bluuebunny/crossref_metadata_2025 huggingface dataset:
Anti‐Inflammatory Effect of Novel 7‐Substituted Coumarin Derivatives through Inhibition of NF‐κB Signaling Pathway
Authors: Mu Chaoyu , Wu Mingfei , Li Zeng
Published: December 2018

A series of novel 7‐substituted coumarin derivatives were synthesized and evaluated. Biological screening results obtained by the evaluation of the compounds’ inhibition against LPS‐induced IL‐6 and TNF‐α release in RAW 264.7 cells indicated that most compounds exhibited potent anti‐inflammatory activity. Among them, N‐(3‐methoxybenzyl)‐2‐[(2‐oxo‐2H‐chromen‐7‐yl)oxy]acetamide (2d) showed the best activity. The potential targets of title compound 2d were reversely screened with the molecular modeling software, Discovery Studio 2017 R2. Screening and molecule docking results showed that 2d could bind to the active site (NLS Polypeptide) of NF‐κB p65, and this binding affinity was confirmed by surface plasmon resonance (SPR) analysis. Furthermore, Western blot assay showed that 2d remarkably blocked the NF‐κB signaling pathway in vitro. Collectively, all these findings suggested that compound 2d might be a promising lead compound worthy of further pursuit.
Involvement of β‐Alkylation Machinery and Two Sets of Ketosynthase‐Chain‐Length Factors in the Biosynthesis of Fogacin Polyketides in Actinoplanes missouriensis
Authors: Sato Kei , Katsuyama Yohei , Yokota Kousuke , Awakawa Takayoshi , Tezuka Takeaki , Ohnishi Yasuo
Published: December 2018

Fogacin and two novel fogacin derivatives, fogacins B and C, were isolated from the rare actinomycete Actinoplanes missouriensis. Biosynthesis of fogacin C apparently requires β alkylation of a polyketide chain. The fogacin biosynthetic type II polyketide synthase (PKS) gene cluster contains a hydroxymethylglutaryl‐coenzyme A synthase (HCS) cassette, which is usually responsible for β alkylation in the type I PKS system. Another characteristic of the fog cluster is that it encodes two sets of ketosynthase (KS) and chain‐length factor (CLF). Inactivation of either of the two KS genes in A. missouriensis and heterologous expression of the HCS cassette with either of the two KS‐CLF genes in Streptomyces albus indicated that each KS‐CLF had a different starter substrate specificity: one preferred an unusual β‐alkylated starter and the other preferred a normal acetyl starter. This study expands knowledge of HCS cassette‐dependent β alkylation into the type II PKS system and provides a natural example of combinatorial biosynthesis for producing diverse polyketides from different starter substrates.
Armeniaspirol Antibiotic Biosynthesis: Chlorination and Oxidative Dechlorination Steps Affording Spiro[4.4]non‐8‐ene
Authors: Fu Chengzhang , Xie Feng , Hoffmann Judith , Wang Qiushui , Bauer Armin , Brönstrup Mark , Mahmud Taifo , Müller Rolf
Published: December 2018

Armeniaspirols are potent antibiotics containing an unusual spiro[4.4]non‐8‐ene moiety. Herein, we describe the cloning and functional analysis of the armeniaspirol biosynthetic gene cluster. Gene‐inactivation studies and subsequent isolation of previously unknown biosynthetic intermediates shed light on intriguing biosynthetic details. Remarkably, deletion of ams15, which encodes a protein bearing a flavin‐binding domain, led to the accumulation of several non‐spiro intermediates with various numbers of chlorine substitutions on the pyrrole moiety. The di‐ and trichloropyrrole species were converted by Streptomyces albus expressing Ams15 into mono‐ and dichlorinated spiro derivatives, respectively. In addition, in vitro conversion of these non‐spiro intermediates into des‐N‐methyl spiro intermediates by the cell lysate of the same recombinant strain proved Ams15 to be responsible for spiro formation through oxidative dehalogenation.
Hollow Structured Carbon@FeSe Nanocomposite as a Promising Anode Material for Li‐Ion Batteries
Authors: Chen Yu , Shao Jie , Lin Xiaoyu , Gu Yuanyuan , Holze Rudolf , Yun Yuanxing , Qu Qunting , Zheng Honghe
Published: December 2018

Carbon@FeSe nanocomposites with homogeneous hollow microspherical and nanotubular structures are prepared using sulfonated polystyrene microspheres and sulfonated poly(divinylbenzene) nanotubes as both the template and carbon source. Benefiting from their hollow core‐shell and hierarchical micro/nanostructures, the carbon@FeSe nanocomposites as the anode material of Li‐ion batteries exhibit high capacities with a steady discharge plateau of 1.5 V (vs. Li/Li+), stable cycling performance (700 mAh g−1 in the 200th cycle at 800 mA g−1), and good rate behavior (620 mAh g−1 at 16 A g−1). The steady discharge plateau of carbon@FeSe, together with its high capacity, renders it a promising anode material for Li‐ion batteries.
4“‐O‐Alkylated α‐Galactosylceramide Analogues as iNKT‐Cell Antigens: Synthetic, Biological, and Structural Studies
Authors: Janssens Jonas , Bitra Aruna , Wang Jing , Decruy Tine , Venken Koen , van der Eycken Johan , Elewaut Dirk , Zajonc Dirk M. , van Calenbergh Serge
Published: December 2018

Invariant natural killer T‐cells (iNKT) are a glycolipid‐responsive subset of T‐lymphocytes that fulfill a pivotal role in the immune system. The archetypical synthetic glycolipid, α‐galactosylceramide (α‐GalCer), whose molecular framework is inspired by a group of amphiphilic natural products, remains the most studied antigen for iNKT‐cells. Nonetheless, the potential of α‐GalCer as an immunostimulating agent is compromised by the fact that this glycolipid elicits simultaneous secretion of Th1‐ and Th2‐cytokines. This has incited medicinal chemistry efforts to identify analogues that are able to perturb the Th1/Th2 balance. In this work, we present the synthesis of an extensive set of 4“‐O‐alkylated α‐GalCer analogues, which were evaluated in vivo for their cytokine induction. We have found that conversion of the 4”‐OH group to ether moieties decreases the immunogenic potential in mice relative to α‐GalCer. Yet, the benzyl‐modified glycolipids are able to produce a distinct pro‐inflammatory immune response. The crystal structures suggest an extra hydrophobic interaction between the benzyl moiety and the α2‐helix of CD1d.
Where have all the tree diameters grown? Patterns in Fagus sylvatica L. diameter growth on their run to the upper canopy
Authors: Janík David , Vrška Tomáš , Hort Libor , Unar Pavel , Král Kamil
Published: December 2018

The diameter growth of a tree reflects the success of that tree in competition. We investigated patterns of Fagus sylvatica diameter growth in the Žofín Forest Dynamics Plot, which is part of Smithsonian's Forest Global Earth Observatory as a research plot representing European natural mixed temperate forests. We focused primarily on the spatial patterns of beech diameter growth from the viewpoint of the most successful individuals in different ontogenetic stages. We analyzed the reaction of trees along a gradient of disturbance intensity as well as the effects of neighborhood competition. We used stem maps of trees with a diameter at breast height (dbh) ≥ 10 cm carried out in 1997 and 2012. Various types of the pair correlation function were applied to the data to describe the tree density variability. Tree spatial pattern analyses were performed on six 1.5‐ha square plots. Our results show an increasing trend of general increment growth in the interval between dbh 10 cm and dbh 40 cm. Average increment first peaked between dbh 40–42 cm with values higher than 5 mm/year, after which the absolute average increment slightly decreased and stagnated; dbh increment again increased only after dbh 79 cm, but with a much wider range of confidence intervals. An analysis of the variability in diameter growth at intermediate spatial scales showed that disturbance events influence diameter growth differently in connection with dbh. Diameter growth in thinner trees was strongly positively correlated with disturbance intensity, while disturbance had no effect on the variability in diameter growth in larger trees. The spatial pattern of elite‐growth recruits differed from the generally clustered pattern of recruits, with mutual negative interactions up to 2 m. Elite‐growth small‐sized trees (dbh 10–19 cm) showed a positive association with dead individuals in the same size category. In contrast, elite‐growth medium‐sized trees (dbh 20–39 cm) had no positive associations at all. At the same time, negative correlations with canopy beeches were observed across all categories. In conclusion, current tree spatial patterns of trees and their diameter growth are the results of multiple interactions accumulated over the long term with high inertia.
Variability in fire‐induced change to vegetation physiognomy and biomass in semi‐arid savanna
Authors: Singh Jenia , Levick Shaun R. , Guderle Marcus , Schmullius Christiane , Trumbore Susan E.
Published: December 2018

Fire plays an intrinsic role in shaping the biophysical attributes of savanna ecosystems. Savanna fires limit vegetation biomass below their climatically determined potential, but the magnitude of this effect and how it varies across heterogeneous landscapes are poorly understood. In this study, we explore woody tree structure and canopy characteristics across a fire manipulation experiment that has been maintained for 63 yr in South Africa's Kruger National Park. Our study design assessed three late dry‐season fire regimes (biennial, triennial, and unburnt) across a precipitation gradient (737–496 mm/yr) spanning four different landscapes with a mixture of sandy and clay soils. We used terrestrial laser scanning (TLS) to quantify tree height, canopy cover, and aboveground carbon storage across the experimental treatments. Vegetation physiognomy was influenced by the interaction between landscape and fire frequency. In the absence of fire, woody height, cover, and biomass increased with increasing rainfall. The presence of fire acted to reduce structure and biomass as expected, but the magnitude of this effect increased with increasing rainfall. We found minimal difference between the effects of biennial or triennial burning—except at the wettest site where the triennial fire plots had half the biomass of those burnt biennially. The rainfall dependent fire–vegetation relationships shown here provide empirical quantification of top‐down constraint by fire and highlight the challenges of predicting responses to disturbances in these inherently heterogeneous ecosystems. Robust quantification of 3D structure and dynamics through TLS will be useful for constraining carbon stock models and predicting trajectories of change under future climate and land‐use conditions.
Reactivity Differences for the Oxidation of FeIIFeII to FeIII(µ‐O)FeIII Complexes Caused by Pyridyl versus 6‐Methyl‐Pyridyl Ligands
Authors: Zimmermann Thomas Philipp , Dammers Susanne , Stammler Anja , Bögge Hartmut , Glaser Thorsten
Published: December 2018

The dinucleating bis(tetradentate) ligand susan [= 4,7‐dimethyl‐1,1,10,10‐tetra(2‐pyridylmethyl)‐1,4,7,10‐tetraazadecane] reacts with [Fe(OH2)6](BF4)2 to the complex [(susan){FeIIIF(µ‐O)FeIIIF}](BF4)2. In contrast, the reaction of the ligand derivative susan6‐Me with 6‐methylpyridyl instead of pyridyl donors with [Fe(OH2)6](BF4)2 results in the complexes [(susanMe){FeII(µ‐F)2FeII}](BF4)2 and [(susanMe){FeIIF(µ‐F)FeIIIF}](BF4)2. The synthesis of the µ‐oxo diferric complex [(susan6‐Me){FeIIIF(µ‐O)FeIIIF}]2+ requires the addition of H2O2 as oxidant. The best synthesis is the H2O2 oxidation of the new diferrous precursor [(susan6‐Me){FeII(µ‐F)2FeII}](ClO4)2. The introduction of the 6‐methylpyridine donors results in an elongation of the Fe–Npy bonds. The resulting lower electron donation is not compensated by the µ‐oxo bond but slightly by the Fe–Namine bonds. These structural changes are correlated with the νas(FeOFe) stretching mode, a smaller Mössbauer quadrupole splitting, a smaller ligand field splitting, a weaker antiferromagnetic exchange, and an anodic shift of the redox potentials. This destabilization of the ferric state correlates with the different reactivity of the diferrous precursors to the µ‐oxo diferric complexes: air for susan and H2O2 for for susan6‐Me. Structural analysis indicates a steric repulsion of the 6‐methyl group with the fluorido ligand in cis‐position as origin for the longer Fe–Npy bonds, which seems to be a general phenomenon.
Molecular Insights into Bulk and Porous κ2P,N‐PTA Metal‐Organic Polymers by Simultaneous Raman Spectroscopy and Inelastic Neutron Scattering
Authors: Scalambra Franco , Rudić Svemir , Romerosa Antonio
Published: December 2018

Simultaneous Raman spectroscopy and inelastic neutron scattering have been used to obtain structural information about the isomeric metal‐organic polymers trans‐[{RuCp(PTA)2‐µ‐CN‐1κC:2κ2N‐RuCp(PTA)2}‐µ‐CoCl3]n·(DMSO)n (2), cis‐{[{RuCp(PTA)2‐µ‐CN‐1κC:2κ2N‐RuCp(PTA)2}‐µ‐CoCl3]}n·{[RuCp(PTA)2‐µ‐CN‐1κC:2κ2N‐RuCp(PTA)2]Cl}0.5n·(15H2O)n (3) and {[{RuCp(PTA)2‐µ‐CN‐1κC:2κ2N‐RuCp(PTA)2}‐µ‐CoCl3]}n·{[RuCp(PTA)2‐µ‐CN‐1κC:2κ2N‐RuCp(PTA)2]Cl}0.5n (4) (PTA = 1,3,5‐triaza‐7‐phosphaadamantane). Despite the complexity of the compounds, the combination of both techniques has been useful to understand the conformation‐dependent fingerprint of the polymers and, at the same time, to obtain preliminary information about how the water molecules are confined in the structural channels of 3.
Evaluation of the microhaplotype markers in kinship analysis
Authors: Zhu Jing , Chen Peng , Qu Shengqiu , Wang Yinji , Jian Hui , Cao Shuqiang , Liu Yuqing , Zhang Ranran , Lv Meili , Liang Weibo , Zhang Lin
Published: December 2018

Microhaplotype markers are emerging forensic genetic markers, which may supplement existing markers. Consisting of two to four SNPs with an extent of <200 bp, microhaplotype can be genotyped through massively parallel sequencing technology. Articles that have been published suggested that microhaplotype markers have good application prospect in forensics. Multiallelic haplotype loci are potentially important in certain forensic works, as the stutter and high mutation rate of short tandem repeats and the low polymorphism of single nucleotide polymorphisms may limit the power of these two kind of regular markers. In this study, we explored the potential of 11 new microhaplotype loci in kinship analysis. The results suggested that these loci have relatively high polymorphic information in different populations worldwide and relatively high system effectiveness in the kinship analysis. Microhaplotypes have potential for forensic kinshipg analysis.
Microfluidic based impedance biosensor for pathogens detection in food products
Authors: Abdullah Amjed , Dastider Shibajyoti Ghosh , Jasim Ibrahem , Shen Zhenyu , Yuksek Nuh , Zhang Shuping , Dweik Majed , Almasri Mahmoud
Published: December 2018

A MEMS‐based impedance biosensor was designed, fabricated, and tested to effectively detect the presence of bacterial cells including E. coli O157:H7 and Salmonella typhimurium in raw chicken products using detection region made of multiple interdigitated electrode arrays. A positive dielectrophoresis based focusing electrode was used in order to focus and concentrate the bacterial cells at the centerline of the fluidic microchannel and direct them toward the detection microchannel. The biosensor was fabricated using surface micromachining technology on a glass substrate. The results demonstrate that the device can detect Salmonella with concentrations as low as 10 cells/mL in less than 1 h. The device sensitivity was improved by the addition of the focusing electrodes, which increased the signal response by a factor between 6 and 18 times higher than without the use of the focusing electrodes. The biosensor is selective and can detect other types of pathogen by changing the type of the antibody immobilized on the detection electrodes. The device was able to differentiate live from dead bacteria.
Suitability of anodic stripping voltammetry for routine analysis of venous blood from raptors
Authors: González Fernando , Camacho María , Tiburón Natalia Pastor , Peña Manuel Zumbado , Rueda Luis Revuelta , Luzardo Octavio P.
Published: December 2018

Lead (Pb) poisoning is a significant threat faced by raptors. Hence, rapid Pb diagnosis has become a priority during the admission of raptors in wildlife recovery centers, and bench-top analyzers, such as LeadCare II ®, are routinely employed for this purpose. However, this device has been designed for conducting analyses of human blood Pb levels (BLLs), and the validity of this methodology for whole blood from raptors has, to date, rarely been assessed. In addition, a recent recall by the US Food and Drug Administration has recommended discontinuing the use of this analyzer for human venous blood because it may underestimate the BLL. We evaluated the precision of BLL measurements taken with LeadCare II by comparing them with those obtained with inductively coupled plasma mass spectrometry (ICP-MS). Our sample contained venous blood from 105 raptors belonging to 4 species. The results showed a good correlation between the 2 techniques (Spearman's r = 0.927, p < 0.0001). The mean BLL with ICP-MS was 19.6 μg/dL; it was found to be 18.7 μg/dL with LeadCare II. A Bland-Altman analysis indicated that the bias between the mean differences was only 0.5 μg/dL, but it had a high standard deviation of bias (5.7 μg/dL) and 95% limits of agreement from –10.75 to 11.74 μg/dL. The present results indicated that LeadCare II has an overall sensitivity of 71.8% and a positive predictive value of 76.3%. The specificity of LeadCare II for detecting animals with low BLL (<3.4 μg/dL) was 96.4%, and the negative predictive value (the probability that a value below the limit of detection of LeadCare II has a true correspondence with the actual value) was 100%. The present results indicated that, although LeadCare II might be imperfect in the estimation of BLLs in raptors, it performs reasonably well and might be employed in the clinical setting to assess patients potentially suffering from Pb poisoning. Environ Toxicol Chem 2019;38:737–747. © 2018 SETAC

Abstract

Use of LeadCare II in analyzing raptor venous blood.
Extended hybrid directional DRX with auxiliary active cycles for light traffic in 5G networks
Authors: Philip Ninu Rachel , Malarkodi B.
Published: December 2018

In recent years, energy efficiency has become a major cause of concern in mobile networks. The overwhelming applications and services provided by the evolving fifth‐generation (5G) technologies consume a substantial amount of energy, especially at the user equipment (UE). The 3rd Generation Partnership Project has proposed discontinuous reception (DRX) as a power saving technique for the UE. The DRX protocol has been used by different generation mobile standards. In this paper, the performance of hybrid directional DRX (HD‐DRX) for 5G communication with beam searching is improved upon by augmenting intermediate single packet active states in the short and long sleep cycles for light traffic in 5G networks. The supplementary active states save power by allowing the UE to receive packets within the sleep periods up to a certain threshold without transitioning to the active state. The short bursts of packets in the light traffic are received directly through the intermediate active states without beam searching. Once the given threshold exceeds, the system functions as normal HD‐DRX for the heavy traffic without the intermediate states. The proposed model is analyzed as a semi‐Markov process with the bursty packet data traffic model. The numerical results of the proposed model show 3.1% improvement in power saving and reduction in average delay by around 2.5 s compared to the HD‐DRX. Further studies can help deep dive into operationalizing this on a mass scale.
Three stories of Noah: Navigating religious climate change narratives in the Pacific Island region
Authors: Fair Hannah
Published: December 2018

This paper makes a case for spiritualising climate change, outlining the importance of bringing diverse religious understandings into climate change responses, particularly in the Pacific Island region. It situates this as part of a wider geographical project of rendering climate change locally meaningful, and story‐telling multiple climate change narratives, including Christian ones. It identifies one of the major obstacles to this spiritualisation: the treatment of religious thought as a barrier to climate change action by much of the existing social science research in the Pacific Islands. Rather than attempting to purify scientific and religious knowledge, this paper proposes an alternative approach, tufala save: the balancing of multiple epistemologies of climate change, exploring their convergences and tensions. This paper draws on four months of ethnographic fieldwork in Vanuatu, and over 60 semi‐structured interviews with religious figures and individuals engaged in climate change adaptation and advocacy across the Pacific Island region. It applies the tufala save approach in order to explore one recurring narrative, the biblical story of Noah and the flood, due to the contentious associations between this story and climate change denial in Oceania. The paper traces three discursive manifestations of the Noah story within the Pacific Islands: rainbow covenant as a basis for denial, Noah as an icon of preparation, and Islanders as unjustly outside of the ark. The contrasts between these three articulations – in terms of the relations between the different knowledges and the possibilities for climate change action they encourage and foreclose – demonstrate the heterogeneity of religious responses to climate change and the potential for fruitful connections between religious and scientific knowledges. They highlight the potential for more‐than‐scientific yet not anti‐scientific responses to climate change that are locally meaningful and morally compelling.
The syncollisional granitoid magmatism and crust growth during the West Qinling Orogeny, China: Insights from the Jiaochangba pluton
Authors: Kong Juanjuan , Niu Yaoling , Duan Meng , Shao Fengli , Xiao Yuanyuan , Zhang Yu , Guo Pengyuan , Sun Pu , Gong Hongmei
Published: December 2018

The West Qinling Orogenic Belt (WQOB) is a major portion of the Qinling‐Dabie‐Sulu Orogen and holds essential information for understanding the protracted evolution of the north‐eastern branch of the Paleo‐Tethys in East Asia. In this study, we report our petrological, geochemical, and geochronological study on the five Triassic granitoid plutons of West Qinling with emphasis on the poorly studied Jiaochangba pluton with zircon U–Pb ages of 217.5 ± 1.6 Ma and 215.2 ± 1.2 Ma. The new data and the existing data on the other four plutons support the view that the West Qinling granitoids represent a magmatic response to the continental collision of the Yangtze Block (YB) with the North China Craton (NCC) in the Triassic. Like the other four plutons, the Jiaochangba pluton shows strong light rare earth element (REE) enrichment and weak heavy REE depletion ([La/Sm]N ≈ 7.14 ± 1.89; [Sm/Yb]N ≈ 4.63 ± 1.85) with varying negative Eu anomalies (Eu/Eu* ≈ 0.65 ± 0.20). In the N‐MORB normalized diagram, all the samples show relative enrichment in Rb, Pb, U, and K with negative Nb, Ta, P, and Ti anomalies, resembling those of the model continental crust. The Jiaochangba pluton has relatively lower (87Sr/86Sr)i(0.7062 to 0.7081), higher εNd(t) (−6.91 to −2.09), and εHf(t) (−5.57 to −0.14) than mature continental crust, which are consistent with their source being dominated by lower crust with significant mantle contributions. Mantle‐derived melt, which formed from partial melting of mantle wedge peridotite facilitated by dehydration of the subducted/subducting Mianlue ocean crust, provide the required heat for the crustal melting while also contributing to the compositions of these granitoids. Evolution of such parental magmas in open system crustal magma chambers with continued evolution/replenishment and crustal contamination and assimilation give rise to the observed petrological and geochemical characteristics of these granitoids.
Role of magma mixing in generating of the Gheshlagh–Aftabrow intrusions, SW Buin Zahra, Iran: Evidence for a juvenile origin from geochemical and Sr–Nd isotopic data
Authors: Kazemi Kazem , Kananian Ali , Xiao Yilin , Sarjoughian Fatemeh
Published: December 2018

In this paper, we investigate host granodiorites and associated mafic microgranular enclaves (MMEs), including gabbroic to quartz diorite enclaves from the Middle Eocene Gheshlagh–Aftabrow granitoid, to assess magma mixing and crust–mantle interaction in the Urumieh–Dokhtar magmatic arc. The host granodiorites yield zircon U–Pb ages of ca. 40 Ma. Geochemical and bulk rock Nd–Sr isotopic modelling, together with the widespread occurrence of mafic microgranular enclaves with ellipsoidal and spherical shapes and chilled margins, K‐feldspar and plagioclase megacrysts in the enclaves, and the presence of acicular apatite, ocellar quartz, plagioclase with oscillatory zoning and resorption surfaces, suggests that the mafic microgranular enclaves are globules of a more mafic magma derived from the mantle that was injected into and mixed/mingled with the magma derived from partial melting of a lower crust. Geochemically, the granitoid rocks are high‐K calc‐alkaline and metaluminous (A/CNK = 0.87–0.92) and belong to I‐type suite. These granitoid host rocks have much higher SiO2 (65.4–67.3 wt%) and relatively low Fe2O3 (1.8–2.1 wt%) and MgO (1–1.58 wt%), so compared with the host rocks, the mafic microgranular enclaves have much lower SiO2 contents (50.5–55 wt%), considerably higher Fe2O3 (3.4–4.2 wt%) and MgO (3.9–4.8 wt%). Both the host intrusion and enclaves are enriched in LREE relative to HREEs (LREE/HREE = 3.1–4.1; (La/Yb)N = 2.1–4.1) and show slightly negative Eu anomalies (δEu = 0.75–0.90) and nearly flat HREE patterns ((Gd/Yb)N = 0.86–1.26). Analyses of Sr–Nd isotopes in the host granodiorites and associated enclaves show (87Sr/86Sr)i host = 0.705070–0.705174, εNd(t) host = 0.21–2.31, TDM1 host = 782–983 Ma, (87Sr/86Sr)i enclave = 0.704997–0.705170, εNd(t) enclave = 2.15–2.17, and TDM1 enclave = 874–980 Ma, indicating of juvenile nature for these granites. This characteristic together with similar trace‐element compositions indicates intense magma mixing and a high degree of geochemical equilibration between the host granodiorites and their enclaves.

A binary mixing model based on Sr–Nd isotopic compositions of the GAG indicates that rocks were mostly generated by mixing of 7–12% melts produced by partial melting of meta‐igneous old lower crust rocks with 88–93% contribution of mantle‐derived juvenile basaltic magmas.
Comparison of homofugality among alkyl groups attached to tin atom
Authors: Kamimura Akio , Yoshinaga Tatsuro , Miyazaki Koichiro , Kawamoto Takuji
Published: December 2018

Dibutylmethyltin hydride and tert‐butyldibutyltin hydride were employed to examine radical cascade reaction of aza‐1,6‐enyne for the preliminary estimation of homofugality between alkyl groups by product distribution analysis. Use of either dibutylmethyltin hydride or tert‐butyldibutyltin hydride preferentially produced butylmethylstannolane, in which butyl group was mainly substituted by vinyl radical.
PI3‐kinase pathway biomarkers in oral cancer and tumor immune cells
Authors: Ibrahim Mohammad Y. , Nunez Maria I. , Harun Nusrat , Lee J. Jack , El‐Naggar Adel K. , Ferrarotto Renata , Wistuba Ignacio , Myers Jeffrey , Glisson Bonnie S. , William William N.
Published: December 2018

Background

This study investigated the hypothesis that phosphoinositide 3‐kinase (PI3‐kinase) pathway dysregulation in either head and neck cancer cells and/or tumor infiltrating immune cells would influence outcomes of patients with surgically treated oral tongue squamous cell carcinomas (SCC).

Methods

We constructed tissue microarrays containing 123 oral tongue SCC samples and performed immunohistochemistry using antibodies against 7 PI3‐kinase pathway markers: phosphatase and tensin homolog (PTEN), Akt, p‐Akt, mammalian target of rapamycin (mTOR), phosphorylated‐mammalian target of rapamycin (p‐mTOR), survivin, and Ki‐67). Expression levels in cancer cells or tumor infiltrating immune cells were correlated with outcomes.

Results

Higher levels of PTEN expression in immune cells were significantly associated with improved recurrence‐free survival (heart rate (HR) = 0.45, 95% confidence interval (CI) 0.23‐0.90, P = .03), and overall survival (HR = 0.34, 95% CI 0.15‐0.76, P = .01) on univariate and multicovariate models.

Conclusions

We identified a novel, negative prognostic role of PI3‐kinase activation (as determined by PTEN loss) in oral SCC infiltrating immune cells. These findings could be relevant for clinical development of PI‐3 kinase inhibitors for this disease.
Initial experience with image‐guided surgical navigation in transoral surgery
Authors: Paydarfar Joseph A. , Wu Xiaotian , Halter Ryan J.
Published: December 2018

Background

Surgical navigation using image guidance may improve the safety and efficacy of transoral surgery (TOS); however, preoperative imaging cannot be accurately registered to the intraoperative state due to deformations resulting from placement of the laryngoscope or retractor. This proof of concept study explores feasibility and registration accuracy of surgical navigation for TOS by utilizing intraoperative imaging.

Methods

Four patients undergoing TOS were recruited. Suspension laryngoscopy was performed with a CT‐compatible laryngoscope. An intraoperative contrast enhanced CT scan was obtained and registered to fiducials placed on the neck, face, and laryngoscope.

Results

All patients were successfully scanned and registered. Registration accuracy within the pharynx and larynx was 1 mm or less. Target registration was confirmed by localizing endoscopic and surface structures to the CT images. Successful tracking was performed in all 4 patients.

Conclusion

For surgical navigation during TOS, although a high level of registration accuracy can be achieved by utilizing intraoperative imaging, significant limitations of the existing technology have been identified. These limitations, as well as areas for future investigation, are discussed.
Radiation therapy for patients with newly diagnosed metastatic head and neck squamous cell carcinoma
Authors: Kabarriti Rafi , Baliga Sujith , Ohri Nitin , Guha Chandan , Kalnicki Shalom , Garg Madhur K.
Published: December 2018

Background

To assess the association between radiation therapy (RT) use and overall survival (OS) for patients with metastatic head and neck squamous cell carcinomas (HNSCC).

Methods

We analyzed the National Cancer Database to identify patients with newly diagnosed metastatic HNSCC from 2004 to 2013 who were treated with up‐front chemotherapy. Associations between the use of RT and OS were evaluated.

Results

We identified 3516 patients with metastatic HNSCC who were treated with chemotherapy; 2288 (65%) were also treated with RT. The addition of RT to chemotherapy was associated with prolonged survival (median: 13.6 vs 11.3 months, log‐rank P < .001). After adjusting for other prognostic factors in a multivariable Cox model, propensity score matching and landmark analyses limited to patients who survived at least 3, 6, and 12 months after diagnosis, the use of RT remained associated with prolonged survival.

Conclusion

The addition of RT to chemotherapy in the up‐front management of metastatic HNSCC was associated with prolonged OS in this study.
Observational and predictive uncertainties for multiple variables in a spatially distributed hydrological model
Authors: Ehlers Lennart Benjamin , Sonnenborg Torben Obel , Refsgaard Jens Christian
Published: December 2018

In this study, uncertainty in model input data (precipitation) and parameters is propagated through a physically based, spatially distributed hydrological model based on the MIKE SHE code. Precipitation uncertainty is accounted for using an ensemble of daily rainfall fields that incorporate four different sources of uncertainty, whereas parameter uncertainty is considered using Latin hypercube sampling. Model predictive uncertainty is assessed for multiple simulated hydrological variables (discharge, groundwater head, evapotranspiration, and soil moisture). Utilizing an extensive set of observational data, effective observational uncertainties for each hydrological variable are assessed. Considering not only model predictive uncertainty but also effective observational uncertainty leads to a notable increase in the number of instances, for which model simulation and observations are in good agreement (e.g., 47% vs. 91% for discharge and 0% vs. 98% for soil moisture). Effective observational uncertainty is in several cases larger than model predictive uncertainty. We conclude that the use of precipitation uncertainty with a realistic spatio‐temporal correlation structure, analyses of multiple variables with different spatial support, and the consideration of observational uncertainty are crucial for adequately evaluating the performance of physically based, spatially distributed hydrological models.
RAB27A promotes melanoma cell invasion and metastasis via regulation of pro‐invasive exosomes
Authors: Guo Dajiang , Lui Goldie Y.L. , Lai Siew Li , Wilmott James S. , Tikoo Shweta , Jackett Louise A. , Quek Camelia , Brown Darren L. , Sharp Danae M. , Kwan Rain Y.Q. , Chacon Diego , Wong Jason H. , Beck Dominik , van Geldermalsen Michelle , Holst Jeff , Thompson John F. , Mann Graham J. , Scolyer Richard A. , Stow Jennifer L. , Weninger Wolfgang , Haass Nikolas K. , Beaumont Kimberley A.
Published: December 2018

Despite recent advances in targeted and immune‐based therapies, advanced stage melanoma remains a clinical challenge with a poor prognosis. Understanding the genes and cellular processes that drive progression and metastasis is critical for identifying new therapeutic strategies. Here, we found that the GTPase RAB27A was overexpressed in a subset of melanomas, which correlated with poor patient survival. Loss of RAB27A expression in melanoma cell lines inhibited 3D spheroid invasion and cell motility in vitro, and spontaneous metastasis in vivo. The reduced invasion phenotype was rescued by RAB27A‐replete exosomes, but not RAB27A‐knockdown exosomes, indicating that RAB27A is responsible for the generation of pro‐invasive exosomes. Furthermore, while RAB27A loss did not alter the number of exosomes secreted, it did change exosome size and altered the composition and abundance of exosomal proteins, some of which are known to regulate cancer cell movement. Our data suggest that RAB27A promotes the biogenesis of a distinct pro‐invasive exosome population. These findings support RAB27A as a key cancer regulator, as well as a potential prognostic marker and therapeutic target in melanoma.
Rs1894720 polymorphism in MIAT increased susceptibility to age‐related hearing loss by modulating the activation of miR‐29b/SIRT1/PGC‐1α signaling
Authors: Hao Shaojuan , Wang Le , Zhao Kun , Zhu Xiaodan , Ye Fanglei
Published: December 2018

Background

MIAT may be implicated in the pathogenesis of age‐related hearing loss (AHL). This study aimed to clarify the effect of a MIAT signaling pathway on the risk of AHL.

Methods

Terminal deoxynucleotidyl transferase dUTP nick‐end labeling assay, auditory brainstem response (ABR) and quantitative hair cell counts were used to compare the hearing functions in different groups of mice. 5,5,6,6‐Tetrachloro‐1,1,3,3‐tetraethylbenzimidazolylcarbocyanine iodide (JC‐1) dye method was used to establish the potential association between mitochondrial dysfunction and aging. Real‐time polymerase chain reaction, Western blot analysis, computational analysis, and luciferase assay were conducted to establish a myocardial infarction associated transcript (MIAT) signaling pathway, whose role in the pathogenesis of AHL was further validated by 3‐[4,5‐dimethylthiazol‐2‐yl]‐2,5 diphenyl tetrazolium bromide (MTT) assay and flow cytometry.

Results

Aged C57BL/6 mice were associated with a more severe level of hair cell loss, while exhibiting a higher ABR threshold at various frequencies as well as a lower percentage of inner/outer hair cells. A reduced mitochondrial membrane potential in the cochleae of aged C57BL/6 mice indicated the presence of mitochondrial dysfunction in these mice. Relative expression of MIAT, Sirtuin1 (SIRT1), and peroxisome proliferator‐activated receptor γ coactivator 1α (PGC‐1α) was downregulated in aged mice, with microRNA‐29b (miR‐29b) being highly expressed. Also, MIAT binds to miR‐29b, an inhibitor of SIRT1 expression. The regulatory relationship among MIAT, miR‐29b, and SIRT1 was further validated by comparing the differentiated expression of these factors in cells treated with phosphate‐buffered saline + H2O2, a negative control + H2O2, MIAT + H2O2, or H2O2 + anti‐miR‐29b.

Conclusion

MIAT could elevate the expression of SIRT1/PGC‐1α via downregulating miR‐29b. And the downregulated SIRT/PGC‐1α increased the incidence of AHL via promoting the apoptosis of cochlear hair cells.
Engineered zinc‐finger nuclease to generate site‐directed modification in the KLF1 gene for fetal hemoglobin induction
Authors: Shariati Laleh , Modarressi Mohammad Hossein , Tabatabaiefar Mohammad Amin , Kouhpayeh Shirin , Hejazi Zahra , Shahbazi Mansoureh , Sabzehei Faezeh , Salehi Mansoor , Khanahmad Hossein
Published: December 2018

Elevation of hemoglobin F (HbF) ameliorates symptoms of β‐thalassemia, as a common autosomal recessive disorder. In this study, the ability of an engineered zinc‐finger nuclease (ZFN) system was assesed to disrupt the KLF1 gene to inhibit the γ to β hemoglobin switching in K562 cells. This study was performed using a second generation integration‐deficient lentiviral vector assigned to transient gene targeting. The sequences coding for zinc finger protein arrays were designed and subcloned in TDH plus as a transfer vector. Transduction of K562 cells was performed with the integrase minus lentivirus containing ZFN. The indel percentage of the transducted cells with lentivirus containing ZFN was about 29%. Differentiation of K562 cell line into erythroid cell lineage was induced with cisplatin concentration of 15 µg/mL. After differentiation, γ‐globin and HbF expression were evaluated using real‐time reverse‐transcription polymerase chain reaction and hemoglobin electrophoresis methods. The levels of γ‐globin messenger RNA were nine‐fold higher in the ZFN treated cells compared with untreated cells 5 days after differentiation. Hemoglobin electrophoresis method showed the same results for HbF level measurement. Application of the ZFN tool to induce KLF1 gene mutation in adult erythroid progenitors might be a candidate to stimulate HbF expression in β‐thalassemia patients.
Association study between two polymorphisms of tumor necrosis factor ligand superfamily member 15 (TNFSF15) gene and ulcerative colitis in south‐west of Iran
Authors: Taheri Marzieh , Ghandil Pegah , Hashemi Seyyed Jalal , Ghafourian Mehri , Masjedi Zadeh Abdol Rahim , Ghadiri Ata Allah
Published: December 2018

Background and aims

Ulcerative colitis (UC) is the most prevalent clinical manifestation of the inflammatory bowel disease (IBD). Several candidate genes have been suggested to be involved in the genetic susceptibility or resistance in the development of UC. Among them, tumor necrosis factor ligand superfamily member 15 (TNFSF15) have been reported in association with IBD in several studies. The aim of this study was to investigate the association of TNFSF15 gene polymorphisms located in the promoter region, including rs6478108 (G/A −9706) and rs3810936 (G/A −15524) in Iranian patients with UC.

Methods

In this way, the two single nucleotide polymorphisms were studied in 115 patients with UC and 115 healthy controls with the same ethnic group from south‐west of Iran. The genomic DNA of samples was genotyped using TaqMan Real‐time PCR assay. This case‐control study was conducted at the Department of Immunology, Jundishapur University of Medical Sciences, Ahvaz, Iran.

Results and conclusion

Our results did not confirm the formerly reported association of the studied polymorphisms with UC disease in comparison with healthy controls, neither with the type of the clinical forms of Colitis in the studied Iranian population. Comparing the genotype frequency of single nucleotide polymorphism (SNP) rs6478108, wild‐type homozygous and heterozygote and mutant homozygote were 33%, 55.7%, and 11.3% in cases vs. 34.8%, 50.4%, and 14.8% in the controls (P = 0.6). The genotype frequency of SNP rs3810936 were 20.9%, 40.9%, and 38.2% in the cases compared to 18.3%, 44.3%, and 37.4% in controls, which was not significant (
P = 0.8). As multiple ethnic groups reside in all around the country, further studies using different ethnicities and/or larger sample size are required to clarify the role of these polymorphisms in the genetic susceptibility of UC in Iranian populations.
NK cell and macrophages confer prognosis and reflect immune status in osteosarcoma
Authors: Yang Xianliang , Zhang Wenbin , Xu Panfeng
Published: December 2018

Osteosarcoma (OS) is a common primary malignant bone tumor in young adolescents. About 30% of patients with OS have a recurrence, and the overall survival after OS recurrence is not good. In this study, we aimed to analyze and identify factors that influence prognosis after OS relapse. We retrieved the Gene Expression Omnibus data set and collected a series of transcriptome data with clinical information, including microRNA (miRNA) and messenger RNA (mRNA) expression profiles in recurrent OS. Upon comparison of the dysregulated genes of survival status in the recurrent OS samples, it was found that there were 268 differential expressed (DE) mRNAs and six DE miRNAs. These genes are related to pathways in cancer. We also predicted the interaction networks of these DE mRNAs and miRNAs. Further, we applied cibersort to estimate the proportion of immune cell types and we discovered that natural killer cells and macrophages have different abundance between good prognosis and poor prognosis. Our study indicates that for recurrent OS samples, there are several differences between these two groups, including gene expression and the status of immune activation. The immunity status is a candidate signature for disease prediction, prevention, and therapy choices.
Elevated expression of circular RNA circ_0008450 predicts dismal prognosis in hepatocellular carcinoma and regulates cell proliferation, apoptosis, and invasion via sponging miR‐548p
Authors: Zhang Juan , Chang Yuxia , Xu Lijun , Qin Lijie
Published: December 2018

Hepatocellular carcinoma (HCC) is one of the most frequent malignancies and a main cause of global cancer mortality. In the past decade, circular RNAs (circRNAs) have been proved to play key roles in various cancers. Previously, circ_0008450 was identified upregulated in HCC tissues by high‐throughput circRNA sequencing. In this study, quantitative real‐time polymerase chain reaction was used to evaluate the expression level of circ_0008450 in human HCC tumor and corresponding nontumor tissue samples, and the association between circ_0008450 expression and clinicopathologic features of patients with HCC was also analyzed. After that, the functions of circ_0008450 in biological behaviors of HCC cells were determined by cell counting kit‐8, colony formation, flow cytometry, and the transwell assays. The mechanism of circ_0008450 was explored by the bioinformatic analysis and dual‐luciferase reporter assay. The expression of circ_0008450 is upregulated in HCC tissue specimens and cell lines. Patients with a high circ_0008450 expression usually bear a lower 5‐year survival rate. Silencing of circ_0008450 in Huh‐7 cells inhibited cell viability, migration, and invasion, whereas cell apoptosis was increased. Conversely, its overexpression in HepG2 cells leads to absolutely inverse results. In addition, circ_0008450 was proved to be a sponge of miR‐548p. The oncogenic role of circ_0008450 was partially attributed to its suppression on miR‐548p. This study implies a new target for the treatment of HCC.
The influence of receptor activity–modifying protein‐1 overexpression on angiogenesis in mouse brain capillary endothelial cells
Authors: Zhang Qin , Guo Yanjun , Chen Huilu , Jiang Yixuan , Tang Haiyang , Gong Ping , Xiang Lin
Published: December 2018

Receptor activity–modifying protein‐1 (RAMP1) is highly expressed in the heart and vasculature, indicating that it might be related to the vascular system. However, the effects of RAMP1 on angiogenesis and the intrinsic mechanisms underlying this process remain unclear. Here, we verified that RAMP1 is a critical regulator of angiogenesis in a mouse brain capillary endothelial cell line (bEnd.3). We first constructed a RAMP1 overexpression lentiviral vector system and stably transfected bEnd.3 cells. We further showed that RAMP1 overexpression could lead to bEnd.3 migration and capillary tube formation in Matrigel without exogenous calcitonin gene–related peptide (CGRP) treatment. At the same time, RAMP1 overexpression had little effect on proliferation. More importantly, vascular endothelial growth factor (VEGF) and CGRP expression levels were not significantly higher in RAMP1‐overexpressing cells than in control cells (P > 0.05), indicating that RAMP1 did not function through upregulating VEGF or CGRP expression in bEnd.3 cells. Strikingly, RAMP1 transfection increased adrenomedullin 2 (AM2) expression levels (
P < 0.05). Taken together, these data contribute to a better understanding of the molecular mechanisms of RAMP1 in angiogenesis.
Evaluation of vitamin D3 deficiency: A population‐based study in northeastern Iran
Authors: Esmaeili Seyed‐Alireza , Mohammadian Saeed , Radbakhsh Shabnam , Momtazi‐Borojeni Amir Abbas , Kheirmand Parizi Payam , Atabati Hadi , Mardani Fatemeh , Saburi Ehsan , Moghaddam Abbas Shapouri
Published: December 2018

Background and Aim

In recent years, vitamin D deficiency has become a major worldwide problem that can exert harmful effects. The aim of the present study was to evaluate the sex‐ and age‐related prevalence of vitamin D deficiency in people from Mashhad, northeastern Iran.

Methods

In this cross‐sectional study conducted over a period of 1 year (2015‐2016), 7504 subjects who referred to Mashhad medical centers were randomly enrolled in the study. The study population was divided into four groups based on sex and age, as following: group 1, 6 to 18 years; group 2, 19 to 35 years; group 3, 36 to 50 years; and group 4, 51 to 65 years. Since vitamin D levels <10, 10 to 20, and 20 to 30 ng/mL are considered as severe, moderate, and mild deficiency, respectively, we used these criteria for categorizing our population.

Results

Of the total population in our study, 65.26% (4902; 57.81% of men and 72.07% of women) showed some degree of vitamin D deficiency. In addition, we found that vitamin D deficiency was common in all age groups (6‐18, 19‐35, 36‐50, and 51‐65 years), and more common in women (58.5%, 80.12%, 63.83%, and 88.44%, respectively) than men (41.66%, 59.86%, 44.97%, and 84.75%, respectively).

Conclusion

Vitamin D deficiency is a major health problem in all age groups and is more common in women. This information would help to provide a progressive prevention program to maintain health and manage some of the vitamin‐related disorders and diseases that especially affect women.
Role of the transforming growth factor‐β signaling pathway in the pathogenesis of colorectal cancer
Authors: Soleimani Atena , Pashirzad Mehran , Avan Amir , Ferns Gordon A. , Khazaei Majid , Hassanian Seyed Mahdi
Published: December 2018

The transforming growth factor‐β (TGF‐β) signaling pathway plays an important role in cancer cell proliferation, growth, metastasis, and apoptosis. It has been shown that TGF‐β acts as a tumor suppressor in the early stages of the disease, and as a tumor promoter in its late stages. Mutations in the TGF‐β signaling components, the TGF‐β receptors and cytoplasmic signaling transducers, are frequently observed in colorectal carcinomas. Exploiting specific TGF‐β receptor agonist and antagonist with antitumor properties may be a way of controlling cancer progression. This review summarizes the regulatory role of TGF‐β signaling in the pathogenesis of colorectal cancer.