bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Outdooring’ the Historical Corpus of English in Ghana
Authors: Brato Thorsten
Published: January 2018

Over the last 30 years there has been an upsurge in research and theorising on postcolonial Englishes. Beginning with Kachru's (1985)Three Circlesmodel, more recently the focus has shifted to models focusing on identity construction and historical developments (Schneider, 2007), central and peripheral varieties and their spheres of influence (Mair, 2013), and those aiming to provide a more integrated approach to postcolonial and non-postcolonial Englishes (Buschfeld & Kautzsch, 2017). Dedicated corpora such as the International Corpus of English (ICE; Greenbaum, 1991) and the Corpus of Global Web-based English (GloWbe; Davies & Fuchs, 2015) have been designed to allow for a synchronic comparison of Englishes around the world and have since been widely used to study variation on the different levels of linguistic description within and across varieties. Recently, ICE corpora have also been used to test assumptions laid out by Schneider (2007), e.g. by comparing data from ICE corpora of varieties which have progressed to different phases (Mukherjee & Gries, 2009) or by taking an apparent-time approach to test developments within one variety (Fuchs & Gut, 2015).
On the finite-element approximation of ∞-harmonic functions
Authors: Pryer Tristan
Published: January 2018

In this paper we show that conforming Galerkin approximations for p-harmonic functions tend to ∞-harmonic functions in the limit p → ∞ and h → 0, where h denotes the Galerkin discretization parameter.
Omega–Phi compensated GID in side inclination mode for measurement of residual stress in polycrystalline thin films
Authors: Wang Xiaodong , van Riessen Arie
Published: January 2018

The grazing incidence diffraction (GID) method in side inclination mode, described by Ma et al. in 2002, of polycrystalline thin-film residual stress was revisited and explained using simple geometric relations. To overcome the issue of decreasing peak intensity of this method, which is induced by the decreasing incident angle because of the Eulerian cradle Chi-tilt, an improvement of Omega (ω)–Phi (φ) compensation was devised and applied to a NiFe thin-film sample. The geometry of this improved ω–φ compensated GID method in side inclination mode is detailed in this paper. This improvement guarantees a constant incident angle on the sample surface and a fixed sample illumination volume during measurement. The measured data were analysed using parametric refinement in DIFFRAC.TOPAS v6 software in Launch Mode, and details of the input file (.INP) are explained in this paper. The tensile stress of the NiFe thin-film sample was measured to be 1181 ± 85 MPa using this improved method.
High-energy X-ray applications: current status and new opportunities
Authors: Šišak Jung Dubravka , Donath Tilman , Magdysyuk Oxana , Bednarcik Jozef
Published: January 2018

Characterization of semi and noncrystalline materials, monitoring structural phase transitionsin situ, and obtaining structural information together with spatial distribution of the investigated material are only a few applications that hugely benefitted from the combination of high-energy X-rays and modern algorithms for data processing. This work examines the possibility of advancing these applications by shortening the data acquisition and improving the data quality by using the new high-energy PILATUS3 CdTe detector.
The Chicken and Egg Question: Satisfaction with Democracy and Voter Turnout
Authors: Kostelka Filip , Blais André
Published: January 2018

Political scientists, analysts and journalists alike have long believed that the degree of satisfaction with the functioning of democracy determines voter turnout. We use survey data from 24 panel studies to demonstrate that this causal relationship is actually reversed: voter turnout affects satisfaction with democracy. We also show that this reversed relationship is conditioned by election type, electoral system, and election outcomes. These findings are important because: (1) They question conventional wisdom and a large body of scientific literature; (2) They invite a more nuanced approach towards the study of the relationship between evaluations of regime performance and political participation; and (3) They emphasize the vital role of elections in shaping citizens’ perception of the democratic process.
OIL PRICE SHOCKS, INVENTORIES, AND MACROECONOMIC DYNAMICS
Authors: Herrera Ana María
Published: January 2018

This paper investigates the time delay in the transmission of oil price shocks using disaggregated manufacturing data on inventories and sales. VAR estimates indicate that industry-level inventories and sales respond faster to an oil price shock than aggregate gross domestic product, especially in industries that are energy-intensive. In response to an unexpected oil price increase, sales drop and inventories are accumulated. This leads to future reductions in production. We estimate a modified linear–quadratic inventory model to inquire whether the patterns observed in the VAR impulse responses are consistent with rational behavior by the firms. Estimation results suggest that three mechanisms play a role in the industry-level dynamics. First, oil prices act as a negative demand shock. Second, the shock catches manufacturers by surprise, resulting in higher-than-anticipated inventories. Third, because of their desire to smooth production, manufacturers deviate from the target level of inventories and spread the decline in production over various quarters; hence the delay in the response of aggregate output.
Synergistic Effects of Continuous Low Level Heat Wraps and Vitamins in Improving Balance and Gait in Adults
Authors: Petrofsky Jerrold , Laymon Michael , Khowailed Iman , Lee Haneul
Published: January 2018

Abstract.Ageing is associated with a loss of balance and mobility. This study was conducted to determine if the use of heat, vitamins alone or heat with vitamins could increase mobility and balance in adults with mobility impairments. Eighty adults in the age range between 55 and 64 were randomly divided into 4 different groups; low level continues heat (LLCH), vitamins (VT) alone, vitamins combined with heat (VT + H), and control group. Subjects were sedentary individuals that were not participating in any balance or walking exercises regularly and were not taking vitamins for at least 1 year. 4000 units vitamin D, 1000 units vitamin E, 300mg CoQ10, 600 mg Calcium, 1 tablet multivitamin were taken each day in the VT and VT + H groups. LLCH was applied with a dry chemical heat wrap, average temperature 42°C for 4 hours per day over the upper leg. The outcome was assessed through postural sway and tremor during standing, tremor, gait speed, symmetry, ground reaction force, and muscle activity during gait. All experimental groups showed significant improvement in balance and walking ability after 4 months of interventions (p < 0.05) but no significant changes were found in the control group. The difference between the control group and all other groups was significant (p < 0.05). The greatest improvements were found in VT + H group after 4 months. This is evidenced by better balance, less muscle tremor and faster and more stable gait, especially with the heat and vitamins used together. Heat and vitamins used together were synergistic.
How Offshore Groundwater Shapes the Seafloor
Authors: Micallef Aaron , Mountjoy Joshu , Schwalenberg Katrin , Jegen Marion , Weymer Bradley , Woelz Susi , Gerring Peter , Luebben Neeske , Spatola Daniele , Cunarro Otero Daniel , Mueller Christof
Published: January 2018

The MARCAN project, launched last January, is working to fill a gap in our knowledge of how freshwater flowing underground shapes and alters the continental margins.
The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms
Authors: Grohme Markus Alexander , Schloissnig Siegfried , Rozanski Andrei , Pippel Martin , Young George Robert , Winkler Sylke , Brandl Holger , Henry Ian , Dahl Andreas , Powell Sean , Hiller Michael , Myers Eugene , Rink Jochen Christian
Published: January 2018

The planarian Schmidtea mediterranea is an important model for stem cell research and regeneration, but adequate genome resources for this species have been lacking. Here we report a highly contiguous genome assembly of S. mediterranea, using long-read sequencing and a de novo assembler (MARVEL) enhanced for low-complexity reads. The S. mediterranea genome is highly polymorphic and repetitive, and harbours a novel class of giant retroelements. Furthermore, the genome assembly lacks a number of highly conserved genes, including critical components of the mitotic spindle assembly checkpoint, but planarians maintain checkpoint function. Our genome assembly provides a key model system resource that will be useful for studying regeneration and the evolutionary plasticity of core cell biological mechanisms.
mTOR signaling in skeletal development and disease
Authors: Chen Jianquan , Long Fanxin
Published: January 2018

The mammalian/mechanistic target of rapamycin (mTOR) is a serine/threonine protein kinase that integrates inputs from nutrients and growth factors to control many fundamental cellular processes through two distinct protein complexes mTORC1 and mTORC2. Recent mouse genetic studies have established that mTOR pathways play important roles in regulating multiple aspects of skeletal development and homeostasis. In addition, mTORC1 has emerged as a common effector mediating the bone anabolic effect of Igf1, Wnt and Bmp. Dysregulation of mTORC1 could contribute to various skeletal diseases including osteoarthritis and osteoporosis. Here we review the current understanding of mTOR signaling in skeletal development and bone homeostasis, as well as in the maintenance of articular cartilage. We speculate that targeting mTOR signaling may be a valuable approach for treating skeletal diseases.
Ubiquitin C decrement plays a pivotal role in replicative senescence of bone marrow mesenchymal stromal cells
Authors: Kim Jiyeon , Kim Yonggoo , Choi Hayoung , Kwon Ahlm , Jekarl Dong Wook , Lee Seungok , Jang Woori , Chae Hyojin , Kim Jung Rok , Kim Jung Min , Kim Myungshin
Published: January 2018

Human bone marrow-mesenchymal stromal cells (hBM-MSCs) undergo cellular senescence during in vitro culture. In this study, we defined this replicative senescence as impaired proliferation, deterioration in representative cell characteristics, accumulated DNA damage, and decreased telomere length and telomerase activity with or without genomic abnormalities. The UBC gene expression gradually decreased during passaging along with the reduction in series of molecules including hub genes; CDK1, CCNA2, MCM10, E2F1, BRCA1, HIST1H1A and HIST1H3B. UBC knockdown in hBM-MSCs induced impaired proliferation in dose-dependent manner and showed replicative senescence-like phenomenon. Gene expression changes after UBC knockdown were similar to late passage hBM-MSCs. Additionally, UBC overexpession improved the proliferation activity of hBM-MSCs accompanied by increased expression of the hub genes. Consequently, UBC worked in higher-order through regulation of the hub genes controlling cell cycle and proliferation. These results indicate that the decrement of UBC expression plays a pivotal role in replicative senescence of hBM-MSCs.
Regulation of chitinase-3-like-1 in T cell elicits Th1 and cytotoxic responses to inhibit lung metastasis
Authors: Kim Do-Hyun , Park Hong-Jai , Lim Sangho , Koo Ja-Hyun , Lee Hong-Gyun , Choi Jin Ouk , Oh Ji Hoon , Ha Sang-Jun , Kang Min-Jong , Lee Chang-Min , Lee Chun Geun , Elias Jack A. , Choi Je-Min
Published: January 2018

Chitinase-3-like-1 (Chi3l1) is known to play a significant role in the pathogenesis of Type 2 inflammation and cancer. However, the function of Chi3l1 in T cell and its clinical implications are largely unknown. Here we show that Chi3l1 expression was increased in activated T cells, especially in Th2 cells. In addition, Chi3l1-deficient T cells are hyper-responsive to TcR stimulation and are prone to differentiating into Th1 cells. Chi3l1-deficient Th1 cells show increased expression of anti-tumor immunity genes and decreased Th1 negative regulators. Deletion of Chi3l1 in T cells in mice show reduced melanoma lung metastasis with increased IFNγ and TNFα-producing T cells in the lung. Furthermore, silencing of Chi3l1 expression in the lung using peptide-siRNA complex (dNP2-siChi3l1) efficiently inhibit lung metastasis with enhanced Th1 and CTL responses. Collectively, this study demonstrates Chi3l1 is a regulator of Th1 and CTL which could be a therapeutic target to enhance anti-tumor immunity.
BMI1 regulates androgen receptor in prostate cancer independently of the polycomb repressive complex 1
Authors: Zhu Sen , Zhao Dongyu , Yan Lin , Jiang Weihua , Kim Jung-Sun , Gu Bingnan , Liu Qipeng , Wang Rui , Xia Bo , Zhao Jonathan C. , Song Gang , Mi Wenyi , Wang Rong-Fu , Shi Xiaobing , Lam Hung-Ming , Dong Xuesen , Yu Jindan , Chen Kaifu , Cao Qi
Published: January 2018

Abstract

BMI1, a polycomb group (PcG) protein, plays a critical role in epigenetic regulation of cell differentiation and proliferation, and cancer stem cell self-renewal. BMI1 is upregulated in multiple types of cancer, including prostate cancer. As a key component of polycomb repressive complex 1 (PRC1), BMI1 exerts its oncogenic functions by enhancing the enzymatic activities of RING1B to ubiquitinate histone H2A at lysine 119 and repress gene transcription. Here, we report a PRC1-independent role of BMI1 that is critical for castration-resistant prostate cancer (CRPC) progression. BMI1 binds the androgen receptor (AR) and prevents MDM2-mediated AR protein degradation, resulting in sustained AR signaling in prostate cancer cells. More importantly, we demonstrate that targeting BMI1 effectively inhibits tumor growth of xenografts that have developed resistance to surgical castration and enzalutamide treatment. These results suggest that blocking BMI1 alone or in combination with anti-AR therapy can be more efficient to suppress prostate tumor growth.
Steric exclusion and protein conformation determine the localization of plasma membrane transporters
Authors: Bianchi Frans , Syga Łukasz , Moiset Gemma , Spakman Dian , Schavemaker Paul E. , Punter Christiaan M. , Seinen Anne-Bart , van Oijen Antoine M. , Robinson Andrew , Poolman Bert
Published: January 2018

The plasma membrane (PM) of Saccharomyces cerevisiae contains membrane compartments, MCC/eisosomes and MCPs, named after the protein residents Can1 and Pma1, respectively. Using high-resolution fluorescence microscopy techniques we show that Can1 and the homologous transporter Lyp1 are able to diffuse into the MCC/eisosomes, where a limited number of proteins are conditionally trapped at the (outer) edge of the compartment. Upon addition of substrate, the immobilized proteins diffuse away from the MCC/eisosomes, presumably after taking a different conformation in the substrate-bound state. Our data indicate that the mobile fraction of all integral plasma membrane proteins tested shows extremely slow Brownian diffusion through most of the PM. We also show that proteins with large cytoplasmic domains, such as Pma1 and synthetic chimera of Can1 and Lyp1, are excluded from the MCC/eisosomes. We hypothesize that the distinct localization patterns found for these integral membrane proteins in S. cerevisiae arises from a combination of slow lateral diffusion, steric exclusion, and conditional trapping in membrane compartments.
Amorphous martensite in β-Ti alloys
Authors: Zhang Long , Zhang Haifeng , Ren Xiaobing , Eckert Jürgen , Wang Yandong , Zhu Zhengwang , Gemming Thomas , Pauly Simon
Published: January 2018

Martensitic transformations originate from a rigidity instability, which causes a crystal to change its lattice in a displacive manner. Here, we report that the martensitic transformation on cooling in Ti–Zr–Cu–Fe alloys yields an amorphous phase instead. Metastable β-Ti partially transforms into an intragranular amorphous phase due to local lattice shear and distortion. The lenticular amorphous plates, which very much resemble α′/α″ martensite in conventional Ti alloys, have a well-defined orientation relationship with the surrounding β-Ti crystal. The present solid-state amorphization process is reversible, largely cooling rate independent and constitutes a rare case of congruent inverse melting. The observed combination of elastic softening and local lattice shear, thus, is the unifying mechanism underlying both martensitic transformations and catastrophic (inverse) melting. Not only do we reveal an alternative mechanism for solid-state amorphization but also establish an explicit experimental link between martensitic transformations and catastrophic melting.
Advancing behavioural genomics by considering timescale
Authors: Rittschof Clare C. , Hughes Kimberly A.
Published: January 2018

Animal behavioural traits often covary with gene expression, pointing towards a genomic constraint on organismal responses to environmental cues. This pattern highlights a gap in our understanding of the time course of environmentally responsive gene expression, and moreover, how these dynamics are regulated. Advances in behavioural genomics explore how gene expression dynamics are correlated with behavioural traits that range from stable to highly labile. We consider the idea that certain genomic regulatory mechanisms may predict the timescale of an environmental effect on behaviour. This temporally minded approach could inform both organismal and evolutionary questions ranging from the remediation of early life social trauma to understanding the evolution of trait plasticity.
Author Correction: Conventional CD4+ T cells present bacterial antigens to induce cytotoxic and memory CD8+ T cell responses
Authors: Cruz-Adalia Aránzazu , Ramirez-Santiago Guillermo , Osuna-Pérez Jesús , Torres-Torresano Mónica , Zorita Virgina , Martínez-Riaño Ana , Boccasavia Viola , Borroto Aldo , Martínez del Hoyo Gloria , González-Granado José María , Alarcón Balbino , Sánchez-Madrid Francisco , Veiga Esteban
Published: January 2018

The original version of this Article contained an error in the spelling of the author José María González-Granado, which was incorrectly given as José María Gozález-Granado. This has now been corrected in both the PDF and HTML versions of the Article.
Statistical Approach for Gene Set Analysis with Trait Specific Quantitative Trait Loci
Authors: Das Samarendra , Rai Anil , Mishra D. C. , Rai Shesh N.
Published: January 2018

The analysis of gene sets is usually carried out based on gene ontology terms and known biological pathways. These approaches may not establish any formal relation between genotype and trait specific phenotype. In plant biology and breeding, analysis of gene sets with trait specific Quantitative Trait Loci (QTL) data are considered as great source for biological knowledge discovery. Therefore, we proposed an innovative statistical approach called Gene Set Analysis with QTLs (GSAQ) for interpreting gene expression data in context of gene sets with traits. The utility of GSAQ was studied on five different complex abiotic and biotic stress scenarios in rice, which yields specific trait/stress enriched gene sets. Further, the GSAQ approach was more innovative and effective in performing gene set analysis with underlying QTLs and identifying QTL candidate genes than the existing approach. The GSAQ approach also provided two potential biological relevant criteria for performance analysis of gene selection methods. Based on this proposed approach, an R package, i.e., GSAQ (https://cran.r-project.org/web/packages/GSAQ) has been developed. The GSAQ approach provides a valuable platform for integrating the gene expression data with genetically rich QTL data.
Clathrin heavy chain 22 contributes to the control of neuropeptide degradation and secretion during neuronal development
Authors: Nahorski Michael S. , Borner Georg H. H. , Shaikh Samiha S. , Davies Alexandra K. , Al-Gazali Lihadh , Antrobus Robin , Woods C. Geoffrey
Published: January 2018

The repertoire of cell types in the human nervous system arises through a highly orchestrated process, the complexity of which is still being discovered. Here, we present evidence that CHC22 has a non-redundant role in an early stage of neural precursor differentiation, providing a potential explanation of why CHC22 deficient patients are unable to feel touch or pain. We show the CHC22 effect on neural differentiation is independent of the more common clathrin heavy chain CHC17, and that CHC22-dependent differentiation is mediated through an autocrine/paracrine mechanism. Using quantitative proteomics, we define the composition of clathrin-coated vesicles in SH-SY5Y cells, and determine proteome changes induced by CHC22 depletion. In the absence of CHC22 a subset of dense core granule (DCG) neuropeptides accumulated, were processed into biologically active ‘mature’ forms, and secreted in sufficient quantity to trigger neural differentiation. When CHC22 is present, however, these DCG neuropeptides are directed to the lysosome and degraded, thus preventing differentiation. This suggests that the brief reduction seen in CHC22 expression in sensory neural precursors may license a step in neuron precursor neurodevelopment; and that this step is mediated through control of a novel neuropeptide processing pathway.
Comprehensive network of miRNA-induced intergenic interactions and a biological role of its core in cancer
Authors: Galatenko Vladimir V. , Galatenko Alexey V. , Samatov Timur R. , Turchinovich Andrey A. , Shkurnikov Maxim Yu. , Makarova Julia A. , Tonevitsky Alexander G.
Published: January 2018

MicroRNAs (miRNAs) are a family of short noncoding RNAs that posttranscriptionally regulate gene expression and play an important role in multiple cellular processes. A significant percentage of miRNAs are intragenic, which is often functionally related to their host genes playing either antagonistic or synergistic roles. In this study, we constructed and analyzed the entire network of intergenic interactions induced by intragenic miRNAs. We further focused on the core of this network, which was defined as a union of nontrivial strongly connected components, i.e., sets of nodes (genes) mutually connected via directed paths. Both the entire network and its core possessed statistically significant non-random properties. Specifically, genes forming the core had high expression levels and low expression variance. Furthermore, the network core did not split into separate components corresponding to individual signalling or metabolic pathways, but integrated genes involved in key cellular processes, including DNA replication, transcription, protein homeostasis and cell metabolism. We suggest that the network core, consisting of genes mutually regulated by their intragenic miRNAs, could coordinate adjacent pathways or homeostatic control circuits, serving as a horizontal inter-circuit link. Notably, expression patterns of these genes had an efficient prognostic potential for breast and colorectal cancer patients.
Visualization and quantification of dynamic STAT3 homodimerization in living cells using homoFluoppi
Authors: Okada Yusuke , Watanabe Taku , Shoji Toru , Taguchi Kyoko , Ogo Naohisa , Asai Akira
Published: January 2018

Dimerization in signal transduction is a dynamically regulated process and a key regulatory mechanism. Signal transducer and activator of transcription 3 (STAT3) dimerizes after tyrosine phosphorylation upon cytokine stimulation. Because only the STAT3 dimer possesses the trans-activation activity, dimerization is an indispensable process for cytokine signaling. Here we report the detection of dynamic STAT3 dimerization in living cells using the homoFluoppi system. This method allowed us to validate the presence of an intact Src homology 2 domain and STAT3 Tyr705 phosphorylation, which facilitate puncta formation and homodimerization. Puncta formation was reversible, as determined by a decreased punctate signal after washout of oncostatin M. We analyzed STAT3 mutants, which have been reported in patients with hyper IgE syndrome and inflammatory hepatocellular adenoma (IHCA). Analysis of the IHCA mutants using homoFluoppi revealed constitutive activity independent of cytokine stimulation and novel insight into kinetics of dimer dissociation process. Next, we used homoFluoppi to screen for inhibitors of STAT3 dimerization, and identified 3,4-methylenedioxy-β-nitrostyrene as a novel inhibitor. The results of this study show that homoFluoppi is a useful research tool for the analysis of proteins like STAT3 that dynamically dimerize, and is applicable for the screening of dimerization modulators.
miR-429 suppresses tumor migration and invasion by targeting CRKL in hepatocellular carcinoma via inhibiting Raf/MEK/ERK pathway and epithelial-mesenchymal transition
Authors: Guo Chunmei , Zhao Dongting , Zhang Qiuling , Liu Shuqing , Sun Ming-Zhong
Published: January 2018

Tumor metastasis is one of the main causes of hepatocellular carcinoma (HCC) high mortality. CRKL (v-crk sarcoma virus CT10 oncogene homologue (avian)-like) play important roles in tumor metastasis, however, the exact role and underlying mechanism of CRKL in HCC is still unknown. In our study, we demonstrated miR-429 negatively regulated CRKL expression via selectively binding to CRKL-3′-UTR at 3728–3735 bp site by post-transcriptionally mediating its functionality. Re-expression and silencing of miR-429 was remarkably effective in suppressing and promoting HepG2 cell migration and invasion in vitro. Knockdown or overexpression of CRKL exhibited similar effects as the overexpression or silencing of miR-429, whereas, CRKL overexpression (without the 3′-UTR) abrogated miR-429-induced inhibition on HepG2 migration and invasion. Moreover, miR-429-CRKL axis affected HepG2 migration and invasion potentials by regulating the adhesion ability, cytoskeleton F-actin expression and arrangement of HepG2. Furthermore, interference of Raf/MEK/ERK pathway and EMT contributed to miR-429-CRKL axis mediated metastasis inhibition. Nevertheless, miR-429 could not inhibit HepG2 proliferation through CRKL/c-Jun pathway. Taken together, our data demonstrated that miR-429 might function as an antimetastatic miRNA to regulate HCC metastasis by directly targeting CRKL via modulating Raf/MEK/ERK-EMT pathway. The newly identified miR-429-CRKL axis represents a novel potential therapeutic target for HCC treatment.
Enhanced Reality Showing Long-Lasting Analgesia after Total Knee Arthroplasty: Prospective, Randomized Clinical Trial
Authors: Koo Kyo-in , Park Dae Kwon , Youm Yoon Seok , Cho Sung Do , Hwang Chang Ho
Published: January 2018

To overcome the limitation of short-term efficacy of virtual reality (VR), an enhanced reality (ER) analgesia, (combination of the VR, real-time motion capture, mirror therapy [MT]) involving a high degree of patients’ presence or embodiment was explored. Patients, who underwent unilateral total knee arthroplasty (TKA), received ER analgesia. The duration was 5 times a week, for 2 weeks for one group and 5 times a week, for 1 week in the other. Visual Analogue Scale (VAS) at rest and during movement, active knee range of motion (ROM) for flexion and extension were measured repeatedly. After screening 157 patients, 60 were included. Pre-interventional evaluation was performed at 6.7 days and ER was initiated at 12.4 days after surgery. Evaluation was performed at 5, 12, 33 days after the initiation of ER. Analgesia in the 2 week therapy group was effective until the third evaluation (p = 0.000), whereas in the other group, it was effective only until the second evaluation (p = 0.010). Improvement in ROM in the 2 week group was also maintained until the third evaluation (p = 0.037, p = 0.009). It could lay the foundations for the development of safe and long-lasting analgesic tools.
Exploring coral microbiome assemblages in the South China Sea
Authors: Cai Lin , Tian Ren-Mao , Zhou Guowei , Tong Haoya , Wong Yue Him , Zhang Weipeng , Chui Apple Pui Yi , Xie James Y. , Qiu Jian-Wen , Ang Put O. , Liu Sheng , Huang Hui , Qian Pei-Yuan
Published: January 2018

Coral reefs are significant ecosystems. The ecological success of coral reefs relies on not only coral-algal symbiosis but also coral-microbial partnership. However, microbiome assemblages in the South China Sea corals remain largely unexplored. Here, we compared the microbiome assemblages of reef-building corals Galaxea (G. fascicularis) and Montipora (M. venosa, M. peltiformis, M. monasteriata) collected from five different locations in the South China Sea using massively-parallel sequencing of 16S rRNA gene and multivariate analysis. The results indicated that microbiome assemblages for each coral species were unique regardless of location and were different from the corresponding seawater. Host type appeared to drive the coral microbiome assemblages rather than location and seawater. Network analysis was employed to explore coral microbiome co-occurrence patterns, which revealed 61 and 80 co-occurring microbial species assembling the Galaxea and Montipora microbiomes, respectively. Most of these co-occurring microbial species were commonly found in corals and were inferred to play potential roles in host nutrient metabolism; carbon, nitrogen, sulfur cycles; host detoxification; and climate change. These findings suggest that the co-occurring microbial species explored might be essential to maintain the critical coral-microbial partnership. The present study provides new insights into coral microbiome assemblages in the South China Sea.
Deep learning for real-time single-pixel video
Authors: Higham Catherine F. , Murray-Smith Roderick , Padgett Miles J. , Edgar Matthew P.
Published: January 2018

Single-pixel cameras capture images without the requirement for a multi-pixel sensor, enabling the use of state-of-the-art detector technologies and providing a potentially low-cost solution for sensing beyond the visible spectrum. One limitation of single-pixel cameras is the inherent trade-off between image resolution and frame rate, with current compressive (compressed) sensing techniques being unable to support real-time video. In this work we demonstrate the application of deep learning with convolutional auto-encoder networks to recover real-time 128 × 128 pixel video at 30 frames-per-second from a single-pixel camera sampling at a compression ratio of 2%. In addition, by training the network on a large database of images we are able to optimise the first layer of the convolutional network, equivalent to optimising the basis used for scanning the image intensities. This work develops and implements a novel approach to solving the inverse problem for single-pixel cameras efficiently and represents a significant step towards real-time operation of computational imagers. By learning from examples in a particular context, our approach opens up the possibility of high resolution for task-specific adaptation, with importance for applications in gas sensing, 3D imaging and metrology.
DNA assay based on Nanoceria as Fluorescence Quenchers (NanoCeracQ DNA assay)
Authors: Bülbül Gonca , Hayat Akhtar , Mustafa Fatima , Andreescu Silvana
Published: January 2018

Functional nanomaterials with fluorescent or quenching abilities are important for the development of molecular probes for detection and studies of nucleic acids. Here, we describe a new class of molecular nanoprobes, the NanoCeracQ that uses nanoceria particles as a nanoquencher of fluorescent oligonucleotides for rapid and sensitive detection of DNA sequences and hybridization events. We show that nanoceria forms stable and reversible bionanoconjugates with oligonucleotides and can specifically recognize and detect DNA sequences in a single step. In absence of the target DNA, the nanoprobe produced minimal background fluorescence due to the high quenching efficiency of nanoceria. Competitive binding of the target induced a concentration dependent increase in the fluorescence signal due to hybridization and release of the fluorescent tag from the nanoparticle surface. The nanoprobe enabled sensitive detection of the complementary strand with a detection limit of 0.12 nM, using a single step procedure. The results show that biofunctionalized nanoceria can be used as a universal nanoquencher and nanosensing platform for fluorescent DNA detection and studies of nucleic acid interactions. This approach can find broad applications in molecular diagnostics, sensor development, gene expression profiling, imaging and forensic analysis.
Combining Turing and 3D vertex models reproduces autonomous multicellular morphogenesis with undulation, tubulation, and branching
Authors: Okuda Satoru , Miura Takashi , Inoue Yasuhiro , Adachi Taiji , Eiraku Mototsugu
Published: January 2018

This study demonstrates computational simulations of multicellular deformation coupled with chemical patterning in the three-dimensional (3D) space. To address these aspects, we proposes a novel mathematical model, where a reaction–diffusion system is discretely expressed at a single cell level and combined with a 3D vertex model. To investigate complex phenomena emerging from the coupling of patterning and deformation, as an example, we employed an activator–inhibitor system and converted the activator concentration of individual cells into their growth rate. Despite the simplicity of the model, by growing a monolayer cell vesicle, the coupling system provided rich morphological dynamics such as undulation, tubulation, and branching. Interestingly, the morphological variety depends on the difference in time scales between patterning and deformation, and can be partially understood by the intrinsic hysteresis in the activator-inhibitor system with domain growth. Importantly, the model can be applied to 3D multicellular dynamics that couple the reaction–diffusion patterning with various cell behaviors, such as deformation, rearrangement, division, apoptosis, differentiation, and proliferation. Thus, the results demonstrate the significant advantage of the proposed model as well as the biophysical importance of exploring spatiotemporal dynamics of the coupling phenomena of patterning and deformation in 3D space.
Long non-coding and coding RNAs characterization in Peripheral Blood Mononuclear Cells and Spinal Cord from Amyotrophic Lateral Sclerosis patients
Authors: Gagliardi Stella , Zucca Susanna , Pandini Cecilia , Diamanti Luca , Bordoni Matteo , Sproviero Daisy , Arigoni Maddalena , Olivero Martina , Pansarasa Orietta , Ceroni Mauro , Calogero Raffaele , Cereda Cristina
Published: January 2018

Alteration in RNA metabolism, concerning both coding and long non-coding RNAs (lncRNAs), may play an important role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. In this work, we performed a whole transcriptome RNA-seq analysis to investigate the regulation of non-coding and coding RNAs in Sporadic ALS patients (SALS), mutated ALS patients (FUS, TARDBP and SOD1) and matched controls in Peripheral Blood Mononuclear Cells (PBMC). Selected transcripts were validated in spinal cord tissues. A total of 293 differentially expressed (DE) lncRNAs was found in SALS patients, whereas a limited amount of lncRNAs was deregulated in mutated patients. A total of 87 mRNAs was differentially expressed in SALS patients; affected genes showed an association with transcription regulation, immunity and apoptosis pathways. Taken together our data highlighted the importance of extending the knowledge on transcriptomic molecular alterations and on the significance of regulatory lncRNAs classes in the understanding of ALS disease. Our data brought the light on the importance of lncRNAs and mRNAs regulation in central and peripheral systems, offering starting points for new investigations about pathogenic mechanism involved in ALS disease.
Clinical-pathological study on β-APP, IL-1β, GFAP, NFL, Spectrin II, 8OHdG, TUNEL, miR-21, miR-16, miR-92 expressions to verify DAI-diagnosis, grade and prognosis
Authors: Pinchi Enrica , Frati Alessandro , Cipolloni Luigi , Aromatario Mariarosaria , Gatto Vittorio , La Russa Raffaele , Pesce Alessandro , Santurro Alessandro , Fraschetti Flavia , Frati Paola , Fineschi Vittorio
Published: January 2018

Traumatic brain injury (TBI) is one of the most important death and disability cause, involving substantial costs, also in economic terms, when considering the young age of the involved subject. Aim of this paper is to report a series of patients treated at our institutions, to verify neurological results at six months or survival; in fatal cases we searched for βAPP, GFAP, IL-1β, NFL, Spectrin II, TUNEL and miR-21, miR-16, and miR-92 expressions in brain samples, to verify DAI diagnosis and grade as strong predictor of survival and inflammatory response. Concentrations of 8OHdG as measurement of oxidative stress was performed. Immunoreaction of β-APP, IL-1β, GFAP, NFL, Spectrin II and 8OHdG were significantly increased in the TBI group with respect to control group subjects. Cell apoptosis, measured by TUNEL assay, were significantly higher in the study group than control cases. Results indicated that miR-21, miR-92 and miR-16 have a high predictive power in discriminating trauma brain cases from controls and could represent promising biomarkers as strong predictor of survival, and for the diagnosis of postmortem traumatic brain injury.
Genetic variability affects absolute and relative potencies and kinetics of the anesthetics isoflurane and sevoflurane in Drosophila melanogaster
Authors: Olufs Zachariah P. G. , Loewen Carin A. , Ganetzky Barry , Wassarman David A. , Perouansky Misha
Published: January 2018

Genetic variability affects the response to numerous xenobiotics but its role in the clinically-observed irregular responses to general anesthetics remains uncertain. To investigate the pharmacogenetics of volatile general anesthetics (VGAs), we developed a Serial Anesthesia Array apparatus to expose multiple Drosophila melanogaster samples to VGAs and behavioral assays to determine pharmacokinetic and pharmacodynamic properties of VGAs. We studied the VGAs isoflurane and sevoflurane in four wild type strains from the Drosophila Genetic Reference Panel, two commonly used laboratory strains (Canton S and w
1118
), and a mutant in Complex I of the mitochondrial electron transport chain (ND23
60114
). In all seven strains, isoflurane was more potent than sevoflurane, as predicted by their relative lipid solubilities, and emergence from isoflurane was slower than from sevoflurane, reproducing cardinal pharmacokinetic and pharmacodynamic properties in mammals. In addition, ND23
60114
flies were more sensitive to both agents, as observed in worms, mice, and humans carrying Complex I mutations. Moreover, we found substantial variability among the fly strains both in absolute and in relative pharmacokinetic and pharmacodynamic profiles of isoflurane and sevoflurane. These data indicate that naturally occurring genetic variations measurably influence cardinal pharmacologic properties of VGAs and that flies can be used to identify relevant genetic variations.
Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells
Authors: Udagawa Tomohiro , Harita Yutaka , Miura Kenichiro , Mitsui Jun , Ode Koji L. , Morishita Shinichi , Urae Seiya , Kanda Shoichiro , Kajiho Yuko , Tsurumi Haruko , Ueda Hiroki R. , Tsuji Shoji , Saito Akihiko , Oka Akira
Published: January 2018

Mutations in either cubilin (CUBN) or amnionless (AMN) genes cause Imerslund–Gräsbeck syndrome (IGS), a hereditary disease characterised by anaemia attributed to selective intestinal malabsorption of cobalamin and low-molecular weight proteinuria. Although cubilin protein does not have a transmembrane segment, it functions as a multi-ligand receptor by binding to the transmembrane protein, amnionless. We established a system to quantitatively analyse membrane targeting of the protein complex in cultured renal and intestinal cells and analysed the pathogenic mechanisms of mutations found in IGS patients. A novel CUBN mutation, several previously reported CUBN missense mutations and all previously reported AMN missense mutations resulted in endoplasmic reticulum (ER) retention and completely inhibited amnionless-dependent plasma membrane expression of cubilin. The ER retention of cubilin and amnionless was confirmed in renal proximal tubular cells of a patient with IGS. Notably, the interaction between cubilin and amnionless was not sufficient, but amnionless-mediated glycosylation of cubilin was necessary for their surface expression. Quantitative mass spectrometry and mutagenesis demonstrated that N-linked glycosylation of at least 4 residues of cubilin protein was required for its surface targeting. These results delineated the molecular mechanisms of membrane trafficking of cubilin in renal and intestinal cells.
Transcriptomic changes in the pre-implantation uterus highlight histotrophic nutrition of the developing marsupial embryo
Authors: Whittington Camilla M. , O’Meally Denis , Laird Melanie K. , Belov Katherine , Thompson Michael B. , McAllan Bronwyn M.
Published: January 2018

Early pregnancy is a critical time for successful reproduction; up to half of human pregnancies fail before the development of the definitive chorioallantoic placenta. Unlike the situation in eutherian mammals, marsupial pregnancy is characterised by a long pre-implantation period prior to the development of the short-lived placenta, making them ideal models for study of the uterine environment promoting embryonic survival pre-implantation. Here we present a transcriptomic study of pre-implantation marsupial pregnancy, and identify differentially expressed genes in the Sminthopsis crassicaudata uterus involved in metabolism and biosynthesis, transport, immunity, tissue remodelling, and uterine receptivity. Interestingly, almost one quarter of the top 50 genes that are differentially upregulated in early pregnancy are putatively involved in histotrophy, highlighting the importance of nutrient transport to the conceptus prior to the development of the placenta. This work furthers our understanding of the mechanisms underlying survival of pre-implantation embryos in the earliest live bearing ancestors of mammals.
Extreme plasma states in laser-governed vacuum breakdown
Authors: Efimenko Evgeny S. , Bashinov Aleksei V. , Bastrakov Sergei I. , Gonoskov Arkady A. , Muraviev Alexander A. , Meyerov Iosif B. , Kim Arkady V. , Sergeev Alexander M.
Published: January 2018

Triggering vacuum breakdown at laser facility is expected to provide rapid electron-positron pair production for studies in laboratory astrophysics and fundamental physics. However, the density of the produced plasma may cease to increase at a relativistic critical density, when the plasma becomes opaque. Here, we identify the opportunity of breaking this limit using optimal beam configuration of petawatt-class lasers. Tightly focused laser fields allow generating plasma in a small focal volume much less than λ3 and creating extreme plasma states in terms of density and produced currents. These states can be regarded to be a new object of nonlinear plasma physics. Using 3D QED-PIC simulations we demonstrate a possibility of reaching densities over 1025 cm−3, which is an order of magnitude higher than expected earlier. Controlling the process via initial target parameters provides an opportunity to reach the discovered plasma states at the upcoming laser facilities.
Droplet microfluidics for the highly controlled synthesis of branched gold nanoparticles
Authors: Abalde-Cela Sara , Taladriz-Blanco Patricia , de Oliveira Marcelo Ganzarolli , Abell Chris
Published: January 2018

The synthesis of anisotropic metallic nanoparticles (NPs) has been a field of intense and challenging research in the past decade. In this communication, we report on the reproducible and highly controllable synthesis of monodisperse branched gold nanoparticles in a droplet-based microfluidics platform. The process has been automated by adapting two different bulk synthetic strategies to microdroplets, acting as microreactors, for NP synthesis: a surfactant-free synthesis and a surfactant-assisted synthesis. Microdroplets were generated in two different microfluidic devices designed to accommodate the requirements of both bulk syntheses. The epitaxial growth of AuNSTs inside the microdroplets allowed for a fine control of reagent mixing and local concentrations during particle formation. This is the first time branched gold NPs have been synthesised in a microfluidics platform. The monodispersity of the product was comparable to the synthesis in bulk, proving the potential of this technology for the continuous synthesis of high quality anisotropic NPs with improved reproducibility.
Slow Wave Applications of Electromagnetically Induced Transparency in Microstrip Resonator
Authors: Amin Muhammad , Ramzan Rashad , Siddiqui Omar
Published: January 2018

We report a novel guided-wave resonator that supports multiple bands of electromagnetically induced transparency (EIT). The platform for the spatial and spectral interference is obtained by a microstrip transmission line loaded with proximity-coupled open-circuited stubs. We show experimentally that with two microstrip open stubs, a complete destructive interference takes place leading to a single EIT band with near-unity transmission efficiency. More interestingly, the addition of a third stub results in a supplementary EIT band with a Q-factor of 147 and an effective group refractive index of 530. With the open-stub configuration, the EIT phase response can be dynamically controlled by varying the capacitance between the adjacent stubs without breaking the transmission path of the underlying electromagnetic waves. Therefore, the proposed structure is well suited for buffering and tunable phase modulation applications. Since the proposed structures are compact and fully planar, we anticipate seamless integration with low-profile high frequency electronics.
Ubiquinone binding site of yeast NADH dehydrogenase revealed by structures binding novel competitive- and mixed-type inhibitors
Authors: Yamashita Tetsuo , Inaoka Daniel Ken , Shiba Tomoo , Oohashi Takumi , Iwata So , Yagi Takao , Kosaka Hiroaki , Miyoshi Hideto , Harada Shigeharu , Kita Kiyoshi , Hirano Katsuya
Published: January 2018

Yeast Ndi1 is a monotopic alternative NADH dehydrogenase. Its crystal structure in complex with the electron acceptor, ubiquinone, has been determined. However, there has been controversy regarding the ubiquinone binding site. To address these points, we identified the first competitive inhibitor of Ndi1, stigmatellin, along with new mixed-type inhibitors, AC0-12 and myxothiazol, and thereby determined the crystal structures of Ndi1 in complexes with the inhibitors. Two separate binding sites of stigmatellin, STG-1 and STG-2, were observed. The electron density at STG-1, located at the vicinity of the FAD cofactor, further demonstrated two binding modes: STG-1a and STG-1b. AC0-12 and myxothiazol are also located at the vicinity of FAD. The comparison of the binding modes among stigmatellin at STG-1, AC0-12, and myxothiazol revealed a unique position for the aliphatic tail of stigmatellin at STG-1a. Mutations of amino acid residues that interact with this aliphatic tail at STG-1a reduced the affinity of Ndi1 for ubiquinone. In conclusion, the position of the aliphatic tail of stigmatellin at STG-1a provides a structural basis for its competitive inhibition of Ndi1. The inherent binding site of ubiquinone is suggested to overlap with STG-1a that is distinct from the binding site for NADH.