bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of food neophobia in pre-school children from southern Poland and its association with eating habits, dietary intake and anthropometric parameters: a cross-sectional study
Authors: Kozioł-Kozakowska Agnieszka , Piórecka Beata , Schlegel-Zawadzka Małgorzata 
Published: December 2017

AbstractObjectivesThe present study aimed to assess the prevalence of food neophobia in pre-school children and its association with eating habits, dietary intake and anthropometric parameters.DesignCross-sectional survey performed in 2012–2013. The Child Food Neophobia Scale (CFNS) adapted by Wardle, Carnell and Cooke was used to assess the level of food neophobia. Dietary intake was measured using an FFQ and dietary records from three days. Anthropometric measurements were taken to determine children’s nutritional status and BMI was computed based on Polish growth charts. Wilcoxon’s rank test and Pearson’s rank-correlation coefficient were applied to compare the level of food neophobia and frequency of consumption of food products and nutrient intakes.SettingKindergartens in southern Poland located in or near Cracow.SubjectsThree hundred and twenty-five pre-school children and their parents.ResultsLow neophobia was observed in 12·3 % and high neophobia in 10·8 % of the children examined. Children with a high level of neophobia were significantly less likely (P<0·05) to eat eggs, raw or cooked vegetables and legumes, whereas they tended to eat sweets and snacks more frequently; these foodstuffs were also eaten more often between meals. Because the neophobic children ate vegetables very rarely, their intakes of vitamin C (36 % of RDA) and thiamin (84 % of RDA) were far below the norms. No differences in anthropometric parameters according to level of food neophobia were observed.ConclusionsHigh levels of neophobia are associated with diet variation and may enhance the risk of nutritional deficiencies in children.
Double mimicry evades tRNA synthetase editing by toxic vegetable-sourced non-proteinogenic amino acid
Authors: Song Youngzee , Zhou Huihao , Vo My-Nuong , Shi Yi , Nawaz Mir Hussain , Vargas-Rodriguez Oscar , Diedrich Jolene K. , Yates John R. , Kishi Shuji , Musier-Forsyth Karin , Schimmel Paul 
Published: December 2017

AbstractHundreds of non-proteinogenic (np) amino acids (AA) are found in plants and can in principle enter human protein synthesis through foods. While aminoacyl-tRNA synthetase (AARS) editing potentially provides a mechanism to reject np AAs, some have pathological associations. Co-crystal structures show that vegetable-sourced azetidine-2-carboxylic acid (Aze), a dual mimic of proline and alanine, is activated by both human prolyl- and alanyl-tRNA synthetases. However, it inserts into proteins as proline, with toxic consequences in vivo. Thus, dual mimicry increases odds for mistranslation through evasion of one but not both tRNA synthetase editing systems.
Excitotoxic inactivation of constitutive oxidative stress detoxification pathway in neurons can be rescued by PKD1
Authors: Pose-Utrilla Julia , García-Guerra Lucía , Del Puerto Ana , Martín Abraham , Jurado-Arjona Jerónimo , De León-Reyes Noelia S. , Gamir-Morralla Andrea , Sebastián-Serrano Álvaro , García-Gallo Mónica , Kremer Leonor , Fielitz Jens , Ireson Christofer , Pérez-Álvarez Mª José , Ferrer Isidro , Hernández Félix , Ávila Jesús , Lasa Marina , Campanero Miguel R. , Iglesias Teresa 
Published: December 2017

AbstractExcitotoxicity, a critical process in neurodegeneration, induces oxidative stress and neuronal death through mechanisms largely unknown. Since oxidative stress activates protein kinase D1 (PKD1) in tumor cells, we investigated the effect of excitotoxicity on neuronal PKD1 activity. Unexpectedly, we find that excitotoxicity provokes an early inactivation of PKD1 through a dephosphorylation-dependent mechanism mediated by protein phosphatase-1 (PP1) and dual specificity phosphatase-1 (DUSP1). This step turns off the IKK/NF-κB/SOD2 antioxidant pathway. Neuronal PKD1 inactivation by pharmacological inhibition or lentiviral silencing in vitro, or by genetic inactivation in neurons in vivo, strongly enhances excitotoxic neuronal death. In contrast, expression of an active dephosphorylation-resistant PKD1 mutant potentiates the IKK/NF-κB/SOD2 oxidative stress detoxification pathway and confers neuroprotection from in vitro and in vivo excitotoxicity. Our results indicate that PKD1 inactivation underlies excitotoxicity-induced neuronal death and suggest that PKD1 inactivation may be critical for the accumulation of oxidation-induced neuronal damage during aging and in neurodegenerative disorders.
Small-molecule TFEB pathway agonists that ameliorate metabolic syndrome in mice and extend C. elegans lifespan
Authors: Wang Chensu , Niederstrasser Hanspeter , Douglas Peter M. , Lin Rueyling , Jaramillo Juan , Li Yang , Oswald Nathaniel W. , Zhou Anwu , McMillan Elizabeth A. , Mendiratta Saurabh , Wang Zhaohui , Zhao Tian , Lin Zhiqaing , Luo Min , Huang Gang , Brekken Rolf A. , Posner Bruce A. , MacMillan John B. , Gao Jinming , White Michael A. 
Published: December 2017

AbstractDrugs that mirror the cellular effects of starvation mimics are considered promising therapeutics for common metabolic disorders, such as obesity, liver steatosis, and for ageing. Starvation, or caloric restriction, is known to activate the transcription factor EB (TFEB), a master regulator of lipid metabolism and lysosomal biogenesis and function. Here, we report a nanotechnology-enabled high-throughput screen to identify small-molecule agonists of TFEB and discover three novel compounds that promote autophagolysosomal activity. The three lead compounds include the clinically approved drug, digoxin; the marine-derived natural product, ikarugamycin; and the synthetic compound, alexidine dihydrochloride, which is known to act on a mitochondrial target. Mode of action studies reveal that these compounds activate TFEB via three distinct Ca2+-dependent mechanisms. Formulation of these compounds in liver-tropic biodegradable, biocompatible nanoparticles confers hepatoprotection against diet-induced steatosis in murine models and extends lifespan of Caenorhabditis elegans. These results support the therapeutic potential of small-molecule TFEB activators for the treatment of metabolic and age-related disorders.
Diurnal cloud cycle biases in climate models
Authors: Yin Jun , Porporato Amilcare 
Published: December 2017

AbstractClouds’ efficiency at reflecting solar radiation and trapping the terrestrial radiation is strongly modulated by the diurnal cycle of clouds (DCC). Much attention has been paid to mean cloud properties due to their critical role in climate projections; however, less research has been devoted to the DCC. Here we quantify the mean, amplitude, and phase of the DCC in climate models and compare them with satellite observations and reanalysis data. While the mean appears to be reliable, the amplitude and phase of the DCC show marked inconsistencies, inducing overestimation of radiation in most climate models. In some models, DCC appears slightly shifted over the ocean, likely as a result of tuning and fortuitously compensating the large DCC errors over the land. While this model tuning does not seem to invalidate climate projections because of the limited DCC response to global warming, it may potentially increase the uncertainty of climate predictions.
Dehydrogenative desaturation-relay via formation of multicenter-stabilized radical intermediates
Authors: Shang Yaping , Jie Xiaoming , Jonnada Krishna , Zafar Syeda Nahid , Su Weiping 
Published: December 2017

AbstractIn organic molecules, the reactivity at the carbon atom next to the functional group is dramatically different from that at other carbon atoms. Herein, we report that a versatile copper-catalyzed method enables successive dehydrogenation or dehydrogenation of ketones, aldehydes, alcohols, α,β-unsaturated diesters, and N-heterocycles to furnish stereodefined conjugated dienecarbonyls, polyenecarbonyls, and nitrogen-containing heteroarenes. On the basis of mechanistic studies, the copper-catalyzed successive dehydrogenation process proceeds via the initial α,β-desaturation followed by further dehydrogenative desaturation of the resultant enone intermediate, demonstrating that the reactivity at α-carbon is transferred through carbon–carbon double bond or longer π-system to the carbon atoms at the positions γ, ε, and η to carbonyl groups. The dehydrogenative desaturation–relay is ascribed to the formation of an unusual radical intermediate stabilized by 5- or 7,- or 9-center π-systems. The discovery of successive dehydrogenation may open the door to functionalizations of the positions distant from functional groups in organic molecules.
Chromatin state changes during neural development revealed by in vivo cell-type specific profiling
Authors: Marshall Owen J. , Brand Andrea H. 
Published: December 2017

AbstractA key question in developmental biology is how cellular differentiation is controlled during development. While transitions between trithorax-group (TrxG) and polycomb-group (PcG) chromatin states are vital for the differentiation of ES cells to multipotent stem cells, little is known regarding the role of chromatin states during development of the brain. Here we show that large-scale chromatin remodelling occurs during Drosophila neural development. We demonstrate that the majority of genes activated during neuronal differentiation are silent in neural stem cells (NSCs) and occupy black chromatin and a TrxG-repressive state. In neurons, almost all key NSC genes are switched off via HP1-mediated repression. PcG-mediated repression does not play a significant role in regulating these genes, but instead regulates lineage-specific transcription factors that control spatial and temporal patterning in the brain. Combined, our data suggest that forms of chromatin other than canonical PcG/TrxG transitions take over key roles during neural development.
Timing and pacing of the Late Devonian mass extinction event regulated by eccentricity and obliquity
Authors: De Vleeschouwer David , Da Silva Anne-Christine , Sinnesael Matthias , Chen Daizhao , Day James E. , Whalen Michael T. , Guo Zenghui , Claeys Philippe 
Published: December 2017

AbstractThe Late Devonian envelops one of Earth’s big five mass extinction events at the Frasnian–Famennian boundary (374 Ma). Environmental change across the extinction severely affected Devonian reef-builders, besides many other forms of marine life. Yet, cause-and-effect chains leading to the extinction remain poorly constrained as Late Devonian stratigraphy is poorly resolved, compared to younger cataclysmic intervals. In this study we present a global orbitally calibrated chronology across this momentous interval, applying cyclostratigraphic techniques. Our timescale stipulates that 600 kyr separate the lower and upper Kellwasser positive δ13C excursions. The latter excursion is paced by obliquity and is therein similar to Mesozoic intervals of environmental upheaval, like the Cretaceous Ocean-Anoxic-Event-2 (OAE-2). This obliquity signature implies coincidence with a minimum of the 2.4 Myr eccentricity cycle, during which obliquity prevails over precession, and highlights the decisive role of astronomically forced “Milankovitch” climate change in timing and pacing the Late Devonian mass extinction.
Quantum Hall states observed in thin films of Dirac semimetal Cd3As2
Authors: Uchida Masaki , Nakazawa Yusuke , Nishihaya Shinichi , Akiba Kazuto , Kriener Markus , Kozuka Yusuke , Miyake Atsushi , Taguchi Yasujiro , Tokunaga Masashi , Nagaosa Naoto , Tokura Yoshinori , Kawasaki Masashi 
Published: December 2017

AbstractA well known semiconductor Cd3As2 has reentered the spotlight due to its unique electronic structure and quantum transport phenomena as a topological Dirac semimetal. For elucidating and controlling its topological quantum state, high-quality Cd3As2 thin films have been highly desired. Here we report the development of an elaborate growth technique of high-crystallinity and high-mobility Cd3As2 films with controlled thicknesses and the observation of quantum Hall effect dependent on the film thickness. With decreasing the film thickness to 10 nm, the quantum Hall states exhibit variations such as a change in the spin degeneracy reflecting the Dirac dispersion with a large Fermi velocity. Details of the electronic structure including subband splitting and gap opening are identified from the quantum transport depending on the confinement thickness, suggesting the presence of a two-dimensional topological insulating phase. The demonstration of quantum Hall states in our high-quality Cd3As2 films paves a road to study quantum transport and device application in topological Dirac semimetal and its derivative phases.
Imaging the square of the correlated two-electron wave function of a hydrogen molecule
Authors: Waitz M. , Bello R. Y. , Metz D. , Lower J. , Trinter F. , Schober C. , Keiling M. , Lenz U. , Pitzer M. , Mertens K. , Martins M. , Viefhaus J. , Klumpp S. , Weber T. , Schmidt L. Ph. H. , Williams J. B. , Schöffler M. S. , Serov V. V. , Kheifets A. S. , Argenti L. , Palacios A. , Martín F. , Jahnke T. , Dörner R. 
Published: December 2017

AbstractThe toolbox for imaging molecules is well-equipped today. Some techniques visualize the geometrical structure, others the electron density or electron orbitals. Molecules are many-body systems for which the correlation between the constituents is decisive and the spatial and the momentum distribution of one electron depends on those of the other electrons and the nuclei. Such correlations have escaped direct observation by imaging techniques so far. Here, we implement an imaging scheme which visualizes correlations between electrons by coincident detection of the reaction fragments after high energy photofragmentation. With this technique, we examine the H2 two-electron wave function in which electron–electron correlation beyond the mean-field level is prominent. We visualize the dependence of the wave function on the internuclear distance. High energy photoelectrons are shown to be a powerful tool for molecular imaging. Our study paves the way for future time resolved correlation imaging at FELs and laser based X-ray sources.
RNA sequencing provides insights into the evolution of lettuce and the regulation of flavonoid biosynthesis
Authors: Zhang Lei , Su Wenqing , Tao Rong , Zhang Weiyi , Chen Jiongjiong , Wu Peiyao , Yan Chenghuan , Jia Yue , Larkin Robert M. , Lavelle Dean , Truco Maria-Jose , Chin-Wo Sebastian Reyes , Michelmore Richard W. , Kuang Hanhui 
Published: December 2017

AbstractDifferent horticultural types of lettuce exhibit tremendous morphological variation. However, the molecular basis for domestication and divergence among the different horticultural types of lettuce remains unknown. Here, we report the RNA sequencing of 240 lettuce accessions sampled from the major horticultural types and wild relatives, generating 1.1 million single-nucleotide polymorphisms (SNPs). Demographic modeling indicates that there was a single domestication event for lettuce. We identify a list of regions as putative selective sweeps that occurred during domestication and divergence, respectively. Genome-wide association studies (GWAS) identify 5311 expression quantitative trait loci (eQTL) regulating the expression of 4105 genes, including nine eQTLs regulating genes associated with flavonoid biosynthesis. GWAS for leaf color detects six candidate loci responsible for the variation of anthocyanins in lettuce leaves. Our study provides a comprehensive understanding of the domestication and the accumulation of anthocyanins in lettuce, and will facilitate the breeding of cultivars with improved nutritional value.
Rainbow peacock spiders inspire miniature super-iridescent optics
Authors: Hsiung Bor-Kai , Siddique Radwanul Hasan , Stavenga Doekele G. , Otto Jürgen C. , Allen Michael C. , Liu Ying , Lu Yong-Feng , Deheyn Dimitri D. , Shawkey Matthew D. , Blackledge Todd A. 
Published: December 2017

AbstractColour produced by wavelength-dependent light scattering is a key component of visual communication in nature and acts particularly strongly in visual signalling by structurally-coloured animals during courtship. Two miniature peacock spiders (Maratus robinsoniandM. chrysomelas) court females using tiny structured scales (~ 40 × 10 μm2) that reflect the full visual spectrum. Using TEM and optical modelling, we show that the spiders’ scales have 2D nanogratings on microscale 3D convex surfaces with at least twice the resolving power of a conventional 2D diffraction grating of the same period. Whereas the long optical path lengths required for light-dispersive components to resolve individual wavelengths constrain current spectrometers to bulky sizes, our nano-3D printed prototypes demonstrate that the design principle of the peacock spiders’ scales could inspire novel, miniature light-dispersive components.
The F-box protein FKF1 inhibits dimerization of COP1 in the control of photoperiodic flowering
Authors: Lee Byoung-Doo , Kim Mi Ri , Kang Min-Young , Cha Joon-Yung , Han Su-Hyun , Nawkar Ganesh M. , Sakuraba Yasuhito , Lee Sang Yeol , Imaizumi Takato , McClung C. Robertson , Kim Woe-Yeon , Paek Nam-Chon 
Published: December 2017

AbstractInArabidopsis thaliana, CONSTANS (CO) plays an essential role in the regulation of photoperiodic flowering under long-day conditions. CO protein is stable only in the afternoon of long days, when it induces the expression ofFLOWERING LOCUS T(FT), which promotes flowering. The blue-light photoreceptor FLAVIN-BINDING, KELCH REPEAT, F-BOX1 (FKF1) interacts with CO and stabilizes it by an unknown mechanism. Here, we provide genetic and biochemical evidence that FKF1 inhibits CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1)-dependent CO degradation. Light-activated FKF1 has no apparent effect on COP1 stability but can interact with and negatively regulate COP1. We show that FKF1 can inhibit COP1 homo-dimerization. Mutation of the coiled-coil domain in COP1, which prevents dimer formation, impairs COP1 function in coordinating flowering time. Based on these results, we propose a model whereby the light- and day length-dependent interaction between FKF1 and COP1 controls CO stability to regulate flowering time.
The opposing forces of shear flow and sphingosine-1-phosphate control marginal zone B cell shuttling
Authors: Tedford Kerry , Steiner Michael , Koshutin Stanislav , Richter Karin , Tech Laura , Eggers Yannik , Jansing Inga , Schilling Kerstin , Hauser Anja Erika , Korthals Mark , Fischer Klaus-Dieter 
Published: December 2017

AbstractSplenic marginal zone B cells (MZB) shuttle between the blood-filled marginal zone for antigen collection and the follicle for antigen delivery. However, it is unclear how MZBs migrate directionally from the marginal zone to the follicle. Here, we show that murine MZBs migrate up shear flow via the LFA-1 (αLβ2) integrin ligand ICAM-1, but adhere or migrate down the flow via the VLA-4 integrin (α4β1) ligand VCAM-1. MZBs lacking Arhgef6 (Pak-interacting exchange factor (αPIX)) or functional LFA-1 are impaired in shuttling due to mislocalization toward the VCAM-1-rich red pulp. Sphingosine-1-phosphate (S1P) signaling through the S1PR3 receptor inhibits MZB migration up the flow, and deletion of S1pr3 in Arhgef6−/− mice rescues mislocalized MZBs. These findings establish shear flow as a directional cue for MZB migration to the follicle, and define S1PR3 and VCAM-1 as counteracting forces that inhibit this migration.
96 perfusable blood vessels to study vascular permeability in vitro
Authors: van Duinen V. , van den Heuvel A. , Trietsch S. J. , Lanz H. L. , van Gils J. M , van Zonneveld A. J. , Vulto P. , Hankemeier T. 
Published: December 2017

AbstractCurrent in vitro models to test the barrier function of vasculature are based on flat, two-dimensional monolayers. These monolayers do not have the tubular morphology of vasculature found in vivo and lack important environmental cues from the cellular microenvironment, such as interaction with an extracellular matrix (ECM) and exposure to flow. To increase the physiological relevance of in vitro models of the vasculature, it is crucial to implement these cues and better mimic the native three-dimensional vascular architecture. We established a robust, high-throughput method to culture endothelial cells as 96 three-dimensional and perfusable microvessels and developed a quantitative, real-time permeability assay to assess their barrier function. Culture conditions were optimized for microvessel formation in 7 days and were viable for over 60 days. The microvessels exhibited a permeability to 20 kDa dextran but not to 150 kDa dextran, which mimics the functionality of vasculature in vivo. Also, a dose-dependent effect of VEGF, TNFα and several cytokines confirmed a physiologically relevant response. The throughput and robustness of this method and assay will allow end-users in vascular biology to make the transition from two-dimensional to three-dimensional culture methods to study vasculature.
A re-engineered immunotoxin shows promising preclinical activity in ovarian cancer
Authors: Kollmorgen Gwendlyn , Palme Klara , Seidl Annette , Scheiblich Stefan , Birzele Fabian , Wilson Sabine , Clemens Christian , Voss Edgar , Kaufmann Martin , Hirzel Klaus , Rieder Natascha , Krippendorff Ben-Fillippo , Herting Frank , Niederfellner Gerhard 
Published: December 2017

AbstractRG7787 is a re-engineered mesothelin-targeted immunotoxin with reduced immunogenicity composed of a humanized anti-mesothelin Fab fragment and a B-cell epitope silenced 24 kD fragment of Pseudomonas exotoxin A. High prevalence of mesothelin-positive cases and a large unmet medical need make ovarian cancer a promising indication for the clinical development of RG7787. However, ovarian cancer patients also frequently have elevated serum levels of the cancer antigen 125 (CA-125). In principle this could pose a problem, since the binding sites for CA-125 and RG7787 on mesothelin were reported to overlap. However, we show here that RG7787 can readily displace even excess amounts of CA-125 in different cellular assays. Moreover when tested in-vitro on a panel of 12 ovarian cancer cell lines, RG7787 had high cytotoxic activity on COV644, Caov-4, and SNU-119 cells and fully inhibited growth of EFO-21, KURAMOCHI, OVSAHO, and Caov-3 cells with potency values ranging from 1 to 86 pM. Finally, we evaluated the in-vivo efficacy of RG7787 in OvCa6668, a patient-derived ovarian cancer model with high levels of CA-125 expression. RG7787 had moderate monotherapy efficacy but in combination with standard chemotherapies (cisplatin, paclitaxel) achieved pronounced tumor regressions. In summary our data support clinical testing of RG7787 in ovarian cancer.