bluuebunny/crossref_metadata_2025 huggingface dataset:
FORMAL QUALITATIVE PROBABILITY
Authors: KIAN Mc KIERNAN DANIEL
Published: February 2020

Choices rarely deal with certainties; and, where assertoric logic and modal logic are insufficient, those seeking to be reasonable turn to one or more things called “probability.” These things typically have a shared mathematical form, which is an arithmetic construct. The construct is often felt to be unsatisfactory for various reasons. A more general construct is that of a preordering, which may even be incomplete, allowing for cases in which there is no known probability relation between two propositions or between two events. Previous discussion of incomplete preorderings has been as if incidental, with researchers focusing upon preorderings for which quantifications are possible. This article presents formal axioms for the more general case. Challenges peculiar to some specific interpretations of the nature of probability are brought to light in the context of these propositions. A qualitative interpretation is offered for probability differences that are often taken to be quantified. A generalization of Bayesian updating is defended without dependence upon coherence. Qualitative hypothesis testing is offered as a possible alternative in cases for which quantitative hypothesis testing is shown to be unsuitable.
Mediation of the association between maternal pre-pregnancy overweight/obesity and childhood overweight/obesity by birth anthropometry
Authors: Stevens Danielle R. , Neelon Brian , Roberts James R. , Taylor Sarah N. , Newman Roger B. , Vena John E. , Hunt Kelly J.
Published: February 2020

The mechanism through which developmental programming of offspring overweight/obesity following in utero exposure to maternal overweight/obesity operates is unknown but may operate through biologic pathways involving offspring anthropometry at birth. Thus, we sought to examine to what extent the association between in utero exposure to maternal overweight/obesity and childhood overweight/obesity is mediated by birth anthropometry. Analyses were conducted on a retrospective cohort with data obtained from one hospital system. A natural effects model framework was used to estimate the natural direct effect and natural indirect effect of birth anthropometry (weight, length, head circumference, ponderal index, and small-for-gestational age [SGA] or large-for-gestational age [LGA]) for the association between pre-pregnancy maternal body mass index (BMI) category (overweight/obese vs normal weight) and offspring overweight/obesity in childhood. Models were adjusted for maternal and child socio-demographics. Three thousand nine hundred and fifty mother–child dyads were included in analyses (1467 [57.8%] of mothers and 913 [34.4%] of children were overweight/obese). Results suggest that a small percentage of the effect of maternal pre-pregnancy BMI overweight/obesity on offspring overweight/obesity operated through offspring anthropometry at birth (weight: 15.5%, length: 5.2%, head circumference: 8.5%, ponderal index: 2.2%, SGA: 2.9%, and LGA: 4.2%). There was a small increase in the percentage mediated when gestational diabetes or hypertensive disorders were added to the models. Our study suggests that some measures of birth anthropometry mediate the association between maternal pre-pregnancy overweight/obesity and offspring overweight/obesity in childhood and that the size of this mediated effect is small.
Band sowing with hoeing in organic grains: II. Evidence of improved weed management in spring wheat, oats, field peas, and flax
Authors: McCollough Margaret R. , Gallandt Eric R. , Molloy Thomas
Published: February 2020

The long-term success of weed management programs requires that all crops in a rotation receive satisfactory weed control. Band sowing with inter-band hoeing has been proposed as an innovative weed management strategy for grain crops. In the band-sowing system, crops are sown in a broadcast pattern within a band of some chosen width (here we selected 12.7 cm); weeds between bands are controlled with inter-band hoeing, with or without so-called “blind cultivation,” for example, tine harrowing. Alteration of the crop spatial arrangement from typical single-line rows to a more evenly distributed pattern aims to enhance interspecific competition while reducing intraspecific competition. Field experiments, conducted in Maine in 2016 and 2017, compared band sowing with inter-band hoeing to the region’s standard practice of planting in 16.5-cm rows and tine harrowing in four test crops: spring wheat (Triticum aestivum L. ‘Glenn’), oat (Avena sativa L. ‘Colt’), field pea (Pisum sativum L. ‘Jetset’), and flax (Linum usitatissimum L. ‘Prairie Thunder’). Band sowing improved weed control relative to the standard practice, especially in crops with greater competitive ability (wheat and oat). Despite improved weed control, in most cases, yields were unaffected by treatment. While band sowing with hoeing provided improved weed control in multiple crops, further study is warranted to optimize seeding rate, band width, and inter-band width to improve crop yields.
Can Terrestrial Water Storage Dynamics be Estimated From Climate Anomalies?
Authors: Jing Wenlong , Zhao Xiaodan , Yao Ling , Di Liping , Yang Ji , Li Yong , Guo Liying , Zhou Chenghu
Published: February 2020

Freshwater stored on land is an extremely vital resource for all the terrestrial life on Earth. But our ability to record the change of land water storage is weak despite its importance. In this study, we attempt to establish a data‐driven model for simulating terrestrial water storage dynamics by relating climate forcings with terrestrial water storage anomalies (TWSAs) from the Gravity Recovery and Climate Experiment (GRACE) satellites. In the case study in Pearl River basin, China, the relationships were learned by using two ensemble learning algorithms, the Random Forest (RF) and eXtreme Gradient Boost (XGB), respectively. The TWSA in the basin was reconstructed back to past decades and compared with the TWSA derived from global land surface models. As a result, the RF and XGB algorithms both perform well and could nicely reproduce the spatial pattern and value range of GRACE observations, outperforming the land surface models. Temporal behaviors of the reconstructed TWSA time series well capture those of both GRACE and land surface models time series. A multiscale GRACE‐based drought index was proposed, and the index matches the Standardized Precipitation‐Evapotranspiration Index time series at different time scales. The case analysis for years of 1963 and 1998 indicates the ability of the reconstructed TWSA for identifying past drought and flood extremes. The importance of different input variables to the TWSA estimation model was quantified, and the precipitation of the prior 2 months is the most important variable for simulating the TWSA of the current month in the model. Results of this study highlight the great potentials for estimating terrestrial water storage dynamics from climate forcing data by using machine learning to achieve comparable results than complex physical models.
Dictionary‐Based Automated Information Extraction From Geological Documents Using a Deep Learning Algorithm
Authors: Qiu Qinjun , Xie Zhong , Wu Liang , Tao Liufeng
Published: February 2020

Massive unstructured geoscience data are buried in geological reports. Geological text classification provides opportunities to leverage this wealth of data for geology and mineralization research. Existing studies of massive geoscience documents/reports have not provided effective classification results for further knowledge discovery and data mining and often lack adequate domain‐specific knowledge. In this paper, we present a novel and unified framework (namely, Dic‐Att‐BiLSTM) that combines domain‐specific knowledge and bidirectional long short‐term memory (BiLSTM) for effective geological text classification. Dic‐Att‐BiLSTM benefits from a matching strategy by incorporating domain‐specific knowledge developed based on geoscience ontology to grasp the linguistic geoscience clues. Furthermore, Dic‐Att‐BiLSTM brings together the capacity of a geoscience dictionary matching approach and an attention mechanism to construct a dictionary attention layer. Finally, the network framework of Dic‐Att‐BiLSTM can utilize domain‐specific knowledge and classify geological text automatically. Experimental verifications are conducted on two constructed data sets, and the results clearly indicate that Dic‐Att‐BiLSTM outperforms other state‐of‐the‐art text classification models.
Characterizing Mars's Magnetotail Topology With Respect to the Upstream Interplanetary Magnetic Fields
Authors: Xu Shaosui , Mitchell David L. , Weber Tristan , Brain David A. , Luhmann Janet G. , Dong Chuanfei , Curry Shannon M. , Ma Yingjuan , DiBraccio Gina A. , Halekas Jasper , Dong Yaxue , Mazelle Christian
Published: February 2020

The canonical picture of the magnetotail of unmagnetized planets consists of draped interplanetary magnetic fields (IMFs) forming opposite‐directed lobes, separated by the current sheet. DiBraccio et al. (2018, https://doi.org/10.1029/2018GL077251) showed that Mars's magnetotail has a twist departing from this picture. Magnetohydrodynamic (MHD) results suggest that the asymmetry in how open field lines connected to the planet populate the tail causes the apparent twist. To validate this interpretation, we compare the tail topology determined from MHD simulations to that inferred from data collected by the Mars Atmosphere and Volatile EvolutioN (MAVEN) spacecraft, in particular, how each topology responds to the upstream IMF orientation. The occurrence rates for open topology from both data and MHD vary with IMF polarities in a similar fashion as the tail twisting. This suggests that Mars's crustal fields have a global effect on the magnetosphere configuration, supporting the picture of a “hybrid” magnetotail that is partly induced/draped and partly intrinsic/planetary in origin.
In Situ Quantitative Tensile Testing of Antigorite in a Transmission Electron Microscope
Authors: Idrissi Hosni , Samaee Vahid , Lumbeeck Gunnar , van der Werf Thomas , Pardoen Thomas , Schryvers Dominique , Cordier Patrick
Published: February 2020

The determination of the mechanical properties of serpentinites is essential toward the understanding of the mechanics of faulting and subduction. Here we present the first in situ tensile tests on antigorite in a transmission electron microscope. A push‐to‐pull deformation device is used to perform quantitative tensile tests, during which force and displacement are measured, while the evolving microstructure is imaged with the microscope. The experiments have been performed at room temperature on 2 × 1 × 0.2 μm3 beams prepared by focused ion beam. The specimens are not single crystals despite their small sizes. Orientation mapping indicated that several grains were well oriented for plastic slip. However, no dislocation activity has been observed even though the engineering tensile stress went up to 700 MPa. We show also that antigorite does not exhibit a purely elastic‐brittle behavior since, despite the presence of defects, the specimens accumulate permanent deformation and did not fail within the elastic regime. Instead, we observe that strain localizes at grain boundaries. All observations concur to show that under these experimental conditions, grain boundary sliding is the dominant deformation mechanism. This study sheds a new light on the mechanical properties of antigorite and calls for further studies on the structure and properties of grain boundaries in antigorite and more generally in phyllosilicates.
Effective Fluid Bulk Modulus in the Partially Saturated Rock and the Amplitude Dispersion Effects
Authors: Rozhko Alexander Y.
Published: February 2020

Frequency dispersion is a well‐known effect in geophysics, which means that waves of different wavelengths propagate at different velocities. Amplitude dispersion is a less‐known effect, which means that waves of different amplitudes propagate at different velocities. Herewith, we consider the alteration of the interfacial energy during wave‐induced two‐phase fluid flow in a partially saturated rock and demonstrate that this leads to a nonlinear amplitude dispersion effect. When the wave amplitude is small, seismic waves cause bending of the interface menisci between immiscible fluids at the pore scale. However, when the wave amplitude is sufficiently large, the interface menisci will slip at the pore scale, causing attenuation of the elastic energy by the contact line friction mechanism. At the zero frequency limit, all viscous dissipation models predict zero attenuation of the elastic wave energy, while this approach predicts a nonzero attenuation due to a static contact angle hysteresis effect. Herein, we extend the Gassmann's theory with three extra terms, which can be obtained from standard laboratory tests: pore‐size distribution and interfacial tension between immiscible fluids and rock wettability (advancing and receding contact angles). We derive closed‐form analytical expressions predicting the effective fluid modulus in partially saturated rock, which falls between Voigt and Reuss averages. Next, we demonstrate that the nonlinear amplitude dispersion effect leads to energy transfer between different frequencies. This may explain the low‐frequency microtremor anomalies, frequently observed above hydrocarbon reservoirs, when the low‐frequency energy of ocean waves (0.1–1 Hz) is converted to higher frequencies (2–6 Hz) by partially saturated reservoirs.
Orientation of Initial Breakdown Pulses and Leader Discharges by Magnetic Direction Finder
Authors: Lu Zhigang , Qiu Shi , Wang Ruichao , Shi Lihua , Zhang Peng
Published: February 2020

For decades, the magnetic direction finder (MDF) technique has been used to give the azimuth of return stroke (RS) in cloud‐to‐ground lightning (CG). Due to the possible polarization error produced by inclined lightning channels, cloud flashes are excluded by most MDF waveform discrimination procedures. In this study, the capability of the orthogonal magnetic coils in determining the azimuth of the initial breakdown pulses (IBPs) and leaders in CG is analyzed and discussed. First, a lightning orthogonal magnetic field sensor with high sensitivity (about 33 nT/V) as well as broad bandwidth (3 kHz to 2 MHz) has been developed. According to the transmission line model, RSs with current 10 kA occurred within 500 km could be detected by this system theoretically. Thereafter, a theoretical analysis was derived in order to evaluate its polarization error with arbitrarily oriented lightning channels. In order to overcome the effect of random nonvertical channels on orientation results, a statistical MDF method is proposed. A field lightning observation was conducted in the year 2017, in which RSs, leaders, and IBPs in CG or cloud flash from two thunderstorms are oriented by the proposed MDF technique. The average azimuth difference between the mathematic expectation of leaders and corresponding RSs is 2.4°. Most of the azimuth in IBPs lies within the region of radar composite reflectivity above 45 dBZ, which indicates that the initiation location of lightning flashes in this study mostly located in these strong echo regions.
Light Competition and Biodiversity Loss Cause Saturation Response of Aboveground Net Primary Productivity to Nitrogen Enrichment
Authors: Ma Fangfang , Song Bing , Quan Quan , Zhang Fangyue , Wang Jinsong , Zhou Qingping , Niu Shuli
Published: February 2020

The continually increasing nitrogen (N) deposition is expected to cause a saturation response of ecosystem aboveground net primary productivity (ANPP). However, its underlying mechanisms, especially for the decrease of ANPP under high N addition rate, remain poorly understood. A field manipulative experiment was conducted to investigate the response of ANPP to six levels of N addition rate (0, 2, 4, 8, 16, and 32 g N·m−2·year−1) in an alpine meadow during 2015–2017. We specifically explored four possible mechanisms, light limitation, biodiversity loss, soil acidification, and ammonium toxicity, underlying the saturation response of ANPP to increasing N addition. The results showed that ANPP increased linearly with N addition rates in 2015, while converted to a saturation response with N addition rates in 2016–2017. With increasing N addition rate, species richness and soil pH significantly reduced while standing litter, light limitation, and NH4+‐N content significantly increased. Under low N addition rate (N0 to N4), increases in N availability significantly improved ANPP although it was partly offset by the indirect N effect via increasing litter accumulation and thus light competition. Under high N addition rate (N8–N32), the decreases in species richness mostly explained the N‐induced reduction in ANPP, leading to a saturation response. This study provides empirical evidences on interpreting N saturation response of ANPP in the alpine meadow. The findings will advance our current understanding of N enrichment effects on ANPP and benefit biogeochemical models in parameterization and benchmark analysis.
Pore Network Model Predictions of Darcy‐Scale Multiphase Flow Heterogeneity Validated by Experiments
Authors: Zahasky Christopher , Jackson Samuel J. , Lin Qingyang , Krevor Samuel
Published: February 2020

Small‐scale heterogeneities in multiphase flow properties fundamentally control the flow of fluids from very small to very large scales in geologic systems. Inability to characterize these heterogeneities often limits numerical model descriptions and predictions of multiphase flow across scales. In this study, we evaluate the ability of pore network models (PNMs) to characterize multiphase flow heterogeneity at the millimeter scale using X‐ray micro‐computed tomography images of centimeter‐scale rock cores. Specifically, PNM capillary pressure and relative permeability output are used to populate a Darcy‐scale numerical model of the rock cores. These pore‐network‐derived Darcy‐scale simulations lead to accurate predictions of core‐average relative permeability, and water saturation, as validated by independent experimental data sets from the same cores and robust uncertainty analysis. Results highlight that heterogeneity in capillary pressure characteristics is more important for predicting local and upscaled flow behavior than heterogeneity in permeability or relative permeability. The leading uncertainty in core‐average relative permeability is driven not by the image processing or PNM extraction but rather by ambiguity in capillary pressure boundary condition definition in the Darcy‐scale simulator. This workflow enables characterization of local capillary heterogeneity and core‐averaged multiphase flow properties while circumventing the need for the most complex experimental observations conventionally required to obtain these properties.
Development of an early-warning system for high-risk patients for suicide attempt using deep learning and electronic health records
Authors: Zheng Le , Wang Oliver , Hao Shiying , Ye Chengyin , Liu Modi , Xia Minjie , Sabo Alex N. , Markovic Liliana , Stearns Frank , Kanov Laura , Sylvester Karl G. , Widen Eric , McElhinney Doff B. , Zhang Wei , Liao Jiayu , Ling Xuefeng B.
Published: February 2020

Suicide is the tenth leading cause of death in the United States (US). An early-warning system (EWS) for suicide attempt could prove valuable for identifying those at risk of suicide attempts, and analyzing the contribution of repeated attempts to the risk of eventual death by suicide. In this study we sought to develop an EWS for high-risk suicide attempt patients through the development of a population-based risk stratification surveillance system. Advanced machine-learning algorithms and deep neural networks were utilized to build models with the data from electronic health records (EHRs). A final risk score was calculated for each individual and calibrated to indicate the probability of a suicide attempt in the following 1-year time period. Risk scores were subjected to individual-level analysis in order to aid in the interpretation of the results for health-care providers managing the at-risk cohorts. The 1-year suicide attempt risk model attained an area under the curve (AUC ROC) of 0.792 and 0.769 in the retrospective and prospective cohorts, respectively. The suicide attempt rate in the “very high risk” category was 60 times greater than the population baseline when tested in the prospective cohorts. Mental health disorders including depression, bipolar disorders and anxiety, along with substance abuse, impulse control disorders, clinical utilization indicators, and socioeconomic determinants were recognized as significant features associated with incident suicide attempt.
A case of malignant hyperlactaemic acidosis appearing upon treatment with the mono-carboxylase transporter 1 inhibitor AZD3965
Authors: McNeillis Rosie , Greystoke Alastair , Walton Jon , Bacon Chris , Keun Hector , Siskos Alexandros , Petrides George , Leech Nicola , Jenkinson Fiona , Bowron Ann , Halford Sarah , Plummer Ruth
Published: February 2020

A 47-year-old man with metastatic melanoma presented with refractory hyperlactaemic acidosis following the first dose of the mono-carboxylase transporter 1 inhibitor AZD3965 within a “first time in man” clinical trial. The mechanism of the agent and the temporal relationship suggested that this event was potentially drug related and recruitment was suspended. However, urinary metabolomics showed extensive abnormalities even prior to drug administration, leading to investigations for an underlying metabolic disorder. The lack of clinical symptoms from the elevated lactate and low blood glucose suggested a diagnosis of “hyper-Warburgism”, where the high tumour burden was associated with extensive glucose uptake and lactate efflux from malignant cells, and the subsequent impact on blood biochemistry. This was supported by an FDG-PET scan showing extensive glucose uptake in numerous metastases and lack of uptake in the brain. A review of the literature showed 16 case reports of “hyper-Warburgism” in non-haematological malignancies, none of them with melanoma, with most associated with a poor outcome. The patient was treated symptomatically, but died 2 months later. The development of AZD3965 continues with the exclusion of patients with elevated plasma lactate at screening added to the protocol as a safety measure.

Trial identification number ClinicalTrials.Gov. NCT01791595.
Squamous differentiation requires G2/mitosis slippage to avoid apoptosis
Authors: Sanz-Gómez Natalia , de Pedro Isabel , Ortigosa Beatriz , Santamaría David , Malumbres Marcos , de Cárcer Guillermo , Gandarillas Alberto
Published: February 2020

The cellular mechanisms controlling cell fate in self-renewal tissues remain unclear. Cell cycle failure often leads to an apoptosis anti-oncogenic response. We have inactivated Cdk1 or Polo-like-1 kinases, essential targets of the mitotic checkpoints, in the epithelia of skin and oral mucosa. Here, we show that inactivation of the mitotic kinases leading to polyploidy in vivo, produces a fully differentiated epithelium. Cells within the basal layer aberrantly differentiate and contain large or various nuclei. Freshly isolated KO cells were also differentiated and polyploid. However, sustained metaphase arrest downstream of the spindle anaphase checkpoint (SAC) due to abrogation of CDC20 (essential cofactor of anaphase-promoting complex), impaired squamous differentiation and resulted in apoptosis. Therefore, upon prolonged arrest keratinocytes need to slip beyond G2 or mitosis in order to initiate differentiation. The results altogether demonstrate that mitotic checkpoints drive squamous cell fate towards differentiation or apoptosis in response to genetic damage.
PUMA-mediated epithelial cell apoptosis promotes Helicobacter pylori infection-mediated gastritis
Authors: Dang Yini , Zhang Yifeng , Xu Lingyan , Zhou Xiaoying , Gu Yanhong , Yu Jian , Jin Shidai , Ji Haoming , Shu Yongqian , Zhang Guoxin , Cui Shiyun , Sun Jing
Published: February 2020

The molecular mechanism responsible forHelicobacter pyloriinfection-mediated gastritis and carcinogenesis is not yet clear. Increased evidence suggests that chronic gastritis and elevated gastric epithelial cell (GEC) apoptosis are crucial events during stomach carcinoma transformation. PUMA is a potent proapoptotic Bcl-2 protein and mediates acute tissue injury. In this study, we aimed to investigate the role of PUMA in GEC apoptosis and inflammation induced byH. pyloriinfection. As a result, we found that PUMA expression was elevated in gastritis tissues compared with uninvolved tissues, and it was correlated with the severity of apoptosis and gastritis. In mice,PUMAmRNA and protein were markedly induced in GECs upon induction of gastritis byH. pylori.PUMA-deficient mice were highly resistant to apoptosis and gastritis induced byH. pylori. Furthermore, the transcription factor NF-κB p65 binds toPUMApromoter to activatePUMAtranscription afterH. pyloriinfection. In addition, NF-κB inhibitor could rescueH. pylori-induced apoptosis and gastritis. Finally,H. pylori-induced activation ofp-p65andPUMAwas mediated via Toll-like receptor 2 (TLR2) and blocked inTLR2knockout mice. Taken together, these results verified the pro-inflammatory effect of PUMA inH. pylori-infected gastric tissue. Moreover, TLR2/NF-κB-mediated transcriptional regulation ofPUMAcontributes to the pathogenesis ofH. pylori-infected gastritis.
An intellectual disability syndrome with single-nucleotide variants in O-GlcNAc transferase
Authors: Pravata Veronica M. , Omelková Michaela , Stavridis Marios P. , Desbiens Chelsea M. , Stephen Hannah M. , Lefeber Dirk J. , Gecz Jozef , Gundogdu Mehmet , Õunap Katrin , Joss Shelagh , Schwartz Charles E. , Wells Lance , van Aalten Daan M. F.
Published: February 2020

Intellectual disability (ID) is a neurodevelopmental condition that affects ~1% of the world population. In total 5−10% of ID cases are due to variants in genes located on the X chromosome. Recently, variants in OGT have been shown to co-segregate with X-linked intellectual disability (XLID) in multiple families. OGT encodes O-GlcNAc transferase (OGT), an essential enzyme that catalyses O-linked glycosylation with β-N-acetylglucosamine (O-GlcNAc) on serine/threonine residues of thousands of nuclear and cytosolic proteins. In this review, we compile the work from the last few years that clearly delineates a new syndromic form of ID, which we propose to classify as a novel Congenital Disorder of Glycosylation (OGT-CDG). We discuss potential hypotheses for the underpinning molecular mechanism(s) that provide impetus for future research studies geared towards informed interventions.
Reversible structural evolution of sodium-rich rhombohedral Prussian blue for sodium-ion batteries
Authors: Wang Wanlin , Gang Yong , Hu Zhe , Yan Zichao , Li Weijie , Li Yongcheng , Gu Qin-Fen , Wang Zhixing , Chou Shu-Lei , Liu Hua-Kun , Dou Shi-Xue
Published: February 2020

Iron-based Prussian blue analogs are promising low-cost and easily prepared cathode materials for sodium-ion batteries. Their materials quality and electrochemical performance are heavily reliant on the precipitation process. Here we report a controllable precipitation method to synthesize high-performance Prussian blue for sodium-ion storage. Characterization of the nucleation and evolution processes of the highly crystalline Prussian blue microcubes reveals a rhombohedral structure that exhibits high initial Coulombic efficiency, excellent rate performance, and cycling properties. The phase transitions in the as-obtained material are investigated by synchrotron in situ powder X-ray diffraction, which shows highly reversible structural transformations between rhombohedral, cubic, and tetragonal structures upon sodium-ion (de)intercalations. Moreover, the Prussian blue material from a large-scale synthesis process shows stable cycling performance in a pouch full cell over 1000 times. We believe that this work could pave the way for the real application of Prussian blue materials in sodium-ion batteries.
Naturally-occurring cholesterol analogues in lipid nanoparticles induce polymorphic shape and enhance intracellular delivery of mRNA
Authors: Patel Siddharth , Ashwanikumar N. , Robinson Ema , Xia Yan , Mihai Cosmin , Griffith Joseph P. , Hou Shangguo , Esposito Adam A. , Ketova Tatiana , Welsher Kevin , Joyal John L. , Almarsson Örn , Sahay Gaurav
Published: February 2020

Endosomal sequestration of lipid-based nanoparticles (LNPs) remains a formidable barrier to delivery. Herein, structure-activity analysis of cholesterol analogues reveals that incorporation of C-24 alkyl phytosterols into LNPs (eLNPs) enhances gene transfection and the length of alkyl tail, flexibility of sterol ring and polarity due to -OH group is required to maintain high transfection. Cryo-TEM displays a polyhedral shape for eLNPs compared to spherical LNPs, while x-ray scattering shows little disparity in internal structure. eLNPs exhibit higher cellular uptake and retention, potentially leading to a steady release from the endosomes over time. 3D single-particle tracking shows enhanced intracellular diffusivity of eLNPs relative to LNPs, suggesting eLNP traffic to productive pathways for escape. Our findings show the importance of cholesterol in subcellular transport of LNPs carrying mRNA and emphasize the need for greater insights into surface composition and structural properties of nanoparticles, and their subcellular interactions which enable designs to improve endosomal escape.
Spatially inhomogeneous competition between superconductivity and the charge density wave in YBa2Cu3O6.67
Authors: Choi J. , Ivashko O. , Blackburn E. , Liang R. , Bonn D. A. , Hardy W. N. , Holmes A. T. , Christensen N. B. , Hücker M. , Gerber S. , Gutowski O. , Rütt U. , Zimmermann M. v. , Forgan E. M. , Hayden S. M. , Chang J.
Published: February 2020

The charge density wave in the high-temperature superconductor YBa2Cu3O7−x (YBCO) has two different ordering tendencies differentiated by their c-axis correlations. These correspond to ferro- (F-CDW) and antiferro- (AF-CDW) couplings between CDWs in neighbouring CuO2 bilayers. This discovery has prompted several fundamental questions: how does superconductivity adjust to two competing orders and are either of these orders responsible for the electronic reconstruction? Here we use x-ray diffraction to study YBa2Cu3O6.67 as a function of magnetic field and temperature. We show that regions with F-CDW correlations suppress superconductivity more strongly than those with AF-CDW correlations. This implies that an inhomogeneous superconducting state exists, in which some regions show a fragile form of superconductivity. By comparison of F-CDW and AF-CDW correlation lengths, it is concluded that F-CDW ordering is sufficiently long-range to modify the electronic structure. Our study thus suggests that F-CDW correlations impact both the superconducting and normal state properties of YBCO.
Publisher Correction: Metabolic engineering of Escherichia coli for shikimate pathway derivative production from glucose-xylose co-substrate
Authors: Fujiwara Ryosuke , Noda Shuhei , Tanaka Tsutomu , Kondo Akihiko
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Chromosome-level assemblies of multiple Arabidopsis genomes reveal hotspots of rearrangements with altered evolutionary dynamics
Authors: Jiao Wen-Biao , Schneeberger Korbinian
Published: February 2020

Despite hundreds of sequenced Arabidopsis genomes, very little is known about the degree of genomic collinearity within single species, due to the low number of chromosome-level assemblies. Here, we report chromosome-level reference-quality assemblies of seven Arabidopsis thaliana accessions selected across its global range. Each genome reveals between 13–17 Mb rearranged, and 5–6 Mb non-reference sequences introducing copy-number changes in ~5000 genes, including ~1900 non-reference genes. Quantifying the collinearity between the genomes reveals ~350 euchromatic regions, where accession-specific tandem duplications destroy the collinearity between the genomes. These hotspots of rearrangements are characterized by reduced meiotic recombination in hybrids and genes implicated in biotic stress response. This suggests that hotspots of rearrangements undergo altered evolutionary dynamics, as compared to the rest of the genome, which are mostly based on the accumulation of new mutations and not on the recombination of existing variation, and thereby enable a quick response to the biotic stress.
Publisher Correction: Copper adparticle enabled selective electrosynthesis of n-propanol
Authors: Li Jun , Che Fanglin , Pang Yuanjie , Zou Chengqin , Howe Jane Y. , Burdyny Thomas , Edwards Jonathan P. , Wang Yuhang , Li Fengwang , Wang Ziyun , De Luna Phil , Dinh Cao-Thang , Zhuang Tao-Tao , Saidaminov Makhsud I. , Cheng Shaobo , Wu Tianpin , Finfrock Y. Zou , Ma Lu , Hsieh Shang-Hsien , Liu Yi-Sheng , Botton Gianluigi A. , Pong Way-Faung , Du Xiwen , Guo Jinghua , Sham Tsun-Kong , Sargent Edward H. , Sinton David
Published: February 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Annexin A1 accounts for an anti-inflammatory binding target of sesamin metabolites
Authors: Kabe Yasuaki , Takemoto Daisuke , Kanai Ayaka , Hirai Miwa , Ono Yoshiko , Akazawa Sota , Horikawa Manabu , Kitagawa Yoshinori , Handa Hiroshi , Rogi Tomohiro , Shibata Hiroshi , Suematsu Makoto
Published: February 2020

Sesamin [(7α,7′α,8α,8′α)-3,4:3′,4′-bis(methylenedioxy)-7,9′:7′,9-diepoxylignane] is a major lignan in sesame seeds. Sesamin is converted to the catechol metabolite, SC1 [(7α,7′α,8α,8′α)-3′,4′-methylenedioxy-7,9′:7′,9-diepoxylignane-3,4-diol] with anti-inflammatory effects after oral administration. However, its molecular target remains unknown. Analysis using high-performance affinity nanobeads led to the identification of annexin A1 (ANX A1) as an SC1-binding protein. SC1 was found to bind to the annexin repeat 3 region of ANX A1 with a high-affinity constant (Kd = 2.77 μmol L−1). In U937 cells, SC1 exhibited an anti-inflammatory effect dependent on ANX A1. Furthermore, administration of sesamin or SC1 attenuated carbon tetrachloride-induced liver damage in mice and concurrently suppressed inflammatory responses dependent on ANX A1. The mechanism involved SC1-induced ANX A1 phosphorylation at serine 27 that facilitates extracellular ANX A1 release. Consequently, the ANX A1 released into the extracellular space suppressed the production of tumor necrosis factor α. This study demonstrates that ANX A1 acts as a pivotal target of sesamin metabolites to attenuate inflammatory responses.
Global karst springs hydrograph dataset for research and management of the world’s fastest-flowing groundwater
Authors: Olarinoye Tunde , Gleeson Tom , Marx Vera , Seeger Stefan , Adinehvand Rouhollah , Allocca Vincenzo , Andreo Bartolome , Apaéstegui James , Apolit Christophe , Arfib Bruno , Auler Augusto , Bailly-Comte Vincent , Barberá Juan Antonio , Batiot-Guilhe Christelle , Bechtel Timothy , Binet Stephane , Bittner Daniel , Blatnik Matej , Bolger Terry , Brunet Pascal , Charlier Jean-Baptiste , Chen Zhao , Chiogna Gabriele , Coxon Gemma , De Vita Pantaleone , Doummar Joanna , Epting Jannis , Fleury Perrine , Fournier Matthieu , Goldscheider Nico , Gunn John , Guo Fang , Guyot Jean Loup , Howden Nicholas , Huggenberger Peter , Hunt Brian , Jeannin Pierre-Yves , Jiang Guanghui , Jones Greg , Jourde Herve , Karmann Ivo , Koit Oliver , Kordilla Jannes , Labat David , Ladouche Bernard , Liso Isabella Serena , Liu Zaihua , Maréchal Jean-Christophe , Massei Nicolas , Mazzilli Naomi , Mudarra Matías , Parise Mario , Pu Junbing , Ravbar Nataša , Sanchez Liz Hidalgo , Santo Antonio , Sauter Martin , Seidel Jean-Luc , Sivelle Vianney , Skoglund Rannveig Øvrevik , Stevanovic Zoran , Wood Cameron , Worthington Stephen , Hartmann Andreas
Published: February 2020

Karst aquifers provide drinking water for 10% of the world’s population, support agriculture, groundwater-dependent activities, and ecosystems. These aquifers are characterised by complex groundwater-flow systems, hence, they are extremely vulnerable and protecting them requires an in-depth understanding of the systems. Poor data accessibility has limited advances in karst research and realistic representation of karst processes in large-scale hydrological studies. In this study, we present World Karst Spring hydrograph (WoKaS) database, a community-wide effort to improve data accessibility. WoKaS is the first global karst springs discharge database with over 400 spring observations collected from articles, hydrological databases and researchers. The dataset’s coverage compares to the global distribution of carbonate rocks with some bias towards the latitudes of more developed countries. WoKaS database will ensure easy access to a large-sample of good quality datasets suitable for a wide range of applications: comparative studies, trend analysis and model evaluation. This database will largely contribute to research advancement in karst hydrology, supports karst groundwater management, and promotes international and interdisciplinary collaborations.
Rapid Assessment of Surface Markers on Cancer Cells Using Immuno-Magnetic Separation and Multi-frequency Impedance Cytometry for Targeted Therapy
Authors: Lin Zhongtian , Lin Siang-Yo , Xie Pengfei , Lin Chen-Yong , Rather Gulam M. , Bertino Joseph R. , Javanmard Mehdi
Published: February 2020

The rapid qualitative assessment of surface markers on cancer cells can allow for point-of-care prediction of patient response to various cancer drugs. Preclinical studies targeting cells with an antibody to “activated” matriptase conjugated to a potent toxin show promise as a selective treatment for a variety of solid tumors. In this paper, we implemented a novel technique for electrical detection of proteins on surfaces of cancer cells using multi-frequency microfluidic impedance cytometry. The biosensor, consists of two gold microelectrodes on a glass substrate embedded in a PDMS microfluidic channel, is used in conjugation with immuno-magnetic separation of cancer cells, and is capable of differentiating between bare magnetic beads, cancer cells and bead-cell aggregates based on their various impedance and frequency responses. We demonstrated proof-of-concept based on detection of “activated” matriptase proteins on the surface of cultured Mantle cells.
Modeling the allosteric modulation on a G-Protein Coupled Receptor: the case of M2 muscarinic Acetylcholine Receptor in complex with LY211960
Authors: Maggi L. , Carloni P. , Rossetti G.
Published: February 2020

Allosteric modulation is involved in a plethora of diverse protein functions, which are fundamental for cells’ life. This phenomenon can be thought as communication between two topographically distinct site of a protein structure. How this communication occurs is still matter of debate. Many different descriptions have been presented so far. Here we consider a specific case where any significant conformational change is involved upon allosteric modulator binding and the phenomenon is depicted as a vibrational energy diffusion process between distant protein regions. We applied this model, by employing computational tools, to the human muscarinic receptor M2, a transmembrane protein G-protein coupled receptor known to undergo allosteric modulation whose recently X-ray structure has been recently resolved both with and without the presence of a particular allosteric modulator. Our calculations, performed on these two receptor structures, suggest that for this case the allosteric modulator modifies the energy current between functionally relevant regions of the protein; this allows to identify the main residues responsible for this modulation. These results contribute to shed light on the molecular basis of allosteric modulation and may help design new allosteric ligands.
Study on antibiotic susceptibility of Salmonella typhimurium L forms to the third and forth generation cephalosporins
Authors: Yang Cuiping , Li Huihui , Zhang Tao , Chu Yifan , Zuo Junli , Chen Dengyu
Published: February 2020

Salmonella typhimurium is a pathogenic gram-negative bacterium, which is found primarily in the intestinal lumen. It often causes diarrhea in infants and young children and leads to food poisoning. Drug resistance of Salmonella typhimurium presented serious complications in clinical patients. In this study, we investigated the antibiotic susceptibility of Salmonella typhimurium standard strain L forms to the third and forth generation cephalosporins, in order to control and eliminate Salmonella typhimurium L forms in infection treatment. Salmonella typhimurium L forms were induced by β-lactam antibiotic cefazolin in the culture medium of bacterial L forms. The antibiotic susceptibility of Salmonella typhimurium L forms was analyzed by K-B drug susceptibility testing. The change trend of drug susceptibility and resistance of Salmonella typhimurium L forms was obtained in accordance with USA clinical and laboratory standards institute (CLSI) evaluation data and statistical analysis. Drug resistance of Salmonella typhimurium L forms showed little increasing trend compared with their parent bacteria. The L form inhibition zone was smaller than in the parent bacteria. However, the drug susceptibility of L forms of Salmonella typhimurium to the third and forth generation cephalosporins remained sensitive.The antibiotic susceptibility of Salmonella typhimurium L forms to the third and forth generation cephalosporins remains sensitive, and the combined use of multi-antibiotics is a convenient and effective method to reduce Salmonella typhimurium L forms occurrence.
c-di-GMP-related phenotypes are modulated by the interaction between a diguanylate cyclase and a polar hub protein
Authors: Nicastro Gianlucca G. , Kaihami Gilberto H. , Pulschen André A. , Hernandez-Montelongo Jacobo , Boechat Ana Laura , de Oliveira Pereira Thays , Rosa Caio Gomes Tavares , Stefanello Eliezer , Colepicolo Pio , Bordi Christophe , Baldini Regina L.
Published: February 2020

c-di-GMP is a major player in the switch between biofilm and motile lifestyles. Several bacteria exhibit a large number of c-di-GMP metabolizing proteins, thus a fine-tuning of this nucleotide levels may occur. It is hypothesized that some c-di-GMP metabolizing proteins would provide the global c-di-GMP levels inside the cell whereas others would maintain a localized pool, with the resulting c-di-GMP acting at the vicinity of its production. Although attractive, this hypothesis has yet to be demonstrated in Pseudomonas aeruginosa. We found that the diguanylate cyclase DgcP interacts with the cytosolic region of FimV, a polar peptidoglycan-binding protein involved in type IV pilus assembly. Moreover, DgcP is located at the cell poles in wild type cells but scattered in the cytoplasm of cells lacking FimV. Overexpression of dgcP leads to the classical phenotypes of high c-di-GMP levels (increased biofilm and impaired motilities) in the wild-type strain, but not in a ΔfimV background. Therefore, our findings suggest that DgcP activity is regulated by FimV. The polar localization of DgcP might contribute to a local c-di-GMP pool that can be sensed by other proteins at the cell pole, bringing to light a specialized function for a specific diguanylate cyclase.
Genome-wide analysis of WRKY transcription factors in Aquilaria sinensis (Lour.) Gilg
Authors: Xu Yan-Hong , Sun Pei-Wen , Tang Xiao-Lin , Gao Zhi-Hui , Zhang Zheng , Wei Jian-He
Published: February 2020

The WRKY proteins are a superfamily of transcription factor that regulate diverse developmental and physiological processes in plants. Completion of the whole-genome sequencing of Aquilaria sinensis allowed us to perform a genome-wide investigation for WRKY proteins. Here, we predicted 70 WRKY genes from the A. sinensis genome and undertaken a comprehensive bioinformatic analysis. Due to their diverse structural features, the 70 AsWRKY genes are classified into three main groups (group I–III), with five subgroups (IIa–IIe) in group II, except two belong to none of them. Distinct expression profiles of AsWRKYs with RNA sequencing data revealed their diverse expression patterns among different tissues and in the process of whole-tree-inducing agarwood formation. Based on the expression characteristics, we predict some AsWRKYs are pseudogenes, and some may be involved in the biosynthesis of agarwood sesquiterpenes as activators or repressors. Among the tested genes treated with MeJA and H2O2, most of them are induced by H2O2, but downregulated by MeJA, implying the complexity of their involvement in signal transduction regulation. Our results not only provide a basic platform for functional identification of WRKYs in A. sinensis but important clues for further analysis their regulation role in agarwood formation.
Complementary molecular methods reveal comprehensive phylogenetic diversity integrating inconspicuous lineages of early-diverged wood-decaying mushrooms
Authors: Shirouzu Takashi , Matsuoka Shunsuke , Doi Hideyuki , Nagata Nobuaki , Ushio Masayuki , Hosaka Kentaro
Published: February 2020

Among terrestrial microorganisms, mushroom-forming fungi have been relatively well investigated, however the inconspicuous strains may be overlooked by conventional visual investigations causing underestimation of their phylogenetic diversity. Herein, we sought to obtain a comprehensive phylogenetic diversity profile for the early-diverging wood-decaying mushrooms Dacrymycetes, using an approach that combines fruiting-body collection, culture isolation, and environmental DNA (eDNA) metabarcoding of decaying branches. Among the 28 operational taxonomic units (OTUs) detected during a three-year investigation, 10 each were from fruiting bodies and cultured mycelia and 27 were detected as eDNA sequences. eDNA metabarcoding revealed various lineages across the Dacrymycetes phylogeny. Alternatively, fruiting-body and culture surveys uncovered only ~50% of the OTUs detected through eDNA metabarcoding, suggesting that several inconspicuous or difficult-to-isolate strains are latent in the environment. Further, eDNA and culture surveys revealed early-diverging clades that were not identified in the fruiting-body survey. Thus, eDNA and culture-based techniques can uncover inconspicuous yet phylogenetically important mushroom lineages that may otherwise be overlooked via typical visual investigations.
Exogenously overexpressed intronic long noncoding RNAs activate host gene expression by affecting histone modification in Arabidopsis
Authors: Liu Zhang-Wei , Zhao Nan , Su Yin-Na , Chen Shan-Shan , He Xin-Jian
Published: February 2020

Involvement of long non-coding RNAs (lncRNAs) in the regulation of gene expression in cis has been well studied in eukaryotes but relatively little is known whether and how lncRNAs affect gene expression in tans. In Arabidopsis thaliana, COLDAIR, a previously reported lncRNA, is produced from the first intron of FLOWERING LOCUS C (FLC), which encodes a repressor of flowering time. Our results indicated that the exogenously overexpressed COLDAIR enhances the expression of FLC in trans, resulting in a late-flowering phenotype. In 35S-COLDAIR lines, the enhanced expression of FLC is correlated with the down-regulation of the repressive histone mark H3K27me3 and with the up-regulation of the active histone mark H3K4me3 at the FLC chromatin. Furthermore, we demonstrated that overexpression of intronic lncRNAs from several other H3K27me3-enriched MADS-box genes also activates the expression of their host genes. This study suggests that the involvement of overexpressed intronic lncRNAs in gene activation may be conserved in H3K27me3-enriched genes in eukaryotes.