bluuebunny/crossref_metadata_2025 huggingface dataset:
IL CASO ITALIANO: SALVARE IL PLURALISMO E SUPERARE LA POLARIZZAZIONE
Authors: Sartori Giovanni
Published: May 2019

Introduzione

Luciano Pellicani si chiede, e chiede, se l'Italia sia ancora un sistema di ≪ pluralismo polarizzato ≫. Non saprei pensare, con i tempi che corrono, a un interrogativo di maggiore momento. E mi sento in dovere di rispondere subito e per primo. Subito perché gli eventi incalzano e siamo all'ora della verità; e per primo non tanto perché io sia il padre del modello del pluralismo polarizzato, ma per rilanciare il dibattito in seconda battuta, e cioè per promuovere un piú largo dibattito. Ogni terapia presuppone una diagnosi, e cioè una chiara ed esatta percezione dei mali che ci affliggono. E per avere idee chiare occorre discuterle e confrontarle.
Analyses of the genetic diversity and population structures ofHistoplasma capsulatumclinical isolates from Mexico, Guatemala, Colombia and Argentina, using a randomly amplified polymorphic DNA-PCR assay
Authors: Sahaza J. H. , Duarte-Escalante E. , Canteros C. , Rodríguez-Arellanes G. , Reyes-Montes M. R. , Taylor M. L.
Published: May 2019

We studied the genetic diversity and the population structure of human isolates ofHistoplasma capsulatum, the causative agent of histoplasmosis, using a randomly amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) assay to identify associations with the geographic distribution of isolates from Mexico, Guatemala, Colombia and Argentina. The RAPD-PCR pattern analyses revealed the genetic diversity by estimating the percentage of polymorphic loci, effective number of alleles, Shannon's index and heterozygosity. Population structure was identified by the index of association (IA) test. Thirty-seven isolates were studied and clustered into three groups by the unweighted pair-group method with arithmetic mean (UPGMA). Group I contained five subgroups based on geographic origin. The consistency of the UPGMA dendrogram was estimated by the cophenetic correlation coefficient (CCCr= 0.94,P= 0.001). Isolates from Mexico and Colombia presented higher genetic diversity than isolates from Argentina. Isolates from Guatemala grouped together with the reference strains from the United States of America and Panama. TheIAvalues suggest the presence of a clonal population structure in the ArgentinianH. capsulatumisolates and also validate the presence of recombining populations in the Colombian and Mexican isolates. These data contribute to the knowledge on the molecular epidemiology of histoplasmosis in Latin America.
Complete sequence analysis of human norovirus GII.17 detected in South Korea
Authors: Kim H. , Won Y. J. , Kang L. H. , Lee A. R. , Han J. I. , Suh C. I. , Paik S. Y.
Published: May 2019

Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI–GVII, with GII.4 being the most prevalent. However, in 2012–2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013–2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.
Altered ascending aortic wall shear stress in patients with corrected atrioventricular septal defect: a comprehensive cardiovascular magnetic resonance and 4D flow MRI evaluation
Authors: Elders Bernadette , Westenberg Jos , van den Boogaard Pieter , Calkoen Emmeline , Blom Nico , Kroft Lucia , de Roos Albert , Roest Arno
Published: May 2019

Aim:

In patients after atrioventricular septal defect correction, altered geometry leads to a changed position and subsequent flow over the left ventricular outflow tract. We hypothesised that this altered flow may influence haemodynamics in the ascending aorta.

Methods:

In total, 30 patients after atrioventricular septal defect correction (age 27.6 ± 12.8 years) and 28 healthy volunteers (age 24.8 ± 13.7 years) underwent 4D flow cardiovascular magnetic resonance. Left ventricular ejection fraction and mean and peak wall shear stress calculated at ascending aortic peak systole were obtained from cardiovascular magnetic resonance. Left ventricular outflow tract data including velocity and diameter were obtained from echocardiography.

Results:

Patients showed a higher mean (911 ± 173 versus 703 ± 154 mPa, p = 0.001) and peak ascending aortic wall shear stress (1264 ± 302 versus 1009 ± 240 mPa, p = 0.001) compared to healthy volunteers. Increased blood flow velocities over the left ventricular outflow tract (1.49 ± 0.30 m/s versus 1.22 ± 0.20 m/s, p < 0.001) correlated well with mean and peak ascending aortic wall shear stress (r = 0.67, p < 0.001 and r = 0.77, p < 0.001).

Conclusion:

After atrioventricular septal defect correction, increased wall shear stress was observed, which correlated to velocities over the left ventricular outflow tract. These findings imply that altered outflow tract geometry contributes to changed aortic haemodynamics.
Prospects for Climate Change Litigation in China
Authors: Zhao Yue , Lyu Shuang , Wang Zhu
Published: May 2019

While legal scholarship seeks mainly to assess the impact of climate change litigation (CCL) on the regulatory state and on climate change policy in common law countries, the potential influence of government climate policy on the judicial practices of jurisdictions with different legal traditions attracts much less attention. This article fills the gaps by exploring how courts in China, an authoritarian country with a civil law tradition, react to government climate policies and how this judicial response might affect relevant legal rules and eventually contribute to climate regulation. An empirical analysis of 177 Chinese judicial cases reveals that CCL in China consists mostly of contract-based civil actions steered by the government's low-carbon policies. Moreover, although the prospects of CCL against public authorities in China remain very bleak, there is scope for the emergence of tort-based CCL, backed by government policies. In this respect, recent tort-based public interest litigation on air pollution in China may serve as a substitute or, more promisingly, a gateway to the emergence of a tort-based branch of Chinese CCL.
Health Implications of Bioactive Peptides: A Review
Authors: Nourmohammadi Elham , Mahoonak Alireza Sadeghi
Published: May 2019

Abstract. Today, due to immobility, improper food habits, and changes in lifestyle, communities are faced with an increase in health problems such as blood pressure, cholesterol, diabetes, and thrombosis. Bioactive peptides are considered as being the main products of protein hydrolysis which exert high effects on the nervous, immune, and gastrointestinal systems. Unlike synthetic drugs, bioactive peptides have no side effects and this advantage has qualified them as an alternative to such drugs. Due to the above-mentioned properties, this paper focuses on the study of health-improving attributes of bioactive peptides such as anti-oxidative, anti-hypertensive, immunomodulatory, anti-microbial, anti-allergenic, opioid, anti-thrombotic, mineral-binding, anti-inflammatory, hypocholesterolemic, and anti-cancer effects. We also discuss the formation of bioactive peptides during fermentation, the main restrictions on the use of bioactive peptides and their applications in the field of functional foods. In general, food-derived biologically active peptides play an important role in human health and may be used in the development of novel foods with certain health claims.
Functional and structural neural plasticity effects of literacy acquisition in adulthood
Authors: Boltzmann Melanie , Münte Thomas , Mohammadi Bahram , Rüsseler Jascha
Published: May 2019

Abstract. In Germany, 7.5 Million individuals between 18 and 64 years are considered to be functionally illiterate (Grotlüschen & Riekmann, 2012). Functional illiterates have only rudimentary literacy skills despite attending school for several years. Although they can use written language to a very limited extent, only few functional illiterates attend literacy courses for adults. In addition, most adult literacy courses primarily aim at promoting basic reading and writing skills. Offers specific to workplace literacy are scarce.

This review gives an overview of the definition of functional illiteracy. Afterwards, a specific literacy program (AlphaPlus) and its effectiveness will be presented. The reviewed studies indicate that learning to read in adulthood is associated with structural and functional brain changes.
Understanding functional illiteracy from a policy, adult education, and cognition point of view: Towards a joint referent framework
Authors: Bulajić Aleksandar , Despotović Miomir , Lachmann Thomas
Published: May 2019

Abstract. The article discusses the emergence of a functional literacy construct and the rediscovery of illiteracy in industrialized countries during the second half of the 20thcentury. It offers a short explanation of how the construct evolved over time. In addition, it explores how functional (il)literacy is conceived differently by research discourses of cognitive and neural studies, on the one hand, and by prescriptive and normative international policy documents and adult education, on the other hand. Furthermore, it analyses how literacy skills surveys such as the Level One Study (leo.) or the PIAAC may help to bridge the gap between cognitive and more practical and educational approaches to literacy, the goal being to place the functional illiteracy (FI) construct within its existing scale levels. It also sheds more light on the way in which FI can be perceived in terms of different cognitive processes and underlying components of reading. By building on the previous work of other authors and previous definitions, the article brings together different views of FI and offers a perspective for a needed operational definition of the concept, which would be an appropriate reference point for future educational, political, and scientific utilization.
A Modeling Study of the Effects of Vertical Wind Shear on the Raindrop Size Distribution in Typhoon Nida (2016)
Authors: Deng Lin , Gao Wenhua , Duan Yihong
Published: May 2019

In this study, the effects of vertical wind shear (VWS) on the raindrop size distribution in tropical cyclone are investigated, based on the theoretical analyses that intense VWS, which commonly appears in the lower layers of tropical cyclones, can enhance the collisional breakup of raindrops. This is achieved by comparing the numerical sensitivity experiments of Typhoon Nida (2016) using Weather Research and Forecasting model against the polarimetric radar and disdrometer observations. In the control run with the default Morrison microphysics, unrealistic large raindrops are produced with excessively large differential reflectivity and heavier precipitation. An obvious decrease of raindrop size is present when the constant value of cloud droplet number concentration reduces from 250 to 30 cm−3 (NC30), leading to more comparable microphysics characteristics with the observations due to the enhancement of autoconversion rate from cloud droplets to raindrops; however, some unrealistic large‐sized raindrops still exist. A semiempirical raindrop collection/breakup parameterization is further proposed in NC30_WS run by modifying the threshold diameter of raindrops at which breakup occurs as a function of VWS. The certain improvements of simulating raindrop size distribution and precipitation in Typhoon Nida are present in NC30_WS run, owing to the efficient collisional breakup and the induced stronger raindrop evaporation cooling. Our results indicate that the combined effects of reasonable cloud droplet numbers as well as reliable raindrop breakup parameterization are pronounced and highlight the impacts of VWS on raindrop size distribution, which should be involved in current microphysical schemes to forecast the TCs more accurately.
Scaling of an Atmospheric Model to Simulate Turbulence and Cloud Microphysics in the Pi Chamber
Authors: Thomas Subin , Ovchinnikov Mikhail , Yang Fan , van der Voort Dennis , Cantrell Will , Krueger Steven K. , Shaw Raymond A.
Published: May 2019

The Pi Cloud Chamber offers a unique opportunity to study aerosol‐cloud microphysics interactions in a steady‐state, turbulent environment. In this work, an atmospheric large‐eddy simulation (LES) model with spectral bin microphysics is scaled down to simulate these interactions, allowing comparison with experimental results. A simple scalar flux budget model is developed and used to explore the effect of sidewalls on the bulk mixing temperature, water vapor mixing ratio, and supersaturation. The scaled simulation and the simple scalar flux budget model produce comparable bulk mixing scalar values. The LES dynamics results are compared with particle image velocimetry measurements of turbulent kinetic energy, energy dissipation rates, and large‐scale oscillation frequencies from the cloud chamber. These simulated results match quantitatively to experimental results. Finally, with the bin microphysics included the LES is able to simulate steady‐state cloud conditions and broadening of the cloud droplet size distributions with decreasing droplet number concentration, as observed in the experiments. The results further suggest that collision‐coalescence does not contribute significantly to this broadening. This opens a path for further detailed intercomparison of laboratory and simulation results for model validation and exploration of specific physical processes.
Global Core Top Calibration of δ18O in Planktic Foraminifera to Sea Surface Temperature
Authors: Malevich Steven B. , Vetter Lael , Tierney Jessica E.
Published: May 2019

The oxygen isotopic composition of planktic foraminiferal calcite (
) is one of the most prevalent proxies used in the paleoceanographic community. The relationship between
, temperature, and seawater oxygen isotopic composition (
) is firmly rooted in thermodynamics, and experimental constraints are commonly used for sea surface temperature (SST) reconstructions. However, in marine sedimentary applications, additional sources of uncertainty emerge, and these uncertainty constraints have not as of yet been included in global calibration models. Here, we compile a global data set of over 2,600 marine sediment core top samples for five planktic species: Globigerinoides ruber, Trilobatus sacculifer, Globigerina bulloides, Neogloboquadrina incompta, and Neogloboquadrina pachyderma. We developed a suite of Bayesian regression models to calibrate the relationship between
and SST. Spanning SSTs from 0.0 to 29.5 °C, our annual model with species pooled together has a mean standard error of approximately 0.54‰. Accounting for seasonality and species‐specific differences improves model validation, reducing the mean standard error to 0.47‰. Example applications spanning the Late Quaternary show good agreement with independent alkenone‐based estimates. Our pooled calibration model may also be used for reconstruction in the deeper geological past, using modern planktic foraminifera as an analog for non‐extant species. Our core top‐based models provide a robust assessment of uncertainty in the
paleothermometer that can be used in statistical assessments of interproxy and model‐proxy comparisons. The suite of models is publicly available as the Open Source software library bayfox, for Python, R, and MATLAB/Octave.
High-efficiency, large-area, topology-optimized metasurfaces
Authors: Phan Thaibao , Sell David , Wang Evan W. , Doshay Sage , Edee Kofi , Yang Jianji , Fan Jonathan A.
Published: May 2019

Metasurfaces are ultrathin optical elements that are highly promising for constructing lightweight and compact optical systems. For their practical implementation, it is imperative to maximize the metasurface efficiency. Topology optimization provides a pathway for pushing the limits of metasurface efficiency; however, topology optimization methods have been limited to the design of microscale devices due to the extensive computational resources that are required. We introduce a new strategy for optimizing large-area metasurfaces in a computationally efficient manner. By stitching together individually optimized sections of the metasurface, we can reduce the computational complexity of the optimization from high-polynomial to linear. As a proof of concept, we design and experimentally demonstrate large-area, high-numerical-aperture silicon metasurface lenses with focusing efficiencies exceeding 90%. These concepts can be generalized to the design of multifunctional, broadband diffractive optical devices and will enable the implementation of large-area, high-performance metasurfaces in practical optical systems.
Photonic Hall effect and helical Zitterbewegung in a synthetic Weyl system
Authors: Ye Weimin , Liu Yachao , Liu Jianlong , Horsley Simon A. R. , Wen Shuangchun , Zhang Shuang
Published: May 2019

Systems supporting Weyl points have gained increasing attention in condensed physics, photonics and acoustics due to their rich physics, such as Fermi arcs and chiral anomalies. Acting as sources or drains of Berry curvature, Weyl points exhibit a singularity of the Berry curvature at their core. It is, therefore, expected that the induced effect of the Berry curvature can be dramatically enhanced in systems supporting Weyl points. In this work, we construct synthetic Weyl points in a photonic crystal that consists of a honeycomb array of coupled rods with slowly varying radii along the direction of propagation. The system possesses photonic Weyl points in the synthetic space of two momenta plus an additional physical parameter with an enhanced Hall effect resulting from the large Berry curvature in the vicinity of the Weyl point. Interestingly, a helical Zitterbewegung (ZB) is observed when the wave packet traverses very close to a Weyl point, which is attributed to the contribution of the non-Abelian Berry connection arising from the near degenerate eigenstates.
Canagliflozin inhibits growth of hepatocellular carcinoma via blocking glucose-influx-induced β-catenin activation
Authors: Hung Man-Hsin , Chen Yao-Li , Chen Li-Ju , Chu Pei-Yi , Hsieh Feng-Shu , Tsai Ming-Hsien , Shih Chih-Ting , Chao Tzu-I , Huang Chao-Yuan , Chen Kuen-Feng
Published: May 2019

Accelerated glucose metabolism is critical in hepatocarcinogenesis, but the utilities of different glucose transporter inhibitors in treating hepatocellular carcinoma (HCC) remain largely uncharacterized. In this study, we examined a collection of glucose transporter inhibitors and found differential anti-HCC effects among these compounds. Canagliflozin (CANA), phloretin, and WZB117 decreased cellular glucose influx, but only CANA showed potent growth inhibition in HCC, which indicated a glucose-independent anti-HCC mechanism. Notably, we found that CANA treatment significantly downregulated the expression of β-catenin in HCC cells in. By co-treating cells with cycloheximide and MG-132, we proved that CANA promoted proteasomal degradation of β-catenin protein by increasing phosphorylation of β-catenin, and CANA-induced inactivation of protein phosphatase 2A was identified being responsible for this effect. Moreover, using Huh7 xenografted tumor model, CANA treatment was shown to delay tumor growth and improved the survival of HCC bearing mice. Our study highlights the unique dual β-catenin-inhibition mechanisms of CANA, which may provide new thoughts on treating HCC patient with concurrent diabetes, and, furthermore, on developing novel treatment targeting metabolic reprogram and/or WNT/β-catenin signaling in HCC.
A single layer spin-orbit torque nano-oscillator
Authors: Haidar Mohammad , Awad Ahmad A. , Dvornik Mykola , Khymyn Roman , Houshang Afshin , Åkerman Johan
Published: May 2019

Spin torque and spin Hall effect nano-oscillators generate high intensity spin wave auto-oscillations on the nanoscale enabling novel microwave applications in spintronics, magnonics, and neuromorphic computing. For their operation, these devices require externally generated spin currents either from an additional ferromagnetic layer or a material with a high spin Hall angle. Here we demonstrate highly coherent field and current tunable microwave signals from nano-constrictions in single 15–20 nm thick permalloy layers with oxide interfaces. Using a combination of spin torque ferromagnetic resonance measurements, scanning micro-Brillouin light scattering microscopy, and micromagnetic simulations, we identify the auto-oscillations as emanating from a localized edge mode of the nano-constriction driven by spin-orbit torques. Our results pave the way for greatly simplified designs of auto-oscillating nano-magnetic systems only requiring single ferromagnetic layers with oxide interfaces.
Are microtubules tension sensors?
Authors: Hamant Olivier , Inoue Daisuke , Bouchez David , Dumais Jacques , Mjolsness Eric
Published: May 2019

Mechanical signals play many roles in cell and developmental biology. Several mechanotransduction pathways have been uncovered, but the mechanisms identified so far only address the perception of stress intensity. Mechanical stresses are tensorial in nature, and thus provide dual mechanical information: stress magnitude and direction. Here we propose a parsimonious mechanism for the perception of the principal stress direction. In vitro experiments show that microtubules are stabilized under tension. Based on these results, we explore the possibility that such microtubule stabilization operates in vivo, most notably in plant cells where turgor-driven tensile stresses exceed greatly those observed in animal cells.
The UbiX flavin prenyltransferase reaction mechanism resembles class I terpene cyclase chemistry
Authors: Marshall Stephen A. , Payne Karl A. P. , Fisher Karl , White Mark D. , Ní Cheallaigh Aisling , Balaikaite Arune , Rigby Stephen E. J. , Leys David
Published: May 2019

The UbiX-UbiD enzymes are widespread in microbes, acting in concert to decarboxylate alpha-beta unsaturated carboxylic acids using a highly modified flavin cofactor, prenylated FMN (prFMN). UbiX serves as the flavin prenyltransferase, extending the isoalloxazine ring system with a fourth non-aromatic ring, derived from sequential linkage between a dimethylallyl moiety and the FMN N5 and C6. Using structure determination and solution studies of both dimethylallyl monophosphate (DMAP) and dimethyallyl pyrophosphate (DMAPP) dependent UbiX enzymes, we reveal the first step, N5-C1’ bond formation, is contingent on the presence of a dimethylallyl substrate moiety. Hence, an SN1 mechanism similar to other prenyltransferases is proposed. Selected variants of the (pyro)phosphate binding site are unable to catalyse subsequent Friedel-Crafts alkylation of the flavin C6, but can be rescued by addition of (pyro)phosphate. Thus, retention of the (pyro)phosphate leaving group is required for C6-C3’ bond formation, resembling pyrophosphate initiated class I terpene cyclase reaction chemistry.
Atypical function of a centrosomal module in WNT signalling drives contextual cancer cell motility
Authors: Luo Yi , Barrios-Rodiles Miriam , Gupta Gagan D. , Zhang Ying Y. , Ogunjimi Abiodun A. , Bashkurov Mikhail , Tkach Johnny M. , Underhill Ainsley Q. , Zhang Liang , Bourmoum Mohamed , Wrana Jeffrey L. , Pelletier Laurence
Published: May 2019

Centrosomes control cell motility, polarity and migration that is thought to be mediated by their microtubule-organizing capacity. Here we demonstrate that WNT signalling drives a distinct form of non-directional cell motility that requires a key centrosome module, but not microtubules or centrosomes. Upon exosome mobilization of PCP-proteins, we show that DVL2 orchestrates recruitment of a CEP192-PLK4/AURKB complex to the cell cortex where PLK4/AURKB act redundantly to drive protrusive activity and cell motility. This is mediated by coordination of formin-dependent actin remodelling through displacement of cortically localized DAAM1 for DAAM2. Furthermore, abnormal expression of PLK4, AURKB and DAAM1 is associated with poor outcomes in breast and bladder cancers. Thus, a centrosomal module plays an atypical function in WNT signalling and actin nucleation that is critical for cancer cell motility and is associated with more aggressive cancers. These studies have broad implications in how contextual signalling controls distinct modes of cell migration.
Ep400 deficiency in Schwann cells causes persistent expression of early developmental regulators and peripheral neuropathy
Authors: Fröb Franziska , Sock Elisabeth , Tamm Ernst. R. , Saur Anna-Lena , Hillgärtner Simone , Williams Trevor J. , Fujii Toshihiro , Fukunaga Rikiro , Wegner Michael
Published: May 2019

Schwann cells ensure efficient nerve impulse conduction in the peripheral nervous system. Their development is accompanied by defined chromatin changes, including variant histone deposition and redistribution. To study the importance of variant histones for Schwann cell development, we altered their genomic distribution by conditionally deleting Ep400, the central subunit of the Tip60/Ep400 complex. Ep400 absence causes peripheral neuropathy in mice, characterized by terminal differentiation defects in myelinating and non-myelinating Schwann cells and immune cell activation. Variant histone H2A.Z is differently distributed throughout the genome and remains at promoters of Tfap2a, Pax3 and other transcriptional regulator genes with transient function at earlier developmental stages. Tfap2a deletion in Ep400-deficient Schwann cells causes a partial rescue arguing that continued expression of early regulators mediates the phenotypic defects. Our results show that proper genomic distribution of variant histones is essential for Schwann cell differentiation, and assign importance to Ep400-containing chromatin remodelers in the process.
Publisher Correction: Chromatin dysregulation and DNA methylation at transcription start sites associated with transcriptional repression in cancers
Authors: Ando Mizuo , Saito Yuki , Xu Guorong , Bui Nam Q. , Medetgul-Ernar Kate , Pu Minya , Fisch Kathleen , Ren Shuling , Sakai Akihiro , Fukusumi Takahito , Liu Chao , Haft Sunny , Pang John , Mark Adam , Gaykalova Daria A. , Guo Theresa , Favorov Alexander V. , Yegnasubramanian Srinivasan , Fertig Elana J. , Ha Patrick , Tamayo Pablo , Yamasoba Tatsuya , Ideker Trey , Messer Karen , Califano Joseph A.
Published: May 2019

The original version of this Article contained an error in the author affiliations. Trey Ideker was incorrectly associated with ‘Department of Medicine (Oncology), Stanford University School of Medicine, 875 Blake Wilbur Dr, Palo Alto, CA 94304, USA.’ This has now been corrected in both the PDF and HTML versions of the Article.
Confinement of magnetism in atomically thin La0.7Sr0.3CrO3/La0.7Sr0.3MnO3 heterostructures
Authors: Koohfar Sanaz , Georgescu Alexandru B. , Penn Aubrey N. , LeBeau James M. , Arenholz Elke , Kumah Divine P.
Published: May 2019

At crystalline interfaces where a valence-mismatch exists, electronic, and structural interactions may occur to relieve the polar mismatch, leading to the stabilization of non-bulk-like phases. We show that spontaneous reconstructions at polar La0.7Sr0.3MnO3 interfaces are correlated with suppressed ferromagnetism for film thicknesses on the order of a unit cell. We investigate the structural and magnetic properties of valence-matched La0.7Sr0.3CrO3/La0.7Sr0.3MnO3 interfaces using a combination of high-resolution electron microscopy, first principles theory, synchrotron X-ray scattering and magnetic spectroscopy and temperature-dependent magnetometry. A combination of an antiferromagnetic coupling between the La0.7Sr0.3CrO3 and La0.7Sr0.3MnO3 layers and a suppression of interfacial polar distortions are found to result in robust long-range ferromagnetic ordering for ultrathin La0.7Sr0.3MnO3. These results underscore the critical importance of interfacial structural and magnetic interactions in the design of devices based on two-dimensional oxide magnetic systems.
Heterologous prime-boost with A(H5N1) pandemic influenza vaccines induces broader cross-clade antibody responses than homologous prime-boost
Authors: Levine Min Z. , Holiday Crystal , Jefferson Stacie , Gross F. Liaini , Liu Feng , Li Sheng , Friel Damien , Boutet Philippe , Innis Bruce L. , Mallett Corey P. , Tumpey Terrence M. , Stevens James , Katz Jacqueline M.
Published: May 2019

Highly pathogenic avian influenza (HPAI) A(H5Nx) viruses continue to pose a pandemic threat. US national vaccine stockpiles are a cornerstone of the influenza pandemic preparedness plans. However, continual genetic and antigenic divergence of A(H5Nx) viruses requires the development of effective vaccination strategies using stockpiled vaccines and adjuvants for pandemic preparedness. Human sera collected from healthy adults who received either homologous (2 doses of a AS03A-adjuvanted A/turkey/Turkey/1/2005, A/Turkey), or heterologous (primed with AS03A-adjuvanted A/Indonesia/5/2005, A/Indo, followed by A/Turkey boost) prime-boost vaccination regimens were analyzed by hemagglutination inhibition and microneutralization assays against 8 wild-type HPAI A(H5Nx) viruses from 6 genetic clades. Molecular, structural and antigenic features of the A(H5Nx) viruses that could influence the cross-clade antibody responses were also explored. Compared with homologous prime-boost vaccinations, priming with a clade 2.1.3.2 antigen (A/Indo) followed by one booster dose of a clade 2.2.1 antigen (A/Turkey) administered 18 months apart did not compromise the antibody responses to the booster vaccine (A/Turkey), it also broadened the cross-clade antibody responses to several antigenically drifted variants from 6 heterologous clades, including an antigenically distant A(H5N8) virus (A/gyrfalcon/Washington/410886/2014, clade 2.3.4.4) that caused recent outbreaks in US poultry. The magnitude and breadth of the cross-clade antibody responses against emerging HPAI A(H5Nx) viruses are associated with genetic, structural and antigenic differences from the vaccine viruses and enhanced by the inclusion of an adjuvant. Heterologous prime-boost vaccination with AS03A adjuvanted vaccine offers a vaccination strategy to use existing stockpiled vaccines for pandemic preparedness against new emerging HPAI A(H5Nx) viruses.
Longitudinal multi-omics of host–microbe dynamics in prediabetes
Authors: Zhou Wenyu , Sailani M. Reza , Contrepois Kévin , Zhou Yanjiao , Ahadi Sara , Leopold Shana R. , Zhang Martin J. , Rao Varsha , Avina Monika , Mishra Tejaswini , Johnson Jethro , Lee-McMullen Brittany , Chen Songjie , Metwally Ahmed A. , Tran Thi Dong Binh , Nguyen Hoan , Zhou Xin , Albright Brandon , Hong Bo-Young , Petersen Lauren , Bautista Eddy , Hanson Blake , Chen Lei , Spakowicz Daniel , Bahmani Amir , Salins Denis , Leopold Benjamin , Ashland Melanie , Dagan-Rosenfeld Orit , Rego Shannon , Limcaoco Patricia , Colbert Elizabeth , Allister Candice , Perelman Dalia , Craig Colleen , Wei Eric , Chaib Hassan , Hornburg Daniel , Dunn Jessilyn , Liang Liang , Rose Sophia Miryam Schüssler-Fiorenza , Kukurba Kim , Piening Brian , Rost Hannes , Tse David , McLaughlin Tracey , Sodergren Erica , Weinstock George M. , Snyder Michael
Published: May 2019

Type 2 diabetes mellitus (T2D) is a growing health problem, but little is known about its early disease stages, its effects on biological processes or the transition to clinical T2D. To understand the earliest stages of T2D better, we obtained samples from 106 healthy individuals and individuals with prediabetes over approximately four years and performed deep profiling of transcriptomes, metabolomes, cytokines, and proteomes, as well as changes in the microbiome. This rich longitudinal data set revealed many insights: first, healthy profiles are distinct among individuals while displaying diverse patterns of intra- and/or inter-personal variability. Second, extensive host and microbial changes occur during respiratory viral infections and immunization, and immunization triggers potentially protective responses that are distinct from responses to respiratory viral infections. Moreover, during respiratory viral infections, insulin-resistant participants respond differently than insulin-sensitive participants. Third, global co-association analyses among the thousands of profiled molecules reveal specific host–microbe interactions that differ between insulin-resistant and insulin-sensitive individuals. Last, we identified early personal molecular signatures in one individual that preceded the onset of T2D, including the inflammation markers interleukin-1 receptor agonist (IL-1RA) and high-sensitivity C-reactive protein (CRP) paired with xenobiotic-induced immune signalling. Our study reveals insights into pathways and responses that differ between glucose-dysregulated and healthy individuals during health and disease and provides an open-access data resource to enable further research into healthy, prediabetic and T2D states.
Copper sulfide nanoparticles as high-performance cathode materials for Mg-ion batteries
Authors: Kravchyk Kostiantyn V. , Widmer Roland , Erni Rolf , Dubey Romain J.-C. , Krumeich Frank , Kovalenko Maksym V. , Bodnarchuk Maryna I.
Published: May 2019

Rechargeable magnesium batteries are appealing as safe, low-cost systems with high-energy-density storage that employ predominantly dendrite-free magnesium metal as the anode. While significant progress has been achieved with magnesium electrolytes in recent years, the further development of Mg-ion batteries, however, is inherently limited by the lack of suitable cathode materials, mainly due to the slow diffusion of high-charge-density Mg-ions in the intercalation-type host structures and kinetic limitations of conversion-type cathodes that often causes poor cyclic stability. Nanostructuring the cathode materials offers an effective means of mitigating these challenges, due to the reduced diffusion length and higher surface areas. In this context, we present the highly reversible insertion of Mg-ions into nanostructured conversion-type CuS cathode, delivering high capacities of 300 mAh g−1 at room temperature and high cyclic stability over 200 cycles at a current density of 0.1 A g−1 with a high coulombic efficiency of 99.9%. These materials clearly outperform bulk CuS, which is electrochemically active only at an elevated temperature of 50 °C. Our results not only point to the important role of nanomaterials in the enhancement of the kinetics of conversion reactions but also suggest that nanostructuring should be used as an integral tool in the exploration of new cathodes for multivalent, i.e., (Mg, Ca, Al)-ion batteries.
Author Correction: Exquisitely-preserved, high-definition skin traces in diminutive theropod tracks from the Cretaceous of Korea
Authors: Kim Kyung Soo , Lockley Martin G. , Lim Jong Deock , Xing Lida
Published: May 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.
Climate controls on snow reliability in French Alps ski resorts
Authors: Spandre P. , François H. , Verfaillie D. , Lafaysse M. , Déqué M. , Eckert N. , George E. , Morin S.
Published: May 2019

Ski tourism is a major sector of mountain regions economy, which is under the threat of long-term climate change. Snow management, and in particular grooming and artificial snowmaking, has become a routine component of ski resort operations, holding potential for counteracting the detrimental effect of natural snow decline. However, conventional snowmaking can only operate under specific meteorological conditions. Whether snowmaking is a relevant adaptation measure under future climate change is a widely debated issue in mountainous regions, with major implications on the supply side of this tourism industry. This often lacks comprehensive scientific studies for informing public and private decisions in this sector. Here we show how climate change influences the operating conditions of one of the main ski tourism markets worldwide, the French Alps. Our study addresses snow reliability in 129 ski resorts in the French Alps in the 21st century, using a dedicated snowpack model explicitly accounting for grooming and snowmaking driven by a large ensemble of adjusted and downscaled regional climate projections, and using a geospatial model of ski resorts organization. A 45% snowmaking fractional coverage, representative of the infrastructures in the early 2020s, is projected to improve snow reliability over grooming-only snow conditions, both during the reference period 1986–2005 and below 2 °C global warming since pre-industrial. Beyond 3 °C of global warming, with 45% snowmaking coverage, snow conditions would become frequently unreliable and induce higher water requirements.
Systemic and intrathecal immune activation in association with cerebral and cognitive outcomes in paediatric HIV
Authors: Blokhuis C. , Peeters C. F. W. , Cohen S. , Scherpbier H. J. , Kuijpers T. W. , Reiss P. , Kootstra N. A. , Teunissen C. E. , Pajkrt D.
Published: May 2019

Despite treatment, immune activation is thought to contribute to cerebral injury in children perinatally infected with human immunodeficiency virus (HIV). We aimed to characterize immune activation in relation to neuroimaging and cognitive outcomes. We therefore measured immunological, coagulation, and neuronal biomarkers in plasma and cerebrospinal fluid (CSF) samples of 34 perinatally HIV-infected children aged 8–18 years, and in plasma samples of 37 controls of comparable age, sex, ethnicity, and socio-economic status. We then compared plasma biomarker levels between groups, and explored associations between plasma/CSF biomarkers and neuroimaging and cognitive outcomes using network analysis. HIV-infected children showed higher plasma levels of C-reactive protein, interferon-gamma, interferon-gamma-inducible protein-10, and monocyte chemoattractant protein-1 than controls. In HIV-infected participants, plasma soluble CD14 was positively associated with microstructural white matter (WM) damage, and plasma D-dimer was negatively associated with WM blood flow. In CSF, IL-6 was negatively associated with WM volume, and neurofilament heavy-chain (NFH) was negatively associated with intelligence quotient and working memory. These markers of ongoing inflammation, immune activation, coagulation, and neuronal damage could be used to further evaluate the pathophysiology and clinical course of cerebral and cognitive deficits in perinatally acquired HIV.
Varying levels of X chromosome coalescence in female somatic cells alters the balance of X-linked dosage compensation and is implicated in female-dominant systemic lupus erythematosus
Authors: Laskowski Agnieszka I. , Neems Daniel S. , Laster Kyle , Strojny-Okyere Chelsee , Rice Ellen L. , Konieczna Iwona M. , Voss Jessica H. , Mathew James M. , Leventhal Joseph R. , Ramsey-Goldman Rosalind , Smith Erica D. , Kosak Steven T.
Published: May 2019

The three-dimensional organization of the genome in mammalian interphase nuclei is intrinsically linked to the regulation of gene expression. Whole chromosome territories and their encoded gene loci occupy preferential positions within the nucleus that changes according to the expression profile of a given cell lineage or stage. To further illuminate the relationship between chromosome organization, epigenetic environment, and gene expression, here we examine the functional organization of chromosome X and corresponding X-linked genes in a variety of healthy human and disease state X diploid (XX) cells. We observe high frequencies of homologous chromosome X colocalization (or coalescence), typically associated with initiation of X-chromosome inactivation, occurring in XX cells outside of early embryogenesis. Moreover, during chromosome X coalescence significant changes in Xist, H3K27me3, and X-linked gene expression occur, suggesting the potential exchange of gene regulatory information between the active and inactive X chromosomes. We also observe significant differences in chromosome X coalescence in disease-implicated lymphocytes isolated from systemic lupus erythematosus (SLE) patients compared to healthy controls. These results demonstrate that X chromosomes can functionally interact outside of embryogenesis when X inactivation is initiated and suggest a potential gene regulatory mechanism aberration underlying the increased frequency of autoimmunity in XX individuals.
Assessing the freshwater flux from the continents to the Mediterranean Sea
Authors: Wang Fuxing , Polcher Jan
Published: May 2019

Precipitation minus evaporation over continents is the freshwater flux which can be sustainably exploited by mankind. Over a catchment and longer time periods, this flux is also the amount of water which flows into the ocean. An essential question for semi-arid areas of the world is how well this freshwater flux can be estimated and predicted to evolve under climate change and human water use. Knowing this flux is thus an essential element in regional water resources management. Here we examine this question over the catchment of the Mediterranean Sea. Using a novel data assimilation methodology that incorporates observed discharges of rivers in a land surface model, new estimates of the freshwater flux to the Mediterranean Sea for the period 1980–2013 are proposed. We find that more freshwater (40–60%) flows into the sea than previously estimated. The hypothesis we advance is that previous estimates have underestimated the discharges of the large number of unmonitored coastal basins and neglected submarine ground water flows. The proposed error bars on the estimate indicate that the degrading river gauging station network limits our ability to monitor this branch of the water cycle reliably. Nevertheless, the uncertainty is small enough to allow the identification of regions in which non-climatic decreases in the freshwater flows exist over the period.
Generation of new hair cells by DNA methyltransferase (Dnmt) inhibitor 5-azacytidine in a chemically-deafened mouse model
Authors: Deng Xin , Liu Zhenjie , Li Xiaoyang , Zhou Yang , Hu Zhengqing
Published: May 2019

Regeneration of mature mammalian inner ear hair cells remains to be a challenge. This study aims to evaluate the ability of DNA methyltransferase (Dnmt) inhibitor 5-azacytidine (5-aza) to generate outer hair cells (OHCs) in a chemically-deafened adult mouse model. 5-aza was administrated into the mouse inner ear via the round window. Immunofluorescence was used to examine the expression of hair cell specific proteins following 5-aza treatment. The results showed that in the chemically-deafened mouse cochlea, new OHCs were found post 5-aza treatment, whereas OHCs were completely lost in saline-treated mice. New hair cells expressed multiple hair cell markers included Myosin VIIa, Pou4f3 and Myosin VI. Newly-generated hair cells presented in three cochlear turns and were able to survive for at least six weeks. The effects of new hair cells generation by 5-aza were concentration dependent. Quantitative PCR study indicates that 5-aza may function through Dnmt1 inhibition. The results of this report suggest that the Dnmt inhibitor 5-aza may promote hair cell regeneration in a chemically-deafened mouse model.
Intermittent parathyroid hormone 1–34 induces oxidation and deterioration of mineral and collagen quality in newly formed mandibular bone
Authors: Yoshioka Yohsuke , Yamachika Eiki , Nakanishi Makoto , Ninomiya Tadashi , Akashi Sho , Kondo Sei , Moritani Norifumi , Kobayashi Yasuhiro , Fujii Tatsuo , Iida Seiji
Published: May 2019

Intermittent parathyroid hormone (PTH) administration is known to promote bone healing after surgical procedures. However, the mechanism and influence of PTH on the mineral and collagen quality of the jaw are not well understood. Most studies have focused on analyzing the bone density and microstructure of the mandible, and have insufficiently investigated its mineral and collagen quality. Oxidative stress activates osteoclasts, produces advanced glycation end products, and worsens mineral and collagen quality. We hypothesized that PTH induces oxidation and affects the mineral and collagen quality of newly formed mandibular bone. To test this, we examined the mineral and collagen quality of newly formed mandibular bone in rats administered PTH, and analyzed serum after intermittent PTH administration to examine the degree of oxidation. PTH administration reduced mineralization and worsened mineral and collagen quality in newly formed bone. In addition, total anti-oxidant capacity in serum was significantly decreased and the oxidative-INDEX was increased among PTH-treated compared to vehicle-treated rats, indicating serum oxidation. In conclusion, intermittent administration of PTH reduced mineral and collagen quality in newly formed mandibular bone. This effect may have been induced by oxidation.
Metabolomics reveals diet-derived plant polyphenols accumulate in physiological bone
Authors: Alldritt Isabelle , Whitham-Agut Beatrice , Sipin Miguel , Studholme Jacob , Trentacoste Angela , Tripp Jennifer A. , Cappai Maria Grazia , Ditchfield Peter , Devièse Thibaut , Hedges Robert E. M. , McCullagh James S. O.
Published: May 2019

Plant-derived secondary metabolites consumed in the diet, especially polyphenolic compounds, are known to have a range of positive health effects. They are present in circulation after ingestion and absorption and can be sequestered into cells within particular organs, but have rarely been investigated systematically in osteological tissues. However, a small number of polyphenols and similar molecules are known to bind to bone. For example alizarin, a plant derived anthraquinone and tetracycline (a naturally occurring antibiotic), are both absorbed into bone from circulation during bone formation and are used to monitor mineralization in osteological studies. Both molecules have also been identified serendipitously in archaeological human bones derived from natural sources in the diet. Whether an analogous mechanism of sequestration extends to additional diet-derived plant-polyphenols has not previously been systematically studied. We investigated whether a range of diet-derived polyphenol-like compounds bind to bone using untargeted metabolomics applied to the analysis of bone extracts from pigs fed an acorn-based diet. We analysed the diet which was rich in ellagitannins, extracts from the pig bones and surrounding tissue, post-mortem. We found direct evidence of multiple polyphenolic compounds in these extracts and matched them to the diet. We also showed that these compounds were present in the bone but not surrounding tissues. We also provide data showing that a range of polyphenolic compounds bind to hydroxyapatite in vitro. The evidence for polyphenol sequestration into physiological bone, and the range and specificity of polyphenols in human and animal diets, raises intriguing questions about potential effects on bone formation and bone health. Further studies are needed to determine the stability of the sequestered molecules post-mortem but there is also potential for (palaeo)dietary reconstruction and forensic applications.