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  • 1
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    Clinical, genetic, and structural basis of apparent mineralocorticoid excess due to 11β-hydroxysteroid dehydrogenase type 2 deficiency (2017)
    National Academy of Sciences
    Details
    Publication Date: 2017-12-11
    Description: Mutations in 11β-hydroxysteroid dehydrogenase type 2 gene (HSD11B2) cause an extraordinarily rare autosomal recessive disorder, apparent mineralocorticoid excess (AME). AME is a form of low renin hypertension that is potentially fatal if untreated. Mutations in the HSD11B2 gene result either in severe AME or a milder phenotype (type 2 AME). To date, ∼40 causative mutations have been identified. As part of the International Consortium for Rare Steroid Disorders, we have diagnosed and followed the largest single worldwide cohort of 36 AME patients. Here, we present the genotype and clinical phenotype of these patients, prominently from consanguineous marriages in the Middle East, who display profound hypertension and hypokalemic alkalosis. To correlate mutations with phenotypic severity, we constructed a computational model of the HSD11B2 protein. Having used a similar strategy for the in silico evaluation of 150 mutations of CYP21A2, the disease-causing gene in congenital adrenal hyperplasia, we now provide a full structural explanation for the clinical severity of AME resulting from each known HSD11B2 missense mutation. We find that mutations that allow the formation of an inactive dimer, alter substrate/coenzyme binding, or impair structural stability of HSD11B2 yield severe AME. In contrast, mutations that cause an indirect disruption of substrate binding or mildly alter intramolecular interactions result in type 2 AME. A simple in silico evaluation of novel missense mutations could help predict the often-diverse phenotypes of an extremely rare monogenic disorder.
    Print ISSN: 0027-8424
    Electronic ISSN: 1091-6490
    Topics: Biology , Medicine , Natural Sciences in General
    Published by National Academy of Sciences
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  • 2
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    Mobile Device Based Dynamic Key Management Protocols for Wireless Sensor Networks (2015)
    Hindawi
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    Publication Date: 2015-08-17
    Description: In recent years, wireless sensor network (WSN) applications have tended to transmit data hop by hop, from sensor nodes through cluster nodes to the base station. As a result, users must collect data from the base station. This study considers two different applications: hop by hop transmission of data from cluster nodes to the base station and the direct access to cluster nodes data by mobile users via mobile devices. Due to the hardware limitations of WSNs, some low-cost operations such as symmetric cryptographic algorithms and hash functions are used to implement a dynamic key management. The session key can be updated to prevent threats of attack from each communication. With these methods, the data gathered in wireless sensor networks can be more securely communicated. Moreover, the proposed scheme is analyzed and compared with related schemes. In addition, an NS2 simulation is developed in which the experimental results show that the designed communication protocol is workable.
    Print ISSN: 1687-725X
    Electronic ISSN: 1687-7268
    Topics: Electrical Engineering, Measurement and Control Technology
    Published by Hindawi
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  • 3
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    Reactive oxygen species mediate Terbufos-induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro-apoptotic proteins (2015)
    Wiley
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    Publication Date: 2015-09-16
    Description: ABSTRACT Terbufos ( S - t -butylthiomethyl- O,O -diethyl phosphorodithioate) is a highly toxic organophosphate which is extensively used as an insecticide and nematicide. Chronic exposure to terbufos causes neuronal injury and predisposes to neurodegenerative diseases. Accumulating evidence has shown that the exposure to terbufos, as an occupational risk factor, may also cause reproductive disorders. However, the exact mechanisms of reproductive toxicity remain unclear. The present study aimed to investigate the toxic effect of terbufos on testicular cells and to explore the mechanism of toxicity on a cellular level. The cytotoxic effects of terbufos on mouse immortalized spermatogonia (GC-1), spermatocytes (GC-2), Leydig (TM3), and Sertoli (TM4) cell lines were assessed by MTT assays, caspase activation, flow cytometry, TUNEL assay, Western blot, and cell cycle analysis. The exposure to different concentrations of terbufos ranging from 50 to 800 μM for 6 h caused significant death in all the used testicular cell lines. Terbufos increased reactive oxygen species (ROS) production, reduced mitochondrial membrane potential, and initiated apoptosis, which was confirmed by a dose-dependent increase in the number of TUNEL-positive apoptotic cells. Blocking ROS production by N -acetyl cysteine (NAC) protected GC-1 cells from terbufos-induced cell death. The results demonstrated that terbufos induces ROS, apoptosis, and DNA damage in testicular cell lines and it should be considered potentially hazardous to testis. Together, this study provided potential molecular mechanisms of terbufos-induced toxicity in testicular cells and suggests a possible protective measure. © 2015 Wiley Periodicals, Inc. Environ Toxicol, 2015.
    Print ISSN: 1520-4081
    Electronic ISSN: 1522-7278
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Published by Wiley
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  • 4
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    Determination of Nicotine in Tobacco by Chemometric Optimization and Cation-Selective Exhaustive Injection in Combination with Sweeping-Micellar Electrokinetic Chromatography (2015)
    Hindawi
    Details
    Publication Date: 2015-05-27
    Description: Nicotine is a potent chemical that excites the central nervous system and refreshes people. It is also physically addictive and causes dependence. To reduce the harm of tobacco products for smokers, a law was introduced that requires tobacco product containers to be marked with the amount of nicotine as well as tar. In this paper, an online stacking capillary electrophoresis (CE) method with cation-selective exhaustive injection sweeping-micellar electrokinetic chromatography (CSEI-sweeping-MEKC) is proposed for the optimized analysis of nicotine in tobacco. A higher conductivity buffer (160 mM phosphate buffer (pH 3)) zone was injected into the capillary, allowing for the analytes to be electrokinetically injected at a voltage of 15 kV for 15 min. Using 50 mM sodium dodecyl sulfate and 25% methanol in the sweeping buffer, nicotine was detected with high sensitivity. Thus, optimized conditions adapted from a chemometric approach provided a 6000-fold increase in the nicotine detection sensitivity using the CSEI-sweeping-MEKC method in comparison to normal CZE. The limits of detection were 0.5 nM for nicotine. The stacking method in combination with direct injection which matrix components would not interfere with assay performance was successfully applied to the detection of nicotine in tobacco samples.
    Print ISSN: 2090-8865
    Electronic ISSN: 2090-8873
    Topics: Chemistry and Pharmacology
    Published by Hindawi
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  • 5
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    Argininosuccinate synthetase 1 suppression and arginine restriction inhibit cell migration in gastric cancer cell lines (2015)
    Springer Nature
    Details
    Publication Date: 2015-05-01
    Description: Gastric cancer metastasis remains a major cause of cancer-related deaths. There is an urgent need to develop new therapeutic approaches targeting metastatic gastric cancer. Argininosuccinate synthetase 1 (ASS1) expression is increased in gastric cancer. We detected the protein expression of ASS1 in human gastric cancer cell lines (AGS, NCI-N87, and MKN45) and in murine gastric cancer cell lines (3I and 3IB2). We used vector-mediated short hairpin RNA (shRNA) expression to silence ASS1 expression in the MKN45 and 3IB2 cell lines, and analyzed the effects of this protein on cell migration and metastasis. We demonstrated that ASS1 silencing suppressed cell migration in the MKN45 and 3IB2 cell lines. ASS1 knockdown significantly reduced liver metastasis in mice after the intrasplenic implantation of 3IB2 cancer cell clones. To determine whether arginine restriction may represent a therapeutic approach to treat gastric cancer, the sensitivity of tumor cells to arginine depletion was determined in gastric cancer cells. Arginine depletion significantly inhibited cell migration in the gastric cancer cell line. The silencing of ASS1 expression in MKN45 and 3IB2 gastric cancer cells markedly decreased STAT3 protein expression. In conclusion, our results indicate that the ASS1 protein is required for cell migration in gastric cancer cell lines. Scientific Reports 5 doi: 10.1038/srep09783
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 6
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    The lycopene β-cyclase plays a significant role in provitamin A biosynthesis in wheat endosperm (2015)
    BioMed Central
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    Publication Date: 2015-05-08
    Description: Background: Lycopene β-cyclase (LCYB) is a key enzyme catalyzing the biosynthesis of β-carotene, the main source of provitamin A. However, there is no documented research about this key cyclase gene’s function and relationship with β-carotene content in wheat. Therefore, the objectives of this study were to clone TaLCYB and characterize its function and relationship with β-carotene biosynthesis in wheat grains. We also aimed to obtain more information about the endogenous carotenoid biosynthetic pathway and thus provide experimental support for carotenoid metabolic engineering in wheat. Results: In the present study, a lycopene β-cyclase gene, designated TaLCYB, was cloned from the hexaploid wheat cultivar Chinese Spring. The cyclization activity of the encoded protein was demonstrated by heterologous complementation analysis. The TaLCYB gene was expressed differentially in different tissues of wheat. Although TaLCYB had a higher expression level in the later stages of grain development, the β-carotene content still showed a decreasing tendency. The expression of TaLCYB in leaves was dramatically induced by strong light and the β-carotene content variation corresponded with changes of TaLCYB expression. A post-transcriptional gene silencing strategy was used to down-regulate the expression of TaLCYB in transgenic wheat, resulting in a decrease in the content of β-carotene and lutein, accompanied by the accumulation of lycopene to partly compensate for the total carotenoid content. In addition, changes in TaLCYB expression also affected the expression of several endogenous carotenogenic genes to varying degrees. Conclusion: Our results suggest that TaLCYB is a genuine lycopene cyclase gene and plays a crucial role in β-carotene biosynthesis in wheat. Our attempt to silence it not only contributes to elucidating the mechanism of carotenoid accumulation in wheat but may also help in breeding wheat varieties with high provitamin A content through RNA interference (RNAi) to block specific carotenogenic genes in the wheat endosperm.
    Electronic ISSN: 1471-2229
    Topics: Biology
    Published by BioMed Central
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  • 7
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    CART treatment improves memory and synaptic structure in APP/PS1 mice (2015)
    Springer Nature
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    Publication Date: 2015-05-12
    Description: Major characteristics of Alzheimer’s disease (AD) include deposits of β-amyloid (Aβ) peptide in the brain, loss of synapses, and cognitive dysfunction. Cocaine- and amphetamine-regulated transcript (CART) has recently been reported to attenuate Aβ-induced toxicity. In this study, CART localization in APP/PS1 mice was characterized and the protective effects of exogenous CART treatment were examined. Compared to age-matched wild type mice, 8-month-old APP/PS1 mice had significantly greater CART immunoreactivity in the hippocampus and cortex. A strikingly similar pattern of Aβ plaque-associated CART immunoreactivity was observed in the cortex of AD cases. Treatment of APP/PS1 mice with exogenous CART ameliorated memory deficits; this effect was associated with improvements in synaptic ultrastructure and long-term potentiation, but not a reduction of the Aβ plaques. Exogenous CART treatment in APP/PS1 mice prevented depolarization of the mitochondrial membrane and stimulated mitochondrial complex I and II activities, resulting in an increase in ATP levels. CART treatment of APP/PS1 mice also reduced reactive oxygen species and 4-hydroxynonenal, and mitigated oxidative DNA damage. In summary, CART treatment reduced multiple neuropathological measures and improved memory in APP/PS1 mice, and may therefore be a promising and novel therapy for AD. Scientific Reports 5 doi: 10.1038/srep10224
    Electronic ISSN: 2045-2322
    Topics: Natural Sciences in General
    Published by Springer Nature
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  • 8
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    An Energy-Efficient and Relay Hop Bounded Mobile Data Gathering Algorithm in Wireless Sensor Networks (2015)
    Hindawi
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    Publication Date: 2015-05-15
    Description: Recent studies reveal that great benefit can be achieved by employing mobile collectors to gather data in wireless sensor networks. Since the mobile collector can traverse the transmission range of each sensor, the energy of nodes may be saved near maximally. However, for directly receiving data packet from every node, the length of mobile collector route should be very long. Hence it may significantly increase the data gathering latency. To solve this problem, several algorithms have been proposed. One of them called BRH-MDG found that data gathering latency can be effectively shortened by performing proper local aggregation via multihop transmissions and then uploading the aggregated data to the mobile collector. But, the BRH-MDG algorithm did not carefully analyze and optimize the energy consumption of the entire network. In this paper, we propose a mathematical model for the energy consumption of the LNs and present a new algorithm called EEBRHM. The simulation results show that under the premise of bounded relay hop, compared with BRH-MDG, EEBRHM can prolong the networks lifetime by 730%.
    Print ISSN: 1550-1329
    Electronic ISSN: 1550-1477
    Topics: Electrical Engineering, Measurement and Control Technology
    Published by Hindawi
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  • 9
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    Assembly of Binuclear, Tetranuclear, and Multinuclear Complexes from Pincer-Like Mononuclear Metallotectons: Structural Diversity Dependent on Precursors (2015)
    American Chemical Society (ACS)
    Details
    Publication Date: 2015-01-23
    Description: Crystal Growth & Design DOI: 10.1021/cg501306n
    Print ISSN: 1528-7483
    Electronic ISSN: 1528-7505
    Topics: Chemistry and Pharmacology , Geosciences , Physics
    Published by American Chemical Society (ACS)
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  • 10
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    Minerals, Vol. 9, Pages 410: Constraining Mantle Heterogeneity beneath the South China Sea: A New Perspective on Magma Water Content (2019)
    MDPI
    In: Minerals
    Details
    Publication Date: 2019
    Description: The nature of upper mantle is important to understand the evolution of the South China Sea (SCS); thus, we need better constrains on its mantle heterogeneity. Magma water concentration is a good indicator, but few data have been reported. However, the rarity of glass and melt inclusions and the special genesis for phenocrysts in SCS basalts present challenges to analyzing magmatic water content. Therefore, it is possible to estimate the water variations through the characteristics of partial melting and magma crystallization. We evaluated variations in Fe depletion, degree of melt fractions, and mantle source composition along the fossil spreading ridge (FSR) using SCS basalt data from published papers. We found that lava from the FSR 116.2° E, FSR 117.7° E, and non-FSR regions can be considered normal lava with normal water content; in contrast, lava from the FSR 117° E-carbonatite and 114.9–115.0° E basalts have higher water content and show evidence of strong Fe depletion during the fractional crystallization after elimination of the effects of plagioclase oversaturation. The enriched water in the 117° E-carbonatite basalts is contained in carbonated silicate melts, and that in the 114.9–115.0° E basalts results from mantle contamination with the lower continental crust. The lava from the 117° E-normal basalt has much lower water content because of the lesser influence of the Hainan plume. Therefore, there must be a mantle source compositional transition area between the southwestern and eastern sub-basins of the SCS, which have different mantle evolution histories. The mantle in the west is more affected by contamination with continental materials, while that in the east is more affected by the Hainan mantle plume.
    Electronic ISSN: 2075-163X
    Topics: Geosciences
    Published by MDPI
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