bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seizure activity results in calcium- and mitochondria-independent ROS production via NADPH and xanthine oxidase activation
Authors: Kovac S , Domijan A-M , Walker M C , Abramov A Y 
Published: October 2014

AbstractSeizure activity has been proposed to result in the generation of reactive oxygen species (ROS), which then contribute to seizure-induced neuronal damage and eventually cell death. Although the mechanisms of seizure-induced ROS generation are unclear, mitochondria and cellular calcium overload have been proposed to have a crucial role. We aim to determine the sources of seizure-induced ROS and their contribution to seizure-induced cell death. Using live cell imaging techniques in glioneuronal cultures, we show that prolonged seizure-like activity increases ROS production in an NMDA receptor-dependent manner. Unexpectedly, however, mitochondria did not contribute to ROS production during seizure-like activity. ROS were generated primarily by NADPH oxidase and later by xanthine oxidase (XO) activity in a calcium-independent manner. This calcium-independent neuronal ROS production was accompanied by an increase in intracellular [Na+] through NMDA receptor activation. Inhibition of NADPH or XO markedly reduced seizure-like activity-induced neuronal apoptosis. These findings demonstrate a critical role for ROS in seizure-induced neuronal cell death and identify novel therapeutic targets.
The activation of G protein-coupled receptor 30 (GPR30) inhibits proliferation of estrogen receptor-negative breast cancer cells in vitro and in vivo
Authors: Wei W , Chen Z-J , Zhang K-S , Yang X-L , Wu Y-M , Chen X-H , Huang H-B , Liu H-L , Cai S-H , Du J , Wang H-S 
Published: October 2014

AbstractThere is an urgent clinical need for safe and effective treatment agents and therapy targets for estrogen receptor negative (ER−) breast cancer. G protein-coupled receptor 30 (GPR30), which mediates non-genomic signaling of estrogen to regulate cell growth, is highly expressed in ER− breast cancer cells. We here showed that activation of GPR30 by the receptor-specific agonist G-1 inhibited the growth of ER− breast cancer cells in vitro. Treatment of ER− breast cancer cells with G-1 resulted in G2/M-phase arrest, downregulation of G2-checkpoint regulator cyclin B, and induction of mitochondrial-related apoptosis. The G-1 treatment increased expression of p53 and its phosphorylation levels at Serine 15, promoted its nuclear translocation, and inhibited its ubiquitylation, which mediated the growth arrest effects on cell proliferation. Further, the G-1 induced sustained activation and nuclear translocation of ERK1/2, which was mediated by GPR30/epidermal growth factor receptor (EGFR) signals, also mediated its inhibition effects of G-1. With extensive use of siRNA-knockdown experiments and inhibitors, we found that upregulation of p21 by the cross-talk of GPR30/EGFR and p53 was also involved in G-1-induced cell growth arrest. In vivo experiments showed that G-1 treatment significantly suppressed the growth of SkBr3 xenograft tumors and increased the survival rate, associated with proliferation suppression and upregulation of p53, p21 while downregulation of cyclin B. The discovery of multiple signal pathways mediated the suppression effects of G-1 makes it a promising candidate drug and lays the foundation for future development of GPR30-based therapies for ER− breast cancer treatment.
Histone deacetylase inhibitors promote glioma cell death by G2 checkpoint abrogation leading to mitotic catastrophe
Authors: Cornago M , Garcia-Alberich C , Blasco-Angulo N , Vall-llaura N , Nager M , Herreros J , Comella J X , Sanchis D , Llovera M 
Published: October 2014

AbstractGlioblastoma multiforme is resistant to conventional anti-tumoral treatments due to its infiltrative nature and capability of relapse; therefore, research efforts focus on characterizing gliomagenesis and identifying molecular targets useful on therapy. New therapeutic strategies are being tested in patients, such as Histone deacetylase inhibitors (HDACi) either alone or in combination with other therapies. Here two HDACi included in clinical trials have been tested, suberanilohydroxamic acid (SAHA) and valproic acid (VPA), to characterize their effects on glioma cell growth in vitro and to determine the molecular changes that promote cancer cell death. We found that both HDACi reduce glioma cell viability, proliferation and clonogenicity. They have multiple effects, such as inducing the production of reactive oxygen species (ROS) and activating the mitochondrial apoptotic pathway, nevertheless cell death is not prevented by the pan-caspase inhibitor Q-VD-OPh. Importantly, we found that HDACi alter cell cycle progression by decreasing the expression of G2 checkpoint kinases Wee1 and checkpoint kinase 1 (Chk1). In addition, HDACi reduce the expression of proteins involved in DNA repair (Rad51), mitotic spindle formation (TPX2) and chromosome segregation (Survivin) in glioma cells and in human glioblastoma multiforme primary cultures. Therefore, HDACi treatment causes glioma cell entry into mitosis before DNA damage could be repaired and to the formation of an aberrant mitotic spindle that results in glioma cell death through mitotic catastrophe-induced apoptosis.
ANG-2 for quantitative Na+ determination in living cells by time-resolved fluorescence microscopy
Authors: Roder Phillip , Hille Carsten 
Published: October 2014

AbstractSodium ions (Na+) play an important role in a plethora of cellular processes, which are complex and partly still unexplored. For the investigation of these processes and quantification of intracellular Na+concentrations ([Na+]i), two-photon coupled fluorescence lifetime imaging microscopy (2P-FLIM) was performed in the salivary glands of the cockroachPeriplaneta americana. For this, the novel Na+-sensitive fluorescent dye Asante NaTRIUM Green-2 (ANG-2) was evaluated, bothin vitroandin situ. In this context, absorption coefficients, fluorescence quantum yields and 2P action cross-sections were determined for the first time. ANG-2 was 2P-excitable over a broad spectral range and displayed fluorescence in the visible spectral range. Although the fluorescence decay behaviour of ANG-2 was triexponentialin vitro, its analysis indicates a Na+-sensitivity appropriate for recordings in living cells. The Na+-sensitivity was reducedin situ, but the biexponential fluorescence decay behaviour could be successfully analysed in terms of quantitative [Na+]irecordings. Thus, physiological 2P-FLIM measurements revealed a dopamine-induced [Na+]irise in cockroach salivary gland cells, which was dependent on a Na+-K+-2Cl−cotransporter (NKCC) activity. It was concluded that ANG-2 is a promising new sodium indicator applicable for diverse biological systems.
In‐the‐ear spiral monopole antenna for hearing instruments
Authors: Kammersgaard N.P.I. , Kvist S.H. , Thaysen J. , Jakobsen K.B. 
Published: October 2014

A novel in‐the‐ear (ITE) antenna solution for hearing instruments that operates at 2.45 GHz is presented. The antenna consists of a quarter wave monopole and a ground plane that are placed in the ear. The simulated path gain |S21| is −86 dB and the measured path gain is −80 dB. Simulations and measurements show that the antenna covers the entire 2.40–2.48 GHz industrial, scientific and medical (ISM) band. It is the first ever ITE‐antenna solution that demonstrates the possibility of establishing an ear‐to‐ear link by using a standard Bluetooth chip.
Towards 1 Tbit/s SOA‐based 1310 nm transmission for local area network/data centre applications
Authors: Mazurek Paweł , de Waardt Huug , Turkiewicz Jarosław Piotr 
Published: October 2014

The growing data traffic in the local area networks is driving development of the cost‐effective transmission systems that can carry it effectively. In this study, firstly, we investigate the influence of a semiconductor optical amplifier (SOA) on the transmission quality in the 1310 nm wavelength‐division‐multiplexed system. We examine the differences in the channels gain and power penalty depending on the applied channel spacing. Moreover, we analyse the transmission‐related power penalty suffered during the transmission over the link consisting of the standard single‐mode fibre (SSMF) and a SOA. Furthermore, we propose the 1310 nm dense‐wavelength‐division multiplexed and polarisation multiplexed transmission system architecture which counteracts the key performance limitation that can be encountered in the 1310 nm window transmission systems. The demonstrated n × 2 × 40 Gbit/s transmission system is based exclusively on semiconductor components without any form of the chromatic dispersion compensation or error correction. Results of the conducted experiments show the excellent error‐free 8 × 2 × 40 Gbit/s all‐semiconductor transmission over 25 km of SSMF. The demonstrated transmission system can be utilised to realise ultra‐high‐speed connections like the next generation 400 Gbit/s and 1 Tbit/s Ethernet.
Tunable lens driven by dielectric elastomer actuator with ionic electrodes
Authors: Liang Dao , Lin Zi‐Fang , Huang Cheng‐Chun , Shih Wen‐Pin 
Published: October 2014

A tunable lens driven by a dielectric elastomer actuator is developed. A solution of NaCl was used as the deformable lens and one of the electrodes for applying a bias voltage across the actuator. The dielectric elastomer actuator was made of a curved polydimethylsiloxane (PDMS) thin film sandwiched between a gold electrode and the NaCl solution. When a bias voltage was applied, the electrostatic force induced a radial compression, causing a lateral deflection of the PDMS. The radius of the curvature of the NaCl lens was consequently changed. The variation of the focal length under different bias voltages was characterised separately using two different approaches, and consistent results were obtained. The lens diameter was 4 mm. The focus lens can be tuned from 16.1 to 13.1 mm when the bias voltage is increased from 0 to 900 V.
Network histograms and universality of blockmodel approximation
Authors: Olhede Sofia C. , Wolfe Patrick J. 
Published: October 2014

Significance
Representing and understanding large networks remains a major challenge across the sciences, with a strong focus on communities: groups of network nodes whose connectivity properties are similar. Here we argue that, independently of the presence or absence of actual communities in the data, this notion leads to something stronger: a histogram representation, in which blocks of network edges that result from community groupings can be interpreted as two-dimensional histogram bins. We provide an automatic procedure to determine bin widths for any given network and illustrate our methodology using two publicly available network datasets.
Structure of a PE–PPE–EspG complex fromMycobacterium tuberculosisreveals molecular specificity of ESX protein secretion
Authors: Ekiert Damian C. , Cox Jeffery S. 
Published: October 2014

SignificanceMycobacterium tuberculosis(Mtb) infects nearly a third of the global population, and understanding howMtbestablishes infection and evades host responses is key to development of improved therapies. Two mysterious protein families, called Pro-Glu motif–containing (PE) and Pro-Pro-Glu motif–containing (PPE) proteins, are highly expanded inMtband have been linked to virulence, but their function remains unknown. We have determined the crystal structure of a PE-PPE protein dimer bound to ESAT-6 secretion system (ESX) secretion-associated protein G (EspG), a component of the secretion system that translocates PE-PPE proteins to the bacterial cell surface. This structure reveals how each of the four EspGs inMtbinteracts with a different subset of the ∼100 PE and ∼70 PPE proteins, directing specific classes of PE-PPE “effector” proteins through separate secretory pathways.
Rethinking fat as a fuel for endurance exercise
Authors: Volek Jeff S. , Noakes Timothy , Phinney Stephen D. 
Published: October 2014

AbstractA key element contributing to deteriorating exercise capacity during physically demanding sport appears to be reduced carbohydrate availability coupled with an inability to effectively utilize alternative lipid fuel sources. Paradoxically, cognitive and physical decline associated with glycogen depletion occurs in the presence of an over‐abundance of fuel stored as body fat that the athlete is apparently unable to access effectively. Current fuelling tactics that emphasize high‐carbohydrate intakes before and during exercise inhibit fat utilization. The most efficient approach to accelerate the body's ability to oxidize fat is to lower dietary carbohydrate intake to a level that results in nutritional ketosis (i.e., circulating ketone levels >0.5 mmol/L) while increasing fat intake for a period of several weeks. The coordinated set of metabolic adaptations that ensures proper interorgan fuel supply in the face of low‐carbohydrate availability is referred to as keto‐adaptation. Beyond simply providing a stable source of fuel for the brain, the major circulating ketone body, beta‐hydroxybutyrate, has recently been shown to act as a signalling molecule capable of altering gene expression, eliciting complementary effects of keto‐adaptation that could extend human physical and mental performance beyond current expectation. In this paper, we review these new findings and propose that the shift to fatty acids and ketones as primary fuels when dietary carbohydrate is restricted could be of benefit for some athletes.
Christianity: A Very Short Introduction
Authors: Woodhead Linda 
Published: October 2014

Abstract
At a time when Christianity is flourishing in the Southern hemisphere but declining in much of the West, Christianity: A Very Short Introduction offers an important overview of the world's largest religion. Exploring the cultural and institutional dimensions of Christianity, and tracing its course over two millennia, it provides a candid portrait of Christianity's past and present. Addressing topics including the competition for power between different forms of Christianity, the churches' use of power, and its struggles with modernity, this VSI includes up-to-date information on the growth and geographical spread of Eastern Christianity, reflecting the global nature of Christianity in our ever-shifting contemporary culture.
The Induced Innovation Hypothesis and U.S. Public Agricultural Research
Authors: Cowan Benjamin W. , Lee Daegoon , Shumway C. Richard 
Published: October 2014

AbstractApplicability of the induced innovation hypothesis—that a change in relative input prices induces innovation to economize use of the increasingly expensive input (Hicks 1932)—is examined for U.S. public agricultural research. A reduced‐form test is developed using input prices from the agricultural production sector, expenditures from the public research sector aimed at developing new technology to save specific agricultural inputs, and variables to control for innovation marginal cost differences and nonhomotheticity. Unlike recent demand‐side studies that soundly reject the induced innovation hypothesis for agriculture, support for the hypothesis is found for several input pairings through these tests of public agricultural research using state‐level panel data.
A Python package for parsing, validating, mapping and formatting sequence variants using HGVS nomenclature
Authors: Hart Reece K. , Rico Rudolph , Hare Emily , Garcia John , Westbrook Jody , Fusaro Vincent A. 
Published: October 2014

Abstract
Summary: Biological sequence variants are commonly represented in scientific literature, clinical reports and databases of variation using the mutation nomenclature guidelines endorsed by the Human Genome Variation Society (HGVS). Despite the widespread use of the standard, no freely available and comprehensive programming libraries are available. Here we report an open-source and easy-to-use Python library that facilitates the parsing, manipulation, formatting and validation of variants according to the HGVS specification. The current implementation focuses on the subset of the HGVS recommendations that precisely describe sequence-level variation relevant to the application of high-throughput sequencing to clinical diagnostics.
Availability and implementation: The package is released under the Apache 2.0 open-source license. Source code, documentation and issue tracking are available at http://bitbucket.org/hgvs/hgvs/ . Python packages are available at PyPI ( https://pypi.python.org/pypi/hgvs ).
Contact: reecehart@gmail.com
Supplementary information: Supplementary data are available at Bioinformatics online.
PROPER: comprehensive power evaluation for differential expression using RNA-seq
Authors: Wu Hao , Wang Chi , Wu Zhijin 
Published: October 2014

Abstract
Motivation : RNA-seq has become a routine technique in differential expression (DE) identification. Scientists face a number of experimental design decisions, including the sample size. The power for detecting differential expression is affected by several factors, including the fraction of DE genes, distribution of the magnitude of DE, distribution of gene expression level, sequencing coverage and the choice of type I error control. The complexity and flexibility of RNA-seq experiments, the high-throughput nature of transcriptome-wide expression measurements and the unique characteristics of RNA-seq data make the power assessment particularly challenging.
Results : We propose prospective power assessment instead of a direct sample size calculation by making assumptions on all of these factors. Our power assessment tool includes two components: (i) a semi-parametric simulation that generates data based on actual RNA-seq experiments with flexible choices on baseline expressions, biological variations and patterns of DE; and (ii) a power assessment component that provides a comprehensive view of power. We introduce the concepts of stratified power and false discovery cost, and demonstrate the usefulness of our method in experimental design (such as sample size and sequencing depth), as well as analysis plan (gene filtering).
Availability : The proposed method is implemented in a freely available R software package PROPER.
Contact : hao.wu@emory.edu , zhijin_wu@brown.edu .
Supplementary information: Supplementary data are available at Bioinformatics online.
MulRF: a software package for phylogenetic analysis using multi-copy gene trees
Authors: Chaudhary Ruchi , Fernández-Baca David , Burleigh John Gordon 
Published: October 2014

Abstract
Summary: MulRF is a platform-independent software package for phylogenetic analysis using multi-copy gene trees. It seeks the species tree that minimizes the Robinson–Foulds (RF) distance to the input trees using a generalization of the RF distance to multi-labeled trees. The underlying generic tree distance measure and fast running time make MulRF useful for inferring phylogenies from large collections of gene trees, in which multiple evolutionary processes as well as phylogenetic error may contribute to gene tree discord. MulRF implements several features for customizing the species tree search and assessing the results, and it provides a user-friendly graphical user interface (GUI) with tree visualization. The species tree search is implemented in C++ and the GUI in Java Swing.
Availability: MulRF’s executable as well as sample datasets and manual are available at http://genome.cs.iastate.edu/CBL/MulRF/ , and the source code is available at https://github.com/ruchiherself/MulRFRepo .
Contact: ruchic@ufl.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Anesthesia and Increased Hypercarbic Drive Impair the Coordination between Breathing and Swallowing
Authors: D’Angelo Olivia M. , Diaz-Gil Daniel , Nunn Danuza , Simons Jeroen C. P. , Gianatasio Chloe , Mueller Noomi , Meyer Matthew J. , Pierce Eric , Rosow Carl , Eikermann Matthias 
Published: October 2014

Abstract

Background:
Coordination between breathing and swallowing helps prevent aspiration of foreign material into the respiratory tract. The authors examined the effects of anesthesia and hypercapnia on swallowing–breathing coordination.

Methods:
In a randomized controlled crossover study, general anesthesia with propofol or sevoflurane was titrated using an up-down method to identify the threshold for suppression of the motor response to electrical stimulation of the forearm. Additional measurements included bispectral index, genioglossus electromyogram, ventilation (pneumotachometer), and hypopharyngeal pressure. During wakefulness and at each level of anesthesia, carbon dioxide was added to increase the end-tidal pressure by 4 and 8 mmHg. A swallow was defined as increased genioglossus activity with deglutition apnea and an increase in hypopharyngeal pressure. Spontaneous swallows were categorized as physiological (during expiration or followed by expiration) or pathological (during inspiration or followed by an inspiration).

Results:
A total of 224 swallows were analyzed. Anesthesia increased the proportion of pathological swallows (25.9% vs. 4.9%) and decreased the number of swallows per hour (1.7 ± 3.3 vs. 28.0 ± 22.3) compared to wakefulness. During anesthesia, hypercapnia decreased hypopharyngeal pressure during inspiration (−14.1 ± 3.7 vs. −8.7 ± 2 mmHg) and increased minute ventilation, the proportion of pathological swallows (19.1% vs. 12.3%), and the number of swallows per hour (5.5 ± 17.0. vs. 1.3 ± 5.5).

Conclusions:
Anesthesia impaired the coordination between swallowing and respiration. Mild hypercapnia increased the frequency of swallowing during anesthesia and the likelihood of pathological swallowing. During anesthesia, the risk for aspiration may be further increased when ventilatory drive is stimulated.
Quantitative differences in developmental profiles of spontaneous activity in cortical and hippocampal cultures
Authors: Charlesworth Paul , Cotterill Ellese , Morton Andrew , Grant Seth G. N. , Eglen Stephen J. 
Published: October 2014

AbstractBackgroundNeural circuits can spontaneously generate complex spatiotemporal firing patterns during development. This spontaneous activity is thought to help guide development of the nervous system. In this study, we had two aims. First, to characterise the changes in spontaneous activity in cultures of developing networks of either hippocampal or cortical neurons dissociated from mouse. Second, to assess whether there are any functional differences in the patterns of activity in hippocampal and cortical networks.ResultsWe used multielectrode arrays to record the development of spontaneous activity in cultured networks of either hippocampal or cortical neurons every two or three days for the first month after plating. Within a few days of culturing, networks exhibited spontaneous activity. This activity strengthened and then stabilised typically around 21 daysin vitro. We quantified the activity patterns in hippocampal and cortical networks using eleven features. Three out of eleven features showed striking differences in activity between hippocampal and cortical networks. 1: Interburst intervals are less variable in spike trains from hippocampal cultures. 2: Hippocampal networks have higher correlations. 3: Hippocampal networks generate more robust theta bursting patterns. Machine learning techniques confirmed that these differences in patterning are sufficient to reliably classify recordings at any given age as either hippocampal or cortical networks.ConclusionsAlthough cultured networks of hippocampal and cortical networks both generate spontaneous activity that changes over time, at any given time we can reliably detect differences in the activity patterns. We anticipate that this quantitative framework could have applications in many areas, including neurotoxicity testing and for characterising phenotype of different mutant mice. All code and data relating to this report are freely available for others to use.