bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Trend of Suicide Reporting in the Media: an Effectiveness Study of Daily Surveillance over Nine Years
Authors: Wu Chia-Yi , Lee Ming-Been , Liao Shih-Cheng , Chan Chia-Ta , Chen Chun-Ying 
Published: September 2019

AbstractInadequate suicide reports can cause copycat suicide attempts, but legal regulations for the media are rarely seen worldwide. In Taiwan, daily media surveillance with immediate feedback to correct inappropriate reports has been an interactive policy in the national suicide prevention strategy for a decade. We aimed to evaluate the effectiveness of current surveillance program via assessing the adherence rates with 12-item WHO responsible reporting guideline in print newspapers (2010-2018) and online media (2017-2018). The results showed that media reporting of suicide significantly improved in most guideline items under surveillance. But the development of psychiatric-media liaisons should further improve reporting quality.
Whole genome sequence analysis reveals broad distribution of the RtxA type 1 secretion system and four novel type 1 secretion systems throughout theLegionellagenus
Authors: Brown Connor L. , Garner Emily , Jospin Guillaume , Coil David A. , Schwake David O. , Eisen Jonathan A. , Mukhopadhyay Biswarup , Pruden Amy J. 
Published: September 2019

ABSTRACTType 1 secretion systems (T1SSs) are broadly distributed among bacteria and translocate effectors with diverse function across the bacterial cell membrane.Legionella pneumophila, the species most commonly associated with Legionellosis, encodes a T1SS at thelssXYZABDlocus which is responsible for the secretion of the virulence factor RtxA. Many investigations have failed to detectlssD, the gene encoding the membrane fusion protein of the RtxA T1SS, in non-pneumophila Legionella, suggesting that this system is a conserved virulence factor inL. pneumophila.Here we discovered RtxA and its associated T1SS in a novelLegionella taurinensisstrain, leading us to question whether this system may be more widespread than previously thought. Through a bioinformatic analysis of publicly available data, we classified and determined the distribution of four T1SSs including the RtxA T1SS and four novel T1SSs among diverseLegionellaspp. The ABC transporter of the novelLegionellaT1SSLegonellarepeat protein secretion system (LRPSS) shares structural similarity to those of diverse T1SS families, including the alkaline protease T1SS inPseudomonas aeruginosa.TheLegionellabacteriocin (1–3) secretion systems (LB1SS-LB3SS) T1SSs are novel putative bacteriocin transporting T1SSs as their ABC transporters include C-39 peptidase domains in their N-terminal regions, with LB2SS and LB3SS likely constituting a nitrile hydratase leader peptide transport T1SSs. The LB1SS is more closely related to the colicin V T1SS inEscherichia coli.Of 45Legionellaspp. whole genomes examined, 19 (42%) were determined to possesslssBandlssDhomologs. Of these 19, only 7 (37%) are known pathogens. There was no difference in the proportions of disease associated and non-disease associated species that possessed the RtxA T1SS (p = 0.4), contrary to the current consensus regarding the RtxA T1SS. These results draw into question the nature of RtxA and its T1SS as a genetic virulence determinant.
Minimally invasive, pressure probe based sampling allows for in-situ gene expression analyses in plant cells
Authors: Wada Hiroshi , Castellarin Simone D. , Matthews Mark A. , Shackel Kenneth A. , Gambetta Gregory A. 
Published: September 2019

AbstractBackgroundGene expression analyses are conducted using multiple approaches and increasingly research has been focused on assessing gene expression at the level of a tissue or even single-cells. To date, methods to assess gene expression at the single-cell in plant tissues have been semi-quantitative, require tissue disruption, and/or involve laborious, possibly artifact-inducing manipulation. In this work, we used grape berries (Vitis vinifera L. Zinfandel) as a model in order to examine the validity and reproducibility of an in-situ gene expression analysis method combining a cell pressure probe (CPP) with quantitative PCR (qPCR).ResultsWe developed a method to directly assess gene expression levels via qPCR from cellular fluids sampled in-situ with a CPP. Cellular fluids, with volumes in the picoliter range, were collected from intact berries with a CPP at various depths across skin and mesocarp tissues. The expression of a key anthocyanin biosynthetic gene, UDP-glucose: flavonoid 3-O-glucosyltransferase (VviUFGT), was analyzed as a test case since its expression is restricted to cells producing anthocyanins in grape berry skins during ripening. The method identifies samples contaminated with significant levels of genomic DNA by amplifying a region of VviUFGT that spans an intron. Therefore false positives were discarded which occurred in 28% of the samples tested. Shallow probing of skin cells showed high VviUFGT expression as expected while deeper probing of mesocarp cells resulted in no VviUFGT expression.ConclusionsThe clear correspondence of VviUFGT expression to the targeted cell samples suggests that the in-situ gene expression analysis using a CPP is reliable and does not result in contamination as the probe moves through tissues. This method can be paired to single-cell transcriptomic analyses in the future. We conclude that this technique represents a minimally invasive method of sampling plant cells in-situ which creates an opportunity for the analysis of cellular level, spatiotemporal responses in heterogeneous plant tissues.
LncRNA MIR4435-2HG mediates cisplatin resistance in HCT116 cells by regulating Nrf2 and HO-1
Authors: Luo Ping , Wu ShuGui , Zhou ChaoMing , Yuan Xia , Li HongMi , Chen JinPing , Tian YunFei , Qiu Yang , Zhong XiaoMing 
Published: September 2019

AbstractPURPOSECisplatin resistance is still a serious problem in clinic. However, the underlying mechanism remains unclear. In this study investigated the drug resistance of cisplatin by the cisplatin resistance cell line HCT116R.RESULTSIn this study, we found that LncRNA MIR4435-2HG level dramatically increased in the cisplatin resistance cell line HCT116R. Knockdown of MIR4435-2HG in HCR116R significantly restored the sensitivity to cisplatin, inhibited cell proliferation and promoted cell apoptosis. Furthermore, Nrf2 and HO-1 mRNA level, as the critical molecular of the oxidative stress pathway, was inhibited by the siRNA targeting to MIR4435-2HG, displaying MIR4435-2HG-mediated cisplatin resistance through the Nrf2/HO-1 pathway.CONCLUSIONOur findings demonstrated that LncRNA MIR4435-2HG as a main factor could drive the cisplatin resistance of HCT116.
Prevalence of UGT1A1 Genetic Variants in Argentinean Population, Potential Implications for Pharmacogenomic Testing
Authors: Cruz Cintia V. , Scibona Paula , Belloso Waldo H. 
Published: September 2019

ABSTRACTThe four groups of uridine diphosphate glucuronosyltransferase (UGT) enzymes form a superfamily responsible for the glucuronidation of target substrates. These include hormones, flavonoids, environmental mutagens and pharmaceutical drugs. Thus, UGT enzymes are relevant for pharmacogenetic research.Most of the members of the UGT family are expressed in the liver, but are also present in intestinal, stomach or breast tissue.The incidences and types of polymorphisms for different enzymes vary with geographical regions and ethnic groups. This is the first study that examined the frequency of polymorphisms for UGT1 isozymes for a population of 100 healthy argentinians.The distribution of UGT1A1 in our population was: 70.5% (70.5) for the *1 allele, 21.5% for the *28 allele and 1% for the *36 allele. 48% (48) presented the *1/*1 genotype, while 43 % (43) had *1/*28, 2% (2) had *1/*36 and 7% (7) showed *28/*28. There was no preferential sex distribution.Since most Argentinians are of Caucasian descent, a European genotype frequency profile is to be expected. That is evident in the wild type prevalence in our population. However, the contribution of Native American ancestry to gene pool components may in part explain the higher prevalence of the *28 genotype in UGT1A1 *1 in our population, in comparison with European cohorts.
Creating Artificial Human Genomes Using Generative Models
Authors: Yelmen Burak , Decelle Aurélien , Ongaro Linda , Marnetto Davide , Tallec Corentin , Montinaro Francesco , Furtlehner Cyril , Pagani Luca , Jay Flora 
Published: September 2019

AbstractGenerative models have shown breakthroughs in a wide spectrum of domains due to recent advancements in machine learning algorithms and increased computational power. Despite these impressive achievements, the ability of generative models to create realistic synthetic data is still under-exploited in genetics and absent from population genetics.Yet a known limitation of this field is the reduced access to many genetic databases due to concerns about violations of individual privacy, although they would provide a rich resource for data mining and integration towards advancing genetic studies. In this study, we demonstrated that deep generative adversarial networks (GANs) and restricted Boltzmann machines (RBMs) can be trained to learn the high dimensional distributions of real genomic datasets and create high quality artificial genomes (AGs) with none to little privacy loss. To illustrate the promising outcomes of our method, we showed that (i) imputation quality for low frequency alleles can be improved by augmenting reference panels with AGs, (ii) scores obtained from selection tests on AGs and real genomes are highly correlated and (iii) AGs can inherit genotype-phenotype associations. AGs have the potential to become valuable assets in genetic studies by providing high quality anonymous substitutes for private databases.
Arabidopsis PAD4 lipase-like domain is a minimal functional unit in resistance to green peach aphid
Authors: Dongus Joram A. , Bhandari Deepak D. , Patel Monika , Archer Lani , Dijkgraaf Lucas , Deslandes Laurent , Shah Jyoti , Parker Jane E. 
Published: September 2019

AbstractPlants have evolved mechanisms to attract beneficial microbes and insects while protecting themselves against pathogenic microbes and pests. In Arabidopsis, the immune regulator PAD4 functions with its cognate partner EDS1 to limit pathogen growth. PAD4, independently of EDS1, reduces infestation by Green Peach Aphid (GPA). How PAD4 regulates these defense outputs is unclear. By expressing the N-terminal PAD4-lipase-like domain (LLD) without its C-terminal ‘EDS1-PAD4’ (EP) domain, we interrogated PAD4 functions in plant defense. Here we show that transgenic expression of PAD4LLDin Arabidopsis is sufficient for limiting GPA infestation, but not for conferring basal and effector-triggered pathogen immunity. This suggests that the C-terminal PAD4-EP domain is necessary for EDS1-dependent immune functions. Moreover, PAD4LLDis not sufficient to interact with EDS1, indicating the PAD4-EP domain is required for heterodimerisation. These data provide molecular evidence that PAD4 has domain specific functions.
RNA-dependent RNA polymerase speed and fidelity are not the only determinants of the mechanism or efficiency of recombination
Authors: Kim Hyejeong , Ellis Victor D. , Woodman Andrew , Zhao Yan , Arnold Jamie J. , Cameron Craig E. 
Published: September 2019

AbstractUsing the RNA-dependent RNA polymerase (RdRp) from poliovirus (PV) as our model system, we have shown that Lys-359 in motif-D functions as a general acid in the mechanism of nucleotidyl transfer. A K359H (KH) RdRp derivative is slow and faithful relative to wild-type enzyme. In the context of the virus, RdRp-coding sequence evolves, selecting for the following substitutions: I331F (IF, motif-C) and P356S (PS, motif-D). We have evaluated IF-KH, PS-KH, and IF-PS-KH viruses and enzymes. The speed and fidelity of each double mutant are equivalent. Each exhibits a unique recombination phenotype, with IF-KH being competent for copy-choice recombination and PS-KH being competent for forced-copy-choice recombination. Although the IF-PS-KH RdRp exhibits biochemical properties within twofold of wild type, the virus is impaired substantially for recombination in cells. We conclude that there are biochemical properties of the RdRp in addition to speed and fidelity that determine the mechanism and efficiency of recombination. The interwoven nature of speed, fidelity, the undefined property suggested here, and recombination makes it impossible to attribute a single property of the RdRp to fitness. However, the derivatives described here may permit elucidation of the importance of recombination on the fitness of the viral population in a background of constant polymerase speed and fidelity.SignificanceThe availability of a “universal” method to create attenuated viruses for use as vaccine strains would permit a rapid response to outbreaks of newly emerging viruses. Targeting RdRp fidelity has emerged as such a universal approach. However, because polymerase fidelity and speed are inextricably linked, the effort to attribute the attenuated phenotype to a single biochemical property of the RdRp may be futile. Here, we show that this circumstance is even more complex. We provide evidence for the existence of a biochemical parameter that combines with fidelity and speed to govern the mechanism and/or efficiency of recombination. We conclude that the field will be served best by continued emphasis on discovery of manipulatable functions of the RdRp instead of debating the importance of individual properties.
A cross-scale assessment of productivity-diversity relationships
Authors: Craven Dylan , van der Sande Masha T. , Meyer Carsten , Gerstner Katharina , Bennett Joanne M. , Giling Darren P. , Hines Jes , Phillips Helen R. P. , May Felix , Bannar-Martin Katherine H. , Chase Jonathan M. , Keil Petr 
Published: September 2019

AbstractAimBiodiversity and ecosystem productivity vary across the globe and considerable effort has been made to describe their relationships. Biodiversity-ecosystem functioning research has traditionally focused on how experimentally controlled species richness affects net primary productivity (S→NPP) at small spatial grains. In contrast, the influence of productivity on richness (NPP→S) has been explored at many grains in naturally assembled communities. Mismatches in spatial scale between approaches have fostered debate about the strength and direction of biodiversity-productivity relationships. Here we examine the direction and strength of productivity’s influence on diversity (NPP→S) and of diversity’s influence on productivity (S→NPP), and how this varies across spatial grains.Locationcontiguous USATime period1999 - 2015Major taxa studiedwoody species (angiosperms and gymnosperms)MethodsUsing data from North American forests at grains from local (672 m2) to coarse spatial units (median area = 35,677 km2), we assess relationships between diversity and productivity using structural equation and random forest models, while accounting for variation in climate, environmental heterogeneity, management, and forest age.ResultsWe show that relationships between S and NPP strengthen with spatial grain. Within each grain, S→NPP and NPP→S have similar magnitudes, meaning that processes underlying S→NPP and NPP→S either operate simultaneously, or that one of them is real and the other is an artifact. At all spatial grains, S was one of the weakest predictors of forest productivity, which was largely driven by biomass, temperature, and forest management and age.Main conclusionsWe conclude that spatial grain mediates relationships between biodiversity and productivity in real-world ecosystems and that results supporting predictions from each approach (NPP→S and S→NPP) serve as an impetus for future studies testing underlying mechanisms. Productivity-diversity relationships emerge at multiple spatial grains, which should widen the focus of national and global policy and research to larger spatial grains.
ASlive: a database for alternative splicing atlas in livestock animals
Authors: Liu Jinding , Tan Suxu , Huang Shuiqing , Huang Wen 
Published: September 2019

AbstractWe present in this study the development and implementation of a database for alternative splicing atlas in livestock animals (ASlive.org). Alternative splicing is an important biological process whose precision must be tightly regulated during growth and development. Using publicly available RNASeq data sets across many tissues, cell types, and biological conditions totaling 28.6 tera bases, we built a database of alternative splicing events in five major livestock animal species (cattle, sheep, pigs, horses, and chickens). The database contains many types of information on alternative splicing events, including basic information such as genomic locations, genes, and event types, quantitative measurements of alternative splicing in the form of percent spliced in (PSI), overlap with known DNA variants, as well as orthologous events across different lineage groups. This database, the first of its kind in livestock animals, will provide a useful exploratory tool to assist functional annotation of animal genomes.
miRCoop: Identifying Cooperating miRNAs via Kernel Based Interaction Tests
Authors: Olgun Gulden , Tastan Oznur 
Published: September 2019

AbstractAlthough miRNAs can cause widespread changes in expression programs, single miRNAs typically induce mild repression on their targets. Cooperativity is reported as one strategy to overcome this constraint. Expanding the catalog of synergistic miRNAs is critical for understanding gene regulation and for developing miRNA-based therapeutics. In this study, we develop miRCoop to identify synergistic miRNA pairs that have weak or no repression on the target mRNA, but when bound together, induce strong repression. miRCoop uses kernel-based interaction tests together with miRNA and mRNA target information. We apply our approach to kidney tumor patient data and identify 66 putative triplets. For 64 of these triplets, there is at least one common transcription factor that potentially regulates all participating RNAs of the triplet, supporting a functional association among them. Furthermore, we find that triplets are enriched for certain biological processes that are relevant to kidney cancer. Some of the synergistic miRNAs are very closely encoded in the genome, hinting a functional association among them. We believe miRCoop can aid our understanding of the complex regulatory interactions in different health and disease states of the cell and can help in designing miRNA-based therapies. Matlab code for the methodology is provided inhttps://github.com/guldenolgun/miRCoop.
Brain dynamics for confidence-weighted learning
Authors: Meyniel Florent 
Published: September 2019

AbstractLearning in a changing and uncertain environment is a difficult problem. A popular solution is to predict future observations and then use surprising outcomes to update those predictions. However, humans also have a sense of confidence that characterizes the precision of their predictions. Bayesian models use this confidence to regulate learning: for a given surprise, the update is smaller when confidence is higher. We explored the human brain dynamics sub-tending such a confidence-weighting using magneto-encephalography. During our volatile probability learning task, subjects’ confidence reports conformed with Bayesian inference. Several stimulus-evoked brain responses reflected surprise, and some of them were indeed further modulated by confidence. Confidence about predictions also modulated pupil-linked arousal and beta-range (15-30 Hz) oscillations, which in turn modulated specific stimulus-evoked surprise responses. Our results suggest thus that confidence about predictions modulates intrinsic properties of the brain state to amplify or dampen surprise responses evoked by discrepant observations.
Dissociable neural effects of temporal expectations due to passage of time and contextual probability
Authors: Todorovic Ana , Auksztulewicz Ryszard 
Published: September 2019

ABSTRACTThe human brain is equipped with complex mechanisms to track the changing probability of events in time. While the passage of time itself usually leads to a mounting expectation, context can provide additional information about when events are likely to happen. In this study we dissociate these two sources of temporal expectation in terms of their neural correlates and underlying brain connectivity patterns. We analysed magnetoencephalographic (MEG) data acquired from N=24 healthy participants listening to auditory stimuli. These stimuli could be presented at different temporal intervals but occurred most often at intermediate intervals, forming a contextual probability distribution. Evoked MEG response amplitude was sensitive to both passage of time and contextual probability, albeit at different latencies: the effects of passage of time were observed earlier than the effects of context. The underlying sources of MEG activity were also different across the two types of temporal prediction: the effects of passage of time were localised to early auditory regions and superior temporal gyri, while context was additionally linked to activity in inferior parietal cortices. Finally, these differences were modelled using biophysical (dynamic causal) modelling: passage of time was explained in terms of widespread gain modulation and decreased prediction error signalling at lower levels of the hierarchy, while contextual expectation led to more localised gain modulation and decreased prediction error signalling at higher levels of the hierarchy. These results present a comprehensive account of how independent sources of temporal prediction may be differentially expressed in cortical circuits.HIGHLIGHTS- Predictability of tone onset times affects auditory network connectivity- Foreperiod and distribution of events in time have dissociable neural substrates- Decreased prediction error at different levels of cortical hierarchy
Green, orange, red, and far-red optogenetic tools derived from cyanobacteriochromes
Authors: Jang Jaewan , McDonald Sherin , Uppalapati Maruti , Woolley G. Andrew 
Published: September 2019

AbstractExisting optogenetic tools for controlling protein-protein interactions are available in a limited number of wavelengths thereby limiting opportunities for multiplexing. The cyanobacteriochrome (CBCR) family of photoreceptors responds to an extraordinary range of colors, but light-dependent binding partners for CBCR domains are not currently known. We used a phage-display based approach to develop small (~50-residue) monomeric binders selective for the green absorbing state (Pg), or for the red absorbing state (Pr) of the CBCR Am1_c0023g2 with a phycocyanobilin chromophore and also for the far-red absorbing state (Pfr) of Am1_c0023g2 with a biliverdin chromophore. These bind in a 1:1 mole ratio with KDs for the target state from 0.2 to 2 μM and selectivities from 10 to 500-fold. We demonstrate green, orange, red, and far-red light-dependent control of protein-protein interactions in vitro and also in vivo where these multicolor optogenetic tools are used to control transcription in yeast.