bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural dissection of human metapneumovirus phosphoprotein using small angle x-ray scattering
Authors: Renner Max , Paesen Guido C. , Grison Claire M. , Granier Sébastien , Grimes Jonathan M. , Leyrat Cédric
Published: October 2017

The phosphoprotein (P) is the main and essential cofactor of the RNA polymerase (L) of non-segmented, negative‐strand RNA viruses. P positions the viral polymerase onto its nucleoprotein–RNA template and acts as a chaperone of the nucleoprotein (N), thereby preventing nonspecific encapsidation of cellular RNAs. The phosphoprotein of human metapneumovirus (HMPV) forms homotetramers composed of a stable oligomerization domain (Pcore) flanked by large intrinsically disordered regions (IDRs). Here we combined x-ray crystallography of Pcore with small angle x-ray scattering (SAXS)-based ensemble modeling of the full-length P protein and several of its fragments to provide a structural description of P that captures its dynamic character, and highlights the presence of varyingly stable structural elements within the IDRs. We discuss the implications of the structural properties of HMPV P for the assembly and functioning of the viral transcription/replication machinery.
Graphene-Like-Graphite as Fast-Chargeable and High-Capacity Anode Materials for Lithium Ion Batteries
Authors: Cheng Qian , Okamoto Yasuharu , Tamura Noriyuki , Tsuji Masayoshi , Maruyama Shunya , Matsuo Yoshiaki
Published: October 2017

Here we propose the use of a carbon material called graphene-like-graphite (GLG) as anode material of lithium ion batteries that delivers a high capacity of 608 mAh/g and provides superior rate capability. The morphology and crystal structure of GLG are quite similar to those of graphite, which is currently used as the anode material of lithium ion batteries. Therefore, it is expected to be used in the same manner of conventional graphite materials to fabricate the cells. Based on the data obtained from various spectroscopic techniques, we propose a structural GLG model in which nanopores and pairs of C-O-C units are introduced within the carbon layers stacked with three-dimensional regularity. Three types of highly ionic lithium ions are found in fully charged GLG and stored between its layers. The oxygen atoms introduced within the carbon layers seem to play an important role in accommodating a large amount of lithium ions in GLG. Moreover, the large increase in the interlayer spacing observed for fully charged GLG is ascribed to the migration of oxygen atoms within the carbon layer introduced in the state of C-O-C to the interlayer space maintaining one of the C-O bonds.
TREM-1 promotes intestinal tumorigenesis
Authors: Saurer Leslie , Zysset Daniel , Rihs Silvia , Mager Lukas , Gusberti Matteo , Simillion Cedric , Lugli Alessandro , Zlobec Inti , Krebs Philippe , Mueller Christoph
Published: October 2017

Triggering receptor expressed on myeloid cells-1 (TREM-1) is a potent amplifier of pro-inflammatory innate immune responses. Increasing evidence suggests a role for TREM-1 not only in acute pathogen-induced reactions but also in chronic and non-infectious inflammatory disorders, including various types of cancer. Here, we demonstrate that genetic deficiency in Trem1 protects from colorectal cancer. In particular, Trem1−/− mice exhibited reduced tumor numbers and load in an experimental model of inflammation-driven tumorigenesis. Gene expression analysis of Trem1−/− versus Trem1+/+ tumor tissue demonstrated distinct immune signatures. Whereas Trem1−/− tumors showed an increased abundance of transcripts linked to adaptive immunity, Trem1+/+ tumors were characterized by overexpression of innate pro-inflammatory genes associated with tumorigenesis. Compared to adjacent tumor-free colonic mucosa, expression of Trem1 was increased in murine and human colorectal tumors. Unexpectedly, TREM-1 was not detected on tumor-associated Ly6C− MHC class II+ macrophages. In contrast, TREM-1 was highly expressed by tumor-infiltrating neutrophils which represented the predominant myeloid population in Trem1+/+ but not in Trem1−/− tumors. Collectively, our findings demonstrate a clear role of TREM-1 for intestinal tumorigenesis and indicate TREM-1-expressing neutrophils as critical players in colorectal tumor development.
Shape Tailored Magnetic Nanorings for Intracellular Hyperthermia Cancer Therapy
Authors: Dias Carlos S. B. , Hanchuk Talita D. M. , Wender Heberton , Shigeyosi Willian T. , Kobarg Jörg , Rossi André L. , Tanaka Marcelo N. , Cardoso Mateus B. , Garcia Flávio
Published: October 2017

Abstarct

This work explores a new class of vortex/magnetite/iron oxide nanoparticles designed for magnetic hyperthermia applications. These nanoparticles, named Vortex Iron oxide Particles (VIPs), are an alternative to the traditional Superparamagnetic Iron Oxide Nanoparticles (SPIONs), since VIPs present superior heating power while fulfilling the main requirements for biomedical applications (low cytotoxicity and nonremanent state). In addition, the present work demonstrates that the synthesized VIPs also promote an internalization and aggregation of the particles inside the cell, resulting in a highly localized hyperthermia in the presence of an alternating magnetic field. Thereby, we demonstrate a new and efficient magnetic hyperthermia strategy in which a small, but well localized, concentration of VIPs can promote an intracellular hyperthermia process.
Proteomic Analysis of Thiol Modifications and Assessment of Structural Changes in Hemoglobin Induced by the Aniline Metabolites N-Phenylhydroxylamine and Nitrosobenzene
Authors: Möller Carolina , Davis W. Clay , Thompson Vanessa R. , Marí Frank , DeCaprio Anthony P.
Published: October 2017

MS-based proteomic analysis was combined with in silico quantum mechanical calculations to improve understanding of protein adduction by N-phenylhydroxylamine (PhNHOH) and nitrosobenzene (NOB), metabolic products of aniline. In vitro adduction of model peptides containing nucleophilic sidechains (Cys, His, and Lys) and selected proteins (bovine and human hemoglobin and β-lactoglobulin-A) were characterized. Peptide studies identified the Cys thiolate as the most reactive nucleophile for these metabolites, a result consistent with in silico calculations of reactivity parameters. For PhNHOH, sulfinamides were identified as the primary adduction products, which were stable following tryptic digestion. Conversely, reactions with NOB yielded an additional oxidized adduct, the sulfonamide. In vitro exposure of human whole blood to PhNHOH and NOB demonstrated that only sulfinamides were formed. In addition to previously reported adduction of β93Cys of human Hb, two novel sites of adduction were found; α104Cys and β112Cys. We also report CD and UV-Vis spectroscopy studies of adducted human Hb that revealed loss of α-helical content and deoxygenation. The results provide additional understanding of the covalent interaction of aromatic amine metabolites with protein nucleophiles.
A Study of the Brain Functional Network of Post-Stroke Depression in Three Different Lesion Locations
Authors: Shi Yu , Zeng Yanyan , Wu Lei , Liu Ziping , Zhang Shanshan , Yang Jianming , Wu Wen
Published: October 2017

Research on the mechanism of post stroke depression (PSD) is the key way to improve the treatment of PSD. However, the functional brain network of PSD has not been entirely supported by the results of functional magnetic resonance imaging (fMRI) studies. The aims of this study are to investigate the brain response of PSD in three different lesions. The brain responses of the three PSD subgroups were similar. However, each subgroup had its own characteristics of the brain network. In the temporal lobe subgroup, the right thalamus had increased degree centrality (DC) values which were different from the other two subgroups. In the frontal lobe subgroup, the left dorsolateral prefrontal cortex, caudate, and postcentral gyrus had increased DC values which were different from the other two subgroups. The hemodynamic response of PSD indicates that PSD has activities of similar emotional networks, of which the negative network realizes its function through the limbic system and default mode network. The brain network has unique characteristics for different lesion locations. The neurological function of the lesion location, the compensatory mechanism of the brain, and the mechanism of integrity and locality of the brain are the important factors in the individual emotional network.
On the occurrence of intracolonial genotypic variability in highly clonal populations of the hydrocoral Millepora platyphylla at Moorea (French Polynesia)
Authors: Dubé Caroline E. , Planes Serge , Zhou Yuxiang , Berteaux-Lecellier Véronique , Boissin Emilie
Published: October 2017

Intracolonial genotypic variability is described in many colonial organisms and arises from mosaicism (somatic mutation) and/or chimerism (allogenic fusion). Both processes provide an additional source of genotypic variation in natural populations and raise questions on the biological significance of colonies having more than one genotype. Using fifteen microsatellite markers, we screened for potential genetic heterogeneity withinMillepora platyphyllacolonies, a hydrocoral species known for its extensive morphological plasticity among reef habitats. We aimed to determine whether mosaicism and chimerism were related to specific reef habitats and/or colony morphologies. Our results show that intracolonial genotypic variability was common (31.4%) inM. platyphyllaat Moorea, French Polynesia, with important variations in its frequency among habitats (0–60%), while no effect of morphology was observed. Mosaicism seemed responsible for most of the genetic heterogeneity (87.5%), while chimerism was rarer. Some mosaics were shared among fire coral clones indicating that mutations could be spread via colony fragmentation. Further, the genotypic variability among clones suggests that colonies produced asexually through fragmentation have the potential to accumulate their own mutations over time. Such mutation dynamics might have important implications for the adaptive potential of long-lived reef-builder populations that are predominantly sustained through asexual reproduction.
Non-noble, efficient catalyst of unsupported α-Cr2O3 nanoparticles for low temperature CO Oxidation
Authors: Bumajdad Ali , Al-Ghareeb Shaimaa , Madkour Metwally , Sagheer Fakhreia Al
Published: October 2017

Herein, we report the synthesis of chromium oxide nanoparticles, α -Cr2O3NPs, followed by full characterization via XRD, SEM, XPS, and N2sorptiometry. The synthesized nanoparticles were tested as catalysts toward the oxidation of CO. The impact of calcination temperature on the catalytic activity was also investigated. CO conversion (%), light-off temperature, T50, data were determined. The results revealed that chromia obtained at low calcination temperature (400 °C) is more active than those obtained at high calcination temperatures (600° or 800 °C) and this is ascribed to the smaller particle size and higher surface area of this sample. The results revealed a superior catalytic activity of Cr2O3NPs at lower temperature as we reached a complete conversion at 200 °C which is high value in the forefront of the published results of other non-noble catalysts. The high activity of Cr2O3nanoparticles (T50as low as 98 °C) where found to be dependent on a careful selection of the calcination temperature. These results may provide effective and economic solutions to overcome one of the major environmental threats.
Chemical Stability of Graphene Coated Silver Substrates for Surface-Enhanced Raman Scattering
Authors: Suzuki Seiya , Yoshimura Masamichi
Published: October 2017

Surface enhanced Raman spectroscopy (SERS) is a novel method to sense molecular and lattice vibrations at a high sensitivity. Although nanostructured silver surface provides intense SERS signals, the silver surface is unstable under acidic environment and heated environment. Graphene, a single atomic carbon layer, has a prominent stability for chemical agents, and its honeycomb lattice completely prevents the penetration of small molecules. Here, we fabricated a SERS substrate by combining nanostructured silver surface and single-crystal monolayer graphene (G-SERS), and focused on its chemical stability. The G-SERS substrate showed SERS even in concentrated hydrochloric acid (35–37%) and heated air up to 400 °C, which is hardly obtainable by normal silver SERS substrates. The chemically stable G-SERS substrate posesses a practical and feasible application, and its high chemical stability provides a new type of SERS technique such as molecular detections at high temperatures or in extreme acidic conditions.
Bandwidth-enhanced and Wide-angle-of-incidence Metamaterial Absorber using a Hybrid Unit Cell
Authors: Nguyen Toan Trung , Lim Sungjoon
Published: October 2017

In this paper, a bandwidth-enhanced and wide-angle-of-incidence metamaterial absorber is proposed using a hybrid unit cell. Owing to symmetric unit cells, high absorptivity is maintained for all polarization angles. A circular-sector unit cell enables high absorptivity under the oblique incidence of both transverse electric (TE) and transverse magnetic (TM) modes. To enhance the bandwidth, we introduced a hybrid unit cell comprising four circular sectors. Two sectors resonate at 10.38 GHz, and two resonate at 10.55 GHz. Since the two absorption frequencies are near each other, the bandwidth increases. The proposed idea is demonstrated with both full-wave simulations and measurements. The simulated absorptivity exceeds 91% around 10.45 GHz at an angle of incidence up to 70° in both TM and TE polarizations. The measured absorptivity at 10.45 GHz is close to 96.5% for all polarization angles under normal incidence. As the angle of incidence changes from 0° to 70°, the measured absorptivity at 10.45 GHz remains above 90% in the TE mode and higher than 94% in the TM mode. Under an oblique incidence, the measured 90% absorption bandwidth is 1.95% from 10.1–10.2 GHz and 10.4–10.5 GHz up to 70° at the TE mode, and 3.39% from 10.15–10.5 GHz up to 70° at the TM mode.
Asymmetric BMP4 signalling improves the realism of kidney organoids
Authors: Mills Christopher G. , Lawrence Melanie L. , Munro David A. D. , Elhendawi Mona , Mullins John J. , Davies Jamie A.
Published: October 2017

We present a strategy for increasing the anatomical realism of organoids by applying asymmetric cues to mimic spatial information that is present in natural embryonic development, and demonstrate it using mouse kidney organoids. Existing methods for making kidney organoids in mice yield developing nephrons arranged around a symmetrical collecting duct tree that has no ureter. We use transplant experiments to demonstrate plasticity in the fate choice between collecting duct and ureter, and show that an environment rich in BMP4 promotes differentiation of early collecting ducts into uroplakin-positive, unbranched, ureter-like epithelial tubules. Further, we show that application of BMP4-releasing beads in one place in an organoid can break the symmetry of the system, causing a nearby collecting duct to develop into a uroplakin-positive, broad, unbranched, ureter-like ‘trunk’ from one end of which true collecting duct branches radiate and induce nephron development in an arrangement similar to natural kidneys. The idea of using local symmetry-breaking cues to improve the realism of organoids may have applications to organoid systems other than the kidney.
Quantifying the anisotropy and tortuosity of permeable pathways in clay-rich mudstones using models based on X-ray tomography
Authors: Backeberg Nils R. , Iacoviello Francesco , Rittner Martin , Mitchell Thomas M. , Jones Adrian P. , Day Richard , Wheeler John , Shearing Paul R. , Vermeesch Pieter , Striolo Alberto
Published: October 2017

The permeability of shales is important, because it controls where oil and gas resources can migrate to and where in the Earth hydrocarbons are ultimately stored. Shales have a well-known anisotropic directional permeability that is inherited from the depositional layering of sedimentary laminations, where the highest permeability is measured parallel to laminations and the lowest permeability is perpendicular to laminations. We combine state of the art laboratory permeability experiments with high-resolution X-ray computed tomography and for the first time can quantify the three-dimensional interconnected pathways through a rock that define the anisotropic behaviour of shales. Experiments record a physical anisotropy in permeability of one to two orders of magnitude. Two- and three-dimensional analyses of micro- and nano-scale X-ray computed tomography illuminate the interconnected pathways through the porous/permeable phases in shales. The tortuosity factor quantifies the apparent decrease in diffusive transport resulting from convolutions of the flow paths through porous media and predicts that the directional anisotropy is fundamentally controlled by the bulk rock mineral geometry. Understanding the mineral-scale control on permeability will allow for better estimations of the extent of recoverable reserves in shale gas plays globally.
The Prevalence of Double Eyelid and the 3D Measurement of Orbital Soft Tissue in Malays and Chinese
Authors: Lu Ting Yin , Kadir Kathreena , Ngeow Wei Cheong , Othman Siti Adibah
Published: October 2017

This study aimed to determine the prevalence of double eyelid among two main Mongoloid ethnicities, the Malays and Chinese who reside in Malaysia. We also measured their periorbital tissue parameters for application in anthropology, optometry, ophthalmology, oculoplastic surgery and maxillofacial trauma surgery. The images of the 103 Malay and 97 Chinese volunteers were captured using indirect 3D photogrammetry, and quantitative measurement was obtained using the software provided by the manufacturer. All Malays and 70.1% of Chinese in this cross section population had double eyelid on both eyes. The mean pretarsal skin height was 3.99 mm for the Malays and 2.29 mm for the Chinese. The Malays appeared to have shorter eyebrow height (11.10 mm) compared to the Chinese (11.79 mm). An opposite pattern could be seen in the measurement of upper eyelid crease height between the Malays (8.33 mm) and the Chinese (4.91 mm). Of note, the intercanthal distance of the Chinese (IDC = 35.85 mm) was wider and their interpupillary distance was narrower (IPD = 62.85 mm) compared to the Malays’ (ICD = 34.21 mm; IPD = 64.04 mm). In conclusion, there were significant differences in the prevalence of double eyelid and periorbital tissue measurements between the Malays and Chinese.
Analysis of the CRISPR-Cas system in bacteriophages active on epidemic strains of Vibrio cholerae in Bangladesh
Authors: Naser Iftekhar Bin , Hoque M. Mozammel , Nahid M. Ausrafuggaman , Tareq Tokee M. , Rocky M. Kamruzzaman , Faruque Shah M.
Published: October 2017

CRISPR-Cas (clustered regularly interspersed short palindromic repeats-CRISPR-associated proteins) are microbial nuclease systems involved in defense against phages. Bacteria also resist phages by hosting phage-inducible chromosomal islands (PICI) which prevent phage reproduction. Vibrio cholerae which causes cholera epidemics, interacts with numerous phages in the environment and in cholera patients. Although CRISPR-Cas systems are usually carried by bacteria and archea, recently V. cholerae specific ICP1 phages were found to host a CRISPR-Cas system that inactivates PICI-like elements (PLE) in V. cholerae. We analyzed a collection of phages and V. cholerae isolated during seasonal cholera epidemics in Bangladesh, to study the distribution, and recent evolution of the phage-encoded CRISPR-Cas system. Five distinct but related phages carrying the CRISPR-Cas system, and possible CRISPR-Cas negative progenitor phages were identified. Furthermore, CRISPR arrays in the phages were found to have evolved by acquisition of new spacers targeting diverse regions of PLEs carried by the V. cholerae strains, enabling the phages to efficiently grow on PLE positive strains. Our results demonstrate a continuing arms-race involving genetic determinants of phage-resistance in V. cholerae, and the phage-encoded CRISPR-Cas system in the co-evolution of V. cholerae and its phages, presumably fostered by their enhanced interactions during seasonal epidemics of cholera.
Dynamic changes in binding interaction networks of sex steroids establish their non-classical effects
Authors: Bálint Mónika , Jeszenői Norbert , Horváth István , Ábrahám István M. , Hetényi Csaba
Published: October 2017

Non-classical signaling in the intracellular second messenger system plays a pivotal role in the cytoprotective effect of estradiol. Estrogen receptor is a common target of sex steroids and important in mediating estradiol-induced neuroprotection. Whereas the mechanism of genomic effects of sex steroids is fairly understood, their non-classical effects have not been elucidated completely. We use real time molecular dynamics calculations to uncover the interaction network of estradiol and activator estren. Besides steroid interactions, we also investigate the co-activation of the receptor. We show how steroid binding to the alternative binding site of the non-classical action is facilitated by the presence of a steroid in the classical binding site and the absence of the co-activator peptide. Uncovering such dynamic mechanisms behind steroid action will help the structure-based design of new drugs with non-classical responses and cytoprotective potential.
Progressive and Prognosis Value of Notch Receptors and Ligands in Hepatocellular Carcinoma: A Systematic Review and Meta-analysis
Authors: Zhang Yingshi , Li Dandan , Feng Fan , An Li , Hui Fuhai , Dang Dasheng , Zhao Qingchun
Published: October 2017

Hepatocellular carcinoma (HCC) is not sensitive to radiotherapy and chemotherapy and experiences postoperative relapse extremely easy, which is the major cause of the high mortality rate. The Notch signaling pathway is expected to become a new target for the biological treatment of HCC. We searched databases for studies that evaluated the expression of Notch receptors and/or ligands in human HCC tissue. The search yielded 15 studies that enrolled 1643 patients. Compared with non-HCC tissues, Notch 1 was associated with a higher expression level (odds risk 1.59, 95% confidence interval 0.34 to 7.45), as well as Notch 3 (2.63, 0.69 to 10.02), Notch 4 (1.33, 0.74 to 2.38) and Jagged 1 (1.47, 0.23 to 9.53); however, Notch 2 showed the opposite result (0.60, 0.30 to 1.20). Larger tumor size (>5 cm), metastasis positive, and micro vascular invasion positive were features that were associated with over-expression in Notch 1 according to the clinicopathological features. The expression levels of Notch 1, 3, 4 and Jagged 1 were associated with higher expression in HCC tissues, while Notch 2 had the opposite result. This study is registered with PROSPERO (CRD42017055782).
The emergent rhizosphere: imaging the development of the porous architecture at the root-soil interface
Authors: Helliwell J. R. , Sturrock C. J. , Mairhofer S. , Craigon J. , Ashton R. W. , Miller A. J. , Whalley W. R. , Mooney S. J.
Published: October 2017

The rhizosphere is the zone of soil influenced by a plant root and is critical for plant health and nutrient acquisition. All below ground resources must pass through this dynamic zone prior to their capture by plant roots. However, researching the undisturbed rhizosphere has proved very challenging. Here we compare the temporal changes to the intact rhizosphere pore structure during the emergence of a developing root system in different soils. High resolution X-ray Computed Tomography (CT) was used to quantify the impact of root development on soil structural change, at scales relevant to individual micro-pores and aggregates (µm). A comparison of micro-scale structural evolution in homogenously packed soils highlighted the impacts of a penetrating root system in changing the surrounding porous architecture and morphology. Results indicate the structural zone of influence of a root can be more localised than previously reported (µm scale rather than mm scale). With time, growing roots significantly alter the soil physical environment in their immediate vicinity through reducing root-soil contact and crucially increasing porosity at the root-soil interface and not the converse as has often been postulated. This ‘rhizosphere pore structure’ and its impact on associated dynamics are discussed.
The characterisation of shellac resin by flow injection and liquid chromatography coupled with electrospray ionisation and mass spectrometry
Authors: Tamburini Diego , Dyer Joanne , Bonaduce Ilaria
Published: October 2017

A strategy based on electrospray ionisation (ESI) in negative mode coupled with quadrupole-time of flight (Q-ToF) detection techniques was adopted to characterise some samples of shellac resin. Flow injection analysis (FIA) was used to investigate the distribution of the components of the resin. Eight groups of compounds with increasing masses were detected and assigned to free acids, esters and polyesters with up to eight units. High pressure liquid chromatography (HPLC) enabled the compounds to be chromatographically separated. Accurate molecular masses and tandem mass (MS/MS) spectra interpretation were used to characterise the different compounds, assigning and/or suggesting molecular structures. In some cases, highly detailed information about the ester linkages was provided by the MS/MS spectra, enabling the different isomers to be distinguished. Oxidation products were also identified in the samples and differences were observed in terms of hydrolysis and oxidation. In addition to providing the first characterisation of shellac by HPLC-ESI-Q-ToF and an atlas of MS/MS spectra of shellac components, this work demonstrates the suitability of the proposed strategy for characterising the resin, and provides the identification of previously unknown degradation products and minor components. This represents a significant step forward in the chemical knowledge of this material.
A Method for Quantifying Molecular Interactions Using Stochastic Modelling and Super-Resolution Microscopy
Authors: Bermudez-Hernandez Keria , Keegan Sarah , Whelan Donna R. , Reid Dylan A. , Zagelbaum Jennifer , Yin Yandong , Ma Sisi , Rothenberg Eli , Fenyö David
Published: October 2017

We introduce the Interaction Factor (IF), a measure for quantifying the interaction of molecular clusters in super-resolution microscopy images. The IF is robust in the sense that it is independent of cluster density, and it only depends on the extent of the pair-wise interaction between different types of molecular clusters in the image. The IF for a single or a collection of images is estimated by first using stochastic modelling where the locations of clusters in the images are repeatedly randomized to estimate the distribution of the overlaps between the clusters in the absence of interaction (IF = 0). Second, an analytical form of the relationship between IF and the overlap (which has the random overlap as its only parameter) is used to estimate the IF for the experimentally observed overlap. The advantage of IF compared to conventional methods to quantify interaction in microscopy images is that it is insensitive to changing cluster density and is an absolute measure of interaction, making the interpretation of experiments easier. We validate the IF method by using both simulated and experimental data and provide an ImageJ plugin for determining the IF of an image.
Hamp1 but not Hamp2 regulates ferroportin in fish with two functionally distinct hepcidin types
Authors: Neves João V. , Ramos Miguel F. , Moreira Ana C. , Silva Tânia , Gomes Maria S. , Rodrigues Pedro N. S.
Published: October 2017

Hepcidin is a small cysteine rich peptide that regulates the sole known cellular iron exporter, ferroportin, effectively controlling iron metabolism. Contrary to humans, where a single hepcidin exists, many fish have two functionally distinct hepcidin types, despite having a single ferroportin gene. This raises the question of whether ferroportin is similarly regulated by the iron regulator Hamp1 and the antimicrobial Hamp2. In sea bass (Dicentrarchus labrax), iron overload prompted a downregulation of ferroportin, associated with an upregulation of hamp1, whereas an opposite response was observed during anemia, with no changes in hamp2 in either situation. During infection, ferroportin expression decreased, indicating iron withholding to avoid microbial proliferation. In vivo administration of Hamp1 but not Hamp2 synthetic peptides caused significant reduction in ferroportin expression, indicating that in teleost fish with two hepcidin types, ferroportin activity is mediated through the iron-regulator Hamp1, and not through the dedicated antimicrobial Hamp2. Additionally, in vitro treatment of mouse macrophages with fish Hamp1 but not Hamp2 caused a decrease in ferroportin levels. These results raise questions on the evolution of hepcidin and ferroportin functional partnership and open new possibilities for the pharmaceutical use of selected fish Hamp2 hepcidins during infections, with no impact on iron homeostasis.
Genome-wide profiling of nardilysin target genes reveals its role in epigenetic regulation and cell cycle progression
Authors: Morita Yusuke , Ohno Mikiko , Nishi Kiyoto , Hiraoka Yoshinori , Saijo Sayaka , Matsuda Shintaro , Kita Toru , Kimura Takeshi , Nishi Eiichiro
Published: October 2017

Post-translational histone modifications, such as acetylation and methylation, are prerequisites for transcriptional regulation. The metalloendopeptidase nardilysin (Nrdc) is a H3K4me2-binding protein that controls thermoregulation and β-cell functions through its transcriptional coregulator function. We herein combined high-throughput ChIP-seq and RNA-seq to achieve the first genome-wide identification of Nrdc target genes. A ChIP-seq analysis of immortalized mouse embryo fibroblasts (iMEF) identified 4053 Nrdc-binding sites, most of which were located in proximal promoter sites (2587 Nrdc-binding genes). Global H3K4me2 levels at Nrdc-binding promoters slightly increased, while H3K9ac levels decreased in the absence of Nrdc. Among Nrdc-binding genes, a comparative RNA-seq analysis identified 448 candidates for Nrdc target genes, among which cell cycle-related genes were significantly enriched. We confirmed decreased mRNA and H3K9ac levels at the promoters of individual genes in Nrdc-deficient iMEF, which were restored by the ectopic introduction of Nrdc. Reduced mRNA levels, but not H3K9ac levels were fully restored by the reintroduction of the peptidase-dead mutant of Nrdc. Furthermore, Nrdc promoted cell cycle progression at multiple stages, which enhanced cell proliferation in vivo. Collectively, our integrative studies emphasize the importance of Nrdc for maintaining a proper epigenetic status and cell growth.
Usefulness and limitations of sample pooling for environmental DNA metabarcoding of freshwater fish communities
Authors: Sato Hirotoshi , Sogo Yuki , Doi Hideyuki , Yamanaka Hiroki
Published: October 2017

Environmental DNA (eDNA) metabarcoding has been used increasingly to assess biodiversity of aquatic vertebrates. However, there still remains to be developed a sampling design of eDNA metabarcoding that can ensure high detection rates of species with minimum total survey effort, especially for large-scale surveys of aquatic organisms. We here tested whether pooling of eDNA samples can be used to evaluate biodiversity of freshwater fishes in four satellite lakes of Lake Biwa, Japan. Fish communities detected by eDNA metabarcoding of the mitochondrial 12S region were compared between the individual and pooled samples. In the individual samples, 31, 22, 33, and 31 fish lineages (proxies for species) were observed at the respective sites, within which moderate spatial autocorrelation existed. In the pooled samples, 30, 20, 29, and 27, lineages were detected, respectively, even after 15 PCR replicates. Lineages accounting for < 0.05% of the total read count of each site’s individual samples were mostly undetectable in the pooled samples. Moreover, fish communities detected were similar among PCR replicates in the pooled samples. Because of the decreased detection rates, the pooling strategy is unsuitable for estimating fish species richness. However, this procedure is useful potentially for among-site comparison of representative fish communities.
Sequencing of glycosaminoglycans with potential to interrogate sequence-specific interactions
Authors: van Kuppevelt Toin H. , Oosterhof Arie , Versteeg Elly M. M. , Podhumljak Emina , van de Westerlo Els M. A. , Daamen Willeke F.
Published: October 2017

Technologies to sequence nucleic acids/proteins are widely available, but straightforward methodologies to sequence complex polysaccharides are lacking. We here put forward a strategy to sequence glycosaminoglycans, long linear polysaccharides involved in many biochemical processes. The method is based on the covalent immobilization and (immuno)chemical characterization of only those size-separated saccharides that harbor the original reducing end of the full-length chain. Using this methodology, the saccharide sequence of the chondroitin sulfate chain of the proteoglycan bikunin was determined. The method can be performed in any standard biochemical lab and opens studies to the interaction of complex saccharide sequences with other biomolecules.
Organometallic Compounds in Chemotherapy Against Leishmania
Authors: do Prado Bruno Rodrigues , Islam Arshad , Frézard Frédéric , Demicheli Cynthia
Published: October 2017

Leishmaniasis today constitutes a major health problem and a mammoth task in the field of drug discovery. This is due to the limited arsenal of effective anti-leishmanial chemotherapeutics, painful parenteral administration, exorbitant price and numerous adverse side effects associated with current clinically established leishmanicidal drugs. These include meglumine antimoniate (Glucantime®), stibogluconate (Pentostam®), liposomal amphotericin B (AmBisome®) and miltefosine. Also, due to the frequent manifestation of chemo-resistance in some countries, an exigent and relentless requisite is to develop innovative, innocuous and valuable anti-leishmanials. Metal compounds still offer excellent prospects for finding new ‘leads’ against parasitic diseases, including leishmaniasis. A number of organometallic compounds have already been evaluated in the therapeutic area to treat and eradicate leishmaniasis. In the last two decades, several new antimony-, bismuth-, tin-, tellurium-, palladium-, rhodium-, iridium-, ruthenium- and iron-based organometallic compound have been evaluated for their anti-leishmanial activity, showing great promise for the discovery of new anti-leishmanial drugs. This chapter outlines the old and new trends, and future perspectives for this exciting research field.
New Avenues for Drug Delivery in Leishmania: Using Treatment of Visceral Leishmaniasis with Amphotericin B as an Exemplar
Authors: Carter Katharine C. , Mullen Alexander B.
Published: October 2017

In this review the benefits of using a drug delivery system (DDS) to improve therapeutic outcome will be discussed, using treatment of visceral leishmaniasis with amphotericin B (AMB), a poorly water soluble drug, as an exemplar. Progress in producing AMB formulations that can be given by intravenous, oral and pulmonary routes of administration is discussed.
The Physical Matrix of the Plasma Membrane as a Target: The Charm of Drugs with Low Specificity
Authors: Rivas Luis , Nácher-Vázquez Montserrat , Andreu David
Published: October 2017

Antimicrobial peptides (AMPs) are ubiquitous through living organisms from different kingdoms. Their role is either defense against invading pathogens, or to strive for survival against microorganisms sharing the same ecological niche. Many AMPs are active against a broad variety of target microorganisms. This, together with their low induction of resistance, heralded the use of AMPs as a new generation of antibiotics. However, studies addressing the feasibility of AMP implementation on leishmaniasis are scarce. This review describes the different approaches to leishmaniasis carried out with AMPs regardless their biological origin. The chapter encompasses studies of AMPs both in vitro and in animal models of Leishmania infection. The mechanisms of action of AMPs both on Leishmania and on the macrophage are described, as well as the underlying molecular determinants of AMPs driving their effectiveness on Leishmania. Finally, the prospects for the feasible implementation of a pharmacological strategy for leishmaniasis based on peptide-based therapies are outlined.
DNA Topoisomerases as Promising Targets forLeishmaniaChemotherapy
Authors: Reguera Rosa M , Escudero-Martínez José M. , Domínguez-Asenjo Bárbara , Gutiérrez-Corbo Camino , Balaña-Fouce Rafael
Published: October 2017

DNA topoisomerases (Top) have been identified as promising targets for therapeutic intervention in leishmaniasis. Leishmania parasites have a complete set of six classes of Top enzymes that operate in solving topological problems generated during DNA replication, transcription and recombination, in the nucleus and in the single mitochondrion. Unlike most TopIBs, the Leishmania enzyme is a heterodimeric (AB) complex with poor homology with that of the host, thereby providing a highly selective therapeutic target for drug discovery. The set of Top type IA enzymes of Leishmania includes a true mitochondrial Top type IA and additional Top type IIIα and Top type IIIβ proteins with exclusive decatenase, rather than relaxase, activity. Top type II enzymes, both nuclear and mitochondrial, carry out strand passage through a double-strand break, including decatenating and unknotting activities, and are key enzymes involved in kinetoplast DNA (kDNA) replication. Due to these differences, many compounds clinically tested as Top type IB and Top type II inhibitors in cancer and antibacterial processes, have been evaluated for repurposing as drugs against Leishmania. As such, camptothecin derivatives, indenoisoquinolines, indeno 1,5-naphthyridines and both acetylenic and alkynoic fatty acids are preferential inhibitors of Leishmania Top type IB. For their part, fluoroquinolones, anthracyclines and podophyllotoxins are renowned inhibitors of Top type II, and good correlations have been reported between their anti-leishmanial effect and Top type II inhibition. In the current chapter we update the structure and function of Leishmania topoisomerases, highlighting the importance of these enzymes as targets for drug discovery.
Molecular Basis of Drug Resistance inLeishmania
Authors: Mondelaers Annelies , Hendrickx Sarah , Caljon Guy , Maes Louis
Published: October 2017

Leishmaniasis has been treated for decades with pentavalent antimony preparations until the emergence of antimony resistance has forced a switch in hyperendemic areas towards alternative therapeutics, such as miltefosine, amphotericin B and paromomycin. The use of miltefosine and amphotericin B has particularly been encouraged as first-line therapy for visceral leishmaniasis, however, all are increasingly confronted with treatment failures and/or the emergence of drug resistance. This chapter provides a concise overview of the mode-of-action of the current anti-leishmanial drugs and links this to the different resistance mechanisms that have been proposed over the past years. The pivotal importance of proactive drug-resistance research is highlighted with reference to the most commonly used laboratory methods.
Visual detection of a nerve agent simulant using chemically modified paper strips and dye-assembled inorganic nanocomposite
Authors: Dey Nilanjan , Jha Satadru , Bhattacharya Santanu
Published: October 2017

Chromogenic probe with oxidized bis-indolyl scaffold has been synthesized for the detection of a nerve gas mimicking agent, DCNP (diethyl cyanophosphonate) at pH 8.0 in water.
Towards the electrochemical diagnostic of influenza virus: development of a graphene–Au hybrid nanocomposite modified influenza virus biosensor based on neuraminidase activity
Authors: Anik Ülkü , Tepeli Yudum , Sayhi Maher , Nsiri Jihene , Diouani Mohamed Fethi
Published: October 2017

An effective electrochemical influenza A biosensor based on a graphene–gold (Au) hybrid nanocomposite modified Au-screen printed electrode has been developed.
Modular synthesis of 4-aminocarbonyl substituted 1,8-naphthalimides and application in single molecule fluorescence detection
Authors: Hearn K. N. , Nalder T. D. , Cox R. P. , Maynard H. D. , Bell T. D. M. , Pfeffer F. M. , Ashton T. D.
Published: October 2017

Robust 1,8-naphthalimide cross-coupling methodology unlocks access to derivatives with interesting photophysical properties and diverse applications.
Highly shape- and regio-selective peroxy–trifluoromethylation of styrene by metal–organic framework Cu3(BTC)2
Authors: Qi Bo , Zhang Tiexin , Li Mochen , He Cheng , Duan Chunying
Published: October 2017

The peroxy and trifluoromethyl groups play important roles in pharmacy, but it is challenging to introduce both of them selectively into the target molecules in a homogeneous catalytic system.
Correction: Efficient n-type dopants with extremely low doping ratios for high performance inverted perovskite solar cells
Authors: Bin Zhengyang , Li Jiangwei , Wang Liduo , Duan Lian
Published: October 2017

Correction for ‘Efficient n-type dopants with extremely low doping ratios for high performance inverted perovskite solar cells’ by Zhengyang Bin et al., Energy Environ. Sci., 2016, 9, 3424–3428.
Transgenerational toxicity of nanopolystyrene particles in the range of μg L−1in the nematodeCaenorhabditis elegans
Authors: Zhao Li , Qu Man , Wong Garry , Wang Dayong
Published: October 2017

We detected the transgenerational toxicity of nanopolystyrene particles in the range of μg L−1in nematodes.
Impact of daily strawberry consumption on blood pressure and arterial stiffness in pre- and stage 1-hypertensive postmenopausal women: a randomized controlled trial
Authors: Feresin Rafaela G. , Johnson Sarah A. , Pourafshar Shirin , Campbell Jeremiah C. , Jaime Salvador J. , Navaei Negin , Elam Marcus L. , Akhavan Neda S. , Alvarez-Alvarado Stacey , Tenenbaum Gershon , Brummel-Smith Kenneth , Salazar Gloria , Figueroa Arturo , Arjmandi Bahram H.
Published: October 2017

Strawberries may improve health of hypertensive postmenopausal women.
Triazolopyrimidines identified as reversible myeloperoxidase inhibitors
Authors: Duclos Franck , Abell Lynn M. , Harden David G. , Pike Kristen , Nowak Kimberly , Locke Gregory A. , Duke Gerald J. , Liu Xiaoqin , Fernando Gayani , Shaw Scott A. , Vokits Benjamin P. , Wurtz Nicholas R. , Viet Andrew , Valente Meriah N. , Stachura Sylwia , Sleph Paul , Khan Javed A. , Gao Ji , Dongre Ashok R. , Zhao Lei , Wexler Ruth R. , Gordon David A. , Kick Ellen K.
Published: October 2017

A novel myeloperoxidase inhibitor, 7-benzylether triazolopyrimidine was discovered which reversibly inhibits enzyme activity and shows pharmacodynamic effects in mouse models.
Dark chemical matter in public screening assays and derivation of target hypotheses
Authors: Jasial Swarit , Bajorath Jürgen
Published: October 2017

Inactive and active analogs, shown is a dark chemical matter (DCM) compound with statistics for primary and confirmatory assays and a bioactive analog with target annotation.
The cytochromeb5CybE is regulated by iron availability and is crucial for azole resistance inA. fumigatus
Authors: Misslinger Matthias , Gsaller Fabio , Hortschansky Peter , Müller Christoph , Bracher Franz , Bromley Michael J. , Haas Hubertus
Published: October 2017

Cytochrome P450 enzymes (P450) play essential roles in redox metabolism in all domains of life including detoxification reactions and sterol biosynthesis.
Correlations in the elemental and metabolic profiles of the lichenDirinaria pictaafter road traffic exposure
Authors: Huang Xulei , Wang Lei , Laserna Anna Karen Carrasco , Li Sam Fong Yau
Published: October 2017

Diverse metabolites were identified in lichens and their correlations with heavy metals revealed metabolic toxicity and the detoxification mechanism.
The role of non-covalent interactions in some 2-trifluoromethylchromones in the solid state
Authors: Alcívar León Christian David , Echeverría Gustavo Alberto , Piro Oscar Enrique , Ulic Sonia Elizabeth , Jios Jorge Luis , Pereañez Jaime Andrés , Henao Castañeda Isabel Cristina , Pérez Hiram
Published: October 2017

Intermolecular interactions in chromone systems and criteria for the existence of C–H⋯F hydrogen bonds involving organic fluorine have been focused on in this work.
g-C3N4 and tetrabutylammonium bromide catalyzed efficient conversion of epoxide to cyclic carbonate under ambient conditions
Authors: Biswas Tanmoy , Mahalingam Venkataramanan
Published: October 2017

A g-C3N4 and n-Bu4N+Br− combination was found to be an efficient catalyst for the conversion of epoxides to cyclic carbonates under CO2 filled balloon conditions.
Easily fabricated and lightweight PPy/PDA/AgNW composites for excellent electromagnetic interference shielding
Authors: Wang Yan , Gu Fu-qiang , Ni Li-juan , Liang Kun , Marcus Kyle , Liu Shu-li , Yang Fan , Chen Jin-ju , Feng Zhe-sheng
Published: October 2017

Conductive polymer composites (CPCs) containing nanoscale conductive fillers have been widely studied for their potential use in various applications.
Deposition of a titania layer on spherical porous silica particles and their nanostructure-induced vapor sensing properties
Authors: Shiba K. , Takei T. , Yoshikawa G. , Ogawa M.
Published: October 2017

A porous titania layer with different nanostructures was formed on monodispersed nanoporous silica spherical particles to demonstrate unique sensitive/selective vapor sensing properties.
Enhanced thermoelectric properties of In2O3(ZnO)5 intrinsic superlattice ceramics by optimizing the sintering process
Authors: Cui Li-Jun , Ge Zhen-Hua , Qin Peng , Feng Jing
Published: October 2017

Thermoelectric (TE) materials have a promising application as they can interconvert thermal energy to electrical energy directly.
Non-equilibrium ultrasound-assisted solid–liquid extraction of boron present in different phases within plants by ICP-OES
Authors: Sun Aide , Xu Qingcai , Ren Liying , Cao Guangjie , Gou Dianda
Published: October 2017

Non-equilibrium ultrasound-assisted solid–liquid extraction of boron present in different phases within plants.
Rapid detection of hexamethylenetetramine based on the substrate UC@SiO2@Au@Ag using SERS
Authors: Tong Rui , Hu Xiaopeng , Fang Guozhen , Sun Shiming , Liu Jingmin , Wang Shuo
Published: October 2017

UC@SiO2@Au@Ag was employed for the first time as a SERS substrate to detect HMT.
The economic and CO2 reduction benefits of a coal-to-olefins plant using a CO2-ECBM process and fuel substitution
Authors: Yu Han , Jiang Qingzhe , Song Zhaozheng , Ma Qian , Yuan Bo , Xiong Huanxi
Published: October 2017

A CO2 reduction method for a coal-to-olefins plant involving CO2 sequestration and fuel switching was proposed. The reduction potential and economical performance of the process were analyzed. Sensitivity analysis was also conducted.
Synthesis, structure–property and flame retardancy relationships of polyphosphonamide and its application on epoxy resins
Authors: Zhao Wei , Wang Gong , Liu Jiping , Ban Daming , Cheng Tianjin , Liu Xiaodong , Li Yongxiang , Huang Yongqing
Published: October 2017

A series of polyphosphonamides (PPDA) with heteroatoms and phosphonamide structures are proposed as highly effective flame retardants in epoxy resins (EP).
Fenton degradation of 4-chlorophenol using H2O2in situ generated by Zn-CNTs/O2 system
Authors: Liu Yong , Liu Yanlan , Yang Zhao , Wang Jianlong
Published: October 2017

In this study, Zn-CNT composites were prepared by the infiltration fusion method and characterized by TEM, XPS and N2 adsorption/desorption experiments.
Metabolomics reveals that PPARα activation protects against lithocholic acid-induced liver injury
Authors: Zhao Qi , Yang Rui , Liu Fang , Wang Jing , Hu Dan-Dan , Yang Xiu-Wei , Li Fei
Published: October 2017

Fenofibrate protected against LCA-induced liver injury.