bluuebunny/crossref_metadata_2025 huggingface dataset:
Significance of Acetate as a Microbial Carbon and Energy Source in the Water Column of Gulf of Mexico: Implications for Marine Carbon Cycling
Authors: Zhuang Guang‐Chao , Peña‐Montenegro Tito D. , Montgomery Andrew , Montoya Joseph P. , Joye Samantha B.
Published: February 2019

Acetate is a key intermediate of organic matter mineralization, but its metabolism remains largely unconstrained in the pelagic ocean. We conducted an integrated biogeochemical study to investigate microbial acetate cycling in the northern Gulf of Mexico with the goal of elucidating the importance of acetate as a carbon and energy source. Acetate was used primarily as an energy source, as evidenced by observed oxidation rates (rate constant k: 0.06–0.22 day−1) that varied between 42% and 96% of total biological acetate uptake (i.e., assimilation + oxidation; k: 0.06–0.34 day−1). The assimilation of acetate into biomass (k: 0.01–0.20 day−1) illustrated the potential significance of acetate as a biomass carbon source, particularly in nutrient‐rich coastal waters. No relationship between acetate assimilation or oxidation and environmental factors, such as chlorophyll and nutrients, was observed. However, elevated acetate uptake in reduced oxygen waters characterized by particulate organic carbon mineralization suggests that acetate metabolism may be a good proxy for particulate organic carbon breakdown. Molecular genetic analysis revealed that SAR11 Alphaproteobacteria were the most abundant heterotrophic bacteria and suggest that they may utilize acetate. At some sites, acetate carbon may have accounted for up to 50.4% of the bacterial carbon production. These results suggest that acetate may serve as an important carbon and energy source for heterotrophic bacteria thus revealing a potentially significant role of acetate for dissolved organic carbon cycling in the ocean.
Seismic Imaging and Physical Properties of the Endeavour Segment: Evidence that Skew Between Mantle and Crustal Magmatic Systems Governs Spreading Center Processes
Authors: Arnoux G. M. , Toomey D. R. , Hooft E. E. E. , Wilcock W. S. D.
Published: February 2019

We invert Pg, PmP, and Pn traveltimes from an active‐source, multiscale tomography experiment to constrain the three‐dimensional isotropic and anisotropic P wave velocity structure of the topmost oceanic mantle and crust and crustal thickness variations beneath the entire Endeavour segment of the Juan de Fuca Ridge. The isotropic velocity structure is characterized by a semicontinuous, narrow (5‐km‐wide) crustal low‐velocity volume that tracks the sinuous ridge axis. Across the Moho, the low‐velocity volume abruptly broadens to approximately 20 km in width and displays a north‐south linear trend that connects the two overlapping spreading centers bounding the segment. From the seismic results, we estimate the thermal structure and melt distribution beneath the Endeavour segment. The thermal structure indicates that the observed skew, or lateral offset, between the crustal and mantle magmatic systems is a consequence of differences in mechanisms of heat transfer at crustal and mantle depths, with the crust and mantle dominated by advection and conduction, respectively. Melt volume estimates exhibit significant along‐axis variations that coincide with the observed skew between the mantle and crustal magmatic systems, with sites of enhanced crustal melt volumes and vigorous hydrothermal activity corresponding to regions where the mantle and crustal magmatic systems are vertically aligned. These results contradict models of ridge segmentation that predict enhanced and reduced melt supply beneath the segment center and ends, respectively. Our results instead support a model in which segment‐scale skew between the crustal and mantle magmatic systems governs magmatic and hydrothermal processes at mid‐ocean ridges.
An Approximate Approach to Nonisothermal Emplacement of Kilometer‐Sized Kilometer‐Deep Sills at Calderas
Authors: Amoruso Antonella , Crescentini Luca
Published: February 2019

Caldera unrest is often caused by kilometer‐sized kilometer‐deep sills. Still unanswered questions include the following: How do sills spread? Why can magma propagate for kilometers without solidifying? Why do ground deformation data rarely, if ever, detect sill propagation? We show that kilometer‐sized kilometer‐deep magmatic sills spread like hydraulic fractures in an infinite medium. How magma propagates depends on overburden pressure, magma viscosity, injection rate, and difference between magma and rock temperatures. A small lag, filled with vapors from the fluid and/or the rock, exists between the propagating magma and fracture fronts. If the sill spreads along an interface, the lag slightly affects isothermal sill spreading but takes a key role in the case of nonisothermal propagation: A sill would stop after few tens of meters without it, unless magma intrudes rocks that are as hot as the solidification temperature or has unrealistic overpressures, because spreading velocity decreases soon to the critical value at which the tip becomes blocked with solidified magma. The lag defers magma solidification as heat exchange between the magma and the rock is effective only behind the thermal‐insulating lag, where magma has some finite thickness and sill opening grows with distance from the tip faster than thickness of solidified magma. Thus, the critical velocity decreases, allowing greater maximum sill sizes. We also show that the ground deformation pattern does not change appreciably over time if the final sill radius is smaller than 2 to 3 km, explaining why deformation is usually attributed to the inflation of a stationary source.
The Effect of Water on Fe‐Mg Interdiffusion Rates in Ringwoodite and Implications for the Electrical Conductivity in the Mantle Transition Zone
Authors: Zhang Baohua , Yoshino Takashi , Zhao Chengcheng
Published: February 2019

We determined the kinetics of Fe‐Mg interdiffusion in ringwoodite aggregates as a function of water content (up to ~6,000 wt. ppm H2O) at 20 GPa and 1,373–1,673 K by the diffusion couple method. The dependence of Fe‐Mg interdiffusivity (DFe‐Mg) on Fe concentration was determined using the Boltzmann‐Matano method. The experimentally reported DFe‐Mg in ringwoodite within 0 ≤ XFe ≤ 0.1 could be fitted by the relation
, where E* = (1 − XFe)EMg + XFeEFe (EMg = 140 ± 5 kJ/mol, EFe = 4 ± 2 kJ/mol), D0 =
 × 10−10 m2/s, n = −0.21 ± 0.10, r = 0.25 ± 0.03, and α = −24 ± 4. The water content exponent r of 0.25 suggests a nonnegligible role of water in enhancing Fe‐Mg interdiffusion in ringwoodite. The length scale over which the chemical heterogeneities are homogenized by Fe‐Mg interdiffusion in the mantle transition zone is estimated to be only a few hundred meters even assuming the whole Earth age. Comparison between the conductivities predicted from Fe‐Mg interdiffusion and those obtained from magnetotelluric surveys suggests that around 0.1 wt.% water can account for the high conductivity anomalies (~10−0.6–10−1 S/m) observed in the lower part of the mantle transition zone.
Electrical Conductivity of NaCl‐Bearing Aqueous Fluids to 900 °C and 5 GPa
Authors: Guo Haihao , Keppler Hans
Published: February 2019

The electrical conductivity of aqueous fluids containing 0.01, 0.1, and 1 M NaCl was measured in a piston‐cylinder apparatus up to 900 °C and 5 GPa. The conductivity generally increases with NaCl concentration, while the pressure and temperature effects are more complex. At 1–2 GPa, the effect of temperature on conductivity is small, while at higher pressures, conductivity increases with temperature. Pressure also enhances conductivity, but only above 300–400 °C. This effect may be due to enhanced ion dissociation in response to an increasing dielectric constant. However, at lower temperatures, conductivity decreases with pressure, probably due to an increase in fluid viscosity. The measured conductivities of NaCl‐H2O fluids up to 900 °C and 5 GPa are reproduced (R2 = 0.953) by a numerical model with log σ = −0.919 − 872.5/T + 7.61 log ρ + 0.852 log c + log Λ0, where σ is the conductivity in S/m, T is temperature in K, c is NaCl concentration in wt%, ρ is the density of pure water (in g/cm3) at given pressure and temperature, and Λ0 is the molar conductivity of NaCl in water at infinite dilution (in S·cm2·mol−1), Λ0 = 1,573 − 1,212 ρ + 537,062/T – 208,122,721/T2. We use our data to model the elevated electrical conductivity in the mantle wedge above subducted slabs. We find that due to the strong conductivity enhancement, in most cases less than one volume percent of aqueous fluid with moderate salinity is sufficient to explain the observed conductivity anomalies.
Evidence of Freezing Pressure in Sea Ice Discrete Brine Inclusions and Its Impact on Aqueous‐Gaseous Equilibrium
Authors: Crabeck O. , Galley R. J. , Mercury L. , Delille B. , Tison J.‐L. , Rysgaard S.
Published: February 2019

Sea ice in part controls surface water properties and the ocean‐atmosphere exchange of greenhouse gases at high latitudes. In sea ice, gas exists dissolved in brine and as air bubbles contained in liquid brine inclusions or as bubbles trapped directly within the ice matrix. Current research on gas dynamics within the ocean‐sea ice‐atmosphere interface has been based on the premise that brine with dissolved air becomes supersaturated with respect to the atmosphere during ice growth. Based on Henry's law, gas bubbles within brine should grow when brine reaches saturation during cooling, given that the total partial pressure of atmospheric gases is above the implicit pressure in brine of 1 atm. Using high‐resolution light microscopy time series imagery of gas bubble evolution inside discrete brine pockets, we observed bubbles shrinking during cooling events in response to the development of freezing pressure above 3 atm. During warming of discrete brine pockets, existing bubbles expand and new bubbles nucleate in response to depressurization. Pressure variation within these inclusions has direct impacts on aqueous‐gaseous equilibrium, indicating that Henry's law at a constant pressure of 1 atm is inadequate to assess the partitioning between dissolved and gaseous fractions of gas in sea ice. This new evidence of pressure build‐up in discrete brine inclusions controlling the solubility of gas and nucleation of bubbles in these inclusions has the potential to affect the transport pathways of air bubbles and dissolved gases within sea ice‐ocean‐atmosphere interface and modifies brine biochemical properties.
CO2 Dynamics Are Strongly Influenced by Low Frequency Atmospheric Pressure Changes in Semiarid Grasslands
Authors: Moya M. R. , Sánchez‐Cañete E. P. , Vargas R. , López‐Ballesteros A. , Oyonarte C. , Kowalski A. S. , Serrano‐Ortiz P. , Domingo F.
Published: February 2019

Due to their large carbon storage capacity and ability to exchange subterranean CO2 with the atmosphere, soils are key components in the carbon balance in semi‐arid ecosystems. Most studies have focused on shallow (e.g., <30 cm depth) soil CO2 dynamics neglecting processes in deeper soil layers where highly CO2‐enriched air can be stored or transported through soil pores and fissures. Here, we examine the relationship among variations in subterranean CO2 molar fraction, volumetric water content, soil temperature and atmospheric pressure during three years within soil profiles (0.15, 0.50, and 1.50 m depths) in two semi‐arid grasslands located in southeastern Spain. We applied a wavelet coherence analysis to study the temporal variability and temporal correlation between the CO2 molar fraction and its covariates (soil temperature, soil moisture and atmospheric pressure). Our results show that CO2 dynamics are strongly influenced by changes in atmospheric pressure from semidiurnal, diurnal and synoptic to monthly time‐scales for all soil depths. In contrast, only weak daily dependencies were found at the surface level (0.15 m) regarding soil temperature and volumetric water content. Atmospheric pressure changes substantially influence variations in the CO2 content (with daily fluctuations of up to 2000 ppm) denoting transportation through soil layers. These results provide insights into the importance of subterranean storage and non‐diffusive gas transport that could influence soil CO2 efflux rates, processes that are not considered when applying the flux‐gradient approach and, which can be especially important in ecosystems with high air permeability between the unsaturated porous media and the atmosphere.
On Inconsistent ROTI Derived From Multiconstellation GNSS Measurements of Globally Distributed GNSS Receivers for Ionospheric Irregularities Characterization
Authors: Liu Zhizhao , Yang Zhe , Xu Dongyang , Morton Y. Jade
Published: February 2019

This study for the first time presents an investigation into the exploitation of multi‐Global Navigation Satellite System (GNSS) observations (Global Positioning System, Globalnaya Navigazionnaya Sputnikovaya Sistema, Galileo, and BeiDou) to characterize ionospheric plasma irregularities, based on the rate of change of total electron content index (ROTI) sampled at 1 s. It is demonstrated that the multi‐GNSS ROTIs can represent temporal evolutions of ionospheric plasma irregularities during a large geomagnetic storm. However, an inconsistency in the magnitudes of multi‐GNSS ROTIs is found among a variety of GNSS receivers (i.e., Javad, Leica, Trimble, and Septentrio). Through cross comparisons between GNSS receivers installed at zero/short baselines and validations by receivers distributed separately, it is observed that the magnitude of ROTI corresponding to each system differs between closely installed and even collocated receivers of different models, as well as between the GNSS signals on the same frequency. From 1‐year (i.e., 2015) data analysis, it is found that the magnitudes of multi‐GNSS ROTIs exhibit the dependence on the receiver type. Among the four GNSS receiver types, the largest discrepancy in the multi‐GNSS ROTIs is observed from Septentrio receivers, while the smallest one is shown by Trimble receivers. A one‐to‐one comparison indicates that the ROTI difference is noticeable and can increase to 4–6 TECu/min under ionospheric irregularities conditions, that is, in the postsunset period of 18–02 local time. To investigate the inconsistency, the effect of adopting different equivalent noise bandwidths in the tracking loop design is discussed, via cross comparisons between a GNSS software‐defined receiver and a collocated Septentrio receiver. The result shows that adopting 15‐ and 2‐Hz noise bandwidths in the tracking loop can cause 0.2‐ to 0.5‐TECu/min differences in the magnitude of ROTI, suggesting that the diverse tracking techniques deployed by various receivers are very likely a major contributor to the inconsistency of multi‐GNSS ROTIs.
Thermochronological Evidence of Early Orogenesis, Eastern Pyrenees, France
Authors: Ternois Sébastien , Odlum Margaret , Ford Mary , Pik Raphaël , Stockli Daniel , Tibari Bouchaïb , Vacherat Arnaud , Bernard Vincent
Published: February 2019

In collisional orogens, distinguishing the thermal signature of early orogenesis from the preceding rift or from subsequent thermal events is a major challenge. We present an integrated geological and low‐temperature thermochronology study of the Paleozoic Agly‐Salvezines crustal block in the retrowedge of the eastern Pyrenees (France). The northern Pyrenees preserves one of the best geological records of a rift‐to‐collision transition. The Agly‐Salvezines block represents the inverted distal European margin of an Aptian–Cenomanian rift system. Seventeen samples were collected throughout the external orogenic massif and analyzed for low‐temperature thermochronology: zircon (U‐Th)/He dating documents the cooling history of the massif during the initiation and early phase of Pyrenean convergence, while apatite (U‐Th)/He dating completes the record of plate collision. Using inverse and forward modeling of new low‐temperature thermochronology data, we show that the Pyrenean retrowedge records two clear phases of orogenic cooling, Late Campanian–Maastrichtian and Ypresian–Bartonian, which we relate to early inversion of the distal rifted margin and main collision, respectively. An earlier, late Aptian–Turonian cooling history is detected, possibly related to rifting and/or postrift. No cooling is evidenced during the Paleocene during which tectonic quiescence is recorded in the adjacent Aquitaine retroforeland basin. Using our low‐temperature thermochronology data and geological constraints, we propose a crustal‐scale sequentially restored model for the tectonic and thermal transition from extension to peak orogenesis in the eastern Pyrenees, which suggests that both thrusting and underplating processes contributed to early inversion of the Aptian–Cenomanian rift system.
RETRACTED ARTICLE: Evolution of substrate-specific gene expression and RNA editing in brown rot wood-decaying fungi
Authors: Wu Baojun , Gaskell Jill , Zhang Jiwei , Toapanta Christina , Ahrendt Steven , Grigoriev Igor V , Blanchette Robert A , Schilling Jonathan S , Master Emma , Cullen Daniel , Hibbett David S
Published: February 2019

Fungi that decay wood have characteristic associations with certain tree species, but the mechanistic bases for these associations are poorly understood. We studied substrate-specific gene expression and RNA editing in six species of wood-decaying fungi from the ‘Antrodia clade’ (Polyporales, Agaricomycetes) on three different wood substrates (pine, spruce, and aspen) in submerged cultures. We identified dozens to hundreds of substrate-biased genes (i.e., genes that are significantly upregulated in one substrate relative to the other two substrates) in each species, and these biased genes are correlated with their host ranges. Evolution of substrate-biased genes is associated with gene family expansion, gain and loss of genes, and variation in cis- and trans- regulatory elements, rather than changes in protein coding sequences. We also demonstrated widespread RNA editing events in the Antrodia clade, which differ from those observed in the Ascomycota in their distribution, substitution types, and the genomic environment. Moreover, we found that substrates could affect editing positions and frequency, including editing events occurring in mRNA transcribed from wood-decay-related genes. This work shows the extent to which gene expression and RNA editing differ among species and substrates, and provides clues into mechanisms by which wood-decaying fungi may adapt to different hosts.
DAP5 increases axonal outgrowth of hippocampal neurons by enhancing the cap-independent translation of DSCR1.4 mRNA
Authors: Seo Ji-Young , Jung Youngseob , Kim Do-Yeon , Ryu Hye Guk , Lee Juhyun , Kim Sung Wook , Kim Kyong-Tai
Published: February 2019

Proper wiring between neurons is indispensable for proper brain function. From the early developmental stage, axons grow and navigate to connect to targets according to specific guidance cues. The accuracy of axonal outgrowth and navigation are controlled by a variety of genes, and mutations and/or deficiencies in these genes are closely related to several brain disorders, such as autism. DSCR1 is one of these genes and regulates actin filament formation in axons. Thus, identifying the detailed regulatory mechanisms of DSCR1 expression is crucial for the understanding of the axon development of neurons; however, these regulatory mechanisms of DSCR1 remain unknown. Here, we discovered that mRNA encoding the DSCR1 isoform DSCR1.4 is present and mainly translated by the cap-independent initiation mechanisms in both the soma and axons of hippocampal neurons. We found that translation of DSCR1.4 mRNA is enhanced by death-associated protein 5 (DAP5), which can bind to DSCR1.4 5′UTR. BDNF-stimulus induced an increase in DAP5 expression and the cap-independent translation efficiency of DSCR1.4 mRNA in axon as well as soma. Furthermore, we showed the importance of the cap-independent translation of DSCR1.4 on enhancement of DSCR1.4 expression by BDNF-stimulus and axonal outgrowth of hippocampal neurons. Our findings suggest a new translational regulatory mechanism for DSCR1.4 expressions and a novel function of DAP5 as a positive regulator of DSCR1.4 mRNA translation induced in soma and axon of hippocampal neurons.
β-arrestin-2 in PAR-1-biased signaling has a crucial role in endothelial function via PDGF-β in stroke
Authors: Kanki Hideaki , Sasaki Tsutomu , Matsumura Shigenobu , Yokawa Satoru , Yukami Toshiro , Shimamura Munehisa , Sakaguchi Manabu , Furuno Tadahide , Suzuki Takahiro , Mochizuki Hideki
Published: February 2019

Thrombin aggravates ischemic stroke and activated protein C (APC) has a neuroprotective effect. Both proteases interact with protease-activated receptor 1, which exhibits functional selectivity and leads to G-protein- and β-arrestin-mediated-biased signal transduction. We focused on the effect of β-arrestin in PAR-1-biased signaling on endothelial function after stroke or high-fat diet (HFD). Thrombin had a rapid disruptive effect on endothelial function, but APC had a slow protective effect. Paralleled by prolonged MAPK 42/44 signaling activation by APC via β-arrestin-2, a lower cleavage rate of PAR-1 for APC than thrombin was quantitatively visualized by bioluminescence video imaging. HFD-fed mice showed lower β-arrestin-2 levels and more severe ischemic injury. The expression of β-arrestin-2 in capillaries and PDGF-β secretion in HFD-fed mice were reduced in penumbra lesions. These results suggested that β-arrestin-2-MAPK-PDGF-β signaling enhanced protection of endothelial function and barrier integrity after stroke.
Correction: Epalrestat, an Aldose Reductase Inhibitor, Restores Erectile Function in Streptozocin-induced Diabetic Rats
Authors: Yang Bai-Bing , Hong Zhi-Wei , Zhang Zheng , Yu Wen , Song Tao , Zhu Lei-Lei , Jiang He-Song , Chen Guo-Tao , Chen Yun , Dai Yu-Tian
Published: February 2019

This Article was originally published under Nature Research’s License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
CDK4/6 inhibitors target SMARCA4-determined cyclin D1 deficiency in hypercalcemic small cell carcinoma of the ovary
Authors: Xue Yibo , Meehan Brian , Macdonald Elizabeth , Venneti Sriram , Wang Xue Qing D. , Witkowski Leora , Jelinic Petar , Kong Tim , Martinez Daniel , Morin Geneviève , Firlit Michelle , Abedini Atefeh , Johnson Radia M. , Cencic Regina , Patibandla Jay , Chen Hongbo , Papadakis Andreas I. , Auguste Aurelie , de Rink Iris , Kerkhoven Ron M. , Bertos Nicholas , Gotlieb Walter H. , Clarke Blaise A. , Leary Alexandra , Witcher Michael , Guiot Marie-Christine , Pelletier Jerry , Dostie Josée , Park Morag , Judkins Alexander R. , Hass Ralf , Levine Douglas A. , Rak Janusz , Vanderhyden Barbara , Foulkes William D. , Huang Sidong
Published: February 2019

Inactivating mutations in SMARCA4 (BRG1), a key SWI/SNF chromatin remodelling gene, underlie small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). To reveal its druggable vulnerabilities, we perform kinase-focused RNAi screens and uncover that SMARCA4-deficient SCCOHT cells are highly sensitive to the inhibition of cyclin-dependent kinase 4/6 (CDK4/6). SMARCA4 loss causes profound downregulation of cyclin D1, which limits CDK4/6 kinase activity in SCCOHT cells and leads to in vitro and in vivo susceptibility to CDK4/6 inhibitors. SCCOHT patient tumors are deficient in cyclin D1 yet retain the retinoblastoma-proficient/p16INK4a-deficient profile associated with positive responses to CDK4/6 inhibitors. Thus, our findings indicate that CDK4/6 inhibitors, approved for a breast cancer subtype addicted to CDK4/6 activation, could be repurposed to treat SCCOHT. Moreover, our study suggests a novel paradigm whereby critically low oncogene levels, caused by loss of a driver tumor suppressor, may also be exploited therapeutically.
Brain songs framework used for discovering the relevant timescale of the human brain
Authors: Deco Gustavo , Cruzat Josephine , Kringelbach Morten L.
Published: February 2019

A key unresolved problem in neuroscience is to determine the relevant timescale for understanding spatiotemporal dynamics across the whole brain. While resting state fMRI reveals networks at an ultraslow timescale (below 0.1 Hz), other neuroimaging modalities such as MEG and EEG suggest that much faster timescales may be equally or more relevant for discovering spatiotemporal structure. Here, we introduce a novel way to generate whole-brain neural dynamical activity at the millisecond scale from fMRI signals. This method allows us to study the different timescales through binning the output of the model. These timescales can then be investigated using a method (poetically named brain songs) to extract the spacetime motifs at a given timescale. Using independent measures of entropy and hierarchy to characterize the richness of the dynamical repertoire, we show that both methods find a similar optimum at a timescale of around 200 ms in resting state and in task data.
The CENP-A centromere targeting domain facilitates H4K20 monomethylation in the nucleosome by structural polymorphism
Authors: Arimura Yasuhiro , Tachiwana Hiroaki , Takagi Hiroki , Hori Tetsuya , Kimura Hiroshi , Fukagawa Tatsuo , Kurumizaka Hitoshi
Published: February 2019

Centromeric nucleosomes are composed of the centromere-specific histone H3 variant CENP-A and the core histones H2A, H2B, and H4. To establish a functional kinetochore, histone H4 lysine-20 (H4K20) must be monomethylated, but the underlying mechanism has remained enigmatic. To provide structural insights into H4K20 methylation, we here solve the crystal structure of a nucleosome containing an H3.1-CENP-A chimera, H3.1CATD, which has a CENP-A centromere targeting domain and preserves essential CENP-A functions in vivo. Compared to the canonical H3.1 nucleosome, the H3.1CATD nucleosome exhibits conformational changes in the H4 N-terminal tail leading to a relocation of H4K20. In particular, the H4 N-terminal tail interacts with glutamine-76 and aspartate-77 of canonical H3.1 while these interactions are cancelled in the presence of the CENP-A-specific residues valine-76 and lysine-77. Mutations of valine-76 and lysine-77 impair H4K20 monomethylation both in vitro and in vivo. These findings suggest that a CENP-A-mediated structural polymorphism may explain the preferential H4K20 monomethylation in centromeric nucleosomes.
Large orbital polarization in nickelate-cuprate heterostructures by dimensional control of oxygen coordination
Authors: Liao Zhaoliang , Skoropata Elizabeth , Freeland J. W. , Guo Er-Jia , Desautels Ryan , Gao Xiang , Sohn Changhee , Rastogi Ankur , Ward T. Zac , Zou Tao , Charlton Timothy , Fitzsimmons Michael R. , Lee Ho Nyung
Published: February 2019

Artificial heterostructures composed of dissimilar transition metal oxides provide unprecedented opportunities to create remarkable physical phenomena. Here, we report a means to deliberately control the orbital polarization in LaNiO3 (LNO) through interfacing with SrCuO2 (SCO), which has an infinite-layer structure for CuO2. Dimensional control of SCO results in a planar-type (P–SCO) to chain-type (C–SCO) structure transition depending on the SCO thickness. This transition is exploited to induce either a NiO5 pyramidal or a NiO6 octahedral structure at the SCO/LNO interface. Consequently, a large change in the Ni d orbital occupation up to ~30% is achieved in P–SCO/LNO superlattices, whereas the Ni eg orbital splitting is negligible in C–SCO/LNO superlattices. The engineered oxygen coordination triggers a metal-to-insulator transition in SCO/LNO superlattices. Our results demonstrate that interfacial oxygen coordination engineering provides an effective means to manipulate the orbital configuration and associated physical properties, paving a pathway towards the advancement of oxide electronics.
Air-stable redox-active nanomagnets with lanthanide spins radical-bridged by a metal–metal bond
Authors: Liu Fupin , Velkos Georgios , Krylov Denis S. , Spree Lukas , Zalibera Michal , Ray Rajyavardhan , Samoylova Nataliya A. , Chen Chia-Hsiang , Rosenkranz Marco , Schiemenz Sandra , Ziegs Frank , Nenkov Konstantin , Kostanyan Aram , Greber Thomas , Wolter Anja U. B. , Richter Manuel , Büchner Bernd , Avdoshenko Stanislav M. , Popov Alexey A.
Published: February 2019

Engineering intramolecular exchange interactions between magnetic metal atoms is a ubiquitous strategy for designing molecular magnets. For lanthanides, the localized nature of 4f electrons usually results in weak exchange coupling. Mediating magnetic interactions between lanthanide ions via radical bridges is a fruitful strategy towards stronger coupling. In this work we explore the limiting case when the role of a radical bridge is played by a single unpaired electron. We synthesize an array of air-stable Ln2@C80(CH2Ph) dimetallofullerenes (Ln2 = Y2, Gd2, Tb2, Dy2, Ho2, Er2, TbY, TbGd) featuring a covalent lanthanide-lanthanide bond. The lanthanide spins are glued together by very strong exchange interactions between 4f moments and a single electron residing on the metal–metal bonding orbital. Tb2@C80(CH2Ph) shows a gigantic coercivity of 8.2 Tesla at 5 K and a high 100-s blocking temperature of magnetization of 25.2 K. The Ln-Ln bonding orbital in Ln2@C80(CH2Ph) is redox active, enabling electrochemical tuning of the magnetism.
Efficient cross-trait penalized regression increases prediction accuracy in large cohorts using secondary phenotypes
Authors: Chung Wonil , Chen Jun , Turman Constance , Lindstrom Sara , Zhu Zhaozhong , Loh Po-Ru , Kraft Peter , Liang Liming
Published: February 2019

We introduce cross-trait penalized regression (CTPR), a powerful and practical approach for multi-trait polygenic risk prediction in large cohorts. Specifically, we propose a novel cross-trait penalty function with the Lasso and the minimax concave penalty (MCP) to incorporate the shared genetic effects across multiple traits for large-sample GWAS data. Our approach extracts information from the secondary traits that is beneficial for predicting the primary trait based on individual-level genotypes and/or summary statistics. Our novel implementation of a parallel computing algorithm makes it feasible to apply our method to biobank-scale GWAS data. We illustrate our method using large-scale GWAS data (~1M SNPs) from the UK Biobank (N = 456,837). We show that our multi-trait method outperforms the recently proposed multi-trait analysis of GWAS (MTAG) for predictive performance. The prediction accuracy for height by the aid of BMI improves fromR2 = 35.8% (MTAG) to 42.5% (MCP + CTPR) or 42.8% (Lasso + CTPR) with UK Biobank data.
Author Correction: The disease resistance protein SNC1 represses the biogenesis of microRNAs and phased siRNAs
Authors: Cai Qiang , Liang Chao , Wang Suikang , Hou Yingnan , Gao Lei , Liu Li , He Wenrong , Ma Wenbo , Mo Beixin , Chen Xuemei
Published: February 2019

The original version of this Article contained an error in the spelling of the author Beixin Mo, which was incorrectly given as Beixing Mo. This has now been corrected in both the PDF and HTML versions of the Article.
A Predictive Model for Cochlear Implant Outcome in Children with Cochlear Nerve Deficiency
Authors: Han Jae Joon , Suh Myung-Whan , Park Moo Kyun , Koo Ja-Won , Lee Jun Ho , Oh Seung Ha
Published: February 2019

The outcome of cochlear implantation (CI) in patients with cochlear nerve deficiency (CND) is variable, resulting in a wide range of speech perception performance, from degrees of environmental sound perception to conversation without lip-reading. Twenty-five cochlear implantees with CND were enrolled retrospectively to determine the factors correlated with CI outcome in patients with CND and to develop a predictive model for CI outcome. CI outcome was evaluated using the Categories of Auditory Performance (CAP) score at 2 years after CI. Patients with negative auditory brainstem response (ABR) showed a significantly lower CAP score than those with positive ABR (2.5 ± 1.7, 4.8 ± 0.7; p = 0.001). The area ratio of vestibulocochlear nerve (VCN) to facial nerve (FN) at the cerebellopontine angle on magnetic resonance images was positively correlated with CI outcome (p < 0.001). With multiple regression analysis, a predictive equation accounting for 66% of variance of CAP score at 2 years after CI was $${\bf{deduced}}:{\bf{CAP}}\,{\bf{score}}{\boldsymbol{=}}{\bf{0.7}}{\boldsymbol{+}}{\bf{1.9}}{\boldsymbol{\ast }}{\boldsymbol{(}}{\bf{ABR}}{\boldsymbol{)}}{\boldsymbol{+}}{\bf{1.2}}{\boldsymbol{\ast }}(\frac{{\boldsymbol{V}}{\boldsymbol{C}}{\boldsymbol{N}}}{{\boldsymbol{F}}{\boldsymbol{N}}})$$
deduced
:
CAP

score
=
0.7
+
1.9
∗

(

ABR

)

+
1.2
∗

(

V
C
N

F
N

)

. We found that preoperative ABR and area ratio of VCN to FN at the cerebellopontine angle could predict CI outcome in patients with CND. Preoperative counselling based on our predictive model might be helpful to determine treatment modality for auditory rehabilitation and which ear to implant.
High-resolution experimental and computational electrophysiology reveals weak β-lactam binding events in the porin PorB
Authors: Bartsch Annika , Llabrés Salomé , Pein Florian , Kattner Christof , Schön Markus , Diehn Manuel , Tanabe Mikio , Munk Axel , Zachariae Ulrich , Steinem Claudia
Published: February 2019

The permeation of most antibiotics through the outer membrane of Gram-negative bacteria occurs through porin channels. To design drugs with increased activity against Gram-negative bacteria in the face of the antibiotic resistance crisis, the strict constraints on the physicochemical properties of the permeants imposed by these channels must be better understood. Here we show that a combination of high-resolution electrophysiology, new noise-filtering analysis protocols and atomistic biomolecular simulations reveals weak binding events between the β-lactam antibiotic ampicillin and the porin PorB from the pathogenic bacterium Neisseria meningitidis. In particular, an asymmetry often seen in the electrophysiological characteristics of ligand-bound channels is utilised to characterise the binding site and molecular interactions in detail, based on the principles of electro-osmotic flow through the channel. Our results provide a rationale for the determinants that govern the binding and permeation of zwitterionic antibiotics in porin channels.
An investigation into non-covalent functionalization of a single-walled carbon nanotube and a graphene sheet with protein G:A combined experimental and molecular dynamics study
Authors: Ebrahim-Habibi Mohammad-Bagher , Ghobeh Maryam , Mahyari Farzaneh Aghakhani , Rafii-Tabar Hashem , Sasanpour Pezhman
Published: February 2019

Investigation of non-covalent interaction of hydrophobic surfaces with the protein G (PrG) is necessary due to their frequent utilization in immunosensors and ELISA. It has been confirmed that surfaces, including carbonous-nanostructures (CNS) could orient proteins for a better activation. Herein, PrG interaction with single-walled carbon nanotube (SWCNT) and graphene (Gra) nanostructures was studied by employing experimental and MD simulation techniques. It is confirmed that the PrG could adequately interact with both SWCNT and Gra and therefore fine dispersion for them was achieved in the media. Results indicated that even though SWCNT was loaded with more content of PrG in comparison with the Gra, the adsorption of the PrG on Gra did not induce significant changes in the IgG tendency. Several orientations of the PrG were adopted in the presence of SWCNT or Gra; however, SWCNT could block the PrG-FcR. Moreover, it was confirmed that SWCNT reduced the α-helical structure content in the PrG. Reduction of α-helical structure of the PrG and improper orientation of the PrG-SWCNT could remarkably decrease the PrG tendency to the Fc of the IgG. Importantly, the Gra could appropriately orient the PrG by both exposing the PrG-FcR and also by blocking the fragment of the PrG that had tendency to interact with Fab in IgG.
Micro-Particle Operations Using Asymmetric Traps
Authors: Lee Jaesung , Mena Sarah E. , Burns Mark A.
Published: February 2019

Micro-particle operations in many lab-on-a-chip devices require active-type techniques that are accompanied by complex fabrication and operation. The present study describes an alternative method using a passive microfluidic scheme that allows for simpler operation and, therefore, potentially less expensive devices. We present three practical micro-particle operations using our previously developed passive mechanical trap, the asymmetric trap, in a non-acoustic oscillatory flow field. First, we demonstrate size-based segregation of both binary and ternary micro-particle mixtures using size-dependent trap-particle interactions to induce different transport speeds for each particle type. The degree of segregation, yield, and purity of the binary segregations are 0.97 ± 0.02, 0.96 ± 0.06, and 0.95 ± 0.05, respectively. Next, we perform a solution exchange by displacing particles from one solution into another in a trap array. Lastly, we focus and split groups of micro-particles by exploiting the transport polarity of asymmetric traps. These operations can be implemented in any closed fluidic circuit containing asymmetric traps using non-acoustic oscillatory flow, and they open new opportunities to flexibly control micro-particles in integrated lab-on-a-chip platforms with minimal external equipment.
Biophysical Insights on the Enrichment of Cancer Cells from Whole Blood by (Affinity) Filtration
Authors: Zinggeler Marc , Brandstetter Thomas , Rühe Jürgen
Published: February 2019

Circulating tumor cells (CTCs) play a key role during the metastatic process of human cancers and their reliable detection and characterization could enable new and effective ways of cancer diagnosis, monitoring and treatment. However, due to their ultralow concentration in patient blood, the CTCs must first be enriched before such analysis can be performed. Classical microfiltration is an important and widely used method for the mechanical enrichment of CTCs. This method exploits that CTCs are generally larger than the accompanying blood cells, however, does not differentiate the cells in other ways. In an affinity filtration, selectivity is added by functionalizing the membrane with specific antibodies against a CTC-characteristic surface protein such as the epithelial cell adhesion molecule (EpCAM). A common shortcoming of both filtration approaches is that there is still a poor understanding of the enrichment process and the systems developed so far are frequently operated under non-optimized conditions. To address this, systematic filtration experiments are performed in this work using the EpCAM+ cell line MCF-7 as CTC-model and standard track-etched membranes modified with or without antibodies against EpCAM. The influences of the key filtration parameters time and applied pressure are studied and it is found that in all cases the extent of cell recovery is limited by a lysis process which occurs on the membrane surface. Counterintuitively, it is found that filtration at rather high pressures is advantageous to ensure high recovery rates. To describe the pressure-induced lysis process a biophysical model is developed. This model allows the determination of optimum filtration conditions to achieve both high cancer cell recovery and large blood sample throughput. It is demonstrated that this way practically 100% of spiked cancer cells can be recovered from milliliters of undiluted whole blood within seconds.
Sandwich-structured nanoparticles-grafted functionalized graphene based 3D nanocomposites for high-performance biosensors to detect ascorbic acid biomolecule
Authors: Salahandish Razieh , Ghaffarinejad Ali , Naghib Seyed Morteza , Niyazi Asghar , Majidzadeh-A Keivan , Janmaleki Mohsen , Sanati-Nezhad Amir
Published: February 2019

We present a highly sensitive and selective nano-biosensor for rapid, stable and highly reproducible detection of ascorbic acid (AA) in the presence of dopamine, uric acid and other interferences by a three-layer sandwich arrangement of nitrogen-doped functionalized graphene (NFG), silver nanoparticles (AgNPs) and nanostructured polyaniline (PANI) nanocomposite. The enhanced AA electrochemical properties of the NFG/AgNPs/PANI electrode is attributed to the superior conductivity of the NFG-PANI and the excellent catalytic activity of AgNPs. The critical modification of the AgNPs-grafted NFG-PANI coated on very low-cost fluorine doped tin oxide electrode (FTOE) increased the charge transfer conductivity of the electrode (the resistance drops down from 11,000 Ω to 6 Ω). The nano-biosensor was used to accurately detect AA in vitamin C tablets with the recovery of 98%. The sensor demonstrated a low detection limit of 8 µM (S/N = 3) with a very wide linear detection range of 10–11,460 µM, good reproducibility and excellent selectivity performance for AA detection. The results demonstrate that this nanocomposite is a promising candidate for rapid and selective detection of AA in practical clinical samples.
The Effect of Body-Related Stimuli on Mental Rotation in Children, Young and Elderly Adults
Authors: Iachini Tina , Ruggiero Gennaro , Bartolo Angela , Rapuano Mariachiara , Ruotolo Francesco
Published: February 2019

This study aimed to explore the development of mental rotation ability throughout life by comparing different kinds of stimuli. Thirty-six children (6–9 years-old), 30 young (20–28 years-old) and 30 elderly people (60–82 years-old) performed mental rotation tasks with abstract (i.e. two-dimensional lines) and concrete stimuli (i.e. hands, human/animal faces). The results showed that overall young people outperformed children and elderly people, while children were less accurate than the elderly. However, the effect of age was shaped by the kinds of stimuli: (a) young people were more accurate than children and elderly people particularly with abstract stimuli; (b) elderly people improved their performance with images depicting faces; (c) children performed better with body-related stimuli than animal faces. Finally, performance was more difficult when stimuli were rotated by 180°, especially for younger and older females. We may conclude that the effects of age are modulated by the characteristics of the stimuli with a specific difficulty for abstract stimuli and a facilitation for concrete stimuli. As an innovative aspect, during childhood there appeared a specific facilitation for body-related stimuli, not just for concrete ones. These findings are interpreted according to embodied models of cognitive development and the effects of ageing on the brain.
Supplementation with rumen-protected proteins induces resistance to Haemonchus contortus in goats
Authors: Cériac S. , Archimède H. , Feuillet D. , Félicité Y. , Giorgi M. , Bambou J.-C.
Published: February 2019

Resistance to gastro-intestinal nematode (GIN) in small ruminant is expected to arise from protein-rich rather than from energy-rich feeds. The objective of this study was to investigate the effect of the quality of the dietary proteins on the response of Creole goats to Haemonchus contortus. Three diets were compared: no supplementation (Hay: hay ad libitum), Control supplement (CS: hay ad libitum +2% BW of CS at 70 g of by-pass proteins/kg) and supplement enriched in rumen-protected proteins (RPP: hay ad libitum +2% BW of RPP at 139 g of by-pass proteins/kg). The FEC (faecal eggs counts) and the TFEC (total faecal eggs excreted/day) were significantly lower in the RPP. No difference was found between the supplemented diets for the total number of nematodes, but the RPP reduced the parasite prolificacy. The highest IgA responses were observed in animals with the highest nematode burden (Hay compared with CS diets). However, while the FEC and the TFEC were lower in animals feed with the RPP the IgA response were similar to those of the Hay. The IgA response that control GIN egg production in sheep could be one mediator of the resistance to H. contortus induced with by-pass proteins in goats.
The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits
Authors: Moon Sanghoon , Kim Young Jin , Han Sohee , Hwang Mi Yeong , Shin Dong Mun , Park Min Young , Lu Yontao , Yoon Kyungheon , Jang Hye-Mi , Kim Yun Kyoung , Park Tae-Joon , Song Dae Sub , Park Jae Kyung , Lee Jong-Eun , Kim Bong-Jo
Published: February 2019

We introduce the design and implementation of a new array, the Korea Biobank Array (referred to as KoreanChip), optimized for the Korean population and demonstrate findings from GWAS of blood biochemical traits. KoreanChip comprised >833,000 markers including >247,000 rare-frequency or functional variants estimated from >2,500 sequencing data in Koreans. Of the 833 K markers, 208 K functional markers were directly genotyped. Particularly, >89 K markers were presented in East Asians. KoreanChip achieved higher imputation performance owing to the excellent genomic coverage of 95.38% for common and 73.65% for low-frequency variants. From GWAS (Genome-wide association study) using 6,949 individuals, 28 associations were successfully recapitulated. Moreover, 9 missense variants were newly identified, of which we identified new associations between a common population-specific missense variant, rs671 (p.Glu457Lys) of ALDH2, and two traits including aspartate aminotransferase (P = 5.20 × 10−13) and alanine aminotransferase (P = 4.98 × 10−8). Furthermore, two novel missense variants of GPT with rare frequency in East Asians but extreme rarity in other populations were associated with alanine aminotransferase (rs200088103; p.Arg133Trp, P = 2.02 × 10−9 and rs748547625; p.Arg143Cys, P = 1.41 × 10−6). These variants were successfully replicated in 6,000 individuals (P = 5.30 × 10−8 and P = 1.24 × 10−6). GWAS results suggest the promising utility of KoreanChip with a substantial number of damaging variants to identify new population-specific disease-associated rare/functional variants.
Evolution and functional divergence of MADS-box genes in Pyrus
Authors: Meng Dandan , Cao Yunpeng , Chen Tianzhe , Abdullah Muhammad , Jin Qing , Fan Honghong , Lin Yi , Cai Yongping
Published: February 2019

MADS-box transcription factors widely regulate all aspects of plant growth including development and reproduction. Although the MADS-box gene family genes have been extensively characterized in many plants, they have not been studied in closely related species. In this study, 73 and 74 MADS-box genes were identified in European pear (Pyrus communis) and Chinese pear (Pyrus bretschneideri), respectively. Based on the phylogenetic relationship, these genes could be clustered into five groups (Mα, Mβ, Mr, MIKCC, MIKC*) and the MIKCC group was further categorized into 10 subfamilies. The distribution of MADS-box genes on each chromosome was significantly nonrandom. Thirty-seven orthologs, twenty-five PcpMADS (P. communis MADS-box) paralogs and nineteen PbrMADS (P. bretschneideri MADS-box) paralogs were predicted. Among these paralogous genes, two pairs arose from tandem duplications (TD), nineteen from segmental duplication (SD) events and twenty-three from whole genome duplication (WGD) events, indicating SD/WGD events led to the expansion of MADS-box gene family. The MADS-box genes expression profiles in pear fruits indicated functional divergence and neo-functionalization or sub-functionalization of some orthologous genes originated from a common ancestor. This study provided a useful reference for further analysis the mechanisms of species differentiation and biodiversity formation among closely related species.