bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuronal evidence for good-based economic decisions under variable action costs
Authors: Cai Xinying , Padoa-Schioppa Camillo 
Published: January 2019

AbstractPrevious work showed that economic decisions can be made independently of spatial contingencies. However, when goods available for choice bear different action costs, the decision necessarily reflects aspects of the action. One possibility is that “stimulus values” are combined with the corresponding action costs in a motor representation, and decisions are then made in actions space. Alternatively, action costs could be integrated with other determinants of value in a non-spatial representation. If so, decisions under variable action costs could take place in goods space. Here, we recorded from orbitofrontal cortex while monkeys chose between different juices offered in variable amounts. We manipulated action costs by varying the saccade amplitude, and we dissociated in time and space offer presentation from action planning. Neurons encoding the binary choice outcome did so well before the presentation of saccade targets, indicating that decisions were made in goods space.
Comparative oncogenomics identifies combinations of driver genes and drug targets in BRCA1-mutated breast cancer
Authors: Annunziato Stefano , de Ruiter Julian R. , Henneman Linda , Brambillasca Chiara S. , Lutz Catrin , Vaillant François , Ferrante Federica , Drenth Anne Paulien , van der Burg Eline , Siteur Bjørn , van Gerwen Bas , de Bruijn Roebi , van Miltenburg Martine H. , Huijbers Ivo J. , van de Ven Marieke , Visvader Jane E. , Lindeman Geoffrey J. , Wessels Lodewyk F. A. , Jonkers Jos 
Published: January 2019

AbstractBRCA1-mutated breast cancer is primarily driven by DNA copy-number alterations (CNAs) containing large numbers of candidate driver genes. Validation of these candidates requires novel approaches for high-throughput in vivo perturbation of gene function. Here we develop genetically engineered mouse models (GEMMs) of BRCA1-deficient breast cancer that permit rapid introduction of putative drivers by either retargeting of GEMM-derived embryonic stem cells, lentivirus-mediated somatic overexpression or in situ CRISPR/Cas9-mediated gene disruption. We use these approaches to validate Myc, Met, Pten and Rb1 as bona fide drivers in BRCA1-associated mammary tumorigenesis. Iterative mouse modeling and comparative oncogenomics analysis show that MYC-overexpression strongly reshapes the CNA landscape of BRCA1-deficient mammary tumors and identify MCL1 as a collaborating driver in these tumors. Moreover, MCL1 inhibition potentiates the in vivo efficacy of PARP inhibition (PARPi), underscoring the therapeutic potential of this combination for treatment of BRCA1-mutated cancer patients with poor response to PARPi monotherapy.
Ultrafast hole transfer mediated by polaron pairs in all-polymer photovoltaic blends
Authors: Wang Rui , Yao Yao , Zhang Chunfeng , Zhang Yindong , Bin Haijun , Xue Lingwei , Zhang Zhi-Guo , Xie Xiaoyu , Ma Haibo , Wang Xiaoyong , Li Yongfang , Xiao Min 
Published: January 2019

AbstractThe charge separation yield at a bulk heterojunction sets the upper efficiency limit of an organic solar cell. Ultrafast charge transfer processes in polymer/fullerene blends have been intensively studied but much less is known about these processes in all-polymer systems. Here, we show that interfacial charge separation can occur through a polaron pair-derived hole transfer process in all-polymer photovoltaic blends, which is a fundamentally different mechanism compared to the exciton-dominated pathway in the polymer/fullerene blends. By utilizing ultrafast optical measurements, we have clearly identified an ultrafast hole transfer process with a lifetime of about 3 ps mediated by photo-excited polaron pairs which has a markedly high quantum efficiency of about 97%. Spectroscopic data show that excitons act as spectators during the efficient hole transfer process. Our findings suggest an alternative route to improve the efficiency of all-polymer solar devices by manipulating polaron pairs.
OVX836 a recombinant nucleoprotein vaccine inducing cellular responses and protective efficacy against multiple influenza A subtypes
Authors: Del Campo Judith , Pizzorno Andres , Djebali Sophia , Bouley Julien , Haller Marjorie , Pérez-Vargas Jimena , Lina Bruno , Boivin Guy , Hamelin Marie-Eve , Nicolas Florence , Le Vert Alexandre , Leverrier Yann , Rosa-Calatrava Manuel , Marvel Jacqueline , Hill Fergal 
Published: January 2019

AbstractInactivated influenza vaccines (IIVs) lack broad efficacy. Cellular immunity to a conserved internal antigen, the nucleoprotein (NP), has been correlated to protection against pandemic and seasonal influenza and thus could have the potential to broaden vaccine efficacy. We developed OVX836, a recombinant protein vaccine based on an oligomerized NP, which shows increased uptake by dendritic cells and immunogenicity compared with NP. Intramuscular immunization in mice with OVX836 induced strong NP-specific CD4+ and CD8+ T-cell systemic responses and established CD8+ tissue memory T cells in the lung parenchyma. Strikingly, OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load. When co-administered with IIV, OVX836 was even more effective in reducing lung viral load.
Using Baidu Search Engine to Monitor AIDS Epidemics Inform for Targeted intervention of HIV/AIDS in China
Authors: Li Kang , Liu Meiliang , Feng Yi , Ning Chuanyi , Ou Weidong , Sun Jia , Wei Wudi , Liang Hao , Shao Yiming 
Published: January 2019

AbstractChina’s reported cases of Human Immunodeficiency Virus (HIV) and AIDS increased from over 50000 in 2011 to more than 130000 in 2017, while AIDS related search indices on Baidu from 2.1 million to 3.7 million in the same time periods. In China, people seek AIDS related knowledge from Baidu which one of the world’s largest search engine. We study the relationship of national HIV surveillance data with the Baidu index (BDI) and use it to monitor AIDS epidemic and inform targeted intervention. After screening keywords and making index composition, we used seasonal autoregressive integrated moving average (ARIMA) modeling. The most correlated search engine query data was obtained by using ARIMA with external variables (ARIMAX) model for epidemic prediction. A significant correlation between monthly HIV/AIDS report cases and Baidu Composite Index (r = 0.845, P < 0.001) was observed using time series plot. Compared with the ARIMA model based on AIDS surveillance data, the ARIMAX model with Baidu Composite Index had the minimal an Akaike information criterion (AIC, 839.42) and the most exact prediction (MAPE of 6.11%). We showed that there are close correlations of the same trends between BDI and HIV/AIDS reports cases for both increasing and decreasing AIDS epidemic. Therefore, the Baidu search query data may be a good useful indicator for reliably monitoring and predicting HIV/AIDS epidemic in China.
De novo assembly of Agave sisalana transcriptome in response to drought stress provides insight into the tolerance mechanisms
Authors: Sarwar Muhammad Bilal , Ahmad Zarnab , Rashid Bushra , Hassan Sameera , Gregersen Per L. , Leyva Maria De la O. , Nagy Istvan , Asp Torben , Husnain Tayyab 
Published: January 2019

AbstractAgave, monocotyledonous succulent plants, is endemic to arid regions of North America, exhibiting exceptional tolerance to their xeric environments. They employ various strategies to overcome environmental constraints, such as crassulacean acid metabolism, wax depositions, and protective leaf morphology. Genomic resources of Agave species have received little attention irrespective of their cultural, economic and ecological importance, which so far prevented the understanding of the molecular bases underlying their adaptations to the arid environment. In this study, we aimed to elucidate molecular mechanism(s) using transcriptome sequencing ofA. sisalana. Ade novoapproach was applied to assemble paired-end reads. The expression study unveiled 3,095 differentially expressed unigenes between well-irrigated and drought-stressed leaf samples. Gene ontology and KEGG analysis specified a significant number of abiotic stress responsive genes and pathways involved in processes like hormonal responses, antioxidant activity, response to stress stimuli, wax biosynthesis, and ROS metabolism. We also identified transcripts belonging to several families harboring important drought-responsive genes. Our study provides the first insight into the genomic structure ofA. sisalanaunderlying adaptations to drought stress, thus providing diverse genetic resources for drought tolerance breeding research.
Probabilistic Assessment of Glass Forming Ability Rules for Metallic Glasses Aided by Automated Analysis of Phase Diagrams
Authors: Dasgupta Aparajita , Broderick Scott R. , Mack Connor , Kota Bhargava U. , Subramanian Ramachandran , Setlur Srirangaraj , Govindaraju Venu , Rajan Krishna 
Published: January 2019

AbstractThe use of machine learning techniques to expedite the discovery and development of new materials is an essential step towards the acceleration of a new generation of domain-specific highly functional material systems. In this paper, we use the test case of bulk metallic glasses to highlight the key issues in the field of high throughput predictions and propose a new probabilistic analysis of rules for glass forming ability using rough set theory. This approach has been applied to a broad range of binary alloy compositions in order to predict new metallic glass compositions. Our data driven approach takes into account not only a broad variety of thermodynamic, structural and kinetic based criteria, but also incorporates qualitative and descriptive attributes associated with eutectic points in phase diagrams. For the latter, we demonstrate the use of automated machine learning methods that go far beyond text recognition approaches by also being able to interpret phase diagrams. When combined with structural descriptors, this approach provides the foundations to develop a hierarchical probabilistic predication tool that can rank the feasibility of glass formation.
Illuminating the catalytic core of ectoine synthase through structural and biochemical analysis
Authors: Czech Laura , Höppner Astrid , Kobus Stefanie , Seubert Andreas , Riclea Ramona , Dickschat Jeroen S. , Heider Johann , Smits Sander H. J. , Bremer Erhard 
Published: January 2019

AbstractEctoine synthase (EctC) is the signature enzyme for the production of ectoine, a compatible solute and chemical chaperone widely synthesized by bacteria as a cellular defense against the detrimental effects of osmotic stress. EctC catalyzes the last step in ectoine synthesis through cyclo-condensation of the EctA-formed substrate N-gamma-acetyl-L-2,4-diaminobutyric acid via a water elimination reaction. We have biochemically and structurally characterized the EctC enzyme from the thermo-tolerant bacterium Paenibacillus lautus (Pl). EctC is a member of the cupin superfamily and forms dimers, both in solution and in crystals. We obtained high-resolution crystal structures of the (Pl)EctC protein in forms that contain (i) the catalytically important iron, (ii) iron and the substrate N-gamma-acetyl-L-2,4-diaminobutyric acid, and (iii) iron and the enzyme reaction product ectoine. These crystal structures lay the framework for a proposal for the EctC-mediated water-elimination reaction mechanism. Residues involved in coordinating the metal, the substrate, or the product within the active site of ectoine synthase are highly conserved among a large group of EctC-type proteins. Collectively, the biochemical, mutational, and structural data reported here yielded detailed insight into the structure-function relationship of the (Pl)EctC enzyme and are relevant for a deeper understanding of the ectoine synthase family as a whole.
Comprehensive Analysis of TCR-β Repertoire in Patients with Neurological Immune-mediated Disorders
Authors: Alves Sousa Alessandra de Paula , Johnson Kory R. , Ohayon Joan , Zhu Jun , Muraro Paolo A. , Jacobson Steven 
Published: January 2019

AbstractIn this study we characterized the TCR repertoire profiles in patients with chronic progressive inflammatory neurological disorders including HAM/TSP, associated with human T-cell lymphotropic virus type I (HTLV-I) infection, and multiple sclerosis (MS), an inflammatory, demyelinating disease of the CNS of unknown etiology. We hypothesized that a T-cell receptor (TCR) clonal repertoire ‘signature’ could distinguish HAM/TSP patients from healthy controls, as well as from patients with a more heterogeneous CNS-reactive inflammatory disease such as MS. In this study, we applied an unbiased molecular technique – unique molecular identifier (UMI) library-based strategy to investigate with high accuracy the TCR clonal repertoire by high throughput sequencing (HTS) technology. cDNA-TCR β-chain libraries were sequenced from 2 million peripheral mononuclear cells (PBMCs) in 14 HAM/TSP patients, 34 MS patients and 20 healthy controls (HC). While HAM/TSP patients showed a higher clonal T-cell expansion compared to MS and HC, increase of the TCR clonal expansion was inversely correlated with the diversity of TCR repertoire in all subjects. In addition, longitudinal analysis of TCR repertoires from HAM/TSP patients demonstrated a correlation of the TCR clonal expansion with HTLV-I proviral load. Surprisingly, MS patients showed a higher diversity of TCR repertoires than other groups. Despite higher TCR clonal expansions in HAM/TSP patients, no disease-specific TCRs were shared among patients. Only non-shared or “private” TCR repertoires was observed. While no clones that shared the same CDR3 amino acid sequences were seen in either HC or MS patients, there was a cluster of related CDR3 amino acid sequences observed for 18 out of 34 MS patients when evaluated by phylogenetic tree analysis. This suggests that a TCR-repertoire signature may be identified in a subset of patients with MS.
Robust in-silico identification of Cancer Cell Lines based on RNA and targeted DNA sequencing data
Authors: Otto Raik , Rössler Jan-Niklas , Sers Christine , Mamlouk Soulafa , Leser Ulf 
Published: January 2019

AbstractCancer cell lines (CCL) are an integral part of modern cancer research but are susceptible to misidentification. The increasing popularity of sequencing technologies motivates the in-silico identification of CCLs based on their mutational fingerprint, but care must be taken when identifying heterogeneous data. We recently developed the proof-of-concept Uniquorn 1 method which could reliably identify heterogeneous sequencing data from selected sequencing technologies. Here we present Uniquorn 2, a generic and robust in-silico identification method for CCLs with DNA/RNA-seq and panel-seq information. We benchmarked Uniquorn 2 by cross-identifying 1612 RNA and 3596 panel-sized NGS profiles derived from 1516 CCLs, five repositories, four technologies and three major cancer panel-designs. Our method achieves an accuracy of 96% for RNA-seq and 95% for mixed DNA-seq and RNA-seq identification. Even for a panel of only 94 cancer-related genes, accuracy remains at 82% but decreases when using smaller panels. Uniquorn 2 is freely available as R-Bioconductor-package ‘Uniquorn’.
Quorum sensing in Pseudomonas aeruginosa mediated by RhlR is regulated by a small RNA PhrD
Authors: Malgaonkar Anuja , Nair Mrinalini 
Published: January 2019

AbstractPseudomonas aeruginosa is a highly invasive human pathogen in spite of the absence of classical host specific virulence factors. Virulence factors regulated by quorum sensing (QS) in P. aeruginosa cause acute infections to shift to chronic diseases. Several small regulatory RNAs (sRNAs) mediate fine-tuning of bacterial responses to environmental signals and regulate quorum sensing. In this study, we show that the quorum sensing regulator RhlR is positively influenced upon over expression of the Hfq dependent small RNA PhrD in Pseudomonas. RhlR transcripts starting from two of the four different promoters have same sequence predicted to base pair with PhrD. Over expression of PhrD increased RhlR transcript levels and production of the biosurfactant rhamnolipid and the redox active pyocyanin pigment. A rhlR::lacZ translational fusion from one of the four promoters showed 2.5-fold higher expression and, a 9-fold increase in overall rhlR transcription was seen in the wild type when compared to the isogenic phrD disruption mutant. Expression, in an E. coli host background, of a rhlR::lacZ fusion in comparison to a construct that harboured a scrambled interaction region resulted in a 10-fold increase under phrD over expression. The interaction of RhlR-5′UTR with PhrD in E. coli indicated that this regulation could function without the involvement of any Pseudomonas specific proteins. Overall, this study demonstrates that PhrD has a positive effect on RhlR and its associated physiology in P. aeruginosa.
Sad faces increase the heartbeat-associated interoceptive information flow within the salience network: a MEG study
Authors: Kim Jaejoong , Park Hyeong-Dong , Kim Ko Woon , Shin Dong Woo , Lim Sanghyun , Kwon Hyukchan , Kim Min-Young , Kim Kiwoong , Jeong Bumseok 
Published: January 2019

AbstractThe somatic marker hypothesis proposes that the cortical representation of visceral signals is a crucial component of emotional processing. No previous study has investigated the information flow among brain regions that process visceral information during emotional perception. In this magnetoencephalography study of 32 healthy subjects of either sex, heartbeat-evoked responses (HERs), which reflect the cortical processing of heartbeats, were modulated by the perception of a sad face. The modulation effect was localized to the prefrontal cortices, the globus pallidus, and an interoceptive network including the right anterior insula (RAI) and dorsal anterior cingulate cortex (RdACC). Importantly, our Granger causality analysis provides the first evidence for the increased flow of heartbeat information from the RAI to the RdACC during sad face perception. Moreover, using a surrogate R-peak analysis, we have shown that this HER modulation effect was time-locked to heartbeats. These findings advance the understanding of brain-body interactions during emotional processing.
Structural and Electrochemical Kinetic Properties of 0.5Li2MnO3∙0.5LiCoO2 Cathode Materials with Different Li2MnO3 Domain Sizes
Authors: Kaewmala Songyoot , Limphirat Wanwisa , Yordsri Visittapong , Kim Hyunwoo , Muhammad Shoaib , Yoon Won-Sub , Srilomsak Sutham , Limthongkul Pimpa , Meethong Nonglak 
Published: January 2019

AbstractLithium rich layered oxide xLi2MnO3∙(1−x)LiMO2 (M = Mn, Co, Ni, etc.) materials are promising cathode materials for next generation lithium ion batteries. However, the understanding of their electrochemical kinetic behaviors is limited. In this work, the phase separation behaviors and electrochemical kinetics of 0.5Li2MnO3∙0.5LiCoO2 materials with various Li2MnO3 domain sizes were studied. Despite having similar morphological, crystal and local atomic structures, materials with various Li2MnO3 domain sizes exhibited different phase separation behavior resulting in disparate lithium ion transport kinetics. For the first few cycles, the 0.5Li2MnO3∙0.5LiCoO2 material with a small Li2MnO3 domain size had higher lithium ion diffusion coefficients due to shorter diffusion path lengths. However, after extended cycles, the 0.5Li2MnO3∙0.5LiCoO2 material with larger Li2MnO3 domain size showed higher lithium ion diffusion coefficients, since the larger Li2MnO3 domain size could retard structural transitions. This leads to fewer structural rearrangements, reduced structural disorders and defects, which allows better lithium ion mobility in the material.
Sex-specific moderation by lifestyle and psychosocial factors on the genetic contributions to adiposity in 112,151 individuals from UK Biobank
Authors: Calvin Catherine M. , Hagenaars Saskia P. , Gallacher John , Harris Sarah E. , Davies Gail , Liewald David C. , Gale Catharine R. , Deary Ian J. 
Published: January 2019

AbstractEvidence suggests that lifestyle factors, e.g. physical activity, moderate the manifestation of genetic susceptibility to obesity. The present study uses UK Biobank data to investigate interaction between polygenic scores (PGS) for two obesity indicators, and lifestyle and psychosocial factors in the prediction of the two indicators, with attention to sex-specific effects. Analyses were of 112 151 participants (58 914 females; 40 to 73 years) whose genetic data passed quality control. Moderation effects were analysed in linear regression models predicting body mass index (BMI) and waist-to-hip ratio (WHR), including interaction terms for PGS and each exposure. Greater physical activity, more education, higher income, moderatevslow alcohol consumption, and low material deprivation were each associated with a relatively lower risk for manifestation of genetic susceptibility to obesity (p < 0.001); the moderating effects of physical activity and alcohol consumption were greater in women than men (three-way interaction: p = 0.009 and p = 0.008, respectively). More income and less neuroticism were related to reduced manifestation of genetic susceptibility to high WHR (p = 0.007; p = 0.003); the effect of income was greater in women (three-way interaction: p = 0.001). Lifestyle and psychosocial factors appear to offset genetic risk for adiposity in mid to late adulthood, with some sex-specific associations.
A VEGF-A/SOX2/SRSF2 network controls VEGFR1 pre-mRNA alternative splicing in lung carcinoma cells
Authors: Abou Faycal Cherine , Gazzeri Sylvie , Eymin Beatrice 
Published: January 2019

AbstractThe splice variantsVEGFR1-i13is a truncated version of the cell membrane-spanning VEGFR1 receptor that is devoid of its transmembrane and tyrosine kinase domains. We recently showed the contribution of sVEGFR1-i13 to the progression and the response of squamous lung carcinoma to anti-angiogenic therapies. In this study, we identify VEGF165, a splice variant of VEGF-A, as a regulator of sVEGFR1-i13 expression in these tumors, and further show that VEGF165cooperates with the transcription factor SOX2 and the splicing factor SRSF2 to control sVEGFR1-i13 expression. We also demonstrate that anti-angiogenic therapies up-regulate sVEGFR1-i13 protein level in squamous lung carcinoma cells by a mechanism involving the VEGF165/SOX2/SRSF2 network. Collectively, our results identify for the first time a signaling network that controlsVEGFR1pre-mRNA alternative splicing in cancer cells.