bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydrogen Sulfide-Mediated Activation of O-Acetylserine (Thiol) Lyase and l/d-Cysteine Desulfhydrase Enhance Dehydration Tolerance in Eruca sativa Mill
Authors: Khan M. Nasir , AlZuaibr Fahad M. , Al-Huqail Asma A. , Siddiqui Manzer H. , M. Ali Hayssam , Al-Muwayhi Mohammed A. , Al-Haque Hafiz N.
Published: December 2018

Hydrogen sulfide (H2S) has emerged as an important signaling molecule and plays a significant role during different environmental stresses in plants. The present work was carried out to explore the potential role of H2S in reversal of dehydration stress-inhibited O-acetylserine (thiol) lyase (OAS-TL), l-cysteine desulfhydrase (LCD), and d-cysteine desulfhydrase (DCD) response in arugula (Eruca sativa Mill.) plants. Dehydration-stressed plants exhibited reduced water status and increased levels of hydrogen peroxide (H2O2) and superoxide (O2•−) content that increased membrane permeability and lipid peroxidation, and caused a reduction in chlorophyll content. However, H2S donor sodium hydrosulfide (NaHS), at the rate of 2 mM, substantially reduced oxidative stress (lower H2O2 and O2•−) by upregulating activities of antioxidant enzymes (superoxide dismutase, peroxidase, and catalase) and increasing accumulation of osmolytes viz. proline and glycine betaine (GB). All these, together, resulted in reduced membrane permeability, lipid peroxidation, water loss, and improved hydration level of plants. The beneficial role of H2S in the tolerance of plants to dehydration stress was traced with H2S-mediated activation of carbonic anhydrase activity and enzyme involved in the biosynthesis of cysteine (Cys), such as OAS-TL. H2S-treated plants showed maximum Cys content. The exogenous application of H2S also induced the activity of LCD and DCD enzymes that assisted the plants to synthesize more H2S from accumulated Cys. Therefore, an adequate concentration of H2S was maintained, that improved the efficiency of plants to mitigate dehydration stress-induced alterations. The central role of H2S in the reversal of dehydration stress-induced damage was evident with the use of the H2S scavenger, hypotaurine.
Heterologous Expression of Salvia miltiorrhiza MicroRNA408 Enhances Tolerance to Salt Stress in Nicotiana benthamiana
Authors: Guo Xiaorong , Niu Junfeng , Cao Xiaoyan
Published: December 2018

MicroRNAs (miRNAs) are a class of endogenous small RNAs that regulate the expression of target genes post-transcriptionally; they are known to play major roles in development and responses to abiotic stress. MicroRNA408 (miR408) is a conserved small RNA in plants; it was reported that miR408 genes were involved in abiotic stress in Arabidopsis. However, miR408 in Salvia miltiorrhiza has been rarely investigated. In this study, we cloned Sm-MIR408, the miR408 precursor sequence, and its promoter sequence from S. miltiorrhiza and the role in tolerance to salt stress is described. The effects of salt stress on miR408 expression were studied by using β-glucuronidase (GUS) staining. Our data indicated that transgenic tobacco overexpressing Sm-MIR408 promoted seed germination and reduced the accumulation of reactive oxygen species under salt stress. Transcript levels of antioxidative genes, i.e., NbSOD, NbPOD, and NbCAT, and their enzyme activities increased in salinity-stressed transgenic tobacco plants, suggesting a better antioxidant system to cope the oxidative damage caused by salinity stress. Taken together, these findings indicated that miR408 functions in positive responses to salt tolerance in tobacco.
The Stress-Inducible Protein DRR1 Exerts Distinct Effects on Actin Dynamics
Authors: Kretzschmar Anja , Schülke Jan-Philip , Masana Mercè , Dürre Katharina , Müller Marianne B. , Bausch Andreas R. , Rein Theo
Published: December 2018

Cytoskeletal dynamics are pivotal to memory, learning, and stress physiology, and thus psychiatric diseases. Downregulated in renal cell carcinoma 1 (DRR1) protein was characterized as the link between stress, actin dynamics, neuronal function, and cognition. To elucidate the underlying molecular mechanisms, we undertook a domain analysis of DRR1 and probed the effects on actin binding, polymerization, and bundling, as well as on actin-dependent cellular processes. Methods: DRR1 domains were cloned and expressed as recombinant proteins to perform in vitro analysis of actin dynamics (binding, bundling, polymerization, and nucleation). Cellular actin-dependent processes were analyzed in transfected HeLa cells with fluorescence recovery after photobleaching (FRAP) and confocal microscopy. Results: DRR1 features an actin binding site at each terminus, separated by a coiled coil domain. DRR1 enhances actin bundling, the cellular F-actin content, and serum response factor (SRF)-dependent transcription, while it diminishes actin filament elongation, cell spreading, and actin treadmilling. We also provide evidence for a nucleation effect of DRR1. Blocking of pointed end elongation by addition of profilin indicates DRR1 as a novel barbed end capping factor. Conclusions: DRR1 impacts actin dynamics in several ways with implications for cytoskeletal dynamics in stress physiology and pathophysiology.
Neuroprotective and Neurological/Cognitive Enhancement Effects of Curcumin after Brain Ischemia Injury with Alzheimer’s Disease Phenotype
Authors: Pluta Ryszard , Ułamek-Kozioł Marzena , Czuczwar Stanisław J.
Published: December 2018

In recent years, ongoing interest in ischemic brain injury research has provided data showing that ischemic episodes are involved in the development of Alzheimer’s disease-like neuropathology. Brain ischemia is the second naturally occurring neuropathology, such as Alzheimer’s disease, which causes the death of neurons in the CA1 region of the hippocampus. In addition, brain ischemia was considered the most effective predictor of the development of full-blown dementia of Alzheimer’s disease phenotype with a debilitating effect on the patient. Recent knowledge on the activation of Alzheimer’s disease-related genes and proteins—e.g., amyloid protein precursor and tau protein—as well as brain ischemia and Alzheimer’s disease neuropathology indicate that similar processes contribute to neuronal death and disintegration of brain tissue in both disorders. Although brain ischemia is one of the main causes of death in the world, there is no effective therapy to improve the structural and functional outcomes of this disorder. In this review, we consider the promising role of the protective action of curcumin after ischemic brain injury. Studies of the pharmacological properties of curcumin after brain ischemia have shown that curcumin has several therapeutic properties that include anti-excitotoxic, anti-oxidant, anti-apoptotic, anti-hyperhomocysteinemia and anti-inflammatory effects, mitochondrial protection, as well as increasing neuronal lifespan and promoting neurogenesis. In addition, curcumin also exerts anti-amyloidogenic effects and affects the brain’s tau protein. These results suggest that curcumin may be able to serve as a potential preventive and therapeutic agent in neurodegenerative brain disorders.
Inhibitors of the VEGF Receptor Suppress HeLa S3 Cell Proliferation via Misalignment of Chromosomes and Rotation of the Mitotic Spindle, Causing a Delay in M-Phase Progression
Authors: Okumura Daiki , Hagino Mari , Yamagishi Akane , Kaibori Yuichiro , Munira Sirajam , Saito Youhei , Nakayama Yuji
Published: December 2018

Cell division is the process by which replicated chromosomes are separated into two daughter cells. Although regulation of M phase has been extensively investigated, not all regulating factors have been identified. Over the course of our research, small molecules were screened to identify those that regulate M phase. In the present study, the vascular endothelial growth factor receptor (VEGFR) inhibitors A83-01, SU4312, and Ki8751 were examined to determine their effects on M phase. Treatment of HeLa S3 cells with these inhibitors suppressed cell proliferation in a concentration-dependent manner, and also suppressed Akt phosphorylation at Ser473, a marker of Akt activation. Interestingly, cleaved caspase-3 was detected in Adriamycin-treated cells but not in inhibitor-treated cells, suggesting that these inhibitors do not suppress cell proliferation by causing apoptosis. A cell cycle synchronization experiment showed that these inhibitors delayed M phase progression, whereas immunofluorescence staining and time-lapse imaging revealed that the M phase delay was accompanied by misalignment of chromosomes and rotation of the mitotic spindle. Treatment with the Mps1 inhibitor AZ3146 prevented the SU4312-induced M phase delay. In conclusion, the VEGFR inhibitors investigated here suppress cell proliferation by spindle assembly checkpoint-induced M phase delay, via misalignment of chromosomes and rotation of the mitotic spindle.
Interstitial Fluid in Gynecologic Tumors and Its Possible Application in the Clinical Practice
Authors: Ura Blendi , Di Lorenzo Giovanni , Romano Federico , Monasta Lorenzo , Mirenda Giuseppe , Scrimin Federica , Ricci Giuseppe
Published: December 2018

Gynecologic cancers are an important cause of worldwide mortality. The interstitium consists of solid and fluid phases, situated between the blood vessels and cells. The interstitial fluid (IF), or fluid phase, is an extracellular fluid bathing and surrounding the tissue cells. The TIF (tumor interstitial fluid) is a dynamic fluid rich in lipids, proteins and enzyme-derived substances. The molecules found in the IF may be associated with pathological changes in tissues leading to cancer growth and metastatization. Proteomic techniques have allowed an extensive study of the composition of the TIF as a source of biomarkers for gynecologic cancers. In our review, we analyze the composition of the TIF, its formation process, the sampling methods, the consequences of its accumulation and the proteomic analyses performed, that make TIF valuable for monitoring different types of cancers.
Transcriptome Sequence Analysis Elaborates a Complex Defensive Mechanism of Grapevine (Vitis vinifera L.) in Response to Salt Stress
Authors: Guan Le , Haider Muhammad Salman , Khan Nadeem , Nasim Maazullah , Jiu Songtao , Fiaz Muhammad , Zhu Xudong , Zhang Kekun , Fang Jinggui
Published: December 2018

Salinity is ubiquitous abiotic stress factor limiting viticulture productivity worldwide. However, the grapevine is vulnerable to salt stress, which severely affects growth and development of the vine. Hence, it is crucial to delve into the salt resistance mechanism and screen out salt-resistance prediction marker genes; we implicated RNA-sequence (RNA-seq) technology to compare the grapevine transcriptome profile to salt stress. Results showed 2472 differentially-expressed genes (DEGs) in total in salt-responsive grapevine leaves, including 1067 up-regulated and 1405 down-regulated DEGs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations suggested that many DEGs were involved in various defense-related biological pathways, including ROS scavenging, ion transportation, heat shock proteins (HSPs), pathogenesis-related proteins (PRs) and hormone signaling. Furthermore, many DEGs were encoded transcription factors (TFs) and essential regulatory proteins involved in signal transduction by regulating the salt resistance-related genes in grapevine. The antioxidant enzyme analysis showed that salt stress significantly affected the superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and glutathione S-transferase (GST) activities in grapevine leaves. Moreover, the uptake and distribution of sodium (Na+), potassium (K+) and chlorine (Cl−) in source and sink tissues of grapevine was significantly affected by salt stress. Finally, the qRT-PCR analysis of DE validated the data and findings were significantly consistent with RNA-seq data, which further assisted in the selection of salt stress-responsive candidate genes in grapevine. This study contributes in new perspicacity into the underlying molecular mechanism of grapevine salt stress-tolerance at the transcriptome level and explore new approaches to applying the gene information in genetic engineering and breeding purposes.
Identification of Two Novel Wheat Drought Tolerance-Related Proteins by Comparative Proteomic Analysis Combined with Virus-Induced Gene Silencing
Authors: Wang Xinbo , Xu Yanhua , Li Jingjing , Ren Yongzhe , Wang Zhiqiang , Xin Zeyu , Lin Tongbao
Published: December 2018

Drought is a major adversity that limits crop yields. Further exploration of wheat drought tolerance-related genes is critical for the genetic improvement of drought tolerance in this crop. Here, comparative proteomic analysis of two wheat varieties, XN979 and LA379, with contrasting drought tolerance was conducted to screen for drought tolerance-related proteins/genes. Virus-induced gene silencing (VIGS) technology was used to verify the functions of candidate proteins. A total of 335 differentially abundant proteins (DAPs) were exclusively identified in the drought-tolerant variety XN979. Most DAPs were mainly involved in photosynthesis, carbon fixation, glyoxylate and dicarboxylate metabolism, and several other pathways. Two DAPs (W5DYH0 and W5ERN8), dubbed TaDrSR1 and TaDrSR2, respectively, were selected for further functional analysis using VIGS. The relative electrolyte leakage rate and malonaldehyde content increased significantly, while the relative water content and proline content significantly decreased in the TaDrSR1- and TaDrSR2-knock-down plants compared to that in non-knocked-down plants under drought stress conditions. TaDrSR1- and TaDrSR2-knock-down plants exhibited more severe drooping and wilting phenotypes than non-knocked-down plants under drought stress conditions, suggesting that the former were more sensitive to drought stress. These results indicate that TaDrSR1 and TaDrSR2 potentially play vital roles in conferring drought tolerance in common wheat.
Photoacoustic Ophthalmoscopy: Principle, Application, and Future Directions
Authors: Nguyen Van Phuc , Paulus Yannis M.
Published: December 2018

Photoacoustic ophthalmoscopy (PAOM) is a novel, hybrid, non-ionizing, and non-invasive imaging technology that has been used to assess the retina. PAOM can provide both anatomic and functional retinal characterizations with high resolution, high sensitivity, high contrast, and a high depth of penetration. Thus, ocular diseases can be precisely detected and visualized at earlier stages, resulting in an improved understanding of pathophysiology, improved management, and the improved monitoring of retinal treatment to prevent vision loss. To better visualize ocular components such as retinal vessels, choroidal vessels, choroidal neovascularization, retinal neovascularization, and the retinal pigment epithelium, an advanced multimodal ocular imaging platform has been developed by a combination of PAOM with other optical imaging techniques such as optical coherence tomography (OCT), scanning laser ophthalmoscopy (SLO), and fluorescence microscopy. The multimodal images can be acquired from a single imaging system and co-registered on the same image plane, enabling an improved evaluation of disease. In this review, the potential application of photoacoustic ophthalmoscopy in both research and clinical diagnosis are discussed as a medical screening technique for the visualization of various ocular diseases. The basic principle and requirements of photoacoustic ocular imaging are introduced. Then, various photoacoustic microscopy imaging systems of the retina in animals are presented. Finally, the future development of PAOM and multimodal imaging is discussed.
In Vivo 3D Imaging of Retinal Neovascularization Using Multimodal Photoacoustic Microscopy and Optical Coherence Tomography Imaging
Authors: Nguyen Van Phuc , Li Yanxiu , Aaberg Michael , Zhang Wei , Wang Xueding , Paulus Yannis M.
Published: December 2018

The pathological process of neovascularization of the retina plays a critical role in causing vision loss in several diseases, including diabetes, retinal vein occlusion, and sickle cell disease. Retinal neovascularization can lead to vitreous hemorrhage and retinal detachment, yet the pathological process of neovascularization is a complex phenomenon under active investigation. Understanding and monitoring retinal neovascularization is critically important in clinical ophthalmology. This study describes a novel multimodal ocular imaging system which combines photoacoustic microscopy (PAM) and a spectral domain optical coherence tomography (SD-OCT) to improve the visualization of retinal neovascularization (RNV), their depth, and the surrounding anatomy in living rabbits. RNV was induced in New Zealand rabbits by intravitreal injection of vascular endothelial growth factor (VEGF). The retinal vasculature before and after injection at various times was monitored and evaluated using multimodal imaging including color fundus photography, fluorescein angiography (FA), OCT, and PAM. In vivo experiments demonstrate that PAM imaging distinctly characterized the location as well as the morphology of individual RNV with high contrast at a safe laser energy of 80 nJ. SD-OCT was used to identify a cross-sectional structure of RNV. In addition, dynamic changes in the retinal morphology and retinal neovascularization were observed at day 4, 5, 6, 7, 9, 11, 14, 28, and day 35 after VEGF injection. PAM demonstrated high-resolution optical absorption of hemoglobin and vascular imaging of the retina and choroid with increased depth of penetration. With the current multimodal imaging system, RNV can be easily visualized in both 2D and 3D angiography. This multimodal ocular imaging system provides improved characterization of the microvasculature in a safe manner in larger rabbit eyes.
Refined Analysis of RADARSAT-2 Measurements to Discriminate Two Petrogenic Oil-Slick Categories: Seeps versus Spills
Authors: Carvalho Gustavo de Araújo , Minnett Peter J. , Paes Eduardo Tavares , De Miranda Fernando Pellon , Landau Luiz
Published: December 2018

Our research focuses on refining the ability to discriminate two petrogenic oil-slick categories: the sea surface expression of naturally-occurring oil seeps and man-made oil spills. For that, a long-term RADARSAT-2 dataset (244 scenes imaged between 2008 and 2012) is analyzed to investigate oil slicks (4562) observed in the Gulf of Mexico (Campeche Bay, Mexico). As the scientific literature on the use of satellite-derived measurements to discriminate the oil-slick category is sparse, our research addresses this gap by extending our previous investigations aimed at discriminating seeps from spills. To reveal hidden traits of the available satellite information and to evaluate an existing Oil-Slick Discrimination Algorithm, distinct processing segments methodically inspect the data at several levels: input data repository, data transformation, attribute selection, and multivariate data analysis. Different attribute selection strategies similarly excel at the seep-spill differentiation. The combination of different Oil-Slick Information Descriptors presents comparable discrimination accuracies. Among 8 non-linear transformations, the Logarithm and Cube Root normalizations disclose the most effective discrimination power of almost 70%. Our refined analysis corroborates and consolidates our earlier findings, providing a firmer basis and useful accuracies of the seep-spill discrimination practice using information acquired with space-borne surveillance systems based on Synthetic Aperture Radars.
On Air-Cavity Formation during Water Entry of Flexible Wedges
Authors: Panciroli Riccardo , Pagliaroli Tiziano , Minak Giangiacomo
Published: December 2018

Elastic bodies entering water might experience fluid–structure interaction phenomena introduced by the mutual interaction between structural deformation and fluid motion. Cavity formation, often misleadingly named cavitation, is one of these. This work presents the results of an experimental investigation on the water entry of deformable wedges impacting a quiescent water surface with pure vertical velocity in free fall. The experimental campaign is conducted on flexible wedges parametrically varying the flexural stiffness, deadrise angle, and drop height. It is found that, under given experimental conditions, cavity pockets form beneath the wedge. Their generation mechanism might be ascribed to a differential between structural and fluid velocities, which is introduced by structural vibrations. Results show that the impact force during water entry of stiff wedges are always opposing gravity, while, in case flexible wedges temporarily reverse their direction, with the body that is being sucked into the water within the time frame between the cavity formation and its collapse. Severe impact might also generate a series of cavity generation and collapses.
Comparison of Analytical Approaches Predicting the Compressive Strength of Fibre Reinforced Polymers
Authors: Leopold Christian , Harder Sergej , Philipkowski Timo , Liebig Wilfried V. , Fiedler Bodo
Published: December 2018

Common analytical models to predict the unidirectional compressive strength of fibre reinforced polymers are analysed in terms of their accuracy. Several tests were performed to determine parameters for the models and the compressive strength of carbon fibre reinforced polymer (CFRP) and glass fibre reinforced polymer (GFRP). The analytical models are validated for composites with glass and carbon fibres by using the same epoxy matrix system in order to examine whether different fibre types are taken into account. The variation in fibre diameter is smaller for CFRP. The experimental results show that CFRP has about 50% higher compressive strength than GFRP. The models exhibit significantly different results. In general, the analytical models are more precise for CFRP. Only one fibre kinking model’s prediction is in good agreement with the experimental results. This is in contrast to previous findings, where a combined modes model achieves the best prediction accuracy. However, in the original form, the combined modes model is not able to predict the compressive strength for GFRP and was adapted to address this issue. The fibre volume fraction is found to determine the dominating failure mechanisms under compression and thus has a high influence on the prediction accuracy of the various models.
Investigations of the Tribological Performance of A390 Alloy Hybrid Aluminum Matrix Composite
Authors: Edacherian Abhilash , Algahtani Ali , Tirth Vineet
Published: December 2018

Several challenges stand in the way of the production of metal matrix composites (MMCs) such as higher processing temperatures, particulate mixing, particulate–matrix interface bonding issues, and the ability to process into desired geometrical shapes. Although there are many studies showing composites with single particulate reinforcements, studies on composites with multiple reinforcing agents (hybrid composites) are found to be limited. Development of a hybrid particulate composite with optimized mechanical and tribological properties is very significant to suit modern engineering applications. In this study, Al–Si hypereutectic alloy (A390) was used as the matrix and silicon carbide (SiC), graphite (Gr), and molybdenum di-sulphide (MoS2) were used as particulates. Particulate volume (wt %) was varied and sample test castings were made using a squeeze casting process through a stir casting processing route. The evaluation of the mechanical testing indicates that the presence of both the hard phase (SiC) and the soft phase had distinct effect on the properties of the hybrid aluminum matrix composites (HAMCs). Composite samples were characterized to understand the performance and to meet the tribological applications. The 3D profilometry of the fractured surfaces revealed poor ductility and scanning electron microscopy fractography study indicated an intra-granular brittle fracture for HAMCs. Also, the dry sliding wear tests indicated that the newly developed HAMCs had better tribological performance compared to that of A390 alloy.
Oxidation Behavior of Refractory AlNbTiVZr0.25 High-Entropy Alloy
Authors: Yurchenko Nikita , Panina Evgeniya , Zherebtsov Sergey , Salishchev Gennady , Stepanov Nikita
Published: December 2018

Oxidation behavior of a refractory AlNbTiVZr0.25 high-entropy alloy at 600–900 °C was investigated. At 600–700 °C, two-stage oxidation kinetics was found: Nearly parabolic oxidation (n = 0.46–0.48) at the first stage, transitioned to breakaway oxidation (n = 0.75–0.72) at the second stage. At 800 °C, the oxidation kinetics was nearly linear (n = 0.92) throughout the entire duration of testing. At 900 °C, the specimen disintegrated after 50 h of testing. The specific mass gains were estimated to be 7.2, 38.1, and 107.5, and 225.5 mg/cm2 at 600, 700, and 800 °C for 100 h, and 900 °C for 50 h, respectively. Phase compositions and morphology of the oxide scales were analyzed using X-ray diffraction (XRD) and scanning electron microscopy (SEM). It was shown that the surface layer at 600 °C consisted of the V2O5, VO2, TiO2, Nb2O5, and TiNb2O7 oxides. Meanwhile, the scale at 900 °C comprised of complex TiNb2O7, AlNbO4, and Nb2Zr6O17 oxides. The oxidation mechanisms operating at different temperatures were discussed and a comparison of oxidation characteristics with the other alloys was conducted.
Freeform Perfusable Microfluidics Embedded in Hydrogel Matrices
Authors: Štumberger Gabriela , Vihar Boštjan
Published: December 2018

We report a modification of the freeform reversible embedding of suspended hydrogels (FRESH) 3D printing method for the fabrication of freeform perfusable microfluidics inside a hydrogel matrix. Xanthan gum is deposited into a CaCl2 infused gelatine slurry to form filaments, which are consequently rinsed to produce hollow channels. This provides a simple method for rapid prototyping of microfluidic devices based on biopolymers and potentially a new approach to the construction of vascular grafts for tissue engineering.
Two Dimensional Magnetic Coordination Polymers Formed by Lanthanoids and Chlorocyananilato
Authors: Benmansour Samia , Hernández-Paredes Antonio , Gómez-García Carlos J.
Published: December 2018

Here we show the important role played by the size of the lanthanoid and the solvent used in the final structures of several two-dimensional magnetic coordination polymers with the ligand chlorocyananilato, (C6O4(CN)Cl)2−. With this aim we have prepared five compounds: [Nd2(C6O4(CN)Cl)3(DMF)6] (1) (DMF = dimethylformamide), [Dy2(C6O4(CN)Cl)3(DMF)6]·4H2O (2), [Ho2(C6O4(CN)Cl)3(DMF)6]·2H2O (3), and [Ln2(C6O4(CN)Cl)3(DMSO)6] with Ln = Ce (4) and Nd (5) (DMSO = dimethylsulfoxide). These compounds are formed by two dimensional networks with a (6,3)-topology but, depending on the size of the lanthanoid and on the solvent used, show important structural differences, including the size, shape, distortion and content of the cavities as well as the flatness of the layers. The comparison of compounds 1–3 and 4–5 shows the role played by the size of the lanthanoid while keeping constant the solvent, whereas, the comparison of compounds 1 and 5 shows the role of the solvent (DMF vs. DMSO) while keeping constant the lanthanoid. The magnetic properties of all of them show the absence of noticeable magnetic interactions, in agreement with previous results that can be explained by the internal character of the 4f electron and the weak magnetic coupling mediated by these anilato-based ligands.
Bayesian and Non-Bayesian Inference for the Generalized Pareto Distribution Based on Progressive Type II Censored Sample
Authors: Hu Xuehua , Gui Wenhao
Published: December 2018

In this paper, first we consider the maximum likelihood estimators for two unknown parameters, reliability and hazard functions of the generalized Pareto distribution under progressively Type II censored sample. Next, we discuss the asymptotic confidence intervals for two unknown parameters, reliability and hazard functions by using the delta method. Then, based on the bootstrap algorithm, we obtain another two pairs of approximate confidence intervals. Furthermore, by applying the Markov Chain Monte Carlo techniques, we derive the Bayesian estimates of the two unknown parameters, reliability and hazard functions under various balanced loss functions and the corresponding confidence intervals. A simulation study was conducted to compare the performances of the proposed estimators. A real dataset analysis was carried out to illustrate the proposed methods.
Ni- and Co-Based Superalloys and their Coatings
Authors: Cormier Jonathan
Published: December 2018

Nickel- and Cobalt-based superalloys are state-of-the art materials for the manufacturing of components in the hottest sections of aero-engines and land-based power generation gas turbines. [...]
Solvents to Fragments to Drugs: MD Applications in Drug Design
Authors: Defelipe Lucas A. , Arcon Juan Pablo , Modenutti Carlos P. , Marti Marcelo A. , Turjanski Adrián G. , Barril Xavier
Published: December 2018

Simulations of molecular dynamics (MD) are playing an increasingly important role in structure-based drug discovery (SBDD). Here we review the use of MD for proteins in aqueous solvation, organic/aqueous mixed solvents (MDmix) and with small ligands, to the classic SBDD problems: Binding mode and binding free energy predictions. The simulation of proteins in their condensed state reveals solvent structures and preferential interaction sites (hot spots) on the protein surface. The information provided by water and its cosolvents can be used very effectively to understand protein ligand recognition and to improve the predictive capability of well-established methods such as molecular docking. The application of MD simulations to the study of the association of proteins with drug-like compounds is currently only possible for specific cases, as it remains computationally very expensive and labor intensive. MDmix simulations on the other hand, can be used systematically to address some of the common tasks in SBDD. With the advent of new tools and faster computers we expect to see an increase in the application of mixed solvent MD simulations to a plethora of protein targets to identify new drug candidates.
Bioactive Compounds and Volatile Profiles of Five Transylvanian Wild Edible Mushrooms
Authors: Fogarasi Melinda , Socaci Sonia Ancuţa , Dulf Francisc Vasile , Diaconeasa Zorița Maria , Fărcaș Anca Corina , Tofană Maria , Semeniuc Cristina Anamaria
Published: December 2018

This study aimed to determine the chemical composition, fatty acids, volatile profile and phenolic compounds profiles from five wild edible mushrooms (Agaricus bisporus, Pleurotus ostreatus, Cantharellus cibarius, Boletus edulis, Lactarius piperatus) from Romania. The results indicated that the dried fruiting bodies of selected mushrooms were rich in proteins (36.24 g/100 g dw-Boletus edulis) and carbohydrates (62.45 g/100 g dw-Lactarius piperatus). 4-Hydroxybenzoic acid and cinnamic acid, were the main phenolic compound present in all selected species. Additionally, the fatty acid pattern included polyunsaturated acids in more than 60% of all fatty acids followed by monounsaturated fatty acids (30%). For the studied mushroom samples, the main volatile compounds identified by the gas chromatography-mass spectrometry were hexanal, benzaldehyde and dodecanoic acid. According to the obtained results, the fruiting bodies of selected Romanian mushrooms are a rich source of bioactive molecules indicating that they may be further exploited as functional ingredients in the composition of innovative food products.
Construction of Highly Stable Cytotoxic Nuclear-Directed Ribonucleases
Authors: Roura Padrosa David , Castro Jessica , Romero-Casañas Alejandro , Ribó Marc , Vilanova Maria , Benito Antoni
Published: December 2018

Ribonucleases are proteins whose use is promising in anticancer therapy. We have previously constructed different human pancreatic ribonuclease variants that are selectively cytotoxic for tumor cells by introducing a nuclear localization signal into their sequence. However, these modifications produced an important decrease in their stability compromising their behavior in vivo. Here, we show that we can significantly increase the thermal stability of these cytotoxic proteins by introducing additional disulfide bonds by site-directed mutagenesis. One of these variants increases its thermal stability by around 17 °C, without affecting its catalytic activity while maintaining the cytotoxic activity against tumor cells. We also show that the most stable variant is significantly more resistant to proteolysis when incubated with proteinase K or with human sera, suggesting that its half-live could be increased in vivo once administered.
Determination of Flavonoid and Proanthocyanidin Profile of Hungarian Sour Cherry
Authors: Nemes Andrea , Szőllősi Erzsébet , Stündl László , Biró Attila , Homoki Judit Rita , Szarvas Mária Magdolna , Balogh Péter , Cziáky Zoltán , Remenyik Judit
Published: December 2018

Hungarian sour cherries (SC) are excellent source of anthocyanin (concentrations (100–300 mg in 100 g fresh fruit) and melatonin (0.15 mg in 100 g fresh fruit), but other flavonoid derivatives also can be isolated by aqueous alcoholic extraction. We have developed a new process for extracting non-extractable procyanidines bound to the membrane, proteins, and fibers. These compounds were seperated with UHPLC-MS methods, and the structure of individual components were identified on the basis of their mass fragmentation spectra. The antioxidant capacity of soluble and non-soluble antioxidants were measured with ferric reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl radical scavenging activity (DPPH), trolox equivalent antioxidant capacity (TEAC) assays, and compared to the new measurement methods of water-soluble antioxidant capacity (ACW), lipid-soluble antioxidant capacity (ACL). Furthermore, total phenolic content (TPC) and total procyanidin content (PAC) were determinated. As a result of our investigation, we found that the solvent combination, where in the first step is water–ethanol (1:1), then 100% ethanol were suitable for the extraction of the extractable antioxidants. However, the chemiluminescence method that is based on the elimination of the superoxide radical is more accurate than other colorimetric methods which measure antioxidant capacity.
Ionic Liquid–Ultrasound-Based Extraction of Biflavonoids from Selaginella helvetica and Investigation of Their Antioxidant Activity
Authors: Jiang Yongmei , Li Dan , Ma Xiankui , Jiang Fengqin , He Qun , Qiu Shaoliang , Li Yan , Wang Gang
Published: December 2018

As a new and green solvent, ionic liquids (ILs) have received more attention during the green extraction and separation process for natural medicines. In this paper, IL-ultrasound-assisted extraction (IL-UAE) of total biflavonoids (TBFs) from Selaginella helvetica was firstly developed, and different ILs were employed and compared. Based on single-factor experiment, solid–liquid ratio (1:10–1:14 g/mL), IL concentration (0.6–1.0 mmol/mL), and extract temperature (40–60 °C) were further explored, according to response surface methodology (RSM), with TBF yields as the index. Moreover, antioxidant activity of TBF extract was analyzed by four methods, i.e., 2,2-di(4-tert-octylphenyl)-1-picrylhydrazyl (DPPH) and 2,2′-azinobis-(3-ethylbenzth-iazoline-6-sulphonate (ABTS) free radical scavenging assay, ferric ion reducing power assay, and chelation of ferrous ions assay. The results indicated that [C6mim]PF6 had a high selectivity and efficiency. Moreover, important parameters for the extraction process were investigated and optimized. Through parameter optimization (0.8 mmol/L, 250 W, 40 min, 1:12.7 g/mL, and 47 °C), a yield of 18.69 mg/g biflavonoids was obtained from the extract of S. helvetica. Compared with ethanol-UAE, heat-reflux extraction, Soxhlet extraction, and percolation extraction, IL-UAE could not only obtain higher yield in a shorter time, but also reduce the solvent consumption. In addition, TBF extract showed potential antioxidant activity based on the above four antioxidant methods. In short, IL-UAE was first employed to develop a novel and green extraction method for TBF content, and this experiment provides valuable references for further utilization of S. helvetica.
Synthesis, Antibacterial, and Anti HepG2 Cell Line Human Hepatocyte Carcinoma Activity of Some New Potentially Benzimidazole-5-(Aryldiazenyl)Thiazole Derivatives
Authors: Khalifa Mohamed E. , Gobouri Adil A. , Kabli Fahad M. , Altalhi Tarik A. , Almalki Abdulraheem S. A. , Mohamed Mahmoud A.
Published: December 2018

The paper describes the synthesis and biological evaluation of some new benzimidazole derivatives as potent clinical drugs that are useful in the treatment of some microbial infections and tumor inhibition. The starting compound 2-(bromomethyl)-1H-benzimidazole (1) was prepared, and hence underwent interesting functionalization reactions to afford several series of benzimidazole-5-(aryldiazenyl)thiazole derivatives: 3a–c, 7a–c, and 8a–c. The antibacterial activities of the synthesized compounds were evaluated by calculation of the inhibition zone diameter (mm) and the determination of minimum inhibitory concentration (µg/mL) against selected pathogenic bacteria Staphylococcus aureus (Gram-positive bacteria) and Escherichia coli (Gram-negative bacteria).Noticeable efficiency was found based on in vitro screening for their antioxidant activity and cytotoxicity effect against the human liver cancer cell line (HepG2) and human hepatocyte carcinoma cells at relatively high concentrations.
Evolution of Volatile Compounds and Spoilage Bacteria in Smoked Bacon during Refrigeration Using an E-Nose and GC-MS Combined with Partial Least Squares Regression
Authors: Li Xinfu , Zhu Jiancai , Li Cong , Ye Hua , Wang Zhouping , Wu Xiang , Xu Baocai
Published: December 2018

The changes in the concentration of volatile organic compounds (VOCs) and biogenic amines (BAs) in smoked bacon during 45-day refrigerated storage is investigated using solid-phase micro-extraction coupled with gas chromatography-mass spectrometry and high-performance liquid chromatography. In total, 56 VOCs and 6 BAs were identified and quantified. The possible pathways leading to their formation are analyzed and considered as the potential signs of microbial activity, especially by specific spoilage microorganisms (SSOs). Leuconostoc and Lactobacillus, which levels increased markedly with the extension of storage time, were recognized as SSOs. An electronic nose (e-nose) was employed to determine the changes in concentration of the odor components per sample present within half an hour. Partial least squares regression was then carried out to analyze the correlation between SSO growth, metabolite concentration, BA accumulation, and e-nose response. The results show that ten VOCs (ethanol, 2-furanmethanol, 1-hexanol, 1-propanol, phenol, 2-methoxyphenol, acetic acid, 3-ethyl-2-cyclopenten-1-one, furfural, and ethyl hexanoate) and three BAs (putrescine, cadaverine, and tyramine) can be associated with the growth of SSOs. Thus, they can be adopted as potential indicators to evaluate and monitor the quality of the bacon and develop appropriate detection methods. E-noses can used to recognize odors and diagnose quality of bacon.
Lamiophlomis rotata Identification via ITS2 Barcode and Quality Evaluation by UPLC-QTOF-MS Couple with Multivariate Analyses
Authors: Wang Jian , Gao YunLing , Chen YiLong , Chen YiWen , Zhang Yi , Xiang Li , Pan Zheng
Published: December 2018

Lamiophlomis rotata (L. rotata), is known as “Daba” in the Tibetan region, Ajuga ovalifolia and Oreosolen wartii have also been utilized as substitutes for “Daba”, however, only L. rotata has been officially listed in the Chinese Pharmacopoeia for hemostasis preparations. To safely apply the traditional uses of the herb, internal transcribed spacer 2 (ITS2) DNA barcodes were employed to discriminate L. rotata from its adulterants. For further evaluation of the quality of different originating habitats, the chemical profiles of 25 samples were determined by ultra-high-performance liquid chromatography coupled with time-of-flight mass spectrometry (UPLC-QTOF-MS) coupled with multivariate analyses. ITS2 DNA barcodes differentiated L. rotata from O. wartii and A. ovalifolia accurately. A neighbor-joining (NJ) tree showed that three origins clustered into three clades. Forty-nine compounds were identified in the total ion current (TIC) profile of L. rotata. Additionally, two pairs of isomers were identified for the first time by using mass spectrometry fragmentation. The differences between the variable habitats were determined by multivariate statistical analysis of the UPLC-QTOF-MS data from 25 specimens. Ten compounds were identified as the characteristic markers distinguishing the sample from four geographical origins. The results also suggest that samples from Qinghai and Sichuan province would be the most suitable choice for traditional prescriptions and preparations.
Long-Term Zinc Supplementation Improves Liver Function and Decreases the Risk of Developing Hepatocellular Carcinoma
Authors: Hosui Atsushi , Kimura Eiji , Abe Sumiko , Tanimoto Takashi , Onishi Kousaku , Kusumoto Yukihiro , Sueyoshi Yuka , Matsumoto Kengo , Hirao Motohiro , Yamada Takuya , Hiramatsu Naoki
Published: December 2018

Zinc plays a pivotal role in various zinc enzymes, which are crucial in the maintenance of liver function. Patients with chronic liver diseases (CLDs) usually have lower concentrations of zinc, which decrease further as liver fibrosis progresses. Whether long-term zinc supplementation improves liver function and reduces the risk of hepatocellular carcinoma (HCC) development remains unknown. Two hundred and sixty-seven patients with CLDs who received a zinc preparation (Zn-group; 196 patients), or who did not receive zinc (no Zn-treatment group; 71 patients), were retrospectively analyzed in this study. The Zn-group was divided into 4 groups according to their serum Zn concentrations at 6 months after the start of Zn treatment. Liver function significantly deteriorated in the no Zn-treatment group, while no notable change was observed in the Zn-group. The cumulative incidence rates of events and HCC at 3 years were observed to be lower in the Zn-group (9.5%, 7.6%) than in the no Zn-treatment group (24.9%, 19.2%) (p < 0.001). According to serum Zn concentrations, the cumulative incidence rates of events and HCC were significantly decreased in patients with Zn concentrations ≥ 70 µg/dL (p < 0.001). Zinc supplementation appears to be effective at maintaining liver function and suppressing events and HCC development, especially among patients whose Zn concentration is greater than 70 µg/dL.
Assessing Food Liking: Comparison of Food Liking Questionnaires and Direct Food Tasting in Two Cultures
Authors: Wanich Uracha , Sayompark Dhoungsiri , Riddell Lynn , Cicerale Sara , Liem Djin Gie , Mohebbi Mohammadreza , Macfarlane Susie , Keast Russell
Published: December 2018

Food liking can be directly measured in specialised sensory testing facilities; however, this method is not feasible for large population samples. The aim of the study was to compare a Food Liking Questionnaire (FLQ) against lab-based sensory testing in two countries. The study was conducted with 70 Australian and Thai participants (35 Australian, 35 Thai, mean (SD) age 19 (3.01) years, 51% men). Participants completed a FLQ (consisting of 73 food items Australia, 89 Thai) and then, after tasting the food, rated their liking of a selection of 10 commercially available food items using a nine-point hedonic scale. Both tasks were completed on the same day and were repeated one week later. The reliability of and a comparison between methods was determined using Intra-Class Correlation Coefficients (ICC), and the difference was assessed using an independent sample t-test. The results indicate that the test-retest reliability of FLQ and the laboratory-based liking assessment range was moderate (0.40–0.59) to excellent (0.75–1.00). There were significant differences for the FLQ and the laboratory-based liking assessment between countries for three food items: soft drink, instant vegetable soup, and broccoli (p < 0.01). However, the data produced from the FLQ reflects the laboratory-based liking assessment. Therefore, it provides representative liking data in large population-based studies including cross-cultural studies.
The Dietary Intervention of Transgenic Low-Gliadin Wheat Bread in Patients with Non-Celiac Gluten Sensitivity (NCGS) Showed No Differences with Gluten Free Diet (GFD) but Provides Better Gut Microbiota Profile
Authors: Haro Carmen , Villatoro Myriam , Vaquero Luis , Pastor Jorge , Giménez María J. , Ozuna Carmen V. , Sánchez-León Susana , García-Molina María D. , Segura Verónica , Comino Isabel , Sousa Carolina , Vivas Santiago , Landa Blanca B. , Barro Francisco
Published: December 2018

The study evaluated the symptoms, acceptance, and digestibility of bread made from transgenic low-gliadin wheat, in comparison with gluten free bread, in Non-coeliac gluten sensitivity (NCGS) patients, considering clinical/sensory parameters and gut microbiota composition. This study was performed in two phases of seven days each, comprising a basal phase with gluten free bread and an E82 phase with low-gliadin bread. Gastrointestinal clinical symptoms were evaluated using the Gastrointestinal Symptom Rating Scale (GSRS) questionnaire, and stool samples were collected for gluten immunogenic peptides (GIP) determination and the extraction of gut microbial DNA. For the basal and E82 phases, seven and five patients, respectively, showed undetectable GIPs content. The bacterial 16S rRNA gene V1-V2 hypervariable regions were sequenced using the Illumina MiSeq platform and downstream analysis was done using a Quantitative Insights into Microbial Ecology (QIIME) pipeline. No significant differences in the GSRS questionnaires were observed between the two phases. However, we observed a significantly lower abundance of some gut genera Oscillospira, Dorea, Blautia, Bacteroides, Coprococcus, and Collinsella, and a significantly higher abundance of Roseburia and Faecalibacterium genera during the E82 phase compared with the basal phase. The consumption of low-gliadin bread E82 by NCGS subjects induced potentially positive changes in the gut microbiota composition, increasing the butyrate-producing bacteria and favoring a microbial profile that is suggested to have a key role in the maintenance or improvement of gut permeability.
Established and Emerging Concepts to Treat Imbalances of Iron Homeostasis in Inflammatory Diseases
Authors: Petzer Verena , Theurl Igor , Weiss Günter
Published: December 2018

Inflammation, being a hallmark of many chronic diseases, including cancer, inflammatory bowel disease, rheumatoid arthritis, and chronic kidney disease, negatively affects iron homeostasis, leading to iron retention in macrophages of the mononuclear phagocyte system. Functional iron deficiency is the consequence, leading to anemia of inflammation (AI). Iron deficiency, regardless of anemia, has a detrimental impact on quality of life so that treatment is warranted. Therapeutic strategies include (1) resolution of the underlying disease, (2) iron supplementation, and (3) iron redistribution strategies. Deeper insights into the pathophysiology of AI has led to the development of new therapeutics targeting inflammatory cytokines and the introduction of new iron formulations. Moreover, the discovery that the hormone, hepcidin, plays a key regulatory role in AI has stimulated the development of several therapeutic approaches targeting the function of this peptide. Hence, inflammation-driven hepcidin elevation causes iron retention in cells and tissues. Besides pathophysiological concepts and diagnostic approaches for AI, this review discusses current guidelines for iron replacement therapies with special emphasis on benefits, limitations, and unresolved questions concerning oral versus parenteral iron supplementation in chronic inflammatory diseases. Furthermore, the review explores how therapies aiming at curing the disease underlying AI can also affect anemia and discusses emerging hepcidin antagonizing drugs, which are currently under preclinical or clinical investigation.