bluuebunny/crossref_metadata_2025 huggingface dataset:
A “Black Cult” in Early Medieval China: Iranian-Zoroastrian Influence in the Northern Dynasties
Authors: CHEN SANPING , MAIR VICTOR H
Published: January 2017

Through an analysis of Chinese theophoric names - a genre that emerged in the early medieval period largely under heavy Iranian-Sogdian influence - we suggest that there was a contemporary ‘black worship’ or ‘black cult’ in northern China that has since vanished. The followers of this ‘black cult’ ranged from common people living in ethnically mixed frontier communities to the ruling echelons of the Northern Dynasties. By tapping into the fragmentary pre-Islamic Iranian-Sogdian data, we link this ‘black cult’ to the now nearly forgotten ancient Iranic worship of the Avestan family of heroes centered around Sāma. This religio-cultural exchange prompts an examination of the deliberate policy by the ethnic rulers of the Northern Dynasties to attract Central Asian immigrants for political reasons, a precursor to the Semu, the Mongols’ ‘assistant conquerors’ in the Yuan dynasty.
Kinder als Akteure in der Zusammenarbeit von Bildungsinstitutionen und Familien?
Authors: Betz Tanja , Eunicke Nicoletta
Published: January 2017

Zusammenfassung. Die Zusammenarbeit zwischen Familien und Bildungsinstitutionen gilt als Standard professionellen pädagogischen Handelns. Sie ist in allen Bildungs- und Erziehungsplänen der Länder verankert und soll dem Wohl des Kindes dienen. Der Beitrag geht der bislang nicht untersuchten Frage nach wie Kinder in den Plänen im Kontext Zusammenarbeit konzeptualisiert werden. Die Inhaltsanalyse der 16 Pläne zeigt, dass Kinder vielfach als Objekte des Handelns Erwachsener konzeptualisiert werden. Die Akteurschaft von Kindern und ihre Perspektiven auf Zusammenarbeit bleiben damit unsichtbar. Aus den Befunden werden Schlussfolgerungen für die Professionalisierungsdebatte abgeleitet.
RNA-binding protein SAMD4 regulates skeleton development through translational inhibition of Mig6 expression
Authors: Niu Ningning , Xiang Jian-Feng , Yang Qin , Wang Lijun , Wei Zhanying , Chen Ling-Ling , Yang Li , Zou Weiguo
Published: January 2017

Protein translation regulation has essential roles in inflammatory responses, cancer initiation and the pathogenesis of several neurodegenerative disorders. However, the role of the regulation of protein translation in mammalian skeleton development has been rarely elaborated. Here we report that the lack of the RNA-binding protein sterile alpha motif domain containing protein 4 (SAMD4) resulted in multiple developmental defects in mice, including delayed bone development and decreased osteogenesis. Samd4-deficient mesenchymal progenitors exhibit impaired osteoblast differentiation and function. Mechanism study demonstrates that SAMD4 binds the Mig6 mRNA and inhibits MIG6 protein synthesis. Consistent with this, Samd4-deficient cells have increased MIG6 protein level and knockdown of Mig6 rescues the impaired osteogenesis in Samd4-deficient cells. Furthermore, Samd4-deficient mice also display chondrocyte defects, which is consistent with the regulation of MIG6 protein level by SAMD4. These findings define SAMD4 as a previously unreported key regulator of osteoblastogenesis and bone development, implying that regulation of protein translation is an important mechanism governing skeletogenesis and that control of protein translation could have therapeutic potential in metabolic bone diseases, such as osteoporosis.
Erratum: Global occurrence and heterogeneity of the Roseobacter-clade species Ruegeria mobilis
Authors: Sonnenschein Eva C , Nielsen Kristian F , D’Alvise Paul , Porsby Cisse H , Melchiorsen Jette , Heilmann Jens , Kalatzis Panos G , López-Pérez Mario , Bunk Boyke , Spröer Cathrin , Middelboe Mathias , Gram Lone
Published: January 2017

Correction to: The ISME Journal (2016) 11, 569–583; doi:10.1038/ismej.2016.111; published online 23 August 2016 The affiliation listed for Boyke Bunk and Cathrin Spröer was incorrectly listed as ‘Helmholtz Centre for Infection Research, Braunschweig, Germany’. The correct affiliation is ‘Leibniz-Institute DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Braunschweig, Germany’.
Refined Ordovician timescale reveals no link between asteroid breakup and biodiversification
Authors: Lindskog A. , Costa M. M. , Rasmussen C.M.Ø. , Connelly J. N. , Eriksson M. E.
Published: January 2017

The catastrophic disruption of the L chondrite parent body in the asteroid belt c. 470 Ma initiated a prolonged meteorite bombardment of Earth that started in the Ordovician and continues today. Abundant L chondrite meteorites in Middle Ordovician strata have been interpreted to be the consequence of the asteroid breakup event. Here we report a zircon U-Pb date of 467.50±0.28 Ma from a distinct bed within the meteorite-bearing interval of southern Sweden that, combined with published cosmic-ray exposure ages of co-occurring meteoritic material, provides a precise age for the L chondrite breakup at 468.0±0.3 Ma. The new zircon date requires significant revision of the Ordovician timescale that has implications for the understanding of the astrogeobiologic development during this period. It has been suggested that the Middle Ordovician meteorite bombardment played a crucial role in the Great Ordovician Biodiversification Event, but this study shows that the two phenomena were unrelated.
Mineral inclusions in diamonds may be synchronous but not syngenetic
Authors: Nestola Fabrizio , Jung Haemyeong , Taylor Lawrence A.
Published: January 2017

It is widely assumed that mineral inclusions and their host diamonds are ‘syngenetic’ in origin, which means that they formed simultaneously and from the same chemical processes. Mineral inclusions that, instead, were formed earlier with respect to diamonds are termed protogenetic. However, minerals can have the same age as the diamonds in that they become enclosed in and isolated from any further isotopic exchange. But this is termed ‘synchronous’ not ‘syngenetic’. Here we demonstrate conclusively the protogenesis of inclusions in diamonds, based upon data from an exceptional fragment of a diamond-bearing peridotite, its clinopyroxene and a gem-quality diamond. Clinopyroxenes in the xenolith had the same chemistry and crystallographic orientation as those for inclusions in the diamond. With our results with garnets, olivines and sulfides, we can state that a major portion of the mineral inclusions in non-coated, monocrystalline-lithospheric diamonds are protogenetic. Our discovery here presented has implications for all genetic aspects of diamond growth, including their ages.
Scalable high-precision tuning of photonic resonators by resonant cavity-enhanced photoelectrochemical etching
Authors: Gil-Santos Eduardo , Baker Christopher , Lemaître Aristide , Ducci Sara , Gomez Carmen , Leo Giuseppe , Favero Ivan
Published: January 2017

Photonic lattices of mutually interacting indistinguishable cavities represent a cornerstone of collective phenomena in optics and could become important in advanced sensing or communication devices. The disorder induced by fabrication technologies has so far hindered the development of such resonant cavity architectures, while post-fabrication tuning methods have been limited by complexity and poor scalability. Here we present a new simple and scalable tuning method for ensembles of microphotonic and nanophotonic resonators, which enables their permanent collective spectral alignment. The method introduces an approach of cavity-enhanced photoelectrochemical etching in a fluid, a resonant process triggered by sub-bandgap light that allows for high selectivity and precision. The technique is presented on a gallium arsenide nanophotonic platform and illustrated by finely tuning one, two and up to five resonators. It opens the way to applications requiring large networks of identical resonators and their spectral referencing to external etalons.
Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies
Authors: Módos Dezső , Bulusu Krishna C. , Fazekas Dávid , Kubisch János , Brooks Johanne , Marczell István , Szabó Péter M. , Vellai Tibor , Csermely Péter , Lenti Katalin , Bender Andreas , Korcsmáros Tamás
Published: January 2017

Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein–protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type. We found that first neighbours have at least as high degree, betweenness centrality and clustering coefficient as cancer-related proteins themselves, indicating a previously unknown central network position. We identified a complementary strategy for mutated and differentially expressed proteins, where the affect of differentially expressed proteins having smaller network centrality is compensated with high centrality first neighbours. These first neighbours can be considered as key, so far hidden, components in cancer rewiring, with similar importance as mutated proteins. These observations strikingly suggest targeting first neighbours as a novel strategy for disrupting cancer-specific networks. Remarkably, our survey revealed 223 marketed drugs already targeting first neighbour proteins but applied mostly outside oncology, providing a potential list for drug repurposing against solid cancers. For the very central first neighbours, whose direct targeting would cause several side effects, we suggest a cancer-mimicking strategy by targeting their interactors (second neighbours of cancer-related proteins, having a central protein affecting position, similarly to the cancer-related proteins). Hence, we propose to include first neighbours to network medicine based approaches for (but not limited to) anticancer therapies.
Utility of baseline, interim and end-of-treatment 18F-FDG PET/CT in extranodal natural killer/T-cell lymphoma patients treated with L-asparaginase/pegaspargase
Authors: Chang Yu , Fu Xiaorui , Sun Zhenchang , Xie Xinli , Wang Ruihua , Li Zhaoming , Zhang Xudong , Sheng Guangyao , Zhang Mingzhi
Published: January 2017

Positron emission tomography-computed tomography (PET/CT) is widely used for initial staging and monitoring treatment responses in Hodgkin and diffuse large B-cell lymphoma. However, its prognostic value in extranodal natural killer (NK)/T-cell lymphoma (ENKL) remains unclear. Here, we conducted a retrospective study to determine the impact of PET/CT in ENKL. Fifty-two patients newly diagnosed with ENKL were enrolled. Baseline maximum standardized uptake values (SUVmax), whole-body metabolic tumor volume (WBMTV) and whole-body total lesion glycolysis (WBTLG) were recorded. Additionally, interim PET/CT (I-PET) and end-of-treatment PET/CT (E-PET) results were scored using a 5-point scale. Patients were divided into groups using baseline parameter cut-off values; significant differences were found in overall survival (OS) and progression-free survival (PFS) between the high and low WBMTV and WBTLG groups and in OS between the two SUVmax groups. Positive I-PET and E-PET results predicted inferior PFS and OS. A multivariate analysis showed that baseline WBTLG, I-PET and E-PET results were associated with PFS and OS, and baseline SUVmax was an independent predictor of OS. Thus, baseline WBTLG, I-PET and E-PET results are good predictors of PFS and OS in ENKL patients who received L-asparaginase/pegaspargase in their first-line treatment, and baseline SUVmax is a valuable tool for assessing OS.
The Global Relationship between Chromatin Physical Topology, Fractal Structure, and Gene Expression
Authors: Almassalha L. M. , Tiwari A. , Ruhoff P. T. , Stypula-Cyrus Y. , Cherkezyan L. , Matsuda H. , Dela Cruz M. A. , Chandler J. E. , White C. , Maneval C. , Subramanian H. , Szleifer I. , Roy H. K. , Backman V.
Published: January 2017

Most of what we know about gene transcription comes from the view of cells as molecular machines: focusing on the role of molecular modifications to the proteins carrying out transcriptional reactions at a loci-by-loci basis. This view ignores a critical reality: biological reactions do not happen in an empty space, but in a highly complex, interrelated, and dense nanoenvironment that profoundly influences chemical interactions. We explored the relationship between the physical nanoenvironment of chromatin and gene transcription in vitro. We analytically show that changes in the fractal dimension, D, of chromatin correspond to simultaneous increases in chromatin accessibility and compaction heterogeneity. Using these predictions, we demonstrate experimentally that nanoscopic changes to chromatin D within thirty minutes correlate with concomitant enhancement and suppression of transcription. Further, we show that the increased heterogeneity of physical structure of chromatin due to increase in fractal dimension correlates with increased heterogeneity of gene networks. These findings indicate that the higher order folding of chromatin topology may act as a molecular-pathway independent code regulating global patterns of gene expression. Since physical organization of chromatin is frequently altered in oncogenesis, this work provides evidence pairing molecular function to physical structure for processes frequently altered during tumorigenesis.
Piperine regulates UCP1 through the AMPK pathway by generating intracellular lactate production in muscle cells
Authors: Kim Nami , Nam Miso , Kang Mi Sun , Lee Jung Ok , Lee Yong Woo , Hwang Geum-Sook , Kim Hyeon Soo
Published: January 2017

This study characterizes the human metabolic response to piperine, a curcumin extract, and the details of its underlying molecular mechanism. Using1H-NMR-based metabolome analysis, we showed the metabolic effect of piperine on skeletal muscle and found that piperine increased the level of intracellular lactate, an important metabolic intermediate that controls expression of several genes involved in mitochondrial activity. Piperine also induced the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target, acetyl-CoA carboxylase (ACC), while additionally stimulating glucose uptake in an AMPK dependent manner. Piperine also stimulates the p38 mitogen-activated protein kinase (p38 MAPK), an effect that was reversed by pretreatment with compound C, an AMPK inhibitor. Inhibition of p38 MAPK resulted in no piperine-induced glucose uptake. Increased level of lactate resulted in increased expression of mitochondrial uncoupling protein 1 (UCP1), which regulates energy expenditure, thermogenesis, and fat browning. Knock-down of AMPK blocked piperine-induced UCP1 up-regulation, demonstrating the required role of AMPK in this effect. Taken together, these results suggest that piperine leads to benign metabolic effects by activating the AMPK-p38 MAPK signaling pathway and UCP1 expression by activating intracellular lactate production in skeletal muscle.
Allosteric Inhibition of Phosphoenolpyruvate Carboxylases is Determined by a Single Amino Acid Residue in Cyanobacteria
Authors: Takeya Masahiro , Hirai Masami Yokota , Osanai Takashi
Published: January 2017

Phosphoenolpyruvate carboxylase (PEPC) is an important enzyme for CO2 fixation and primary metabolism in photosynthetic organisms including cyanobacteria. The kinetics and allosteric regulation of PEPCs have been studied in many organisms, but the biochemical properties of PEPC in the unicellular, non-nitrogen-fixing cyanobacterium Synechocystis sp. PCC 6803 have not been clarified. In this study, biochemical analysis revealed that the optimum pH and temperature of Synechocystis 6803 PEPC proteins were 7.3 and 30 °C, respectively. Synechocystis 6803 PEPC was found to be tolerant to allosteric inhibition by several metabolic effectors such as malate, aspartate, and fumarate compared with other cyanobacterial PEPCs. Comparative sequence and biochemical analysis showed that substitution of the glutamate residue at position 954 with lysine altered the enzyme so that it was inhibited by malate, aspartate, and fumarate. PEPC of the nitrogen-fixing cyanobacterium Anabaena sp. PCC 7120 was purified, and its activity was inhibited in the presence of malate. Substitution of the lysine at position 946 (equivalent to position 954 in Synechocystis 6803) with glutamate made Anabaena 7120 PEPC tolerant to malate. These results demonstrate that the allosteric regulation of PEPC in cyanobacteria is determined by a single amino acid residue, a characteristic that is conserved in different orders.
Correction: Corrigendum: Differential expression of lncRNAs during the HIV replication cycle: an underestimated layer in the HIV-host interplay
Authors: Trypsteen Wim , Mohammadi Pejman , Van Hecke Clarissa , Mestdagh Pieter , Lefever Steve , Saeys Yvan , De Bleser Pieter , Vandesompele Jo , Ciuffi Angela , Vandekerckhove Linos , De Spiegelaere Ward
Published: January 2017

Scientific Reports 6: Article number: 36111; published online: 26 October 2016; updated: 24 January 2017 In this Article, Yvan Saeys is incorrectly listed as being affiliated with ‘Department of Biomedical Molecular Biology Ghent University, Ghent, Belgium’. The correct affiliations are listed below:
NLRP3 inflammasome: Pathogenic role and potential therapeutic target for IgA nephropathy
Authors: Tsai Yu-Ling , Hua Kuo-Feng , Chen Ann , Wei Chyou-Wei , Chen Wen-Shiang , Wu Cheng-Yeu , Chu Ching-Liang , Yu Yung-Luen , Lo Chia-Wen , Ka Shuk-Man
Published: January 2017

We have previously showed that IL-1β is involved in the pathogenesis of both spontaneously occurring and passively induced IgA nephropathy (IgAN) models. However, the exact causal-relationship between NLRP3 inflammasome and the pathogenesis of IgAN remains unknown. In the present study, we showed that [1] IgA immune complexes (ICs) activated NLRP3 inflammasome in macrophages involving disruption of mitochondrial integrity and induction of mitochondrial ROS, bone marrow-derived dendritic cells (BMDCs) and renal intrinsic cells; [2] knockout of NLRP3 inhibited IgA ICs-mediated activation of BMDCs and T cells; and [3] knockout of NLRP3 or a kidney-targeting delivery of shRNA of NLRP3 improved renal function and renal injury in a mouse IgAN model. These results strongly suggest that NLRP3 inflammasome serves as a key player in the pathogenesis of IgAN partly through activation of T cells and mitochondrial ROS production and that a local, kidney-targeting suppression of NLRP3 be a therapeutic strategy for IgAN.
A visual processing advantage for young-adolescent deaf observers: Evidence from face and object matching tasks
Authors: Megreya Ahmed M. , Bindemann Markus
Published: January 2017

It is unresolved whether the permanent auditory deprivation that deaf people experience leads to the enhanced visual processing of faces. The current study explored this question with a matching task in which observers searched for a target face among a concurrent lineup of ten faces. This was compared with a control task in which the same stimuli were presented upside down, to disrupt typical face processing, and an object matching task. A sample of young-adolescent deaf observers performed with higher accuracy than hearing controls across all of these tasks. These results clarify previous findings and provide evidence for a general visual processing advantage in deaf observers rather than a face-specific effect.
Interacting ultracold atomic kicked rotors: loss of dynamical localization
Authors: Qin Pinquan , Andreanov Alexei , Park Hee Chul , Flach Sergej
Published: January 2017

We study the fate of dynamical localization of two quantum kicked rotors with contact interaction, which relates to experimental realizations of the rotors with ultra-cold atomic gases. A single kicked rotor is known to exhibit dynamical localization, which takes place in momentum space. The contact interaction affects the evolution of the relative momentum k of a pair of interacting rotors in a non-analytic way. Consequently the evolution operator U is exciting large relative momenta with amplitudes which decay only as a power law 1/k4. This is in contrast to the center-of-mass momentum K for which the amplitudes excited by U decay superexponentially fast with K. Therefore dynamical localization is preserved for the center-of-mass momentum, but destroyed for the relative momentum for any nonzero strength of interaction.
IL-22-producing CD4+T cells in the treatment response of rheumatoid arthritis to combination therapy with methotrexate and leflunomide
Authors: Zhong Wei , Zhao Ling , Liu Tao , Jiang Zhenyu
Published: January 2017

T cells are key players in immune-mediated rheumatoid arthritis (RA). We previously reported that interleukin (IL)-22+CD4+T helper (IL-22+Th) cells and IL-22 critically control the pathogenesis of RA. Here we monitored circulating levels of different IL-22+Th cell subsets and measured plasma levels of IL-22, IL-17, and interferon (IFN)-γ in 60 patients with active RA following 12-week combination methotrexate (MTX) and leflunomide (LEF) therapy (MTX+LEF) and 20 healthy individuals. We found the frequencies of circulating IFN-γ−IL-17−IL-22+(Th22), IFN-γ−IL-17+(total Th17), IFN-γ+IL-17−IL-22+(IL-22+Th1) cells, and IFN-γ−IL-17+IL-22+(IL-22+Th17) cells, as well as the plasma levels of IL-22, IL-17 and IFN-γ to be significantly reduced in RA patients that responded to treatment, but not in non-responders. Reductions in plasma IL-22 level significantly correlated with percentage of circulating Th22 cells and the decrease of plasma IL-22 level correlated with the reduction of DAS28 in responders. Our data suggests that circulating Th22 cells and plasma IL-22 level play a detrimental role in RA. The combination MTX+LEF therapy, by targeting Th22 cells and reducing IL-22 level, relieves the immune defects and ameliorates symptoms of RA. This study provides novel mechanistic understanding of the pathogenesis of RA, which may promote a design of better therapies for RA.
MoVrp1, a putative verprolin protein, is required for asexual development and infection in the rice blast fungus Magnaporthe oryzae
Authors: Huang Lin , Zhang Shengpei , Yin Ziyi , Liu Muxing , Li Bing , Zhang Haifeng , Zheng Xiaobo , Wang Ping , Zhang Zhengguang
Published: January 2017

Endocytosis is a crucial cellular process in eukaryotic cells which involves clathrin and/or adaptor proteins, lipid kinases, phosphatases and the actin cytoskeleton. Verprolin proteins, such as Vrp1 in Saccharomyces cerevisiae, are conserved family proteins that regulate actin binding and endocytosis. Here, we identified and characterized MoVrp1 as the yeast Vrp1 homolog in Magnaporthe oryzae. Deletion of the MoVRP1 gene resulted in defects in vegetative growth, asexual development, and infection of the host plant. The ∆Movrp1 mutants also exhibited decreased extracellular peroxidase and laccase activities and showed defects in colony pigmentation, hyphal surface hydrophobicity, cell wall integrity, autophagy, endocytosis, and secretion of avirulent effector. Our studies provided new evidences that MoVrp1 involved in actin cytoskeleton is important for growth, morphogenesis, cellular trafficking, and fungal pathogenesis.
Holographic image generation with a thin-film resonance caused by chalcogenide phase-change material
Authors: Lee Seung-Yeol , Kim Yong-Hae , Cho Seong-M. , Kim Gi Heon , Kim Tae-Youb , Ryu Hojun , Kim Han Na , Kang Han Byeol , Hwang Chi-Young , Hwang Chi-Sun
Published: January 2017

The development of digital holography is anticipated for the viewing of 3D images by reconstructing both the amplitude and phase information of the object. Compared to analog holograms written by a laser interference, digital hologram technology has the potential to realize a moving 3D image using a spatial light modulator. However, to ensure a high-resolution 3D image with a large viewing angle, the hologram panel requires a near-wavelength scale pixel pitch with a sufficient large numbers of pixels. In this manuscript, we demonstrate a digital hologram panel based on a chalcogenide phase-change material (PCM) which has a pixel pitch of 1 μm and a panel size of 1.6 × 1.6 cm2. A thin film of PCM encapsulated by dielectric layers can be used for the hologram panel by means of excimer laser lithography. By tuning the thicknesses of upper and lower dielectric layers, a color-selective diffraction panel is demonstrated since a thin film resonance caused by dielectric can affect to the absorption and diffraction spectrum of the proposed hologram panel. We also show reflection color of a small active region (1 μm × 4 μm) made by ultra-thin PCM layer can be electrically changed.
Focusing and alignment of erythrocytes in a viscoelastic medium
Authors: Go Taesik , Byeon Hyeokjun , Lee Sang Joon
Published: January 2017

Viscoelastic fluid flow-induced cross-streamline migration has recently received considerable attention because this process provides simple focusing and alignment over a wide range of flow rates. The lateral migration of particles depends on the channel geometry and physicochemical properties of particles. In this study, digital in-line holographic microscopy (DIHM) is employed to investigate the lateral migration of human erythrocytes induced by viscoelastic fluid flow in a rectangular microchannel. DIHM provides 3D spatial distributions of particles and information on particle orientation in the microchannel. The elastic forces generated in the pressure-driven flows of a viscoelastic fluid push suspended particles away from the walls and enforce erythrocytes to have a fixed orientation. Blood cell deformability influences the lateral focusing and fixed orientation in the microchannel. Different from rigid spheres and hardened erythrocytes, deformable normal erythrocytes disperse from the channel center plane, as the flow rate increases. Furthermore, normal erythrocytes have a higher angle of inclination than hardened erythrocytes in the region near the side-walls of the channel. These results may guide the label-free diagnosis of hematological diseases caused by abnormal erythrocyte deformability.
Fine mapping genetic associations between the HLA region and extremely high intelligence
Authors: Zabaneh Delilah , Krapohl Eva , Simpson Michael A. , Miller Mike B. , Iacono William G. , McGue Matt , Putallaz Martha , Lubinski David , Plomin Robert , Breen Gerome
Published: January 2017

General cognitive ability (intelligence) is one of the most heritable behavioural traits and most predictive of socially important outcomes and health. We hypothesized that some of the missing heritability of IQ might lie hidden in the human leukocyte antigen (HLA) region, which plays a critical role in many diseases and traits but is not well tagged in conventional GWAS. Using a uniquely powered design, we investigated whether fine-mapping of the HLA region could narrow the missing heritability gap. Our case-control design included 1,393 cases with extremely high intelligence scores (top 0.0003 of the population equivalent to IQ > 147) and 3,253 unselected population controls. We imputed variants in 200 genes across the HLA region, one SNP (rs444921) reached our criterion for study-wide significance. SNP-based heritability of the HLA variants was small and not significant (h2 = 0.3%, SE = 0.2%). A polygenic score from the case-control genetic association analysis of SNPs in the HLA region did not significantly predict individual differences in intelligence in an independent unselected sample. We conclude that although genetic variation in the HLA region is important to the aetiology of many disorders, it does not appear to be hiding much of the missing heritability of intelligence.
The sorting receptor Rer1 controls Purkinje cell function via voltage gated sodium channels
Authors: Valkova Christina , Liebmann Lutz , Krämer Andreas , Hübner Christian A. , Kaether Christoph
Published: January 2017

Rer1 is a sorting receptor in the early secretory pathway that controls the assembly and the cell surface transport of selected multimeric membrane protein complexes. Mice with a Purkinje cell (PC) specific deletion of Rer1 showed normal polarization and differentiation of PCs and normal development of the cerebellum. However, PC-specific loss of Rer1 led to age-dependent motor deficits in beam walk, ladder climbing and gait. Analysis of brain sections revealed a specific degeneration of PCs in the anterior cerebellar lobe in old animals. Electrophysiological recordings demonstrated severe deficits in spontaneous action potential generation. Measurements of resurgent currents indicated decreased surface densities of voltage-gated sodium channels (Nav), but not changes in individual channels. Analysis of mice with a whole brain Rer1-deletion demonstrated a strong down-regulation of Nav1.6 and 1.1 in the absence of Rer1, whereas protein levels of the related Cav2.1 and of Kv3.3 and 7.2 channels were not affected. The data suggest that Rer1 controls the assembly and transport of Nav1.1 and 1.6, the principal sodium channels responsible for recurrent firing, in PCs.
Ligand binding pocket of a novel Allatostatin receptor type C of stick insect, Carausius morosus
Authors: Duan Sahbaz Burcin , Sezerman Osman Ugur , Torun Hamdi , Birgül Iyison Necla
Published: January 2017

Allatostatins (AST) are neuropeptides with variable function ranging from regulation of developmental processes to the feeding behavior in insects. They exert their effects by binding to cognate GPCRs, called Allatostatin receptors (AlstR), which emerge as promising targets for pesticide design. However, AlstRs are rarely studied. This study is the first reported structural study on AlstR-AST interaction. In this work, the first C type AlstR from the stick insectCarausius morosus(CamAlstR-C) was identified and its interaction with type C AST peptide was shown to be physically consistent with the experimental results. The proposed structure of CamAlstR-C revealed a conserved motif within the third extracellular loop, which, together with the N-terminus is essential for ligand binding. In this work, computational studies were combined with molecular and nano-scale approaches in order to introduce an unknown GPCR-ligand system. Consequently, the data obtained provided a reliable target region for future agonist/inverse agonist studies on AlstRs.
Males develop faster and more severe hepatocellular carcinoma than females in krasV12 transgenic zebrafish
Authors: Li Yan , Li Hankun , Spitsbergen Jan M. , Gong Zhiyuan
Published: January 2017

Hepatocellular carcinoma (HCC) is more prevalent in men than women, but the reason for this gender disparity is not well understood. To investigate whether zebrafish could be used to study the gender disparity of HCC, we compared the difference of liver tumorigenesis between female and male fish during early tumorigenesis and long-term tumor progression in our previously established inducible and reversible HCC model – the krasV12 transgenic zebrafish. We found that male fish developed HCC faster than females. The male tumors were more severe from the initiation stage, characteristic of higher proliferation, activation of WNT/β-catenin pathway and loss of cell adhesion. During long-term tumor progression, the male tumors developed into more advanced multi-nodular tumors, whereas the female tumors remain uniform and homogenous. Moreover, regression of male tumors required longer time. We further investigated the role of sex hormones in krasV12 transgenic fish. Estrogen treatment showed tumor suppressing effect during early tumorigenesis through inhibiting cell proliferation, whereas androgen accelerated tumor growth by promoting cell proliferation. Overall, our study presented the zebrafish as a useful animal model for study of gender disparity of HCC.
Culture adaptation of malaria parasites selects for convergent loss-of-function mutants
Authors: Claessens Antoine , Affara Muna , Assefa Samuel A. , Kwiatkowski Dominic P. , Conway David J.
Published: January 2017

Cultured human pathogens may differ significantly from source populations. To investigate the genetic basis of laboratory adaptation in malaria parasites, clinical Plasmodium falciparum isolates were sampled from patients and cultured in vitro for up to three months. Genome sequence analysis was performed on multiple culture time point samples from six monoclonal isolates, and single nucleotide polymorphism (SNP) variants emerging over time were detected. Out of a total of five positively selected SNPs, four represented nonsense mutations resulting in stop codons, three of these in a single ApiAP2 transcription factor gene, and one in SRPK1. To survey further for nonsense mutants associated with culture, genome sequences of eleven long-term laboratory-adapted parasite strains were examined, revealing four independently acquired nonsense mutations in two other ApiAP2 genes, and five in Epac. No mutants of these genes exist in a large database of parasite sequences from uncultured clinical samples. This implicates putative master regulator genes in which multiple independent stop codon mutations have convergently led to culture adaptation, affecting most laboratory lines of P. falciparum. Understanding the adaptive processes should guide development of experimental models, which could include targeted gene disruption to adapt fastidious malaria parasite species to culture.
Treatment effects of lysozyme-shelled microbubbles and ultrasound in inflammatory skin disease
Authors: Liao Ai-Ho , Hung Chi-Ray , Lin Chieh-Fu , Lin Yi-Chun , Chen Hang-Kang
Published: January 2017

Acne vulgaris is the most common skin disorder, and is caused by Propionibacterium acnes (P. acnes) and can induce inflammation. Antibiotic therapy often needs to be administered for long durations in acne therapy, which results in extensive antibiotic exposure. The present study investigated a new treatment model for evaluating the antibacterial effects of lysozyme (LY)-shelled microbubbles (MBs) and ultrasound (US)-mediated LY-shelled MBs cavitation against P. acnes both in vitro and in vivo, with the aims of reducing the dose and treatment duration and improving the prognosis of acne vulgaris. In terms of the in vitro treatment efficacy, the growth of P. acnes was inhibited by 86.08 ± 2.99% in the LY-shelled MBs group and by 57.74 ± 3.09% in the LY solution group. For US power densities of 1, 2, and 3 W/cm2 in the LY-shelled MBs group, the growth of P. acnes was inhibited by 95.79 ± 3.30%, 97.99 ± 1.16%, and 98.69 ± 1.13%, respectively. The in vivo results showed that the recovery rate on day 13 was higher in the US group with LY-shelled MBs (97.8 ± 19.8%) than in the LY-shelled MBs group (90.3 ± 23.3%). Our results show that combined treatments of US and LY-shelled MBs can significantly reduce the treatment duration and inhibit P.-acnes-induced inflammatory skin diseases.
The identification and molecular mechanism of anti-stroke traditional Chinese medicinal compounds
Authors: Liu Jia-Qian , Dai Shao-Xing , Zheng Jun-Juan , Guo Yi-Cheng , Li Wen-Xing , Li Gong-Hua , Huang Jing-Fei
Published: January 2017

Stroke is a worldwide epidemic disease with high morbidity and mortality. The continuously exploration of anti-stroke medicines and molecular mechanism has a long way to go. In this study, in order to screen candidate anti-stroke compounds, more than 60000 compounds from traditional Chinese medicine (TCM) database were computationally analyzed then docked to the 15 known anti-stroke targets. 192 anti-stroke plants for clinical therapy and 51 current anti-stroke drugs were used to validate docking results. Totally 2355 candidate anti-stroke compounds were obtained. Among these compounds, 19 compounds are structurally identical with 16 existing drugs in which part of them have been used for anti-stroke treatment. Furthermore, these candidate compounds were significantly enriched in anti-stroke plants. Based on the above results, the compound-target-plant network was constructed. The network reveals the potential molecular mechanism of anti-stroke for these compounds. Most of candidate compounds and anti-stroke plants are tended to interact with target NOS3, PSD-95 and PDE5A. Finally, using ADMET filter, we identified 35 anti-stroke compounds with favorable properties. The 35 candidate anti-stroke compounds offer an opportunity to develop new anti-stroke drugs and will improve the research on molecular mechanism of anti-stroke.
Default mode network deactivation during emotion processing predicts early antidepressant response
Authors: Spies M , Kraus C , Geissberger N , Auer B , Klöbl M , Tik M , Stürkat I-L , Hahn A , Woletz M , Pfabigan D M , Kasper S , Lamm C , Windischberger C , Lanzenberger R
Published: January 2017

Several previous functional magnetic resonance imaging (fMRI) studies have demonstrated the predictive value of brain activity during emotion processing for antidepressant response, with a focus on clinical outcome after 6–8 weeks. However, longitudinal studies emphasize the paramount importance of early symptom improvement for the course of disease in major depressive disorder (MDD). We therefore aimed to assess whether neural activity during the emotion discrimination task (EDT) predicts early antidepressant effects, and how these predictive measures relate to more sustained response. Twenty-three MDD patients were investigated once with ultrahigh-field 7T fMRI and the EDT. Following fMRI, patients received Escitalopram in a flexible dose schema and were assessed with the Hamilton Depression Rating Scale (HAMD) before, and after 2 and 4 weeks of treatment. Deactivation of the precuneus and posterior cingulate cortex (PCC) during the EDT predicted change in HAMD scores after 2 weeks of treatment. Baseline EDT activity was not predictive of HAMD change after 4 weeks of treatment. The precuneus and PCC are integral components of the default mode network (DMN). We show that patients who exhibit stronger DMN suppression during emotion processing are more likely to show antidepressant response after 2 weeks. This is, to our knowledge, the first study to show that DMN activity predicts early antidepressant effects. However, DMN deactivation did not predict response at 4 weeks, suggesting that our finding is representative of early, likely treatment-related, yet unspecific symptom improvement. Regardless, early effects may be harnessed for optimization of treatment regimens and patient care.
Nanostructured ZnO as a structural template for the growth of ZIF-8 with tunable hierarchical porosity for CO2 conversion
Authors: Kim Min-Kyeong , Kim Daeok , Seo Jung Yoon , Buyukcakir Onur , Coskun Ali
Published: January 2017

We report a new approach to introduce hierarchical porosity into ZIF-8 by using three-dimensional nanostructured porous ZnO as a structural template.
Strategies for the design of porous polymers as efficient heterogeneous catalysts: from co-polymerization to self-polymerization
Authors: Dong Ke , Sun Qi , Meng Xiangju , Xiao Feng-Shou
Published: January 2017

Porous organic polymers serve as a versatile platform for the development of highly efficient heterogeneous catalysts.
High K-storage performance based on the synergy of dipotassium terephthalate and ether-based electrolytes
Authors: Lei Kaixiang , Li Fujun , Mu Chaonan , Wang Jianbin , Zhao Qing , Chen Chengcheng , Chen Jun
Published: January 2017

Dipotassium terephthalate coupled with an ether-based electrolyte is used as a novel anode for potassium-ion batteries and exhibits superior electrochemical performance.
Effect of flexible linker length on the activity of fusion protein 4-coumaroyl-CoA ligase::stilbene synthase
Authors: Guo Huili , Yang Yadong , Xue Feiyan , Zhang Hong , Huang Tiran , Liu Wenbin , Liu Huan , Zhang Fenqiang , Yang Mingfeng , Liu Chunmei , Lu Heshu , Zhang Yansheng , Ma Lanqing
Published: January 2017

The flexible linker length has a direct effect on the catalytic efficiency of fusion protein 4CL::STS.
Pseudocapacitive behaviors of mesoporous nickel–cobalt oxide nanoplate electrodes in different electrolyte systems
Authors: Qiu Yang , Li Xuehua , Bai Mengru , Wang Hui , Xue Dan , Wang Wei , Cheng Jinbing
Published: January 2017

A freestanding mesoporous NiCo2O4nanoplate electrode exhibits superior pseudocapacitive performance and long-life stability.
Stereocontrolled semi-syntheses of deguelin and tephrosin
Authors: Russell David A. , Freudenreich Julien J. , Ciardiello Joe J. , Sore Hannah F. , Spring David R.
Published: January 2017

We describe stereocontrolled semi-syntheses of deguelin and tephrosin, anti-cancer rotenoids isolated fromTephrosia vogelii.
DNA as an environmental sensor: detection and identification of pesticide contaminants in water with fluorescent nucleobases
Authors: Kwon Hyukin , Chan Ke Min , Kool Eric T.
Published: January 2017

Fluorescent chemosensors built on a DNA backbone were able to differentiate micromolar levels of 14 different common pesticides in water.
The photo-controlled polymerization-induced self-assembly and reorganization process for fabrication of polymeric nanomaterials
Authors: Zhou Jiemei , Hong Chunyan , Pan Caiyuan
Published: January 2017

A visible light mediated reversible addition–fragmentation chain transfer (RAFT) dispersion polymerization of benzyl methacrylate (BzMA) is conducted in ethanol using poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) as a macro-chain transfer agent (macro-CTA), affording polymeric nanomaterials with various morphologies.
Silver-catalyzed phosphonylation of unprotected propargylic alcohols for the synthesis of allenylphosphoryl compounds
Authors: Mao Liu-Liang , Li Yong-Hong , Yang Shang-Dong
Published: January 2017

A facile and efficient method for the synthesis of a variety of allenylphosphine oxides by silver-catalyzed phosphonylation of unprotected propargylic alcohols with P(O)H compounds has been established.
Thermomechanical analysis of picograms of polymers using a suspended microchannel cantilever
Authors: Manzoor Bukhari Syed Asad , Khan M. Faheem , Goswami Ankur , McGee Ryan , Thundat Thomas
Published: January 2017

Suspended microchannel cantilever offers high sensitivity of detecting various thermal transitions of picogram amount of polymers which is showed by the schematic and the SEM of the actual device and the data obtained from it.
QD-aptamer as a donor for a FRET-based chemosensor and evaluation of affinity between acetamiprid and its aptamer
Authors: Xiang Li , Tang Jianshe
Published: January 2017

The sensitive and convenient detection of pesticides has become an important issue in food safety and environmental pollution.
In situ DRIFTS study of the NO + CO reaction on Fe–Co binary metal oxides over activated semi-coke supports
Authors: Wang Luyuan , Wang Zhiqiang , Cheng Xingxing , Zhang Mengze , Qin Yukun , Ma Chunyuan
Published: January 2017

Activated semi-coke loaded with Fe and Co species by a hydrothermal method exhibited excellent CO-deNOx performance.
Synthesis and in vivo proof of concept of a BODIPY-based fluorescent probe as a tracer for biodistribution studies of a new anti-Chagas agent
Authors: Rodríguez Gonzalo , Nargoli Javier , López Andrés , Moyna Guillermo , Álvarez Guzmán , Fernández Marcelo , Osorio-Martínez Carlos A. , González Mercedes , Cerecetto Hugo
Published: January 2017

A BODIPY-fluorophore based probe (1-BODIPY) for compound 1 was developed and investigated for its potential as in vivo tracer.
Formation, location and beneficial role of PbI2 in lead halide perovskite solar cells
Authors: Du Tian , Burgess Claire H. , Kim Jinhyun , Zhang Jiaqi , Durrant James R. , McLachlan Martyn A.
Published: January 2017

Here we report the investigation of controlled PbI2 secondary phase formation in CH3NH3PbI3 (MAPI) photovoltaics through post-deposition thermal annealing, identifying the location of PbI2 in the active layer and its beneficial role on device performance.
Synthesis of novel nonlinear optical chromophores: achieving enhanced electro-optic activity and thermal stability by introducing rigid steric hindrance groups into the julolidine donor
Authors: Zhang Hua , Xiao Hongyan , Liu Fenggang , Huo Fuyang , He Yanling , Chen Zhuo , Liu Xinhou , Bo Shuhui , Qiu Ling , Zhen Zhen
Published: January 2017

A series of chromophores based on julolidine donors modified by four different rigid steric hindrance groups with the same thiophene bridges and strong tricyanovinyldihydrofuran acceptors were synthesised.
Diarylmaleic anhydrides: unusual organic luminescence, multi-stimuli response and photochromism
Authors: Mei Xiaofei , Wang Jingwei , Zhou Zhonggao , Wu Shiyi , Huang Limei , Lin Zhenghuan , Ling Qidan
Published: January 2017

Novel maleic anhydrides symmetrically substituted by two aromatic rings exhibit distinct emission behaviours: aggregation-caused quenching (ACQ), aggregation-induced emission (AIE), and dual-state emission (DSE) in both solution and the solid state. Appropriate modifications were made to turn ACQ/AIE into DSE and realize full-color DSE.
Correction: New particle formation and growth from methanesulfonic acid, trimethylamine and water
Authors: Chen Haihan , Ezell Michael J. , Arquero Kristine D. , Varner Mychel E. , Dawson Matthew L. , Gerber R. Benny , Finlayson-Pitts Barbara J.
Published: January 2017

Correction for ‘New particle formation and growth from methanesulfonic acid, trimethylamine and water’ by Haihan Chen et al., Phys. Chem. Chem. Phys., 2015, 17, 13699–13709.
Antibacterial efficacy of Ocimum sanctum leaf extract-treated iron oxide nanoparticles
Authors: Ahmad Tokeer , Phul Ruby , Khatoon Nafeesa , Sardar Meryam
Published: January 2017

Iron oxide nanoparticles (IONPs) were preparedviaa co-precipitation method and were then characterized and evaluated for their antibacterial activity after modification withOcimum sanctumleaf extract.
Effect of lithium on ventricular remodelling in infarcted rats via the Akt/mTOR signalling pathways
Authors: Lee Tsung-Ming , Lin Shinn-Zong , Chang Nen-Chung
Published: January 2017

Activation of phosphoinositide 3-kinase (PI3K)/Akt signalling is the molecular pathway driving physiological hypertrophy. As lithium, a PI3K agonist, is highly toxic at regular doses, we assessed the effect of lithium at a lower dose on ventricular hypertrophy after myocardial infarction (MI). Male Wistar rats after induction of MI were randomized to either vehicle or lithium (1 mmol/kg per day) for 4 weeks. The dose of lithium led to a mean serum level of 0.39 mM, substantially lower than the therapeutic concentrations (0.8–1.2 mM). Infarction in the vehicle was characterized by pathological hypertrophy in the remote zone; histologically, by increased cardiomyocyte sizes, interstitial fibrosis and left ventricular dilatation; functionally, by impaired cardiac contractility; and molecularly, by an increase of p-extracellular-signal-regulated kinase (ERK) levels, nuclear factor of activated T cells (NFAT) activity, GATA4 expression and foetal gene expressions. Lithium administration mitigated pathological remodelling. Furthermore, lithium caused increased phosphorylation of eukaryotic initiation factor 4E binding protein 1 (p-4E-BP1), the downstream target of mammalian target of rapamycin (mTOR). Blockade of the Akt and mTOR signalling pathway with deguelin and rapamycin resulted in markedly diminished levels of p-4E-BP1, but not ERK. The present study demonstrated that chronic lithium treatment at low doses mitigates pathological hypertrophy through an Akt/mTOR dependent pathway.