bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are We Getting Better in Using Nitrogen?: Variations in Nitrogen Use Efficiency of Two Cereal Crops Across the United States
Authors: Lu Chaoqun , Zhang Jien , Cao Peiyu , Hatfield Jerry L. 
Published: July 2019

AbstractSpatial variation and temporal trajectory of crop nitrogen use efficiency (NUE) have important implications for nitrogen management and environmental conservation. Previous studies have examined cross‐nation divergences in crop NUE but often overlooked its spatial heterogeneity and cross‐crop differences at subnational scales. We examined the relationship between state‐level NUE and nitrogen fertilizer use for two major fertilizer‐consuming crops, corn and winter wheat, which account for over half of national N fertilizer use in the United States. Since 1970, as N fertilizer use rates have changed, the responses of crop yield and NUE have exhibited large temporal and spatial variations. It is evident that NUE of corn begins to decline when N fertilizer application rate exceeds ~150 kg N ha−1 yr−1, and that yield response of winter wheat slows down with annual N fertilizer input above ~50 kg N ha−1 yr−1. State‐level NUE in both crops has risen in recent decades, which could potentially reduce N loss from agricultural production. Across the United States, some major corn‐producing states demonstrate a shift from an increasing trend of NUE during the period 1970 to 1999 to a decreasing trend after 2000, whereas winter wheat‐producing states present an opposite pattern. Furthermore, this study indicates that annual dynamics of N surplus in corn is closely tied with grain yields, while that in winter wheat significantly correlates with N fertilizer input. A larger proportion of N loss would be anticipated if no further increase in corn yield was obtained or fertilizer use kept rising in winter wheat.
Covalently-assembled single-chain protein nanostructures with ultra-high stability
Authors: Bai Wenqin , Sargent Cameron J. , Choi Jeong-Mo , Pappu Rohit V. , Zhang Fuzhong 
Published: July 2019

AbstractProtein nanostructures with precisely defined geometries have many potential applications in catalysis, sensing, signal processing, and drug delivery. While many de novo protein nanostructures have been assembled via non-covalent intramolecular and intermolecular interactions, a largely unexplored strategy is to construct nanostructures by covalently linking multiple individually folded proteins through site-specific ligations. Here, we report the synthesis of single-chain protein nanostructures with triangular and square shapes made using multiple copies of a three-helix bundle protein and split intein chemistry. Coarse-grained simulations confirm the experimentally observed flexibility of these nanostructures, which is optimized to produce triangular structures with high regularity. These single-chain nanostructures also display ultra-high thermostability, resist denaturation by chaotropes and organic solvents, and have applicability as scaffolds for assembling materials with nanometer resolution. Our results show that site-specific covalent ligation can be used to assemble individually folded proteins into single-chain nanostructures with bespoke architectures and high stabilities.
FDA-ARGOS is a database with public quality-controlled reference genomes for diagnostic use and regulatory science
Authors: Sichtig Heike , Minogue Timothy , Yan Yi , Stefan Christopher , Hall Adrienne , Tallon Luke , Sadzewicz Lisa , Nadendla Suvarna , Klimke William , Hatcher Eneida , Shumway Martin , Aldea Dayanara Lebron , Allen Jonathan , Koehler Jeffrey , Slezak Tom , Lovell Stephen , Schoepp Randal , Scherf Uwe 
Published: July 2019

AbstractFDA proactively invests in tools to support innovation of emerging technologies, such as infectious disease next generation sequencing (ID-NGS). Here, we introduce FDA-ARGOS quality-controlled reference genomes as a public database for diagnostic purposes and demonstrate its utility on the example of two use cases. We provide quality control metrics for the FDA-ARGOS genomic database resource and outline the need for genome quality gap filling in the public domain. In the first use case, we show more accurate microbial identification of Enterococcus avium from metagenomic samples with FDA-ARGOS reference genomes compared to non-curated GenBank genomes. In the second use case, we demonstrate the utility of FDA-ARGOS reference genomes for Ebola virus target sequence comparison as part of a composite validation strategy for ID-NGS diagnostic tests. The use of FDA-ARGOS as an in silico target sequence comparator tool combined with representative clinical testing could reduce the burden for completing ID-NGS clinical trials.
Single-crosslink microscopy in a biopolymer network dissects local elasticity from molecular fluctuations
Authors: Jiang Lingxiang , Xie Qingqiao , Tsang Boyce , Granick Steve 
Published: July 2019

AbstractPolymer networks are fundamental from cellular biology to plastics technology but their intrinsic inhomogeneity is masked by the usual ensemble-averaged measurements. Here, we construct direct maps of crosslinks—symbolic depiction of spatially-distributed elements highlighting their physical features and the relationships between them—in an actin network. We selectively label crosslinks with fluorescent markers, track their thermal fluctuations, and characterize the local elasticity and cross-correlations between crosslinks. Such maps display massive heterogeneity, reveal abundant anticorrelations, and may contribute to address how local responses scale up to produce macroscopic elasticity. Single-crosslink microscopy offers a general, microscopic framework to better understand crosslinked molecular networks in undeformed or strained states.
Universal optimal geometry of minimal phoretic pumps
Authors: Michelin Sébastien , Lauga Eric 
Published: July 2019

AbstractUnlike pressure-driven flows, surface-mediated phoretic flows provide efficient means to drive fluid motion on very small scales. Colloidal particles covered with chemically-active patches with nonzero phoretic mobility (e.g. Janus particles) swim using self-generated gradients, and similar physics can be exploited to create phoretic pumps. Here we analyse in detail the design principles of phoretic pumps and show that for a minimal phoretic pump, consisting of 3 distinct chemical patches, the optimal arrangement of the patches maximizing the flow rate is universal and independent of chemistry.
Mast cells play role in wound healing through the ZnT2/GPR39/IL-6 axis
Authors: Nishida Keigo , Hasegawa Aiko , Yamasaki Satoru , Uchida Ryota , Ohashi Wakana , Kurashima Yosuke , Kunisawa Jun , Kimura Shunsuke , Iwanaga Toshihiko , Watarai Hiroshi , Hase Koji , Ogura Hideki , Nakayama Manabu , Kashiwakura Jun-ichi , Okayama Yoshimichi , Kubo Masato , Ohara Osamu , Kiyono Hiroshi , Koseki Haruhiko , Murakami Masaaki , Hirano Toshio 
Published: July 2019

AbstractZinc (Zn) is an essential nutrient and its deficiency causes immunodeficiency and skin disorders. Various cells including mast cells release Zn-containing granules when activated; however, the biological role of the released Zn is currently unclear. Here we report our findings that Zn transporter ZnT2 is required for the release of Zn from mast cells. In addition, we found that Zn and mast cells induce IL-6 production from inflammatory cells such as skin fibroblasts and promote wound healing, a process that involves inflammation. Zn induces the production of a variety of pro-inflammatory cytokines including IL-6 through signaling pathways mediated by the Zn receptor GPR39. Consistent with these findings, wound healing was impaired in mice lacking IL-6 or GPR39. Thus, our results show that Zn and mast cells play a critical role in wound healing through activation of the GPR39/IL-6 signaling axis.
Natural killer cells impede the engraftment of cardiomyocytes derived from induced pluripotent stem cells in syngeneic mouse model
Authors: Nakamura Yuki , Miyagawa Shigeru , Yoshida Shohei , Sasawatari Shigemi , Toyofuku Toshihiko , Toda Koichi , Sawa Yoshiki 
Published: July 2019

AbstractTransplantation of cardiomyocytes derived from induced pluripotent stem cell (iPSC-CMs) is a promising approach for increasing functional CMs during end-stage heart failure. Although major histocompatibility complex (MHC) class I matching between donor cells and recipient could reduce acquired immune rejection, innate immune responses may have negative effects on transplanted iPSC-CMs. Here, we demonstrated that natural killer cells (NKCs) infiltrated in iPSC-CM transplants even in a syngeneic mouse model. The depletion of NKCs using an anti-NKC antibody rescued transplanted iPSC-CMs, suggesting that iPSC-CMs activated NKC-mediated innate immunity. Surprisingly, iPSC-CMs lost inhibitory MHCs but not activating ligands for NKCs. Re-expression of MHC class I induced by IFN-γ as well as suppression of activating ligands by an antibody rescued the transplanted iPSC-CMs. Thus, NKCs impede the engraftment of transplanted iPSC-CMs because of lost MHC class I, and our results provide a basis for an approach to improve iPSC-CM engraftment.
Phylogeographic and genetic characterization of porcine circovirus type 2 in Taiwan from 2001–2017
Authors: Tsai Guang-Ting , Lin Yung-Cheng , Lin Wei-Hao , Lin Jih-Hui , Chiou Ming-Tang , Liu Hsin-Fu , Lin Chao-Nan 
Published: July 2019

AbstractPorcine circovirus type 2 (PCV2) is an important pathogen that causes significant economic losses in the swine industry worldwide. Five major PCV2 genotypes have been identified, including PCV2a, PCV2b, PCV2c, PCV2d, and PCV2e. To investigate the prevalence and phylodynamics of the different PCV2 genotypes in Taiwan, 214 PCV2 ORF2 sequences from Taiwan and other countries were analyzed. Genotypic differences were observed among PCV2a, 2b, and 2d at amino acid position 89 in ORF2, with isoleucine (I), arginine (R), and leucine (L), respectively. Similar to other countries, a genotypic shift was also observed in Taiwan, where the predominant genotype shifted from PCV2b to 2d after 2010. The estimated nucleotide substitution rate of Taiwanese strains in the ORF2 region was 8.467 × 10−4 substitutions per site per year. This rapid evolution rate of PCV2 may lead to the genotypic shift observed in Taiwan. The times to the most recent common ancestor (TMRCA) for PCV2a, -2b, and -2d-2 was dated to 1970, 1992 and 2004, respectively. Thus, the PCV2a, -2b, and -2d genotypes were already present in Taiwan before the introduction of the PCV2 vaccine.
Differential binding affinity of tau repeat region R2 with neuronal-specific β-tubulin isotypes
Authors: Bhandare Vishwambhar Vishnu , Kumbhar Bajarang Vasant , Kunwar Ambarish 
Published: July 2019

AbstractTau is a microtubule-associated protein whose C-terminal domain consisting of four repeat regions R1, R2, R3 and R4 binds to microtubules to stabilize them. In several neurodegenerative diseases, tau detaches from microtubules to form insoluble aggregates leading to tauopathy. Microtubules are made up of αβ tubulin subunits. Seven α-tubulin and nine β-tubulin isotypes have been reported to be present in humans till date. These tubulin isotypes show residue composition variations mainly at C-terminal region and bind to motor proteins and anti-mitotic drugs differently. These tubulin isotypes show tissue specific expression as their relative proportion varies significantly in different type of cells. It is also known that tau binds differently to different cell lines and can either promote or demote microtubule polymerization. However, the relative binding affinity of tau to the different β-tubulin isotypes present in different cell lines is completely unknown. Here, we study relative binding affinity of Tau repeat region R2 to neuronal specific tubulin isotypes βI, βIIb, and βIII using molecular modelling approach. The order of binding energy of tau with tubulin is βIII > βIIb > βI. Our strategy can be potentially adapted to understand differential binding affinity of tau towards β-tubulin isotypes present in other cell lines.
Parylene Based Memristive Devices with Multilevel Resistive Switching for Neuromorphic Applications
Authors: Minnekhanov Anton A. , Emelyanov Andrey V. , Lapkin Dmitry A. , Nikiruy Kristina E. , Shvetsov Boris S. , Nesmelov Alexander A. , Rylkov Vladimir V. , Demin Vyacheslav A. , Erokhin Victor V. 
Published: July 2019

AbstractIn this paper, the resistive switching and neuromorphic behaviour of memristive devices based on parylene, a polymer both low-cost and safe for the human body, is comprehensively studied. The Metal/Parylene/ITO sandwich structures were prepared by means of the standard gas phase surface polymerization method with different top active metal electrodes (Ag, Al, Cu or Ti of ~500 nm thickness). These organic memristive devices exhibit excellent performance: low switching voltage (down to 1 V), large OFF/ON resistance ratio (up to 104), retention (≥104 s) and high multilevel resistance switching (at least 16 stable resistive states in the case of Cu electrodes). We have experimentally shown that parylene-based memristive elements can be trained by a biologically inspired spike-timing-dependent plasticity (STDP) mechanism. The obtained results have been used to implement a simple neuromorphic network model of classical conditioning. The described advantages allow considering parylene-based organic memristors as prospective devices for hardware realization of spiking artificial neuron networks capable of supervised and unsupervised learning and suitable for biomedical applications.
A suite of kinetically superior AEP ligases can cyclise an intrinsically disordered protein
Authors: Harris Karen S. , Guarino Rosemary F. , Dissanayake Ravindu S. , Quimbar Pedro , McCorkelle Owen C. , Poon Simon , Kaas Quentin , Durek Thomas , Gilding Edward K. , Jackson Mark A. , Craik David J. , van der Weerden Nicole L. , Anders Robin F. , Anderson Marilyn A. 
Published: July 2019

AbstractAsparaginyl endopeptidases (AEPs) are a class of enzymes commonly associated with proteolysis in the maturation of seed storage proteins. However, a subset of AEPs work preferentially as peptide ligases, coupling release of a leaving group to formation of a new peptide bond. These “ligase-type” AEPs require only short recognition motifs to ligate a range of targets, making them useful tools in peptide and protein engineering for cyclisation of peptides or ligation of separate peptides into larger products. Here we report the recombinant expression, ligase activity and cyclisation kinetics of three new AEPs from the cyclotide producing plant Oldenlandia affinis with superior kinetics to the prototypical recombinant AEP ligase OaAEP1b. These AEPs work preferentially as ligases at both acidic and neutral pH and we term them “canonical AEP ligases” to distinguish them from other AEPs where activity preferences shift according to pH. We show that these ligases intrinsically favour ligation over hydrolysis, are highly efficient at cyclising two unrelated peptides and are compatible with organic co-solvents. Finally, we demonstrate the broad scope of recombinant AEPs in biotechnology by the backbone cyclisation of an intrinsically disordered protein, the 25 kDa malarial vaccine candidate Plasmodium falciparum merozoite surface protein 2 (MSP2).
Generation of TD50 values for carcinogenicity study data
Authors: Thresher Andrew , Gosling John Paul , Williams Richard 
Published: July 2019

AbstractCarcinogenic potency is a key factor in the understanding of chemical risk assessment. Measures of carcinogenic potency, for example TD50, are instrumental in the determination of metrics such as the threshold of toxicological concern (TTC), acceptable intake (AI) and permitted daily exposure (PDE), which in turn impact on human exposure. The Carcinogenic Potency Data Base (CPDB) has provided a source of study information, complete with calculated TD50 values. However, this is no longer actively updated. An understanding of carcinogenic potency, which can be derived from dose–response data, can be used as part of human risk assessments to generate safety thresholds under which cancer risk is judged to be minimal. The aim of this paper is to produce a transparent methodology for calculating TD50 values from experimental data in a manner consistent with the CPDB. This was then applied across the same data as used in the CPDB and analysis done on the correlation with the CPDB TD50 values. While the two sets of values showed a high level of correlation overall, there were some significant discrepancies. These were predominantly due to a lack of clarity in the CPDB methodology and inappropriate use of a linear model in TD50 calculation where the data was not suitable for such an approach.
Protective effects of delphinidin against H2O2–induced oxidative injuries in human retinal pigment epithelial cells
Authors: Ni Timin , Yang Wanju , Xing Yiqiao 
Published: July 2019

Abstract
Age-related macular degeneration (AMD) is now one of the leading causes of blindness in the elderly population and oxidative stress-induced damage to retinal pigment epithelial (RPE) cells occurs as part of the pathogenesis of AMD. In the present study, we evaluated the protective effect of delphinidin (2-(3,4,5-trihydroxyphenyl) chromenylium-3,5,7-triol) against hydrogen peroxide (H2O2)-induced toxicity in human ARPE-19 cells and its molecular mechanism. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and flow cytometry demonstrated that pretreatment of ARPE-19 cells with delphinidin (25, 50, and 100 μg/ml) significantly increased cell viability and reduced the apoptosis from H2O2 (0.5 mM)-induced oxidative stress in a concentration-dependent manner, which was achieved by the inhibition of Bax, cytochrome c, and caspase-3 protein expression and enhancement of Bcl-2 protein. The same tendency was observed in ARPE-19 cells pre-treated with 15 mM of N-acetylcysteine (NAC) before the addition of H2O2. Furthermore, pre-incubation of ARPE-19 cells with delphinidin markedly inhibited the intracellular reactive oxygen species (ROS) generation and Nox1 protein expression induced by H2O2. Moreover, the decreased antioxidant enzymes activities of superoxide dismutase (SOD), catalase (CAT), and glutathione-peroxidase (GSH-PX) and elevated (MDA) level in H2O2-treated cells were reversed to the normal standard by the addition of delphinidin, which was regulated by increasing nuclear Nrf2 protein expression in ARPE-19 cells. Our results suggest that delphinidin effectively protects human ARPE-19 cells from H2O2-induced oxidative damage via anti-apoptotic and antioxidant effects.
New therapeutic targets for the prevention of infectious acute exacerbations of COPD: role of epithelial adhesion molecules and inflammatory pathways
Authors: Atto Brianna , Eapen Mathew Suji , Sharma Pawan , Frey Urs , Ammit Alaina J. , Markos James , Chia Collin , Larby Josie , Haug Greg , Weber Heinrich C. , Mabeza George , Tristram Stephen , Myers Stephen , Geraghty Dominic P. , Flanagan Katie L. , Hansbro Philip M. , Sohal Sukhwinder Singh 
Published: July 2019

AbstractChronic respiratory diseases are among the leading causes of mortality worldwide, with the major contributor, chronic obstructive pulmonary disease (COPD) accounting for approximately 3 million deaths annually. Frequent acute exacerbations (AEs) of COPD (AECOPD) drive clinical and functional decline in COPD and are associated with accelerated loss of lung function, increased mortality, decreased health-related quality of life and significant economic costs. Infections with a small subgroup of pathogens precipitate the majority of AEs and consequently constitute a significant comorbidity in COPD. However, current pharmacological interventions are ineffective in preventing infectious exacerbations and their treatment is compromised by the rapid development of antibiotic resistance. Thus, alternative preventative therapies need to be considered. Pathogen adherence to the pulmonary epithelium through host receptors is the prerequisite step for invasion and subsequent infection of surrounding structures. Thus, disruption of bacterial–host cell interactions with receptor antagonists or modulation of the ensuing inflammatory profile present attractive avenues for therapeutic development. This review explores key mediators of pathogen–host interactions that may offer new therapeutic targets with the potential to prevent viral/bacterial-mediated AECOPD. There are several conceptual and methodological hurdles hampering the development of new therapies that require further research and resolution.
Prevalence and subtype distribution of Blastocystis in ethnic minority groups on both sides of the China–Myanmar border, and assessment of risk factors
Authors: Gong Baiyan , Liu Xiaohua , Wu Yanchen , Xu Ning , Xu Meng , Yang Fengkun , Tong Lei , Zhou Kexin , Cao Jianping , Liu Aiqin , Shen Yujuan 
Published: July 2019

Blastocystis is one of the most common intestinal parasites in humans worldwide. To understand its prevalence and to explore the risk factors for Blastocystis in humans in developing countries, a molecular epidemiological investigation of Blastocystis was conducted in ethnic minority groups on both sides of the China–Myanmar border. A total of 461 fecal specimens were collected from 289 Yao people in China and 172 Wa people in Myanmar, together with a questionnaire for each participant. Based on sequence analysis of the partial small subunit of ribosomal RNA (SSU rRNA) gene (barcode region or 260 bp region), an average prevalence of 6.29% (29/461) was observed, with 4.50% (13/289) in Yao people and 9.30% (16/172) in Wa people. Twenty-two Blastocystis isolates were successfully subtyped by sequence analysis of the barcode region. Three subtypes were identified: ST1 (n = 7), ST3 (n = 13) and ST4 (n = 2). A statistical difference in the prevalence of Blastocystis was only observed between children (12.37%, 12/97) and adults (4.95%, 16/323), and between not washing hands (11.02%, 14/127) and washing hands (4.76%, 15/315) after using toilets, emphasizing the importance and necessity of health education in people in the investigated areas, especially in children.
Diagnosis of Huntington’s disease via sequential 18F-DOPA and 18F-FDG PET/MRI
Authors: Michler Enrico , Hoberück Sebastian , Martino Filippo , Platzek Ivan , Kotzerke Jörg 
Published: July 2019

IntroductionCases of rare movement disorders like Huntington’s disease (HD) are not easy to diagnose, especially when occurring sporadically, without documented family history. In HD patients, MRI scans commonly feature atrophy of the striatum and reduced volume of white matter. But if morphological findings remain unspecific, functional PET imaging could provide valuable information to further clarify diagnosis. We present a case report of a 56-year-old woman suffering from mild hypokinetic-rigid syndrome and depression, suspicious of Parkinson’s disease, who was referred to 18F-DOPA and 18F-FDG PET/MRI scans at our department.