bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detecting heritable phenotypes without a model using fast permutation testing for heritability and set-tests
Authors: Schweiger Regev , Fisher Eyal , Weissbrod Omer , Rahmani Elior , Müller-Nurasyid Martina , Kunze Sonja , Gieger Christian , Waldenberger Melanie , Rosset Saharon , Halperin Eran 
Published: November 2018

AbstractTesting for association between a set of genetic markers and a phenotype is a fundamental task in genetic studies. Standard approaches for heritability and set testing strongly rely on parametric models that make specific assumptions regarding phenotypic variability. Here, we show that resulting p-values may be inflated by up to 15 orders of magnitude, in a heritability study of methylation measurements, and in a heritability and expression quantitative trait loci analysis of gene expression profiles. We propose FEATHER, a method for fast permutation-based testing of marker sets and of heritability, which properly controls for false-positive results. FEATHER eliminated 47% of methylation sites found to be heritable by the parametric test, suggesting a substantial inflation of false-positive findings by alternative methods. Our approach can rapidly identify heritable phenotypes out of millions of phenotypes acquired via high-throughput technologies, does not suffer from model misspecification and is highly efficient.
Tuning the balance between dispersion and entropy to design temperature-responsive flexible metal-organic frameworks
Authors: Wieme J. , Lejaeghere K. , Kresse G. , Van Speybroeck V. 
Published: November 2018

AbstractTemperature-responsive flexibility in metal-organic frameworks (MOFs) appeals to the imagination. The ability to transform upon thermal stimuli while retaining a given crystalline topology is desired for specialized sensors and actuators. However, rational design of such shape-memory nanopores is hampered by a lack of knowledge on the nanoscopic interactions governing the observed behavior. Using the prototypical MIL-53(Al) as a starting point, we show that the phase transformation between a narrow-pore and large-pore phase is determined by a delicate balance between dispersion stabilization at low temperatures and entropic effects at higher ones. We present an accurate theoretical framework that allows designing breathing thermo-responsive MOFs, based on many-electron data for the dispersion interactions and density-functional theory entropy contributions. Within an isoreticular series of materials, MIL-53(Al), MIL-53(Al)-FA, DUT-4, DUT-5 and MIL-53(Ga), only MIL-53(Al) and MIL-53(Ga) are proven to switch phases within a realistic temperature range.
Determination of the two-dimensional distributions of gold nanorods by multiwavelength analytical ultracentrifugation
Authors: Wawra Simon E. , Pflug Lukas , Thajudeen Thaseem , Kryschi Carola , Stingl Michael , Peukert Wolfgang 
Published: November 2018

AbstractProperties of nanoparticles are influenced by various parameters like size, shape or composition. Comprehensive high throughput characterization techniques are urgently needed to improve synthesis, scale up to production and make way for new applications of multidimensional particulate systems. In this study, we present a method for measuring two-dimensional size distributions of plasmonic nanorods in a single experiment. Analytical ultracentrifuge equipped with a multiwavelength extinction detector is used to record the optical and sedimentation properties of gold nanorods simultaneously. A combination of sedimentation and extinction properties, both depending on diameter and length of the dispersed nanorods, is used to measure two-dimensional distributions of gold nanorod samples. The length, diameter, aspect ratio, volume, surface and cross-sectional distributions can be readily obtained from these results. As the technique can be extended to other non-spherical plasmonic particles and can be used for determining relative amounts of particles of different shapes it provides complete and quantitative insights into particulate systems.
Graphene controlled Brewster angle device for ultra broadband terahertz modulation
Authors: Chen Zefeng , Chen Xuequan , Tao Li , Chen Kun , Long Mingzhu , Liu Xudong , Yan Keyou , Stantchev Rayko I. , Pickwell-MacPherson Emma , Xu Jian-Bin 
Published: November 2018

AbstractTerahertz modulators with high tunability of both intensity and phase are essential for effective control of electromagnetic properties. Due to the underlying physics behind existing approaches there is still a lack of broadband devices able to achieve deep modulation. Here, we demonstrate the effect of tunable Brewster angle controlled by graphene, and develop a highly-tunable solid-state graphene/quartz modulator based on this mechanism. The Brewster angle of the device can be tuned by varying the conductivity of the graphene through an electrical gate. In this way, we achieve near perfect intensity modulation with spectrally flat modulation depth of 99.3 to 99.9 percent and phase tunability of up to 140 degree in the frequency range from 0.5 to 1.6 THz. Different from using electromagnetic resonance effects (for example, metamaterials), this principle ensures that our device can operate in ultra-broadband. Thus it is an effective principle for terahertz modulation.
The Trans Golgi Region is a Labile Intracellular Ca2+ Store Sensitive to Emetine
Authors: Gallegos-Gómez Martín-Leonardo , Greotti Elisa , López-Méndez María-Cristina , Sánchez-Vázquez Víctor-Hugo , Arias Juan-Manuel , Guerrero-Hernández Agustín 
Published: November 2018

AbstractThe Golgi apparatus (GA) is a bona fide Ca2+ store; however, there is a lack of GA-specific Ca2+ mobilizing agents. Here, we report that emetine specifically releases Ca2+ from GA in HeLa and HL-1 atrial myocytes. Additionally, it has become evident that the trans-Golgi is a labile Ca2+ store that requires a continuous source of Ca2+ from either the external milieu or from the ER, to enable it to produce a detectable transient increase in cytosolic Ca2+. Our data indicates that the emetine-sensitive Ca2+ mobilizing mechanism is different from the two classical Ca2+ release mechanisms, i.e. IP3 and ryanodine receptors. This newly discovered ability of emetine to release Ca2+ from the GA may explain why chronic consumption of ipecac syrup has muscle side effects.
Deterioration of willow seeds during storage
Authors: López-Fernández María Paula , Moyano Laura , Correa María Daniela , Vasile Franco , Burrieza Hernán Pablo , Maldonado Sara 
Published: November 2018

AbstractWillow (Salix spp.) seeds are able to tolerate desiccation, but differ from typical orthodox seeds in that they lose viability in a few days at room temperature, and in that the chloroplasts in embryo tissues do not dedifferentiate during maturation drying, thus retaining chlorophyll and maintaining intact their thylakoid membranes. In the present study, we investigated the damage generated in willow seeds during storage under appropriate conditions to exclude the eventual generation of reactive oxygen species by photooxidation. To this end, we measured different indicators of molecular damage, such as changes in the fatty acid profile, protein degradation, nuclease activities, and DNA damage, and evaluated normal germination and total germination in seeds stored for one, ten and sixteen years. We found: (i) a decrease in the fraction of unsaturated fatty acids; (ii) changes in the protein profile due to a decrease in protein solubility; (iii) activation of nucleases; and (iv) DNA fragmentation. Taken together, our findings identified programmed cell death as a key mechanism in seed deterioration during storage. We also found that, although the seeds maintained high percentages of total germination, the death program had already started in the seeds stored for ten years and was more advanced in those stored for sixteen years.
Optical coherence tomography angiography analysis of changes in the retina and the choroid after haemodialysis
Authors: Shin Yong Un , Lee Dong Eik , Kang Min Ho , Seong Mincheol , Yi Joo-Hark , Han Sang-Woong , Cho Heeyoon 
Published: November 2018

AbstractThe purpose of this study is to evaluate the effect of haemodialysis on perfused vessel density, choroidal thickness (CT), and retinal thickness in end-stage renal disease (ESRD) using swept-source optical coherence tomography angiography (SS-OCTA). We studied twenty-nine eyes of 29 ESRD patients by ophthalmologic examination and SS-OCTA before and after haemodialysis. The colour-coded perfusion density maps were generated and perfused vessel density was calculated. Changes in systemic and other ocular parameters such as retinal and choroidal thickness were measured and analysed. Total perfused vessel density decreased significantly after haemodialysis in the choriocapillaris; it was not significantly different in the superficial capillary plexus (SCP) and the deep capillary plexus (DCP). Total CT decreased significantly, but total retinal thickness was not significantly different. There was no significant correlation between choriocapillaris perfused vessel density and CT. The reduction in choriocapillaris perfused vessel density correlated with the decrease in systolic and mean arterial blood pressures. The decrease in CT correlated with the ultrafiltration volume. There were no significant systemic and ocular factors affecting change in retinal thickness and perfused vessel density of SCP and DCP. This is the first study to assess the effect of haemodialysis on blood flow changes using SS-OCTA; changes may be more prominent in the choroidal compared to the retinal layer.
A split luciferase-based probe for quantitative proximal determination of Gαq signalling in live cells
Authors: Littmann Timo , Ozawa Takeaki , Hoffmann Carsten , Buschauer Armin , Bernhardt Günther 
Published: November 2018

AbstractThe earlier an activation of a G protein-dependent signalling cascade at a G protein-coupled receptor (GPCR) is probed, the less amplificatory effects contribute to the measured signal. This is especially useful in case of a precise quantification of agonist efficacies, and is of paramount importance, when determining agonist bias in relation to the β-arrestin pathway. As most canonical assays with medium to high throughput rely on the quantification of second messengers, and assays affording more proximal readouts are often limited in throughput, we developed a technique with a proximal readout and sufficiently high throughput that can be used in live cells. Split luciferase complementation (SLC) was applied to assess the interaction of Gαqwith its effector phospholipase C-β3. The resulting probe yielded an excellent Z’ value of 0.7 and offers a broad and easy applicability to various Gαq-coupling GPCRs (hH1R, hM1,3,5R, hNTS1R), expressed in HEK293T cells, allowing the functional characterisation of agonists and antagonists. Furthermore, the developed sensor enabled imaging of live cells by luminescence microscopy, as demonstrated for the hM3R. The versatile SLC-based probe is broadly applicable e.g. to the screening and the pharmacological characterisation of GPCR ligands as well as to molecular imaging.
Digital mapping and spatial characteristics analyses of heavy metal content in reclaimed soil of industrial and mining abandoned land
Authors: Zhang Shiwen , Liu Huilin , Luo Ming , Zhou Xu , Lei Mei , Huang Yuanfang , Zhou Yan , Ge Chang 
Published: November 2018

AbstractThe reclaimed soil properties of industrial and mining wasteland have strong spatial specificity. The paper aimed to screen out a hybrid multifractal and kriging (Named as Mkriging) method for digital mapping and scientifically reveal the spatial distribution characteristics in view of heavy metal in reclaimed soil of industrial and mining abandoned land. The results of the study showed that for reasons of history and reclamation, the original samples of heavy metals in reclaimed soil of industrial and mining abandoned land showed a very large range and variation degree, theC0/(C0 + C1) values of different heavy metals basically were all greater than 50%, random factors played a dominant role. The five kinds of heavy metals in reclaimed soil were in the following descending order in terms of homogeneity: Cd, As, Hg, Ni and Cr. Compared with ordinary Kriging method, the relative improvement of root mean squared errors of elements Cd, Hg, As, Cr and Ni based on Mkriging were 95.28%, 61.74%, 78.54%, 82.51% and 83.58% respectively. The higher the fractal degree of heavy metals in reclaimed soil was, the higher the prediction accuracy will be. Mkriging method is more suitable for spatial prediction of heavy metals in reclaimed soil of industrial and mining abandoned land.
Wide-field choroidal thickness profile in healthy eyes
Authors: Rasheed Mohammed Abdul , Singh Sumit Randhir , Invernizzi Alessandro , Cagini Carlo , Goud Abhilash , Sahoo Niroj Kumar , Cozzi Mariano , Lupidi Marco , Chhablani Jay 
Published: November 2018

AbstractThe introduction of wide field optical coherence tomography (WF-OCT) has provided newer insights in the imaging of peripheral choroid. We evaluated choroidal thickness (CT) and large choroidal vessel thickness (LCVT) of 20 eyes in horizontal and vertical meridians using WF-OCT. A high-definition line scan through the fovea in both horizontal and vertical meridian was captured in primary and extremes of gaze to obtain scans up to mid-equator. CT and LCVT measurements were done across predefined points in macular area and all quadrants. LCVT was calculated after identifying a large choroidal vessel near choroidoscleral interface. The main outcome measures were differences in CT and LCVT in macular and four quadrants. Mean CT (331.23 ± 76.34 µ) and LCVT (201.46 ± 54.31 µ) in vertical macular segment were significantly more than CT (245.79 ± 55.38 µ; p = 0.0002) and LCVT (150.48 ± 52.58 µ; p = 0.004) in horizontal macular segment. CT at peripheral points in all quadrants was significantly reduced as compared to subfoveal CT (all p values < 0.05) with maximum reduction in inferior quadrant (64.5%). Using linear regression, only quadrant had a significant effect on CT and LCVT (both p < 0.001). CT and LCVT are highest at the macular area with reduction towards the periphery. The contribution of LCVT to CT is less at the fovea compared to other peripheral points.
Live E. coli bacteria label-free sensing using a microcavity in-line Mach-Zehnder interferometer
Authors: Janik Monika , Koba Marcin , Celebańska Anna , Bock Wojtek J. , Śmietana Mateusz 
Published: November 2018

AbstractThe paper presents the first study to date on selective label-free biosensing with a microcavity in-line Mach-Zehnder interferometer induced in an optical fiber. The sensing structures were fabricated in a single-mode fiber by femtosecond laser micromachining. In contrast to other studies of this sensing scheme, where only the sensitivity to refractive index changes in the cavity was investigated, this research used chemical surface treatment of the sensor to ensure detection specificity. Immobilized MS2 bacteriophages were applied as recognition elements specifically targeting live E. coli C3000 bacteria. It is shown that the sensor allows for real-time monitoring of biological phenomena taking place on the surface of the microcavity. The developed biosensor exhibits ultrahigh refractive index sensitivity of 15,000 nm/RIU and is capable of detecting live E. coli bacteria concentrations as low as 100 colony forming units (CFU)/mL in liquid volume as low as picoliters.
Synthetic bovine lactoferrin peptide Lfampin killsEntamoeba histolyticatrophozoites by necrosis and resolves amoebic intracecal infection in mice
Authors: Díaz-Godínez César , González-Galindo Ximena , Meza-Menchaca Thuluz , Bobes Raúl J. , de la Garza Mireya , León-Sicairos Nidia , Laclette Juan P. , Carrero Julio C. 
Published: November 2018

AbstractAmoebiasis caused by the protozoan parasite Entamoeba histolytica remains a public health problem in developing countries, making the identification of new anti-amoebic compounds a continuing priority. Previously, we have shown that lactoferrin (Lf) and several Lf-derived peptides exhibit in vitro anti-amoebic activity independently of their iron-binding activity. Here, we evaluated the amoebicidal effect of synthetic Lf-derived peptides Lfcin-B, Lfcin 17-30, and Lfampin, analyzed the mechanism of death induced by the peptides and determined their therapeutic effects on murine intestinal amoebiasis. MTT assays in trophozoite cultures of E. histolytica exposed to each peptide (1–1000 μM) showed that Lfampin is far more amoebicidal than Lfcins. Lfampin killed 80% of trophozoites at doses higher than 100 μM in 24 h, and FACs analysis using Annexin V/propidium iodide showed that death occurred mainly by necrosis. In contrast, Lfcin-B and Lfcin 17-30 appeared to have no significant effect on amoebic viability. FACs and confocal microscopy analysis using FITC-labeled peptides showed that all three peptides are internalized by the amoeba mainly using receptor (PI3K signaling) and actin-dependent pathways but independent of clathrin. Docking studies identified cholesterol in the amoeba’s plasma membrane as a possible target of Lfampin. Oral treatment of intracecally infected mice with the abovementioned peptides at 10 mg/kg for 4 days showed that Lfampin resolved 100% of the cases of intestinal amoebiasis, whereas Lfcin 17-30 and Lfcin-B were effective in resolving infection in 80 and 70% of cases, respectively. These data show that although synthetic bovine Lf-derived peptides exhibit varying amoebicidal potentials in vitro, they do resolve murine intestinal amoebiasis efficiently, suggesting that they may be useful as a therapeutic treatment.
The association between peroxisome proliferator-activated receptor Δ rs3777744, rs3798343, and rs6922548 and coronary artery disease
Authors: Zhang Jing , Liu Xiu-ling , Jia Qiao-wei , Zhao Chen-hui , Liu Jie-yin , An Feng-hui , Li Li-hua , Chen Zhao-hong , Wang Lian-sheng , Ma Wen-zhu , Yang Zhi-jian , Jia En-zhi 
Published: November 2018

Abstract
Objective: The aim of the present study is to investigate the association between the single nucleotide polymorphism (SNP) sites of peroxisome proliferator-activated receptor Δ (PPARD) and the risk of coronary artery disease (CAD). To this end, a prospective observational single-center study of the clinical data from 880 subjects in a Chinese population was conducted. Methods: A total of 880 subjects, including 609 CAD patients and 271 control subjects, were selected for the present study. All inpatients had 4 ml of venous blood drawn after 12 h of fasting, and then clinical tests were conducted to obtain the biochemical parameters. CAD patients and Controls were distinguished by coronary angiography. Statistical analysis was conducted with SPSS software (ver 16.0). Results: A significant association between the G-alleles of PPARD rs3777744 and rs3798343 and a decreased risk for CAD was found. Moreover, we found an interaction between high fasting high-density lipoprotein cholesterol (HDL-C) serum levels, low serum glucose levels and their genotypes, ultimately decreasing the risk of CAD. Haplotype analysis was conducted on the three SNP sites, rs3777744 and rs3798343 to form a block [r2 = 0.79, D′ = 0.99). The A-C haplotypes were associated with an increased risk of CAD (odds ratio (OR), 95% confidence interval (CI): 1.321 (1.060–1.647), P=0.013], and the G-G haplotypes were associated with a decreased risk [OR, 95% CI: 0.714 (0.567–0.849), P=0.004]. Conclusions: Our study indicates a significant association between the G-alleles of PPARD rs3777744 and rs3798343 and a decreased CAD risk. In addition, genotypes interact with high serum HDL-C levels and low serum glucose levels, resulting in decreased prevalence of CAD.
Immunglobulin-A-Isotyp bei Anti-HLA-Antikörpern und Organüberleben von Patienten nach Nierentransplantation
Authors: Arnold Marie-Luise , Bach Christian , Spriewald Bernd 
Published: November 2018

ZusammenfassungAnti-Human-Leukocyte-Antigen-Antikörper (HLA-Ak) des Isotyps Immunglobulin A (IgA) erkennen ihr Zielantigen mit einer sehr hohen Affinität und Avidität. Eine systematische Erforschung des Einflusses von Anti-HLA-IgA-Antikörpern auf die Organabstoßung und den Organfunktionsverlust nach Organtransplantation hat gerade erst begonnen. Anhand der hier vorgestellten Arbeit soll gezeigt werden, dass neben der bekannten Beteiligung von Anti-HLA-Immunglobulin G (IgG) auch Anti-HLA-IgA eine Rolle bei der Organabstoßung spielen könnte. Im Rahmen der Studie wurden Seren von 276 Patienten untersucht. Alle Patienten hatten bereits mindestens eine Nierentransplantation bekommen und wurden aufgrund eines Funktionsverlusts des transplantierten Organs wieder dialysepflichtig. Als Messparameter für das Organüberleben wurde die in Monaten gemessene Dauer zwischen erfolgter Nierentransplantation und erneuter Dialyse nach Transplantation („Time to Dialysis“, TtD, Median) herangezogen. Die Testung des Ak-Profils der Patientenseren für die Isotpyen IgG und IgA wurde mittels Luminex-basierter Methode durchgeführt. Von den 276 getesteten Seren waren 89 Ak-positiv für Anti-HLA-IgA und 243 positiv für Anti-HLA-IgG. Es wurde eine starke Korrelation der beiden untersuchten Isotypen beobachtet (p < 0,0001). 86 von 89 der Anti-HLA-IgA-positiven Seren waren ebenfalls IgG-positiv. Wie erwartet hatten Patienten ohne Anti-HLA-Ak das längste Organüberleben (TtD 127 Monate). Patienten mit ausschließlich Anti-HLA-IgG zeigten im Vergleich dazu ein verringertes mittleres Organüberleben (TtD 116 Monate). Interessanterweise wurde ein signifikant verringertes Organüberleben bei IgA- und IgG-Ak doppelt positiven Patienten (TtD 88 Monate, p < 0,001) beobachtet. Nur 3 Patienten zeigten ausschließlich IgA-Ak, eine statistische Auswertung der TtD-Zeit ist hier nicht möglich. In einer früheren Studie mit 694 Patienten konnte bereits gezeigt werden, dass bei Patienten mit Anti-HLA-IgA-Ak, die spezifisch gegen das Spenderorgan gerichtet waren, das Organüberleben deutlich auf 76 Monate verringert war – wogegen Patienten mit nicht spenderspezifischen Anti-HLA-IgA-Ak im Median erst nach 82 Monaten wieder dialysepflichtig wurden. Die gleichzeitige Anwesenheit von Anti-HLA-IgA- und Anti-HLA-IgG-Ak im Serum von Patienten nach Nierentransplantation stellt eine hohe Risikoprognose für ein mögliches Organversagen dar. Dies zeigte sich in einer signifikant kürzeren Organüberlebenszeit verglichen mit transplantierten Patienten, bei denen lediglich Anti-HLA-IgG-Ak nachgewiesen wurden. Diese Daten deuten darauf hin, dass die – momentan nicht routinemäßig durchgeführte – Testung von Anti-HLA-IgA als neuer Parameter für eine bessere Risikostratifizierung sowohl vor als auch nach Nierentransplantation dienen könnte.