bluuebunny/crossref_metadata_2025 huggingface dataset:
LES of Flow Through and Around a Finite Patch of Thin Plates
Authors: Gong Yiqing , Stoesser Thorsten , Mao Jingqiao , McSherry Richard
Published: July 2019

Large eddy simulations (LESs) are performed for turbulent flow through and around a porous patch of thin vertical plates at a plate Reynolds number of Rep=5,800. The plates are arranged in a staggered pattern, presenting an elliptical planform and mimicking streamwise‐oriented blades of emergent vegetation. The immersed boundary method is employed to explicitly resolve the interaction between flow and plates. Three flow cases, each with a different number of plates within the same planform area, that is, different patch density, are studied. The Reynolds number based on freestream velocity and plate length is the same in all cases. Inspection of the distribution of velocity and vorticity in the horizontal plane reveals that downstream plates are significantly impacted by the wakes from upstream plates. It is therefore proposed that the plates can be divided into two groups based on the local flow characteristics, which are a function of position within the patch: a free group and a wake group. This classification is subsequently used in the quantitative analysis of boundary layer development and drag force at plate scale. The thickness and character of the simulated boundary layers on the plates differ significantly from predictions based on analytical or empirical relationships, which is due to wake effects and the finite length of the plates. The simulations demonstrate the so‐called sheltering effect; that is, the drag forces acting on downstream plates (in the wake group) are significantly lower than those acting on upstream plates, a result of the lower approach flow speed. Although the front‐area‐to‐lateral‐area ratio of the plates is low (1/40), pressure drag is observed to be larger than friction drag for each plate. The ratio of pressure drag to the total drag at patch scale shows only very little dependence on the plate density of the patch.
How Cassini Ran Rings Around Saturn and What It Helped Us Learn
Authors: Benningfield Damond
Published: July 2019

Once and future rings: During its final 22 orbits, the Cassini spacecraft provided a completely new look at one of our solar system’s most famous features.
Limiting Factor Was a Science Opportunity for a Deep-Sea Geologist
Authors: Loomis Ilima
Published: July 2019

For Mariana Trench expert Patricia Fryer, an extreme explorer’s record-setting dive was a chance to retrieve some of the deepest samples ever collected.
Separation and Quantification of Ionospheric Convection Sources: 1. A New Technique
Authors: Reistad J. P. , Laundal K. M. , Østgaard N. , Ohma A. , Haaland S. , Oksavik K. , Milan S. E.
Published: July 2019

This paper describes a novel technique that allows separation and quantification of different sources of convection in the high‐latitude ionosphere. To represent the ionospheric convection electric field, we use the Spherical Elementary Convection Systems representation. We demonstrate how this technique can separate and quantify the contributions from different magnetospheric source regions to the overall ionospheric convection pattern. The technique is in particular useful for distinguishing the contributions of high‐latitude reconnection associated with lobe cells from the low‐latitude reconnection associated with Dungey two‐cell circulation. The results from the current paper are utilized in a companion paper (Reistad et al., 2019, https://doi.org/10.1029/2019JA026641) to quantify how the dipole tilt angle influences lobe convection cells. We also describe a relation bridging other representations of the ionospheric convection electric field or potential to the Spherical Elementary Convection Systems description, enabling a similar separation of convection sources from existing models.
WINDII Observations and WACCM‐X Simulations of High‐Latitude Winds Under Different Solar Radio Flux and Geomagnetic Disturbance Conditions
Authors: Liu Shushi , Shepherd Gordon G. , Chen Yongsheng , Shepherd Marianna G. , Bhutia Sangay
Published: July 2019

Thermospheric zonal winds at altitudes of 140 to 250 km are shown to reverse from eastward to strong westward between 100° and 200° in geographic longitude and 60°S to 70°S latitude in the Southern Hemisphere. The reversal also occurs at the same latitude in the Northern Hemisphere, but from 200° to 340° longitude. The phenomenon has been previously described as a “wind wall.” Observations by the Wind Imaging Interferometer (WINDII) on the National Aeronautics and Space Administration's Upper Atmosphere Research Satellite (UARS) and simulations by the Whole Atmosphere Community Climate Model with thermosphere and ionosphere extension (WACCM‐X) are utilized to explore the characteristics of what has been called a wind wall. In order to study the dependence on solar radio flux and geomagnetic activity, the relationships of the maximum zonal wind and F10.7 (the solar radio flux at 10.7 cm) and ap indices are investigated. The results show that WINDII observations and WACCM‐X simulations agree well in describing this wind signature. Moreover, the appearance of the wind wall is found to have a strong dependence on the solar radio flux and geomagnetic activity. In addition, WINDII winds have a stronger response to geomagnetic activity than WACCM‐X winds.
Climate Change Trends and Impacts on Vegetation Greening Over the Tibetan Plateau
Authors: Zhong Lei , Ma Yaoming , Xue Yongkang , Piao Shilong
Published: July 2019

The Tibetan Plateau (TP) is an ecologically fragile region that is sensitive to climate change. In the context of global climate change, the climate change trends of the TP and the vegetation dynamic response need to be investigated. Based on in situ meteorological data, Satellite Pour l'Observation de la Terre vegetation data, and Moderate Resolution Imaging Spectroradiometer land cover data, a comprehensive analysis was conducted to determine the trends of climate parameters in the TP region at different time scales (long term: 1960–2014; midterm: 1980–2014; short term 1999–2014). A consistent warming trend was observed for different temporal scales, while a warming slowdown was identified during 1999 and 2014. The warming rate was also shown to be much higher in the high‐altitude regions (>4,000 m), especially at midterm and short‐term time scales. A new cloud‐free time series of vegetation index data sets was reconstructed, and the vegetation density showed a general increasing trend along with a warming trend in the TP. The regions showing significant increases accounted for 7.63% of the total Tibetan territory. The major significant greening trend of the TP was mainly caused by climate factors. The reforestation projects may have played a minor role in the vegetation greening in specific regions of the TP. In addition, various vegetation types showed markedly different responses to climate changes. The grassland in semiarid regions, which accounted for 41.9% of the territory of the TP, was identified to be very sensitive to variations in both temperature and precipitation.
Author Correction: The wide utility of rabbits as models of human diseases
Authors: Esteves Pedro J. , Abrantes Joana , Baldauf Hanna-Mari , BenMohamed Lbachir , Chen Yuxing , Christensen Neil , González-Gallego Javier , Giacani Lorenzo , Hu Jiafen , Kaplan Gilla , Keppler Oliver T. , Knight Katherine L. , Kong Xiang-Peng , Lanning Dennis K. , Le Pendu Jacques , de Matos Ana Lemos , Liu Jia , Liu Shuying , Lopes Ana M. , Lu Shan , Lukehart Sheila , Manabe Yukari C. , Neves Fabiana , McFadden Grant , Pan Ruimin , Peng Xuwen , de Sousa-Pereira Patricia , Pinheiro Ana , Rahman Masmudur , Ruvoën-Clouet Natalie , Subbian Selvakumar , Tuñón Maria Jesús , van der Loo Wessel , Vaine Michael , Via Laura E. , Wang Shixia , Mage Rose
Published: July 2019

This article was originally published under a CC BY-NC-SA License, but has now been made available under a CC BY 4.0 License.
Single-cell biomagnifier for optical nanoscopes and nanotweezers
Authors: Li Yuchao , Liu Xiaoshuai , Li Baojun
Published: July 2019

Optical microscopes and optical tweezers, which were invented to image and manipulate microscale objects, have revolutionized cellular and molecular biology. However, the optical resolution is hampered by the diffraction limit; thus, optical microscopes and optical tweezers cannot be directly used to image and manipulate nano-objects. The emerging plasmonic/photonic nanoscopes and nanotweezers can achieve nanometer resolution, but the high-index material structures will easily cause mechanical and photothermal damage to biospecimens. Here, we demonstrate subdiffraction-limit imaging and manipulation of nano-objects by a noninvasive device that was constructed by trapping a cell on a fiber tip. The trapped cell, acting as a biomagnifier, could magnify nanostructures with a resolution of 100 nm (λ/5.5) under white-light microscopy. The focus of the biomagnifier formed a nano-optical trap that allowed precise manipulation of an individual nanoparticle with a radius of 50 nm. This biomagnifier provides a high-precision tool for optical imaging, sensing, and assembly of bionanomaterials.
Halophilic microbial community compositional shift after a rare rainfall in the Atacama Desert
Authors: Uritskiy Gherman , Getsin Samantha , Munn Adam , Gomez-Silva Benito , Davila Alfonso , Glass Brian , Taylor James , DiRuggiero Jocelyne
Published: July 2019

Understanding the mechanisms underlying microbial resistance and resilience to perturbations is essential to predict the impact of climate change on Earth’s ecosystems. However, the resilience and adaptation mechanisms of microbial communities to natural perturbations remain relatively unexplored, particularly in extreme environments. The response of an extremophile community inhabiting halite (salt rocks) in the Atacama Desert to a catastrophic rainfall provided the opportunity to characterize and de-convolute the temporal response of a highly specialized community to a major disturbance. With shotgun metagenomic sequencing, we investigated the halite microbiome taxonomic composition and functional potential over a 4-year longitudinal study, uncovering the dynamics of the initial response and of the recovery of the community after a rainfall event. The observed changes can be recapitulated by two general modes of community shifts—a rapid Type 1 shift and a more gradual Type 2 adjustment. In the initial response, the community entered an unstable intermediate state after stochastic niche re-colonization, resulting in broad predicted protein adaptations to increased water availability. In contrast, during recovery, the community returned to its former functional potential by a gradual shift in abundances of the newly acquired taxa. The general characterization and proposed quantitation of these two modes of community response could potentially be applied to other ecosystems, providing a theoretical framework for prediction of taxonomic and functional flux following environmental changes.
Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients
Authors: Bhattacharyya Sudeepa , Ahmed Ahmed T. , Arnold Matthias , Liu Duan , Luo Chunqiao , Zhu Hongjie , Mahmoudiandehkordi Siamak , Neavin Drew , Louie Gregory , Dunlop Boadie W. , Frye Mark A. , Wang Liewei , Weinshilboum Richard M. , Krishnan Ranga R. , Rush A. John , Kaddurah-Daouk Rima
Published: July 2019

Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment. The 17-item Hamilton Depression Rating Scale (HRSD17) scores gauged depressive symptom severity. More significant metabolic changes were found after 8 weeks than 4 weeks post baseline.Within the tryptophan pathway, we noted significant reductions in serotonin (5HT) and increases in indoles that are known to be influenced by human gut microbial cometabolism. 5HT, 5-hydroxyindoleacetate (5HIAA), and the ratio of 5HIAA/5HT showed significant correlations to temporal changes in HRSD17scores.In the tyrosine pathway, changes were observed in the end products of the catecholamines, 3-methoxy-4-hydroxyphenylethyleneglycol and vinylmandelic acid. Furthermore, two phenolic acids, 4-hydroxyphenylacetic acid and 4-hydroxybenzoic acid, produced through noncanconical pathways, were increased with drug exposure.In the purine pathway, significant reductions in hypoxanthine and xanthine levels were observed. Examination of metabolite interactions through differential partial correlation networks revealed changes in guanosine–homogentisic acid and methionine–tyrosine interactions associated with HRSD17. Genetic association studies using the ratios of these interacting pairs of metabolites highlighted two genetic loci harboring genes previously linked to depression, neurotransmission, or neurodegeneration. Overall, exposure to escitalopram/citalopram results in shifts in metabolism through noncanonical pathways, which suggest possible roles for the gut microbiome, oxidative stress, and inflammation-related mechanisms.
ATF3 promotes erastin-induced ferroptosis by suppressing system Xc–
Authors: Wang Liyuan , Liu Yichen , Du Tingting , Yang Heng , Lei Lei , Guo Mengqi , Ding Han-Fei , Zhang Junran , Wang Hongbo , Chen Xiaoguang , Yan Chunhong
Published: July 2019

The amino acid antiporter system Xc− is important for the synthesis of glutathione (GSH) that functions to prevent lipid peroxidation and protect cells from nonapoptotic, iron-dependent death (i.e., ferroptosis). While the activity of system Xc− often positively correlates with the expression level of its light chain encoded by SLC7A11, inhibition of system Xc− activity by small molecules (e.g., erastin) causes a decrease in the intracellular GSH level, leading to ferroptotic cell death. How system Xc− is regulated during ferroptosis remains largely unknown. Here we report that activating transcription factor 3 (ATF3), a common stress sensor, can promote ferroptosis induced by erastin. ATF3 suppressed system Xc−, depleted intracellular GSH, and thereby promoted lipid peroxidation induced by erastin. ATF3 achieved this activity through binding to the SLC7A11 promoter and repressing SLC7A11 expression in a p53-independent manner. These findings thus add ATF3 to a short list of proteins that can regulate system Xc− and promote ferroptosis repressed by this antiporter.
Dephosphorylation of HDAC4 by PP2A-Bδ unravels a new role for the HDAC4/MEF2 axis in myoblast fusion
Authors: Veloso Alexandra , Martin Maud , Bruyr Jonathan , O’Grady Tina , Deroanne Christophe , Mottet Denis , Twizere Jean-Claude , Cherrier Thomas , Dequiedt Franck
Published: July 2019

Muscle formation is controlled by a number of key myogenic transcriptional regulators that govern stage-specific gene expression programs and act as terminal effectors of intracellular signaling pathways. To date, the role of phosphatases in the signaling cascades instructing muscle development remains poorly understood. Here, we show that a specific PP2A-B55δ holoenzyme is necessary for skeletal myogenesis. The primary role of PP2A-B55δ is to dephosphorylate histone deacetylase 4 (HDAC4) following myocyte differentiation and ensure repression of Myocyte enhancer factor 2D (MEF2D)-dependent gene expression programs during myogenic fusion. As a crucial HDAC4/MEF2D target gene that governs myocyte fusion, we identify ArgBP2, an upstream inhibitor of Abl, which itself is a repressor of CrkII signaling. Consequently, cells lacking PP2A-B55δ show upregulation of ArgBP2 and hyperactivation of CrkII downstream effectors, including Rac1 and FAK, precluding cytoskeletal and membrane rearrangements associated with myoblast fusion. Both in vitro and in zebrafish, loss-of-function of PP2A-B55δ severely impairs fusion of myocytes and formation of multinucleated muscle fibers, without affecting myoblast differentiation. Taken together, our results establish PP2A-B55δ as the first protein phosphatase to be involved in myoblast fusion and suggest that reversible phosphorylation of HDAC4 may coordinate differentiation and fusion events during myogenesis.
Systemically administered peptain-1 inhibits retinal ganglion cell death in animal models: implications for neuroprotection in glaucoma
Authors: Stankowska Dorota L. , Nam Mi-Hyun , Nahomi Rooban B. , Chaphalkar Renuka M. , Nandi Sandip K. , Fudala Rafal , Krishnamoorthy Raghu R. , Nagaraj Ram H.
Published: July 2019

Axonal degeneration and death of retinal ganglion cells (RGCs) are the primary causes of vision loss in glaucoma. In this study, we evaluated the efficacy of a peptide (peptain-1) that exhibits robust chaperone and anti-apoptotic activities against RGC loss in two rodent models and in cultured RGCs. In cultures of rat primary RGCs and in rat retinal explants peptain-1 significantly decreased hypoxia-induced RGC loss when compared to a scrambled peptide. Intraperitoneally (i.p.) injected peptain-1 (conjugated to a Cy7 fluorophore) was detected in the retina indicative of its ability to cross the blood-retinal barrier. Peptain-1 treatment inhibited RGC loss in the retina of mice subjected to ischemia/reperfusion (I/R) injury. A reduction in anterograde axonal transport was also ameliorated by peptain-1 treatment in the retina of I/R injured mice. Furthermore, i.p. injections of peptain-1 significantly reduced RGC death and axonal loss and partially restored retinal mitochondrial cytochrome c oxidase subunit 6b2 (COX 6b2) levels in rats subjected to five weeks of elevated intraocular pressure. We conclude that i.p. injected peptain-1 gains access to the retina and protects both RGC somas and axons against the injury caused by I/R and ocular hypertension. Based on these findings, peptain-1 has the potential to be developed as an efficacious neuroprotective agent for the treatment of glaucoma.
Interplay between superconductivity and itinerant magnetism in underdoped Ba1−xKxFe2As2 (x = 0.2) probed by the response to controlled point-like disorder
Authors: Prozorov Ruslan , Kończykowski Marcin , Tanatar Makariy A. , Wen Hai-Hu , Fernandes Rafael M. , Canfield Paul C.
Published: July 2019

The response of superconductors to controlled introduction of point-like disorder is an important tool to probe their microscopic electronic collective behavior. In the case of iron-based superconductors, magnetic fluctuations presumably play an important role in inducing high-temperature superconductivity. In some cases, these two seemingly incompatible orders coexist microscopically. Therefore, understanding how this unique coexistence state is affected by disorder can provide important information about the microscopic mechanisms involved. In one of the most studied pnictide family, hole-doped Ba1−xKxFe2As2 (BaK122), this coexistence occurs over a wide range of doping levels, 0.16 ≲ x ≲ 0.25. We used relativistic 2.5 MeV electrons to induce vacancy-interstitial (Frenkel) pairs that act as efficient point-like scattering centers. Upon increasing dose of irradiation, the superconducting transition temperature Tc decreases dramatically. In the absence of nodes in the order parameter this provides a strong support for a sign-changing s± pairing. Simultaneously, in the normal state, there is a strong violation of the Matthiessen’s rule and a decrease (surprisingly, at the same rate as Tc) of the magnetic transition temperature Tsm, which indicates the itinerant nature of the long-range magnetic order. Comparison of the hole-doped BaK122 with electron-doped Ba(FexCo1−x)2As2 (FeCo122) with similar Tsm ~ 110 K, x = 0.02, reveals significant differences in the normal states, with no apparent Matthiessen’s rule violation above Tsm on the electron-doped side. We interpret these results in terms of the distinct impact of impurity scattering on the competing itinerant antiferromagnetic and s± superconducting orders.
High-throughput analysis of the human thymic Vδ1+ T cell receptor repertoire
Authors: Di Lorenzo Biagio , Ravens Sarina , Silva-Santos Bruno
Published: July 2019

γδ T cells are a relatively rare subset of lymphocytes in the human peripheral blood, but they play important roles at the interface between the innate and the adaptive immune systems. The γδ T cell lineage is characterized by a signature γδ T cell receptor (γδTCR) that displays extensive sequence variability originated by DNA rearrangement of the corresponding V(D)J loci. Human γδ T cells comprise Vγ9Vδ2 T cells, the major subset in the peripheral blood; and Vδ1+ T cells, the predominant subpopulation in the post-natal thymus and in peripheral tissues. While less studied, Vδ1+ T cells recently gathered significant attention due to their anti-cancer and anti-viral activities. In this study we applied next-generation sequencing (NGS) to analyse the γδTCR repertoire of highly (FACS-)purified Vδ1+ T cells from human thymic biopsies. Our analysis reveals unsuspected aspects of thymically rearranged and expressed (at the mRNA level) TRG and TRD genes, thus constituting a data resource that qualifies previous conclusions on the TCR repertoire of γδ T cells developing in the human thymus.
A DNA barcode reference library of French Polynesian shore fishes
Authors: Delrieu-Trottin Erwan , Williams Jeffrey T. , Pitassy Diane , Driskell Amy , Hubert Nicolas , Viviani Jérémie , Cribb Thomas H. , Espiau Benoit , Galzin René , Kulbicki Michel , Lison de Loma Thierry , Meyer Christopher , Mourier Johann , Mou-Tham Gérard , Parravicini Valeriano , Plantard Patrick , Sasal Pierre , Siu Gilles , Tolou Nathalie , Veuille Michel , Weigt Lee , Planes Serge
Published: July 2019

The emergence of DNA barcoding and metabarcoding opened new ways to study biological diversity, however, the completion of DNA barcode libraries is fundamental for such approaches to succeed. This dataset is a DNA barcode reference library (fragment of Cytochrome Oxydase I gene) for 2,190 specimens representing at least 540 species of shore fishes collected over 10 years at 154 sites across the four volcanic archipelagos of French Polynesia; the Austral, Gambier, Marquesas and Society Islands, a 5,000,000 km2 area. At present, 65% of the known shore fish species of these archipelagoes possess a DNA barcode associated with preserved, photographed, tissue sampled and cataloged specimens, and extensive collection locality data. This dataset represents one of the most comprehensive DNA barcoding efforts for a vertebrate fauna to date. Considering the challenges associated with the conservation of coral reef fishes and the difficulties of accurately identifying species using morphological characters, this publicly available library is expected to be helpful for both authorities and academics in various fields.
Bone growth as the main determinant of mouse digit tip regeneration after amputation
Authors: Sensiate L. A. , Marques-Souza H.
Published: July 2019

Regeneration is classically demonstrated in mammals using mice digit tip. In this study, we compared different amputation plans and show that distally amputated digits regrow with morphology close to normal but fail to regrow the fat pad. Proximally amputated digits do not regrow the phalangeal bone, but the remaining structures (nail, skin and connective tissue), all with intrinsic regenerative capacity, re-establishing integrity indistinguishably in distally and proximally amputated digits. Thus, we suggest that the bone growth promoted by signals and progenitor cells not removed by distal amputations is responsible for the re-establishment of a drastically different final morphology after distal or proximal digit tip amputations. Despite challenging the use of mouse digit tip as a model system for limb regeneration in mammals, these findings evidence a main role of bone growth in digit tip regeneration and suggest that mechanisms that promote joint structures formation should be the main goal of regenerative medicine for limb and digit regrowth.
Fractionated mitochondrial magnetic separation for isolation of synaptic mitochondria from brain tissue
Authors: Hubbard W. Brad , Harwood Christopher L. , Prajapati Paresh , Springer Joe E. , Saatman Kathryn E. , Sullivan Patrick G.
Published: July 2019

While mitochondria maintain essential cellular functions, such as energy production, calcium homeostasis, and regulating programmed cellular death, they also play a major role in pathophysiology of many neurological disorders. Furthermore, several neurodegenerative diseases are closely linked with synaptic damage and synaptic mitochondrial dysfunction. Unfortunately, the ability to assess mitochondrial dysfunction and the efficacy of mitochondrial-targeted therapies in experimental models of neurodegenerative disease and CNS injury is limited by current mitochondrial isolation techniques. Density gradient ultracentrifugation (UC) is currently the only technique that can separate synaptic and non-synaptic mitochondrial sub-populations, though small brain regions cannot be assayed due to low mitochondrial yield. To address this limitation, we used fractionated mitochondrial magnetic separation (FMMS), employing magnetic anti-Tom22 antibodies, to develop a novel strategy for isolation of functional synaptic and non-synaptic mitochondria from mouse cortex and hippocampus without the usage of UC. We compared the yield and functionality of mitochondria derived using FMMS to those derived by UC. FMMS produced 3x more synaptic mitochondrial protein yield compared to UC from the same amount of tissue, a mouse hippocampus. FMMS also has increased sensitivity, compared to UC separation, to measure decreased mitochondrial respiration, demonstrated in a paradigm of mild closed head injury. Taken together, FMMS enables improved brain-derived mitochondrial yield for mitochondrial assessments and better detection of mitochondrial impairment in CNS injury and neurodegenerative disease.
A repository of protein abundance data of drug metabolizing enzymes and transporters for applications in physiologically based pharmacokinetic (PBPK) modelling and simulation
Authors: Ladumor Mayur K. , Thakur Aarzoo , Sharma Sheena , Rachapally Aravind , Mishra Sarang , Bobe Priyanka , Rao V. Kameswara , Pammi Praneetha , Kangne Hari , Levi David , Balhara Ankit , Ghandikota Sriram , Joshi Anupama , Nautiyal Vivek , Prasad Bhagwat , Singh Saranjit
Published: July 2019

Population factors such as age, gender, ethnicity, genotype and disease state can cause inter-individual variability in pharmacokinetic (PK) profile of drugs. Primarily, this variability arises from differences in abundance of drug metabolizing enzymes and transporters (DMET) among individuals and/or groups. Hence, availability of compiled data on abundance of DMET proteins in different populations can be useful for developing physiologically based pharmacokinetic (PBPK) models. The latter are routinely employed for prediction of PK profiles and drug interactions during drug development and in case of special populations, where clinical studies either are not feasible or have ethical concerns. Therefore, the main aim of this work was to develop a repository of literature-reported DMET abundance data in various human tissues, which included compilation of information on sample size, technique(s) involved, and the demographic factors. The collation of literature reported data revealed high inter-laboratory variability in abundance of DMET proteins. We carried out unbiased meta-analysis to obtain weighted mean and percent coefficient of variation (%CV) values. The obtained %CV values were then integrated into a PBPK model to highlight the variability in drug PK in healthy adults, taking lamotrigine as a model drug. The validated PBPK model was extrapolated to predict PK of lamotrigine in paediatric and hepatic impaired populations. This study thus exemplifies importance of the DMET protein abundance database, and use of determined values of weighted mean and %CV after meta-analysis in PBPK modelling for the prediction of PK of drugs in healthy and special populations.
Spatio-temporal temperature variations in MarkSim multimodel data and their impact on voltinism of fruit fly, Bactrocera species on mango
Authors: Choudhary Jaipal Singh , Mali Santosh S. , Mukherjee Debu , Kumari Anjali , Moanaro L. , Rao M. Srinivasa , Das Bikash , Singh A. K. , Bhatt B. P.
Published: July 2019

Fruit flies are the most serious economic insect pests of mango in India and other parts of the world. Under future climate change, shifts in temperature will be a key driver of ecosystem function especially in terms of insect pest dynamics. In this study, we predicted the voltinism of the three economically important fruit fly species viz.,Bactrocera dorsalis(Hendel),Bactrocera correcta(Bezzi) andBactrocera zonata(Saunders) of mango from 10 geographical locations in India using well established degree day approaches. Daily minimum and maximum temperature data were generated by using seven General Circulation Models (GCMs) along with their ensemble, in conjunction with the four representative concentration pathways (RCPs) scenarios (RCP 2.6, RCP 4.5, RCP 6.0 and RCP 8.5) and three time periods (2020, 2050 and 2080) generated from MarkSim® DSSAT weather file generator. Historical data from 1969–2005 of these 10 locations were considered as baseline period. Under future predicted climates, model outputs indicates that all three fruit fly species will produce higher number of generations (1–2 additional generations) with 15–24% reduced generation time over the baseline period. The increased voltinism of fruit fly species due to increased temperature may lead to ≃5% higher infestation of mango fruits in India by the year 2050. Analysis of variance revealed that ‘geographical locations’ explained 77% of the total variation in voltinism followed by ‘time periods’ (11%). Such increase in the voltinism of fruit flies and the consequent increases in the infestation of mango fruits are likely to have significant negative impacts on mango protection and production.
Whole-genome re-sequencing association study for direct genetic effects and social genetic effects of six growth traits in Large White pigs
Authors: Wu Pingxian , Wang Kai , Yang Qiang , Zhou Jie , Chen Dejuan , Liu Yihui , Ma Jideng , Tang Qianzi , Jin Long , Xiao Weihang , Lou Pinger , Jiang Anan , Jiang Yanzhi , Zhu Li , Li Mingzhou , Li Xuewei , Tang Guoqing
Published: July 2019

Socially affected traits are affected by direct genetic effects (DGE) and social genetic effects (SGE). DGE and SGE of an individual directly quantify the genetic influence of its own phenotypes and the phenotypes of other individuals, respectively. In the current study, a total of 3,276 Large White pigs from different pens were used, and each pen contained 10 piglets. DGE and SGE were estimated for six socially affected traits, and then a GWAS was conducted to identify SNPs associated with DGE and SGE. Based on the whole-genome re-sequencing, 40 Large White pigs were genotyped and 10,501,384 high quality SNPs were retained for single-locus and multi-locus GWAS. For single-locus GWAS, a total of 54 SNPs associated with DGE and 33 SNPs with SGE exceeded the threshold (P < 5.00E-07) were detected for six growth traits. Of these, 22 SNPs with pleiotropic effects were shared by DGE and SGE. For multi-locus GWAS, a total of 72 and 110 putative QTNs were detected for DGE and SGE, respectively. Of these, 5 SNPs with pleiotropic effects were shared by DGE and SGE. It is noteworthy that 2 SNPs (SSC8: 16438396 for DGE and SSC17: 9697454 for SGE) were detected in single-locus and multi-locus GWAS. Furthermore, 15 positional candidate genes shared by SGE and DGE were identified because of their roles in behaviour, health and disease. Identification of genetic variants and candidate genes for DGE and SGE for socially affected traits will provide a new insight to understand the genetic architecture of socially affected traits in pigs.
Vasopressin enhances human preemptive strike in both males and females
Authors: Kawada Atsushi , Nagasawa Miho , Murata Aiko , Mogi Kazutaka , Watanabe Katsumi , Kikusui Takefumi , Kameda Tatsuya
Published: July 2019

The neuropeptide arginine vasopressin (AVP), which is known to modulate a wide range of social behaviors in animals, has been identified as a modulator of various negative responses to social stimuli in humans. However, behavioral evidence directly supporting its involvement in human defensive aggression has been rare. We investigated the effect of intranasal AVP on defensive aggression in a laboratory experiment, using an incentivized economic game called the “preemptive strike game” (PSG). Participants played PSG individually (1 on 1) as well as in pairs (2 on 2) under either AVP or saline. We observed that exogenous but not basal AVP modulated the attack rate in PSG for both male and female participants. A model-based analysis of the aggregation of individual attack preferences into pair decisions revealed that the AVP effect on defensive aggression occurred mainly at the individual level and was not amplified at the pair level. Overall, these results present the first evidence that intranasal AVP promotes human defensive aggression for both males and females in a bilateral situation where each party can potentially damage the resources of the other party. These findings also parallel accumulating evidence from non-human animals concerning AVP’s involvement in territorial defense against potential intruders.
Anthropogenic pollutant-driven geographical distribution of mesozooplankton communities in estuarine areas of the Bohai Sea, China
Authors: Gao Yangchun , Yang Qing , Li Hongjun , Wang Xiaocheng , Zhan Aibin
Published: July 2019

Mesozooplankton communities in marine ecosystems are mainly influenced by both anthropogenic pollutants (e.g. nutrients and heavy metals) and natural variables (e.g. temperature, salinity and geographic distance). To achieve a deeper understanding of the effects of anthropogenic pollutants on mesozooplankton communities, we analyzed the community structure of mesozooplankton from 91 stations representing five typical estuarine regions in the Bohai Sea and assessed the relative importance of anthropogenic pollutants and natural variables by using multiple statistical approaches. Cd was identified as the leading pollutant for observed community variation among the five regions, followed by NH4-N and COD. Redundancy analysis (RDA) model demonstrated that mesozooplankton communities were largely determined by both anthropogenic pollutants and natural variables, and the indicator species of mesozooplankton also varied when responding to different factors. Variance partitioning analysis showed both anthropogenic pollutants and natural variables posed significant influences (ANOVA,P < 0.05) on the mesozooplankton community structure, but the explanatory power of anthropogenic pollutants overrode the natural variables. These observations highlighted the importance of anthropogenic pollutants in the shifts of zooplankton structures among different regions. Our results obtained in this study provided new insights into the mechanism of the influence of anthropogenic pollutants on mesozooplankton communities in estuarine areas.
Establishing a many-cytokine signature via multivariate anomaly detection
Authors: Dingle K. , Zimek A. , Azizieh F. , Ansari A. R.
Published: July 2019

Establishing a cytokine signature associated to some medical condition is an important task in immunology. Increasingly, large numbers of cytokines are used for signatures, via lists of reference ranges for each individual cytokine or ratios of cytokines. Here we argue that this common approach has weaknesses, especially when many different cytokines are analysed. Instead, we propose that establishing signatures can be framed as a multivariate anomaly detection problem, and hence exploit the many statistical methods available for this. In this framework, whether or not a given subject’s profile matches the cytokine signature of some condition is determined by whether or not the profile is typical of reference samples of that condition, as judged by an anomaly detection algorithm. We examine previously published cytokine data sets associated to pregnancy complications, brain tumours, and rheumatoid arthritis, as well as normal healthy control samples, and test the performance of a range of anomaly detection algorithms on these data, identifying the best performing methods. Finally, we suggest that this anomaly detection approach could be adopted more widely for general multi-biomarker signatures.
Dual usage of a stage-specific fluorescent reporter system based on a helper-dependent adenoviral vector to visualize osteogenic differentiation
Authors: Sone Takefumi , Shin Masashi , Ouchi Takehito , Sasanuma Hiroki , Miyamoto Arei , Ohte Satoshi , Tsukamoto Sho , Nakanishi Mahito , Okano Hideyuki , Katagiri Takenobu , Mitani Kohnosuke
Published: July 2019

We developed a reporter system that can be used in a dual manner in visualizing mature osteoblast formation. The system is based on a helper-dependent adenoviral vector (HDAdV), in which a fluorescent protein, Venus, is expressed under the control of the 19-kb human osteocalcin (OC) genomic locus. By infecting human and murine primary osteoblast (POB) cultures with this reporter vector, the cells forming bone-like nodules were specifically visualized by the reporter. In addition, the same vector was utilized to efficiently knock-in the reporter into the endogenous OC gene of human induced pluripotent stem cells (iPSCs), by homologous recombination. Neural crest-like cells (NCLCs) derived from the knock-in reporter iPSCs were differentiated into osteoblasts forming bone-like nodules and could be visualized by the expression of the fluorescent reporter. Living mature osteoblasts were then isolated from the murine mixed POB culture by fluorescence-activated cell sorting (FACS), and their mRNA expression profile was analyzed. Our study presents unique utility of reporter HDAdVs in stem cell biology and related applications.
Discovery of food identity markers by metabolomics and machine learning technology
Authors: Erban Alexander , Fehrle Ines , Martinez-Seidel Federico , Brigante Federico , Más Agustín Lucini , Baroni Veronica , Wunderlin Daniel , Kopka Joachim
Published: July 2019

Verification of food authenticity establishes consumer trust in food ingredients and components of processed food. Next to genetic or protein markers, chemicals are unique identifiers of food components. Non-targeted metabolomics is ideally suited to screen food markers when coupled to efficient data analysis. This study explored feasibility of random forest (RF) machine learning, specifically its inherent feature extraction for non-targeted metabolic marker discovery. The distinction of chia, linseed, and sesame that have gained attention as “superfoods” served as test case. Chemical fractions of non-processed seeds and of wheat cookies with seed ingredients were profiled. RF technology classified original seeds unambiguously but appeared overdesigned for material with unique secondary metabolites, like sesamol or rosmarinic acid in the Lamiaceae, chia. Most unique metabolites were diluted or lost during cookie production but RF technology classified the presence of the seed ingredients in cookies with 6.7% overall error and revealed food processing markers, like 4-hydroxybenzaldehyde for chia and succinic acid monomethylester for linseed additions. RF based feature extraction was adequate for difficult classifications but marker selection should not be without human supervision. Combination with alternative data analysis technologies is advised and further testing of a wide range of seeds and food processing methods.
Engineering a humanized telomerase reverse transcriptase gene in mouse embryonic stem cells
Authors: Cheng De , Zhao Yuanjun , Zhang Fan , Zhang Jinglong , Wang Shuwen , Zhu Jiyue
Published: July 2019

Telomerase is expressed in adult mouse, but not in most human, tissues and mouse telomeres are much longer than those in humans. This interspecies difference of telomere homeostasis poses a challenge in modeling human diseases using laboratory mice. Using chromatinized bacterial artificial chromosome reporters, we discovered that the 5′ intergenic region, introns 2 and 6 of human telomerase gene (hTERT) were critical for regulating its promoter in somatic cells. Accordingly, we engineered a humanized gene, hmTert, by knocking-in a 47-kilobase hybrid fragment containing these human non-coding sequences into the mTert locus in mouse embryonic stem cells (mESCs). The hmTert gene, encoding the wildtype mTert protein, was fully functional, as a mESC line with homozygous hmTert alleles proliferated for over 400 population doublings without exhibiting chromosomal abnormalities. Like human ESCs, the engineered mESCs contained high telomerase activity, which was repressed upon their differentiation into fibroblast-like cells in a histone deacetylase-dependent manner. Fibroblast-like cells differentiated from these mESCs contained little telomerase activity. Thus, telomerase in mESCs with the hmTert alleles was subjected to human-like regulation. Our study revealed a novel approach to engineer a humanized telomerase gene in mice, achieving a milestone in creating a mouse model with humanized telomere homeostasis.
Rapid MALDI mass spectrometry imaging for surgical pathology
Authors: Basu Sankha S. , Regan Michael S. , Randall Elizabeth C. , Abdelmoula Walid M. , Clark Amanda R. , Gimenez-Cassina Lopez Begoña , Cornett Dale S. , Haase Andreas , Santagata Sandro , Agar Nathalie Y. R.
Published: July 2019

Matrix assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) is an emerging analytical technique, which generates spatially resolved proteomic and metabolomic images from tissue specimens. Conventional MALDI MSI processing and data acquisition can take over 30 min, limiting its clinical utility for intraoperative diagnostics. We present a rapid MALDI MSI method, completed under 5 min, including sample preparation and analysis, providing a workflow compatible with the clinical frozen section procedure.
Publisher Correction: Calaxin is required for cilia-driven determination of vertebrate laterality
Authors: Sasaki Keita , Shiba Kogiku , Nakamura Akihiro , Kawano Natsuko , Satouh Yuhkoh , Yamaguchi Hiroshi , Morikawa Motohiro , Shibata Daisuke , Yanase Ryuji , Jokura Kei , Nomura Mami , Miyado Mami , Takada Shuji , Ueno Hironori , Nonaka Shigenori , Baba Tadashi , Ikawa Masahito , Kikkawa Masahide , Miyado Kenji , Inaba Kazuo
Published: July 2019

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Novel fluorescent probe with a bridged Si–O–Si bond for the reversible detection of hypochlorous acid and biothiol amino acids in live cells and zebrafish
Authors: Zhang Yu , Zuo Yujing , Yang Tingxin , Gou Zhiming , Wang Xiaoni , Lin Weiying
Published: July 2019

Herein, we report the design of a novel fluorescent probe consisting of a naphthalimide fluorophore and a silicone small molecule for the reversible detection of hypochlorous acid and biothiol amino acids.
Atmospheric pressure chemical ionisation (APCI) and photoionisation (APPI) mass spectrometry for detection of unsaturated fatty acids: potential for rapid detection of adulteration of vegetable oils
Authors: Strashnov Ilya , Gilmour Jamie D. , Cannavan Andrew , Chen Gang , Dissanayake Champa , Fernando Biyagamage Ruchika , Kelly Simon , Muhammad Syahidah Akmal , Singh Dileep Kumar , Xu Zhenzhen
Published: July 2019

Unsaturated fatty acids of vegetable oils can be rapidly determined with APCI and APPI mass spectrometry by comparison to standards. The difference in the ionization efficiencies of FA can be addressed by calculation of correction factors.
A PEGylated alternating copolymer with oxidation-sensitive phenylboronic ester pendants for anticancer drug delivery
Authors: Zhang Yu , He Pan , Liu Xinming , Yang Huailin , Zhang Hongyu , Xiao Chunsheng , Chen Xuesi
Published: July 2019

An oxidation sensitive PEGylated alternating copolymer was designed for doxorubicin delivery with improved anticancer efficacy and low toxicity in vivo.
Asynchronous reactions of “self-matrix” dual-crystals effectively accommodating volume expansion/shrinkage of electrode materials with enhanced sodium storage
Authors: Hao Youchen , Li Xifei , Liu Wen , Maleki Kheimeh Sari Hirbod , Qin Jian , Li Yingying
Published: July 2019

The dual-crystal FeS2 shows a better tolerance towards large volume changes because of the asynchronous reaction.
Flavonoid–alkylphospholipid conjugates elicit dual inhibition of cancer cell growth and lipid accumulation
Authors: Zhou Zhengwei , Luo Biyao , Liu Xi , Chen Mimi , Lan Wenjun , Iovanna Juan L. , Peng Ling , Xia Yi
Published: July 2019

Quercetin–alkylphospholipid conjugates are promising chemical entities with anticancer activity and the ability to inhibit lipid synthesis and metabolism.
Short-range ordering in a battery electrode, the ‘cation-disordered’ rocksalt Li1.25Nb0.25Mn0.5O2
Authors: Jones Michael A. , Reeves Philip J. , Seymour Ieuan D. , Cliffe Matthew J. , Dutton Siân E. , Grey Clare P.
Published: July 2019

We demonstrate short-range ordering in Li-ion battery material Li1.25Nb0.25Mn0.5O2, and identify its local structure and correlation length—which is sensitive to synthesis conditions and has important consequences for the material's electrochemistry.
Diborane heterolysis and P(v) reduction by Ph3PO coordination to magnesium
Authors: Pécharman Anne-Frédérique , Rajabi Nasir A. , Hill Michael S. , McMullin Claire L. , Mahon Mary F.
Published: July 2019

Inner sphere attack of Ph3PO provides a terminal magnesium boryl, which is a potent reagent for the deoxygenation of P(v).
Nitrogen-doped heptazethrene and octazethrene diradicaloids
Authors: Chow Chi Hao Eugene , Han Yi , Phan Hoa , Wu Jishan
Published: July 2019

Nitrogen-doped heptazethrene and octazethrene diradicaloids were synthesized. The N-aryl dications show larger diradical character and enhanced stability than the parent ones.
Asymmetric synthesis of hetero-1,2,3,4,5-pentasubstituted ferrocenes
Authors: Erb William , Roisnel Thierry
Published: July 2019

A four-step approach toward the first hetero-1,2,3,4,5-pentasubstituted ferrocene derivatives was successfully explored. Starting from Ugi's amine, enantioenriched compounds were made through the first asymmetric halogen ‘dance’ reaction reported.
Conformational variation of ligands in mercury halide complexes; high and low Z′ structures
Authors: Samie Ali , Salimi Alireza
Published: July 2019

Small changes in the ligand resulted in a conformational variation of LPy to LPz which led to high and low Z′ structures in the corresponding metal complexes.
Ferromagnetic interactions in a 1D Heisenberg linear chain of 1-phenyl-3,7-bis(trifluoromethyl)-1,4-dihydro-1,2,4-benzotriazin-4-yls
Authors: Constantinides Christos P. , Lawson Daniel B. , Berezin Andrey A. , Zissimou Georgia A. , Manoli Maria , Leitus Gregory M. , Koutentis Panayiotis A.
Published: July 2019

1-Phenyl-3,7-bis(trifluoromethyl)-1,4-dihydro-1,2,4-benzotriazin-4-yl (2), was characterized by single crystal X-ray diffractometry and variable temperature SQUID magnetometry to investigate its structure-magnetism correlation.
High spin polarization in formamidinium transition metal iodides: first principles prediction of novel half-metals and spin gapless semiconductors
Authors: Huang Hai-Ming , Cao Ming-Lei , Jiang Zhen-Yi , Xiong Yong-Chen , Zhang Xiong , Luo Shi-Jun , Laref Amel
Published: July 2019

The electronic structure shows that FAVI3 is a novel organic–inorganic hybrid perovskite-type spin gapless semiconductor.
Transmission mechanism and quantum interference in fused thienoacenes coupling to Au electrodes through the thiophene rings
Authors: Li Yang , Yu Xi , Zhen Yonggang , Dong Huanli , Hu Wenping
Published: July 2019

Revealing the influence of molecular structure on the coupling mechanism and quantum interference in Au–thienoacene–Au junctions formed through Au–S donor–acceptor interactions.