bluuebunny/crossref_metadata_2025 huggingface dataset:
Inclusion Complexes of Non‐Granular Maize Starch with Fatty Acids and Ibuprofen. A Comparative Study of Their Morphology and Structure
Authors: Marinopoulou Anna , Papastergiadis Efthimios , Raphaelides Stylianos N.
Published: July 2018

Drum dried pregelatinized normal maize starch complexes with fatty acids (decanoic, myristic, palmitic, stearic, and oleic acid) and ibuprofen are studied by various techniques. The aim of the study is to investigate the structural and morphological characteristics of the starch complexes and assess whether any differences might exist between the starch‐fatty acid systems and the starch‐ibuprofen system. The complexes are prepared at 30, 50, or 70 °C. X‐ray diffraction analysis reveals the semicrystalline V‐type structure of all complexes regardless the temperature of their preparation. The degree of crystallinity (%) of complexes increases with the increase in the preparation temperature while the size of crystals decreases. The crystal size of ibuprofen complexes is smaller than that of the fatty acid ones. DSC thermal analysis shows that the dissociation temperature of the complexes ranged from 95 to 125 °C. The enthalpy of dissociation of ibuprofen complexes is much lower than that of the fatty acid ones. SEM microscopy reveales the formation of spherulites or lamellae in the matrix of the complexes. FTIR spectroscopy and light microscopy confirmed the formation of starch complexes with fatty acids and ibuprofen.
Nimbolide induced apoptosis by activating ERK‐mediated inhibition of c‐IAP1 expression in human hepatocellular carcinoma cells
Authors: Hsueh Kuan‐Chun , Lin Chia‐Liang , Tung Jai‐Nien , Yang Shun‐Fa , Hsieh Yi‐Hsien
Published: July 2018

Nimbolide is one of the major compounds from the leaves and flowers of the neem tree and exhibits antitumor properties on various cancer cells. However, no report has shown that nimbolide induces apoptosis in vitro and in vivo in human hepatocellular carcinoma cells. Our results indicated that it inhibited cell growth in Huh‐7 and PLC/PRF/5 cells. We also found that nimbolide induced cell death through the induction of G2/M phase arrest and mitochondrial dysfunction, accompanied by the increased expression of cleaved caspase‐7, caspase‐9, caspase‐3, caspase‐PARP, and Bax and decreased expression of Mcl‐1 and Bcl‐2. A human apoptosis antibody array analysis demonstrated that inhibition of the apoptosis family proteins (XIAP, c‐IAP1, and c‐IAP2) was one of the major targets of nimbolide. Additionally, nimbolide sustained activation of ERK expression. Moreover, pretreatment with U0126 (MEK inhibitor) markedly abolished nimbolide‐inhibited cell viability, induced cell apoptosis, ERK phosphorylation, cleaved caspase‐9, caspase‐3, cleaved‐PARP activation, and increased c‐IAP1 expression in Huh‐7 cells. An in vivo study showed that nimbolide significantly reduced Huh‐7 tumor growth and weight in a xenograft mouse model. This study indicated the antitumor potential of nimbolide in human hepatocellular carcinoma cells.
Antimetastatic effects of Eclipta prostrata extract on oral cancer cells
Authors: Liao Miao‐Yu , Chuang Chun‐Yi , Hsieh Ming‐Ju , Chou Ying‐Erh , Lin Chiao‐Wen , Chen Wen‐Rong , Lai Chih‐Ting , Chen Mu‐Kuan , Yang Shun‐Fa
Published: July 2018

Eclipta prostrata, a traditional Chinese medication, has been used for the treatment of several diseases. However, the molecular mechanism underlying the effects of Eclipta prostrata extracts (EPE) on human oral cancer cell metastasis remains unclear. We thus examined the effects of EPE on metastasis promoting proteins in oral cancer. Our results revealed that the EPE attenuated SCC‐9, HSC‐3, and TW2.6 cell migration and invasiveness by reducing matrix metalloproteinase (MMP)‐2 enzyme activities. In addition, Western blot analysis revealed that EPE significantly reduced the levels of phosphorylated extracellular signal‐regulated kinase 1/2 (ERK 1/2) but not those of c‐Jun N‐terminal kinase (JNK) 1/2 and p38. In conclusion, we found that EPE could inhibit oral cancer metastasis through the inhibition of MMP‐2 expression. Therefore, EPE may be used to prevent the metastasis of oral cancer, and has the potential to be applied to cancer treatment.
Employment and the role of workers and employers in a green economy
Authors: Montt Guillermo , Capaldo Jeronim , Esposito Michela , Harsdorff Marek , Maitre Nicolas , Samaan Daniel
Published: July 2018

Many jobs can be created by achieving sustainability in the energy sector. Limiting global warming to 2 degrees Celsius by 2100 will 24 million jobs in construction, electrical machinery manufacturing, copper mining, renewable energy production and biomass crop cultivation. 6 million jobs can be created by adopting the circular economy. Promoting sustainability in agriculture will change rural economies. Workers and employers are key actors in the transition towards environmental sustainability.
Multivariate calibration in TXRF analysis of water
Authors: Shulyumova A. , Maltsev A. , Umarova N.
Published: July 2018

The aim of this paper is the application of multivariate linear calibration for quantitative determination of elements (K, Cd, Co, Hg, As, Pb, Ni, and Al) in water by using Total Reflection X‐ray Fluorescence Analysis with partial least squares (PLS) as a regression method to improve a result of common univariate method. In purpose of elimination of matrix effects in X‐ray fluorescence analysis, experimental design was applied. As a set of standard samples for multivariate calibration, a five‐level eight‐factor calibration design of 25 samples was chosen, ensuring mutual orthogonality of factors. For model's validation, the independent test set of 15 samples was examined. The collection of spectra and quantitative measurements was carried out on S2 PICOFOX. The PLS regression was performed by using software package STATISTICA. Quality indicators of multivariate calibration as slope (b) and intercept (a) of calibration, correlation coefficient (r), determination coefficient (R2), root mean square errors of calibration and of prediction, standard errors of calibration and of prediction, biases of calibration, and biases of prediction were calculated. These results were compared with the univariate model, and as a result, the multivariate calibration method exceeds the univariate one. The obtained results could be applied in a laboratory for an analysis of water solutions in the concentration range 0.05–2.00 mg/L. In many real situations, when analytical chemist deals with multi‐element mixtures, multivariate calibration approach combined with orthogonal design for multivariate calibration set could be successfully used to improve a conventional univariate calibration.
Canonical Quantum Observables for Molecular Systems Approximated by Ab Initio Molecular Dynamics
Authors: Kammonen Aku , Plecháč Petr , Sandberg Mattias , Szepessy Anders
Published: July 2018

It is known that ab initio molecular dynamics based on the electron ground-state eigenvalue can be used to approximate quantum observables in the canonical ensemble when the temperature is low compared to the first electron eigenvalue gap. This work proves that a certain weighted average of the different ab initio dynamics, corresponding to each electron eigenvalue, approximates quantum observables for any temperature. The proof uses the semiclassical Weyl law to show that canonical quantum observables of nuclei–electron systems, based on matrix-valued Hamiltonian symbols, can be approximated by ab initio molecular dynamics with the error proportional to the electron–nuclei mass ratio. The result covers observables that depend on time correlations. A combination of the Hilbert–Schmidt inner product for quantum operators and Weyl’s law shows that the error estimate holds for observables and Hamiltonian symbols that have three and five bounded derivatives, respectively, provided the electron eigenvalues are distinct for any nuclei position and the observables are in the diagonal form with respect to the electron eigenstates.
Event‐related potentials during sustained attention and memory tasks: Utility as biomarkers for mild cognitive impairment
Authors: Waninger Shani , Berka Chris , Meghdadi Amir , Karic Marija S. , Stevens Kimberly , Aguero Cinthya , Sitnikova Tatiana , Salat David H. , Verma Ajay
Published: July 2018

Introduction

The objective of the study is to validate attention and memory tasks that elicit event‐related potentials (ERPs) for utility as sensitive biomarkers for early dementia.

Methods

A 3‐choice vigilance task designed to evaluate sustained attention and standard image recognition memory task designed to evaluate attention, encoding, and image recognition memory were administered with concurrent electroencephalography acquisition to elicit ERPs in mild cognitive impairment (MCI) and healthy cohorts. ERPs were averaged, and mean or maximum amplitude of components was measured and compared between and within cohorts.

Results

There was significant suppression of the amplitude of the late positive potential in the MCI cohort compared with the healthy controls during 3‐choice vigilance task, predominantly over occipital and right temporal‐parietal region, and standard image recognition memory task over all regions. During standard image recognition memory task, diminished performance showed strong correlation with electroencephalography measurements. The old/new effects observed in the healthy controls cohort correlated with performance and were lost in MCI.

Discussion

ERPs obtained during cognitive tasks may provide a powerful tool for assessing MCI and have strong potential as sensitive and robust biomarkers for tracking disease progression and evaluating response to investigative therapeutics.
Diminished Kinesthetic and Visual Motor Imagery Ability in Adults With Chronic Low Back Pain
Authors: La Touche Roy , Grande‐Alonso Mónica , Cuenca‐Martínez Ferran , Gónzález‐Ferrero Luis , Suso‐Martí Luis , Paris‐Alemany Alba
Published: July 2018

Background

Low back pain (LBP) is the most prevalent musculoskeletal problem among adults. It has been observed that patients with chronic pain have maladaptive neuroplastic changes and difficulty in imagination processes.

Objective

To assess the ability of patients with chronic LBP (CLBP) to generate kinesthetic and visual motor images and the time they spent on this mental task compared with asymptomatic participants.

Design

A prospective, cross‐sectional study.

Setting

Primary health care center in Madrid, Spain.

Participants

A total of 200 participants were classified into 2 groups: asymptomatic participants (n = 100) and patients with CLBP (n = 100).

Methods

After consenting to participate, all recruited participants received a sociodemographic questionnaire, a set of self‐report measures and completed the Revised Movement Imagery Questionnaire.

Main Outcomes Measurements

Visual and Kinesthetic Motor Imagery Ability using the Revised Movement Imagery Questionnaire. A mental chronometry using a stopwatch and psychosocial variables using self‐reported questionnaires.

Results

Our results indicated that patients with CLBP had difficulty generating kinesthetic and visual motor images and also took a longer time to imagine them. A regression analysis indicated that in the CLBP group, the predictor variable for fear of activity and coping symptom self‐efficacy was visual motor imagery (explaining 16.2% of the variance); however, the predictor variable for LBP disability and pain management self‐efficacy was kinesthetic motor imagery (explaining 17.8% of the variance).

Conclusions

It appears that patients with CLBP have greater difficulty generating visual and kinesthetic motor images compared with asymptomatic participants, and they also need more time to perform these mental tasks.

Level of Evidence

II
Longitudinal Pochhammer — Chree Waves in Mild Auxetics and Non-Auxetics
Authors: Ilyashenko A. V. , Kuznetsov S. V.
Published: July 2018

The exact solutions of Pochhammer — Chree equation for propagating harmonic waves in isotropic elastic cylindrical rods, are analyzed. Spectral analysis of the matrix dispersion equation for the longitudinal axially symmetric modes is performed. Analytical expressions for displacement fields are obtained. Variation of the wave polarization due to variation of Poisson’s ratio for mild auxetics (Poisson’s ratio is greater than -0.5) is analyzed and compared with the non-auxetics. It is observed that polarization of the waves for both considered cases (auxetics and non-auxetics) exhibits abnormal behavior in the vicinity of the bulk shear wave speed.
Optical Identification of the Millisecond Pulsar J0621+2514
Authors: Karpova A. V. , Zyuzin D. A. , Shibanov Yu. A. , Kirichenko A. Yu. , Zharikov S. V.
Published: July 2018

Using the SDSS and Pan-STARRS1 survey data, we found a likely companion of the recently discovered binary γ-ray radio-loud millisecond pulsar J0621+2514. Its visual brightness is about 22 mag. The broadband magnitudes and colours suggest that this is a white dwarf. Comparing the data with various white dwarfs evolutionary tracks, we found that it likely belongs to a class of He-core white dwarfs with a temperature of about 10 000 K and a mass of ≲ 0.5 M⊙. For a thin hydrogen envelope of the white dwarf, its cooling age is ≲ 0.5 Gyr which is smaller than the pulsar characteristic age of 1.8 Gyr. This may indicate that the pulsar age is overestimated. Otherwise, this may be explained by the presence of a thick hydrogen envelope or a low metallicity of the white dwarf progenitor.
Healthy functioning as the key to fairness in a divinely determined world
Authors: HERSHENOV DAVID B.
Published: July 2018

Defending a traditional conception of Hell against the charge of unfairness is difficult for any theorist. It would seem to be even more difficult for the Christian semi-compatibilist who believes we can be responsible when determined. If God determined the wrongdoer's choices, then it seems unfair that he is punished for his actions that were manipulated rather than autonomous. I'll argue that healthy mental functioning can explain how some causally determined actions are manipulative while others are under our control. I'll also argue that God can punish even if He lacks the standing to blame.
UNA CONCHA ESGRAFIADA TOLTECA: APUNTES TECNOLÓGICOS E ICONOGRÁFICOS
Authors: Bernal Stephen Castillo , Castro Adrián Velázquez , Maldonado Norma Valentín
Published: July 2018

En este artículo realizamos un análisis tecnológico de una concha esgrafiada tolteca, recientemente excavada en las periferias de la antigua ciudad de Tula, Hidalgo, México. Asimismo, efectuamos un análisis iconográfico de los motivos esgrafiados en la pieza. Proponemos la técnica de manufactura del objeto, su probable lugar de producción, así como la función ritual que el objeto pudo tener. Así, postulamos que la concha representa a un integrante de los linajes hegemónicos de Tula y que la inhumación del objeto pudo ser similar a los dones depositados en La Casa de las Águilas, en México-Tenochtitlan.
Editorial
Authors: Burger Martin , King John , Ward Michael
Published: July 2018

The lead article for this issue of EJAM is Prof. Bernard J. Matkowsky's personalized survey-style article on the theory and application of singular perturbation methods to noisy dynamical systems in the limit of small noise. This article is based on his John von Neumann Prize lecture presented at the Society of Industrial and Applied Mathematics (SIAM) Annual Meeting in July 2017. The John von Neumann Lecture is awarded by SIAM for outstanding and distinguished contributions to the field of applied mathematical sciences and for the effective communication of these ideas to the community. From 1990–1996, Matkowsky was an inaugural editorial board member for EJAM.
What is the Optimal Age for Students to Receive Cardiopulmonary Resuscitation Training?
Authors: He Ding-xiu , Huang Kai-sen , Yang YI , Jiang Wei , Yang Nan-lan , Yang Hu
Published: July 2018

Objectives

Training students has been proven to be the optimal way to deliver cardiopulmonary resuscitation (CPR) skills. However, it is somehow unknown whether or not the current recommendations appropriate for Caucasian students are also suitable for East Asian students. The purpose of this study is to explore the best age for East Asian students to receive CPR training.

Methods

Students were recruited from six schools. Students participated in a standard CPR training program provided by tutors. Each student attended a 60-minute training session with a manikin. After being trained, within one hour, the student’s compression quality was assessed.

Results

A total of 360 students who constituted 12 continuous grades were recruited for this study. Adequate compression depth and satisfactory compression rate with correct hand position could be achieved since the age of 12. However, successful compression rate and complete release could be achieved since the younger age of six.

Conclusions

Current recommendations for Caucasian students to cultivate a full-capacity CPR rescuer at the age of 12 are also appropriate for East Asian students. However, the optimal age for students to receive CPR training should be decided based on evidence and importance assessment of CPR.

He D, Huang K, Yang Y, Jiang W, Yang N, Yang H. What is the optimal age for students to receive cardiopulmonary resuscitation training? Prehosp Disaster Med. 2018;33(4):394–398.
A New Assessment of Mesoscale Eddies in the South China Sea: Surface Features, Three‐Dimensional Structures, and Thermohaline Transports
Authors: He Qingyou , Zhan Haigang , Cai Shuqun , He Yinghui , Huang Gaolong , Zhan Weikang
Published: July 2018

By analyzing 22 years (1993–2015) of daily eddy data, statistics of surface eddy properties were refreshed in the South China Sea. More than 7,000 of historical Argo profiles were collocated into eddy‐centered coordinates to reveal the composite mean three‐dimensional structure of eddies. The results indicate that eddies of both polarities have long conical shape, with a maximum (minimum) density anomaly of 0.55 kg/m3 (−0.51 kg/m3) at 60 m (90 m) in the composite cyclonic (anticyclonic) eddy. Temperature and salinity anomalies also peak at eddy cores, with values of −1.5 °C and 0.15 psu in the cyclonic eddy and 1.4 °C and −0.16 psu in the anticyclonic eddy. The temperature and density anomalies extend vertically to 400–500 m, while the salinity anomalies are apparent only in the upper 150 m. The temperature anomalies contribute about 90% of the density anomalies. Mixed layer depths in cyclonic eddies are on average 15 m shallower than those in anticyclonic eddies. The rotation of the composite cyclonic (anticyclonic) eddy generates meridional heat transport of 1.4 × 1012 W (−3.1 × 1012 W) and salt transport of −4.0 × 104 kg/s (5.6 × 104 kg/s). More than 90% of the heat and salt transports are concentrated in the upper 300 and 100 m, respectively. Compared to the meridional transports, the westward propagation of eddies results in zonal heat and salt transports on the same orders of magnitudes. The westward propagation of eddies also generates a basin‐scale westward water transport of 1.4 Sv, equivalent to about 30% of the annual‐mean Luzon Strait transport.
Initiation and Evolution of Elevated Convection in a Nocturnal Squall Line Along the Meiyu Front
Authors: He Zhiwei , Zhang Qinghong , Zhao Kun , Hu Huiqin
Published: July 2018

Observations and analyses from the Variational Doppler Radar Assimilation and Analysis System (VDRAS) were used to investigate the convection initiation mechanism of a nocturnal squall line along the Meiyu Front over central East China on 11–12 July 2014. The squall line occurred on the warm side of the Meiyu Front. The main convection in the squall line was initiated along a mesoscale convergence line above a stable boundary layer at about 2330 local standard time (LST) on 11 July. The convergence line intensified due to enhancement of southerly winds. Momentum budget analyses further revealed that the enhancement of the southerly winds was mainly contributed by an increasing horizontal pressure gradient term, which was associated with the eastward movement of a preexisting mesoscale vortex above the boundary layer and the strengthening of subtropical high. In the early morning of 12 July, a jump propagation of the squall line occurred. As the squall line matured, surface cold pools strengthened due to diabatic heating (most likely evaporative cooling). Then new convection began to initiate in front of the surface cold pools. During the jump propagation of the squall line, the elevated convection in the squall line transitioned to surface‐based convection. This is the first study demonstrating the occurrence of elevated convection along the Meiyu Front and its transitioning to surface‐based convection by jump propagation.
Typhoon‐Enhanced Silicon and Nitrogen Exports in a Mountainous Catchment
Authors: Su Ni , Yang Shouye , Xie Xiaolei
Published: July 2018

Tropical storms play a profound role in driving global terrestrial material from continents to oceans. We investigated the continuous changes in the major ion chemistry, hydrogen and oxygen stable isotopes of water (δD and δ18O), nitrogen and oxygen stable isotopes of nitrate (δ15N‐NO3− and δ18O‐NO3−), and radiogenic strontium isotopes (87Sr/86Sr) for the Mulanxi River catchment in southeast China when a strong typhoon made landfall on the coasts to acquire a rapid increase in river discharge (~50 times). High rates of carbonate weathering and thus CO2 consumption during an intense precipitation event suggested the increased active weathering of carbonate minerals, while the release of silicate solute‐rich soil waters during the storm could induce a greater relative contribution of surface weathering to the solute load, rather than active weathering of silicate bedrock. The related total dissolved Si flux of 940 t accounted for ~5.8% of the whole year, particularly revealing a flux contribution of the Si‐rich soil waters for 37% at least. Additionally, we observed a significant increase in δ18O‐NO3− and a slight decrease in δ15N‐NO3− after the storm, whereas the concentrations of major elements overall recovered to pretyphoon levels. We infer that the posttyphoon change in the nitrate isotopic composition is caused by the coupled effects of nitrification and denitrification processes at the sediment‐water interface, which thus modify isotopic compositions. This work expands our understanding of extreme climate events that may play in element sources and cycling processes in rivers.
Exploiting limited valence patchy particles to understand autocatalytic kinetics
Authors: Corezzi Silvia , Sciortino Francesco , De Michele Cristiano
Published: July 2018

Autocatalysis, i.e., the speeding up of a reaction through the very same molecule which is produced, is common in chemistry, biophysics, and material science. Rate-equation-based approaches are often used to model the time dependence of products, but the key physical mechanisms behind the reaction cannot be properly recognized. Here, we develop a patchy particle model inspired by a bicomponent reactive mixture and endowed with adjustable autocatalytic ability. Such a coarse-grained model captures all general features of an autocatalytic aggregation process that takes place under controlled and realistic conditions, including crowded environments. Simulation reveals that a full understanding of the kinetics involves an unexpected effect that eludes the chemistry of the reaction, and which is crucially related to the presence of an activation barrier. The resulting analytical description can be exported to real systems, as confirmed by experimental data on epoxy–amine polymerizations, solving a long-standing issue in their mechanistic description.
Metallization and molecular dissociation of dense fluid nitrogen
Authors: Jiang Shuqing , Holtgrewe Nicholas , Lobanov Sergey S. , Su Fuhai , Mahmood Mohammad F. , McWilliams R. Stewart , Goncharov Alexander F.
Published: July 2018

Diatomic nitrogen is an archetypal molecular system known for its exceptional stability and complex behavior at high pressures and temperatures, including rich solid polymorphism, formation of energetic states, and an insulator-to-metal transformation coupled to a change in chemical bonding. However, the thermobaric conditions of the fluid molecular–polymer phase boundary and associated metallization have not been experimentally established. Here, by applying dynamic laser heating of compressed nitrogen and using fast optical spectroscopy to study electronic properties, we observe a transformation from insulating (molecular) to conducting dense fluid nitrogen at temperatures that decrease with pressure and establish that metallization, and presumably fluid polymerization, occurs above 125 GPa at 2500 K. Our observations create a better understanding of the interplay between molecular dissociation, melting, and metallization revealing features that are common in simple molecular systems.
A mosaic monoploid reference sequence for the highly complex genome of sugarcane
Authors: Garsmeur Olivier , Droc Gaetan , Antonise Rudie , Grimwood Jane , Potier Bernard , Aitken Karen , Jenkins Jerry , Martin Guillaume , Charron Carine , Hervouet Catherine , Costet Laurent , Yahiaoui Nabila , Healey Adam , Sims David , Cherukuri Yesesri , Sreedasyam Avinash , Kilian Andrzej , Chan Agnes , Van Sluys Marie-Anne , Swaminathan Kankshita , Town Christopher , Bergès Hélène , Simmons Blake , Glaszmann Jean Christophe , van der Vossen Edwin , Henry Robert , Schmutz Jeremy , D’Hont Angélique
Published: July 2018

Sugarcane (Saccharum spp.) is a major crop for sugar and bioenergy production. Its highly polyploid, aneuploid, heterozygous, and interspecific genome poses major challenges for producing a reference sequence. We exploited colinearity with sorghum to produce a BAC-based monoploid genome sequence of sugarcane. A minimum tiling path of 4660 sugarcane BAC that best covers the gene-rich part of the sorghum genome was selected based on whole-genome profiling, sequenced, and assembled in a 382-Mb single tiling path of a high-quality sequence. A total of 25,316 protein-coding gene models are predicted, 17% of which display no colinearity with their sorghum orthologs. We show that the two species, S. officinarum and S. spontaneum, involved in modern cultivars differ by their transposable elements and by a few large chromosomal rearrangements, explaining their distinct genome size and distinct basic chromosome numbers while also suggesting that polyploidization arose in both lineages after their divergence.
Intermedin protects against sepsis by concurrently re-establishing the endothelial barrier and alleviating inflammatory responses
Authors: Xiao Fei , Wang Denian , Kong Lingmiao , Li Min , Feng Zhongxue , Shuai Bingxing , Wang Lijun , Wei Yong’gang , Li Hongyu , Wu Sisi , Tan Chun , Zhao Huan , Hu Xuejiao , Liu Jin , Kang Yan , Liao Xuelian , Zhou Yan , Zhang Wei
Published: July 2018

Sepsis is a life-threatening condition caused by dysregulated host responses to infection. Widespread vascular hyperpermeability and a “cytokine storm” are two pathophysiological hallmarks of sepsis. Here, we show that intermedin (IMD), a member of the calcitonin family, alleviates organ injury and decreases mortality in septic mice by concurrently alleviating vascular leakage and inflammatory responses. IMD promotes the relocation of vascular endothelial cadherin through a Rab11-dependent pathway to dynamically repair the disrupted endothelial junction. Additionally, IMD decreases inflammatory responses by reducing macrophage infiltration via downregulating CCR2 expression. IMD peptide administration ameliorates organ injuries and significantly improves the survival of septic mice, and the experimental results correlate with the clinical data. Patients with high IMD levels exhibit a lower risk of shock, lower severity scores, and greatly improved survival outcomes than those with low IMD levels. Based on our data, IMD may be an important self-protective factor in response to sepsis.
ETS transcription factors induce a unique UV damage signature that drives recurrent mutagenesis in melanoma
Authors: Mao Peng , Brown Alexander J. , Esaki Shingo , Lockwood Svetlana , Poon Gregory M. K. , Smerdon Michael J. , Roberts Steven A. , Wyrick John J.
Published: July 2018

Recurrent mutations are frequently associated with transcription factor (TF) binding sites (TFBS) in melanoma, but the mechanism driving mutagenesis at TFBS is unclear. Here, we use a method called CPD-seq to map the distribution of UV-induced cyclobutane pyrimidine dimers (CPDs) across the human genome at single nucleotide resolution. Our results indicate that CPD lesions are elevated at active TFBS, an effect that is primarily due to E26 transformation-specific (ETS) TFs. We show that ETS TFs induce a unique signature of CPD hotspots that are highly correlated with recurrent mutations in melanomas, despite high repair activity at these sites. ETS1 protein renders its DNA binding targets extremely susceptible to UV damage in vitro, due to binding-induced perturbations in the DNA structure that favor CPD formation. These findings define a mechanism responsible for recurrent mutations in melanoma and reveal that DNA binding by ETS TFs is inherently mutagenic in UV-exposed cells.
Altered thymic differentiation and modulation of arthritis by invariant NKT cells expressing mutant ZAP70
Authors: Zhao Meng , Svensson Mattias N. D. , Venken Koen , Chawla Ashu , Liang Shu , Engel Isaac , Mydel Piotr , Day Jeremy , Elewaut Dirk , Bottini Nunzio , Kronenberg Mitchell
Published: July 2018

Various subsets of invariant natural killer T (iNKT) cells with different cytokine productions develop in the mouse thymus, but the factors driving their differentiation remain unclear. Here we show that hypomorphic alleles of Zap70 or chemical inhibition of Zap70 catalysis leads to an increase of IFN-γ-producing iNKT cells (NKT1 cells), suggesting that NKT1 cells may require a lower TCR signal threshold. Zap70 mutant mice develop IL-17-dependent arthritis. In a mouse experimental arthritis model, NKT17 cells are increased as the disease progresses, while NKT1 numbers negatively correlates with disease severity, with this protective effect of NKT1 linked to their IFN-γ expression. NKT1 cells are also present in the synovial fluid of arthritis patients. Our data therefore suggest that TCR signal strength during thymic differentiation may influence not only IFN-γ production, but also the protective function of iNKT cells in arthritis.
Engineering circular RNA for potent and stable translation in eukaryotic cells
Authors: Wesselhoeft R. Alexander , Kowalski Piotr S. , Anderson Daniel G.
Published: July 2018

Messenger RNA (mRNA) has broad potential for application in biological systems. However, one fundamental limitation to its use is its relatively short half-life in biological systems. Here we develop exogenous circular RNA (circRNA) to extend the duration of protein expression from full-length RNA messages. First, we engineer a self-splicing intron to efficiently circularize a wide range of RNAs up to 5 kb in length in vitro by rationally designing ubiquitous accessory sequences that aid in splicing. We maximize translation of functional protein from these circRNAs in eukaryotic cells, and we find that engineered circRNA purified by high performance liquid chromatography displays exceptional protein production qualities in terms of both quantity of protein produced and stability of production. This study pioneers the use of exogenous circRNA for robust and stable protein expression in eukaryotic cells and demonstrates that circRNA is a promising alternative to linear mRNA.
Highly stretchable and transparent ionic conducting elastomers
Authors: Shi Lei , Zhu Tianxiang , Gao Guoxin , Zhang Xinyu , Wei Wei , Liu Wenfeng , Ding Shujiang
Published: July 2018

Traditional elastomers are mostly dielectrics; existing conductive elastomers are conductive composites with electric conductors. Herein, we introduce a series of ionic conducting elastomers (ICE) by salt in polymer strategy. The ICEs possess good stretchability, transparency and ionic conductivity. Moreover, the ICEs exhibit very high stability in air, under high temperature and voltage, with excellent adhesion properties and no corrosive effects to metal electrodes. Touch sensors are fabricated using these ICEs—impedance spectra and impedance complex plane are tested and analyzed to clarify different stimulus of the touch sensors. These ICEs provide possibilities for flexible electronics and soft machines.
PID/WAG-mediated phosphorylation of the Arabidopsis PIN3 auxin transporter mediates polarity switches during gravitropism
Authors: Grones Peter , Abas Melinda , Hajný Jakub , Jones Angharad , Waidmann Sascha , Kleine-Vehn Jürgen , Friml Jiří
Published: July 2018

Intercellular distribution of the plant hormone auxin largely depends on the polar subcellular distribution of the plasma membrane PIN-FORMED (PIN) auxin transporters. PIN polarity switches in response to different developmental and environmental signals have been shown to redirect auxin fluxes mediating certain developmental responses. PIN phosphorylation at different sites and by different kinases is crucial for PIN function. Here we investigate the role of PIN phosphorylation during gravitropic response. Loss- and gain-of-function mutants in PINOID and related kinases but not in D6PK kinase as well as mutations mimicking constitutive dephosphorylated or phosphorylated status of two clusters of predicted phosphorylation sites partially disrupted PIN3 phosphorylation and caused defects in gravitropic bending in roots and hypocotyls. In particular, they impacted PIN3 polarity rearrangements in response to gravity and during feed-back regulation by auxin itself. Thus PIN phosphorylation, besides regulating transport activity and apical-basal targeting, is also important for the rapid polarity switches in response to environmental and endogenous signals.
Author Correction: Neuronal activity regulates DROSHA via autophagy in spinal muscular atrophy
Authors: Gonçalves Inês do Carmo G. , Brecht Johanna , Thelen Maximilian P. , Rehorst Wiebke A. , Peters Miriam , Lee Hyun Ju , Motameny Susanne , Torres-Benito Laura , Ebrahimi-Fakhari Darius , Kononenko Natalia L. , Altmüller Janine , Vilchez David , Sahin Mustafa , Wirth Brunhilde , Kye Min Jeong
Published: July 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Anti-survivin effect of the small molecule inhibitor YM155 in RCC cells is mediated by time-dependent inhibition of the NF-κB pathway
Authors: Sim Mei Yi , Yuen John Shyi Peng , Go Mei Lin
Published: July 2018

Constitutive activation of the NF-κB signaling cascade is associated with tumourigenesis and poor prognosis in many human cancers including RCC. YM155, a small molecule inhibitor of survivin, was previously shown to potently inhibit the viability of immortalized and patient derived renal cell carcinoma (RCC) cell lines. Here we investigated the role of NF-κB signaling to the anti-cancer properties of YM155 in RCC786.0 cells. YM155 diminished nuclear levels of p65 and phosphorylated p65 and attenuated the transcriptional competencies of the p65/p50 heterodimers. Accordingly, we found that YM155 diminished the transcription of NF-κB target gene survivin. Events that led to the interception of the nuclear translocation of p65/p50 were the activation of the deubiquinating enzyme CYLD by YM155, which led to the inhibition of IKKβ, stabilization of IκBα and retention of NF-κB heterodimers in the cytosol. Importantly, the suppressive effects of YM155 were time-dependent and observed at the 24 h time point, and not earlier. TNF-α, a stimulator of NF-κB signaling did not affect its inhibitory properties. The ability of YM155 to intercept a major transcriptional pathway like NF-κB, would have important ramifications on the pharmacodynamics effects elicited by this unusual molecule.
Moth oviposition shapes the species-specific transcriptional and phytohormonal response of Nicotiana attenuata to larval feeding
Authors: Drok Sylvia , Bandoly Michele , Stelzer Sandra , Lortzing Tobias , Steppuhn Anke
Published: July 2018

Oviposition by lepidopteran herbivores on Nicotiana attenuata primes plant defence responses that are induced by the feeding larvae. While oviposition by both the generalist Spodoptera exigua and the specialist Manduca sexta primes the production of defensive phenylpropanoids, their larvae are differentially affected. We investigate here the impact of prior oviposition on the transcriptome and phytohormone levels of plants that were later attacked by larvae to find regulatory signals of this priming. In a full-factorial design, we evaluated the effects of oviposition and herbivory by both species. Oviposition alone had only subtle effects at the transcriptional level. Laval feeding alone induced species-specific plant responses. Larvae of the generalist regulated phytohormones and gene expression stronger than larvae of the specialist. A day after larvae started to feed, we detected no significant alterations of the plant’s response to larval feeding due to prior oviposition by conspecific moths. Yet, oviposition by each of the species profoundly influenced the plant’s transcriptional and phytohormonal response to feeding larvae of the other species. Remarkably, the species-specific plant responses to larval feeding shifted towards the response normally elicited by larvae of the ovipositing species. Thus, plants may already recognise an insect’s identity upon its oviposition.
Plasma-Induced Phase Transformation of SnS2 to SnS
Authors: Kim Jung Ho , Yun Seok Joon , Lee Hyun Seok , Zhao Jiong , Bouzid Houcine , Lee Young Hee
Published: July 2018

Layered van der Waals materials have recently attracted attention owing to their exceptional electrical and optical properties in thin layer form. One way to extend their utility is to form a heterostructure which combines various properties of layered materials to reveal intriguing behavior. Conventional heterostructure synthesis methods are difficult to develop and the heterostructure formed can be limited to a small area. Here, we investigate the phase transformation of SnS2 to SnS by removing sulfur atoms at the top surface using Ar plasma. By varying the plasma power and exposure time, we observed that SnS is subsequently formed on top of the mogul-like structure of SnS2. Since SnS is a p-type semiconductor and SnS2 is an n-type semiconductor, we naturally formed a vertical p-n junction. By using graphene at the top and bottom as transparent electrodes, a vertical p-n diode device is constructed. The device demonstrates good rectifying behavior and large photocurrent generation under white light. This method can be applied to large-area heterostructure synthesis using plasma via phase transformation of various metal dichalcogenides to metal monochalcogenides.
Author Correction: Towards Millimeter-wavelength: Transmission-Mode Fresnel-Zone Plate Lens Antennas using Plastic Material Porosity Control in Homogeneous Medium
Authors: Pourahmadazar Javad , Denidni Tayeb A.
Published: July 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
A compact diffractive sorter for high-resolution demultiplexing of orbital angular momentum beams
Authors: Ruffato Gianluca , Girardi Marcello , Massari Michele , Mafakheri Erfan , Sephton Bereneice , Capaldo Pietro , Forbes Andrew , Romanato Filippo
Published: July 2018

The design and fabrication of a compact diffractive optical element is presented for the sorting of beams carrying orbital angular momentum (OAM) of light. The sorter combines a conformal mapping transformation with an optical fan-out, performing demultiplexing with unprecedented levels of miniaturization and OAM resolution. Moreover, an innovative configuration is proposed which simplifies alignment procedures and further improves the compactness of the optical device. Samples have been fabricated in the form of phase-only diffractive optics with high-resolution electron-beam lithography (EBL) over a glass substrate. A soft-lithography process has been optimized for fast and cheap replica production of the EBL masters. Optical tests with OAM beams confirm the designed performance, showing excellent efficiency and low cross-talk, with high fidelity even with multiplexed input beams. This work paves the way for practical OAM multiplexing and demultiplexing devices for use in classical and quantum communication.
Iron-Overload triggers ADAM-17 mediated inflammation in Severe Alcoholic Hepatitis
Authors: Maras Jaswinder Singh , Das Sukanta , Sharma Sachin , Sukriti Sukriti , kumar Jitendra , Vyas Ashish Kumar , Kumar Dhananjay , Bhat Adil , Yadav Gaurav , Choudhary Manish Chandra , Sharma Shvetank , kumar Guresh , Bihari Chhagan , Trehanpati Nirupma , Maiwall Rakhi , Sarin Shiv Kumar
Published: July 2018

Severe alcoholic hepatitis (SAH) is associated with iron accumulation in hepatocytes/macrophages. This possibly correlates with inflammation and stress but the exact mechanism still remains obscure. To understand the role of iron and the mechanisms of systemic iron-overload, a transcriptomic study of liver and Peripheral Blood -Mononuclear-Cells (PBMCs) was undertaken in SAH patients, with and without hepatic iron-overload. Our results show that iron-overload in hepatocytes/macrophages is due to an increased expression of iron-loading receptors and CD163 signaling cascade. Increase in labile iron pool induces expression of iron-loading, oxidative-stress and inflammatory genes along with expression of CD163 and ADAM17. Increased liver iron correlated with circulatory iron, TNF-α, macrophage activation (sCD163) and peroxide-stress in CD163+macrophages in patients who were iron-overloaded and died. Circulatory TNF-α and sCD163 levels were associated with poor outcome. Temporal iron/Fenton stress induced in healthy monocyte-derived-macrophage (MDM)/Tohoku-Hospital-Pediatrics-1(THP1) cells showed higher expression of iron-regulatory, inflammatory and oxidative-stress genes. These genes could be suppressed by iron-chelation. These results suggest that iron mediates inflammation through ADAM17 induction, resulting in macrophage activation and increased shedding of TNF-α and sCD163. These events could be inhibited with iron chelation or with ADAM17-blockade, postulating a therapeutic strategy for SAH patients with iron overload.
Spinal PKCα inhibition and gene-silencing for pain relief: AMPAR trafficking at the synapses between primary afferents and sensory interneurons
Authors: Kopach Olga , Krotov Volodymyr , Shysh Angela , Sotnic Andrij , Viatchenko-Karpinski Viacheslav , Dosenko Victor , Voitenko Nana
Published: July 2018

Upregulation of Ca2+-permeable AMPA receptors (CP-AMPARs) in dorsal horn (DH) neurons has been causally linked to persistent inflammatory pain. This upregulation, demonstrated for both synaptic and extrasynaptic AMPARs, depends on the protein kinase C alpha (PKCα) activation; hence, spinal PKC inhibition has alleviated peripheral nociceptive hypersensitivity. However, whether targeting the spinal PKCα would alleviate both pain development and maintenance has not been explored yet (essential to pharmacological translation). Similarly, if it could balance the upregulated postsynaptic CP-AMPARs also remains unknown. Here, we utilized pharmacological and genetic inhibition of spinal PKCα in various schemes of pain treatment in an animal model of long-lasting peripheral inflammation. Pharmacological inhibition (pre- or post-treatment) reduced the peripheral nociceptive hypersensitivity and accompanying locomotive deficit and anxiety in rats with induced inflammation. These effects were dose-dependent and observed for both pain development and maintenance. Gene-therapy (knockdown of PKCα) was also found to relieve inflammatory pain when applied as pre- or post-treatment. Moreover, the revealed therapeutic effects were accompanied with the declined upregulation of CP-AMPARs at the DH synapses between primary afferents and sensory interneurons. Our results provide a new focus on the mechanism-based pain treatment through interference with molecular mechanisms of AMPAR trafficking in central pain pathways.
Comparative and phylogenetic analysis of a novel family of Enterobacteriaceae-associated genomic islands that share a conserved excision/integration module
Authors: Piña-Iturbe Alejandro , Ulloa-Allendes Diego , Pardo-Roa Catalina , Coronado-Arrázola Irenice , Salazar-Echegarai Francisco J. , Sclavi Bianca , González Pablo A. , Bueno Susan M.
Published: July 2018

Genomic Islands (GIs) are DNA regions acquired through horizontal gene transfer that encode advantageous traits for bacteria. Many GIs harbor genes that encode the molecular machinery required for their excision from the bacterial chromosome. Notably, the excision/integration dynamics of GIs may modulate the virulence of some pathogens. Here, we report a novel family of GIs found in plant and animal Enterobacteriaceae pathogens that share genes with those found in ROD21, a pathogenicity island whose excision is involved in the virulence of Salmonella enterica serovar Enteritidis. In these GIs we identified a conserved set of genes that includes an excision/integration module, suggesting that they are excisable. Indeed, we found that GIs within carbapenem-resistant Klebsiella pneumoniae ST258 KP35 and enteropathogenic Escherichia coli O127:H6 E2348/69 are excised from the bacterial genome. In addition to putative virulence factors, these GIs encode conjugative transfer-related proteins and short and full-length homologues of the global transcriptional regulator H-NS. Phylogenetic analyses suggest that the identified GIs likely originated in phytopathogenic bacteria. Taken together, our findings indicate that these GIs are excisable and may play a role in bacterial interactions with their hosts.
Listening to earthworms burrowing and roots growing - acoustic signatures of soil biological activity
Authors: Lacoste Marine , Ruiz Siul , Or Dani
Published: July 2018

We report observations of acoustic emissions (AE) from growing plant roots and burrowing earthworms in soil, as a noninvasive method for monitoring biophysical processes that modify soil structure. AE emanating from earthworm and plants root activity were linked with time-lapse imaging in glass cells. Acoustic waveguides where installed in soil columns to monitor root growth in real time (mimicking field application). The cumulative AE events were in correlation with earthworm burrow lengths and with root growth. The number of AE events recorded from the soil columns with growing maize roots were several orders of magnitude larger than AE emanating from bare soil under similar conditions. The results suggest that AE monitoring may offer a window into largely unobservable dynamics of soil biomechanical processes such as root growth or patterns of earthworm activity - both important soil structure forming processes.