bluuebunny/crossref_metadata_2025 huggingface dataset:
High-resolution patterning of solution-processable materials via externally engineered pinning of capillary bridges
Authors: Li Shunpu , Chun Young Tea , Zhao Shuo , Ahn Hyungju , Ahn Docheon , Sohn Jung Inn , Xu Yongbing , Shrestha Pawan , Pivnenko Mike , Chu Daping
Published: January 2018

Electronics based on solution-processable materials are promising for applications in many fields which stimulated enormous research interest in liquid-drying and pattern formation. However, assembling of structure with submicrometre/nanometre resolution through liquid process is very challenging. We show a simple method to rapidly generate polymer structures with deep-submicrometre-sized features over large areas. In this method, a solution film is dried on a substrate under a suspended flexible template with groove/ridge surface topography. Upon solvent evaporation, the solution splits in the grooves and forms capillary bridges between the template and substrate, which are firmly pinned by the edges of the template grooves. This groove pinning stabilizes the contact lines, thereby allowing the formation of fine patterned structures with high aspect ratios which were used to fabricate various functional materials and electronic devices. We also produced secondary self-assembled nano-stripe patterns with resolutions of about 50 nm on the primary lines.
Measurements of growing surface tension of amorphous–amorphous interfaces on approaching the colloidal glass transition
Authors: Ganapathi Divya , Nagamanasa K. Hima , Sood A. K. , Ganapathy Rajesh
Published: January 2018

There is mounting evidence indicating that relaxation dynamics in liquids approaching their glass transition not only become increasingly cooperative, but the relaxing regions also become more compact in shape. Of the many theories of the glass transition, only the random first-order theory—a thermodynamic framework—anticipates the surface tension of relaxing regions to play a role in deciding both their size and morphology. However, owing to the amorphous nature of the relaxing regions, even the identification of their interfaces has not been possible in experiments hitherto. Here, we devise a method to directly quantify the dynamics of amorphous–amorphous interfaces in bulk supercooled colloidal liquids. Our procedure also helped unveil a non-monotonic evolution in dynamical correlations with supercooling in bulk liquids. We measure the surface tension of the interfaces and show that it increases rapidly across the mode-coupling area fraction. Our experiments support a thermodynamic origin of the glass transition.
Pronounced centennial-scale Atlantic Ocean climate variability correlated with Western Hemisphere hydroclimate
Authors: Thirumalai Kaustubh , Quinn Terrence M. , Okumura Yuko , Richey Julie N. , Partin Judson W. , Poore Richard Z. , Moreno-Chamarro Eduardo
Published: January 2018

Surface-ocean circulation in the northern Atlantic Ocean influences Northern Hemisphere climate. Century-scale circulation variability in the Atlantic Ocean, however, is poorly constrained due to insufficiently-resolved paleoceanographic records. Here we present a replicated reconstruction of sea-surface temperature and salinity from a site sensitive to North Atlantic circulation in the Gulf of Mexico which reveals pronounced centennial-scale variability over the late Holocene. We find significant correlations on these timescales between salinity changes in the Atlantic, a diagnostic parameter of circulation, and widespread precipitation anomalies using three approaches: multiproxy synthesis, observational datasets, and a transient simulation. Our results demonstrate links between centennial changes in northern Atlantic surface-circulation and hydroclimate changes in the adjacent continents over the late Holocene. Notably, our findings reveal that weakened surface-circulation in the Atlantic Ocean was concomitant with well-documented rainfall anomalies in the Western Hemisphere during the Little Ice Age.
Strong indirect coupling between graphene-based mechanical resonators via a phonon cavity
Authors: Luo Gang , Zhang Zhuo-Zhi , Deng Guang-Wei , Li Hai-Ou , Cao Gang , Xiao Ming , Guo Guang-Can , Tian Lin , Guo Guo-Ping
Published: January 2018

Mechanical resonators are promising systems for storing and manipulating information. To transfer information between mechanical modes, either direct coupling or an interface between these modes is needed. In previous works, strong coupling between different modes in a single mechanical resonator and direct interaction between neighboring mechanical resonators have been demonstrated. However, coupling between distant mechanical resonators, which is a crucial request for long-distance classical and quantum information processing using mechanical devices, remains an experimental challenge. Here, we report the experimental observation of strong indirect coupling between separated mechanical resonators in a graphene-based electromechanical system. The coupling is mediated by a far-off-resonant phonon cavity through virtual excitations via a Raman-like process. By controlling the resonant frequency of the phonon cavity, the indirect coupling can be tuned in a wide range. Our results may lead to the development of gate-controlled all-mechanical devices and open up the possibility of long-distance quantum mechanical experiments.
Generalized Fano lineshapes reveal exceptional points in photonic molecules
Authors: Caselli Niccolò , Intonti Francesca , La China Federico , Biccari Francesco , Riboli Francesco , Gerardino Annamaria , Li Lianhe , Linfield Edmund H. , Pagliano Francesco , Fiore Andrea , Gurioli Massimo
Published: January 2018

The optical behavior of coupled systems, in which the breaking of parity and time-reversal symmetry occurs, is drawing increasing attention to address the physics of the exceptional point singularity, i.e., when the real and imaginary parts of the normal-mode eigenfrequencies coincide. At this stage, fascinating phenomena are predicted, including electromagnetic-induced transparency and phase transitions. To experimentally observe the exceptional points, the near-field coupling to waveguide proposed so far was proved to work only in peculiar cases. Here, we extend the interference detection scheme, which lies at the heart of the Fano lineshape, by introducing generalized Fano lineshapes as a signature of the exceptional point occurrence in resonant-scattering experiments. We investigate photonic molecules and necklace states in disordered media by means of a near-field hyperspectral mapping. Generalized Fano profiles in material science could extend the characterization of composite nanoresonators, semiconductor nanostructures, and plasmonic and metamaterial devices.
Lipopolysaccharide O-antigen delays plant innate immune recognition of Xylella fastidiosa
Authors: Rapicavoli Jeannette N. , Blanco-Ulate Barbara , Muszyński Artur , Figueroa-Balderas Rosa , Morales-Cruz Abraham , Azadi Parastoo , Dobruchowska Justyna M. , Castro Claudia , Cantu Dario , Roper M. Caroline
Published: January 2018

Lipopolysaccharides (LPS) are among the known pathogen-associated molecular patterns (PAMPs). LPSs are potent elicitors of PAMP-triggered immunity (PTI), and bacteria have evolved intricate mechanisms to dampen PTI. Here we demonstrate that Xylella fastidiosa (Xf), a hemibiotrophic plant pathogenic bacterium, possesses a long chain O-antigen that enables it to delay initial plant recognition, thereby allowing it to effectively skirt initial elicitation of innate immunity and establish itself in the host. Lack of the O-antigen modifies plant perception of Xf and enables elicitation of hallmarks of PTI, such as ROS production specifically in the plant xylem tissue compartment, a tissue not traditionally considered a spatial location of PTI. To explore translational applications of our findings, we demonstrate that pre-treatment of plants with Xf LPS primes grapevine defenses to confer tolerance to Xf challenge.
Characterizing hepatitis C virus epidemiology in Egypt: systematic reviews, meta-analyses, and meta-regressions
Authors: Kouyoumjian Silva P. , Chemaitelly Hiam , Abu-Raddad Laith J.
Published: January 2018

Egypt is the most affected nation by hepatitis C virus (HCV) and needs a comprehensive characterization of HCV epidemiology to inform the scale-up of treatment and prevention programs. Systematic reviews, meta-analyses, and meta-regressions were conducted. A total of 25 incidence, 259 prevalence, and 47 genotype studies were identified. Incidence and prevalence levels were high across all populations. Genotype 4 accounted for 94.1% of infections with a relative Shannon Diversity Index of only 14.4%. Pooled mean HCV prevalence was estimated at 11.9% (95% CI = 11.1–12.6%) among the general population, 55.6% (95% CI = 49.4–61.7%) among populations at high risk, 14.3% (95% CI = 10.3–18.8%) among populations at intermediate risk, 56.0% (95% CI = 50.4–61.6%) among populations with liver-related conditions, and 35.0% (95% CI = 27.3–43.1%) among special clinical populations. Mean HCV viremic rate was estimated at 66.7% (95% CI = 61.7–71.5%). Meta-regression indicated 6% lower odds for HCV prevalence for each one-year increment in publication year (AOR = 0.94; 95% CI = 0.92–0.96). HCV prevalence is high with evidence for ongoing transmission mainly through healthcare. Genotype diversity is low with genotype 4 dominance. Two-thirds of antibody-positive Egyptians are chronically infected and need treatment. Clinical populations should be prioritized for screening. Despite the large-scale epidemic, prevalence appears to be declining rapidly consistent with a contracting epidemic.
C-reactive protein and pentraxin-3 binding of factor H-like protein 1 differs from complement factor H: implications for retinal inflammation
Authors: Swinkels Maurice , Zhang Justine H. , Tilakaratna Viranga , Black Graeme , Perveen Rahat , McHarg Selina , Inforzato Antonio , Day Anthony J. , Clark Simon J.
Published: January 2018

Retinal inflammation plays a key role in the progression of age-related macular degeneration (AMD), a condition that leads to loss of central vision. The deposition of the acute phase pentraxin C-reactive protein (CRP) in the macula activates the complement system, thereby contributing to dysregulated inflammation. The complement protein factor H (FH) can bind CRP and down-regulate an inflammatory response. However, it is not known whether a truncated form of FH, called factor H-like protein 1 (FHL-1), which plays a significant regulatory role in the eye, also interacts with CRP. Here, we compare the binding properties of FHL-1 and FH to both CRP and the related protein pentraxin-3 (PTX3). We find that, unlike FH, FHL-1 can bind pro-inflammatory monomeric CRP (mCRP) as well as the circulating pentameric form. Furthermore, the four-amino acid C-terminal tail of FHL-1 (not present in FH) plays a role in mediating its binding to mCRP. PTX3 was found to be present in the macula of donor eyes and the AMD-associated Y402H polymorphism altered the binding of FHL-1 to PTX3. Our findings reveal that the binding characteristics of FHL-1 differ from those of FH, likely underpinning independent immune regulatory functions in the context of the human retina.
HIV-1 Infection in Cyprus, the Eastern Mediterranean European Frontier: A Densely Sampled Transmission Dynamics Analysis from 1986 to 2012
Authors: Pineda-Peña Andrea-Clemencia , Theys Kristof , Stylianou Dora C. , Demetriades Ioannis ,   SPREAD/ESAR Program, Puchhammer Elisabeth , Vandamme Anne-Mieke , Aleksiev Ivailo , Lepej Snjezana Zidovec , Linka Marek , Fonager Jannik , Liitsola Kirsi , Kaiser Rolf , Hamouda Osamah , Paraskevis Dimitrios , Coughlan Suzie , Grossman Zehava , Mor Orna , Zazzi Maurizio , Griskevicius Algirdas , Lipnickiene Vilnele , Devaux Carole , Boucher Charles , Hofstra Marije , Wensing Annemarie , Bakken-Kran Anne-Marte , Horban Andrzej , Camacho Ricardo , Paraschiv Simona , Otelea Dan , Stanojevic Maja , Stanekova Danika , Poljak Mario , Garcia Federico , Paredes Roger , Albert Jan , Abecasis Ana B. , Kostrikis Leondios G.
Published: January 2018

Since HIV-1 treatment is increasingly considered an effective preventionstrategy, it is important to study local HIV-1 epidemics to formulate tailored preventionpolicies. The prevalence of HIV-1 in Cyprus was historically low until 2005. To investigatethe shift in epidemiological trends, we studied the transmission dynamics of HIV-1 in Cyprususing a densely sampled Cypriot HIV-1 transmission cohort that included 85 percent ofHIV-1-infected individuals linked to clinical care between 1986 and 2012 based on detailedclinical, epidemiological, behavioral and HIV-1 genetic information. Subtyping andtransmission cluster reconstruction were performed using maximum likelihood and Bayesianmethods, and the transmission chain network was linked to the clinical, epidemiological andbehavioral data. The results reveal that for the main HIV-1 subtype A1 and B sub-epidemics,young and drug-naïve HIV-1-infected individuals in Cyprus are driving the dynamics of thelocal HIV-1 epidemic. The results of this study provide a better understanding of thedynamics of the HIV-1 infection in Cyprus, which may impact the development of preventionstrategies. Furthermore, this methodology for analyzing densely sampled transmissiondynamics is applicable to other geographic regions to implement effective HIV-1 preventionstrategies in local settings.
A new bound on polymer quantization via an opto-mechanical setup
Authors: Khodadi Mohsen , Nozari Kourosh , Dey Sanjib , Bhat Anha , Faizal Mir
Published: January 2018

The existence of a minimal measurable length as a characteristic length in the Planck scale is one of the main features of quantum gravity and has been widely explored in the context. Various different deformations of spacetime have been employed successfully for the purpose. However, polymer quantization approach is a relatively new and dynamic field towards the quantum gravity phenomenology, which emerges from the symmetric sector of the loop quantum gravity. In this article, we extend the standard ideas of polymer quantization to find a new and tighter bound on the polymer deformation parameter. Our protocol relies on an opto-mechanical experimental setup that was originally proposed to explore some interesting phenomena by embedding the minimal length into the standard canonical commutation relation. We extend this scheme to probe the polymer length deformed canonical commutation relation of the center of mass mode of a mechanical oscillator with a mass around the Planck scale. The method utilizes the novelty of exchanging the relevant mechanical information with a high intensity optical pulse inside an optical cavity. We also demonstrate that our proposal is within the reach of the current technologies and, thus, it could uncover a decent realization of quantum gravitational phenomena thorough a simple table-top experiment.
Impact of left atrial appendage morphology on thrombus formation after successful left atrial appendage occlusion: Assessment with cardiac-computed-tomography
Authors: Dieker Wulf , Behnes Michael , Fastner Christian , Sartorius Benjamin , Wenke Annika , Sing-Gill Ishar , El-Battrawy Ibrahim , Kuschyk Jürgen , Papavassiliu Theano , Hoffmann Ursula , Mashayekhi Kambis , Schoenberg Stefan O. , Borggrefe Martin , Henzler Thomas , Akin Ibrahim
Published: January 2018

A standardized imaging algorithm by cardiac computed tomography angiography (cCTA) (LOVE-view) was used in 30 patients to evaluate the influence of different left atrial appendage (LAA) morphologies on development of thrombosis in the LAA 6 months after implantation of an occlusion device (Watchman or Amplatzer-Cardiac-Plug) in patients with non-valvular atrial fibrillation, CHA2DS2-VASc-Score >1 and a contraindication for oral anticoagulation. The distribution of different LAA morphologies was 40% windsock, 17% broccoli and 43% chicken wing type. There was no significant difference in the level of thrombosis regarding LAA morphology or the type of chosen occlusion device. The rates of complete LAA thrombosis was 40% in broccoli type, 33% in windsock and 15% in chicken wing type. Independently of LAA type, 13% had none and 60% incomplete thrombosis. The ratio of density (LA/LAA) was 0.14 in patients with complete thrombosis and 0.67 in those with none or incomplete thrombosis. cCTA and the LOVE-view-imaging-algorithm were shown to be a valuable method for standardized imaging in clinical routine in a greater set of patients. Surprisingly thrombosis of the occluded LAA was still in progress in most cases at 6 months, whereas further studies are needed defining its clinical consequences, especially for the selection of the optimal post-procedural antithrombotic treatment strategy.
Three-dimensional reconstruction and NURBS-based structured meshing of coronary arteries from the conventional X-ray angiography projection images
Authors: Vukicevic Arso M. , Çimen Serkan , Jagic Nikola , Jovicic Gordana , Frangi Alejandro F. , Filipovic Nenad
Published: January 2018

Despite its two-dimensional nature, X-ray angiography (XRA) has served as the gold standard imaging technique in the interventional cardiology for over five decades. Accordingly, demands for tools that could increase efficiency of the XRA procedure for the quantitative analysis of coronary arteries (CA) are constantly increasing. The aim of this study was to propose a novel procedure for three-dimensional modeling of CA from uncalibrated XRA projections. A comprehensive mathematical model of the image formation was developed and used with a robust genetic algorithm optimizer to determine the calibration parameters across XRA views. The frames correspondences between XRA acquisitions were found using a partial-matching approach. Using the same matching method, an efficient procedure for vessel centerline reconstruction was developed. Finally, the problem of meshing complex CA trees was simplified to independent reconstruction and meshing of connected branches using the proposed nonuniform rational B-spline (NURBS)-based method. Because it enables structured quadrilateral and hexahedral meshing, our method is suitable for the subsequent computational modelling of CA physiology (i.e. coronary blood flow, fractional flow reverse, virtual stenting and plaque progression). Extensive validations using digital, physical, and clinical datasets showed competitive performances and potential for further application on a wider scale.
HIV-1 with HBV-associated Q151M substitution in RT becomes highly susceptible to entecavir: structural insights into HBV-RT inhibition by entecavir
Authors: Yasutake Yoshiaki , Hattori Shin-ichiro , Hayashi Hironori , Matsuda Kouki , Tamura Noriko , Kohgo Satoru , Maeda Kenji , Mitsuya Hiroaki
Published: January 2018

Hepatitis B virus (HBV) reverse transcriptase (RT) is essential for viral replication and is an important drug target. Nonetheless, the notorious insolubility of HBV RT has hindered experimental structural studies and structure-based drug design. Here, we demonstrate that a Q151M substitution alone at the nucleotide-binding site (N-site) of human immunodeficiency virus type-1 (HIV-1) RT renders HIV-1 highly sensitive to entecavir (ETV), a potent nucleoside analogue RT inhibitor (NRTI) against HBV. The results suggest that Met151 forms a transient hydrophobic interaction with the cyclopentyl methylene of ETV, a characteristic hydrophobic moiety of ETV. We thus solved the crystal structures of HIV-1 RTQ151M:DNA complex with bound dGTP or ETV-triphosphate (ETV-TP). The structures revealed that ETV-TP is accommodated at the N-site slightly apart from the ribose ring of the 3′-end nucleotide, compared to the position of bound dGTP and previously reported NRTI/dNTP. In addition, the protruding methylene group of bound ETV-TP directly pushes the side-chain of Met184 backward. Met184 is a key residue that confers ETV resistance upon substitution with smaller Ile/Val. These results provide novel insights into NRTI binding to the N-site and further provide important clues for the development of novel anti-HBV/HIV-1 RT inhibitors to overcome critical drug resistance.
Nanopillars with E-field accessible multi-state (N ≥ 4) magnetization having giant magnetization changes in self-assembled BiFeO3-CoFe2O4/Pb(Mg1/3Nb2/3)-38at%PbTiO3 heterostructures
Authors: Tang Xiao , Viswan Ravindranath , Gao Min , Leung Chung Ming , Folger Carlos , Luo Haosu , Howe Brandon , Li Jiefang , Viehland Dwight
Published: January 2018

We have deposited self-assembled BiFeO3-CoFe2O4 (BFO-CFO) thin films on (100)-oriented SrRuO3-buffered Pb(Mg1/3Nb2/3)0.62Ti0.38O3 (PMN-38PT) single crystal substrates. These heterostructures were used for the study of real-time changes in the magnetization with applied DC electric field (E
DC
). With increasing E
DC
, a giant magnetization change was observed along the out-of-plane (easy) axis. The induced magnetization changes of the CFO nanopillars in the BFO/CFO layer were about ΔM/M
rDC
 = 93% at E
DC
 = −3 kv/cm. A giant converse magnetoelectric (CME) coefficient of 1.3 × 10−7 s/m was estimated from the data. By changing E
DC
, we found multiple(N ≥ 4) unique possible values of a stable magnetization with memory on the removal of the field.
Three-dimensional histochemistry and imaging of human gingiva
Authors: Azaripour Adriano , Lagerweij Tonny , Scharfbillig Christina , Jadczak Anna Elisabeth , Swaan Britt van der , Molenaar Manon , Waal Rens van der , Kielbassa Karoline , Tigchelaar Wikky , Picavet Daisy I. , Jonker Ard , Hendrikx Esther M. L. , Hira Vashendriya V. V. , Khurshed Mohammed , Noorden Cornelis J. F. Van
Published: January 2018

In the present study, 3D histochemistry and imaging methodology is described for human gingiva to analyze its vascular network. Fifteen human gingiva samples without signs of inflammation were cleared using a mixture of 2-parts benzyl benzoate and 1-part benzyl alcohol (BABB), after being immunofluorescently stained for CD31, marker of endothelial cells to visualize blood vessels in combination with fluorescent DNA dyes. Samples were imaged in 3D with the use of confocal microscopy and light-sheet microscopy and image processing. BABB clearing caused limited tissue shrinkage 13 ± 7% as surface area and 24 ± 1% as volume. Fluorescence remained intact in BABB-cleared gingiva samples and light-sheet microscopy was an excellent tool to image gingivae whereas confocal microscopy was not. Histochemistry on cryostat sections of gingiva samples after 3D imaging validated structures visualized in 3D. Three-dimensional images showed the vascular network in the stroma of gingiva with one capillary loop in each stromal papilla invading into the epithelium. The capillary loops were tortuous with structural irregularities that were not apparent in 2D images. It is concluded that 3D histochemistry and imaging methodology described here is a promising novel approach to study structural aspects of human gingiva in health and disease.
Development and characterisation of a panel of phosphatidylinositide 3-kinase – mammalian target of rapamycin inhibitor resistant lung cancer cell lines
Authors: Heavey Susan , Dowling Paul , Moore Gillian , Barr Martin P. , Kelly Niamh , Maher Stephen G. , Cuffe Sinead , Finn Stephen P. , O’Byrne Kenneth J. , Gately Kathy
Published: January 2018

The PI3K-mTOR pathway is involved in regulating all hallmarks of cancer, and is often dysregulated in NSCLC, making it an attractive therapeutic target in this setting. Acquired resistance to PI3K-mTOR inhibition is a major hurdle to overcome in the success of PI3K-mTOR targeted agents. H460, A549, and H1975 resistant cells were generated by prolonged treatment in culture with Apitolisib (GDC-0980), a dual PI3K-mTOR inhibitor over a period of several months, from age-matched parent cells. Resistance was deemed to have developed when a log fold difference in IC50 had been achieved. Resistant cell lines also exhibited resistance to another widely investigated PI3K-mTOR dual inhibitor; Dactolisib (BEZ235). Cell lines were characterised at the level of mRNA (expression array profiling expression of >150 genes), miRNA (expression array profiling of 2100 miRNAs), protein (bottoms-up label-free mass spectrometry) and phosphoprotein (expression array profiling of 84 phospho/total proteins). Key alterations were validated by qPCR and Western blot. H1975 cells were initially most sensitive to Apitolisib (GDC-0980), but developed resistance more quickly than the other cell lines, perhaps due to increased selective pressure from the impressive initial effect. In-depth molecular profiling suggested epithelial-mesenchymal transition (EMT) may play a role in resistance to PI3K-mTOR dual inhibition in NSCLC.
High-resolution seismic event detection using local similarity for Large-N arrays
Authors: Li Zefeng , Peng Zhigang , Hollis Dan , Zhu Lijun , McClellan James
Published: January 2018

We develop a novel method for seismic event detection that can be applied to large-N arrays. The method is based on a new detection function named local similarity, which quantifies the signal consistency between the examined station and its nearest neighbors. Using the 5200-station Long Beach nodal array, we demonstrate that stacked local similarity functions can be used to detect seismic events with amplitudes near or below noise levels. We apply the method to one-week continuous data around the 03/11/2011 Mw 9.1 Tohoku-Oki earthquake, to detect local and distant events. In the 5–10 Hz range, we detect various events of natural and anthropogenic origins, but without a clear increase in local seismicity during and following the surface waves of the Tohoku-Oki mainshock. In the 1-Hz low-pass-filtered range, we detect numerous events, likely representing aftershocks from the Tohoku-Oki mainshock region. This high-resolution detection technique can be applied to both ultra-dense and regular array recordings for monitoring ultra-weak micro-seismicity and detecting unusual seismic events in noisy environments.
Oxidative stress induced by Cu nutritional disorders in Citrus depends on nitrogen and calcium availability
Authors: Hippler Franz Walter Rieger , Boaretto Rodrigo Marcelli , Dovis Veronica Lorena , Quaggio José Antônio , Azevedo Ricardo Antunes , Mattos-Jr Dirceu
Published: January 2018

Nutritional stress caused by copper (Cu) deficiency or toxicity affects fruit production of citrus orchards worldwide, but this could be minimised by fine-tuned fertilisation in the orchards. Two experiments were performed aiming to evaluate the photosynthetic capacity and the antioxidant enzyme activities of Swingle citrumelo seedlings, grown in nutrient solution (NS) with two levels of nitrogen (N) in the first experiment (adequate-N and high-N) and two levels of calcium (Ca) in the second (low-Ca and adequate-Ca). Plants were then exposed to various Cu levels (low, medium and high) for 15 days. Plants under Cu-toxicity exhibited specific effects on reactive oxygen species formation and root-to-shoot plant signalling. Copper absorption was greater with increased Cu concentration in the NS, which reduced plant biomass accumulation, gas exchange measurements, the activity of nitrate reductase and affected Cu partitioning between roots and shoots. Despite these effects, oxidative stress induced by excess-Cu was reduced at the highest N dose when compared to control and, on the contrary, increased with low-Ca supply. Therefore, a rational supply of N or Ca minimises Cu-induced stress damages to roots and leaves of plants, by directly enhancing the antioxidant system and protecting the associated antioxidative enzyme activities, whilst maintaining photosynthesis.
Interplay between TETs and microRNAs in the adult brain for memory formation
Authors: Kremer Eloïse A. , Gaur Niharika , Lee Melissa A. , Engmann Olivia , Bohacek Johannes , Mansuy Isabelle M.
Published: January 2018

5-hydroxymethylation (5-hmC) is an epigenetic modification on DNA that results from the conversion of 5-methylcytosine by Ten-Eleven Translocation (TET) proteins. 5-hmC is widely present in the brain and is subjected to dynamic regulation during development and upon neuronal activity. It was recently shown to be involved in memory processes but currently, little is known about how it is controlled in the brain during memory formation. Here, we show that Tet3 is selectively up-regulated by activity in hippocampal neurons in vitro, and after formation of fear memory in the hippocampus. This is accompanied by a decrease in miR-29b expression that, through complementary sequences, regulates the level of Tet3 by preferential binding to its 3′UTR. We newly reveal that SAM68, a nuclear RNA-binding protein known to regulate splicing, acts upstream of miR-29 by modulating its biogenesis. Together, these findings identify novel players in the adult brain necessary for the regulation of 5-hmC during memory formation.
Transcriptomic characterization and potential marker development of contrasting sugarcane cultivars
Authors: Xu Shiqiang , Wang Jihua , Shang Heyang , Huang Youzong , Yao Wei , Chen Baoshan , Zhang Muqing
Published: January 2018

Sugarcane (Saccharum officinarumL.) is an important crop for sugar production and bioenergy worldwide. In this study, we performed transcriptome sequencing for six contrasting sugarcane genotypes involved in leaf abscission, tolerance to pokkah boeng disease and drought stress. More than 465 million high-quality reads were generated, which werede novoassembled into 93,115 unigenes. Based on a similarity search, 43,526 (46.74%) unigenes were annotated against at least one of the public databases. Functional classification analyses showed that these unigenes are involved in a wide range of metabolic pathways. Comparative transcriptome analysis revealed that many unigenes involved in response to abscisic acid and ethylene were up-regulated in the easy leaf abscission genotype, and unigenes associated with response to jasmonic acid and salicylic acid were up-regulated in response to the pokkah boeng disease in the tolerance genotype. Moreover, unigenes related to peroxidase, antioxidant activity and signal transduction were up-regulated in response to drought stress in the tolerant genotype. Finally, we identified a number of putative markers, including 8,630 simple sequence repeats (SSRs) and 442,152 single-nucleotide polymorphisms (SNPs). Our data will be important resources for future gene discovery, molecular marker development, and genome studies in sugarcane.
A retrospective cohort study on the outcomes of ischemic stroke patients with adjuvant Korean Medicine treatment
Authors: Lee Ye-Seul , Kwon Seungwon , Chae Younbyoung , Jang Bo-Hyoung , Ko Seong-Gyu
Published: January 2018

This study aims to examine the long-term effect of adjuvant treatment in Korean Medicine (KM) clinics in ischemic stroke patients, using a national sample cohort from the National Health Insurance Service in Korea between 2010 and 2013. The National Health Insurance Service – National Sample Cohort database from 2002 to 2013 was used in this study. Ischemic stroke patients were defined and covariates were included to account for socioeconomic variables, comorbidities and disease severity. Propensity score matching was applied. Cox proportional hazards modeling and Kaplan-Meier analysis were applied to determine the differences between KM and non-KM treated groups. The results shows that KM-treated group had a higher probability of survival than non-KM group patients. No significant difference was observed between the risk of readmission between the treated and non-treated patients. Kaplan-Meier analysis showed a weak effect of KM treatments in the patients with 8 to 28 days of hospital stay for a lower risk of recurrence than in non-treated patients. In conclusion, KM treatment of mild to moderate ischemic stroke patients has a mild effect on the survival probability of stroke. Its effect for improving long-term recurrence need to be explored in the future studies.
2-Phenylquinazolinones as dual-activity tankyrase-kinase inhibitors
Authors: Nkizinkiko Yves , Desantis Jenny , Koivunen Jarkko , Haikarainen Teemu , Murthy Sudarshan , Sancineto Luca , Massari Serena , Ianni Federica , Obaji Ezeogo , Loza Maria I. , Pihlajaniemi Taina , Brea Jose , Tabarrini Oriana , Lehtiö Lari
Published: January 2018

Tankyrases (TNKSs) are enzymes specialized in catalyzing poly-ADP-ribosylation of target proteins. Several studies have validated TNKSs as anti-cancer drug targets due to their regulatory role in Wnt/β-catenin pathway. Recently a lot of effort has been put into developing more potent and selective TNKS inhibitors and optimizing them towards anti-cancer agents. We noticed that some 2-phenylquinazolinones (2-PQs) reported as CDK9 inhibitors were similar to previously published TNKS inhibitors. In this study, we profiled this series of 2-PQs against TNKS and selected kinases that are involved in the Wnt/β-catenin pathway. We found that they were much more potent TNKS inhibitors than they were CDK9/kinase inhibitors. We evaluated the compound selectivity to tankyrases over the ARTD enzyme family and solved co-crystal structures of the compounds with TNKS2. Comparative structure-based studies of the catalytic domain of TNKS2 with selected CDK9 inhibitors and docking studies of the inhibitors with two kinases (CDK9 and Akt) revealed important structural features, which could explain the selectivity of the compounds towards either tankyrases or kinases. We also discovered a compound, which was able to inhibit tankyrases, CDK9 and Akt kinases with equal µM potency.
Chirality recognition of winding vine-shaped heterobiaryls with molecular asymmetry. Kinetic and dynamic kinetic resolution by Shi’s asymmetric epoxidation
Authors: Maruhashi Kazuki , Okayama Yoichi , Inoue Ryo , Ashida Shiomi , Toyomori Yuka , Okano Kentaro , Mori Atsunori
Published: January 2018

The chirality of winding vine-shaped heterobiaryls with molecular asymmetry is recognized by a sugar-based chiral oxidant. Kinetic resolution of (±)-bisbenzoimidazole bearing an olefin moiety takes place with Shi’s asymmetric epoxidation to observe krel value up to ca. 35 affording the corresponding epoxide. The reaction of a (±)-bithiophene derivative also recognized the chirality to give the corresponding epoxide with er of 96:4 at 39% conversion. Dynamic kinetic resolution is found to take place when unsymmetrical biaryl composed of benzoimidazole/thiophene is subjected to Shi’s epoxidation, whose conversion of the racemic substrate exceeds to 50%.
Variability in phase and amplitude of diurnal rhythms is related to variation of mood in bipolar and borderline personality disorder
Authors: Carr O. , Saunders K. E. A. , Tsanas A. , Bilderbeck A. C. , Palmius N. , Geddes J. R. , Foster R. , Goodwin G. M. , De Vos M.
Published: January 2018

Variable mood is an important feature of psychiatric disorders. However, its measurement and relationship to objective measureas of physiology and behaviour have rarely been studied. Smart-phones facilitate continuous personalized prospective monitoring of subjective experience and behavioural and physiological signals can be measured through wearable devices. Such passive data streams allow novel estimates of diurnal variability. Phase and amplitude of diurnal rhythms were quantified using new techniques that fitted sinusoids to heart rate (HR) and acceleration signals. We investigated mood and diurnal variation for four days in 20 outpatients with bipolar disorder (BD), 14 with borderline personality disorder (BPD) and 20 healthy controls (HC) using a smart-phone app, portable electrocardiogram (ECG), and actigraphy. Variability in negative affect, positive affect, and irritability was elevated in patient groups compared with HC. The study demonstrated convincing associations between variability in subjective mood and objective variability in diurnal physiology. For BPD there was a pattern of positive correlations between mood variability and variation in activity, sleep and HR. The findings suggest BPD is linked more than currently believed with a disorder of diurnal rhythm; in both BPD and BD reducing the variability of sleep phase may be a way to reduce variability of subjective mood.
Mitonuclear interactions may contribute to fitness of fungal hybrids
Authors: Giordano Luana , Sillo Fabiano , Garbelotto Matteo , Gonthier Paolo
Published: January 2018

Hybridization between species is being recognized as a major force in the rapid adaptive evolution of fungal plant pathogens. The first stages of interspecific hybridization necessarily involve nuclear-mitochondrial chimeras. In their 2001 publication, Olson and Stenlid reported that mitochondria control the virulence of first generation hybrids between the North American fungal pathogen Heterobasidion irregulare and its congeneric H. occidentale. By assessing saprobic ability and gene expression of H. irregulare × H. annosum sensu stricto hybrids and of their parental genotypes, we demonstrate that mitochondria also influence saprobic growth of hybrids. Moreover, gene expression data suggest that fungal fitness is modulated by an intimate interplay between nuclear genes and mitochondrial type, and is dependent on the specific mitonuclear combination.
Effect of secondary phase on the electromagnetic shielding effectiveness of magnesium alloy
Authors: Gao Shangyu , Chen Xianhua , Pan Fusheng , Song Kai , Zhao Chaoyue , Liu Lizi , Liu Xiaofang , Zhao Di
Published: January 2018

The microstructure, electrical conductivity, and electromagnetic interference (EMI) shielding effectiveness (SE) of Mg-xZn and Mg-xSn (x = 3,5) alloys prepared under different rolling and heat treatment conditions were systematically investigated to understand the effect of secondary-phase orientation on the electromagnetic-shielding property of magnesium alloys. Alloys were rolled to form basal textures and then subjected to different durations of solid-solution treatment and aging to induce the precipitation of secondary-phase particles along a specific direction. Experimental results indicated that in Mg-Zn and Mg-Sn alloys, secondary phases precipitated along directions perpendicular and parallel to the basal plane, respectively. When the direction of the incident electromagnetic wave is perpendicular to the basal plane, precipitates in Mg-Sn alloy parallel to the basal plane improve SE. The increment in SE is mainly attributed to the improvement in the reflection and multiple reflection losses of incident electromagnetic waves, which are caused by increasing the amounts of precipitates with specific orientations. Mg-5Sn alloy subjected to 16 h of solution treatment at 480 °C and 60 h of artificial aging at 170 °C for 60 h exhibited the maximum value of 107–89 dB and maximum increment in SE of 13 dB at 1200 MHz.
Different milk diets have substantial effects on the jejunal mucosal immune system of pre-weaning calves, as demonstrated by whole transcriptome sequencing
Authors: Hammon H. M. , Frieten D. , Gerbert C. , Koch C. , Dusel G. , Weikard R. , Kühn C.
Published: January 2018

There is increasing evidence that nutrition during early mammalian life has a strong influence on health and performance in later life. However, there are conflicting data concerning the appropriate milk diet. This discrepancy particularly applies to ruminants, a group of mammals that switch from monogastric status to rumination during weaning. Little is known regarding how the whole genome expression pattern in the juvenile ruminant gut is affected by alternative milk diets. Thus, we performed a next-generation-sequencing-based holistic whole transcriptome analysis of the jejunum in male pre-weaned German Holstein calves fed diets with restricted or unlimited access to milk during the first 8 weeks of life. Both groups were provided hay and concentratead libitum. The analysis of jejunal mucosa samples collected 80 days after birth and four weeks after the end of the feeding regimes revealed 275 differentially expressed loci. While the differentially expressed loci comprised 67 genes encoding proteins relevant to metabolism or metabolic adaptation, the most distinct difference between the two groups was the consistently lower activation of the immune system in calves that experienced restricted milk access compared to calves fed milkad libitum. In conclusion, different early life milk diets had significant prolonged effects on the intestinal immune system.
Interplay of bimolecular and Auger recombination in photoexcited carrier dynamics in silicon nanocrystal/silicon dioxide superlattices
Authors: Chlouba T. , Trojánek F. , Laube J. , Hiller D. , Gutsch S. , Zacharias M. , Malý P.
Published: January 2018

We report results of investigating carrier recombination in silicon nanocrystal/silicon dioxide superlattices. The superlattices prepared by nitrogen-free plasma enhanced chemical vapour deposition contained layers of silicon nanocrystals. Femtosecond transient transmission optical spectroscopy was used to monitor carrier mechanisms in the samples. The three-particle Auger recombination was observed in accord with previous reports. However, under high pump intensities (high photoexcited carrier densities) the bimolecular process dominated the recombination. Detailed analysis of measured data and fitting procedure made it possible to follow and quantify the interplay between the two recombination processes. The bimolecular recombination was interpreted in terms of the trap-assisted Auger recombination.
Depletion of HDAC1, 7 and 8 by Histone Deacetylase Inhibition Confers Elimination of Pancreatic Cancer Stem Cells in Combination with Gemcitabine
Authors: Cai Mao-Hua , Xu Xiao-Gang , Yan Shi-Li , Sun Ze , Ying Yin , Wang Bai-Kui , Tu Yue-Xing
Published: January 2018

Trichostatin A (TSA) possess histone deacetylase (HDAC) inhibitory potential, can reverse the deactivation of tumor suppressor genes and inhibit tumor cell proliferation. We evaluated the effect of TSA on HDAC expression, tumor cell proliferation, and cancer stem cells (CSCs) activities in pancreatic ductal adenocarnoma (PDAC) cells. The PDAC cell lines MiaPaCa-2 and PANC-1 were distinctly sensitive to TSA, with enhanced apoptosis, compared to SAHA. TSA or SAHA inhibited vimentin, HDACs 1, 7 and 8, upregulated E-cadherin mRNA and protein levels in the PDAC cells, and time-dependently downregulated Oct-4, Sox-2, and Nanog, as well as inhibited PDAC tumorsphere formation. TSA also induces accumulation of acetylated histones, while increasing histone 3 lysine 4 or 9 dimethylation levels in PDAC cells and enhancing the epigenetic activity of SAHA. The anti-CSCs effect of TSA was like that obtained by silencing HDAC-1 or 7 using siRNA, and enhances Gemcitabine activity. Our study highlights the molecular targetability of HDACs 1, 7, and 8, confirm their PDAC-CSCs maintaining role, and demonstrate that compared to SAHA, TSA modulates the epigenetically- mediated oncogenic activity of PDAC-CSCs, and potentiate Gemcitabine therapeutic activity, making a case for further exploration of TSA activity alone or in combination with Gemcitabine in PDAC therapy.
Population coding of grasp and laterality-related information in the macaque fronto-parietal network
Authors: Michaels Jonathan A. , Scherberger Hansjörg
Published: January 2018

Preparing and executing grasping movements demands the coordination of sensory information across multiple scales. The position of an object, required hand shape, and which of our hands to extend must all be coordinated in parallel. The network formed by the macaque anterior intraparietal area (AIP) and hand area (F5) of the ventral premotor cortex is essential in the generation of grasping movements. Yet, the role of this circuit in hand selection is unclear. We recorded from 1342 single- and multi-units in AIP and F5 of two macaque monkeys (Macaca mulatta) during a delayed grasping task in which monkeys were instructed by a visual cue to perform power or precision grips on a handle presented in five different orientations with either the left or right hand, as instructed by an auditory tone. In AIP, intended hand use (left vs. right) was only weakly represented during preparation, while hand use was robustly present in F5 during preparation. Interestingly, visual-centric handle orientation information dominated AIP, while F5 contained an additional body-centric frame during preparation and movement. Together, our results implicate F5 as a site of visuo-motor transformation and advocate a strong transition between hand-independent and hand-dependent representations in this parieto-frontal circuit.
Modulation of oncogenic miRNA biogenesis using functionalized polyamines
Authors: Staedel Cathy , Tran Thi Phuong Anh , Giraud Julie , Darfeuille Fabien , Di Giorgio Audrey , Tourasse Nicolas J. , Salin Franck , Uriac Philippe , Duca Maria
Published: January 2018

MicroRNAs are key factors in the regulation of gene expression and their deregulation has been directly linked to various pathologies such as cancer. The use of small molecules to tackle the overexpression of oncogenic miRNAs has proved its efficacy and holds the promise for therapeutic applications. Here we describe the screening of a 640-compound library and the identification of polyamine derivatives interfering with in vitro Dicer-mediated processing of the oncogenic miR-372 precursor (pre-miR-372). The most active inhibitor is a spermine-amidine conjugate that binds to the pre-miR-372 with a KD of 0.15 µM, and inhibits its in vitro processing with a IC50 of 1.06 µM. The inhibition of miR-372 biogenesis was confirmed in gastric cancer cells overexpressing miR-372 and a specific inhibition of proliferation through de-repression of the tumor suppressor LATS2 protein, a miR-372 target, was observed. This compound modifies the expression of a small set of miRNAs and its selective biological activity has been confirmed in patient-derived ex vivo cultures of gastric carcinoma. Polyamine derivatives are promising starting materials for future studies about the inhibition of oncogenic miRNAs and, to the best of our knowledge, this is the first report about the application of functionalized polyamines as miRNAs interfering agents.
Ribosome Incorporation into Somatic Cells Promotes Lineage Transdifferentiation towards Multipotency
Authors: Ito Naofumi , Katoh Kaoru , Kushige Hiroko , Saito Yutaka , Umemoto Terumasa , Matsuzaki Yu , Kiyonari Hiroshi , Kobayashi Daiki , Soga Minami , Era Takumi , Araki Norie , Furuta Yasuhide , Suda Toshio , Kida Yasuyuki , Ohta Kunimasa
Published: January 2018

Recently, we reported that bacterial incorporation induces cellular transdifferentiation of human fibroblasts. However, the bacterium-intrinsic cellular- transdifferentiation factor remained unknown. Here, we found that cellular transdifferentiation is caused by ribosomes. Ribosomes, isolated from both prokaryotic and eukaryotic cells, induce the formation of embryoid body-like cell clusters. Numerous ribosomes are incorporated into both the cytoplasm and nucleus through trypsin-activated endocytosis, which leads to cell-cluster formation. Although ribosome-induced cell clusters (RICs) express several stemness markers and differentiate into derivatives of all three germ layers in heterogeneous cell populations, RICs fail to proliferate, alter the methylation states of pluripotent genes, or contribute to teratoma or chimera formation. However, RICs express markers of epithelial–mesenchymal transition without altering the cell cycle, despite their proliferation obstruction. These findings demonstrate that incorporation of ribosomes into host cells induces cell transdifferentiation and alters cellular plasticity.