bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeled Gravity Wave‐Like Perturbations in the Brightness of Far Ultraviolet Emissions for the GOLD Mission
Authors: Greer K. R. , England S. L. , Becker E. , Rusch D. , Eastes R.
Published: June 2018

The NASA Global‐scale Observations of Limb and Disk (GOLD) mission will study the coupling of the thermosphere with the lower atmosphere through an examination of temperature and composition, allowing the study of atmospheric waves. A key mechanism of energy and momentum transport between atmospheric regions is gravity waves. GOLD is an imaging spectrograph that will measure Earth's airglow emissions (both nightglow and dayglow) in the far ultraviolet range from 132 to 162 nm, including the atomic oxygen doublet at 135.6 nm and molecular nitrogen Lyman‐Birge‐Hopfield bands. GOLD will be the first instrument to make such measurements from the perspective of a geostationary orbit, which creates unique challenges and opportunities for observing atmospheric waves. Here we model the ability of the GOLD imager to detect a gravity wave‐like perturbation from the emergent brightness variations using a combination of a general circulation model and a model of the thermospheric airglow in the far ultraviolet. A 10% perturbation in temperature (±59 K at 150 km) and constituent densities is introduced into the vertical columns of the atmosphere, which results in a ±1.5 Rayleigh perturbation to the brightness of both spectral features, with the same wave period as the introduced perturbation. For the expected total signal, particle background counts, and chosen spectral feature, signal‐to‐noise calculations indicate that integration for several minutes will allow gravity wave perturbations to be observed in brightness perturbations on a single pixel of an image.
Response of Different Ion Species to Local Magnetic Dipolarization Inside Geosynchronous Orbit
Authors: Motoba T. , Ohtani S. , Gkioulidou M. , Ukhorskiy A. Y. , Mitchell D. G. , Takahashi K. , Lanzerotti L. J. , Kletzing C. A. , Spence H. E. , Wygant J. R.
Published: June 2018

This paper examines how hydrogen, helium, and oxygen (H, He, and O) ion fluxes at 1–1,000 keV typically respond to local magnetic dipolarization inside geosynchronous orbit. We extracted 144 dipolarizations that occurred at magnetic inclination >30° from the 2012–2016 tail seasons' observations of the Van Allen Probes spacecraft and then defined typical flux changes of these ion species by performing a superposed epoch analysis. On average, the dipolarization inside geosynchronous orbit is accompanied by a precursory transient decrease in the northward magnetic field component, transient impulsive enhancement in the westward electric field component, and decrease (increase) in the proton density (temperature). The coincident ion species experience an energy‐dependent flux change, consisting of enhancement (depression) at energies above (below) ~50 keV. These properties morphologically resemble those around dipolarization fronts (or fast flows) in the near‐Earth tail. A distinction among the ion species is the average energy of the flux ratio peak, being at 200–400 keV (100–200 keV) for He (H and O) ions. The flux ratio peaks at different energies likely reflect the different charge states of injected ionospheric and/or solar wind origin ion species. The ion spectra become harder for sharp dipolarizations, suggesting the importance of accompanying electric field in transporting and/or energizing the ions efficiently. Interestingly, the average flux ratio peak does not differ significantly among the ion species for ~2 min after onset, which implies that mass‐dependent acceleration process is less important in the initial stage of dipolarization.
Closed‐Form Expressions of Seismic Deformation in a Homogeneous Maxwell Earth Model
Authors: Tang He , Sun Wenke
Published: June 2018

Earthquake activities involve coseismic and postseismic deformations, and these seismic deformations can be computed using corresponding dislocation theories. However, conventional dislocation theories are usually given using numerical dislocation Love numbers and numerical Green's functions. In this study, we present explicit expressions of the time‐dependent dislocation Love numbers for a point source in a homogeneous viscoelastic (Maxwell rheology) spherical Earth model and the displacement Green's functions. Other surface variables, such as tilt and strain, can be obtained in a similar manner. The analytical Green's functions are derived from the degenerate deformation system without considering self‐gravitation. The Green's functions can be applied to efficiently compute viscoelastic seismic and volcanic deformations in an approximate manner.
Tidally Modulated Internal Hydraulic Flow and Energetics in the Central Canadian Arctic Archipelago
Authors: Hughes Kenneth G. , Klymak Jody M. , Williams William J. , Melling Humfrey
Published: June 2018

The Canadian Arctic Archipelago is a key conduit for comparatively fresh Arctic waters flowing to the Atlantic. Model estimates of the freshwater outflow, which is strongly correlated with the volume flux, contain major uncertainties because most existing models exclude tides, marginally resolve the internal Rossby radius, or both. At the same time, barotropic tidal models preclude stratified flow effects. Here we assess the relative importance of barotropic and baroclinic processes to water mass transformation, friction, and energy losses motivated by processes observed in a fine‐scale survey in the central Archipelago. A sharp separation of warmed Canada Basin water and locally formed water is observed over a long sill in a narrow channel and coincides with an internal hydraulic jump caused by the mean flow. Tidal currents, however, modulate the jump, as demonstrated by both scale analysis and a two‐dimensional simulation. The jump, together with internal tides propagating as Kelvin waves, leads to isopycnal displacements up to 50 m. The generation of these internal Kelvin waves has a leading‐order role in a regional energy budget. It is small, however, relative to bottom boundary layer dissipation, which accounts for an estimated 50% of the total tidal energy losses. Consequently, adding tides needs to be a priority for regional models.
A Numerical Study of Sheet Flow Under Monochromatic Nonbreaking Waves Using a Free Surface Resolving Eulerian Two‐Phase Flow Model
Authors: Kim Yeulwoo , Cheng Zhen , Hsu Tian‐Jian , Chauchat Julien
Published: June 2018

We present a new methodology that is able to concurrently resolve free surface wavefield, bottom boundary layer, and sediment transport processes throughout the entire water column. The new model, called SedWaveFoam, is developed by integrating an Eulerian two‐phase model for sediment transport, SedFoam, and a surface wave solver, InterFoam/waves2Foam, in the OpenFOAM framework. SedWaveFoam is validated with a large wave flume data for sheet flow driven by monochromatic nonbreaking waves. To isolate the effect of free surface, SedWaveFoam results are contrasted with one‐dimensional‐vertical SedFoam results, where the latter represents the oscillating water tunnel condition. Results demonstrate that wave‐averaged total sediment fluxes in both models are onshore‐directed; however, this onshore transport is significantly enhanced under surface waves. Onshore‐directed near‐bed sediment flux is driven by a small mean current mainly associated with velocity skewness. More importantly, progressive wave streaming drives onshore transport mostly in suspended load region due to an intrawave sediment flux. Further analysis suggests that the enhanced onshore transport in suspended load is due to a “wave‐stirring” mechanism, which signifies a nonlinear interaction between waves, streaming currents, and sediment suspension. We present some preliminary efforts to parameterize the wave‐stirring mechanism in intrawave sediment transport formulations.
The Assimilation of Phytoplankton Functional Types for Operational Forecasting in the Northwest European Shelf
Authors: Skákala Jozef , Ford David , Brewin Robert J.W. , McEwan Robert , Kay Susan , Taylor Benjamin , de Mora Lee , Ciavatta Stefano
Published: June 2018

This paper proposes the use of assimilation of phytoplankton functional types (PFTs) surface chlorophyll for operational forecasting of biogeochemistry on the North‐West European (NWE) Shelf. We explicitly compare the 5‐day forecasting skill of three runs of a physical‐biogeochemical model: (a) a free reference run, (b) a run with daily data assimilation (DA) of total surface chlorophyll (ChlTot), and (c) a run with daily PFTs DA. We show that small total chlorophyll model bias hides comparatively large biases in PFTs chlorophyll, which ChlTot DA fails to correct. This is because the ChlTot DA splits the assimilated total chlorophyll into PFTs by preserving their simulated ratios, rather than taking account of the observed PFT concentrations. Unlike ChlTot DA, PFTs DA substantially improves model representation of PFTs chlorophyll. During forecasting the DA reanalysis skill in representing PFTs chlorophyll degrades toward the free run skill; however, PFTs DA outperforms free run within the whole 5‐day forecasting period. We validated our results with in situ data, and we demonstrated that (in both DA cases) the DA substantially improves the model representation of CO2 fugacity (PFTs DA more than ChlTot DA). ChlTot DA has a positive impact on the representation of silicate, while the PFTs DA seems to have a negative impact. The impact of DA on nitrate and phosphate is not significant. The implications of using a univariate assimilation method, which preserves the phytoplankton stochiometry, and the impact of model biases on the nonassimilated variables are discussed.
Top‐Down Estimates of NOx and CO Emissions From Washington, D.C.‐Baltimore During the WINTER Campaign
Authors: Salmon O. E. , Shepson P. B. , Ren X. , He H. , Hall D. L. , Dickerson R. R. , Stirm B. H. , Brown S. S. , Fibiger D. L. , McDuffie E. E. , Campos T. L. , Gurney K. R. , Thornton J. A.
Published: June 2018

Airborne mass balance experiments were conducted around the Washington, D.C.‐Baltimore area using research aircraft from Purdue University and the University of Maryland to quantify emissions of nitrogen oxides (NOx = NO + NO2) and carbon monoxide (CO). The airborne mass balance experiments supported the Wintertime INvestigation of Transport, Emissions, and Reactivity (WINTER) campaign, an intensive airborne study of anthropogenic emissions along the Northeastern United States in February–March 2015, and the Fluxes of Atmospheric Greenhouse Gases in Maryland project which seeks to provide best estimates of anthropogenic emissions from the Washington, D.C.‐Baltimore area. Top‐down emission rates of NOx and CO estimated from the mass balance flights are compared with the Environmental Protection Agency's 2011 and 2014 National Emissions Inventory (NEI‐11 and NEI‐14). Inventory and observation‐derived NOx emission rates are consistent within the measurement uncertainty. Observed CO emission rates are a factor of 2 lower than reported by the NEI. The NEI's accuracy has been evaluated for decades by studies of anthropogenic emissions, yet despite continuous inventory updates, observation‐inventory discrepancies persist. WINTER NOx/CO2 enhancement ratios are consistent with inventories, but WINTER CO/NOx and CO/CO2 enhancement ratios are lower than those reported by other urban summertime studies, suggesting a strong influence of CO seasonal trends and/or nationwide CO reductions. There is a need for reliable observation‐based criterion pollutant emission rate measurements independent of the NEI. Such determinations could be supplied by the community's reporting of sector‐specific criteria pollutant/CO2 enhancement ratios and subsequent multiplication with currently available and forthcoming high‐resolution CO2 inventories.
Downregulation of the neuronal opioid gene expression concomitantly with neuronal decline in dorsolateral prefrontal cortex of human alcoholics
Authors: Bazov Igor , Sarkisyan Daniil , Kononenko Olga , Watanabe Hiroyuki , Karpyak Victor M. , Yakovleva Tatiana , Bakalkin Georgy
Published: June 2018

Molecular changes in cortical areas of addicted brain may underlie cognitive impairment and loss of control over intake of addictive substances and alcohol. Prodynorphin (PDYN) gives rise to dynorphin (DYNs) opioid peptides which target kappa-opioid receptor (KOR). DYNs mediate alcohol-induced impairment of learning and memory, while KOR antagonists block excessive, compulsive-like drug and alcohol self-administration in animal models. In human brain, the DYN/KOR system may undergo adaptive changes, which along with neuronal loss, may contribute to alcohol-associated cognitive deficit. We addressed this hypothesis by comparing the expression levels and co-expression (transcriptionally coordinated) patterns of PDYN and KOR (OPRK1) genes in dorsolateral prefrontal cortex (dlPFC) between human alcoholics and controls. Postmortem brain specimens of 53 alcoholics and 55 controls were analyzed. PDYN was found to be downregulated in dlPFC of alcoholics, while OPRK1 transcription was not altered. PDYN downregulation was confined to subgroup of subjects carrying C, a high-risk allele of PDYN promoter SNP rs1997794 associated with alcoholism. Changes in PDYN expression did not depend on the decline in neuronal proportion in alcoholics, and thereby may be attributed to transcriptional adaptations in alcoholic brain. Absolute expression levels of PDYN were lower compared to those of OPRK1, suggesting that PDYN expression is a limiting factor in the DYN/KOR signaling, and that the PDYN downregulation diminishes efficacy of DYN/KOR signaling in dlPFC of human alcoholics. The overall outcome of the DYN/KOR downregulation may be disinhibition of neurotransmission, which when overactivated could contribute to formation of alcohol-related behavior.
An effect of serotonergic stimulation on learning rates for rewards apparent after long intertrial intervals
Authors: Iigaya Kiyohito , Fonseca Madalena S. , Murakami Masayoshi , Mainen Zachary F. , Dayan Peter
Published: June 2018

Serotonin has widespread, but computationally obscure, modulatory effects on learning and cognition. Here, we studied the impact of optogenetic stimulation of dorsal raphe serotonin neurons in mice performing a non-stationary, reward-driven decision-making task. Animals showed two distinct choice strategies. Choices after short inter-trial-intervals (ITIs) depended only on the last trial outcome and followed a win-stay-lose-switch pattern. In contrast, choices after long ITIs reflected outcome history over multiple trials, as described by reinforcement learning models. We found that optogenetic stimulation during a trial significantly boosted the rate of learning that occurred due to the outcome of that trial, but these effects were only exhibited on choices after long ITIs. This suggests that serotonin neurons modulate reinforcement learning rates, and that this influence is masked by alternate, unaffected, decision mechanisms. These results provide insight into the role of serotonin in treating psychiatric disorders, particularly its modulation of neural plasticity and learning.
Structural basis for terminal loop recognition and stimulation of pri-miRNA-18a processing by hnRNP A1
Authors: Kooshapur Hamed , Choudhury Nila Roy , Simon Bernd , Mühlbauer Max , Jussupow Alexander , Fernandez Noemi , Jones Alisha N. , Dallmann Andre , Gabel Frank , Camilloni Carlo , Michlewski Gracjan , Caceres Javier F. , Sattler Michael
Published: June 2018

Post-transcriptional mechanisms play a predominant role in the control of microRNA (miRNA) production. Recognition of the terminal loop of precursor miRNAs by RNA-binding proteins (RBPs) influences their processing; however, the mechanistic basis for how levels of individual or subsets of miRNAs are regulated is mostly unexplored. We previously showed that hnRNP A1, an RBP implicated in many aspects of RNA processing, acts as an auxiliary factor that promotes the Microprocessor-mediated processing of pri-mir-18a. Here, by using an integrative structural biology approach, we show that hnRNP A1 forms a 1:1 complex with pri-mir-18a where both RNA recognition motifs (RRMs) bind to cognate RNA sequence motifs in the terminal loop of pri-mir-18a. Terminal loop binding induces an allosteric destabilization of base-pairing in the pri-mir-18a stem that promotes its downstream processing. Our results highlight terminal loop RNA recognition by RBPs as a potential general principle of miRNA biogenesis and regulation.
Pooled CRISPR interference screening enables genome-scale functional genomics study in bacteria with superior performance
Authors: Wang Tianmin , Guan Changge , Guo Jiahui , Liu Bing , Wu Yinan , Xie Zhen , Zhang Chong , Xing Xin-Hui
Published: June 2018

To fully exploit the microbial genome resources, a high-throughput experimental platform is needed to associate genes with phenotypes at the genome level. We present here a novel method that enables investigation of the cellular consequences of repressing individual transcripts based on the CRISPR interference (CRISPRi) pooled screening in bacteria. We identify rules for guide RNA library design to handle the unique structure of prokaryotic genomes by tiling screening and construct an E. coli genome-scale guide RNA library (~60,000 members) accordingly. We show that CRISPRi outperforms transposon sequencing, the benchmark method in the microbial functional genomics field, when similar library sizes are used or gene length is short. This tool is also effective for mapping phenotypes to non-coding RNAs (ncRNAs), as elucidated by a comprehensive tRNA-fitness map constructed here. Our results establish CRISPRi pooled screening as a powerful tool for mapping complex prokaryotic genetic networks in a precise and high-throughput manner.
Identifying patients with asthma-chronic obstructive pulmonary disease overlap syndrome using latent class analysis of electronic health record data: a study protocol
Authors: Al Sallakh Mohammad A , Rodgers Sarah E , Lyons Ronan A , Sheikh Aziz , Davies Gwyneth A
Published: June 2018

Asthma and chronic obstructive pulmonary disease (COPD) are two common different clinical diagnoses with overlapping clinical features. Both conditions have been increasingly studied using electronic health records (EHR). Asthma-COPD overlap syndrome (ACOS) is an emerging concept where clinical features from both conditions co-exist, and for which, however, there is no consensus definition. Nonetheless, we expect EHR data of people with ACOS to be systematically different from those with “asthma only” or “COPD only”. We aim to develop a latent class model to understand the overlap between asthma and COPD in EHR data. From the Secure Anonymised Information Linkage (SAIL) databank, we will use routinely collected primary care data recorded in or before 2014 in Wales for people who aged 40 years or more on 1st Jan 2014. Based on this latent class model, we will train a classification algorithm and compare its performance with commonly used objective and self-reported case definitions for asthma and COPD. The resulting classification algorithm is intended to be used to identify people with ACOS, ‘asthma only’, and ‘COPD only’ in primary care datasets.
Ab initio description of highly correlated states in defects for realizing quantum bits
Authors: Bockstedte Michel , Schütz Felix , Garratt Thomas , Ivády Viktor , Gali Adam
Published: June 2018

Coupled localized electron spins hosted by defects in semiconductors implement quantum bits with the potential to revolutionize nanoscale sensors and quantum information processing. The present understanding of optical means of spin state manipulation and read-out calls for quantitative theoretical description of the active states, built-up from correlated electrons in a bath of extended electron states. Hitherto we propose a first-principles scheme based on many body perturbation theory and configuration interaction and address two room temperature point defect qubits, the nitrogen vacancy in diamond and the divacancy in silicon carbide. We provide a complete quantitative description of the electronic structure and analyze the crossings and local minima of the energy surface of triplet and singlet states. Our numerical results not only extend the knowledge of the spin-dependent optical cycle of these defects, but also demonstrate the potential of our method for quantitative theoretical studies of point defect qubits.
Selection of validated hypervariable regions is crucial in 16S-based microbiota studies of the female genital tract
Authors: Graspeuntner Simon , Loeper Nathalie , Künzel Sven , Baines John F. , Rupp Jan
Published: June 2018

Next-generation sequencing-based methods are extensively applied in studies of the human microbiota using partial 16 S rRNA gene amplicons. However, they carry drawbacks that are critical to consider when interpreting results, including differences in outcome based on the hypervariable region(s) used. Here, we show that primers spanning the V3/V4 region identify a greater number of taxa in the vaginal microbiota than those spanning the V1/V2 region. In particular, taxa such as Gardnerella vaginalis, Bifidobacterium bifidum and Chlamydia trachomatis, all species that influence vaginal health and disease, are not represented in V1/V2-based community profiles. Accordingly, missing or underestimating the frequency of these species overestimates the abundance of other taxa and fails to correctly assess the bacterial diversity in the urogenital tract. We elaborate that covering these taxa using the V3/V4 region leads to profound changes in the assignment of community state types. Altogether, we show that the choice of primers used for studying the vaginal microbiota has deep implications on the biological evaluation of the results.
Recovery of coral assemblages despite acute and recurrent disturbances on a South Central Pacific reef
Authors: Adjeroud Mehdi , Kayal Mohsen , Iborra-Cantonnet Claudie , Vercelloni Julie , Bosserelle Pauline , Liao Vetea , Chancerelle Yannick , Claudet Joachim , Penin Lucie
Published: June 2018

Coral reefs are increasingly threatened by various types of disturbances, and their recovery is challenged by accelerating, human-induced environmental changes. Recurrent disturbances reduce the pool of mature adult colonies of reef-building corals and undermine post-disturbance recovery from newly settled recruits. Using a long-term interannual data set, we show that coral assemblages on the reef slope of Moorea, French Polynesia, have maintained a high capacity to recover despite a unique frequency of large-scale disturbances which, since the 1990s, have caused catastrophic declines in coral cover and abundance. In 2014, only four years after one of the most extreme cases of coral decline documented, abundance of juvenile and adult colonies had regained or exceeded pre-disturbance levels, and no phase-shift to macroalgal dominance was recorded. This rapid recovery has been achieved despite constantly low coral recruitment rates, suggesting a high post-disturbance survivorship of recruits. However, taxonomic differences in coral susceptibility to disturbances and contrasting recovery trajectories have resulted in changes in the relative composition of species. In the present context of global coral reef decline, our study establishes a new benchmark for the capacity of certain benthic reef communities to sustain and recover their coral cover from repeated, intense disturbances.
Double Strand Break DNA Repair occurs via Non-Homologous End-Joining in Mouse MII Oocytes
Authors: Martin Jacinta H. , Bromfield Elizabeth G. , Aitken R. John , Lord Tessa , Nixon Brett
Published: June 2018

The unique biology of the oocyte means that accepted paradigms for DNA repair and protection are not of direct relevance to the female gamete. Instead, preservation of the integrity of the maternal genome depends on endogenous protein stores and/or mRNA transcripts accumulated during oogenesis. The aim of this study was to determine whether mature (MII) oocytes have the capacity to detect DNA damage and subsequently mount effective repair. For this purpose, DNA double strand breaks (DSB) were elicited using the topoisomerase II inhibitor, etoposide (ETP). ETP challenge led to a rapid and significant increase in DSB (P = 0.0002) and the consequential incidence of metaphase plate abnormalities (P = 0.0031). Despite this, ETP-treated MII oocytes retained their ability to participate in in vitro fertilisation, though displayed reduced developmental competence beyond the 2-cell stage (P = 0.02). To account for these findings, we analysed the efficacy of DSB resolution, revealing a significant reduction in DSB lesions 4 h post-ETP treatment. Notably, this response was completely abrogated by pharmacological inhibition of key elements (DNA-PKcs and DNA ligase IV) of the canonical non-homologous end joining DNA repair pathway, thus providing the first evidence implicating this reparative cascade in the protection of the maternal genome.
S-nitrosation of protein phosphatase 1 mediates alcohol-induced ciliary dysfunction
Authors: Price Michael E. , Case Adam J. , Pavlik Jacqueline A. , DeVasure Jane M. , Wyatt Todd A. , Zimmerman Matthew C. , Sisson Joseph H.
Published: June 2018

Alcohol use disorder (AUD) is a strong risk factor for development and mortality of pneumonia. Mucociliary clearance, a key innate defense against pneumonia, is perturbed by alcohol use. Specifically, ciliated airway cells lose the ability to increase ciliary beat frequency (CBF) to β-agonist stimulation after prolonged alcohol exposure. We previously found that alcohol activates protein phosphatase 1 (PP1) through a redox mechanism to cause ciliary dysfunction. Therefore, we hypothesized that PP1 activity is enhanced by alcohol exposure through an S-nitrosothiol-dependent mechanism resulting in desensitization of CBF stimulation. Bronchoalveolar S-nitrosothiol (SNO) content and tracheal PP1 activity was increased in wild-type (WT) mice drinking alcohol for 6-weeks compared to control mice. In contrast, alcohol drinking did not increase SNO content or PP1 activity in nitric oxide synthase 3-deficient mice. S-nitrosoglutathione induced PP1-dependent CBF desensitization in mouse tracheal rings, cultured cells and isolated cilia. In vitro expression of mutant PP1 (cysteine 155 to alanine) in primary human airway epithelial cells prevented CBF desensitization after prolonged alcohol exposure compared to cells expressing WT PP1. Thus, redox modulation in the airways by alcohol is an important ciliary regulatory mechanism. Pharmacologic strategies to reduce S-nitrosation may enhance mucociliary clearance and reduce pneumonia prevalence, mortality and morbidity with AUD.
Aquatic behaviour of polar bears (Ursus maritimus) in an increasingly ice-free Arctic
Authors: Lone Karen , Kovacs Kit M. , Lydersen Christian , Fedak Mike , Andersen Magnus , Lovell Philip , Aars Jon
Published: June 2018

Polar bears are ice-associated marine mammals that are known to swim and dive, yet their aquatic behaviour is poorly documented. Reductions in Arctic sea ice are clearly a major threat to this species, but understanding polar bears’ potential behavioural plasticity with respect to the ongoing changes requires knowledge of their swimming and diving skills. This study quantified time spent in water by adult female polar bears (n = 57) via deployment of various instruments bearing saltwater switches, and in some case pressure sensors (79 deployments, 64.8 bear-years of data). There were marked seasonal patterns in aquatic behaviour, with more time spent in the water during summer, when 75% of the polar bears swam daily (May-July). Females with cubs-of-the-year spent less time in the water than other females from den emergence (April) until mid-summer, consistent with small cubs being vulnerable to hypothermia and drowning. Some bears undertook notable long-distance-swims. Dive depths up to 13.9 m were recorded, with dives ≥5 m being common. The considerable swimming and diving capacities of polar bears might provide them with tools to exploit aquatic environments previously not utilized. This is likely to be increasingly important to the species’ survival in an Arctic with little or no persistent sea ice.
Metformin add-on continuous subcutaneous insulin infusion on precise insulin doses in patients with type 2 diabetes
Authors: Li Feng-fei , Liu Bing-li , Yin Guo-ping , Yan Reng-na , Zhang Dan-feng , Wu Jin-dan , Ye Lei , Su Xiao-fei , Ma Jian-hua
Published: June 2018

To investigate whether metformin add-on to the continuous subcutaneous insulin infusion (Met + CSII) therapy leads to a significant reduction in insulin doses required by type 2 diabetes (T2D) patients to maintain glycemic control, and an improvement in glycemic variation (GV) compared to CSII only therapy. We analyzed data from our two randomized, controlled open-label trials. Newly diagnoses T2D patients were randomized assigned to receive either CSII therapy or Met + CSII therapy for 4 weeks. Subjects were subjected to a 4-day continuous glucose monitoring (CGM) at the endpoint. Insulin doses and GV profiles were analyzed. The primary endpoint was differences in insulin doses and GV between the two groups. A total of 188 subjects were admitted as inpatients. Subjects in metformin add-on therapy required significantly lower total, basal and bolus insulin doses than those of control group. CGM data showed that patients in Met + CSII group exhibited significant reduction in the 24-hr mean amplitude of glycemic excursions (MAGE), the standard deviation, and the coefficient of variation compared to those of control group. Our data suggest that metformin add-on to CSII therapy leads to a significant reduction in insulin doses required by T2D patients to control glycemic variations.
Genome-wide bisulphite-sequencing reveals organ-specific methylation patterns in chickpea
Authors: Bhatia Himanshi , Khemka Niraj , Jain Mukesh , Garg Rohini
Published: June 2018

DNA methylation is widely known to regulate gene expression in eukaryotes. Here, we unraveled DNA methylation patterns in cultivated chickpea to understand the regulation of gene expression in different organs. We analyzed the methylation pattern in leaf tissue of wild chickpea too, and compared it with cultivated chickpea. Our analysis indicated abundant CG methylation within gene-body and CHH methylation in intergenic regions of the chickpea genome in all the organs examined. Analysis of differentially methylated regions (DMRs) demonstrated a higher number of CG context DMRs in wild chickpea and CHH context DMRs in cultivated chickpea. We observed increased preponderance of hypermethylated DMRs in the promoter regions and hypomethylated DMRs in the genic regions in cultivated chickpea. Genomic location and context of the DMRs correlated well with expression of proximal genes. Our results put forth a positive correlation of promoter hypermethylation with increased transcript abundance via identification of DMR-associated genes involved in flower development in cultivated chickpea. The atypical correlation observed between promoter hypermethylation and increased transcript abundance might be dependent on 24-nt small RNAs and transcription factors binding to the promoter region. This study provides novel insights into DNA methylation patterns in chickpea and their role in regulation of gene expression.
2-carba cyclic phosphatidic acid suppresses inflammation via regulation of microglial polarisation in the stab-wounded mouse cerebral cortex
Authors: Hashimoto Kei , Nakashima Mari , Hamano Ayana , Gotoh Mari , Ikeshima-Kataoka Hiroko , Murakami-Murofushi Kimiko , Miyamoto Yasunori
Published: June 2018

Traumatic brain injury (TBI) is caused by physical damage to the brain and it induces blood-brain barrier (BBB) breakdown and inflammation. To diminish the sequelae of TBI, it is important to decrease haemorrhage and alleviate inflammation. In this study, we aimed to determine the effects of 2-carba-cyclic phosphatidic acid (2ccPA) on the repair mechanisms after a stab wound injury as a murine TBI model. The administration of 2ccPA suppressed serum immunoglobulin extravasation after the injury. To elucidate the effects of 2ccPA on inflammation resulting from TBI, we analysed the mRNA expression of inflammatory cytokines. We found that 2ccPA prevents a TBI-induced increase in the mRNA expression of Il-1β, Il-6, Tnf-α and Tgf-β1. In addition, 2ccPA reduces the elevation of Iba1 levels. These data suggest that 2ccPA attenuates the inflammation after a stab wound injury via the modulation of pro-inflammatory cytokines release from microglial cells. Therefore, we focused on the function of 2ccPA in microglial polarisation towards M1 or M2 phenotypes. The administration of 2ccPA decreased the number of M1 and increased the number of M2 type microglial cells, indicating that 2ccPA modulates the microglial polarisation and shifts them towards M2 phenotype. These data suggest that 2ccPA treatment suppresses the extent of BBB breakdown and inflammation after TBI.
Activation of the p53-MDM4 regulatory axis defines the anti-tumour response to PRMT5 inhibition through its role in regulating cellular splicing
Authors: Gerhart Sarah V. , Kellner Wendy A. , Thompson Christine , Pappalardi Melissa B. , Zhang Xi-Ping , Montes de Oca Rocio , Penebre Elayne , Duncan Kenneth , Boriack-Sjodin Ann , Le BaoChau , Majer Christina , McCabe Michael T. , Carpenter Chris , Johnson Neil , Kruger Ryan G. , Barbash Olena
Published: June 2018

Evasion of the potent tumour suppressor activity of p53 is one of the hurdles that must be overcome for cancer cells to escape normal regulation of cellular proliferation and survival. In addition to frequent loss of function mutations, p53 wild-type activity can also be suppressed post-translationally through several mechanisms, including the activity of PRMT5. Here we describe broad anti-proliferative activity of potent, selective, reversible inhibitors of protein arginine methyltransferase 5 (PRMT5) including GSK3326595 in human cancer cell lines representing both hematologic and solid malignancies. Interestingly, PRMT5 inhibition activates the p53 pathway via the induction of alternative splicing of MDM4. The MDM4 isoform switch and subsequent p53 activation are critical determinants of the response to PRMT5 inhibition suggesting that the integrity of the p53-MDM4 regulatory axis defines a subset of patients that could benefit from treatment with GSK3326595.
Viscoelastic properties of Pseudomonas aeruginosa variant biofilms
Authors: Gloag Erin S. , German Guy K. , Stoodley Paul , Wozniak Daniel J.
Published: June 2018

Pseudomonas aeruginosa evolves during chronic pulmonary infections of cystic fibrosis (CF) patients, forming pathoadapted variants that are persistent. Mucoid and rugose small-colony variants (RSCVs) are typically isolated from sputum of CF patients. These variants overproduce exopolysaccharides in the biofilm extracellular polymeric substance (EPS). Currently, changes to the biophysical properties of RSCV and mucoid biofilms due to variations in EPS are not well understood. This knowledge may reveal how lung infections resist host clearance mechanisms. Here, we used mechanical indentation and shear rheometry to analyse the viscoelasticity of RSCV and mucoid colony-biofilms compared to their isogenic parent at 2-, 4-, and 6-d. While the viscoelasticity of parental colony-biofilms underwent fluctuating temporal changes, in contrast, RSCV and mucoid colony-biofilms showed a gradual progression to more elastic-solid behaviour. Theoretical indices of mucociliary and cough clearance predict that mature 6-d parental and RSCV biofilms may show reduced cough clearance from the lung, while early mucoid biofilms may show reduced clearance by both mechanisms. We propose that viscoelasticity be considered a virulence property of biofilms.
Consistent signatures of selection from genomic analysis of pairs of temporal and spatial Plasmodium falciparum populations from The Gambia
Authors: Amambua-Ngwa Alfred , Jeffries David , Amato Roberto , Worwui Archibald , Karim Mane , Ceesay Sukai , Nyang Haddy , Nwakanma Davis , Okebe Joseph , Kwiatkowski Dominic , Conway David J. , D’Alessandro Umberto
Published: June 2018

Genome sequences of 247 Plasmodium falciparum isolates collected in The Gambia in 2008 and 2014 were analysed to identify changes possibly related to the scale-up of antimalarial interventions that occurred during this period. Overall, there were 15 regions across the genomes with signatures of positive selection. Five of these were sweeps around known drug resistance and antigenic loci. Signatures at antigenic loci such as thrombospodin related adhesive protein (Pftrap) were most frequent in eastern Gambia, where parasite prevalence and transmission remain high. There was a strong temporal differentiation at a non-synonymous SNP in a cysteine desulfarase (Pfnfs) involved in iron-sulphur complex biogenesis. During the 7-year period, the frequency of the lysine variant at codon 65 (Pfnfs-Q65K) increased by 22% (10% to 32%) in the Greater Banjul area. Between 2014 and 2015, the frequency of this variant increased by 6% (20% to 26%) in eastern Gambia. IC50 for lumefantrine was significantly higher in Pfnfs-65K isolates. This is probably the first evidence of directional selection on Pfnfs or linked loci by lumefantrine. Given the declining malaria transmission, the consequent loss of population immunity, and sustained drug pressure, it is important to monitor Gambian P. falciparum populations for further signs of adaptation.
Click communication in wild harbour porpoises (Phocoena phocoena)
Authors: Sørensen P. M. , Wisniewska D. M. , Jensen F. H. , Johnson M. , Teilmann J. , Madsen P. T.
Published: June 2018

Social delphinids employ a vocal repertoire of clicks for echolocation and whistles for communication. Conversely, the less social and acoustically cryptic harbour porpoises (Phocoena phocoena) only produce narrow-band high-frequency (NBHF) clicks with properties that appear poorly suited for communication. Nevertheless, these small odontocetes likely mediate social interactions, such as mate choice and mother-calf contact, with sound. Here, we deployed six tags (DTAG3) on wild porpoises in Danish waters for a total of 96 hours to investigate if the patterns and use of stereotyped NBHF click trains are consistent with a communication function. We show that wild porpoises produce frequent (up to 27 $$\bullet $$

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min−1), high-repetition rate click series with repetition rates and output levels different from those of foraging buzzes. These sounds are produced in bouts and frequently co-occur with emission of similar sounds by nearby conspecifics, audible on the tags for >10% of the time. These results suggest that social interactions are more important to this species than their limited social encounters at the surface may indicate and that these interactions are mediated by at least two broad categories of calls composed of short, high-repetition rate click trains that may encode information via the repetition rate of their stereotyped NBHF clicks.
A new technique for nanoparticle transport and its application in a novel nano-sieve
Authors: Wang Shuai , Wang Chao , Peng Zhilong , Chen Shaohua
Published: June 2018

A new technique is proposed to transport and further classify nanoparticles of different sizes. A graphene sheet is used as the substrate; a nanoparticle is placed on the substrate and a sliding block is located below the substrate. As the sliding block moves under the graphene substrate, a driving force is yielded from the van der Waals interaction between the sliding block and the nanoparticle. The effects of the pre-tension of the graphene substrate, size and number of layers of the nanoparticle, slip velocity, the interface commensurability and temperature on nanoparticle transportation are systematically investigated. It is found that a pre-tensioned graphene substrate could provide easier nanoparticle transport. The initial movement of the nanoparticle depends on the competition between the in-plane force and the driving force, while the subsequent transport depends on the slip velocity of the sliding block and the viscous damping force. Based on such a new transport mechanism, a novel nano-sieve can be designed, with which nanoparticles of different sizes can be screened and classified spontaneously. Our findings may be useful for promising designs of transportation, manipulation and classification of nanoparticles.
A sensitive electrochemical immunosensor for label-free detection of Zika-virus protein
Authors: Kaushik Ajeet , Yndart Adriana , Kumar Sanjeev , Jayant Rahul Dev , Vashist Arti , Brown Ashley N. , Li Chen-Zhong , Nair Madhavan
Published: June 2018

This work, as a proof of principle, presents a sensitive and selective electrochemical immunosensor for Zika-virus (ZIKV)-protein detection using a functionalized interdigitated micro-electrode of gold (IDE-Au) array. A miniaturized IDE-Au immunosensing chip was prepared via immobilization of ZIKV specific envelop protein antibody (Zev-Abs) onto dithiobis(succinimidyl propionate) i.e., (DTSP) functionalized IDE-Au (electrode gap/width of 10 µm). Electrochemical impedance spectroscopy (EIS) was performed to measure the electrical response of developed sensing chip as a function of ZIKV-protein concentrations. The results of EIS studies confirmed that sensing chip detected ZIKV-protein selectively and exhibited a detection range from 10 pM to 1 nM and a detection limit of 10 pM along with a high sensitivity of 12 kΩM−1. Such developed ZIKV immune-sensing chip can be integrated with a miniaturized potentiostat (MP)-interfaced with a smartphone for rapid ZIKV-infection detection required for early stage diagnostics at point-of-care application.
The atypical subunit composition of respiratory complexes I and IV is associated with original extra structural domains in Euglena gracilis
Authors: Miranda-Astudillo H. V. , Yadav K. N. S. , Colina-Tenorio L. , Bouillenne F. , Degand H. , Morsomme P. , Boekema E. J. , Cardol P.
Published: June 2018

In mitochondrial oxidative phosphorylation, electron transfer from NADH or succinate to oxygen by a series of large protein complexes in the inner mitochondrial membrane (complexes I–IV) is coupled to the generation of an electrochemical proton gradient, the energy of which is utilized by complex V to generate ATP. In Euglena gracilis, a non-parasitic secondary green alga related to trypanosomes, these respiratory complexes totalize more than 40 Euglenozoa-specific subunits along with about 50 classical subunits described in other eukaryotes. In the present study the Euglena proton-pumping complexes I, III, and IV were purified from isolated mitochondria by a two-steps liquid chromatography approach. Their atypical subunit composition was further resolved and confirmed using a three-steps PAGE analysis coupled to mass spectrometry identification of peptides. The purified complexes were also observed by electron microscopy followed by single-particle analysis. Even if the overall structures of the three oxidases are similar to the structure of canonical enzymes (e.g. from mammals), additional atypical domains were observed in complexes I and IV: an extra domain located at the tip of the peripheral arm of complex I and a “helmet-like” domain on the top of the cytochrome c binding region in complex IV.
Publisher Correction: Investigation of brain tissue infiltration by medulloblastoma cells in an ex vivo model
Authors: Neve Anuja , Santhana Kumar Karthiga , Tripolitsioti Dimitra , Grotzer Michael A. , Baumgartner Martin
Published: June 2018

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.
Nonlinear associations between working hours and overwork-related cerebrovascular and cardiovascular diseases (CCVD)
Authors: Lin Ro-Ting , Chien Lung-Chang , Kawachi Ichiro
Published: June 2018

Long working hours are recognized as a risk factor for cerebrovascular and cardiovascular diseases (CCVD). We investigated the relationship between working hours and different CCVD severity outcomes—death, disability, and illness—across industries in Taiwan from 2006 to 2016. We applied a generalized additive mixed model to estimate the association between working hours and the rate of each severity outcome, adjusted for salary, unemployment rate, time, and a random intercept. Industry-average working hours were significantly associated with each outcome level of overwork-related CCVD, especially when monthly working hours increased from 169 (relative risk [RR] = 1.46, 95% confidence interval [CI] 1.002–2.12) to 187 (RR = 5.73, 95% CI 3.61–9.08). Although RR trends declined after monthly working hours exceeded 187, excess risks remained statistically significant. Each 1-hour increase in working hours had a stronger effect on the RR increase in death and disability than on illness. Variations in CCVD risks existed across industries, with the highest risk in transportation and information. Reducing working hours is essential to preventing overwork-related CCVD, especially the more severe outcomes. We recommend further research to address possible underreporting of less severe cases, and to explore actions to narrow the gaps in risk across industries.
C3a triggers formation of sub-retinal pigment epithelium deposits via the ubiquitin proteasome pathway
Authors: Fernandez-Godino Rosario , Pierce Eric A.
Published: June 2018

The mechanisms that connect complement system activation and basal deposit formation in early stages of age-related macular degeneration (AMD) are insufficiently understood, which complicates the design of efficient therapies to prevent disease progression. Using human fetal (hf) retinal pigment epithelial (RPE) cells, we have established anin vitromodel to investigate the effect of complement C3a on RPE cells and its role in the formation of sub-RPE deposits. The results of these studies revealed that C3a produced after C3 activation is sufficient to induce the formation of sub-RPE deposits via complement-driven proteasome inhibition. C3a binds the C3a receptor (C3aR), stimulates deposition of collagens IV and VI underneath the RPE, and impairs the extracellular matrix (ECM) turnover by increased MMP-2 activity, all mediated by downregulation of the ubiquitin proteasome pathway (UPP). The formation of basal deposits can be prevented by the addition of a C3aR antagonist, which restores the UPP activity and ECM turnover. These findings indicate that the cell-based model can be used to test potential therapeutic agentsin vitro. The data suggest that modulation of C3aR-mediated events could be a therapeutic approach for treatment of early AMD.
Piperazine-tuned NBD-based colorimetric and fluorescent turn-off probes for hydrogen sulfide
Authors: Xu Zhong-yong , Wu Zi-ying , Tan Hui-ya , Yan Jin-wu , Liu Xiao-lin , Li Jia-ying , Xu Zi-yan , Dong Chang-zhi , Zhang Lei
Published: June 2018

The piperazine ring is a very important factor in governing molecular structure to generate the special properties of a compound.
Evaluation of analytical instrumentation. Part XXVII: a guide to good practice in the purchase of analytical instrumentation
Authors: Potts Philip J.
Published: June 2018

This guide is designed for those involved in the purchase of analytical instrumentation, including analysts and laboratory staff, purchasing officers and senior managers.
In situ anchoring of metal nanoparticles in the N-doped carbon framework derived from conjugated microporous polymers towards an efficient oxygen reduction reaction
Authors: Li Qiang , Shao Qi , Wu Qiong , Duan Qian , Li Yanhui , Wang Heng-guo
Published: June 2018

A series of efficient catalysts derived from metallophthalocyanine based conjugated microporous polymers show superior ORR activity in Zn–air batteries.
Enhanced electrocatalytic ethanol oxidation reaction in alkaline media over Pt on a 2D BiVO4-modified electrode under visible light irradiation
Authors: Hu Jiayue , Zhai Chunyang , Zeng Lixi , Du Yukou , Zhu Mingshan
Published: June 2018

2D BiVO4 is extended to be a visible-light-responsive support for opening a new application of electrocatalytic ethanol oxidation reaction (EOR).