bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrative epigenome-wide analysis demonstrates that DNA methylation may mediate genetic risk in inflammatory bowel disease
Authors: Ventham N. T. , Kennedy N. A. , Adams A. T. , Kalla R. , Heath S. , O'Leary K. R. , Drummond H. ,   IBD BIOM consortium, Lauc Gordan , Campbell Harry , McGovern Dermot P. B. , Annese Vito , Zoldoš Vlatka , Permberton Iain K. , Wuhrer Manfred , Kolarich Daniel , Fernandes Daryl L. , Theorodorou Evropi , Merrick Victoria , Spencer Daniel I. , Gardner Richard A. , Doran Ray , Shubhakar Archana , Boyapati Ray , Rudan Igor , Lionetti Paolo , Akmačić Irena Trbojević , Krištić Jasminka , Vučković Frano , Štambuk Jerko , Novokmet Mislav , Pučić-Baković Maja , Gornik Olga , Andriulli Angelo , Cantoro Laura , Sturniolo Giancarlo , Fiorino Gionata , Manetti Natalia , Latiano Anna , Kohn Anna , D’Incà Renata , Danese Silvio , Arnott Ian D. , Noble Colin L. , Lees Charlie W. , Shand Alan G. , Ho Gwo-Tzer , Dunlop Malcolm G. , Murphy Lee , Gibson Jude , Evenden Louise , Wrobel Nicola , Gilchrist Tamara , Fawkes Angie , Kammeijer Guinevere S. M. , Clerc Florent , de Haan Noortje , Vojta Aleksandar , Samaržija Ivana , Markulin Dora , Klasić Marija , Dobrinić Paula , Aulchenko Yurii , van den Heuve Tim , Jonkers Daisy , Pierik Marieke ,   IBD CHARACTER consortium, Vatn Simen , Ricanek Petr , Jahnsen Jørgen , You Panpan , Sølvernes Janne , Frengen Anna B. , Tannæs Tone M. , Moen Aina E. F. , Dahl Fredrik A. , Lindstrøm Jonas Christoffer , Ekeland Gunn S. , Detlie Trond Espen , Keita Åsa V. , Söderholm Johan D. , Hjortswang Henrik , Halfvarson Jonas , Bergemalm Daniel , Gomollón Fernando , D'Amato Mauro , Törkvist Leif , Hjelm Fredrik , Gullberg Mats , Nordberg Niklas , Ocklind Anette , Pettersson Erik , Ekman Daniel , Sundell Mikael , Modig Eddie , Veillard Anne- Clémence , Schoemans Renaud , Poncelet Dominique , Sabatel Céline , Gut Marta , Bayes Monica , Casén Christina , Lindahl Torbjørn , Ciemniejewska Ewa , Vatn Morten H. , Wilson D. C. , Gut I. G. , Nimmo E. R. , Satsangi J. 
Published: November 2016

AbstractEpigenetic alterations may provide important insights into gene-environment interaction in inflammatory bowel disease (IBD). Here we observe epigenome-wide DNA methylation differences in 240 newly-diagnosed IBD cases and 190 controls. These include 439 differentially methylated positions (DMPs) and 5 differentially methylated regions (DMRs), which we study in detail using whole genome bisulphite sequencing. We replicate the top DMP (RPS6KA2) and DMRs (VMP1, ITGB2andTXK) in an independent cohort. Using paired genetic and epigenetic data, we delineate methylation quantitative trait loci;VMP1/microRNA-21methylation associates with two polymorphisms in linkage disequilibrium with a known IBD susceptibility variant. Separated cell data shows that IBD-associated hypermethylation within theTXKpromoter region negatively correlates with gene expression in whole-blood and CD8+T cells, but not other cell types. Thus, site-specific DNA methylation changes in IBD relate to underlying genotype and associate with cell-specific alteration in gene expression.
Tuning charge and correlation effects for a single molecule on a graphene device
Authors: Wickenburg Sebastian , Lu Jiong , Lischner Johannes , Tsai Hsin-Zon , Omrani Arash A. , Riss Alexander , Karrasch Christoph , Bradley Aaron , Jung Han Sae , Khajeh Ramin , Wong Dillon , Watanabe Kenji , Taniguchi Takashi , Zettl Alex , Neto A.H. Castro , Louie Steven G. , Crommie Michael F. 
Published: November 2016

AbstractThe ability to understand and control the electronic properties of individual molecules in a device environment is crucial for developing future technologies at the nanometre scale and below. Achieving this, however, requires the creation of three-terminal devices that allow single molecules to be both gated and imaged at the atomic scale. We have accomplished this by integrating a graphene field effect transistor with a scanning tunnelling microscope, thus allowing gate-controlled charging and spectroscopic interrogation of individual tetrafluoro-tetracyanoquinodimethane molecules. We observe a non-rigid shift in the molecule’s lowest unoccupied molecular orbital energy (relative to the Dirac point) as a function of gate voltage due to graphene polarization effects. Our results show that electron–electron interactions play an important role in how molecular energy levels align to the graphene Dirac point, and may significantly influence charge transport through individual molecules incorporated in graphene-based nanodevices.
Genome-wide RNAi screening identifies TMIGD3 isoform1 as a suppressor of NF-κB and osteosarcoma progression
Authors: Iyer Swathi V. , Ranjan Atul , Elias Harold K. , Parrales Alejandro , Sasaki Hiromi , Roy Badal C. , Umar Shahid , Tawfik Ossama W. , Iwakuma Tomoo 
Published: November 2016

AbstractThe ability of cancer cells to survive and grow in anchorage- and serum-independent conditions is well correlated with their aggressiveness. Here, using a human whole-genome shRNA library, we identify TMIGD3 isoform1 (i1) as a factor that suppresses this ability in osteosarcoma (OS) cells, mainly by inhibiting NF-κB activity. Knockdown of TMIGD3 increases proliferation, tumour formation and metastasis of OS cells. Overexpression of TMIGD3 isoform1 (i1), but not isoform3 (i3) which shares a common C-terminal region, suppresses these malignant properties. Adenosine A3 receptor (A3AR) having an identical N-terminal region shows similar biological profiles to TMIGD3 i1. Protein expression of TMIGD3 and A3AR is lower in human OS tissues than normal tissues. Mechanistically, TMIGD3 i1 and A3AR commonly inhibit the PKA−Akt−NF-κB axis. However, TMIGD3 i1 only partially rescues phenotypes induced by A3AR knockdown, suggesting the presence of distinct pathways. Our findings reveal an unappreciated role for TMIGD3 i1 as a suppressor of NF-κB activity and OS progression.
Astrocytic GABA transporter activity modulates excitatory neurotransmission
Authors: Boddum Kim , Jensen Thomas P. , Magloire Vincent , Kristiansen Uffe , Rusakov Dmitri A. , Pavlov Ivan , Walker Matthew C. 
Published: November 2016

AbstractAstrocytes are ideally placed to detect and respond to network activity. They express ionotropic and metabotropic receptors, and can release gliotransmitters. Astrocytes also express transporters that regulate the extracellular concentration of neurotransmitters. Here we report a previously unrecognized role for the astrocytic GABA transporter, GAT-3. GAT-3 activity results in a rise in astrocytic Na+ concentrations and a consequent increase in astrocytic Ca2+ through Na+/Ca2+ exchange. This leads to the release of ATP/adenosine by astrocytes, which then diffusely inhibits neuronal glutamate release via activation of presynaptic adenosine receptors. Through this mechanism, increases in astrocytic GAT-3 activity due to GABA released from interneurons contribute to 'diffuse' heterosynaptic depression. This provides a mechanism for homeostatic regulation of excitatory transmission in the hippocampus.
Development of a validated algorithm for the diagnosis of paediatric asthma in electronic medical records
Authors: Cave Andrew J , Davey Christina , Ahmadi Elaheh , Drummond Neil , Fuentes Sonia , Kazemi-Bajestani Seyyed Mohammad Reza , Sharpe Heather , Taylor Matt 
Published: November 2016

AbstractAn accurate estimation of the prevalence of paediatric asthma in Alberta and elsewhere is hampered by uncertainty regarding disease definition and diagnosis. Electronic medical records (EMRs) provide a rich source of clinical data from primary-care practices that can be used in better understanding the occurrence of the disease. The Canadian Primary Care Sentinel Surveillance Network (CPCSSN) database includes cleaned data extracted from the EMRs of primary-care practitioners. The purpose of the study was to develop and validate a case definition of asthma in children 1–17 who consult family physicians, in order to provide primary-care estimates of childhood asthma in Alberta as accurately as possible. The validation involved the comparison of the application of a theoretical algorithm (to identify patients with asthma) to a physician review of records included in the CPCSSN database (to confirm an accurate diagnosis). The comparison yielded 87.4% sensitivity, 98.6% specificity and a positive and negative predictive value of 91.2% and 97.9%, respectively, in the age group 1–17 years. The algorithm was also run for ages 3–17 and 6–17 years, and was found to have comparable statistical values. Overall, the case definition and algorithm yielded strong sensitivity and specificity metrics and was found valid for use in research in CPCSSN primary-care practices. The use of the validated asthma algorithm may improve insight into the prevalence, diagnosis, and management of paediatric asthma in Alberta and Canada.
Seeing is believing: anti-PD-1/PD-L1 monoclonal antibodies in action for checkpoint blockade tumor immunotherapy
Authors: Tan Shuguang , Zhang Catherine W-H , Gao George F 
Published: November 2016

AbstractStructural immunology, focusing on structures of host immune related molecules, enables the immunologists to see what the molecules look like, and more importantly, how they work together. Antibody-based PD-1/PD-L1 blockade therapy has achieved brilliant successes in clinical applications. The recent breakthrough of the complex structures of checkpoint blockade antibodies with their counterparts, pembrolizumab with PD-1 and avelumab with PD-L1, have made it clear how these monoclonal antibodies compete the binding of PD-1/PD-L1 and function to blockade the receptor-ligand interaction. Herein, we summarize the structural findings of these two reports and look into the future for how this information would facilitate the development of more efficient PD-1/PD-L1 targeting antibodies, small molecule drugs, and other protein or non-protein inhibitors.
Characterization of Structural Connectivity of the Default Mode Network in Dogs using Diffusion Tensor Imaging
Authors: Robinson Jennifer L. , Baxi Madhura , Katz Jeffrey S. , Waggoner Paul , Beyers Ronald , Morrison Edward , Salibi Nouha , Denney Thomas S. , Vodyanoy Vitaly , Deshpande Gopikrishna 
Published: November 2016

AbstractDiffusion tensor imaging (DTI) provides us an insight into the micro-architecture of white-matter tracts in the brain. This method has proved promising in understanding and investigating the neuronal tracts and structural connectivity between the brain regions in primates as well as rodents. The close evolutionary relationship between canines and humans may have spawned a unique bond in regard to social cognition rendering them useful as an animal model in translational research. In this study, we acquired diffusion data from anaesthetized dogs and created a DTI-based atlas for a canine model which could be used to investigate various white matter diseases. We illustrate the application of this atlas by calculating DTI tractography based structural connectivity between the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) regions of the default mode network (DMN) in dogs. White matter connectivity was investigated to provide structural basis for the functional dissociation observed between the anterior and posterior parts of DMN. A comparison of the integrity of long range structural connections (such as in the DMN) between dogs and humans is likely to provide us with new perspectives on the neural basis of the evolution of cognitive functions.
The antidepressant-like activity of AC-5216, a ligand for 18KDa translocator protein (TSPO), in an animal model of diabetes mellitus
Authors: Qiu Zhi-Kun , He Jia-Li , Liu Xu , Zhang Guan-Hua , Zeng Jia , Nie Hong , Shen Yong-Gang , Chen Ji-Sheng 
Published: November 2016

AbstractDiabetes mellitus is a chronic disease that is associated with depression. Also, depression is common in adults with type 2 diabetes mellitus (T2DM). Translocator protein (18kDa) (TSPO) and allopregnanolone play an important role in the depression treatment. However, few studies have evaluated TSPO and allopregnanolone in the treatment of depression in T2DM. AC-5216, a ligand for TSPO, produces anxiolytic- and antidepressant-like effects in animal models. The present study aimed to explore antidepressant-like effects of AC-5216 on diabetic rats. Following the development of diabetic model induced by high fat diet (HFD) feeding and streptozotocin (STZ), AC-5216 (0.3 and 1 mg/kg, i.g.) elicited the antidepressant-like effects in behavioral tests while these activities were blocked by TSPO antagonist PK11195 (3 mg/kg, i.p.). The levels of allopregnanolone in the prefrontal cortex and hippocampus were increased by AC-5216 (0.3 and 1 mg/kg, i.g.), which was antagonized by PK11195 (3 mg/kg, i.p.). The increased plasma glucose (PG) and decreased insulin (INS) in HFD-STZ rats were reversed by AC-5216 (0.3 and 1 mg/kg, i.g.). This study indicates that the antidepressant-like effects of AC-5216 on HFD-STZ rats, suggesting that TSPO may represent a novel therapeutic target for depression in T2DM.
Hydrocarbon degraders establish at the costs of microbial richness, abundance and keystone taxa after crude oil contamination in permafrost environments
Authors: Yang Sizhong , Wen Xi , Shi Yulan , Liebner Susanne , Jin Huijun , Perfumo Amedea 
Published: November 2016

AbstractOil spills from pipeline ruptures are a major source of terrestrial petroleum pollution in cold regions. However, our knowledge of the bacterial response to crude oil contamination in cold regions remains to be further expanded, especially in terms of community shifts and potential development of hydrocarbon degraders. In this study we investigated changes of microbial diversity, population size and keystone taxa in permafrost soils at four different sites along the China-Russia crude oil pipeline prior to and after perturbation with crude oil. We found that crude oil caused a decrease of cell numbers together with a reduction of the species richness and shifts in the dominant phylotypes, while bacterial community diversity was highly site-specific after exposure to crude oil, reflecting different environmental conditions. Keystone taxa that strongly co-occurred were found to form networks based on trophic interactions, that is co-metabolism regarding degradation of hydrocarbons (in contaminated samples) or syntrophic carbon cycling (in uncontaminated samples). With this study we demonstrate that after severe crude oil contamination a rapid establishment of endemic hydrocarbon degrading communities takes place under favorable temperature conditions. Therefore, both endemism and trophic correlations of bacterial degraders need to be considered in order to develop effective cleanup strategies.
Epigenetic Enhancement of the Post-replicative DNA Mismatch Repair of Mammalian Genomes by a Hemi-mCpG-Np95-Dnmt1 Axis
Authors: Wang Keh-Yang , Chen Chun-Chang , Tsai Shih-Feng , Shen Che-Kun James 
Published: November 2016

AbstractDNA methylation at C of CpG dyads (mCpG) in vertebrate genomes is essential for gene regulation, genome stability and development. We show in this study that proper functioning of post-replicative DNA mismatch repair (MMR) in mammalian cells relies on the presence of genomic mCpG, as well as on the maintenance DNA methyltransferase Dnmt1 independently of its catalytic activity. More importantly, high efficiency of mammalian MMR surveillance is achieved through a hemi-mCpG-Np95(Uhrf1)-Dnmt1 axis, in which the MMR surveillance complex(es) is recruited to post-replicative DNA by Dnmt1, requiring its interactions with MutSα, as well as with Np95 bound at the hemi-methylated CpG sites. Thus, efficiency of MMR surveillance over the mammalian genome in vivo is enhanced at the epigenetic level. This synergy endows vertebrate CpG methylation with a new biological significance and, consequently, an additional mechanism for the maintenance of vertebrate genome stability.
Cytotoxic and genotoxic potential of food-borne nitriles in a liver in vitro model
Authors: Kupke Franziska , Herz Corinna , Hanschen Franziska S. , Platz Stefanie , Odongo Grace A. , Helmig Simone , Bartolomé Rodríguez María M. , Schreiner Monika , Rohn Sascha , Lamy Evelyn 
Published: November 2016

AbstractIsothiocyanates are the most intensively studied breakdown products of glucosinolates fromBrassicaplants and well recognized for their pleiotropic effects against cancer but also for their genotoxic potential. However, knowledge about the bioactivity of glucosinolate-borne nitriles in foods is very poor. As determined by GC-MS, broccoli glucosinolates mainly degrade to nitriles as breakdown products. The cytotoxicity of nitriles in human HepG2 cells and primary murine hepatocytes was marginal as compared to isothiocyanates. Toxicity of nitriles was not enhanced in CYP2E1-overexpressing HepG2 cells. In contrast, the genotoxic potential of nitriles was found to be comparable to isothiocyanates. DNA damage was persistent over a certain time period and CYP2E1-overexpression further increased the genotoxic potential of the nitriles. Based on actualin vitrodata, no indications are given that food-borne nitriles could be relevant for cancer prevention, but could pose a certain genotoxic risk under conditions relevant for food consumption.
Hyperinvasiveness of Salmonella enterica serovar Choleraesuis linked to hyperexpression of type III secretion systems in vitro
Authors: Huang Kuan-Yeh , Wang Yi-Hsin , Chien Kun-Yi , Janapatla Rajendra Prasad , Chiu Cheng-Hsun 
Published: November 2016

AbstractSalmonella enterica serovars Choleraesuis and Typhimurium are among the non-typhoid Salmonella serovars that are important zoonotic pathogens. In clinical observation, S. Typhimurium typically causes diarrheal diseases; however, S. Choleraesuis shows high predilection to cause bacteremia. The mechanism why S. Choleraesuis is more invasive to humans remains unknown. In this study, we compared the S. Typhimurium LT2 and S. Choleraesuis SC-B67 proteomes through stable isotope labeling of amino acid in cell culture (SILAC). In SILAC, the expression of many virulence proteins in two type III secretion systems (T3SSs) were significantly higher in S. Choleraesuis than in S. Typhimurium. Similar differences were also found at the transcriptional level. Compared to S. Typhimurium, S. Choleraesuis showed a higher penetration level to Caco-2 (>100-fold) and MDCK (>10-fold) monolayers. In mice after oral challenge, the invasion of spleen and liver was also higher in S. Choleraesuis than in S. Typhimurium. The transcription of hilD in S. Choleraesuis was increased in physiological (1 mM) or high (10 mM) concentrations of Mg2+, but not in low (8 μM) concentration. We conclude that S. Choleraesuis showed hyperinvasiveness in cellular as well as mouse models due to hyperexpression of T3SS genes.
Functional Improvement and Regression of Medial Hypertrophy in the Remodeled Pulmonary Artery after Correction of Systemic Left-to-Right Shunt
Authors: Hsu Chih-Hsin , Roan Jun-Neng , Chen Jyh-Hong , Lam Chen-Fuh 
Published: November 2016

AbstractThe presence of systemic left-to-right shunt and increased pulmonary blood flow can result in right heart failure and pulmonary arteriopathy. Correction of left-to-right shunt has been shown to improve cardiac function and physical performance. However, the cardiopulmonary remodeling processes following cessation of left-to-right shunt have yet to be reported. In this experimental study, excessive pulmonary flow was restored through ligation of the aortocaval fistula in rats with flow-induced pulmonary hypertension. The cardiopulmonary morphometric functions were assessed, and phenotypic switching of pulmonary vascular smooth muscle cells (VSMC) was determined. Ligation of aortocaval fistula significantly attenuated pulmonary blood flow and right ventricular mass, and potentiated the isometric contraction of pulmonary artery. Inflammatory cytokines IL-1β and IL-6 were reduced in the lung after ligation. Reduction of pulmonary blood flow restored the expressions of smooth muscle myosin heavy chain and α-smooth muscle actin in pulmonary artery, indicating the switching of VSMCs to the contractile phenotype. Our study demonstrated that normalization of pulmonary blood flow in flow-induced pulmonary hypertension reverses the remodeling in the right ventricle and pulmonary artery. The remodeling process of flow-induced pulmonary hypertension is functionally and morphometrically reversible by inducing transdifferentiation of pulmonary VSMC to contractile phenotypes and modulation of tissue inflammatory cytokines.
Proteomic profile of the Bradysia odoriphaga in response to the microbial secondary metabolite benzothiazole
Authors: Zhao Yunhe , Cui Kaidi , Xu Chunmei , Wang Qiuhong , Wang Yao , Zhang Zhengqun , Liu Feng , Mu Wei 
Published: November 2016

AbstractBenzothiazole, a microbial secondary metabolite, has been demonstrated to possess fumigant activity against Sclerotinia sclerotiorum, Ditylenchus destructor and Bradysia odoriphaga. However, to facilitate the development of novel microbial pesticides, the mode of action of benzothiazole needs to be elucidated. Here, we employed iTRAQ-based quantitative proteomics analysis to investigate the effects of benzothiazole on the proteomic expression of B. odoriphaga. In response to benzothiazole, 92 of 863 identified proteins in B. odoriphaga exhibited altered levels of expression, among which 14 proteins were related to the action mechanism of benzothiazole, 11 proteins were involved in stress responses, and 67 proteins were associated with the adaptation of B. odoriphaga to benzothiazole. Further bioinformatics analysis indicated that the reduction in energy metabolism, inhibition of the detoxification process and interference with DNA and RNA synthesis were potentially associated with the mode of action of benzothiazole. The myosin heavy chain, succinyl-CoA synthetase and Ca+-transporting ATPase proteins may be related to the stress response. Increased expression of proteins involved in carbohydrate metabolism, energy production and conversion pathways was responsible for the adaptive response of B. odoriphaga. The results of this study provide novel insight into the molecular mechanisms of benzothiazole at a large-scale translation level and will facilitate the elucidation of the mechanism of action of benzothiazole.
Ultrasensitive, rapid and inexpensive detection of DNA using paper based lateral flow assay
Authors: Jauset-Rubio Miriam , Svobodová Markéta , Mairal Teresa , McNeil Calum , Keegan Neil , Saeed Ayman , Abbas Mohammad Nooredeen , El-Shahawi Mohammad S. , Bashammakh Abdulaziz S. , Alyoubi Abdulrahman O. , O´Sullivan Ciara K. 
Published: November 2016

AbstractSensitive, specific, rapid, inexpensive and easy-to-use nucleic acid tests for use at the point-of-need are critical for the emerging field of personalised medicine for which companion diagnostics are essential, as well as for application in low resource settings. Here we report on the development of a point-of-care nucleic acid lateral flow test for the direct detection of isothermally amplified DNA. The recombinase polymerase amplification method is modified slightly to use tailed primers, resulting in an amplicon with a duplex flanked by two single stranded DNA tails. This tailed amplicon facilitates detection via hybridisation to a surface immobilised oligonucleotide capture probe and a gold nanoparticle labelled reporter probe. A detection limit of 1 × 10−11 M (190 amol), equivalent to 8.67 × 105 copies of DNA was achieved, with the entire assay, both amplification and detection, being completed in less than 15 minutes at a constant temperature of 37 °C. The use of the tailed primers obviates the need for hapten labelling and consequent use of capture and reporter antibodies, whilst also avoiding the need for any post-amplification processing for the generation of single stranded DNA, thus presenting an assay that can facilely find application at the point of need.