bluuebunny/crossref_metadata_2025 huggingface dataset:
Measuring Thiols in Single Cultivar South African Red Wines Using 4,4-Dithiodipyridine (DTDP) Derivatization and Ultraperformance Convergence Chromatography-Tandem Mass Spectrometry
Authors: Mafata Mpho , Stander Maria A. , Thomachot Baptiste , Buica Astrid
Published: August 2018

Wine varietal thiols are important contributors to wine aroma. The chemical nature of thiols makes them difficult to measure due to low concentrations, high sensitivity to oxidation, and low ionization. Methods for the measurement of thiols usually consist of multiple steps of sample preparation followed by instrumental measurement. Studies have collected large datasets of thiols in white wine but not in red wine, due to the lack of availability of suitable methods. In this study, for the first time, convergence chromatography was used to measure thiols in red wine at ultratrace levels with improved sensitivity compared to previous methods. Performance parameters (selectivity, linearity, limits of detection, precision, accuracy) were tested to demonstrate the suitability of the method for the proposed application. Red wine thiols were measured in South African Pinotage, Shiraz, and Cabernet Sauvignon wines (n = 16 each). Cultivar differentiation using the thiol profile was demonstrated.
Functional Analyses of a Putative, Membrane-Bound, Peroxisomal Protein Import Mechanism from the Apicomplexan Protozoan Toxoplasma gondii
Authors: Mbekeani Alison J. , Stanley Will A. , Kalel Vishal C. , Dahan Noa , Zalckvar Einat , Sheiner Lilach , Schliebs Wolfgang , Erdmann Ralf , Pohl Ehmke , Denny Paul W.
Published: August 2018

Peroxisomes are central to eukaryotic metabolism, including the oxidation of fatty acids—which subsequently provide an important source of metabolic energy—and in the biosynthesis of cholesterol and plasmalogens. However, the presence and nature of peroxisomes in the parasitic apicomplexan protozoa remains controversial. A survey of the available genomes revealed that genes encoding peroxisome biogenesis factors, so-called peroxins (Pex), are only present in a subset of these parasites, the coccidia. The basic principle of peroxisomal protein import is evolutionarily conserved, proteins harbouring a peroxisomal-targeting signal 1 (PTS1) interact in the cytosol with the shuttling receptor Pex5 and are then imported into the peroxisome via the membrane-bound protein complex formed by Pex13 and Pex14. Surprisingly, whilst Pex5 is clearly identifiable, Pex13 and, perhaps, Pex14 are apparently absent from the coccidian genomes. To investigate the functionality of the PTS1 import mechanism in these parasites, expression of Pex5 from the model coccidian Toxoplasma gondii was shown to rescue the import defect of Pex5-deleted Saccharomyces cerevisiae. In support of these data, green fluorescent protein (GFP) bearing the enhanced (e)PTS1 known to efficiently localise to peroxisomes in yeast, localised to peroxisome-like bodies when expressed in Toxoplasma. Furthermore, the PTS1-binding domain of Pex5 and a PTS1 ligand from the putatively peroxisome-localised Toxoplasma sterol carrier protein (SCP2) were shown to interact in vitro. Taken together, these data demonstrate that the Pex5–PTS1 interaction is functional in the coccidia and indicate that a nonconventional peroxisomal import mechanism may operate in the absence of Pex13 and Pex14.
An Improved Data-Driven Approach for the Prediction of Rainfall-Triggered Soil Slides Using Downscaled Remotely Sensed Soil Moisture
Authors: Dahigamuwa Thilanki , Gunaratne Manjriker , Li Mingyang
Published: August 2018

The infiltration of rainwater into soil slopes leads to an increase of porewater pressure and destruction of matric suction, which causes a reduction in soil shear strength and slope instability. Hence, surface moisture and infiltration properties must be direct inputs in reliable landslide hazard assessment methods. Since the in situ measurement of pore pressure is expensive, the use of remotely sensed soil moisture is practically feasible. Downscaling improves the spatial resolution of soil moisture for a better representation of specific local conditions. Downscaled soil moisture, the relevant geotechnical properties of saturated hydraulic conductivity and soil type, and the conditioning factors of elevation, slope, and distance to roads are used to develop an improved logistic regression model to predict the soil slide hazard of soil slopes using data from two geographically different regions. A soil moisture downscaling model with a better accuracy than the downscaling models that have been used in previous landslide studies is employed in this study. This model provides a good classification accuracy and performs better than the alternative water drainage-based indices that are conventionally used to quantify the effect that elevated soil moisture has upon the soil slide hazard. Furthermore, the downscaling of soil moisture content is shown to improve the prediction accuracy. Finally, a technique that can provide the threshold probability for identifying locations with a high soil slide hazard is proposed.
An Exploration of Parent-Youth Agreement on Functional Impairment in Adolescents Utilizing Outpatient Mental Health Services
Authors: Yeh May , Zerr Argero , La Raymond , McCabe Kristen
Published: August 2018

Parent-youth agreement on the youth’s functional impairment may have important implications for mental health service utilization, assessment, therapy goal development, and treatment engagement for adolescents. The present study examines parent-youth agreement on their perceptions of youth functional impairment in a predominantly racial/ethnic minority sample of adolescents utilizing outpatient mental health services. Parent and youth functional impairment ratings were compared, and agreement was estimated in multiple ways. On average, parents indicated higher levels of youth functional impairment compared to youth in their overall scores, and when differences existed between parents and youth at the functioning domain and item level. Although there was similarity in the proportion of parents and youth who reported total impairment above the clinical cut-off, actual agreement between parent-youth pairs was only slight. There appeared to be substantial variation in agreement levels when identifying problems in functional impairment at the domain and item levels, and some areas of strong consensus were identified. These findings highlight the need to consider parent-youth agreement in perceptions of functional impairment and the complexities that may underlie this agreement.
Healthy Indoor Environments: The Need for a Holistic Approach
Authors: Wierzbicka Aneta , Pedersen Eja , Persson Roger , Nordquist Birgitta , Stålne Kristian , Gao Chuansi , Harderup Lars-Erik , Borell Jonas , Caltenco Héctor , Ness Barry , Stroh Emilie , Li Yujing , Dahlblom Mats , Lundgren-Kownacki Karin , Isaxon Christina , Gudmundsson Anders , Wargocki Pawel
Published: August 2018

Indoor environments have a large impact on health and well-being, so it is important to understand what makes them healthy and sustainable. There is substantial knowledge on individual factors and their effects, though understanding how factors interact and what role occupants play in these interactions (both causative and receptive) is lacking. We aimed to: (i) explore interactions between factors and potential risks if these are not considered from holistic perspective; and (ii) identify components needed to advance research on indoor environments. The paper is based on collaboration between researchers from disciplines covering technical, behavioural, and medical perspectives. Outcomes were identified through literature reviews, discussions and workshops with invited experts and representatives from various stakeholder groups. Four themes emerged and were discussed with an emphasis on occupant health: (a) the bio-psycho-social aspects of health; (b) interaction between occupants, buildings and indoor environment; (c) climate change and its impact on indoor environment quality, thermal comfort and health; and (d) energy efficiency measures and indoor environment. To advance the relevant research, the indoor environment must be considered a dynamic and complex system with multiple interactions. This calls for a transdisciplinary and holistic approach and effective collaboration with various stakeholders.
Mitigation Policy Acceptance Model: An Analysis of Individual Decision Making Process toward Residential Seismic Strengthening
Authors: Cheng Hao-Teng , Tsou Ko-Wan
Published: August 2018

Mitigation policy is regarded as an effective strategy to achieve the purpose of building health resilience and reducing disaster risk with the current high frequency of environmental event occurrences. To enhance public acceptance of mitigation policy, the issue of decision-making behavior has been a concern of researchers and planners. In the past literature, qualitative measures employed to reveal the behavioral intention of hazard risk mitigation cause restricted outcomes due to the problem of sample representativeness and the fact that quantitative research is restricted to discuss the linear relationship between the two selected variables. The purpose of this article is to attempt to construct a Mitigation Policy Acceptance Model (MPAM) to analyze the behavioral intention of seismic risk mitigation strategies. Based on Dual Processing Theory, affective is conducted as the core variable for constructing two types of thinking processes, and the variables of risk perception, trust and responsibility are selected in MPAM from theories and past research. In this study, the mitigation policy of residential seismic strengthening, adapted in Yongkang District of Tainan, has been conducted as the case study. According to the results, the result of model fit test has confirmed the MPAM framework, and two thinking modes could be associated together when people face a risky decision-making process. The variable of affective is the most effective factor to influence each variable, and a direct effect on intention is also shown in this model. The results could provide suggestions in communication risk strategies for the government.
Spatial-Temporal Analysis of Human Dynamics on Urban Land Use Patterns Using Social Media Data by Gender
Authors: Lei Chengcheng , Zhang An , Qi Qingwen , Su Huimin , Wang Jianghao
Published: August 2018

The relationship between urban human dynamics and land use types has always been an important issue in the study of urban problems in China. This paper used location data from Sina Location Microblog (commonly known as Weibo) users to study the human dynamics of the spatial-temporal characteristics of gender differences in Beijing’s Olympic Village in June 2014. We applied mathematical statistics and Local Moran’s I to analyze the spatial-temporal distribution of Sina Microblog users in 100 m × 100 m grids and land use patterns. The female users outnumbered male users, and the sex ratio ( S R varied under different land use types at different times. Female users outnumbered male users regarding residential land and public green land, but male users outnumbered female users regarding workplace, especially on weekends, as the S R on weekends ( S R was 120.5) was greater than that on weekdays ( S R was 118.8). After a Local Moran’s I analysis, we found that High–High grids are primarily distributed across education and scientific research land and residential land; these grids and their surrounding grids have more female users than male users. Low–Low grids are mainly distributed across sports centers and workplaces on weekdays; these grids and their surrounding grids have fewer female users than male users. The average number of users on Saturday was the highest value and, on weekends, the number of female and male users both increased in commercial land, but male users were more active than female users ( S R was 110).
Comparative Metabolic Phenotyping of Tomato (Solanum lycopersicum) for the Identification of Metabolic Signatures in Cultivars Differing in Resistance to Ralstonia solanacearum
Authors: Zeiss Dylan R. , Mhlongo Msizi I. , Tugizimana Fidele , Steenkamp Paul A. , Dubery Ian A.
Published: August 2018

Tomato (Solanum lycopersicum) is an important dietary source which contains numerous bioactive phytochemicals. Active breeding programs constantly produce new cultivars possessing superior and desirable traits. However, the underlying molecular signatures that functionally describe these traits are yet to be elucidated. Thus, in this study we used an untargeted metabolomic approach to describe differential metabolic profiles of four cultivars described as having high to intermediate resistance to Ralstonia solanacearum. Metabolites were methanol-extracted from leaves, stems and root tissues and analyzed by liquid chromatography coupled with high definition mass spectrometry. Multivariate data analysis revealed cultivar-related differential metabolic phenotypes. A total of 41 metabolites were statistically selected and annotated, consisting of amino acids, organic acids, lipids, derivatives of cinnamic acid and benzoic acids, flavonoids and steroidal glycoalkaloids which were especially prominent in the two highly resistant cultivars. Interestingly, the less resistant cultivars had various fatty acid derivatives in root extracts that contributed to the differentiated metabolic signatures. Moreover, the metabolic phenotype of the STAR9008 (8SC) cultivar with intermediate resistance, was characterized by derivatives of cinnamic acids and flavonoids but at lower levels compared to the resistant cultivars. The 8SC cultivar also exhibited a lack of hydroxybenzoic acid biomarkers, which may be attributed to its lower resistance. These metabolic phenotypes provide insights into the differential metabolic signatures underlying the metabolism of these four cultivars, defining their respective phenotypic traits such as their resistance, tolerance or susceptibility to Ralstonia solanacearum.
The HSP90 Family: Structure, Regulation, Function, and Implications in Health and Disease
Authors: Hoter Abdullah , El-Sabban Marwan E. , Naim Hassan Y.
Published: August 2018

The mammalian HSP90 family of proteins is a cluster of highly conserved molecules that are involved in myriad cellular processes. Their distribution in various cellular compartments underlines their essential roles in cellular homeostasis. HSP90 and its co-chaperones orchestrate crucial physiological processes such as cell survival, cell cycle control, hormone signaling, and apoptosis. Conversely, HSP90, and its secreted forms, contribute to the development and progress of serious pathologies, including cancer and neurodegenerative diseases. Therefore, targeting HSP90 is an attractive strategy for the treatment of neoplasms and other diseases. This manuscript will review the general structure, regulation and function of HSP90 family and their potential role in pathophysiology.
Effects of Antioxidants in Reducing Accumulation of Fat in Hepatocyte
Authors: Yang Jung-Pyo , Shin Ji-Hun , Seo Seung-Hwan , Kim Sang-Gyun , Lee Sang Hyung , Shin Eun-Hee
Published: August 2018

The progress of the hepatic steatosis (HS), a clinicopathological status, is influenced by cellular oxidative stress, lipogenesis, fatty acid (FA) oxidation, and inflammatory responses. Because antioxidants are gaining attention as potent preventive agents for HS, we aimed to investigate anti-lipogenic effects of the antioxidants vitamin C (VC), N-acetylcysteine (NAC), and astaxanthin (ATX) using hepatocytes. For this, we established an in vitro model using 1 mM oleic acid (OA) and human liver hepatocellular carcinoma (HepG2) cells; 10 μM antioxidants were evaluated for their ability to reduce fat accumulation in hepatocytes. Our results showed that all three antioxidants were effective to reduce fat accumulation for the molecular targets such as reduction in lipid droplets, triglyceride (TG) concentration, reactive oxygen species (ROS) production, and cell apoptosis, as well as in gene expressions of endoplasmic reticulum (ER) stress-related effectors, lipogenesis, and inflammatory cytokines. There were simultaneous increases in diphenyl-1-picrylhydrazyl (DPPH) radical scavenging effect, cell survival, AMPK phosphorylation, NRF2-related gene expression for cellular defense, and FA β-oxidation. However, among these, ATX more effectively inhibited ER stress and lipogenesis at the intracellular level than VC or NAC. Consequently, ATX was also more effective in inhibiting cell death, lipotoxicity, and inflammation. Our result emphasizes that ATX achieved greater lipotoxicity reduction than VC and NAC.
Fenofibrate Reduces the Asthma-Related Fibroblast-To-Myofibroblast Transition by TGF-Β/Smad2/3 Signaling Attenuation and Connexin 43-Dependent Phenotype Destabilization
Authors: Paw Milena , Wnuk Dawid , Kądziołka Dominika , Sęk Aleksandra , Lasota Sławomir , Czyż Jarosław , Madeja Zbigniew , Michalik Marta
Published: August 2018

The activation of human bronchial fibroblasts by transforming growth factor-β1 (TGF-β1) leads to the formation of highly contractile myofibroblasts in the process of the fibroblast–myofibroblast transition (FMT). This process is crucial for subepithelial fibrosis and bronchial wall remodeling in asthma. However, this process evades current therapeutic asthma treatment strategies. Since our previous studies showed the attenuation of the TGF-β1-induced FMT in response to lipid-lowering agents (e.g., statins), we were interested to see whether a corresponding effect could be obtained upon administration of hypolipidemic agents. In this study, we investigated the effect of fenofibrate on FMT efficiency in populations of bronchial fibroblasts derived from asthmatic patients. Fenofibrate exerted a dose-dependent inhibitory effect on the FMT, even though it did not efficiently affect the expression of α-smooth muscle actin (α-SMA; marker of myofibroblasts); however, it considerably reduced its incorporation into stress fibers through connexin 43 regulation. This effect was accompanied by disturbances in the actin cytoskeleton architecture, impairments in the maturation of focal adhesions, and the fenofibrate-induced deactivation of TGF-β1/Smad2/3 signaling. These data suggest that fenofibrate interferes with myofibroblastic differentiation during asthma-related subepithelial fibrosis. The data indicate the potential application of fenofibrate in the therapy and prevention of bronchial remodeling during the asthmatic process.
Proteomic Analysis of the Function of a Novel Cold-Regulated Multispanning Transmembrane Protein COR413-PM1 in Arabidopsis
Authors: Su Chen , Chen Kai , Ding Qingqian , Mou Yongying , Yang Rui , Zhao Mengjie , Ma Bo , Xu Zhaoshi , Ma Youzhi , Pan Yinghong , Chen Ming , Xi Yajun
Published: August 2018

The plasma membrane is the first subcellular organ that senses low temperature, and it includes some spanning transmembrane proteins that play important roles in cold regulation. COR413-PM1 is a novel multispanning transmembrane cold-regulated protein; however, the related functions are not clear in Arabidopsis. We found the tolerance to freezing stress of cor413-pm1 was lower than wild-type (WT). A proteomics method was used to analyze the differentially abundant proteins (DAPs) between cor413-pm1 and WT. A total of 4143 protein groups were identified and 3139 were accurately quantitated. The DAPs associated with COR413-PM1 and freezing treatment were mainly involved in the metabolism of fatty acids, sugars, and purine. Quantitative real-time PCR (qRT-PCR) confirmed the proteomic analysis results of four proteins: fatty acid biosynthesis 1 (FAB1) is involved in fatty acid metabolism and might affect the plasma membrane structure; fructokinase 3 (FRK3) and sucrose phosphate synthase A1 (SPSA1) play roles in sugar metabolism and may influence the ability of osmotic adjustment under freezing stress; and GLN phosphoribosyl pyrophosphate amidotransferase 2 (ASE2) affects freezing tolerance through purine metabolism pathways. In short, our results demonstrate that the multispanning transmembrane protein COR413-PM1 regulates plant tolerance to freezing stress by affecting the metabolism of fatty acids, sugars, and purine in Arabidopsis.
Gut Bacterial Communities of Dendroctonus valens and D. mexicanus (Curculionidae: Scolytinae): A Metagenomic Analysis across Different Geographical Locations in Mexico
Authors: Hernández-García Juan Alfredo , Gonzalez-Escobedo Roman , Briones-Roblero Carlos Iván , Cano-Ramírez Claudia , Rivera-Orduña Flor N. , Zúñiga Gerardo
Published: August 2018

Dendroctonus bark beetles are a worldwide significant pest of conifers. This genus comprises 20 species found in North and Central America, and Eurasia. Several studies have documented the microbiota associated with these bark beetles, but little is known regarding how the gut bacterial communities change across host range distribution. We use pyrosequencing to characterize the gut bacterial communities associated with six populations of Dendroctonus valens and D. mexicanus each across Mexico, determine the core bacteriome of both insects and infer the metabolic pathways of these communities with Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) to evaluate whether these routes are conserved across geographical locations. Our results show that the β-diversity with UniFrac unweighted varies among locations of both bark beetles mainly due to absence/presence of some rare taxa. No association is found between the pairwise phylogenetic distance of bacterial communities and geographic distance. A strict intraspecific core bacteriome is determined for each bark beetle species, but these cores are different in composition and abundance. However, both bark beetles share the interspecific core bacteriome recorded previously for the Dendroctonus genus consisting of Enterobacter, Pantoea, Providencia, Pseudomonas, Rahnella, and Serratia. The predictions of metabolic pathways are the same in the different localities, suggesting that they are conserved through the geographical locations.
Skeleton to Abstraction: An Attentive Information Extraction Schema for Enhancing the Saliency of Text Summarization
Authors: Xiang Xiujuan , Xu Guangluan , Fu Xingyu , Wei Yang , Jin Li , Wang Lei
Published: August 2018

Current popular abstractive summarization is based on an attentional encoder-decoder framework. Based on the architecture, the decoder generates a summary according to the full text that often results in the decoder being interfered by some irrelevant information, thereby causing the generated summaries to suffer from low saliency. Besides, we have observed the process of people writing summaries and find that they write a summary based on the necessary information rather than the full text. Thus, in order to enhance the saliency of the abstractive summarization, we propose an attentive information extraction model. It consists of a multi-layer perceptron (MLP) gated unit that pays more attention to the important information of the source text and a similarity module to encourage high similarity between the reference summary and the important information. Before the summary decoder, the MLP and the similarity module work together to extract the important information for the decoder, thus obtaining the skeleton of the source text. This effectively reduces the interference of irrelevant information to the decoder, therefore improving the saliency of the summary. Our proposed model was tested on CNN/Daily Mail and DUC-2004 datasets, and achieved a 42.01 ROUGE-1 f-score and 33.94 ROUGE-1, recall respectively. The result outperforms the state-of-the-art abstractive model on the same dataset. In addition, by subjective human evaluation, the saliency of the generated summaries was further enhanced.
Genetic Algorithm for Inspection and Maintenance Planning of Deteriorating Structural Systems: Application to Pressure Vessels
Authors: Haladuick Shane , Dann Markus R.
Published: August 2018

For engineering systems, decision analysis can be used to determine the optimal decision from a set of options via utility maximization. Applied to inspection and maintenance planning, decision analysis can determine the best inspection and maintenance plan to follow. Decision analysis is relatively straightforward for simple systems. However, for more complex systems with many components or defects, the set of all possible inspection and maintenance plans can be very large. This paper presents the use of a genetic algorithm to perform inspection and maintenance plan optimization for complex systems. The performance of the genetic algorithm is compared to optimization by exhaustive search. A numerical example of life cycle maintenance planning for a corroding pressure vessel is used to illustrate the method. Genetic algorithms are found to be an effective approach to reduce the computational demand of solving complex inspection and maintenance optimizations.
The Importance of Solvent Effects on the Mechanism of the Pfeiffer Effect
Authors: Lunkley Jamie L. , Nguyen Ngoc M. , Tuminaro Kristina M. , Margittai Dana , Muller Gilles
Published: August 2018

The Pfeiffer effect is observed when an optically active compound such as an amino acid is introduced to a solution containing a labile racemic metal complex, and an equilibrium shift is obtained. The “perturbation” results in an excess of one enantiomer over the other. The shift is a result of a preferential outer sphere interaction between the introduced chiral species and one enantiomeric form (Λ or ∆) of a labile metal complex. Speculations regarding the mechanism of the Pfeiffer effect have attributed observations to a singular factor such as pH, solvent polarity, or numerous other intermolecular interactions. Through the use of the lanthanide(III) complexes [Tb(DPA)3]3− and [Eu(DPA)3]3− (where DPA = 2,6-pyridinedicarboxylate) and the amino acids l-serine and l-proline; it is becoming clear that the mechanism is not so simply described as per the preliminary findings that are discussed in this study. It appears that the true mechanism is far more complicated than the attribute just a singular factor. This work attempts to shine light on the fact that understanding the behavior of the solvent environment may hypothetically be the key to offering a more detailed description of the mechanism.
Risk of Incident Non-Valvular Atrial Fibrillation after Dialysis-Requiring Acute Kidney Injury
Authors: Shiao Chih-Chung , Kan Wei-Chih , Wang Jian-Jhong , Lin Yu-Feng , Chen Likwang , Chueh Eric , Huang Ya-Ting , Chiang Wen-Po , Tseng Li-Jung , Wang Chih-Hsien , Wu Vin-Cent
Published: August 2018

The influence of acute kidney injury (AKI) on subsequent incident atrial fibrillation (AF) has not yet been fully addressed. This retrospective nationwide cohort study was conducted using Taiwan’s National Health Insurance Research Database from 1 January 2000 to 31 December 2010. A total of 41,463 patients without a previous AF, mitral valve disease, and hyperthyroidism who developed de novo dialysis-requiring AKI (AKI-D) during their index hospitalization were enrolled. After propensity score matching, “non-recovery group” (n = 2895), “AKI-recovery group” (n = 2895) and “non-AKI group” (control group, n = 5790) were categorized. Within a follow-up period of 6.52 ± 3.88 years (median, 6.87 years), we found that the adjusted risks for subsequent incident AF were increased in both AKI-recovery group (adjusted hazard ratio (aHR) = 1.30; 95% confidence intervals (CI), 1.07–1.58; p ≤ 0.01) and non-recovery group (aHR = 1.62; 95% CI, 1.36–1.94) compared to the non-AKI group. Furthermore, the development of AF carried elevated risks for major adverse cardiac events (aHR = 2.11; 95% CI, 1.83–2.43), ischemic stroke (aHR = 1.33; 95% CI, 1.19–1.49), and all stroke (aHR = 1.28; 95% CI, 1.15–1.43). (all p ≤ 0.001, except otherwise expressed) The authors concluded that AKI-D, even in those who withdrew from temporary dialysis, independently increases the subsequent risk of de novo AF.
Itraconazole, Voriconazole, and Posaconazole CLSI MIC Distributions for Wild-Type and Azole-Resistant Aspergillus fumigatus Isolates
Authors: Buil Jochem B. , Hagen Ferry , Chowdhary Anuradha , Verweij Paul E. , Meis Jacques F.
Published: August 2018

Azole resistance in Aspergillus fumigatus is most frequently conferred by mutations in the cyp51A gene encoding 14α-sterol demethylases. TR34/L98H and TR46/Y121F/T289A are the two most common mutations associated with environmental resistance selection. We studied the minimal inhibitory concentration (MIC) distribution of clinical A. fumigatus isolates to characterize the Clinical and Laboratory Standards Institute (CLSI) susceptibility profiles of isolates with the wild-type (WT) cyp51A genotype, and isolates with the TR34/L98H and TR46/Y121F/T289A cyp51A mutations. Susceptibility testing was performed according to CLSI M38-A2. The MICs of 363 A. fumigatus isolates were used in this study. Based on the CLSI epidemiological cut-off values (ECVs), 141 isolates were phenotypically non-WT and 222 isolates had a phenotypically WT susceptibility. All isolates with the TR34/L98H mutation had an itraconazole MIC > 1 mg/L which is above the CLSI ECV. Eighty-six of 89 (97%) isolates with the TR34/L98H mutation had voriconazole and posaconazole MICs above the CLSI ECV, i.e., MICs of 1 and 0.25 mg/L, respectively. The isolates with a TR46/Y121F/T289A mutation showed a different phenotype. All 37 isolates with a TR46/Y121F/T289A mutation had a voriconazole MIC above the CLSI ECV, while 28/37 (76%) isolates had an itraconazole MIC > 1 mg/L. Interestingly, only 13 of 37 (35%) isolates had a posaconazole MIC > 0.25 mg/L.
Enhanced Cycling Stability through Erbium Doping of LiMn2O4 Cathode Material Synthesized by Sol-Gel Technique
Authors: Zhao Hongyuan , Bai Xiuzhi , Wang Jing , Li Dongdong , Li Bo , Wang Yashuang , Dong Li , Liu Binbin , Komarneni Sridhar
Published: August 2018

In this work, LiMn2−xErxO4 (x ≤ 0.05) samples were obtained by sol-gel processing with erbium nitrate as the erbium source. XRD measurements showed that the Er-doping had no substantial impact on the crystalline structure of the sample. The optimal LiMn1.97Er0.03O4 sample exhibited an intrinsic spinel structure and a narrow particle size distribution. The introduction of Er3+ ions reduced the content of Mn3+ ions, which seemed to efficiently suppress the Jahn–Teller distortion. Moreover, the decreased lattice parameters suggested that a more stable spinel structure was obtained, because the Er3+ ions in a ErO6 octahedra have stronger bonding energy (615 kJ/mol) than that of the Mn3+ ions in a MnO6 octahedra (402 kJ/mol). The present results suggest that the excellent cycling life of the optimal LiMn1.97Er0.03O4 sample is because of the inhibition of the Jahn-Teller distortion and the improvement of the structural stability. When cycled at 0.5 C, the optimal LiMn1.97Er0.03O4 sample exhibited a high initial capacity of 130.2 mAh g−1 with an excellent retention of 95.2% after 100 cycles. More significantly, this sample showed 83.1 mAh g−1 at 10 C, while the undoped sample showed a much lower capacity. Additionally, when cycled at 55 °C, a satisfactory retention of 91.4% could be achieved at 0.5 C after 100 cycles with a first reversible capacity of 130.1 mAh g−1.
Future Directions of Marine Myxobacterial Natural Product Discovery Inferred from Metagenomics
Authors: Garcia Ronald , La Clair James J. , Müller Rolf
Published: August 2018

Over the last two decades, halophilic (organisms that thrive at high salt concentrations) and halotolerant (organisms that have adapted to high salt concentrations) myxobacteria emerged as an important source of structurally diverse secondary metabolites from the marine environment. This review explores the advance of metagenomics analysis and 16S rRNA gene phylogeny of the cultured and uncultured myxobacteria from marine and other salt-environments up to July 2018. The diversity of novel groups of myxobacteria in these environments appears unprecedented, especially in the Sorangiineae and Nannocystineae suborders. The Sandaracinaceae related clade in the Sorangiineae suborder seems more widely distributed compared to the exclusively marine myxobacterial cluster. Some of the previously identified clones from metagenomic studies were found to be related to the Nannocystineae suborder. This understanding provides the foundation for a vital, unexplored resource. Understanding the conditions required to cultivate these yet “uncultured” myxobacteria in the laboratory, while a key next step, offers a significant potential to further expand access to diverse secondary metabolites.
Schizophrenia and Sleep Disorders: An Introduction
Authors: Van den Noort Maurits , Bosch Peggy
Published: August 2018

This editorial is an introduction to the special issue ‘Schizophrenia and Sleep Disorders’.[…]
Hematological, Biochemical, Histopathological and 1H-NMR Metabolomics Application in Acute Toxicity Evaluation of Clinacanthus nutans Water Leaf Extract
Authors: Khoo Leng Wei , Foong Kow Audrey Siew , Maulidiani M. , Lee Ming Tatt , Tan Chin Ping , Shaari Khozirah , Tham Chau Ling , Abas Faridah
Published: August 2018

The present study aims for the first time to provide the in vivo acute toxicological profile of the highest dose of Clinacanthus nutans (Burm. f.) Lindau water leaf extract according to the Organization for economic co-operation and development (OECD) 423 guidelines through conventional toxicity and advanced proton nuclear magnetic resonance (1H-NMR) serum and urinary metabolomics evaluation methods. A single dose of 5000 mg/kg bw of C. nutans water extract was administered to Sprague Dawley rats, and they were observed for 14 days. Conventional toxicity evaluation methods (physical observation, body and organ weight, food and water consumption, hematology, biochemical testing and histopathological analysis) suggested no abnormal toxicity signs. Serum 1H-NMR metabolome revealed no significant metabolic difference between untreated and treated groups. Urinary 1H-NMR analysis, on the other hand, revealed alteration in carbohydrate metabolism, energy metabolism and amino acid metabolism in extract-treated rats after 2 h of extract administration, but the metabolic expression collected after 24 h and at Day 5, Day 10 and Day 15 indicated that the extract-treated rats did not accumulate any toxicity biomarkers. Importantly, the outcomes further suggest that single oral administration of up to 5000 mg/kg bw of C. nutans water leaf extract is safe for consumption.
Determination of 4-Hexylresorcinol in Shrimp Samples by Solid Phase Extraction Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry
Authors: Hao Yunbin , Gao Xuehui , Xia Wenshui
Published: August 2018

A method for the rapid determination of 4-hexylresorcinol (4-HR) residue in shrimp by solid phase extraction (SPE) ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. 4-HR was extracted twice with methanol, and the extract was formulated into methanol-water solution (1:1). After being cleaned up and concentrated by a PRIME HLB solid phase extraction column, the sample was analyzed by UPLC-MS/MS and quantitatively determined by an external standard method. The separation was performed with a gradient system consisting of water and acetonitrile as the mobile phase. Monitoring was performed by electrospray ionization (ESI) in negative ion mode using multiple ion reaction monitoring (MRM). Good linearity was obtained in the concentration range of 1.0–100.0 μg/L, with correlation coefficients larger than 0.999. The limit of detection (LOD) was 0.25 μg/kg and the limit of quantification (LOQ) was 0.80 μg/kg. The average recoveries of 4-HR at spiked concentrations of 2.40, 6.40 and 16 μg/kg ranged from 81.35% to 94.68% with the relative standard deviations (n = 6) from 3.57% to 6.86%. The results showed that the method is simple, fast, sensitive, reliable, and reproducible; thus, it could be used as a rapid confirmation and quantitative analysis method of 4-HR residue in aquatic products.
Comparative Bioavailability of Two Diosmin Formulations after Oral Administration to Healthy Volunteers
Authors: Russo Rosario , Chandradhara Divya , De Tommasi Nunziatina
Published: August 2018

Diosmin is a flavonoid commonly found in citrus fruits, largely used as adjuvant treatment for circulatory disorders, including chronic venous insufficiency (CVI) and hemorrhoids. Following oral administration, diosmin is not directly absorbed but must first be hydrolyzed into its aglycone, diosmetin, which is then absorbed into the systemic circulation. The aim of the current cross-over clinical study was to assess the pharmacokinetic profile of µSmin® Plus, a micronized diosmin flavonoid complex standardized in diosmin and formulated with a buffering agent (tested formulation). The study compared this to unformulated micronized diosmin (reference), in 16 healthy volunteers. Plasma samples were analyzed by HPLC-MS and plasma diosmetin concentration was measured after deconjugation with β-glucuronidase. For the tested formulation area under the curve (AUC0-t), and maximum plasma and time concentration (Cmax; tmax) were found to be 298.4 ± 163.7, 50.3 ± 22.6 and 2.2 ± 2.9, respectively. AUC0-t and Cmax of the reference were 31.9 ± 100.4 and 2.4 ± 1.9, respectively. The tested formulation showed higher plasmatic concentrations of diosmetin in comparison to those obtained after the administration of unformulated micronized diosmin. The relative bioavailability was 9.4 greater for the tested formulation than in micronized diosmin. In conclusion, our data indicate that µSmin® Plus was rapidly and well absorbed into systemic circulation and may therefore be ideally suitable to deliver diosmin in human interventional trials.
pH Effect and Chemical Mechanisms of Antioxidant Higenamine
Authors: Xie Yulu , Li Xican , Chen Jingyu , Deng Yuman , Lu Wenbiao , Chen Dongfeng
Published: August 2018

In this article, we determine the pH effect and chemical mechanism of antioxidant higenamine by using four spectrophotometric assays: (1) 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide radical (PTIO•)-scavenging assay (at pH 4.5, 6.0, and 7.4); (2) Fe3+-reducing power assay; (3) Cu2+-reducing power assay; and (4) 1,1-diphenyl-2-picryl-hydrazyl (DPPH•)-scavenging assay. The DPPH•-scavenging reaction product is further analyzed by ultra-performance liquid chromatography, coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry (UPLC-ESI-Q-TOF-MS/MS) technology. In the four spectrophotometric assays, higenamine showed good dose-response curves; however, its IC50 values were always lower than those of Trolox. In UPLC-ESI-Q-TOF-MS/MS analysis, the higenamine reaction product with DPPH• displayed three chromatographic peaks (retention time = 0.969, 1.078, and 1.319 min). The first gave m/z 541.2324 and 542.2372 MS peaks; while the last two generated two similar MS peaks (m/z 663.1580 and 664.1885), and two MS/MS peaks (m/z 195.9997 and 225.9971). In the PTIO•-scavenging assays, higenamine greatly decreased its IC50 values with increasing pH. In conclusion, higenamine is a powerful antioxidant—it yields at least two types of final products (i.e., higenamine-radical adduct and higenamine-higenamine dimer). In aqueous media, higenamine may exert its antioxidant action via electron-transfer and proton-transfer pathways. However, its antioxidant action is markedly affected by pH. This is possibly because lower pH value weakens its proton-transfer pathway via ionization suppression by solution H+, and its electron-transfer pathway by withdrawing the inductive effect (-I) from protonated N-atom. These findings will aid the correct use of alkaloid antioxidants.
Plant Growth Modulates Metabolites and Biological Activities in Retama raetam (Forssk.) Webb
Authors: Saada Mariem , Falleh Hanen , Catarino Marcelo D. , Cardoso Susana M. , Ksouri Riadh
Published: August 2018

This work focuses on the variability of Retama raetam (Forssk.) Webb bioactive compounds as a function of the plant cycle. The main results showed that it exhibited the highest percentage of polyunsaturated fatty acids, along with superior levels of vitamin C and total phenolic compounds (66.49%, 645.6 mg·100 g−1 FW and 23.9 mg GAE·g−1, respectively) at the vegetative stage. Instead, at the flowering and mature fruiting stages, R. raetam (Forssk.) Webb exhibited notable contents of proline (25.4 μmol·g−1 DW) and carotenoids (27.2 μg·g−1 FW), respectively. The gathered data concerning the antioxidant activity highlighted the effectiveness of the vegetative stage in comparison to the other periods. Actually, IC50 and EC50 values of the hydromethanolic extract obtained from the plant shoots at the vegetative stage were of 23, 380, 410, 1160 and 960 μg·mL−1 (DPPH• and ABTS•+ radicals scavenging activity, reducing power, chelating power and β-carotene bleaching activity, respectively). Furthermore, the four studied stages showed appreciable antibacterial capacities against human pathogens with a higher efficiency of the vegetative stage extract. Finally, the LC-DAD-ESI/MSn analysis revealed the predominance of isoflavonoids as main class of phenolic compounds and demonstrates that individual phenolic biosynthesis was clearly different as a function of plant growth. These findings highlight that reaching the optimum efficiency of R. raetam (Forssk.) Webb is closely linked to the physiological stage.
Astragaloside IV Promotes Adult Neurogenesis in Hippocampal Dentate Gyrus of Mouse through CXCL1/CXCR2 Signaling
Authors: Huang Fei , Lan Yunyi , Qin Liyue , Dong Huaihuai , Shi Hailian , Wu Hui , Zou Qinrui , Hu Zhibi , Wu Xiaojun
Published: August 2018

Astragaloside IV (ASI) has been reported to promote neural stem cells proliferation in vitro and CXCR2 expression on neutrophils. The present study was aimed to investigate the influence of ASI on adult neurogenesis in hippocampal dentate gyrus (DGs) of mouse and to discuss the possible underlying mechanisms. Total number of proliferative cells (BrdU+), pre-mature neurons (DCX+), early proliferative cells (BrdU+/DCX+), proliferative radial gila-like cells (BrdU+/GFAP+) and newly generated neurons (BrdU+/NeuN+) after ASI or vehicle administration for two weeks were counted, respectively. The results showed that BrdU+ cells and DCX+ cells were significantly increased in DGs of mice administered with ASI. The numbers of BrdU+/DCX+, BrdU+/GFAP+ cells and BrdU+/NeuN+ cells were also elevated in the ASI group. Correspondingly, ASI increased the protein expression of hippocampal DCX, GFAP and NeuN. Further study disclosed that ASI remarkably up-regulated the mRNA and protein expressions of CXCL1 as well as that of CXCR2 in the hippocampus. The promotive effect of ASI on DCX, GFAP and NeuN protein expression was abolished by SB225002, the inhibitor of CXCR2. Our results indicated that ASI modulated the homeostasis of the CXCL1/CXCR2 signaling pathway, which might be responsible for the increased neurogenesis within the hippocampal DGs of mice.
Anti-Bacterial Adhesion Activity of Tropical Microalgae Extracts
Authors: Zea-Obando Claudia , Tunin-Ley Alina , Turquet Jean , Culioli Gérald , Briand Jean-François , Bazire Alexis , Réhel Karine , Faÿ Fabienne , Linossier Isabelle
Published: August 2018

The evolution of regulations concerning biocidal products aimed towards an increased protection of the environment (e.g., EU Regulation No 528/2012) requires the development of new non-toxic anti-fouling (AF) systems. As the marine environment is an important source of inspiration, such AF systems inhibiting the adhesion of organisms without any toxicity could be based on molecules of natural origin. In this context, the antibiofilm potential of tropical microalgal extracts was investigated. The tropics are particularly interesting in terms of solar energy and temperatures which provide a wide marine diversity and a high production of microalgae. Twenty microalgal strains isolated from the Indian Ocean were studied. Their extracts were characterized in terms of global chemical composition by high resolution magic angle spinning (HR-MAS) and nuclear magnetic resonance (NMR) spectroscopy, toxicity against marine bacteria (viability and growth) and anti-adhesion effect. The different observations made by confocal laser scanning microscopy (CLSM) showed a significant activity of three extracts from Dinoflagellate strains against the settlement of selected marine bacteria without any toxicity at a concentration of 50 μg/mL. The Symbiodinium sp. (P-78) extract inhibited the adhesion of Bacillus sp. 4J6 (Atlantic Ocean), Shewanella sp. MVV1 (Indian Ocean) and Pseudoalteromonas lipolytica TC8 (Mediterranean Ocean) at 60, 76 and 52%, respectively. These results underlined the potential of using microalgal extracts to repel fouling organisms.
Natural Scaffolds with Multi-Target Activity for the Potential Treatment of Alzheimer’s Disease
Authors: Piemontese Luca , Vitucci Gabriele , Catto Marco , Laghezza Antonio , Perna Filippo Maria , Rullo Mariagrazia , Loiodice Fulvio , Capriati Vito , Solfrizzo Michele
Published: August 2018

A few symptomatic drugs are currently available for Alzheimer’s Disease (AD) therapy, but these molecules are only able to temporary improve the cognitive capacity of the patients if administered in the first stages of the pathology. Recently, important advances have been achieved about the knowledge of this complex condition, which is now considered a multi-factorial disease. Researchers are, thus, more oriented toward the preparation of molecules being able to contemporaneously act on different pathological features. To date, the inhibition of acetylcholinesterase (AChE) and of β-amyloid (Aβ) aggregation as well as the antioxidant activity and the removal and/or redistribution of metal ions at the level of the nervous system are the most common investigated targets for the treatment of AD. Since many natural compounds show multiple biological properties, a series of secondary metabolites of plants or fungi with suitable structural characteristics have been selected and assayed in order to evaluate their potential role in the preparation of multi-target agents. Out of six compounds evaluated, 1 showed the best activity as an antioxidant (EC50 = 2.6 ± 0.2 μmol/µmol of DPPH) while compound 2 proved to be effective in the inhibition of AChE (IC50 = 6.86 ± 0.67 μM) and Aβ1–40 aggregation (IC50 = 74 ± 1 μM). Furthermore, compound 6 inhibited BChE (IC50 = 1.75 ± 0.59 μM) with a good selectivity toward AChE (IC50 = 86.0 ± 15.0 μM). Moreover, preliminary tests on metal chelation suggested a possible interaction between compounds 1, 3 and 4 and copper (II). Molecules with the best multi-target profiles will be used as starting hit compounds to appropriately address future studies of Structure-Activity Relationships (SARs).