bluuebunny/crossref_metadata_2025_split huggingface dataset:
A virus-encoded protein suppresses methylation of the viral genome in the Cajal body through its interaction with AGO4
Authors: Wang Liping , Ding Yi , He Li , Zhang Guiping , Zhu Jian-Kang , Lozano-Duran Rosa 
Published: October 2019

ABSTRACTIn plants, establishment ofde novoDNA methylation is regulated by the RNA-directed DNA methylation (RdDM) pathway. RdDM machinery is known to concentrate in the Cajal body, but the biological significance of this localization has remained elusive. Here, we show that the anti-viral methylation of theTomato yellow leaf curl virus(TYLCV) genome occurs specifically in the Cajal body ofNicotiana benthamianacells. Methylation of the viral genome is countered by a virus-encoded protein, V2, which interacts with the central RdDM component AGO4, interfering with its binding to the viral DNA; Cajal body localization of the V2-AGO4 interaction is required for the viral protein to exert this function. Taken together, our results draw a long sought-after functional connection between RdDM, the Cajal body, and anti-viral DNA methylation, paving the way for a deeper understanding of DNA methylation and anti-viral defences in plants.
Poor concordance of floxed sequence recombination in single neural stem cells: Implications for cell autonomous studies
Authors: Dause Tyler Joseph , Kirby Elizabeth Diana 
Published: October 2019

SummaryTo manipulate target gene function in specific adult cell populations, tamoxifen-dependent CreERT2 is widely used to drive inducible, site-specific recombination of LoxP flanked sequences. In studies of cell autonomous target gene function, it is common practice to combine these CreERT2-lox systems with a ubiquitously-expressed stop-floxed fluorescent reporter gene to identify single cells supposedly undergoing target gene recombination. Here, we studied the reliability of using Cre-induced recombination of one gene to predict recombination in another gene at the single cell level in adult hippocampal neural stem and progenitor cells. Using two separate stop-floxed reporters plus a Nestin promoter-driven CreERT2, we found that, in individual cells, expression of one reporter was a poor predictor of expression of the other. These findings imply that use of stop-floxed reporters to investigate cell autonomous gene function is likely to lead to false conclusions because recombination in separate genes shows poor concordance in individual cells.
FuzzyVariantsExplorer: Graded exploration of genomic data and fuzzy queries
Authors: Falda Marco 
Published: October 2019

AbstractSummaryFuzzyVariantExplorer is a web interface and a fuzzy search system for exploring richly annotated genomes in a flexible way. The application allows combining vague constraints in expressive logical queries to retrieve graded sets of genes and their associated variants. Results can be further refined in a visual way by selecting keywords and categories that are extracted from the underlying annotations and weighted with a statistical significance score; keywords can then be clustered using Latent Dirichlet Allocation and explored visually. The system has been applied to a set of Saccharomyces cerevisiae genome annotations and a few variants.AvailabilityFuzzyVariantExplorer source code is available at the URL https://bitbucket.org/mfalda/fuzzyvariantsexplorer/src/ and has been developed in Scala, TypeScript and R.Contactmarco.falda@unipd.it
Pattern similarity and connectivity of hippocampal-neocortical regions support empathy for pain
Authors: Wagner Isabella C. , Rütgen Markus , Lamm Claus 
Published: October 2019

AbstractEmpathy is thought to engage mental simulation, which in turn is known to rely on hippocampal-neocortical processing. Here, we tested how hippocampal-neocortical pattern similarity and connectivity contributed to pain empathy. Using this approach, we analyzed a data set of 102 human participants who underwent functional MRI while painful and non-painful electrical stimulation was delivered to themselves or to a confederate. As hypothesized, results revealed increased pattern similarity between fist-hand pain and pain empathy (compared to non-painful control conditions) within the hippocampus, retrosplenial cortex, the temporo-parietal junction and anterior insula. While representations in these regions were unaffected by confederate similarity, pattern similarity in the dorsal MPFC was increased the more dissimilar the other individual was perceived. Moreover, hippocampal connectivity with regions engaged in first-hand pain was also increased during pain empathy, during which hippocampal coupling with the fusiform gyrus positively scaled with self-report measures of individual perspective taking skills. These findings highlight that shared representations and interactions within a hippocampal-neocortical network support pain empathy. This potentially reflects memory-based mental simulation processes, which seem partially modulated by personality traits and the perceived similarity of the other individual in pain.
Phenylpropionc acid produced by gut microbiota alleviates acetaminophen-induced hepatotoxicity
Authors: Cho Sungjoon , Yang Xiaotong , Won Kyoung-Jae , Leone Vanessa , Hubert Nathaniel , Chang Eugene , Chung Eunah , Park Joo-Seop , Guzman Grace , Lee Hyunwoo , Jeong Hyunyoung 
Published: October 2019

ABSTRACTAcetaminophen (APAP) overdose causes hepatic injury and is major contributor to acute liver injury cases. To investigate potential roles of gut microbiota in APAP-induced liver injury, C57BL/6 mice from Jackson (JAX) or Taconic (TAC) were challenged with APAP. TAC mice were more susceptible to APAP toxicity, and this disappeared upon co-housing of JAX and TAC mice. When the cecum contents from JAX and TAC mice were transplanted to germ-free mice, the mice that received TAC gut microbiota exhibited more significant hepatotoxicity after APAP administration. Non-targeted metabolomic analysis using portal vein serum and liver tissue of the mice led to identification of 19 metabolites the levels of which are associated with JAX or TAC gut microbiota. A gut bacteria-derived metabolite phenylpropionic acid (PPA) levels in cecum contents and blood were higher in mice harboring JAX gut microbiota. PPA supplementation in drinking water alleviated APAP-induced hepatotoxicity in TAC mice. This was accompanied by reduced hepatic protein levels of cytochrome P450 (CYP) 2E1, the enzyme responsible for APAP bioactivation to a toxic metabolite. This illustrates a gut microbe-liver interaction mediated by a gut bacteria-derived metabolite in modulating drug-induced liver injury.
A presynaptic spectrin network controls active zone assembly and neurotransmitter release
Authors: Wang Qi , Friend Lindsey , Vicidomini Rosario , Han Tae Hee , Nguyen Peter , Ting Chun-Yuan , Serpe Mihaela 
Published: October 2019

ABSTRACTWe have previously reported thatDrosophilaTenectin (Tnc) recruits αPS2/βPS integrin to ensure structural and functional integrity at larval NMJs (Wang et al., 2018). In muscles, Tnc/integrin engages the spectrin network to regulate the size and architecture of synaptic boutons. In neurons, Tnc/integrin controls neurotransmitter release. Here we show that presynaptic Tnc/integrin modulates the synaptic accumulation of key active zone components, including the Ca2+channel Cac and the active zone scaffold Brp. Presynaptic α-Spectrin appears to be both required and sufficient for the recruitment of Cac and Brp. We visualized the endogenous α-Spectrin and found that Tnc controls spectrin recruitment at synaptic terminals. Thus, Tnc/integrin anchors the presynaptic spectrin network and ensures the proper assembly and function of the active zones. Since pre- and postsynaptic Tnc/integrin limit each other, we hypothesize that this pathway links dynamic changes within the synaptic cleft to changes in synaptic structure and function.
Toxic PR poly-dipeptides encoded by the C9orf72 repeat expansion target Kapβ2 and dysregulate phase separation of low-complexity domains
Authors: Nanaura Hitoki , Kawamukai Honoka , Fujiwara Ayano , Uehara Takeru , Nakanishi Mari , Shiota Tomo , Hibino Masaki , Aiba Yuichiro , Wiriyasermkul Pattama , Kikuchi Sotaro , Nagata Riko , Matsubayashi Masaya , Nagamori Shushi , Shoji Osami , Ishimori Koichiro , Matsumura Hiroyoshi , Sugie Kazuma , Saio Tomohide , Yoshizawa Takuya , Mori Eiichiro 
Published: October 2019

ABSTRACTLow-complexity (LC) domains of proteins are found in about one fifth of human proteome, and a group of LC-domains form labile cross-β polymers and liquid-like droplets. Polymers and droplets formed from LC-domains are dynamically regulated by posttranslational modifications and molecular chaperones including nuclear transport receptors. Repeat expansion in the first intron of a gene designated C9orf72, which is the most prevalent form of familial amyotrophic lateral sclerosis (ALS), causes nucleocytoplasmic transport deficit, however, the detailed mechanism remains unsolved. Here we show that the proline:arginine (PR) poly-dipeptides encoded by the C9orf72 repeat expansion bound nuclear transport receptor Kapβ2 through its nuclear localization signal (NLS) recognition motif, and inhibited the ability of Kapβ2 to melt fused in sarcoma (FUS) droplets by competing interaction with FUS. The findings in this study offer mechanistic insights as to how the C9orf72 repeat expansion disables nucleocytoplasmic transport and causes neurodegenerative diseases.
multiSLIDE: a web server for exploring connected elements of biological pathways in multi-omics data
Authors: Ghosh Soumita , Datta Abhik , Choi Hyungwon 
Published: October 2019

AbstractEmerging multi-omics experiments pose new challenges for exploration of quantitative data sets. We present multiSLIDE, a web-based interactive tool for simultaneous heatmap visualization of interconnected molecular features in multi-omics data sets. multiSLIDE operates by keyword search for visualizing biologically connected molecular features, such as genes in pathways and Gene Ontologies, offering convenient functionalities to rearrange, filter, and cluster data sets on a web browser in a real time basis. Various built-in querying mechanisms make it adaptable to diverse omics types, and visualizations are fully customizable. We demonstrate the versatility of the tool through three example studies, each of which showcases its applicability to a wide range of multi-omics data sets, ability to visualize the links between molecules at different granularities of measurement units, and the interface to incorporate inter-molecular relationship from external data sources into the visualization. Online and standalone versions of multiSLIDE are available athttps://github.com/soumitag/multiSLIDE.
PWAS: Proteome-Wide Association Study
Authors: Brandes Nadav , Linial Nathan , Linial Michal 
Published: October 2019

AbstractOver the last two decades, GWAS (Genome-Wide Association Study) has become a canonical tool for exploratory genetic research, generating countless gene-phenotype associations. Despite its accomplishments, several limitations and drawbacks still hinder its success, including low statistical power and obscurity about the causality of implicated variants. We introduce PWAS (Proteome-Wide Association Study), a new method for detecting protein-coding genes associated with phenotypes through protein function alterations. PWAS aggregates the signal of all variants jointly affecting a protein-coding gene and assesses their overall impact on the protein’s function using machine-learning and probabilistic models. Subsequently, it tests whether the gene exhibits functional variability between individuals that correlates with the phenotype of interest. By collecting the genetic signal across many variants in light of their rich proteomic context, PWAS can detect subtle patterns that standard GWAS and other methods overlook. It can also capture more complex modes of heritability, including recessive inheritance. Furthermore, the discovered associations are supported by a concrete molecular model, thus reducing the gap to inferring causality. To demonstrate its applicability for a wide range of human traits, we applied PWAS on a cohort derived from the UK Biobank (~330K individuals) and evaluated it on 49 prominent phenotypes. We compared PWAS to existing methods, proving its capacity to recover causal protein-coding genes and highlighting new associations with plausible biological mechanism.
Optimal spatial prioritization of control resources for elimination of invasive species under demographic uncertainty
Authors: Pepin Kim M. , Smyser Timothy J. , Davis Amy J. , Miller Ryan S. , McKee Sophie , VerCauteren Kurt C. , Slootmaker Chris 
Published: October 2019

ABSTRACTPopulations of invasive species often spread heterogeneously across a landscape, consisting of local populations that cluster in space but are connected by dispersal. A fundamental dilemma for invasive species control is how to optimally allocate limited fiscal resources across local populations. Theoretical work based on perfect knowledge of demographic connectivity suggests that targeting local populations from which migrants originate (sources) can be optimal. However, demographic processes such as abundance and dispersal can be highly uncertain, and the relationship between local population density and damage costs (damage function) is rarely known. We used a metapopulation model to understand how observational uncertainty in abundance and connectivity, and imperfect knowledge of the damage function, affect return on investment (ROI) for optimal control strategies. Budget, observational uncertainty, and the damage function had strong effects on the optimal resource allocation strategy. Uncertainty in dispersal probability was the least important determinant of ROI. The damage function determined which resource prioritization strategy was optimal when connectivity was symmetric but not when it was asymmetric. When connectivity was asymmetric, prioritizing source populations had a higher ROI than allocating effort equally across local populations, regardless of the damage function, but uncertainty in connectivity structure and abundance reduced ROI of the optimal prioritization strategy by 57% on average depending on the control budget. With low budgets (monthly removal rate of 6.7% of population), there was little advantage to prioritizing resources, especially when connectivity was high or symmetric, and observational uncertainty had only minor effects on ROI. Allotting funding for improved monitoring appeared to be most important when budgets were moderate (monthly removal of 13-20% of the population). Our result showed that multiple sources of observational uncertainty should be considered concurrently for optimizing ROI. Accurate estimates of connectivity direction and abundance were more important than accurate estimates of dispersal rates. Developing cost-effective surveillance methods to reduce observational uncertainties, and quantitative frameworks for determining how resources should be spatially apportioned to multiple monitoring and control activities are important and challenging future directions for optimizing ROI for invasive species control programs.
Cross-species machine learning improves diagnostic classification of human psychiatric disorders
Authors: Zhan Yafeng , Wei Jianze , Liang Jian , Xu Xiu , He Ran , Robbins Trevor W. , Wang Zheng 
Published: October 2019

AbstractPsychiatric disorders often exhibit shared (co-morbid) symptoms, raising controversies over accurate diagnosis and the overlap of their neural underpinnings. Because the complexity of data generated by clinical studies poses a formidable challenge, we have pursued a reductionist framework using brain imaging data of a transgenic primate model of autism spectrum disorder (ASD). Here we report an interpretable cross-species machine learning approach which extracts transgene-related core regions in the monkey brain to construct the classifier for diagnostic classification in humans. The cross-species classifier based on core regions, mainly distributed in frontal and temporal cortex, identified from the transgenic primate model, achieved an accuracy of 82.14% in one clinical ASD cohort obtained from Autism Brain Imaging Data Exchange (ABIDE-I), significantly higher than the human-based classifier (61.31%,p< 0.001), which was validated in another independent ASD cohort obtained from ABIDE-II. Such monkey-based classifier generalized to achieve a better classification in obsessive-compulsive disorder (OCD) cohorts, and enabled parsing of differential connections to right ventrolateral prefrontal cortex being attributable to distinct traits in patients with ASD and OCD. These findings underscore the importance of investigating biologically homogeneous samples, particularly in the absence of real-world data adequate for deconstructing heterogeneity inherited in the clinical cohorts.One Sentence SummaryFeatures learned from transgenic monkeys enable improved diagnosis of autism-related disorders and dissection of their underlying circuits.
The Establishment of CDK9/ RNA PolII/H3K4me3/DNA Methylation Feedback Promotes HOTAIR Expression by RNA Elongation Enhancement in Cancer
Authors: Wong Chi Hin , Li Chi Han , He Qifang , Tong Joanna Hung Man , To Ka-Fai , Chen Yangchao 
Published: October 2019

SUMMARYLong non-coding RNA HOX Transcript Antisense RNA (HOTAIR) is overexpressed in multiple cancers with diverse genetic profiles, which heavily contributed to cancer progression. However, the underlying mechanism leading to HOTAIR deregulation is largely unexplored. Here, we revealed that gene body methylation promoted HOTAIR expression through enhancing the transcription elongation process in cancer. We linked up the aberrant gene body histone and DNA methylation in promoting transcription elongation via phosphorylation of Polymerase II Ser 2 by CDK7-CDK9, and elucidated the mechanism of a positive feedback loop involving CDK7, MLL1 and DNMT3A in promoting gene body methylation and overexpressing HOTAIR. To our knowledge, this is the first time to demonstrate that a positive feedback loop that involved CDK9-mediated phosphorylation of PolII and histone and gene body methylation induced robust transcriptional elongation, which heavily contributed to the upregulation of oncogenic lncRNA in cancer.
Gender and credibility in branded storytelling
Authors: Kang Jin-Ae , Hubbard Glenn T. , Hong Sookyeong 
Published: October 2019

Purpose
This paper aims to explore gender differences regarding how men and women perceive the story of a CEO and a customer of different genders in audio advertising.

Design/methodology/approach
A Web-based three-way factorial experiment was designed with three storyteller types (founder’s story, customer’s story vs informational ad), story teller’s gender (male voice vs female voice) and research participants’ gender (men vs women). In total, 549 participants were recruited through Amazon’s Mechanical Turk.

Findings
Researchers found gender-based differences in how audiences evaluated messages from the founder versus the customer of a company. There was a relationship between a male speaker’s perceived authoritativeness and audiences’ favorability to the ad, but no such relationship when the speaker was a woman.

Practical implications
A female voice elicited more favorable attitudes toward the non-story informational ad. In the customer’s story ad, relatability between the speaker and the audience mattered. Participants perceived the ad as more credible and convincing when the gender of the customer in the ad was the same as their gender.

Social implications
Women showed more favorable attitudes toward the male founder’s story compared to the female founder’s story. In evaluating the credibility of the female founder, audiences cared about her character (likability) rather than authoritativeness (expertise).

Originality/value
This study enriches the gender-related advertising-effect literature based on role congruity theory. The research contributes to the understanding of how gender bias still shapes the audiences’ evaluation of storyteller credibility.
Environmental management accounting practices, management system, and performance
Authors: Fuzi Nursyazwani Mohd , Habidin Nurul Fadly , Janudin Sharul Effendy , Ong Sharon Yong Yee 
Published: October 2019

PurposeThe purpose of this paper is to examine the relationship between environmental management accounting practices (EMAP), environmental management system (EMS) and organizational performance (OPM) for Malaysian manufacturing industry by using structural equation modeling (SEM) approach.Design/methodology/approachThe population of the Malaysian manufacturing industry comprised 2,600 manufacturing companies. The unit of analysis is the organization that participated in the survey comprised of automotive/machinery, plastics/rubber/metal, food/tobacco, electrical/electronics and chemical/woods. Out of the 2,600 questionnaires sent to the respondents, 395 were received from manufacturing companies. The collected data are analyzed with the IBM SPSS Statistics and SEM technique.FindingsFindings found that EMS implementation as a partial mediator to improve EMAP and OPM for Malaysian manufacturing industry. Further, the implementation of EMS was found to mediate the relationship between EMAP and OPM.Research limitations/implicationsThe understanding of the importance of studying the relationship between EMAP, EMS and OPM has been emphasized in the present study. In fact, the findings of this study along with its limitations have paved the way for future research in EMAP, EMS and OPM areas.Practical implicationsThis research provides important guidelines for manufacturers and related companies to implement EMAP and EMS in order to improve OPM. Hence, the Malaysian manufacturing industry may need to consider the measurement of EMAP, EMS and OPM as beneficial to their manufacturing companies.Originality/valueThe research contributes to the environmental management accounting by empirically linking the relationship between EMAP, EMS and OPM for Malaysian manufacturing industry.