bluuebunny/crossref_metadata_2025 huggingface dataset:
VARIATIONS OF BPS STRUCTURE AND A LARGE RANK LIMIT
Authors: Scalise Jacopo , Stoppa Jacopo
Published: March 2019

We study a class of flat bundles, of finite rank $N$, which arise naturally from the Donaldson–Thomas theory of a Calabi–Yau threefold $X$ via the notion of a variation of BPS structure. We prove that in a large $N$ limit their flat sections converge to the solutions to certain infinite-dimensional Riemann–Hilbert problems recently found by Bridgeland. In particular this implies an expression for the positive degree, genus 0 Gopakumar–Vafa contribution to the Gromov–Witten partition function of $X$ in terms of solutions to confluent hypergeometric differential equations.
Deciphering Patterns and Drivers of Heat and Carbon Storage in the Southern Ocean
Authors: Chen Haidi , Morrison Adele K. , Dufour Carolina O. , Sarmiento Jorge L.
Published: March 2019

The storage of anomalous heat and carbon in the Southern Ocean in response to increasing greenhouse gases greatly mitigates atmospheric warming and exerts a large impact on the marine ecosystem. However, the mechanisms driving the ocean storage patterns are uncertain. Here using recent hydrographic observations, we compare for the first time the spatial patterns of heat and carbon storage, which show substantial differences in the Southern Ocean, in contrast with the conventional view of simple passive subduction into the thermocline. Using an eddy‐rich global climate model, we demonstrate that redistribution of the preindustrial temperature field is the dominant control on the heat storage pattern, whereas carbon storage largely results from passive transport of anthropogenic carbon uptake at the surface. Lastly, this study highlights the importance of realistic representation of wind and surface buoyancy flux in climate models to improve future projection of circulation change and thus heat and carbon storage.
The 2015 Gorkha Earthquake: Earthquake Reflection Imaging of the Source Fault and Connecting Seismic Structure With Fault Slip Behavior
Authors: Kurashimo Eiji , Sato Hiroshi , Sakai Shin'ichi , Hirata Naoshi , Gajurel Ananta Prasad , Adhikari Danda Pani , Subedi Krishna Prasad , Yagi Hiroshi , Upreti Bishal Nath
Published: March 2019

A seismic array observation across the central focal area of the 2015 Gorkha earthquake was conducted to investigate aftershock distribution and crustal structure. Most aftershocks near Kathmandu were located above the Main Himalayan Thrust (MHT). Earthquake reflection imaging revealed the geometry of the MHT, which lies at ~10‐km depth at 75 km away from the Main Frontal Thrust. We found three areas of seismic velocity variability around the MHT above 15 km depth: (1) a high‐Vp zone where the MHT changes its dip angle from 5° to 13°, coinciding with a local maximum in coseismic slip, (2) a low‐Vp zone showing less coseismic slip, and (3) a high‐Vp zone where coseismic slip decreased further but afterslip occurred. These differences in slip behavior may indicate changes in frictional properties on the fault, which are reflected in the heterogeneity of the velocity structure.
How Well Can We Estimate Pedersen Conductance From the THEMIS White‐Light All‐Sky Cameras?
Authors: Lam M. M. , Freeman M. P. , Jackman C. M. , Rae I. J. , Kalmoni N. M. E. , Sandhu J. K. , Forsyth C.
Published: March 2019

We show that a white‐light all‐sky imager can estimate Pedersen conductance with an uncertainty of 3 mho or 40%. Using a series of case studies over a wide range of geomagnetic activity, we compare estimates of Pedersen conductance from the backscatter spectrum of the Poker Flat Incoherent Scatter Radar with auroral intensities. We limit this comparison to an area bounding the radar measurements and within a limited area close to (but off) imager zenith. We confirm a linear relationship between conductance and the square root of auroral intensity predicted from a simple theoretical approximation. Hence, we extend a previous empirical result found for green‐line emissions to the case of white‐light off‐zenith emissions. The difference between the radar conductance and the best‐fit relationship has a mean of −0.76 ± 4.8 mho and a relative mean difference of 21% ± 78%. The uncertainties are reduced to −0.72 ± 3.3 mho and 0% ± 40% by averaging conductance over 10 min, which we attribute to the time that auroral features take to move across the imager field being greater than the 1‐min resolution of the radar data. Our results demonstrate and calibrate the use of Time History of Events and Macroscale Interactions during Substorms all‐sky imagers for estimating Pedersen conductance. This technique allows the extension of estimates of Pedersen conductance from Incoherent Scatter Radars to derive continental‐scale estimates on scales of ~1–10 min and ~100 km2. It thus complements estimates from low‐altitude satellites, satellite auroral imagers, and ground‐based magnetometers.
Outer Van Allen Radiation Belt Response to Interacting Interplanetary Coronal Mass Ejections
Authors: Kilpua E. K. J. , Turner D. L. , Jaynes A. N. , Hietala H. , Koskinen H. E. J. , Osmane A. , Palmroth M. , Pulkkinen T. I. , Vainio R. , Baker D. , Claudepierre S. G.
Published: March 2019

We study the response of the outer Van Allen radiation belt during an intense magnetic storm on 15–22 February 2014. Four interplanetary coronal mass ejections (ICMEs) arrived at Earth, of which the three last ones were interacting. Using data from the Van Allen Probes, we report the first detailed investigation of electron fluxes from source (tens of kiloelectron volts) to core (megaelectron volts) energies and possible loss and acceleration mechanisms as a response to substructures (shock, sheath and ejecta, and regions of shock‐compressed ejecta) in multiple interacting ICMEs. After an initial enhancement induced by a shock compression of the magnetosphere, core fluxes strongly depleted and stayed low for 4 days. This sustained depletion can be related to a sequence of ICME substructures and their conditions that influenced the Earth's magnetosphere. In particular, the main depletions occurred during a high‐dynamic pressure sheath and shock‐compressed southward ejecta fields. These structures compressed/eroded the magnetopause close to geostationary orbit and induced intense and diverse wave activity in the inner magnetosphere (ULF Pc5, electromagnetic ion cyclotron, and hiss) facilitating both effective magnetopause shadowing and precipitation losses. Seed and source electrons in turn experienced stronger variations throughout the studied interval. The core fluxes recovered during the last ICME that made a glancing blow to Earth. This period was characterized by a concurrent lack of losses and sustained acceleration by chorus and Pc5 waves. Our study highlights that the seemingly complex behavior of the outer belt during interacting ICMEs can be understood by the knowledge of electron dynamics during different substructures.
Fluid Pressure‐Triggered Foreshock Sequence of the 2008 Mogul Earthquake Sequence: Insights From Stress Inversion and Numerical Modeling
Authors: Jansen G. , Ruhl C. J. , Miller S. A.
Published: March 2019

In Mogul west of Reno, Nevada, USA, in late February 2008 an earthquake sequence occurred that culminated in a magnitude 4.9 mainshock after a foreshock‐rich period lasting approximately 2 months on previously unidentified fault structures. In this article, we show that the foreshock sequence may have been driven by a fluid pressure intrusion. We use 1,082 previously calculated earthquake focal mechanisms to infer the local stress field as well as 1,408 relocated foreshock events to determine the required excess fluid pressure field in the source region of the Mogul earthquake sequence to trigger these events. A model of nonlinear pore pressure diffusion is used to model the fluid flow in a highly fractured subsurface. We find a strong correlation between high fluid pressure fronts and foreshock hypocenters, suggesting a natural fluid‐driven earthquake sequence.
Capillary Pressure Curve Determination Based on a 2‐D Cross‐Section Analysis Via Fractal Geometry: A Bridge Between 2‐D and 3‐D Pore Structure of Porous Media
Authors: Chen Xiaojun , Yao Guangqing , Luo Chengfei , Jiang Ping , Cai Jianchao , Zhou Kun , Herrero‐Bervera E.
Published: March 2019

Pore structure is a crucial attribute in characterizing fluid flow through porous media. However, direct experimental measurements or numerical reconstructions are commonly expensive and not environmentally friendly, with great uncertainty caused by the complex nature of porous media. In this study, we demonstrate that one special bridge function, which is a function of the apparent length and tortuosity fractal dimension, can characterize the relationship of pore structures between two dimensions (2‐D) and three dimensions (3‐D), and it can serve as a conversion bridge of the radius to determine the capillary pressure curve (CPC). We compare estimations by the proposed method with experimental results obtained by mercury intrusion porosimetry in six typical natural sandstones with varying porosities and permeabilities. The result shows that cross sections of the global pore structure, such as thin section, electronic probe, and microcomputed tomography slices, give a reliable estimation of the CPC using the bridge function in porous media with a medium porosity. However, in unconventional porous media with a relatively low porosity (~10%) or extra high porosity (~30%), due to the empirical nature of the equation widely used to calculate the tortuosity fractal dimension, the necessary modification is necessary to obtain the CPC when applying the bridge function in such porous media. This insight can significantly simplify the procedure for obtaining the petrophysical properties of a porous medium, which may shed light on the inherent differences and correlations between the 2‐D and 3‐D pore structures of porous media.
Fluid Distribution in the Central Andes Subduction Zone Imaged With Magnetotellurics
Authors: Araya Vargas J. , Meqbel N. M. , Ritter O. , Brasse H. , Weckmann U. , Yáñez G. , Godoy B.
Published: March 2019

We present a model of the electrical resistivity structure of the lithosphere in the Central Andes between 20° and 24°S from 3‐D inversion of 56 long‐period magnetotelluric sites. Our model shows a complex resistivity structure with significant variability parallel and perpendicular to the trench direction. The continental forearc is characterized mainly by high electrical resistivity (>1,000 Ωm), suggesting overall low volumes of fluids. However, low resistivity zones (LRZs, <5 Ωm) were found in the continental forearc below areas where major trench‐parallel faults systems intersect NW‐SE transverse faults. Forearc LRZs indicate circulation and accumulation of fluids in highly permeable fault zones. The continental crust along the arc shows three distinctive resistivity domains, which coincide with segmentation in the distribution of volcanoes. The northern domain (20°–20.5°S) is characterized by resistivities >1,000 Ωm and the absence of active volcanism, suggesting the presence of a low‐permeability block in the continental crust. The central domain (20.5°–23°S) exhibits a number of LRZs at varying depths, indicating different levels of a magmatic plumbing system. The southern domain (23°–24°S) is characterized by resistivities >1,000 Ωm, suggesting the absence of large magma reservoirs below the volcanic chain at crustal depths. Magma reservoirs located below the base of the crust or in the backarc may fed active volcanism in the southern domain. In the subcontinental mantle, the model exhibits LRZs in the forearc mantle wedge and above clusters of intermediate‐depth seismicity, likely related to fluids produced by serpentinization of the mantle and eclogitization of the slab, respectively.
Constraining a Historical Black Carbon Emission Inventory of the United States for 1960–2000
Authors: Sun T. , Liu L. , Flanner M. G. , Kirchstetter T. W. , Jiao C. , Preble C. V. , Chang W. L. , Bond T. C.
Published: March 2019

We present an observationally constrained United States black carbon emission inventory with explicit representation of activity and technology between 1960 and 2000. We compare measured coefficient of haze data in California and New Jersey between 1965 and 2000 with predicted concentration trends and attribute discrepancies between observations and predicted concentrations among several sources based on seasonal and weekly patterns in observations. Emission factors for sources with distinct fuel trends are then estimated by comparing fuel and concentration trends and further substantiated by in‐depth examination of emission measurements. We recommend (1) increasing emission factors for preregulation vehicles by 80–250%; (2) increasing emission factors for residential heating stoves and boilers by 70% to 200% for 1980s and before; (3) explicitly representing naturally aspired off‐road engines for 1980s and before; and (4) explicitly representing certified wood stoves after 1985. We also evaluate other possible sources for discrepancy between model and measurement, including bias in modeled meteorology, subgrid spatial heterogeneity of concentrations, and inconsistencies in reported fuel consumption. The updated U.S. emissions are higher than thea prioriestimate by 80% between 1960 and 1980, totaling 690 Gg/year in 1960 and 620 Gg/year in 1970 (excluding open burning). The revised inventory shows a strongly decreasing trend that was present in the observations but missing in thea prioriinventory.
Warmer Winter Ground Temperatures Trigger Rapid Growth of Dahurian Larch in the Permafrost Forests of Northeast China
Authors: Zhang Xianliang , Bai Xueping , Hou Meiting , Chen Zhenju , Manzanedo Rubén D.
Published: March 2019

Permafrost degradation due to rapid increase in ground surface temperature (GST) in recent years may strongly affect boreal forest ecosystems. However, comparatively few studies have explored how changes in permafrost affect tree growth dynamics in boreal forest. Here, we used a tree ring network of 12 Dahurian larch (Larix gmelinii) sites across permafrost regions in northeast China. We observed an increase in L. gmelinii growth over the past decade, seemingly linked to a shift in their climatic limitations, where winter GST has become the most strongly limiting factor for L. gmelinii growth. The recent increase in growth was particularly strong in older trees (>300 years), which could be related to older trees having a more developed root system. GST was the main limiting factor for tree growth. While summer GST had a somewhat consistently positive correlation with tree growth, winter GST has shifted from a negative to a strongly positive correlation with growth in the last decade, coincidental with a sharp increase in winter GST since 2004. Winter GST is also strongly correlated with the rapidly thawing permafrost dynamics. Overall, our results suggest a link between recent changes in the permafrost and shifts in climate‐growth correlations for one of the main boreal tree species. As a result, L. gmelinii has experienced an important increase in radial growth that may indicate that, unlike what has been reported for other boreal species, it may temporally benefit from warming climate in the continuous permafrost region of the Asian boreal forests.
Cenozoic Stages of Forearc Evolution Following the Accretion of a Sliver From the Late Cretaceous‐Caribbean Large Igneous Province: SW Ecuador‐NW Peru
Authors: Aizprua Carlos , Witt Cesar , Johansen Ståle E. , Barba Diego
Published: March 2019

The SW Ecuador‐NW Peru forearc region is the southernmost location, where the Caribbean large igneous province (CLIP) interacted with the South American margin since the Late Cretaceous. The accretion of the CLIP to the margin led to the entrapment of the North Andean crustal Sliver, conforming the underlying basement of the forearc region in Ecuador, whereas in NW Peru, forearc depocenters involve rocks of continental affinity. Many existing tectonic reconstructions have treated these two areas independently, largely based on their crustal affinities. In contrast, this study integrates previous studies into an analysis of unpublished seismic profiles, potential field data, outcrop stratigraphy, and recent studies dealing with the dynamics of allochthonous terrane accretion along continental margins. Our integrated approach shows that SW Ecuador was dominated by a Late Cretaceous deforming outer wedge, which may have constituted a remnant of a northeast or northwest dipping obliquely obducted oceanic block at the edge of the CLIP. This tectonic phase was governed by plate instability, affecting NW Peru and SW Ecuador, followed by reestablishment of the margin by early Eocene. The resulting margin configuration and the spatial distribution of the different tectonic elements seem to have played a key role into the further Cenozoic development of the forearc region. The model presented in this study proposes that the accretion of buoyant oceanic terranes may have had a profound impact on the early margin configuration of SW Ecuador and NW Peru and led to the development of localized but genetically related forearc depocenters.
Simulation of Counterstreaming H+ Outflows During Plasmasphere Refilling
Authors: Krall J. , Huba J. D.
Published: March 2019

Plasmasphere refilling is modeled using an upgraded version of the Naval Research Laboratory SAMI2 (Sami2 is Another Model of the Ionosphere) ionosphere/plasmasphere code. In this implementation of SAMI2, two fluid species are used for H+, each having a source in only one magnetic hemisphere. This is the first comprehensive plasmasphere model with two‐stream H+. With two counterstreaming H+ fluids, artificial shocks or compressions at high altitude are avoided during storms and early‐stage refilling. For late‐stage refilling, runs with two‐stream SAMI2 validate previous SAMI2 (one H+ fluid) refilling rates. At ionospheric altitudes (
2,000 km), where the single‐fluid approximation is valid for each ion, two‐stream SAMI2 results agree closely with SAMI2 results.
Direct Evidence for the Dissipation of Small‐Scale Ionospheric Plasma Structures by a Conductive E Region
Authors: Ivarsen Magnus F , Jin Yaqi , Spicher Andres , Clausen Lasse B N
Published: March 2019

The conductivity of the ionospheric E region is known to cause effective dissipation of plasma structures in the F region. We use 3.5 years of 16‐Hz sampling rate electron density measurements from the Swarm advanced data set to investigate seasonal dependencies of plasma structure dissipation. Using a novel algorithm to infer plasma structure dissipation through detection of spectral breaks in density fluctuation power spectra, we analyze 100,000 spectra based on data from Swarm A in both the northern and southern polar caps. For the first time, we can present long‐term development of small‐scale (∼1‐10 km) plasma structure diffusion in the high‐latitude ionospheric F region. We discuss possible reasons for these variations. This study presents evidence for the E region as an important factor in the seasonal variation of F region plasma irregularity amplitudes.
Thank You to Our 2018 Peer Reviewers
Authors: Florindo Fabio , Halekas Jasper S. , Okin Gregory , Robock Alan , Rohling Eelco J.
Published: March 2019

On behalf of the authors and readers of Reviews of Geophysics, the American Geophysical Union (AGU), and the broader scientific community, the Editors wish to wholeheartedly thank those who reviewed the manuscripts for Reviews of Geophysics in 2018. Reviews of Geophysics is the top rated journal in Geophysics and Geochemistry and it could not exist without your investment of time and effort, lending your expertise to ensure that the papers published in this journal meet the standards that the research community expects for it. We sincerely appreciate the time spent reading and commenting on manuscripts, and we are very grateful for your willingness and readiness to serve in this role. Reviews of Geophysics published 20 review papers and an editorial in 2018, covering most of the AGU Section topics, and for this we were able to rely on the efforts of 85 dedicated reviewers from 20 countries. Many reviewers answered the call multiple times. Thank you again. We look forward to a 2019 of exciting advances in the field and communicating those advances to our community and to the broader public.
Thank You to Our 2018 Peer Reviewers
Authors: Salous Sana , Wilkinson Phil
Published: March 2019

Science operates best by sharing accurate new knowledge in clear ways. In order to check our assumptions, our methods, and our interpretations of the observations, experiments, analyses, and calculations that we do, we ask experts who were not involved in the study to critically evaluate our work. We call this peer review. They look for completeness, accuracy, whether work is new, and how clearly we have written the descriptions. We continue to be humbled by the time, effort, and careful insights that our colleagues share with each other through the process of peer review. In 2018, Radio Science benefited from 720 reviews provided by 420 of our peers for papers submitted to the journal. Thank you all for your efforts toward advancing radio science now and for the future.
Tissue resident and follicular Treg cell differentiation is regulated by CRAC channels
Authors: Vaeth Martin , Wang Yin-Hu , Eckstein Miriam , Yang Jun , Silverman Gregg J. , Lacruz Rodrigo S. , Kannan Kasthuri , Feske Stefan
Published: March 2019

T regulatory (Treg) cells maintain immunological tolerance and organ homeostasis. Activated Treg cells differentiate into effector Treg subsets that acquire tissue-specific functions. Ca2+ influx via Ca2+ release-activated Ca2+ (CRAC) channels formed by STIM and ORAI proteins is required for the thymic development of Treg cells, but its function in mature Treg cells remains unclear. Here we show that deletion of Stim1 and Stim2 genes in mature Treg cells abolishes Ca2+ signaling and prevents their differentiation into follicular Treg and tissue-resident Treg cells. Transcriptional profiling of STIM1/STIM2-deficient Treg cells reveals that Ca2+ signaling regulates transcription factors and signaling pathways that control the identity and effector differentiation of Treg cells. In the absence of STIM1/STIM2 in Treg cells, mice develop a broad spectrum of autoantibodies and fatal multiorgan inflammation. Our findings establish a critical role of CRAC channels in controlling lineage identity and effector functions of Treg cells.
Live imaging of alveologenesis in precision-cut lung slices reveals dynamic epithelial cell behaviour
Authors: Akram Khondoker M. , Yates Laura L. , Mongey Róisín , Rothery Stephen , Gaboriau David C. A. , Sanderson Jeremy , Hind Matthew , Griffiths Mark , Dean Charlotte H.
Published: March 2019

Damage to alveoli, the gas-exchanging region of the lungs, is a component of many chronic and acute lung diseases. In addition, insufficient generation of alveoli results in bronchopulmonary dysplasia, a disease of prematurity. Therefore visualising the process of alveolar development (alveologenesis) is critical for our understanding of lung homeostasis and for the development of treatments to repair and regenerate lung tissue. Here we show live alveologenesis, using long-term, time-lapse imaging of precision-cut lung slices. We reveal that during this process, epithelial cells are highly mobile and we identify specific cell behaviours that contribute to alveologenesis: cell clustering, hollowing and cell extension. Using the cytoskeleton inhibitors blebbistatin and cytochalasin D, we show that cell migration is a key driver of alveologenesis. This study reveals important novel information about lung biology and provides a new system in which to manipulate alveologenesis genetically and pharmacologically.
Parallel analysis of tri-molecular biosynthesis with cell identity and function in single cells
Authors: Kimmey Samuel C. , Borges Luciene , Baskar Reema , Bendall Sean C.
Published: March 2019

Cellular products derived from the activity of DNA, RNA, and protein synthesis collectively control cell identity and function. Yet there is little information on how these three biosynthesis activities are coordinated during transient and sparse cellular processes, such as activation and differentiation. Here, we describe Simultaneous Overview of tri-Molecule Biosynthesis (SOM3B), a molecular labeling and simultaneous detection strategy to quantify DNA, RNA, and protein synthesis in individual cells. Comprehensive interrogation of biosynthesis activities during transient cell states, such as progression through cell cycle or cellular differentiation, is achieved by partnering SOM3B with parallel quantification of select biomolecules with conjugated antibody reagents. Here, we investigate differential de novo DNA, RNA, and protein synthesis dynamics in transformed human cell lines, primary activated human immune cells, and across the healthy human hematopoietic continuum, all at a single-cell resolution.
Nuclear lamina integrity is required for proper spatial organization of chromatin in Drosophila
Authors: Ulianov Sergey V. , Doronin Semen A. , Khrameeva Ekaterina E. , Kos Pavel I. , Luzhin Artem V. , Starikov Sergei S. , Galitsyna Aleksandra A. , Nenasheva Valentina V. , Ilyin Artem A. , Flyamer Ilya M. , Mikhaleva Elena A. , Logacheva Mariya D. , Gelfand Mikhail S. , Chertovich Alexander V. , Gavrilov Alexey A. , Razin Sergey V. , Shevelyov Yuri Y.
Published: March 2019

How the nuclear lamina (NL) impacts on global chromatin architecture is poorly understood. Here, we show that NL disruption in Drosophila S2 cells leads to chromatin compaction and repositioning from the nuclear envelope. This increases the chromatin density in a fraction of topologically-associating domains (TADs) enriched in active chromatin and enhances interactions between active and inactive chromatin. Importantly, upon NL disruption the NL-associated TADs become more acetylated at histone H3 and less compact, while background transcription is derepressed. Two-colour FISH confirms that a TAD becomes less compact following its release from the NL. Finally, polymer simulations show that chromatin binding to the NL can per se compact attached TADs. Collectively, our findings demonstrate a dual function of the NL in shaping the 3D genome. Attachment of TADs to the NL makes them more condensed but decreases the overall chromatin density in the nucleus by stretching interphase chromosomes.
Author Correction: Combined inhibition of MEK and nuclear ERK translocation has synergistic antitumor activity in melanoma cells
Authors: Arafeh Rand , Flores Karen , Keren-Paz Alona , Maik-Rachline Galia , Gutkind Naomi , Rosenberg Steven , Seger Rony , Samuels Yardena
Published: March 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.
Mycobacterium tuberculosis Rv3463 induces mycobactericidal activity in macrophages by enhancing phagolysosomal fusion and exhibits therapeutic potential
Authors: Park Hye-Soo , Back Yong Woo , Shin Ki-Won , Bae Hyun Shik , Lee Kang-In , Choi Han-Gyu , Choi Seunga , Lee Hwang-Ho , Choi Chul Hee , Park Jeong-Kyu , Kim Hwa-Jung
Published: March 2019

Macrophages are responsible for innate and adaptive immune response activation necessary for eliminating infections. Optimal activation of macrophages to phagocytize Mycobacterium tuberculosis is critical in anti-mycobacterial defense. Here, we identified a novel Rv3463 hypothetical protein that induces macrophage activation in Mtb culture filtrate. Recombinant Rv3463 activated mouse bone marrow-derived macrophages to induce the expression of surface molecules and secrete pro-inflammatory cytokines via the TLR2 and TLR4 pathways. Mitogen activated protein kinase, phospatidylinositol-4,5-bisphosphate 3-kinases, and the NF-κB signaling pathways are involved in Rv3463-mediated macrophage activation. Furthermore, Rv3463 induced bactericidal effects in Mtb-infected macrophages through phagosome maturation and phagolysosomal fusion enhanced by phospatidylinositol-4,5-bisphosphate 3-kinases and Ca2+ signaling pathways and exhibited therapeutic effects in a short-term Mtb-infection mouse model. Overexpression of Rv3463 in M. smegmatis caused rapid clearance of bacteria in macrophages and mice. Our study suggests that Rv3463 is a promising target for the development of post-exposure tuberculosis vaccines or adjunct immune-therapy.
Apparent absence of Batrachochytrium salamandrivorans in wild urodeles in the United Kingdom
Authors: Cunningham Andrew A. , Smith Freya , McKinley Trevelyan J. , Perkins Matthew W. , Fitzpatrick Liam D. , Wright Owen N. , Lawson Becki
Published: March 2019

Whether an infectious disease threat to wildlife arises from pathogen introduction or the increased incidence of an already-present agent informs mitigation policy and actions. The prior absence of a pathogen can be difficult to establish, particularly in free-living wildlife. Subsequent to the epidemic emergence of the fungus, Batrachochytrium salamandrivorans (Bsal), in mainland Europe in 2010 and prior to its detection in captive amphibians in the United Kingdom (UK), we tested archived skin swabs using a Bsal-specific qPCR. These samples had been collected in 2011 from 2409 wild newts from ponds across the UK. All swabs were negative for Bsal. Bayesian hierarchical modelling suggests that Bsal was absent from, or present at very low levels in, these ponds at the time of sampling. Additionally, surveillance of newt mortality incidents, 2013–2017, failed to detect Bsal. As this pathogen has been shown to be widespread in British captive amphibian collections, there is an urgent need to raise awareness of the importance of effective biosecurity measures, especially amongst people with captive amphibians, to help minimise the risk of Bsal spreading to the wild. Continued and heightened wild amphibian disease surveillance is a priority to provide an early warning system for potential incursion events.
Magnetism in iridate heterostructures leveraged by structural distortions
Authors: Meyers D. , Cao Yue , Fabbris G. , Robinson Neil J. , Hao Lin , Frederick C. , Traynor N. , Yang J. , Lin Jiaqi , Upton M. H. , Casa D. , Kim Jong-Woo , Gog T. , Karapetrova E. , Choi Yongseong , Haskel D. , Ryan P. J. , Horak Lukas , Liu X. , Liu Jian , Dean M. P. M.
Published: March 2019

Fundamental control of magnetic coupling through heterostructure morphology is a prerequisite for rational engineering of magnetic ground states. We report the tuning of magnetic interactions in superlattices composed of single and bilayers of SrIrO3 inter-spaced with SrTiO3 in analogy to the Ruddlesden-Popper series iridates. Magnetic scattering shows predominately c-axis antiferromagnetic orientation of the magnetic moments for the bilayer, as in Sr3Ir2O7. However, the magnetic excitation gap, measured by resonant inelastic x-ray scattering, is quite different between the two structures, evidencing a significant change in the stability of the competing magnetic phases. In contrast, the single layer iridate hosts a more bulk-like gap. We find these changes are driven by bending of the c-axis Ir-O-Ir bond, which is much weaker in the single layer, and subsequent local environment changes, evidenced through x-ray diffraction and magnetic excitation modeling. Our findings demonstrate how large changes in the magnetic interactions can be tailored and probed in spin-orbit coupled heterostructures by engineering subtle structural modulations.
Pivotal role of inter-organ aspartate metabolism for treatment of mitochondrial aspartate-glutamate carrier 2 (citrin) deficiency, based on the mouse model
Authors: Saheki Takeyori , Moriyama Mitsuaki , Kuroda Eishi , Funahashi Aki , Yasuda Izumi , Setogawa Yoshiko , Gao Qinghua , Ushikai Miharu , Furuie Sumie , Yamamura Ken-ichi , Takano Katsura , Nakamura Yoichi , Eto Kazuhiro , Kadowaki Takashi , Sinasac David S. , Furukawa Tatsuhiko , Horiuchi Masahisa , Tai Yen How
Published: March 2019

Previous studies using citrin/mitochondrial glycerol-3-phosphate (G3P) dehydrogenase (mGPD) double-knockout mice have demonstrated that increased dietary protein reduces the extent of carbohydrate-induced hyperammonemia observed in these mice. This study aimed to further elucidate the mechanisms of this effect. Specific amino acids were initially found to decrease hepatic G3P, or increase aspartate or citrulline levels, in mGPD-knockout mice administered ethanol. Unexpectedly, oral glycine increased ammonia in addition to lowering G3P and increasing citrulline. Subsequently, simultaneous glycine-plus-sucrose (Gly + Suc) administration led to a more severe hyperammonemic state in double-KO mice compared to sucrose alone. Oral arginine, ornithine, aspartate, alanine, glutamate and medium-chain triglycerides all lowered blood ammonia following Gly + Suc administration, with combinations of ornithine-plus-aspartate (Orn + Asp) or ornithine-plus-alanine (Orn + Ala) suppressing levels similar to wild-type. Liver perfusion and portal vein-arterial amino acid differences suggest that oral aspartate, similar to alanine, likely activated ureagenesis from ammonia and lowered the cytosolic NADH/NAD+ ratio through conversion to alanine in the small intestine. In conclusion, Gly + Suc administration induces a more severe hyperammonemic state in double-KO mice that Orn + Asp or Orn + Ala both effectively suppress. Aspartate-to-alanine conversion in the small intestine allows for effective oral administration of either, demonstrating a pivotal role of inter-organ aspartate metabolism for the treatment of citrin deficiency.
Novel blaCTX-M variants and genotype-phenotype correlations among clinical isolates of extended spectrum beta lactamase-producing Escherichia coli
Authors: Ramadan Ahmed A. , Abdelaziz Neveen A. , Amin Magdy A. , Aziz Ramy K.
Published: March 2019

The rapid emergence of multiresistant microbial pathogens, dubbed superbugs, is a serious threat to human health. Extended spectrum beta lactamase (ESBL)-producing Escherichia coli is a superbug causing worldwide outbreaks, necessitating timely and accurate tracking of resistant strains. Accordingly, this study was designed to investigate the spread of ESBL-producing Escherichia coli isolates, to analyze the effect of different genotypic and phenotypic factors on in vitro resistance patterns, and to assess the diagnostic value of commonly used ESBL genetic markers. For that purpose, we cultured 250 clinical isolates and screened their susceptibility to beta-lactam antibiotics. Among 12 antibiotics screened, only imipenem seems to have remained resilient. We subsequently analyzed the ESBL phenotype of Escherichia coli isolates and examined potential associations between their resistance phenotypes and patient-related factors. ESBL genotyping of 198 multiresistant isolates indicated that 179 contained at least one blaCTX-M gene. As we statistically dissected the data, we found associations between overall resistance and body site / type of disease. Additionally, we confirmed the diagnostic value of testing both blaCTX-M-1 and blaCTX-M-15 in providing better prediction of overall resistance. Finally, on sequencing the amplification products of detected blaCTX-M genes, we discovered two novel variants, which we named blaCTX-M-14.2 and blaCTX-M-15.2.
Author Correction: Camphor-Engine-Driven Micro-Boat Guides Evolution of Chemical Gardens
Authors: Frenkel Mark , Multanen Victor , Grynyov Roman , Musin Albina , Bormashenko Yelena , Bormashenko Edward
Published: March 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.
Language Outcomes in Adults with a History of Institutionalization: Behavioral and Neurophysiological Characterization
Authors: Kornilov Sergey A. , Zhukova Marina A. , Ovchinnikova Irina V. , Golovanova Irina V. , Naumova Oxana Yu. , Logvinenko Tatiana I. , Davydova Aleksandra O. , Petrov Maxim V. , Chumakova Maria A. , Grigorenko Elena L.
Published: March 2019

Impoverished early care environments are associated with developmental deficits in children raised in institutional settings. Despite the accumulation of evidence regarding deficits in general cognitive functioning in this population, less is known about the impact of institutionalization on language development at the level of brain and behavior. We examined language outcomes in young adults and adolescents raised in institutions (n = 23) as compared to their socioeconomic status and age peers raised in biological families (n = 24) using a behavioral language assessment and linguistic event-related potentials (ERPs). Controlling for intelligence, adults with a history of institutionalization demonstrated deficits in lexical and grammatical development and spelling. Analyses of ERP data revealed significant group differences in the dynamic processing of linguistic stimuli. Adults with a history of institutionalization displayed reduced neural sensitivity to violations of word expectancy, leading to reduced condition effects for temporo-spatial factors that tentatively corresponded to the N200, P300/N400, and phonological mismatch negativity. The results suggest that language is a vulnerable domain in adults with a history of institutionalization, the deficits in which are not explained by general developmental delays, and point to the pivotal role of early linguistic environment in the development of the neural networks involved in language processing.
Author Correction: Angiopep-2/IP10-EGFRvIIIscFv modified nanoparticles and CTL synergistically inhibit malignant glioblastoma
Authors: Wang Xuan , Xiong Zhiyong , Liu Zhen , Huang Xing , Jiang Xiaobing
Published: March 2019

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Acute sublethal exposure to toxic heavy metals alters honey bee (Apis mellifera) feeding behavior
Authors: Burden Christina M. , Morgan Mira O. , Hladun Kristen R. , Amdam Gro V. , Trumble John J. , Smith Brian H.
Published: March 2019

Heavy metal toxicity is an ecological concern in regions affected by processes like mining, industry, and agriculture. At sufficiently high concentrations, heavy metals are lethal to honey bees, but little is known about how sublethal doses affect honey bees or whether they will consume contaminated food. We investigated whether honey bees reject sucrose solutions contaminated with three heavy metals – cadmium, copper, and lead – as a measure of their ability to detect the metals, and whether ingesting these metals altered the bees’ sucrose sensitivity. The metals elicited three different response profiles in honey bees. Cadmium was not rejected in any of the assays, and ingesting cadmium did not alter sucrose sensitivity. Copper was rejected following antennal stimulation, but was readily consumed following proboscis stimulation. Ingestion of copper did not alter sucrose sensitivity. Lead appeared to be palatable at some concentrations and altered the bees’ sensitivity to and/or valuation of sucrose following antennal stimulation or ingestion of the metal. These differences likely represent unique mechanisms for detecting each metal and the pathology of toxicity. The bees’ ability to detect and consume these toxic metals highlights the risk of exposure to these elements for bees living in or near contaminated environments.
Characterization of polydactyly chondrocytes and their use in cartilage engineering
Authors: Cavalli Emma , Levinson Clara , Hertl Matthias , Broguiere Nicolas , Brück Oscar , Mustjoki Satu , Gerstenberg Anja , Weber Daniel , Salzmann Gian , Steinwachs Matthias , Barreto Gonçalo , Zenobi-Wong Marcy
Published: March 2019

Treating cartilage injuries and degenerations represents an open surgical challenge. The recent advances in cell therapies have raised the need for a potent off-the-shelf cell source. Intra-articular injections of TGF-β transduced polydactyly chondrocytes have been proposed as a chronic osteoarthritis treatment but despite promising results, the use of gene therapy still raises safety concerns. In this study, we characterized infant, polydactyly chondrocytes during in vitro expansion and chondrogenic re-differentiation. Polydactyly chondrocytes have a steady proliferative rate and re-differentiate in 3D pellet culture after up to five passages. Additionally, we demonstrated that polydactyly chondrocytes produce cartilage-like matrix in a hyaluronan-based hydrogel, namely transglutaminase cross-linked hyaluronic acid (HA-TG). We utilized the versatility of TG cross-linking to augment the hydrogels with heparin moieties. The heparin chains allowed us to load the scaffolds with TGF-β1, which induced cartilage-like matrix deposition both in vitro and in vivo in a subcutaneous mouse model. This strategy introduces the possibility to use infant, polydactyly chondrocytes for the clinical treatment of joint diseases.
Trimethylamine N-Oxide, Circulating Endothelial Progenitor Cells, and Endothelial Function in Patients with Stable Angina
Authors: Chou Ruey-Hsing , Chen Chi-Yu , Chen I-Chun , Huang Hsin-Lei , Lu Ya-Wen , Kuo Chin-Sung , Chang Chun-Chin , Huang Po-Hsun , Chen Jaw-Wen , Lin Shing-Jong
Published: March 2019

Trimethylamine N-oxide (TMAO) is a metabolite originated from bacterial metabolism of choline-rich foods. Evidence suggests an association between TMAO and atherosclerosis, but the relationship between TMAO and endothelial progenitor cells (EPCs) remains unclear. This study aimed to identify the relationship between TMAO concentrations, circulating EPCs, and endothelial function in patients with stable angina. Eighty-one stable angina subjects who underwent coronary angiography were enrolled. The circulating EPCs and flow-mediated vasodilation (FMD) were measured to evaluate endothelial function. Plasma TMAO and inflammatory markers, such as hsCRP and IL-1β, were determined. Furthermore, the effect of TMAO on EPCs was assessed in vitro. Patients with lower FMD had significantly decreased circulating EPCs, elevated TMAO, hsCRP, and IL-1β concentrations. Plasma TMAO levels were negatively correlated with circulating EPC numbers and the FMD, and positively correlated with hsCRP, IL-1β concentrations. In in vitro studies, incubation of TMAO in cultured EPCs promoted cellular inflammation, elevated oxidative stress, and suppressed EPC functions. Enhanced plasma TMAO levels were associated with reduced circulating EPCs numbers, endothelial dysfunction, and more adverse cardiovascular events. These findings provided evidence of TMAO’s toxicity on EPCs, and delivered new insight into the mechanism of TMAO-mediated atherosclerosis, which could be derived from TMAO-downregulated EPC functions.
The relationship between physiological and mechanical properties of Acer platanoides L. and Tilia cordata Mill. leaves and their seasonal senescence
Authors: Ciupak Anna , Dziwulska-Hunek Agata , Gładyszewska Bożena , Kwaśniewska Anita
Published: March 2019

The seasonal senescence of leaves in the phenological cycle coincides with the change of their strength properties which determine resistance to environmental conditions and the efficiency of the photosynthesis process. That affects the development, growth and condition of the plant. Therefore, the aim of this paper was to observe and compare the results of strength tests performed on the leaves of two species of trees popular in Poland - lime and maple. As well as chlorophyll fluorescence and photosynthetic pigments content in the context of the changes occurring during the entire leaf life cycle. Obtained results showed that the strength properties of the tested leaves reached the minimum values in spring and the maximum in the summer similarly to the leaf greenness index. Whereas the fluorescence increased which the seasonal senescence in opposition to the photosynthesis efficiency of the leaves. Collected data revealed that strength parameters and photosynthetic pigment content were significantly higher for maple leaves than for lime leaves. Studies showed differences between physiological and mechanical properties of the leaves of two trees species, even if they grew under the same environmental conditions. It is concluded from the results that phenotype and physical parameters of leaves are related to seasonal senescence.
Association between self-reported physical activity and incident atrial fibrillation in a young Korean population
Authors: Lee Sung Ho , Ryu Seungho , Lee Jong-Young , Seo Dae Chul , Kim Byung Jin , Sung Ki-Chul
Published: March 2019

The association between physical activity (PA) and atrial fibrillation (AF) remains unclear. We thus investigated association of PA with the development of AF. Type and duration data for PA were acquired from 211,992 AF-free individuals using the validated Korean version of the International Physical Activity Questionnaire Short From between March 2002 and December 2014. Individuals were divided into four groups according to self-reported PA level and previous international PA guidelines: no PA with a sedentary lifestyle, insufficient PA, sufficient PA, and health-enhancing PA. AF was diagnosed by annual 12-lead electrocardiogram. During a median follow-up of 5.6 years, AF occurred in 304 participants (annual AF incidence rate 2.5/10,000 person-years). After adjusting for age and sex, PA level was not associated with AF incidence (P for trend = 0.26). The multivariable-adjusted hazard ratios (95% confidence interval) for incidental AF was 1.00 (0.74–1.37) for the insufficient PA group, 1.34 (0.91–1.97) for the sufficient PA group, and 1.27 (0.72–2.23) for the health-enhancing PA group compared with the no PA group (P for trend = 0.18). Thus, our study does not support an association between the risk of AF and PA level in a young Korean population.