bluuebunny/crossref_metadata_2025 huggingface dataset:
Distribution of Crustal Melt Bodies at the Hot Spot‐Influenced Section of the Galápagos Spreading Centre From Seismic Reflection Images
Authors: Boddupalli B. , Canales J.P.
Published: May 2019

Accretion of the lower crust at mid‐ocean ridges is a debated topic, with modern seismic observations pointing to a complex magmatic system that includes an axial multisill system of middle‐ and lower‐crustal melt lenses and near‐ and off‐axis melt bodies. Here we revisit the hot spot‐influenced section of the western Galápagos Spreading Centre and reprocess multichannel seismic reflection data using a wide‐angle seismic tomography model. Our new images show that the magma reservoir in the lower crust at this ridge section is intruded with partially molten melt lenses. The images also show evidence for off‐axis melt lenses, magmatic‐hydrothermal interactions and Moho reflections in this region. We conclude that the similarities between the axial crustal structure of this hot spot‐influenced mid‐ocean ridge and the multisill magmatic structure imaged at the East Pacific Rise indicate that these features are common along the global mid‐ocean ridge system where seafloor spreading is dominated by magmatic accretion.
Active Boulder Movement at High Martian Latitudes
Authors: Dundas Colin M. , Mellon Michael T. , Conway Susan J. , Gastineau Renaldo
Published: May 2019

Lobate stony landforms occur on steep slopes at high latitudes on Mars. We demonstrate active boulder movement at seven such sites. Submeter‐scale boulders frequently move distances of a few meters. The movement is concentrated in the vicinity of the lobate landforms but also occurs on other slopes. This provides evidence for a newly discovered, common style of activity on Mars, which may play an important role in slope degradation. It also opens the possibility that the lobate features are currently forming in the absence of significant volumes of liquid water.
Modeling Wind‐Driven Ionospheric Dynamo Currents at Mars: Expectations for InSight Magnetic Field Measurements
Authors: Lillis Robert J. , Fillingim Matthew O. , Ma Yingjuan , Gonzalez‐Galindo Francisco , Forget François , Johnson Catherine L. , Mittelholz Anna , Russell Christopher T. , Andersson Laila , Fowler Christopher M.
Published: May 2019

We model expected dynamo currents above, and resulting magnetic field profiles at, InSight's landing site on Mars, including for the first time the effect of electron‐ion collisions. We calculate their diurnal and seasonal variability using inputs from global models of the Martian thermosphere, ionosphere, and magnetosphere. Modeled currents primarily depend on plasma densities and the strength of the neutral wind component perpendicular to the combined crustal and draped magnetic fields that thread the ionosphere. Negligible at night, currents are the strongest in the late morning and near solstices due to stronger winds and near perihelion due to both stronger winds and higher plasma densities from solar EUV photoionization. Resulting surface magnetic fields of tens of nanotesla and occasionally >100 nT may be expected at the InSight landing site. We expect currents and surface fields to vary significantly with changes in the draped magnetic field caused by Mars' dynamic solar wind environment.
U.S. East Coast Lidar Measurements Show Offshore Wind Turbines Will Encounter Very Low Atmospheric Turbulence
Authors: Bodini Nicola , Lundquist Julie K. , Kirincich Anthony
Published: May 2019

The rapid growth of offshore wind energy requires accurate modeling of the wind resource, which can be depleted by wind farm wakes. Turbulence dissipation rate (ϵ) governs the accuracy of model predictions of hub‐height wind speed and the development and erosion of wakes. Here we assess the variability of turbulence kinetic energy and ϵ using 13 months of observations from a profiling lidar deployed on a platform off the Massachusetts coast. Offshore, ϵ is 2 orders of magnitude smaller than onshore, with a subtle diurnal cycle. Wind direction influences the annual cycle of turbulence, with larger values in winter when the wind flows from the land, and smaller values in summer, when the wind flows from open ocean. Because of the weak turbulence, wind plant wakes will be stronger and persist farther downwind in summer.
Modeling Contributions of Continents and Oceans to the Diurnal Variation of the Global Electric Circuit
Authors: Slyunyaev Nikolay N. , Ilin Nikolay V. , Mareev Evgeny A.
Published: May 2019

Contributions of different land and ocean regions to the diurnal variation of the global electric circuit are simulated using the Weather Research and Forecasting model by estimating the ionospheric potential produced by thunderstorms and electrified shower clouds in each grid column. The model predicts that contributions from land regions have maxima at about 14:00–18:00 local time (LT), whereas contributions from oceans have maxima at about 2:00–6:00 LT, and different ocean regions show nearly the same relative diurnal variation. It is remarkable that contributions from ocean regions with many islands (Maritime Continent and Middle America) have maxima at both 14:00–18:00 and 2:00–6:00 LT.
Ion‐Neutral Coupling in the Upper Atmosphere of Mars: A Dominant Driver of Topside Ionospheric Structure
Authors: Mayyasi Majd , Narvaez C. , Benna Mehdi , Elrod M. , Mahaffy Paul
Published: May 2019

The structure of the upper atmosphere of Mars provides insights into the physical mechanisms that drive escape of species into outer space. Deviations in plasma density profiles with altitude from the theoretical exponentially decaying formulation have been routinely observed for decades yet remain largely unexplained. Proposed mechanisms driving this variability have focused primarily on plasma‐specific processes, as limited by past plasma‐only observations. The Mars Atmosphere and Volatile Evolution mission's Neutral Gas and Ion Mass Spectrometer data set has recently provided unprecedented planetographic coverage for both ions and neutrals in the Martian upper atmosphere. Ion, electron, and neutral density profiles with altitude, collected on the sun‐lit inbound portion of the spacecraft orbit have been analyzed. It was found that neutral species, measured between ~160 and 200 km, behave consistently with the bulk atmosphere and that variations in ion density profiles follow neutral profile variations at the same altitudes in 70% of the observations. In the remaining 30%, additional structure was apparent in the ionized species' profiles that were found to preferentially lie in regions of strong crustal field or to be measured near dawn. A 1‐D ionospheric model was used to show that many observed features in plasma profiles are directly driven by neutral atmospheric features, providing strong evidence for ion‐neutral coupling in the atmosphere of Mars.
Kelvin‐Helmholtz Waves Magnetic Curvature and Vorticity: Four‐Spacecraft Cluster Observations
Authors: Kieokaew Rungployphan , Foullon Claire
Published: May 2019

[1] Magnetopause Kelvin‐Helmholtz (KH) waves are rich in complex magnetic and flow structures which are key to understand the role of these waves in facilitating the solar wind plasma transport into the Earth's magnetosphere. Four spacecraft in tetrahedral configuration provide the tools necessary for characterizing in situ magnetic geometry and vortical flow. We apply the tools on KH waves observed by Cluster inside an electron boundary layer on the duskside magnetopause. Magnetic curvature and flow vorticity properties of the KH waves are obtained for various solar wind conditions. Smaller curvature radius and higher‐positive vorticity are found for longer wavelength. Changes in KH wavelengths observed with relatively fixed tetrahedron size allow us to resolve magnetic curvature in multiscales. For the first time in a space plasma, we report the dependence of the curvature radius measurement on the ratio of the tetrahedron size to the wavelength, consistent with nonlinear spatial variations of magnetic structures that would be resolved by nested cross‐scale spacecraft tetrahedrons. Negative vorticity is found to develop in the rolled‐up vortex, adjacent to positive vorticity in the vortex core. The strength of negative vorticity is found to increase with the solar wind proton density and proton bulk flow speed. This study provides observational evidence of multiscale magnetic structures and is useful for understanding the development of rolled‐up vortex signatures during various stages of solar wind‐controlled KH wave evolution.
Clustering River Profiles to Classify Geomorphic Domains
Authors: Clubb Fiona J. , Bookhagen Bodo , Rheinwalt Aljoscha
Published: May 2019

The structure and organization of river networks has been used for decades to investigate the influence of climate and tectonics on landscapes. The majority of these studies either analyze rivers in profile view by extracting channel steepness or calculate planform metrics such as drainage density. However, these techniques rely on the assumption of homogeneity: that intrinsic and external factors are spatially or temporally invariant over the measured profile. This assumption is violated for the majority of Earth's landscapes, where variations in uplift rate, rock strength, climate, and geomorphic process are almost ubiquitous. We propose a method for classifying river profiles to identify landscape regions with similar characteristics by adapting hierarchical clustering algorithms developed for time series data. We first test our clustering on two landscape evolution scenarios and find that we can successfully cluster regions with different erodibility and detect the transient response to sudden base level fall. We then test our method in two real landscapes: first in Bitterroot National Forest, Idaho, where we demonstrate that our method can detect transient incision waves and the topographic signature of fluvial and debris flow process regimes; and second, on Santa Cruz Island, California, where our technique identifies spatial patterns in lithology not detectable through normalized channel steepness analysis. By calculating channel steepness separately for each cluster, our method allows the extraction of more reliable steepness metrics than if calculated for the landscape as a whole. These examples demonstrate the method's ability to disentangle fluvial morphology in complex lithological and tectonic settings.
Frequency-tunable continuous-wave random lasers at terahertz frequencies
Authors: Biasco Simone , Beere Harvey E. , Ritchie David A. , Li Lianhe , Davies A. Giles , Linfield Edmund H. , Vitiello Miriam S.
Published: May 2019

Random lasers are a class of devices in which feedback arises from multiple elastic scattering in a highly disordered structure, providing an almost ideal light source for artefact-free imaging due to achievable low spatial coherence. However, for many applications ranging from sensing and spectroscopy to speckle-free imaging, it is essential to have high-radiance sources operating in continuous-wave (CW). In this paper, we demonstrate CW operation of a random laser using an electrically pumped quantum-cascade laser gain medium in which a bi-dimensional (2D) random distribution of air holes is patterned into the top metal waveguide. We obtain a highly collimated vertical emission at ~3 THz, with a 430 GHz bandwidth, device operation up to 110 K, peak (pulsed) power of 21 mW, and CW emission of 1.7 mW. Furthermore, we show that an external cavity formed with a movable mirror can be used to tune a random laser, obtaining continuous frequency tuning over 11 GHz.
R406 elicits anti-Warburg effect via Syk-dependent and -independent mechanisms to trigger apoptosis in glioma stem cells
Authors: Sun Shuxin , Xue Dongdong , Chen Zhijie , Ou-yang Ying , Zhang Ji , Mai Jialuo , Gu Jiayv , Lu Wanjun , Liu Xincheng , Liu Wenfeng , Sheng Longxiang , Lu Bingzheng , Lin Yuan , Xing Fan , Chen Zhongping , Mou Yonggao , Yan Guangmei , Zhu Wenbo , Sai Ke
Published: May 2019

Given that glioma stem cells (GSCs) play a critical role in the initiation and chemoresistance in glioblastoma multiforme (GBM), targeting GSCs is an attractive strategy to treat GBM. Utilizing an anti-cancer compound library, we identified R406, the active metabolite of a FDA-approved Syk inhibitor for immune thrombocytopenia (ITP), with remarkable cytotoxicity against GSCs but not normal neural stem cells. R406 significantly inhibited neurosphere formation and triggered apoptosis in GSCs. R406 induced a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS) and subsequently production of excess ROS in GSCs. R406 also diminished tumor growth and efficiently sensitized gliomas to temozolomide in GSC-initiating xenograft mouse models. Mechanistically, the anti-GSC effect of R406 was due to the disruption of Syk/PI3K signaling in Syk-positive GSCs and PI3K/Akt pathway in Syk-negative GSCs respectively. Overall, these findings not only identify R406 as a promising GSC-targeting agent but also reveal the important role of Syk and PI3K pathways in the regulation of energy metabolism in GSCs.
3-deazaneplanocin A protects against cisplatin-induced renal tubular cell apoptosis and acute kidney injury by restoration of E-cadherin expression
Authors: Ni Jun , Hou Xiying , Wang Xueqiao , Shi Yinfeng , Xu Liuqing , Zheng Xiaoqing , Liu Na , Qiu Andong , Zhuang Shougang
Published: May 2019

3-deazaneplanocin A (3-DZNeP) has been used as an inhibitor of enhancer of zeste homolog 2 (EZH2). Here, we explore the role and underlying mechanisms action of 3-DZNeP in abrogating cisplatin nephrotoxicity. Exposure of cultured mouse renal proximal tubular epithelial cells (mTECs) to cisplatin resulted in dose and time-dependent cleavage of caspase-3, decrease of cell viability, and increase of histone H3 lysine 27 trimethylation (H3K27me3), whereas expression levels of EZH2, a major methyltransferase of H3K27me3, were not affected. Treatment with 3-DZNeP significantly inhibited cisplatin-induced activation of caspase-3, apoptosis, loss of cell viability but did not alter levels of EZH2 and H3K27me3 in cultured mTECs. 3-DZNeP treatment did not affect activation of extracellular signal-regulated kinase (ERK) 1/2, p38 or c-Jun N-terminal kinases (JNK) 1/2, which contribute to renal epithelial cell death, but caused dose-dependent restoration of E-cadherin in mTECs exposed to cisplatin. Silencing of E-cadherin expression by siRNA abolished the cytoprotective effects of 3-DZNeP. In contrast, 3-DZNeP treatment potentiated the cytotoxic effect of cisplatin in H1299, a non-small cell lung cancer cell line that expresses lower E-cadherin levels. Finally, administration of 3-DZNeP attenuated renal dysfunction, morphological damage, and renal tubular cell death, which was accompanied by E-cadherin preservation, in a mouse model of cisplatin nephrotoxicity. Overall, these data indicate that 3-DZNeP suppresses cisplatin-induced tubular epithelial cell apoptosis and acute kidney injury via an E-cadherin-dependent mechanism, and suggest that combined application of 3-DZNeP with cisplatin would be a novel chemotherapeutic strategy that enhances the anti-tumor effect of cisplatin and reduces its nephrotoxicity.
Kremen1-induced cell death is regulated by homo- and heterodimerization
Authors: Sumia Iffat , Pierani Alessandra , Causeret Frédéric
Published: May 2019

In multicellular organisms, cell death pathways allow the removal of abnormal or unwanted cells. Their dysregulation can lead either to excessive elimination or to inappropriate cell survival. Evolutionary constraints ensure that such pathways are strictly regulated in order to restrain their activation to the appropriate context. We have previously shown that the transmembrane receptor Kremen1 behaves as a dependence receptor, triggering cell death unless bound to its ligand Dickkopf1. In this study, we reveal that Kremen1 apoptotic signaling requires homodimerization of the receptor. Dickkopf1 binding inhibits Kremen1 multimerization and alleviates cell death, whereas forced dimerization increases apoptotic signaling. Furthermore, we show that Kremen2, a paralog of Kremen1, which bears no intrinsic apoptotic activity, binds and competes with Kremen1. Consequently, Kremen2 is a very potent inhibitor of Kremen1-induced cell death. Kremen1 was proposed to act as a tumor suppressor, preventing cancer cell survival in a ligand-poor environment. We found that KREMEN2 expression is increased in a large majority of cancers, suggesting it may confer increased survival capacity. Consistently, low KREMEN2 expression is a good prognostic for patient survival in a variety of cancers.
CXCL4 assembles DNA into liquid crystalline complexes to amplify TLR9-mediated interferon-α production in systemic sclerosis
Authors: Lande Roberto , Lee Ernest Y. , Palazzo Raffaella , Marinari Barbara , Pietraforte Immacolata , Santos Giancarlo Santiago , Mattenberger Yves , Spadaro Francesca , Stefanantoni Katia , Iannace Nicoletta , Dufour Aleksandra Maria , Falchi Mario , Bianco Manuela , Botti Elisabetta , Bianchi Luca , Alvarez Montserrat , Riccieri Valeria , Truchetet Marie-Elise , C.L. Wong Gerard , Chizzolini Carlo , Frasca Loredana
Published: May 2019

Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by fibrosis and vasculopathy. CXCL4 represents an early serum biomarker of severe SSc and likely contributes to inflammation via chemokine signaling pathways, but the exact role of CXCL4 in SSc pathogenesis is unclear. Here, we elucidate an unanticipated mechanism for CXCL4-mediated immune amplification in SSc, in which CXCL4 organizes “self” and microbial DNA into liquid crystalline immune complexes that amplify TLR9-mediated plasmacytoid dendritic cell (pDC)-hyperactivation and interferon-α production. Surprisingly, this activity does not require CXCR3, the CXCL4 receptor. Importantly, we find that CXCL4-DNA complexes are present in vivo and correlate with type I interferon (IFN-I) in SSc blood, and that CXCL4-positive skin pDCs coexpress IFN-I-related genes. Thus, we establish a direct link between CXCL4 overexpression and the IFN-I-gene signature in SSc and outline a paradigm in which chemokines can drastically modulate innate immune receptors without being direct agonists.
High mitogenic stimulation arrests angiogenesis
Authors: Pontes-Quero Samuel , Fernández-Chacón Macarena , Luo Wen , Lunella Federica Francesca , Casquero-Garcia Verónica , Garcia-Gonzalez Irene , Hermoso Ana , Rocha Susana F. , Bansal Mayank , Benedito Rui
Published: May 2019

Appropriate therapeutic modulation of endothelial proliferation and sprouting is essential for the effective inhibition of angiogenesis in cancer or its induction in cardiovascular disease. The current view is that an increase in growth factor concentration, and the resulting mitogenic activity, increases both endothelial proliferation and sprouting. Here, we modulate mitogenic stimuli in different vascular contexts by interfering with the function of the VEGF and Notch signalling pathways at high spatiotemporal resolution in vivo. Contrary to the prevailing view, our results indicate that high mitogenic stimulation induced by VEGF, or Notch inhibition, arrests the proliferation of angiogenic vessels. This is due to the existence of a bell-shaped dose-response to VEGF and MAPK activity that is counteracted by Notch and p21, determining whether endothelial cells sprout, proliferate, or become quiescent. The identified mechanism should be considered to achieve optimal therapeutic modulation of angiogenesis.
Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly
Authors: Gui Xinrui , Luo Feng , Li Yichen , Zhou Heng , Qin Zhenheng , Liu Zhenying , Gu Jinge , Xie Muyun , Zhao Kun , Dai Bin , Shin Woo Shik , He Jianhua , He Lin , Jiang Lin , Zhao Minglei , Sun Bo , Li Xueming , Liu Cong , Li Dan
Published: May 2019

Subcellular membrane-less organelles consist of proteins with low complexity domains. Many of them, such as hnRNPA1, can assemble into both a polydisperse liquid phase and an ordered solid phase of amyloid fibril. The former mirrors biological granule assembly, while the latter is usually associated with neurodegenerative disease. Here, we observe a reversible amyloid formation of hnRNPA1 that synchronizes with liquid–liquid phase separation, regulates the fluidity and mobility of the liquid-like droplets, and facilitates the recruitment of hnRNPA1 into stress granules. We identify the reversible amyloid-forming cores of hnRNPA1 (named hnRACs). The atomic structures of hnRACs reveal a distinct feature of stacking Asp residues, which contributes to fibril reversibility and explains the irreversible pathological fibril formation caused by the Asp mutations identified in familial ALS. Our work characterizes the structural diversity and heterogeneity of reversible amyloid fibrils and illuminates the biological function of reversible amyloid formation in protein phase separation.
Rapid unimolecular reaction of stabilized Criegee intermediates and implications for atmospheric chemistry
Authors: Long Bo , Bao Junwei Lucas , Truhlar Donald G.
Published: May 2019

Elucidating atmospheric oxidation mechanisms is necessary for estimating the lifetimes of atmospheric species and understanding secondary organic aerosol formation and atmospheric oxidation capacity. We report an unexpectedly fast mechanistic pathway for the unimolecular reactions of large stabilized Criegee intermediates, which involves the formation of bicyclic structures from large Criegee intermediates containing an aldehyde group. The barrier heights of the mechanistic pathways are unexpectedly low – about 2–3 kcal/mol – and are at least 10 kcal/mol lower than those of hydrogen shift processes in large syn Criegee intermediates; and the calculated rate constants show that the mechanistic pathways are 105-109 times faster than those of the corresponding hydrogen shift processes. The present findings indicate that analogous low-energy pathways can now also be expected in other large Criegee intermediates and that oxidative capacity of some Criegee intermediates is smaller than would be predicted by existing models.
A modular degron library for synthetic circuits in mammalian cells
Authors: Chassin Hélène , Müller Marius , Tigges Marcel , Scheller Leo , Lang Moritz , Fussenegger Martin
Published: May 2019

Tight control over protein degradation is a fundamental requirement for cells to respond rapidly to various stimuli and adapt to a fluctuating environment. Here we develop a versatile, easy-to-handle library of destabilizing tags (degrons) for the precise regulation of protein expression profiles in mammalian cells by modulating target protein half-lives in a predictable manner. Using the well-established tetracycline gene-regulation system as a model, we show that the dynamics of protein expression can be tuned by fusing appropriate degron tags to gene regulators. Next, we apply this degron library to tune a synthetic pulse-generating circuit in mammalian cells. With this toolbox we establish a set of pulse generators with tailored pulse lengths and magnitudes of protein expression. This methodology will prove useful in the functional roles of essential proteins, fine-tuning of gene-expression systems, and enabling a higher complexity in the design of synthetic biological systems in mammalian cells.
Vectorizing the spatial structure of high-harmonic radiation from gas
Authors: Kong F. , Zhang C. , Larocque H. , Li Z. , Bouchard F. , Ko D. H. , Brown G. G. , Korobenko A. , Hammond T. J. , Boyd Robert W. , Karimi E. , Corkum P. B.
Published: May 2019

Strong field laser physics has primarily been concerned with controlling beams in time while keeping their spatial profiles invariant. In the case of high harmonic generation, the harmonic beam is the result of the coherent superposition of atomic dipole emissions. Therefore, fundamental beams can be tailored in space, and their spatial characteristics will be imparted onto the harmonics. Here we produce high harmonics using a space-varying polarized fundamental laser beam, which we refer to as a vector beam. By exploiting the natural evolution of a vector beam as it propagates, we convert the fundamental beam into high harmonic radiation at its focus where the polarization is primarily linear. This evolution results in circularly polarized high harmonics in the far field. Such beams will be important for ultrafast probing of magnetic materials.
Inhibition of MYC by the SMARCB1 tumor suppressor
Authors: Weissmiller April M. , Wang Jing , Lorey Shelly L. , Howard Gregory C. , Martinez Ernest , Liu Qi , Tansey William P.
Published: May 2019

SMARCB1 encodes the SNF5 subunit of the SWI/SNF chromatin remodeler. SNF5 also interacts with the oncoprotein transcription factor MYC and is proposed to stimulate MYC activity. The concept that SNF5 is a coactivator for MYC, however, is at odds with its role as a tumor-suppressor, and with observations that loss of SNF5 leads to activation of MYC target genes. Here, we reexamine the relationship between MYC and SNF5 using biochemical and genome-wide approaches. We show that SNF5 inhibits the DNA-binding ability of MYC and impedes target gene recognition by MYC in cells. We further show that MYC regulation by SNF5 is separable from its role in chromatin remodeling, and that reintroduction of SNF5 into SMARCB1-null cells mimics the primary transcriptional effects of MYC inhibition. These observations reveal that SNF5 antagonizes MYC and provide a mechanism to explain how loss of SNF5 can drive malignancy.
Type-I hyperbolic metasurfaces for highly-squeezed designer polaritons with negative group velocity
Authors: Yang Yihao , Qin Pengfei , Lin Xiao , Li Erping , Wang Zuojia , Zhang Baile , Chen Hongsheng
Published: May 2019

Hyperbolic polaritons in van der Waals materials and metamaterial heterostructures provide unprecedented control over light-matter interaction at extreme nanoscales. Here we propose a concept of type-I hyperbolic metasurface supporting highly-squeezed magnetic designer polaritons, which act as magnetic analogs of hyperbolic polaritons in the hexagonal boron nitride (h-BN) in the first Reststrahlen band. Compared with the natural h-BN, the size and spacing of the metasurface unit cell can be readily engineered, allowing for manipulating designer polaritons in frequency and space with greater flexibility. Microwave experimental measurements display a cone-like dispersion in momentum space, exhibiting an effective refractive index up to 60 and a group velocity down to c/400. Tailoring the metasurface, we demonstrate an ultra-compact integrated designer polariton circuit including high-transmission 90° sharp bending waveguides and waveguide splitters. The present metasurface could serve as a platform for polaritonics, and find applications in waveguiding, terahertz sensing, subdiffraction focusing/imaging, low-threshold terahertz Cherenkov radiation, and wireless energy transfer.
Network analysis of synthesizable materials discovery
Authors: Aykol Muratahan , Hegde Vinay I. , Hung Linda , Suram Santosh , Herring Patrick , Wolverton Chris , Hummelshøj Jens S.
Published: May 2019

Assessing the synthesizability of inorganic materials is a grand challenge for accelerating their discovery using computations. Synthesis of a material is a complex process that depends not only on its thermodynamic stability with respect to others, but also on factors from kinetics, to advances in synthesis techniques, to the availability of precursors. This complexity makes the development of a general theory or first-principles approach to synthesizability currently impractical. Here we show how an alternative pathway to predicting synthesizability emerges from the dynamics of the materials stability network: a scale-free network constructed by combining the convex free-energy surface of inorganic materials computed by high-throughput density functional theory and their experimental discovery timelines extracted from citations. The time-evolution of the underlying network properties allows us to use machine-learning to predict the likelihood that hypothetical, computer-generated materials will be amenable to successful experimental synthesis.
Black phosphorene as a hole extraction layer boosting solar water splitting of oxygen evolution catalysts
Authors: Zhang Kan , Jin Bingjun , Park Cheolwoo , Cho Yoonjun , Song Xiufeng , Shi Xinjian , Zhang Shengli , Kim Wooyul , Zeng Haibo , Park Jong Hyeok
Published: May 2019

As the development of oxygen evolution co-catalysts (OECs) is being actively undertaken, the tailored integration of those OECs with photoanodes is expected to be a plausible avenue for achieving highly efficient solar-assisted water splitting. Here, we demonstrate that a black phosphorene (BP) layer, inserted between the OEC and BiVO4 can improve the photoelectrochemical performance of pre-optimized OEC/BiVO4 (OEC: NiOOH, MnOx, and CoOOH) systems by 1.2∼1.6-fold, while the OEC overlayer, in turn, can suppress BP self-oxidation to achieve a high durability. A photocurrent density of 4.48 mA·cm−2 at 1.23 V vs reversible hydrogen electrode (RHE) is achieved by the NiOOH/BP/BiVO4 photoanode. It is found that the intrinsic p-type BP can boost hole extraction from BiVO4 and prolong holes trapping lifetime on BiVO4 surface. This work sheds light on the design of BP-based devices for application in solar to fuel conversion, and also suggests a promising nexus between semiconductor and electrocatalyst.
Hydrogen embrittlement in metallic nanowires
Authors: Yin Sheng , Cheng Guangming , Chang Tzu-Hsuan , Richter Gunther , Zhu Yong , Gao Huajian
Published: May 2019

Although hydrogen embrittlement has been observed and extensively studied in a wide variety of metals and alloys, there still exist controversies over the underlying mechanisms and a fundamental understanding of hydrogen embrittlement in nanostructures is almost non-existent. Here we use metallic nanowires (NWs) as a platform to study hydrogen embrittlement in nanostructures where deformation and failure are dominated by dislocation nucleation. Based on quantitative in-situ transmission electron microscopy nanomechanical testing and molecular dynamics simulations, we report enhanced yield strength and a transition in failure mechanism from distributed plasticity to localized necking in penta-twinned Ag NWs due to the presence of surface-adsorbed hydrogen. In-situ stress relaxation experiments and simulations reveal that the observed embrittlement in metallic nanowires is governed by the hydrogen-induced suppression of dislocation nucleation at the free surface of NWs.
Structural mechanism underlying G protein family-specific regulation of G protein-gated inwardly rectifying potassium channel
Authors: Kano Hanaho , Toyama Yuki , Imai Shunsuke , Iwahashi Yuta , Mase Yoko , Yokogawa Mariko , Osawa Masanori , Shimada Ichio
Published: May 2019

G protein-gated inwardly rectifying potassium channel (GIRK) plays a key role in regulating neurotransmission. GIRK is opened by the direct binding of the G protein βγ subunit (Gβγ), which is released from the heterotrimeric G protein (Gαβγ) upon the activation of G protein-coupled receptors (GPCRs). GIRK contributes to precise cellular responses by specifically and efficiently responding to the Gi/o-coupled GPCRs. However, the detailed mechanisms underlying this family-specific and efficient activation are largely unknown. Here, we investigate the structural mechanism underlying the Gi/o family-specific activation of GIRK, by combining cell-based BRET experiments and NMR analyses in a reconstituted membrane environment. We show that the interaction formed by the αA helix of Gαi/o mediates the formation of the Gαi/oβγ-GIRK complex, which is responsible for the family-specific activation of GIRK. We also present a model structure of the Gαi/oβγ-GIRK complex, which provides the molecular basis underlying the specific and efficient regulation of GIRK.
Targeting the HIV-infected brain to improve ischemic stroke outcome
Authors: Bertrand Luc , Méroth Fannie , Tournebize Marie , Leda Ana Rachel , Sun Enze , Toborek Michal
Published: May 2019

HIV-associated cerebrovascular events remain highly prevalent even in the current era of antiretroviral therapy (ART). We hypothesize that low-level HIV replication and associated inflammation endure despite antiretroviral treatment and affect ischemic stroke severity and outcomes. Using the EcoHIV infection model and the middle cerebral artery occlusion as the ischemic stroke model in mice, we present in vivo analysis of the relationship between HIV and stroke outcome. EcoHIV infection increases infarct size and negatively impacts tissue and functional recovery. Ischemic stroke also results in an increase in EcoHIV presence in the affected regions, suggesting post-stroke reactivation that magnifies pro-inflammatory status. Importantly, ART with a high CNS penetration effectiveness (CPE) is more beneficial than low CPE treatment in limiting tissue injury and accelerating post-stroke recovery. These results provide potential insight for treatment of HIV-infected patients that are at risk of developing cerebrovascular disease, such as ischemic stroke.
Meta-analytic evidence that sexual selection improves population fitness
Authors: Cally Justin G. , Stuart-Fox Devi , Holman Luke
Published: May 2019

Sexual selection has manifold ecological and evolutionary consequences, making its net effect on population fitness difficult to predict. A powerful empirical test is to experimentally manipulate sexual selection and then determine how population fitness evolves. Here, we synthesise 459 effect sizes from 65 experimental evolution studies using meta-analysis. We find that sexual selection on males tends to elevate the mean and reduce the variance for many fitness traits, especially in females and in populations evolving under stressful conditions. Sexual selection had weaker effects on direct measures of population fitness such as extinction rate and proportion of viable offspring, relative to traits that are less closely linked to population fitness. Overall, we conclude that the beneficial population-level consequences of sexual selection typically outweigh the harmful ones and that the effects of sexual selection can differ between sexes and environments. We discuss the implications of these results for conservation and evolutionary biology.
Plasmonic photosynthesis of C1–C3 hydrocarbons from carbon dioxide assisted by an ionic liquid
Authors: Yu Sungju , Jain Prashant K.
Published: May 2019

Photochemical conversion of CO2 into fuels has promise as a strategy for storage of intermittent solar energy in the form of chemical bonds. However, higher-energy-value hydrocarbons are rarely produced by this strategy, because of kinetic challenges. Here we demonstrate a strategy for green-light-driven synthesis of C1–C3 hydrocarbons from CO2 and H2O. In this approach, plasmonic excitation of Au nanoparticles produces a charge-rich environment at the nanoparticle/solution interface conducive for CO2 activation, while an ionic liquid stabilizes charged intermediates formed at this interface, facilitating multi-step reduction and C–C coupling. Methane, ethylene, acetylene, propane, and propene are photosynthesized with a C2+ selectivity of ~50% under the most optimal conditions. Hydrocarbon turnover exhibits a volcano relationship as a function of the ionic liquid concentration, the kinetic analysis of which coupled with density functional theory simulations provides mechanistic insights into the synergy between plasmonic excitation and the ionic liquid.
Publisher Correction: Parent of origin genetic effects on methylation in humans are common and influence complex trait variation
Authors: Zeng Yanni , Amador Carmen , Xia Charley , Marioni Riccardo , Sproul Duncan , Walker Rosie M. , Morris Stewart W. , Bretherick Andrew , Canela-Xandri Oriol , Boutin Thibaud S. , Clark David W. , Campbell Archie , Rawlik Konrad , Hayward Caroline , Nagy Reka , Tenesa Albert , Porteous David J. , Wilson James F. , Deary Ian J. , Evans Kathryn L. , McIntosh Andrew M. , Navarro Pau , Haley Chris S.
Published: May 2019

In the original version of this Article, the legend in the upper panel of Figure 2 incorrectly read ‘paternal imprinting’ and should have read ‘maternal imprinting’. This has been corrected in both the PDF and HTML versions of the Article.
Author Correction: Hurricane María tripled stem breaks and doubled tree mortality relative to other major storms
Authors: Uriarte María , Thompson Jill , Zimmerman Jess K.
Published: May 2019

The original version of this Article omitted the following from the Acknowledgements: Gabriel Arellano was instrumental in collecting post-María Hurricane data, as part of the Next Generation Ecosystem Experiments-Tropics, funded by the U.S. Department of Energy, Office of Science, Office of Biological and Environmental Research. This has now been corrected in both the PDF and HTML versions of the Article.
Publisher Correction: A space–time tradeoff for implementing a function with master equation dynamics
Authors: Wolpert David H. , Kolchinsky Artemy , Owen Jeremy A.
Published: May 2019

The original version of the Supplementary Information associated with this Article contained an error throughout in which all inline references to Theorems, Definitions and Lemmas given in the main Article were incorrectly given as ‘??’. The HTML has been updated to include a corrected version of the Supplementary Information.
Recent advances in the production of recombinant glycoconjugate vaccines
Authors: Kay Emily , Cuccui Jon , Wren Brendan W.
Published: May 2019

Glycoconjugate vaccines against bacteria are one of the success stories of modern medicine and have led to a significant reduction in the global occurrence of bacterial meningitis and pneumonia. Glycoconjugate vaccines are produced by covalently linking a bacterial polysaccharide (usually capsule, or more recently O-antigen), to a carrier protein. Given the success of glycoconjugate vaccines, it is surprising that to date only vaccines againstHaemophilus influenzaetype b,Neisseria meningitisandStreptococcus pneumoniaehave been fully licenced. This is set to change through the glycoengineering of recombinant vaccines in bacteria, such asEscherichia coli, that act as mini factories for the production of an inexhaustible and renewable supply of pure vaccine product. The recombinant process, termed Protein Glycan Coupling Technology (PGCT) or bioconjugation, offers a low-cost option for the production of pure glycoconjugate vaccines, with the in-built flexibility of adding different glycan/protein combinations for custom made vaccines. Numerous vaccine candidates have now been made using PGCT, which include those improving existing licenced vaccines (e.g., pneumococcal), entirely new vaccines for both Gram-positive and Gram-negative bacteria, and (because of the low production costs) veterinary pathogens. Given the continued threat of antimicrobial resistance and the potential peril of bioterrorist agents, the production of new glycoconjugate vaccines against old and new bacterial foes is particularly timely. In this review, we will outline the component parts of bacterial PGCT, including recent advances, the advantages and limitations of the technology, and future applications and perspectives.
In-planta expression of insecticidal proteins provides protection against lepidopteran insects
Authors: Rauf Imran , Javaid Shaista , Naqvi Rubab Zahra , Mustafa Tanveer , Amin Imran , Mukhtar Zahid , Jander Georg , Mansoor Shahid
Published: May 2019

The development of advanced biotechnological control strategies opens a new era of environment friendly pest management. The current study is part of such an effort, in which we developed a control strategy based on gene pyramiding that confers broad-spectrum resistance against lepidopteran (Helicoverpa armigera and Spodoptera litura) and hemipteran (Myzus persicae, Phenacoccus solenopsis, and Bemisia tabaci) insect pests. Previously, we reported a double gene construct expressing Hvt and lectin in tobacco (Nicotiana tabacum) plants under phloem specific promoters which confers resistance against hemipteran insects. Here we extended our studies by evaluating the advanced generation of these tobacco plants expressing hvt-lectin against lepidopteran insects. Tobacco plants expressing both toxins were tested against H. armigera and S. litura. Insect bioassay results showed 100% mortality of H. armigera within 48–72 hours and 100% mortality of S. litura within 72–96 hours. Our results suggest that the use of both toxins as a gene pyramiding strategy to control both lepidopteran and hemipterans insects on commercial basis to reduce the use of chemical pesticides.
Mouse models and strain-dependency of Chédiak-Higashi syndrome-associated neurologic dysfunction
Authors: Hedberg-Buenz Adam , Dutca Laura M. , Larson Demelza R. , Meyer Kacie J. , Soukup Dana A. , van der Heide Carly J. , Mercer Hannah E. , Wang Kai , Anderson Michael G.
Published: May 2019

Chédiak-Higashi syndrome (CHS) is a lethal disorder caused by mutations in the LYST gene that involves progressive neurologic dysfunction. Lyst-mutant mice exhibit neurologic phenotypes that are sensitive to genetic background. On the DBA/2J-, but not on the C57BL/6J-background, Lyst-mutant mice exhibit overt tremor phenotypes associated with loss of cerebellar Purkinje cells. Here, we tested whether assays for ataxia could measure this observed strain-dependency, and if so, establish parameters for empowering phenotype- and candidate-driven approaches to identify genetic modifier(s). A composite phenotypic scoring system distinguished phenotypes in Lyst-mutants and uncovered a previously unrecognized background difference between wild-type C57BL/6J and DBA/2J mice. Accelerating rotarod performance also distinguished phenotypes in Lyst-mutants, but at more advanced ages. These results establish that genetic background, Lyst genotype, and age significantly influence the severity of CHS-associated neurologic deficits. Purkinje cell quantifications likewise distinguished phenotypes of Lyst-mutant mice, as well as background differences between wild-type C57BL/6J and DBA/2J mice. To aid identification of potential genetic modifier genes causing these effects, we searched public datasets for cerebellar-expressed genes that are differentially expressed and/or contain potentially detrimental genetic variants. From these approaches, Nos1, Prdx2, Cbln3, Gnb1, Pttg1 were confirmed to be differentially expressed and leading candidates.
Author Correction: Spatiotemporal dynamics and risk factors for human Leptospirosis in Brazil
Authors: Baquero Oswaldo Santos , Machado Gustavo
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.
RNA-seq analysis of the salivary glands and midgut of the Argasid tick Ornithodoros rostratus
Authors: Araujo Ricardo N. , Silva Naylene C. S. , Mendes-Sousa Antonio , Paim Rafaela , Costa Gabriel C. A. , Dias Luciana R. , Oliveira Karla , Sant’Anna Mauricio R. V. , Gontijo Nelder F. , Pereira Marcos H. , Pessoa Grasielle D. , Valenzuela Jesus G. , Koerich Leonardo B. , Oliveira Fabiano
Published: May 2019

Ornithodoros rostratus is a South American argasid tick which importance relies on its itchy bite and potential as disease vector. They feed on a wide variety of hosts and secrete different molecules in their saliva and intestinal content that counteract host defences and help to accommodate and metabolize the relatively large quantity of blood upon feeding. The present work describes the transcriptome profile of salivary gland (SG) and midgut (MG) of O. rostratus using Illumina sequencing. A total of 8,031 contigs were assembled and assigned to different functional classes. Secreted proteins were the most abundant in the SG and accounted for ~67% of all expressed transcripts with contigs with identity to lipocalins and acid tail proteins being the most representative. On the other hand, immunity genes were upregulated in MG with a predominance of defensins and lysozymes. Only 10 transcripts in SG and 8 in MG represented ~30% of all RNA expressed in each tissue and one single contig (the acid tail protein ORN-9707) represented ~7% of all expressed contigs in SG. Results highlight the functional difference of each organ and identified the most expressed classes and contigs of O. rostratus SG and MG.
Comparison of livestock-associated and community-associated Staphylococcus aureus pathogenicity in a mouse model of skin and soft tissue infection
Authors: Randad Pranay R. , Dillen Carly A. , Ortines Roger V. , Mohr David , Aziz Maliha , Price Lance B. , Kaya Hülya , Larsen Jesper , Carroll Karen C. , Smith Tara C. , Miller Lloyd S. , Heaney Christopher D.
Published: May 2019

Industrial hog operation (IHO) workers are at increased risk of carrying Staphylococcus aureus in their nares, particularly strains that are livestock-associated (LA) and multidrug-resistant. The pathogenicity of LA-S. aureus strains remains unclear, with some prior studies suggesting reduced transmission and virulence in humans compared to community-associated methicillin-resistant (CA-MRSA) S. aureus. The objective of this study was to determine the degree to which LA-S. aureus strains contracted by IHO workers cause disease relative to a representative CA-MRSA strain in a mouse model of skin and soft tissue infection (SSTI). Mice infected with CC398 LA-S. aureus strains (IHW398-1 and IHW398-2) developed larger lesion sizes with higher bacterial burden than mice infected with CA-MRSA (SF8300) (p < 0.05). The greatest lesion size and bacterial burden was seen with a CC398 strain that produced a recurrent SSTI in an IHO worker. The LA-S. aureus infected mice had decreased IL-1β protein levels compared with CA-MRSA-infected mice (p < 0.05), suggesting a suboptimal host response to LA-S. aureus SSTIs. WGSA revealed heterogeneity in virulence factor and antimicrobial resistance genes carried by LA-S. aureus and CA-MRSA strains. The observed pathogenicity suggest that more attention should be placed on preventing the spread of LA-S. aureus into human populations.
Serum Concentrations of Citrate, Tyrosine, 2- and 3- Hydroxybutyrate are Associated with Increased 3-Month Mortality in Acute Heart Failure Patients
Authors: Stryeck Sarah , Gastrager Michaela , Degoricija Vesna , Trbušić Matias , Potočnjak Ines , Radulović Bojana , Pregartner Gudrun , Berghold Andrea , Madl Tobias , Frank Saša
Published: May 2019

Considering the already established relationship between the extent of the metabolic dysfunction and the severity of heart failure (HF), it is conceivable that the metabolomic profile of the serum may have a prognostic capacity for 3-month mortality in acute heart failure (AHF). Out of 152 recruited patients, 130 serum samples were subjected to the metabolomic analyses. The 3-month mortality rate was 24.6% (32 patients). Metabolomic profiling by nuclear magnetic resonance spectroscopy found that the serum levels of 2-hydroxybutyrate (2-HB), 3-hydoxybutyrate (3-HB), lactate, citrate, and tyrosine, were higher in patients who died within 3 months compared to those who were alive 3 months after onset of AHF, which was confirmed by univariable logistic regression analyses (p = 0.009, p = 0.005, p = 0.008, p<0.001, and p<0.001, respectively). These associations still remained significant for all tested metabolites except for lactate after adjusting for established prognostic parameters in HF. In conclusion, serum levels of 2-HB, 3-HB, tyrosine, and citrate measured at admission are associated with an increased 3-month mortality rate in AHF patients and might thus be of prognostic value in AHF.
Author Correction: Immune evasion of Borrelia miyamotoi: CbiA, a novel outer surface protein exhibiting complement binding and inactivating properties
Authors: Röttgerding Florian , Wagemakers Alex , Koetsveld Joris , Fingerle Volker , Kirschfink Michael , Hovius Joppe W. , Zipfel Peter F. , Wallich Reinhard , Kraiczy Peter
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.