bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dramatic increase in SHP2 binding activity of Helicobacter pylori Western CagA by EPIYA-C duplication: its implications in gastric carcinogenesis
Authors: Nagase Lisa , Hayashi Takeru , Senda Toshiya , Hatakeyama Masanori 
Published: October 2015

AbstractInfection with cagA-positive Helicobacter pylori is critically associated with the development of gastric cancer. The cagA-encoded CagA is delivered into gastric epithelial cells via type IV secretion, where it interacts with and thereby deregulates the pro-oncogenic phosphatase SHP2. East Asian CagA and Western CagA are two major CagA species produced by H. pylori circulating in East Asian countries and in the rest of the world, respectively. The SHP2 binding site of Western CagA, termed the EPIYA-C segment, variably duplicates and infection with H. pylori carrying Western CagA with multiple EPIYA-C segments is a distinct risk factor of gastric cancer. Here we show that duplication of EPIYA-C from one to two or more increases SHP2 binding of Western CagA by more than one hundredfold. Based on the decisive difference in SHP2 binding, Western CagA can be divided into two types: type I CagA carrying a single EPIYA-C segment and type II CagA carrying multiple EPIYA-C segments. Gastric epithelial cells expressing type II CagA acquire the ability to invade extracellular matrices, a malignant cellular trait associated with deregulated SHP2. A big leap in SHP2 binding activity may therefore provide molecular basis that makes type II Western CagA a distinct gastric cancer risk.
Systemic Risk Analysis on Reconstructed Economic and Financial Networks
Authors: Cimini Giulio , Squartini Tiziano , Garlaschelli Diego , Gabrielli Andrea 
Published: October 2015

AbstractWe address a fundamental problem that is systematically encountered when modeling real-world complex systems of societal relevance: the limitedness of the information available. In the case of economic and financial networks, privacy issues severely limit the information that can be accessed and, as a consequence, the possibility of correctly estimating the resilience of these systems to events such as financial shocks, crises and cascade failures. Here we present an innovative method to reconstruct the structure of such partially-accessible systems, based on the knowledge of intrinsic node-specific properties and of the number of connections of only a limited subset of nodes. This information is used to calibrate an inference procedure based on fundamental concepts derived from statistical physics, which allows to generate ensembles of directed weighted networks intended to represent the real system—so that the real network properties can be estimated as their average values within the ensemble. We test the method both on synthetic and empirical networks, focusing on the properties that are commonly used to measure systemic risk. Indeed, the method shows a remarkable robustness with respect to the limitedness of the information available, thus representing a valuable tool for gaining insights on privacy-protected economic and financial systems.
Bifidobacteria exhibit social behavior through carbohydrate resource sharing in the gut
Authors: Milani Christian , Lugli Gabriele Andrea , Duranti Sabrina , Turroni Francesca , Mancabelli Leonardo , Ferrario Chiara , Mangifesta Marta , Hevia Arancha , Viappiani Alice , Scholz Matthias , Arioli Stefania , Sanchez Borja , Lane Jonathan , Ward Doyle V. , Hickey Rita , Mora Diego , Segata Nicola , Margolles Abelardo , van Sinderen Douwe , Ventura Marco 
Published: October 2015

AbstractBifidobacteria are common and frequently dominant members of the gut microbiota of many animals, including mammals and insects. Carbohydrates are considered key carbon sources for the gut microbiota, imposing strong selective pressure on the complex microbial consortium of the gut. Despite its importance, the genetic traits that facilitate carbohydrate utilization by gut microbiota members are still poorly characterized. Here, genome analyses of 47 representative Bifidobacterium (sub)species revealed the genes predicted to be required for the degradation and internalization of a wide range of carbohydrates, outnumbering those found in many other gut microbiota members. The glycan-degrading abilities of bifidobacteria are believed to reflect available carbon sources in the mammalian gut. Furthermore, transcriptome profiling of bifidobacterial genomes supported the involvement of various chromosomal loci in glycan metabolism. The widespread occurrence of bifidobacterial saccharolytic features is in line with metagenomic and metatranscriptomic datasets obtained from human adult/infant faecal samples, thereby supporting the notion that bifidobacteria expand the human glycobiome. This study also underscores the hypothesis of saccharidic resource sharing among bifidobacteria through species-specific metabolic specialization and cross feeding, thereby forging trophic relationships between members of the gut microbiota.
Messenger RNA-based therapeutics for the treatment of apoptosis-associated diseases
Authors: Matsui Akitsugu , Uchida Satoshi , Ishii Takehiko , Itaka Keiji , Kataoka Kazunori 
Published: October 2015

AbstractGene therapy is a promising approach for treating diseases that are closely associated with excessive apoptosis, because the gene can effectively and sustainably introduce anti-apoptotic factors into cells. However, DNA delivery poses the risk of random genomic integration, leading to overexpression of the delivered gene and cancer development. Messenger RNA (mRNA) can evade integration events in target cells. We examined the use of mRNA-based therapeutics for introducing anti-apoptotic factors by using a mouse model of fulminant hepatitis. For introducing mRNA into the liver, a synthesised polymer-based carrier of polyplex nanomicelles was used for hydrodynamic intravenous injection. Using GFP as a reporter, we demonstrate that mRNA delivery induced efficient protein expression in almost 100% of liver cells, while plasmid DNA (pDNA) delivery provided a smaller percentage of GFP-positive cells. Analyses using Cy5-labelled mRNA and pDNA revealed that efficient expression by mRNA was attributed to a simple intracellular mechanism, without the need for nuclear entry. Consistent with this observation, Bcl-2 mRNA was more effective on reducing apoptosis in the liver of mice with fulminant hepatitis than Bcl-2 pDNA. Therefore, mRNA-based therapeutics combined with an effective delivery system such as polyplex nanomicelles is a promising treatment for intractable diseases associated with excessive apoptosis.
Inferring Infection Patterns Based on a Connectivity Map of Host Transcriptional Responses
Authors: Han Lu , He Haochen , Li Fei , Cui Xiuliang , Xie Dafei , Liu Yang , Zheng Xiaofei , Bai Hui , Wang Shengqi , Bo Xiaochen 
Published: October 2015

AbstractHost responses to infections represent an important pathogenicity determiner and delineation of host responses can elucidate pathogenesis processes and inform the development of anti-infection therapies. Low cost, high throughput, easy quantitation and rich descriptions have made gene expression profiling generated by DNA microarrays an optimal approach for describing host transcriptional responses (HTRs). However, efforts to characterize the landscape of HTRs to diverse pathogens are far from offering a comprehensive view. Here, we developed an HTR Connectivity Map based on systematic assessment of pairwise similarities of HTRs to 50 clinically important human pathogens using 1353 gene-expression profiles generated from >60 human cells/tissues. These 50 pathogens were further partitioned into eight robust “HTR communities” (i.e., groups with more consensus internal HTR similarities). These communities showed enrichment in specific infection attributes and differential gene expression patterns. Using query signatures of HTRs to external pathogens, we demonstrated four distinct modes of HTR associations among different pathogens types/class and validated the reliability of the HTR community divisions for differentiating and categorizing pathogens from a host-oriented perspective. These findings provide a first-generation HTR Connectivity Map of 50 diverse pathogens and demonstrate the potential for using annotated HTR community to detect functional associations among infectious pathogens.
QTL mapping of cucumber fruit flesh thickness by SLAF-seq
Authors: Xu Xuewen , Lu Lu , Zhu Biyun , Xu Qiang , Qi Xiaohua , Chen Xuehao 
Published: October 2015

AbstractCucumber is an agriculturally and economically important vegetable crop worldwide. Fruit flesh thickness is an important trait for cucumber and also a central determinant of yield, yet little is known about the underlying mechanism of this trait. In this study, bulked segregant analysis (BSA) combined with specific length amplified fragment sequencing (SLAF-seq) was applied to finely map the gene that underlies fruit flesh thickness in cucumber. A 0.19-Mb-long quantitative trait locus on chromosome 2 controlling fruit flesh thickness (QTL fft2.1) was identified and further confirmed by simple sequence repeat (SSR) marker-based classical QTL mapping in 138 F2 individuals. Gene prediction of this 0.19-Mb region identified 20 genes. Quantitative RT-PCR revealed higher expression levels of Csa2 M058670.1 (SET domain protein-lysine methyltransferase) in D8 (thick fruit flesh parent) compared with that in XUE1 (thin fruit flesh parent) during fruit development. Sequence alignment analysis of Csa2M058670.1 from thick and thin fruit flesh cucumber lines revealed a 4-bp deletion mutation in the promoter region of this candidate gene, which may result in the loss of Csa2M058670.1 activation in thin fruit flesh lines. The data presented herein suggest that Csa2M058670.1 is a possible candidate gene for controlling flesh thickness in cucumber.
In silico approach to reveal viral populations in grapevine cultivar Tannat using transcriptome data
Authors: Jo Yeonhwa , Choi Hoseong , Kyong Cho Jin , Yoon Ju-Yeon , Choi Seung-Kook , Kyong Cho Won 
Published: October 2015

AbstractViruses are ubiquitous and present in a wide range of settings, from living organisms to various environments. Although viruses are regarded as important pathogens in higher plants, viral populations in specific host plants have not yet been fully examined. This study revealed viral populations in grape berries obtained from a cultivar from a single vineyard using currently available grapevine transcriptomes. Eight viruses and two viroids were identified using 11 grapevine libraries. Virus-associated sequences in each transcriptome ranged from 0.2% (seed) to 8.8% (skin). The amount of viral RNAs and virus copy numbers was quantified, thus revealing the dominant virus or viroid in each individual library. In addition, five viral genomes were successfully assembled de novo using transcriptome data. Phylogenetic analyses revealed that the viruses and viroids might have originated from Europe, along with the host. Single nucleotide variation studies revealed the quasispecies of RNA viruses. Taken together, this study defines complex viral populations in three different grape tissues from a single vineyard.
Evaluation of regulatory genetic variants in POU5F1 and risk of congenital heart disease in Han Chinese
Authors: Lin Yuan , Ding Chenyue , Zhang Kai , Ni Bixian , Da Min , Hu Liang , Hu Yuanli , Xu Jing , Wang Xiaowei , Chen Yijiang , Mo Xuming , Cui Yugui , Shen Hongbing , Sha Jiahao , Liu Jiayin , Hu Zhibin 
Published: October 2015

AbstractOCT4 is a transcription factor of the POU family, which plays a key role in embryonic development and stem cell pluripotency. Previous studies have shown that Oct4 is required for cardiomyocyte differentiation in mice and its depletion could result in cardiac morphogenesis in embryo. However, whether the genetic variations in OCT4 coding gene, POU5F1, confer the predisposition to congenital heart disease (CHD) is unclear. This study sought to investigate the associations between low-frequency (defined here as having minor allele frequency (MAF) between 0.1%–5%) and rare (MAF below 0.1%) variants with potential function in POU5F1 and risk of CHD. We conducted association analysis in a two-stage case-control study with a total of 2,720 CHD cases and 3,331 controls in Chinese. The low-frequency variant rs3130933 was observed to be associated with a significantly increased risk of CHD [additive model: adjusted odds ratio (OR) = 2.15, adjusted P = 3.37 × 10−6]. Furthermore, luciferase activity assay showed that the variant A allele led to significantly lower expression levels as compared to the G allele. These findings indicate for the first time that low-frequency functional variant in POU5F1 may contribute to the risk of congenital heart malformations.
Maternal TET3 is dispensable for embryonic development but is required for neonatal growth
Authors: Tsukada Yu-ichi , Akiyama Tomohiko , Nakayama Keiichi I. 
Published: October 2015

AbstractThe development of multicellular organisms is accompanied by reprogramming of the epigenome in specific cells, with the epigenome of most cell types becoming fixed after differentiation. Genome-wide reprogramming of DNA methylation occurs in primordial germ cells and in fertilized eggs during mammalian embryogenesis. The 5-methylcytosine (5mC) content of DNA thus undergoes a marked decrease in the paternal pronucleus of mammalian zygotes. This loss of DNA methylation has been thought to be mediated by an active demethylation mechanism independent of replication and to be required for development. TET3-mediated sequential oxidation of 5mC has recently been shown to contribute to the genome-wide loss of 5mC in the paternal pronucleus of mouse zygotes. We now show that TET3 localizes not only to the paternal pronucleus but also to the maternal pronucleus and oxidizes both paternal and maternal DNA in mouse zygotes, although these phenomena are less pronounced in the female pronucleus. Genetic ablation of TET3 in oocytes had no significant effect on oocyte development, maturation, or fertilization or on pregnancy, but it resulted in neonatal sublethality. Our results thus indicate that zygotic 5mC oxidation mediated by maternal TET3 is required for neonatal growth but is not essential for development.
Smac mimetic with TNF-α targets Pim-1 isoforms and reactive oxygen species production to abrogate transformation from blebbishields
Authors: Jinesh Goodwin G. , Laing Naomi M. , Kamat Ashish M. 
Published: October 2015

Cancer cells are capable of sphere formation (transformation) through reactive oxygen species (ROS) and glycolysis shift. Transformation is linked to tumorigenesis and therapy resistance, hence targeting regulators of ROS and glycolysis is important for cancer therapeutic candidates. Here, we demonstrate that Smac mimetic AZ58 in combination with tumour necrosis factor-α (TNF-α) was able to inhibit the production of ROS, inhibit glycolysis through Pim-1 kinase-mediated Ser-112 phosphorylation of BAD, and increase depolarization of mitochondria. We also identified mitochondrial isoforms of Pim-1 kinase that were targeted for degradation by AZ58 in combination with TNF-α or AZ58 in combination with Fas ligand (FasL) plus cycloheximide (CHX) through caspase-3 to block transformation. Our study demonstrates that Smac mimetic in combination with TNF-α is an ideal candidate to target Pim-1 expression, inhibit ROS production and to block transformation from blebbishields.
Short‐range visible light ranging and detecting system using illumination light emitting diodes
Authors: Wu Dehao , Zhong Wen‐De , Ghassemlooy Zabih , Chen Chen 
Published: October 2015

A visible light object ranging and detecting system utilising light emitting diodes (LEDs) is proposed and investigated. The LEDs are used not only as illuminating devices but also as ranging and detecting sensors. LED is intensity modulated with a predetermined sinusoid signal at a certain frequency with an initial phase. After propagation, the backscatter signals from the object are received and detected. The direction of the object is estimated by an optical imaging receiver. The distance between the object and the LED is obtained based on a differential phase‐shift measurement. The theoretical model of the system is derived and evaluated, and the fundamental channel characteristics of the proposed system are simulated and analysed. The numerical results show that with a proper design, the presence or position of an object can be identified with a detection range of up to ∼6 m, with an estimation error as small as ∼5 cm for the system employing commercially available illumination LEDs.
Foxg1 localizes to mitochondria and coordinates cell differentiation and bioenergetics
Authors: Pancrazi Laura , Di Benedetto Giulietta , Colombaioni Laura , Della Sala Grazia , Testa Giovanna , Olimpico Francesco , Reyes Aurelio , Zeviani Massimo , Pozzan Tullio , Costa Mario 
Published: October 2015

Significance
The correct interplay between mitochondria and nuclear functions is essential to generate the mature functional six-layered structure of the mammalian cerebral cortex. Thus, alteration in this interaction results in pathological conditions such as cancer or neurodevelopmental disorders. The molecules and signaling mechanisms responsible for the nucleus–mitochondria communication and functional coordination are still largely unknown. The here-reported nuclear and mitochondrial localization of Forkhead box g1 (Foxg1), a transcription factor essential for brain development and cerebral cortex layering, provides insights on the molecular mechanisms through which Foxg1 acts as a link among mitochondrial function, neuronal differentiation, and pathological conditions.
N-terminal additions to the WE14 peptide of chromogranin A create strong autoantigen agonists in type 1 diabetes
Authors: Jin Niyun , Wang Yang , Crawford Frances , White Janice , Marrack Philippa , Dai Shaodong , Kappler John W. 
Published: October 2015

SignificanceType 1 diabetes is an autoimmune disease in which the insulin-producing beta cells within the islets of Langerhans of the pancreas are destroyed by T cell-mediated immune attack. The peptide epitopes derived from islet proteins that are targeted by CD4+T cells have been difficult to determine. We show in the nonobese diabetic (NOD) mouse model of the disease that a peptide (WE14) derived from chromogranin A is likely posttranslationally modified to create a target epitope. We hypothesize that the modification is caused by transpeptidation in which other peptides are fused to the N terminus of WE14. We propose that, in autoimmunity, new epitopes created in the target organs can be attacked by T cells that are normally nonreactive to natural self-antigens.
Physical activity intensity can be accurately monitored by smartphone global positioning system ‘app’
Authors: Gordon Brett Ashley , Bruce Lyndell , Benson Amanda Clare 
Published: October 2015

AbstractMonitoring physical activity is important to better individualise health and fitness benefits. This study assessed the concurrent validity of a smartphone global positioning system (GPS) ‘app’ and a sport‐specific GPS device with a similar sampling rate, to measure physical activity components of speed and distance, compared to a higher sampling sport‐specific GPS device. Thirty‐eight (21 female, 17 male) participants, mean age of 24.68, s = 6.46 years, completed two 2.400 km trials around an all‐weather athletics track wearing GPSports Pro™ (PRO), GPSports WiSpi™ (WISPI) and an iPhone™ with a Motion X GPS™ ‘app’ (MOTIONX). Statistical agreement, assessed using t‐tests and Bland–Altman plots, indicated an (mean; 95% LOA) underestimation of 2% for average speed (0.126 km·h−1; –0.389 to 0.642; p < .001), 1.7% for maximal speed (0.442 km·h−1; –2.676 to 3.561; p = .018) and 1.9% for distance (0.045 km; –0.140 to 0.232; p < .001) by MOTIONX compared to that measured by PRO. In contrast, compared to PRO, WISPI overestimated average speed (0.232 km·h−1; –0.376 to 0.088; p < .001) and distance (0.083 km; –0.129 to –0.038; p < .001) by 3.5% whilst underestimating maximal speed by 2.5% (0.474 km·h−1; –1.152 to 2.099; p < .001). Despite the statistically significant difference, the MOTIONX measures intensity of physical activity, with a similar error as WISPI, to an acceptable level for population‐based monitoring in unimpeded open‐air environments. This presents a low‐cost, minimal burden opportunity to remotely monitor physical activity participation to improve the prescription of exercise as medicine.
Painlevé transcendents and

-symmetric Hamiltonians
Authors: Bender Carl M , Komijani Javad 
Published: October 2015

Abstract
Unstable separatrix solutions for the first and second Painlevé transcendents are studied both numerically and analytically. For a fixed initial condition, say

there is a discrete set of initial slopes

that give rise to separatrix solutions. Similarly, for a fixed initial slope, say y’(0) = 0, there is a discrete set of initial values

that give rise to separatrix solutions. For Painlevé I the large-n asymptotic behavior of b

n
is

(

) and that of c

n
is

(

), and for Painlevé II the large-n asymptotic behavior of b

n
is

(

) and that of c

n
is

(

). The constants

and

which are the coefficients in these asymptotic behaviors, are first determined numerically. Then, by using asymptotic methods, they are found analytically by reducing the nonlinear equations to the linear eigenvalue problems associated with the cubic and quartic

-symmetric Hamiltonians

and
openBIS ELN-LIMS: an open-source database for academic laboratories
Authors: Barillari Caterina , Ottoz Diana S. M. , Fuentes-Serna Juan Mariano , Ramakrishnan Chandrasekhar , Rinn Bernd , Rudolf Fabian 
Published: October 2015

Abstract
Summary: The open-source platform openBIS (open Biology Information System) offers an Electronic Laboratory Notebook and a Laboratory Information Management System (ELN-LIMS) solution suitable for the academic life science laboratories. openBIS ELN-LIMS allows researchers to efficiently document their work, to describe materials and methods and to collect raw and analyzed data. The system comes with a user-friendly web interface where data can be added, edited, browsed and searched.
Availability and implementation: The openBIS software, a user guide and a demo instance are available at https://openbis-eln-lims.ethz.ch. The demo instance contains some data from our laboratory as an example to demonstrate the possibilities of the ELN-LIMS (Ottoz et al., 2014). For rapid local testing, a VirtualBox image of the ELN-LIMS is also available.
Contact: brinn@ethz.ch or fabian.rudolf@bsse.ethz.ch
LOLA: enrichment analysis for genomic region sets and regulatory elements in R and Bioconductor
Authors: Sheffield Nathan C. , Bock Christoph 
Published: October 2015

Abstract
Summary: Genomic datasets are often interpreted in the context of large-scale reference databases. One approach is to identify significantly overlapping gene sets, which works well for gene-centric data. However, many types of high-throughput data are based on genomic regions. Locus Overlap Analysis (LOLA) provides easy and automatable enrichment analysis for genomic region sets, thus facilitating the interpretation of functional genomics and epigenomics data.
Availability and Implementation: R package available in Bioconductor and on the following website: http://lola.computational-epigenetics.org.
Contact: nsheffield@cemm.oeaw.ac.at or cbock@cemm.oeaw.ac.at