bluuebunny/crossref_metadata_2025 huggingface dataset:
Impaired quality of life in treatment-seeking obese children of Dutch, Moroccan, Turkish and Surinamese descent
Authors: Radhakishun Nalini NE , de Wit Maartje , van Vliet Mariska , von Rosenstiel Ines A , Beijnen Jos H , Brandjes Dees PM , Diamant Michaela
Published: July 2015

Objective

To determine the health-related quality of life (HRQOL) of overweight and obese multi-ethnic children compared with normal-weight children; and to investigate differences in HRQOL between self- and parent-proxy reports and ethnic groups.

Design

Prospective cross-sectional study.

Setting

Out-patient clinic where children and their parents filled out a validated HRQOL questionnaire (KIDSCREEN-52) and height, weight, waist circumference and fat percentage were measured.

Subjects

Overweight and obese children, aged 8–18 years (mean BMIZ-score 3·2 (sd0·6)), from the obesity out-patient clinic.

Results

Three hundred and eight self- and 213 parent-proxy reported questionnaires were completed. Global HRQOL and the Physical Wellbeing, Moods & Emotions and Self-Perception subscales were markedly reduced in our multi-ethnic obese cohort, relative to the Dutch reference values. Parent proxies reported significantly lower on the global HRQOL and the Physical Wellbeing, Moods & Emotions and Bullying subscales. In Caucasian children, multivariate analyses showed that BMI was associated with the quality-of-life subscales Moods & Emotions, Self-Perception and Bullying.

Conclusions

HRQOL was markedly reduced in our multi-ethnic overweight and obese out-patient clinic cohort, with significantly lower parent-proxy scores compared with self-reported scores. We believe intervention programmes aiming to improve HRQOL should be directed to both parents and children, while ethnic-specific programmes to enhance HRQOL seem of less importance.
Dietary guidelines to nourish humanity and the planet in the twenty-first century. A blueprint from Brazil
Authors: Monteiro Carlos Augusto , Cannon Geoffrey , Moubarac Jean-Claude , Martins Ana Paula Bortoletto , Martins Carla Adriano , Garzillo Josefa , Canella Daniela Silva , Baraldi Larissa Galastri , Barciotte Maluh , Louzada Maria Laura da Costa , Levy Renata Bertazzi , Claro Rafael Moreira , Jaime Patrícia Constante
Published: July 2015

Objective

To present and discuss the dietary guidelines issued by the Brazilian government in 2014.

Design

The present paper describes the aims of the guidelines, their shaping principles and the approach used in the development of recommendations. The main recommendations are outlined, their significance for the cultural, socio-economic and environmental aspects of sustainability is discussed, and their application to other countries is considered.

Setting

Brazil in the twenty-first century.

Subjects

All people in Brazil, now and in future.

Results

The food- and meal-based Brazilian Dietary Guidelines address dietary patterns as a whole and so are different from nutrient-based guidelines, even those with some recommendations on specific foods or food groups. The guidelines are based on explicit principles. They take mental and emotional well-being into account, as well as physical health and disease prevention. They identify diet as having cultural, socio-economic and environmental as well as biological and behavioural dimensions. They emphasize the benefits of dietary patterns based on a variety of natural or minimally processed foods, mostly plants, and freshly prepared meals eaten in company, for health, well-being and all relevant aspects of sustainability, as well as the multiple negative effects of ready-to-consume ultra-processed food and drink products.

Conclusions

The guidelines’ recommendations are designed to be sustainable personally, culturally, socially, economically and environmentally, and thus fit to face this century. They are for foods, meals and dietary patterns of types that are already established in Brazil, which can be adapted to suit the climate, terrain and customs of all countries.
Surface magnetic fields across the HR Diagram
Authors: Landstreet John D.
Published: July 2015

The past 20 years have seen remarkable advances in spectropolarimetric instrumentation that have allowed us, for the first time, to identify some magnetic stars in most major stages of stellar evolution. We are beginning to see the broad outline of how such fields change during stellar evolution, to confront theoretical hypotheses and models of magnetic field structure and evolution with detailed data, and to understand more of the ways in which the presence of a field in turn affects stellar structure and evolution.
Magnetic fields in early-type stars
Authors: Grunhut Jason H. , Neiner Coralie
Published: July 2015

For several decades we have been cognizant of the presence of magnetic fields in early-type stars, but our understanding of their magnetic properties has recently (over the last decade) expanded due to the new generation of high-resolution spectropolarimeters (ESPaDOnS at CFHT, Narval at TBL, HARPSpol at ESO). The most detailed surface magnetic field maps of intermediate-mass stars have been obtained through Doppler imaging techniques, allowing us to probe the small-scale structure of these stars. Thanks to the effort of large programmes (e.g. the MiMeS project), we have, for the first time, addressed key issues regarding our understanding of the magnetic properties of massive (M> 8M⊙) stars, whose magnetic fields were only first detected about fifteen years ago. In this proceedings article we review the spectropolarimetric observations and statistics derived in recent years that have formed our general understanding of stellar magnetism in early-type stars. We also discuss how these observations have furthered our understanding of the interactions between the magnetic field and stellar wind, as well as the consequences and connections of this interaction with other observed phenomena.
Ultra-weak magnetic fields in Am stars: β UMa and θ Leo
Authors: Blazère A. , Petit P. , Lignières F. , Aurière M. , Ballot J. , Böhm T. , Folsom C. , Ariste A. López , Wade G.A.
Published: July 2015

An extremely weak circularly-polarized signature was recently detected in the spectral lines of the Am star Sirius A. With a prominent positive lobe, the shape of the phase-averaged Stokes V line profile is atypical of stellar Zeeman signatures, casting doubts on its magnetic origin. We report here on ultra-deep spectropolarimetric observations of two more bright Am stars: β Uma and θ Leo. Stokes V line signatures are detected in both objects, with a shape and amplitude similar to the one observed on Sirius A. We demonstrate that the amplitude of the Stokes V line profiles depend on various line parameters (Landé factor, wavelength, depth) as expected from a Zeeman signature, confirming that extremely weak magnetic fields are likely present in a large fraction of Am stars. We suggest that the strong asymmetry of the polarized signatures, systematically observed so far in Am stars and never reported in strongly magnetic Ap stars, bears unique information about the structure and dynamics of the thin surface convective shell of Am stars.
Polarization calibration techniques and scheduling for the Daniel K. Inouye Solar Telescope
Authors: Elmore David F.
Published: July 2015

The Daniel K. Inouye Solar Telescope (DKIST), formerly Advanced Technology Solar Telescope when it begins operation in 2019 will be by a significant margin Earth's largest solar research telescope. Science priorities dictate an initial suite of instruments that includes four spectro-polarimeters. Accurate polarization calibration of the individual instruments and of the telescope optics shared by those instruments is of critical importance. The telescope and instruments have been examined end-to-end for sources of polarization calibration error, allowable contributions from each of the sources quantified, and techniques identified for calibrating each of the contributors. Efficient use of telescope observing time leads to a requirement of sharing polarization calibrations of common path telescope components among the spectro-polarimeters and for those calibrations to be repeated only as often as dictated by degradation of optical coatings and instrument reconfigurations. As a consequence the polarization calibration of the DKIST is a facility function that requires facility wide techniques.
The Polarimetric and Helioseismic Imager for Solar Orbiter: SO/PHI
Authors: Solanki Sami K. , del Toro Iniesta Jose Carlos , Woch Joachim , Gandorfer Achim , Hirzberger Johann , Schmidt Wolfgang , Appourchaux Thierry , Alvarez-Herrero Alberto ,   the SO/PHI team
Published: July 2015

The Solar Orbiter is the next solar physics mission of the European Space Agency, ESA, in collaboration with NASA, with a launch planned in 2018. The spacecraft is designed to approach the Sun to within 0.28 AU at perihelion of a highly eccentric orbit. The proximity with the Sun will also allow its observation at uniformly high resolution at EUV and visible wavelengths. Such observations are central for learning more about the magnetic coupling of the solar atmosphere. At a later phase in the mission the spacecraft will leave the ecliptic and study the enigmatic poles of the Sun from a heliographic latitude of up to 33○.

A central instrument of Solar Orbiter} is the Polarimetric and Helioseismic Imager, SO/PHI. It will do full Stokes imaging in the Landé g = 2.5 Fe I 617.3 nm line. It is composed of two telescopes, a full-disk telescope and a high-resolution telescope, that will allow observations at a resolution as high as 200 km on the solar surface. SO/PHI will also be the first solar polarimeter to leave the Sun-Earth line, opening up new possibilities, such as stereoscopic polarimetry (besides stereoscopic imaging of the photosphere and stereoscopic helioseismology). Finally, SO/PHI will have a unique view of the solar poles, allowing not just more precise and exact measurements of the polar field than possible so far, but also enabling us to follow the dynamics of individual magnetic features at high latitudes and to determine solar surface and sub-surface flows right up to the poles.

In this paper an introduction to the science goals and the capabilities of SO/PHI will be given, as well as a brief overview of the instrument and of the current status of its development.
Waves and Magnetism in the Solar Atmosphere (WAMIS)
Authors: Strachan L. , Ko Y.-K. , Moses J. D. , Laming J. M. , Auchere F. , Casini R. , Fineschi S. , Gibson S. , Knoelker M. , Korendyke C. , Mcintosh S. , Romoli M. , Rybak J. , Socker D. , Tomczyk S. , Vourlidas A. , Wu Q.
Published: July 2015

Magnetic fields in the solar atmosphere provide the energy for most varieties of solar activity, including high-energy electromagnetic radiation, solar energetic particles, flares, and coronal mass ejections, as well as powering the solar wind. Despite the fundamental role of magnetic fields in solar and heliospheric physics, there exist only very limited measurements of the field above the base of the corona. What is needed are direct measurements of not only the strength and orientation of the magnetic field but also the signatures of wave motions in order to better understand coronal structure, solar activity, and the role of MHD waves in heating and accelerating the solar wind. Fortunately, the remote sensing instrumentation used to make magnetic field measurements is also well suited to measure the Doppler signature of waves in the solar structures. We present here a mission concept for the Waves And Magnetism In the Solar Atmosphere (WAMIS) experiment which is proposed for a NASA long-duration balloon flight.
The importance of non-photon noise in astronomical spectropolarimetry
Authors: Bagnulo S. , Fossati L. , Landstreet J. D. , Kochukhov O.
Published: July 2015

Stellar spectropolarimetry has become an extremely popular technique during the last decade or two, and has led to major advances in the studies of stellar magnetic fields. Many important discoveries have been made thanks to ultra-precise measurements of very small polarimetric signals, which require very stable instruments and special observing strategies. The so called beam-swapping technique is a well-known polarimetric technique capable of suppressing many spurious signals due to various instrumental effects. However, when one is interested in ultra-high signal-to-noise ratio measurements, observers start to hit various limitations introduced by the instrument, by the atmosphere, and even by the software for data-reduction. These limitations cannot be overcome by the observing strategies, and sources of errors other than photon-noise must be taken into account. Here we discuss the advantages of the beam-swapping technique, and the impact of small instrument and atmospheric instabilities, and how these issues offer an explanation for the origin of the apparently significant observed polarisation signals produced by effects other than those intrinsic to the observed target.
Design of a Full Stokes Polarimeter for Chromospheric Measurements with SOLIS/VSM
Authors: Gosain S. , Harvey J. W.
Published: July 2015

The synoptic observations of the magnetic field of the Sun have continued at the National Solar Observatory (NSO) since 1970s. The daily full-disk maps of the longitudinal magnetic field are regularly combined to form Carrington maps of the photospheric magnetic flux per solar rotation. These maps continue to be used by the international research community for a variety of studies related to solar magnetism as well as for space weather studies. The current NSO synoptic facility is the Synoptic Optical Long-term Investigation of the Sun (SOLIS), which regularly provides photospheric vector and chromospheric longitudinal full-disk magnetograms, among other data products. In the near future, an upgrade of SOLIS to produce chromospheric vector magnetograms is planned. We present the design of a new polarization modulator package for full Stokes polarimetry of the chromospheric Ca II 854.2 nm spectral line.
Commissioning Results of a New Polarimeter: Denver University Small Telescope Polarimeter (DUSTPol)
Authors: Wolfe T. M. , Stencel R. , Cole G.
Published: July 2015

DUSTPol is a dual-beam polarimeter that operates in optical wavelengths, and was built to promote the study of linear polarimetry with smaller telescopes. DUSTPol's performance has demonstrated low instrumental polarization at 0.05 ± 0.02%. This poster presents commissioning results as well as early science observations, and describes software used for data reduction. Recent polarimetric results of RS CVn systems and Wolf-Rayet stars, discussed herein, indicate shape and interaction parameters. By promoting the development of similar polarimeters at other institutions, DUSTPol will serve to establish new collaborative surveys of cool active stars, as well as systems showing evidence of containing complex stellar environments.
New generation Stokes inversion codes
Authors: Ramos A. Asensio , de la Cruz Rodríguez J.
Published: July 2015

We utilize the concept of sparsity or compressibility to develop an new generation of inversion codes for the Stokes parameters. The inversion code uses numerical optimization techniques based on the idea of proximal algorithms to impose sparsity. In so doing, we allow to exploit the presence of spatial correlation on the maps of physical parameters. Sparsity also regularizes the solution by reducing the number of unknowns. The solution has an increased robustness.
Study of resonance scattering polarization in O i 130 nm lines
Authors: Anusha L. S. , Nagendra K. N. , Uitenbroek Han
Published: July 2015

Here we address the importance of frequency cross-redistribution on the scattering polarization of the O i line at 130.2 nm. We compute the polarized profiles of this line with ordinary partial frequency redistribution and cross-redistribution using a two-dimensional radiative transfer code.
Polarimetry as a window into supernova explosions and progenitors
Authors: Hoffman Jennifer L.
Published: July 2015

Supernovae of all types exhibit time-dependent spectropolarimetric signatures produced primarily by electron scattering. These reveal the presence of aspherical and variable phenomena such as complex velocity structures, changing illumination, and asymmetric or clumpy morphologies within the ejecta or surrounding circumstellar material. In addition, the gradual thinning of the ejecta over time allows us to probe different scattering regions as the supernova evolves. Interpreting the time variations of these spectropolarimetric signatures yields unprecedentedly detailed information about supernova explosion mechanisms, the physical processes that shape the density and velocity distributions of the ejecta and circumstellar material, and the properties of the progenitor star.

I present an overview of supernova spectropolarimetry, highlighting recent observational and computational results. This versatile technique helps us to constrain explosion mechanisms, connect SNe with their massive progenitors (as well as other high-energy transient phenomena such as GRBs), and investigate the process of stellar evolution in other galaxies.
Polarimetric measurements in prominences and “tornadoes” observed by THEMIS
Authors: Schmieder Brigitte , Ariste Arturo López , Levens Peter , Labrosse Nicolas , Dalmasse Kévin
Published: July 2015

Since 2013, coordinated campaigns with the THEMIS spectropolarimeter in Tenerife and other instruments (space based: Hinode/SOT, IRIS or ground based: Sac Peak, Meudon) are organized to observe prominences. THEMIS records spectropolarimetry at the He I D3 and we use the PCA inversion technique to derive their field strength, inclination and azimuth.

All of the observed prominences are quiescent, as they were stable as filaments for at least three days and not eruptive. They present similar characteristics, they are highly dynamic and present horizontal magnetic fields. Statistically, the inclination from the local vertical is around 90 degrees, with some points around 60 and 120 degrees. The field strength is between 5 and 15 Gauss. We tested the effects of adding a turbulent field component to the horizontal field. For those pixels showing inclinations around 60 and 120 degrees, we find that such a model is compatible with the polarimetric observations. In some of these prominences, identified as “tornadoes” the field strength may reach 50 Gauss, and in the top of the tornadoes some points exhibit an inclination which cannot correspond to any model in our grid of models. We investigate different solutions.
Atmospheres, magnetism, mass loss of red supergiant stars
Authors: Josselin E. , Lambert J. , Aurière M. , Petit P. , Ryde N.
Published: July 2015

Red supergiant stars (RSGs) are not only a key evolutionary stage of massive stars participating in the chemical evolution of galaxies, they also represent a fantastic and challenging laboratory of (magneto-)hydrodynamics. We present recent results and on-going research on mass loss, atmospheres, and polarimetric studies of RSGs that reveal a magnetic field of unknown origin. We discuss the potential interplay between these different processes.
Linear spectropolarimetry: a new tool for the physical characterization of asteroids
Authors: Bagnulo S. , Cellino A. , Sterzik M. F.
Published: July 2015

The surfaces of the atmosphere-less objects of our solar system are traditionally probed via reflectance measurements and/or broadband linear polarimetry. Little attention has been paid so far to the wavelength dependence of the linear polarization of the scattered light. We decided to explore the potential of spectropolarimetry as a remote sensing tool for asteroids in addition to the more traditional reflectance measurements, and we carried out a spectropolarimetric survey of asteroids – to our best knolwedge, the first of its kind. We observed a sample of asteroids of different albedo and taxonomic classes, as well as a few regions at the limb of the Moon. We show that objects exhibiting similar reflectance spectra may display totally different polarization spectra, and we suggest that both intensity and polarization spectra should be used for asteroid classification. We also found that in some cases the Umov law is violated, that is, in contrast to what is expected from simple physical considerations, the fraction of linear polarization and the reflectance spectra may be correlated positively. We conclude that future modelling attempts of the surface structure of asteroids should be aimed at explaining both reflectance and polarization spectra.
Line Profile Variations of Solar Analog Stars: Chromospheric Indexes vs. Li Abundance. The Host Star Search.
Authors: Amazo-Gómez E. M. , Harutyunyan G. , Alvarado-Gómez J. D. , Strassmeier K. G. , Weber M. , Carroll T. A.
Published: July 2015

PolarBase contains stellar spectropolarimetric data collected with the NARVAL & ESPaDOnS instruments (Petitet al. 2014). Their respective spectral resolutions are 65 000 and 68 000, in spectropolarimetric mode. As the first part of this work, we use the NARVAL spectropolarimetric repositories. We selected spectra from a sample of cool stars with effective Temperature (Teff) ranging between 4900 to 6000 K. This sample contains stellar systems with and without reported exoplanets. We exploit the full wavelength range from 380 to 900 nm in order to obtain chromospheric indexes such as the CaiiH&K S-Index, and a CaiiIRT and Hα index. We calibrated our measurements using the Mount Wilson S-Index values. Furthermore, we employ lithium (Li) abundance measurements from the literature (Gonzalezet al. 2010; Delgado Menaet al. 2014; Israelianet al. 2004), investigating in this way a possible correlation between the chromospheric activity measurements and the Li abundance in 32 selected cool stars.
On the importance of partial frequency redistribution in modeling the scattering polarization
Authors: Nagendra K. N.
Published: July 2015

It is well-known that partial frequency redistribution (PRD) is the basic physical mechanism to correctly describe radiative transfer in spectral lines. In the case of polarized line scattering, the PRD becomes particularly important to describe the line-wing polarization, instead of the well-known mechanism of complete redistribution (CRD). Historically, the two-level atom PRD scattering matrices for polarized line scattering were first derived in the 1970's, and later generalized to the case of arbitrary fields in 1997. The latter formulation of the PRD matrices have subsequently been used in the solution of the line transfer equation to successfully model the non-magnetic (resonance scattering) and the magnetic (Hanle scattering) polarization observations. In recent years, using the Kramers-Heisenberg approach, we formulated PRD matrices for various physical mechanisms like quantum interference involving fine- and hyperfine-structure states in a two-term atom. The effect of collisions is included in an approximate way. We have used these PRD matrices to model the observed linear polarization in several interesting lines of the Second Solar Spectrum. In this paper I present a few results which highlight the importance of PRD in the interpretation of the polarized Stokes profiles.
The impact of surface dynamo magnetic fields on the chemical abundance determination
Authors: Shchukina Nataliya G. , Sukhorukov Andrii V. , Bueno Javier Trujillo
Published: July 2015

The solar abundances of Fe and of the CNO elements play an important role in addressing a number of important issues such as the formation, structure, and evolution of the Sun and the solar system, the origin of the chemical elements, and the evolution of stars and galaxies. Despite the large number of papers published on this issue, debates about the solar abundances of these elements continue. The aim of the present investigation is to quantify the impact of photospheric magnetic fields on the determination of the solar chemical abundances. To this end, we used two 3D snapshot models of the quiet solar photosphere with a different magnetization taken from recent magneto-convection simulations with small-scale dynamo action. Using such 3D models we have carried out spectral synthesis for a large set of Fei, Ci, Ni, and Oi lines, in order to derive abundance corrections caused by the magnetic, Zeeman broadening of the intensity profiles and the magnetically induced changes of the photospheric temperature structure. We find that if the magnetism of the quiet solar photosphere is mainly produced by a small-scale dynamo, then its impact on the determination of the abundances of iron, carbon, nitrogen and oxygen is negligible.
Modeling the center-to-limb variation of the Ca i 4227 Å line using FCHHT models
Authors: Supriya H. D. , Smitha H. N. , Nagendra K. N. , Stenflo J. O. , Bianda M. , Ravindra B. , Ramelli R. , Anusha L. S.
Published: July 2015

The Ca i 4227 Å is a chromospheric line exhibiting the largest degree of linear polarization near the limb, in the visible spectrum of the Sun. Modeling the observations of the center-to-limb variations (CLV) of different lines in the Second Solar Spectrum helps to sample the height dependence of the magnetic field, as the observations made at different lines of sight sample different heights in the solar atmosphere. Supriya et al. (2014) attempted to simultaneously model the CLV of the (I, Q/I) spectra of the Ca i 4227 Å line using the standard 1-D FAL model atmospheres. They found that the standard FAL model atmospheres and also any appropriate combination of them, fail to simultaneously fit the observed Stokes (I, Q/I) profiles at all the limb distances (μ) satisfying at the same time all the observational constraints. This failure of 1-D modeling approach can probably be overcome by using multi-dimensional modeling which is computationally expensive. To eliminate an even wider choice of 1-D models, we attempt here to simultaneously model the CLV of the (I, Q/I) spectra using the FCHHT solar model atmospheres which are updated and recent versions of the FAL models. The details of our modeling efforts and the results are presented.
Formation of polarized spectral lines in atmospheres with horizontal inhomogeneities
Authors: Tichý A. , Štěpán J. , Bueno J. Trujillo , Kubát J.
Published: July 2015

We study the problem of the generation and transfer of spectral line intensity and polarization in models of stellar atmospheres with horizontal plasma inhomogeneities. We solve the non-LTE radiative transfer problem in full 3D geometry taking into account resonant scattering polarization and its modification by magnetic fields via the Hanle effect. We show that horizontal fluctuations of the thermodynamical conditions of stellar atmospheres can have a significant impact on the linear polarization of the emergent spectral line radiation and its center-to-limb variation.
Genetic and Environmental Contributions to Personality Trait Stability and Change Across Adolescence: Results From a Japanese Twin Sample
Authors: Kawamoto Tetsuya , Endo Toshihiko
Published: July 2015

We examined developmental trends and sources of stability and change in adolescent personality by using twin data collected from 1981 to 2010 (273 monozygotic (MZ) and 48 dizygotic (DZ) twin pairs) from a secondary school affiliated with the University of Tokyo. Phenotypic analyses showed high rank-order stability and substantial mean-level increases in neuroticism and declines in extraversion over the adolescent years. Longitudinal bivariate genetic analyses revealed that the best-fitting model for adolescent personality includes additive genetic and non-shared environmental influences. Heritability estimates ranged approximately from 0.30 to 0.60. Additionally, three-year stability in adolescent personality was influenced mainly by genetic factors, and there were both genetic and environmental innovations in mid-adolescence. Our findings suggest that both genetic and environmental effects have significant roles in the etiology of personality development across adolescence.
Histone deacetylase inhibition protects hearing against acute ototoxicity by activating the Nf-κB pathway
Authors: Layman W S , Williams D M , Dearman J A , Sauceda M A , Zuo J
Published: July 2015

Auditory hair cells have repeatedly been shown to be susceptible to ototoxicity from a multitude of drugs including aminoglycoside antibiotics. Here, we found that systemic HDAC inhibition using suberoylanilide hydroxamic acid (SAHA) on adult mice offers almost complete protection against hair cell loss and hearing threshold shifts from acute ototoxic insult from kanamycin potentiated with furosemide. We also found that the apparent lack of hair cell loss was completely independent of spontaneous or facilitated (ectopic Atoh1 induction) hair cell regeneration. Rather, SAHA treatment correlated with RelA acetylation (K310) and subsequent activation of the Nf-κB pro-survival pathway leading to expression of pro-survival genes such as Cflar (cFLIP) and Bcl2l1 (Bcl-xL). In addition, we also detected increased expression of pro-survival genes Cdkn1a (p21) and Hspa1a (Hsp70), and decreased expression of the pro-apoptosis gene Bcl2l11 (Bim). These data combined provide evidence that class I HDACs control the transcriptional activation of pro-survival pathways in response to ototoxic insult by regulating the acetylation status of transcription factors found at the crossroads of cell death and survival in the mammalian inner ear.
Stereospecific induction of apoptosis in tumor cells via endogenous C16-ceramide and distinct transcripts
Authors: Blaess M , Le HP , Claus RA , Kohl M , Deigner H-P
Published: July 2015

Concentration and distribution of individual endogenous ceramide species is crucial for apoptosis induction in response to various stimuli. Exogenous ceramide analogs induce apoptosis and can in turn modify the composition/concentrations of endogenous ceramide species and associated signaling. In this study, we show here that the elevation of endogenous C16-ceramide levels is a common feature of several known apoptosis-inducing triggers like mmLDL, TNF-alpha, H2O2and exogenous C6-ceramide.Vice versaapoptosis requires elevation of endogenous C16-ceramide levels in cells. Enantiomers of a synthetic ceramide analog HPL-1RS36N have been developed as probes and vary in their capacity to inducing apoptosis in macrophages and HT-29 cells. Apoptosis induction by the two synthetic ceramide analogs HPL-39N and HPL-1R36N correlates with generation of cellular C16-ceramide concentration. In contrast to the S-enantiomer HPL-1S36N, the R-enantiomer HPL-1R36N shows significant effects on the expression of distinct genes known to be involved in cell cycle, cell growth and cell death (CXCL10, CCL5 and TNF-alpha), similarly on apoptosis induction. Enantioselective effects on transcription induced by metabolically stable synthetic probes provide clues on molecular mechanisms of ceramide-induced signaling, as well as leads for future anti-cancer agents.
Mechanism of potassium ion uptake by the Na+/K+-ATPase
Authors: Castillo Juan P. , Rui Huan , Basilio Daniel , Das Avisek , Roux Benoît , Latorre Ramon , Bezanilla Francisco , Holmgren Miguel
Published: July 2015

The Na+/K+-ATPase restores sodium (Na+) and potassium (K+) electrochemical gradients dissipated by action potentials and ion-coupled transport processes. As ions are transported, they become transiently trapped between intracellular and extracellular gates. Once the external gate opens, three Na+ ions are released, followed by the binding and occlusion of two K+ ions. While the mechanisms of Na+ release have been well characterized by the study of transient Na+ currents, smaller and faster transient currents mediated by external K+ have been more difficult to study. Here we show that external K+ ions travelling to their binding sites sense only a small fraction of the electric field as they rapidly and simultaneously become occluded. Consistent with these results, molecular dynamics simulations of a pump model show a wide water-filled access channel connecting the binding site to the external solution. These results suggest a mechanism of K+ gating different from that of Na+ occlusion.
Plasmodium falciparum full life cycle and Plasmodium ovale liver stages in humanized mice
Authors: Soulard Valérie , Bosson-Vanga Henriette , Lorthiois Audrey , Roucher Clémentine , Franetich Jean- François , Zanghi Gigliola , Bordessoulles Mallaury , Tefit Maurel , Thellier Marc , Morosan Serban , Le Naour Gilles , Capron Frédérique , Suemizu Hiroshi , Snounou Georges , Moreno-Sabater Alicia , Mazier Dominique
Published: July 2015

Experimental studies of Plasmodium parasites that infect humans are restricted by their host specificity. Humanized mice offer a means to overcome this and further provide the opportunity to observe the parasites in vivo. Here we improve on previous protocols to achieve efficient double engraftment of TK-NOG mice by human primary hepatocytes and red blood cells. Thus, we obtain the complete hepatic development of P. falciparum, the transition to the erythrocytic stages, their subsequent multiplication, and the appearance of mature gametocytes over an extended period of observation. Furthermore, using sporozoites derived from two P. ovale-infected patients, we show that human hepatocytes engrafted in TK-NOG mice sustain maturation of the liver stages, and the presence of late-developing schizonts indicate the eventual activation of quiescent parasites. Thus, TK-NOG mice are highly suited for in vivo observations on the Plasmodium species of humans.
MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA–DNA triplex structures
Authors: Mondal Tanmoy , Subhash Santhilal , Vaid Roshan , Enroth Stefan , Uday Sireesha , Reinius Björn , Mitra Sanhita , Mohammed Arif , James Alva Rani , Hoberg Emily , Moustakas Aristidis , Gyllensten Ulf , Jones Steven J.M. , Gustafsson Claes M , Sims Andrew H , Westerlund Fredrik , Gorab Eduardo , Kanduri Chandrasekhar
Published: July 2015

Long noncoding RNAs (lncRNAs) regulate gene expression by association with chromatin, but how they target chromatin remains poorly understood. We have used chromatin RNA immunoprecipitation-coupled high-throughput sequencing to identify 276 lncRNAs enriched in repressive chromatin from breast cancer cells. Using one of the chromatin-interacting lncRNAs, MEG3, we explore the mechanisms by which lncRNAs target chromatin. Here we show that MEG3 and EZH2 share common target genes, including the TGF-β pathway genes. Genome-wide mapping of MEG3 binding sites reveals that MEG3 modulates the activity of TGF-β genes by binding to distal regulatory elements. MEG3 binding sites have GA-rich sequences, which guide MEG3 to the chromatin through RNA–DNA triplex formation. We have found that RNA–DNA triplex structures are widespread and are present over the MEG3 binding sites associated with the TGF-β pathway genes. Our findings suggest that RNA–DNA triplex formation could be a general characteristic of target gene recognition by the chromatin-interacting lncRNAs.
Fgf and Esrrb integrate epigenetic and transcriptional networks that regulate self-renewal of trophoblast stem cells
Authors: Latos Paulina A. , Goncalves Angela , Oxley David , Mohammed Hisham , Turro Ernest , Hemberger Myriam
Published: July 2015

Esrrb (oestrogen-related receptor beta) is a transcription factor implicated in embryonic stem (ES) cell self-renewal, yet its knockout causes intrauterine lethality due to defects in trophoblast development. Here we show that in trophoblast stem (TS) cells, Esrrb is a downstream target of fibroblast growth factor (Fgf) signalling and is critical to drive TS cell self-renewal. In contrast to its occupancy of pluripotency-associated loci in ES cells, Esrrb sustains the stemness of TS cells by direct binding and regulation of TS cell-specific transcription factors including Elf5 and Eomes. To elucidate the mechanisms whereby Esrrb controls the expression of its targets, we characterized its TS cell-specific interactome using mass spectrometry. Unlike in ES cells, Esrrb interacts in TS cells with the histone demethylase Lsd1 and with the RNA Polymerase II-associated Integrator complex. Our findings provide new insights into both the general and context-dependent wiring of transcription factor networks in stem cells by master transcription factors.
Engineering a dirhodium artificial metalloenzyme for selective olefin cyclopropanation
Authors: Srivastava Poonam , Yang Hao , Ellis-Guardiola Ken , Lewis Jared C.
Published: July 2015

Artificial metalloenzymes (ArMs) formed by incorporating synthetic metal catalysts into protein scaffolds have the potential to impart to chemical reactions selectivity that would be difficult to achieve using metal catalysts alone. In this work, we covalently link an alkyne-substituted dirhodium catalyst to a prolyl oligopeptidase containing a genetically encoded L-4-azidophenylalanine residue to create an ArM that catalyses olefin cyclopropanation. Scaffold mutagenesis is then used to improve the enantioselectivity of this reaction, and cyclopropanation of a range of styrenes and donor–acceptor carbene precursors were accepted. The ArM reduces the formation of byproducts, including those resulting from the reaction of dirhodium–carbene intermediates with water. This shows that an ArM can improve the substrate specificity of a catalyst and, for the first time, the water tolerance of a metal-catalysed reaction. Given the diversity of reactions catalysed by dirhodium complexes, we anticipate that dirhodium ArMs will provide many unique opportunities for selective catalysis.
Developmental disruptions underlying brain abnormalities in ciliopathies
Authors: Guo Jiami , Higginbotham Holden , Li Jingjun , Nichols Jackie , Hirt Josua , Ghukasyan Vladimir , Anton E.S.
Published: July 2015

Primary cilia are essential conveyors of signals underlying major cell functions. Cerebral cortical progenitors and neurons have a primary cilium. The significance of cilia function for brain development and function is evident in the plethora of developmental brain disorders associated with human ciliopathies. Nevertheless, the role of primary cilia function in corticogenesis remains largely unknown. Here we delineate the functions of primary cilia in the construction of cerebral cortex and their relevance to ciliopathies, using an shRNA library targeting ciliopathy genes known to cause brain disorders, but whose roles in brain development are unclear. We used the library to query how ciliopathy genes affect distinct stages of mouse cortical development, in particular neural progenitor development, neuronal migration, neuronal differentiation and early neuronal connectivity. Our results define the developmental functions of ciliopathy genes and delineate disrupted developmental events that are integrally related to the emergence of brain abnormalities in ciliopathies.
Unusual fast secondary relaxation in metallic glass
Authors: Wang Q. , Zhang S.T. , Yang Y. , Dong Y.D. , Liu C.T. , Lu J.
Published: July 2015

The relaxation spectrum of glassy solids has long been used to probe their dynamic structural features and the fundamental deformation mechanisms. Structurally complicated glasses, such as molecular glasses, often exhibit multiple relaxation processes. By comparison, metallic glasses have a simple atomic structure with dense atomic packing, and their relaxation spectra were commonly found to be simpler than those of molecular glasses. Here we show the compelling evidence obtained across a wide range of temperatures and frequencies from a La-based metallic glass, which clearly shows two peaks of secondary relaxations (fast versus slow) in addition to the primary relaxation peak. The discovery of the unusual fast secondary relaxation unveils the complicated relaxation dynamics in metallic glasses and, more importantly, provides us the clues which help decode the structural features serving as the ‘trigger’ of inelasticity on mechanical agitations.
CCR2 inhibition sequesters multiple subsets of leukocytes in the bone marrow
Authors: Fujimura Naoki , Xu Baohui , Dalman Jackson , Deng Hongping , Aoyama Kohji , Dalman Ronald L
Published: July 2015

Chemokine receptor CCR2 mediates monocyte mobilization from the bone marrow (BM) and subsequent migration into target tissues. The degree to which CCR2 is differentially expressed in leukocyte subsets and the contribution of CCR2 to these leukocyte mobilization from the BM are poorly understood. Using red fluorescence protein CCR2 reporter mice, we found heterogeneity in CCR2 expression among leukocyte subsets in varying tissues. CCR2 was highly expressed by inflammatory monocytes, dendritic cells, plasmacytoid dendritic cells and NK cells in all tissues. Unexpectedly, more than 60% of neutrophils expressed CCR2, albeit at low levels. CCR2 expression in T cells, B cells and NK T cells was greatest in the BM compared to other tissues. Genetic CCR2 deficiency markedly sequestered all leukocyte subsets in the BM, with reciprocal reduction noted in the peripheral blood and spleen. CCR2 inhibition via treatment with CCR2 signaling inhibitor propagermanium produced similar effects. Propagermanium also mitigated lipopolysaccharide-induced BM leukocyte egress. Consistent with its functional significance, CCR2 antibody staining revealed surface CCR2 expression within a subset of BM neutrophils. These results demonstrate the central role CCR2 plays in mediating leukocyte mobilization from the BM and suggest a role for CCR2 inhibition in managing monocytes/macrophages-mediated chronic inflammatory conditions.
Quasiparticle self-consistent GW study of cuprates: electronic structure, model parameters and the two-band theory for Tc
Authors: Jang Seung Woo , Kotani Takao , Kino Hiori , Kuroki Kazuhiko , Han Myung Joon
Published: July 2015

Despite decades of progress, an understanding of unconventional superconductivity still remains elusive. An important open question is about the material dependence of the superconducting properties. Using the quasiparticle self-consistent GW method, we re-examine the electronic structure of copper oxide high-Tc materials. We show that QSGW captures several important features, distinctive from the conventional LDA results. The energy level splitting between "Equation missing" and "Equation missing" is significantly enlarged and the van Hove singularity point is lowered. The calculated results compare better than LDA with recent experimental results from resonant inelastic xray scattering and angle resolved photoemission experiments. This agreement with the experiments supports the previously suggested two-band theory for the material dependence of the superconducting transition temperature, Tc.
Spatiotemporal dynamics of Aurora B-PLK1-MCAK signaling axis orchestrates kinetochore bi-orientation and faithful chromosome segregation
Authors: Shao Hengyi , Huang Yuejia , Zhang Liangyu , Yuan Kai , Chu Youjun , Dou Zhen , Jin Changjiang , Garcia-Barrio Minerva , Liu Xing , Yao Xuebiao
Published: July 2015

Chromosome segregation in mitosis is orchestrated by the dynamic interactions between the kinetochore and spindle microtubules. The microtubule depolymerase mitotic centromere-associated kinesin (MCAK) is a key regulator for an accurate kinetochore-microtubule attachment. However, the regulatory mechanism underlying precise MCAK depolymerase activity control during mitosis remains elusive. Here, we describe a novel pathway involving an Aurora B-PLK1 axis for regulation of MCAK activity in mitosis. Aurora B phosphorylates PLK1 on Thr210 to activate its kinase activity at the kinetochores during mitosis. Aurora B-orchestrated PLK1 kinase activity was examined in real-time mitosis using a fluorescence resonance energy transfer-based reporter and quantitative analysis of native PLK1 substrate phosphorylation. Active PLK1, in turn, phosphorylates MCAK at Ser715 which promotes its microtubule depolymerase activity essential for faithful chromosome segregation. Importantly, inhibition of PLK1 kinase activity or expression of a non-phosphorylatable MCAK mutant prevents correct kinetochore-microtubule attachment, resulting in abnormal anaphase with chromosome bridges. We reason that the Aurora B-PLK1 signaling at the kinetochore orchestrates MCAK activity, which is essential for timely correction of aberrant kinetochore attachment to ensure accurate chromosome segregation during mitosis.
Stratospheric Ozone destruction by the Bronze-Age Minoan eruption (Santorini Volcano, Greece)
Authors: Cadoux Anita , Scaillet Bruno , Bekki Slimane , Oppenheimer Clive , Druitt Timothy H.
Published: July 2015

The role of volcanogenic halogen-bearing (i.e. chlorine and bromine) compounds in stratospheric ozone chemistry and climate forcing is poorly constrained. While the 1991 eruption of Pinatubo resulted in stratospheric ozone loss, it was due to heterogeneous chemistry on volcanic sulfate aerosols involving chlorine of anthropogenic rather than volcanogenic origin, since co-erupted chlorine was scavenged within the plume. Therefore, it is not known what effect volcanism had on ozone in pre-industrial times, nor what will be its role on future atmospheres with reduced anthropogenic halogens present. By combining petrologic constraints on eruption volatile yields with a global atmospheric chemistry-transport model, we show here that the Bronze-Age ‘Minoan’ eruption of Santorini Volcano released far more halogens than sulfur and that, even if only 2% of these halogens reached the stratosphere, it would have resulted in strong global ozone depletion. The model predicts reductions in ozone columns of 20 to >90% at Northern high latitudes and an ozone recovery taking up to a decade. Our findings emphasise the significance of volcanic halogens for stratosphere chemistry and suggest that modelling of past and future volcanic impacts on Earth’s ozone, climate and ecosystems should systematically consider volcanic halogen emissions in addition to sulfur emissions.
A pre-screening FISH-based method to detect CRISPR/Cas9 off-targets in mouse embryonic stem cells
Authors: Paulis Marianna , Castelli Alessandra , Lizier Michela , Susani Lucia , Lucchini Franco , Villa Anna , Vezzoni Paolo
Published: July 2015

The clustered regularly interspaced short palindromic repeat (CRISPR)/associated 9 (Cas9) technology has been recently added to the tools allowing efficient and easy DNA targeting, representing a very promising approach to gene engineering. Using the CRISPR/Cas9 system we have driven the integration of exogenous DNA sequences to the X-linked Hprt gene of mouse embryonic stem cells. We show here that a simple fluorescence in situ hybridization (FISH)-based strategy allows the detection and the frequency evaluation of non-specific integrations of a given plasmid. FISH analysis revealed that these integrations do not match the software predicted off-target loci. We conclude that the frequency of these CRISPR-mediated off-target DNA cuts is negligible, since, due to the occurrence of spontaneous double-strand breaks, we observed more aspecific plasmid integrations than those corresponding to predicted off-target sites.
Method for Controlling Electrical Properties of Single-Layer Graphene Nanoribbons via Adsorbed Planar Molecular Nanoparticles
Authors: Tanaka Hirofumi , Arima Ryo , Fukumori Minoru , Tanaka Daisuke , Negishi Ryota , Kobayashi Yoshihiro , Kasai Seiya , Yamada Toyo Kazu , Ogawa Takuji
Published: July 2015

A simple method for fabricating single-layer graphene nanoribbons (sGNRs) from double-walled carbon nanotubes (DWNTs) was developed. A sonication treatment was employed to unzip the DWNTs by inducing defects in them through annealing at 500 °C. The unzipped DWNTs yielded double-layered GNRs (dGNRs). Further sonication allowed each dGNR to be unpeeled into two sGNRs. Purification performed using a high-speed centrifuge ensured that more than 99% of the formed GNRs were sGNRs. The changes induced in the electrical properties of the obtained sGNR by the absorption of nanoparticles of planar molecule, naphthalenediimide (NDI), were investigated. The shape of the I-V curve of the sGNRs varied with the number of NDI nanoparticles adsorbed. This was suggestive of the existence of a band gap at the narrow-necked part near the NDI-adsorbing area of the sGNRs.