bluuebunny/crossref_metadata_2025_split huggingface dataset:
hiPSC-CM Monolayer Maturation State Determines Drug Responsiveness in High Throughput Pro-Arrhythmia Screen
Authors: da Rocha André Monteiro , Campbell Katherine , Mironov Sergey , Jiang Jiang , Mundada Lakshmi , Guerrero-Serna Guadalupe , Jalife José , Herron Todd J. 
Published: October 2017

AbstractHuman induced pluripotent stem cell derived cardiomyocytes (hiPSC-CMs) offer a novel in vitro platform for pre-clinical cardiotoxicity and pro-arrhythmia screening of drugs in development. To date hiPSC-CMs used for cardiotoxicity testing display an immature, fetal-like cardiomyocyte structural and electrophysiological phenotype which has called into question the applicability of hiPSC-CM findings to the adult heart. The aim of the current work was to determine the effect of cardiomyocyte maturation state on hiPSC-CM drug responsiveness. To this end, here we developed a high content pro-arrhythmia screening platform consisting of either fetal-like or mature hiPSC-CM monolayers. Compounds tested in the screen were selected based on the pro-arrhythmia risk classification (Low risk, Intermediate risk, or High risk) established recently by the FDA and major stakeholders in the Drug Discovery field for the validation of the Comprehensive In vitro Pro-Arrhythmia Assay (CiPA). Here we show that maturation state of hiPSC-CMs determines the absolute pro-arrhythmia risk score calculated for these compounds. Thus, the maturation state of hiPSC-CMs should be considered prior to pro-arrhythmia and cardiotoxicity screening in drug discovery programs.
White matter microstructure is associated with functional, cognitive and emotional symptoms 12 months after mild traumatic brain injury
Authors: Hellstrøm Torgeir , Westlye Lars T. , Kaufmann Tobias , Trung Doan Nhat , Søberg Helene L. , Sigurdardottir Solrun , Nordhøy Wibeke , Helseth Eirik , Andreassen Ole A. , Andelic Nada 
Published: October 2017

AbstractIdentifying patients at risk of poor outcome after mild traumatic brain injury (MTBI) is essential to aid prognostics and treatment. Diffuse axonal injury (DAI) may be the primary pathologic feature of MTBI but is normally not detectable by conventional imaging technology. This lack of sensitivity of clinical imaging techniques has impeded a pathophysiologic understanding of the long-term cognitive and emotional consequences of MTBI, which often remain unnoticed and are attributed to factors other than the injury. Diffusion tensor imaging (DTI) is sensitive to microstructural properties of brain tissue and has been suggested to be a promising candidate for the detection of DAIin vivo. In this study, we report strong associations between brain white matter DTI and self-reported cognitive, somatic and emotional symptoms at 12 months post-injury in 134 MTBI patients. The anatomical distribution suggested global associations, in line with the diffuse symptomatology, although the strongest effects were found in frontal regions including the genu of the corpus callosum and the forceps minor. These findings support the hypothesis that DTI may provide increased sensitivity to the diffuse pathophysiology of MTBI and suggest an important role of advanced Magnetic Resonance Imaging (MRI) in trauma care.
Arrhythmogenic cardiomyopathy related DSG2 mutations affect desmosomal cadherin binding kinetics
Authors: Dieding Mareike , Debus Jana Davina , Kerkhoff Raimund , Gaertner-Rommel Anna , Walhorn Volker , Milting Hendrik , Anselmetti Dario 
Published: October 2017

AbstractCadherins are calcium dependent adhesion proteins that establish the intercellular mechanical contact by bridging the gap to adjacent cells. Desmoglein-2 (Dsg2) is a specific cadherin of the cell-cell contact in cardiac desmosomes. Mutations in the DSG2-gene are regarded to cause arrhythmogenic (right ventricular) cardiomyopathy (ARVC) which is a rare but severe heart muscle disease. The molecular pathomechanisms of the vast majority of DSG2 mutations, however, are unknown. Here, we investigated the homophilic binding of wildtype Dsg2 and two mutations which are associated with ARVC. Using single molecule force spectroscopy and applying Jarzynski’s equality we determined the kinetics and thermodynamics of Dsg2 homophilic binding. Notably, the free energy landscape of Dsg2 dimerization exposes a high activation barrier which is in line with the proposed strand-swapping binding motif. Although the binding motif is not directly affected by the mutations the binding kinetics differ significantly from the wildtype. Furthermore, we applied a dispase based cell dissociation assay using HT1080 cell lines over expressing Dsg2 wildtype and mutants, respectively. Our molecular and cellular results consistently demonstrate that Dsg2 mutations can heavily affect homophilic Dsg2 interactions. Furthermore, the full thermodynamic and kinetic description of Dsg2 dimerization provides a consistent model of the so far discussed homophilic cadherin binding.
Palaeobiology of red and white blood cell-like structures, collagen and cholesterol in an ichthyosaur bone
Authors: Plet Chloé , Grice Kliti , Pagès Anais , Verrall Michael , Coolen Marco J. L. , Ruebsam Wolfgang , Rickard William D. A. , Schwark Lorenz 
Published: October 2017

AbstractCarbonate concretions are known to contain well-preserved fossils and soft tissues. Recently, biomolecules (e.g. cholesterol) and molecular fossils (biomarkers) were also discovered in a 380 million-year-old concretion, revealing their importance in exceptional preservation of biosignatures. Here, we used a range of microanalytical techniques, biomarkers and compound specific isotope analyses to report the presence of red and white blood cell-like structures as well as platelet-like structures, collagen and cholesterol in an ichthyosaur bone encapsulated in a carbonate concretion from the Early Jurassic (~182.7 Ma). The red blood cell-like structures are four to five times smaller than those identified in modern organisms. Transmission electron microscopy (TEM) analysis revealed that the red blood cell-like structures are organic in composition. We propose that the small size of the blood cell-like structures results from an evolutionary adaptation to the prolonged low oxygen atmospheric levels prevailing during the 70 Ma when ichthyosaurs thrived. The δ13C of the ichthyosaur bone cholesterol indicates that it largely derives from a higher level in the food chain and is consistent with a fish and cephalopod diet. The combined findings above demonstrate that carbonate concretions create isolated environments that promote exceptional preservation of fragile tissues and biomolecules.
Association between post-transplant red cell distribution width and prognosis of kidney transplant recipients
Authors: Park Sehoon , Kim Young Hoon , Kim Yong Chul , Yu Mi-Yeon , Lee Jung Pyo , Han Duck Jong , Kim Yon Su , Park Su-Kil 
Published: October 2017

AbstractThe role of elevated post-transplant red cell distribution width (RDW) as a predictive factor for graft loss remains unclear, although RDW was reported to be significantly associated with poor prognosis in various clinical fields. We performed a retrospective cohort study with 2,939 kidney transplant patients from two tertiary teaching hospitals in Korea. RDW level at transplantation and 3-months post-transplantation were collected. Those with RDW in the upper quartile range were considered to have increased RDW (>14.9%). Death-with-graft-function (DWGF), death-censored graft failure (DCGF), and composite graft loss were assessed as the study outcomes, using multivariable cox proportional hazard model. At the median follow-up duration of 6.6 (3.6–11.4) years, 336 patients experienced graft loss. There were 679 patients with elevated RDW at 3-months post-transplant. Elevated RDW was associated with composite graft loss (adjusted hazard ratio, 1.60, 95% confidence interval, 1.23–2.07, P < 0.001), even after adjusted for hemoglobin and various clinical factors. The 1% increment of post-transplant RDW was also significantly associated with the outcome, regardless of the presence of anemia. The worst prognosis was seen in patients with elevated RDW after transplantation, but not at baseline. Therefore, post-transplant RDW level may be significantly associated with patient prognosis, independent of hemoglobin values.
Tunable two-dimensional assembly of colloidal particles in rotating electric fields
Authors: Yakovlev Egor V. , Komarov Kirill A. , Zaytsev Kirill I. , Kryuchkov Nikita P. , Koshelev Kirill I. , Zotov Arsen K. , Shelestov Dmitry A. , Tolstoguzov Victor L. , Kurlov Vladimir N. , Ivlev Alexei V. , Yurchenko Stanislav O. 
Published: October 2017

AbstractTunable interparticle interactions in colloidal suspensions are of great interest because of their fundamental and practical significance. In this paper we present a new experimental setup for self-assembly of colloidal particles in two-dimensional systems, where the interactions are controlled by external rotating electric fields. The maximal magnitude of the field in a suspension is 25 V/mm, the field homogeneity is better than 1% over the horizontal distance of 250 μm, and the rotation frequency is in the range of 40 Hz to 30 kHz. Based on numerical electrostatic calculations for the developed setup with eight planar electrodes, we found optimal experimental conditions and performed demonstration experiments with a suspension of 2.12 μm silica particles in water. Thanks to its technological flexibility, the setup is well suited for particle-resolved studies of fundamental generic phenomena occurring in classical liquids and solids, and therefore it should be of interest for a broad community of soft matter, photonics, and material science.
Long-lived laser-induced arc discharges for energy channeling applications
Authors: Point Guillaume , Arantchouk Leonid , Thouin Emmanuelle , Carbonnel Jérôme , Mysyrowicz André , Houard Aurélien 
Published: October 2017

AbstractLaser filamentation offers a promising way for the remote handling of large electrical power in the form of guided arc discharges. We here report that it is possible to increase by several orders of magnitude the lifetime of straight plasma channels from filamentation-guided sparks in atmospheric air. A 30 ms lifetime can be reached using a low-intensity, 100 mA current pulse. Stability of the plasma shape is maintained over such a timescale through a continuous Joule heating from the current. This paves the way for applications based on the generation of straight, long duration plasma channels, like virtual plasma antennas or contactless transfer of electric energy.
Active modulation of the calcifying fluid carbonate chemistry (δ11B, B/Ca) and seasonally invariant coral calcification at sub-tropical limits
Authors: Ross Claire L. , Falter James L. , McCulloch Malcolm T. 
Published: October 2017

AbstractCoral calcification is dependent on both the supply of dissolved inorganic carbon (DIC) and the up-regulation of pH in the calcifying fluid (cf). Using geochemical proxies (δ11B, B/Ca, Sr/Ca, Li/Mg), we show seasonal changes in the pHcf and DICcf for Acropora yongei and Pocillopora damicornis growing in-situ at Rottnest Island (32°S) in Western Australia. Changes in pHcf range from 8.38 in summer to 8.60 in winter, while DICcf is 25 to 30% higher during summer compared to winter (×1.5 to ×2 seawater). Thus, both variables are up-regulated well above seawater values and are seasonally out of phase with one another. The net effect of this counter-cyclical behaviour between DICcf and pHcf is that the aragonite saturation state of the calcifying fluid (Ωcf) is elevated ~4 times above seawater values and is ~25 to 40% higher during winter compared to summer. Thus, these corals control the chemical composition of the calcifying fluid to help sustain near-constant year-round calcification rates, despite a seasonal seawater temperature range from just ~19° to 24 °C. The ability of corals to up-regulate Ωcf is a key mechanism to optimise biomineralization, and is thus critical for the future of coral calcification under high CO2 conditions.
Optogenetic Neuronal Silencing in Drosophila during Visual Processing
Authors: Mauss Alex S. , Busch Christian , Borst Alexander 
Published: October 2017

AbstractOptogenetic channels and ion pumps have become indispensable tools in neuroscience to manipulate neuronal activity and thus to establish synaptic connectivity and behavioral causality. Inhibitory channels are particularly advantageous to explore signal processing in neural circuits since they permit the functional removal of selected neurons on a trial-by-trial basis. However, applying these tools to study the visual system poses a considerable challenge because the illumination required for their activation usually also stimulates photoreceptors substantially, precluding the simultaneous probing of visual responses. Here, we explore the utility of the recently discovered anion channelrhodopsins GtACR1 and GtACR2 for application in the visual system of Drosophila. We first characterized their properties using a larval crawling assay. We further obtained whole-cell recordings from cells expressing GtACR1, which mediated strong and light-sensitive photocurrents. Finally, using physiological recordings and a behavioral readout, we demonstrate that GtACR1 enables the fast and reversible silencing of genetically targeted neurons within circuits engaged in visual processing.
Cytolytic toxin production by Staphylococcus aureus is dependent upon the activity of the protoheme IX farnesyltransferase
Authors: Stevens Emily , Laabei Maisem , Gardner Stewart , Somerville Greg A. , Massey Ruth C. 
Published: October 2017

AbstractStaphylococcus aureus is a medically important pathogen with an abundance of virulence factors that are necessary for survival within a host, including the production of cytolytic toxins. The regulation of toxin production is mediated by the Agr quorum sensing system, and a poorly defined post-exponential growth phase signal independent of Agr. As part of a recent genome wide association study (GWAS) to identify novel loci that alter the expression of cytolytic toxins, a polymorphism in the cyoE gene, which encodes a protoheme IX farnesyltransferase, was identified. This enzyme is essential for processing heme into the electron transport chain for use as an electron acceptor. Interestingly, without this enzyme S. aureus were repressed in their ability to secrete cytolytic toxins, and this appears to be mediated through repression of the Agr quorum sensing system. We hypothesize that the loss of electron transport is inducing feedback inhibition of metabolic capabilities that suppress the TCA cycle, and that this coupled with decreased RNAIII transcription prevents synthesis of cytolytic toxins.
FTY720-induced endocytosis of yeast and human amino acid transporters is preceded by reduction of their inherent activity and TORC1 inhibition
Authors: Barthelemy Céline , Barry Abdoulaye Oury , Twyffels Laure , André Bruno 
Published: October 2017

AbstractFTY720 is a sphingoid base analog that acts as an anticancer agent in animal models. Its effect on tumor cells stems largely from its ability to trigger endocytosis of several nutrient transporters. The observation that FTY720 similarly stimulates downregulation of amino acid permeases in yeast suggests that the cellular mechanisms it targets, which are still poorly characterized, are evolutionarily conserved. We here report that adding FTY720 to yeast cells results in rapid inhibition of the intrinsic activity of multiple permeases. This effect is associated with inhibition of the TORC1 kinase complex, which in turn promotes ubiquitin-dependent permease endocytosis. Further analysis of the Gap1 permease showed that FTY720 elicits its ubiquitylation via the same factors that promote this modification when TORC1 is inhibited by rapamycin. We also show that FTY720 promotes endocytosis of the LAT1/SLC7A5 amino acid transporter in HeLa cells, this being preceded by loss of its transport activity and by mTORC1 inhibition. Our data suggest that in yeast, TORC1 deactivation resulting from FTY720-mediated inhibition of membrane transport elicits permease endocytosis. The same process seems to occur in human cells even though our data and previous reports suggest that FTY720 promotes transporter endocytosis via an additional mechanism insensitive to rapamycin.
Deciphering pore-level precipitation mechanisms
Authors: Prasianakis N. I. , Curti E. , Kosakowski G. , Poonoosamy J. , Churakov S. V. 
Published: October 2017

AbstractMineral precipitation and dissolution in aqueous solutions has a significant effect on solute transport and structural properties of porous media. The understanding of the involved physical mechanisms, which cover a large range of spatial and temporal scales, plays a key role in several geochemical and industrial processes. Here, by coupling pore scale reactive transport simulations with classical nucleation theory, we demonstrate how the interplay between homogeneous and heterogeneous precipitation kinetics along with the non-linear dependence on solute concentration affects the evolution of the system. Such phenomena are usually neglected in pure macroscopic modelling. Comprehensive parametric analysis and comparison with laboratory experiments confirm that incorporation of detailed microscale physical processes in the models is compulsory. This sheds light on the inherent coupling mechanisms and bridges the gap between atomistic processes and macroscopic observations.
Transcriptomics and proteomics reveal genetic and biological basis of superior biomass crop Miscanthus
Authors: Sheng Jiajing , Zheng Xingfei , Wang Jia , Zeng Xiaofei , Zhou Fasong , Jin Surong , Hu Zhongli , Diao Ying 
Published: October 2017

AbstractMiscanthus is a rhizomatous C4 grass which is considered as potential high-yielding energy crop with the low-nutrient requirements, high water-use efficiency, and capability of C mitigation. To better understand the genetic basis, an integrative analysis of the transcriptome and proteome was performed to identify important genes and pathways involved in Miscanthus leaves. At the transcript level, 64,663 transcripts in M. lutarioriparius, 97,043 in M. sacchariflorus, 97,043 in M. sinensis, 67,323 in M. floridulus and 70,021 in M. × giganteus were detected by an RNA sequencing approach. At the protein level, 1964 peptide-represented proteins were identified and 1933 proteins differed by 1.5-fold or more in their relative abundance, as indicated by iTRAQ (isobaric tags for relative and absolute quantitation) analysis. Phylogenies were constructed from the nearly taxa of Miscanthus. A large number of genes closely related to biomass production were found. And SSR markers and their corresponding primers were derived from Miscanthus transcripts and 90% of them were successfully detected by PCR amplification among Miacanthus species. These similarities and variations on the transcriptional and proteomic level between Miscanthus species will serve as a resource for research in Miscanthus and other lignocellulose crops.
Spatial Heterogeneity of SOM Concentrations Associated with White-rot Versus Brown-rot Wood Decay
Authors: Bai Zhen , Ma Qiang , Dai Yucheng , Yuan Haisheng , Ye Ji , Yu Wantai 
Published: October 2017

AbstractWhite- and brown-rot fungal decay via distinct pathways imparts characteristic molecular imprints on decomposing wood. However, the effect that a specific wood-rotting type of fungus has on proximal soil organic matter (SOM) accumulation remains unexplored. We investigated the potential influence of white- and brown-rot fungi-decayedAbies nephrolepislogs on forest SOM stocks (i.e., soil total carbon (C) and nitrogen (N)) and the concentrations of amino sugars (microbial necromass) at different depths and horizontal distances from decaying woody debris. The brown-rot fungal wood decay resulted in higher concentrations of soil C and N and a greater increase in microbial necromass (i.e., 1.3- to 1.7-fold greater) than the white-rot fungal wood decay. The white-rot sets were accompanied by significant differences in the proportions of the bacterial residue index (muramic acid%) with soil depth; however, the brown-rot-associated soils showed complementary shifts, primarily in fungal necromass, across horizontal distances. Soil C and N concentrations were significantly correlated with fungal rather than bacterial necromass in the brown-rot systems. Our findings confirmed that the brown-rot fungi-dominated degradation of lignocellulosic residues resulted in a greater SOM buildup than the white-rot fungi-dominated degradation.
A chloroquine-induced macrophage-preconditioning strategy for improved nanodelivery
Authors: Wolfram Joy , Nizzero Sara , Liu Haoran , Li Feng , Zhang Guodong , Li Zheng , Shen Haifa , Blanco Elvin , Ferrari Mauro 
Published: October 2017

AbstractSite-specific localization is critical for improving the therapeutic efficacy and safety of drugs. Nanoparticles have emerged as promising tools for localized drug delivery. However, over 90% of systemically injected nanocarriers typically accumulate in the liver and spleen due to resident macrophages that form the mononuclear phagocyte system. In this study, the clinically approved antimalarial agent chloroquine was shown to reduce nanoparticle uptake in macrophages by suppressing endocytosis. Pretreatment of mice with a clinically relevant dose of chloroquine substantially decreased the accumulation of liposomes and silicon particles in the mononuclear phagocyte system and improved tumoritropic and organotropic delivery. The novel use of chloroquine as a macrophage-preconditioning agent presents a straightforward approach for addressing a major barrier in nanomedicine. Moreover, this priming strategy has broad applicability for improving the biodistribution and performance of particulate delivery systems. Ultimately, this study defines a paradigm for the combined use of macrophage-modulating agents with nanotherapeutics for improved site-specific delivery.
Dimethyl pyrazol-based nitrification inhibitors effect on nitrifying and denitrifying bacteria to mitigate N2O emission
Authors: Torralbo Fernando , Menéndez Sergio , Barrena Iskander , Estavillo José M. , Marino Daniel , González-Murua Carmen 
Published: October 2017

AbstractNitrous oxide (N2O) emissions have been increasing as a result of intensive nitrogen (N) fertilisation. Soil nitrification and denitrification are the main sources of N2O, and the use of ammonium-based fertilisers combined with nitrification inhibitors (NIs) could be useful in mitigating N2O emissions from agricultural systems. In this work we looked at the N2O mitigation capacity of two dimethylpyrazol-based NIs, 3,4-dimethylpyrazole phosphate (DMPP) and 2-(N-3,4-dimethyl-1H-pyrazol-1-yl) succinic acid isomeric mixture (DMPSA), on soil nitrifying and denitrifying microbial populations under two contrasting soil water contents (40% and 80% soil water filled pore space; WFPS). Our results show that DMPP and DMPSA are equally efficient at reducing N2O emissions under 40% WFPS conditions by inhibiting bacterial ammonia oxidation. In contrast, at 80% WFPS DMPSA was less efficient than DMPP at reducing N2O emissions. Interestingly, at 80% WFPS, where lowered oxygen availability limits nitrification, both DMPP and DMPSA not only inhibited nitrification but also stimulated N2O reduction to molecular nitrogen (N2) via nitrous oxide reductase activity (Nos activity). Therefore, in this work we observed that DMP-based NIs stimulated the reduction of N2O to N2by nitrous oxide reductase during the denitrification process.