bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induction of COX-2-PGE2 synthesis by activation of the MAPK/ERK pathway contributes to neuronal death triggered by TDP-43-depleted microglia
Authors: Xia Q , Hu Q , Wang H , Yang H , Gao F , Ren H , Chen D , Fu C , Zheng L , Zhen X , Ying Z , Wang G 
Published: March 2015

AbstractNeuroinflammation is a striking hallmark of amyotrophic lateral sclerosis (ALS) and other neurodegenerative disorders. Previous studies have shown the contribution of glial cells such as astrocytes in TDP-43-linked ALS. However, the role of microglia in TDP-43-mediated motor neuron degeneration remains poorly understood. In this study, we show that depletion of TDP-43 in microglia, but not in astrocytes, strikingly upregulates cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) production through the activation of MAPK/ERK signaling and initiates neurotoxicity. Moreover, we find that administration of celecoxib, a specific COX-2 inhibitor, greatly diminishes the neurotoxicity triggered by TDP-43-depleted microglia. Taken together, our results reveal a previously unrecognized non-cell-autonomous mechanism in TDP-43-mediated neurodegeneration, identifying COX-2-PGE2 as the molecular events of microglia- but not astrocyte-initiated neurotoxicity and identifying celecoxib as a novel potential therapy for TDP-43-linked ALS and possibly other types of ALS.
Loss of fibroblast growth factor 21 action induces insulin resistance, pancreatic islet hyperplasia and dysfunction in mice
Authors: So W Y , Cheng Q , Xu A , Lam K S L , Leung P S 
Published: March 2015

AbstractFibroblast growth factor (FGF) 21 is an endocrine factor that normalizes glucose homeostasis and reduces insulin resistance in diabetes. Although the pancreas is an FGF21 target organ, its role in pancreatic islets remains obscure. This study aimed to elucidate the physiological role of FGF21 in pancreatic islets using FGF21-knockout (FGF21-KO) mice. Twenty-four-week-old male global FGF21-KO mice were used in this study. Glucose and insulin tolerance were assessed. Expression of genes and proteins related to islet function and underlying mechanisms were also examined. Islet morphology and insulin-secreting capacity were further evaluated. FGF21-KO mice exhibited insulin resistance while being normoglycemic, associated with increases in beta-cell proliferation and insulin synthesis, acting as compensatory responses. This phenotype probably results from enhanced growth hormone (GH) sensitivity in FGF21-KO mouse islets. In addition, ex vivo FGF21 treatment in normal C57BL/6J mouse islets reduced GH signaling, probably via upregulation of peroxisome proliferator-activated receptor gamma (PPARγ) and cytokine-inducible SH-2 containing (CIS) protein, whereas KO mouse islets displayed reduced PPARγ and CIS expression. FGF21 treatment also reversed GH-induced insulin expression, beta-cell proliferation and GH-impaired glucose-stimulated insulin secretion (GSIS) in islets. Furthermore, distorted islet morphology and impaired GSIS were observed in KO mice, suggestive of islet dysfunction, whereas the enhanced insulin expression and impaired GSIS in FGF21-KO mouse islets could be reversed by blockade of GH signaling. Our data indicate that FGF21 is important in the regulation of beta-cell proliferation and insulin synthesis, probably via modulation of GH signaling. These findings provide evidence that FGF21 is an obligatory metabolic regulator in pancreatic islets and shed new light onto the role of endogenous FGF21 in the pathogenesis of insulin resistance and islet dysfunction.
Ultrafast helicity control of surface currents in topological insulators with near-unity fidelity
Authors: Kastl Christoph , Karnetzky Christoph , Karl Helmut , Holleitner Alexander W. 
Published: March 2015

AbstractIn recent years, a class of solid-state materials, called three-dimensional topological insulators, has emerged. In the bulk, a topological insulator behaves like an ordinary insulator with a band gap. At the surface, conducting gapless states exist showing remarkable properties such as helical Dirac dispersion and suppression of backscattering of spin-polarized charge carriers. The characterization and control of the surface states via transport experiments is often hindered by residual bulk contributions. Here we show that surface currents in Bi2Se3 can be controlled by circularly polarized light on a picosecond timescale with a fidelity near unity even at room temperature. We reveal the temporal separation of such ultrafast helicity-dependent surface currents from photo-induced thermoelectric and drift currents in the bulk. Our results uncover the functionality of ultrafast optoelectronic devices based on surface currents in topological insulators.
Ternary metal fluorides as high-energy cathodes with low cycling hysteresis
Authors: Wang Feng , Kim Sung-Wook , Seo Dong-Hwa , Kang Kisuk , Wang Liping , Su Dong , Vajo John J. , Wang John , Graetz Jason 
Published: March 2015

AbstractTransition metal fluorides are an appealing alternative to conventional intercalation compounds for use as cathodes in next-generation lithium batteries due to their extremely high capacity (3–4 times greater than the current state-of-the-art). However, issues related to reversibility, energy efficiency and kinetics prevent their practical application. Here we report on the synthesis, structural and electrochemical properties of ternary metal fluorides (M1yM21-yFx: M1, M2=Fe, Cu), which may overcome these issues. By substituting Cu into the Fe lattice, forming the solid–solution CuyFe1-yF2, reversible Cu and Fe redox reactions are achieved with surprisingly small hysteresis (<150 mV). This finding indicates that cation substitution may provide a new avenue for tailoring key electrochemical properties of conversion electrodes. Although the reversible capacity of Cu conversion fades rapidly, likely due to Cu+ dissolution, the low hysteresis and high energy suggest that a Cu-based fluoride cathode remains an intriguing candidate for rechargeable lithium batteries.
Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature
Authors: Kolaczkowska Elzbieta , Jenne Craig N. , Surewaard Bas G. J. , Thanabalasuriar Ajitha , Lee Woo-Yong , Sanz Maria-Jesus , Mowen Kerri , Opdenakker Ghislain , Kubes Paul 
Published: March 2015

AbstractNeutrophil extracellular traps (NETs) composed of DNA decorated with histones and proteases trap and kill bacteria but also injure host tissue. Here we show that during a bloodstream infection with methicillin-resistant Staphylococcus aureus, the majority of bacteria are sequestered immediately by hepatic Kupffer cells, resulting in transient increases in liver enzymes, focal ischaemic areas and a robust neutrophil infiltration into the liver. The neutrophils release NETs into the liver vasculature, which remain anchored to the vascular wall via von Willebrand factor and reveal significant neutrophil elastase (NE) proteolytic activity. Importantly, DNase although very effective at DNA removal, and somewhat effective at inhibiting NE proteolytic activity, fails to remove the majority of histones from the vessel wall and only partly reduces injury. By contrast, inhibition of NET production as modelled by PAD4-deficiency, or prevention of NET formation and proteolytic activity as modelled in NE−/− mice prevent collateral host tissue damage.
Emergence of reconfigurable wires and spinners via dynamic self-assembly
Authors: Kokot Gasper , Piet David , Whitesides George M. , Aranson Igor S. , Snezhko Alexey 
Published: March 2015

AbstractDissipative colloidal materials use energy to generate and maintain structural complexity. The energy injection rate and properties of the environment are important control parameters that influence the outcome of dynamic self-assembly. Here we demonstrate that dispersions of magnetic microparticles confined at the air-liquid interface and energized by a uniaxial in-plane alternating magnetic field, self-assemble into a variety of structures that range from pulsating clusters and single-particle-thick wires to dynamic arrays of spinners (self-assembled short chains) rotating in either direction. The spinners emerge via spontaneous breaking of the uniaxial symmetry of the energizing magnetic field. Demonstration of the formation and disaggregation of particle assemblies suggests strategies to form new meso-scale structures with the potential to perform functions such as mixing and sensing.
In vitro reconstitution of co-translational D1 insertion reveals a role of the cpSec–Alb3 translocase and Vipp1 in photosystem II biogenesis
Authors: Walter Björn , Hristou Athina , Nowaczyk Marc M. , Schünemann Danja 
Published: March 2015

Photosystem II (PS II) is a multi-subunit complex localized in the thylakoid membrane that performs the light-dependent photosynthetic charge separation. The PS II reaction centre comprises, among others, the D1 protein. De novo synthesis and repair of PS II require efficient mechanisms for transport and insertion of plastid encoded D1 into the thylakoid membrane. To elucidate the process of D1 insertion, we used an in vitro translation system derived from pea chloroplasts to reconstitute the D1 insertion. Thereby, truncated D1 encoding psbA mRNAs lacking a stop codon were translated in the presence of thylakoid membranes and the translation was stalled by addition of chloramphenicol. The generated ribosome nascent chain complexes (RNCs) were tightly associated with the thylakoids. Subsequently, these D1 insertion intermediates were enriched from solubilized thylakoids by sucrose cushion centrifugation. Immunological analyses demonstrated the presence of the cpSec translocase, Alb3, cpFtsY, cpSRP54 and Vipp1 (vesicle-inducing protein in plastids 1) in the enriched D1 insertion intermediates. A complex formation between cpSecY, Alb3, cpFtsY and Vipp1 in thylakoid membranes was shown by gel filtration chromatography, BN (Blue Native)/SDS-PAGE and co-immunoprecipitation experiments. Furthermore, a stimulating effect of recombinant Vipp1 on the formation of a D1 insertion intermediate was observed in vitro. These results suggest a co-operative function of these proteins in D1 insertion.
Interleukin-34 sustains inflammatory pathways in the gut
Authors: Franzè Eleonora , Monteleone Ivan , Cupi Maria Laura , Mancia Pamela , Caprioli Flavio , Marafini Irene , Colantoni Alfredo , Ortenzi Angela , Laudisi Federica , Sica Giuseppe , Sileri PierPaolo , Pallone Francesco , Monteleone Giovanni 
Published: March 2015

IBD (inflammatory bowel disease)-related tissue damage occurs in areas which are massively infiltrated with monocytes/macrophages. These cells respond to inflammatory stimuli with enhanced production of cytokines/chemokines. In the present study, we analysed the expression and role of IL (interleukin)-34, a regulator of monocyte/macrophage differentiation, survival and function, in IBD. A significant increase in IL-34 mRNA and protein expression was seen in inflamed mucosa of patients with CD (Crohn's disease) and patients with UC (ulcerative colitis) compared with the uninvolved areas of the same patients and normal controls. IL-34 was up-regulated in LPMCs (lamina propria mononuclear cells) isolated from normal colon by TNF-α (tumour necrosis factor α) and TLR (Toll-like receptor) ligands and was down-regulated in intestinal biopsies and LPMCs of IBD patients upon treatment with infliximab. Treatment of normal LPMCs with IL-34 increased TNF-α expression in an ERK1/2 (extracellular-signal-regulated kinase 1/2)-dependent fashion and neutralization of IL-34 in IBD mucosal explants reduced TNF-α and IL-6 synthesis. In conclusion, our results indicate that IL-34 is up-regulated in IBD and suggest a role for this cytokine in sustaining the inflammatory responses in this disease.
Aging Affects Identification of Vocal Emotions in Semantically Neutral Sentences
Authors: Dupuis Kate , Pichora-Fuller M. Kathleen 
Published: March 2015

PurposeThe authors determined the accuracy of younger and older adults in identifying vocal emotions using the Toronto Emotional Speech Set (TESS; Dupuis & Pichora-Fuller, 2010a) and investigated the possible contributions of auditory acuity and suprathreshold processing to emotion identification accuracy.MethodIn 2 experiments, younger and older adults with normal hearing listened to and identified vocal emotions in the TESS stimuli. The TESS consists of phrases with controlled syntactic, lexical, and phonological properties spoken by an older female talker and a younger female talker to convey 7 emotion conditions (anger, disgust, fear, sadness, neutral, happiness, and pleasant surprise). Participants in both experiments completed audiometric testing; participants in Experiment 2 also completed 3 tests of suprathreshold auditory processing.ResultsIdentification by both age groups was above chance for all emotions. Accuracy was lower for older adults in both experiments. The pattern of results was similar across age groups and experiments. Auditory acuity did not predict identification accuracy for either age group in either experiment, nor did performance on tests of auditory processing in Experiment 2.ConclusionsThese results replicate and extend previous findings concerning age-related differences in ability to identify vocal emotions and suggest that older adults' auditory abilities do not explain their difficulties in identifying vocal emotions.
Replicate Measurements of Haemoglobin Mass during a Single Day are Feasible and Precise
Authors: Naef N. , Steiner T. , Wehrlin J. 
Published: March 2015

AbstractDuplicate haemoglobin mass (Hbmass) measurements are recommended before and after altitude training sojourns to identify individual adaptations in athletes with a high level of certainty. Duplicate measurements reduce typical error (TE) and disclose measurement outliers, but are usually made on separate days, which is not a practical protocol for routine services in elite sport settings. The aim of this study was therefore to investigate whether it is safe (carboxyhaemoglobin<10%) to measure Hbmass twice on the same day and to compare TE with measurements made on separate days. 18 healthy men completed 3 different procedures to measure Hbmass twice a day with the carbon monoxide rebreathing method: A (Hbmass measured twice within 6 h), B (dito A, combined with 1 h of hyperoxic training between the tests), C (dito B, within 2 h). First Hbmass measurements of the 3 test days served as procedure D. Carboxyhaemoglobin did not exceed 10% in any procedure. TE and confidence limits for procedures A, B, C and D were 1.4% (1.0–2.1%), 1.1% (0.8–1.7%), 1.3% (1.0–2.0%) and 1.5% (1.2–2.1%), respectively. Duplicate measurements of Hbmass on the same day are feasible and show TE similar to triplicate measurements on separate days.
RNA transcribed from a distal enhancer is required for activating the chromatin at the promoter of the gonadotropin α-subunit gene
Authors: Pnueli Lilach , Rudnizky Sergei , Yosefzon Yahav , Melamed Philippa 
Published: March 2015

Significance
Much of the mammalian genome recently was shown to be transcribed to long noncoding RNAs, one class of which is the enhancer RNAs (eRNAs) whose levels largely correlate with the mRNA levels of the target gene but whose functions are not yet clear. We examined the eRNA produced from a functional enhancer that directs cell-specific expression of the gonadotropin hormone α-subunit gene, chorionic gonadotropin alpha, in the pituitary. We show that this eRNA plays a crucial role in facilitating DNA looping between the enhancer and promoter and directs histone modifications that are essential for transcription initiation and without which the chromatin becomes repressive to transcription. In this way, the eRNA mediates the function of the enhancer in directing basal gene expression.
RNA virus replication depends on enrichment of phosphatidylethanolamine at replication sites in subcellular membranes
Authors: Xu Kai , Nagy Peter D. 
Published: March 2015

Significance
Positive-strand RNA viruses are major pathogens of plants, animals, and humans. These viruses subvert intracellular membranes for virus replication, and lipids are critical due to interaction with viral and coopted host proteins. To dissect the roles of various lipids in Tomato bushy stunt virus (TBSV) replication, we have developed artificial vesicle-based replication assay. Vesicles consisting of a major phospholipid, namely phosphatidylethanolamine (PE), can support TBSV replication by assembling viral replicase complexes and performing a complete replication cycle. Monitoring PE distribution reveals that PE is enriched at the sites of TBSV replication in plant and yeast cells. Increasing PE level in cells leads to enhanced replication of TBSV and other viruses, suggesting that abundant PE in subcellular membranes has proviral function.
A statistical physics perspective on alignment-independent protein sequence comparison
Authors: Chattopadhyay Amit K. , Nasiev Diar , Flower Darren R. 
Published: March 2015

Abstract
Motivation: Within bioinformatics, the textual alignment of amino acid sequences has long dominated the determination of similarity between proteins, with all that implies for shared structure, function and evolutionary descent. Despite the relative success of modern-day sequence alignment algorithms, so-called alignment-free approaches offer a complementary means of determining and expressing similarity, with potential benefits in certain key applications, such as regression analysis of protein structure-function studies, where alignment-base similarity has performed poorly.
Results: Here, we offer a fresh, statistical physics-based perspective focusing on the question of alignment-free comparison, in the process adapting results from ‘first passage probability distribution’ to summarize statistics of ensemble averaged amino acid propensity values. In this article, we introduce and elaborate this approach.
Contact: d.r.flower@aston.ac.uk
DISSCO: direct imputation of summary statistics allowing covariates
Authors: Xu Zheng , Duan Qing , Yan Song , Chen Wei , Li Mingyao , Lange Ethan , Li Yun 
Published: March 2015

Abstract
Background: Imputation of individual level genotypes at untyped markers using an external reference panel of genotyped or sequenced individuals has become standard practice in genetic association studies. Direct imputation of summary statistics can also be valuable, for example in meta-analyses where individual level genotype data are not available. Two methods (DIST and ImpG-Summary/LD), that assume a multivariate Gaussian distribution for the association summary statistics, have been proposed for imputing association summary statistics. However, both methods assume that the correlations between association summary statistics are the same as the correlations between the corresponding genotypes. This assumption can be violated in the presence of confounding covariates.
Methods: We analytically show that in the absence of covariates, correlation among association summary statistics is indeed the same as that among the corresponding genotypes, thus serving as a theoretical justification for the recently proposed methods. We continue to prove that in the presence of covariates, correlation among association summary statistics becomes the partial correlation of the corresponding genotypes controlling for covariates. We therefore develop direct imputation of summary statistics allowing covariates (DISSCO).
Results: We consider two real-life scenarios where the correlation and partial correlation likely make practical difference: (i) association studies in admixed populations; (ii) association studies in presence of other confounding covariate(s). Application of DISSCO to real datasets under both scenarios shows at least comparable, if not better, performance compared with existing correlation-based methods, particularly for lower frequency variants. For example, DISSCO can reduce the absolute deviation from the truth by 3.9–15.2% for variants with minor allele frequency &lt;5%.
Availability and implementation: http://www.unc.edu/∼yunmli/DISSCO.
Contact: yunli@med.unc.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
ASBench: benchmarking sets for allosteric discovery
Authors: Huang Wenkang , Wang Guanqiao , Shen Qiancheng , Liu Xinyi , Lu Shaoyong , Geng Lv , Huang Zhimin , Zhang Jian 
Published: March 2015

Abstract
Summary: Allostery allows for the fine-tuning of protein function. Targeting allosteric sites is gaining increasing recognition as a novel strategy in drug design. The key challenge in the discovery of allosteric sites has strongly motivated the development of computational methods and thus high-quality, publicly accessible standard data have become indispensable. Here, we report benchmarking data for experimentally determined allosteric sites through a complex process, including a ‘Core set’ with 235 unique allosteric sites and a ‘Core-Diversity set’ with 147 structurally diverse allosteric sites. These benchmarking sets can be exploited to develop efficient computational methods to predict unknown allosteric sites in proteins and reveal unique allosteric ligand–protein interactions to guide allosteric drug design.
Availability and implementation: The benchmarking sets are freely available at http://mdl.shsmu.edu.cn/asbench.
Contact: jian.zhang@sjtu.edu.cn
Supplementary information: Supplementary data are available at Bioinformatics online
Computational modeling of the expansion of human cord blood CD133+ hematopoietic stem/progenitor cells with different cytokine combinations
Authors: Gullo Francesca , van der Garde Mark , Russo Giulia , Pennisi Marzio , Motta Santo , Pappalardo Francesco , Watt Suzanne 
Published: March 2015

Abstract
Motivation: Many important problems in cell biology require dense non-linear interactions between functional modules to be considered. The importance of computer simulation in understanding cellular processes is now widely accepted, and a variety of simulation algorithms useful for studying certain subsystems have been designed. Expansion of hematopoietic stem and progenitor cells (HSC/HPC) in ex vivo culture with cytokines and small molecules is a method to increase the restricted numbers of stem cells found in umbilical cord blood (CB), while also enhancing the content of early engrafting neutrophil and platelet precursors. The efficacy of the expanded product depends on the composition of the cocktail of cytokines and small molecules used for culture. Testing the influence of a cytokine or small molecule on the expansion of HSC/HPC is a laborious and expensive process. We therefore developed a computational model based on cellular signaling interactions that predict the influence of a cytokine on the survival, duplication and differentiation of the CD133+ HSC/HPC subset from human umbilical CB.
Results: We have used results from in vitro expansion cultures with different combinations of one or more cytokines to develop an ordinary differential equation model that includes the effect of cytokines on survival, duplication and differentiation of the CD133+ HSC/HPC. Comparing the results of in vitro and in silico experiments, we show that the model can predict the effect of a cytokine on the fold expansion and differentiation of CB CD133+ HSC/HPC after 8-day culture on a 3D scaffold.
Availability and implementation: The model is available visiting the following URL: http://www.francescopappalardo.net/Bioinformatics_CD133_Model.
Contact: francesco.pappalardo@unict.it or suzanne.watt@nhsbt.nhs.uk
Supplementary information: Supplementary data are available at Bioinformatics online.