bluuebunny/crossref_metadata_2025 huggingface dataset:
Oppositional Religious Speech: Understanding Hate Preaching
Authors: Edge Peter W
Published: August 2018

Hate preaching is capable of constituting both hate crime and hate speech, lies at the centre of many religions’ understanding of the manifestation of their religion, and frequently raises the contentious issue of regulation of the use of sacred scriptures. This brief article explores the regulation of hate preaching by criminal law, discussing the particular problems posed by oppositional religious speech, before concluding with suggestions for a number of ways to reduce these problems.
THE DANCE OF THE DYNAMICS: THE INTERPLAY OF TRADE AND GROWTH
Authors: Ji Lei , Seater John J.
Published: August 2018

We study the interaction between endogenous growth and Ricardian trade working solely through comparative advantage. The model is built on several facts about research and development and trade. Trade and growth affect each other in ways previously unexplored. The model can explain and reconcile in a single framework several phenomena usually analyzed separately. Because of a possible dynamic inefficiency, trade may raise or lower the growth rate of each trading partner. Trade leads to “effective technology transfer,” with the growth rate looking as if a country adopts its partner’s technology even though it does not. Economic growth can endogenously change the trading regime from incomplete to complete specialization (the Ricardian corner and interior, respectively), which can explain why trade helps some countries catch up but leaves others behind. Trade may raise or lower social welfare. The model specifies the conditions under which each possible outcome occurs. We examine a few of the model’s many testable implications and find them in agreement with the data.
Connection Between Root Zone Soil Moisture and Surface Energy Flux Partitioning Using Modeling, Observations, and Data Assimilation for a Temperate Grassland Site in Germany
Authors: Shrestha P. , Kurtz W. , Vogel G. , Schulz J.‐P. , Sulis M. , Hendricks Franssen H.‐J. , Kollet S. , Simmer C.
Published: August 2018

Land surface models (LSMs) with different degrees of complexity are in use as lower boundary conditions for atmospheric models with the simpler LSMs preferentially used in numerical weather forecasting. This study evaluates the second‐generation TERRA Multi‐Layer and the third‐generation Community Land Model (CLM) to better understand the connection between root zone soil moisture and surface energy fluxes, which is important for predictions. Both LSMs were compared in multiyear, observation‐driven simulations at the Falkenberg grassland site (Germany), and their results were compared to observations. With their default settings for the site, both LSMs tend to overestimate the Bowen ratio, while CLM additionally exhibited a wet bias and a too low soil moisture variance. With modified photosynthetic parameters in CLM, the Bowen ratio improved considerably, but the soil moisture bias and its too low variance remained. Joint data assimilation with soil parameter update significantly improved the soil moisture variance but degraded the Bowen ratio. We could identify the default shallow root fraction distribution to be responsible for the overestimated Bowen ratio, which could be largely reduced by increasing the root fractions in deeper layers. This study demonstrates how observations and data assimilation with joint state‐parameter updating can be used to improve the realism of third‐generation LSMs and thus our understanding of the connection between root zone soil moisture and surface energy flux partitioning.
The Instantaneous Retrieval of Precipitation Over Land by Temporal Variation at 19 GHz
Authors: You Yalei , Peters‐Lidard Christa , Wang Nai‐Yu , Turk Joseph , Ringerud Sarah , Yang Song , Ferraro Ralph
Published: August 2018

The primary signal used in all current passive microwave precipitation retrieval algorithms over land is the depression of the instantaneous brightness temperature (TB) caused by ice scattering. This study presents a new methodology to retrieve instantaneous precipitation rate over land by using TB temporal variation (ΔTB) at 19 GHz, which primarily reflects the surface emissivity variation due to the precipitation impact. As a proof‐of‐concept, we exploit observations from five polar‐orbiting satellites over the Southern Great Plains of the United States. Results show that ΔTB at 19 GHz correlate well with the instantaneous precipitation rate. Further analysis shows that ΔTB at 19 GHz is better correlated with the precipitation rate when multiple satellite observations are used due to the much shorter revisit time for a certain location. The retrieved instantaneous precipitation rate over Southern Great Plains from ΔTB at 19 GHz reasonably agrees with the surface radar observations, with the correlation, the root‐mean‐square error and the bias being 0.49, 2.39 mm/hr, and 6.54%, respectively. Future work seeks to combine the ice scattering signal at high frequencies and this surface emissivity variation signal at low frequencies to achieve an optimal retrieval performance.
Nonlinear Trends and Nonstationary Oscillations as Extracted From Annual Accumulated Precipitation at Mexico City
Authors: Martinez‐Lopez B. , Quintanar A. I. , Cabos‐Narvaez W. D. , Gay‐Garcia C. , Sein D. V.
Published: August 2018

Extracted nonstationary oscillations and nonlinear trends of precipitation and sea surface temperature (SST) data reveal that rainfall variability in Mexico City is mainly composed by a long‐term positive trend, a multidecadal oscillation highly correlated with the Atlantic Multidecadal Oscillation (AMO), and year‐to‐year variability. The precipitation trend, lasting for more than a century, cannot be attributed to global warming or urbanization alone; rather, it can be thought of as part of a natural oscillation composed of alternating wet‐dry anomalies with a period of a couple of centuries, as past evidence indicates. To further test the dependence of the AMO‐related component, yearly SST time series were derived from a simplified model of the atmosphere‐ocean system forced by white noise. The simulated SST time series exhibits AMO‐like variability entirely consistent with the observed one, implying that North Atlantic SST multidecadal variability can be seen as the integrated response of surface ocean layers to external stochastic atmospheric forcing.
Projected Centennial Oxygen Trends and Their Attribution to Distinct Ocean Climate Forcings
Authors: Takano Yohei , Ito Takamitsu , Deutsch Curtis
Published: August 2018

We explore centennial changes in tropical Pacific oxygen (O2) using numerical models to illustrate the dominant patterns and mechanisms under centennial climate change. Future projections from state‐of‐the‐art Earth System Models exhibit significant model to model differences, but decreased solubility and weakened ventilation together deplete thermocline O2 in middle to high latitudes. In contrast, the tropical thermocline O2 undergoes much smaller changes or even a slight increase. A suite of sensitivity experiments using a coarse resolution ocean circulation and biogeochemistry model show that ocean warming is the leading cause of global deoxygenation in the thermocline across all latitudes with secondary contributions from changes in hydrological cycles and wind stress modulating regional changes in O2. The small O2 changes in the tropical Pacific thermocline reflect near‐complete compensation between the solubility decrease due to warming and reduction in apparent oxygen utilization (AOU). We further quantified the changes in AOU due to contributions from changes in water mass age and biological remineralization from the sensitivity experiments. The two effects almost equally contribute to the reduction of AOU in the tropical Pacific thermocline (43% for physical circulations and 57% for biology). Our results suggest that better understanding of water mass changes in the tropical oceans is key to improving projections and reducing the uncertainties of future O2 changes.
Imaging the Eastern Trans‐Mexican Volcanic Belt With Ambient Seismic Noise: Evidence for a Slab Tear
Authors: Castellanos Jorge C. , Clayton Robert W. , Pérez‐Campos Xyoli
Published: August 2018

The eastern sector of the Trans‐Mexican Volcanic Belt (TMVB) is an enigmatic narrow zone that lies just above where the Cocos plate displays a sharp transition in dipping angle in central Mexico. Current plate models indicate that the transition from flat to steeper subduction is continuous through this region, but the abrupt end of the TMVB suggests that the difference in subduction styles is more likely to be accommodated by a slab tear. Based on a high‐resolution shear wave velocity and radial anisotropy model of the region, we argue that a slab tear within South Cocos can explain the abrupt end of the TMVB. We also quantify the azimuthal anisotropy beneath each seismic station and present a well‐defined flow pattern that shows how mantle material is being displaced from beneath the slab to the mantle wedge through the tear in the subducted Cocos plate. We suggest that the toroidal mantle flow formed around the slab edges is responsible for the existence of the volcanic gap in central Mexico. Moreover, we propose that the temperature increase caused by the influx of hot, less dense mantle material flowing through the tear to the Veracruz area may have significant implications for the thermomechanical state of the subducted slab and explain why the intermediate‐depth seismicity ends suddenly at the southern boundary of the Veracruz basin. The composite mantle flow formed by the movement of mantle material through the slab tears in western and southern Mexico may be allowing the Cocos plate to roll back in segments.
Atlantic Water Transformation Along Its Poleward Pathway Across the Nordic Seas
Authors: Bosse Anthony , Fer Ilker , Søiland Henrik , Rossby Thomas
Published: August 2018

The warm and salty Atlantic Water is substantially modified along its poleward transit across the Nordic Seas, where it reaches deeper isopycnals. In particular, the Lofoten Basin, exposed to intense air‐sea interactions, plays a crucial role in the transformation of Atlantic Water. Averaged over a seasonal cycle, Atlantic Water releases approximately 80 W/m2 of heat to the atmosphere over a large area, leading to winter mixed layer depths of up to 500 m (locally exceeding 1,000 m in the Lofoten Basin Eddy, a permanent vortex located in the basin center) and substantial water mass transformation. We investigate spiciness injection (temperature and salinity increase) by winter mixing, by performing an isopycnal analysis using a comprehensive observational data set covering the 2000–2017 period. Compared to the Atlantic Water properties at the Svinøy section, representative of the inflowing Atlantic Water, some isopycnals reveal an important warming (up to 1.5°C) and salinification (up to 0.2 g/kg). Key areas for spiciness injection are the western Lofoten Basin and west of Bear Island. The modified spicy Atlantic Waters coincide with low potential vorticity with strongly density‐compensated layers at their base, allowing double‐diffusion processes to occur farther downstream toward the Arctic. Despite its limited spatial extent, the Lofoten Basin Eddy exhibits the greatest spiciness injection, as well as the deepest mixed layer and thickest low potential vorticity layer of the Norwegian Seas. The Atlantic Water spiciness at Svinøy shows a downstream correlation in the Lofoten Basin and farther north toward the Arctic with a lag of 1 to 1.5 years.
Mass and Fine‐Scale Morphological Changes Induced by Changing Seawater pH in the Coccolith Gephyrocapsa oceanica
Authors: Hermoso Michaël , Minoletti Fabrice
Published: August 2018

Coccolithophores have been extensively studied to understand the environmental control on calcification in a key biological group influencing the alkalinity of seawater. Previous studies have established that bulk calcification scales with cell division rates under a wide range of pH conditions. Yet the fine‐scale ultrastructural changes of the coccoliths and therefore the pH‐sensitive underlying mechanisms altering biomineralization of the coccoliths remain largely underconstrained. Using circularly polarized light and high‐resolution microscopy, we have generated mass estimates of cultured Gephyrocapsa oceanica coccoliths grown in media with pH values ranging from 7.4 to 9.0. These mass estimates representing a bulk calcification response were related to the morphological changes within the coccoliths. From optimal (pH 8.6) down to pH 7.4 conditions, we have observed that impaired cell growth and lower calcite quota are accompanied by a 35% decrease in mean coccolith mass. The data further show that seawater acidification does not homogenously affect calcification of the coccoliths, as a clear decrease of the breadth of the tube (a structure surrounding the central area of the coccoliths) was detected, whereas all other ultrastructural components were far less impacted. We discuss this specific sensitivity to acidification as the possible consequence of the altered interaction of the acidic polysaccharides used for biomineralization and ambient concentration of protons released by calcification that substantially modify the growth patterns, the morphology, and ultimately the mass of the coccoliths.
Metamorphic Zonation by Out‐of‐Sequence Thrusting at Back‐Stepping Subduction Zones: Sequential Accretion of the Caledonian Internides, Central Sweden
Authors: Bender H. , Ring U. , Almqvist B. S. G. , Grasemann B. , Stephens M. B.
Published: August 2018

Exhumation of the high‐grade metamorphic Seve Nappe Complex and its emplacement between lower‐grade nappes has been related to wedge extrusion in the central Scandinavian Caledonides. To test this hypothesis, the kinematic evolution of the Caledonian nappe pile is studied by systematic structural mapping in central and northern Jämtland, Sweden. Structural data, combined with petrological and quartz microstructure observations, document pervasive top‐to‐the‐ESE, foreland‐directed shearing under progressively decreasing metamorphic grade across the entire nappe pile. Mylonitic foliation, foliation‐parallel boudinage, and abundant top‐to‐the‐ESE and rare, scattered top‐to‐the‐WNW shear‐sense indicators imply foreland‐directed general shear. This deformation regime caused exhumation by concurrent thrusting and vertical ductile thinning. We propose a specific succession of in‐ and out‐of‐sequence thrusts that generated the metamorphic zonation. Our model envisions in‐sequence propagation of thrusts during exhumation of the Seve Nappe Complex, related to subduction of Baltica beneath a volcanic arc within Iapetus. Concurrently, Iapetus subducted beneath Laurentia farther to the west. When Iapetus was closed, Baltica subduction stepped westward and continued beneath Laurentia. The back stepping of subduction at the onset of continental collision caused out‐of‐sequence propagation of the orogenic wedge. Thrusting cut downsection across the existing tectonostratigraphy, emplacing units of lower metamorphic grade above the high‐grade Seve Nappe Complex. This imbrication generated the present metamorphic zonation of the Caledonian nappe pile during sustained convergence between Laurentia and Baltica.
Design rules for a tunable merged-tip microneedle
Authors: Lim Jungeun , Tahk Dongha , Yu James , Min Dal-Hee , Jeon Noo Li
Published: August 2018

This publication proposes the use of an elasto-capillarity-driven self-assembly for fabricating a microscale merged-tip structure out of a variety of biocompatible UV-curable polymers for use as a microneedle platform. In addition, the novel merged-tip microstructure constitutes a new class of microneedles, which incorporates the convergence of biocompatible polymer micropillars, leading to the formation of a sharp tip and an open cavity capable of both liquid trapping and volume control. When combined with biocompatible photopolymer micropillar arrays fabricated with photolithography, elasto-capillarity-driven self-assembly provides a means for producing a complex microneedle-like structure without the use of micromolding or micromachining. This publication also explores and defines the design rules by which several fabrication aspects, such as micropillar dimensions, shapes, pattern array configurations, and materials, can be manipulated to produce a customizable microneedle array with controllable cavity volumes, fracture points, and merge profiles. In addition, the incorporation of a modular through-hole micropore membrane base was also investigated as a method for constitutive payload delivery and fluid-sampling functionalities. The flexibility and fabrication simplicity of the merged-tip microneedle platform holds promise in transdermal drug delivery applications.
MYC dephosphorylation by the PP1/PNUTS phosphatase complex regulates chromatin binding and protein stability
Authors: Dingar Dharmendra , Tu William B. , Resetca Diana , Lourenco Corey , Tamachi Aaliya , De Melo Jason , Houlahan Kathleen E. , Kalkat Manpreet , Chan Pak-Kei , Boutros Paul C. , Raught Brian , Penn Linda Z.
Published: August 2018

The c-MYC (MYC) oncoprotein is deregulated in over 50% of cancers, yet regulatory mechanisms controlling MYC remain unclear. To this end, we interrogated the MYC interactome using BioID mass spectrometry (MS) and identified PP1 (protein phosphatase 1) and its regulatory subunit PNUTS (protein phosphatase-1 nuclear-targeting subunit) as MYC interactors. We demonstrate that endogenous MYC and PNUTS interact across multiple cell types and that they co-occupy MYC target gene promoters. Inhibiting PP1 by RNAi or pharmacological inhibition results in MYC hyperphosphorylation at multiple serine and threonine residues, leading to a decrease in MYC protein levels due to proteasomal degradation through the canonical SCFFBXW7 pathway. MYC hyperphosphorylation can be rescued specifically with exogenous PP1, but not other phosphatases. Hyperphosphorylated MYC retained interaction with its transcriptional partner MAX, but binding to chromatin is significantly compromised. Our work demonstrates that PP1/PNUTS stabilizes chromatin-bound MYC in proliferating cells.
Oxidising agents in sub-arc mantle melts link slab devolatilisation and arc magmas
Authors: Bénard Antoine , Klimm Kevin , Woodland Alan B. , Arculus Richard J. , Wilke Max , Botcharnikov Roman E. , Shimizu Nobumichi , Nebel Oliver , Rivard Camille , Ionov Dmitri A.
Published: August 2018

Subduction zone magmas are more oxidised on eruption than those at mid-ocean ridges. This is attributed either to oxidising components, derived from subducted lithosphere (slab) and added to the mantle wedge, or to oxidation processes occurring during magma ascent via differentiation. Here we provide direct evidence for contributions of oxidising slab agents to melts trapped in the sub-arc mantle. Measurements of sulfur (S) valence state in sub-arc mantle peridotites identify sulfate, both as crystalline anhydrite (CaSO4) and dissolved SO42− in spinel-hosted glass (formerly melt) inclusions. Copper-rich sulfide precipitates in the inclusions and increased Fe3+/∑Fe in spinel record a S6+–Fe2+ redox coupling during melt percolation through the sub-arc mantle. Sulfate-rich glass inclusions exhibit high U/Th, Pb/Ce, Sr/Nd and δ34S (+ 7 to + 11‰), indicating the involvement of dehydration products of serpentinised slab rocks in their parental melt sources. These observations provide a link between liberated slab components and oxidised arc magmas.
Intrinsic neuronal dynamics predict distinct functional roles during working memory
Authors: Wasmuht D. F. , Spaak E. , Buschman T. J. , Miller E. K. , Stokes M. G.
Published: August 2018

Working memory (WM) is characterized by the ability to maintain stable representations over time; however, neural activity associated with WM maintenance can be highly dynamic. We explore whether complex population coding dynamics during WM relate to the intrinsic temporal properties of single neurons in lateral prefrontal cortex (lPFC), the frontal eye fields (FEF), and lateral intraparietal cortex (LIP) of two monkeys (Macaca mulatta). We find that cells with short timescales carry memory information relatively early during memory encoding in lPFC; whereas long-timescale cells play a greater role later during processing, dominating coding in the delay period. We also observe a link between functional connectivity at rest and the intrinsic timescale in FEF and LIP. Our results indicate that individual differences in the temporal processing capacity predict complex neuronal dynamics during WM, ranging from rapid dynamic encoding of stimuli to slower, but stable, maintenance of mnemonic information.
Argininosuccinic aciduria fosters neuronal nitrosative stress reversed by Asl gene transfer
Authors: Baruteau Julien , Perocheau Dany P. , Hanley Joanna , Lorvellec Maëlle , Rocha-Ferreira Eridan , Karda Rajvinder , Ng Joanne , Suff Natalie , Diaz Juan Antinao , Rahim Ahad A. , Hughes Michael P. , Banushi Blerida , Prunty Helen , Hristova Mariya , Ridout Deborah A. , Virasami Alex , Heales Simon , Howe Stewen J. , Buckley Suzanne M. K. , Mills Philippa B. , Gissen Paul , Waddington Simon N.
Published: August 2018

Argininosuccinate lyase (ASL) belongs to the hepatic urea cycle detoxifying ammonia, and the citrulline-nitric oxide (NO) cycle producing NO. ASL-deficient patients present argininosuccinic aciduria characterised by hyperammonaemia, multiorgan disease and neurocognitive impairment despite treatment aiming to normalise ammonaemia without considering NO imbalance. Here we show that cerebral disease in argininosuccinic aciduria involves neuronal oxidative/nitrosative stress independent of hyperammonaemia. Intravenous injection of AAV8 vector into adult or neonatal ASL-deficient mice demonstrates long-term correction of the hepatic urea cycle and the cerebral citrulline-NO cycle, respectively. Cerebral disease persists if ammonaemia only is normalised but is dramatically reduced after correction of both ammonaemia and neuronal ASL activity. This correlates with behavioural improvement and reduced cortical cell death. Thus, neuronal oxidative/nitrosative stress is a distinct pathophysiological mechanism from hyperammonaemia. Disease amelioration by simultaneous brain and liver gene transfer with one vector, to treat both metabolic pathways, provides new hope for hepatocerebral metabolic diseases.
A general deoxygenation approach for synthesis of ketones from aromatic carboxylic acids and alkenes
Authors: Zhang Muliang , Xie Jin , Zhu Chengjian
Published: August 2018

The construction of an aryl ketone structural unit by means of catalytic carbon–carbon coupling reactions represents the state-of-the-art in organic chemistry. Herein we achieved the direct deoxygenative ketone synthesis in aqueous solution from readily available aromatic carboxylic acids and alkenes, affording structurally diverse ketones in moderate to good yields. Visible-light photoredox catalysis enables the direct deoxygenation of acids as acyl sources with triphenylphosphine and represents a distinct perspective on activation. The synthetic robustness is supported by the late-stage modification of several pharmaceutical compounds and complex molecules. This ketone synthetic strategy is further applied to the synthesis of the drug zolpidem in three steps with 50% total yield and a concise construction of cyclophane-braced 18–20 membered macrocycloketones. It represents not only the advancement for the streamlined synthesis of aromatic ketones from feedstock chemicals, but also a photoredox radical activation mode beyond the redox potential of carboxylic acids.
System immunology-based identification of blood transcriptional modules correlating to antibody responses in sheep
Authors: Braun Roman Othmar , Brunner Livia , Wyler Kurt , Auray Gaël , García-Nicolás Obdulio , Python Sylvie , Zumkehr Beatrice , Gaschen Véronique , Stoffel Michael Hubert , Collin Nicolas , Barnier-Quer Christophe , Bruggmann Rémy , Summerfield Artur
Published: August 2018

Lacking immunogenicity, inactivated vaccines require potent adjuvants. To understand their effects, we used a system immunology-based analysis of ovine blood transcriptional modules (BTMs) to dissect innate immune responses relating to either antibody or haptoglobin levels. Using inactivated foot-and-mouth disease virus as an antigen, we compared non-adjuvanted to liposomal-formulated vaccines complemented or not with TLR4 and TLR7 ligands. Early after vaccination, BTM relating to myeloid cells, innate immune responses, dendritic cells, and antigen presentation correlated positively, whereas BTM relating to T and natural killer cells, as well as cell cycle correlated negatively with antibody responses. Interestingly, BTM relating to myeloid cells, inflammation and antigen presentation also correlated with haptoglobin, but in a reversed manner, indicating that acute systemic inflammation is not beneficial for early antibody responses. Analysis of vaccine-dependent BTM modulation showed that liposomal formulations induced similar responses to those correlating to antibody levels, while addition of TLR ligands reduced myeloid cells, inflammation and antigen presentation BTM expression despite promoting antibody responses. Furthermore, this vaccine was more potent at downregulating T and natural killer cell BTM. When pre-vaccination BTM were analyzed, we found that high vaccine responders expressed higher levels of cell cycle and myeloid cell BTMs as compared with low responders. In conclusion, we have transferred human BTM to sheep and identified early vaccine-induced responses associated with antibody levels or unwanted inflammation. Such readouts are applicable to other veterinary species and very useful to identify efficient vaccine adjuvants, their mechanism of action, and factors related to low responders.
OsPIN1b is Involved in Rice Seminal Root Elongation by Regulating Root Apical Meristem Activity in Response to Low Nitrogen and Phosphate
Authors: Sun Huwei , Tao Jinyuan , Bi Yang , Hou Mengmeng , Lou Jiajing , Chen Xinni , Zhang Xuhong , Luo Le , Xie Xiaonan , Yoneyama Koichi , Zhao Quanzhi , Xu Guohua , Zhang Yali
Published: August 2018

The response of plant root development to nutrient deficiencies is critical for crop production. Auxin, nitric oxide (NO), and strigolactones (SLs) are important regulators of root growth under low-nitrogen and -phosphate (LN and LP) conditions. Polar auxin transport in plants, which is mainly dependent on auxin efflux protein PINs, creates local auxin maxima to form the basis for root initiation and elongation; however, the PIN genes that play an important role in LN- and LP-modulated root growth remain unclear. qRT-PCR analysis of OsPIN family genes showed that the expression of OsPIN1b is most abundant in root tip and is significantly downregulated by LN, LP, sodium nitroprusside (SNP, NO donor), and GR24 (analogue of SLs) treatments. Seminal roots in ospin1b mutants were shorter than those of the wild type; and the seminal root, [3H]IAA transport, and IAA concentration responses to LN, LP, SNP, and GR24 application were attenuated in ospin1b-1 mutants. pCYCB1;1::GUS expression was upregulated by LN, LP, SNP, and GR24 treatments in wild type, but not in the ospin1b-1 mutant, suggesting that OsPIN1b is involved in auxin transport and acts as a downstream mediator of NO and SLs to induce meristem activity in root tip in rice under LN and LP.
Domestic horses (Equus caballus) discriminate between negative and positive human nonverbal vocalisations
Authors: Smith Amy Victoria , Proops Leanne , Grounds Kate , Wathan Jennifer , Scott Sophie K , McComb Karen
Published: August 2018

The ability to discriminate between emotion in vocal signals is highly adaptive in social species. It may also be adaptive for domestic species to distinguish such signals in humans. Here we present a playback study investigating whether horses spontaneously respond in a functionally relevant way towards positive and negative emotion in human nonverbal vocalisations. We presented horses with positively- and negatively-valenced human vocalisations (laughter and growling, respectively) in the absence of all other emotional cues. Horses were found to adopt a freeze posture for significantly longer immediately after hearing negative versus positive human vocalisations, suggesting that negative voices promote vigilance behaviours and may therefore be perceived as more threatening. In support of this interpretation, horses held their ears forwards for longer and performed fewer ear movements in response to negative voices, which further suggest increased vigilance. In addition, horses showed a right-ear/left-hemisphere bias when attending to positive compared with negative voices, suggesting that horses perceive laughter as more positive than growling. These findings raise interesting questions about the potential for universal discrimination of vocal affect and the role of lifetime learning versus other factors in interspecific communication.
Ras-dva small GTPases lost during evolution of amniotes regulate regeneration in anamniotes
Authors: Ivanova Anastasiya S. , Korotkova Daria D. , Ermakova Galina V. , Martynova Natalia Yu. , Zaraisky Andrey G. , Tereshina Maria B.
Published: August 2018

In contrast to amniotes (reptiles, birds and mammals), anamniotes (fishes and amphibians) can effectively regenerate body appendages such as fins, limbs and tails. Why such a useful capability was progressively lost in amniotes remains unknown. As we have hypothesized recently, one of the reasons for this could be loss of some genes regulating the regeneration in evolution of amniotes. Here, we demonstrate the validity of this hypothesis by showing that genes of small GTPases Ras-dva1 and Ras-dva2, that had been lost in a stepwise manner during evolution of amniotes and disappeared completely in placental mammals, are important for regeneration in anamniotes. Both Ras-dva genes are quickly activated in regenerative wound epithelium and blastema forming in the amputated adult Danio rerio fins and Xenopus laevis tadpoles’ tails and hindlimb buds. Down-regulation of any of two Ras-dva genes in fish and frog resulted in a retardation of regeneration accompanied by down-regulation of the regeneration marker genes. On the other hand, Ras-dva over-expression in tadpoles’ tails restores regeneration capacity during the refractory period when regeneration is blocked due to natural reasons. Thus our data on Ras-dva genes, which were eliminated in amniotes but play role in anamniotes regeneration regulation, satisfy our hypothesis.
Reconciling material cultures in archaeology with genetic data: The nomenclature of clusters emerging from archaeogenomic analysis
Authors: Eisenmann Stefanie , Bánffy Eszter , van Dommelen Peter , Hofmann Kerstin P. , Maran Joseph , Lazaridis Iosif , Mittnik Alissa , McCormick Michael , Krause Johannes , Reich David , Stockhammer Philipp W.
Published: August 2018

Genome-wide ancient DNA analysis of skeletons retrieved from archaeological excavations has provided a powerful new tool for the investigation of past populations and migrations. An important objective for the coming years is to properly integrate ancient genomics into archaeological research. This article aims to contribute to developing a better understanding and cooperation between the two disciplines and beyond. It focuses on the question of how best to name clusters encountered when analysing the genetic makeup of past human populations. Recent studies have frequently borrowed archaeological cultural designations to name these genetic groups, while neglecting the historically problematic nature of the concept of cultures in archaeology. After reviewing current practices in naming genetic clusters, we introduce three possible nomenclature systems (‘numeric system’, ‘mixed system (a)’, ‘geographic-temporal system’) along with their advantages and challenges.
Development of a Novel 3D Tumor-tissue Invasion Model for High-throughput, High-content Phenotypic Drug Screening
Authors: Puls T. J. , Tan Xiaohong , Husain Mahera , Whittington Catherine F. , Fishel Melissa L. , Voytik-Harbin Sherry L.
Published: August 2018

While much progress has been made in the war on cancer, highly invasive cancers such as pancreatic cancer remain difficult to treat and anti-cancer clinical trial success rates remain low. One shortcoming of the drug development process that underlies these problems is the lack of predictive, pathophysiologically relevant preclinical models of invasive tumor phenotypes. While present-day 3D spheroid invasion models more accurately recreate tumor invasion than traditional 2D models, their shortcomings include poor reproducibility and inability to interface with automated, high-throughput systems. To address this gap, a novel 3D tumor-tissue invasion model which supports rapid, reproducible setup and user-definition of tumor and surrounding tissue compartments was developed. High-cell density tumor compartments were created using a custom-designed fabrication system and standardized oligomeric type I collagen to define and modulate ECM physical properties. Pancreatic cancer cell lines used within this model showed expected differential invasive phenotypes. Low-passage, patient-derived pancreatic cancer cells and cancer-associated fibroblasts were used to increase model pathophysiologic relevance, yielding fibroblast-mediated tumor invasion and matrix alignment. Additionally, a proof-of-concept multiplex drug screening assay was applied to highlight this model’s ability to interface with automated imaging systems and showcase its potential as a predictive tool for high-throughput, high-content drug screening.
Septins are critical regulators of osteoclastic bone resorption
Authors: Møller Anaïs M. J. , Füchtbauer Ernst-Martin , Brüel Annemarie , Andersen Thomas L. , Borggaard Xenia G. , Pavlos Nathan J. , Thomsen Jesper S. , Pedersen Finn S. , Delaisse Jean-Marie , Søe Kent
Published: August 2018

Septins are known to play key roles in supporting cytoskeletal stability, vesicular transport, endo-/exocytosis, stabilizing cellular membranes and forming diffusion barriers. Their function in mammalian cells is poorly investigated. The osteoclast offers an interesting tool to investigate septins because all cellular activities septins were reported to be involved in are critical for osteoclasts. However, the existence of septins in osteoclasts has not even been reported. Here we show that theSEPT9gene and Septin 9 (SEPT9) protein are expressed and synthesized during differentiation of human osteoclasts. Pharmacological stabilization of septin filaments dose dependently inhibits bone resorption of human osteoclastsin vitrosuggesting a role for septins in bone resorption. Attesting to this, conditional deletion ofSept9in mice leads to elevated levels of trabecular bone and diminished femoral growthin vivo. Finally, systematic interrogation of the spatial organization of SEPT9 by confocal microscopy reveals that SEPT9 is closely associated to the structures known to be critical for osteoclast activity. We propose that septins in general and SEPT9 in particular play a previously unappreciated role in osteoclastic bone resorption.
Ovary abortion is prevalent in diverse maize inbred lines and is under genetic control
Authors: Gustin Jeffery L. , Boehlein Susan K. , Shaw Janine R. , Junior Weschester , Settles A. Mark , Webster Ashley , Tracy William F. , Hannah L. Curtis
Published: August 2018

Crop improvement programs focus on characteristics that are important for plant productivity. Typically genes underlying these traits are identified and stacked to create improved cultivars. Hence, identification of valuable traits for plant productivity is critical for plant improvement. Here we describe an important characteristic for maize productivity. Despite the fact mature maize ears are typically covered with kernels, we find that only a fraction of ovaries give rise to mature kernels. Non-developed ovaries degenerate while neighboring fertilized ovaries produce kernels that fill the ear. Abortion occurs throughout the ear, not just at the tip. We show that the fraction of aborted ovaries/kernels is genetically controlled and varies widely among maize lines, and low abortion genotypes are rare. Reducing or eliminating ovary abortion could substantially increase yield, making this characteristic a new target for selection in maize improvement programs.
Corticosterone levels reflect variation in metabolic rate, independent of ‘stress’
Authors: Jimeno Blanca , Hau Michaela , Verhulst Simon
Published: August 2018

Variation in glucocorticoid hormones (GCs) is often interpreted as reflecting ‘stress’, but this interpretation is subject of intense debate. GCs induce gluconeogenesis, and we hypothesized therefore that GC variation can be explained by changes in current and anticipated metabolic rate (MR). Alternatively, GC levels may respond to psychological ‘stress’ over and above its effect on metabolic rate. We tested these hypotheses in captive zebra finches, by inducing an increase in MR using a psychological stressor (noise), and compared its effect on corticosterone (CORT, the primary avian GC) with the effect induced by a decrease in ambient temperature increasing MR to a similar extent. We found the increase in CORT induced by the psychological stressor to be indistinguishable from the level expected based on the noise effect on MR. We further found that a handling and restraint stressor that increased CORT levels also resulted in increased blood glucose levels, corroborating a key assumption underlying our hypothesis. Thus, GC variation primarily reflected variation in energy expenditure, independently of psychological stress. GC levels have many downstream effects besides glucose mobilization, and we propose that these effects can be interpreted as adjustments of physiological functions to the metabolic level at which an organism operates.
Low-energy band structure and even-odd layer number effect in AB-stacked multilayer graphene
Authors: Yagi Ryuta , Hirahara Taiki , Ebisuoka Ryoya , Nakasuga Tomoaki , Tajima Shingo , Watanabe Kenji , Taniguchi Takashi
Published: August 2018

How atoms acquire three-dimensional bulk character is one of the fundamental questions in materials science. Before addressing this question, how atomic layers become a bulk crystal might give a hint to the answer. While atomically thin films have been studied in a limited range of materials, a recent discovery showing how to mechanically exfoliate bulk crystals has opened up the field to study the atomic layers of various materials. Here, we show systematic variation in the band structure of high mobility graphene with one to seven layers by measuring the quantum oscillation of magnetoresistance. The Landau fan diagram showed distinct structures that reflected differences in the band structure, as if they were finger prints of multilayer graphene. In particular, an even-odd layer number effect was clearly observed, with the number of bands increasing by one for every two layers and a Dirac cone observed only for an odd number of layers. The electronic structure is significantly influenced by the potential energy arising from carrier screening associated with a gate electric field.
High prevalence of ventricular repolarization abnormalities in people carrying TGFβR2 mutations
Authors: Extramiana F. , Milleron O. , Elbitar S. , Uccellini A. , Langeois M. , Spentchian M. , Delorme G. , Arnoult F. , Denjoy I. , Bouleti C. , Fressart V. , Iserin F. , Maison-Blanche P. , Abifadel M. , Leenhardt A. , Boileau C. , Jondeau G.
Published: August 2018

Mutations in the TGFβR2 gene have been associated with a life threatening risk of aortic dissection but no arrhythmic death has been previously reported. Two young females carrying a TGFβR2 mutation, initially diagnosed as Marfan syndrome or Loeys Dietz syndrome, presented sudden death with autopsy ruling out dissection. The ECGs of the 2 Sudden Cardiac Deaths revealed profound ventricular repolarization abnormalities with a sinusoidal T-U morphology associated with normal left ventricular ejection fraction. These data strongly suggest sudden cardiac arrhythmic deaths and prompted us to systematically study the repolarization pattern in the patients with TGFβR2 mutations. ECG findings from 58 mutation carriers patients (TGFβR2 group) were compared with those of 46 non-affected first degree relatives (control group). TGFβR2 mutation was associated with ventricular repolarization abnormalities in 47% of patients (p < 0.001 vs. controls), including a 19.6 ms (95%CI 8.7; 30.5) QTc interval prolongation compared to the non-affected first degree relatives (p < 0.001), higher prevalence of abnormal U waves (16% vs. 2%), and sinusoidal T-U morphology (10% vs. 0%). TGFβR2 mutations can be associated with abnormal ventricular repolarization pattern, longer QT interval than non-carrier relatives and an increased risk for sudden death.
Nanospectroscopy Captures Nanoscale Compositional Zonation in Barite Solid Solutions
Authors: Ling Florence T. , Hunter Heather A. , Fitts Jeffrey P. , Peters Catherine A. , Acerbo Alvin S. , Huang Xiaojing , Yan Hanfei , Nazaretski Evgeny , Chu Yong S.
Published: August 2018

Scientists have long suspected that compositionally zoned particles can form under far-from equilibrium precipitation conditions, but their inferences have been based on bulk solid and solution measurements. We are the first to directly observe nanoscale trace element compositional zonation in <10 µm-sized particles using X-ray fluorescence nanospectroscopy at the Hard X-ray Nanoprobe (HXN) Beamline at National Synchrotron Light Source II (NSLS-II). Through high-resolution images, compositional zonation was observed in barite (BaSO4) particles precipitated from aqueous solution, in which Sr2+ cations as well as HAsO42− anions were co-precipitated into (Ba,Sr)SO4 or Ba(SO4,HAsO4) solid solutions. Under high salinity conditions (NaCl ≥ 1.0 M), bands contained ~3.5 to ~5 times more trace element compared to the center of the particle formed in early stages of particle growth. Quantitative analysis of Sr and As fractional substitution allowed us to determine that different crystallographic growth directions incorporated trace elements to different extents. These findings provide supporting evidence that barite solid solutions have great potential for trace element incorporation; this has significant implications for environmental and engineered systems that remove hazardous substances from water.
Gut microbiota mediates the anti-obesity effect of calorie restriction in mice
Authors: Wang Shuo , Huang Meiqin , You Xue , Zhao Jingyu , Chen Lanlan , Wang Lin , Luo Yangjun , Chen Yan
Published: August 2018

Calorie restriction (CR) extends lifespan and elicits numerous effects beneficial to health and metabolism in various model organisms, but the underlying mechanisms are not completely understood. Gut microbiota has been reported to be associated with the beneficial effects of CR; however, it is unknown whether these effects of CR are causally mediated by gut microbiota. In this study, we employed an antibiotic-induced microbiota-depleted mouse model to investigate the functional role of gut microbiota in CR. Depletion of gut microbiota rendered mice resistant to CR-induced loss of body weight, accompanied by the increase in fat mass, the reduction in lean mass and the decline in metabolic rate. Depletion of gut microbiota led to increases in fasting blood glucose and cholesterol levels independent of CR. A few metabolism-modulating hormones including leptin and insulin were altered by CR and/or gut microbiota depletion. In addition, CR altered the composition of gut microbiota with significant increases in major probiotic genera such as Lactobacillus and Bifidobacterium, together with the decrease of Helicobacter. In addition, we performed fecal microbiota transplantation in mice fed with high-fat diet. Mice with transferred microbiota from calorie-restricted mice resisted high fat diet-induced obesity and exhibited metabolic improvement such as alleviated hepatic lipid accumulation. Collectively, these data indicate that CR-induced metabolic improvement especially in body weight reduction is mediated by intestinal microbiota to a certain extent.
Schlafen2 mutation in mice causes an osteopetrotic phenotype due to a decrease in the number of osteoclast progenitors
Authors: Omar Ibrahim , Guterman-Ram Gali , Rahat Dolev , Tabach Yuval , Berger Michael , Levaot Noam
Published: August 2018

Osteoclasts are the bone resorbing cells that derive from myeloid progenitor cells. Although there have been recent advancements in the ability to identify osteoclast progenitors, very little is known about the molecular mechanisms governing their homeostasis. Here, by analyzing the normalized phylogenetic profiles of the Schlafen (Slfn) gene family, we found that it co-evolved with osteoclast-related genes. Following these findings, we used a Slfn2 loss-of-function mutant mouse, elektra, to study the direct role of Slfn2 in osteoclast development and function. Slfn2eka/eka mice exhibited a profound increase in their cancellous bone mass and a significant reduction in osteoclast numbers. In addition, monocyte cultures from the bone marrow of Slfn2eka/eka mice showed a reduction in osteoclast number and total resorption area. Finally, we show that the bone marrow of Slfn2eka/eka mice have significantly less CD11b–Ly6Chi osteoclast precursors. Overall, our data suggest that Slfn2 is required for normal osteoclast differentiation and that loss of its function in mice results in an osteopetrotic phenotype.
Comprehensive Investigation on Controlling for CT Imaging Variabilities in Radiomics Studies
Authors: Ger Rachel B. , Zhou Shouhao , Chi Pai-Chun Melinda , Lee Hannah J. , Layman Rick R. , Jones A. Kyle , Goff David L. , Fuller Clifton D. , Howell Rebecca M. , Li Heng , Stafford R. Jason , Court Laurence E. , Mackin Dennis S.
Published: August 2018

Radiomics has shown promise in improving models for predicting patient outcomes. However, to maximize the information gain of the radiomics features, especially in larger patient cohorts, the variability in radiomics features owing to differences between scanners and scanning protocols must be accounted for. To this aim, the imaging variability of radiomics feature values was evaluated on 100 computed tomography scanners at 35 clinics by imaging a radiomics phantom using a controlled protocol and the commonly used chest and head protocols of the local clinic. We used a linear mixed-effects model to determine the degree to which the manufacturer and individual scanners contribute to the overall variability. Using a controlled protocol reduced the overall variability by 57% and 52% compared to the local chest and head protocols respectively. The controlled protocol also reduced the relative contribution of the manufacturer to the total variability. For almost all variabilities (manufacturer, scanner, and residual with different preprocesssing), the controlled protocol scans had a significantly smaller variability than the local protocol scans did. For most radiomics features, the imaging variability was small relative to the inter-patient feature variability in non–small cell lung cancer and head and neck squamous cell carcinoma patient cohorts. From this study, we conclude that using controlled scans can reduce the variability in radiomics features, and our results demonstrate the importance of using controlled protocols in prospective radiomics studies.
Primary tumor and pre-metastatic niches co-targeting “peptides-lego” hybrid hydroxyapatite nanoparticles for metastatic breast cancer treatment
Authors: Xiong Hui , Du Shi , Zhang Ping , Jiang Zhijie , Zhou Jianping , Yao Jing
Published: August 2018

Hybrid hydroxyapatite nanoparticles orchestrating tumor metastasis resisting therapy (TMRT) and tumor metastasis targeting therapy (TMTT).
Fast and reliable generation of [18F]triflyl fluoride, a gaseous [18F]fluoride source
Authors: Pees A. , Sewing C. , Vosjan M. J. W. D. , Tadino V. , Herscheid J. D. M. , Windhorst A. D. , Vugts D. J.
Published: August 2018

Reactive [18F]fluoride was generated from gaseous [18F]triflyl fluoride and used for a wide range of radiofluorination reactions.