Adaptation of an avian virus-like virus resulted in the canonical PB2 E627K mutation that is required for efficient replication in other mammals. None of the adaptive mutations occurred in the gene for viral hemagglutinin, a gene that frequently acquires changes to recognize host-specific variations in sialic acid receptors. We showed that human influenza A virus uses canonical sialic acid receptors to infect bat cells, even though bat influenza A viruses do not appear to use these receptors for virus entry. Our results demonstrate that bats are unique hosts that select for both a novel mutation and a well-known adaptive mutation in the viral polymerase to support replication.
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Analysis of prevacuolar compartment-mediated vacuolar proteins transport.
Methods Mol. Biol.
PUBLISHED: 08-14-2014
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Transient expression using protoplasts is a quick and powerful tool for studying protein trafficking and subcellular localization in plant cells. Prevacuolar compartments (PVCs) or multivesicular bodies (MVBs) are intermediate compartments that mediate protein transport between late Golgi or trans-Golgi network (TGN) and vacuole. Both wortmannin treatment and ARA7(Q69L) expression can induce PVC homotypic fusion and PVC enlargement in plant cells. Here, we describe detailed protocols to use transient expression of protoplasts derived from Arabidopsis suspension culture cells for studying protein trafficking and localization. Using three GFP-tagged vacuolar cargo proteins and RFP-tagged PVC membrane marker as examples, we illustrate the major tools and methods, including wortmannin treatment, ARA7(Q69L) expression and immunoblot analysis, to analyze PVC-mediated vacuolar protein transport in plant cells.
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Clinicopathological and genetic features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC).
Med. Oncol.
PUBLISHED: 08-10-2014
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The aim of this study was to investigate the clinical value of different criteria and to understand the relationship between genotype and phenotype in Chinese hereditary nonpolyposis colorectal cancer (HNPCC). A total of 116 unrelated probands of suspected HNPCC families from the Fudan Colorectal Registry were studied. A total of 32, 28, and 56 families fulfilled the Amsterdam criteria, the Fudan criteria and the revised Bethesda guideline, respectively. Direct DNA sequencing of all exons of hMSH2 and hMLH1 genes were performed on all 116 samples. Mutations and clinicopathological features were compared between the groups. Thirty-two pathological germline mutations were identified. Out of 32 mutations, 16 were located at hMLH1 and 16 at hMSH2. The sensitivity of Amsterdam criteria was 50%, specificity was 81%, and Youden's index was 31%. The sensitivity of Fudan criteria was 75%, specificity was 58%, and Youden's index was 33%. Among all the 32 families with mutations, families with hMSH2 mutation had a higher ratio of synchronous and metachronous colon cancers than families with hMLH1 mutation (33 vs. 6%, P=0.04). Patients with hMSH2 mutation more frequently harbour synchronous and metachronous colon cancers. Fudan criteria had a little higher sensitivity and accuracy than Amsterdam criteria for identification of Chinese HNPCC.
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PIM1 kinase phosphorylates the human transcription factor FOXP3 at serine 422 to negatively regulate its activity under inflammation.
J. Biol. Chem.
PUBLISHED: 08-05-2014
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Previous reports have suggested that human CD4(+) CD25(hi)FOXP3(+) T regulatory cells (Tregs) have functional plasticity and may differentiate into effector T cells under inflammation. The molecular mechanisms underlying these findings remain unclear. Here we identified the residue serine 422 of human FOXP3 as a phosphorylation site that regulates its function, which is not present in murine Foxp3. PIM1 kinase, which is highly expressed in human Tregs, was found to be able to interact with and to phosphorylate human FOXP3 at serine 422. T cell receptor (TCR) signaling inhibits PIM1 induction, whereas IL-6 promotes PIM1 expression in in vitro expanded human Tregs. PIM1 negatively regulates FOXP3 chromatin binding activity by specifically phosphorylating FOXP3 at Ser(422). Our data also suggest that phosphorylation of FOXP3 at the Ser(418) site could prevent FOXP3 phosphorylation at Ser(422) mediated by PIM1. Knockdown of PIM1 in in vitro expanded human Tregs promoted FOXP3-induced target gene expression, including CD25, CTLA4, and glucocorticoid-induced tumor necrosis factor receptor (GITR), or weakened FOXP3-suppressed IL-2 gene expression and enhanced the immunosuppressive activity of Tregs. Furthermore, PIM1-specific inhibitor boosted FOXP3 DNA binding activity in in vitro expanded primary Tregs and also enhanced their suppressive activity toward the proliferation of T effector cells. Taken together, our findings suggest that PIM1 could be a new potential therapeutic target in the prevention and treatment of human-specific autoimmune diseases because of its ability to modulate the immunosuppressive activity of human Tregs.
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Use of Hematopoietic Growth Factors in Elderly Lung Cancer Patients Receiving Chemotherapy: A SEER-Medicare-based Study.
Am. J. Clin. Oncol.
PUBLISHED: 07-29-2014
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Hematopoietic growth factors (HGFs) are essential for successful completion of chemotherapy in lung cancer patients. However, because of their adverse effects, clinical guidelines recommend their use in only selective clinical scenarios. This study, for the first time, explores patient characteristics and temporal trends associated with HGF utilization among elderly lung cancer patients receiving chemotherapy.
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Cell entry by a novel European filovirus requires host endosomal cysteine proteases and Niemann-Pick C1.
Virology
PUBLISHED: 07-06-2014
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Lloviu virus (LLOV), a phylogenetically divergent filovirus, is the proposed etiologic agent of die-offs of Schreibers?s long-fingered bats (Miniopterus schreibersii) in western Europe. Studies of LLOV remain limited because the infectious agent has not yet been isolated. Here, we generated a recombinant vesicular stomatitis virus expressing the LLOV spike glycoprotein (GP) and used it to show that LLOV GP resembles other filovirus GP proteins in structure and function. LLOV GP must be cleaved by endosomal cysteine proteases during entry, but is much more protease-sensitive than EBOV GP. The EBOV/MARV receptor, Niemann-Pick C1 (NPC1), is also required for LLOV entry, and its second luminal domain is recognized with high affinity by a cleaved form of LLOV GP, suggesting that receptor binding would not impose a barrier to LLOV infection of humans and non-human primates. The use of NPC1 as an intracellular entry receptor may be a universal property of filoviruses.
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Modified THz electro-optic sampling for high optical modulation depth, large dynamical range, and low background noises.
Opt Lett
PUBLISHED: 07-01-2014
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We present a modified THz electro-optic sampling method to combine the advantages of its two traditional counterparts at near 0° and 45° optical biases: excellent ability to cancel the background noises, high optical modulation, and large dynamical range. The first advantage results from the method's symmetrical layout to get dynamical noise cancellation. By setting the static birefringent phases of the two balanced beams with a pair of opposite numbers, our setup can record THz waveforms without distortion with its maximal modulation depth, thus optimal signal-to-noise ratio (SNR). The setting also releases the linearity of the measured signal from the static birefringence, thus enlarging greatly the linear dynamical range. For a given THz field, the recorded SNR with our setup, without a lock-in, is more than 10 times higher than that with the "crossed and balanced" design [IEEE Trans. Microwave Theory Tech. 47, 2644 (1999)].
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[Prediction of efficacy of neoadjuvant radiochemotherapy based on depth of invasion in T3 rectal cancer].
Zhonghua Wei Chang Wai Ke Za Zhi
PUBLISHED: 06-24-2014
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To investigate the association of mesorectal invasion depth before neoadjuvant radiochemotherapy with pathological outcome and to provide evidence for individualized treatment in T3 rectal cancer.
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Exploring personalized searches using tag-based user profiles and resource profiles in folksonomy.
Neural Netw
PUBLISHED: 05-25-2014
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With the increase in resource-sharing websites such as YouTube and Flickr, many shared resources have arisen on the Web. Personalized searches have become more important and challenging since users demand higher retrieval quality. To achieve this goal, personalized searches need to take users' personalized profiles and information needs into consideration. Collaborative tagging (also known as folksonomy) systems allow users to annotate resources with their own tags, which provides a simple but powerful way for organizing, retrieving and sharing different types of social resources. In this article, we examine the limitations of previous tag-based personalized searches. To handle these limitations, we propose a new method to model user profiles and resource profiles in collaborative tagging systems. We use a normalized term frequency to indicate the preference degree of a user on a tag. A novel search method using such profiles of users and resources is proposed to facilitate the desired personalization in resource searches. In our framework, instead of the keyword matching or similarity measurement used in previous works, the relevance measurement between a resource and a user query (termed the query relevance) is treated as a fuzzy satisfaction problem of a user's query requirements. We implement a prototype system called the Folksonomy-based Multimedia Retrieval System (FMRS). Experiments using the FMRS data set and the MovieLens data set show that our proposed method outperforms baseline methods.
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Engineering single crystalline Mn3O4 nano-octahedra with exposed highly active {011} facets for high performance lithium ion batteries.
Nanoscale
PUBLISHED: 05-16-2014
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Well shaped single crystalline Mn3O4 nano-octahedra with exposed highly active {011} facets at different particle sizes have been synthesized and used as anode materials for lithium ion batteries. The electrochemical results show that the smallest sized Mn3O4 nano-octahedra show the best cycling performance with a high initial charge capacity of 907 mA h g(-1) and a 50th charge capacity of 500 mA h g(-1) at a current density of 50 mA g(-1) and the best rate capability with a charge capacity of 350 mA h g(-1) when cycled at 500 mA g(-1). In particular, the nano-octahedra samples demonstrate a much better electrochemical performance in comparison with irregular shaped Mn3O4 nanoparticles. The best electrochemical properties of the smallest Mn3O4 nano-octahedra are ascribed to the lower charge transfer resistance due to the exposed highly active {011} facets, which can facilitate the conversion reaction of Mn3O4 and Li owing to the alternating Mn and O atom layers, resulting in easy formation and decomposition of the amorphous Li2O and the multi-electron reaction. On the other hand, the best electrochemical properties of the smallest Mn3O4 nano-octahedra can also be attributed to the smallest size resulting in the highest specific surface area, which provides maximum contact with the electrolyte and facilitates the rapid Li-ion diffusion at the electrode/electrolyte interface and fast lithium-ion transportation within the particles. The synergy of the exposed {011} facets and the smallest size (and/or the highest surface area) led to the best performance for the Mn3O4 nano-octahedra. Furthermore, HRTEM observations verify the oxidation of MnO to Mn3O4 during the charging process and confirm that the Mn3O4 octahedral structure can still be partly maintained after 50 discharge-charge cycles. The high Li-ion storage capacity and excellent cycling performance suggest that Mn3O4 nano-octahedra with exposed highly active {011} facets could be excellent anode materials for high-performance lithium-ion batteries.
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The Arabidopsis Endosomal Sorting Complex Required for Transport III Regulates Internal Vesicle Formation of the Prevacuolar Compartment and Is Required for Plant Development.
Plant Physiol.
PUBLISHED: 05-08-2014
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We have established an efficient transient expression system with several vacuolar reporters to study the roles of endosomal sorting complex required for transport (ESCRT)-III subunits in regulating the formation of intraluminal vesicles of prevacuolar compartments (PVCs)/multivesicular bodies (MVBs) in plant cells. By measuring the distributions of reporters on/within the membrane of PVC/MVB or tonoplast, we have identified dominant negative mutants of ESCRT-III subunits that affect membrane protein degradation from both secretory and endocytic pathways. In addition, induced expression of these mutants resulted in reduction in luminal vesicles of PVC/MVB, along with increased detection of membrane-attaching vesicles inside the PVC/MVB. Transgenic Arabidopsis (Arabidopsis thaliana) plants with induced expression of ESCRT-III dominant negative mutants also displayed severe cotyledon developmental defects with reduced cell size, loss of the central vacuole, and abnormal chloroplast development in mesophyll cells, pointing out an essential role of the ESCRT-III complex in postembryonic development in plants. Finally, membrane dissociation of ESCRT-III components is important for their biological functions and is regulated by direct interaction among Vacuolar Protein Sorting-Associated Protein20-1 (VPS20.1), Sucrose Nonfermenting7-1, VPS2.1, and the adenosine triphosphatase VPS4/SUPPRESSOR OF K(+) TRANSPORT GROWTH DEFECT1.
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The effect of colonoscopy on whole blood gene expression profile: an experimental investigation for colorectal cancer biomarker discovery.
J. Cancer Res. Clin. Oncol.
PUBLISHED: 05-07-2014
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Gene expression profiling of whole blood is showing great promise for the discovery of novel biomarkers for colorectal cancer (CRC) detection. Given the relatively low incidence rate of CRC in the general population, most blood samples collected prior to a colonoscopy were confirmed to be noncancerous afterward. Previous studies have relied on blood samples collected after a colonoscopy to reach the sufficient number of CRC cases. The present study aimed to determine the colonoscopy-induced variability in the blood transcriptome and its potential impact on biomarker discovery.
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Community-aware user profile enrichment in folksonomy.
Neural Netw
PUBLISHED: 05-04-2014
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In the era of big data, collaborative tagging (a.k.a. folksonomy) systems have proliferated as a consequence of the growth of Web 2.0 communities. Constructing user profiles from folksonomy systems is useful for many applications such as personalized search and recommender systems. The identification of latent user communities is one way to better understand and meet user needs. The behavior of users is highly influenced by the behavior of their neighbors or community members, and this can be utilized in constructing user profiles. However, conventional user profiling techniques often encounter data sparsity problems as data from a single user is insufficient to build a powerful profile. Hence, in this paper we propose a method of enriching user profiles based on latent user communities in folksonomy data. Specifically, the proposed approach contains four sub-processes: (i) tag-based user profiles are extracted from a folksonomy tripartite graph; (ii) a multi-faceted folksonomy graph is constructed by integrating tag and image affinity subgraphs with the folksonomy tripartite graph; (iii) random walk distance is used to unify various relationships and measure user similarities; (iv) a novel prototype-based clustering method based on user similarities is used to identify user communities, which are further used to enrich the extracted user profiles. To evaluate the proposed method, we conducted experiments using a public dataset, the results of which show that our approach outperforms previous ones in user profile enrichment.
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Low expression of novel lncRNA RP11-462C24.1 suggests a biomarker of poor prognosis in colorectal cancer.
Med. Oncol.
PUBLISHED: 04-09-2014
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Long noncoding RNAs (lncRNAs) have recently emerged as a major class of regulatory molecules, which were involved in a broad range of biological processes and complex diseases. Research on lncRNAs may shed light on tumorigenesis and progression of colorectal cancer (CRC). The purpose of the present study was to identify lncRNAs correlated with CRC and then investigate their potential functions. We selected 92 patients for this prospective study and then collected the tumor samples and clinical records. First, the global lncRNA expression profiles in tumor and adjacent normal tissues of patients with non-metastatic CRC and patients with metastatic CRC were measured by microarray assay. Then, a noteworthy lncRNAs RP11-462C24.1 whose function was previously unknown was explored in detail on the aspect of the association of its expression level and clinicopathological features of CRC and patients' survival. We found that RP11-462C24.1 expression level was lower in cancer tissues compared with adjacent normal samples (P < 0.001). Furthermore, its expression level was lower in CRC patients with metastasis than those without metastasis (P = 0.049). That is, RP11-462C24.1 expression level decreased as the malignant degree of CRC increased. In addition, low expression of RP11-462C24.1 significantly correlated with more distant metastasis (P = 0.011). The areas under ROC curves were 0.78 and 0.65 for RP11-462C24.1, distinguishing CRC from normal tissue and distinguishing CRC without metastasis from CRC with metastasis, respectively. Multivariate analysis identified that RP11-462C24.1 was an independent predictor for patients prognosis (P = 0.005). Furthermore, Kaplan-Meier analysis showed that patients with low expression of RP11-462C24.1 had a poor disease-free survival (P < 0.001). This is the first study that correlates RP11-462C24.1 expression profile with malignancy grade in human CRC. Our results showed that RP11-462C24.1 could be a potential novel prognostic marker for CRC, and thus, provided a new strategy for CRC diagnosis. Meanwhile, our findings indicated the potential roles of RP11-462C24.1 in tumorigenesis and progression of CRC, which gave a clue for future studies.
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Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival.
Mol. Cancer
PUBLISHED: 04-06-2014
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The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs.
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Performance comparison of spectrum-narrowing equalizations with maximum likelihood sequence estimation and soft-decision output.
Opt Express
PUBLISHED: 03-26-2014
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Maximum likelihood sequence estimation (MLSE) offers effective equalizations for bandwidth-limited optical signal on mitigation towards inter-symbol-interference (ISI) impairment. In this paper, we provide the first comprehensive comparisons and analysis of three post-compensation algorithms on the same modeling platform for high spectral-efficiency (SE) optical systems employing the spectral prefiltering. Those algorithms include 1-tap constant modulus algorithm (CMA) and 3-tap MLSE, regular CMA and digital filter with 2-tap MLSE, and constant multi-modulus algorithm (CMMA) with 2-tap MLSE. Furthermore, a novel and effective approach is proposed and verified for the generation of both hard value and soft value at the output of MLSE in order to be compatible with the implementation of soft-decision forward error correction (SD-FEC) decoding process.
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Coupling of ultrafast LC with mass spectrometry by DESI.
J. Am. Soc. Mass Spectrom.
PUBLISHED: 03-25-2014
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Recently we reported a desorption electrospray ionization (DESI) interface to combine liquid chromatography (LC) with mass spectrometry (MS) using a new LC eluent splitting strategy through a tiny orifice on LC capillary tube [J. Am. Soc. Mass Spectrom. 25, 286 (2014)]. The interface introduces negligible dead volume and back pressure, thereby allowing "near real-time" MS detection, fast LC elution, and online MS-directed purification. This study further evaluates the LC/DESI-MS performance with focus of using ultra-fast LC. Using a monolithic C18 column, metabolites in urine can be separated within 1.6 min and can be online collected for subsequent structure elucidation (e.g., by NMR, UV, IR) in a recovery yield up to 99%. Using a spray solvent with alkaline pH, negative ions could be directly generated for acidic analytes (e.g., ibuprofen) in acidic LC eluent by DESI, offering a novel protocol to realize "wrong-way around" ionization for LC/MS analysis. In addition, DESI-MS is found to be compatible with ultra-performance liquid chromatography (UPLC) for the first time.
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CXCL10 mRNA expression predicts response to neoadjuvant chemoradiotherapy in rectal cancer patients.
Tumour Biol.
PUBLISHED: 03-25-2014
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Chemoradiotherapy has been commonly used as neoadjuvant therapy for rectal cancer to allow for less aggressive surgical approaches and to improve quality of life. In cancer, it has been reported that CXCL10 has an anti-tumor function. However, the association between CXCL10 and chemoradiosensitivity has not been fully investigated. We performed this study to investigate the relationship between CXCL10 expression and chemoradiosensitivity in rectal cancer patients. Ninety-five patients with rectal cancer who received neoadjuvant chemoradiotherapy (NCRT) were included. Clinical parameters were compared with the outcome of NCRT and CXCL10 messenger RNA (mRNA) expression between the pathological complete response (pCR) group and non-pathological complete response (npCR) group. CXCL10 mRNA and protein expressions between groups were analyzed using the Student's t test and chi-square test. The mean mRNA level of CXCL10 in the pCR group was significantly higher than that in the npCR group (p?=?0.010). In the pCR group, 73.7 % of the patients had high CXCL10 mRNA expression, and 61.4 % of the patients in the npCR group had low CXCL10 mRNA expression. Subjects with high CXCL10 mRNA expression demonstrated a higher sensitivity to NCRT (p?=?0.011). The receiver operating characteristic curve showed that the diagnostic performance of CXCL10 mRNA expression had an area under the curve of 0.720 (95 % confidence interval, 0.573-0.867). There were no differences between the pCR and npCR groups in CXCL10 protein expression (p?>?0.05). High CXCL10 mRNA expression is associated with a better tumor response to NCRT in rectal cancer patients and may predict the outcome of NCRT in this malignancy.
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MicroRNA-223 enhances radiation sensitivity of U87MG cells in vitro and in vivo by targeting ataxia telangiectasia mutated.
Int. J. Radiat. Oncol. Biol. Phys.
PUBLISHED: 03-11-2014
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Ataxia telangiectasia mutated (ATM) protein is important in the DNA damage response because it repairs radiation-induced damage in cancers. We examined the effect of microRNA-223 (miR-223), a regulator of ATM expression, on radiation sensitivity of cancer cells.
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Glucocorticoid receptor activity contributes to resistance to androgen-targeted therapy in prostate cancer.
Horm Cancer
PUBLISHED: 02-18-2014
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Despite new treatments for castrate-resistant prostate cancer (CRPC), the prognosis of patients with CRPC remains bleak due to acquired resistance to androgen receptor (AR)-directed therapy. The glucocorticoid receptor (GR) and AR share several transcriptional targets, including the anti-apoptotic genes serum and g lucocorticoid-regulated kinase 1 (SGK1) and Map kinase phosphatase 1 (MKP1)/dual specificity phosphatase 1 (DUSP1). Because GR expression increases in a subset of primary prostate cancer (PC) following androgen deprivation therapy, we sought to determine whether GR activation can contribute to resistance to AR-directed therapy. We studied CWR-22Rv1 and LAPC4 AR/GR-expressing PC cell lines following treatment with combinations of the androgen R1881, AR antagonist MDV3100, GR agonist dexamethasone, GR antagonists mifepristone and CORT 122928, or the SGK1 inhibitor GSK650394. Cell lines stably expressing GR (NR3C1)-targeted shRNA or ectopic SGK1-Flag were also studied in vivo. GR activation diminished the effects of the AR antagonist MDV3100 on tumor cell viability. In addition, GR activation increased prostate-specific antigen (PSA) secretion and induced SGKI and MKP1/DUSP gene expression. Glucocorticoid-mediated cell viability was diminished by a GR antagonist or by co-treatment with the SGK1 inhibitor GSK650394. In vivo, GR depletion delayed castrate-resistant tumor formation, while SGK1-Flag-overexpressing PC xenografts displayed accelerated castrate-resistant tumor initiation, supporting a role for SGK1 in GR-mediated CRPC progression. We studied several PC models before and following treatment with androgen blockade and found that increased GR expression and activity contributed to tumor-promoting PC cell viability. Increased GR-regulated SGK1 expression appears, at least in part, to mediate enhanced PC cell survival. Therefore, GR and/or SGK1 inhibition may be useful adjuncts to AR blockade for treating CRPC.
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A distinct metabolic signature of human colorectal cancer with prognostic potential.
Clin. Cancer Res.
PUBLISHED: 02-13-2014
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Metabolic phenotyping has provided important biomarker findings, which, unfortunately, are rarely replicated across different sample sets due to the variations from different analytical and clinical protocols used in the studies. To date, very few metabolic hallmarks in a given cancer type have been confirmed and validated by use of a metabolomic approach and other clinical modalities. Here, we report a metabolomics study to identify potential metabolite biomarkers of colorectal cancer with potential theranostic value.
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Facile synthesis of hierarchical and porous V2O5 microspheres as cathode materials for lithium ion batteries.
J Colloid Interface Sci
PUBLISHED: 01-28-2014
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Hierarchical and porous V2O5 microspheres have been fabricated by a refluxing approach followed by annealing in air. The resulting porous V2O5 microspheres typically have diameters of 3-6 ?m and are constructed of intertwined laminar nanocrystals or crosslinked nanobricks. It is found that the vanadyl glycolates rinsed with water have pronounced pore structures than that rinsed with ethanol alone. In addition, the configuration of the vanadyl glycolates microspheres can be tuned during the refluxing along with stirring. The possible formation processes of the vanadyl glycolates and V2O5 products have been discussed based on the experimental data. Electrochemical tests indicate that the hierarchical and porous V2O5 microspheres exhibit relatively high and stable Li(+) storage properties. The porous V2O5 microspheres assembled by intertwined nanoparticles maintain reversible Li(+) storage capacities of 102 and 80 mAh g(-1), respectively; whilst the porous V2O5 microspheres assembled by crosslinked nanobricks maintain reversible Li(+) storage capacities of 100 and 85 mAh g(-1) over 100 cycles at current rates of 0.5 and 1 C, respectively. The superior Li(+) storage performance of the hierarchical and porous V2O5 microspheres could mainly be ascribed to the improved electrode/electrolyte interface, reduced Li(+) diffusion paths, and relieved volume variation during lithiation and delithiation processes.
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Retention mechanisms for ER and Golgi membrane proteins.
Trends Plant Sci.
PUBLISHED: 01-23-2014
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Unless there are mechanisms to selectively retain membrane proteins in the endoplasmic reticulum (ER) or in the Golgi apparatus, they automatically proceed downstream to the plasma or vacuole membranes. Two types of coat protein complex I (COPI)-interacting motifs in the cytosolic tails of membrane proteins seem to facilitate membrane retention in the early secretory pathway of plants: a dilysine (KKXX) motif (which is typical of p24 proteins) for the ER and a KXE/D motif (which occurs in the Arabidopsis endomembrane protein EMP12) for the Golgi apparatus. The KXE/D motif is highly conserved in all eukaryotic EMPs and is additionally present in hundreds of other proteins of unknown subcellular localization and function. This novel signal may represent a new general mechanism for Golgi targeting and the retention of polytopic integral membrane proteins.
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Solitary lymph node metastasis is a distinct subset of colon cancer associated with good survival: a retrospective study of surveillance, epidemiology, and end-results population-based data.
BMC Cancer
PUBLISHED: 01-15-2014
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Colon cancer with lymph node metastases has been considered as advanced stage and to have poor survival. We postulated that patients with solitary lymph node metastasis are a distinct subset with better colon cancer-specific survival than those with multiple lymph node metastases.
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Development of a miniature dielectric barrier discharge-optical emission spectrometric system for bromide and bromate screening in environmental water samples.
Anal. Chim. Acta
PUBLISHED: 01-15-2014
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Dielectric barrier discharge (DBD) at atmospheric pressure provides an efficient radiation source for the excitation of bromine and it is used for the first time for optical emission spectrometric (OES) detection of bromide and bromate. A portable DBD-OES system is developed for screening potential pollution from bromide and bromate in environmental waters. Bromide is on-line oxidized to bromine for in-situ generation of volatile bromine. Meanwhile, a helium stream carries bromine into the DBD micro-plasma for its excitation at a discharging voltage of 3.7 kV and optical emission spectrometric detection with a QE65000 charge-coupled device (CCD) spectrometer in the near-infrared spectral region. Similarly, the quantification of bromate is performed by its pre-reduction into bromide and then oxidized to bromine. The spectral characteristics and configuration of the DBD micro-plasma excitation source in addition to the oxidation vapor generation of bromine have been thoroughly investigated. With a sampling volume of 1 mL, a linear range of 0.05-10.0 mg L(-1) is obtained with a detection limit of 0.014 mg L(-1) by measuring the emission at 827 nm. A precision of 2.3% is achieved at 3 mg L(-1) bromide. The system is validated by bromine detection in certified reference material of laver (GBW10023) at mg L(-1) level, giving rise to satisfactory agreement. In addition, it is further demonstrated by screening trace bromide and bromate as well as spiking recoveries in a series of environmental water samples.
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Prognostic and predictive value of CpG island methylator phenotype in patients with locally advanced nonmetastatic sporadic colorectal cancer.
Gastroenterol Res Pract
PUBLISHED: 01-14-2014
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Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P = 0.049) and CIMP positive (P = 0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193-7.220 (P = 0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P = 0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy.
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Facile and fast synthesis of porous TiO2 spheres for use in lithium ion batteries.
J Colloid Interface Sci
PUBLISHED: 01-11-2014
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Porous anatase TiO2 spheres have been synthesized by a microwave-assisted hydrothermal reaction of spherical particle precursors followed by annealing in air. The synthesized TiO2 spheres are formed by interconnected nanocrystals with size of 8.7 nm in average and have grain diameters of 250-400 nm. After annealing at 500°C, the TiO2 samples maintain spherical shape and develop highly mesoporous characteristics with a specific surface area of 151 m(2) g(-1). The TiO2 samples annealed at 750°C consist of larger aggregated particles with diameters of 500-900 nm and still retain mesoporous anatase structure, but with a reduced specific surface area of 25.6 m(2) g(-1). Electrochemical studies reveal that the porous TiO2 spheres annealed at 500°C own very high and stable lithium ion (Li(+)) storage capacities of 207, 184, 166, and 119 mA h g(-1) at 0.5, 1, 2, and 5C (850 mA g(-1)) rates, respectively, owing to their highly porous nanostructures and fine spherical morphology. In contrast, the TiO2 spheres annealed at 700°C exhibit modest electrochemical performance due to their reduced pore structures and larger crystallite size. The prepared porous TiO2 spherical particles show great promise for use as high performance anode materials for lithium ion batteries (LIBs).
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Concomitant boost IMRT-based neoadjuvant chemoradiotherapy for clinical stage II/III rectal adenocarcinoma: results of a phase II study.
Radiat Oncol
PUBLISHED: 01-08-2014
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This study was designed to evaluate the efficacy and toxicities of concomitant boost intensity-modulated radiation therapy (IMRT) along with capecitabine and oxaliplatin, followed by a cycle of Xelox, in neoadjuvant course for locally advanced rectal cancer.
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CD26/DPP4 Cell-Surface Expression in Bat Cells Correlates with Bat Cell Susceptibility to Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection and Evolution of Persistent Infection.
PLoS ONE
PUBLISHED: 01-01-2014
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Middle East respiratory syndrome coronavirus (MERS-CoV) is a recently isolated betacoronavirus identified as the etiologic agent of a frequently fatal disease in Western Asia, Middle East respiratory syndrome. Attempts to identify the natural reservoirs of MERS-CoV have focused in part on dromedaries. Bats are also suspected to be reservoirs based on frequent detection of other betacoronaviruses in these mammals. For this study, ten distinct cell lines derived from bats of divergent species were exposed to MERS-CoV. Plaque assays, immunofluorescence assays, and transmission electron microscopy confirmed that six bat cell lines can be productively infected. We found that the susceptibility or resistance of these bat cell lines directly correlates with the presence or absence of cell surface-expressed CD26/DPP4, the functional human receptor for MERS-CoV. Human anti-CD26/DPP4 antibodies inhibited infection of susceptible bat cells in a dose-dependent manner. Overexpression of human CD26/DPP4 receptor conferred MERS-CoV susceptibility to resistant bat cell lines. Finally, sequential passage of MERS-CoV in permissive bat cells established persistent infection with concomitant downregulation of CD26/DPP4 surface expression. Together, these results imply that bats indeed could be among the MERS-CoV host spectrum, and that cellular restriction of MERS-CoV is determined by CD26/DPP4 expression rather than by downstream restriction factors.
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Impaired Autophagy Contributes to Adverse Cardiac Remodeling in Acute Myocardial Infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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Autophagy is activated in ischemic heart diseases, but its dynamics and functional roles remain unclear and controversial. In this study, we investigated the dynamics and role of autophagy and the mechanism(s), if any, during postinfarction cardiac remodeling.
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Human RAD6 Promotes G1-S Transition and Cell Proliferation through Upregulation of Cyclin D1 Expression.
PLoS ONE
PUBLISHED: 01-01-2014
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Protein ubiquitinylation regulates protein stability and activity. RAD6, an E2 ubiquitin-conjugating enzyme, which that has been substantially biochemically characterized, functions in a number of biologically relevant pathways, including cell cycle progression. In this study, we show that RAD6 promotes the G1-S transition and cell proliferation by regulating the expression of cyclin D1 (CCND1) in human cells. Furthermore, our data indicate that RAD6 influences the transcription of CCND1 by increasing monoubiquitinylation of histone H2B and trimethylation of H3K4 in the CCND1 promoter region. Our study presents, for the first time, an evidence for the function of RAD6 in cell cycle progression and cell proliferation in human cells, raising the possibility that RAD6 could be a new target for molecular diagnosis and prognosis in cancer therapeutics.
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Risk Factors of Synchronous Inguinal Lymph Nodes Metastasis for Lower Rectal Cancer Involving the Anal Canal.
PLoS ONE
PUBLISHED: 01-01-2014
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The aim of the study is to identify the risk factors of synchronous ILN metastasis for lower rectal cancer involving the anal canal.
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Reliability Analysis of the Electrical Control System of Subsea Blowout Preventers Using Markov Models.
PLoS ONE
PUBLISHED: 01-01-2014
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Reliability analysis of the electrical control system of a subsea blowout preventer (BOP) stack is carried out based on Markov method. For the subsea BOP electrical control system used in the current work, the 3-2-1-0 and 3-2-0 input voting schemes are available. The effects of the voting schemes on system performance are evaluated based on Markov models. In addition, the effects of failure rates of the modules and repair time on system reliability indices are also investigated.
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Hypomethylation-Associated Up-Regulation of TCF3 Expression and Recurrence in Stage II and III Colorectal Cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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Transcription factor 3 (TCF3) implicates Wnt signaling pathway and regulates E-cadherin expression, which is involved in aggressiveness of tumors. This study aims to investigate the role of TCF3 in predicting prognosis of patients with stage II and III colorectal cancer (CRC).
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Influence of electrical resistivity and machining parameters on electrical discharge machining performance of engineering ceramics.
PLoS ONE
PUBLISHED: 01-01-2014
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Engineering ceramics have been widely used in modern industry for their excellent physical and mechanical properties, and they are difficult to machine owing to their high hardness and brittleness. Electrical discharge machining (EDM) is the appropriate process for machining engineering ceramics provided they are electrically conducting. However, the electrical resistivity of the popular engineering ceramics is higher, and there has been no research on the relationship between the EDM parameters and the electrical resistivity of the engineering ceramics. This paper investigates the effects of the electrical resistivity and EDM parameters such as tool polarity, pulse interval, and electrode material, on the ZnO/Al2O3 ceramic's EDM performance, in terms of the material removal rate (MRR), electrode wear ratio (EWR), and surface roughness (SR). The results show that the electrical resistivity and the EDM parameters have the great influence on the EDM performance. The ZnO/Al2O3 ceramic with the electrical resistivity up to 3410 ?·cm can be effectively machined by EDM with the copper electrode, the negative tool polarity, and the shorter pulse interval. Under most machining conditions, the MRR increases, and the SR decreases with the decrease of electrical resistivity. Moreover, the tool polarity, and pulse interval affect the EWR, respectively, and the electrical resistivity and electrode material have a combined effect on the EWR. Furthermore, the EDM performance of ZnO/Al2O3 ceramic with the electrical resistivity higher than 687 ?·cm is obviously different from that with the electrical resistivity lower than 687 ?·cm, when the electrode material changes. The microstructure character analysis of the machined ZnO/Al2O3 ceramic surface shows that the ZnO/Al2O3 ceramic is removed by melting, evaporation and thermal spalling, and the material from the working fluid and the graphite electrode can transfer to the workpiece surface during electrical discharge machining ZnO/Al2O3 ceramic.
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Apparent Diffusion Coefficient (ADC) Value: A Potential Imaging Biomarker That Reflects the Biological Features of Rectal Cancer.
PLoS ONE
PUBLISHED: 01-01-2014
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We elected to analyze the correlation between the pre-treatment apparent diffusion coefficient (ADC) and the clinical, histological, and immunohistochemical status of rectal cancers.
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Pathological features and survival outcomes of young patients with operable colon cancer: are they homogeneous?
PLoS ONE
PUBLISHED: 01-01-2014
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To compare the pathological features and survival outcomes at different age subgroups of young patients with colon cancer.
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Better long-term survival in young patients with non-metastatic colorectal cancer after surgery, an analysis of 69,835 patients in SEER database.
PLoS ONE
PUBLISHED: 01-01-2014
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To compare the long-term survival of colorectal cancer (CRC) in young patients with elderly ones.
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Increased complement C1q level marks active disease in human tuberculosis.
PLoS ONE
PUBLISHED: 01-01-2014
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Complement functions as an important host defense system and complement C5 and C7 have been implicated in immunopathology of tuberculosis. However, little is known about the role of other complement components in tuberculosis.
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Sirtuin 6 protects cardiomyocytes from hypertrophy in vitro via inhibition of NF-?B-dependent transcriptional activity.
Br. J. Pharmacol.
PUBLISHED: 12-18-2013
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Sirtuin 6 (SIRT6) is involved in regulation of glucose and fat metabolism. However, its possible contribution to cardiac dysfunction remains to be determined. In the present study, the effect of SIRT6 on cardiac hypertrophy induced by angiotensin II (AngII) and the underlying molecular mechanisms were investigated.
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Exo70E2 is essential for exocyst subunit recruitment and for EXPO formation in both plants and animals.
Mol. Biol. Cell
PUBLISHED: 12-04-2013
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In contrast to a single copy of Exo70 in yeast and mammals, the Arabidopsis genome contains 23 paralogs of Exo70 (AtExo70). Using AtExo70E2 and its GFP fusion as probes, we have recently identified a novel double-membrane organelle termed EXPO (exocyst-positive organelle) that mediates an unconventional protein secretion in plant cells. Here we further demonstrate that AtExo70E2 is essential for exocyst subunit recruitment and for EXPO formation in both plants and animals. By performing transient expression in Arabidopsis protoplasts we have established that a number of exocyst subunits (especially the members of the Sec family) are unable to be recruited to EXPO in the absence of AtExo70E2. The paralog AtExo70A1 is unable to substitute for AtExo70E2 in this regard. FRET and BiFC analyses have confirmed the interaction between AtExo70E2 and Sec6 and Sec10. AtExo70E2, but not its yeast counterpart, is also capable of inducing EXPO formation in an animal cell line (HEK293A cells). Electron microscopy confirmed the presence of double membraned EXPO-like structures in HEK293A cells expressing AtExo70E2. Inversely, neither human nor yeast Exo70 homologues are able to cause the formation of EXPO in Arabidopsis protoplasts. These results point to a specific and crucial role for AtExo70E2 in EXPO formation.
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Medication Treatment Complexity and Adherence in Children with CKD.
Clin J Am Soc Nephrol
PUBLISHED: 11-21-2013
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The complexity of CKD management in children is increased by the number of comorbid conditions. This study assessed the prevalence of comorbidities in pediatric CKD and the frequency with which multiple comorbidities present together by assessing prevalent medication use by CKD stage and diagnosis and their association with clinical or sociodemographic factors. The association between number and frequency of dosing of medications prescribed and self-report of nonadherence was also assessed.
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Complementary and alternative medicine is expected to make greater contribution in controlling the prevalence of influenza.
Biosci Trends
PUBLISHED: 11-19-2013
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Influenza pandemics are a serious threat to public health in todays world. In the past 10 years, the outbreak of three forms of severe influenza--H5N1, H1N1, and H7N9--has caused tremendous loss of life and property. In order to better cope with pandemics, antivirals such as oseltamivir are being stockpiled in great quantities, placing a substantial burden on government budgets and potentially resulting in massive waste because of the uncertainty as to when an influenza pandemic will strike and whether emerging virus strains will be resistant to the stockpiled drugs. Complementary and alternative medicine (CAM) is generally available, affordable, and commonly used in China and many other countries and CAM has a long track record of fighting influenza. The Chinese Government appropriated funds to intensively investigate herbal medicines in accordance with the principles of evidence-based medicine in order to identify effective, inexpensive, and easily stockpiled medicines. Thus far, several drugs including Shufeng Jiedu capsules, Lianhua Qingwen capsules, Maxing Shigan decoction, Yinqiao powder, and Jinhua Qinggan granules have demonstrated effectiveness in fighting influenza. In the future, CAM is expected to make greater contribution in controlling the prevalence of influenza pandemics.
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A BAR-Domain Protein SH3P2, Which Binds to Phosphatidylinositol 3-Phosphate and ATG8, Regulates Autophagosome Formation in Arabidopsis.
Plant Cell
PUBLISHED: 11-18-2013
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Autophagy is a well-defined catabolic mechanism whereby cytoplasmic materials are engulfed into a structure termed the autophagosome. In plants, little is known about the underlying mechanism of autophagosome formation. In this study, we report that SH3 DOMAIN-CONTAINING PROTEIN2 (SH3P2), a Bin-Amphiphysin-Rvs domain-containing protein, translocates to the phagophore assembly site/preautophagosome structure (PAS) upon autophagy induction and actively participates in the membrane deformation process. Using the SH3P2-green fluorescent protein fusion as a reporter, we found that the PAS develops from a cup-shaped isolation membranes or endoplasmic reticulum-derived omegasome-like structures. Using an inducible RNA interference (RNAi) approach, we show that RNAi knockdown of SH3P2 is developmentally lethal and significantly suppresses autophagosome formation. An in vitro membrane/lipid binding assay demonstrates that SH3P2 is a membrane-associated protein that binds to phosphatidylinositol 3-phosphate. SH3P2 may facilitate membrane expansion or maturation in coordination with the phosphatidylinositol 3-kinase (PI3K) complex during autophagy, as SH3P2 promotes PI3K foci formation, while PI3K inhibitor treatment inhibits SH3P2 from translocating to autophagosomes. Further interaction analysis shows that SH3P2 associates with the PI3K complex and interacts with ATG8s in Arabidopsis thaliana, whereby SH3P2 may mediate autophagy. Thus, our study has identified SH3P2 as a novel regulator of autophagy and provided a conserved model for autophagosome biogenesis in Arabidopsis.
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Association of single nucleotide polymorphisms in MTHFR and ABCG2 with the different efficacy of first-line chemotherapy in metastatic colorectal cancer.
Med. Oncol.
PUBLISHED: 11-12-2013
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Either oxaliplatin- or irinotecan-containing regimen could receive a good effectiveness in patients with metastatic colorectal cancer as the first-line chemotherapy, but not all patients would benefit from the treatment they have received. This study was to investigate the role of single nucleotide polymorphisms (SNPs) of methylenetetrahydrofolate reductase (MTHFR) and ATP-binding cassette sub-family G member 2 (ABCG2) in selecting the most appropriate treatment for individual patients. Ninety-two metastatic colorectal cancer patients treated with first-line 5-fluoropyrimidine (5-FU), leucovorin, and oxaliplatin (FOLFOX), capecitabine, and oxaliplatin (XELOX) and sixty-two patients receiving 5-FU, leucovorin, and irinotecan (FOLFIRI) were reviewed. The SNPs of MTHFR and ABCG2 were detected using gene sequencing method after DNA PCR amplification, which was extracted from peripheral blood karyocytes. Clinical characteristics and gene polymorphisms were evaluated in univariate and multivariate analysis as predictive factors for response rate (RR) and progression-free survival (PFS). In patients bearing 2-4 genotypes of MTHFR 677C/C, MTHFR 1298 A/C or C/C, ABCG2 34G/G, and ABCG2 421C/A or A/A, those who received oxaliplatin-based chemotherapy achieved a higher RR (41.7 vs. 18.8 %, P = 0.027) and longer median PFS (mPFS) than irinotecan-based therapy [8.9 vs. 7.1 m, FOLFIRI: hazard ratio (HR) = 1.722, 95 % confidence interval (CI) 1.026-2.892, P = 0.040, compared with FOLFOX/XELOX]; on the contrary, patients carrying 0 or 1 above genotype exhibited better outcomes after receiving FOLFIRI chemotherapy (mPFS: 9.3 vs. 6.4 m, FOLFIRI: HR = 0.422, 95 % CI 0.205-0.870, P = 0.019, compared with FOLFOX/XELOX). Combination of SNPs with MTHFR and ABCG2 may play a role in helping clinicians to select first-line chemotherapy for patients with metastatic colorectal cancer.
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Pyrosequencing analysis of BRCA1 methylation level in breast cancer cells.
Tumour Biol.
PUBLISHED: 11-07-2013
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BRCA1 and BRCA2 genes are crucial for double-strand break repair by homologous recombination, and mutations in these genes are responsible for most familial breast carcinomas. Cells with inactivating mutations of the BRCA1 or BRCA2 tumor suppressor genes are sensitive to poly (ADP-ribose) polymerase-1 (PARP1) inhibitors. Already in 2010, it has been predicted, that BRCA1 hypermethylation might be sensitive to PARP1 inhibitor. However, till today, a statistically significant proof has been missing, and the effectiveness of PARP1 inhibitors for breast cancer caused by BRCA1 promoter hypermethylation remained elusive. Pyrosequencing has been proposed as an optimal method to investigate the methylation status of the BRCA1 genes. Here, we show for the first time that BRCA1 CpG island hypermethylation is sensitive to PARP1 inhibitors. In clinical settings, this might improve treatment response and provide a more personalized therapy for breast cancer patients. Furthermore, the determination of methylation status of BRCA1 and other genes of the BRCA/homologous recombination (HR) pathway may be an important predictive classifier of response to PARP inhibitor therapy.
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Nonhuman transferrin receptor 1 is an efficient cell entry receptor for ocozocoautla de espinosa virus.
J. Virol.
PUBLISHED: 10-09-2013
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Ocozocoautla de Espinosa virus (OCEV) is a novel, uncultured arenavirus. We found that the OCEV glycoprotein mediates entry into grivet and bat cells through transferrin receptor 1 (TfR1) binding but that OCEV glycoprotein precursor (GPC)-pseudotyped retroviruses poorly entered 53 human cancer cell lines. Interestingly, OCEV and Tacaribe virus could use bat, but not human, TfR1. Replacing three human TfR1 amino acids with their bat ortholog counterparts transformed human TfR1 into an efficient OCEV and Tacaribe virus receptor.
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False-positive Anti-retinal Antibodies as a Cause of Psychogenic Vision Loss.
Ocul. Immunol. Inflamm.
PUBLISHED: 10-08-2013
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Abstract Purpose: To report a case of psychogenic vision loss caused by false-positive anti-retinal antibody testing. Methods: We describe a case of visual and systemic symptoms following anti-retinal antibody detection. The case was analyzed for clinical presentation, diagnosis, and consequences of false-positive testing. Results: The patient presented with decreased vision without detectable pathology on ophthalmic examination. Tests were ordered in search of a diagnosis, including an antibody test. Following detection of anti-retinal antibodies, the patient developed worsening visual symptoms and systemic manifestations. A repeat antibody test performed at our institution revealed negative results, which, in conjunction with lack of visual field expansion, confirmed our suspicion of psychogenic vision loss. Conclusions: Laboratory screening may be limited by test specificity and can lead to false-positive results, affecting the patient psychologically and clinically. Care must be taken in patients with positive anti-retinal antibodies to ensure the presence of definitive disease before initiation of treatment.
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Glucocorticoid receptor antagonism as a novel therapy for triple-negative breast cancer.
Clin. Cancer Res.
PUBLISHED: 09-09-2013
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Triple-negative breast cancer (TNBC) accounts for 10% to 20% of newly diagnosed invasive breast cancer. Finding effective targets for chemotherapy-resistant TNBC has proven difficult in part because of TNBCs molecular heterogeneity. We have previously reported that likely because of the antiapoptotic activity of glucocorticoid receptor (GR) in estrogen receptor (ER)-negative breast epithelial and cancer cells, high GR expression/activity in early-stage TNBC significantly correlates with chemotherapy resistance and increased recurrence. We hypothesized that pretreatment with mifepristone, a GR antagonist, would potentiate the efficacy of chemotherapy in GR+ TNBCs by inhibiting the antiapoptotic signaling pathways of GR and increasing the cytotoxic efficiency of chemotherapy.
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TPX2 is a novel prognostic marker for the growth and metastasis of colon cancer.
J Transl Med
PUBLISHED: 09-04-2013
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We have previously demonstrated an aberrant overexpression of the microtubule-associated protein TPX2 in colon cancer using a genome-wide gene expression profiling analysis. Here, we aim to investigate its expression pattern, clinical significance, and biological function in colon cancer.
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Mitochondrial binding of ?-enolase stabilizes mitochondrial membrane: Its role in doxorubicin-induced cardiomyocyte apoptosis.
Arch. Biochem. Biophys.
PUBLISHED: 09-01-2013
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?-Enolase is a metabolic enzyme in the catabolic glycolytic pathway. In eukaryotic cells, the subcellular compartmentalization of ?-enolase as well as its multifaceted functions has been identified. Here, we report that ?-enolase is a regulator of cardiac mitochondria; it partially located in the mitochondria of rat cardiomyocytes. Doxorubicin treatment displaced ?-enolase from mitochondria, accompanied by activation of mitochondrial cell death pathway. Furthermore, in isolated mitochondria, recombinant ?-enolase significantly alleviated Ca(2+)-induced loss of membrane potential, swelling of matrix and permeabilization of membrane. In contrast, mitochondria from ?-enolase knockdown H9c2 myoblasts underwent more severe membrane depolarization and swelling after Ca(2+) stimulation. In addition, ?-enolase was further identified to interact with voltage dependent anion channel 1 in the outer membrane of mitochondria, which was weakened by doxorubicin. Collectively, the present study indicates that mitochondria-located ?-enolase has a beneficial role in stabilizing mitochondrial membrane. In cardiomyocytes, the displacement of ?-enolase from mitochondria by doxorubicin may involve in activation of the intrinsic cell death pathway.
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A New Splitting Method for Both Analytical and Preparative LC/MS.
J. Am. Soc. Mass Spectrom.
PUBLISHED: 08-23-2013
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This paper presents a novel splitting method for liquid chromatography/mass spectrometry (LC/MS) application, which allows fast MS detection of LC-separated analytes and subsequent online analyte collection. In this approach, a PEEK capillary tube with a micro-orifice drilled on the tube side wall is used to connect with LC column. A small portion of LC eluent emerging from the orifice can be directly ionized by desorption electrospray ionization (DESI) with negligible time delay (6~10 ms) while the remaining analytes exiting the tube outlet can be collected. The DESI-MS analysis of eluted compounds shows narrow peaks and high sensitivity because of the extremely small dead volume of the orifice used for LC eluent splitting (as low as 4 nL) and the freedom to choose favorable DESI spray solvent. In addition, online derivatization using reactive DESI is possible for supercharging proteins and for enhancing their signals without introducing extra dead volume. Unlike UV detector used in traditional preparative LC experiments, this method is applicable to compounds without chromophores (e.g., saccharides) due to the use of MS detector. Furthermore, this splitting method well suits monolithic column-based ultra-fast LC separation at a high elution flow rate of 4 mL/min. Figure ?
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Association between the cytotoxic T-lymphocyte antigen 4 +49A/G polymorphism and bladder cancer risk.
Tumour Biol.
PUBLISHED: 08-13-2013
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Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is a potent immunoregulatory molecule that suppresses antitumor response by downregulating T cell activation. The most studied CTLA-4 +49A/G polymorphism has been associated with various cancers risks. However, little is known about the association between CTLA-4 +49A/G polymorphism and bladder cancer risk. A hospital-based case-control study was conducted in 300 patients with bladder cancer and 300 healthy controls matched with age and sex. The CTLA-4 +49A/G polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism. Patients with bladder cancer had a significantly lower frequency of CTLA-4 +49GG genotype [odds ratio (OR)?=?0.44, 95 % confidence interval (CI)?=?0.23, 0.85; P?=?0.01] and G allele (OR?=?0.73, 95 % CI?=?0.56, 0.96; P?=?0.02) than healthy controls. When stratifying by the stage, grade, and histological type of bladder cancer, we found no statistical association. This is the first study to highlight the significant association between CTLA-4 +49A/G polymorphism and bladder cancer risk. Additional studies are needed to confirm this finding.
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Is adjuvant radiotherapy warranted in resected pT1-2 node-positive rectal cancer?
Radiat Oncol
PUBLISHED: 07-25-2013
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Stage T1-2 rectal cancers are unlikely to have lymph node metastases and neoadjuvant therapy is not routinely administered. Postoperative management is controversial if lymph node metastases are detected in the resected specimen. We studied the outcomes of patients with pT1-2 node-positive rectal cancer in order to determine whether adjuvant radiotherapy was beneficial.
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Virus nomenclature below the species level: a standardized nomenclature for filovirus strains and variants rescued from cDNA.
Arch. Virol.
PUBLISHED: 07-24-2013
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Specific alterations (mutations, deletions, insertions) of virus genomes are crucial for the functional characterization of their regulatory elements and their expression products, as well as a prerequisite for the creation of attenuated viruses that could serve as vaccine candidates. Virus genome tailoring can be performed either by using traditionally cloned genomes as starting materials, followed by site-directed mutagenesis, or by de novo synthesis of modified virus genomes or parts thereof. A systematic nomenclature for such recombinant viruses is necessary to set them apart from wild-type and laboratory-adapted viruses, and to improve communication and collaborations among researchers who may want to use recombinant viruses or create novel viruses based on them. A large group of filovirus experts has recently proposed nomenclatures for natural and laboratory animal-adapted filoviruses that aim to simplify the retrieval of sequence data from electronic databases. Here, this work is extended to include nomenclature for filoviruses obtained in the laboratory via reverse genetics systems. The previously developed template for natural filovirus genetic variant naming, (/)///-, is retained, but we propose to adapt the type of information added to each field for cDNA clone-derived filoviruses. For instance, the full-length designation of an Ebola virus Kikwit variant rescued from a plasmid developed at the US Centers for Disease Control and Prevention could be akin to "Ebola virus H.sapiens-rec/COD/1995/Kikwit-abc1" (with the suffix "rec" identifying the recombinant nature of the virus and "abc1" being a placeholder for any meaningful isolate designator). Such a full-length designation should be used in databases and the methods section of publications. Shortened designations (such as "EBOV H.sap/COD/95/Kik-abc1") and abbreviations (such as "EBOV/Kik-abc1") could be used in the remainder of the text, depending on how critical it is to convey information contained in the full-length name. "EBOV" would suffice if only one EBOV strain/variant/isolate is addressed.
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Factors Associated With Traditional Chinese Medicine Utilization Among Urban Community Health Centers in Hubei Province of China.
Asia Pac J Public Health
PUBLISHED: 07-17-2013
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This study aims to examine resources and utilization of traditional Chinese medicine (TCM) and factors influencing TCM utilization in urban community health centers (CHCs) in Hubei Province of China. A cross-sectional survey including 234 government-owned CHCs was conducted in 2009. One-way analysis of variance analysis and a Poisson regression model were used to examine distribution of TCM resources and factors influencing TCM utilization. This study found unequal distribution of TCM resources among districts. TCM outpatient visits were positively associated with higher economic development districts, lower initial capital investment of the CHCs, health services covered by health insurance, higher qualification of TCM physicians, provision of TCM health records and rehabilitation, and greater availability of herbal medicine. To achieve equal access to TCM services, policy makers should consider the socioeconomic differences and income groups, provide training for TCM physicians, build pathway to recruit senior TCM physicians, and cover more TCM therapies by health insurance.
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Formation of human prostate epithelium using tissue recombination of rodent urogenital sinus mesenchyme and human stem cells.
J Vis Exp
PUBLISHED: 07-16-2013
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Progress in prostate cancer research is severely limited by the availability of human-derived and hormone-naïve model systems, which limit our ability to understand genetic and molecular events underlying prostate disease initiation. Toward developing better model systems for studying human prostate carcinogenesis, we and others have taken advantage of the unique pro-prostatic inductive potential of embryonic rodent prostate stroma, termed urogenital sinus mesenchyme (UGSM). When recombined with certain pluripotent cell populations such as embryonic stem cells, UGSM induces the formation of normal human prostate epithelia in a testosterone-dependent manner. Such a human model system can be used to investigate and experimentally test the ability of candidate prostate cancer susceptibility genes at an accelerated pace compared to typical rodent transgenic studies. Since Human embryonic stem cells (hESCs) can be genetically modified in culture using inducible gene expression or siRNA knock-down vectors prior to tissue recombination, such a model facilitates testing the functional consequences of genes, or combinations of genes, which are thought to promote or prevent carcinogenesis. The technique of isolating pure populations of UGSM cells, however, is challenging and learning often requires someone with previous expertise to personally teach. Moreover, inoculation of cell mixtures under the renal capsule of an immunocompromised host can be technically challenging. Here we outline and illustrate proper isolation of UGSM from rodent embryos and renal capsule implantation of tissue mixtures to form human prostate epithelium. Such an approach, at its current stage, requires in vivo xenografting of embryonic stem cells; future applications could potentially include in vitro gland formation or the use of induced pluripotent stem cell populations (iPSCs).
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Apical F-actin-regulated exocytic targeting of NtPPME1 is essential for construction and rigidity of the pollen tube cell wall.
Plant J.
PUBLISHED: 07-15-2013
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In tip-confined growing pollen tubes, delivery of newly synthesized cell wall materials to the rapidly expanding apical surface requires spatial organization and temporal regulation of the apical F-actin filament and exocytosis. In this study, we demonstrate that apical F-actin is essential for the rigidity and construction of the pollen tube cell wall by regulating exocytosis of Nicotiana tabacum pectin methylesterase (NtPPME1). Wortmannin disrupts the spatial organization of apical F-actin in the pollen tube tip and inhibits polar targeting of NtPPME1, which subsequently alters the rigidity and pectic composition of the pollen tube cell wall, finally causing growth arrest of the pollen tube. In addition to mechanistically linking cell wall construction and apical F-actin, wortmannin can be used as a useful tool for studying endomembrane trafficking and cytoskeletal organization in pollen tubes.
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Transmission of 8 × 480-Gb/s super-Nyquist-filtering 9-QAM-like signal at 100 GHz-grid over 5000-km SMF-28 and twenty-five 100 GHz-grid ROADMs.
Opt Express
PUBLISHED: 07-12-2013
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We experimentally demonstrate a highly filtering-tolerant multi-modulus equalization (MMEQ) process for very aggressively spectrum-shaped 9-ary quadrature-amplitude-modulation (9-QAM)-like polarization division multiplexing quadrature phase shift keying (PDM-QPSK) signal to achieve 400-Gb/s wavelength-division-multiplexing (WDM) channels on the 100-GHz grid for ultra-long-haul reach and high tolerance of the filter narrowing effect caused by reconfigurable optical add-drop multiplexers (ROADMs). We successfully transmitted 8 channels 480-Gb/s super-Nyquist (channel occupancy much less than signal baud rate) WDM signals at 100-GHz grid over 25 × 200 km conventional single-mode fiber-28 (SMF-28) with post Raman amplification and 25 ROADMs at a net spectral efficiency (SE) of 4b/s/Hz, after excluding the 20% soft-decision forward-error-correction (FEC) overhead. The system performance is significantly enhanced by the MMEQ based on 9-QAM-like constellations compared to the conventional 4 point QPSK constellation. A record transmission distance over conventional SMF-28 with a large number of ROADMs is firstly reported on the 400-Gb/s channels at 100-GHz grid.
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Maternal residential atrazine exposure and gastroschisis by maternal age.
Matern Child Health J
PUBLISHED: 06-25-2013
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Previous literature has suggested a link between maternal exposure to atrazine (the most commonly used herbicide in the US) and risk for gastroschisis (a birth defect that involves incomplete closure of the abdominal wall). Our objective was to evaluate the relationship between maternal atrazine exposure and gastroschisis risk by maternal age. We analyzed data for 1,161 cases with isolated gastroschisis and 8,390 controls delivered in Texas from 1999 through 2008. We estimated atrazine exposure based on maternal county of residence and data from the United States Geological Survey. Logistic regression was conducted among all subjects, and separately among offspring of women <25 and ?25 years. Risk for gastroschisis in offspring was significantly increased for women ?25 years with high levels of residential atrazine exposure compared to low (adjusted odds ratio: 1.97, 95 % confidence interval 1.19-3.26). This association was not observed among women <25 years. Our results provide additional insight into the suspected relationship of gastroschisis with atrazine. This relationship appears to be different in older versus younger mothers, providing further evidence that the etiology of gastroschisis may vary based on maternal age.
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Proteinase-activated receptor 2 modulates corticotropin releasing hormone-induced brain-derived neurotrophic factor release from microglial cells.
Cell Biol. Int.
PUBLISHED: 06-22-2013
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Brain-derived neurotrophic factor (BDNF) plays a critical role in the pathogenesis of neuropathic pain, but its regulation of BDNF release is not fully understood. To further understand the regulation of BDNF release, the microglial cell line, C8-D1A (microglia, in short), were cultured as a model. The levels of BDNF were determined by enzyme-linked immunoassay. Apoptotic microglia were assessed by flow cytometry. The protease-activated receptor 2 (PAR2) was activated by tryptase. Exposure to corticotripin releasing hormone (CRH) induced BDNF release from microglia. Apoptosis was evident in microglia after activation by CRH. Tryptase-induced PAR2 activation reduced the frequency of apoptosis of microglia, but enhanced the BDNF levels in the culture medium, which was partially blocked by PAR2 antagonists. We conclude that PAR2 agonists can promote the BDNF release from microglia; the PAR2 antagonists may be a potential therapeutic target to attenuate the BDNF-related neuropathic pain.
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What is Visualize?

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.

Video X seems to be unrelated to Abstract Y...

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.