bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy suppresses Ras-driven epithelial tumourigenesis by limiting the accumulation of reactive oxygen species
Authors: Manent J , Banerjee S , de Matos Simoes R , Zoranovic T , Mitsiades C , Penninger J M , Simpson K J , Humbert P O , Richardson H E 
Published: June 2017

AbstractActivation of Ras signalling occurs in ~30% of human cancers; however, activated Ras alone is not sufficient for tumourigenesis. In a screen for tumour suppressors that cooperate with oncogenic Ras (RasV12) inDrosophila, we identified genes involved in the autophagy pathway. Bioinformatic analysis of human tumours revealed that several core autophagy genes, includingGABARAP, correlate with oncogenicKRASmutations and poor prognosis in human pancreatic cancer, supporting a potential tumour-suppressive effect of the pathway in Ras-driven human cancers. InDrosophila,we demonstrate that blocking autophagy at any step of the pathway enhancesRasV12-driven epithelial tissue overgrowth via the accumulation of reactive oxygen species and activation of the Jun kinase stress response pathway. Blocking autophagy inRasV12clones also results in non-cell-autonomous effects with autophagy, cell proliferation and caspase activation induced in adjacent wild-type cells. Our study has implications for understanding the interplay between perturbations in Ras signalling and autophagy in tumourigenesis, which might inform the development of novel therapeutics targeting Ras-driven cancers.
Regulation of cargo transfer between ESCRT-0 and ESCRT-I complexes by flotillin-1 during endosomal sorting of ubiquitinated cargo
Authors: Meister M , Bänfer S , Gärtner U , Koskimies J , Amaddii M , Jacob R , Tikkanen R 
Published: June 2017

AbstractUbiquitin-dependent sorting of membrane proteins in endosomes directs them to lysosomal degradation. In the case of receptors such as the epidermal growth factor receptor (EGFR), lysosomal degradation is important for the regulation of downstream signalling. Ubiquitinated proteins are recognised in endosomes by the endosomal sorting complexes required for transport (ESCRT) complexes, which sequentially interact with the ubiquitinated cargo. Although the role of each ESCRT complex in sorting is well established, it is not clear how the cargo is passed on from one ESCRT to the next. We here show that flotillin-1 is required for EGFR degradation, and that it interacts with the subunits of ESCRT-0 and -I complexes (hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) and Tsg101). Flotillin-1 is required for cargo recognition and sorting by ESCRT-0/Hrs and for its interaction with Tsg101. In addition, flotillin-1 is also required for the sorting of human immunodeficiency virus 1 Gag polyprotein, which mimics ESCRT-0 complex during viral assembly. We propose that flotillin-1 functions in cargo transfer between ESCRT-0 and -I complexes.
Initial assessment of the nutritional quality of the space food system over three years of ambient storage
Authors: Cooper Maya , Perchonok Michele , Douglas Grace L. 
Published: June 2017

AbstractProcessed and prepackaged space food is the main source of nutrition for crew aboard the International Space Station, and likely will continue to be the main source of nutrition for future exploration missions. However, very little information is available on the nutritional stability of space foods. To better understand their nutritional stability, 24 micronutrients were measured in 109 space foods stored over 3 years at room temperature. Our analysis indicated that potassium, calcium, vitamin D, and vitamin K concentrations in the food may not be adequate to meet the recommended daily intake requirements even before storage. Decreases in vitamins A, C, B1, and B6 were observed during storage. Notably, vitamins B1 and C may degrade to inadequate levels after 1 year and 3 years, respectively. This assessment suggests that different technological approaches will be required to stabilize processed foods to enable spaceflight missions over 1 year.
Coherent shuttle of electron-spin states
Authors: Fujita Takafumi , Baart Timothy Alexander , Reichl Christian , Wegscheider Werner , Vandersypen Lieven Mark Koenraad 
Published: June 2017

AbstractWe demonstrate a coherent spin shuttle through a GaAs/AlGaAs quadruple-quantum-dot array. Starting with two electrons in a spin-singlet state in the first dot, we shuttle one electron over to either the second, third, or fourth dot. We observe that the separated spin-singlet evolves periodically into the m = 0 spin-triplet and back before it dephases due to nuclear spin noise. We attribute the time evolution to differences in the local Zeeman splitting between the respective dots. With the help of numerical simulations, we analyze and discuss the visibility of the singlet-triplet oscillations and connect it to the requirements for coherent spin shuttling in terms of the inter-dot tunnel coupling strength and rise time of the pulses. The distribution of entangled spin pairs through tunnel coupled structures may be of great utility for connecting distant qubit registers on a chip.
Quantum ferromagnet in the proximity of the tricritical point
Authors: Opletal Petr , Prokleška Jan , Valenta Jaroslav , Proschek Petr , Tkáč Vladimír , Tarasenko Róbert , Běhounková Marie , Matoušková Šárka , Abd-Elmeguid Mohsen M. , Sechovský Vladimír 
Published: June 2017

AbstractEchoes of quantum phase transitions at finite temperatures are theoretically and experimentally challenging and unexplored topics. Particularly in metallic quantum ferromagnets the experimental investigations are hampered by an intricate preparation of sufficiently pure samples and the access to the proper coordinates in parameter space. The present study shows that it is possible to tune a specific system at easily accessible conditions to the vicinity of its quantum phase transition. The physics is demonstrated on Ru-doped UCoAl, driven by pressure or substitution to and across the tricritical point and follows the first-order transition line to the theoretically presumed quantum phase transition. These findings open the possibilities for further in-depth studies of classical and quantum critical phenomena at easily reachable conditions.
Translational cardiac stem cell therapy: advancing from first-generation to next-generation cell types
Authors: Cambria Elena , Pasqualini Francesco S. , Wolint Petra , Günter Julia , Steiger Julia , Bopp Annina , Hoerstrup Simon P. , Emmert Maximilian Y. 
Published: June 2017

AbstractAcute myocardial infarction and chronic heart failure rank among the major causes of morbidity and mortality worldwide. Except for heart transplantation, current therapy options only treat the symptoms but do not cure the disease. Stem cell-based therapies represent a possible paradigm shift for cardiac repair. However, most of the first-generation approaches displayed heterogeneous clinical outcomes regarding efficacy. Stemming from the desire to closely match the target organ, second-generation cell types were introduced and rapidly moved from bench to bedside. Unfortunately, debates remain around the benefit of stem cell therapy, optimal trial design parameters, and the ideal cell type. Aiming at highlighting controversies, this article provides a critical overview of the translation of first-generation and second-generation cell types. It further emphasizes the importance of understanding the mechanisms of cardiac repair and the lessons learned from first-generation trials, in order to improve cell-based therapies and to potentially finally implement cell-free therapies.
Development and Evaluation of 18F-IRS for Molecular Imaging Mutant EGF Receptors in NSCLC
Authors: Song Yan , Xiao Zunyu , Wang Kai , Wang Xiance , Zhang Chongqing , Fang Fang , Sun Xilin , Shen Baozhong 
Published: June 2017

AbstractTo prepare and evaluate a new radiotracer 18F-IRS for molecular imaging mutant EGF Receptors in vitro and vivo. Uptake and efflux of 18F-IRS were performed with four NSCLC cell lines including HCC827, H1975, H358 and H520. In vivo tumor targeting and pharmacokinetics of the radiotracers were also evaluated in HCC827, H1975, H358 and H520 tumor-bearing nude mice by PET/CT imaging. Ex vivo biodistribution assays were performed to quantify the accumulation of 18F-IRS in vivo. We also performed 18F-IRS PET/CT imaging of three patients with NSCLC. We labeled this small molecule with QD620 for flow cytometry and confocal imaging analyses. The uptakes of 18F-IRS by HCC827 and HCC827 tumors were significantly higher than those of H358, H1975 and H520, and they were reduced by the addition of 100 μM of gefitinib. Biodistribution experiments showed an accumulation of 18F-IRS in tumors of HCC827 xenografts. Flow cytometry and confocal imaging with QD620-IRS further demonstrated that binding specifically to HCC827 cells. 18F-IRS accumulation was preferential in the tumor, which was NSCLC with responsive EGFR exon 19 deleted. 18F-IRS showed high binding stability and specificity to 19 exon deleted EGFR mutation in vitro and vivo.
An effective molecular approach for assessing cereal aphid-parasitoid-endosymbiont networks
Authors: Ye Zhengpei , Vollhardt Ines M. G. , Girtler Susanne , Wallinger Corinna , Tomanovic Zeljko , Traugott Michael 
Published: June 2017

AbstractMolecular approaches are increasingly being used to analyse host-parasitoid food webs as they overcome several hurdles inherent to conventional approaches. However, such studies have focused primarily on the detection and identification of aphids and their aphidiid primary parasitoids, largely ignoring primary parasitoid-hyperparasitoid interactions or limiting these to a few common species within a small geographical area. Furthermore, the detection of bacterial secondary endosymbionts has not been considered in such assays despite the fact that endosymbionts may alter aphid-parasitoid interactions, as they can confer protection against parasitoids. Here we present a novel two-step multiplex PCR (MP-PCR) protocol to assess cereal aphid-primary parasitoid-hyperparasitoid-endosymbiont interactions. The first step of the assay allows detection of parasitoid DNA at a general level (24 primary and 16 hyperparasitoid species) as well as the species-specific detection of endosymbionts (3 species) and cereal aphids (3 species). The second step of the MP-PCR assay targets seven primary and six hyperparasitoid species that commonly occur in Central Europe. Additional parasitoid species not covered by the second-step of the assay can be identified via sequencing 16S rRNA amplicons generated in the first step of the assay. The approach presented here provides an efficient, highly sensitive, and cost-effective (~consumable costs of 1.3 € per sample) tool for assessing cereal aphid-parasitoid-endosymbiont interactions.
Flexible Indium–Tin Oxide Crystal on Plastic Substrates Supported by Graphene Monolayer
Authors: Lee Sang Jin , Kim Yekyung , Hwang Jun-Yeon , Lee Ju-Ho , Jung Seungon , Park Hyesung , Cho Seungmin , Nahm Sahn , Yang Woo Seok , Kim Hyeongkeun , Han Seung Ho 
Published: June 2017

AbstractFlexible and crystallized indium–tin oxide (ITO) thin films were successfully obtained on plastic polyethylene terephthalate (PET) films with monolayered graphene as a platform. The highly crystalline ITO (c-ITO) was first fabricated on a rigid substrate of graphene on copper foil and it was subsequently transferred onto a PET substrate by a well-established technique. Despite the plasma damage during ITO deposition, the graphene layer effectively acted as a Cu-diffusion barrier. The c-ITO/graphene/PET electrode with the 60-nm-thick ITO exhibited a reasonable sheet resistance of ~45 Ω sq−1 and a transmittance of ~92% at a wavelength of 550 nm. The c-ITO on the monolayered graphene support showed significant enhancement in flexibility compared with the ITO/PET film without graphene because the atomically controlled monolayered graphene acted as a mechanically robust support. The prepared flexible transparent c-ITO/graphene/PET electrode was applied as the anode in a bulk heterojunction polymer solar cell (PSC) to evaluate its performance, which was comparable with that of the commonly used c-ITO/glass electrode. These results represent important progress in the fabrication of flexible transparent electrodes for future optoelectronics applications.
Deregulation of miRNAs in malignant pleural mesothelioma is associated with prognosis and suggests an alteration of cell metabolism
Authors: De Santi Chiara , Melaiu Ombretta , Bonotti Alessandra , Cascione Luciano , Di Leva Gianpiero , Foddis Rudy , Cristaudo Alfonso , Lucchi Marco , Mora Marco , Truini Anna , Tironi Andrea , Murer Bruno , Boldorini Renzo , Cipollini Monica , Gemignani Federica , Gasparini Pierluigi , Mutti Luciano , Landi Stefano 
Published: June 2017

AbstractMalignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. In silico analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM.
Permeability-driven selection in a semi-empirical protocell model: the roots of prebiotic systems evolution
Authors: Piedrafita Gabriel , Monnard Pierre-Alain , Mavelli Fabio , Ruiz-Mirazo Kepa 
Published: June 2017

AbstractThe origin-of-life problem has been traditionally conceived as the chemical challenge to find the type of molecule and free-solution reaction dynamics that could have started Darwinian evolution. Different autocatalytic and ‘self-replicative’ molecular species have been extensively investigated, together with plausible synthetic pathways that might have led, abiotically, to such a minimalist scenario. However, in addition to molecular kinetics or molecular evolutionary dynamics, other physical and chemical constraints (like compartmentalization, differential diffusion, selective transport, osmotic forces, energetic couplings) could have been crucial for the cohesion, functional integration, and intrinsic stability/robustness of intermediate systems between chemistry and biology. These less acknowledged mechanisms of interaction and molecular control might have made the initial pathways to prebiotic systems evolution more intricate, but were surely essential for sustaining far-from-equilibrium chemical dynamics, given their functional relevance in all modern cells. Here we explore a protocellular scenario in which some of those additional constraints/mechanisms are addressed, demonstrating their ‘system-level’ implications. In particular, an experimental study on the permeability of prebiotic vesicle membranes composed of binary lipid mixtures allows us to construct a semi-empirical model where protocells are able to reproduce and undergo an evolutionary process based on their coupling with an internal chemistry that supports lipid synthesis.
Innate And Adaptive Immunity are Progressively Activated in Parallel with Renal Injury in the 5/6 Renal Ablation Model
Authors: Fanelli Camilla , Arias Simone C. A. , Machado Flavia G. , Okuma Jessica K. , Malheiros Denise M. A. C. , Azevedo Hatylas , Moreira-Filho Carlos A. , Camara Niels O. S. , Fujihara Clarice K. , Zatz Roberto 
Published: June 2017

AbstractThe mechanisms triggering renal inflammation in chronic kidney disease (CKD) are unclear. We performed a detailed analysis of the time course of innate and adaptive immunity activation in the 5/6 renal ablation (Nx) model. Munich-Wistar rats undergoing Nx were studied 15, 60 and 120 days after ablation. Hypertension, albuminuria, creatinine retention, interstitial expansion and infiltration by macrophages and T-lymphocytes were already evident 15 days after Nx. PCR-array was used to screen for altered gene expression, whereas gene and protein expressions of TLR4, CASP1, IL-1β and NLRP3 were individually assessed. Tlr4, Tlr5, Lbp, Nlrp3, Casp1, Irf7 and Il1b were already upregulated 15 days after Nx, while activation of Tlr2, Tlr7, Tlr9, Nod2, Tnf and Il6 was seen after 60 days post-ablation. The number of genes related to innate or adaptive immunity grew steadily with time. These observations indicate that parallel activation of innate and adaptive immunity antecedes glomerular injury and involves a growing number of intricate signaling pathways, helping to explain the difficulty in detaining renal injury in Nx as CKD advances, and, stressing the need for early treatment. Additionally, these findings may contribute to the search of therapeutic targets specific for advanced phases of CKD.
Global temporal patterns of pancreatic cancer and association with socioeconomic development
Authors: Wong Martin C. S. , Jiang Johnny Y. , Liang Miaoyin , Fang Yuan , Yeung Ming Sze , Sung Joseph J. Y. 
Published: June 2017

AbstractPancreatic cancer induces a substantial global burden. We examined its global incidence/mortality rates and their correlation with socioeconomic development (Human Development Index [HDI] and Gross Domestic Product [GDP] in 2000 as proxy measures). Data on age-standardized incidence/mortality rates in 2012 were retrieved from the GLOBOCAN database. Temporal patterns in 1998–2007 were assessed for 39 countries according to gender. The Average Annual Percent Change (AAPC) of the incidence/mortality trends was evaluated using joinpoint regression analysis. The age-standardized incidence ranged between 0.8–8.9/100,000. When compared among countries, Brazil (AAPC = 10.4, 95%C.I. = 0.8,21) and France (AAPC = 4.7, 95%C.I. = 3.6,5.9) reported the highest incidence rise in men. The greatest increase in women was reported in Thailand (AAPC = 7, 95%C.I. = 2.1,12.1) and Ecuador (AAPC = 4.3, 95%C.I. = 1.3,7.3). For mortality, the Philippines (APCC = 4.3, 95%C.I. = 2,6.6) and Croatia (AAPC = 2, 95% C.I. = 0,3.9) reported the biggest increase among men. The Philippines (AAPC = 5.8, 95% C.I. 4.5,7.2) and Slovakia (AAPC = 3.1, 95% C.I. 0.9,5.3) showed the most prominent rise among women. Its incidence was positively correlated with HDI (men: r = 0.66; women: r = 0.70) and GDP (men: r = 0.29; women: r = 0.28, all p < 0.05), and similarly for mortality (men: r = 0.67; women: r = 0.72 [HDI]; men: r = 0.23; women: r = 0.28 [GDP]). In summary, the incidence and mortality of pancreatic cancer were rising in many countries, requiring regular surveillance.
Pwp2 mediates UTP-B assembly via two structurally independent domains
Authors: Boissier Fanny , Schmidt Christina Maria , Linnemann Jan , Fribourg Sébastien , Perez-Fernandez Jorge 
Published: June 2017

AbstractThe SSU processome constitutes a large ribonucleoprotein complex involved in the early steps of ribosome biogenesis. UTP-B is one of the first multi-subunit protein complexes that associates with the pre-ribosomal RNA to form the SSU processome. To understand the molecular basis of the hierarchical assembly of the SSU-processome, we have undergone a structural and functional analysis of the UTP-B subunit Pwp2p. We show that Pwp2p is required for the proper assembly of UTP-B and for a productive association of UTP-B with pre-rRNA. These two functions are mediated by two distinct structural domains. The N-terminal domain of Pwp2p folds into a tandem WD-repeat (tWD) that associates with Utp21p, Utp18p, and Utp6p to form a core complex. The CTDs of Pwp2p and Utp21p mediate the assembly of the heterodimer Utp12p:Utp13p that is required for the stable incorporation of the UTP-B complex in the SSU processome. Finally, we provide evidence suggesting a role of UTP-B as a platform for the binding of assembly factors during the maturation of 20S rRNA precursors.
Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
Authors: Arya Ashutosh Kumar , Bhadada Sanjay Kumar , Singh Priyanka , Sachdeva Naresh , Saikia Uma Nahar , Dahiya Divya , Behera Arunanshu , Bhansali Anil , Rao Sudhaker D. 
Published: June 2017

AbstractCyclin D1, a G1-S phase regulator, is upregulated in parathyroid adenomas. Since cyclin-dependent kinase (CDK) inhibitors, CDKN2A and CDKN2B, and RASSF1A (Ras-association domain family 1, isoform A) are involved in G1-S phase arrest and act as potential tumor suppressor genes, we aimed to study potential methylation-mediated inactivation of these genes in parathyroid adenomas. Gene expressions of cyclin D1 (CCND1) and regulatory molecules (CDKN2A, CDKN2B and RASSF1A) was analysed in parathyroid adenoma tissues (n = 30). DNA promoter methylation of cyclin D1 regulators were assessed and correlated with clinicopathological features of the patients. Gene expression analysis showed a relative fold reductions of 0.35 for CDKN2A (p = 0.01), 0.45 for CDKN2B (P = 0.02), and 0.39 for RASSF1A (p < 0.01) in adenomatous compared to normal parathyroid tissue. There was an inverse relationship between the expressions of CDKN2A and CDKN2B with CCND1. In addition, the promoter regions of CDKN2A, CDKN2B, and of RASSF1A were significantly hyper-methylated in 50% (n = 15), 47% (n = 14), and 90% (n = 27) of adenomas respectively. In contrast, no such aberrant methylation of these genes was observed in normal parathyroid tissue. So, promoter hypermethylation is associated with down-regulation of CCND1 regulatory genes in sporadic parathyroid adenomas. This dysregulated cell cycle mechanism may contribute to parathyroid tumorigenesis.
Action sequencing in the spontaneous swimming behavior of zebrafish larvae - implications for drug development
Authors: Palmér Tobias , Ek Fredrik , Enqvist Olof , Olsson Roger , Åström Kalle , Petersson Per 
Published: June 2017

AbstractAll motile organisms need to organize their motor output to obtain functional goals. In vertebrates, natural behaviors are generally composed of a relatively large set of motor components which in turn are combined into a rich repertoire of complex actions. It is therefore an experimental challenge to investigate the organizational principles of natural behaviors. Using the relatively simple locomotion pattern of 10 days old zebrafish larvae we have here characterized the basic organizational principles governing the swimming behavior. Our results show that transitions between different behavioral states can be described by a model combining a stochastic component with a control signal. By dividing swimming bouts into a limited number of categories, we show that similar types of swimming behavior as well as stand-stills between bouts were temporally clustered, indicating a basic level of action sequencing. Finally, we show that pharmacological manipulations known to induce alterations in the organization of motor behavior in mammals, mainly through basal ganglia interactions, have related effects in zebrafish larvae. This latter finding may be of specific relevance to the field of drug development given the growing importance of zebrafish larvae in phenotypic screening for novel drug candidates acting on central nervous system targets.