bluuebunny/crossref_metadata_2025_split huggingface dataset:
TRIB2 regulates normal and stress-induced thymocyte proliferation
Authors: Liang Kai Ling , O’Connor Caitriona , Veiga J Pedro , McCarthy Tommie V , Keeshan Karen 
Published: March 2016

AbstractTRIB2, a serine/threonine pseudokinase identified as an oncogene, is expressed at high levels in the T-cell compartment of hematopoiesis. The proliferation of developing thymocytes is tightly controlled to prevent leukemic transformation of T cells. Here we examine Trib2 loss in murine hematopoiesis under steady state and proliferative stress conditions, including genotoxic and oncogenic stress. Trib2−/− developing thymocytes show increased proliferation, and Trib2−/− mice have significantly higher thymic cellularity at steady state. During stress hematopoiesis, Trib2−/− developing thymocytes undergo accelerated proliferation and demonstrate hypersensitivity to 5-fluorouracil (5-FU)-induced cell death. Despite the increased cell death post 5-FU-induced proliferative stress, Trib2−/− mice exhibit accelerated thymopoietic recovery post treatment due to increased cell division kinetics of developing thymocytes. The increased proliferation in Trib2−/− thymocytes was exacerbated under oncogenic stress. In an experimental murine T-cell acute lymphoblastic leukemia (T-ALL) model, Trib2−/− mice had reduced latency in vivo, which associated with impaired MAP kinase (MAPK) activation. High and low expression levels of Trib2 correlate with immature and mature subtypes of human T-ALL, respectively, and associate with MAPK. Thus, TRIB2 emerges as a novel regulator of thymocyte cellular proliferation, important for the thymopoietic response to genotoxic and oncogenic stress, and possessing tumor suppressor function.
Understanding congested travel in urban areas
Authors: Çolak Serdar , Lima Antonio , González Marta C. 
Published: March 2016

AbstractRapid urbanization and increasing demand for transportation burdens urban road infrastructures. The interplay of number of vehicles and available road capacity on their routes determines the level of congestion. Although approaches to modify demand and capacity exist, the possible limits of congestion alleviation by only modifying route choices have not been systematically studied. Here we couple the road networks of five diverse cities with the travel demand profiles in the morning peak hour obtained from billions of mobile phone traces to comprehensively analyse urban traffic. We present that a dimensionless ratio of the road supply to the travel demand explains the percentage of time lost in congestion. Finally, we examine congestion relief under a centralized routing scheme with varying levels of awareness of social good and quantify the benefits to show that moderate levels are enough to achieve significant collective travel time savings.
G6PD protects from oxidative damage and improves healthspan in mice
Authors: Nóbrega-Pereira Sandrina , Fernandez-Marcos Pablo J. , Brioche Thomas , Gomez-Cabrera Mari Carmen , Salvador-Pascual Andrea , Flores Juana M. , Viña Jose , Serrano Manuel 
Published: March 2016

AbstractReactive oxygen species (ROS) are constantly generated by cells and ROS-derived damage contributes to ageing. Protection against oxidative damage largely relies on the reductive power of NAPDH, whose levels are mostly determined by the enzyme glucose-6-phosphate dehydrogenase (G6PD). Here, we report a transgenic mouse model with moderate overexpression of human G6PD under its endogenous promoter. Importantly, G6PD-Tg mice have higher levels of NADPH, lower levels of ROS-derived damage, and better protection from ageing-associated functional decline, including extended median lifespan in females. The G6PD transgene has no effect on tumour development, even after combining with various tumour-prone genetic alterations. We conclude that a modest increase in G6PD activity is beneficial for healthspan through increased NADPH levels and protection from the deleterious effects of ROS.
Integrative analyses reveal a long noncoding RNA-mediated sponge regulatory network in prostate cancer
Authors: Du Zhou , Sun Tong , Hacisuleyman Ezgi , Fei Teng , Wang Xiaodong , Brown Myles , Rinn John L. , Lee Mary Gwo-Shu , Chen Yiwen , Kantoff Philip W. , Liu X. Shirley 
Published: March 2016

AbstractMounting evidence suggests that long noncoding RNAs (lncRNAs) can function as microRNA sponges and compete for microRNA binding to protein-coding transcripts. However, the prevalence, functional significance and targets of lncRNA-mediated sponge regulation of cancer are mostly unknown. Here we identify a lncRNA-mediated sponge regulatory network that affects the expression of many protein-coding prostate cancer driver genes, by integrating analysis of sequence features and gene expression profiles of both lncRNAs and protein-coding genes in tumours. We confirm the tumour-suppressive function of two lncRNAs (TUG1 and CTB-89H12.4) and their regulation of PTEN expression in prostate cancer. Surprisingly, one of the two lncRNAs, TUG1, was previously known for its function in polycomb repressive complex 2 (PRC2)-mediated transcriptional regulation, suggesting its sub-cellular localization-dependent function. Our findings not only suggest an important role of lncRNA-mediated sponge regulation in cancer, but also underscore the critical influence of cytoplasmic localization on the efficacy of a sponge lncRNA.
Type 1 diabetes vaccine candidates promote human Foxp3+Treg induction in humanized mice
Authors: Serr Isabelle , Fürst Rainer W. , Achenbach Peter , Scherm Martin G. , Gökmen Füsun , Haupt Florian , Sedlmeier Eva-Maria , Knopff Annette , Shultz Leonard , Willis Richard A. , Ziegler Anette-Gabriele , Daniel Carolin 
Published: March 2016

AbstractImmune tolerance is executed partly by Foxp3+regulatory T (Treg) cells, which suppress autoreactive T cells. In autoimmune type 1 diabetes (T1D) impaired tolerance promotes destruction of insulin-producing β-cells. The development of autoantigen-specific vaccination strategies for Foxp3+Treg-induction and prevention of islet autoimmunity in patients is still in its infancy. Here, using human haematopoietic stem cell-engrafted NSG-HLA-DQ8 transgenic mice, we provide direct evidence for human autoantigen-specific Foxp3+Treg-induction in vivo. We identify HLA-DQ8-restricted insulin-specific CD4+T cells and demonstrate efficient human insulin-specific Foxp3+Treg-induction upon subimmunogenic vaccination with strong agonistic insulin mimetopes in vivo. Induced human Tregs are stable, show increased expression of Treg signature genes such as Foxp3, CTLA4, IL-2Rα and TIGIT and can efficiently suppress effector T cells. Such Foxp3+Treg-induction does not trigger any effector T cells. These T1D vaccine candidates could therefore represent an expedient improvement in the challenge to induce human Foxp3+Tregs and to develop novel precision medicines for prevention of islet autoimmunity in children at risk of T1D.
Therapeutic targeting and rapid mobilization of endosteal HSC using a small molecule integrin antagonist
Authors: Cao Benjamin , Zhang Zhen , Grassinger Jochen , Williams Brenda , Heazlewood Chad K. , Churches Quentin I. , James Simon A. , Li Songhui , Papayannopoulou Thalia , Nilsson Susan K. 
Published: March 2016

AbstractThe inherent disadvantages of using granulocyte colony-stimulating factor (G-CSF) for hematopoietic stem cell (HSC) mobilization have driven efforts to identify alternate strategies based on single doses of small molecules. Here, we show targeting α9β1/α4β1 integrins with a single dose of a small molecule antagonist (BOP (N-(benzenesulfonyl)-L-prolyl-L-O-(1-pyrrolidinylcarbonyl)tyrosine)) rapidly mobilizes long-term multi-lineage reconstituting HSC. Synergistic engraftment augmentation is observed when BOP is co-administered with AMD3100. Impressively, HSC in equal volumes of peripheral blood (PB) mobilized with this combination effectively out-competes PB mobilized with G-CSF. The enhanced mobilization observed using BOP and AMD3100 is recapitulated in a humanized NODSCIDIL2Rγ−/− model, demonstrated by a significant increase in PB CD34+ cells. Using a related fluorescent analogue of BOP (R-BC154), we show that this class of antagonists preferentially bind human and mouse HSC and progenitors via endogenously primed/activated α9β1/α4β1 within the endosteal niche. These results support using dual α9β1/α4β1 inhibitors as effective, rapid and transient mobilization agents with promising clinical applications.
A large dataset of protein dynamics in the mammalian heart proteome
Authors: Lau Edward , Cao Quan , Ng Dominic C.M. , Bleakley Brian J. , Dincer T. Umut , Bot Brian M. , Wang Ding , Liem David A. , Lam Maggie P.Y. , Ge Junbo , Ping Peipei 
Published: March 2016

AbstractProtein stability is a major regulatory principle of protein function and cellular homeostasis. Despite limited understanding on mechanisms, disruption of protein turnover is widely implicated in diverse pathologies from heart failure to neurodegenerations. Information on global protein dynamics therefore has the potential to expand the depth and scope of disease phenotyping and therapeutic strategies. Using an integrated platform of metabolic labeling, high-resolution mass spectrometry and computational analysis, we report here a comprehensive dataset of the in vivo half-life of 3,228 and the expression of 8,064 cardiac proteins, quantified under healthy and hypertrophic conditions across six mouse genetic strains commonly employed in biomedical research. We anticipate these data will aid in understanding key mitochondrial and metabolic pathways in heart diseases, and further serve as a reference for methodology development in dynamics studies in multiple organ systems.
The FAIR Guiding Principles for scientific data management and stewardship
Authors: Wilkinson Mark D. , Dumontier Michel , Aalbersberg IJsbrand Jan , Appleton Gabrielle , Axton Myles , Baak Arie , Blomberg Niklas , Boiten Jan-Willem , da Silva Santos Luiz Bonino , Bourne Philip E. , Bouwman Jildau , Brookes Anthony J. , Clark Tim , Crosas Mercè , Dillo Ingrid , Dumon Olivier , Edmunds Scott , Evelo Chris T. , Finkers Richard , Gonzalez-Beltran Alejandra , Gray Alasdair J.G. , Groth Paul , Goble Carole , Grethe Jeffrey S. , Heringa Jaap , ’t Hoen Peter A.C , Hooft Rob , Kuhn Tobias , Kok Ruben , Kok Joost , Lusher Scott J. , Martone Maryann E. , Mons Albert , Packer Abel L. , Persson Bengt , Rocca-Serra Philippe , Roos Marco , van Schaik Rene , Sansone Susanna-Assunta , Schultes Erik , Sengstag Thierry , Slater Ted , Strawn George , Swertz Morris A. , Thompson Mark , van der Lei Johan , van Mulligen Erik , Velterop Jan , Waagmeester Andra , Wittenburg Peter , Wolstencroft Katherine , Zhao Jun , Mons Barend 
Published: March 2016

AbstractThere is an urgent need to improve the infrastructure supporting the reuse of scholarly data. A diverse set of stakeholders—representing academia, industry, funding agencies, and scholarly publishers—have come together to design and jointly endorse a concise and measureable set of principles that we refer to as the FAIR Data Principles. The intent is that these may act as a guideline for those wishing to enhance the reusability of their data holdings. Distinct from peer initiatives that focus on the human scholar, the FAIR Principles put specific emphasis on enhancing the ability of machines to automatically find and use the data, in addition to supporting its reuse by individuals. This Comment is the first formal publication of the FAIR Principles, and includes the rationale behind them, and some exemplar implementations in the community.
Development of a double-antibody sandwich ELISA for rapid detection of Bacillus Cereus in food
Authors: Zhu Longjiao , He Jing , Cao Xiaohan , Huang Kunlun , Luo Yunbo , Xu Wentao 
Published: March 2016

AbstractBacillus cereus is increasingly recognized as one of the major causes of food poisoning in the industrialized world. In this paper, we describe a sensitive double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) that was developed for rapid detection of B. cereus in food to minimize the risk of contamination. The polyclonal antibody (pAb) and monoclonal antibodies (mAbs) specific to B. cereus were generated from rabbit antiserum and mouse ascites, respectively, using the octanoic acid/saturated ammonium sulfate precipitation method and protein A-sepharose columns. IgG-isotype mAbs were specially developed to undergo a novel peripheral multiple sites immunization for rapid gain of hybridomas and a subtractive screen was used to eliminate cross reactivity with closely related species such as Bacillus thuringiensis, B. subtilis, B. licheniformis and B. perfringens. The linear detection range of the method was approximately 1 × 104–2.8 × 106 cells/mL with a detection limit (LOD) of 0.9 × 103 cells/mL. The assay was able to detect B. cereus when the samples were prepared in meat with various pathogens. The newly developed analytical method provides a rapid method to sensitively detect B. cereus in food specimens.
Clinical Practice Pattern of Immediate Intravesical Chemotherapy following Transurethral Resection of a Bladder Tumor in Korea: National Health Insurance Database Study
Authors: Seo Gi Hyeon , Kim Jae Heon , Ku Ja Hyeon 
Published: March 2016

AbstractWe evaluated the frequency and practice pattern of immediate postoperative intravesical chemotherapy (PIC) after transurethral resection of a bladder tumor (TURBT) in suspected non-muscle-invasive bladder cancer (NMIBC). Information from the Health Insurance Review and Assessment Service database from January 1, 2008 to December 31, 2013 was used. Patients with bladder cancer who received TURBT were considered as the cases (37,941 patients and 59,568 cases). The time of PIC after TURBT, types of PIC regimens, and the potential effect of PIC on the delay for additional treatment were analyzed. The study cohort included 23,726 subjects and 30,473 cases with a mean age of 66.8 ± 12.0 years, including 19,362 (81.6%) male patients. The rate of immediate PIC was 11.0% of cases (3,359 cases). There was significant difference in the frequency rate of additional treatment among patients with immediate PIC and patients without immediate PIC within 1 year from the first TURBT (15.2% vs 16.6%, p = 0.035). However, no difference was revealed for whole observational period (33.7% vs 34.5%, p = 0.373). The frequency rate of immediate PIC after TURBT for suspected NMIBC was low in real clinical practice. More efforts are needed to improve the usage rate of PIC after TURBT for suspected NMIBC.
A generic screening platform for inhibitors of virus induced cell fusion using cellular electrical impedance
Authors: Watterson Daniel , Robinson Jodie , Chappell Keith J. , Butler Mark S. , Edwards David J. , Fry Scott R. , Bermingham Imogen M. , Cooper Matthew A. , Young Paul R. 
Published: March 2016

AbstractFusion of the viral envelope with host cell membranes is an essential step in the life cycle of all enveloped viruses. Despite such a clear target for antiviral drug development, few anti-fusion drugs have progressed to market. One significant hurdle is the absence of a generic, high-throughput, reproducible fusion assay. Here we report that real time, label-free measurement of cellular electrical impedance can quantify cell-cell fusion mediated by either individually expressed recombinant viral fusion proteins, or native virus infection. We validated this approach for all three classes of viral fusion and demonstrated utility in quantifying fusion inhibition using antibodies and small molecule inhibitors specific for dengue virus and respiratory syncytial virus.
Development of a method for detection and quantification of B. brongniartii and B. bassiana in soil
Authors: Canfora L. , Malusà E. , Tkaczuk C. , Tartanus M. , Łabanowska B.H. , Pinzari F. 
Published: March 2016

AbstractA culture independent method based on qPCR was developed for the detection and quantification of two fungal inoculants in soil. The aim was to adapt a genotyping approach based on SSR (Simple Sequence Repeat) marker to a discriminating tracing of two different species of bioinoculants in soil, after their in-field release. Two entomopathogenic fungi, Beauveria bassiana and B. brongniartii, were traced and quantified in soil samples obtained from field trials. These two fungal species were used as biological agents in Poland to control Melolontha melolontha (European cockchafer), whose larvae live in soil menacing horticultural crops. Specificity of SSR markers was verified using controls consisting of: i) soil samples containing fungal spores of B. bassiana and B. brongniartii in known dilutions; ii) the DNA of the fungal microorganisms; iii) soil samples singly inoculated with each fungus species. An initial evaluation of the protocol was performed with analyses of soil DNA and mycelial DNA. Further, the simultaneous detection and quantification of B. bassiana and B. brongniartii in soil was achieved in field samples after application of the bio-inoculants. The protocol can be considered as a relatively low cost solution for the detection, identification and traceability of fungal bio-inoculants in soil.
Pharyngeal pumping in Caenorhabditis elegans depends on tonic and phasic signaling from the nervous system
Authors: Trojanowski Nicholas F. , Raizen David M. , Fang-Yen Christopher 
Published: March 2016

AbstractRhythmic movements are ubiquitous in animal locomotion, feeding and circulatory systems. In some systems, the muscle itself generates rhythmic contractions. In others, rhythms are generated by the nervous system or by interactions between the nervous system and muscles. In the nematode Caenorhabditis elegans, feeding occurs via rhythmic contractions (pumping) of the pharynx, a neuromuscular feeding organ. Here, we use pharmacology, optogenetics, genetics and electrophysiology to investigate the roles of the nervous system and muscle in generating pharyngeal pumping. Hyperpolarization of the nervous system using a histamine-gated chloride channel abolishes pumping and optogenetic stimulation of pharyngeal muscle in these animals causes abnormal contractions, demonstrating that normal pumping requires nervous system function. In mutants that pump slowly due to defective nervous system function, tonic muscle stimulation causes rapid pumping, suggesting tonic neurotransmitter release may regulate pumping. However, tonic cholinergic motor neuron stimulation, but not tonic muscle stimulation, triggers pumps that electrophysiologically resemble typical rapid pumps. This suggests that pharyngeal cholinergic motor neurons are normally rhythmically and not tonically active. These results demonstrate that the pharynx generates a myogenic rhythm in the presence of tonically released acetylcholine and suggest that the pharyngeal nervous system entrains contraction rate and timing through phasic neurotransmitter release.
A novel framework of classical and quantum prisoner’s dilemma games on coupled networks
Authors: Deng Xinyang , Zhang Qi , Deng Yong , Wang Zhen 
Published: March 2016

AbstractEvolutionary games on multilayer networks are attracting growing interest. While among previous studies, the role of quantum games in such a infrastructure is still virgin and may become a fascinating issue across a myriad of research realms. To mimick two kinds of different interactive environments and mechanisms, in this paper a new framework of classical and quantum prisoner’s dilemma games on two-layer coupled networks is considered. Within the proposed model, the impact of coupling factor of networks and entanglement degree in quantum games on the evolutionary process has been studied. Simulation results show that the entanglement has no impact on the evolution of the classical prisoner’s dilemma, while the rise of the coupling factor obviously impedes cooperation in this game and the evolution of quantum prisoner’s dilemma is greatly impacted by the combined effect of entanglement and coupling.
Towards understanding of heat effects in metallic glasses on the basis of macroscopic shear elasticity
Authors: Mitrofanov Y. P. , Wang D. P. , Makarov A. S. , Wang W. H. , Khonik V. A. 
Published: March 2016

AbstractIt is shown that all heat effects taking place upon annealing of a metallic glass within the glassy and supercooled liquid states, i.e. heat release below the glass transition temperature and heat absorption above it, as well as crystallization-induced heat release, are related to the macroscopic shear elasticity. The underlying physical reason can be understood as relaxation in the system of interstitialcy-type ”defects” (elastic dipoles) frozen-in from the melt upon glass production.
Universally Conserved Relationships between Nuclear Shape and Cytoplasmic Mechanical Properties in Human Stem Cells
Authors: Lozoya Oswaldo A. , Gilchrist Christopher L. , Guilak Farshid 
Published: March 2016

AbstractThe ability of cells to proliferate, differentiate, transduce extracellular signals and assemble tissues involves structural connections between nucleus and cytoskeleton. Yet, how the mechanics of these connections vary inside stem cells is not fully understood. To address those questions, we combined two-dimensional particle-tracking microrheology and morphological measures using variable reduction techniques to measure whether cytoplasmic mechanics allow for discrimination between different human adherent stem cell types and across different culture conditions. Here we show that nuclear shape is a quantifiable discriminant of mechanical properties in the perinuclear cytoskeleton (pnCSK) of various stem cell types. Also, we find the pnCSK is a region with different mechanical properties than elsewhere in the cytoskeleton, with heterogeneously distributed locations exhibiting subdiffusive features and which obeys physical relations conserved among various stem cell types. Finally, we offer a prospective basis to discriminate between stem cell types by coupling perinuclear mechanical properties to nuclear shape.
EMD in periodontal regenerative surgery modulates cytokine profiles: A randomised controlled clinical trial
Authors: Villa Oscar , Wohlfahrt Johan C. , Koldsland Odd Carsten , Brookes Steven J. , Lyngstadaas Staale P. , Aass Anne M. , Reseland Janne E. 
Published: March 2016

AbstractThe enamel matrix derivative (EMD) contains hundreds of peptides in different levels of proteolytic processing that may provide a range of biological effects of importance in wound healing. The aim of the present study was to compare the effect of EMD and its fractions on the cytokine profiles from human gingival fibroblasts in vitro and in gingival crevicular fluid (GCF) in a randomized controlled split-mouth clinical study (n = 12). Levels of cytokines in cell culture medium and in GCF were measured by Luminex over a 2-week period. In the clinical study, levels of pro-inflammatory cytokines and chemokines were increased, whereas the levels of transforming growth factor-α (TGF-α) and platelet-derived growth factor-BB (PDGF-BB) were reduced. The in vitro study showed that EMD and its high and low molecular weight fractions reduced the secretion of pro-inflammatory cytokines and chemokines compared to untreated cells. EMD had an effect on levels of cytokines related to fibroplasia, angiogenesis, inflammation and chemotaxis both in vitro and in vivo, however, the anti-inflammatory effect induced by EMD observed in the in vitro study could not be confirmed clinically.