bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative mRNA and miRNA expression in European mouflon (Ovis musimon) and sheep (Ovis aries) provides novel insights into the genetic mechanisms for female reproductive success
Authors: Yang Ji , Li Xin , Cao Yin-Hong , Pokharel Kisun , Hu Xiao-Ju , Chen Ze-Hui , Xu Song-Song , Peippo Jaana , Honkatukia Mervi , Kantanen Juha , Li Meng-Hua
Published: May 2018

Prolific breeds of domestic sheep (Ovis aries) are important genetic resources due to their reproductive performance, which is characterized by multiple lambs per birth and out-of-season breeding. However, the lack of a comprehensive understanding of the genetic mechanisms underlying the important reproductive traits, particularly from the evolutionary genomics perspective, has impeded the efficient advancement of sheep breeding. Here, for the first time, by performing RNA-sequencing we built a de novo transcriptome assembly of ovarian and endometrial tissues in European mouflon (Ovis musimon) and performed an mRNA–miRNA integrated expression profiling analysis of the wild species and a highly prolific domestic sheep breed, the Finnsheep. We identified several novel genes with differentially expressed mRNAs (e.g., EREG, INHBA, SPP1, AMH, TDRD5, and ZP2) between the wild and domestic sheep, which are functionally involved in oocyte and follicle development and fertilization, and are significantly (adjusted P-value < 0.05) enriched in the Gene Ontology (GO) terms of various reproductive process, including the regulation of fertilization, oogenesis, ovarian follicle development, and sperm–egg recognition. Additionally, we characterized 58 differentially expressed miRNAs and 210 associated target genes that are essential for the regulation of female reproduction cycles through specific regulatory networks [e.g., (miR-136, miR-374a, miR-9-5p)-(EREG, INHBA)]. Furthermore, our integrated mRNA and miRNA expression profiling analysis elucidated novel direct and indirect miRNA/mRNA causal regulatory relationships related to the reproductive traits of the Ovis species. This study provides in-depth insights into the genomic evolution underlying the reproductive traits of the Ovis species and valuable resources for ovine genomics.
Human single neuron activity precedes emergence of conscious perception
Authors: Gelbard-Sagiv Hagar , Mudrik Liad , Hill Michael R. , Koch Christof , Fried Itzhak
Published: May 2018

Identifying the neuronal basis of spontaneous changes in conscious experience in the absence of changes in the external environment is a major challenge. Binocular rivalry, in which two stationary monocular images lead to continuously changing perception, provides a unique opportunity to address this issue. We studied the activity of human single neurons in the medial temporal and frontal lobes while patients were engaged in binocular rivalry. Here we report that internal changes in the content of perception are signaled by very early (~-2000 ms) nonselective medial frontal activity, followed by selective activity of medial temporal lobe neurons that precedes the perceptual change by ~1000 ms. Such early activations are not found for externally driven perceptual changes. These results suggest that a medial fronto-temporal network may be involved in the preconscious internal generation of perceptual transitions.
Publisher Correction: A DHODH inhibitor increases p53 synthesis and enhances tumor cell killing by p53 degradation blockage
Authors: Ladds Marcus J. G. W. , van Leeuwen Ingeborg M. M. , Drummond Catherine J. , Chu Su , Healy Alan R. , Popova Gergana , Pastor Fernández Andrés , Mollick Tanzina , Darekar Suhas , Sedimbi Saikiran K. , Nekulova Marta , Sachweh Marijke C. C. , Campbell Johanna , Higgins Maureen , Tuck Chloe , Popa Mihaela , Safont Mireia Mayoral , Gelebart Pascal , Fandalyuk Zinayida , Thompson Alastair M. , Svensson Richard , Gustavsson Anna-Lena , Johansson Lars , Färnegårdh Katarina , Yngve Ulrika , Saleh Aljona , Haraldsson Martin , D’Hollander Agathe C. A. , Franco Marcela , Zhao Yan , Håkansson Maria , Walse Björn , Larsson Karin , Peat Emma M. , Pelechano Vicent , Lunec John , Vojtesek Borivoj , Carmena Mar , Earnshaw William C. , McCarthy Anna R. , Westwood Nicholas J. , Arsenian-Henriksson Marie , Lane David P. , Bhatia Ravi , McCormack Emmet , Laín Sonia
Published: May 2018

The original PDF version of this Article listed the authors as “Marcus J.G.W. Ladds,” where it should have read “Marcus J. G. W. Ladds, Ingeborg M. M. van Leeuwen, Catherine J. Drummond et al.#”.

Also in the PDF version, it was incorrectly stated that “Correspondence and requests for materials should be addressed to S. Lín.”, instead of the correct “Correspondence and requests for materials should be addressed to S. Laín.”

This has been corrected in the PDF version of the Article. The HTML version was correct from the time of publication.
High temperature deformability of ductile flash-sintered ceramics via in-situ compression
Authors: Cho Jaehun , Li Qiang , Wang Han , Fan Zhe , Li Jin , Xue Sichuang , Vikrant K. S. N. , Wang Haiyan , Holland Troy B. , Mukherjee Amiya K. , García R. Edwin , Zhang Xinghang
Published: May 2018

Flash sintering has attracted significant attention as its remarkably rapid densification process at low sintering furnace temperature leads to the retention of fine grains and enhanced dielectric properties. However, high-temperature mechanical behaviors of flash-sintered ceramics remain poorly understood. Here, we present high-temperature (up to 600 °C) in situ compression studies on flash-sintered yttria-stabilized zirconia (YSZ). Below 400 °C, the YSZ exhibits high ultimate compressive strength exceeding 3.5 GPa and high inelastic strain (~8%) due primarily to phase transformation toughening. At higher temperatures, crack nucleation and propagation are significantly retarded, and prominent plasticity arises mainly from dislocation activity. The high dislocation density induced in flash-sintered ceramics may have general implications for improving the plasticity of sintered ceramic materials.
Fibrotic microtissue array to predict anti-fibrosis drug efficacy
Authors: Asmani Mohammadnabi , Velumani Sanjana , Li Yan , Wawrzyniak Nicole , Hsia Isaac , Chen Zhaowei , Hinz Boris , Zhao Ruogang
Published: May 2018

Fibrosis is a severe health problem characterized by progressive stiffening of tissues which causes organ malfunction and failure. A major bottleneck in developing new anti-fibrosis therapies is the lack of in vitro models that recapitulate dynamic changes in tissue mechanics during fibrogenesis. Here we create membranous human lung microtissues to model key biomechanical events occurred during lung fibrogenesis including progressive stiffening and contraction of alveolar tissue, decline in alveolar tissue compliance and traction force-induced bronchial dilation. With these capabilities, we provide proof of principle for using this fibrotic tissue array for multi-parameter, phenotypic analysis of the therapeutic efficacy of two anti-fibrosis drugs recently approved by the FDA. Preventative treatments with Pirfenidone and Nintedanib reduce tissue contractility and prevent tissue stiffening and decline in tissue compliance. In a therapeutic treatment regimen, both drugs restore tissue compliance. These results highlight the pathophysiologically relevant modeling capability of our novel fibrotic microtissue system.
Photonic force optical coherence elastography for three-dimensional mechanical microscopy
Authors: Leartprapun Nichaluk , Iyer Rishyashring R. , Untracht Gavrielle R. , Mulligan Jeffrey A. , Adie Steven G.
Published: May 2018

Optical tweezers are an invaluable tool for non-contact trapping and micro-manipulation, but their ability to facilitate high-throughput volumetric microrheology of biological samples for mechanobiology research is limited by the precise alignment associated with the excitation and detection of individual bead oscillations. In contrast, radiation pressure from a low-numerical aperture optical beam can apply transversely localized force over an extended depth range. Here we present photonic force optical coherence elastography (PF-OCE), leveraging phase-sensitive interferometric detection to track sub-nanometer oscillations of beads, embedded in viscoelastic hydrogels, induced by modulated radiation pressure. Since the displacements caused by ultra-low radiation-pressure force are typically obscured by absorption-mediated thermal effects, mechanical responses of the beads were isolated after independent measurement and decoupling of the photothermal response of the hydrogels. Volumetric imaging of bead mechanical responses in hydrogels with different agarose concentrations by PF-OCE was consistent with bulk mechanical characterization of the hydrogels by shear rheometry.
Stark control of electrons along nanojunctions
Authors: Chen Liping , Zhang Yu , Chen GuanHua , Franco Ignacio
Published: May 2018

Ultrafast control of currents on the nanoscale is essential for future innovations in nanoelectronics. Recently it was experimentally demonstrated that strong non-resonant few-cycle 4 fs laser pulses can be used to induce phase-controllable currents along gold–silica–gold nanojunctions in the absence of a bias voltage. However, since the effect depends on a highly non-equilibrium state of matter, its microscopic origin is unclear and the subject of recent controversy. Here we present atomistically detailed (time-dependent non-equilibrium Green’s function) electronic transport simulations that recover the main experimental observations and offer a simple intuitive picture of the effect. The photoinduced currents are seen to arise due to a difference in effective silica-metal coupling for negative and positive field amplitudes induced by lasers with low temporal symmetry. These insights can be employed to interpret related experiments, and advance our ability to control electrons in matter using lasers.
Self-activated surface dynamics in gold catalysts under reaction environments
Authors: Kamiuchi Naoto , Sun Keju , Aso Ryotaro , Tane Masakazu , Tamaoka Takehiro , Yoshida Hideto , Takeda Seiji
Published: May 2018

Nanoporous gold (NPG) with sponge-like structures has been studied by atomic-scale and microsecond-resolution environmental transmission electron microscopy (ETEM) combined with ab initio energy calculations. Peculiar surface dynamics were found in the reaction environment for the oxidation of CO at room temperature, involving residual silver in the NPG leaves as well as gold and oxygen atoms, especially on {110} facets. The NPG is thus classified as a novel self-activating catalyst. The essential structure unit for catalytic activity was identified as Au–AgO surface clusters, implying that the NPG is regarded as a nano-structured silver oxide catalyst supported on the matrix of NPG, or an inverse catalyst of a supported gold nanoparticulate (AuNP) catalyst. Hence, the catalytically active structure in the gold catalysts (supported AuNP and NPG catalysts) can now be experimentally unified in low-temperature CO oxidation, a step forward towards elucidating the fascinating catalysis mechanism of gold.
The CaMKII/NMDA receptor complex controls hippocampal synaptic transmission by kinase-dependent and independent mechanisms
Authors: Incontro Salvatore , Díaz-Alonso Javier , Iafrati Jillian , Vieira Marta , Asensio Cedric S. , Sohal Vikaas S. , Roche Katherine W. , Bender Kevin J. , Nicoll Roger A.
Published: May 2018

CaMKII is one of the most studied synaptic proteins, but many critical issues regarding its role in synaptic function remain unresolved. Using a CRISPR-based system to delete CaMKII and replace it with mutated forms in single neurons, we have rigorously addressed its various synaptic roles. In brief, basal AMPAR and NMDAR synaptic transmission both require CaMKIIα, but not CaMKIIβ, indicating that, even in the adult, synaptic transmission is determined by the ongoing action of CaMKIIα. While AMPAR transmission requires kinase activity, NMDAR transmission does not, implying a scaffolding role for the CaMKII protein instead. LTP is abolished in the absence of CaMKIIα and/or CaMKIIβ and with an autophosphorylation impaired CaMKIIα (T286A). With the exception of NMDAR synaptic currents, all aspects of CaMKIIα signaling examined require binding to the NMDAR, emphasizing the essential role of this receptor as a master synaptic signaling hub.
Fossilized skin reveals coevolution with feathers and metabolism in feathered dinosaurs and early birds
Authors: McNamara Maria E. , Zhang Fucheng , Kearns Stuart L. , Orr Patrick J. , Toulouse André , Foley Tara , Hone David W. E. , Rogers Chris S. , Benton Michael J. , Johnson Diane , Xu Xing , Zhou Zhonghe
Published: May 2018

Feathers are remarkable evolutionary innovations that are associated with complex adaptations of the skin in modern birds. Fossilised feathers in non-avian dinosaurs and basal birds provide insights into feather evolution, but how associated integumentary adaptations evolved is unclear. Here we report the discovery of fossil skin, preserved with remarkable nanoscale fidelity, in three non-avian maniraptoran dinosaurs and a basal bird from the Cretaceous Jehol biota (China). The skin comprises patches of desquamating epidermal corneocytes that preserve a cytoskeletal array of helically coiled α-keratin tonofibrils. This structure confirms that basal birds and non-avian dinosaurs shed small epidermal flakes as in modern mammals and birds, but structural differences imply that these Cretaceous taxa had lower body heat production than modern birds. Feathered epidermis acquired many, but not all, anatomically modern attributes close to the base of the Maniraptora by the Middle Jurassic.
In vivo reprogramming drives Kras-induced cancer development
Authors: Shibata Hirofumi , Komura Shingo , Yamada Yosuke , Sankoda Nao , Tanaka Akito , Ukai Tomoyo , Kabata Mio , Sakurai Satoko , Kuze Bunya , Woltjen Knut , Haga Hironori , Ito Yatsuji , Kawaguchi Yoshiya , Yamamoto Takuya , Yamada Yasuhiro
Published: May 2018

The faithful shutdown of the somatic program occurs in the early stage of reprogramming. Here, we examined the effect of in vivo reprogramming on Kras-induced cancer development. We show that the transient expression of reprogramming factors (1–3 days) in pancreatic acinar cells results in the transient repression of acinar cell enhancers, which are similarly observed in pancreatitis. We next demonstrate that Kras and p53 mutations are insufficient to induce ERK signaling in the pancreas. Notably, the transient expression of reprogramming factors in Kras mutant mice is sufficient to induce the robust and persistent activation of ERK signaling in acinar cells and rapid formation of pancreatic ductal adenocarcinoma. In contrast, the forced expression of acinar cell-related transcription factors inhibits the pancreatitis-induced activation of ERK signaling and development of precancerous lesions in Kras-mutated acinar cells. These results underscore a crucial role of dedifferentiation-associated epigenetic regulations in the initiation of pancreatic cancers.
Light storage for one second in room-temperature alkali vapor
Authors: Katz Or , Firstenberg Ofer
Published: May 2018

Light storage, the controlled and reversible mapping of photons onto long-lived states of matter, enables memory capability in optical quantum networks. Prominent storage media are warm alkali vapors due to their strong optical coupling and long-lived spin states. In a dense gas, the random atomic collisions dominate the lifetime of the spin coherence, limiting the storage time to a few milliseconds. Here we present and experimentally demonstrate a storage scheme that is insensitive to spin-exchange collisions, thus enabling long storage times at high atomic densities. This unique property is achieved by mapping the light field onto spin orientation within a decoherence-free subspace of spin states. We report on a record storage time of 1 s in room-temperature cesium vapor, a 100-fold improvement over existing storage schemes. Furthermore, our scheme lays the foundations for hour-long quantum memories using rare-gas nuclear spins.
The development of human social learning across seven societies
Authors: van Leeuwen Edwin J. C. , Cohen Emma , Collier-Baker Emma , Rapold Christian J. , Schäfer Marie , Schütte Sebastian , Haun Daniel B. M.
Published: May 2018

Social information use is a pivotal characteristic of the human species. Avoiding the cost of individual exploration, social learning confers substantial fitness benefits under a wide variety of environmental conditions, especially when the process is governed by biases toward relative superiority (e.g., experts, the majority). Here, we examine the development of social information use in children aged 4–14 years (n = 605) across seven societies in a standardised social learning task. We measured two key aspects of social information use: general reliance on social information and majority preference. We show that the extent to which children rely on social information depends on children’s cultural background. The extent of children’s majority preference also varies cross-culturally, but in contrast to social information use, the ontogeny of majority preference follows a U-shaped trajectory across all societies. Our results demonstrate both cultural continuity and diversity in the realm of human social learning.
Metamaterials with index ellipsoids at arbitrary k-points
Authors: Chen Wen-Jie , Hou Bo , Zhang Zhao-Qing , Pendry John B. , Chan C. T.
Published: May 2018

Propagation behaviors of electromagnetic waves are governed by the equifrequency surface of the medium. Up to now, ordinary materials, including the medium exist in nature and the man-made metamaterials, always have an equifrequency surface (ellipsoid or hyperboloid) centered at zero k-point. Here we propose a new type of metamaterial possessing multiple index ellipsoids centered at arbitrary nonzero k-points. Their locations in momentum space are determined by the connectivity of a set of interpenetrating metallic scaffolds, whereas the group velocities of the modes are determined by the geometrical details. Such system is a new class of metamaterial whose properties arise from global connectivity and hence can have broadband functionality in applications such as negative refraction, orientation-dependent coupling effect, and cavity without walls, and they are fundamentally different from ordinary resonant metamaterials that are inherently bandwidth limited. We perform microwave experiments to confirm our findings.
Demonstration of Ru as the 4th ferromagnetic element at room temperature
Authors: Quarterman P. , Sun Congli , Garcia-Barriocanal Javier , DC Mahendra , Lv Yang , Manipatruni Sasikanth , Nikonov Dmitri E. , Young Ian A. , Voyles Paul M. , Wang Jian-Ping
Published: May 2018

Development of novel magnetic materials is of interest for fundamental studies and applications such as spintronics, permanent magnetics, and sensors. We report on the first experimental realization of single element ferromagnetism, since Fe, Co, and Ni, in metastable tetragonal Ru, which has been predicted. Body-centered tetragonal Ru phase is realized by use of strain via seed layer engineering. X-ray diffraction and electron microscopy confirm the epitaxial mechanism to obtain tetragonal phase Ru. We observed a saturation magnetization of 148 and 160 emu cm−3 at room temperature and 10 K, respectively. Control samples ensure the ferromagnetism we report on is from tetragonal Ru and not from magnetic contamination. The effect of thickness on the magnetic properties is also studied, and it is observed that increasing thickness results in strain relaxation, and thus diluting the magnetization. Anomalous Hall measurements are used to confirm its ferromagnetic behavior.
Identification of rare de novo epigenetic variations in congenital disorders
Authors: Barbosa Mafalda , Joshi Ricky S. , Garg Paras , Martin-Trujillo Alejandro , Patel Nihir , Jadhav Bharati , Watson Corey T. , Gibson William , Chetnik Kelsey , Tessereau Chloe , Mei Hui , De Rubeis Silvia , Reichert Jennifer , Lopes Fatima , Vissers Lisenka E. L. M. , Kleefstra Tjitske , Grice Dorothy E. , Edelmann Lisa , Soares Gabriela , Maciel Patricia , Brunner Han G. , Buxbaum Joseph D. , Gelb Bruce D. , Sharp Andrew J.
Published: May 2018

Certain human traits such as neurodevelopmental disorders (NDs) and congenital anomalies (CAs) are believed to be primarily genetic in origin. However, even after whole-genome sequencing (WGS), a substantial fraction of such disorders remain unexplained. We hypothesize that some cases of ND–CA are caused by aberrant DNA methylation leading to dysregulated genome function. Comparing DNA methylation profiles from 489 individuals with ND–CAs against 1534 controls, we identify epivariations as a frequent occurrence in the human genome. De novo epivariations are significantly enriched in cases, while RNAseq analysis shows that epivariations often have an impact on gene expression comparable to loss-of-function mutations. Additionally, we detect and replicate an enrichment of rare sequence mutations overlapping CTCF binding sites close to epivariations, providing a rationale for interpreting non-coding variation. We propose that epivariations contribute to the pathogenesis of some patients with unexplained ND–CAs, and as such likely have diagnostic relevance.
Quantum simulation of ultrafast dynamics using trapped ultracold atoms
Authors: Senaratne Ruwan , Rajagopal Shankari V. , Shimasaki Toshihiko , Dotti Peter E. , Fujiwara Kurt M. , Singh Kevin , Geiger Zachary A. , Weld David M.
Published: May 2018

Ultrafast electronic dynamics are typically studied using pulsed lasers. Here we demonstrate a complementary experimental approach: quantum simulation of ultrafast dynamics using trapped ultracold atoms. Counter-intuitively, this technique emulates some of the fastest processes in atomic physics with some of the slowest, leading to a temporal magnification factor of up to 12 orders of magnitude. In these experiments, time-varying forces on neutral atoms in the ground state of a tunable optical trap emulate the electric fields of a pulsed laser acting on bound charged particles. We demonstrate the correspondence with ultrafast science by a sequence of experiments: nonlinear spectroscopy of a many-body bound state, control of the excitation spectrum by potential shaping, observation of sub-cycle unbinding dynamics during strong few-cycle pulses, and direct measurement of carrier-envelope phase dependence of the response to an ultrafast-equivalent pulse. These results establish cold-atom quantum simulation as a complementary tool for studying ultrafast dynamics.
Impact of rural-urban environment on metabolic profile and response to a 5-day high-fat diet
Authors: Tahapary Dicky L. , de Ruiter Karin , Kurniawan Farid , Djuardi Yenny , Wang Yanan , Nurdin Siti M. E. , Iskandar Elisa , Minggu Dominggus , Yunir Em , Guigas Bruno , Supali Taniawati , Rensen Patrick C. N. , Sartono Erliyani , Soewondo Pradana , Harbuwono Dante S. , Smit Johannes W. A. , Yazdanbakhsh Maria
Published: May 2018

Epidemiological studies have indicated that rural living might be protective against type 2 diabetes development. We compared the metabolic profile and response to a short-term high-fat high-calorie diet (HFD) of men with the same genetic background living in an urban and rural area of Indonesia. First, we recruited 154 Floresian male subjects (18–65 years old), of whom 105 lived in a rural area (Flores) and 49 had migrated and lived in urban area (Jakarta) for more than 1 year. The urban group had significantly higher whole-body insulin resistance (IR), as assessed by homeostatic-model-assessment of IR (HOMA-IR), [mean difference (95% CI), p-value: 0.10 (0.02–0.17), p = 0.01]. Next, we recruited 17 urban and 17 rural age-and-BMI-matched healthy-young-male volunteers for a 5-day HFD challenge. The HOMA-IR increased in both groups similarly −0.77 (−2.03–0.49), p = 0.22]. Neither rural living nor factors associated with rural living, such as current helminth infection or total IgE, were associated with protection against acute induction of IR by HFD.
Author Correction: Long-term effects of mild traumatic brain injuries to oculomotor tracking performances and reaction times to simple environmental stimuli
Authors: Danna-Dos-Santos Alessander , Mohapatra Sambit , Santos Maria , Degani Adriana M.
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Altered Cerebellar Biochemical Profiles in Infants Born Prematurely
Authors: Brossard-Racine Marie , Murnick Jonathan , Bouyssi-Kobar Marine , Coulombe Janie , Chang Taeun , Limperopoulos Catherine
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Author Correction: Enabling Controlling Complex Networks with Local Topological Information
Authors: Li Guoqi , Deng Lei , Xiao Gaoxi , Tang Pei , Wen Changyun , Hu Wuhua , Pei Jing , Shi Luping , Stanley H. Eugene
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Proteomic identification of Axc, a novel beta-lactamase with carbapenemase activity in a meropenem-resistant clinical isolate of Achromobacter xylosoxidans
Authors: Fleurbaaij Frank , Henneman Alex A. , Corver Jeroen , Knetsch Cornelis W. , Smits Wiep Klaas , Nauta Sjoerd T. , Giera Martin , Dragan Irina , Kumar Nitin , Lawley Trevor D. , Verhoeven Aswin , van Leeuwen Hans C. , Kuijper Ed J. , Hensbergen Paul J.
Published: May 2018

The development of antibiotic resistance during treatment is a threat to patients and their environment. Insight in the mechanisms of resistance development is important for appropriate therapy and infection control. Here, we describe how through the application of mass spectrometry-based proteomics, a novel beta-lactamase Axc was identified as an indicator of acquired carbapenem resistance in a clinical isolate of Achromobacter xylosoxidans. Comparative proteomic analysis of consecutively collected susceptible and resistant isolates from the same patient revealed that high Axc protein levels were only observed in the resistant isolate. Heterologous expression of Axc in Escherichia coli significantly increased the resistance towards carbapenems. Importantly, direct Axc mediated hydrolysis of imipenem was demonstrated using pH shift assays and 1H-NMR, confirming Axc as a legitimate carbapenemase. Whole genome sequencing revealed that the susceptible and resistant isolates were remarkably similar. Together these findings provide a molecular context for the fast development of meropenem resistance in A. xylosoxidans during treatment and demonstrate the use of mass spectrometric techniques in identifying novel resistance determinants.
Author Correction: Rapid signal enhancement method for nanoprobe-based biosensing
Authors: Dias Jorge T. , Svedberg Gustav , Nystrand Mats , Andersson-Svahn Helene , Gantelius Jesper
Published: May 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Metabolic alterations in the bone tissues of aged osteoporotic mice
Authors: Nam Miso , Huh Jeong-Eun , Kim Min-Sun , Ryu Do Hyun , Park Jihyeong , Kim Han-Sung , Lee Soo Young , Hwang Geum-Sook
Published: May 2018

Age-related osteoporosis is characterized by reduced bone mineralization and reduced bone strength, which increases the risk of fractures. We examined metabolic changes associated with age-related bone loss by profiling lipids and polar metabolites in tibia and femur bone tissues from young (5 months old) and old (28 months old) male C57BL/6J mice using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry. Partial least-squares discriminant analysis showed clear differences in metabolite levels in bone tissues of young and old mice. We identified 93 lipid species, including free fatty acids, sphingolipids, phospholipids, and glycerolipids, that were significantly altered in bone tissues of old mice. In addition, the expression of 26 polar metabolites differed significantly in bone tissues of old mice and young mice. Specifically, uremic toxin metabolite levels (p-cresyl sulfate, hippuric acid, and indoxylsulfate) were higher in bone tissues of old mice than in young mice. The increase in p-cresyl sulfate, hippuric acid, and indoxylsulfate levels were determined using targeted analysis of plasma polar extracts to determine whether these metabolites could serve as potential osteoporosis biomarkers. This study demonstrates that LC-MS-based global profiling of lipid and polar metabolites can elucidate metabolic changes that occur during age-related bone loss and identify potential biomarkers of osteoporosis.
Uneven-Layered Coding Metamaterial Tile for Ultra-wideband RCS Reduction and Diffuse Scattering
Authors: Su Jianxun , He Huan , Li Zengrui , Yang Yaoqing , Yin Hongcheng , Wang Junhong
Published: May 2018

In this paper, a novel uneven-layered coding metamaterial tile is proposed for ultra-wideband radar cross section (RCS) reduction and diffuse scattering. The metamaterial tile is composed of two kinds of square ring unit cells with different layer thickness. The reflection phase difference of 180° (±37°) between two unit cells covers an ultra-wide frequency range. Due to the phase cancellation between two unit cells, the metamaterial tile has the scattering pattern of four strong lobes deviating from normal direction. The metamaterial tile and its 90-degree rotation can be encoded as the ‘0’ and ‘1’ elements to cover an object, and diffuse scattering pattern can be realized by optimizing phase distribution, leading to reductions of the monostatic and bi-static RCSs simultaneously. The metamaterial tile can achieve −10 dB RCS reduction from 6.2 GHz to 25.7 GHz with the ratio bandwidth of 4.15:1 at normal incidence. The measured and simulated results are in good agreement and validate the proposed uneven-layered coding metamaterial tile can greatly expanding the bandwidth for RCS reduction and diffuse scattering.
Multiplexed profiling of GPCR activities by combining split TEV assays and EXT-based barcoded readouts
Authors: Galinski Sabrina , Wichert Sven P. , Rossner Moritz J. , Wehr Michael C.
Published: May 2018

G protein-coupled receptors (GPCRs) are the largest class of cell surface receptors and are implicated in the physiological regulation of many biological processes. The high diversity of GPCRs and their physiological functions make them primary targets for therapeutic drugs. For the generation of novel compounds, however, selectivity towards a given target is a critical issue in drug development as structural similarities between members of GPCR subfamilies exist. Therefore, the activities of multiple GPCRs that are both closely and distantly related to assess compound selectivity need to be tested simultaneously. Here, we present a cell-based multiplexed GPCR activity assay, termed GPCRprofiler, which uses a β-arrestin recruitment strategy and combines split TEV protein-protein interaction and EXT-based barcode technologies. This approach enables simultaneous measurements of receptor activities of multiple GPCR-ligand combinations by applying massively parallelized reporter assays. In proof-of-principle experiments covering 19 different GPCRs, both the specificity of endogenous agonists and the polypharmacological effects of two known antipsychotics on GPCR activities were demonstrated. Technically, normalization of barcode reporters across individual assays allows quantitative pharmacological assays in a parallelized manner. In summary, the GPCRprofiler technique constitutes a flexible and scalable approach, which enables simultaneous profiling of compound actions on multiple receptor activities in living cells.
Evolutionarily Conserved and Divergent Roles of Unfolded Protein Response (UPR) in the Pathogenic Cryptococcus Species Complex
Authors: Jung Kwang-Woo , Lee Kyung-Tae , Averette Anna F. , Hoy Michael J. , Everitt Jeffrey , Heitman Joseph , Bahn Yong-Sun
Published: May 2018

The unfolded protein response (UPR) pathway, consisting of the evolutionarily conserved Ire1 kinase/endonuclease and the bZIP transcription factor Hxl1, is critical for the pathogenicity of Cryptococcus neoformans; however, its role remains unknown in other pathogenic Cryptococcus species. Here, we investigated the role of the UPR pathway in C. deuterogattii, which causes pneumonia and systemic cryptococcosis, even in immunocompetent individuals. In response to ER stress, C. deuterogattii Ire1 triggers unconventional splicing of HXL1 to induce the expression of UPR target genes such as KAR2, DER1, ALG7, and ERG29. Furthermore, C. deuterogattii Ire1 is required for growth at mammalian body temperature, similar to C. neoformans Ire1. However, deletion of HXL1 does not significantly affect the growth of C. deuterogattii at 37 °C, which is in contrast to the indispensable role of HXL1 in the growth of C. neoformans at 37 °C. Nevertheless, both C. deuterogattii ire1Δ and hxl1Δ mutants are avirulent in a murine model of systemic cryptococcosis, suggesting that a non-thermotolerance phenotypic trait also contributes to the role of the UPR pathway in the virulence of pathogenic Cryptococcus species. In conclusion, the UPR pathway plays redundant and distinct roles in the virulence of members of the pathogenic Cryptococcus species complex.
Single step synthesis of Schottky-like hybrid graphene - titania interfaces for efficient photocatalysis
Authors: Yi Zhifeng , Merenda Andrea , Kong Lingxue , Radenovic Aleksandra , Majumder Mainak , Dumée Ludovic F.
Published: May 2018

The development of 2D nanomaterial coatings across metal surfaces is a challenge due to the mismatch between the metal microstructure and the nanoscale materials. The naturally occurring thin oxidative layer present across all metal surfaces, may lead to low adherence and connectivity. In this paper, graphene/titania/Titanium hybrid films were for the first time fabricated by a single step chemical vapour deposition process across Titanium foils. The presence of graphene as a dopant was found to enhance the photocatalytic performance of the final products, applied to the degradation of organic molecules and to lead to Schottky-like junction formation at the metal/oxide interface. These Schottky junctions, where vacancies are present across the titania material due to the graphene doping and where Ti3+ ions are predominantly located, yield enhanced catalytic performance. The highest degradation rate was found to be 9.66 × 10−6 min−1, achieved by the sample grown at 700 °C for 5 min, which was 62% higher than the sample just treated at that temperature without graphene growth. This work provides evidence that graphene may be grown across pure Titanium metal and opens new avenues in biomedical devices design, tribological or separation applications.
Cognition During and After Multiple Sclerosis Relapse as Assessed With the Brief International Cognitive Assessment for Multiple Sclerosis
Authors: Giedraitiene Natasa , Kaubrys Gintaras , Kizlaitiene Rasa
Published: May 2018

There is some evidence that cognition may be impaired during multiple sclerosis (MS) relapse. The aims of this study were to assess the cognitive status with the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) in MS patients during relapse, in stable patients, and in healthy controls; to evaluate cognitive changes up to 3 months after relapse; and to estimate the impact of different factors on cognition after relapse. BICAMS was performed in 60 relapsing, 30 stable patients and 30 controls. Relapsing MS patients were assessed during relapse and one and three months after relapse. SDMT score was lower in relapsing than in stable patients. The mean scores of all BICAMS tests were higher one month after relapse than during relapse (p < 0.001). SDMT score after relapse improved in younger patients, who had more severe relapse (p < 0.05). BVMT-R score improved more in men, in patients with biologically active interferon-beta, in patients treated with methylprednisolone and in patients who were rehabilitated (p < 0.05). CVLT-II score improved in women and in patients with shorter relapse (p < 0.05). A neuropsychological assessment, like the evaluation of physical disability, is important during relapse. BICAMS may be suitable for a quick and effective assessment of cognition during relapse.
Rapid Optimization of External Quantum Efficiency of Thin Film Solar Cells Using Surrogate Modeling of Absorptivity
Authors: Kaya Mine , Hajimirza Shima
Published: May 2018

This paper uses surrogate modeling for very fast design of thin film solar cells with improved solar-to-electricity conversion efficiency. We demonstrate that the wavelength-specific optical absorptivity of a thin film multi-layered amorphous-silicon-based solar cell can be modeled accurately with Neural Networks and can be efficiently approximated as a function of cell geometry and wavelength. Consequently, the external quantum efficiency can be computed by averaging surrogate absorption and carrier recombination contributions over the entire irradiance spectrum in an efficient way. Using this framework, we optimize a multi-layer structure consisting of ITO front coating, metallic back-reflector and oxide layers for achieving maximum efficiency. Our required computation time for an entire model fitting and optimization is 5 to 20 times less than the best previous optimization results based on direct Finite Difference Time Domain (FDTD) simulations, therefore proving the value of surrogate modeling. The resulting optimization solution suggests at least 50% improvement in the external quantum efficiency compared to bare silicon, and 25% improvement compared to a random design.
Serum Autotaxin Is a Useful Disease Progression Marker in Patients with Primary Biliary Cholangitis
Authors: Joshita Satoru , Umemura Takeji , Usami Yoko , Yamashita Yuki , Norman Gary L. , Sugiura Ayumi , Yamazaki Tomoo , Fujimori Naoyuki , Kimura Takefumi , Matsumoto Akihiro , Igarashi Koji , Yoshizawa Kaname , Ota Masao , Tanaka Eiji
Published: May 2018

Autotaxin (ATX) is a secreted enzyme metabolized by liver sinusoidal endothelial cells that has been associated with liver fibrosis. We evaluated serum ATX values in 128 treatment-naïve, histologically assessed primary biliary cholangitis (PBC) patients and 80 healthy controls for comparisons of clinical parameters in a case-control study. The median ATX concentrations in controls and PBC patients of Nakanuma’s stage I, II, III, and IV were 0.70, 0.80, 0.87, 1.03, and 1.70 mg/L, respectively, which increased significantly with disease stage (r = 0.53, P < 0.0001) as confirmed by Scheuer’s classification (r = 0.43, P < 0.0001). ATX correlated with Wisteria floribunda agglutinin-positive Mac-2 binding protein (M2BPGi) (r = 0.51, P < 0.0001) and fibrosis index based on four factors (FIB-4) index (r = 0.51, P < 0.0001). While ALP and M2BPGi levels had decreased significantly (both P < 0.001) by 12 months of ursodeoxycholic acid treatment, ATX had not (0.95 to 0.96 mg/L) (P = 0.07). We observed in a longitudinal study that ATX increased significantly (P < 0.00001) over 18 years in an independent group of 29 patients. Patients succumbing to disease-related death showed a significantly higher ATX increase rate (0.05 mg/L/year) than did survivors (0.02 mg/L/year) (P < 0.01). ATX therefore appears useful for assessing disease stage and prognosis in PBC.
Acaricidal target and mite indicator as color alteration using 3,7-dimethyl-2,6-octadienal and its derivatives derived from Melissa officinalis leaves
Authors: Park Jun-Hwan , Lee Hoi-Seon
Published: May 2018

Toxicities and color deformation were evaluated of essential oils of Melissa officinalis cultivated in France, Ireland, and Serbia and their constituents, along with the control efficacy of spray formulations (0.25, 0.5, and 1%) containing M. officinalis oils cultivated in France and its main compound against Dermatophagoides farinae and D. pteronyssinus adults. In a contact + fumigant bioassay, M. officinalis oil (France) was more active against D. farinae and D. pteronyssinus, compared to M. officinalis oils (Ireland and Serbia). Interestingly, color alteration of D. farinae and D. pteronyssinus was exhibited, changing from colorless to golden brown through the treatment with M. officinalis oils. The acaricidal and color alteration principle of three M. officinalis oils was determined to be 3,7-dimethyl-2,6-octadienal. M. officinalis oil (France) and 3,7-dimethyl-2,6-octadienal were significantly more effective in closed containers than in open containers, indicating that their acaricidal route of action was largely a result of vapor action. Sprays (0.5 and 1%) containing 3,7-dimethyl-2,6-octadienal and 1% spray containing M. officinalis oil (France) resulted in 100% mortality and color alteration against D. farinae and D. pteronyssinus. These results indicated that M. officinalis oil and 3,7-dimethyl-2,6-octadienal could be developed as a suitable acaricidal and mite indicator ingredient for the control of dust mites.
Effects of dietary supplementation of formaldehyde and crystalline amino acids on gut microbial composition of nursery pigs
Authors: Williams H. E. , Cochrane R. A. , Woodworth J. C. , DeRouchey J. M. , Dritz S. S. , Tokach M. D. , Jones C. K. , Fernando S. C. , Burkey T. E. , Li Y. S. , Goodband R. D. , Amachawadi R. G.
Published: May 2018

Formaldehyde-based feed additives are approved in the US for Salmonella control and reducing bacterial contamination in animal feed. However, we hypothesize formaldehyde inclusion in swine diets may influence gut microbial composition due to its antimicrobial properties which might negatively influence microbial populations and pig growth performance. Also, formaldehyde inclusion in diets is known to reduce the dietary availability of amino acids. Therefore, our study was conducted to characterize if the effects of feed formaldehyde-treatment are due to influences on microbial population or diet amino acid (AA) sources. Dietary treatments were arranged in a (2 × 2) + 1 factorial with formaldehyde treatment (none vs. 1000 ppm formaldehyde) and crystalline AA inclusion (low vs. high) with deficient AA content plus a positive control diet to contain adequate AA content without dietary formaldehyde. Treating diets with formaldehyde reduced growth rate (P = 0.001) while the AA inclusion had no evidence of impact. Formaldehyde reduced feed bacterial content and altered fecal microbial communities (P < 0.05). Therefore, we conclude that the negative influence on growth was due to the impact on the fecal microbial community. Implications are that strategies for feed pathogen control need to take into account potential negative impacts on the gut microbial community.
An in vitro erythrocyte preference assay reveals that Plasmodium falciparum parasites prefer Type O over Type A erythrocytes
Authors: Theron Michel , Cross Nadia , Cawkill Paula , Bustamante Leyla Y. , Rayner Julian C.
Published: May 2018

Malaria has been one of the strongest selective forces on the human genome. The increased frequency of haemoglobinopathies, as well as numerous other blood groups, in malaria endemic regions is commonly attributed to a protective effect of these alleles against malaria. In the majority of these cases however there have been no systematic functional studies to test protective mechanisms, in large part because most host-parasite interaction assays are not quantitative or scalable. We describe the development of an erythrocyte preference assay which uses differential labelling with fluorescent dyes to distinguish invasion into four different erythrocyte populations which are all co-incubated with a single Plasmodium falciparum parasite culture. Testing this assay on erythrocytes across the ABO blood system from forty independent donors reveals for the first time that P. falciparum parasites preferentially invade group O over Group A erythrocytes. This runs counter to the known protective effect of group O against severe malaria, but emphasises the complexities of host-pathogen interactions, and the need for highly quantitative and scalable assays to systematically explore them.
Observing Kelvin–Helmholtz instability in solar blowout jet
Authors: Li Xiaohong , Zhang Jun , Yang Shuhong , Hou Yijun , Erdélyi Robert
Published: May 2018

Kelvin–Helmholtz instability (KHI) is a basic physical process in fluids and magnetized plasmas, with applications successfully modelling e.g. exponentially growing instabilities observed at magnetospheric and heliospheric boundaries, in the solar or Earth’s atmosphere and within astrophysical jets. Here, we report the discovery of the KHI in solar blowout jets and analyse the detailed evolution by employing high-resolution data from the Interface Region Imaging Spectrograph (IRIS) satellite launched in 2013. The particular jet we focus on is rooted in the surrounding penumbra of the main negative polarity sunspot of Active Region 12365, where the main body of the jet is a super-penumbral structure. At its maximum, the jet has a length of 90 Mm, a width of 19.7 Mm, and its density is about 40 times higher than its surroundings. During the evolution of the jet, a cavity appears near the base of the jet, and bi-directional flows originated from the top and bottom of the cavity start to develop, indicating that magnetic reconnection takes place around the cavity. Two upward flows pass along the left boundary of the jet successively. Next, KHI develops due to a strong velocity shear (∼204 km s−1) between these two flows, and subsequently the smooth left boundary exhibits a sawtooth pattern, evidencing the onset of the instability.
Deterministic Current Induced Magnetic Switching Without External Field using Giant Spin Hall Effect of β-W
Authors: Chen Wenzhe , Qian Lijuan , Xiao Gang
Published: May 2018

Giant spin Hall effect (GSHE) has received significant attention for its potential in future spintronic applications. Spin current via GSHE-based thin films provides an effective and promising means to manipulate magnetization. However, an external in-plane magnetic field is required to consistently switch the perpendicular magnetic moment. We present an approach to realize field-free deterministic perpendicular magnetic switching with a new structure of FM/NM/FM. Our method takes advantage of the large spin Hall angle of transition metal β-W, so that the critical switching current density is only on the order of 106A/cm2 in the absence of magnetic field.
Obstructive sleep apnoea is associated with progression of arterial stiffness independent of obesity in participants without hypertension: A KoGES Prospective Cohort Study
Authors: Kim Jinkwan , Lee Seung Ku , Yoon Dae Wui , Shin Chol
Published: May 2018

Accumulating evidence shows that obstructive sleep apnoea (OSA) is associated with an increased risk of cardiovascular disease. However, there are no published prospective studies on the relationship between OSA and the progression of arterial stiffness. We hypothesised that OSA would increase the risk of arterial stiffness progression, independent of obesity. In the present large cohort study, 1921 participants were randomly selected and underwent polysomnography. The brachial ankle pulse wave velocity (baPWV) was measured at baseline and during the follow-period using a standard protocol. Elevated baPWV was defined as a value greater than the cut-off of highest tertile level in the complete study cohort. The percentage of elevated baPWV and the ΔbaPWV significantly increased with OSA severity. After adjusting for potential confounding factors, participants with moderate-to-severe OSA without hypertension had a significantly higher risk of elevated ΔbaPWV than those without OSA. More importantly, using multivariate mixed-effect models, we found that the ΔbaPWV over 6 years significantly differed according to OSA severity. Therefore, moderate-to-severe OSA in participants without hypertension was a predictor of future burden of arterial stiffness progression, independent of obesity, suggesting that it may contribute to the increased risk of cardiovascular disease.