bluuebunny/crossref_metadata_2025 huggingface dataset:
A New Enceladus Global Control Network, Image Mosaic, and Updated Pointing Kernels From Cassini's 13‐Year Mission
Authors: Bland M. T. , Becker T. L. , Edmundson K. L. , Roatsch Th. , Archinal B. A. , Takir D. , Patterson G. W. , Collins G. C. , Schenk P. M. , Pappalardo R. T. , Cook D. A.
Published: September 2018

NASA's Cassini spacecraft spent 13 years exploring the Saturn system, including 23 targeted flybys of the small, geologically active moon Enceladus. These flybys provided a wealth of image data from Cassini's Imaging Science Subsystem. To improve the usability of the Enceladus data set, we created a new, global photogrammetric control network for Enceladus that enabled compilation of a versatile cartographic package to support geologic mapping and other investigations. The network used 586 images in four image filters with a pixel scale generally between 50 and 500 m per pixel and a phase angle less than 120° and consisted of 10,362 tie points and 173,704 individual image measures, averaging nearly 17 measures per tie point. Least squares bundle adjustment resulted in a root‐mean‐square residual of 0.45 pixel, corresponding to root‐mean‐square ground point uncertainties of 66, 51, and 46 m in latitude, longitude, and radius, respectively. Using our geodetic control network, we created new global image mosaics, coregistered flyby mosaics to support geologic mapping, and updated pointing kernels for every image used in the solution. These products, including the updated pointing kernels, are available to the community through NASA's Planetary Data System Imaging Annex. The bundle adjustment solution also yielded independently determined shape information, resulting in radii within the stated uncertainty of International Astronomical Union values. The challenges of the data set, and the technical methodology described here are applicable to bodies imaged during multiple flybys with variable viewing and illumination geometry, including other midsized satellites of Saturn, and the Europa Clipper mission.
Subsurface Fluid Pressure and Rock Deformation Monitoring Using Seismic Velocity Observations
Authors: Doetsch Joseph , Gischig Valentin S. , Villiger Linus , Krietsch Hannes , Nejati Morteza , Amann Florian , Jalali Mohammadreza , Madonna Claudio , Maurer Hansruedi , Wiemer Stefan , Driesner Thomas , Giardini Domenico
Published: September 2018

Fluid pressure within the Earth's crust is a key driver for triggering natural and human‐induced seismicity. Measuring fluid pressure evolution would be highly beneficial for understanding the underlying driving mechanisms and supporting seismic hazard assessment. Here we show that seismic velocities monitored on the 20‐m scale respond directly to changes in fluid pressure. Our data show that volumetric strain resulting from effective stress changes is sensed by seismic velocity, while shear dislocation is not. We are able to calibrate seismic velocity evolution against fluid pressure and strain with in situ measurements during a decameter‐scale fluid injection experiment in crystalline rock. Thus, our 4‐D seismic tomograms enable tracking of fluid pressure and strain evolution. Our findings demonstrate a strong potential toward monitoring transient fluid pressure variations and stress changes for well‐instrumented field sites and could be extended to monitoring hydraulic stimulations in deep reservoirs.
Large Midlatitude Stratospheric Temperature Variability Caused by Inertial Instability: A Potential Source of Bias for Gravity Wave Climatologies
Authors: Rapp M. , Dörnbrack A. , Preusse P.
Published: September 2018

Stratospheric temperature perturbations (TP) that have previously been misinterpreted as due to gravity waves are revisited. The perturbations observed by radio occultations during December 2015 had peak‐to‐peak amplitudes of 10 K extending from the equator to midlatitudes. The vertically stacked and horizontally flat structures had a vertical wavelength of 12 km. The signs of the TP were 180∘ phase shifted between equatorial and midlatitudes at fixed altitude levels. High‐resolution operational analyses reveal that these shallow temperature structures were caused by inertial instability due to the large meridional shear of the polar night jet at its equatorward flank in combination with Rossby wave breaking. Large stratospheric TP owing to inertial instability do frequently occur in the Northern Hemisphere (Southern Hemisphere) from October to April (April to October) in the 39 years of ECMWF Re‐Analysis‐Interim data. During 10% of the days, TP exceed 5 K (peak to peak).
A Turbulence‐Based Bed‐Load Transport Model for Bare and Vegetated Channels
Authors: Yang J. Q. , Nepf H. M.
Published: September 2018

Previous studies have shown that sediment transport models based on bed shear stress (τ) are not accurate for regions with vegetation. The present study demonstrated that the inaccuracy arises from the influence of vegetation‐generated turbulence. Bed‐load transport rate, Qs, and near‐bed velocity were measured in a sediment‐recirculating flume with model vegetation of different vegetation volume fractions (ϕ) and with bare sand beds. At the same τ, the measured Qs increased with increasing ϕ, suggesting that vegetation‐generated turbulence, which also increased with increasing ϕ, was augmenting the bed‐load transport. At the same near‐bed turbulent kinetic energy, kt, the Qs measured in both bare and vegetated channels agreed within uncertainty, suggesting that kt may be a more universal predictor of bed‐load transport than bed shear stress. A τ‐based bed‐load transport model was reinterpreted as a kt‐based model. The new kt‐based model predicted the Qs measurements for both bare and vegetated channels.
Net Community Production in the Southern Ocean: Insights From Comparing Atmospheric Potential Oxygen to Satellite Ocean Color Algorithms and Ocean Models
Authors: Nevison Cynthia , Munro David , Lovenduski Nicole , Cassar Nicolas , Keeling Ralph , Krummel Paul , Tjiputra Jerry
Published: September 2018

The contribution of oceanic net community production (NCP) to the observed seasonal cycle in atmospheric potential oxygen (APO) is estimated at Cape Grim, Tasmania. The resulting APONCP signal is compared to satellite and ocean model‐based estimates of POC export and NCP across the Southern Ocean. The satellite products underestimate the amplitude of the observed APONCP seasonal cycle by more than a factor of 2. Ocean models suggest two reasons for this underestimate: (1) Current satellite products substantially underestimate the magnitude of NCP in early spring. (2) Seasonal O2 outgassing is supported in large part by storage of carbon in DOC and living biomass. More DOC observations are needed to help evaluate this latter model prediction. Satellite products could be improved by developing seasonally dependent relationships between remote sensing chlorophyll data and in situ NCP, recognizing that the former is a measure of mass, the latter of flux.
Abundance and Emission Flux of the Anthropogenic Iron Oxide Aerosols From the East Asian Continental Outflow
Authors: Yoshida Atsushi , Ohata Sho , Moteki Nobuhiro , Adachi Kouji , Mori Tatsuhiro , Koike Makoto , Takami Akinori
Published: September 2018

Anthropogenic iron oxide (FeOx) aerosols can affect atmospheric radiation, marine biogeochemistry, and human health. However, due to lack of observational data, their atmospheric abundance and emission flux are not well understood. In this study, we observed size‐resolved concentrations of FeOx (170–2100 nm) and black carbon (BC, 70–850 nm) aerosols at a remote site in the East China Sea in March 2016 using a modified single‐particle soot photometer (SP2). Light signals measured by the SP2 and particle morphology and compositions analyzed by a transmission electron microscope revealed that most of the observed FeOx aerosols are of anthropogenic origin. Clear correlations were found between mass concentrations of FeOx and BC (R2 = 0.717) and between FeOx and carbon monoxide (CO) (R2 = 0.718) in air masses from China, indicating that their emission sources are spatially similar. The correlation slopes of mass concentration (ng/m3) are ~0.3 and 0.0015, respectively. Based on the correlation slopes and emission inventories of BC and CO in China, we estimated emission flux of anthropogenic FeOx aerosols from China to be 0.21–0.49 FeTg/yr. Based on the observed size distribution and previous studies on mass fraction of FeOx and non‐FeOx, we also estimated emission flux of anthropogenic Fe (FeOx + non‐FeOx) in PM10 as 0.74–1.7 FeTg/yr. These emission fluxes from China are comparable to global emission fluxes in currently reported inventories of anthropogenic Fe (0.51–1.91 FeTg/yr). Our results suggest that the current emission inventories of anthropogenic Fe are underestimated.
Cold Tropical Pacific Sea Surface Temperatures During the Late Sixteenth‐Century North American Megadrought
Authors: Cook Benjamin I. , Williams A. Park , Smerdon Jason E. , Palmer Jonathan G. , Cook Edward R. , Stahle David W. , Coats Sloan
Published: September 2018

The late 16th‐century North American megadrought was notable for its persistence, extent, intensity, and occurrence after the main interval of megadrought activity during the Medieval Climate Anomaly. Forcing from sea surface temperatures (SSTs) in the tropical Pacific is considered a possible driver of megadroughts, and we investigate this hypothesis for the late 16th‐century event using two new 600‐year long hydroclimate field reconstructions from Mexico and Australia. Areas represented by these reconstructions have strong teleconnections to tropical Pacific SSTs, evidenced by the leading principal component in each region explaining ∼40% of local hydroclimate variability and correlating significantly with the boreal winter (December‐January‐February) NINO 3.4 index. Using these two principal components as predictors, we develop a skillful reconstruction of the December‐January‐February NINO 3.4 index. The reconstruction reveals that the late 16th‐century megadrought likely occurred during one of the most persistent and intense periods of cold tropical Pacific SST anomalies of the last 600 years (1566–1590 C.E.; median NINO 3.4 = −0.79 K). This anomalously cold period coincided with a major filling episode for Kati Thanda‐Lake Eyre in Australia, a hydroclimate response dynamically consistent with the reconstructed SST state. These results offer new evidence that tropical Pacific forcing was an important driver of the late 16th‐century North American megadrought over the Southwest and Mexico, highlighting the large amplitude of natural variability that can occur within the climate system.
The Influence of Spatial Variability of Width Functions on Regional Peak Flow Regressions
Authors: Perez Gabriel , Mantilla Ricardo , Krajewski Witold F.
Published: September 2018

The authors investigated the relation between the width function and the regional variability of peak flows. The authors explored 34 width function descriptors (WFDs), in addition to drainage area, as potential candidates for explaining the regional peak flow variability. First, using hydrologic simulations of uniform rainfall events with variable rainfall duration and constant rainfall intensity for 147 watersheds across the state of Iowa, they demonstrated that WFDs are capable of explaining spatial variability of peak flows for individual rainfall‐runoff events under idealized physical conditions. This theoretical exercise indicates that the inclusion of WFDs should drastically improve regional peak flow estimates with a reduction of the root mean square error by more than half in comparison with a regression model based on drainage area only. The authors followed the simulation with an analysis of estimated peak flow quantiles from 94 stream gauges in Iowa to determine if the WFDs have a similar explanatory power. The correlations between WFDs and peak flow quantiles are not as high as those found for simulated events, which indicates that results from event scale simulations do not translate directly to peak flow quantiles. The spatial variability of peak flow quantiles is influenced by other physical and statistical processes that are also variable in space. These results are consistent with recent work on event‐based scaling of peak flows that shows that the spatiotemporal variability of flood mechanisms is larger than the one expected from geomorphology alone.
Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
Authors: Herrera Alberto , Herrera Mercedes , Guerra-Perez Natalia , Galindo-Pumariño Cristina , Larriba María Jesús , García-Barberán Vanesa , Gil Beatriz , Giménez-Moyano Sara , Ferreiro-Monteagudo Reyes , Veguillas Pilar , Candia Antonio , Peña Raúl , Pinto Jesús , García-Bermejo Mª Laura , Muñoz Alberto , García de Herreros Antonio , Bonilla Félix , Carrato Alfredo , Peña Cristina
Published: September 2018

Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as “tracks”, facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the co-adjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.
Long non-coding RNA CCAL/miR-149/FOXM1 axis promotes metastasis in gastric cancer
Authors: Luo Xi , Wang Gui-Hua , Bian Zhao-Lian , Li Xi-Wen , Zhu Bing-Ying , Jin Chun-Jing , Ju Shao-Qing
Published: September 2018

Early evidence indicates that the long non-coding RNA CCAL plays a critical role in cancer progression and metastasis. However, the overall biological role and clinical significance of CCAL in gastric tumourigenesis and progression remain largely unknown. We observed that CCAL was upregulated in gastric cancer tissues and was associated with the tumour-node-metastasis stage. Functional experiments showed that CCAL promoted gastric cancer cell proliferation and metastasis in vitro and in vivo. Luciferase reporter assay indicated that CCAL directly bind to miR-149. Moreover, knockdown of CCAL significantly reduced the expression of FOXM1, a direct target of miR-149. We also showed that FOXM1 suppression by miR-149 could be partially rescued by CCAL overexpression. In addition, we identified a negative correlation between the mRNA expression of CCAL and miR-149 in gastric cancer tissues. Furthermore, we observed a negative correlation between the expression of miR-149 and FOXM1 and a positive correlation between CCAL and FOXM1 levels. These results demonstrated that the CCAL/miR-149/FOXM1 axis functions as a key regulator in gastric cancer metastasis and CCAL potentially represents a biomarker for diagnosis and potential target for therapy in the future.
E4BP4 promotes thyroid cancer proliferation by modulating iron homeostasis through repression of hepcidin
Authors: Zhou Qinyi , Chen Jun , Feng Jialin , Wang Jiadong
Published: September 2018

Iron homeostasis is critical to mammals, and dysregulation in iron homeostasis usually leads to severe disorders including various cancers. Massive hepcidin secretion is an indicator of thyroid cancer, but the molecular mechanisms responsible for this dysregulation are unknown. Hepcidin secretion from thyroid cancer cells also leads to decreased expression of the iron exporter, ferroportin (FPN), and increased intracellular iron retention, which promote cancer proliferation. In this study, we examined the role of hepcidin in thyroid cancer (TC) and the molecular bases of its signaling. Synthesis of hepcidin is regulated by the BMP4/7 agonist SOSTDC1, which was downregulated in TC; SOSTDC1 downregulation was correlated with G9a-mediated hypermethylation in its promoter. The binding of G9a to the SOSTDC1 promoter requires E4BP4, which interacts with G9a to form a multi-molecular complex that contributes to SOSTDC1 silencing. Silencing of E4BP4 or G9a has similar effects to SOSTDC1 overexpression, which suppresses secretion of hepcidin and inhibits TC cell proliferation. Furthermore, our in vivo xenograft data indicated that depletion of E4BP4 also inhibits cancer growth, reduces hepcidin secretion, and reduces G9a nuclear transportation. Iron homeostasis and tumor growth in TC may be regulated by an E4BP4-dependent epigenetic mechanism. These findings suggest a new mechanism of cellular iron dysfunction through the E4BP4/G9a/SOSTDC1/hepcidin pathway, which is an essential link in TC.
Sensitizing non-small cell lung cancer to BCL-xL-targeted apoptosis
Authors: Shen Qi , Li Jun , Mai Junhua , Zhang Zhe , Fisher Andrew , Wu Xiaoyan , Li Zhaoqi , Ramirez Maricela R. , Chen Shuqing , Shen Haifa
Published: September 2018

Lung cancer is the leading cause of death in the United States, with non-small cell lung cancers (NSCLC) accounting for 85% of all cases. By analyzing the expression profile of the pro-apoptotic and anti-apoptotic proteins, we have assigned NSCLCs into two distinct groups. While single agent treatment with the BCL-2/BCL-xL/BCL-w inhibitor ABT-263 (navitoclax) did not trigger apoptosis in either group, cells with a moderate to high level of MCL-1 expression were sensitive to ABT-263 treatment when MCL-1 expression was suppressed with a gene-specific siRNA. In contrast, those with a low MCL-1 expression did not undergo apoptosis upon combination treatment with ABT-263 and MCL-1 siRNA. Further studies revealed that cells with a low MCL-1 expression had low mitochondrial priming, and treatment with the chemotherapy drug docetaxel raised the mitochondrial priming level and consequently sensitized cells to ABT-263. These results establish a rationale for molecular profiling and a therapeutic strategy to treat NSCLC patients with pro-apoptotic anti-cancer drugs based on their MCL-1 expression level.
Rapamycin and fasting sustain autophagy response activated by ischemia/reperfusion injury and promote retinal ganglion cell survival
Authors: Russo Rossella , Varano Giuseppe Pasquale , Adornetto Annagrazia , Nazio Francesca , Tettamanti Gianluca , Girardello Rossana , Cianfanelli Valentina , Cavaliere Federica , Morrone Luigi Antonio , Corasaniti Maria Tiziana , Cecconi Francesco , Bagetta Giacinto , Nucci Carlo
Published: September 2018

Autophagy, the cellular process responsible for degradation and recycling of cytoplasmic components through the autophagosomal–lysosomal pathway, is fundamental for neuronal homeostasis and its deregulation has been identified as a hallmark of neurodegeneration. Retinal hypoxic–ischemic events occur in several sight-treating disorders, such as central retinal artery occlusion, diabetic retinopathy, and glaucoma, leading to degeneration and loss of retinal ganglion cells. Here we analyzed the autophagic response in the retinas of mice subjected to ischemia induced by transient elevation of intraocular pressure, reporting a biphasic and reperfusion time-dependent modulation of the process. Ischemic insult triggered in the retina an acute induction of autophagy that lasted during the first hours of reperfusion. This early upregulation of the autophagic flux limited RGC death, as demonstrated by the increased neuronal loss observed in mice with genetic impairment of basal autophagy owing to heterozygous ablation of the autophagy-positive modulator Ambra1 (Ambra1+/gt). Upregulation of autophagy was exhausted 24 h after the ischemic event and reduced autophagosomal turnover was associated with build up of the autophagic substrate SQSTM-1/p62, decreased ATG12-ATG5 conjugate, ATG4 and BECN1/Beclin1 expression. Animal fasting or subchronic systemic treatment with rapamycin sustained and prolonged autophagy activation and improved RGC survival, providing proof of principle for autophagy induction as a potential therapeutic strategy in retinal neurodegenerative conditions associated with hypoxic/ischemic stresses.
Systems biology approach reveals a link between mTORC1 and G2/M DNA damage checkpoint recovery
Authors: Hsieh Hui-Ju , Zhang Wei , Lin Shu-Hong , Yang Wen-Hao , Wang Jun-Zhong , Shen Jianfeng , Zhang Yiran , Lu Yiling , Wang Hua , Yu Jane , Mills Gordon B. , Peng Guang
Published: September 2018

Checkpoint recovery, the process that checkpoint-arrested cells with normal DNA repair capacity resume cell cycle progression, is essential for genome stability. However, the signaling network of the process has not been clearly defined. Here, we combine functional proteomics, mathematical modeling, and molecular biology to identify mTORC1, the nutrient signaling integrator, as the determinant for G2/M checkpoint recovery. Inhibition of the mTORC1 pathway delays mitotic entry after DNA damage through KDM4B-mediated regulation of CCNB1 and PLK1 transcription. Cells with hyper-mTORC1 activity caused by TSC2 depletion exhibit accelerated G2/M checkpoint recovery. Those Tsc2-null cells are sensitive to WEE1 inhibition in vitro and in vivo by driving unscheduled mitotic entry and inducing mitotic catastrophe. These results reveal that mTORC1 functions as a mediator between nutrition availability sensing and cell fate determination after DNA damage, suggesting that checkpoint inhibitors may be used to treat mTORC1-hyperactivated tumors such as those associated with tuberous sclerosis complex.
Structural basis of neurosteroid anesthetic action on GABAA receptors
Authors: Chen Qiang , Wells Marta M. , Arjunan Palaniappa , Tillman Tommy S. , Cohen Aina E. , Xu Yan , Tang Pei
Published: September 2018

Type A γ-aminobutyric acid receptors (GABAARs) are inhibitory pentameric ligand-gated ion channels in the brain. Many anesthetics and neurosteroids act through binding to the GABAAR transmembrane domain (TMD), but the structural basis of their actions is not well understood and no resting-state GABAAR structure has been determined. Here, we report crystal structures of apo and the neurosteroid anesthetic alphaxalone-bound desensitized chimeric α1GABAAR (ELIC-α1GABAAR). The chimera retains the functional and pharmacological properties of GABAARs, including potentiation, activation and desensitization by alphaxalone. The apo-state structure reveals an unconventional activation gate at the intracellular end of the pore. The desensitized structure illustrates molecular determinants for alphaxalone binding to an inter-subunit TMD site. These structures suggest a plausible signaling pathway from alphaxalone binding at the bottom of the TMD to the channel gate in the pore-lining TM2 through the TM1–TM2 linker. The study provides a framework to discover new GABAAR modulators with therapeutic potential.
Cooperative supramolecular polymers with anthracene‒endoperoxide photo-switching for fluorescent anti-counterfeiting
Authors: Gao Zhao , Han Yifei , Wang Feng
Published: September 2018

Innovative technologies are highly pursued for the detection and avoidance of counterfeiting in modern information society. Herein, we report the construction of photo-responsive supramolecular polymers toward fluorescent anti-counterfeit applications, by taking advantage of multicycle anthracene‒endoperoxide switching properties. Due to σ-metalation effect, photo-oxygenation of anthracene to endoperoxide is proceeded under the mild visible light irradiation conditions, while the backward conversion occurs spontaneously at room temperature. Supramolecular polymers are formed with cooperative nucleation‒elongation mechanism, which facilitate fluorescence resonance energy transfer process via two-component co-assembly strategy. Fluorescence resonance energy transfer efficiency is delicately regulated by either light-triggered anthracene‒endoperoxide conversion or vapor-induced monomer–polymer transition, leading to high-contrast fluorescent changes among three different states. On this basis, dual-mode anti-counterfeiting patterns have been successfully fabricated via inkjet printing techniques. Hence, cooperative supramolecular polymerization of photo-fluorochromic molecules represents an efficient approach toward high-performance anti-counterfeit materials with enhanced security reliability, fast response, and ease of operation.
Resonant torsion magnetometry in anisotropic quantum materials
Authors: Modic K. A. , Bachmann Maja D. , Ramshaw B. J. , Arnold F. , Shirer K. R. , Estry Amelia , Betts J. B. , Ghimire Nirmal J. , Bauer E. D. , Schmidt Marcus , Baenitz Michael , Svanidze E. , McDonald Ross D. , Shekhter Arkady , Moll Philip J. W.
Published: September 2018

Unusual behavior in quantum materials commonly arises from their effective low-dimensional physics, reflecting the underlying anisotropy in the spin and charge degrees of freedom. Here we introduce the magnetotropic coefficient k = ∂2F/∂θ2, the second derivative of the free energy F with respect to the magnetic field orientation θ in the crystal. We show that the magnetotropic coefficient can be quantitatively determined from a shift in the resonant frequency of a commercially available atomic force microscopy cantilever under magnetic field. This detection method enables part per 100 million sensitivity and the ability to measure magnetic anisotropy in nanogram-scale samples, as demonstrated on the Weyl semimetal NbP. Measurement of the magnetotropic coefficient in the spin-liquid candidate RuCl3 highlights its sensitivity to anisotropic phase transitions and allows a quantitative comparison to other thermodynamic coefficients via the Ehrenfest relations.
A modified serine cycle in Escherichia coli coverts methanol and CO2 to two-carbon compounds
Authors: Yu Hong , Liao James C.
Published: September 2018

Microbial utilization of renewable one-carbon compounds, such as methane, methanol, formic acid, and CO2, has emerged as a potential approach to increase the range of carbon sources for bioproduction and address climate change issues. Here, we modify the natural serine cycle present in methylotrophs and build an adapted pathway forEscherichia coli, which allows microorganism to condense methanol (or formate) together with bicarbonate to produce various products. We introduce the modified cycle intoE. coliand demonstrate its capability for one-carbon assimilation through growth complementation and isotope labeling experiments. We also demonstrate conversion of methanol to ethanol by utilizing the modified serine cycle in an engineeredE. colistrain, achieving a reaction yet to be accomplished by a one-pot chemical process. This work provides a platform to utilize various renewable one-carbon compounds as carbon sources for biosynthesis through a modified serine cycle inE. coli.
Mechanism-based rescue of Munc18-1 dysfunction in varied encephalopathies by chemical chaperones
Authors: Guiberson Noah Guy Lewis , Pineda André , Abramov Debra , Kharel Parinati , Carnazza Kathryn E. , Wragg Rachel T. , Dittman Jeremy S. , Burré Jacqueline
Published: September 2018

Heterozygous de novo mutations in the neuronal protein Munc18-1 are linked to epilepsies, intellectual disability, movement disorders, and neurodegeneration. These devastating diseases have a poor prognosis and no known cure, due to lack of understanding of the underlying disease mechanism. To determine how mutations in Munc18-1 cause disease, we use newly generated S. cerevisiae strains, C. elegans models, and conditional Munc18-1 knockout mouse neurons expressing wild-type or mutant Munc18-1, as well as in vitro studies. We find that at least five disease-linked missense mutations of Munc18-1 result in destabilization and aggregation of the mutant protein. Aggregates of mutant Munc18-1 incorporate wild-type Munc18-1, depleting functional Munc18-1 levels beyond hemizygous levels. We demonstrate that the three chemical chaperones 4-phenylbutyrate, sorbitol, and trehalose reverse the deficits caused by mutations in Munc18-1 in vitro and in vivo in multiple models, offering a novel strategy for the treatment of varied encephalopathies.
Author Correction: An intercross population study reveals genes associated with body size and plumage color in ducks
Authors: Zhou Zhengkui , Li Ming , Cheng Hong , Fan Wenlei , Yuan Zhengrong , Gao Qiang , Xu Yaxi , Guo Zhanbao , Zhang Yunsheng , Hu Jian , Liu Hehe , Liu Dapeng , Chen Weihuang , Zheng Zhuqing , Jiang Yong , Wen Zhiguo , Liu Yongming , Chen Hua , Xie Ming , Zhang Qi , Huang Wei , Wang Wen , Hou Shuisheng , Jiang Yu
Published: September 2018

In the original version of this Article, there was an error in the legend for Figure 2, whereby the descriptions of panels a, b and c were presented in a different order to the corresponding figure panels. The text ‘a GWAS of duck plumage color, including 76 colored ducks and 30 white Pekin ducks. The gray horizontal dashed lines indicate the Bonferroni significance threshold of the GWAS (1 × 10−9). b Fixation index (FST) of all SNPs along chromosome 13 between mallards and Pekin ducks. Red dots indicate fixed SNPs. c The nucleotide diversity (π) of mallards (blue line) and Pekin ducks (red line) from 16.0 to 17.0 Mb on chromosome 13.’ should have read ‘a Fixation index (FST) of all SNPs along chromosome 13 between mallards and Pekin ducks. Red dots indicate fixed SNPs. b The nucleotide diversity (π) of mallards (blue line) and Pekin ducks (red line) from 16.0 to 17.0 Mb on chromosome 13. c GWAS of duck plumage color, including 76 colored ducks and 30 white Pekin ducks. The gray horizontal dashed lines indicate the Bonferroni significance threshold of the GWAS (1 × 10−9).’ This has been corrected in both the PDF and HTML versions of the Article.
Population-based study of LAMA monotherapy effectiveness compared with LABA/LAMA as initial treatment for COPD in primary care
Authors: Barrecheguren Miriam , Monteagudo Mónica , Miravitlles Marc
Published: September 2018

This epidemiological study aimed to describe and compare the characteristics and outcomes of COPD patients starting treatment with a long-acting anti-muscarinic (LAMA) or a combination of a long-acting beta-2 agonist (LABA)/LAMA in primary care in Catalonia (Spain) over a one-year period. Data were obtained from the Information System for the Development in Research in Primary Care (SIDIAP), a population database containing information of 5.8 million inhabitants (80% of the population of Catalonia). Patients initiating treatment with a LAMA or LABA/LAMA in 2015 were identified, and information about demographic and clinical characteristics was collected. Then, patients were matched 1:1 for age, sex, FEV1%, history of exacerbations, history of asthma and duration of treatment, and the outcomes between the two groups were compared. During 2015, 5729 individuals with COPD started treatment with a LAMA (69.8%) or LAMA/LABA (30.2%). There were no remarkable differences between groups except for a lower FEV1 and more previous hospital admissions in individuals on LABA/LAMA. The number of tests and referrals was low and decreased in both groups during follow-up. For the same severity status, the evolution was similar with a reduction in exacerbations in both groups. Treatment was changed during follow-up in up to 34.2% of patients in the LABA/LAMA and 26.3% in the LAMA group, but adherence was equally good for both. Our results suggest that initial therapy with LAMA in monotherapy may be adequate in a significant group of mild to moderate patients with COPD and a low risk of exacerbations managed in primary care.
Changes in circRNA expression profiles related to the antagonistic effects of Escherichia coli F17 in lamb spleens
Authors: Jin Chengyan , Bao Jianjun , Wang Yue , Chen Weihao , Zou Shuangxia , Wu Tianyi , Wang Lihong , Lv Xiaoyang , Gao Wen , Wang Buzhong , Zhu Guoqiang , Dai Guojun , Shi Dongfang , Sun Wei
Published: September 2018

Sheep colibacillosis is one of the most common bacterial diseases in large-scale sheep farms. In this study, we orally administered Escherichia coli F17 (E. coli F17) to lambs to obtain antagonistic and sensitive individuals. We used RNA-seq to screen for differential circRNAs in the spleens of both antagonist and sensitive individuals to explore the effect of circRNA on anti-diarrhoea in sheep. The results showed that 60 differentially expressed (DE) circRNAs were screened by RNA-seq in the spleen of antagonistic and sensitive lambs, among which 31 were up-regulated and 29 were down-regulated; q-PCR was used to validate the relative expression levels of six randomly selected circRNAs in antagonist and susceptible lambs and found to be consistent with the results of RNA-seq. Using Miranda analysis of circRNA-miRNA-mRNA interactions, we found a certain target relationship between 6 circRNAs, 5 miRNAs and 9 mRNAs. The relative expression levels of mRNA in antagonistic and sensitive lambs were verified by q-PCR and were consistent with the results of RNA-seq. This study explored the expression profile of circRNA in the spleen of an antagonistic and susceptible lamb with diarrhoea and found that differentially expressed circRNAs were helpful for determining how the lambs resist the pathogenesis of diarrhoea and provided a scientific basis for lambs to resist diarrhoea.
Runge-Kutta 4th-order method analysis for viscoelastic Oldroyd 8-constant fluid used as coating material for wire with temperature dependent viscosity
Authors: Khan Zeeshan , Rasheed Haroon Ur , Tlili Iskander , Khan Ilyas , Abbas Tariq
Published: September 2018

Polymer flow during wire coating dragged from a bath of viscoelastic incompreesible and laminar fluid inside pressure type die is carried out numerically. In wire coating the flow depends on the velcocity of the wire, geometry of the die and viscosity of the fluid. The governing equations expressing the heat transfer and flow solved numerically by Runge-Kutta fourth order method with shooting technique. Reynolds model and Vogel’s models are encountered for temperature dependent viscosity. The umerical solutions are obtained for velocity field and temperature distribution. It is seen that the non-Newtonian parameter of the fluid accelerates the velcoty profile in the absence of porous and magnetic parameters. For large value of magnetic parameter the reverse effect is observed. It is observed that the temperature profiles decreases with increasing psedoplastic parameter in the presence and absence of porous matrix as well as magnetic parameter. The Brinkman number contributes to increase the temperature for both Reynolds and Vogel’smmodels. With the increasing of pressure gradient parameter of both Reynolds and Vogel’s models, the velocity and temperature profile increases significantly in the presence of non-Newtonian parameter. The solutions are computed for different physical parameters. Furthermore, the present result is also compared with published results as a particular case.
A dual role for the transcription factor Sp8 in postnatal neurogenesis
Authors: Gaborieau Elodie , Hurtado-Chong Anahi , Fernández Maria , Azim Kasum , Raineteau Olivier
Published: September 2018

Neural stem cells (NSCs) of the postnatal subventricular zone (SVZ) continue producing distinct subtypes of olfactory bulb (OB) interneurons throughout life. Understanding the transcriptional coding of this diversity remains a great challenge of modern neurosciences. Interneurons expressing calretinin (CalR) represent the main interneuron subtype produced in the glomerular cell layer (GL) after birth. Previous studies have suggested that their specification relies on expression of the transcription factor Sp8 by SVZ NSCs. In this study, we performed fate mapping of NSCs that generate CalR+ or non-CalR+ interneurons, in order to assess the pattern of Sp8 expression during postnatal neurogenesis. We highlight a complex pattern of Sp8 expression, which appears to be expressed in all interneurons lineages, before getting gradually restricted to maturing CalR+ interneurons. To decipher the early and late functions of Sp8 in postnatal OB neurogenesis, we combined transient, permanent and conditional genetic approaches to manipulate Sp8 at distinct neurogenic stages. While Sp8 plays an early role in controlling proliferation in all lineages, it is not involved in the early specification of CalR+ periglomerular interneurons, but plays a crucial role in their long term survival. Together, our results highlight a crucial and dual role for Sp8 during postnatal neurogenesis.
qSE7 is a major quantitative trait locus (QTL) influencing stigma exsertion rate in rice (Oryza sativa L.)
Authors: Zhang Keqin , Zhang Yingxin , Wu Weixun , Zhan Xiaodeng , Anis Galal Bakr , Rahman Md Habibur , Hong Yongbo , Riaz Aamir , Zhu Aike , Cao Yongrun , Sun Lianping , Yang Zhengfu , Yang Qinqin , Cao Liyong , Cheng Shihua
Published: September 2018

Stigma exsertion is a key determinant to increase the efficiency of commercial hybrid rice seed production. The major quantitative trait locus (QTL) qSE7 for stigma exsertion rate was previously detected on the chromosome 7 using 75 Chromosome Segment Substitution Lines (CSSLs) derived from a cross between the high stigma exsertion indica maintainer XieqingzaoB (XQZB) and low stigma exsertion indica restorer Zhonghui9308 (ZH9308). The C51 line, a CSSL population with an introgression from XQZB, was backcrossed with ZH9308 to produce the secondary F2 (BC5F2) and F2:3 (BC5F2:3) populations. As a result, the Near Isogenic Line (NIL qSE7XB) was developed. Analysis indicated qSE7 acted as a single Mendelian factor and decreased the stigma exsertion. We hypothesized qSE7 regulates single, dual, and total stigma exsertion rate, provided experimental support. qSE7 was mapped and localized between RM5436 and RM5499 markers, within a physical distance of 1000-kb. With use of new insertion-deletion (InDel) markers and analysis of the heterozygous and phenotypic data, it was ultimately dissected to a 322.9-kb region between InDel SER4-1 and RM5436. The results are useful for additional identification and isolation of this candidate gene controlling stigma exsertion rate, and provide a basis for further fine mapping, gene cloning, and Marker Assisted Selection (MAS) breeding later.
Involvement of DHH and GLI1 in adrenocortical autograft regeneration in rats
Authors: Takizawa Nae , Tanaka Susumu , Oe Souichi , Koike Taro , Yoshida Takashi , Hirahara Yukie , Matsuda Tadashi , Yamada Hisao
Published: September 2018

Bilateral adrenalectomy forces the patient to undergo glucocorticoid replacement therapy and bear a lifetime risk of adrenal crisis. Adrenal autotransplantation is considered useful to avoid adrenal crisis and glucocorticoid replacement therapy. However, the basic process of regeneration in adrenal autografts is poorly understood. Here, we investigated the essential regeneration factors in rat adrenocortical autografts, with a focus on the factors involved in adrenal development and steroidogenesis, such as Hh signalling. A remarkable renewal in cell proliferation and increase in Cyp11b1, which encodes 11-beta-hydroxylase, occurred in adrenocortical autografts from 2–3 weeks after autotransplantation. Serum corticosterone and adrenocorticotropic hormone levels were almost recovered to sham level at 4 weeks after autotransplantation. The adrenocortical autografts showed increased Dhh expression at 3 weeks after autotransplantation, but not Shh, which is the only Hh family member to have been reported to be expressed in the adrenal gland. Increased Gli1 expression was also found in the regenerated capsule at 3 weeks after autotransplantation. Dhh and Gli1 might function in concert to regenerate adrenocortical autografts. This is the first report to clearly show Dhh expression and its elevation in the adrenal gland.
Universal cancer screening: revolutionary, rational, and realizable
Authors: Ahlquist David A.
Published: September 2018

Cancer remains the second leading cause of mortality worldwide, and overall cancer-related deaths are increasing. Despite the survival benefit from early detection, screening has to date targeted only those few organs that harbor tumors of sufficient prevalence to show cost-effectiveness at population levels, leaving most cancer types unscreened. In this perspective overview, a case is made for universal cancer screening as a logical and more inclusive approach with potentially high impact. The centrally important conceptual drivers to universal screening are biological and epidemiological. The shared biology of tumor marker release into a common distant medium, like blood, can be exploited for multi-cancer detection from a single test. And, by aggregating prevalence rates, universal screening allows all cancers (including less common ones) to be included as targets, increases screening efficiency and integration across tumor types, and potentially improves cost-effectiveness over single-organ approaches. The identification of new tumor marker classes with both broad expression across tumor types and site-prediction, remarkable advances in assay technologies, and compelling early clinical data increase the likelihood of actualizing this new paradigm. Multi-organ screening could be achieved by targeting markers within or stemming from the circulation (including blood, urine, saliva, and expired breath) or those exfoliated into common excretory pathways (including the gastrointestinal and female reproductive tracts). Rigorous clinical studies in intended use populations and collaborations between academia, industry, professional societies, and government will be required to bring this lofty vision to a population application.
Electronic origin of hydrogen storage in MOF-covered palladium nanocubes investigated by synchrotron X-rays
Authors: Chen Yanna , Sakata Osami , Nanba Yusuke , Kumara Loku Singgappulige Rosantha , Yang Anli , Song Chulho , Koyama Michihisa , Li Guangqin , Kobayashi Hirokazu , Kitagawa Hiroshi
Published: September 2018

Hybrid materials composed of metal nanoparticles and metal-organic frameworks have attracted attention for various applications because of the synergistic functionality between their constituent materials. Interfacial interaction is expected however the mechanism remains ambiguous. Here we report the valence bands of palladium nanocubes covered by copper(II) 1, 3, 5-benzenetricarboxylate (HKUST-1), denoted as Pd@HKUST-1,  and the charge transfer from the palladium nanocubes to HKUST-1 at the Pd/HKUST-1 interface is investigated quantitatively. Interfacial density of states are different from those of internal constituents and imply that the Cu–O group in HKUST-1 acts as a charge accepter. The role of Cu–O group in charge transfer behaviour is also observed experimentally. Finally, we reveal the charge transfer mechanism from the Pd 4dbands to the Cu 3d(4sp) – O 2phybridization bands of HKUST-1 at the Pd/HKUST-1 interface, which explains the enhanced hydrogen storage capacity in Pd@HKUST-1.
A high electron mobility phonotransistor
Authors: Poyser Caroline L. , Li Lianhe H. , Campion Richard P. , Akimov Andrey V. , Linfield Edmund H. , Davies A. Giles , Cunningham John E. , Kent Anthony J.
Published: September 2018

Acoustoelectric devices convert acoustic energy to electrical energy and vice versa. Devices working at much higher acoustic frequencies than those currently available have potential scientific and technological applications, for example, as detectors in phononics experiments and as transducers in bulk acoustic wave filters at terahertz (THz) frequencies. Here we demonstrated an active acoustoelectronic device based on a GaAs heterostructure: an acoustically gated transistor or phonotransistor. Instead of being controlled in the conventional manner by an electrical signal applied to a metallic or semiconductor gate as in a high electron mobility transistor (HEMT), the drain-source current was controlled by a bulk sub-THz acoustic wave passing through the channel in a direction perpendicular to the current flow.
Machine learning classification for field distributions of photonic modes
Authors: Barth Carlo , Becker Christiane
Published: September 2018

Machine learning techniques can reveal hidden structures in large amounts of data and have the potential to replace analytical scientific methods. Electromagnetic simulations of photonic nanostructures often produce data in significant amounts, particularly when three-dimensional field distributions are calculated. An optimisation task, aiming at increased light yield from emitters interacting with photonic nanostructures, enforces systematic analysis of these data. Here we present a method that combines finite element simulations and clustering for the identification of photonic modes with large local field energies and specific spatial properties. For illustration, we use an experimental–numerical data set of quantum dot fluorescence on a photonic crystal surface. The application of Gaussian mixture model-based clustering allows to reduce the electric field distributions to a minimal subset of prototypes and the identification of characteristic spatial mode profiles. The presented clustering method potentially enables systematic optimisation of nanostructures for biosensing, bioimaging, and photon upconversion applications.
Fine-tuning the assemblies of carbon nanodots and porphyrins
Authors: Scharl Tobias , Cadranel Alejandro , Haines Philipp , Strauss Volker , Bernhardt Sarah , Vela Sonia , Atienza Carmen , Gröhn Franziska , Martín Nazario , Guldi Dirk M.
Published: September 2018

We present charge-transfer assemblies of electron accepting, pressure-synthesized carbon nanodots (pCNDs) and an electron donating porphyrin.
Paclitaxel-induced formation of 3D nanocrystal superlattices within injectable protein-based hybrid nanoparticles
Authors: Lee Jeong Yu , Son Ho Yeon , Park Jae Chul , Park Jongnam , Nam Yoon Sung
Published: September 2018

Self-assembly of monodisperse superparamagnetic iron oxide nanocrystals into a close-packed, three-dimensional (3D) superlattice is designed within cross-linked protein-based nanoparticles composed of human serum albumin and polyethylene glycol.
A synthetic model of the nonheme iron–superoxo intermediate of cysteine dioxygenase
Authors: Fischer Anne A. , Lindeman Sergey V. , Fiedler Adam T.
Published: September 2018

A nonheme Fe(ii) complex that models substrate-bound cysteine dioxygenase reacts with O2 at low temperature to yield an iron–superoxo intermediate.
Highly enantioselective addition of dimethylzinc to fluorinated alkyl ketones, and the mechanism behind it
Authors: Neves-Garcia Tomaz , Vélez Andrea , Martínez-Ilarduya Jesús M. , Espinet Pablo
Published: September 2018

Switching the solvent from toluene to dichloromethane results in a very important enhancement in the yield and enantiomeric excess of nucleophilic addition.
Local ionic liquid environment at a modified iron porphyrin catalyst enhances the electrocatalytic performance of CO2 to CO reduction in water
Authors: Khadhraoui Asma , Gotico Philipp , Boitrel Bernard , Leibl Winfried , Halime Zakaria , Aukauloo Ally
Published: September 2018

In this study we report a strategy to attach methylimidazolium fragments as ionic liquid units on an established iron porphyrin catalyst for the selective reduction of CO2 to CO in water, precluding the need for external proton source.