bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary fatty acids promote sleep through a taste-independent mechanism
Authors: Sah Pamboro Estelle Laure , Brown Elizabeth B. , Keene Alex C. 
Published: June 2019

AbstractConsumption of foods that are high in fat contributes to obesity and metabolism-related disorders that are increasing in prevalence and present an enormous health burden throughout the world. Dietary lipids are comprised of triglycerides and fatty acids, and the highly palatable taste of dietary fatty acids promotes food consumption, activates reward centers in mammals, and underlies hedonic feeding. Despite a central role of dietary fats in the regulation of food intake and the etiology of metabolic diseases, little is known about how fat consumption regulates sleep. The fruit fly,Drosophila melanogaster, provides a powerful model system for the study of sleep and metabolic traits, and flies potently regulate sleep in accordance with food availability. To investigate the effects of dietary fats on sleep regulation, we have supplemented fatty acids into the diet ofDrosophilaand measured their effects on sleep and activity. We found that feeding flies a diet of hexanoic acid, a medium-chain fatty acid that is a by-product of yeast fermentation, promotes sleep by increasing the number of sleep episodes. This increase in sleep is dose-dependent and independent of the light-dark cues. Diets consisting of other fatty acids, including medium- and long-chain fatty acids, also increase sleep, suggesting many fatty acid types promote sleep. To assess whether dietary fatty acids regulate sleep through the taste system, we assessed sleep in flies with a mutation in the hexanoic acid receptorIonotropic receptor 56d, which is required for fatty acid taste perception. We found that these flies also increase their sleep when fed a hexanoic acid diet, suggesting the sleep promoting effect of hexanoic acid is not dependent on sensory perception. Overall, these results define a role for fatty acids in sleep regulation, providing a foundation to investigate the molecular and neural basis for fatty acid-dependent modulation of sleep duration.
PRC2 activates interferon-stimulated genes indirectly by repressing miRNAs in glioblastoma
Authors: Shivram Haridha , Le Steven V. , Iyer Vishwanath R. 
Published: June 2019

AbstractPolycomb repressive complex 2 (PRC2) is a chromatin binding complex that represses gene expression by methylating histone H3 at K27 to establish repressed chromatin domains. PRC2 can either regulate genes directly through the methyltransferase activity of its component EZH2 or indirectly by regulating other gene regulators. Gene expression analysis of glioblastoma (GBM) cells lacking EZH2 showed that PRC2 regulates hundreds of interferon-stimulated genes (ISGs). We found that PRC2 directly represses several ISGs and also indirectly activates a distinct set of ISGs. Assessment of EZH2 binding proximal to miRNAs showed that PRC2 directly represses miRNAs encoded in the chromosome 14 imprinted DLK1-DIO3 locus. We found that repression of this locus by PRC2 occurs in immortalized GBM-derived cell lines as well as in primary bulk tumors from GBM and anaplastic astrocytoma patients. Through repression of these miRNAs and several other miRNAs, PRC2 activates a set of ISGs that are targeted by these miRNAs. This PRC2-miRNA-ISG network is likely to be important in regulating gene expression programs in GBM.
A twisted visual field map in the primate cortex predicted by topographic continuity
Authors: Yu Hsin-Hao , Rowley Declan P. , Price Nicholas S.C. , Rosa Marcello G.P. , Zavitz Elizabeth 
Published: June 2019

AbstractAdjacent neurons in visual cortex have overlapping receptive fields within and across area boundaries, an arrangement which is theorized to minimize wiring cost. This constraint is thought to create retinotopic maps of opposing field sign (mirror and non-mirror representations of the visual field) in adjacent visual areas, a concept which has become central in current attempts to subdivide the cortex. We modelled a realistic developmental scenario in which adjacent areas do not mature simultaneously, but need to maintain topographic continuity across their borders. This showed that the same mechanism that is hypothesized to maintain topographic continuity within each area can lead to a more complex type of retinotopic map, consisting of sectors with opposing field sign within a same area. Using fully quantitative electrode array recordings, we then demonstrate that this type of map exists in the primate extrastriate cortex.
The long non-coding RNAGHSROSreprograms prostate cancer cell lines toward a more aggressive phenotype
Authors: Thomas Patrick B. , Jeffery Penny L. , Gahete Manuel D. , Whiteside Eliza J. , Walpole Carina , Maugham Michelle L. , Jovanovic Lidija , Gunter Jennifer H. , Williams Elizabeth D. , Nelson Colleen C. , Herington Adrian C. , Luque Raúl M. , Veedu Rakesh N. , Chopin Lisa K. , Seim Inge 
Published: June 2019

ABSTRACTIt is now appreciated that long non-coding RNAs (lncRNAs) are important players in the orchestration of cancer progression. In this study we characterizedGHSROS, a human lncRNA gene on the opposite DNA strand (antisense) to the ghrelin receptor gene, in prostate cancer. The lncRNA was upregulated by prostate tumors from different clinical datasets. Consistently, transcriptome data revealed thatGHSROSalters the expression of cancer-associated genes. Functional analysesin vitroshowed thatGHSROSmediates tumor growth, migration, and survival and resistance to the cytotoxic drug docetaxel. Increased cellular proliferation ofGHSROS-overexpressing PC3, DU145, and LNCaP prostate cancer cell linesin vitrowas recapitulated in a subcutaneous xenograft model. Conversely,in vitroantisense oligonucleotide inhibition of the lncRNA reciprocally regulated cell growth and migration, and gene expression. Notably,GHSROSmodulates the expression of PPP2R2C, the loss of which may drive androgen receptor pathway-independent prostate tumor progression in a subset of prostate cancers. Collectively, our findings suggest thatGHSROScan reprogram prostate cancer cells toward a more aggressive phenotype and that this lncRNA may represent a potential therapeutic target.
Mendelian randomization accounting for correlated and uncorrelated pleiotropic effects using genome-wide summary statistics
Authors: Morrison Jean , Knoblauch Nicholas , Marcus Joseph , Stephens Matthew , He Xin 
Published: June 2019

AbstractMendelian randomization (MR) is a valuable tool for detecting evidence of causal relationships using genetic variant associations. Opportunities to apply MR are growing rapidly with the number of genome-wide association studies (GWAS) with publicly available results. However, existing MR methods rely on strong assumptions that are often violated, leading to false positives. Many methods have been proposed loosening these assumptions. However, it has remained challenging to account for correlated pleiotropy, which arises when variants affect both traits through a heritable shared factor. We propose a new MR method, Causal Analysis Using Summary Effect Estimates (CAUSE), that accounts for correlated and uncorrelated horizontal pleiotropic effects. We demonstrate in simulations that CAUSE is more robust to correlated pleiotropy than other methods. Applied to traits studied in recent GWAS, we find that CAUSE detects causal relationships with strong literature support and avoids identifying most unlikely relationships. Our results suggest that many pairs of traits identified as causal using alternative methods may be false positives due to horizontal pleiotropy.
Generating high-quality libraries for DIA-MS with empirically-corrected peptide predictions
Authors: Searle Brian C. , Swearingen Kristian E. , Barnes Christopher A. , Schmidt Tobias , Gessulat Siegfried , Kuster Bernhard , Wilhelm Mathias 
Published: June 2019

ABSTRACTData-independent acquisition approaches typically rely on sample-specific spectrum libraries requiring offline fractionation and tens to hundreds of injections. We demonstrate a new library generation workflow that leverages fragmentation and retention time prediction to build libraries containing every peptide in a proteome, and then refines those libraries with empirical data. Our method specifically enables rapid library generation for non-model organisms, which we demonstrate using the malaria parasite Plasmodium falciparum, and non-canonical databases, which we show by detecting missense variants in HeLa.
Biodiversity of Magnetotactic Bacteria in the Freshwater Lake Beloe Bordukovskoe, Russia
Authors: Koziaeva V. V. , Alekseeva L. M. , Uzun M. M. , Leão P. , Sukhacheva M. V. , Patutina E. O. , Kolganova T. V. , Grouzdev D. S. 
Published: June 2019

AbstractAccording to 16S rRNA gene- or genome-based phylogeny, magnetotactic bacteria (MTB) belong to diverse taxonomic groups. Here we analyzed the diversity of MTB in a sample taken from the freshwater lake Beloe Bordukovskoe near Moscow, Russia, by using molecular identification based on sequencing of the 16S rRNA gene andmamK, a specific marker gene for these bacteria. A protein encoded by themamKgene is involved in magnetosome chain arrangement inside the cell. As a result, six operational taxonomic units (OTUs) of MTB were identified. Among them, OTUs affiliated with the phylumNitrospiraewere predominant. ‘Ca. Etaproteobacteria’ andAlphaproteobacteriarepresented the minor groups of MTB. We also identified a novel MTB belonging to the familySyntrophaceaeof theDeltaproteobacteriaclass. Using a combination of fluorescence and transmission electron microscopy, the bacteria belonging to these new MTB groups were visualized. Electron microscopy revealed thatSyntrophaceaeMTB were rod-shaped and synthesized elongated magnetosomes, arranged as a disorganized cluster. Among theNitrospiraegroup, two groups with vibrioid cell shape and one group of ovoid-shaped bacteria were identified, all of which had elongated magnetosome crystals consisting of magnetite.
The common neoantigens in colorectal cancer are predicted and validated to be presented or immunogenic
Authors: Liang Zhaoduan , Qin Lili , Chen Lei , Li Wenhui , Chen Chao , Huang Yaling , Zhang Le , Liu Songming , Qiu Si , Ge Yuping , Peng Wenting , Lin Xinxin , Dong Xuan , Zhang Xiuqing , Li Bo 
Published: June 2019

ABSTRACTColorectal cancer (CRC) is a malignant cancer with high incidence and mortality in the world, as the result of the traditional treatments. Immunotherapy targeting neoantigens can induce durable tumor regression in cancer patients, but is almost limited to individual treatment, resulting from the unique neoantigens. Many shared oncogenic mutations are detected, but whether the common neoantigens can be identified in CRC is unknown. Using the somatic mutations data from 321 CRC patients combined with a filter standard and 7 predicted algorithms, we screened and obtained 25 HLA-A*11:01 restricted common neoantigens with high binding affinity (IC50<50 nM) and presentation score (>0.9). Except the positive epitope KRAS_G12V8-16, 11 out of 25 common neoantigens were proved to be naturally processed and presented on constructed K562 cell surface by mass spectroscopy (MS), and 11 out of 25 common neoantigens specifically induced in vitro pre-stimulated cytotoxic lymphocyte (CTL) to secrete IFN-γ. However, only 2 out of 25 common neoantigens were simultaneously presented and immunogenic. Moreover, using cell-sorting technology combined with single-cell RNA sequencing, the immune repertoire profiles of C1orf170_S418G413-421 and KRAS_G12V8-16-specific CTL were clarified. Therefore, common neoantigens with presentation and immunogenicity could be found in CRC, which would be developed as the universal targets for CRC immunotherapy.
Determining the scale at which variation in WUE traits changes population yields
Authors: McGale Erica , Valim Henrique , Mittal Deepika , Jimenez Jesús Morales , Halitschke Rayko , Schuman Meredith C. , Baldwin Ian T. 
Published: June 2019

AbstractFunctional variation is known to influence population yield, but the scale at which this happens is still unknown. Relevant signals might only reach immediate neighbors of a phenotypically diverse plant (neighbor-scale) or conversely may distribute across the population (population-scale). We useNicotiana attenuatasilenced in mitogen-activated protein kinase 4 (irMPK4), plants with low water-use efficiency (WUE), to study the scale at which water-use traits alter intraspecific population yields. In the field and glasshouse, populations with low percentages of irMPK4 plants planted among isogenic control plants produced maximum overall growth and yield. Through paired-plant and local-plant-configuration analyses, we determined that this occurred at the population scale. However, we find that this effect was not due to irMPK4’s WUE phenotype. With micro-grafting, we additionally show thatMPK4-deficiency may mediate the response at the population-scale: shoot-expressedMPK4is required forN. attenuatato change yield in response to a neighbor.
Antibody Complementarity Determining Region Design Using High-Capacity Machine Learning
Authors: Liu Ge , Zeng Haoyang , Mueller Jonas , Carter Brandon , Wang Ziheng , Schilz Jonas , Horny Geraldine , Birnbaum Michael E. , Ewert Stefan , Gifford David K. 
Published: June 2019

AbstractThe precise targeting of antibodies and other protein therapeutics is required for their proper function and the elimination of deleterious off-target effects. Often the molecular structure of a therapeutic target is unknown and randomized methods are used to design antibodies without a model that relates antibody sequence to desired properties. Here we present a machine learning method that can design human Immunoglobulin G (IgG) antibodies with target affinities that are superior to candidates from phage display panning experiments within a limited design budget. We also demonstrate that machine learning can improve target-specificity by the modular composition of models from different experimental campaigns, enabling a new integrative approach to improving target specificity. Our results suggest a new path for the discovery of therapeutic molecules by demonstrating that predictive and differentiable models of antibody binding can be learned from high-throughput experimental data without the need for target structural data.SignificanceAntibody based therapeutics must meet both affinity and specificity metrics, and existing in vitro methods for meeting these metrics are based upon randomization and empirical testing. We demonstrate that with sufficient target-specific training data machine learning can suggest novel antibody variable domain sequences that are superior to those observed during training. Our machine learning method does not require any target structural information. We further show that data from disparate antibody campaigns can be combined by machine learning to improve antibody specificity.
TREM-1 activation is a key regulator in driving severe pathogenesis of enterovirus 71 infection
Authors: Amrun Siti Naqiah , Tan Jeslin J.L. , Rickett Natasha Y. , Cox Jonathan A. , Lee Bernett , Griffiths Michael J. , Solomon Tom , Perera David , Ooi Mong How , Hiscox Julian A. , Ng Lisa F.P. 
Published: June 2019

AbstractHand, foot and mouth disease (HFMD), caused by enterovirus 71 (EV71), presents mild to severe disease, and sometimes fatal neurological and respiratory manifestations. However, reasons for the severe pathogenesis remain undefined. To investigate this, infection and viral kinetics of EV71 isolates from clinical disease (mild, moderate and severe) from Sarawak, Malaysia, were characterized in human rhabdomyosarcoma (RD), neuroblastoma (SH-SY5Y) and peripheral blood mononuclear cells (PBMCs). High resolution transcriptomics was used to decipher EV71-host interactions in PBMCs. Ingenuity analyses revealed similar pathways triggered by all EV71 isolates, although the extent of activation varied. Importantly, several pathways were found to be specific to the severe isolate, including triggering receptor expressed on myeloid cells 1 (TREM-1) signaling. Depletion of TREM-1 in EV71-infected PBMCs with peptide LP17 resulted in decreased levels of pro-inflammatory genes, and reduced viral loads for the moderate and severe isolates. Mechanistically, this is the first report describing the transcriptome profiles during EV71 infections in primary human cells, and the involvement of TREM-1 in the severe disease pathogenesis, thus providing new insights for future treatment targets.
Mitochondrial impairment activates the Wallerian pathway through depletion of NMNAT2 leading to SARM1-dependent axon degeneration
Authors: Loreto Andrea , Hill Ciaran S. , Hewitt Victoria L. , Orsomando Giuseppe , Angeletti Carlo , Gilley Jonathan , Lucci Cristiano , Sanchez-Martinez Alvaro , Whitworth Alexander J. , Conforti Laura , Dajas-Bailador Federico , Coleman Michael P. 
Published: June 2019

ABSTRACTWallerian degeneration of physically injured axons involves a well-defined molecular pathway linking loss of axonal survival factor NMNAT2 to activation of pro-degenerative protein SARM1. Manipulating the pathway through these proteins led to the identification of non-axotomy insults causing axon degeneration by a Wallerian-like mechanism, including several involving mitochondrial impairment. Mitochondrial dysfunction is heavily implicated in Parkinson’s disease, Charcot-Marie-Tooth disease, hereditary spastic paraplegia and other axonal disorders. However, whether and how mitochondrial impairment activates Wallerian degeneration has remained unclear. Here, we show that disruption of mitochondrial membrane potential leads to axonal NMNAT2 depletion in mouse sympathetic neurons, increasing the substrate-to-product ratio (NMN/NAD) of this NAD-synthesising enzyme, a metabolic fingerprint of Wallerian degeneration. The mechanism appears to involve both impaired NMNAT2 synthesis and reduced axonal transport. Expression of WLDS and Sarm1 deletion both protect axons after mitochondrial uncoupling. Blocking the pathway also confers neuroprotection and increases the lifespan of flies with Pink1 loss-of-function mutation, which causes severe mitochondrial defects. These data indicate that mitochondrial impairment replicates all the major steps of Wallerian degeneration, placing it upstream of NMNAT2 loss, with the potential to contribute to axon pathology in mitochondrial disorders.
A solvable model of entrainment ranges for the circadian rhythm under light/dark cycles
Authors: Takakura Ren , Ichikawa Masatoshi , Oyama Tokitaka 
Published: June 2019

ABSTRACTA continuous model for entrainment of the circadian clock responding to light/dark cycles is analytically studied. The circadian rhythm is entrained to light/dark cycles in a certain range of periods including the 24 hour period. Entrainment ranges vary among organisms; plants show much larger ranges than mammals. To analyze entrainment manners, we exploit a simplified model in which the angular velocity of the circadian rhythm is modulated by a sinusoidal function of phase difference between the circadian rhythm and reference phases. This model contains only one parameter called entrainment strength (K). For light and dark states, we set two reference phases. Using this model, we characterized the entrainment manners of circadian rhythms under non-24 hour light/dark cycles. The conditions of the K value for the entrainment were analytically calculated and a phase diagram showing entrainment/non-entrainment boundaries was drawn. In the diagram we found a region where disordered orbitals emerge. Then, critical values for the entrainment and the disordered irregular motion of the oscillation were derived. Simulation results near a critical value were comparable with the experimental results of the entrainment manners of plant circadian rhythms, suggesting the compatibility of self-oscillation and a strong light/dark response in plants. The diagram clearly represents an overview of the relationship between entrainment strengths and entrainment manners of circadian rhythms in general, and enables us to uniformly compare strengths of periodic stimuli in the environment and degrees of responsiveness for the stimuli among various circadian rhythms.
World Heritage Site as the place for education: the case of the Gango-ji Temple in Japan
Authors: Serizawa Satohiro , Sunami Soichiro 
Published: June 2019

Purpose
The purpose of this paper is to investigate educational functions of the World Heritage Site by examining the case of cultural tourism in a Japanese Buddhist temple.

Design/methodology/approach
Japan accepted the World Heritage Convention in 1992. “Historic Monuments of Ancient Nara” were decided to be listed on the World Cultural Heritage in 1998. It was composed of buildings, monuments and related cultural landscape, including five Buddhist temples and one Shinto shrine. Among them, the Gango-ji, focused in this paper, is one of the oldest Buddhist temples in Japan.

Findings
It has been keeping many cultural properties related to the folk religious practice and providing many activities for the local community. The material culture of folk-belief is now preserved in a building in the temple yard. And there is an exhibition room. The main hall and the exhibition room are the important facilities for social education, where the visitors can watch and touch the real materials. According to the staffs of the temple, the tourists had better stay in the main hall after 1 h study at the exhibition room.

Originality/value
Heritage is a process of the contemporary people engaging in the usage of past as resources. The buildings as the tangible heritage used by the present community are combined with the actions as the intangible heritage of the people who preserve the heritage. The temporal tourists are also permitted to enjoy the process as participants. They can learn many things through their experiences at the heritage site.
Comorbid mental health disorders in children and young people with intellectual disabilities and autism spectrum disorders
Authors: Gobrial Ereny 
Published: June 2019

Purpose
Children and young people with comorbid intellectual disabilities (ID) and autism spectrum disorders (ASD) are more likely to exhibit comorbid mental health disorders (MHD) and other significant behaviours (SB) in addition to the core symptoms of ASD. The purpose of this paper is to identify the prevalence of comorbid MHD and behaviours in children and young people with ID and ASD in Egypt.

Design/methodology/approach
The Reiss scale for children’s dual diagnosis was administered by parents and teachers of 222 Egyptian children and young people with mild/moderate ID and ASD to screen for MHD and SB. The mean age of children and young people was 12.3 years (SD = 3.64), with 75.6 per cent male.

Findings
The results revealed that 62.2 per cent of children and young people with ID and ASD had high rates of comorbid MHD and behaviour disorders were shown in 64.4 per cent of the participated children and young people. The results identified anger, anxiety and psychosis being the most frequently diagnosed disorders while crying spells and pica were the most SB. No differences were found between the male and female with ID and ASD in the current study.

Research limitations/implications
Mental health assessment of children and young people with ID and ASD will help to highlight the needs of these vulnerable children and develop the appropriate services.

Originality/value
The findings highlight the prevalence of MHD in children and young people with ID and ASD in Egypt. This has implications on the assessment of comorbid disorders and services needed for children with ID and ASD in Egypt.