bluuebunny/crossref_metadata_2025 huggingface dataset:
MUSICAL CRYPTOGRAPHY AND THE EARLY HISTORY OF THE ‘LEÓN ANTIPHONER’
Authors: De Luca Elsa
Published: September 2017

The ‘León Antiphoner’, León, Cathedral Library, MS 8, is the most complete manuscript containing Old Hispanic chant, comprising Office and Mass chants for the whole church year. As such, the León Antiphoner is the most studied Old Hispanic manuscript. Despite this, its dating is controversial and hypotheses have ranged from c. 906 (Menéndez Pidal) up to the eleventh century (Zapke and others). In this article, the dating and early history of the manuscript are reconsidered and an entirely new perspective is brought to bear on the questions of when, where, and for whom the manuscript was written. The reinterpretation of the cryptographic inscriptions found at the bottom of fols. 128vand 149rhas made it possible to identify the patron of the Antiphoner as San Froilán, Bishop of León, and to date the manuscript’s production to the years 900–5. The scriptorium of the monastery of SS Cosmas and Damian in Abellar is suggested as the likeliest place of production of the Antiphoner.
SIMPLE, ROBUST, AND ACCURATEFANDtTESTS IN COINTEGRATED SYSTEMS
Authors: Hwang Jungbin , Sun Yixiao
Published: September 2017

This paper proposes new, simple, and more accurate statistical tests in a cointegrated system that allows for endogenous regressors and serially dependent errors. The approach involves first transforming the time series using orthonormal basis functions inL2[0, 1], which have energy concentrated at low frequencies, and then running an augmented regression based on the transformed data and constructing the test statistics in the usual way. The approach is essentially the same as the trend instrumental variable approach of Phillips (2014), but the number of orthonormal basis functions is held fixed for the development of the standardFandtasymptotic theory. The tests are extremely simple to implement, as they can be carried out in exactly the same way as if the transformed regression is a classical linear normal regression. In particular, critical values are from the standardFortdistribution. The proposedFandttests are robust in that they are asymptotically valid regardless of whether the number of basis functions is held fixed or allowed to grow with the sample size. TheFandttests have more accurate size in finite samples than existing tests such as the asymptotic chi-squared and normal tests based on the fully modified OLS estimator of Phillips and Hansen (1990) and can be made as powerful as the latter test.
Granular cells in the presence of magnetic field
Authors: Jurčák J. , Lemmerer B. , van Noort M.
Published: September 2017

We present a statistical study of the dependencies of the shapes and sizes of the photospheric convective cells on the magnetic field properties. This analysis is based on a 2.5 hour long SST observations of active region NOAA 11768. We have blue continuum images taken with a cadence of 5.6 sec that are used for segmentation of individual granules and 270 maps of spectropolarimetric CRISP data allowing us to determine the properties of the magnetic field along with the line-of-sight velocities. The sizes and shapes of the granular cells are dependent on the the magnetic field strength, where the granules tend to be smaller in regions with stronger magnetic field. In the presence of highly inclined magnetic fields, the eccentricity of granules is high and we do not observe symmetric granules in these regions. The mean up-flow velocities in granules as well as the granules intensities decrease with increasing magnetic field strength.
A long-duration active region: Evolution and quadrature observations of ejective events
Authors: Cremades H. , Mandrini C. H. , Fuentes M. C. López , Merenda L. , Cabello I. , López F. M. , Poisson M.
Published: September 2017

Unknown aspects of the initiation, evolution, and associated phenomena of coronal mass ejections (CMEs), together with their capability of perturbing the fragile technological equilibrium on which nowadays society depends, turn them a compelling subject of study. While space weather forecasts are thus far not able to predict when and where in the Sun will the next CME take place, various CME triggering mechanisms have been proposed, without reaching consensus on which is the predominant one. To improve our knowledge in these respects, we investigate a long-duration active region throughout its life, from birth until decay along five solar rotations, in connection with its production of ejective events. We benefit from the wealth of solar remote-sensing data with improved temporal, spatial, and spectral resolution provided by the ground-breaking space missions STEREO, SDO, and SOHO. During the investigated time interval, which covers the months July – November 2010, the STEREO spacecraft were nearly 180 degrees apart, allowing for the uninterrupted tracking of the active region and its ensuing CMEs. The ejective aspect is examined from multi-viewpoint coronagraphic images, while the dynamics of the active region photospheric magnetic field are inspected by means of SDO/HMI data for specific subintervals of interest. The ultimate goal of this work in progress is to identify common patterns in the ejective aspect that can be connected with the active region characteristics.
A Python-based interface to examine motions in time series of solar images
Authors: Campos-Rozo J. I. , Domínguez S. Vargas
Published: September 2017

Python is considered to be a mature programming language, besides of being widely accepted as an engaging option for scientific analysis in multiple areas, as will be presented in this work for the particular case of solar physics research. SunPy is an open-source library based on Python that has been recently developed to furnish software tools to solar data analysis and visualization. In this work we present a graphical user interface (GUI) based on Python and Qt to effectively compute proper motions for the analysis of time series of solar data. This user-friendly computing interface, that is intended to be incorporated to the Sunpy library, uses a local correlation tracking technique and some extra tools that allows the selection of different parameters to calculate, vizualize and analyze vector velocity fields of solar data, i.e. time series of solar filtergrams and magnetograms.
A study on Electron Oscillations in the Magnetosheath of Mars with Mars Express observations
Authors: de Souza Adriane M. , Echer Ezequiel , Bolzam Mauricio J. A. , Fränz Markus
Published: September 2017

Wavelet analysis was employed to identify the major frequencies of low-frequency waves present in the Martian magnetosheath. The Morlet wavelet transform was selected and applied to the electron density data, obtained from the Analyzer of Space Plasmas and Energetic Atoms experiment (ASPERA-3), onboard the Mars Express (MEX) spacecraft. We have selected magnetosheath crossings and analyzed electron density data. From a preliminary study of 502 magnetosheath crossings (observed during the year of 2005), we have found 1409 periods between 0.005 and 0.06Hz. The major frequencies observed were in the range 0.005-0.02 Hz with 58.5% of the 1409 frequencies identified.
Atmospheric Parameters and Luminosities of Nearby M Dwarfs – Estimating Habitable Exoplanet Detectability with the E-ELT
Authors: Porto de Mello Gustavo F. , Giribaldi Riano E. , Lorenzo-Oliveira Diego , Leme Nathália M. Paes
Published: September 2017

We derive Teff and [Fe/H] for a sample of 72 nearby M-dwarfs with Hipparcos parallaxes and δ < +30. Spectra, acquired at the Observatório do Pico dos Dias, Brazil, have R = 10,000 and S/N ≳ 100 for nearly all targets in the λλ8380-8880 range. Atmospheric parameters were derived from VJHK colors and a system of spectral line indices calibrated against sample stars with interferometric Teff and [Fe/H] from detailed analysis of FGK binary companions. A PCA method of calibration yields internal errors within 70 K and 0.1 dex for Teff and [Fe/H]. For 18 stars we present the first Teff or [Fe/H] derivation in the literature. We compute the star's luminosities, calculate the position of their habitable zones and estimate that, were all of they to harbour rocky planets inside their HZ, 15–20 of these would be detectable by the E-ELT Planetary Camera and Spectrograph.
Deriving the solar activity cycle modulation on cosmic ray intensity observed by Nagoya muon detector from October 1970 until December 2012
Authors: de Mendonça Rafael R. S. , Braga Carlos. R. , Echer Ezequiel , Lago Alisson Dal , Rockenbach Marlos , Schuch Nelson J. , Munakata Kazuoki
Published: September 2017

It is well known that the cosmic ray intensity observed at the Earth's surface presents an 11 and 22-yr variations associated with the solar activity cycle. However, the observation and analysis of this modulation through ground muon detectors datahave been difficult due to the temperature effect. Furthermore, instrumental changes or temporary problems may difficult the analysis of these variations. In this work, we analyze the cosmic ray intensity observed since October 1970 until December 2012 by the Nagoya muon detector. We show the results obtained after analyzing all discontinuities and gaps present in this data and removing changes not related to natural phenomena. We also show the results found using the mass weighted method for eliminate the influence of atmospheric temperature changes on muon intensity observed at ground. As a preliminary result of our analyses, we show the solar cycle modulation in the muon intensity observed for more than 40 years.
Exploring shallow sunspot formation by using Implicit Large-eddy simulations
Authors: Camacho F. J. , Guerrero G. , Smolarkiewicz P. K. , Kosovichev A. G. , Mansour N. N.
Published: September 2017

The mechanism by which sunspots are generated at the surface of the sun remains unclear. In the current literature two types of explanations can be found. The first one is related to the buoyant emergence of toroidal magnetic fields generated at the tachocline. The second one states that active regions are formed, from initially diffused magnetic flux, by MHD instabilities that develop in the near-surface layers of the Sun. Using the anelastic MHD code EULAG we address the problem of sunspot formation by performing implicit large-eddy simulations of stratified magneto-convection in a domain that resembles the near-surface layers of the Sun. The development of magnetic structures is explored as well as their effect on the convection dynamics. By applying a homogeneous magnetic field over an initially stationary hydrodynamic convective state, we investigate the formation of self-organized magnetic structures in the range of the initial magnetic field strength, 0.01 < B0/Beq < 0.5, where Beq is the characteristic equipartition field strength.
Hunting for Stellar Coronal Mass Ejections
Authors: Korhonen Heidi , Vida Krisztián , Leitzinger Martin , Odert Petra , Kovács Orsolya Eszter
Published: September 2017

Coronal mass ejections (CMEs) are explosive events that occur basically daily on the Sun. It is thought that these events play a crucial role in the angular momentum and mass loss of late-type stars, and also shape the environment in which planets form and live. Stellar CMEs can be detected in optical spectra in the Balmer lines, especially in Hα, as blue-shifted extra emission/absorption. To increase the detection probability one can monitor young open clusters, in which the stars are due to their youth still rapid rotators, and thus magnetically active and likely to exhibit a large number of CMEs. Using ESO facilities and the Nordic Optical Telescope we have obtained time series of multi-object spectroscopic observations of late-type stars in six open clusters with ages ranging from 15 Myrs to 300 Myrs. Additionally, we have studied archival data of numerous active stars. These observations will allow us to obtain information on the occurrence rate of CMEs in late-type stars with different ages and spectral types. Here we report on the preliminary outcome of our studies.
Magnetic field generation in PMS stars with and without radiative core
Authors: Zaire B. , Guerrero G. , Kosovichev A. G. , Smolarkiewicz P. K. , Landin N. R.
Published: September 2017

Recent observations of the magnetic field in pre-main sequence stars suggest that the magnetic field topology changes as a function of age. The presence of a tachocline could be an important factor in the development of magnetic field with higher multipolar modes. In this work we performed MHD simulations using the EULAG-MHD code to study the magnetic field generation and evolution in models that mimic stars at two evolutionary stages. The stratification for both stellar phases was computed by fitting stellar structure profiles obtained with the ATON stellar evolution code. The first stage is at 1.1Myr, when the star is completely convective. The second stage is at 14Myrs, when the star is partly convective, with a radiative core developed up to 30% of the stellar radius. In this proceedings we present a preliminary analysis of the resulting mean-flows and magnetic field. The mean-flow analysis shown that the star rotate almost rigidly on the fully convective phase, whereas at the partially convective phase there is differential rotation with conical contours of iso-rotation. As for the mean magnetic field both simulations show similarities with respect to the field evolution. However, the topology of the magnetic field is different.
Initiation and chromospheric effects of a M1.0 class solar flare from high-resolution multi-wavelength observations
Authors: Sadykov V. M. , Kosovichev A. G. , Sharykin I. N. , Zimovets I. V. , Dominguez S. Vargas
Published: September 2017

Initiation and development of a M 1.0 class flare of June 12, 2014, was observed by space and ground-based telescopes, including EUV and X-ray imaging spectroscopy by IRIS and RHESSI, and high-resolution optical imaging by 1.6 m New Solar Telescope (NST). Analyzing the NST data, we found small-scale loop-like structures in the region of the magnetic field Polarity Inversion Line (PIL), the emergence and interaction of which caused photospheric brightenings temporarily coinciding with hard X-ray impulses. Detailed studies of the PIL region reveal signatures of photospheric plasma downflows and dissipation of electric currents. The reconstructed magnetic field topology shows a bundle of lines connecting the PIL region with the flare ribbons which were places of chromospheric evaporation observed by IRIS. The observations suggest a scenario with the primary energy release processes located in the low atmospheric layers of the PIL, energizing the overlying large-scale magnetic structure and causing “gentle” chromospheric evaporation.
P-mode induced convective collapse in vertical expanding magnetic flux tubes?
Authors: Utz D. , Van Doorsselaere T. , Magyar N. , Bárta M. , Campos Rozo J. I.
Published: September 2017

Small-scale kG strong magnetic field elements in the solar photosphere are often identified as so-called magnetic bright points (MBPs). In principle these MBPs represent the cross-section of a vertical, strong, magnetic flux tube which is expanding with height in the solar atmosphere. As these magnetic elements represent possible MHD wave guides, a significant interest has been already paid to them from the viewpoint of observations and simulations. In this work we would like to shed more light on a possible scenario for the creation of such strong magnetic field concentrations. The accepted standard scenario involves the convective collapse process. In this ongoing work we will show indications that this convective collapse process may become triggered by sufficiently strong pressure disturbances. However, it is highly unlikely that p-mode waves can be of such a strength.
Social Motives Predict Loneliness During a Developmental Transition
Authors: Nikitin Jana , Freund Alexandra M.
Published: September 2017

Abstract. Establishing new social relationships is important for mastering developmental transitions in young adulthood. In a 2-year longitudinal study with four measurement occasions (T1: n = 245, T2: n = 96, T3: n = 103, T4: n = 85), we investigated the role of social motives in college students’ mastery of the transition of moving out of the parental home, using loneliness as an indicator of poor adjustment to the transition. Students with strong social approach motivation reported stable and low levels of loneliness. In contrast, students with strong social avoidance motivation reported high levels of loneliness. However, this effect dissipated relatively quickly as most of the young adults adapted to the transition over a period of several weeks. The present study also provides evidence for an interaction between social approach and social avoidance motives: Social approach motives buffered the negative effect on social well-being of social avoidance motives. These results illustrate the importance of social approach and social avoidance motives and their interplay during developmental transitions.
Common variants in MMP20 at 11q22.2 predispose to 11q deletion and neuroblastoma risk
Authors: Chang Xiao , Zhao Yan , Hou Cuiping , Glessner Joseph , McDaniel Lee , Diamond Maura A. , Thomas Kelly , Li Jin , Wei Zhi , Liu Yichuan , Guo Yiran , Mentch Frank D. , Qiu Haijun , Kim Cecilia , Evans Perry , Vaksman Zalman , Diskin Sharon J. , Attiyeh Edward F. , Sleiman Patrick , Maris John M. , Hakonarson Hakon
Published: September 2017

MYCN amplification and 11q deletion are two inversely correlated prognostic factors of poor outcome in neuroblastoma. Here we identify common variants at 11q22.2 within MMP20 that associate with neuroblastoma cases harboring 11q deletion (rs10895322), using GWAS in 113 European-American cases and 5109 ancestry-matched controls. The association is replicated in 44 independent cases and 1902 controls. Our study yields novel insights into the genetic underpinnings of neuroblastoma, demonstrating that the inherited common variants reported contribute to the origin of intra-tumor genetic heterogeneity in neuroblastoma.
SRpHi ratiometric pH biosensors for super-resolution microscopy
Authors: Richardson Douglas S. , Gregor Carola , Winter Franziska R. , Urban Nicolai T. , Sahl Steffen J. , Willig Katrin I. , Hell Stefan W.
Published: September 2017

Fluorescence-based biosensors have become essential tools for modern biology, allowing real-time monitoring of biological processes within living cells. Intracellular fluorescent pH probes comprise one of the most widely used families of biosensors in microscopy. One key application of pH probes has been to monitor the acidification of vesicles during endocytosis, an essential function that aids in cargo sorting and degradation. Prior to the development of super-resolution fluorescence microscopy (nanoscopy), investigation of endosomal dynamics in live cells remained difficult as these structures lie at or below the ~250 nm diffraction limit of light microscopy. Therefore, to aid in investigations of pH dynamics during endocytosis at the nanoscale, we have specifically designed a family of ratiometric endosomal pH probes for use in live-cell STED nanoscopy.
Novel ecto-tagged integrins reveal their trafficking in live cells
Authors: Huet-Calderwood Clotilde , Rivera-Molina Felix , Iwamoto Daniel V. , Kromann Emil B. , Toomre Derek , Calderwood David A.
Published: September 2017

Integrins are abundant heterodimeric cell-surface adhesion receptors essential in multicellular organisms. Integrin function is dynamically modulated by endo-exocytic trafficking, however, major mysteries remain about where, when, and how this occurs in living cells. To address this, here we report the generation of functional recombinant β1 integrins with traceable tags inserted in an extracellular loop. We demonstrate that these ‘ecto-tagged’ integrins are cell-surface expressed, localize to adhesions, exhibit normal integrin activation, and restore adhesion in β1 integrin knockout fibroblasts. Importantly, β1 integrins containing an extracellular pH-sensitive pHluorin tag allow direct visualization of integrin exocytosis in live cells and revealed targeted delivery of integrin vesicles to focal adhesions. Further, using β1 integrins containing a HaloTag in combination with membrane-permeant and -impermeant Halo dyes allows imaging of integrin endocytosis and recycling. Thus, ecto-tagged integrins provide novel powerful tools to characterize integrin function and trafficking.
Rational development of catalytic Au(I)/Au(III) arylation involving mild oxidative addition of aryl halides
Authors: Zeineddine Abdallah , Estévez Laura , Mallet-Ladeira Sonia , Miqueu Karinne , Amgoune Abderrahmane , Bourissou Didier
Published: September 2017

The reluctance of gold to achieve oxidative addition reaction is considered as an intrinsic limitation for the development of gold-catalyzed cross-coupling reactions with simple and ubiquitous aryl halide electrophiles. Here, we report the rational construction of a Au(I)/Au(III) catalytic cycle involving a sequence of Csp2–X oxidative addition, Csp2–H auration and reductive elimination, allowing a gold-catalyzed direct arylation of arenes with aryl halides. Key to this discovery is the use of Me-Dalphos, a simple ancillary (P,N) ligand, that allows the bottleneck oxidative addition of aryl iodides and bromides to readily proceed under mild conditions. The hemilabile character of the amino group plays a crucial role in this transformation, as substantiated by density functional theory calculations.
Two genomes of highly polyphagous lepidopteran pests (Spodoptera frugiperda, Noctuidae) with different host-plant ranges
Authors: Gouin Anaïs , Bretaudeau Anthony , Nam Kiwoong , Gimenez Sylvie , Aury Jean-Marc , Duvic Bernard , Hilliou Frédérique , Durand Nicolas , Montagné Nicolas , Darboux Isabelle , Kuwar Suyog , Chertemps Thomas , Siaussat David , Bretschneider Anne , Moné Yves , Ahn Seung-Joon , Hänniger Sabine , Grenet Anne-Sophie Gosselin , Neunemann David , Maumus Florian , Luyten Isabelle , Labadie Karine , Xu Wei , Koutroumpa Fotini , Escoubas Jean-Michel , Llopis Angel , Maïbèche-Coisne Martine , Salasc Fanny , Tomar Archana , Anderson Alisha R. , Khan Sher Afzal , Dumas Pascaline , Orsucci Marion , Guy Julie , Belser Caroline , Alberti Adriana , Noel Benjamin , Couloux Arnaud , Mercier Jonathan , Nidelet Sabine , Dubois Emeric , Liu Nai-Yong , Boulogne Isabelle , Mirabeau Olivier , Le Goff Gaelle , Gordon Karl , Oakeshott John , Consoli Fernando L. , Volkoff Anne-Nathalie , Fescemyer Howard W. , Marden James H. , Luthe Dawn S. , Herrero Salvador , Heckel David G. , Wincker Patrick , Kergoat Gael J. , Amselem Joelle , Quesneville Hadi , Groot Astrid T. , Jacquin-Joly Emmanuelle , Nègre Nicolas , Lemaitre Claire , Legeai Fabrice , d’Alençon Emmanuelle , Fournier Philippe
Published: September 2017

Emergence of polyphagous herbivorous insects entails significant adaptation to recognize, detoxify and digest a variety of host-plants. Despite of its biological and practical importance - since insects eat 20% of crops - no exhaustive analysis of gene repertoires required for adaptations in generalist insect herbivores has previously been performed. The noctuid moth Spodoptera frugiperda ranks as one of the world’s worst agricultural pests. This insect is polyphagous while the majority of other lepidopteran herbivores are specialist. It consists of two morphologically indistinguishable strains (“C” and “R”) that have different host plant ranges. To describe the evolutionary mechanisms that both enable the emergence of polyphagous herbivory and lead to the shift in the host preference, we analyzed whole genome sequences from laboratory and natural populations of both strains. We observed huge expansions of genes associated with chemosensation and detoxification compared with specialist Lepidoptera. These expansions are largely due to tandem duplication, a possible adaptation mechanism enabling polyphagy. Individuals from natural C and R populations show significant genomic differentiation. We found signatures of positive selection in genes involved in chemoreception, detoxification and digestion, and copy number variation in the two latter gene families, suggesting an adaptive role for structural variation.
Mesoscopic model for DNA G-quadruplex unfolding
Authors: Bergues-Pupo A. E. , Gutiérrez I. , Arias-Gonzalez J. R. , Falo F. , Fiasconaro A.
Published: September 2017

Genomes contain rare guanine-rich sequences capable of assembling into four-stranded helical structures, termed G-quadruplexes, with potential roles in gene regulation and chromosome stability. Their mechanical unfolding has only been reported to date by all-atom simulations, which cannot dissect the major physical interactions responsible for their cohesion. Here, we propose a mesoscopic model to describe both the mechanical and thermal stability of DNA G-quadruplexes, where each nucleotide of the structure, as well as each central cation located at the inner channel, is mapped onto a single bead. In this framework we are able to simulate loading rates similar to the experimental ones, which are not reachable in simulations with atomistic resolution. In this regard, we present single-molecule force-induced unfolding experiments by a high-resolution optical tweezers on a DNA telomeric sequence capable of adopting a G-quadruplex conformation. Fitting the parameters of the model to the experiments we find a correct prediction of the rupture-force kinetics and a good agreement with previous near equilibrium measurements. Since G-quadruplex unfolding dynamics is halfway in complexity between secondary nucleic acids and tertiary protein structures, our model entails a nanoscale paradigm for non-equilibrium processes in the cell.
Determination of unique power conversion efficiency of solar cell showing hysteresis in the I-V curve under various light intensities
Authors: Cojocaru Ludmila , Uchida Satoshi , Tamaki Koichi , Jayaweera Piyankarage V. V. , Kaneko Shoji , Nakazaki Jotaro , Kubo Takaya , Segawa Hiroshi
Published: September 2017

Energy harvesting at low light intensities has recently attracted a great deal of attention of perovskite solar cells (PSCs) which are regarded as promising candidate for indoor application. Anomalous hysteresis of the PSCs a complex issue for reliable evaluation of the cell performance. In order to address these challenges, we constructed two new evaluation methods to determinate the power conversion efficiencies (PCEs) of PSCs. The first setup is a solar simulator based on light emitting diodes (LEDs) allowing evaluation of the solar cells at wider range of light intensities, ranging from 102 to 10−3 mW·cm−2. As the overestimate error, we found that the PCEs of dye sensitized solar cell (DSC) and PSCs increase dramatically at low light intensities conditions. Due to the internal capacitance at the interfaces on hybrid solar cells, the measurement of current below 10−2 mW·cm−2 shows constant value given high PCE, which is related to the capacitive current and origin of the hysteresis. The second setup is a photovoltaic power analyzing system, designed for tracking the maximum power (﻿Pmax) with time. The paper suggests the combination of the LED solar simulator and Pmax tracking technique as a standard to evaluate the PCE of capacitive solar cells.
Logical gates in actin monomer
Authors: Adamatzky Andrew
Published: September 2017

We evaluate information processing capacity of a single actin molecule by calculating distributions of logical gates implemented by the molecule via propagating patterns of excitation. We represent a filamentous actin molecule as an excitable automaton network (F-actin automaton). where every atom updates its state depending on states of atoms its connected to with chemical bonds (hard neighbours) and atoms being in physical proximity to the atom (soft neighbours). A resting atom excites if a sum of its excited hard neighbours and a weighted sum of its soft neighbours belong to some specified interval. We demonstrate that F-actin automata implement OR, AND, XOR and AND-NOT gates via interacting patterns of excitation. Gate AND is the most common gate and gate XOR is the rarest. Using the architectures of gates discovered we implement one bit half-adder and controlled-not circuits in the F-actin automata. Speed and space values of the F-actin molecular computers are discussed.
HMGA1 regulates the Plasminogen activation system in the secretome of breast cancer cells
Authors: Resmini Giulia , Rizzo Serena , Franchin Cinzia , Zanin Rossella , Penzo Carlotta , Pegoraro Silvia , Ciani Yari , Piazza Silvano , Arrigoni Giorgio , Sgarra Riccardo , Manfioletti Guidalberto
Published: September 2017

Cancer cells secrete proteins that modify the extracellular environment acting as autocrine and paracrine stimulatory factors and have a relevant role in cancer progression. The HMGA1 oncofetal protein has a prominent role in controlling the expression of an articulated set of genes involved in various aspect of cancer cell transformation. However, little is known about its role in influencing the secretome of cancer cells. Performing an iTRAQ LC–MS/MS screening for the identification of secreted proteins, in an inducible model of HMGA1 silencing in breast cancer cells, we found that HMGA1 has a profound impact on cancer cell secretome. We demonstrated that the pool of HMGA1–linked secreted proteins has pro–migratory and pro-invasive stimulatory roles. From an inspection of the HMGA1–dependent secreted factors it turned out that HMGA1 influences the presence in the extra cellular milieu of key components of the Plasminogen activation system (PLAU, SERPINE1, and PLAUR) that has a prominent role in promoting metastasis, and that HMGA1 has a direct role in regulating the transcription of two of them, i.e. PLAU and SERPINE1. The ability of HMGA1 to regulate the plasminogen activator system may constitute an important mechanism by which HMGA1 promotes cancer progression.
Proxies of energy expenditure for marine mammals: an experimental test of “the time trap”
Authors: Ladds Monique A. , Rosen David A. S. , Slip David J. , Harcourt Robert G.
Published: September 2017

Direct measures of energy expenditure are difficult to obtain in marine mammals, and accelerometry may be a useful proxy. Recently its utility has been questioned as some analyses derived their measure of activity level by calculating the sum of accelerometry-based values and then comparing this summation to summed (total) energy expenditure (the so-called “time trap”). To test this hypothesis, we measured oxygen consumption of captive fur seals and sea lions wearing accelerometers during submerged swimming and calculated total and rate of energy expenditure. We compared these values with two potential proxies of energy expenditure derived from accelerometry data: flipper strokes and dynamic body acceleration (DBA). Total number of strokes, total DBA, and submergence time all predicted total oxygen consumption $$({\boldsymbol{sV}}{{\boldsymbol{O}}}_{{\boldsymbol{2}}}$$
(
sV

O

2

ml kg−1). However, both total DBA and total number of strokes were correlated with submergence time. Neither stroke rate nor mean DBA could predict the rate of oxygen consumption ($$s\mathop{{\boldsymbol{V}}}\limits^{{\boldsymbol{.}}}{{\boldsymbol{O}}}_{{\boldsymbol{2}}}$$
s

V
.

O

2

ml min−1 kg−1). The relationship of total DBA and total strokes with total oxygen consumption is apparently a result of introducing a constant (time) into both sides of the relationship. This experimental evidence supports the conclusion that proxies derived from accelerometers cannot estimate the energy expenditure of marine mammals.
Variations in oral microbiota associated with oral cancer
Authors: Zhao Hongsen , Chu Min , Huang Zhengwei , Yang Xi , Ran Shujun , Hu Bin , Zhang Chenping , Liang Jingping
Published: September 2017

Individual bacteria and shifts in microbiome composition are associated with human disease, including cancer. To unravel the connections underlying oral bacterial dysbiosis and oral squamous cell carcinoma (OSCC), cancer lesion samples and anatomically matched normal samples were obtained from the same patients. We then profiled the bacteria within OSCC lesion surface samples at the species level using next-generation sequencing to comprehensively investigate bacterial community composition and functional genes in these samples. Significantly greater bacterial diversity was observed in the cancer samples than in the normal samples. Compared with previous studies, we identified many more taxa demonstrating remarkably different distributions between the groups. In particular, a group of periodontitis-correlated taxa, includingFusobacterium, Dialister, Peptostreptococcus, Filifactor, Peptococcus, CatonellaandParvimonas, was significantly enriched in OSCC samples. Additionally, several operational taxonomic units (OTUs) associated withFusobacteriumwere highly involved in OSCC and demonstrated good diagnostic power. Our study revealed drastic changes in surface bacterial communities of OSCC. The findings enrich knowledge of the association between oral bacterial communities and oral cancer.
Microbiome of Pacific Whiteleg shrimp reveals differential bacterial community composition between Wild, Aquacultured and AHPND/EMS outbreak conditions
Authors: Cornejo-Granados Fernanda , Lopez-Zavala Alonso A. , Gallardo-Becerra Luigui , Mendoza-Vargas Alfredo , Sánchez Filiberto , Vichido Rodrigo , Brieba Luis G. , Viana Maria Teresa , Sotelo-Mundo Rogerio R. , Ochoa-Leyva Adrián
Published: September 2017

Crustaceans form the second largest subphylum on Earth, which includes Litopeneaus vannamei (Pacific whiteleg shrimp), one of the most cultured shrimp worldwide. Despite efforts to study the shrimp microbiota, little is known about it from shrimp obtained from the open sea and the role that aquaculture plays in microbiota remodeling. Here, the microbiota from the hepatopancreas and intestine of wild type (wt) and aquacultured whiteleg shrimp and pond sediment from hatcheries were characterized using sequencing of seven hypervariable regions of the 16S rRNA gene. Cultured shrimp with AHPND/EMS disease symptoms were also included. We found that (i) microbiota and their predicted metagenomic functions were different between wt and cultured shrimp; (ii) independent of the shrimp source, the microbiota of the hepatopancreas and intestine was different; (iii) the microbial diversity between the sediment and intestines of cultured shrimp was similar; and (iv) associated to an early development of AHPND/EMS disease, we found changes in the microbiome and the appearance of disease-specific bacteria. Notably, under cultured conditions, we identified bacterial taxa enriched in healthy shrimp, such as Faecalibacterium prausnitzii and Pantoea agglomerans, and communities enriched in diseased shrimp, such as Aeromonas taiwanensis, Simiduia agarivorans and Photobacterium angustum.
Tumor suppression via inhibition of SWI/SNF complex-dependent NF-κB activation
Authors: Kobayashi Kazuyoshi , Hiramatsu Hiroaki , Nakamura Shinya , Kobayashi Kyousuke , Haraguchi Takeshi , Iba Hideo
Published: September 2017

The transcription factor NF-κB is constitutively activated in many epithelial tumors but few NF-κB inhibitors are suitable for cancer therapy because of its broad biological effects. We previously reported that the d4-family proteins (DPF1, DPF2, DPF3a/b) function as adaptor proteins linking NF-κB with the SWI/SNF complex. Here, using epithelial tumor cell lines, A549 and HeLaS3, we demonstrate that exogenous expression of the highly-conserved N-terminal 84-amino acid region (designated “CT1”) of either DPF2 or DPF3a/b has stronger inhibitory effects on anchorage-independent growth than the single knockdown of any d4-family protein. This indicates that CT1 can function as an efficient dominant-negative mutant of the entire d4-family proteins. By in situ proximity ligation assay, CT1 was found to retain full adaptor function, indicating that the C-terminal region of d4-family proteins lacking in CT1 would include essential domains for SWI/SNF-dependent NF-κB activation. Microarray analysis revealed that CT1 suppresses only a portion of the NF-κB target genes, including representative SWI/SNF-dependent genes. Among these genes, IL6 was shown to strongly contribute to anchorage-independent growth. Finally, exogenous CT1 expression efficiently suppressed tumor formation in a mouse xenograft model, suggesting that the d4-family proteins are promising cancer therapy targets.
Cyclipostins and Cyclophostin analogs as promising compounds in the fight against tuberculosis
Authors: Nguyen Phuong Chi , Delorme Vincent , Bénarouche Anaïs , Martin Benjamin P. , Paudel Rishi , Gnawali Giri R. , Madani Abdeldjalil , Puppo Rémy , Landry Valérie , Kremer Laurent , Brodin Priscille , Spilling Christopher D. , Cavalier Jean-François , Canaan Stéphane
Published: September 2017

A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC
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exhibited the best extracellular antitubercular activity (MIC50 = 500 nM). This compound was selected and further used in a competitive labelling/enrichment assay against the activity-based probe Desthiobiotin-FP in order to identify its putative target(s). This approach, combined with mass spectrometry, identified 23 potential candidates, most of them being serine or cysteine enzymes involved in M. tb lipid metabolism and/or in cell wall biosynthesis. Among them, Ag85A, CaeA and HsaD, have previously been reported as essential for in vitro growth of M. tb and/or survival and persistence in macrophages. Overall, our findings support the assumption that CyC
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may thus represent a novel class of multi-target inhibitor leading to the arrest of M. tb growth through a cumulative inhibition of a large number of Ser- and Cys-containing enzymes participating in important physiological processes.
The epistemic and aleatory uncertainties of the ETAS-type models: an application to the Central Italy seismicity
Authors: Lombardi A. M.
Published: September 2017

Stochastic models provide quantitative evaluations about the occurrence of earthquakes. A basic component of this type of models are the uncertainties in defining main features of an intrinsically random process. Even if, at a very basic level, any attempting to distinguish between types of uncertainty is questionable, an usual way to deal with this topic is to separate epistemic uncertainty, due to lack of knowledge, from aleatory variability, due to randomness. In the present study this problem is addressed in the narrow context of short-term modeling of earthquakes and, specifically, of ETAS modeling. By mean of an application of a specific version of the ETAS model to seismicity of Central Italy, recently struck by a sequence with a main event of Mw6.5, the aleatory and epistemic (parametric) uncertainty are separated and quantified. The main result of the paper is that the parametric uncertainty of the ETAS-type model, adopted here, is much lower than the aleatory variability in the process. This result points out two main aspects: an analyst has good chances to set the ETAS-type models, but he may retrospectively describe and forecast the earthquake occurrences with still limited precision and accuracy.
The multifunctional polydnavirus TnBVANK1 protein: impact on host apoptotic pathway
Authors: Salvia Rosanna , Grossi Gerarda , Amoresano Angela , Scieuzo Carmen , Nardiello Marisa , Giangrande Chiara , Laurenzana Ilaria , Ruggieri Vitalba , Bufo Sabino A. , Vinson S. Bradleigh , Carmosino Monica , Neunemann David , Vogel Heiko , Pucci Pietro , Falabella Patrizia
Published: September 2017

Toxoneuron nigriceps (Hymenoptera, Braconidae) is an endophagous parasitoid of the larval stages of the tobacco budworm, Heliothis virescens (Lepidoptera, Noctuidae). The bracovirus associated with this wasp (TnBV) is currently being studied. Several genes expressed in parasitised host larvae have been isolated and their possible roles partly elucidated. TnBVank1 encodes an ankyrin motif protein similar to insect and mammalian IκB, an inhibitor of the transcription nuclear factor κB (NF-κB). Here we show that, when TnBVank1 was stably expressed in polyclonal Drosophila S2 cells, apoptosis is induced. Furthermore, we observed the same effects in haemocytes of H. virescens larvae, after TnBVank1 in vivo transient transfection, and in haemocytes of parasitised larvae. Coimmunoprecipitation experiments showed that TnBVANK1 binds to ALG-2 interacting protein X (Alix/AIP1), an interactor of apoptosis-linked gene protein 2 (ALG-2). Using double-immunofluorescence labeling, we observed the potential colocalization of TnBVANK1 and Alix proteins in the cytoplasm of polyclonal S2 cells. When Alix was silenced by RNA interference, TnBVANK1 was no longer able to cause apoptosis in both S2 cells and H. virescens haemocytes. Collectively, these results indicate that TnBVANK1 induces apoptosis by interacting with Alix, suggesting a role of TnBVANK1 in the suppression of host immune response observed after parasitisation by T. nigriceps.
Conjugation of wildtype and hypoallergenic mugwort allergen Art v 1 to flagellin induces IL-10-DC and suppresses allergen-specific TH2-responses in vivo
Authors: Schülke Stefan , Kuttich Kirsten , Wolfheimer Sonja , Duschek Nadine , Wangorsch Andrea , Reuter Andreas , Briza Peter , Pablos Isabel , Gadermaier Gabriele , Ferreira Fatima , Vieths Stefan , Toda Masako , Scheurer Stephan
Published: September 2017

Allergies to weed pollen including members of the Compositae family, such as mugwort, ragweed, and feverfew are spreading worldwide. To efficiently treat these newly arising allergies, allergen specific immunotherapy needs to be improved. Therefore, we generated novel vaccine candidates consisting of the TLR5-ligand Flagellin A from Listeria and the major mugwort allergen Art v 1 including either the wild type Art v 1 sequence (rFlaA:Artv1) or a hypoallergenic variant (rFlaA:Artv1hyp) with reduced IgE-binding capacity. Immune modulating capacity of these constructs and respective controls was evaluated in vitro and in vivo. Incorporation of hypoallergenic Art v 1 derivative did not interfere with the resulting fusion proteins’ immune stimulatory capacity. Both rFlaA:Artv1 and rFlaA:Artv1hyp induced a prominent, mTOR-dependent, IL-10 secretion from murine dendritic cells, and suppressed allergen-specific TH2-cytokine secretion in vitro and in vivo. Both conjugates retained the capacity to induce rFlaA-specific antibody responses while efficiently inducing production of Art v 1-specific IgG1 and IgG2a antibodies in mice. Interestingly, only the suppression of TH2-cytokine secretion by rFlaA:Artv1 (but not rFlaA:Artv1hyp) was paralleled by a strong secretion of IFN-γ. In summary, we provided evidence that incorporating hypoallergens into flagellin:allergen fusion proteins is a suitable strategy to further improve these promising vaccine candidates.
Detrimental effect of Hypoxia-inducible factor-1α-induced autophagy on multiterritory perforator flap survival in rats
Authors: Wang Long , Jin Zhicheng , Wang Jieke , Chen Shao , Dai Li , Lin Dingsheng , Wu Lingfeng , Gao Weiyang
Published: September 2017

Hypoxia-inducible factor-1α (HIF-1α) plays a key role in angiogenesis, improves flap survival, and activates autophagy. The effect of HIF-1α-induced autophagy is still debatable. Thus, we investigated the effect of HIF-1α-induced autophagy on multiterritory perforator flap survival. In this study, 99 male Sprague-Dawley rats received multiterritory perforator flap procedure and were divided into three groups with 33 each. The dimethyloxalylglycine (DMOG) plus 3-methyladenine (3-MA) group received intraperitoneal injection of DMOG (40 mg/kg) and 3-MA (10 mg/kg). The DMOG group and control group received comparative DMOG and saline respectively. On postoperative day (POD) 7, HIF-1α’s activities of flap survival and perfusion improvement were confirmed in DMOG group, however, its positive effects were further enhanced by co-administration of autophagy inhibitor, 3-MA. On POD 1, vascular endothelial growth factor, mean microvascular density and blood perfusion were not affected by HIF-1α up-regulation or autophagy inactivation. However, HIF-1α-induced autophagy augments apoptosis and oxidative stress. The increased level of apoptosis and oxidative stress was reversed by 3-MA and resulted in further flap survival improvement. In conclusion, HIF-1α-induced autophagy has a detrimental effect on multiterritory perforator flap survival and the flap survival was determined by the combined effects of ischemia and reperfusion injury.
DNA Methylomes Reveal Biological Networks Involved in Human Eye Development, Functions and Associated Disorders
Authors: Berdasco María , Gómez Antonio , Rubio Marcos J. , Català-Mora Jaume , Zanón-Moreno Vicente , Lopez Miguel , Hernández Cristina , Yoshida Shigeo , Nakama Takahito , Ishikawa Keijiro , Ishibashi Tatsuro , Boubekeur Amina M. , Louhibi Lotfi , Pujana Miguel A , Sayols Sergi , Setien Fernando , Corella Dolores , de Torres Carmen , Parareda Andreu , Mora Jaume , Zhao Ling , Zhang Kang , Lleonart Matilde E. , Alonso Javier , Simó Rafael , Caminal Josep M. , Esteller Manel
Published: September 2017

This work provides a comprehensive CpG methylation landscape of the different layers of the human eye that unveils the gene networks associated with their biological functions and how these are disrupted in common visual disorders. Herein, we firstly determined the role of CpG methylation in the regulation of ocular tissue-specification and described hypermethylation of retinal transcription factors (i.e., PAX6, RAX, SIX6) in a tissue-dependent manner. Second, we have characterized the DNA methylome of visual disorders linked to internal and external environmental factors. Main conclusions allow certifying that crucial pathways related to Wnt-MAPK signaling pathways or neuroinflammation are epigenetically controlled in the fibrotic disorders involved in retinal detachment, but results also reinforced the contribution of neurovascularization (ETS1, HES5, PRDM16) in diabetic retinopathy. Finally, we had studied the methylome in the most frequent intraocular tumors in adults and children (uveal melanoma and retinoblastoma, respectively). We observed that hypermethylation of tumor suppressor genes is a frequent event in ocular tumors, but also unmethylation is associated with tumorogenesis. Interestingly, unmethylation of the proto-oncogen RAB31 was a predictor of metastasis risk in uveal melanoma. Loss of methylation of the oncogenic mir-17-92 cluster was detected in primary tissues but also in blood from patients.