bluuebunny/crossref_metadata_2025 huggingface dataset:
Women and leasehold in rural Flanders, c. 1290 to c. 1570
Authors: Vervaet Lies
Published: March 2019

Research has emphasised the stability in female landholding between the thirteenth and seventeenth centuries, despite demographic shocks and fundamental economic changes. However, in this period, a new type of land exploitation emerges: leasehold. This article wants to introduce a gender perspective into the history of leasehold. It investigates women’s activities on the lease market in late medieval and sixteenth-century Flanders, a region where short-term and competitive leasehold spread early and widely. An analysis of the actual practice, making use of landlords’ manuals and accounts, demonstrates women’s decreasing participation at the lease market. Moreover, their marital status increasingly mattered: from the beginning of the fifteenth century only widows could hold land. This article also demonstrates that, next to marital status, the size of the holding had a marked influence on women’s opportunities. Finally, these results invite us to rethink the grounds of women’s growing participation at the labour market in post-Black Death Europe, since especially single women lost access to land, particularly to land offered on the lease market.
EU–Fatty Alcohols (Indonesia): Corporate Structure, Transfer Pricing, and Dumping
Authors: HAKOBYAN SHUSHANIK , TRACHTMAN JOEL P.
Published: March 2019

The EU–Fatty Alcohols decision of the Appellate Body addressed an important issue of the scope of permissible adjustments under Article 2.4 of the Agreement on Interpretation of Article VI of the GATT 1994, focusing on the ‘mark-up’ paid by an Indonesian exporter to a related company as a difference affecting price comparability between the export price and the normal value. The Appellate Body confirmed that the primary focus of the investigating authority's assessment is on whether the relationship between related companies can be demonstrated to be a factor that impacts the prices of the relevant transactions. This case raises the question of whether a harmonized approach to transfer pricing across different regulatory areas would be useful to bring greater consistency of treatment and certainty to international transactions.
THE “MORAL BASIS” OF RECONSTRUCTION? HUMANITARIANISM, INTELLECTUAL RELIEF AND THE LEAGUE OF NATIONS, 1918–1925
Authors: IRISH TOMÁS
Published: March 2019

This article analyses the post-First World War emergence of intellectual relief. This is defined here as aid given to intellectuals and scholarly institutions. Relief included the provision of food and medicines to individuals as well as the supply of relevant scholarly literature and laboratory equipment to academic institutions. After 1918, significant humanitarian interventions targeted Central and Eastern Europe, which had been ravaged by war and its myriad consequences. The article argues that intellectual relief, while frequently using the language of the “crisis of civilization,” was part of the broader effort to safeguard the postwar liberal democratic order against Bolshevism. The article pays particular attention to the League of Nations' Committee on Intellectual Cooperation (CIC) to show how states like Hungary used intellectual deprivation to agitate for treaty revision. It argues that the CIC's development was shaped by the wider dynamics of intellectual relief.
POLARRIS: A POLArimetric Radar Retrieval and Instrument Simulator
Authors: Matsui Toshi , Dolan Brenda , Rutledge Steven A. , Tao Wei‐Kuo , Iguchi Takamichi , Barnum Julie , Lang Stephen E.
Published: March 2019

This paper introduces a synthetic polarimetric radar simulator and retrieval package, POLArimetric Radar Retrieval and Instrument Simulator (POLARRIS), for evaluating cloud‐resolving models (CRMs). POLARRIS is composed of forward (POLARRIS‐f) and inverse (retrieval and diagnostic) components (iPOLARRIS) to generate not only polarimetric radar observables (Zh, Zdr, Kdp, ρhv) but also radar‐consistent geophysical parameters such as hydrometeor identification, vertical velocity, and rainfall rates retrieved from CRM data. To demonstrate its application and uncertainties, POLARRIS is applied to simulations of a mesoscale convective system over the Southern Great Plains on 23 May 2011, using the Weather Research and Forecasting model with both spectral bin microphysics (SBM) and the Goddard single‐moment bulk 4ICE microphysics. Statistical composites reveal a significant dependence of simulated polarimetric observables (Zdr, Kdp) on the assumptions of the particle axis ratio (oblateness) and orientation angle distributions. The simulated polarimetric variables differ considerably between the SBM and 4ICE microphysics in part due to the differences in their ice particle size distributions as revealed by comparisons with aircraft measurements. Regardless of these uncertainties, simulated hydrometeor identification distributions overestimate graupel and hail fractions, especially from the simulation with SBM. To minimize uncertainties in forward model, the particle shape and orientation angle distributions of frozen particles should be predicted in a microphysics scheme in addition to the size distributions and particle densities.
Midlatitude Oceanic Cloud and Precipitation Properties as Sampled by the ARM Eastern North Atlantic Observatory
Authors: Giangrande Scott E. , Wang Die , Bartholomew Mary Jane , Jensen Michael P. , Mechem David B. , Hardin Joseph C. , Wood Robert
Published: March 2019

Marine low clouds are critical to the climate system because of their extensive coverage and associated controls on boundary layer dynamics and radiative energy balance. The primary foci for this study are marine low cloud observations over a heavily instrumented site on the Azores archipelago in the Eastern North Atlantic and their associated raindrop size distribution (DSD) properties, relative low cloud contributions to the precipitation, and additional sampling (instrument, environmental) considerations. The contribution from low clouds (e.g., cloud top < 4 km) to the overall precipitation over midlatitude oceans is poorly understood, in part because of the lack of coupled, high‐quality measurements of precipitation and low cloud properties. Cloud regime and precipitation breakdowns performed for a multiyear (2014–2017) record emphasize diurnal precipitation and raindrop size distribution characteristics for both low and deeper clouds, as well as differences between the two disdrometer types used. Results demonstrate that marine low clouds over this Eastern North Atlantic location account for a significant (45%) contribution to the total rainfall and exhibit a diurnal cycle in cloud (thickness, top, and base) and precipitation characteristics similar to satellite records. Additional controls on observed surface rainfall characteristics of low clouds allowed by the extended ground‐based facility data sets are also explored. From those analyses, it is suggested that the synoptic state exerts a significant control on low cloud and surface precipitation properties.
Spatially Variable Increase in Rock Uplift in the Northern U.S. Cordillera Recorded in the Distribution of River Knickpoints and Incision Depths
Authors: Mitchell Nate A. , Yanites Brian J.
Published: March 2019

Landscape evolution is driven by factors like tectonics and climate, and unraveling such factors can reveal the history recorded in landscape morphology. The northern U.S. Cordillera features many potential drivers, such as the Yellowstone plume, the extrusion of a large igneous province, and the drainage of large lakes. Among this complex geologic history, the drivers of transient incision in the Clearwater and Salmon watersheds of central Idaho are not well understood. To constrain the pattern of regional incision, we analyze the morphologies of 80 individual tributaries underlain by single lithologies. From north to south across our study area, knickpoint elevations increase from about 800 to 2,200 m, and incision depths increase from about 300 to 1,200 m. We use both numerical and analytical models to demonstrate that such a gradient could represent spatial variations in rock uplift. These findings suggest that transience is driven by a spatially variable increase in rock uplift that has disrupted a low‐relief paleolandscape, and the high steepness values of main drainages suggest that high rock‐uplift rates are still maintained to the present. Changes in rock uplift may be related to interactions between the Yellowstone plume and the lithosphere, although base level fall from the drainage of the Lake Idaho down the proto‐Snake River may be superimposed over these patterns in rock uplift. We show that careful, quantitative analyses of river profiles in geologically complex regions can differentiate between the influences of rock uplift and far‐field base level changes.
Leveraging Environmental Research and Observation Networks to Advance Soil Carbon Science
Authors: Weintraub Samantha R. , Flores Alejandro N. , Wieder William R. , Sihi Debjani , Cagnarini Claudia , Gonçalves Daniel Ruiz Potma , Young Michael H. , Li Li , Olshansky Yaniv , Baatz Roland , Sullivan Pamela L. , Groffman Peter M.
Published: March 2019

Soil organic matter (SOM) is a critical ecosystem variable regulated by interacting physical, chemical, and biological processes. Collaborative efforts to integrate perspectives, data, and models from interdisciplinary research and observation networks can significantly advance predictive understanding of SOM. We outline how integrating three networks—the Long‐Term Ecological Research with a focus on ecological dynamics, the Critical Zone Observatories with strengths in landscape/geologic context, and the National Ecological Observatory Network with standardized multiscale measurements—can advance SOM knowledge. This integration requires improved data dissemination and sharing, coordinated data collection activities, and enhanced collaboration between empiricists and modelers within and across networks.
The Renaissance of Hydrology
Authors: Gabrielle Vincent
Published: March 2019

Hydrology has evolved as a transdisciplinary, data-driven science in a remarkably short period of time.
Primary tumor-induced immunity eradicates disseminated tumor cells in syngeneic mouse model
Authors: Piranlioglu Raziye , Lee EunMi , Ouzounova Maria , Bollag Roni J. , Vinyard Alicia H. , Arbab Ali S. , Marasco Daniela , Guzel Mustafa , Cowell John K. , Thangaraju Muthushamy , Chadli Ahmed , Hassan Khaled A. , Wicha Max S. , Celis Esteban , Korkaya Hasan
Published: March 2019

Although clinically apparent metastasis is associated with late stages of cancer development, micro-metastatic dissemination may be an early event. However, the fate of these early disseminated tumor cells (DTC) remains elusive. We show that despite their capacity to disseminate into secondary organs, 4T1 tumor models develop overt metastasis while EMT6-tumor bearing mice clear DTCs shed from primary tumors as well as those introduced by intravenous (IV) injection. Following the surgical resection of primary EMT6 tumors, mice do not develop detectable metastasis and reject IV-injected tumor cells. In contrast, these cells readily grow and metastasize in immuno-deficient athymic or Rag2−/− mice, an effect mimicked by CD8+ T-cell depletion in immunocompetent mice. Furthermore, recombinant G-CSF or adoptive transfer of granulocytic-MDSCs isolated from 4T1 tumor-bearing mice, induce metastasis by suppressing CD8+ T-cells in EMT6-primed mice. Our studies support the concept of immune surveillance providing molecular insights into the immune mechanisms during tumor progression.
Side-group chemical gating via reversible optical and electric control in a single molecule transistor
Authors: Meng Linan , Xin Na , Hu Chen , Wang Jinying , Gui Bo , Shi Junjie , Wang Cheng , Shen Cheng , Zhang Guangyu , Guo Hong , Meng Sheng , Guo Xuefeng
Published: March 2019

By taking advantage of large changes in geometric and electronic structure during the reversible trans–cis isomerisation, azobenzene derivatives have been widely studied for potential applications in information processing and digital storage devices. Here we report an unusual discovery of unambiguous conductance switching upon light and electric field-induced isomerisation of azobenzene in a robust single-molecule electronic device for the first time. Both experimental and theoretical data consistently demonstrate that the azobenzene sidegroup serves as a viable chemical gate controlled by electric field, which efficiently modulates the energy difference of trans and cis forms as well as the energy barrier of isomerisation. In conjunction with photoinduced switching at low biases, these results afford a chemically-gateable, fully-reversible, two-mode, single-molecule transistor, offering a fresh perspective for creating future multifunctional single-molecule optoelectronic devices in a practical way.
Exploring the colloid-to-polymer transition for ultra-low crosslinked microgels from three to two dimensions
Authors: Scotti A. , Bochenek S. , Brugnoni M. , Fernandez-Rodriguez M. A. , Schulte M. F. , Houston J. E. , Gelissen A. P. H. , Potemkin I. I. , Isa L. , Richtering W.
Published: March 2019

Microgels are solvent-swollen nano- and microparticles that show prevalent colloidal-like behavior despite their polymeric nature. Here we study ultra-low crosslinked poly(N-isopropylacrylamide) microgels (ULC), which can behave like colloids or flexible polymers depending on dimensionality, compression or other external stimuli. Small-angle neutron scattering shows that the structure of the ULC microgels in bulk aqueous solution is characterized by a density profile that decays smoothly from the center to a fuzzy surface. Their phase behavior and rheological properties are those of soft colloids. However, when these microgels are confined at an oil-water interface, their behavior resembles that of flexible macromolecules. Once monolayers of ultra-low crosslinked microgels are compressed, deposited on solid substrate and studied with atomic-force microscopy, a concentration-dependent topography is observed. Depending on the compression, these microgels can behave as flexible polymers, covering the substrate with a uniform film, or as colloidal microgels leading to a monolayer of particles.
Over-exploitation of natural resources is followed by inevitable declines in economic growth and discount rate
Authors: Lampert Adam
Published: March 2019

A major challenge in environmental policymaking is determining whether and how fast our society should adopt sustainable management methods. These decisions may have long-lasting effects on the environment, and therefore, they depend critically on the discount factor, which determines the relative values given to future environmental goods compared to present ones. The discount factor has been a major focus of debate in recent decades, and nevertheless, the potential effect of the environment and its management on the discount factor has been largely ignored. Here we show that to maximize social welfare, policymakers need to consider discount factors that depend on changes in natural resource harvest at the global scale. Particularly, the more our society over-harvests today, the more policymakers should discount the near future, but the less they should discount the far future. This results in a novel discount formula that implies significantly higher values for future environmental goods.
Targeting bivalency de-represses Indian Hedgehog and inhibits self-renewal of colorectal cancer-initiating cells
Authors: Lima-Fernandes Evelyne , Murison Alex , da Silva Medina Tiago , Wang Yadong , Ma Anqi , Leung Cherry , Luciani Genna M. , Haynes Jennifer , Pollett Aaron , Zeller Constanze , Duan Shili , Kreso Antonija , Barsyte-Lovejoy Dalia , Wouters Bradly G. , Jin Jian , Carvalho Daniel D. De , Lupien Mathieu , Arrowsmith Cheryl H. , O’Brien Catherine A.
Published: March 2019

In embryonic stem cells, promoters of key lineage-specific differentiation genes are found in a bivalent state, having both activating H3K4me3 and repressive H3K27me3 histone marks, making them poised for transcription upon loss of H3K27me3. Whether cancer-initiating cells (C-ICs) have similar epigenetic mechanisms that prevent lineage commitment is unknown. Here we show that colorectal C-ICs (CC-ICs) are maintained in a stem-like state through a bivalent epigenetic mechanism. Disruption of the bivalent state through inhibition of the H3K27 methyltransferase EZH2, resulted in decreased self-renewal of patient-derived C-ICs. Epigenomic analyses revealed that the promoter of Indian Hedgehog (IHH), a canonical driver of normal colonocyte differentiation, exists in a bivalent chromatin state. Inhibition of EZH2 resulted in de-repression of IHH, decreased self-renewal, and increased sensitivity to chemotherapy in vivo. Our results reveal an epigenetic block to differentiation in CC-ICs and demonstrate the potential for epigenetic differentiation therapy of a solid tumour through EZH2 inhibition.
Scale law of complex deformation transitions of nanotwins in stainless steel
Authors: Chen A. Y. , Zhu L. L. , Sun L. G. , Liu J. B. , Wang H. T. , Wang X. Y. , Yang J. H. , Lu J.
Published: March 2019

Understanding the deformation behavior of metallic materials containing nanotwins (NTs), which can enhance both strength and ductility, is useful for tailoring microstructures at the micro- and nano- scale to enhance mechanical properties. Here, we construct a clear deformation pattern of NTs in austenitic stainless steel by combining in situ tensile tests with a dislocation-based theoretical model and molecular dynamics simulations. Deformation NTs are observed in situ using a transmission electron microscope in different sample regions containing NTs with twin-lamella-spacing (λ) varying from a few nanometers to hundreds of nanometers. Two deformation transitions are found experimentally: from coactivated twinning/detwinning (λ < 5 nm) to secondary twinning (5 nm < λ < 129 nm), and then to the dislocation glide (λ > 129 nm). The simulation results are highly consistent with the observed strong λ-effect, and reveal the intrinsic transition mechanisms induced by partial dislocation slip.
Automatic mapping of atoms across both simple and complex chemical reactions
Authors: Jaworski Wojciech , Szymkuć Sara , Mikulak-Klucznik Barbara , Piecuch Krzysztof , Klucznik Tomasz , Kaźmierowski Michał , Rydzewski Jan , Gambin Anna , Grzybowski Bartosz A.
Published: March 2019

Mapping atoms across chemical reactions is important for substructure searches, automatic extraction of reaction rules, identification of metabolic pathways, and more. Unfortunately, the existing mapping algorithms can deal adequately only with relatively simple reactions but not those in which expert chemists would benefit from computer’s help. Here we report how a combination of algorithmics and expert chemical knowledge significantly improves the performance of atom mapping, allowing the machine to deal with even the most mechanistically complex chemical and biochemical transformations. The key feature of our approach is the use of few but judiciously chosen reaction templates that are used to generate plausible “intermediate” atom assignments which then guide a graph-theoretical algorithm towards the chemically correct isomorphic mappings. The algorithm performs significantly better than the available state-of-the-art reaction mappers, suggesting its uses in database curation, mechanism assignments, and – above all – machine extraction of reaction rules underlying modern synthesis-planning programs.
Assembly of complex viruses exemplified by a halophilic euryarchaeal virus
Authors: De Colibus Luigi , Roine Elina , Walter Thomas S. , Ilca Serban L. , Wang Xiangxi , Wang Nan , Roseman Alan M. , Bamford Dennis , Huiskonen Juha T. , Stuart David I.
Published: March 2019

Many of the largest known viruses belong to the PRD1-adeno structural lineage characterised by conserved pseudo-hexameric capsomers composed of three copies of a single major capsid protein (MCP). Here, by high-resolution cryo-EM analysis, we show that a class of archaeal viruses possess hetero-hexameric MCPs which mimic the PRD1-adeno lineage trimer. These hetero-hexamers are built from heterodimers and utilise a jigsaw-puzzle system of pegs and holes, and underlying minor capsid proteins, to assemble the capsid laterally from the 5-fold vertices. At these vertices proteins engage inwards with the internal membrane vesicle whilst 2-fold symmetric horn-like structures protrude outwards. The horns are assembled from repeated globular domains attached to a central spine, presumably facilitating multimeric attachment to the cell receptor. Such viruses may represent precursors of the main PRD1-adeno lineage, similarly engaging cell-receptors via 5-fold spikes and using minor proteins to define particle size.
Quantifying the triboelectric series
Authors: Zou Haiyang , Zhang Ying , Guo Litong , Wang Peihong , He Xu , Dai Guozhang , Zheng Haiwu , Chen Chaoyu , Wang Aurelia Chi , Xu Cheng , Wang Zhong Lin
Published: March 2019

Triboelectrification is a well-known phenomenon that commonly occurs in nature and in our lives at any time and any place. Although each and every material exhibits triboelectrification, its quantification has not been standardized. A triboelectric series has been qualitatively ranked with regards to triboelectric polarization. Here, we introduce a universal standard method to quantify the triboelectric series for a wide range of polymers, establishing quantitative triboelectrification as a fundamental materials property. By measuring the tested materials with a liquid metal in an environment under well-defined conditions, the proposed method standardizes the experimental set up for uniformly quantifying the surface triboelectrification of general materials. The normalized triboelectric charge density is derived to reveal the intrinsic character of polymers for gaining or losing electrons. This quantitative triboelectric series may serve as a textbook standard for implementing the application of triboelectrification for energy harvesting and self-powered sensing.
Prominence of the tropics in the recent rise of global nitrogen pollution
Authors: Lee Minjin , Shevliakova Elena , Stock Charles A. , Malyshev Sergey , Milly P. C. D.
Published: March 2019

Nitrogen (N) pollution is shaped by multiple processes, the combined effects of which remain uncertain, particularly in the tropics. We use a global land biosphere model to analyze historical terrestrial-freshwater N budgets, considering the effects of anthropogenic N inputs, atmospheric CO2, land use, and climate. We estimate that globally, land currently sequesters 11 (10–13)% of annual N inputs. Some river basins, however, sequester >50% of their N inputs, buffering coastal waters against eutrophication and society against greenhouse gas-induced warming. Other basins, releasing >25% more than they receive, are mostly located in the tropics, where recent deforestation, agricultural intensification, and/or exports of land N storage can create large N pollution sources. The tropics produce 56 ± 6% of global land N pollution despite covering only 34% of global land area and receiving far lower amounts of fertilizers than the extratropics. Tropical land use should thus be thoroughly considered in managing global N pollution.
Uncertainty in ensembles of global biodiversity scenarios
Authors: Thuiller Wilfried , Guéguen Maya , Renaud Julien , Karger Dirk N. , Zimmermann Niklaus E.
Published: March 2019

While there is a clear demand for scenarios that provide alternative states in biodiversity with respect to future emissions, a thorough analysis and communication of the associated uncertainties is still missing. Here, we modelled the global distribution of ~11,500 amphibian, bird and mammal species and project their climatic suitability into the time horizon 2050 and 2070, while varying the input data used. By this, we explore the uncertainties originating from selecting species distribution models (SDMs), dispersal strategies, global circulation models (GCMs), and representative concentration pathways (RCPs). We demonstrate the overwhelming influence of SDMs and RCPs on future biodiversity projections, followed by dispersal strategies and GCMs. The relative importance of each component varies in space but also with the selected sensitivity metrics and with species’ range size. Overall, this means using multiple SDMs, RCPs, dispersal assumptions and GCMs is a necessity in any biodiversity scenario assessment, to explicitly report associated uncertainties.
Publisher Correction: Accurate autocorrelation modeling substantially improves fMRI reliability
Authors: Olszowy Wiktor , Aston John , Rua Catarina , Williams Guy B.
Published: March 2019

The original HTML version of this Article had an incorrect Published online date of 25 December 2019; it should have been 21 March 2019. This has been corrected in the HTML version of the Article. The PDF version was correct from the time of publication.
Automated estimation of materials parameter from X-ray absorption and electron energy-loss spectra with similarity measures
Authors: Suzuki Yuta , Hino Hideitsu , Kotsugi Masato , Ono Kanta
Published: March 2019

Materials informatics has significantly accelerated the discovery and analysis of materials in the past decade. One of the key contributors to accelerated materials discovery is the use of on-the-fly data analysis with high-throughput experiments, which has given rise to the need for accelerated and accurate automated estimation of the properties of materials. In this regard, spectroscopic data are widely used for materials discovery because these data include essential information about materials. An important requirement for the realisation of the automated estimation of materials parameters is the selection of a similarity measure, or kernel function. The required measure should be robust in terms of peak shifting, peak broadening, and noise. However, the determination of appropriate similarity measures for spectra and the automated estimation of materials parameters from these spectra currently remain unresolved. We examined major similarity measures to evaluate the similarity of both X-ray absorption and electron energy-loss spectra. The similarity measures show good correspondence with the materials parameter, that is, the crystal-field parameter, in all measures. The Pearson's correlation coefficient was the highest for the robustness against noise and peak broadening. We obtained the regression model for the crystal-field parameter 10 Dq from the similarity of the spectra. The regression model enabled the materials parameter, that is, 10 Dq, to be automatically estimated from the spectra. With regard to research progress in similarity measures, this methodology would make it possible to extract the materials parameter from a large-scale dataset of experimental data.
An artificial neuron implemented on an actual quantum processor
Authors: Tacchino Francesco , Macchiavello Chiara , Gerace Dario , Bajoni Daniele
Published: March 2019

Artificial neural networks are the heart of machine learning algorithms and artificial intelligence. Historically, the simplest implementation of an artificial neuron traces back to the classical Rosenblatt’s “perceptron”, but its long term practical applications may be hindered by the fast scaling up of computational complexity, especially relevant for the training of multilayered perceptron networks. Here we introduce a quantum information-based algorithm implementing the quantum computer version of a binary-valued perceptron, which shows exponential advantage in storage resources over alternative realizations. We experimentally test a few qubits version of this model on an actual small-scale quantum processor, which gives answers consistent with the expected results. We show that this quantum model of a perceptron can be trained in a hybrid quantum-classical scheme employing a modified version of the perceptron update rule and used as an elementary nonlinear classifier of simple patterns, as a first step towards practical quantum neural networks efficiently implemented on near-term quantum processing hardware.
A coupled microscopy approach to assess the nano-landscape of weathering
Authors: Lybrand Rebecca A. , Austin Jason C. , Fedenko Jennifer , Gallery Rachel E. , Rooney Erin , Schroeder Paul A. , Zaharescu Dragos G. , Qafoku Odeta
Published: March 2019

Mineral weathering is a balanced interplay among physical, chemical, and biological processes. Fundamental knowledge gaps exist in characterizing the biogeochemical mechanisms that transform microbe-mineral interfaces at submicron scales, particularly in complex field systems. Our objective was to develop methods targeting the nanoscale by using high-resolution microscopy to assess biological and geochemical drivers of weathering in natural settings. Basalt, granite, and quartz (53–250 µm) were deployed in surface soils (10 cm) of three ecosystems (semiarid, subhumid, humid) for one year. We successfully developed a reference grid method to analyze individual grains using: (1) helium ion microscopy to capture micron to sub-nanometer imagery of mineral-organic interactions; and (2) scanning electron microscopy to quantify elemental distribution on the same surfaces via element mapping and point analyses. We detected locations of biomechanical weathering, secondary mineral precipitation, biofilm formation, and grain coatings across the three contrasting climates. To our knowledge, this is the first time these coupled microscopy techniques were applied in the earth and ecosystem sciences to assess microbe-mineral interfaces and in situ biological contributors to incipient weathering.
Pretreatment and gaseous radiocarbon dating of 40–100 mg archaeological bone
Authors: Fewlass H. , Tuna T. , Fagault Y. , Hublin J.-J. , Kromer B. , Bard E. , Talamo S.
Published: March 2019

Radiocarbon dating archaeological bone typically requires 300–1000 mg material using standard protocols. We report the results of reducing sample size at both the pretreatment and 14C measurement stages for eight archaeological bones spanning the radiocarbon timescale at different levels of preservation. We adapted our standard collagen extraction protocol specifically for <100 mg bone material. Collagen was extracted at least twice (from 37–100 mg material) from each bone. Collagen aliquots containing <100 μg carbon were measured in replicate using the gas ion source of the AixMICADAS. The effect of sample size reduction in the EA-GIS-AMS system was explored by measuring 14C of collagen containing either ca. 30 μg carbon or ca. 90 μg carbon. The gas dates were compared to standard-sized graphite dates extracted from large amounts (500–700 mg) of bone material pretreated with our standard protocol. The results reported here demonstrate that we are able to reproduce accurate radiocarbon dates from <100 mg archaeological bone material back to 40,000 BP.
Regional variation in life history traits and plastic responses to temperature of the major malaria vector Nyssorhynchus darlingi in Brazil
Authors: Chu V. M. , Sallum M. A. M. , Moore T. E. , Lainhart W. , Schlichting C. D. , Conn J. E.
Published: March 2019

The primary Brazilian malaria vector, Nyssorhynchus darlingi (formerly Anopheles darlingi), ranges from 0°S–23°S across three biomes (Amazonia, Cerrado, Mata Atlântica). Rising temperatures will increase mosquito developmental rates, and models predict future malaria transmission by Ny. darlingi in Brazil will shift southward. We reared F1Ny. darlingi (progeny of field-collected females from 4 state populations across Brazil) at three temperatures (20, 24, 28 °C) and measured key life-history traits. Our results reveal geographic variation due to both genetic differences among localities and plastic responses to temperature differences. Temperature significantly altered all traits: faster larval development, shorter adult life and overall lifespan, and smaller body sizes were seen at 28 °C versus 20 °C. Low-latitude Amazonia mosquitoes had the fastest larval development at all temperatures, but at 28 °C, average development rate of high-latitude Mata Atlântica mosquitoes was accelerated and equivalent to low-latitude Amazonia. Body size of adult mosquitoes from the Mata Atlântica remained larger at all temperatures. We detected genetic variation in the plastic responses among mosquitoes from different localities, with implications for malaria transmission under climate change. Faster development combined with larger body size, without a tradeoff in adult longevity, suggests vectorial capacities of some Mata Atlântica populations may significantly increase under warming climates.
The same domain of Su(Hw) is required for enhancer blocking and direct promoter repression
Authors: Melnikova Larisa , Elizar’ev Pavel , Erokhin Maksim , Molodina Varvara , Chetverina Darya , Kostyuchenko Margarita , Georgiev Pavel , Golovnin Anton
Published: March 2019

Suppressor of Hairy-wing [Su(Hw)] is a DNA-binding architectural protein that participates in the organization of insulators and repression of promoters in Drosophila. This protein contains acidic regions at both ends and a central cluster of 12 zinc finger domains, some of which are involved in the specific recognition of the binding site. One of the well-described in vivo function of Su(Hw) is the repression of transcription of neuronal genes in oocytes. Here, we have found that the same Su(Hw) C-terminal region (aa 720–892) is required for insulation as well as for promoter repression. The best characterized partners of Su(Hw), CP190 and Mod(mdg4)-67.2, are not involved in the repression of neuronal genes. Taken together, these results suggest that an unknown protein or protein complex binds to the C-terminal region of Su(Hw) and is responsible for the direct repression activity of Su(Hw).
Proximal and distal control for ligand binding in neuroglobin: role of the CD loop and evidence for His64 gating
Authors: Exertier Cécile , Milazzo Lisa , Freda Ida , Montemiglio Linda Celeste , Scaglione Antonella , Cerutti Gabriele , Parisi Giacomo , Anselmi Massimiliano , Smulevich Giulietta , Savino Carmelinda , Vallone Beatrice
Published: March 2019

Neuroglobin (Ngb) is predominantly expressed in neurons of the central and peripheral nervous systems and it clearly seems to be involved in neuroprotection. Engineering Ngb to observe structural and dynamic alterations associated with perturbation in ligand binding might reveal important structural determinants, and could shed light on key features related to its mechanism of action. Our results highlight the relevance of the CD loop and of Phe106 as distal and proximal controls involved in ligand binding in murine neuroglobin. We observed the effects of individual and combined mutations of the CD loop and Phe106 that conferred to Ngb higher CO binding velocities, which we correlate with the following structural observations: the mutant F106A shows, upon CO binding, a reduced heme sliding hindrance, with the heme present in a peculiar double conformation, whereas in the CD loop mutant “Gly-loop”, the original network of interactions between the loop and the heme was abolished, enhancing binding via facilitated gating out of the distal His64. Finally, the double mutant, combining both mutations, showed a synergistic effect on CO binding rates. Resonance Raman spectroscopy and MD simulations support our findings on structural dynamics and heme interactions in wild type and mutated Ngbs.
Temperature directly and indirectly influences food web structure
Authors: Gibert Jean P.
Published: March 2019

Understanding whether and how environmental conditions may impact food web structure at a global scale is central to our ability to predict how food webs will respond to climate change. However, such an understanding is nascent. Using the best resolved available food webs to date, I address whether latitude, temperature, or both, explain the number of species and feeding interactions, the proportion of basal and top species, as well as the degree of omnivory, connectance and the number of trophic levels across food webs. I found that temperature is a more parsimonious predictor of food web structure than latitude. Temperature directly reduces the number of species, the proportion of basal species and the number of interactions while it indirectly increases omnivory levels, connectance and trophic level through its direct effects on the fraction and number of basal species. While direct impacts of temperature are routinely taken into account to predict how ecosystems may respond to global climate change, indirect effects have been largely overlooked. These results thus suggest that food webs may be affected by a combination of biotic and abiotic conditions, both directly and indirectly, in a changing world.
A novel 3-hydroxypropionic acid-inducible promoter regulated by the LysR-type transcriptional activator protein MmsR of Pseudomonas denitrificans
Authors: Nguyen Nam Hoai , Ainala Satish Kumar , Zhou Shengfang , Park Sunghoon
Published: March 2019

MmsR (33.3 kDa) is a putative LysR-type transcriptional activator ofPseudomonas denitrificans. With the help of 3-hydroxypropionic acid (3-HP), an important platform chemical, MmsR positively regulates the expression ofmmsA, which encodes methylmalonylsemialdehyde dehydrogenase, the enzyme involved in valine degradation. In the present study, the cellular function of MmsR and its binding to the regulatory DNA sequence ofmmsAexpression were investigated bothin vivoandin vitro. Transcription of themmsAwas enhanced >140-fold in the presence of 3-HP. In the MmsR-responsive promoter region, two operators showing dyad symmetry, designated O1and O2and centered at the −79 and −28 positions, respectively, were present upstream of themmsAtranscription start site. An electrophoretic mobility shift assay indicated that MmsR binds to both operator sites for transcription activation, probably in cooperative manner. When either O1or O2or both regions were mutated, the inducibility by the MmsR-3-HP complex was significantly reduced or completely removed, indicating that both sites are required for transcription activation. A 3-HP sensor was developed by connecting the activation of MmsR to a green fluorescent readout. A more than 50-fold induction by 25 mM 3-HP was observed.
Mitochondrial DNA and genomic DNA ratio in embryo culture medium is not a reliable predictor for in vitro fertilization outcome
Authors: Zhang Xinyue , Sun Yue , Dong Xin , Zhou Jianming , Sun Fubo , Han Tingting , Lei Ping , Mao Rurong , Guo Xuzhou , Wang Qi , Li Penghao , Qu Ting , Huang Jihua , Li Lingxiao , Huang Tianhua , Zhong Ying , Gu Jiang
Published: March 2019

To investigate the ratio of mitochondrial DNA to genomic DNA (mt/gDNA) in embryo culture medium as a possible predictor for embryonic development and pregnancy outcome, we collected a total of 93 embryo biopsy specimens from 52 women at the corresponding Day 3 (D3) and Day 5 (D5) embryo culture medium of in vitro fertilization. With the multiple annealing and looping-based amplification cycles method of next-generation sequencing for whole genome amplification, we examined the karyotype of the biopsy samples and the mt/gDNA ratio in the culture medium. Results showed that the ratio of mt/gDNA had an upward trend with decreasing trophectoderm levels with no significant difference. At the same time, from D3 to D5, the mt/gDNA ratio in the medium of embryos that failed to become blastocysts showed an upward trend, and the mt/gDNA ratio of medium from embryos that reached blastulation with successful pregnancy showed a decreasing trend, but the differences were not statistically significant. We conclude that there is a certain correlation between mt/gDNA ratio and early embryonic development, but it does not reach a level that can be used as a clinical predictor.
Direct differentiation of bone marrow mononucleated cells into insulin producing cells using pancreatic β-cell-derived components
Authors: Oh Ju Eun , Choi Ok Kyung , Park Ho Seon , Jung Hye Seung , Ryu Su Jeong , Lee Yong Deok , Lee Seung-Ah , Chung Sung Soo , Choi Eun Young , Lee Dong-Sup , Gho Yong Song , Lee Hakmo , Park Kyong Soo
Published: March 2019

Transplantation of stem cell-derived insulin producing cells (IPCs) has been proposed as an alternative to islet transplantation for the treatment of diabetes mellitus. However, current IPC differentiation protocols are focused on generating functional cells from the pluripotent stem cells and tend to rely on multistep, long-term exposure to various exogenous factors. In this study, we addressed the observation that under stress, pancreatic β-cells release essential components that direct the differentiation of the bone marrow nucleated cells (BMNCs) into IPCs. Without any supplementation with known differentiation-inducing factors, IPCs can be generated from BMNCs by in vitro priming for 6 days with conditioned media (CM) from the β-cells. In vitro primed BMNCs expressed the β-cell-specific transcription factors, as well as insulin, and improved hyperglycemia and glucose intolerance after transplantation into the streptozotocin-induced diabetic mice. Furthermore, we have found that components of the CM which trigger the differentiation were enclosed by or integrated into micro particles (MPs), rather than being secreted as soluble factors. Identification of these differentiation-directing factors might enable us to develop novel technologies required for the production of clinically applicable IPCs.
Palaeoecology of Voulteryon parvulus (Eucrustacea, Polychelida) from the Middle Jurassic of La Voulte-sur-Rhône Fossil-Lagerstätte (France)
Authors: Audo Denis , Robin Ninon , Luque Javier , Krobicki Michal , Haug Joachim T. , Haug Carolin , Jauvion Clément , Charbonnier Sylvain
Published: March 2019

Exceptional and extremely rare preservation of soft parts, eyes, or syn-vivo associations provide crucial palaeoecological information on fossil-rich deposits. Here we present exceptionally preserved specimens of the polychelidan lobster Voulteryon parvulus, from the Jurassic of La Voulte-sur-Rhône Fossil-Lagerstätte, France, bearing eyes with hexagonal and square facets, ovaries, and a unique association with epibiont thecideoid brachiopods, giving insights onto the palaeoenvironment of this Lagerstätte. The eyes, mostly covered in hexagonal facets are interpreted as either apposition eyes (poorly adapted to low-light environment) or, less likely, as refractive or parabolic superposition eyes (compatible with dysphotic palaeoenvironments). The interpretation that V. parvulus had apposition eyes suggests an allochthonous, shallow water origin. However, the presence of thecideoid brachiopod ectosymbionts on its carapace, usually associated to dim-light paleoenvironments and/or rock crevices, suggests that V. parvulus lived in a dim-light setting. This would support the less parsimonious interpretation that V. parvulus had superposition eyes. If we accept the hypothesis that V. parvulus had apposition eyes, since the La Voulte palaeoenvironment is considered deep water and had a soft substrate, V. parvulus could have moved into the La Voulte Lagerstätte setting. If this is the case, La Voulte biota would record a combination of multiple palaeoenvironments.
Metformin induces the AP-1 transcription factor network in normal dermal fibroblasts
Authors: Gillespie Zoe E. , Wang Chenxuan , Vadan Flaviu , Yu Topaza Y. , Ausió Juan , Kusalik Anthony , Eskiw Christopher H.
Published: March 2019

Metformin is a widely-used treatment for type 2 diabetes and is reported to extend health and lifespan as a caloric restriction (CR) mimetic. Although the benefits of metformin are well documented, the impact of this compound on the function and organization of the genome in normal tissues is unclear. To explore this impact, primary human fibroblasts were treated in culture with metformin resulting in a significant decrease in cell proliferation without evidence of cell death. Furthermore, metformin induced repositioning of chromosomes 10 and 18 within the nuclear volume indicating altered genome organization. Transcriptome analyses from RNA sequencing datasets revealed that alteration in growth profiles and chromosome positioning occurred concomitantly with changes in gene expression profiles. We further identified that different concentrations of metformin induced different transcript profiles; however, significant enrichment in the activator protein 1 (AP-1) transcription factor network was common between the different treatments. Comparative analyses revealed that metformin induced divergent changes in the transcriptome than that of rapamycin, another proposed mimetic of CR. Promoter analysis and chromatin immunoprecipitation assays of genes that changed expression in response to metformin revealed enrichment of the transcriptional regulator forkhead box O3a (FOXO3a) in normal human fibroblasts, but not of the predicted serum response factor (SRF). Therefore, we have demonstrated that metformin has significant impacts on genome organization and function in normal human fibroblasts, different from those of rapamycin, with FOXO3a likely playing a role in this response.
Functional and structural similarities of D7 proteins in the independently-evolved salivary secretions of sand flies and mosquitoes
Authors: Jablonka Willy , Kim Il Hwan , Alvarenga Patricia H. , Valenzuela Jesus G. , Ribeiro Jose´ M. C. , Andersen John F.
Published: March 2019

The habit of blood feeding evolved independently in many insect orders of families. Sand flies and mosquitoes belong to separate lineages of blood-feeding Diptera and are thus considered to have evolved the trait independently. Because of this, sand fly salivary proteins differ structurally from those of mosquitoes, and orthologous groups are nearly impossible to define. An exception is the long-form D7-like proteins that show conservation with their mosquito counterparts of numerous residues associated with the N-terminal domain binding pocket. In mosquitoes, this pocket is responsible for the scavenging of proinflammatory cysteinyl leukotrienes and thromboxanes at the feeding site. Here we show that long-form D7 proteins AGE83092 and ABI15936 from the sand fly species, Phlebotomus papatasi and P. duboscqi, respectively, inhibit the activation of platelets by collagen and the thromboxane A2 analog U46619. Using isothermal titration calorimetry, we also demonstrate direct binding of U46619 and cysteinyl leukotrienes C4, D4 and E4 to the P. papatasi protein. The crystal structure of P. duboscqi ABI15936 was determined and found to contain two domains oriented similarly to those of the mosquito proteins. The N-terminal domain contains an apparent eicosanoid binding pocket. The C-terminal domain is smaller in overall size than in the mosquito D7s and is missing some helical elements. Consequently, it does not contain an obvious internal binding pocket for small-molecule ligands that bind to many mosquito D7s. Structural similarities indicate that mosquito and sand fly D7 proteins have evolved from similar progenitors, but phylogenetics and differences in intron/exon structure suggest that they may have acquired the ability to bind vertebrate eicosanoids independently, indicating a convergent evolution scenario.