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Find video protocols related to scientific articles indexed in Pubmed.
Establishment of stable MRP1 knockdown by lentivirus-delivered shRNA in the mouse testis Sertoli TM4 cell line.
Toxicol. Mech. Methods
PUBLISHED: 11-19-2014
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Abstract Sertoli cells around germ cells are considered a barrier that protects spermatogenesis from harmful influences. The transporter multidrug-resistance-associated protein 1 (MRP1) is a xenobiotic efflux pump that can export glutathione S-conjugated metabolites and xenobiotics from cells. In this study, the Mrp1 gene was stably knocked down in a mouse Sertoli cell line (TM4) using lentivirus vector-mediated RNA interference (RNAi) technology. Four shRNA interference sequences were chosen and designed to screen for the most effective shRNA in candidate cells. The results indicate that lentivirus vectors with high titres were generated and successfully transfected into TM4 cells with high efficiency. Puromycin was added to the culture medium to maintain constant selection during the establishment of the stable cell lines. The expression levels of Mrp1 mRNA and MRP1 protein in stably transfected TM4 cells were significantly lower than those in the control group. Importantly, the transport activity of MRP1 to Calcein and 5-carboxyseminaptharhodafluor (SNARF-1) were significantly reduced because of MRP1 silencing. Moreover, the silencing of the Mrp1 gene in the transfected TM4 cell lines remained highly stable for more than 6 months. These results suggest that the lentivirus-based RNAi stably knocks down the expression of the Mrp1 gene in the established TM4 cell line. This transfected TM4 cell line will provide a new and powerful tool to study the underlying mechanism of MRP1-mediated drug resistance and detoxication in the reproductive system.
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Anticancer agents from marine sponges.
J Asian Nat Prod Res
PUBLISHED: 11-18-2014
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Marine sponges are currently one of the richest sources of anticancer active compounds found in the marine ecosystems. More than 5300 different known metabolites are from sponges and their associated microorganisms. To survive in the complicated marine environment, most of the sponge species have evolved chemical means to defend against predation. Such chemical adaptation produces many biologically active secondary metabolites including anticancer agents. This review highlights novel secondary metabolites in sponges which inhibited diverse cancer species in the recent 5 years. These natural products of marine sponges are categorized based on various chemical characteristics.
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[Expression and significance of Wnt/?-catenin signaling pathway in vitro natural degenerationmodel of endplate chondrocytes in rats].
Zhonghua Yi Xue Za Zhi
PUBLISHED: 11-18-2014
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To explore the expression and significance of Wnt/?-catenin signaling pathway in the natural degeneration of endplate chondrocytes in rats.
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Organ-specific Responses of Total Body Irradiated Doxycycline-inducible Manganese Superoxide Dismutase Tet/Tet Mice.
In Vivo
PUBLISHED: 11-16-2014
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Background/Aim: We evaluated doxycycline-inducible manganese superoxide dismutase (MnSOD(tet/tet)) mice after 9.25 Gy total-body irradiation (TBI) or 20 Gy thoracic irradiation. Materials and Methods: Six-week-old MnSOD(tet/tet) or control C57BL/6NHsd mice on or off doxycycline (doxy) in food received 9.25 Gy TBI, were sacrificed at day 19 and bone marrow, brain, esophagus, heart, intestine, kidney, liver, lung, spleen and tongue harvested, total RNAs extracted and transcripts for irradiation response genes quantitated by real time-polymerase chain reaction (RT-PCR). Results: MnSOD(tet/tet) mice only survived with daily injections of doxy beginning 5 days after birth until weaning, at which time they were placed on food containing doxy. Manganese superoxide dismutase (MnSOD) transcript levels were reduced in all tissues except the lung. Adult mice survived with low MnSOD levels, but induced by doxy or TBI. Thoracic-irradiated MnSOD(tet/tet) mice survived past day 120. Conclusion: MnSOD(tet/tet) mice should be valuable for elucidating the role of MnSOD in growth and irradiation response.
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PKC? contributes to high NaCl-induced activation of NFAT5 (TonEBP/OREBP) through MAP kinase ERK1/2.
Am. J. Physiol. Renal Physiol.
PUBLISHED: 11-14-2014
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High NaCl in the renal medullary interstitial fluid powers concentration of the urine, but can damage cells. The transcription factor NFAT5 activates expression of osmoprotective genes. We studied whether PKC? contributes to activation of NFAT5. PKC? protein abundance is greater in the renal medulla than in the cortex. Knockout of PKC? reduces NFAT5 protein abundance and expression of its target genes in the inner medulla. In HEK293 cells, high NaCl increases PKC? activity and siRNA-mediated knockdown of PKC? attenuates high NaCl-induced NFAT5 transcriptional activity. Expression of ERK1/2 protein and phosphorylation of ERK1/2 is higher in the renal inner medulla than in the cortex. Knockout of PKC? decreases ERK1/2 phosphorylation in the inner medulla, as does knockdown of PKC? in HEK293 cells. Also, knockdown of ERK2 reduces high NaCl-dependent NFAT5 transcriptional activity in HEK293 cells. Combined knockdown of PKC? and ERK2 has no greater effect than knocking down either alone. Knockdown of either PKC? or ERK2 reduces the high NaCl-induced increase of NFAT5 transactivating activity. We previously found that the high NaCl-induced increase of phosphorylation of SHP-1-S591-P contributes to activation of NFAT5 in cell culture, and we now find high levels of SHP-1-S591-P in the inner medulla. PKC? was previously shown to increase SHP-1-S591-P, which raised the possibility that PKC? might be acting through SHP-1. However, we do not find that knockout of PKC? in the renal medulla or knockdown in HEK293 cells affects SHP-1-S591-P. We conclude that PKC? contributes to high NaCl-dependent activation of NFAT5 through ERK1/2, but not through SHP-1-S591.
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Frontispiece: iridium-catalyst-based autonomous bubble-propelled graphene micromotors with ultralow catalyst loading.
Chemistry
PUBLISHED: 11-01-2014
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Self-Propelled Motors Research on self-propelled micro-/nanoscale motors provides various potential applications ranging from the biomedical field to addressing environmental issues. In their Communication on page 14946?ff., M. Pumera et?al. describe the new concept of self-propelled micromotors with high surface areas and a very low loading of catalyst. The iridium-based graphene micromotor (exemplified here by a graphene fish with an iridium eye over a coral reef in Lombok, Indonesia) can display autonomous bubble propulsion in the presence of hydrogen peroxide, even at a very low concentration of catalyst (0.54 at%).
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Hyperhomocysteinemia and hyperglycemia induce and potentiate endothelial dysfunction via ?-calpain activation.
Diabetes
PUBLISHED: 10-30-2014
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Plasma homocysteine (Hcy) levels are positively correlated with cardiovascular mortality in diabetes. However, the joint effect of hyperhomocysteinemia (HHcy) and hyperglycemia (HG) on endothelial dysfunction (ED) and the underlying mechanisms have not been studied.Mild (22 µmol/L) and moderate HHcy (88 µmol/L) were induced in cystathionine ?-synthase wild type (Cbs(+/+)) and heterozygous deficient (Cbs(-/+)) mice by a high methionine (HM) diet. HG was induced by consecutive injection of streptozotocin. We found that HG worsened HHcy and elevated Hcy levels to 55 µmol/L and 173 µmol/L in Cbs(+/+) and Cbs(-/+) mice fed a HM diet, respectively. Both mild and moderate HHcy aggravated HG-impaired endothelium-dependent vascular relaxation to acetylcholine, which was completely abolished by endothelial nitric oxide synthase (eNOS) inhibitor L-NAME. HHcy potentiated HG-induced calpain activation in aortic endothelial cells isolated from Cbs mice. Calpain inhibitors rescued HHcy- and HHcy/HG-induced ED in vivo and ex vivo. Moderate HHcy and HG-induced ?-calpain activation was potentiated by a combination of HHcy and HG in the mouse aorta. ?-calpain siRNA (?-calpsiRNA) prevented HHcy/HG-induced ED in the mouse aorta and calpain activation in human aortic endothelial cells (HAECs) treated with DL-homocysteine (500 µmol/L) and D-glucose (25 mmol) for 48 hrs. In addition, HHcy accelerated HG-induced superoxide production as determined by DHE and 3-NT staining and urinary 8-isoprostane/creatinine assay. Antioxidants rescued HHcy/HG-induced ED in mouse aortas and calpain activation in cultured HAECs. Finally, HHcy potentiated HG-suppressed NO production and eNOS activity in HAECs, which were prevented by calpain inhibitors or ?-calpain siRNA. HHcy aggravated HG-increased phosphorylation of eNOS at threonine 497/495 in the mouse aorta and HAECs. HHcy/HG induced eNOSp-Thr497/495 was reversed by µ-calpsiRNA and adenoviral transduced dominant negative PKC?2 in HAECs.HHcy and HG induced ED, which was potentiated by the combination of HHcy and HG via ?-calpain/PKC?2 activation-induced eNOSp-Thr497/495 and eNOS inactivation.
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Arrays of High-Aspect Ratio Microchannels for High-Throughput Isolation of Circulating Tumor Cells (CTCs).
Microsyst Technol
PUBLISHED: 10-29-2014
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Microsystem-based technologies are providing new opportunities in the area of in vitro diagnostics due to their ability to provide process automation enabling point-of-care operation. As an example, microsystems used for the isolation and analysis of circulating tumor cells (CTCs) from complex, heterogeneous samples in an automated fashion with improved recoveries and selectivity are providing new opportunities for this important biomarker. Unfortunately, many of the existing microfluidic systems lack the throughput capabilities and/or are too expensive to manufacture to warrant their widespread use in clinical testing scenarios. Here, we describe a disposable, all-polymer, microfluidic system for the high-throughput (HT) isolation of CTCs directly from whole blood inputs. The device employs an array of high aspect ratio (HAR), parallel, sinusoidal microchannels (25 µm × 150 µm; W × D; AR = 6.0) with walls covalently decorated with anti-EpCAM antibodies to provide affinity-based isolation of CTCs. Channel width, which is similar to an average CTC diameter (12-25 µm), plays a critical role in maximizing the probability of cell/wall interactions and allows for achieving high CTC recovery. The extended channel depth allows for increased throughput at the optimized flow velocity (2 mm/s in a microchannel); maximizes cell recovery, and prevents clogging of the microfluidic channels during blood processing. Fluidic addressing of the microchannel array with a minimal device footprint is provided by large cross-sectional area feed and exit channels poised orthogonal to the network of the sinusoidal capillary channels (so-called Z-geometry). Computational modeling was used to confirm uniform addressing of the channels in the isolation bed. Devices with various numbers of parallel microchannels ranging from 50 to 320 have been successfully constructed. Cyclic olefin copolymer (COC) was chosen as the substrate material due to its superior properties during UV-activation of the HAR microchannels surfaces prior to antibody attachment. Operation of the HT-CTC device has been validated by isolation of CTCs directly from blood secured from patients with metastatic prostate cancer. High CTC sample purities (low number of contaminating white blood cells, WBCs) allowed for direct lysis and molecular profiling of isolated CTCs.
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Acetylene bubble-powered autonomous capsules: towards in situ fuel.
Chem. Commun. (Camb.)
PUBLISHED: 10-27-2014
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A fuel-free autonomous self-propelled motor is illustrated. The motor is powered by the chemistry of calcium carbide and utilising water as a co-reactant, through a polymer encapsulation strategy. Expulsion of acetylene bubbles powers the capsule motor. This is an important step, going beyond the toxic hydrogen peroxide fuel used normally, to find alternative propellants for self-propelled machines.
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Potent Inhibitory Effect of ?-Tocopherol on Prostate Cancer Cells Cultured in Vitro and Grown As Xenograft Tumors in Vivo.
J. Agric. Food Chem.
PUBLISHED: 10-27-2014
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In the present study, the effects of ?-tocopherol (?-T) on growth and apoptosis of human prostate cancer cells were determined and compared with that of ?-tocopherol (?-T), a commonly used form of vitamin E. Treatment of human prostate cancer cells with ?-T resulted in strong growth inhibition and apoptosis stimulation, while the effects of ?-T were modest. The strong effects of ?-T on the cells were associated with suppression of androgen receptor (AR) activity and decreased level of prostate specific antigen (PSA) that is a downstream target of the AR signaling. In the in vivo study, we found that ?-T had a more potent inhibitory effect on the formation and growth of prostate xenograft tumors than that of ?-T. Moreover, ?-T inhibited proliferation and stimulated apoptosis in the tumors. The present study identified ?-T as a better form of vitamin E than ?-T for future clinical studies of prostate cancer prevention.
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[Advances of treatment for nature killer/t-cell lymphoma].
Zhongguo Shi Yan Xue Ye Xue Za Zhi
PUBLISHED: 10-24-2014
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NK/T cell lymphoma (NKTCL) is a rare type of non-Hodgkin's lymphoma, occurs more frequently in Asia and Latin America. In China, NKTCL accounts for 30.1% in T-NHL and is highly related with EBV (Epstein-Barr virus) infection. This disease is highly aggressive, not sensitive to chemotherapy, with poor prognosis. The mean survival time is about 12-38 months. It is important to accurately assess the patient's stage of progression for an optimal treatment. For stageI-II, the combined chemotherapy and radiotherapy have better therapeutic effects. As for stage III-IV NKTCL, especially for non-nasal and aggressive subtypes, the chemotherapy is the main treatment method. For advanced disease, combining therapy is the most commonly selected approach, such as high-intensity chemotherapy combined with radiation and a regimen containing L-asparaginase (L-Asp) will benefit to patients. Recently, some studies have demonstrated that promising outcomes have been found in selected cases by high-dose chemotherapy supplemented with auto-or allo-HSCT. Targeting therapy is also an optimal choice. This review mainly focuses on the advance of treatment for NKTCL.
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[Isolation, identification and characterization of a diethylstilbestrol-degrading bacterial strain Serratia sp].
Huan Jing Ke Xue
PUBLISHED: 10-24-2014
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Utilizing the diethylstilbestrol (DES)-degrading bacteria to biodegrade DES is a most reliable technique for cleanup of DES pollutants from the environment. However, little information is available heretofore on the isolation of DES-degrading bacteria and their DES removal performance in the environment. A novel bacterium capable of degrading DES was isolated from the activated sludge of a wastewater treatment plant. According to its morphology, physiochemical characteristics, and 16S rDNA sequence analysis, this strain was identified as Serratia sp.. The strain was an aerobic bacterium, and it could degrade 68.3% of DES (50 mg x L(-1)) after culturing for 7 days at 30 degrees C, 150 r x min(-1) in shaking flasks. The optimal conditions for DES biodegradation by the obtained strain were 30 degrees C, 40-60 mg x L(-1) DES, pH 7.0, 5% of inoculation volume, 0 g x L(-1) of added NaCl, and 10 mL of liquid medium volume in 100 mL flask.
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E2F1 suppresses cardiac neovascularization by down-regulating VEGF and PlGF expression.
Cardiovasc. Res.
PUBLISHED: 10-23-2014
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The E2F transcription factors are best characterized for their roles in cell-cycle regulation, cell growth, and cell death. Here we investigated the potential role of E2F1 in cardiac neovascularization.
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SIRT4 Suppresses Inflammatory Responses in Human Umbilical Vein Endothelial Cells.
Cardiovasc. Toxicol.
PUBLISHED: 10-22-2014
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The most common feature of endothelial dysfunction is endothelial inflammation. A bunch of factors are associated with endothelial dysfunction. These include pro-inflammatory cytokines, cell adhesion molecules, and matrix degrading enzymes. SIRT4, a member of the sirtuin family, is a mitochondrial ADP-ribosyltransferase. The roles of SIRT4 in regulating inflammation in endothelial cells are unknown. In this study, we found that lipopolysaccharide treatment decreased the expression of SIRT4 in human umbilical vein endothelial cells. Silence of SIRT4 exacerbated the expression of pro-inflammatory cytokines (IL-1?, IL-6 and IL-8), COX-prostaglandin system (COX-2), ECM remodeling enzymes MMP-9, and the adhesion molecule ICAM-1. The upregulation of these genes are involved in inflammation, vascular remodeling, and angiogenesis. In contrast, overexpression of SIRT4 attenuated the induction of these factors. Mechanistically, SIRT4 was found to interfere with the NF-?B signaling pathway by preventing NF-?B nuclear translocation and thereby has an anti-inflammatory function. Loss of SIRT4 increased the nuclear translocation as well as the transcriptional activity of NF-?B. However, overexpression of SIRT4 mitigated the nuclear translocation and the transcriptional activity of NF-?B. Our data suggested that SIRT4 might be a potential pharmacological target for inflammatory vascular diseases.
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Association of Copy Numbers of Survival Motor Neuron Gene 2 and Neuronal Apoptosis Inhibitory Protein Gene With the Natural History in a Chinese Spinal Muscular Atrophy Cohort.
J. Child Neurol.
PUBLISHED: 10-22-2014
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We evaluated survival motor neuron 2 (SMN2) and neuronal apoptosis inhibitory protein (NAIP) gene copy distribution and the association of copy number with survival in 232 Chinese spinal muscular atrophy (SMA) patients. The SMN2 and NAIP copy numbers correlated positively with the median onset age (r = 0.72 and 0.377). The risk of death for patients with fewer copies of SMN2 or NAIP was much higher than for those with more copies (P < .01). The survival probabilities at 5 years were 5.1%, 90.7%, and 100% for 2, 3, and 4 SMN2 copies and 27.9%, 66.7%, and 87.2% for 0, 1, and 2 NAIP copies, respectively. Our results indicated that combined SMN1-SMN2-NAIP genotypes with fewer copies were associated with earlier onset age and poorer survival probability. Better survival status for Chinese type I SMA might due to a higher proportion of 3 SMN2 and a lower rate of zero NAIP.
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LED high-beam headlamp based on free-form microlenses.
Appl Opt
PUBLISHED: 10-17-2014
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To eliminate the rainbow phenomenon of white LED sources caused by optical dispersion in a motorcar's headlamp with a thick lens, we propose an LED high-beam headlamp based on free-form microlenses. The free-form microlenses include total reflection surfaces, which collimate the beams emitting from the LED source, and microlens structures, which redistribute the collimated beams to the target plane. We optimize the map relationship between the LED source and the illumination plane according to ECE regulation R112. Simulation and experiment results show that our proposed free-form microlenses could efficiently distribute light radiated from the LED source. All illumination on the test points and zones could reach ECE regulation R112. There is little dispersion in the light pattern in the target plane.
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Stability of in-phase quadruple and vortex solitons in the parity-time-symmetric periodic potentials.
Opt Express
PUBLISHED: 10-17-2014
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We report the stability of in-phase quadruple and off-site vortex solitons in the parity-time-symmetric periodic potentials with defocusing Kerr nonlinearity. All solitons can exist in the first gap and can be stable in a certain range. It is shown that the power of vortex solitons decreases and the stable region shrinks with increase of the topological charge. Especially the stable region is very small for double charge vortex solitons. The power evolutions of vortex solitons along the propagation distance are also analysed. Increasing the lattice depth or decreasing the gain-loss component can stabilize vortex solitons. For both lattice depth and gain-loss component there exists a critical value, below or above which all vortex solitons will become unstable.
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A comparison of unilateral and bilateral pedicle screw fixation combined with transforaminal lumbar interbody fusion for lumbar degenerative diseases.
Chin. Med. J.
PUBLISHED: 10-16-2014
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Bilateral transpedicular screw fixation in conjunction with interbody fusion is widely used to treat lumbar degenerative diseases; however, there are some disadvantages of using this fixation system. This study comparatively analyzes the results of unilateral and bilateral pedicle screw fixation combined with transforaminal lumbar interbody fusion (TLIF) for one-level lumbar degenerative diseases.
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Mucosal immunization with a live attenuated vaccine SPY1 induces humoral and Th2-Th17-Treg cellular immunity and protects against pneumococcal infection.
Infect. Immun.
PUBLISHED: 10-15-2014
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Mucosal immunization with attenuated vaccine can protect against pneumococcal invasion infection, but the function was unknown. Our study found that mucosal delivery with the live attenuated vaccine SPY1 strain can confer T cells and B cells dependent protection against pneumococcal colonization and invasive infection, yet it's still unclear which cell subsets contribute to the protection and their roles in pneumococcal colonization and invasion remain elusive. Adoptive transfer of anti-SPY1 antibody conferred protection to naïve ?MT mice and immune T cells were indispensable to protection examined in nude mice. A critical role of IL-17A in colonization was demonstrated in mice lacking IL-17A and vaccine-specific Th2 immune subset was necessary for systemic protection. Of note, we found that SPY1 could stimulate immunoregulatory response and SPY1-elicited regulatory T cells participated in protection against colonization and lethal infection. The data presented here aid our understanding of how live attenuated strains are able to function as effective vaccines, and may be contribute to a more comprehensive evaluation of live vaccines and other mucosal vaccines.
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Insect pollination and self-incompatibility in edible and/or medicinal crops in southwestern China, a global hotspot of biodiversity.
Am. J. Bot.
PUBLISHED: 10-14-2014
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An increasing global demand for food, coupled with the widespread decline of pollinator diversity, remains an international concern in agriculture and genetic conservation. In particular, there are large gaps in the study of the pollination of economically important and traditionally grown species in China. Many plant species grown in China are both edible and used medicinally. The country retains extensive written records of agricultural and apicultural practices, facilitating contemporary studies of some important taxa. Here, we focus on Yunnan in southwestern China, a mega-biodiversity hotspot for medicinal/food plants. We used plant and insect taxa as model systems to understand the patterns and consequences of pollinator deficit to crops. We identified several gaps and limitations in research on the pollination ecology and breeding systems of domesticated taxa and their wild relatives in Yunnan and asked the following questions: (1) What is known about pollination systems of edible and medicinal plants in Yunnan? (2) What are the most important pollinators of Codonopsis subglobosa (Campanulaceae)? (3) How important are native pollinator species for maximizing yield in Chinese crops compared with the introduced Apis mellifera? We found that some crops that require cross-pollination now depend exclusively on hand pollination. Three domesticated crops are dependent primarily on the native but semidomesticated Apis cerana and the introduced A. mellifera. Other species of wild pollinators often play important roles for certain specialty crops (e.g., Vespa velutina pollinates Codonopsis subglobosa). We propose a more systematic and comprehensive approach to applied research in the future.
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Abnormal methylation of the sex-determining region Y-box 17 (SOX17) promoter predicts poor prognosis in myelodysplastic syndrome.
Clin. Lab.
PUBLISHED: 10-09-2014
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The sex-determining region Y-box 17 (SOX17) is a member of the high mobility group (HMG) transcription factor family, which plays critical roles in the regulation of development and stem/precursor cell function. Recent evidence demonstrated that SOX17 acts as a tumor-suppressor gene, at least partly though repression of Wnt pathway activity.
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Serial intravascular ultrasound analysis of stent strut distribution and fracture: an integrated analysis of the taxus IV, V, and VI trials.
J Invasive Cardiol
PUBLISHED: 10-03-2014
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Non-uniform distribution of drug-eluting stent struts may cause uneven drug deposition associated with an adverse neointimal response and clinical events. This study assesses circumferential stent strut distribution in bare-metal (BMS) and paclitaxel-eluting (Taxus) stents post implantation and at 9-month follow-up, as well as its impact on intimal hyperplasia (IH).
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UBC13, an E2 enzyme for Lys63-linked ubiquitination, functions in root development by affecting auxin signaling and Aux/IAA protein stability.
Plant J.
PUBLISHED: 10-03-2014
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Unlike conventional lysine (K) 48-linked polyubiquitination, K63-linked polyubiquitination plays signaling roles in yeast and animals. Thus far, UBC13 is the only known ubiquitin-conjugating enzyme (E2) specialized in K63-linked polyubiquitination. Previous identification of Arabidopsis genes encoding UBC13 as well as its interacting partner UEV1 indicates that the UBC13-mediated ubiquitination pathway is conserved in plants; however, little is known about functions and signaling mediated through K63-linked polyubiquitination in plants. To address the functions of UBC13-mediated ubiquitination in plants, we created Arabidopsis ubc13 null mutant lines in which the two UBC13 genes were disrupted. The double mutant displayed altered root development, including shorter primary root, fewer lateral roots and only a few short root hairs in comparison with the wild type and single mutant plants, indicating that UBC13 activity is critical for all major aspects of root development. The double mutant plants were insensitive to auxin treatments, suggesting that the strong root phenotypes do not simply result from a reduced level of auxin. Instead, the ubc13 mutant had a reduced auxin response, as indicated by the expression of an auxin-responsive DR5 promoter-GFP. Furthermore, both the enzymatic activity and protein level of an AXR3/IAA17-GUS reporter were greatly increased in the ubc13 mutant, whereas the induction of many auxin-responsive genes was suppressed. Collectively, these results suggest that Aux/IAA proteins accumulate in the ubc13 mutant, resulting in a reduced auxin response and defective root development. Hence, this study provides possible mechanistic links between UBC13-mediated protein ubiquitination, root development and auxin signaling.
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Genetic polymorphisms of VIP variants in the Tajik ethnic group of northwest China.
BMC Genet.
PUBLISHED: 09-30-2014
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BackgroundIndividual response to medications varies significantly among different populations, and great progress in understanding the molecular basis of drug action has been made in the past 50 years. The field of pharmacogenomics seeks to elucidate inherited differences in drug disposition and effects. While we know that different populations and ethnic groups are genetically heterogeneous, we have not found any pharmacogenomics information regarding minority groups, such as the Tajik ethnic group in northwest China.ResultsWe genotyped 85 Very Important Pharmacogene (VIP) variants selected from PharmGKB in 100 unrelated, healthy Tajiks from the Xinjiang Uygur Autonomous Region and compared our data with HapMap data from four major populations around the world: Han Chinese (CHB), Japanese in Tokyo (JPT), Utah Residents with Northern and Western European Ancestry (CEU), and Yorubia in Ibadan, Nigeria (YRI). We found that Tajiks differed from CHB, JPT and YRI in 30, 32, and 32 of the selected VIP genotypes respectively (p¿<¿0.005), while differences between Tajiks and CEU were found in only 6 of the genotypes (p¿<¿0.005). Haplotype analysis also demonstrated differences between the Tajiks and the other four populations.ConclusionOur results contribute to the pharmacogenomics database of the Tajik ethnic group and provide a theoretical basis for safer drug administration that may be useful for diagnosing and treating disease in this population.
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Inhibitors of nucleotidyltransferase superfamily enzymes suppress herpes simplex virus replication.
Antimicrob. Agents Chemother.
PUBLISHED: 09-29-2014
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Herpesviruses are large double-stranded DNA viruses that cause serious human diseases. Herpesvirus DNA replication depends on multiple processes typically catalyzed by nucleotidyltransferase superfamily (NTS) enzymes. Therefore, we investigated whether inhibitors of NTS enzymes would suppress replication of herpes simplex virus 1 (HSV-1) and HSV-2. Eight of 42 NTS inhibitors suppressed HSV-1 and/or HSV-2 replication by >10-fold at 5 ?M, with suppression at 50 ?M reaching ?1 million-fold. Five compounds in two chemical families inhibited HSV replication in Vero and human foreskin fibroblast cells as well as the approved drug acyclovir did. The compounds had 50% effective concentration values as low as 0.22 ?M with negligible cytotoxicity in the assays employed. The inhibitors suppressed accumulation of viral genomes and infectious particles and blocked events in the viral replication cycle before and during viral DNA replication. Acyclovir-resistant mutants of HSV-1 and HSV-2 remained highly sensitive to the NTS inhibitors. Five of six NTS inhibitors of the HSVs also blocked replication of another herpesvirus pathogen, human cytomegalovirus. Therefore, NTS enzyme inhibitors are promising candidates for new herpesvirus treatments that may have broad efficacy against members of the herpesvirus family.
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[Cloning and heterologous expression of laccase genes vv-lac1 and vv-lac6 from Volvaria volvacea].
Wei Sheng Wu Xue Bao
PUBLISHED: 09-26-2014
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To clone the full-length cDNAs of two laccase genes, vv-lac1 and vv-1ac6, from Volvaria volvacea, verify their encoded proteins with laccase activity and develop a heterologous expression and protein purification system for V. volvacea laccase genes.
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Two-dimensional heterostructures: fabrication, characterization, and application.
Nanoscale
PUBLISHED: 09-16-2014
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Two-dimensional (2D) materials such as graphene, hexagonal boron nitrides (hBN), and transition metal dichalcogenides (TMDs, e.g., MoS2) have attracted considerable attention in the past few years because of their novel properties and versatile potential applications. These 2D layers can be integrated into a monolayer (lateral 2D heterostructure) or a multilayer stack (vertical 2D heterostructure). The resulting artificial 2D structures provide access to new properties and applications beyond their component 2D atomic crystals and hence, they are emerging as a new exciting field of research. In this article, we review recent progress on the fabrication, characterization, and applications of various 2D heterostructures.
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[EEG feature extraction based on quantum particle swarm optimizer and independent component analysis].
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi
PUBLISHED: 09-16-2014
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Feature extraction is a very crucial step in P300-based brain-computer interface (BCI) and independent component analysis (ICA) is a suitable P300 feature extraction method. But at present the convergence performance of the general ICA iteration methods are not very satisfactory. In this paper, a method based on quantum particle swarm optimizer (QPSO) algorithm and ICA technique is put forward for P300 extraction. In this method, quantum computing is used to impel ICA iteration to globally converge faster. It achieved the purpose of extracting P300 rapidly and efficiently. The method was tested on two public datasets of BCI Competition II and III, and a simple linear classifier was employed to classify the extracted P300 features. The recognition accuracy reached 94.4% with 15 times averaged. The results showed that the proposed method could extract P300 rapidly and the extraction effect did not reduce. It provides an experimental basis for further study of real-time BCI system.
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JUMP: a tag-based database search tool for peptide identification with high sensitivity and accuracy.
Mol. Cell Proteomics
PUBLISHED: 09-10-2014
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Database search programs are essential tools for identifying peptides by mass spectrometry (MS) in shotgun proteomics. Simultaneously achieving high sensitivity and specificity during database search is crucial for improving proteome coverage. Here we present JUMP, a new hybrid database search program that generates amino acid tags and ranks peptide spectrum matches (PSMs) by an integrated score from the tags and pattern matching. In a typical run of liquid chromatography coupled with high-resolution tandem MS, more than 95% of MS/MS spectra can generate at least one tag, whereas the remaining spectra are usually too poor to derive genuine PSMs. To enhance search sensitivity, the JUMP program enables the use of tags as short as one amino acid. Using the target-decoy strategy, we compared JUMP with other programs (e.g. SEQUEST, Mascot, PEAKS DB, and InsPecT) in the analysis of multiple datasets and demonstrate that JUMP outperforms these pre-existing programs. JUMP also permits the analysis of multiple co-fragmented peptides from mixture spectra to further increase PSMs. In addition, JUMP-derived tags allow partial de novo sequencing and facilitate the assignment of modified residues unambiguously. In summary, JUMP is an effective database search algorithm complementary to current search programs.
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[Influences of life event and coping style on left-behind middle school student mental health in a three-gorge area county].
Wei Sheng Yan Jiu
PUBLISHED: 09-10-2014
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To study the effects of life event and coping style on left-behind middle school student mental health.
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Improved hematopoiesis in GS-nitroxide (JP4-039)-treated mouse long-term bone marrow cultures and radioresistance of derived bone marrow stromal cell lines.
In Vivo
PUBLISHED: 09-06-2014
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To determine if the small-molecule radioprotector GS-nitroxide, JP4-039, improved hematopoiesis in long-term bone marrow cultures (LTBMCs), explanted marrow from in vivo drug-treated C57BL/6NTac mice was maintained in JP4-039 for 25 weeks. Hematopoietic cell production and radiobiology of derived stromal cell lines was measured.
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Pentacene-fused diporphyrins.
Chemistry
PUBLISHED: 09-03-2014
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In this work, we report the synthesis, spectroscopic characterization, and theoretical analysis of a linearly conjugated pentacene-fused porphyrin dimer and cross-conjugated quinone-fused dinaphtho[2,3]porphyrins. These multichromophoric systems display non-typical UV-visible absorptions of either porphyrins or pentacenes/quinones. UV-visible, emission and magnetic circular dichroism (MCD) spectroscopy suggest strong electronic interactions among the multichromophores in the system. DFT calculations revealed the delocalization of the HOMOs and LUMOs spanning the entire dimer and linker assembly. The pentacene-fused porphyrin dimer is significantly more stable than both the corresponding pentacene and the heptacene derivatives. The availability of these huge ?-extended and electronically highly interactive multichromophoric systems promises unprecedented electronic and photophysical properties.
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Increased drought tolerance through the suppression of ESKMO1 gene and overexpression of CBF-related genes in Arabidopsis.
PLoS ONE
PUBLISHED: 09-03-2014
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Improved drought tolerance is always a highly desired trait for agricultural plants. Significantly increased drought tolerance in Arabidopsis thaliana (Columbia-0) has been achieved in our work through the suppression of ESKMO1 (ESK1) gene expression with small-interfering RNA (siRNA) and overexpression of CBF genes with constitutive gene expression. ESK1 has been identified as a gene linked to normal development of the plant vascular system, which is assumed directly related to plant drought response. By using siRNA that specifically targets ESK1, the gene expression has been reduced and drought tolerance of the plant has been enhanced dramatically in the work. However, the plant response to external abscisic acid application has not been changed. ICE1, CBF1, and CBF3 are genes involved in a well-characterized plant stress response pathway, overexpression of them in the plant has demonstrated capable to increase drought tolerance. By overexpression of these genes combining together with suppression of ESK1 gene, the significant increase of plant drought tolerance has been achieved in comparison to single gene manipulation, although the effect is not in an additive way. Accompanying the increase of drought tolerance via suppression of ESK1 gene expression, the negative effect has been observed in seeds yield of transgenic plants in normal watering conditions comparing with wide type plant.
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Controlled functionalization of carbonaceous fibers for asymmetric solid-state micro-supercapacitors with high volumetric energy density.
Adv. Mater. Weinheim
PUBLISHED: 09-02-2014
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A 1.8 V asymmetric solid-state flexible micro-supercapacitor is designed with one MnO2 -coated reduced graphene oxide/single-walled carbon nanotube (rGO/SWCNT) composite fiber as positive electrode and one nitrogen-doped rGO/SWCNT fiber as negative electrode, which demonstrates ultrahigh volumetric energy density, comparable to some thin-film lithium batteries, along with high power density, long cycle life, and good flexibility.
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Inhibition of West Nile virus by calbindin-D28k.
PLoS ONE
PUBLISHED: 09-02-2014
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Evidence indicates that West Nile virus (WNV) employs Ca(2+) influx for its replication. Moreover, calcium buffer proteins, such as calbindin D28k (CB-D28k), may play an important role mitigating cellular destruction due to disease processes, and more specifically, in some neurological diseases. We addressed the hypothesis that CB-D28k inhibits WNV replication in cell culture and infected rodents. WNV envelope immunoreactivity (ir) was not readily co-localized with CB-D28k ir in WNV-infected Vero 76 or motor neuron-like NSC34 cells that were either stably or transiently transfected with plasmids coding for CB-D28k gene. This was confirmed in cultured cells fixed on glass coverslips and by flow cytometry. Moreover, WNV infectious titers were reduced in CB-D28k-transfected cells. As in cell culture studies, WNV env ir was not co-localized with CB-D28k ir in the cortex of an infected WNV hamster, or in the hippocampus of an infected mouse. Motor neurons in the spinal cord typically do not express CB-D28k and are susceptible to WNV infection. Yet, CB-D28k was detected in the surviving motor neurons after the initial phase of WNV infection in hamsters. These data suggested that induction of CB-D28k elicit a neuroprotective response to WNV infection.
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Wogonin Prevents Rat Dorsal Root Ganglion Neurons Death via Inhibiting Tunicamycin-Induced ER Stress In Vitro.
Cell. Mol. Neurobiol.
PUBLISHED: 09-01-2014
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Wogonin is a natural flavonoid isolated from the root of Scutellaria baicalensis Georgi, which has been widely used in various research areas for its anti-oxidant, anti-inflammatory, and anti-cancer activities. It also presents a neuroprotective effect in the brain while encounters stress conditions, but the mechanisms controlling the neuroprotective effect of wogonin are not clear. In this study, we investigated the biomechanism underlying the neuroprotective effect of wogonin on rat dorsal root ganglion (DRG) neurons. Wogonin pre-treatment at 75 ?M significantly increased the cell viability of DRG neurons and decreased the number of the propidium iodide-positive DRG neurons before the endoplasmic reticulum (ER) stress is being induced by tunicamycin (TUN) (0.75 ?g/mL). In addition, Wogonin also inhibited the release of LDH and up-regulated the level of GSH. Furthermore, wogonin decreased the activation of ER stress-related molecules, including glucose-regulated protein 78 (GRP78), GRP94, C/EBP-homologous protein, active caspase12 and active caspase3, phosphorylation of pancreatic ER stress kinase, and eukaryotic initiation factor 2 alpha (eIF2?). In summary, our results indicated that wogonin could protect DRG neurons against TUN-induced ER stress.
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Organic anion composition of human whole saliva as determined by ion chromatography.
Clin. Chim. Acta
PUBLISHED: 08-30-2014
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The majority of studies examining anionic composition in human saliva have focused on inorganic anions only, and accompanying organic anion concentration has often been overlooked in the development of artificial salivas. The purpose of this study was to examine the major organic anionic species profile of human saliva, with a view to gaining further insight into human salivary chemistry.
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[Present state of occupational hazards in automobile maintenance industry in Beijing, China].
Zhonghua Lao Dong Wei Sheng Zhi Ye Bing Za Zhi
PUBLISHED: 08-30-2014
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To explore the present state of occupational hazards and health status of workers in the automobile maintenance industry.
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A new BODIPY-based long-wavelength fluorescent probe for chromatographic analysis of low-molecular-weight thiols.
Anal Bioanal Chem
PUBLISHED: 08-29-2014
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A new long-wavelength fluorescent probe, 1,7-dimethyl-3,5-distyryl-8-phenyl-(4'-iodoacetamido)difluoroboradiaza-s-indacene (DMDSPAB-I), was designed and synthesized for thiol labeling in high-performance liquid chromatography (HPLC). The excitation and emission wavelengths of DMDSPAB-I are 620 and 630 nm, respectively, with a high fluorescence quantum yield of 0.557, which is advantageous in preventing interference of intrinsic fluorescence from complex biological matrices and enabling high sensitivity HPLC. Based on DMDSPAB-I, a reversed-phase HPLC method was developed for measuring low-molecular-weight thiols including glutathione, cysteine, homocysteine, N-acetylcysteine, cysteinylglycine, and penicillamine. After the specific reaction of DMDSPAB-I with thiols, baseline separation of all six stable derivatives was achieved through isocratic elution on a C18 column within 25 min, with the limits of detection (signal-to-noise ratio?=?3) from 0.24 nmol L(-1) for glutathione to 0.72 nmol L(-1) for penicillamine. The proposed method was validated in part by measuring thiols in blood samples from mice, with recoveries of 95.3-104.3%.
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Understanding the Phase Emergence of Mesoporous Silica.
Small
PUBLISHED: 08-26-2014
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The cylinder-to-vesicle phase transition of mesoporous silica and the inter-dependence of the controlling factors are studied. (3-Mercaptopropyl)trimethoxylsilane (MPTMS) is used to alter the phase outcome of mesoporous silica from the cylindrical MCM-41 to the vesicular phase. Exploiting the phase selection at the critical time point of phase emergence allows investigation of the complex interactions among the ingredients. In this system, orderly cylindrical or vesicular phase directly emerges from the "clumps" of randomly mixed surfactant, co-surfactant, and silica precursor. The phase outcome depends on the exact ratio of the ingredients, provided that enough amounts of MPTMS can diffuse into the clumps before the hardening silica prevents the diffusion.
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JNK and Akt signaling pathways regulating TNF-?-induced IL-32 expression in human lung fibroblasts: implications in airway inflammation.
Immunology
PUBLISHED: 08-26-2014
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Airway inflammatory diseases such as chronic obstructive pulmonary disease (COPD) and asthma are associated with elevated expression of IL-32, a recently described cytokine that appears to play a critical role in inflammation. However, thus far, the regulation of pulmonary IL-32 production has not been fully established. We examined the expression of IL-32 by TNF-? in primary human lung fibroblasts. Human lung fibroblasts were cultured in the presence or absence of TNF-? and/or other cytokines/TLR ligands or various signaling molecule inhibitors to analyze the expression of IL-32 by quantitative RT-PCR and enzyme-linked immunosorbent assay. Next, activation of Akt and JNK signaling pathways were investigated by Western blot. IL-32 mRNA of 4 spliced isoforms (?, ?, ?, and ?) was up-regulated upon TNF-? stimulation, which was associated with a significant IL-32 protein release from TNF-?-activated human lung fibroblasts. The combination of IFN-? and TNF-? induced enhanced IL-32 release in human lung fibroblasts, whereas IL-4, IL-17A, IL-27 and TLR ligands did not alter IL-32 release in human lung fibroblasts either alone, or in combination with TNF-?. Furthermore, the activation of Akt and JNK pathways regulated TNF-?-induced IL-32 expression in human lung fibroblasts, and inhibition of the Akt and JNK pathways was able to suppress the increased release of IL-32 to nearly the basal level. These data suggest that TNF-? may be involved in airway inflammation via the induction of IL-32 by activating Akt and JNK signaling pathways. Therefore, the TNF-?/IL-32 axis may be a potential therapeutic target for airway inflammatory diseases. This article is protected by copyright. All rights reserved.
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Snail is an independent prognostic indicator for predicting recurrence and progression in non-muscle-invasive bladder cancer.
Int Urol Nephrol
PUBLISHED: 08-22-2014
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Snail, an inducer of the epithelial-to-mesenchymal transition, increases motility and invasiveness of cancer cells by repressing E-cadherin expression. We investigate the relationship between Snail expression and clinicopathological parameters and evaluate its prognostic significance in patients with non-muscle-invasive bladder cancer (NMIBC).
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Tissue cell assisted fabrication of tubular catalytic platinum microengines.
Nanoscale
PUBLISHED: 08-22-2014
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We report a facile platform for mass production of robust self-propelled tubular microengines. Tissue cells extracted from fruits of banana and apple, Musa acuminata and Malus domestica, are used as the support on which a thin platinum film is deposited by means of physical vapor deposition. Upon sonication of the cells/Pt-coated substrate in water, microscrolls of highly uniform sizes are spontaneously formed. Tubular microengines fabricated with the fruit cell assisted method exhibit a fast motion of ?100 bodylengths per s (?1 mm s(-1)). An extremely simple and affordable platform for mass production of the micromotors is crucial for the envisioned swarms of thousands and millions of autonomous micromotors performing biomedical and environmental remediation tasks.
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Patient-derived Xenografts Reveal that Intraductal Carcinoma of the Prostate Is a Prominent Pathology in BRCA2 Mutation Carriers with Prostate Cancer and Correlates with Poor Prognosis.
Eur. Urol.
PUBLISHED: 08-21-2014
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Intraductal carcinoma of the prostate (IDC-P) is a distinct clinicopathologic entity associated with aggressive prostate cancer (PCa). PCa patients carrying a breast cancer 2, early onset (BRCA2) germline mutation exhibit highly aggressive tumours with poor prognosis.
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Cellular Requirements for Bovine Immunodeficiency Virus Vif-Mediated Inactivation of Bovine APOBEC3 Proteins.
J. Virol.
PUBLISHED: 08-20-2014
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Human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) viral infectivity factor (Vif) form a CRL5 E3 ubiquitin ligase complex to suppress virus restriction by host APOBEC3 (A3) proteins. The primate lentiviral Vif complex is composed of the unique cofactor core binding factor ? (CBF-?) and canonical ligase components Cullin 5 (CUL5), Elongin B/C (ELOB/C), and RBX2. However, the mechanism by which the Vif protein of the related lentivirus bovine immunodeficiency virus (BIV) overcomes its host A3 proteins is less clear. In this study, we show that BIV Vif interacts with Cullin 2 (CUL2), ELOB/C, and RBX1, but not with CBF-? or CUL5, to form a CRL2 E3 ubiquitin ligase and degrade the restrictive bovine A3 proteins (A3Z2Z3 and A3Z3). RNA interference-mediated knockdown of ELOB or CUL2 inhibited BIV Vif-mediated degradation of these A3 proteins, whereas knockdown of CUL5 or CBF-? did not. BIV Vif with mutations in the BC box (Vif SLQ-AAA) or putative VHL box (Vif YI-AA), which cannot interact with ELOB/C or CUL2, respectively, lost the ability to counteract bovine A3 proteins. Moreover, CUL2 and UBE2M dominant negative mutants competitively inhibited the BIV Vif-mediated degradation mechanism. Thus, although the general strategy for inhibiting A3 proteins is conserved between HIV-1/SIV and BIV, the precise mechanisms can differ substantially, with only the HIV-1/SIV Vif proteins requiring CBF-? as a cofactor, HIV-1/SIV Vif using CUL5-RBX2, and BIV Vif using CUL2-RBX1.
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Studies of the in vitro antibacterial activities of several polyphenols against clinical isolates of methicillin-resistant Staphylococcus aureus.
Molecules
PUBLISHED: 08-19-2014
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In this study, we report the antibacterial activities of six polyphenols (i.e., luteolin, quercetin, scutellarin, apigenin, chlorogenic acid, and resveratrol) against 29 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA), and in vitro antibacterial activities of two-drug combinations. All of the MRSA strains evaluated were clinical isolates from patients with MRSA bacteremia. The antibacterial activities were determined by agar dilution method, and the two-drug antibacterial activities were determined by the checkerboard agar dilution method. It was found that luteolin, quercetin and resveratrol show obvious antibacterial activities against MRSA, and the results of two-drug antibacterial activity show either synergy or additivity, without evidences of antagonistic effects.
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Structural insights into RNA recognition properties of glyceraldehyde-3-phosphate dehydrogenase 3 from Saccharomyces cerevisiae.
IUBMB Life
PUBLISHED: 08-18-2014
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Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, EC: 1.2.1.12) is an essential enzyme in the glycolytic pathway. However, recent evidence demonstrates that GAPDH displays a range of new functions unrelated to its glycolytic function. GAPDH has long been known as a 3' AU-rich element-binding protein; however, its RNA recognition mechanism is still not well understood. Here, we present the first crystal structure of GAPDH3 from Saccharomyces cerevisiae and identify its RNA-binding specificity and propose an RNA recognition model based on structural and biochemical studies. This study sheds light on the RNA-binding mechanism of GAPDH3 and contributes to a better understanding of the molecular mechanisms of its RNA-related functions. © 2014 IUBMB Life, 66(9):631-638, 2014.
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Targeted gene suppression by inducing de novo DNA methylation in the gene promoter.
Epigenetics Chromatin
PUBLISHED: 08-18-2014
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Targeted gene silencing is an important approach in both drug development and basic research. However, the selection of a potent suppressor has become a significant hurdle to implementing maximal gene inhibition for this approach. We attempted to construct a 'super suppressor' by combining the activities of two suppressors that function through distinct epigenetic mechanisms.
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Genetic analysis of colon tumors induced by a dietary carcinogen PhIP in CYP1A humanized mice: Identification of mutation of ?-catenin/Ctnnb1 as the driver gene for the carcinogenesis.
Mol. Carcinog.
PUBLISHED: 08-17-2014
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Replacing mouse Cyp1a with human CYP1A enables the humanized CYP1A mice to mimic human metabolism of the dietary carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), by N(2) -hydroxylation to a proximate carcinogen. Our previous study demonstrated that PhIP, combined with the dextrin sulfate sodium (DSS)-induced colitis, induces colon carcinogenesis in hCYP1A mice. Here, we employed whole exome sequencing and found multiple gene mutations in PhIP/DSS-induced colon tumors. Mutations in the exon 3 of Ctnnb1/?-catenin, however, were the predominant events. We further sequenced the key fragments of Apc, Ctnnb1, and Kras, because mutations of these genes in the humans are commonly found as the drivers of colorectal cancer. Mutations on either codon 32 or 34 in the exon 3 of Ctnnb1 were found in 39 out of 42 tumors, but no mutation was found in either Apc or Kras. The sequence context of codons 32 and 34 suggests that PhIP targets +3G in a TGGA motif of Ctnnb1. Since mutations that activate Wnt signal is a major driving force for human colorectal cancers, we conclude that the mutated ?-catenin is the driver in PhIP/DSS-induced colon carcinogenesis. This result suggests that the colon tumors in hCYP1A mice mimic human colorectal carcinogenesis not only in the dietary etiology involving PhIP, but also in the aberrant activation of the Wnt signaling pathway as the driving force. © 2014 Wiley Periodicals, Inc.
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Epigenetic enzymes are the therapeutic targets for CD4(+)CD25(+/high)Foxp3(+) regulatory T cells.
Transl Res
PUBLISHED: 08-15-2014
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CD4(+)CD25(+/high)Foxp3(+) regulatory T (Treg) cells are a subset of CD4(+) T cells that play an essential role in maintaining peripheral immune tolerance. Several transcriptional cofactors have been recently identified, which form complexes with transcription factor Foxp3 of Treg cells and contribute in the suppressive function of Treg cells. However, Foxp3 is still defined as a "master" (multiple pathway) regulator gene that controls the development and stability of Treg cells. Because of its importance, the regulatory mechanisms underlying Foxp3 expression have been a focus of intensive investigation. Recent progress suggests that the epigenetic mechanisms responsible for regulating the Foxp3 gene expression are key components of suppressive activity of Treg cells. This review not only discusses the basic concepts of biology and epigenetic modifications of Treg cells, but also analyzes the translational clinical aspect of epigenetic modifications of Treg cells, focusing on several ongoing clinical trials and the Food and Drugs administration-approved epigenetic-based drugs. The new progress in identifying epigenetic enzymes functional in Treg cells is a new target for the development of novel therapeutic approaches for autoimmune and inflammatory diseases, graft-vs-host disease and cancers.
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Delayed vocal fold paralysis after continuous interscalene level brachial plexus block with catheter placement: a case report.
J Clin Anesth
PUBLISHED: 08-11-2014
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We report an incident of delayed onset of true vocal fold paralysis with continuous interscalene brachial plexus block. A 51 year old woman underwent left shoulder manipulation and lysis of adhesions with fluoroscopy and general anesthesia. An interscalene brachial plexus block was performed and a catheter with a continuous infusion pump was placed for postoperative pain control. Following hospital discharge, approximately 8 hours after the initial catheter bolus the patient developed hoarseness, dysphagia, and dyspnea, secondary to left vocal fold palsy. The patient was admitted for observation and the catheter was discontinued with no intubation required. By the next morning, the patient's dysphagia and dyspnea had resolved and her hoarseness improved.
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Development of phage immuno-loop-mediated isothermal amplification assays for organophosphorus pesticides in agro-products.
Anal. Chem.
PUBLISHED: 08-08-2014
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Two immuno-loop-mediated isothermal amplification assays (iLAMP) were developed by using a phage-borne peptide that was isolated from a cyclic eight-peptide phage library. One assay was used to screen eight organophosphorus (OP) pesticides with limits of detection (LOD) between 2 and 128 ng mL(-1). The iLAMP consisted of the competitive immuno-reaction coupled to the LAMP reaction for detection. This method provides positive results in the visual color of violet, while a negative response results in a sky blue color; therefore, the iLAMP allows one to rapidly detect analytes in yes or no fashion. We validated the iLAMP by detecting parathion-methyl, parathion, and fenitrothion in Chinese cabbage, apple, and greengrocery, and the detection results were consistent with the enzyme-linked immunosorbent assay (ELISA). In conclusion, the iLAMP is a simple, rapid, sensitive, and economical method for detecting OP pesticide residues in agro-products with no instrumental requirement.
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Proteomic signatures associated with p53 mutational status in lung adenocarcinoma.
Proteomics
PUBLISHED: 08-07-2014
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p53 is commonly mutated in lung adenocarcinoma. Mutant p53 loses wild-type function and some missense mutations further acquire oncogenic functions, while p53 wild-type may also induce pro-survival signaling. Therefore identification of signatures based on p53 mutational status has relevance to our understanding of p53 signaling pathways in cancer and identification of new therapeutic targets. To this end, we compared proteomic profiles of three cellular compartments (whole-cell extract, cell surface, and media) from 28 human lung adenocarcinoma cell lines that differ based on p53 mutational status. In total, 11?598, 11?569, and 9090 protein forms were identified in whole-cell extract, cell surface, and media, respectively. Bioinformatic analysis revealed that representative pathways associated with epithelial adhesion, immune and stromal cells, and mitochondrial function were highly significant in p53 missense mutations, p53 loss and wild-type p53 cell lines, respectively. Of note, mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1-?), a transcription coactivator that promotes mitochondrial oxidative phosphorylation and mitochondrial biogenesis, was substantially higher in p53 wild-type cell lines compared to either cell lines with p53 loss or with missense mutation. Small interfering RNA targeting PGC1-? inhibited cell proliferation in p53 wild-type cell lines, indicative of PGC1-? and its downstream molecules as potential therapeutic targets in p53 wild-type lung adenocarcinoma.
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The Combination of Tet1 with Oct4 Generates High-Quality Mouse Induced Pluripotent Stem Cells (iPSCs).
Stem Cells
PUBLISHED: 08-04-2014
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The DNA dioxygenase Tet1 has recently been proposed to play an important role in the reprogramming of somatic cells to pluripotency. Its oxidization product 5-hydroxymethylcytosine (5hmC), formerly considered an intermediate in the demethylation of 5-methylcytosine (5mC), has recently been implicated as being important in epigenetic reprogramming. Here, we provide evidence that Tet1 (T) can replace multiple transcription factors during somatic cell reprogramming and can generate high-quality mouse induced pluripotent stem cells (iPSCs) with Oct4 (O). The OT-iPSCs can efficiently produce viable mice derived entirely from iPSCs through tetraploid complementation; all 47 adult OT-iPSC mice grew healthily, without tumorigenesis, and had a normal life span. Furthermore, a new secondary reprogramming system was established using the OT all-iPSC mice-derived somatic cells. Our results provide the first evidence that the DNA dioxygenase Tet1 can replace multiple pluripotency transcription factors and can generate high-quality iPSCs with Oct4. Stem Cells 2014.
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Atorvastatin treatment improves the effects of mesenchymal stem cell transplantation on acute myocardial infarction: The role of the RhoA/ROCK/ERK pathway.
Int. J. Cardiol.
PUBLISHED: 08-01-2014
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Statins protect mesenchymal stem cells (MSCs) against the harsh microenvironment and improve the efficacy of MSC transplantation after acute myocardial infarction (AMI); however, the mechanism remains uncertain. Furthermore, the transdifferentiation potential of MSCs in the post-infarct heart remains highly controversial. The RhoA/Rho-associated coiled-coil-forming kinase (ROCK) pathway participates in many aspects of the damaged heart after AMI and related to the "pleiotropic" effects of statins. This study aimed to explore whether atorvastatin (ATV) facilitates the survival and therapeutic efficacy of MSCs via the inhibition of RhoA/ROCK pathway and subsequently its downstream molecular extracellular regulated protein kinase (ERK1/2), and to investigate the transdifferentiation potential of MSCs in vivo.
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Immunosuppressive/anti-inflammatory cytokines directly and indirectly inhibit endothelial dysfunction- a novel mechanism for maintaining vascular function.
J Hematol Oncol
PUBLISHED: 07-30-2014
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Endothelial dysfunction is a pathological status of the vascular system, which can be broadly defined as an imbalance between endothelium-dependent vasoconstriction and vasodilation. Endothelial dysfunction is a key event in the progression of many pathological processes including atherosclerosis, type II diabetes and hypertension. Previous reports have demonstrated that pro-inflammatory/immunoeffector cytokines significantly promote endothelial dysfunction while numerous novel anti-inflammatory/immunosuppressive cytokines have recently been identified such as interleukin (IL)-35. However, the effects of anti-inflammatory cytokines on endothelial dysfunction have received much less attention. In this analytical review, we focus on the recent progress attained in characterizing the direct and indirect effects of anti-inflammatory/immunosuppressive cytokines in the inhibition of endothelial dysfunction. Our analyses are not only limited to the importance of endothelial dysfunction in cardiovascular disease progression, but also expand into the molecular mechanisms and pathways underlying the inhibition of endothelial dysfunction by anti-inflammatory/immunosuppressive cytokines. Our review suggests that anti-inflammatory/immunosuppressive cytokines serve as novel therapeutic targets for inhibiting endothelial dysfunction, vascular inflammation and cardio- and cerebro-vascular diseases.
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MiR-23a Functions as a Tumor Suppressor in Osteosarcoma.
Cell. Physiol. Biochem.
PUBLISHED: 07-24-2014
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Background: Osteosarcoma is the most common primary bone malignancy in children and adolescents, and the pathogenesis of this cancer remains unclear. Therefore, the discovery of new biomarkers for the diagnosis, prognosis, and treatment of osteosarcoma remains an important but unmet clinical need. Method: Quantitative real-time PCR was carried out to examine the expression of miR-23a. Methylation-specific PCR was performed to evaluate the DNA methylation status of the miR-23a promoter. Cell proliferation, migration, and invasion were examined by cell counting assays, wound healing assays, and cell invasion assays, respectively. Western blot analysis and luciferase reporter assays were performed to identify miR-23 target genes. Nude mice were used to investigate the function of miR-23a in vivo. Results: The expression of miR-23a was decreased in osteosarcoma cells and tissues compared to normal controls. The promoter region of the miR-23a gene was hypermethylated in osteosarcoma cells, and demethylase treatment increased the expression of miR-23a. The ectopic expression of miR-23a led to retarded proliferation, migration, and invasion of osteosarcoma cells, whereas the depletion of miR-23a resulted in the opposite effects. MiR-23a suppressed the transcription of RUNX2 and CXCL12 by binding to the 3' UTRs of these mRNAs. The cellular function of miR-23a is RUNX2/CXCL12-dependent, and the overexpression of RUNX2 or CXCL12 rescued the impaired cell growth, migration, and invasion induced by miR-23a. Nude mouse experiments indicated that miR-23a may inhibit the proliferation of osteosarcoma cells in vivo. Conclusion: We identified miR-23a as a tumor suppressor in osteosarcoma. Our data clarify the mechanism of osteosarcoma progression and demonstrated the potential for exploiting miR-23a as a diagnostic marker for osteosarcoma. © 2014 S. Karger AG, Basel.
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Sphingosine-1-phosphate/S1P receptors signaling modulates cell migration in human bone marrow-derived mesenchymal stem cells.
Mediators Inflamm.
PUBLISHED: 07-23-2014
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The recruitment of bone marrow-derived mesenchymal stem cells (BMSCs) to damaged tissues and sites of inflammation is an essential step for clinical therapy. However, the signals regulating the motility of these cells are still not fully understood. Sphingosine-1-phosphate (S1P), a bioactive sphingolipid metabolite, is known to have a variety of biological effects on various cells. Here, we investigated the roles of S1P and S1P receptors (S1PRs) in migration of human BMSCs. We found that S1P exerted a powerful migratory action on human BMSCs. Moreover, by employing RNA interference technology and pharmacological tools, we demonstrated that S1PR1 and S1PR3 are responsible for S1P-induced migration of human BMSCs. In contrast, S1PR2 mediates the inhibition of migration. Additionally, we explored the downstream signaling pathway of the S1P/S1PRs axis and found that activation of S1PR1 or S1PR3 increased migration of human BMSCs through a G i /extracellular regulated protein kinases 1/2- (ERK1/2-) dependent pathway, whereas activation of S1PR2 decreased migration through the Rho/Rho-associated protein kinase (ROCK) pathway. In conclusion, we reveal that the S1P/S1PRs signaling axis regulates the migration of human BMSCs via a dual-directional mechanism. Thus, selective modulation of S1PR's activity on human BMSCs may provide an effective approach to immunotherapy or tissue regeneration.
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Some cross-talks between immune cells and epilepsy should not be forgotten.
Neurol. Sci.
PUBLISHED: 07-16-2014
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Recent studies have reported that immune cells were not always found in brain specimens from epileptic patients, then should we stop investigating the relationship between these cells and epilepsy? The answer is no! In addition to immunocyte infiltration in brain parenchyma, a flurry of papers have demonstrated that there were significant alterations in peripheral blood cells (PBCs) immediately after seizure onset, especially changes in some specific transporters of neurotransmitters expressed on the membrane of immunocyte. These transporters may regulate neuronal excitability in mature neurons. Besides, many researchers did find activated leukocytes adhered to the endothelium of blood brain barrier or infiltrated into the brain parenchyma in several types of epilepsy both in human and animal studies; moreover, it is worth noting that different immune cells play different roles in epilepsy development, which was indicated by in vitro and in vivo evidence. This review is going to summarize available evidence supporting changes in PBCs after seizures, and will also focus on some specific effects of immune cells on epilepsy development.
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Light-output enhancement of GaN-based light-emitting diodes with three-dimensional backside reflectors patterned by microscale cone array.
ScientificWorldJournal
PUBLISHED: 07-15-2014
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Three-dimensional (3D) backside reflector, compared with flat reflectors, can improve the probability of finding the escape cone for reflecting lights and thus enhance the light-extraction efficiency (LEE) for GaN-based light-emitting diode (LED) chips. A triangle-lattice of microscale SiO2 cone array followed by a 16-pair Ti3O5/SiO2 distributed Bragg reflector (16-DBR) was proposed to be attached on the backside of sapphire substrate, and the light-output enhancement was demonstrated by numerical simulation and experiments. The LED chips with flat reflectors or 3D reflectors were simulated using Monte Carlo ray tracing method. It is shown that the LEE increases as the reflectivity of backside reflector increases, and the light-output can be significantly improved by 3D reflectors compared to flat counterparts. It can also be observed that the LEE decreases as the refractive index of the cone material increases. The 3D 16-DBR patterned by microscale SiO2 cone array benefits large enhancement of LEE. This microscale pattern was prepared by standard photolithography and wet-etching technique. Measurement results show that the 3D 16-DBR can provide 12.1% enhancement of wall-plug efficiency, which is consistent with the simulated value of 11.73% for the enhancement of LEE.
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Partial anomalous pulmonary venous connection to superior vena cava that overrides across the intact atrial septum and has bi-atrial connection in a 75-year-old female presenting with pulmonary hypertension.
BMC Cardiovasc Disord
PUBLISHED: 07-11-2014
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Partial anomalous venous connection (PAPVC) is a rare congenital heart disease where the blood flow from one or more pulmonary veins (but not all) returns to the right atrium or systemic venous circulation and is often associated with a sinus venosus atrial defect (SVD). Transthoracic echocardiography (TTE) can provide limited information for this anomaly and the diagnosis of this congenital defect has been a clinical challenge.
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Postprandial triglycerides and adipose tissue storage of dietary fatty acids: Impact of menopause and estradiol.
Obesity (Silver Spring)
PUBLISHED: 07-07-2014
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Postprandial lipemia worsens after menopause, but the mechanism remains unknown. The hypothesized menopause-related postprandial lipemia would be (1) associated with reduced storage of dietary fatty acids (FA) as triglyceride (TG) in subcutaneous adipose tissue (SAT) and (2) improved by short-term estradiol (E2 ).
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Iridium-catalyst-based autonomous bubble-propelled graphene micromotors with ultralow catalyst loading.
Chemistry
PUBLISHED: 07-04-2014
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A novel concept of an iridium-based bubble-propelled Janus-particle-type graphene micromotor with very high surface area and with very low catalyst loading is described. The low loading of Ir catalyst (0.54?at?%) allows for fast motion of graphene microparticles with high surface area of 316.2?m(2) ?g(-1) . The micromotor was prepared with a simple and scalable method by thermal exfoliation of iridium-doped graphite oxide precursor composite in hydrogen atmosphere. Oxygen bubbles generated from the decomposition of hydrogen peroxide at the iridium catalytic sites provide robust propulsion thrust for the graphene micromotor. The high surface area and low iridium catalyst loading of the bubble-propelled graphene motors offer great possibilities for dramatically enhanced cargo delivery.
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Novel mutations in the SLC25A13 gene in a patient with NICCD and severe manifestations.
J. Pediatr. Endocrinol. Metab.
PUBLISHED: 06-27-2014
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Abstract Neonatal intrahepatic cholestatic due to citrin deficiency (NICCD) is an autosomal recessive disorder caused by mutations in the SLC25A13 gene and characterized by neonatal/infantile-onset cholestatic hepatitis syndrome associated with conjugated hyperbilirubinemia and multiple aminoacidemias. We report the case of a Chinese female patient with NICCD disease who manifested prominent clinical features. The patient was diagnosed with NICCD based on cholestasis, aminoacidemia, and hypoproteinemia. She exhibited extreme aminoacidemia, coagulation disorders and untypical myocardial damage, which are rare in other NICCD patients genetically confirmed by us. This myocardial damage observed in obstructive jaundice could be caused by both hyperbilirubinemia and redundant blood bile acids. Screening the SLC25A13 gene revealed that this patient was compound heterozygous harboring two novel mutations, the c. 640C>T (p. Gln214X) in exon 7 and the c. 1709_1710insA (p. Ile570fs573X) in exon 16. Both mutations cause a premature stop codon and thereby truncated peptide or nonsense-mediated with loss of natural function accordingly. In conclusion, extremely manifested clinical features, including significant hyperbilirubinemia, multiple aminoacidemia, hypoproteinemia, coagulation disorders, and myocardial damage related to redundant blood bilirubin and bile acids, were observed in a NICCD patients with two novel mutations.
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Study of driving fatigue alleviation by transcutaneous acupoints electrical stimulations.
ScientificWorldJournal
PUBLISHED: 06-20-2014
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Driving fatigue is more likely to bring serious safety trouble to traffic. Therefore, accurately and rapidly detecting driving fatigue state and alleviating fatigue are particularly important. In the present work, the electrical stimulation method stimulating the Láogóng point (PC8) of human body is proposed, which is used to alleviate the mental fatigue of drivers. The wavelet packet decomposition (WPD) is used to extract ?, ?, and ? subbands of drivers' electroencephalogram (EEG) signals. Performances of the two algorithms (? + ?)/(? + ?) and ?/? are also assessed as possible indicators for fatigue detection. Finally, the differences between the drivers with electrical stimulation and normal driving are discussed. It is shown that stimulating the Láogóng point (PC8) using electrical stimulation method can alleviate driver fatigue effectively during longtime driving.
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Association between interleukin 8 -251 A/T and +781 C/T polymorphisms and osteoarthritis risk.
Immunol. Lett.
PUBLISHED: 06-10-2014
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Interleukin 8 (IL-8), as a member of the CXC chemokine family, has a regulatory role in joint inflammation and cartilage degradation, and contribute to the pathophysiology of osteoarthritis. The aim of the current study was to examine the influence of the IL-8 gene polymorphisms at positions -251 (rs4073) and +781 (rs2227306) on the risk of osteoarthritis.
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Sex specific retinoic acid signaling is required for the initiation of urogenital sinus bud development.
Dev. Biol.
PUBLISHED: 06-04-2014
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The mammalian urogenital sinus (UGS) develops in a sex specific manner, giving rise to the prostate in the male and the sinus vagina in the embryonic female. Androgens, produced by the embryonic testis, have been shown to be crucial to this process. In this study we show that retinoic acid signaling is required for the initial stages of bud development from the male UGS. Enzymes involved in retinoic acid synthesis are expressed in the UGS mesenchyme in a sex specific manner and addition of ligand to female tissue is able to induce prostate-like bud formation in the absence of androgens, albeit at reduced potency. Functional studies in mouse organ cultures that faithfully reproduce the initiation of prostate development indicate that one of the roles of retinoic acid signaling in the male is to inhibit the expression of Inhba, which encodes the ?A subunit of Activin, in the UGS mesenchyme. Through in vivo genetic analysis and culture studies we show that inhibition of Activin signaling in the female UGS leads to a similar phenotype to that of retinoic acid treatment, namely bud formation in the absence of androgens. Our data also reveals that both androgens and retinoic acid have extra independent roles to that of repressing Activin signaling in the development of the prostate during fetal stages. This study identifies a novel role for retinoic acid as a mesenchymal factor that acts together with androgens to determine the position and initiation of bud development in the male UGS epithelia.
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Maternal gastric carcinoma with metastasis to the placenta: A case report.
Oncol Lett
PUBLISHED: 05-29-2014
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In the current report a case of maternal gastric carcinoma with metastasis to the placenta is presented. Gastric cancer is a worldwide health issue, which accounts for ~8.6% of newly diagnosed cancer cases annually. However, the simultaneous occurrence of gastric cancer and pregnancy is rare; to date, only 0.1% of all cases of gastric cancer occur during pregnancy. Furthermore, among all cases of gestational gastric cancer, only six cases have been reported to exhibit metastasis to the placenta or fetus. In the current study another such case is presented. Based on the results of previous studies, further discussion regarding the diagnosis and prognosis of gastric cancer during pregnancy in the mother and fetus is presented.
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HIV/AIDS-related Knowledge and Behaviors Among Rural Married Migrant Women in Shandong Province, China: A Comparison Study.
Arch Sex Behav
PUBLISHED: 05-26-2014
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Migrant women in China are disproportionately affected by HIV/AIDS. This study described HIV/AIDS-related knowledge and behaviors among married migrant women in Shandong province in comparison to non-migrant local women and identified factors associated with HIV testing history and extramarital sex among married migrant women. A probability-based sample of 1,076 migrant and 1,195 local women were included in the analyses. Compared to local women, married migrant women had lower levels of HIV/AIDS knowledge and were more likely to have had premarital sex, extramarital sex, history of sexually transmitted diseases, and drug use. Less than a quarter of migrant women used condoms consistently in extramarital sex. Only 31.0 % of married migrant women had ever tested for HIV, and the rate of premarital HIV testing was very low. Multivariable analysis showed that married migrant women with a history of extramarital sex were more likely to be from Yunnan province, be living in Yantai city, be in their first marriage, have lower family income, have poor relationship with spouses, use drug, have a history of sexually transmitted diseases, and have lower social support. Our findings provide further evidence that married migrant women are at higher risk for HIV infection and that targeted interventions need to be developed for this population.
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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.