bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of bioelectrical impedance analysis in Ethiopian adults with HIV
Authors: Hegelund Maria H. , Wells Jonathan C. , Girma Tsinuel , Faurholt-Jepsen Daniel , Zerfu Dilnesaw , Christensen Dirk L. , Friis Henrik , Olsen Mette F.
Published: December 2017

Bioelectrical impedance analysis (BIA) is an inexpensive, quick and non-invasive method to determine body composition. Equations used in BIA are typically derived in healthy individuals of European descent. BIA is specific to health status and ethnicity and may therefore provide inaccurate results in populations of different ethnic origin and health status. The aim of the present study was to test the validity of BIA in Ethiopian antiretroviral-naive HIV patients.

BIA was validated against the2H dilution technique by comparing fat-free mass (FFM) measured by the two methods using pairedttests and Bland–Altman plots. BIA was based on single frequency (50 kHz) whole-body measurements. Data were obtained at three health facilities in Jimma Zone, Oromia Region, South-West Ethiopia. Data from 281 HIV-infected participants were available. Two-thirds were female and the mean age was 32·7 (sd8·6) years. Also, 46 % were underweight with a BMI below 18·5 kg/m2. There were no differences in FFM between the methods. Overall, BIA slightly underestimated FFM by 0·1 kg (−0·1, 95 % CI −0·3, 0·2 kg). The Bland–Altman plot indicated acceptable agreement with an upper limit of agreement of 4·5 kg and a lower limit of agreement of −4·6 kg, but with a small correlation between the mean difference and the average FFM. BIA slightly overestimated FFM at low values compared with the2H dilution technique, while it slightly underestimated FFM at high values. In conclusion, BIA proved to be valid in this population and may therefore be useful for measuring body composition in routine practice in HIV-infected African individuals.
Evidence for trophic transfer ofInodosporus octosporaandOvipleistophora arlon. sp. (Microsporidia) between crustacean and fish hosts
Authors: Stentiford G.D. , Ross S. , Minardi D. , Feist S.W. , Bateman K.S. , Gainey P.A. , Troman C. , Bass D.
Published: December 2017

Within aquatic habitats, the hyper-abundant Order Crustacea appear to be the predominant host group for members of the Phylum Microsporidia. The musculature, a common site of infection, provides access to biochemical (carbohydrate-rich) and physiological (mitochondria-rich) conditions conducive to prolific parasite replication and maturation. The significant proportion of body plan devoted to skeletal musculature in Crustacea provides the location for a highly efficient intracellular parasite factory. In this study, we utilize histological, ultrastructural and phylogenetic evidence to describe a previously known (Inodosporus octospora) and novel (Ovipleistophora arlon. sp.) microsporidian parasites infecting the musculature of the common prawn (Palaemon serratus) from the same site, at the same time of year. Despite similar clinical signs of infection, both parasites are otherwise distinct in terms of pathogenesis, morphology and phylogeny. Based upon partial subunit ribosomal RNA (SSU rDNA) sequence, we show that thatI. octosporamay be identical to aKabatanasp. previously described infecting two-spot goby (Gobiusculus flavescens) in Europe, or at least thatInodosporusandKabatanagenera are synonyms. In addition, SSU rDNA sequence forO. arloplaces it within a distinct clade containingOvipleistophora mirandellaeandOvipleistophora ovariae, both infecting the oocytes of freshwater fish in Europe. Taken together, our data provide strong evidence for trophic-transfer between crustacean and fish hosts for two different microsporidians within clade 5 of the phylum. Furthermore, it demonstrates that morphologically and phylogenetically distinct microsporidians can infect the same tissues of the same host species to impart clinical signs which mimic infection with the other.
Evaluating the electron density model by applying an imaginary modification
Authors: Li Hui , He Meng , Zhang Ze
Published: December 2017

A function has been proposed to evaluate the electron density model constructed by inverse Fourier transform using the observed structure amplitudes and trial phase set. The strategy of this function is applying an imaginary electron density modification to the model, and then measuring how well the calculated structure amplitudes of the modified model matches the expected structure amplitudes for the modified correct model. Since the correct model is not available in advance, a method has been developed to estimate the structure amplitudes of the modified correct model. With the estimated structure amplitudes of the modified correct model, the evaluation function can be calculated approximately. Limited tests on simulated diffraction data indicate that this evaluation function may be valid at the data resolution better than 2.5 Å.
Mechanism of action of vesicular monoamine transporter 2 (VMAT2) inhibitors in tardive dyskinesia: reducing dopamine leads to less “go” and more “stop” from the motor striatum for robust therapeutic effects
Authors: Stahl Stephen M.
Published: December 2017

Tardive dyskinesia can now be successfully treated by inhibiting the vesicular monoamine transporter type 2 (VMAT2).
Social protection in the face of climate change: targeting principles and financing mechanisms
Authors: Carter Michael R. , Janzen Sarah A.
Published: December 2017

This paper builds a multi-generation household model of consumption, accumulation, and risk management to assess the dynamic consequences of climate risk exposure. The model incorporates long-term impacts of consumption shortfalls, induced by optimal ‘asset smoothing’ coping behavior of the vulnerable, on poverty. The analysis shows the long-term level and depth of poverty can be improved by incorporating ‘vulnerability-targeted social protection’ into a conventional social protection system. The paper further shows insurance-based vulnerability-targeted social protection dominates (in economic growth and poverty reduction measures) both in-kind transfers and asset-based vulnerability-targeted protection. We then stress test social protection mechanisms and find the relative performance of insurance-based vulnerability-targeted social protection improves when subjected to current pessimistic projections about increasing drought risk. However, if drought risk increases beyond current climate change projections, then even the vulnerability-targeted policy loses its ability to stabilize the extent and depth of poverty.
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

Objectives

The 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.

Design

Cross-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.

Setting

Kindergartens in southern Poland located in or near Cracow.

Subjects

Three hundred and twenty-five pre-school children and their parents.

Results

Low 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.

Conclusions

High levels of neophobia are associated with diet variation and may enhance the risk of nutritional deficiencies in children.
Planar discrete lens antenna integrated on dielectric substrate for millimeter-wave transceiver module
Authors: Medrar Kossaila , Marnat Loic , Dussopt Laurent
Published: December 2017

A novel topology of high-gain millimeter-wave antenna compatible with substrate integration is presented. The antenna is composed of a planar discrete lens laid on top of a core dielectric, while the planar focal source is assembled on the bottom side. The antenna can be fabricated as a single, robust and compact module using standard low-cost PCB technologies, and is compatible with IC integration such as a transceiver circuit for fully integrated millimeter-wave front-end modules. The proposed architecture is studied with two compact V-band antennas (32 mm × 32 mm × 13.2 mm). The main design rules are demonstrated for unit cells, focal source, and planar lens at V-band. Promising performances in terms of gain (17.6 and 20.4 dBi), aperture efficiency (14 and 26%), and fractional 3-dB gain bandwidth (17 and 18%) are obtained experimentally for the two considered compact antennas.
The role of the tumor necrosis factor (TNF)-related weak inducer of apoptosis (TWEAK) in offspring exposed to prenatal hypoxia
Authors: Reyes L. M. , Shah A. , Quon A. , Morton J. S. , Davidge S. T.
Published: December 2017

Exposure to prenatal hypoxia in rats leads to intrauterine growth restriction (IUGR), decreases fetal cardiomyocyte proliferation and increases the risk to develop cardiovascular diseases (CVD) later in life. The tumor necrosis factor-related weak inducer of apoptosis (TWEAK) induces cardiomyocyte proliferation through activation of the fibroblast growth factor-inducible molecule 14 (Fn-14) receptor. The TWEAK/Fn-14 pathway becomes quiescent shortly after birth, however, it becomes upregulated with CVD; suggesting that it could be a link between the increased susceptibility to CVD in pregnancies complicated by hypoxia/IUGR. We hypothesized that offspring exposed to prenatal hypoxia will exhibit reduced cardiomyocyte proliferation due to reduced Fn-14 expression and that the TWEAK/Fn-14 pathway will be expressed in those adult offspring. We exposed pregnant Sprague Dawley rats to control (21% oxygen) or hypoxic (11% oxygen) conditions from gestational days 15 to 21. Ventricular cardiomyocytes were isolated from male and female, control and hypoxic offspring at postnatal day 1. Proliferation was assessed in the presence or absence of r-TWEAK (72 h, 100 ng/ml). Prenatal hypoxia was not associated with differences in Fn-14 protein expression in either male or female offspring. Cardiomyocytes from prenatal hypoxic male, but not female, offspring had decreased proliferation compared with controls. Addition of r-TWEAK increased cardiomyocyte proliferation in all offspring. In adult offspring of all groups, the TWEAK/Fn-14 pathway was not detectable. Cardiomyocyte proliferation was reduced in only male offspring exposed to prenatal hypoxia but this was not due to changes in the Fn-14 pathway. Studies addressing other pathways associated with CVD and prenatal hypoxia are needed.
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

Hundreds 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

Excitotoxicity, 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

Drugs 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

Clouds’ 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

In 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

A 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

The 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

A 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

The 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

Different 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

Colour 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

InArabidopsis 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

Splenic 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

Current 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.
Publisher Correction: Enhanced unbiased sampling of protein dynamics using evolutionary coupling information
Authors: Shamsi Zahra , Moffett Alexander S. , Shukla Diwakar
Published: December 2017

A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.
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

RG7787 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.
Altered gene expression and metabolism in fetal umbilical cord mesenchymal stem cells correspond with differences in 5-month-old infant adiposity gain
Authors: Baker Peter R. , Patinkin Zachary W. , Shapiro Allison L. B. , de la Houssaye Becky A. , Janssen Rachel C. , Vanderlinden Lauren A. , Dabelea Dana , Friedman Jacob E.
Published: December 2017

The intrauterine period is a critical time wherein developmental exposure can influence risk for chronic disease including childhood obesity. Using umbilical cord-derived mesenchymal stem cells (uMSC) from offspring born to normal-weight and obese mothers, we tested the hypothesis that changes in infant body composition over the first 5 months of life correspond with differences in cellular metabolism and transcriptomic profiles at birth. Higher long-chain acylcarnitine concentrations, lipid transport gene expression, and indicators of oxidative stress in uMSC-adipocytes were related to higher adiposity at 5 months of age. In uMSC-myocytes, lower amino acid concentrations and global differential gene expression for myocyte growth, amino acid biosynthesis, and oxidative stress were related to lower infant percent fat-free mass at 5 months of age, particularly in offspring of obese mothers. This is the first evidence of human infant adipocyte- or myocyte-related alterations in cellular metabolic pathways that correspond with increased adiposity and lower fat-free mass in early infancy. These pathways might reflect the effects of an adverse maternal metabolic environment on the fetal metabolome and genome. Our findings suggest that programmed differences in infant stem cell metabolism correspond with differences in body composition in early life, a known contributor to obesity risk.
Magnetization jump in one dimensional J − Q
2 model with anisotropic exchange
Authors: Mao Bin-Bin , Cheng Chen , Chen Fu-Zhou , Luo Hong-Gang
Published: December 2017

We investigate the adiabatic magnetization process of the one-dimensional J − Q2 model with XXZ anisotropy g in an external magnetic field h by using density matrix renormalization group (DMRG) method. According to the characteristic of the magnetization curves, we draw a magnetization phase diagram consisting of four phases. For a fixed nonzero pair coupling Q, (i) when g < −1, the ground state is always ferromagnetic in spite of h; (ii) when g > −1 but still small, the whole magnetization curve is continuous and smooth; (iii) if further increasing g, there is a macroscopic magnetization jump from partially- to fully-polarized state; (iv) for a sufficiently large g, the magnetization jump is from non- to fully-polarized state. By examining the energy per magnon and the correlation function, we find that the origin of the magnetization jump is the condensation of magnons and the formation of magnetic domains. We also demonstrate that while the experienced states are Heisenberg-like without long-range order, all the jumped-over states have antiferromagnetic or Néel long-range orders, or their mixing.
Effects of prey density, temperature and predator diversity on nonconsumptive predator-driven mortality in a freshwater food web
Authors: Veselý Lukáš , Boukal David S. , Buřič Miloš , Kozák Pavel , Kouba Antonín , Sentis Arnaud
Published: December 2017

Nonconsumptive predator-driven mortality (NCM), defined as prey mortality due to predation that does not result in prey consumption, is an underestimated component of predator-prey interactions with possible implications for population dynamics and ecosystem functioning. However, the biotic and abiotic factors influencing this mortality component remain largely unexplored, leaving a gap in our understanding of the impacts of environmental change on ecological communities. We investigated the effects of temperature, prey density, and predator diversity and density on NCM in an aquatic food web module composed of dragonfly larvae (Aeshna cyanea) and marbled crayfish (Procambarus fallaxf.virginalis) preying on common carp (Cyprinus carpio) fry. We found that NCM increased with prey density and depended on the functional diversity and density of the predator community. Warming significantly reduced NCM only in the dragonfly larvae but the magnitude depended on dragonfly larvae density. Our results indicate that energy transfer across trophic levels is more efficient due to lower NCM in functionally diverse predator communities, at lower resource densities and at higher temperatures. This suggests that environmental changes such as climate warming and reduced resource availability could increase the efficiency of energy transfer in food webs only if functionally diverse predator communities are conserved.
The sleep EEG spectrum is a sexually dimorphic marker of general intelligence
Authors: Ujma Péter P. , Konrad Boris N. , Gombos Ferenc , Simor Péter , Pótári Adrián , Genzel Lisa , Pawlowski Marcel , Steiger Axel , Bódizs Róbert , Dresler Martin
Published: December 2017

The shape of the EEG spectrum in sleep relies on genetic and anatomical factors and forms an individual “EEG fingerprint”. Spectral components of EEG were shown to be connected to mental ability both in sleep and wakefulness. EEG sleep spindle correlates of intelligence, however, exhibit a sexual dimorphism, with a more pronounced association to intelligence in females than males. In a sample of 151 healthy individuals, we investigated how intelligence is related to spectral components of full-night sleep EEG, while controlling for the effects of age. A positive linear association between intelligence and REM anterior beta power was found in females but not males. Transient, spindle-like “REM beta tufts” are described in the EEG of healthy subjects, which may reflect the functioning of a recently described cingular-prefrontal emotion and motor regulation network. REM sleep frontal high delta power was a negative correlate of intelligence. NREM alpha and sigma spectral power correlations with intelligence did not unequivocally remain significant after multiple comparisons correction, but exhibited a similar sexual dimorphism. These results suggest that the neural oscillatory correlates of intelligence in sleep are sexually dimorphic, and they are not restricted to either sleep spindles or NREM sleep.
Construction of engineered corpus cavernosum with primary mesenchymal stem cells in vitro
Authors: Xie Xiaoshuai , Du Xiaohang , Li Kailin , Chen Yuan , Guan Yong , Zhao Xiaofei , Niu Guangzhu , Luan Yun , Zhang Denglu , Sun Chao , Cheng Guanghui , Wang Jue , Xin Qian , Xue Aibing , Wang Peng , Kong Feng , Liu Xiaoli , Wang Hongwei , Liu Yuqiang , Tian Chuan , Yuan Mingzhen , Liu Shuangde , Zhao Shengtian
Published: December 2017

Various methods have been used to reconstruct the penis. The objective of this study was to investigate the feasibility of constructing engineered corpus cavernosum with primary mesenchymal stem cells (MSCs) in a rabbit model in vitro. Acellular corporal matrices (ACMs) were obtained from adult rabbit penile tissues through an established decellularization procedure. MSCs were separated, purified, and then seeded on ACMs to construct engineered corpus cavernosum. The seeded ACMs were subsequently cultured in an incubator for 14 days. Histological analyses showed that MSCs seeded on the ACMs had proliferated and were well distributed. Detection of CD31, vWF, smooth muscle actin (SMA), and myosin protein as well as vWF and myosin mRNA revealed that the MSCs had differentiated into endothelial cells and smooth muscle cells. In addition, cell morphology of the engineered corpus cavernosum was directly observed by transmission electron microscopy. This study demonstrated that engineered corpus cavernosum could be successfully constructed using primary MSCs in vitro. This technology represents another step towards developing engineered corpus cavernosum in vitro.
Urotensin II-induced store-operated Ca2+ entry contributes to glomerular mesangial cell proliferation and extracellular matrix protein production under high glucose conditions
Authors: Soni Hitesh , Adebiyi Adebowale
Published: December 2017

Glomerular mesangial cell (GMC) proliferation and matrix expansion are pathological hallmarks of a wide range of kidney diseases, including diabetic nephropathy. Although the circulating level of peptide hormone urotensin II (UII) and kidney tissue expression of UII and UII receptors (UTR) are increased in diabetic nephropathy, it remains unclear whether UII regulates GMC growth and extracellular matrix (ECM) accumulation. In this study, we tested the hypothesis that UII-induced Ca2+ signaling controls GMC proliferation and ECM production under normal and high glucose conditions. Mouse GMCs cultured under normal glucose conditions proliferated and synthesized ECM proteins in response to stimulation by mouse UII. UII-induced GMC proliferation and ECM protein synthesis were dependent on TRPC4 channel-mediated store-operated Ca2+ entry (SOCE) and sequential activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and Ca2+/cAMP response element-binding protein (CREB) transcription factor. Under high glucose conditions, GMCs synthesized UII. Moreover, proliferation and ECM production in high glucose-challenged GMCs were attenuated by selective UTR antagonist, TRPC4 channel blocker, and CaMKII and CREB-binding protein/p300 inhibitors. These findings indicate that UII-induced SOCE via TRPC4 channels stimulates CaMKII/CREB-dependent GMC proliferation and ECM protein production. Our data also suggest that UII synthesis contributes to GMC proliferation and ECM accumulation under high glucose conditions.
Cropping System Conversion led to Organic Carbon Change in China’s Mollisols Regions
Authors: Tong Yuxin , Liu Jianguo , Li Xiaolin , Sun Jing , Herzberger Anna , Wei Dan , Zhang Weifeng , Dou Zhengxia , Zhang Fusuo
Published: December 2017

Land use change driven by diet, globalization, and technology advancement have greatly influenced agricultural production and environment in the mollisols region of China, with a marked impact on the depletion of soil organic matter, a signature property of mollisols. Here we report findings on soil organic carbon (SOC) change in three different cropping systems (soybean, soybean/maize, corn) in Northeast China during a 10-year time span. The results indicated that the decline rate of SOC in recent ten years (0.27 g kg−1 yr−1) has slowed down considerably compared to previous decades (1.12 g kg−1 yr−1). Crop system conversion from soybean monocropping to corn monocropping or break system was the critical factor for SOC change, and the background SOC was the second influence factor. When approaching a SOC turning point, conversion from low carbon input crop system (soybeans monocropping) to high carbon input crop system helped slow down the SOC decline (break crop) or even improve SOC (corn monocropping) in mollisols regions. This result implied that imported soybean has brought benefit for Northeast China. But for sustainable goal in China’s mollisols region, straw returning, optimized nitrogen fertilization and no tillage are all necessary whatever in continues maize or rotation system.
Integrated transcriptional analysis unveils the dynamics of cellular differentiation in the developing mouse hippocampus
Authors: Iacono Giovanni , Benevento Marco , Dubos Aline , Herault Yann , van Bokhoven Hans , Nadif Kasri Nael , Stunnenberg Hendrik G.
Published: December 2017

The ability to assign expression patterns to the individual cell types that constitute a tissue is a major challenge. This especially applies to brain, given its plethora of different, functionally interconnected cell types. Here, we derived cell type-specific transcriptome signatures from existing single cell RNA data and integrated these signatures with a newly generated dataset of expression (bulk RNA-Seq) of the postnatal developing mouse hippocampus. This integrated analysis allowed us to provide a comprehensive and unbiased prediction of the differentiation drivers for 11 different hippocampal cell types and describe how the different cell types interact to support crucial developmental stages. Our results provide a reliable resource of predicted differentiation drivers and insights into the multifaceted aspects of the cells in hippocampus during development.
Thy-1 dependent uptake of mesenchymal stem cell-derived extracellular vesicles blocks myofibroblastic differentiation
Authors: Shentu Tzu-Pin , Huang Tse-Shun , Cernelc-Kohan Mateja , Chan Joy , Wong Simon S. , Espinoza Celia R. , Tan Chunting , Gramaglia Irene , van der Heyde Henri , Chien Shu , Hagood James S.
Published: December 2017

Bone marrow-derived mesenchymal stem cells (MSC) have been promoted for multiple therapeutic applications. Many beneficial effects of MSCs are paracrine, dependent on extracellular vesicles (EVs). Although MSC-derived EVs (mEVs) are beneficial for acute lung injury and pulmonary fibrosis, mechanisms of mEV uptake by lung fibroblasts and their effects on myofibroblastic differentiation have not been established. We demonstrate that mEVs, but not fibroblast EVs (fEVs), suppress TGFβ1-induced myofibroblastic differentiation of normal and idiopathic pulmonary fibrosis (IPF) lung fibroblasts. MEVs display increased time- and dose-dependent cellular uptake compared to fEVs. Removal or blocking of Thy-1, or blocking Thy-1-beta integrin interactions, decreased mEV uptake and prevented suppression of myofibroblastic differentiation. MicroRNAs (miRs) 199a/b-3p, 21-5p, 630, 22-3p, 196a-5p, 199b-5p, 34a-5p and 148a-3p are selectively packaged in mEVs. In silico analyses indicated that IPF lung fibroblasts have increased expression of genes that are targets of mEV-enriched miRs. MiR-630 mimics blocked TGFβ1 induction of CDH2 in normal and IPF fibroblasts, and antagomiR-630 abrogated the effect of mEV on CDH2 expression. These data suggest that the interaction of Thy-1 with beta integrins mediates mEV uptake by lung fibroblasts, which blocks myofibroblastic differentiation, and that mEVs are enriched for miRs that target profibrotic genes up-regulated in IPF fibroblasts.