bluuebunny/crossref_metadata_2025 huggingface dataset:
The long noncoding RNA GAS5 negatively regulates the adipogenic differentiation of MSCs by modulating the miR-18a/CTGF axis as a ceRNA
Authors: Li Ming , Xie Zhongyu , Wang Peng , Li Jinteng , Liu Wenjie , Tang Su’an , Liu Zhenhua , Wu Xiaohua , Wu Yanfeng , Shen Huiyong
Published: May 2018

Mesenchymal stem cells (MSCs) are important pluripotent stem cells and a major source of adipocytes in the body. However, the mechanism of adipogenic differentiation has not yet been completely elucidated. In this study, the long noncoding RNA GAS5 was found to be negatively correlated with MSC adipogenic differentiation. GAS5 overexpression negatively regulated adipocyte formation, whereas GAS5 knockdown had the opposite effect. Further mechanistic analyses using luciferase reporter assays revealed that GAS5 regulates the adipogenic differentiation of MSCs by acting as competing endogenous RNA (ceRNA) to sponge miR-18a, which promotes adipogenic differentiation. Mutation of the binding sites for GAS5 in miR-18a abolished the effect of the interaction. The miR-18a mimic and inhibitor reversed the negative regulatory effect of GAS5 on MSCs adipogenic differentiation. In addition, GAS5 inhibited miR-18a, which downregulates connective tissue growth factor (CTGF) expression, to negatively regulate the adipogenic differentiation of MSCs. Taken together, the results show that GAS5 serves as a sponge for miR-18a, inhibiting its capability to suppress CTGF protein translation and ultimately decreasing the adipogenic differentiation of MSCs. GAS5 is an important molecule involved in the adipogenic differentiation of MSCs and may contribute to the functional regulation and clinical applications of MSCs.
L-SCRaMbLE as a tool for light-controlled Cre-mediated recombination in yeast
Authors: Hochrein Lena , Mitchell Leslie A. , Schulz Karina , Messerschmidt Katrin , Mueller-Roeber Bernd
Published: May 2018

The synthetic yeast genome constructed by the International Synthetic Yeast Sc2.0 consortium adds thousands of loxPsym recombination sites to all 16 redesigned chromosomes, allowing the shuffling of Sc2.0 chromosome parts by the Cre-loxP recombination system thereby enabling genome evolution experiments. Here, we present L-SCRaMbLE, a light-controlled Cre recombinase for use in the yeast Saccharomyces cerevisiae. L-SCRaMbLE allows tight regulation of recombinase activity with up to 179-fold induction upon exposure to red light. The extent of recombination depends on induction time and concentration of the chromophore phycocyanobilin (PCB), which can be easily adjusted. The tool presented here provides improved recombination control over the previously reported estradiol-dependent SCRaMbLE induction system, mediating a larger variety of possible recombination events in SCRaMbLE-ing a reporter plasmid. Thereby, L-SCRaMbLE boosts the potential for further customization and provides a facile application for use in the S. cerevisiae genome re-engineering project Sc2.0 or in other recombination-based systems.
Publisher Correction: Renal capsular invasion is a prognostic biomarker in localized clear cell renal cell carcinoma
Authors: Ha U-Syn , Lee Kyu Won , Jung Jin-hyung , Byun Seok-Soo , Kwak Cheol , Chung Jinsoo , Hwang Eu Chang , Kim Yong-June , Kwon Tae Gyun , Kang Seok Ho , Hong Sung-Hoo
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 been fixed in the paper.
Author Correction: Transcriptomic signature of drought response in pearl millet (Pennisetum glaucum (L.) and development of web-genomic resources
Authors: Jaiswal Sarika , Antala Tushar J. , Mandavia M. K. , Chopra Meenu , Jasrotia Rahul Singh , Tomar Rukam S. , Kheni Jashminkumar , Angadi U. B. , Iquebal M. A. , Golakia B. A. , Rai Anil , Kumar Dinesh
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 been fixed in the paper.
Emotional reactivity and perspective-taking in individuals with and without severe depressive symptoms
Authors: Imbault Constance , Kuperman Victor
Published: May 2018

The perspective-taking ability to imagine another person’s feelings and thoughts is paramount for successful communication. This study pursued two questions regarding the link between perspective-taking and depressive symptomatology in a task where participants provided responses to words ranging in their positivity. First, we examined in a between-participants experimental manipulation how the presence of depressive symptoms influenced participants’ emotional reactivity. Second, we measured within-participants, how their responses change as a function of the perspective they are assigned to take, that of a depressed or a non-depressed person. Our main interest is in the interaction of the two effects: we examine how one’s emotional state determines the ability to engender someone else’s responses. Our central finding is that depressive symptoms lead to emotional insensitivity, i.e., weaker responses to extremely positive and negative words. Furthermore, depressive symptoms come with a much weaker ability to take a non-depressed perspective. Finally, non-depressed participants demonstrated an excellent ability to mimic the blunt affect of depression when responding for the other group, suggesting that the outlook of a depressed individual is available to people throughout the range of depressive symptomatology. We discuss the implications of these findings for quantifying emotional reactivity during depression, as well as the diagnosis and prognosis of depression.
Increase In Il-31 Serum Levels Is Associated With Reduced Structural Damage In Early Axial Spondyloarthritis
Authors: Rosine Nicolas , Etcheto Adrien , Hendel-Chavez Houria , Seror Raphaèle , Briot Karine , Molto Anna , Chanson Philippe , Taoufik Yassine , Wendling Daniel , Lories Rik , Berenbaum Francis , van den Berg Rosaline , Claudepierre Pascal , Feydy Antoine , Dougados Maxime , Roux Christian , Miceli-Richard Corinne
Published: May 2018

In spondyloarthritis, little is known about the relation between circulating cytokines and patient phenotype. We have quantified serum levels of T helper type 1 cell (Th1), Th2 and Th17 cytokines in patients with recent-onset axial spondyloarthritis (AxSpA) from the DESIR cohort, a prospective, multicenter French cohort consisting of 708 patients with recent-onset inflammatory back pain (duration >3 months but <3 years) suggestive of AxSpA. Serum levels of Th1, Th2, and Th17 cytokines were assessed at baseline in patients from the DESIR cohort fulfilling the ASAS criteria (ASAS+) and were compared with age- and sex-matched healthy controls. At baseline, ASAS+ patients (n = 443) and healthy controls (n = 79) did not differ in levels of most of the Th1, Th2 and Th17 cytokines except for IL-31, and sCD40L, which were significantly higher for ASAS+ patients than controls (p < 0.001 and p = 0.012, respectively). On multivariable analysis of ASAS+ patients, IL-31 level was associated with sCD40L level (p < 0.0001), modified Stoke AS Spine Score (mSASSS) < 1 (p = 0.035). The multivariable analyses showed that IL-31 was an independent factor associated with mSASSS < 1 (p = 0.001) and low bone mineral density (p = 0.01). Increased level of IL-31 might protect against structural damage but is also related to low BMD.
Hcp/fcc nucleation in bcc iron under different anisotropic compressions at high strain rate: Molecular dynamics study
Authors: Shao Jian-Li , Wang Pei , Zhang Feng-Guo , He An-Min
Published: May 2018

Previous researches have revealed the importance of shear and the orientation dependence in the structural transition of iron. In this work, we introduce a series of shear deformations by adjusting the strain ratio between the longitudinal ([001]) and transversal ([010] and [100]) directions, and then investigate this structural transition under different anisotropic compressions with molecular dynamics simulations. It is found that the shear deformation can lower the transition pressure notably, and even change the nucleation structure and morphology. Under 1D-dominated compression (along (001) direction), there only appears hcp nucleation with a few fcc stacking faults. For other cases, more equivalent planes will be activated and fcc structure begins to nucleate. Under 2D-dominated compression (along (010) and (001) directions), the fcc mass fraction is already over the hcp phase. At last, we compare the variations of shear stress and potential energy for different phases, and present the sliding mechanism under typical anisotropic compressions.
Detection of chikungunya virus DNA using two-dimensional MoS2 nanosheets based disposable biosensor
Authors: Singhal Chaitali , Khanuja Manika , Chaudhary Nahid , Pundir C. S. , Narang Jagriti
Published: May 2018

Development of platforms for a reliable, rapid, sensitive and selective detection of chikungunya virus (CHIGV) is the need of the hour in developing countries. To the best of our knowledge, there are no reports available for the electrochemical detection of CHIGVDNA. Therefore, we aim at developing a biosensor based on molybdenum disulphide nanosheets (MoS2NSs) for the point-of-care diagnosis of CHIGV. Briefly, MoS2NSs were synthesized by chemical route and characterized using scanning electron microscopy, transmission electron microscopy, UV-Vis spectroscopy, Raman spectroscopy and X-Ray Diffraction. MoS2NSs were then subjected to physical adsorption onto the screen printed gold electrodes (SPGEs) and then employed for the detection of CHIGV DNA using electrochemical voltammetric techniques. Herein, the role of MoS2NSs is to provide biocompatibility to the biological recognition element on the surface of the screen printed electrodes. The detection strategy employed herein is the ability of methylene blue to interact differentially with the guanine bases of the single and double-stranded DNA which leads to change in the magnitude of the voltammetric signal. The proposed genosensor exhibited a wide linear range of 0.1 nM to 100 µM towards the chikungunya virus DNA.
The opto-locomotor reflex as a tool to measure sensitivity to moving random dot patterns in mice
Authors: Kirkels L. A. M. H. , Zhang W. , Havenith M. N. , Tiesinga P. , Glennon J. , van Wezel R. J. A. , Duijnhouwer J.
Published: May 2018

We designed a method to quantify mice visual function by measuring reflexive opto-locomotor responses. Mice were placed on a Styrofoam ball at the center of a large dome on the inside of which we projected moving random dot patterns. Because we fixed the heads of the mice in space and the ball was floating on pressurized air, locomotion of the mice was translated to rotation of the ball, which we registered. Sudden onsets of rightward or leftward moving patterns caused the mice to reflexively change their running direction. We quantified the opto-locomotor responses to different pattern speeds, luminance contrasts, and dot sizes. We show that the method is fast and reliable and the magnitude of the reflex is stable within sessions. We conclude that this opto-locomotor reflex method is suitable to quantify visual function in mice.
NDE1 positively regulates oligodendrocyte morphological differentiation
Authors: Shimizu Shoko , Ishino Yugo , Tohyama Masaya , Miyata Shingo
Published: May 2018

Oligodendrocytes, the myelin-forming cells in the central nervous system (CNS), undergo morphological differentiation characterized by elaborated branched processes to enwrap neuronal axons. However, the basic molecular mechanisms underlying oligodendrocyte morphogenesis remain unknown. Herein, we describe the essential roles of Nuclear Distribution E Homolog 1 (NDE1), a dynein cofactor, in oligodendrocyte morphological differentiation. In the mouse corpus callosum, Nde1 mRNA expression was detected in oligodendrocyte lineage cells at the postnatal stage. In vitro analysis revealed that downregulation of NDE1 by siRNA impaired the outgrowth and extensive branching of oligodendrocyte processes and led to a decrease in the expression of myelin-related markers, namely, CNPase and MBP. In myelinating co-cultures with dorsal root ganglion (DRG) neurons, NDE1-knockdown oligodendrocyte precursor cells (OPCs) failed to develop into MBP-positive oligodendrocytes with multiple processes contacting DRG axons. Immunoprecipitation studies showed that NDE1 interacts with the dynein intermediate chain (DIC) in oligodendrocytes, and an overexpressed DIC-binding region of NDE1 exerted effects on oligodendrocyte morphogenesis that were similar to those following NDE1 knockdown. Furthermore, NDE1-knockdown-impaired oligodendrocyte process formation was rescued by siRNA-resistant wild-type NDE1 but not by DIC-binding region-deficient NDE1 overexpression. These results suggest that NDE1 plays a crucial role in oligodendrocyte morphological differentiation via interaction with dynein.
Honey bees consider larval nutritional status rather than genetic relatedness when selecting larvae for emergency queen rearing
Authors: Sagili Ramesh R. , Metz Bradley N. , Lucas Hannah M. , Chakrabarti Priyadarshini , Breece Carolyn R.
Published: May 2018

In honey bees and many other social insects, production of queens is a vital task, as colony fitness is dependent on queens. The factors considered by honey bee workers in selecting larvae to rear new queens during emergency queen rearing are poorly understood. Identifying these parameters is critical, both in an evolutionary and apicultural context. As female caste development in honey bees is dependent on larval diet (i.e. nutrition), we hypothesized that larval nutritional state is meticulously assessed and used by workers in selection of larvae for queen rearing. To test this hypothesis, we conducted a series of experiments manipulating the nutritional status of one day old larvae by depriving them of brood food for a four-hour period, and then allowing workers to choose larvae for rearing queens from nutritionally deprived and non-deprived larvae. We simultaneously investigated the role of genetic relatedness in selection of larvae for queen rearing. In all the experiments, significantly greater numbers of non-deprived larvae than deprived larvae were selected for queen rearing irrespective of genetic relatedness. Our results demonstrate that honey bees perceive the nutritional state of larvae and use that information when selecting larvae for rearing queens in the natural emergency queen replacement process.
Explorations on the ecological role of toxin secretion and delivery in jawless predatory Polychaeta
Authors: Cuevas N. , Martins M. , Rodrigo A. P. , Martins C. , Costa P. M.
Published: May 2018

Motivated by biotechnological prospects, there is increasing evidence that we may just be scraping the tip of the iceberg of poisonous marine invertebrates, among which the Polychaeta are promising candidates for bioprospecting. Here we show that an inconspicuous phyllodocid uses toxins in its uncanny feeding strategy. The worm, a jawless active predator characterised by its bright green colour, preys on larger invertebrates (including conspecifics) by extracting tissue portions with its powerful proboscis through suction. The animal is even able to penetrate through the valves and plates of live molluscs and barnacles. Observationsin situand a series of experiments demonstrated that the worm compensates its simple anatomy with secretion of a novel toxin, or mixture of toxins, referred to by us as “phyllotoxins”. These are carried by mucus and delivered via repeated contact with the tip of the proboscis until the prey is relaxed or immobilised (reversibly). Proteolytic action permeabilises material to toxins and softens tissue to enable extraction by suction. The findings show that toxins are a major ecological trait and therefore play a key role in evolutionary success and diversification of Polychaeta, demonstrating also that understanding adaptative features may become the best showcase for novel animal toxins.
Sex-difference in bone architecture and bone fragility in Vietnamese
Authors: Ho-Pham Lan T. , Ho-Le Thao P. , Mai Linh D. , Do Tam M. , Doan Minh C. , Nguyen Tuan V.
Published: May 2018

This study sought to define the sex-difference in trabecular and cortical bone parameters in Vietnamese individuals. The study involved 1404 women and 864 men aged between 20 and 86 years who were recruited from Ho Chi Minh City, Vietnam. Trabecular and cortical volumetric BMD were measured at the proximal tibia and proximal radius at 4%, 38%, and 66% points, using a peripheral quantitative computed tomography XCT2000 (Stratec, Germany). Polar strength strain index was estimated from cortical bone parameters. Changes in bone parameters were assessed by the multiple linear regression model. Among individuals aged 20–39 years, women had significantly lower peak trabecular BMD at both the radius (40%) and tibia (16%) than men, but the age-related reduction in trabecular BMD were similar between two sexes. For cortical BMD, peak values in women and men were comparable, but the age-related diminution was greater in women than men. At any age, polar strength strain index in women was lower than men, and the difference was mainly attributable to cortical bone area and total bone mass. We conclude that in the elderly, sex-related difference in trabecular BMD is originated during growth, but sex-related difference in cortical BMD is determined by differential age-related bone loss.
Indoor wet cells as a habitat for melanized fungi, opportunistic pathogens on humans and other vertebrates
Authors: Wang Xiaofang , Cai Wenying , van den Ende A. H. G. Gerrits , Zhang Junmin , Xie Ting , Xi Liyan , Li Xiqing , Sun Jiufeng , de Hoog Sybren
Published: May 2018

Indoor wet cells serve as an environmental reservoir for a wide diversity of melanized fungi. A total of 313 melanized fungi were isolated at five locations in Guangzhou, China. Internal transcribed spacer (rDNA ITS) sequencing showed a preponderance of 27 species belonging to 10 genera; 64.22% (n = 201) were known as human opportunists in the ordersChaetothyrialesandVenturiales, potentially causing cutaneous and sometimes deep infections.Knufia epidermidiswas the most frequently encountered species in bathrooms (n = 26), while in kitchensOchroconis musae(n = 14),Phialophora oxyspora(n = 12) andP. europaea(n = 10) were prevalent. Since the majority of species isolated are common agents of cutaneous infections and are rarely encountered in the natural environment, it is hypothesized that indoor facilities explain the previously enigmatic sources of infection by these organisms.
The cholinergic contribution to the resting-state functional network in non-demented Parkinson’s disease
Authors: Lee Yoonju , Ham Jee Hyun , Cha Jungho , Park Yeong-Hun , Lee Jae Jung , Sunwoo Mun Kyung , Hong Jin Yong , Sohn Young H. , Lee Jong-Min , Lee Phil Hyu
Published: May 2018

The cholinergic system arising from the basal forebrain plays an important role in cognitive performance in Parkinson’s disease (PD). Here, we analyzed cholinergic status-dependent cortical and subcortical resting-state functional connectivity in PD. A total of 61 drug-naïve PD patients were divided into tertiles based on normalized substantia innominata (SI) volumes. We compared the resting-state network from seed region of interest in the caudate, posterior cingulate cortex (PCC), and SI between the lowest (PD-L) and highest tertile (PD-H) groups. Correlation analysis of the functional networks was also performed in all subjects. The functional network analysis showed that PD-L subjects displayed decreased striato-cortical functional connectivity compared with PD-H subjects. Selecting the PCC as a seed, the PD-L patients displayed decreased functional connectivity compared to PD-H patients. Meanwhile, PD-L subjects had significantly increased cortical functional connectivity with the SI compared with PD-H subjects. Correlation analysis revealed that SI volume had a positive correlation with functional connectivity from the right caudate and PCC. The present study demonstrated that PD patients exhibited unique functional connectivity from the caudate and the PCC that may be closely associated with cholinergic status, suggesting an important role for the cholinergic system in PD-associated cognition.
Changes in L4/5 Intervertebral Foramen Bony Morphology with Age
Authors: Yan Shuaifeng , Wang Kai , Zhang Yunfan , Guo Song , Zhang Yan , Tan Jun
Published: May 2018

The purpose of this study was to explore the morphological changes in L4/5 intervertebral foramen with age using a digital method. The closed boundaries of the intervertebral foramen (IGES) in different sagittal slices (inside, middle and outside) were obtained from Mimics, and then imported to a custom-written program, which provided quantitative distance between the nerve root and the closed curves. The quantitative information of each age group was used to produce radar chart and line chart for morphological and statistical analyses. Overall, the intervertebral foramen changes mainly occurred in the inner part from middle age to old age. The foraminal height decreased with age in the inside sagittal slice, while no significant difference was found in the middle sagittal slice or the outside sagittal slice. The foraminal width showed no decrease in each age group or each sagittal plane. The present study described foraminal geometry of asymptomatic males in different sagittal slices with age. This information enhances the knowledge of anatomical changes in intervertebral foramen with age, which provides better understanding of the pathology of intervertebral foramen diseases.
Economic analysis of implementing virtual reality therapy for pain among hospitalized patients
Authors: Delshad Sean D. , Almario Christopher V. , Fuller Garth , Luong Duong , Spiegel Brennan M. R.
Published: May 2018

Virtual reality (VR) has emerged as a novel and effective non-pharmacologic therapy for pain, and there is growing interest to use VR in the acute hospital setting. We sought to explore the cost and effectiveness thresholds VR therapy must meet to be cost-saving as an inpatient pain management program. The result is a framework for hospital administrators to evaluate the return on investment of implementing inpatient VR programs of varying effectiveness and cost. Utilizing decision analysis software, we compared adjuvant VR therapy for pain management vs. usual care among hospitalized patients. In the VR strategy, we analyzed potential cost-savings from reductions in opioid utilization and hospital length of stay (LOS), as well as increased reimbursements from higher patient satisfaction as measured by the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey. The average overall hospitalization cost-savings per patient for the VR program vs. usual care was $5.39 (95% confidence interval –$11.00 to $156.17). In a probabilistic sensitivity analysis across 1000 hypothetical hospitals of varying size and staffing, VR remained cost-saving in 89.2% of trials. The VR program was cost-saving so long as it reduced LOS by ≥14.6%; the model was not sensitive to differences in opioid use or HCAHPS. We conclude that inpatient VR therapy may be cost-saving for a hospital system primarily if it reduces LOS. In isolation, cost-savings from reductions in opioid utilization and increased HCAHPS-related reimbursements are not sufficient to overcome the costs of VR.
Substrate mediated redox partner selectivity of cytochrome P450
Authors: Gentry Katherine A. , Zhang Meng , Im Sang-Choul , Waskell Lucy , Ramamoorthy Ayyalusamy
Published: May 2018

Investigating the interplay between cytochrome-P450 and its redox partners (CPR and cytochrome-b5) is vital for understanding the metabolism of most hydrophobic drugs.
Inelastic neutron scattering study of the lattice dynamics of the homologous compounds (PbSe)5(Bi2Se3)3m (m = 1, 2 and 3)
Authors: Sassi Selma , Candolfi Christophe , Dauscher Anne , Lenoir Bertrand , Koza Michael Marek
Published: May 2018

High-resolution powder inelastic neutron scattering experiments performed on the homologous series (PbSe)5(Bi2Se3)3m (m = 1, 2 and 3) indicate that their glass-like thermal conductivity is not due to significant anharmonic behavior.
Heterobimetallic triple-decker complexes derived from a dianionic aromatic stannole ligand
Authors: Saito Masaichi , Matsunaga Naoki , Hamada Jumpei , Furukawa Shunsuke , Minoura Mao , Wegner Susann , Barthel Juri , Janiak Christoph
Published: May 2018

A neutral heterobimetallic triple-decker stannole complex was prepared by the reaction of an anionic ruthenocene bearing a stannole dianionic ligand with [Rh(cod)Cl]2 (cod = 1,5-cyclooctadiene), and the resulting Ru–Rh complex exhibits an electronic property different from those of the corresponding Ru–Ru and Rh–Rh complexes.
Hydrothermally synthesized BiVO4–reduced graphene oxide nanocomposite as a high performance supercapacitor electrode with excellent cycle stability
Authors: Dutta Shibsankar , Pal Shreyasi , De Sukanta
Published: May 2018

A BiVO4/rGO hybrid-based symmetric supercapacitor has been fabricated via a simple one-step hydrothermal process, which shows a synergistic effect towards electrochemical performance with excellent cycle stability.
Fabrication of graphene/copper–nickel foam composite for high performance supercapacitors
Authors: Liu Guoxiao , Lu Shixiang , Xu Wenguo , He Ge , Zheng Yu , Cheng Yuanyuan
Published: May 2018

An rGO/PDA/CNF composite electrode is fabricated by an immersing and annealing process and exhibits superior electrochemical performance.
Modeling of canonical and C2′-O-thiophenylmethyl modified hexamers of RNA. Insights into the nature of structural changes and thermal stability
Authors: Dzowo Yannick Kokouvi , Wolfbrandt Carly , Resendiz Marino J. E. , Wang Haobin
Published: May 2018

Modification of the C2′-O-position with thiophenylmethyl groups on both strands leads to thermal stabilization of the duplex. Predicting the effects that modifications will have on structure of RNA is of importance in the development of new RNA technologies.
Electrochromism of alkylene-linked discrete chromophore polymers with broad radical cation light absorption
Authors: Christiansen Dylan T. , Wheeler David L. , Tomlinson Aimée L. , Reynolds John R.
Published: May 2018

This paper details the theoretical calculations, synthesis, and electrochromism of polymeric materials consisting of conjugated chromophores separated by nonconjugated linkers.
An allostatic mechanism for M2 pyruvate kinase as an amino-acid sensor
Authors: Yuan Meng , McNae Iain W. , Chen Yiyuan , Blackburn Elizabeth A. , Wear Martin A. , Michels Paul A.M. , Fothergill-Gilmore Linda A. , Hupp Ted , Walkinshaw Malcolm D.
Published: May 2018

We have tested the effect of all 20 proteinogenic amino acids on the activity of the M2 isoenzyme of pyruvate kinase (M2PYK) and show that, within physiologically relevant concentrations, phenylalanine, alanine, tryptophan, methionine, valine, and proline act as inhibitors, while histidine and serine act as activators. Size exclusion chromatography has been used to show that all amino acids, whether activators or inhibitors, stabilise the tetrameric form of M2PYK. In the absence of amino-acid ligands an apparent tetramer–monomer dissociation Kd is estimated to be ∼0.9 µM with a slow dissociation rate (t1/2 ∼ 15 min). X-ray structures of M2PYK complexes with alanine, phenylalanine, and tryptophan show the M2PYK locked in an inactive T-state conformation, while activators lock the M2PYK tetramer in the active R-state conformation. Amino-acid binding in the allosteric pocket triggers rigid body rotations (11°) stabilising either T or R states. The opposing inhibitory and activating effects of the non-essential amino acids serine and alanine suggest that M2PYK could act as a rapid-response nutrient sensor to rebalance cellular metabolism. This competition at a single allosteric site between activators and inhibitors provides a novel regulatory mechanism by which M2PYK activity is finely tuned by the relative (but not absolute) concentrations of activator and inhibitor amino acids. Such ‘allostatic’ regulation may be important in metabolic reprogramming and influencing cell fate.
Shooting the messenger: RNA-targetting CRISPR-Cas systems
Authors: Zhu Yifan , Klompe Sanne E. , Vlot Marnix , van der Oost John , Staals Raymond H.J.
Published: May 2018

Since the discovery of CRISPR-Cas (Clustered Regularly Interspaced Short Palindromic Repeats, CRISPR-associated genes) immune systems, astonishing progress has been made on revealing their mechanistic foundations. Due to the immense potential as genome engineering tools, research has mainly focussed on a subset of Cas nucleases that target DNA. In addition, however, distinct types of RNA-targetting CRISPR-Cas systems have been identified. The focus of this review will be on the interference mechanisms of the RNA targetting type III and type VI CRISPR-Cas systems, their biological relevance and their potential for applications.
MiR-302e attenuates allergic inflammation in vitro model by targeting RelA
Authors: Xiao Lifeng , Jiang Li , Hu Qi , Li Yuru
Published: May 2018

Allergic inflammation is the foundation of allergic rhinitis and asthma. Although microRNAs are implicated in the pathogenesis of various diseases, information regarding the functional role of microRNAs in allergic diseases is limited. Herein, we reported that microRNA-302e (miR-302e) serves as an important regulator of allergic inflammation in human mast cell line, HMC-1 cells. Our results showed that miR-302e is the dominant member of miR-302 family expressed in HMC-1 cells. Moreover, the expression of miR-302e was significantly decreased in response to phorbol 12-myristate 13-acetate (PMA) and calcium ionophore A23187 or ovalbumin (OVA) stimulation. Overexpression of miR-302e blocked PMA/A23187 or OVA induced the increase in inflammatory cytokines levels, such as IL-1β, IL-6, tumor necrosis factor (TNF)-α and thymic stromal lymphopoietin, while miR-302 inhibition further promoted the release of these cytokines. Mechanistically, we found that miR-302e is a novel miRNA that targets RelA, a gene known to be involved in regulating inflammation, through binding to the 3′-UTR of RelA mRNA. Ectopic miR-302e remarkably suppressed the luciferase activity and expression of RelA, whereas down-regulation of miR-302e increased RelA luciferase activity and expression. Pharmacological inhibition of NF-κB reversed the augmented effect of miR-302e down-regulation on inflammatory cytokines level. Taken together, the present study demonstrates miR-302e limits allergic inflammation through inhibition of NF-κB activation, suggesting miR-302e may play an anti-inflammatory role in allergic diseases and function as a novel therapeutic target for the treatment of these diseases.
Cognitive Predictors of Spoken Word Recognition in Children With and Without Developmental Language Disorders
Authors: Evans Julia L. , Gillam Ronald B. , Montgomery James W.
Published: May 2018

Purpose

This study examined the influence of cognitive factors on spoken word recognition in children with developmental language disorder (DLD) and typically developing (TD) children.

Method

Participants included 234 children (aged 7;0–11;11 years;months), 117 with DLD and 117 TD children, propensity matched for age, gender, socioeconomic status, and maternal education. Children completed a series of standardized assessment measures, a forward gating task, a rapid automatic naming task, and a series of tasks designed to examine cognitive factors hypothesized to influence spoken word recognition including phonological working memory, updating, attention shifting, and interference inhibition.

Results

Spoken word recognition for both initial and final accept gate points did not differ for children with DLD and TD controls after controlling target word knowledge in both groups. The 2 groups also did not differ on measures of updating, attention switching, and interference inhibition. Despite the lack of difference on these measures, for children with DLD, attention shifting and interference inhibition were significant predictors of spoken word recognition, whereas updating and receptive vocabulary were significant predictors of speed of spoken word recognition for the children in the TD group.

Conclusion

Contrary to expectations, after controlling for target word knowledge, spoken word recognition did not differ for children with DLD and TD controls; however, the cognitive processing factors that influenced children's ability to recognize the target word in a stream of speech differed qualitatively for children with and without DLDs.
Non‐coherent detection of digitally phase‐modulated signals with carbon nanotube cantilever vibration
Authors: Tadokoro Y. , Ohno Y. , Tanaka H.
Published: May 2018

Towards the realisation of reliable communication systems using simple nanoscale transceivers, this Letter presents a method for the non‐coherent detection of digitally phase‐modulated signals. Without the synchronisation of the phases of the transmitted and received carrier signals, data transmission cannot be reliably achieved. To address this issue, the proposed method is developed using a nanoscale receiver that receives the binary phase‐modulated signal through the mechanical vibration of a carbon nanotube cantilever. The present analysis reveals that this receiver has an interesting characteristic: the two decision statistics available in the receiver have a phase difference of , which means that at least one of the statistics is fairly reliable regardless of the synchronisation error. Through the selection of the more reliable of the two statistics, the proposed method achieves low error in the estimation of the transmitted data even without carrier phase synchronisation. This Letter presents the derivation of the proposed rule for selecting the statistic and numerical results that demonstrate the effectiveness of the proposed method. This Letter is expected to contribute to the realisation of future communication applications using nanoscale transceivers.
3D radiative transfer: Continuum and line scattering in non-spherical winds from OB stars
Authors: Hennicker L. , Puls J. , Kee N. D. , Sundqvist J. O.
Published: May 2018

Context. State of the art quantitative spectroscopy utilizes synthetic spectra to extract information from observations. For hot, massive stars, these synthetic spectra are calculated by means of 1D, spherically symmetric, NLTE atmosphere and spectrum-synthesis codes. Certain stellar atmospheres, however, show strong deviations from spherical symmetry, and need to be treated in 3D.

Aims. We present and test a newly developed 3D radiative transfer code, tailored to the solution of the radiation field in rapidly expanding stellar atmospheres. We apply our code to the continuum transfer in wind-ablation models, and to the UV resonance line formation in magnetic winds.

Methods. We have used a 3D finite-volume method for the solution of the time-independent equation of radiative transfer, to study continuum- and line-scattering problems, currently approximated by a two-level-atom. Convergence has been accelerated by coupling the formal solver to a non-local approximate Λ-iteration scheme. Particular emphasis has been put on careful tests, by comparing with alternative solutions for 1D, spherically symmetric model atmospheres. These tests allowed us to understand certain shortcomings of the methods, and to estimate limiting cases that can actually be calculated.

Results. The typical errors of the converged source functions, when compared to 1D solutions, are of the order of 10–20%, and rapidly increase for optically thick (τ ≳ 10) continua, mostly due to the order of accuracy of our solution scheme. In circumstellar discs, the radiation temperatures in the (optically thin) transition region from wind to disc are quite similar to corresponding values in the wind. For MHD simulations of dynamical magnetospheres, the line profiles, calculated with our new 3D code, agree well with previous solutions using a 3D-SEI method. When compared with profiles resulting from the so-called analytic dynamical magnetosphere (ADM) model, however, significant differences become apparent.

Conclusions. Due to similar radiation temperatures in the wind and the transition region to the disc, the same line-strength distribution can be applied within radiation hydrodynamic calculations for optically thick circumstellar discs in “accreting high-mass stars”. To properly describe the UV line formation in dynamical magnetospheres, the ADM model needs to be further developed, at least in a large part of the outer wind.
Monitoring near-Earth-object discoveries for imminent impactors
Authors: Solin Otto , Granvik Mikael
Published: May 2018

Aims. We present an automated system calledNEORANGERthat regularly computes asteroid-Earth impact probabilities for objects on the Minor Planet Center’s (MPC) Near-Earth-Object Confirmation Page (NEOCP) and sends out alerts of imminent impactors to registered users. In addition to potential Earth-impacting objects,NEORANGERalso monitors for other types of interesting objects such as Earth’s natural temporarily-captured satellites.

Methods. The system monitors the NEOCP for objects with new data and solves, for each object, the orbital inverse problem, which results in a sample of orbits that describes the, typically highly-nonlinear, orbital-element probability density function (PDF). The PDF is propagated forward in time for seven days and the impact probability is computed as the weighted fraction of the sample orbits that impact the Earth.

Results. The system correctly predicts the then-imminent impacts of 2008 TC3and 2014 AA based on the first data sets available. Using the same code and configuration we find that the impact probabilities for objects typically on the NEOCP, based on eight weeks of continuous operations, are always less than one in ten million, whereas simulated and real Earth-impacting asteroids always have an impact probability greater than 10% based on the first two tracklets available.
The visible and near-infrared spectra of asteroids in cometary orbits
Authors: Licandro J. , Popescu M. , de León J. , Morate D. , Vaduvescu O. , De Prá M. , Ali-Laoga Victor
Published: May 2018

Context. Dynamical and albedo properties suggest that asteroids in cometary orbits (ACOs) are dormant or extinct comets. Their study provides new insights for understanding the end-states of comets and the size of the comet population.

Aims. We intend to study the visible and near-infrared (NIR) spectral properties of different ACO populations and compare them to the independently determined properties of comets.

Methods. We select our ACOs sample based on published dynamical criteria and present our own observational results obtained using the 10.4 m Gran Telescopio Canarias (GTC), the 4.2 m William Herschel Telescope (WHT), the 3.56 m Telescopio Nazionale Galileo (TNG), and the 2.5 m Isaac Newton Telescope (INT), all located at the El Roque de los Muchachos Observatory (La Palma, Spain), and the 3.0 m NASA Infrared Telescope Facility (IRTF), located at the Mauna Kea Observatory, in Hawaii. We include in the analysis the spectra of ACOs obtained from the literature. We derive the spectral class and the visible and NIR spectral slopes. We also study the presence of hydrated minerals by studying the 0.7 μm band and the UV-drop below 0.5 μm associated with phyllosilicates. Results. We present new observations of 17 ACOs, 11 of them observed in the visible, 2 in the NIR and 4 in the visible and NIR. We also discuss the spectra of 12 ACOs obtained from the literature. All but two ACOs have a primitive-like class spectrum (X or D-type). Almost 100% of the ACOs in long-period cometary orbits (Damocloids) are D-types. Those in Jupiter family comet orbits (JFC-ACOs) are ∼60% D-types and ∼40% X-types. The mean spectral slope S′ of JFC-ACOs is 9.7 ± 4.6%/1000 Å and for the Damocloids this is 12.2 ± 2.0%/1000 Å. No evidence of hydration on the surface of ACOs is found from their visible spectra. The spectral slope and spectral class distribution of ACOs is similar to that of comets.

Conclusions. The spectral taxonomical classification and the spectral slope distribution of ACOs, and the lack of spectral features indicative of the presence of hydrated minerals on their surface, strongly suggest that ACOs are likely dormant or extinct comets.
A new and homogeneous metallicity scale for Galactic classical Cepheids
Authors: Proxauf B. , da Silva R. , Kovtyukh V. V. , Bono G. , Inno L. , Lemasle B. , Pritchard J. , Przybilla N. , Storm J. , Urbaneja M. A. , Valenti E. , Bergemann M. , Buonanno R. , D’Orazi V. , Fabrizio M. , Ferraro I. , Fiorentino G. , François P. , Iannicola G. , Laney C. D. , Kudritzki R.-P. , Matsunaga N. , Nonino M. , Primas F. , Romaniello M. , Thévenin F.
Published: May 2018

We gathered more than 1130 high-resolution optical spectra for more than 250 Galactic classical Cepheids. The spectra were collected with the optical spectrographs UVES at VLT, HARPS at 3.6 m, FEROS at 2.2 m MPG/ESO, and STELLA. To improve the effective temperature estimates, we present more than 150 new line depth ratio (LDR) calibrations that together with similar calibrations already available in the literature allowed us to cover a broad range in wavelength (5348 ≤ λ ≤ 8427 Å) and in effective temperature (3500 ≤ Teff ≤ 7700 K). This gives us the unique opportunity to cover both the hottest and coolest phases along the Cepheid pulsation cycle and to limit the intrinsic error on individual measurements at the level of ~100 K. As a consequence of the high signal-to-noise ratio of individual spectra, we identified and measured hundreds of neutral and ionized lines of heavy elements, and in turn, have the opportunity to trace the variation of both surface gravity and microturbulent velocity along the pulsation cycle. The accuracy of the physical parameters and the number of Fe I (more than one hundred) and Fe II (more than ten) lines measured allowed us to estimate mean iron abundances with a precision better than 0.1 dex. We focus on 14 calibrating Cepheids for which the current spectra cover either the entire or a significant portion of the pulsation cycle. The current estimates of the variation of the physical parameters along the pulsation cycle and of the iron abundances agree very well with similar estimates available in the literature. Independent homogeneous estimates of both physical parameters and metal abundances based on different approaches that can constrain possible systematics are highly encouraged.
An analytical solution of stress distribution around underground gas storage cavern in bedded salt rock
Authors: Xie Peng , Wen Haijia , Wang Guijun
Published: May 2018

The main purpose of this study is to investigate the stress distribution around an underground gas storage cavern in a bedded salt rock formation. First, considering the characteristics of the salt rock formations in China, the mechanical model was simplified into a hollow cylinder which contains a non-salt interlayer. Subsequently, based on the theory of elasticity, the Love displacement function was established, and the general solution of stress components was obtained using the boundary and continuity conditions for this problem. To verify the validity of the analytical solution, a numerical simulation was performed. Comparison between the analytical solution results and the numerical simulation results shows a relatively good agreement. Thus, the analytical solution could be used to describe the characteristics of stress distribution around the gas storage cavern containing the non-salt layer, which is constructed in the bedded salt rock.
Review of particle-in-cell modeling for the extraction region of large negative hydrogen ion sources for fusion
Authors: Wünderlich D. , Mochalskyy S. , Montellano I. M. , Revel A.
Published: May 2018

Particle-in-cell (PIC) codes are used since the early 1960s for calculating self-consistently the motion of charged particles in plasmas, taking into account external electric and magnetic fields as well as the fields created by the particles itself. Due to the used very small time steps (in the order of the inverse plasma frequency) and mesh size, the computational requirements can be very high and they drastically increase with increasing plasma density and size of the calculation domain. Thus, usually small computational domains and/or reduced dimensionality are used. In the last years, the available central processing unit (CPU) power strongly increased. Together with a massive parallelization of the codes, it is now possible to describe in 3D the extraction of charged particles from a plasma, using calculation domains with an edge length of several centimeters, consisting of one extraction aperture, the plasma in direct vicinity of the aperture, and a part of the extraction system. Large negative hydrogen or deuterium ion sources are essential parts of the neutral beam injection (NBI) system in future fusion devices like the international fusion experiment ITER and the demonstration reactor (DEMO). For ITER NBI RF driven sources with a source area of 0.9 × 1.9 m2 and 1280 extraction apertures will be used. The extraction of negative ions is accompanied by the co-extraction of electrons which are deflected onto an electron dump. Typically, the maximum negative extracted ion current is limited by the amount and the temporal instability of the co-extracted electrons, especially for operation in deuterium. Different PIC codes are available for the extraction region of large driven negative ion sources for fusion. Additionally, some effort is ongoing in developing codes that describe in a simplified manner (coarser mesh or reduced dimensionality) the plasma of the whole ion source. The presentation first gives a brief overview of the current status of the ion source development for ITER NBI and of the PIC method. Different PIC codes for the extraction region are introduced as well as the coupling to codes describing the whole source (PIC codes or fluid codes). Presented and discussed are different physical and numerical aspects of applying PIC codes to negative hydrogen ion sources for fusion as well as selected code results. The main focus of future calculations will be the meniscus formation and identifying measures for reducing the co-extracted electrons, in particular for deuterium operation. The recent results of the 3D PIC code ONIX (calculation domain: one extraction aperture and its vicinity) for the ITER prototype source (1/8 size of the ITER NBI source) are presented.
Detector for positronium temperature measurements by two-photon angular correlation
Authors: Cecchini G. G. , Jones A. C. L. , Fuentes-Garcia M. , Adams D. J. , Austin M. , Membreno E. , Mills A. P.
Published: May 2018

We report on the design and characterization of a modular γ-ray detector assembly developed for accurate and efficient detection of coincident 511 keV back-to-back γ-rays following electron-positron annihilation. Each modular detector consists of 16 narrow lutetium yttrium oxyorthosilicate scintillators coupled to a multi-anode Hamamatsu H12700B photomultiplier tube. We discuss the operation and optimization of 511 keV γ-ray detection resulting from testing various scintillators and detector arrangements concluding with an estimate of the coincident 511 keV detection efficiency for the intended experiment and a preliminary test representing one-quarter of the completed array.