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Find video protocols related to scientific articles indexed in Pubmed.
Novel synthesis of 5-methyl-5,10-dihydroindolo[3,2-b]indoles by Pd-catalyzed C-C and two-fold C-N coupling reactions.
Org. Biomol. Chem.
PUBLISHED: 11-11-2014
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A series of 5,10-dihydroindolo[3,2-b]indoles was successfully prepared by an efficient two-step strategy based on site-selective Pd-catalyzed cross-coupling reaction with N-methyl-2,3-dibromoindole and subsequent cyclization by two-fold Pd-catalyzed C-N coupling with amines. The products show a strong fluorescence.
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Piezoelectric coupling in a field-effect transistor with a nanohybrid channel of ZnO nanorods grown vertically on graphene.
Nanoscale
PUBLISHED: 11-06-2014
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Piezoelectric coupling phenomena in a graphene field-effect transistor (GFET) with a nano-hybrid channel of chemical-vapor-deposited Gr (CVD Gr) and vertically aligned ZnO nanorods (NRs) under mechanical pressurization were investigated. Transfer characteristics of the hybrid channel GFET clearly indicated that the piezoelectric effect of ZnO NRs under static or dynamic pressure modulated the channel conductivity (?) and caused a positive shift of 0.25% per kPa in the Dirac point. However, the GFET without ZnO NRs showed no change in either ? or the Dirac point. Analysis of the Dirac point shifts indicated transfer of electrons from the CVD Gr to ZnO NRs due to modulation of their interfacial barrier height under pressure. High responsiveness of the hybrid channel device with fast response and recovery times was evident in the time-dependent behavior at a small gate bias. In addition, the hybrid channel FET could be gated by mechanical pressurization only. Therefore, a piezoelectric-coupled hybrid channel GFET can be used as a pressure-sensing device with low power consumption and a fast response time. Hybridization of piezoelectric 1D nanomaterials with a 2D semiconducting channel in FETs enables a new design for future nanodevices.
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IQ-TREE: A fast and effective stochastic algorithm for estimating maximum likelihood phylogenies.
Mol. Biol. Evol.
PUBLISHED: 11-06-2014
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Large phylogenomics data sets require fast tree inference methods, especially for maximum likelihood (ML) phylogenies. Fast programs exist, but due to inherent heuristics to find optimal trees, it is not clear if the best tree is found. Thus, there is need for additional approaches that employ different search strategies to find ML trees and that are at the same time as fast as currently available ML programs. We show that a combination of hill-climbing approaches and a stochastic perturbation method can be time-efficiently implemented. If we allow the same CPU time as RAxML and PhyML, then our software IQ-TREE found higher likelihoods between 62.2% and 87.1% of the studied alignments, thus efficiently exploring the tree-space. If we use the IQ-TREE stopping rule, RAxML and PhyML are faster in 75.7% and 47.1% of the DNA alignments and 42.2% and 100% of the protein alignments, respectively. However, the range of obtaining higher likelihoods with IQ-TREE improves to 73.3% - 97.1%. IQ-TREE is freely available at http://www.cibiv.at/software/iqtree.
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Oral administration of Bifidobacterium spp. improves insulin resistance, induces adiponectin, and prevents inflammatory adipokine expressions.
Biomed. Res.
PUBLISHED: 10-31-2014
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The intestinal microbiome might be an important contributor to the development of type 2 diabetes. This study was designed to test the hypothesis that oral administration of Bifidobacterium species (spp.) (including B. longum, B. bifidum, B. infantis, and B. animalis) may both ameliorate insulin resistance and reduce the expressions of inflammatory adipocytokines. Male Swiss-Webster mice fed a high-fat diet with or without oral administration of Bifidobacterium spp. for 5 weeks were subjected to an insulin tolerance test and an oral glucose tolerance test. Plasma levels of glucose at 30, 60, 90 and 120 min after insulin injection or glucose administration were significantly lower in the Bifidobacterium spp. than in the control group (P < 0.05), showing the beneficial effect of oral administration on insulin resistance in obese Swiss mice. In addition, Bifidobacterium spp. increased the adiponectin mRNA level and decreased those of monocyte chemoattractant protein 1 and interleukin 6 in non-diabetic C57BL/6J mice fed a normal diet, indicating a molecular mechanism which may ameliorate the inflammatory state, thereby reducing insulin resistance. In conclusion, oral administration of Bifidobacterium spp. improves insulin resistance and glucose tolerance in obese mice by reducing inflammation, as it does in the lean state.
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Human Cytomegalovirus Resistance to Deoxyribosylindole Nucleosides Maps to a Transversion Mutation in the Terminase Subunit Encoded Gene UL89.
Antimicrob. Agents Chemother.
PUBLISHED: 10-29-2014
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Human cytomegalovirus (HCMV) infection can cause severe illnesses including encephalopathy and mental retardation in immunocompromised and immunologically immature patients. Current pharmacotherapies for treating systemic HCMV infections include ganciclovir, cidofovir, and foscarnet. However, long-term administration of these agents can result in serious adverse effects (myelosuppression and/or nephrotoxicity) and the development of viral strains with reduced susceptibility to drugs. The deoxyribosylindole (indole) nucleosides demonstrate a 20-fold greater activity in vitro (EC50 = 0.34 ?M) when compared to ganciclovir (EC50 = 7.4 ?M) without any observed increase in cytotoxicity. Based on structural similarity to the benzimidazole nucleosides, we hypothesize that the indole nucleosides target the HCMV terminase, an enzyme responsible for packaging viral DNA into capsids and cleaving the DNA into genome-length units. To test this hypothesis, an indole nucleoside-resistant HCMV was isolated, the open reading frames of the viral terminase were sequenced, and a G766C mutation in exon 1 of UL89 was identified; this mutation resulted in an E256Q change in the amino acid sequence. An HCMV wild-type strain, engineered with this mutation to confirm resistance, demonstrated an 18-fold decrease in susceptibility to the indole nucleosides (EC50 = 3.1 ± 0.7 ?M) when compared to wild-type virus (EC50 = 0.17 ± 0.04 ?M). Interestingly, this mutation did not confer resistance to the benzimidazole nucleosides (EC50 wild-type HCMV = 0.25 ± 0.04 ?M, EC50 HCMV pUL89 E256Q = 0.23 ± 0.04 ?M). We conclude, therefore, that the G766C mutation that results in the E256Q substitution is unique for indole nucleoside resistance and distinct from previously discovered substitutions that confer both indole and benzimidazole nucleoside resistance (D344E and A355T).
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Positron emission tomographic imaging of CXCR4 in cancer: challenges and promises.
Mol Imaging
PUBLISHED: 10-25-2014
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AbstractMolecular imaging is an attractive platform for noninvasive detection and assessment of cancer. In recent years, the targeted imaging of the C-X-C chemokine receptor 4 (CXCR4), a chemokine receptor that has been associated with tumor metastasis, has become an area of intensive research. This review article focuses on positron emission tomography (PET) and aims to provide useful and critical insights into the application of PET to characterize CXCR4 expression, including the chemical, radiosynthetic, and biological requirements for PET radiotracers. This discussion is informed by a summary of the different approaches taken so far and a comparison of their clinical translation. Finally, our expert opinions as to potential future advances in the field are expressed.
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DANN: a deep learning approach for annotating the pathogenicity of genetic variants.
Bioinformatics
PUBLISHED: 10-22-2014
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Annotating genetic variants, especially noncoding variants, for the purpose of identifying pathogenic variants remains a challenge. CADD is an algorithm designed to annotate both coding and noncoding variants, and has been shown to outperform other annotation algorithms. CADD trains a linear kernel support vector machine (SVM) to differentiate evolutionarily derived, likely benign, alleles from simulated, likely deleterious, variants. However, SVMs cannot capture nonlinear relationships among the features, which can limit performance. To address this issue, we have developed DANN. DANN uses the same feature set and training data as CADD to train a deep neural network (DNN). DNNs can capture nonlinear relationships among features and are better suited than SVMs for problems with a large number of samples and features. We exploit CUDA-compatible GPUs and deep learning techniques such as dropout and momentum training to accelerate the DNN training. DANN achieves about a 19% relative reduction in the error rate and about a 14% relative increase in the area under the curve (AUC) metric over CADD's SVM methodology. Availability and implementation: All data and source code are available at https://cbcl.ics.uci.edu/public_data/DANN/.
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FRET Imaging by Laser Scanning Cytometry on Large Populations of Adherent Cells.
Curr Protoc Cytom
PUBLISHED: 10-02-2014
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The application of FRET (fluorescence resonance energy transfer) sensors for monitoring protein-protein interactions under vital conditions is attracting increasing attention in molecular and cell biology. Laser-scanning cytometry (LSC), a slide-based sister procedure to flow cytometry, provides an opportunity to analyze large populations of adherent cells or 2-D solid tissues in their undisturbed physiological settings. Here we provide an LSC-based three-laser protocol for high-throughput ratiometric FRET measurements utilizing cyan and yellow fluorescent proteins as a FRET pair. Membrane labeling with Cy5 dye is used for cell identification and contouring. Pixel-by-pixel and single-cell FRET efficiencies are calculated to estimate the extent of the molecular interactions and their distribution in the cell populations examined. We also present a non-high-throughput donor photobleaching FRET application, for obtaining the required instrument parameters for ratiometric FRET. In the biological model presented, HeLa cells are transfected with the ECFP- or EYFP-tagged Fos and Jun nuclear proteins, which heterodimerize to form active AP1 transcription factor. Curr. Protoc. Cytom. 70:2.23.1-2.23.29. © 2014 by John Wiley & Sons, Inc.
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Biological control of Xanthomonas Oryzae pv. Oryzae causing rice bacterial blight disease by Streptomyces toxytricini VN08-A-12, isolated from soil and leaf-litter samples in Vietnam.
Biocontrol Sci
PUBLISHED: 09-26-2014
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A total of 2690 actinomycete strains were screened as potential biological control agents in controlling rice bacterial blight (BB) in Vietnam. From these microorganisms, seventeen actinomycete strains were found to be capable of inhibiting all 10 major Xoo races isolated from Xoo-infected rice leaves. One strain, namely VN08-A-12, contained effective characteristics in selectively inhibiting all 10 races in vitro, but did not inhibit most of the other tested microorganisms. Therefore, VN08-A-12 was subsequently selected for rice field trials for two seasons on two rice cultivars SS1 and KD18. Results showed VN08-A-12 was not only able to reduce Xoo lesion lengths in the two rice cultivars (lesion length reduction of up to 38.3%), but it also significantly reduced Xoo-related yield loss in infected rice cultivars from the field (yield loss reduction of up to 43.2%). Interestingly, the culture of this strain also increased the rice yield in healthy rice cultivars (from 2.66% to 16.98% for SS1 and from 3.11% to 5.94% for KD18 cultivar). The strain VN08-A-12 was shown to be identical to Streptomyces toxytricini. To our knowledge, this is the first study reporting S. toxytricini as a beneficial biological agent for the control of BB in rice.
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Characterization and Protective Property of Brucella abortus cydC and looP Mutants.
Clin. Vaccine Immunol.
PUBLISHED: 09-24-2014
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Brucella abortus readily multiplies in professional or nonprofessional phagocytes in vitro and is highly virulent in mice. Isogenic mutants of B. abortus biovar 1 strain IVKB9007 lacking the ATP/GDP-binding protein motif A (P-loop) (named looP; designated here the IVKB9007 looP::Tn5 mutant) and the ATP-binding/permease protein (cydC; designated here the IVKB9007 cydC::Tn5 mutant) were identified and characterized by transposon mutagenesis using the mini-Tn5Km2 transposon. Both mutants were found to be virtually incapable of intracellular replication in both murine macrophages (RAW264.7) and the HeLa cell line, and their virulence was significantly impaired in BALB/c mice. Respective complementation of the IVKB9007 looP::Tn5 and IVKB9007 cydC::Tn5 mutants restored their ability to survive in vitro and in vivo to a level comparable with that of the wild type. These findings indicate that the cydC and looP genes play important roles in the virulence of B. abortus. In addition, intraperitoneal immunization of mice with a dose of the live IVKB9007 looP::Tn5 and IVKB9007 cydC::Tn5 mutants provided a high degree of protection against challenge with pathogenic B. abortus strain 544. Both mutants should be evaluated further as a live attenuated vaccine against bovine brucellosis for their ability to stimulate a protective immune response.
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Capacity Building Toward Evidence-Based Medicine Among Healthcare Professionals at the University of Medicine and Pharmacy, Ho Chi Minh City, and Its Related Institutes.
Japan Med Assoc J
PUBLISHED: 09-20-2014
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Research capacity development enhances a country's ownership of activities aimed at strengthening its health system. In Vietnam, continuing medical education (CME) is attracting increasing attention with the establishment of legal and policy frameworks. During 2010-2013, the Japan International Cooperation Agency funded a research capacity building project targeting physicians in Ho Chi Minh City. The project had been developed in four previous courses that were conducted in collaboration with Fukushima Medical University and Ho Chi Minh City University of Medicine and Pharmacy (UMP). The project succeeded in obtaining accreditation as the city's CME course. A total of 262 physicians attended three courses that have a divided set of research competencies. Following the Kirkpatrick Model for evaluating the effectiveness of training programs, we confirmed the participants' positive reaction to the courses (Level 1 evaluation), their perceived increase in knowledge and confidence in research skills (Level 2 evaluation), and application of learned knowledge in their practice (Level 3 evaluation). Presented here is a step-by-step scaling-up model of health research capacity building. Strategies for the further expansion include: further capacity building of instructors; responding to clinicians' specific needs; building a recruiting system with authorization; and improving the Level 3 training evaluation.
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Potential of a tomato MAGIC population to decipher the genetic control of quantitative traits and detect causal variants in the resequencing era.
Plant Biotechnol. J.
PUBLISHED: 09-19-2014
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Identification of the polymorphisms controlling quantitative traits remains a challenge for plant geneticists. Multiparent advanced generation intercross (MAGIC) populations offer an alternative to traditional linkage or association mapping populations by increasing the precision of quantitative trait loci (QTL) mapping. Here, we present the first tomato MAGIC population and highlight its potential for the valorization of intraspecific variation, QTL mapping and causal polymorphism identification. The population was developed by crossing eight founder lines, selected to include a wide range of genetic diversity, whose genomes have been previously resequenced. We selected 1536 SNPs among the 4 million available to enhance haplotype prediction and recombination detection in the population. The linkage map obtained showed an 87% increase in recombination frequencies compared to biparental populations. The prediction of the haplotype origin was possible for 89% of the MAGIC line genomes, allowing QTL detection at the haplotype level. We grew the population in two greenhouse trials and detected QTLs for fruit weight. We mapped three stable QTLs and six specific of a location. Finally, we showed the potential of the MAGIC population when coupled with whole genome sequencing of founder lines to detect candidate SNPs underlying the QTLs. For a previously cloned QTL on chromosome 3, we used the predicted allelic effect of each founder and their genome sequences to select putative causal polymorphisms in the supporting interval. The number of candidate polymorphisms was reduced from 12 284 (in 800 genes) to 96 (in 54 genes), including the actual causal polymorphism. This population represents a new permanent resource for the tomato genetics community.
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Delayed Parasite Clearance after Treatment with Dihydroartemisinin-Piperaquine in Plasmodium falciparum Malaria Patients in Central Vietnam.
Antimicrob. Agents Chemother.
PUBLISHED: 09-15-2014
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Reduced susceptibility of Plasmodium falciparum toward artemisinin derivatives has been reported from the Thai-Cambodian and Thai-Myanmar borders. Following increasing reports from central Vietnam of delayed parasite clearance after treatment with dihydroartemisinin-piperaquine (DHA-PPQ), the current first-line treatment, we carried out a study on the efficacy of this treatment. Between September 2012 and February 2013, we conducted a 42-day in vivo and in vitro efficacy study in Quang Nam Province. Treatment was directly observed, and blood samples were collected twice daily until parasite clearance. In addition, genotyping, quantitative PCR (qPCR), and in vitro sensitivity testing of isolates was performed. The primary endpoints were parasite clearance rate and time. The secondary endpoints included PCR-corrected and uncorrected cure rates, qPCR clearance profiles, in vitro sensitivity results (for chloroquine, dihydroartemisinin, and piperaquine), and genotyping for mutations in the Kelch 13 propeller domain. Out of 672 screened patients, 95 were recruited and 89 available for primary endpoint analyses. The median parasite clearance time (PCT) was 61.7 h (interquartile range [IQR], 47.6 to 83.2 h), and the median parasite clearance rate had a slope half-life of 6.2 h (IQR, 4.4 to 7.5 h). The PCR-corrected efficacy rates were estimated at 100% at day 28 and 97.7% (95% confidence interval, 91.2% to 99.4%) at day 42. At day 3, the P. falciparum prevalence by qPCR was 2.5 times higher than that by microscopy. The 50% inhibitory concentrations (IC50s) of isolates with delayed clearance times (?72 h) were significantly higher than those with normal clearance times for all three drugs. Delayed parasite clearance (PCT, ?72 h) was significantly higher among day 0 samples carrying the 543 mutant allele (47.8%) than those carrying the wild-type allele (1.8%; P = 0.048). In central Vietnam, the efficacy of DHA-PPQ is still satisfactory, but the parasite clearance time and rate are indicative of emerging artemisinin resistance. (This study has been registered at ClinicalTrials.gov under registration no. NCT01775592.).
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Anti-nicastrin monoclonal antibodies elicit pleiotropic anti-tumour pharmacological effects in invasive breast cancer cells.
Breast Cancer Res. Treat.
PUBLISHED: 08-26-2014
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The goal of targeted cancer therapies is to specifically block oncogenic signalling, thus maximising efficacy, while reducing side-effects to patients. The gamma-secretase (GS) complex is an attractive therapeutic target in haematological malignancies and solid tumours with major pharmaceutical activity to identify optimal inhibitors. Within GS, nicastrin (NCSTN) offers an opportunity for therapeutic intervention using blocking monoclonal antibodies (mAbs). Here we explore the role of anti-nicastrin monoclonal antibodies, which we have developed as specific, multi-faceted inhibitors of proliferation and invasive traits of triple-negative breast cancer cells. We use 3D in vitro proliferation and invasion assays as well as an orthotopic and tail vail injection triple-negative breast cancer in vivo xenograft model systems. RNAScope assessed nicastrin in patient samples. Anti-NCSTN mAb clone-2H6 demonstrated a superior anti-tumour efficacy than clone-10C11 and the RO4929097 small molecule GS inhibitor, acting by inhibiting GS enzymatic activity and Notch signalling in vitro and in vivo. Confirming clinical relevance of nicastrin as a target, we report evidence of increased NCSTN mRNA levels by RNA in situ hybridization (RNAScope) in a large cohort of oestrogen receptor negative breast cancers, conferring independent prognostic significance for disease-free survival, in multivariate analysis. We demonstrate here that targeting NCSTN using specific mAbs may represent a novel mode of treatment for invasive triple-negative breast cancer, for which there are few targeted therapeutic options. Furthermore, we propose that measuring NCSTN in patient samples using RNAScope technology may serve as companion diagnostic for anti-NCSTN therapy in the clinic.
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Determinants of influenza transmission in South East Asia: insights from a household cohort study in Vietnam.
PLoS Pathog.
PUBLISHED: 08-21-2014
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To guide control policies, it is important that the determinants of influenza transmission are fully characterized. Such assessment is complex because the risk of influenza infection is multifaceted and depends both on immunity acquired naturally or via vaccination and on the individual level of exposure to influenza in the community or in the household. Here, we analyse a large household cohort study conducted in 2007-2010 in Vietnam using innovative statistical methods to ascertain in an integrative framework the relative contribution of variables that influence the transmission of seasonal (H1N1, H3N2, B) and pandemic H1N1pdm09 influenza. Influenza infection was diagnosed by haemagglutination-inhibition (HI) antibody assay of paired serum samples. We used a Bayesian data augmentation Markov chain Monte Carlo strategy based on digraphs to reconstruct unobserved chains of transmission in households and estimate transmission parameters. The probability of transmission from an infected individual to another household member was 8% (95% CI, 6%, 10%) on average, and varied with pre-season titers, age and household size. Within households of size 3, the probability of transmission from an infected member to a child with low pre-season HI antibody titers was 27% (95% CI 21%-35%). High pre-season HI titers were protective against infection, with a reduction in the hazard of infection of 59% (95% CI, 44%-71%) and 87% (95% CI, 70%-96%) for intermediate (1?20-1?40) and high (?1?80) HI titers, respectively. Even after correcting for pre-season HI titers, adults had half the infection risk of children. Twenty six percent (95% CI: 21%, 30%) of infections may be attributed to household transmission. Our results highlight the importance of integrated analysis by influenza sub-type, age and pre-season HI titers in order to infer influenza transmission risks in and outside of the household.
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Early development of calcific aortic valve disease and left ventricular hypertrophy in a mouse model of combined dyslipidemia and type 2 diabetes mellitus.
Arterioscler. Thromb. Vasc. Biol.
PUBLISHED: 08-14-2014
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This study aimed to determine the potential impact of type 2 diabetes mellitus on left ventricular dysfunction and the development of calcified aortic valve disease using a dyslipidemic mouse model prone to developing type 2 diabetes mellitus.
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Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage: a combined analysis of 12 mathematical models.
Lancet Glob Health
PUBLISHED: 08-09-2014
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New WHO guidelines recommend initiation of antiretroviral therapy for HIV-positive adults with CD4 counts of 500 cells per ?L or less, a higher threshold than was previously recommended. Country decision makers have to decide whether to further expand eligibility for antiretroviral therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage.
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Synchrotron X-ray computed laminography of the three-dimensional anatomy of tomato leaves.
Plant J.
PUBLISHED: 08-04-2014
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Synchrotron radiation computed laminography (SR-CL) is presented as an imaging method for analyzing the three-dimensional (3D) anatomy of leaves. The SR-CL method was used to provide 3D images of 1-mm² samples of intact leaves at a pixel resolution of 750 nm. The method allowed visualization and quantitative analysis of palisade and spongy mesophyll cells, and showed local venation patterns, aspects of xylem vascular structure and stomata. The method failed to image subcellular organelles such as chloroplasts. We constructed 3D computer models of leaves that can provide a basis for calculating gas exchange, light penetration and water and solute transport. The leaf anatomy of two different tomato genotypes grown in saturating light conditions was compared by 3D analysis. Differences were found in calculated values of tissue porosity, cell number density, cell area to volume ratio and cell volume and cell shape distributions of palisade and spongy cell layers. In contrast, the exposed cell area to leaf area ratio in mesophyll, a descriptor that correlates to the maximum rate of photosynthesis in saturated light conditions, was no different between spongy and palisade cells or between genotypes. The use of 3D image processing avoids many of the limitations of anatomical analysis with two-dimensional sections.
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Pre-germinated brown rice reduced both blood glucose concentration and body weight in Vietnamese women with impaired glucose tolerance.
J. Nutr. Sci. Vitaminol.
PUBLISHED: 08-01-2014
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We have reported that newly diagnosed type 2 diabetes mellitus (DM) patients in Vietnam have a low body mass index (BMI) of around 23 and that the major factor for this is high white rice (WR) intake. Brown rice (BR) is known to be beneficial in the control of blood glucose levels; however, it has the property of unpleasant palatability. Pre-germinated brown rice (PGBR) is slightly germinated by soaking BR in water as this reduces the hardness of BR and makes it easier to eat. This study was designed to evaluate the effect of a 4-mo PGBR administration on various parameters in Vietnamese women aged 45-65 y with impaired glucose tolerance (IGT). Sixty subjects were divided into a WR or PGBR group. For the first 2 wk, WR was replaced by 50% PGBR, then for 2 wk by 75% PGBR and from the second month 100%. Before the beginning of the study and at the end of the study, 1) anthropometric measurements, 2) a nutrition survey for 3 nonconsecutive days by the 24 h recall method and 3) blood biochemical examinations were conducted. Fasting plasma concentrations of glucose and lipids and the obesity-related measurements and blood pressure were favorably improved only in the PGBR diet group. The present results suggest that replacing WR with PGBR for 4 mo may be useful in controlling body weight as well as blood glucose and lipid levels in Vietnamese women with IGT.
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Cytotoxic constituents from the Vietnamese fungus Xylaria schweinitzii.
Nat Prod Commun
PUBLISHED: 07-17-2014
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Two new fungal pigments named schweinitzins A and B (1-2), together with (S)-torosachrysone-8-O-methyl ether (3) and emodin-6,8-di-O-methyl ether (4) have been isolated from the methanolic extract of the fruit bodies of Xylaria schweinitzii (Xylariaceae) collected in Cuc Phuong national park, Ninh Binh province, Vietnam, by silica gel column chromatography and preparative HPLC. Their structures were elucidated by spectroscopic analysis such as IR, UV-Vis, 2D NMR and FT-ICR-MS. In addition, two compounds (1 and 3) showed strong cytotoxicity against all four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-I (human lung carcinoma) and HepG2 (hepatocellular carcinoma).
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Discovery of the first light-dependent protochlorophyllide oxidoreductase in anoxygenic phototrophic bacteria.
Mol. Microbiol.
PUBLISHED: 07-14-2014
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In all photosynthetic organisms, chlorophylls function as light-absorbing photopigments allowing the efficient harvesting of light energy. Chlorophyll biosynthesis recurs in similar ways in anoxygenic phototrophic proteobacteria as well as oxygenic phototrophic cyanobacteria and plants. Here, the biocatalytic conversion of protochlorophyllide to chlorophyllide is catalysed by evolutionary and structurally distinct protochlorophyllide reductases (PORs) in anoxygenic and oxygenic phototrophs. It is commonly assumed that anoxygenic phototrophs only contain oxygen-sensitive dark-operative PORs (DPORs), which catalyse protochlorophyllide reduction independent of the presence of light. In contrast, oxygenic phototrophs additionally (or exclusively) possess oxygen-insensitive but light-dependent PORs (LPORs). Based on this observation it was suggested that light-dependent protochlorophyllide reduction first emerged as a consequence of increased atmospheric oxygen levels caused by oxygenic photosynthesis in cyanobacteria. Here, we provide experimental evidence for the presence of an LPOR in the anoxygenic phototrophic ?-proteobacterium Dinoroseobacter shibae?DFL12(T). In vitro and in vivo functional assays unequivocally prove light-dependent protochlorophyllide reduction by this enzyme and reveal that LPORs are not restricted to cyanobacteria and plants. Sequence-based phylogenetic analyses reconcile our findings with current hypotheses about the evolution of LPORs by suggesting that the light-dependent enzyme of D. shibae?DFL12(T) might have been obtained from cyanobacteria by horizontal gene transfer.
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A bioorthogonal (68)Ga-labelling strategy for rapid in vivo imaging.
Chem. Commun. (Camb.)
PUBLISHED: 07-12-2014
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Herein, we describe a fast and robust method for achieving (68)Ga-labelling of the EGFR-selective monoclonal antibody (mAb) Cetuximab using the bioorthogonal Inverse-electron-Demand Diels-Alder (IeDDA) reaction. The in vivo imaging of EGFR is demonstrated, as well as the translation of the method within a two-step pretargeting strategy.
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Preclinical evaluation of 3-18F-fluoro-2,2-dimethylpropionic acid as an imaging agent for tumor detection.
J. Nucl. Med.
PUBLISHED: 07-10-2014
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Deregulated cellular metabolism is a hallmark of many cancers. In addition to increased glycolytic flux, exploited for cancer imaging with (18)F-FDG, tumor cells display aberrant lipid metabolism. Pivalic acid is a short-chain, branched carboxylic acid used to increase oral bioavailability of prodrugs. After prodrug hydrolysis, pivalic acid undergoes intracellular metabolism via the fatty acid oxidation pathway. We have designed a new probe, 3-(18)F-fluoro-2,2-dimethylpropionic acid, also called (18)F-fluoro-pivalic acid ((18)F-FPIA), for the imaging of aberrant lipid metabolism and cancer detection.
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Palladium catalyzed synthesis and physical properties of indolo[2,3-b]quinoxalines.
Org. Biomol. Chem.
PUBLISHED: 07-08-2014
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A series of indolo[2,3-b]quinoxaline derivatives were efficiently synthesized from 2,3-dibromoquinoxaline by two pathways. A one-pot approach using Pd-catalyzed two-fold C-N coupling and C-H activation reactions gave indolo[2,3-b]quinoxaline derivatives in good yields, but with limited substrate scope. In addition, a two-step approach to indolo[2,3-b]quinoxalines was developed which is based on Pd-catalyzed Suzuki coupling reactions and subsequent annulation by Pd-catalyzed two-fold C-N coupling with aromatic and aliphatic amines. The electrochemical and photochemical properties of indolo[2,3-b]quinoxaline derivatives were investigated. These studies show that 6-(4-methoxyphenyl)-6H-indolo[2,3-b]quinoxaline showed the highest HOMO energy level and lowest band gap.
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CTSH regulates ?-cell function and disease progression in newly diagnosed type 1 diabetes patients.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 06-30-2014
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Over 40 susceptibility loci have been identified for type 1 diabetes (T1D). Little is known about how these variants modify disease risk and progression. Here, we combined in vitro and in vivo experiments with clinical studies to determine how genetic variation of the candidate gene cathepsin H (CTSH) affects disease mechanisms and progression in T1D. The T allele of rs3825932 was associated with lower CTSH expression in human lymphoblastoid cell lines and pancreatic tissue. Proinflammatory cytokines decreased the expression of CTSH in human islets and primary rat ?-cells, and overexpression of CTSH protected insulin-secreting cells against cytokine-induced apoptosis. Mechanistic studies indicated that CTSH exerts its antiapoptotic effects through decreased JNK and p38 signaling and reduced expression of the proapoptotic factors Bim, DP5, and c-Myc. CTSH overexpression also up-regulated Ins2 expression and increased insulin secretion. Additionally, islets from Ctsh(-/-) mice contained less insulin than islets from WT mice. Importantly, the TT genotype was associated with higher daily insulin dose and faster disease progression in newly diagnosed T1D patients, indicating agreement between the experimental and clinical data. In line with these observations, healthy human subjects carrying the T allele have lower ?-cell function, which was evaluated by glucose tolerance testing. The data provide strong evidence that CTSH is an important regulator of ?-cell function during progression of T1D and reinforce the concept that candidate genes for T1D may affect disease progression by modulating survival and function of pancreatic ?-cells, the target cells of the autoimmune assault.
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Severe malaria not responsive to artemisinin derivatives in man returning from Angola to Vietnam.
Emerging Infect. Dis.
PUBLISHED: 06-26-2014
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Resistance to artemisinin derivatives, the most potent antimalarial drugs currently used, has emerged in Southeast Asia and threatens to spread to Africa. We report a case of malaria in a man who returned to Vietnam after 3 years in Angola that did not respond to intravenous artesunate and clindamycin or an oral artemisinin-based combination.
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Hepatitis B: Are at-risk individuals vaccinated if screened and found negative for HBV? Results of an online survey conducted in six EU countries.
Vaccine
PUBLISHED: 06-25-2014
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Vaccination is the best way to prevent hepatitis B infection and its consequences. The aim of the present study is to analyze the current vaccination practices within various population subgroups who are offered screening for hepatitis B, when found negative, in Germany, Hungary, Italy, the Netherlands, Spain and the UK.
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Metabolic syndrome among a middle-aged population in the Red River Delta region of Vietnam.
BMC Endocr Disord
PUBLISHED: 06-20-2014
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Metabolic syndrome (MetS) is a clustering of metabolic risk factors for cardiovascular diseases and type 2 diabetes. The study aimed to estimate the prevalence of MetS, its components, and their associations among rural middle-aged population in Vietnam.
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Molecular imaging of the pulmonary circulation in health and disease.
Clin Transl Imaging
PUBLISHED: 06-18-2014
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The pulmonary circulation, at the unique crossroads between the left and the right heart, is submitted to large physiologic hemodynamic variations and possesses numerous important metabolic functions mediated through its vast endothelial surface. There are many pathologic conditions that can directly or indirectly affect the pulmonary vasculature and modify its physiology and functions. Pulmonary hypertension, the end result of many of these affections, is unfortunately diagnosed too late in the disease process, meaning that there is a crying need for earlier diagnosis and surrogate markers of disease progression and regression. By targeting endothelial, medial and adventitial targets of the pulmonary vasculature, novel molecular imaging agents could provide early detection of physiologic and biologic perturbation in the pulmonary circulation. This review provides the rationale for the development of molecular imaging agents for the diagnosis and follow-up of disorders of the pulmonary circulation and discusses promising targets for SPECT and positron emission tomographic imaging.
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Polytype and Stacking Faults in the Li2 CoSiO4 Li-Ion Battery Cathode.
Chemistry
PUBLISHED: 05-27-2014
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Atomic-resolution imaging of the crystal defects of cathode materials is crucial to understand their formation and the correlation between the structure, electrical properties, and electrode performance in rechargeable batteries. The polytype, a stable form of varied crystal structure with uniform chemical composition, holds promise to engineer electronic band structure in nanoscale homojunctions.1-3 Analyzing the exact sites of atoms and the chemistry of the boundary in polytypes would advance our understanding of their formation and properties. Herein, the polytype and stacking faults in the lithium cobalt silicates are observed directly by aberration-corrected scanning transmission electron microscopy. The atomic-scale imaging allows clarification that the polytype is formed by stacking of two different close-packed crystal planes in three-dimensional space. The formation of the polytype was induced by Li-Co cation exchange, the transformation of one phase to the other, and their stacking. This finding provides insight into intrinsic structural defects in an important Li2 CoSiO4 Li-ion battery cathode.
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A novel Fibroblast Growth Factor Receptor family member promotes neuronal outgrowth and synaptic plasticity in Aplysia.
Amino Acids
PUBLISHED: 05-26-2014
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Fibroblast Growth Factor (FGF) Receptors (FGFRs) regulate essential biological processes, including embryogenesis, angiogenesis, cellular growth and memory-related long-term synaptic plasticity. Whereas canonical FGFRs depend exclusively on extracellular Immunoglobulin (Ig)-like domains for ligand binding, other receptor types, including members of the tropomyosin-receptor-kinase (Trk) family, use either Ig-like or Leucine-Rich Repeat (LRR) motifs, or both. Little is known, however, about the evolutionary events leading to the differential incorporation of LRR domains into Ig-containing tyrosine kinase receptors. Moreover, although FGFRs have been identified in many vertebrate species, few reports describe their existence in invertebrates. Information about the biological relevance of invertebrate FGFRs and evolutionary divergences between them and their vertebrate counterparts is therefore limited. Here, we characterized ApLRRTK, a neuronal cell-surface protein recently identified in Aplysia. We unveiled ApLRRTK as the first member of the FGFRs family deprived of Ig-like domains that instead contains extracellular LRR domains. We describe that ApLRRTK exhibits properties typical of canonical vertebrate FGFRs, including promotion of FGF activity, enhancement of neuritic outgrowth and signaling via MAPK and the transcription factor CREB. ApLRRTK also enhanced the synaptic efficiency of neurons known to mediate in vivo memory-related defensive behaviors. These data reveal a novel molecular regulator of neuronal function in invertebrates, provide the first evolutionary linkage between LRR proteins and FGFRs and unveil an unprecedented mechanism of FGFR gene diversification in primeval central nervous systems.
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CXCR4-targeted and MMP-responsive iron oxide nanoparticles for enhanced magnetic resonance imaging.
Angew. Chem. Int. Ed. Engl.
PUBLISHED: 05-23-2014
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MRI offers high spatial resolution with excellent tissue penetration but it has limited sensitivity and the commonly administered contrast agents lack specificity. In this study, two sets of iron oxide nanoparticles (IONPs) were synthesized that were designed to selectively undergo copper-free click conjugation upon sensing of matrix metalloproteinase (MMP) enzymes, thereby leading to a self-assembled superparamagnetic nanocluster network with T2 signal enhancement properties. For this purpose, IONPs with bioorthogonal azide and alkyne surfaces masked by polyethylene glycol (PEG) layers tethered to CXCR4-targeted peptide ligands were synthesized and characterized. The IONPs were tested in?vitro and T2 signal enhancements of around 160?% were measured when the IONPs were incubated with cells expressing MMP2/9 and CXCR4. Simultaneous systemic administration of the bioorthogonal IONPs in tumor-bearing mice demonstrated the signal-enhancing ability of these 'smart' self-assembling nanomaterials.
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CryptoDex: A randomised, double-blind, placebo-controlled phase III trial of adjunctive dexamethasone in HIV-infected adults with cryptococcal meningitis: study protocol for a randomised control trial.
Trials
PUBLISHED: 05-16-2014
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Cryptococcal meningitis (CM) is a severe AIDS-defining illness with 90-day case mortality as high as 70% in sub-Saharan Africa, despite treatment. It is the leading cause of death in HIV patients in Asia and Africa.No major advance has been made in the treatment of CM since the 1970s. The mainstays of induction therapy are amphotericin B and flucytosine, but these are often poorly available where the disease burden is highest. Adjunctive treatments, such as dexamethasone, have had dramatic effects on mortality in other neurologic infections, but are untested in CM. Given the high death rates in patients receiving current optimal treatment, and the lack of new agents on the horizon, adjuvant treatments, which offer the potential to reduce mortality in CM, should be tested.The principal research question posed by this study is as follows: does adding dexamethasone to standard antifungal therapy for CM reduce mortality? Dexamethasone is a cheap, readily available, and practicable intervention.
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Anti-inflammatory activity of methyl ferulate isolated from Stemona tuberosa Lour.
Asian Pac J Trop Med
PUBLISHED: 05-16-2014
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To evaluate the anti-inflammatory activity of methyl ferulate (MF) isolated from the roots of Stemona tuberosa (S. tuberosa) Lour (Stemonaceae) in lipopolysaccharide activated macrophage cells.
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Hemagglutination inhibiting antibodies and protection against seasonal and pandemic influenza infection.
J. Infect.
PUBLISHED: 05-15-2014
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Hemagglutination inhibiting (HI) antibodies correlate with influenza vaccine protection but their association with protection induced by natural infection has received less attention and was studied here.
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FastMG: a simple, fast, and accurate maximum likelihood procedure to estimate amino acid replacement rate matrices from large data sets.
BMC Bioinformatics
PUBLISHED: 05-13-2014
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Amino acid replacement rate matrices are a crucial component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Ideally, the rate matrix reflects the mutational behavior of the actual data under study; however, estimating amino acid replacement rate matrices requires large protein alignments and is computationally expensive and complex. As a compromise, sub-optimal pre-calculated generic matrices are typically used for protein-based phylogeny. Sequence availability has now grown to a point where problem-specific rate matrices can often be calculated if the computational cost can be controlled.
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Protein tyrosine phosphatase 1B inhibitory activity of lavandulyl flavonoids from roots of Sophora flavescens.
Planta Med.
PUBLISHED: 04-29-2014
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Protein tyrosine phosphatase 1B is a non-transmembrane protein tyrosine phosphatase and major negative regulator in insulin signaling cascades, and much attention has been paid to protein tyrosine phosphatase 1B inhibitors as potential therapies for diabetes. The screening of a natural compound library led to the discovery of five lavandulyl flavonoids, which were isolated from the roots of Sophora flavescens, as novel PTP1B inhibitors: kuraridin (1), norkurarinone (2), kurarinone (3), 2'-methoxykurarinone (4), and kushenol T (5). The three most potent compounds, 1, 2, and 4 (IC50
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Highly efficient differentiation of embryonic stem cells into adipocytes by ascorbic acid.
Stem Cell Res
PUBLISHED: 04-18-2014
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Adipocyte differentiation and function have become the major research targets due to the increasing interest in obesity and related metabolic conditions. Although, late stages of adipogenesis have been extensively studied, the early phases remain poorly understood. Here we present that supplementing ascorbic acid (AsA) to the adipogenic differentiation cocktail enables the robust and efficient differentiation of mouse embryonic stem cells (mESCs) to mature adipocytes. Such ESC-derived adipocytes mimic the gene-expression profile of subcutaneous isolated adipocytes in vivo remarkably well, much closer than 3T3-L1 derived ones. Moreover, the differentiated cells are in a monolayer, allowing a broad range of genome-wide studies in early and late stages of adipocyte differentiation to be performed.
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Feasibility of Transoral Robotic-Assisted High Resolution Microendoscopic Imaging of Oropharyngeal Squamous Cell Carcinoma.
Head Neck
PUBLISHED: 04-07-2014
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Background: Transoral robotic-assisted oncologic surgery of the head and neck offers promising functional results. Nonetheless, the efficacy of oncologic surgery remains critically dependent on obtaining negative margins. We aimed to integrate a miniaturized high resolution fiberoptic microendoscope (HRME), which provides real time histological assessment, with the da Vinci robotic system (Intuitive Surgical Inc., Sunnyvale, CA). Methods: Three patients undergoing transoral robotic surgery were prospectively enrolled. Optical imaging of the oropharynx was performed intraoperatively with the robotic-assisted HRME. Results: All patients underwent the procedure successfully with no complications. The HRME was successfully integrated with the Da Vinci Robotic system. Several sites of the oropharynx and associated malignancy were imaged, which correlated with the standard histopathological analysis. Conclusions: Transoral robotic-assisted high resolution microendoscopic imaging of the oropharynx is a safe and technically feasible approach, providing a real time histological assessment and may serve as a valuable aid in oncologic surgery. Head Neck, 2014.
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Anti-influenza sesquiterpene from the roots of Reynoutria japonica.
Nat Prod Commun
PUBLISHED: 04-03-2014
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One new flavonol glycoside, 4'-O-methylmyricitrin 3'-O-beta-D-glucopyranoside (1), one new sesquiterpene, reynoudiol (11), as well as the 12 known compounds (2-10, 12-14) quercetin 3-O-methyl ether (2), quercitrin (3), isorhamnetin 3-alpha-L-rhamnopyranoside (4), tamarixetin 3-alpha-L-rhamnopyranoside (5), myricitrin (6), 4'-O-methylmyricitrin (7), isorhamnetin 3-O-beta-D-xylopyranosyl (1-2)-O-beta- D-glucopyranoside (8), isorhamnetin 3-O-beta- D-apiofuranosyl(1-2)-O-beta- D-glucopyranoside (9), (+)-catechin (10), 7-drimene-3,11,12-triol (12), clovane-2 beta,9 alpha-diol (13), and a-cadinol (14), were isolated from the methanol extract of Reynoutria japonica roots. Based on in vitro screening of the anti-influenza activity of the isolated compounds, reynoudiol showed significantly higher activity than that of oseltamivir phosphate at the same concentration, and did not induce any detectable cytopathic effect in MDCK cells. The CC50 of reynoudiol was above 50 micro M and could inhibit influenza virus infection with an IC50 of 0.29 +/- 0.01 microM. The therapeutic index (TI) of reynoudiol against influenza infection was 172.4, and thus, this compound can be potentially used to treat oseltamivir-resistant influenza virus infection.
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Level IB nodal involvement in oropharyngeal carcinoma: Implications for submandibular gland-sparing intensity-modulated radiotherapy.
Laryngoscope
PUBLISHED: 03-17-2014
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Submandibular gland-sparing intensity-modulated radiotherapy (SMG-sparing IMRT) has been proposed to reduce xerostomia following head and neck irradiation. However, the safety of this practice has been questioned. Data from a large surgical series of oropharyngeal carcinoma patients were extracted to identify clinicopathological correlates for submandibular involvement and to create a risk stratification scheme to guide decision making to refine selection guidelines for SMG-sparing IMRT.
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Efficient synthesis of biscarbazoles by palladium-catalyzed twofold C-N coupling and C-H activation reactions.
Org. Biomol. Chem.
PUBLISHED: 03-14-2014
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A new and efficient strategy for the synthesis of 3,9'- and 2,9'-biscarbazoles was developed. Our strategy relies on the cyclization of 1,1'-biphenyl-2,2'-diyl bis(trifluoromethanesulfonate) with 4- or 3-anisidine, transformation of the methoxy to a triflate group and subsequent oxidative Pd-catalyzed cyclization with various anilines.
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Investigation of dengue and Japanese encephalitis virus transmission in Hanam, Viet Nam.
Am. J. Trop. Med. Hyg.
PUBLISHED: 03-10-2014
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This study investigated whether a large dengue epidemic that struck Hanoi in 2009 also affected a nearby semirural area. Seroconversion (dengue virus-reactive immunoglobulin G enzyme-linked immunosorbent assay) was high during 2009 compared with 2008, but neutralization assays showed that it was caused by both dengue virus and Japanese encephalitis virus infections. The findings highlight the importance of continued Japanese encephalitis virus vaccination and dengue surveillance.
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A novel radiotracer to image glycogen metabolism in tumors by positron emission tomography.
Cancer Res.
PUBLISHED: 03-05-2014
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The high rate of glucose uptake to fuel the bioenergetic and anabolic demands of proliferating cancer cells is well recognized and is exploited with (18)F-2-fluoro-2-deoxy-d-glucose positron emission tomography ((18)F-FDG-PET) to image tumors clinically. In contrast, enhanced glucose storage as glycogen (glycogenesis) in cancer is less well understood and the availability of a noninvasive method to image glycogen in vivo could provide important biologic insights. Here, we demonstrate that (18)F-N-(methyl-(2-fluoroethyl)-1H-[1,2,3]triazole-4-yl)glucosamine ((18)F-NFTG) annotates glycogenesis in cancer cells and tumors in vivo, measured by PET. Specificity of glycogen labeling was demonstrated by isolating (18)F-NFTG-associated glycogen and with stable knockdown of glycogen synthase 1, which inhibited (18)F-NFTG uptake, whereas oncogene (Rab25) activation-associated glycogen synthesis led to increased uptake. We further show that the rate of glycogenesis is cell-cycle regulated, enhanced during the nonproliferative state of cancer cells. We demonstrate that glycogen levels, (18)F-NFTG, but not (18)F-FDG uptake, increase proportionally with cell density and G1-G0 arrest, with potential application in the assessment of activation of oncogenic pathways related to glycogenesis and the detection of posttreatment tumor quiescence.
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Interactive Visualization for Patient-to-Patient Comparison.
Genomics Inform
PUBLISHED: 02-19-2014
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A visual analysis approach and the developed supporting technology provide a comprehensive solution for analyzing large and complex integrated genomic and biomedical data. This paper presents a methodology that is implemented as an interactive visual analysis technology for extracting knowledge from complex genetic and clinical data and then visualizing it in a meaningful and interpretable way. By synergizing the domain knowledge into development and analysis processes, we have developed a comprehensive tool that supports a seamless patient-to-patient analysis, from an overview of the patient population in the similarity space to the detailed views of genes. The system consists of multiple components enabling the complete analysis process, including data mining, interactive visualization, analytical views, and gene comparison. We demonstrate our approach with medical scientists on a case study of childhood cancer patients on how they use the tool to confirm existing hypotheses and to discover new scientific insights.
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EXTREME: an online EM algorithm for motif discovery.
Bioinformatics
PUBLISHED: 02-14-2014
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Identifying regulatory elements is a fundamental problem in the field of gene transcription. Motif discovery-the task of identifying the sequence preference of transcription factor proteins, which bind to these elements-is an important step in this challenge. MEME is a popular motif discovery algorithm. Unfortunately, MEME's running time scales poorly with the size of the dataset. Experiments such as ChIP-Seq and DNase-Seq are providing a rich amount of information on the binding preference of transcription factors. MEME cannot discover motifs in data from these experiments in a practical amount of time without a compromising strategy such as discarding a majority of the sequences.
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SIRT1 activation by a c-MYC oncogenic network promotes the maintenance and drug resistance of human FLT3-ITD acute Myeloid Leukemia stem cells.
Cell Stem Cell
PUBLISHED: 02-04-2014
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The FLT3-ITD mutation is frequently observed in acute myeloid leukemia (AML) and is associated with poor prognosis. In such patients, FLT3 tyrosine kinase inhibitors (TKIs) are only partially effective and do not eliminate the leukemia stem cells (LSCs) that are assumed to be the source of treatment failure. Here, we show that the NAD-dependent SIRT1 deacetylase is selectively overexpressed in primary human FLT3-ITD AML LSCs. This SIRT1 overexpression is related to enhanced expression of the USP22 deubiquitinase induced by c-MYC, leading to reduced SIRT1 ubiquitination and enhanced stability. Inhibition of SIRT1 expression or activity reduced the growth of FLT3-ITD AML LSCs and significantly enhanced TKI-mediated killing of the cells. Therefore, these results identify a c-MYC-related network that enhances SIRT1 protein expression in human FLT3-ITD AML LSCs and contributes to their maintenance. Inhibition of this oncogenic network could be an attractive approach for targeting FLT3-ITD AML LSCs to improve treatment outcomes.
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Positron emission tomography imaging with 18F-labeled ZHER2:2891 affibody for detection of HER2 expression and pharmacodynamic response to HER2-modulating therapies.
Clin. Cancer Res.
PUBLISHED: 02-03-2014
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Expression of HER2 has profound implications on treatment strategies in various types of cancer. We investigated the specificity of radiolabeled HER2-targeting ZHER2:2891 Affibody, [(18)F]GE-226, for positron emission tomography (PET) imaging.
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The atopic skin-like microenvironment modulates the T-cell-polarising cytokine production of myeloid dendritic cells, as determined by laser scanning cytometry.
Exp. Dermatol.
PUBLISHED: 02-02-2014
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Because it is not known exactly when or where myeloid dendritic cells (mDCs) acquire their atopic dermatitis (AD)-specific T-cell-polarising ability in patients with this condition, we used laser scanning cytometry (LSC) to determine whether isolated peripheral blood mDCs from AD patients differed from cells from controls in their cytokine expression profiles de novo and after stimulation with Staphylococcus enterotoxin B (SEB) and thymic stromal lymphopoietin (TSLP), which represents an AD-like microenvironment. Unstimulated mDCs from AD patients showed pluripotent T-cell-polarising capacity, and the surrounding skin microenvironment was essential for the distinctive, disease-specific activity of mDCs (Th2-Th22 bias). We also emphasise that LSC is an attractive technique to study the effect of new DC-targeted therapeutic modalities in AD.
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Pandemic H1N1 virus transmission and shedding dynamics in index case households of a prospective Vietnamese cohort.
J. Infect.
PUBLISHED: 01-21-2014
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Influenza household transmission studies are required to guide prevention strategies but most passively recruit index cases that seek healthcare. We investigated A(H1N1)pdm09 transmission in a household-based cohort during 2009.
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A genetic map of Peromyscus with chromosomal assignment of linkage groups (a Peromyscus genetic map).
Mamm. Genome
PUBLISHED: 01-21-2014
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The rodent genus Peromyscus is the most numerous and species-rich mammalian group in North America. The naturally occurring diversity within this genus allows opportunities to investigate the genetic basis of adaptation, monogamy, behavioral and physiological phenotypes, growth control, genomic imprinting, and disease processes. Increased genomic resources including a high quality genetic map are needed to capitalize on these opportunities. We produced interspecific hybrids between the prairie deer mouse (P. maniculatus bairdii) and the oldfield mouse (P. polionotus) and scored meiotic recombination events in backcross progeny. A genetic map was constructed by genotyping of backcross progeny at 185 gene-based and 155 microsatellite markers representing all autosomes and the X-chromosome. Comparison of the constructed genetic map with the molecular maps of Mus and Rattus and consideration of previous results from interspecific reciprocal whole chromosome painting allowed most linkage groups to be unambiguously assigned to specific Peromyscus chromosomes. Based on genomic comparisons, this Peromyscus genetic map covers ~83% of the Rattus genome and 79% of the Mus genome. This map supports previous results that the Peromyscus genome is more similar to Rattus than Mus. For example, coverage of the 20 Rattus autosomes and the X-chromosome is accomplished with only 28 segments of the Peromyscus map, but coverage of the 19 Mus autosomes and the X-chromosome requires 40 chromosomal segments of the Peromyscus map. Furthermore, a single Peromyscus linkage group corresponds to about 91% of the rat and only 76% of the mouse X-chromosomes.
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Immunogenicity of IMS 1113 plus soluble subunit and chimeric proteins containing Mycoplasma hyopneumoniae P97 C-terminal repeat regions.
FEMS Microbiol. Lett.
PUBLISHED: 01-20-2014
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The surface adhesin P97 mediates the adherence of Mycoplasma hyopneumoniae to swine cilia. Two reiterated repeats R1 and R2 are located at the C-terminus of P97. The purpose of this study was to evaluate the immunogenicity of Montanide adjuvant IMS 1113 plus soluble subunit proteins rR1, rR1R2 and their chimeric forms coupled with B subunit of the heat-labile enterotoxin of Escherichia coli (LTB). Each recombinant protein in this study was capable of eliciting anti-R1 specific humoral antibodies (IgG), mucosal antibodies (IgG and IgA) and IFN-? production. The chimeric protein rLTBR1R2 elicited the quickest humoral antibody response among the recombinant proteins. Serum and bronchoalveolar lavage analysis revealed that each recombinant protein was capable of inducing both Th1 and Th2 responses. Importantly, all of the proteins induced an anti-R1-specific Th2-biased response in both humoral and mucosal compartments, similar to the response observed in a natural infection or vaccination process. These observations indicate that rR1, rR1R2, rLTBR1 and rLTBR1R2 with IMS 1113 might represent a promising subunit vaccine strategy against porcine enzootic pneumonia in pigs.
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Controlling the shape of LiCoPO? nanocrystals by supercritical fluid process for enhanced energy storage properties.
Sci Rep
PUBLISHED: 01-09-2014
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Lithium-ion batteries offer promising opportunities for novel energy storage systems and future application in hybrid electric vehicles or electric vehicles. Cathode materials with high energy density are required for practical application. Herein, high-voltage LiCoPO4 cathode materials with different shapes and well-developed facets such as nanorods and nanoplates with exposed {010} facets have been synthesized by a one-pot supercritical fluid (SCF) processing. The effect of different amines and their roles on the morphology-control has been investigated in detail. It was found that amine having long alkyl chain such as hexamethylenediamine played important roles to manipulate the shape of the nanocrystals by selective adsorption on the specific {010} facets. More importantly, the nanorods and nanoplates showed better electrochemical performance than that of nanoparticles which was attributed to their unique crystallographic orientation with short Li ion diffusion path. The present study emphasizes the importance of crystallographic orientation in improving the electrochemical performance of the high voltage LiCoPO4 cathode materials for Li-ion batteries.
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Comparison of functional outcomes and quality of life between transoral surgery and definitive chemoradiotherapy for oropharyngeal cancer.
Head Neck
PUBLISHED: 01-09-2014
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The purpose of this study was to compare patient-reported outcomes between patients treated by initial transoral resection versus definitive chemoradiotherapy for oropharyngeal cancer.
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Prevalence of comorbidities and their impact on hospital management and short-term outcomes in vietnamese patients hospitalized with a first acute myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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Cardiovascular disease is one of the leading causes of morbidity and mortality in Vietnam. We conducted a pilot study of Hanoi residents hospitalized with a first acute myocardial infarction (AMI) at the Vietnam National Heart Institute in Hanoi for purposes of describing the prevalence of cardiovascular (CVD) and non-CVD comorbidities and their impact on hospital management, in-hospital clinical complications, and short-term mortality in these patients.
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Effects of palladium on the optical and hydrogen sensing characteristics of Pd-doped ZnO nanoparticles.
Beilstein J Nanotechnol
PUBLISHED: 01-01-2014
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The effect of palladium doping of zinc oxide nanoparticles on the photoluminescence (PL) properties and hydrogen sensing characteristics of gas sensors is investigated. The PL intensity shows that the carrier dynamics coincides with the buildup of the Pd-related green emission. The comparison between the deep level emission and the gas sensing response characteristics allows us to suggest that the dissociation of hydrogen takes place at PdZn-vacancies ([Pd (2+)(4d(9))]). The design of this sensor allows for a continuous monitoring in the range of 0-100% LEL H2 concentration with high sensitivity and selectivity.
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Phosphorylation status of thymidine kinase 1 following antiproliferative drug treatment mediates 3'-deoxy-3'-[18F]-fluorothymidine cellular retention.
PLoS ONE
PUBLISHED: 01-01-2014
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3'-Deoxy-3'-[18F]-fluorothymidine ([18F]FLT) is being investigated as a Positron Emission Tomography (PET) proliferation biomarker. The mechanism of cellular [18F]FLT retention has been assigned primarily to alteration of the strict transcriptionally regulated S-phase expression of thymidine kinase 1 (TK1). This, however, does not explain how anticancer agents acting primarily through G2/M arrest affect [18F]FLT uptake. We investigated alternative mechanisms of [18F]FLT cellular retention involving post-translational modification of TK1 during mitosis.
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Systematic fine-mapping of association with BMI and type 2 diabetes at the FTO locus by integrating results from multiple ethnic groups.
PLoS ONE
PUBLISHED: 01-01-2014
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The 16q12.2 locus in the first intron of FTO has been robustly associated with body mass index (BMI) and type 2 diabetes in genome-wide association studies (GWAS). To improve the resolution of fine-scale mapping at FTO, we performed a systematic approach consisting of two parts.
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Sex differences in clinical characteristics, hospital management practices, and in-hospital outcomes in patients hospitalized in a vietnamese hospital with a first acute myocardial infarction.
PLoS ONE
PUBLISHED: 01-01-2014
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Cardiovascular disease is one of the leading causes of morbidity and mortality in Vietnam. We conducted a pilot study of Hanoi residents hospitalized with acute myocardial infarction (AMI) at the Vietnam National Heart Institute in Hanoi. The objectives of this observational study were to examine sex differences in clinical characteristics, hospital management, in-hospital clinical complications, and mortality in patients hospitalized with an initial AMI.
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Learning classification models with soft-label information.
J Am Med Inform Assoc
PUBLISHED: 11-20-2013
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Learning of classification models in medicine often relies on data labeled by a human expert. Since labeling of clinical data may be time-consuming, finding ways of alleviating the labeling costs is critical for our ability to automatically learn such models. In this paper we propose a new machine learning approach that is able to learn improved binary classification models more efficiently by refining the binary class information in the training phase with soft labels that reflect how strongly the human expert feels about the original class labels.
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Decisive Data Sets in Phylogenomics: Lessons from Studies on the Phylogenetic Relationships of Primarily Wingless Insects.
Mol. Biol. Evol.
PUBLISHED: 10-18-2013
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Phylogenetic relationships of the primarily wingless insects are still considered unresolved. Even the most comprehensive phylogenomic studies that addressed this question did not yield congruent results. To get a grip on these problems, we here analyzed the sources of incongruence in these phylogenomic studies by using an extended transcriptome data set. Our analyses showed that unevenly distributed missing data can be severely misleading by inflating node support despite the absence of phylogenetic signal. In consequence, only decisive data sets should be used which exclusively comprise data blocks containing all taxa whose relationships are addressed. Additionally, we used Four-cluster Likelihood Mapping (FcLM) to measure the degree of congruence among genes of a data set, as a measure of support alternative to bootstrap. FcLM showed incongruent signal among genes, which in our case is correlated neither with functional class assignment of these genes nor with model misspecification due to unpartitioned analyses. The herein analyzed data set is the currently largest data set covering primarily wingless insects, but failed to elucidate their interordinal phylogenetic relationships. Although this is unsatisfying from a phylogenetic perspective, we try to show that the analyses of structure and signal within phylogenomic data can protect us from biased phylogenetic inferences due to analytical artifacts.
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Development of an infection screening system for entry inspection at airport quarantine stations using ear temperature, heart and respiration rates.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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After the outbreak of severe acute respiratory syndrome (SARS) in 2003, many international airport quarantine stations conducted fever-based screening to identify infected passengers using infrared thermography for preventing global pandemics. Due to environmental factors affecting measurement of facial skin temperature with thermography, some previous studies revealed the limits of authenticity in detecting infectious symptoms. In order to implement more strict entry screening in the epidemic seasons of emerging infectious diseases, we developed an infection screening system for airport quarantines using multi-parameter vital signs. This system can automatically detect infected individuals within several tens of seconds by a neural-network-based discriminant function using measured vital signs, i.e., heart rate obtained by a reflective photo sensor, respiration rate determined by a 10-GHz non-contact respiration radar, and the ear temperature monitored by a thermography. In this paper, to reduce the environmental effects on thermography measurement, we adopted the ear temperature as a new screening indicator instead of facial skin. We tested the system on 13 influenza patients and 33 normal subjects. The sensitivity of the infection screening system in detecting influenza were 92.3%, which was higher than the sensitivity reported in our previous paper (88.0%) with average facial skin temperature.
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A novel bioelectronic glucose sensor to process distinct electrical activities of pancreatic beta-cells.
Conf Proc IEEE Eng Med Biol Soc
PUBLISHED: 10-11-2013
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Glucose sensors have improved and facilitated therapy for type 1 diabetes. However, they are still not capable to sense all physiological signals and to act in a closed-loop. Pancreatic ?-cells have been shaped during evolution as biological sensors and offer the advantage to integrate all physiological signals in addition to glucose. Moreover, biosensors based on these cells may also serve for non-invasive and continuous long-term characterization of ?-cells, drug research, tissue engineering and pre-transplantation quality control. ?-cells alter their electrical activity upon exposure to glucose and physiological hormones and we have used these properties to design a biosensor. To this end signals were recorded extracellularly from islet cells kept on multi-electrode arrays. Slow and rapid oscillations were observed, both modulated by glucose. Especially slow oscillations are very robust and have an excellent signal/noise ratio. Signal processing functions were designed to separate the two activities to extract and analyze relevant parameters. These parameters correlate very well with either increasing or decreasing glucose concentrations. An electronic device is under construction, based on an embedded FPGA capable of processing multiple channels in parallel. In the future, such a device shall be used as a portable real-time biosensor regulating insulin delivery from a pump.
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Penicillinolide A: a new anti-inflammatory metabolite from the marine fungus Penicillium sp. SF-5292.
Mar Drugs
PUBLISHED: 10-09-2013
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In the course of studies on bioactive metabolites from marine fungi, a new 10-membered lactone, named penicillinolide A (1) was isolated from the organic extract of Penicillium sp. SF-5292 as a potential anti-inflammatory compound. The structure of penicillinolide A (1) was mainly determined by analysis of NMR and MS data and Moshers method. Penicillinolide A (1) inhibited the production of NO and PGE2 due to inhibition of the expression of iNOS and COX-2. Penicillinolide A (1) also reduced TNF-?, IL-1? and IL-6 production, and these anti-inflammatory effects were shown to be correlated with the suppression of the phosphorylation and degradation of I?B-?, NF-?B nuclear translocation, and NF-?B DNA binding activity. In addition, using inhibitor tin protoporphyrin (SnPP), a competitive inhibitor of HO activity, it was verified that the inhibitory effects of compound 1 on the production of pro-inflammatory mediators and NF-?B DNA binding activity were partially associated with HO-1 expression through Nrf2 nuclear translocation.
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Direct observation of antisite defects in LiCoPO4 cathode materials by annular dark- and bright-field electron microscopy.
ACS Appl Mater Interfaces
PUBLISHED: 10-09-2013
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LiCoPO4 cathode materials have been synthesized by a sol-gel route. X-ray diffraction analysis confirmed that LiCoPO4 was well-crystallized in an orthorhombic structure in the Pmna space group. From the high-resolution transmission electron microscopy (HR-TEM) image, the lattice fringes of {001} and {100} are well-resolved. The HR-TEM image and selected area electron diffraction pattern reveal the highly crystalline nature of LiCoPO4 having an ordered olivine structure. The atom-by-atom structure of LiCoPO4 olivine has been observed, for the first time, using high-angle annular dark-field (HAADF) and annual bright-field scanning transmission electron microscopy. We observed the bright contrast in Li columns in the HAADF images and strong contrast in the ABF images, directly indicating the antisite exchange defects in which Co atoms partly occupy the Li sites. The LiCoPO4 cathode materials delivered an initial discharge capacity of 117 mAh/g at a C/10 rate with moderate cyclic performance. The discharge profile of LiCoPO4 shows a plateau at 4.75 V, revealing its importance as a potentially high-voltage cathode. The direct visualization of atom-by-atom structure in this work represents important information for the understanding of the structure of the active cathode materials for Li-ion batteries.
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Adipose-derived cell construct stabilizes heart function and increases microvascular perfusion in an established infarct.
Stem Cells Transl Med
PUBLISHED: 10-08-2013
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We have previously shown that myocardial infarction (MI) immediately treated with an epicardial construct containing stromal vascular fraction (SVF) from adipose tissue preserved microvascular function and left ventricle contractile mechanisms. In order to evaluate a more clinically relevant condition, we investigated the cardiac recovery potential of an SVF construct implanted onto an established infarct. SVF cells were isolated from rat adipose tissue, plated on Vicryl, and cultured for 14 days. Fischer-344 rats were separated into MI groups: (a) 6-week MI (MI), (b) 6-week MI treated with an SVF construct at 2 weeks (MI SVF), (c) 6-week MI with Vicryl construct at 2 weeks (MI Vicryl), and (d) MI 2wk (time point of intervention). Emax, an indicator of systolic performance and contractile function, was lower in the MI and MI Vicryl versus MI SVF. Positron emission tomography imaging ((18)F-fluorodeoxyglucose) revealed a decreased percentage of relative infarct volume in the MI SVF versus MI and MI Vicryl. Total vessel count and percentage of perfusion assessed via immunohistochemistry were both increased in the infarct region of MI SVF versus MI and MI Vicryl. Overall cardiac function, percentage of relative infarct, and percentage of perfusion were similar between MI SVF and MI 2wk; however, total vessel count increased after SVF treatment. These data suggest that SVF treatment of an established infarct stabilizes the heart at the time point of intervention by preventing a worsening of cardiac performance and infarcted volume, and is associated with increased microvessel perfusion in the area of established infarct.
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Radiolabeled RGD Tracer Kinetics Annotates Differential ?v? 3 Integrin Expression Linked to Cell Intrinsic and Vessel Expression.
Mol Imaging Biol
PUBLISHED: 09-12-2013
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The purpose of this paper is to study the association between RGD binding kinetics and ?v?3 integrin receptor density in the complex tumor milieu.
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Preclinical evaluation of a CXCR4-specific (68)Ga-labelled TN14003 derivative for cancer PET imaging.
Bioorg. Med. Chem.
PUBLISHED: 09-11-2013
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Molecular imaging is an ideal platform for non-invasive detection and assessment of cancer. In recent years, the targeted imaging of CXCR4, a chemokine receptor that has been associated with tumour metastasis, has become an area of intensive research. In our pursuit of a CXCR4-specific radiotracer, we designed and synthesised a novel derivative of the CXCR4 peptidic antagonist TN14003, CCIC16, which is amenable to radiolabelling by chelation with a range of PET and SPECT radiometals, such as (68)Ga, (64)Cu and (111)In as well as (18)F (Al(18)F). Potent in vitro binding affinity and inhibition of signalling-dependent cell migration by unlabelled CCIC16 were confirmed by a threefold uptake in CXCR4-over-expressing cells compared to their isogenic counterparts. Furthermore, in vivo experiments demonstrated the favourable pharmacokinetic properties of the (68)Ga-labelled tracer (68)Ga-CCIC16, along with its CXCR4-specific accumulation in tissues with desirable contrast (tumour-to-muscle ratio: 9.5). The specificity of our tracer was confirmed by blocking experiments. Taking into account the attractive intrinsic PET imaging properties of (68)Ga, the comprehensive preclinical evaluation presented here suggests that (68)Ga-CCIC16 is a promising PET tracer for the specific imaging of CXCR4-expressing tumours.
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Three new phenanthrenes, a new stilbenoid isolated from the roots of Stemona tuberosa Lour. and their cytotoxicity.
Nat. Prod. Res.
PUBLISHED: 09-09-2013
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Three new phenanthrenes, stemophenanthrenes A-C (1-3), along with one new stilbenoid, isopinosylvin A (4) and a known compound methyl ferulate (5), were isolated and identified from the roots of Stemona tuberosa Lour. plants, collected in Attapu province (Laos). Their structures were elucidated by spectroscopic analysis (FT-ICR-MS, IR, UV, 1D and 2D NMR). These compounds show moderate cytotoxic activity against four cancer cell lines, KB (a human epidermal carcinoma), MCF7 (human breast carcinoma), SK-LU-1 (human lung carcinoma) and HepG2 (hepatocellular carcinoma).
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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.

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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.