bluuebunny/crossref_metadata_2025 huggingface dataset:
Tracking Counterpart Signatures in Saturn's Auroras and ENA Imagery During Large‐Scale Plasma Injection Events
Authors: Kinrade J. , Badman S. V. , Paranicas C. , Mitchell D. G. , Arridge C. S. , Gray R. L. , Bader A. , Provan G. , Cowley S. W. H. , Martin C. J. , Achilleos N.
Published: February 2020

Saturn's morningside auroras consist mainly of rotating, transient emission patches, following periodic reconnection in the magnetotail. Simultaneous responses in global energetic neutral atom (ENA) emissions have been observed at similar local times, suggesting a link between the auroras and large‐scale injections of hot ions in the outer magnetosphere. In this study, we use Cassini's remote sensing instruments to observe multiple plasma injection signatures within coincident auroral and ENA imagery, captured during 9 April 2014. Kilometric radio emissions also indicate clear injection activity. We track the motion of rotating signatures in the auroras and ENAs to test their local time relationship. Two successive auroral signatures—separated by ~4 hr UT—form postmidnight before rotating to the dayside while moving equatorward. The first has a clear ENA counterpart, maintaining a similar local time mapping throughout ~9 hr observation. Mapping of the ionospheric equatorward motion post‐dawn indicates a factor ~5 reduction of the magnetospheric source region's radial speed at a distance of ~14‐20 RS, possibly a plasma or magnetic boundary. The second auroral signature has no clear ENA counterpart; viewing geometry was relatively unchanged, so the ENAs were likely too weak to detect by this time. A third, older injection signature, seen in both auroral and ENA imagery on the nightside, may have been sustained by field‐aligned currents linked with the southern planetary period oscillation system, or the re‐energization of ENAs around midnight local times. The ENA injection signatures form near magnetic longitudes associated with magnetotail thinning.
Pitch Angle Dependence of Electron and Ion Flux Changes During Local Magnetic Dipolarization Inside Geosynchronous Orbit
Authors: Motoba T. , Ohtani S. , Gkioulidou M. , Mitchell D. G. , Ukhorskiy A. Y. , Takahashi K. , Lanzerotti L. J. , Claudepierre S.G. , Spence H. E. , Reeves G. D.
Published: February 2020

In this study we have statistically examined flux changes of 1–1,000‐keV electrons, and hydrogen, helium, and oxygen ions during local magnetic dipolarization inside geosynchronous orbit, with a focus on their pitch angle dependence. Using 144 dipolarization events that were selected in a previous study with Van Allen Probes observations in 2012–2016, we have performed a superposed epoch analysis of differential flux changes after the dipolarization onset for each species. On average the electron flux increases primarily around pitch angle (α) = 90° at >80 keV and almost isotropically at 10–50 keV. The electron flux at <5 keV increases at α = 0° and 180° but slightly decreases (or remains unchanged) at α = 90°. On the other hand, the ion flux at >80 keV increases around α = 90°, while at <30 keV it decreases nearly independent of pitch angle. Only the low‐energy (<5 keV) helium and oxygen ion flux changes indicate a strong field‐aligned enhancement, which could be attributed to their outflows from the topside ionosphere. After the dipolarization onset, >5‐keV electron and >30‐keV ion fluxes exhibit a perpendicular anisotropy, which is most pronounced for 50–200‐keV electrons. Both distributions become more isotropic with decreasing energy. A noticeable field‐aligned anisotropy is seen for <5‐keV ion fluxes. These statistical pitch angle‐dependent electron and ion properties during dipolarizations may be explained by combining various processes, including adiabatic acceleration and/or transport, wave‐particle interactions, and ion outflow.
Global Assimilation of Ocean‐Color Data of Phytoplankton Functional Types: Impact of Different Data Sets
Authors: Pradhan H. K. , Völker C. , Losa S. N. , Bracher A. , Nerger L.
Published: February 2020

Phytoplankton functional‐type (PFT) data are assimilated into the global coupled ocean‐ecosystem model MITgcm‐REcoM2 for two years using a local ensemble Kalman filter. The ecosystem model has two PFTs: small phytoplankton (SP) and diatoms. Three different sets of satellite PFT data are assimilated: Ocean‐Color‐Phytoplankton Functional Type (OC‐PFT), Phytoplankton Differential Optical Absorption Spectroscopy (PhytoDOAS), and SYNergistic exploitation of hyper‐ and multi‐spectral precursor SENtinel measurements to determine Phytoplankton Functional Types (SynSenPFT), which is a synergistic product combining the independent PFT products OC‐PFT and PhytoDOAS. The effect of assimilating PFT data is compared with the assimilation of total chlorophyll data (TChla), which constrains both PFTs through multivariate assimilation. While the assimilation of TChla already improves both PFTs, the assimilation of PFT data further improves the representation of the phytoplankton community. The effect is particularly large for diatoms where, compared to the assimilation of TChla, the SynSenPFT assimilation results in 57% and 67% reduction of root‐mean‐square error and bias, respectively, while the correlation is increased from 0.45 to 0.54. For SP the assimilation of SynSenPFT data reduces the root‐mean‐square error and bias by 14% each and increases the correlation by 30%. The separate assimilation of the PFT data products OC‐PFT, SynSenPFT, and joint assimilation of OC‐PFT and PhytoDOAS data leads to similar results while the assimilation of PhytoDOAS data alone leads to deteriorated SP but improved diatoms. When both OC‐PFT and PhytoDOAS data are jointly assimilated, the representation of diatoms is improved compared to the assimilation of only OC‐PFT. The results show slightly lower errors than when the synergistic SynSenPFT data are assimilated, which shows that the assimilation successfully combines the separate data sources.
The Role of Englacial Hydrology in the Filling and Drainage of an Ice‐Dammed Lake, Kaskawulsh Glacier, Yukon, Canada
Authors: Bigelow David G. , Flowers Gwenn E. , Schoof Christian G. , Mingo Laurent D. B. , Young Erik M. , Connal Braden G.
Published: February 2020

Outburst floods from ice‐marginal lakes are poised to become more prevalent in a warming climate. As glaciers thin and tributaries detach, water can be impounded in these unstable lakes at valley confluences. To characterize the role of the little‐studied englacial hydrological system during an outburst flood cycle, we deployed a variety of geophysical and hydrometeorological instruments in and around an ice‐marginal lake dammed by the Kaskawulsh Glacier, Yukon, Canada, to capture its 2017 filling and drainage. The subaerial lake reached a maximum volume of 9.9
 m
on 17 August before draining over the course of
19 days. During lake filling, abrupt changes in ice shelf uplift rates are associated with the formation of faults and fractures. These hydromechanical interactions are closely linked to a redistribution of englacial water as evidenced by fluctuations in shallow borehole water pressures, and changes in radar internal reflection power. Water balance calculations reveal that the subaerial, subglacial, and englacial reservoirs respectively store 20 (17–23)%, 40 (25–50)%, and 40 (30–60)% of water in the catchment at peak lake level. The calculated englacial storage volume implies saturated porosities up to 4–10% locally or 2–4% catchment‐wide. The englacial system is therefore both volumetrically important and influenced by the hydromechanical interactions between the lake and glacier. Its spatial extent and storage capacity may play a role in lake drainage initiation, modulation of the flood hydrograph, and lake refilling.
Present‐Day Greenland Ice Sheet Climate and Surface Mass Balance in CESM2
Authors: van Kampenhout Leonardus , Lenaerts Jan T. M. , Lipscomb William H. , Lhermitte Stef , Noël Brice , Vizcaíno Miren , Sacks William J. , van den Broeke Michiel R.
Published: February 2020

The response of the Greenland Ice Sheet (GrIS) to a warmer climate is uncertain on long time scales. Climate models, such as those participating in the Coupled Model Intercomparison Project phase 6 (CMIP6), are used to assess this uncertainty. The Community Earth System Model version 2.1 (CESM2) is a CMIP6 model capable of running climate simulations with either one‐way coupling (fixed ice sheet geometry) or two‐way coupling (dynamic geometry) to the GrIS. The model features prognostic snow albedo, online downscaling using elevation classes, and a firn pack to refreeze percolating melt water. Here we evaluate the representation of the GrIS surface energy balance and surface mass balance in CESM2 at 1° resolution with fixed GrIS geometry. CESM2 agrees closely with ERA‐Interim reanalysis data for key controls on GrIS SMB: surface pressure, sea ice extent, 500 hPa geopotential height, wind speed, and 700 hPa air temperature. Cloudsat‐CALIPSO data show that supercooled liquid‐containing clouds are adequately represented, whereas comparisons to Moderate Resolution Imaging Spectroradiometer and CM SAF Cloud, Albedo, and Surface Radiation data set from Advanced Very High Resolution Radiometer data second edition data suggest that CESM2 underestimates surface albedo. The seasonal cycle and spatial patterns of surface energy balance and surface mass balance components in CESM2 agree well with regional climate model RACMO2.3p2, with GrIS‐integrated melt, refreezing, and runoff bracketed by RACMO2 counterparts at 11 and 1 km. Time series of melt, runoff, and SMB show a break point around 1990, similar to RACMO2. These results suggest that GrIS SMB is realistic in CESM2, which adds confidence to coupled ice sheet‐climate experiments that aim to assess the GrIS contribution to future sea level rise.
A Sediment Trap Evaluation of B/Ca as a Carbonate System Proxy in Asymbiotic and Nondinoflagellate Hosting Planktonic Foraminifera
Authors: Osborne Emily B. , Umling Natalie E. , Bizimis Michael , Buckley Wayne , Sadekov Aleksey , Tappa Eric , Marshall Brittney , Sautter Leslie R. , Thunell Robert C.
Published: February 2020

The ratio of boron to calcium (B/Ca) in a subset of foraminifera has been shown to covary with seawater carbonate chemistry, making this geochemical signature a promising proxy for carbon cycle science. Some studies suggest complications with the B/Ca proxy in photosymbiont‐bearing planktonic foraminifera, while relatively few studies have investigated B/Ca in species that lack large dinoflagellate symbionts. For the first time, we use a sediment trap time series to evaluate B/Ca of subtropical and subpolar planktonic foraminifera species that are asymbiotic (Globigerina bulloides and Neogloboquadrina incompta) and a species that hosts small intrashell photosymbionts (Neogloboquadrina dutertrei). We find that B/Ca measurements across size fractions indicate overall little to no size‐dependent uptake of boron that has previously been reported in some symbiont‐bearing foraminifera. Neogloboquadrina incompta and N. dutertrei B/Ca are strongly correlated with calcite saturation, pH, and carbonate ion concentration, which is in good agreement with the limited number of published core top results. While G. bulloides B/Ca trends with seasonal fluctuations in carbonate chemistry, during discrete periods considerable B/Ca offsets occur when a cryptic G. bulloides species is known to be seasonally present within the region. We confirm presence and significant B/Ca offset between cryptic species by individual LA‐ICP‐MS analyses. This finding calls into question the use of traditional morphological classification to lump what might be genetically distinct species for geochemical analyses. Our overall results highlight the utility of G. bulloides, N. incompta, and N. dutertrei B/Ca while bringing to light new considerations regarding divergent geochemistry of cryptic species.
Orogen‐Parallel Transition From a Decoupled Fore‐Arc Sliver to Andean‐Type Mountain Chain: Paleomagnetic and Geologic Evidence From Southern Chile (37–39°S)
Authors: Siravo Gaia , Speranza Fabio , Hernandez‐Moreno Catalina , Di Chiara Anita
Published: February 2020

The Chiloé fore‐arc sliver is an approximately N‐S elongated crust block detached from South America along the dextral intra‐arc Liquiñe‐Ofqui fault zone (LOFZ). The sliver is internally dissected by active NW‐SE sinistral faults whose relations with the LOFZ are speculative, also due to widespread fluvioglacial and volcanic blanket hiding the substratum. We focus on the northern LOFZ end and on the Biobio fault, supposedly the northernmost of the sinistral fault set, reporting on the results from field investigation and paleomagnetism of 48 (mostly Oligo‐Miocene) volcanic sites. We find that the Biobio fault is an old inherited crust discontinuity that did not yield significant block rotation and deformation during the Cenozoic, thus testifying the end of sinistral shear at about 38°S. At the same latitudes, a northward transition from pure strike‐slip to transpressive LOFZ deformation occurs. Intense tectonic deformation and >90° clockwise rotations characterize the main LOFZ strand. Conversely, a supposedly western LOFZ strand displays counterclockwise rotations, similar to the pattern previously documented in the forearc; thus, it does not represent a LOFZ segment. LOFZ and sinistral fault kinematics must be related, and we suggest that crust pushed northward west of the LOFZ escapes laterally toward the trench along the sinistral faults. We also speculate that the northward increasing age of the subducting Nazca plate implies a concomitant decrease of heat transfer on the upper plate, thus an increasing crust rigidity that eventually inhibits strain partitioning and sliver decoupling from 38°S.
Tailoring Infographics on Water Resources Through Iterative, User‐Centered Design: A Case Study in the Peruvian Andes
Authors: Grainger Sam , Ochoa‐Tocachi Boris F. , Antiporta Javier , Dewulf Art , Buytaert Wouter
Published: February 2020

Effective communication and knowledge sharing across stakeholder groups (e.g., science, government, business, civil society, farmers, and the general public) are essential for more informed water resource management. Visualizations and graphics are powerful tools to engage diverse groups with unfamiliar information. Despite this potential, the design of visuals within applied science settings often does not involve end‐user interaction or explicit consideration of their existing knowledge systems, perspective, requirements, and context of use. As a result, products are often difficult for users to understand and contextualize. While user interaction and the development of tailored visualizations is increasingly promoted as a potential remedy, limited empirical evidence exists that shows the potential impact and can guide the development of specific approaches. We piloted an iterative and user‐centered design methodology toward the tailoring of infographic‐style posters in the context of Peruvian water governance. To test whether tailoring demonstrably improves the perceived effectiveness of products, we designed three products that conveyed similar information but were tailored to three different audiences (an Andean agricultural, urban professional, and urban general). We then compared the tailored posters to those tailored to other audiences by means of interviews and user grading. We found that end‐users perceive products that have undergone tailoring as more interesting, clearer, and more useful than products designed without explicit user consideration. Our findings indicate that identifying groups with shared characteristics and requirements is key for effective tailoring. Our research provides empirical evidence to support the incorporation of user‐centered design methods in water resource management contexts.
DNMT3A mutants provide proliferating advantage with augmentation of self-renewal activity in the pathogenesis of AML in KMT2A-PTD-positive leukemic cells
Authors: Bera Rabindranath , Chiu Ming-Chun , Huang Ying-Jung , Huang Gang , Lee Yun-Shien , Shih Lee-Yung
Published: February 2020

Acute myeloid leukemia (AML) with partial tandem duplication of histone-lysine N-methyltransferase 2A (KMT2A-PTD) is a subtype of AML and is associated with adverse survival, yet the molecular pathogenesis of KMT2A-PTD is not fully understood. DNA methyltransferase 3A (DNMT3A) is mutated in various myeloid neoplasms including AML, especially at the Arg882. Recently, it has been found that DNMT3A mutations frequently coexisted with KMT2A-PTD and are associated with inferior outcomes. We aimed to understand the biological role of DNMT3A mutation in KMT2A-PTD-positive cells. Herein, we found that overexpression of DNMT3A mutants (MT) in KMT2A-PTD-positive EOL-1 cells augmented cell proliferation and clonogenicity. Serial colony replating assays indicated that DNMT3A-MT increased the self-renewal ability of Kmt2a-PTD-expressing mouse bone marrow cells with immature morphology. At 10 months post bone marrow transplantation, mice with the combined Kmt2a-PTD and DNMT3A-MT showed hepatosplenomegaly and leukocytosis with a shorter latency compared to control and DNMT3A-wild-type. Gene expression microarray analyses of bone marrow samples from human AML with KMT2A-PTD/DNMT3A-MT showed a stem cell signature and myeloid hematopoietic lineage with dysregulation of HOXB gene expression. In addition, human bone marrow AML cells carrying KMT2A-PTD/DNMT3A-MT showed abnormal growth and augmented self-renewal activity in primary cell culture. The present study provides information underlying the pathogenic role of DNMT3A-MT with KMT2A-PTD in proliferating advantage with augmentation of self-renewal activity in human leukemia, which may help to better understand the disease and to design better therapy for AML patients with these mutations.
PABPC1-induced stabilization of BDNF-AS inhibits malignant progression of glioblastoma cells through STAU1-mediated decay
Authors: Su Rui , Ma Jun , Zheng Jian , Liu Xiaobai , Liu Yunhui , Ruan Xuelei , Shen Shuyuan , Yang Chunqing , Wang Di , Cai Heng , Li Zhen , Xue Yixue
Published: February 2020

Glioblastoma is the most common and malignant form of primary central nervous tumor in adults. Long noncoding RNAs (lncRNAs) have been reported to play a pivotal role in modulating gene expression and regulating human tumor’s malignant behaviors. In this study, we confirmed that lncRNA brain-derived neurotrophic factor antisense (BDNF-AS) was downregulated in glioblastoma tissues and cells, interacted and stabilized by polyadenylate-binding protein cytoplasmic 1 (PABPC1). Overexpression of BDNF-AS inhibited the proliferation, migration, and invasion, as well as induced the apoptosis of glioblastoma cells. In the in vivo study, PABPC1 overexpression combined with BDNF-AS overexpression produced the smallest tumor and the longest survival. Moreover, BDNF-AS could elicit retina and anterior neural fold homeobox 2 (RAX2) mRNA decay through STAU1-mediated decay (SMD), and thereby regulated the malignant behaviors glioblastoma cells. Knockdown of RAX2 produced tumor-suppressive function in glioblastoma cells and increased the expression of discs large homolog 5 (DLG5), leading to the activation of the Hippo pathway. In general, this study elucidated that the PABPC1-BDNF-AS-RAX2-DLG5 mechanism may contribute to the anticancer potential of glioma cells and may provide potential therapeutic targets for human glioma.
Alpha-synuclein fragments trigger distinct aggregation pathways
Authors: Chakroun Tasnim , Evsyukov Valentin , Nykänen Niko-Petteri , Höllerhage Matthias , Schmidt Andreas , Kamp Frits , Ruf Viktoria C. , Wurst Wolfgang , Rösler Thomas W. , Höglinger Günter U.
Published: February 2020

Aggregation of alpha-synuclein (αSyn) is a crucial event underlying the pathophysiology of synucleinopathies. The existence of various intracellular and extracellular αSyn species, including cleaved αSyn, complicates the quest for an appropriate therapeutic target. Hence, to develop efficient disease-modifying strategies, it is fundamental to achieve a deeper understanding of the relevant spreading and toxic αSyn species. Here, we describe comparative and proof-of-principle approaches to determine the involvement of αSyn fragments in intercellular spreading. We demonstrate that two different αSyn fragments (1–95 and 61–140) fulfill the criteria of spreading species. They efficiently instigate formation of proteinase-K-resistant aggregates from cell-endogenous full-length αSyn, and drive it into different aggregation pathways. The resulting aggregates induce cellular toxicity. Strikingly, these aggregates are only detectable by specific antibodies. Our results suggest that αSyn fragments might be relevant not only for spreading, but also for aggregation-fate determination and differential strain formation.
Diversity of metabolite accumulation patterns in inner and outer seed coats of pomegranate: exploring their relationship with genetic mechanisms of seed coat development
Authors: Qin Gaihua , Liu Chunyan , Li Jiyu , Qi Yongjie , Gao Zhenghui , Zhang Xiaoling , Yi Xingkai , Pan Haifa , Ming Ray , Xu Yiliu
Published: February 2020

The expanded outer seed coat and the rigid inner seed coat of pomegranate seeds, both affect the sensory qualities of the fruit and its acceptability to consumers. Pomegranate seeds are also an appealing model for the study of seed coat differentiation and development. We conducted nontarget metabolic profiling to detect metabolites that contribute to the morphological differentiation of the seed coats along with transcriptomic profiling to unravel the genetic mechanisms underlying this process. Comparisons of metabolites in the lignin biosynthetic pathway accumulating in seed coat layers at different developmental stages revealed that monolignols, including coniferyl alcohol and sinapyl alcohol, greatly accumulated in inner seed coats and monolignol glucosides greatly accumulated in outer seed coats. Strong expression of genes involved in monolignol biosynthesis and transport might explain the spatial patterns of biosynthesis and accumulation of these metabolites. Hemicellulose constituents and flavonoids in particular accumulated in the inner seed coat, and candidate genes that might be involved in their accumulation were also identified. Genes encoding transcription factors regulating monolignol, cellulose, and hemicellulose metabolism were chosen by coexpression analysis. These results provide insights into metabolic factors influencing seed coat differentiation and a reference for studying seed coat developmental biology and pomegranate genetic improvement.
Balancing selection via life-history trade-offs maintains an inversion polymorphism in a seaweed fly
Authors: Mérot Claire , Llaurens Violaine , Normandeau Eric , Bernatchez Louis , Wellenreuther Maren
Published: February 2020

How natural diversity is maintained is an evolutionary puzzle. Genetic variation can be eroded by drift and directional selection but some polymorphisms persist for long time periods, implicating a role for balancing selection. Here, we investigate the maintenance of a chromosomal inversion polymorphism in the seaweed fly Coelopa frigida. Using experimental evolution and quantifying fitness, we show that the inversion underlies a life-history trade-off, whereby each haplotype has opposing effects on larval survival and adult reproduction. Numerical simulations confirm that such antagonistic pleiotropy can maintain polymorphism. Our results also highlight the importance of sex-specific effects, dominance and environmental heterogeneity, whose interaction enhances the maintenance of polymorphism through antagonistic pleiotropy. Overall, our findings directly demonstrate how overdominance and sexual antagonism can emerge from a life-history trade-off, inviting reconsideration of antagonistic pleiotropy as a key part of multi-headed balancing selection processes that enable the persistence of genetic variation.
Conformational plasticity of ligand-bound and ternary GPCR complexes studied by 19F NMR of the β1-adrenergic receptor
Authors: Frei J. Niclas , Broadhurst Richard W. , Bostock Mark J. , Solt Andras , Jones Andrew J. Y. , Gabriel Florian , Tandale Aditi , Shrestha Binesh , Nietlispach Daniel
Published: February 2020

G-protein-coupled receptors (GPCRs) are allosteric signaling proteins that transmit an extracellular stimulus across the cell membrane. Using 19F NMR and site-specific labelling, we investigate the response of the cytoplasmic region of transmembrane helices 6 and 7 of the β1-adrenergic receptor to agonist stimulation and coupling to a Gs-protein-mimetic nanobody. Agonist binding shows the receptor in equilibrium between two inactive states and a pre-active form, increasingly populated with higher ligand efficacy. Nanobody coupling leads to a fully active ternary receptor complex present in amounts correlating directly with agonist efficacy, consistent with partial agonism. While for different agonists the helix 6 environment in the active-state ternary complexes resides in a well-defined conformation, showing little conformational mobility, the environment of the highly conserved NPxxY motif on helix 7 remains dynamic adopting diverse, agonist-specific conformations, implying a further role of this region in receptor function. An inactive nanobody-coupled ternary receptor form is also observed.
A Silicon Photonics Computational Lensless Active-Flat-Optics Imaging System
Authors: White Alexander , Khial Parham , Salehi Fariborz , Hassibi Babak , Hajimiri Ali
Published: February 2020

The need for lightweight, miniature imaging systems is becoming increasingly prevalent in light of the development of wearable electronics, IoT devices, and drones. Computational imaging enables new types of imaging systems that replace standard optical components like lenses with cleverly designed computational processes. Traditionally, many of these types of systems use conventional complementary metal oxide semiconductor (CMOS) or charge coupled device (CCD) sensors for data collection. While this allows for rapid development of large-scale systems, the lack of system-sensor co-design limits the compactness and performance. Here we propose integrated photonics as a candidate platform for the implementation of such co-integrated systems. Using grating couplers and co-designed computational processing in lieu of a lens, we demonstrate the use of silicon photonics as a viable platform for computational imaging with a prototype lensless imaging device. The proof-of-concept device has 20 sensors and a 45-degree field of view, and its optics and sensors are contained within a 2,000 μm × 200 μm × 20 μm volume.
Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil
Authors: Schecklmann Martin , Schmaußer Maximilian , Klinger Felix , Kreuzer Peter M. , Krenkel Lars , Langguth Berthold
Published: February 2020

The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27%) in contrast to the DC coil (about 15%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil.
The in vitro inertial positions and viability of cells in suspension under different in vivo flow conditions
Authors: Connolly Sinead , McGourty Kieran , Newport David
Published: February 2020

The influence of Poiseuille flow on cell viability has applications in the areas of cancer metastasis, lab-on-a-chip devices and flow cytometry. Indeed, retaining cell viability is important in the emerging field of cell therapy as cells need to be returned to patients’ bodies. Despite this, it is unclear how this fundamental fluid regime affects cell viability. This study investigated the influence that varying flow rate, and the corresponding wall shear stress (τw) has on the viability and inertial positions of circulating cells in laminar pipe flow. The viability of two representative cell lines under different shear stresses in two different systems were investigated while particle streak imaging was used to determine their inertial positions. It was found that peristaltic pumps have a negative effect on cell viability in comparison to syringe pumps. Increasing shear stress in a cone and plate above 3 Pa caused an increase in cell death, however, τw as high as 10 Pa in circulation has little to no effect on cell viability. Inertial lift forces that move cells towards the centre of the channel protect them from experiencing detrimental levels of τw, indicating that τw in Poiseuille flow is not a good predictor of cell viability during advection.
Observation of a Correlation Between Internal friction and Urbach Energy in Amorphous Oxides Thin Films
Authors: Amato Alex , Terreni Silvana , Granata Massimo , Michel Christophe , Sassolas Benoit , Pinard Laurent , Canepa Maurizio , Cagnoli Gianpietro
Published: February 2020

We have investigated by spectroscopic ellipsometry (SE, 190–1700 nm) the optical properties of uniform, amorphous thin films of Ta2O5 and Nb2O5 as deposited and after annealing, and after so-called “doping” with Ti atoms which leads to mixed oxides. Ta2O5 and Ti:Ta2O5 are currently used as high-index components in Bragg reflectors for Gravitational Wave Detectors. Parallel to the optical investigation, we measured the mechanical energy dissipation of the same coatings, through the so-called “loss angle” ϕ = Q−1, which quantifies the energy loss in materials. By applying the well-known Cody-Lorentz model in the analysis of SE data we have been able to derive accurate information on the fundamental absorption edge through important parameters related to the electronic density of states, such as the optical gap (Eg) and the energy width of the exponential Urbach tail (the Urbach energy EU). We have found that EU is neatly reduced by suitable annealing as is also perceptible from direct inspection of SE data. Ti-doping also points to a minor decrease of EU. The reduction of EU parallels a lowering of the mechanical losses quantified by the loss angle ϕ. The correlation highlights that both the electronic states responsible of Urbach tail and the internal friction are sensitive to a self-correlation of defects on a medium-range scale, which is promoted by annealing and in our case, to a lesser extent, by doping. These observations may contribute to a better understanding of the relationship between structural and mechanical properties in amorphous oxides.
Improved Calcium Homeostasis and Force by Selenium Treatment and Training in Aged Mouse Skeletal Muscle
Authors: Fodor János , Al-Gaadi Dána , Czirják Tamás , Oláh Tamás , Dienes Beatrix , Csernoch László , Szentesi Péter
Published: February 2020

During aging reduction in muscle mass (sarcopenia) and decrease in physical activity lead to partial loss of muscle force and increased fatigability. Deficiency in the essential trace element selenium might augment these symptoms as it can cause muscle pain, fatigue, and proximal weakness. Average voluntary daily running, maximal twitch and tetanic force, and calcium release from the sarcoplasmic reticulum (SR) decreased while reactive oxygen species (ROS) production associated with tetanic contractions increased in aged – 22-month-old – as compared to young – 4-month-old – mice. These changes were accompanied by a decline in the ryanodine receptor type 1 (RyR1) and Selenoprotein N content and the increased amount of a degraded RyR1. Both lifelong training and selenium supplementation, but not the presence of an increased muscle mass at young age, were able to compensate for the reduction in muscle force and SR calcium release with age. Selenium supplementation was also able to significantly enhance the Selenoprotein N levels in aged mice. Our results describe, for the first time, the beneficial effects of selenium supplementation on calcium release from the SR and muscle force in old age while point out that increased muscle mass does not improve physical performance with aging.
The relationship between abdominal pain and emotional wellbeing in children and adolescents in the Raine Study
Authors: Ayonrinde Oyekoya T. , Ayonrinde Oyedeji A. , Adams Leon A. , Sanfilippo Frank M. , O’ Sullivan Therese A. , Robinson Monique , Oddy Wendy H. , Olynyk John K.
Published: February 2020

Abdominal pain is a common reason for medical visits. We examined the prevalence, gastrointestinal, and emotional significance of abdominal pain in a population-based cohort serially followed up from birth to 17 years. Children and adolescents from Generation 2 of the Raine Study participated in comprehensive cross-sectional assessments at ages 2, 5, 8, 10, 14 and 17 years. At 17 years, medical history, general health, gastrointestinal symptoms, medications, health practitioner attendance, and self-rated unhappiness were recorded. Longitudinal data regarding abdominal pain or unhappiness, from serial questionnaires, were analysed to identify factors associated with abdominal pain and adverse emotional health at age 17 years. Females experienced more abdominal pain than males at all ages (p < 0.05). Seventeen-year-old adolescents with abdominal pain reported a higher prevalence of depression, anxiety, being bullied at school, and poorer health status than those without abdominal pain (p < 0.05 for all). Abdominal pain and unhappiness during childhood and mid-adolescence were prospectively associated with recurrent abdominal pain, anxiety, depression and unhappiness during late adolescence (p < 0.05 for all). In conclusion, abdominal pain in children and adolescents associates with depression, anxiety, being bullied, unhappiness and reduced overall health-rating during adolescence. Awareness of these factors may guide management decisions.
Haploid induction via unpollinated ovule culture in Gerbera hybrida
Authors: Li Fan , Cheng Ying , Zhao Xiaokun , Yu Rongpei , Li Huimin , Wang Lihua , Li Shenchong , Shan Qinli
Published: February 2020

Ovule-derived haploid culture is an effective and important method for genetic study and plant breeding. Gerbera hybrida is a highly heterozygous species, and the lack of homozygous lines presents a challenge for molecular genetic research. Therefore, we performed haploid induction through unpollinated ovule culture and evaluated the effects of several important factors on this culturing procedure in G. hybrida, including genotype, low temperature, and the development seasons of the ovules. Among 45 G. hybrida cultivars analyzed, 29 cultivars exhibited adventitious bud induction via in vitro unpollinated ovule culture with significant different responses, indicating that the genotype of donor plants was a vital factor for inducibility. Four cultivars with significantly different induction rates, including one non-induced cultivar, were selected to analyze seasonal effects. Ovules extracted in the summer consistently had the highest induction rates, and even the non-induced cultivar included in the analysis could be induced at low levels when ovules from summer were used. Low temperature treatment could also promote adventitious bud induction, and in particular, a strong and significant effect was detected after 7 days of cold treatment. Ploidy level measurements by flow cytometry revealed that 288 ovule-derived regenerants were haploid (55.17%) and 218 lines were diploid (41.76%). Moreover, genetic stability analysis of the regenerants indicated 100% similarity to the marker profile of the mother plant. This is the first report of ovule-derived haploids in G. hybrida, which may facilitate the development of homozygous lines for molecular research and plant breeding.
Machine learning decodes chemical features to identify novel agonists of a moth odorant receptor
Authors: Caballero-Vidal Gabriela , Bouysset Cédric , Grunig Hubert , Fiorucci Sébastien , Montagné Nicolas , Golebiowski Jérôme , Jacquin-Joly Emmanuelle
Published: February 2020

Odorant receptors expressed at the peripheral olfactory organs are key proteins for animal volatile sensing. Although they determine the odor space of a given species, their functional characterization is a long process and remains limited. To date, machine learning virtual screening has been used to predict new ligands for such receptors in both mammals and insects, using chemical features of known ligands. In insects, such approach is yet limited to Diptera, whereas insect odorant receptors are known to be highly divergent between orders. Here, we extend this strategy to a Lepidoptera receptor, SlitOR25, involved in the recognition of attractive odorants in the crop pest Spodoptera littoralis larvae. Virtual screening of 3 million molecules predicted 32 purchasable ones whose function has been systematically tested on SlitOR25, revealing 11 novel agonists with a success rate of 28%. Our results show that Support Vector Machine optimizes the discovery of novel agonists and expands the chemical space of a Lepidoptera OR. More, it opens up structure-function relationship analyses through a comparison of the agonist chemical structures. This proof-of-concept in a crop pest could ultimately enable the identification of OR agonists or antagonists, capable of modifying olfactory behaviors in a context of biocontrol.
3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments
Authors: Brüningk Sarah C. , Rivens Ian , Box Carol , Oelfke Uwe , ter Haar Gail
Published: February 2020

For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that more closely resembles that of tumours in vivo and may thus be a superior in vitro cancer model than monolayer cultures. Here, the response of tumour spheroids formed from two established human cancer cell lines (HCT116 and CAL27) to single and combination treatments of radiation (0–20 Gy), and hyperthermia at 47 °C (0–780 CEM43) has been evaluated. Response was analysed in terms of spheroid growth, cell viability and the distribution of live/dead cells. Time-lapse imaging was used to evaluate mechanisms of cell death and cell detachment. It was found that sensitivity to heat in spheroids was significantly less than that seen in monolayer cultures. Spheroids showed different patterns of shrinkage and regrowth when exposed to heat or radiation: heated spheroids shed dead cells within four days of heating and displayed faster growth post-exposure than samples that received radiation or no treatment. Irradiated spheroids maintained a dense structure and exhibited a longer growth delay than spheroids receiving hyperthermia or combination treatment at (thermal) doses that yielded equivalent levels of clonogenic cell survival. We suggest that, unlike radiation, which kills dividing cells, hyperthermia-induced cell death affects cells independent of their proliferation status. This induces microenvironmental changes that promote spheroid growth. In conclusion, 3D tumour spheroid growth studies reveal differences in response to heat and/or radiation that were not apparent in 2D clonogenic assays but that may significantly influence treatment efficacy.
A novel selection strategy for antibody producing hybridoma cells based on a new transgenic fusion cell line
Authors: Listek Martin , Hönow Anja , Gossen Manfred , Hanack Katja
Published: February 2020

The use of monoclonal antibodies is ubiquitous in science and biomedicine but the generation and validation process of antibodies is nevertheless complicated and time-consuming. To address these issues we developed a novel selective technology based on an artificial cell surface construct by which secreted antibodies were connected to the corresponding hybridoma cell when they possess the desired antigen-specificity. Further the system enables the selection of desired isotypes and the screening for potential cross-reactivities in the same context. For the design of the construct we combined the transmembrane domain of the EGF-receptor with a hemagglutinin epitope and a biotin acceptor peptide and performed a transposon-mediated transfection of myeloma cell lines. The stably transfected myeloma cell line was used for the generation of hybridoma cells and an antigen- and isotype-specific screening method was established. The system has been validated for globular protein antigens as well as for haptens and enables a fast and early stage selection and validation of monoclonal antibodies in one step.
Effects of multiple injections on the efficacy and cytotoxicity of folate-targeted magnetite nanoparticles as theranostic agents for MRI detection and magnetic hyperthermia therapy of tumor cells
Authors: Soleymani Meysam , Khalighfard Solmaz , Khodayari Saeed , Khodayari Hamid , Kalhori Mohammad Reza , Hadjighassem Mahmoud Reza , Shaterabadi Zhila , Alizadeh Ali Mohammad
Published: February 2020

Folate-targeted iron oxide nanoparticles (FA@Fe3O4 NPs) were prepared by a one-pot hydrothermal method and then used as cancer theranostic agents by combining magnetic resonance imaging (MRI) and magnetic hyperthermia therapy (MHT). Crystal structure, morphology, magnetic properties, surface functional group, and heating efficacy of the synthesized nanoparticles were characterized by XRD, TEM, VSM, FTIR, and hyperthermia analyses. The results indicated that the crystal structure, magnetic properties, and heating efficacy of the magnetite nanoparticles were improved by hydrothermal treatment. Toxicity of the prepared NPs was assessed in vitro and in vivo on the mammary cells and BALB/c mice, respectively. The results of the in vitro toxicity analysis showed that the FA@Fe3O4 NPs are relatively safe even at high concentrations of the NPs up to 1000 µg mL−1. Also, the targetability of the FA@Fe3O4 NPs for the detection of folate over-expressed cancer cells was evaluated in an animal model of breast tumor using MRI analysis. It was observed that T2-weighted magnetic resonance signal intensity was decreased with the three-time injection of the FA@Fe3O4 NPs with 24 h interval at a safe dose (50 mg kg−1), indicating the accumulation and retention of the NPs within the tumor tissues. Moreover, the therapeutic efficacy of the MHT using the FA@Fe3O4 NPs was evaluated in vivo in breast tumor-bearing mice. Hyperthermia treatment was carried out under a safe alternating magnetic field permissible for magnetic hyperthermia treatment (f = 150 kHz, H = 12.5 mT). The therapeutic effects of the MHT were evaluated by monitoring the tumor volume during the treatment period. The results showed that the mice in the control group experienced an almost 3.5-fold increase in the tumor volume during 15 days, while, the mice in the MHT group had a mild increase in the tumor volume (1.8-fold) within the same period (P < 0.05). These outcomes give promise that FA@Fe3O4 NPs can be used as theranostic agents for the MRI and MHT applications.
Cell-mediated immune response and protective efficacy of porcine reproductive and respiratory syndrome virus modified-live vaccines against co-challenge with PRRSV-1 and PRRSV-2
Authors: Madapong Adthakorn , Saeng-chuto Kepalee , Boonsoongnern Alongkot , Tantituvanont Angkana , Nilubol Dachrit
Published: February 2020

Cell-mediated immunity (CMI), IL-10, and the protective efficacy of modified-live porcine reproductive and respiratory syndrome virus (PRRSV) vaccines (MLV) against co-challenge with PRRSV-1 and PRRSV-2 (HP-PRRSV) were investigated. Seventy, PRRSV-free, 3-week old, pigs were allocated into 7 groups. Six groups were intramuscularly vaccinated with MLV, including Porcilis (PRRSV-1 MLV, MSD Animal Health, The Netherlands), Amervac (PRRSV-1 MLV, Laboratorios Hipra, Spain), Fostera (PRRSV-2 MLV, Zoetis, USA), Ingelvac PRRS MLV and Ingelvac PRRS ATP (PRRSV-2, Boehringer Ingelheim, USA), and Prime Pac PRRS (PRRSV-2 MLV, MSD Animal Health, The Netherlands). Unvaccinated pigs were left as control. Lymphocyte proliferative response, IL-10 and IFN-γ production were determined. At 35 days post-vaccination (DPV), all pigs were inoculated intranasally with 2 ml of each PRRSV-1 (105.4 TCID50/ml) and PRRSV-2 (105.2 TCID50/ml, HP-PRRSV). Following challenge, sera were quantitatively assayed for PRRSV RNA. Pigs were necropsied at 7 days post-challenge. Viremia, macro- and microscopic lung lesion together with PRRSV antigen presence were evaluated in lung tissues. The results demonstrated that, regardless of vaccine genotype, CMI induced by all MLVs was relatively slow. Increased production of IL-10 in all vaccinated groups was observed at 7 and 14 DPV. Pigs in Amervac, Ingelvac MLV and Ingelvac ATP groups had significantly higher levels of IL-10 compared to Porcilis, Fostera and Prime Pac groups at 7 and 14 DPV. Following challenge, regardless to vaccine genotype, vaccinated pigs had significantly lower lung lesion scores and PRRSV antigens than those in the control group. Both PRRSV-1 and PRRSV-2 RNA were significantly reduced. Prime Pac pigs had lowest PRRSV-1 and PRRSV-2 RNA in serum, and micro- and macroscopic lung lesion scores (p < 0.05) compared to other vaccinated groups. In conclusion, PRRSV MLVs, regardless of vaccine genotype, can reduce viremia and lung lesions following co-challenge with PRRSV-1 and PRRSV-2 (HP-PRRSV). The main difference between PRRSV MLV is the production of IL-10 following vaccination.