bluuebunny/crossref_metadata_2025_split huggingface dataset:
CCL2 deficient mesenchymal stem cells fail to establish long-lasting contact with T cells and no longer ameliorate lupus symptoms
Authors: Lee Hong Kyung , Kim Hyung Sook , Kim Ji Sung , Kim Yong Guk , Park Ki Hwan , Lee Jae Hee , Kim Ki Hun , Chang In Young , Bae Sang-Cheol , Kim Youngsoo , Hong Jin Tae , Kehrl John H. , Han Sang-Bae 
Published: January 2017

AbstractSystemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterized by autoantibody production. Mesenchymal stem cells (MSCs) ameliorate SLE symptoms by targeting T cells, whereas the mechanisms of their efficacy remain incompletely understood. In this study, we show that transfer of human MSCs increased MRL.Faslpr mouse survival, decreased T cell infiltration in the kidneys, and reduced T cell cytokine expression. In vitro, allogeneic mouse MSCs inhibited MRL.Faslpr T cell proliferation and cytokine production. Time-lapse imaging revealed that MSCs recruited MRL.Faslpr T cells establishing long-lasting cellular contacts by enhancing T cell VCAM-1 expression in a CCL2-dependent manner. In contrast, CCL2 deficient MSCs did not induce T cell migration and VCAM-1 expression, resulting in insufficient cell-cell contact. Consequently, CCL2 deficient MSCs did not inhibit IFN-γ production by T cells and upon transfer no longer prolonged survival of MRL.Faslpr mice. Taken together, our imaging study demonstrates that CCL2 enables the prolonged MSC–T cell interactions needed for sufficient suppression of autoreactive T cells and helps to understand how MSCs ameliorate symptoms in lupus-prone MRL.Faslpr mice.
A compound-based proteomic approach discloses 15-ketoatractyligenin methyl ester as a new PPARγ partial agonist with anti-proliferative ability
Authors: Vasaturo Michele , Fiengo Lorenzo , De Tommasi Nunziatina , Sabatino Lina , Ziccardi Pamela , Colantuoni Vittorio , Bruno Maurizio , Cerchia Carmen , Novellino Ettore , Lupo Angelo , Lavecchia Antonio , Piaz Fabrizio Dal 
Published: January 2017

AbstractProteomics based approaches are emerging as useful tools to identify the targets of bioactive compounds and elucidate their molecular mechanisms of action. Here, we applied a chemical proteomic strategy to identify the peroxisome proliferator-activated receptor γ (PPARγ) as a molecular target of the pro-apoptotic agent 15-ketoatractyligenin methyl ester (compound 1). We demonstrated that compound 1 interacts with PPARγ, forms a covalent bond with the thiol group of C285 and occupies the sub-pocket between helix H3 and the β-sheet of the ligand-binding domain (LBD) of the receptor by Surface Plasmon Resonance (SPR), mass spectrometry-based studies and docking experiments. 1 displayed partial agonism of PPARγ in cell-based transactivation assays and was found to inhibit the AKT pathway, as well as its downstream targets. Consistently, a selective PPARγ antagonist (GW9662) greatly reduced the anti-proliferative and pro-apoptotic effects of 1, providing the molecular basis of its action. Collectively, we identified 1 as a novel PPARγ partial agonist and elucidated its mode of action, paving the way for therapeutic strategies aimed at tailoring novel PPARγ ligands with reduced undesired harmful side effects.
Advanced Materials From Fungal Mycelium: Fabrication and Tuning of Physical Properties
Authors: Haneef Muhammad , Ceseracciu Luca , Canale Claudio , Bayer Ilker S. , Heredia-Guerrero José A. , Athanassiou Athanassia 
Published: January 2017

AbstractIn this work is presented a new category of self-growing, fibrous, natural composite materials with controlled physical properties that can be produced in large quantities and over wide areas, based on mycelium, the main body of fungi. Mycelia from two types of edible, medicinal fungi, Ganoderma lucidum and Pleurotus ostreatus, have been carefully cultivated, being fed by two bio-substrates: cellulose and cellulose/potato-dextrose, the second being easier to digest by mycelium due to presence of simple sugars in its composition. After specific growing times the mycelia have been processed in order to cease their growth. Depending on their feeding substrate, the final fibrous structures showed different relative concentrations in polysaccharides, lipids, proteins and chitin. Such differences are reflected as alterations in morphology and mechanical properties. The materials grown on cellulose contained more chitin and showed higher Young’s modulus and lower elongation than those grown on dextrose-containing substrates, indicating that the mycelium materials get stiffer when their feeding substrate is harder to digest. All the developed fibrous materials were hydrophobic with water contact angles higher than 120°. The possibility of tailoring mycelium materials’ properties by properly choosing their nutrient substrates paves the way for their use in various scale applications.
Iterative Neighbour-Information Gathering for Ranking Nodes in Complex Networks
Authors: Xu Shuang , Wang Pei , Lü Jinhu 
Published: January 2017

AbstractDesigning node influence ranking algorithms can provide insights into network dynamics, functions and structures. Increasingly evidences reveal that node’s spreading ability largely depends on its neighbours. We introduce an iterative neighbourinformation gathering (Ing) process with three parameters, including a transformation matrix, a priori information and an iteration time. The Ing process iteratively combines priori information from neighbours via the transformation matrix, and iteratively assigns an Ing score to each node to evaluate its influence. The algorithm appropriates for any types of networks, and includes some traditional centralities as special cases, such as degree, semi-local, LeaderRank. The Ing process converges in strongly connected networks with speed relying on the first two largest eigenvalues of the transformation matrix. Interestingly, the eigenvector centrality corresponds to a limit case of the algorithm. By comparing with eight renowned centralities, simulations of susceptible-infected-removed (SIR) model on real-world networks reveal that the Ing can offer more exact rankings, even without a priori information. We also observe that an optimal iteration time is always in existence to realize best characterizing of node influence. The proposed algorithms bridge the gaps among some existing measures, and may have potential applications in infectious disease control, designing of optimal information spreading strategies.
PrimerSuite: A High-Throughput Web-Based Primer Design Program for Multiplex Bisulfite PCR
Authors: Lu Jennifer , Johnston Andrew , Berichon Philippe , Ru Ke-lin , Korbie Darren , Trau Matt 
Published: January 2017

AbstractThe analysis of DNA methylation at CpG dinucleotides has become a major research focus due to its regulatory role in numerous biological processes, but the requisite need for assays which amplify bisulfite-converted DNA represents a major bottleneck due to the unique design constraints imposed on bisulfite-PCR primers. Moreover, a review of the literature indicated no available software solutions which accommodated both high-throughput primer design, support for multiplex amplification assays, and primer-dimer prediction. In response, the tri-modular software package PrimerSuite was developed to support bisulfite multiplex PCR applications. This software was constructed to (i) design bisulfite primers against multiple regions simultaneously ( PrimerSuite ), (ii) screen for primer-primer dimerizing artefacts ( PrimerDimer ), and (iii) support multiplex PCR assays ( PrimerPlex ). Moreover, a major focus in the development of this software package was the emphasis on extensive empirical validation, and over 1300 unique primer pairs have been successfully designed and screened, with over 94% of them producing amplicons of the expected size, and an average mapping efficiency of 93% when screened using bisulfite multiplex resequencing. The potential use of the software in other bisulfite-based applications such as methylation-specific PCR is under consideration for future updates. This resource is freely available for use at PrimerSuite website (www.primer-suite.com).
Functional PTGS2 polymorphism-based models as novel predictive markers in metastatic renal cell carcinoma patients receiving first-line sunitinib
Authors: Cebrián Arancha , Gómez del Pulgar Teresa , Méndez-Vidal María José , Gonzálvez María Luisa , Lainez Nuria , Castellano Daniel , García-Carbonero Iciar , Esteban Emilio , Sáez Maria Isabel , Villatoro Rosa , Suárez Cristina , Carrato Alfredo , Munárriz-Ferrándiz Javier , Basterrechea Laura , García-Alonso Mirta , González-Larriba José Luis , Perez-Valderrama Begoña , Cruz-Jurado Josefina , González del Alba Aránzazu , Moreno Fernando , Reynés Gaspar , Rodríguez-Remírez María , Boni Valentina , Mahillo-Fernández Ignacio , Martin Yolanda , Viqueira Andrea , García-Foncillas Jesús 
Published: January 2017

AbstractSunitinib is the currently standard treatment for metastatic renal cell carcinoma (mRCC). Multiple candidate predictive biomarkers for sunitinib response have been evaluated but none of them has been implemented in the clinic yet. The aim of this study was to analyze single nucleotide polymorphisms (SNPs) in genes linked to mode of action of sunitinib and immune response as biomarkers for mRCC. This is a multicenter, prospective and observational study involving 20 hospitals. Seventy-five mRCC patients treated with sunitinib as first line were used to assess the impact of 63 SNPs in 31 candidate genes on clinical outcome. rs2243250 (IL4) and rs5275 (PTGS2) were found to be significantly associated with shorter cancer-specific survival (CSS). Moreover, allele C (rs5275) was associated with higher PTGS2 expression level confirming its functional role. Combination of rs5275 and rs7651265 or rs2243250 for progression free survival (PFS) or CSS, respectively, was a more valuable predictive biomarker remaining significant after correction for multiple testing. It is the first time that association of rs5275 with survival in mRCC patients is described. Two-SNP models containing this functional variant may serve as more predictive biomarkers for sunitinib and could suppose a clinically relevant tool to improve the mRCC patient management.
Effects of ultrasonic vibration on the microstructure and mechanical properties of high alloying TiAl
Authors: Ruirun Chen , Deshuang Zheng , Tengfei Ma , Hongsheng Ding , Yanqing Su , Jingjie Guo , Hengzhi Fu 
Published: January 2017

AbstractTo modify the microstructure and enhance performances, the ultrasonic vibration is applied in the mould casting of TiAl alloy. The effects and mechanism of ultrasonic vibration on the solidifying microstructure and mechanical properties are investigated and the model for predicting lamellar colony size is established. After ultrasonic vibration, the coarse microstructure is well modified and lamellar colony is refined from 534 μm to 56 μm. Most of precipitated phases are dissolved into the lamellar colony leading to a homogenous element distribution. The phase ratio of α2-Ti3Al and γ-TiAl is increased, and the chemical composition is promoted to more close to equilibrium level by weakening the influence of β-alloying elements. The microhardness and yield strength are gradually improved by 23.72% and 181.88% due to the fine grain strengthening, while the compressive strength is enhanced by 24.47% through solution strengthening. The critical ultrasonic intensity (Ib) for TiAl alloy is estimated at 220 W cm−2 and the model for average lamellar colony size is established as "Equation missing". The ultrasonic refinement efficiency exponentially increases as the ultrasonic vibration time with a theoretic limit maximum value of Elim = 88% and the dominating refinement mechanism by ultrasonic vibration is the cavitation-enhanced nucleation rather than cavitation-induced dendrite fragmentation.
White matter changes in microstructure associated with a maladaptive response to stress in rats
Authors: Magalhães R , Bourgin J , Boumezbeur F , Marques P , Bottlaender M , Poupon C , Djemaï B , Duchesnay E , Mériaux S , Sousa N , Jay T M , Cachia A 
Published: January 2017

AbstractIn today’s society, every individual is subjected to stressful stimuli with different intensities and duration. This exposure can be a key trigger in several mental illnesses greatly affecting one’s quality of life. Yet not all subjects respond equally to the same stimulus and some are able to better adapt to them delaying the onset of its negative consequences. The neural specificities of this adaptation can be essential to understand the true dynamics of stress as well as to design new approaches to reduce its consequences. In the current work, we employed ex vivo high field diffusion magnetic resonance imaging (MRI) to uncover the differences in white matter properties in the entire brain between Fisher 344 (F344) and Sprague–Dawley (SD) rats, known to present different responses to stress, and to examine the effects of a 2-week repeated inescapable stress paradigm. We applied a tract-based spatial statistics (TBSS) analysis approach to a total of 25 animals. After exposure to stress, SD rats were found to have lower values of corticosterone when compared with F344 rats. Overall, stress was found to lead to an overall increase in fractional anisotropy (FA), on top of a reduction in mean and radial diffusivity (MD and RD) in several white matter bundles of the brain. No effect of strain on the white matter diffusion properties was observed. The strain-by-stress interaction revealed an effect on SD rats in MD, RD and axial diffusivity (AD), with lower diffusion metric levels on stressed animals. These effects were localized on the left side of the brain on the external capsule, corpus callosum, deep cerebral white matter, anterior commissure, endopiriform nucleus, dorsal hippocampus and amygdala fibers. The results possibly reveal an adaptation of the SD strain to the stressful stimuli through synaptic and structural plasticity processes, possibly reflecting learning processes.
Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders
Authors: Rapanelli M , Frick L , Pogorelov V , Ohtsu H , Bito H , Pittenger C 
Published: January 2017

AbstractTic disorders affect ~5% of the population and are frequently comorbid with obsessive-compulsive disorder, autism, and attention deficit disorder. Histamine dysregulation has been identified as a rare genetic cause of tic disorders; mice with a knockout of the histidine decarboxylase (Hdc) gene represent a promising pathophysiologically grounded model. How alterations in the histamine system lead to tics and other neuropsychiatric pathology, however, remains unclear. We found elevated expression of the histamine H3 receptor in the striatum of Hdc knockout mice. The H3 receptor has significant basal activity even in the absence of ligand and thus may modulate striatal function in this knockout model. We probed H3R function using specific agonists. The H3 agonists R-aminomethylhistamine (RAMH) and immepip produced behavioral stereotypies in KO mice, but not in controls. H3 agonist treatment elevated intra-striatal dopamine in KO mice, but not in controls. This was associated with elevations in phosphorylation of rpS6, a sensitive marker of neural activity, in the dorsal striatum. We used a novel chemogenetic strategy to demonstrate that this dorsal striatal activity is necessary and sufficient for the development of stereotypy: when RAMH-activated cells in the dorsal striatum were chemogenetically activated (in the absence of RAMH), stereotypy was recapitulated in KO animals, and when they were silenced the ability of RAMH to produce stereotypy was blocked. These results identify the H3 receptor in the dorsal striatum as a contributor to repetitive behavioral pathology.
Contribution of innate immune cells to pathogenesis of severe influenza virus infection
Authors: Cole Suzanne L. , Ho Ling-Pei 
Published: January 2017

Influenza A viruses (IAVs) cause respiratory illness of varying severity based on the virus strains, host predisposition and pre-existing immunity. Ultimately, outcome and recovery from infection rely on an effective immune response comprising both innate and adaptive components. The innate immune response provides the first line of defence and is crucial to the outcome of infection. Airway epithelial cells are the first cell type to encounter the virus in the lungs, providing antiviral and chemotactic molecules that shape the ensuing immune response by rapidly recruiting innate effector cells such as NK cells, monocytes and neutrophils. Each cell type has unique mechanisms to combat virus-infected cells and limit viral replication, however their actions may also lead to pathology. This review focuses how innate cells contribute to protection and pathology, and provides evidence for their involvement in immune pathology in IAV infections.
A novel support vector machine robust model based electrical equaliser for coherent optical orthogonal frequency division multiplexing systems
Authors: Mhatli Sofien , Mrabet Hichem , Dayoub Iyad , Giacoumidis Elias 
Published: January 2017

Classifiers, such as artificial neural networks non‐linear equaliser (ANN‐NLE), Wiener–Hammerstein non‐linear equaliser, Volterra non‐linear equaliser (Volterra‐NLE) and support vector machine non‐linear equaliser (SVM‐NLE), can play a significant role in compensating non‐linear imperfections in the optical communications context. Using classifiers to mitigate the non‐linear effects in coherent optical orthogonal frequency division multiplexing (CO‐OFDM) systems is an interesting idea to be investigated. In this study, a novel support vector machine robust version, specifically adapted to a 100 Gb/s CO‐OFDM data structure for long haul distance, is proposed. Firstly, the authors demonstrate that SVM‐NLE upgrades the system performance by about 10−1 in terms of bit‐error rate compared to Volterra‐NLE at optical signal‐to‐noise ratio equal to 14 dB. Then, they show that it can double the transmission distance up to 1600 km over single mode fibre channel. Furthermore, a performance comparison is performed using 16 quadrature amplitude modulation and 40 Gb/s bit rate for SVM‐NLE, ANN‐NLE and inverse Volterra series transfer function non‐linear equaliser, respectively.
Nickel pincer model of the active site of lactate racemase involves ligand participation in hydride transfer
Authors: Xu Tao , Wodrich Matthew D. , Scopelliti Rosario , Corminboeuf Clemence , Hu Xile 
Published: January 2017

Significance
Pincer complexes are widely applied in homogeneous catalysis. However, only very recently has the first pincer complex been discovered in the active site of a metalloenzyme, namely, lactate racemase. Here, we report a synthetic model of the active site of lactate racemase. The nickel pincer model not only reproduces some key structural features of the active site, but also mediates the dehydrogenation of alcohols, a reaction relevant to lactate racemization. Our work suggests a mechanism in which the unique pyridinium-derived SCS pincer ligand actively participates in the hydride transfer. This work not only represents a successful biomimetic study of this enzyme but also lays the foundation for the development of new bioinspired pincer ligands.
Mutation of a kinase allosteric node uncouples dynamics linked to phosphotransfer
Authors: Ahuja Lalima G. , Kornev Alexandr P. , McClendon Christopher L. , Veglia Gianluigi , Taylor Susan S. 
Published: January 2017

Significance
Our Girvan–Newman-based community network analysis provides a strategy to explore the effects of protein kinase mutations on the dynamic properties of the kinase core and the allosteric network underlying the catalytic cycle. With this approach, which allows us to identify subtle shifts in dynamics and in particular side-chain rotamer preferences, we can explain the underlying mechanism for loss of function in many different scenarios. Our method is especially relevant for disease-causing mutations that lie far from the active site but show no obvious structural perturbations based on X-ray crystallography.
Non-conventional arguments
Authors: Frenda Alessio S. 
Published: January 2017

Abstract
In the Romance context, Sicilian rather unusually allows finite verbs to be governed by a preposition within a subordinate phrasal constituent expressing purpose. In other Romance languages, the verb slotted in this context is normally an infinitive. Sicilian also has the corresponding infinitive construction, and the distribution of these two functionally equivalent structures in a corpus of Sicilian folk tales is analysed, revealing overall conciseness conditions restricting the occurrence of the finite-verb construction. The two structures are then analysed from a semantic and syntactic point of view, employing the formalism of Role and Reference Grammar, in order to understand what distinguishes them in terms of event structure and its expression via core complementation vs. adjunction.
The organizational structure of lexical compound verbs in Japanese
Authors: Toratani Kiyoko 
Published: January 2017

Abstract
This study offers a Construction Morphology account of the organizational structure of the class of lexical compound verbs in Japanese, covering two newly proposed types (thematic and aspectual compound verbs) (Kageyama 2013) and two understudied types (prefixed and lexicalized type compound verbs), as an alternative to a traditional listing of types. It argues that compounds are arranged in two dimensions: one contains the inheritance hierarchy, with its root node diverging according to the position of the semantic head (for thematic, aspectual, and prefixed type compounds); the other covers compounds with extended senses (for the lexicalized type). The study also proposes constructional schemas for compound verbs (e.g. those with affixoids such as -hateru ‘completely’) to illustrate how they are organized in the inheritance hierarchy.
GWAR: robust analysis and meta-analysis of genome-wide association studies
Authors: Dimou Niki L , Tsirigos Konstantinos D , Elofsson Arne , Bagos Pantelis G 
Published: January 2017

AbstractMotivationIn the context of genome-wide association studies (GWAS), there is a variety of statistical techniques in order to conduct the analysis, but, in most cases, the underlying genetic model is usually unknown. Under these circumstances, the classical Cochran-Armitage trend test (CATT) is suboptimal. Robust procedures that maximize the power and preserve the nominal type I error rate are preferable. Moreover, performing a meta-analysis using robust procedures is of great interest and has never been addressed in the past. The primary goal of this work is to implement several robust methods for analysis and meta-analysis in the statistical package Stata and subsequently to make the software available to the scientific community.ResultsThe CATT under a recessive, additive and dominant model of inheritance as well as robust methods based on the Maximum Efficiency Robust Test statistic, the MAX statistic and the MIN2 were implemented in Stata. Concerning MAX and MIN2, we calculated their asymptotic null distributions relying on numerical integration resulting in a great gain in computational time without losing accuracy. All the aforementioned approaches were employed in a fixed or a random effects meta-analysis setting using summary data with weights equal to the reciprocal of the combined cases and controls. Overall, this is the first complete effort to implement procedures for analysis and meta-analysis in GWAS using Stata.Availability and ImplementationA Stata program and a web-server are freely available for academic users at http://www.compgen.org/tools/GWARSupplementary informationSupplementary data are available at Bioinformatics online.