bluuebunny/crossref_metadata_2025_split huggingface dataset:
Y-RNAs Lead an Endogenous Program of RIG-I Agonism Mobilized upon RNA Virus Infection and Targeted by HIV
Authors: Vabret Nicolas , Najburg Valérie , Solovyov Alexander , Šulc Petr , Balan Sreekumar , Beauclair Guillaume , Chazal Maxime , Varet Hugo , Legendre Rachel , Sismeiro Odile , David Raul Y. Sanchez , McClain Christopher , Gopal Ramya , Chauveau Lise , Schwartz Olivier , Jouvenet Nolwenn , Markowitz Martin , Tangy Frédéric , Bhardwaj Nina , Greenbaum Benjamin D. , Komarova Anastasia V. 
Published: September 2019

AbstractPattern recognition receptors (PRRs) protect against host invasion by detecting specific molecular patterns found in pathogens and initiating an immune response. While microbial-derived PRR ligands have been extensively characterized, the contribution and relevance of endogenous ligands to PRR activation during viral infection remain overlooked. In this work, we characterize the landscape of endogenous ligands that engage RIG-I-like receptors (RLRs) upon infection by a positive-sense RNA virus, a negative-sense RNA virus or a retrovirus. We found that several endogenous RNAs transcribed by RNA polymerase 3 (Pol3) specifically engage RLRs, and in particular the family of small non-coding repeats Y-RNAs, which presents the highest affinity as RIG-I ligands. We show that this recognition is dependent on Y-RNA mimicking viral secondary structure and its 5’-triphosphate extremity. Further, we found that HIV-1 infection triggers a VPR-dependent downregulation of RNA triphosphatase DUSP11in vitroandin vivo, leading to an increase of Y-RNA 5’-triphosphorylation that enables their immunogenicity. Importantly, we show that altering DUSP11 expression is sufficient to induce a type-I interferon and T cell activation transcriptional program associated with HIV-1 infection. Overall, our work uncovers the critical contribution of endogenous repeat RNAs ligands to antiviral immunity and demonstrates the role of this pathway in HIV-1 infection.
Environmental decomposition of cuticular hydrocarbons generates a volatile pheromone that guides insect social behavior
Authors: Hatano Eduardo , Wada-Katsumata Ayako , Schal Coby 
Published: September 2019

AbstractOnce emitted, semiochemicals are exposed to reactive environmental factors that may alter them, thus disrupting chemical communication. Some species, however, might have adapted to detect environmentally mediated breakdown products of their natural chemicals as semiochemicals. We demonstrate that air, water vapor, and ultraviolet (UV) radiation break down unsaturated cuticular hydrocarbons (CHCs) of Periplaneta americana (American cockroach), resulting in the emission of volatile organic compounds (VOCs). In behavioral assays, nymphs strongly avoided aggregating in shelters exposed to the breakdown VOCs from cuticular alkenes. The three treatments (air, water vapor, UV) produced the same VOCs, but at different time-courses and ratios. Fourteen VOCs from UV-exposed CHCs elicited electrophysiological responses in nymph antennae; 10 were identified as 1-pentanol, 1-octanol, 1-nonanol, tetradecanal, acetic acid, propanoic acid, butanoic acid, pentanoic acid and hexanoic acid. When short-chain fatty acids were tested as a mix and a blend of the alcohols and aldehyde was tested as a second mix, nymphs exhibited no preference for control or treated shelters. However, nymphs avoided shelters that were exposed to VOCs from the complete 10-compound mix. Conditioned shelters (occupied by cockroaches with feces and CHCs deposited on the shelters), which are normally highly attractive to nymphs, were also avoided after UV-exposure, confirming that breakdown products from deposited metabolites, including CHCs, mediate this behavior. Our results demonstrate that common environmental and anthropogenic agents degrade CHCs into volatile semiochemicals that may serve as necromones or epideictic pheromones, mediating group formation and dissolution.Significance StatementCuticular hydrocarbons (CHCs) cover the outer surface of insects, where they prevent water loss and serve as sex pheromones and in nest-mate recognition in social insects. Although CHCs are not volatile, they can be broken into volatile fragments by reacting with environmental agents. We demonstrate that volatile breakdown products of CHCs affect the social behavior of the American cockroach. A synthetic mix of volatiles dispersed cockroaches away from shelters, signaling an unsuitable shelter. These results highlight that some insect species have evolved communication strategies that exploit environmental and anthropogenic agents to produce bioactive compounds that mediate ecological interactions.
A tale of winglets: evolution of flight morphology in stick insects
Authors: Zeng Yu , O’Malley Conner , Singhal Sonal , Rahim Faszly , Park Sehoon , Chen Xin , Dudley Robert 
Published: September 2019

AbstractThe evolutionary transition between winglessness and a full-winged morphology requires selective advantage for intermediate forms. Conversely, repeated secondary wing reductions among the pterygotes indicates relaxation of such selection. However, evolutionary trajectories of such transitions are not well characterized. The stick insects (Phasmatodea) exhibit diverse wing sizes at both interspecific and intersexual levels, and thus provide a system for examining how selection on flight capability, along with other selective forces, drives the evolution of flight-related morphology. Here, we examine variation in relevant morphology for stick insects using data from 1100+ individuals representing 765 species. Although wing size varies along a continuous spectrum, taxa with either long or miniaturized wings are the most common, whereas those with intermediate-sized wings are relatively rare. In a morphological space defined by wing and body size, the aerodynamically relevant parameter termed wing loading (the average pressure exerted on the air by the wings) varies according to sex-specific scaling laws; volant but also flightless forms are the most common outcomes in both sexes. Using phylogenetically-informed analyses, we show that relative wing size and body size are inversely correlated in long-winged insects regardless of sexual differences in morphology and ecology. These results demonstrate the diversity of flight-related morphology in stick insects, and also provide a general framework for addressing evolutionary coupling between wing and body dimensions. We also find indirect evidence for a ‘fitness valley’ associated with intermediate-sized wings, suggesting relatively rapid evolutionary transitions between wingless and volant forms.
Estimation of Mediation Effect for High-dimensional Omics Mediators with Application to the Framingham Heart Study
Authors: Yang Tianzhong , Niu Jingbo , Chen Han , Wei Peng 
Published: September 2019

SUMMARYEnvironmental exposures can regulate intermediate molecular phenotypes, such as gene expression, by different mechanisms and thereby lead to various health outcomes. It is of significant scientific interest to unravel the role of potentially high-dimensional intermediate phenotypes in the relationship between environmental exposure and traits. Mediation analysis is an important tool for investigating such relationships. However, it has mainly focused on low-dimensional settings, and there is a lack of a good measure of the total mediation effect. Here, we extend an R-squared (Rsq) effect size measure, originally proposed in the single-mediator setting, to the moderate- and high-dimensional mediator settings in the mixed model framework. Based on extensive simulations, we compare our measure and estimation procedure with several frequently used mediation measures, including product, proportion, and ratio measures. Our Rsq measure has small bias and variance under the correctly specified model. To mitigate potential bias induced by non-mediators, we examine two variable selection procedures, i.e., iterative sure independence screening and false discovery rate control, to exclude the non-mediators. We evaluate the consistency of the proposed estimation procedures and introduce a resampling-based confidence interval. By applying the proposed estimation procedure, we find that more than half of the aging-related variations in systolic blood pressure can be explained by gene expression profiles in the Framingham Heart Study.
Mucoidy, a general mechanism for maintaining lytic phage in populations of bacteria
Authors: Chaudhry Waqas , Lee Esther , Worthy Andrew , Weiss Zoe , Grabowicz Marcin , Vega Nicole , Levin Bruce 
Published: September 2019

AbstractWe present evidence that phage resistance resulting from overproduction of exopolysaccharides, mucoidy, provides a general answer to the longstanding question of how lytic viruses are maintained in populations dominated by bacteria upon which they cannot replicate. In serial transfer culture, populations of mucoid E. coli MG1655 that are resistant to lytic phages with different receptors, and thereby requiring independent mutations for surface resistance, are capable of maintaining these phages with little effect on their total density. Based on the results of our analysis of a mathematical model, we postulate that the maintenance of phage in populations dominated by mucoid cells can be attributed primarily to high rates of transition from the resistant mucoid states to susceptible non-mucoid states. Our tests with both population dynamic and single cell experiments as well as DNA sequence analysis are consistent with this hypothesis. We discuss reasons for the generalized resistance of these mucoid E. coli, and the genetic and molecular mechanisms responsible for the high rate of transition from mucoid to sensitive states responsible for the maintenance of lytic phage in mucoid populations of E. coli.
RELA is Sufficient to Mediate Interleukin-1 (IL-1) Repression of Androgen Receptor Expression and Activity in LNCaP Disease Progression Model
Authors: Thomas-Jardin Shayna E. , Dahl Haley , Kanchwala Mohammed S. , Ha Freedom , Jacob Joan , Soundharrajan Reshma , Bautista Monica , Nawas Afshan F. , Robichaux Dexter , Mistry Ragini , Anunobi Vanessa , Xing Chao , Delk Nikki A. 
Published: September 2019

ABSTRACTBackgroundThe Androgen Receptor (AR) nuclear transcription factor is a therapeutic target for prostate cancer (PCa). Unfortunately, patients can develop resistance to AR-targeted therapies and progress to lethal disease, underscoring the importance of understanding the molecular mechanisms that underlie treatment resistance. Inflammation is implicated in PCa initiation and progression and we have previously reported that the inflammatory cytokine, interleukin-1 (IL-1), represses AR mRNA levels and activity in AR-positive (AR+) PCa cell lines concomitant with the upregulation of pro-survival biomolecules. Thus, we contend that IL-1 can select for AR-independent, treatment-resistant PCa cells.MethodsTo begin to explore how IL-1 signaling leads to the repression of AR mRNA levels, we performed comprehensive pathway analysis on our RNA sequencing data from IL-1-treated LNCaP PCa cells. Our pathway analysis predicted Nuclear Factor Kappa B (NF-κB) p65 subunit (RELA), a canonical IL-1 signal transducer, to be significantly active and potentially regulate many genes, including AR. We used siRNA to silence the NF-κB family of transcription factor subunits, RELA, RELB, c-REL, NFKB1, or NFKB2, in IL-1-treated LNCaP, C4-2, and C4-2B PCa cell lines. C4-2 and C4-2B cell lines are castration-resistant LNCaP sublines and represent progression towards metastatic PCa disease; and we have previously shown that IL-1 represses AR mRNA levels in C4-2 and C4-2B cells.ResultssiRNA revealed that RELA alone is sufficient to mediate IL-1 repression of AR mRNA and AR activity. Intriguingly, while LNCaP cells are more sensitive to IL-1-mediated repression of AR than C4-2 and C4-2B cells, RELA siRNA led to a more striking de-repression of AR mRNA levels and AR activity in C4-2 and C4-2B cells than in LNCaP cells.ConclusionsThese data indicate that there are RELA-independent mechanisms that regulate IL-1-mediated AR repression in LNCaP cells and suggest that the switch to RELA-dependent IL-1 repression of AR in C4-2 and C4-2B cells reflects changes in epigenetic and transcriptional programs that evolve during PCa disease progression.
Causal links between parietal alpha activity and spatial auditory attention
Authors: Deng Yuqi , Reinhart Robert M. G. , Choi Inyong , Shinn-Cunningham Barbara 
Published: September 2019

AbstractBoth visual and auditory spatial selective attention result in lateralized alpha (8-14 Hz) oscillatory power in parietal cortex: alpha increases in the hemisphere ipsilateral to attentional focus. Brain stimulation studies suggest a causal relationship between parietal alpha and suppression of the representation of contralateral visual space. However, there is no evidence that parietal alpha controls auditory spatial attention. Here, we performed high definition transcranial alternating current stimulation (HD-tACS) on human subjects performing an auditory task in which they attended either spatial or nonspatial features. Alpha (10 Hz) but not theta (6 Hz) HD-tACS of right parietal cortex interfered with attending left but not right auditory space. Parietal stimulation had no effect for nonspatial auditory attention. Moreover, performance in post-stimulation trials returned rapidly to baseline. These results demonstrate a causal, frequency-, hemispheric-, and task-specific effect of parietal alpha brain stimulation on top-down control of auditory spatial attention.
Steryl ester formation and accumulation in steroid-degrading bacteria
Authors: Holert Johannes , Brown Kirstin , Hashimi Ameena , Eltis Lindsay D. , Mohn William W. 
Published: September 2019

ABSTRACTSteryl esters (SEs) are important storage compounds in many eukaryotes and are often prominent components of intracellular lipid droplets. Here we demonstrate that selected Actino- and Proteobacteria growing on sterols are also able to synthesize SEs and to sequester them in cytoplasmic lipid droplets. We found cholesteryl ester (CE) formation in members of the actinobacterial genera Rhodococcus, Mycobacterium, and Amycolatopsis as well as several members of the proteobacterial Cellvibrionales order. CEs maximally accumulated under nitrogen-limiting conditions, suggesting that steryl ester formation plays a crucial role for storing excess energy and carbon under adverse conditions. Rhodococcus jostii RHA1 was able to synthesize phytosteryl- and cholesteryl esters, the latter reaching up to 7% of its cellular dry weight and 69% of its lipid droplets. Purified lipid droplets from RHA1 contained CEs, free cholesterol and triacylglycerols. In addition, we found formation of CEs in Mycobacterium tuberculosis when grown with cholesterol plus an additional fatty acid substrate. This study provides a basis for the application of bacterial whole cell systems in the biotechnological production of SEs for use in functional foods and cosmetics.IMPORTANCEOleaginous bacteria exhibit great potential for the production of high-value neutral lipids, such as triacylglycerols and wax esters. This study describes the formation of steryl esters (SEs) as neutral lipid storage compounds in sterol-degrading oleaginous bacteria, providing a basis for biotechnological production of SEs using bacterial systems with potential applications in the functional food, nutraceutical, and cosmetic industries. We found cholesteryl ester (CE) formation in several sterol-degrading Actino- and Proteobacteria under nitrogen limiting conditions, suggesting an important role of this process in storing energy and carbon under adverse conditions. In addition, Mycobacterium tuberculosis grown on cholesterol accumulated CEs in the presence of an additional fatty acid substrate.
Evidence of polygenic adaptation at height-associated loci in mainland Europeans and Sardinians
Authors: Chen Minhui , Sidore Carlo , Akiyama Masato , Ishigaki Kazuyoshi , Kamatani Yoichiro , Schlessinger David , Cucca Francesco , Okada Yukinori , Chiang Charleston W. K. 
Published: September 2019

AbstractAdult height was one of the earliest putative examples of polygenic adaptation in human. By constructing polygenic height scores using effect sizes and frequencies from hundreds of genomic loci robustly associated with height, it was reported that Northern Europeans were genetically taller than Southern Europeans beyond neutral expectation. However, this inference was recently challenged. Sohail et al. and Berg et al. showed that the polygenic signature disappeared if summary statistics from UK Biobank (UKB) were used in the analysis, suggesting that residual uncorrected stratification from large-scale consortium studies was responsible for the previously noted genetic difference. It thus remains an open question whether height loci exhibit signals of polygenic adaptation in any human population. In the present study, we re-examined this question, focusing on one of the shortest European populations, the Sardinians, as well as on the mainland European populations in general. We found that summary statistics from UKB significantly correlate with population structure in Europe. To further alleviate concerns of biased ascertainment of GWAS loci, we examined height-associated loci from the Biobank of Japan (BBJ). Applying frequency-based inference over these height-associated loci, we showed that the Sardinians remain significantly shorter than expected (~ 0.35 standard deviation shorter than CEU based on polygenic height scores, P = 1.95e-6). We also found the trajectory of polygenic height scores decreased over at least the last 10,000 years when compared to the British population (P = 0.0123), consistent with a signature of polygenic adaptation at height-associated loci. Although the same approach showed a much subtler signature in mainland European populations, we found a clear and robust adaptive signature in UK population using a haplotype-based statistic, tSDS, driven by the height-increasing alleles (P = 4.8e-4). In summary, by examining frequencies at height loci ascertained in a distant East Asian population, we further supported the evidence of polygenic adaptation at height-associated loci among the Sardinians. In mainland Europeans, we also found an adaptive signature, although becoming more pronounced only in haplotype-based analysis.
Learning with reward prediction errors in a model of the Drosophila mushroom body
Authors: Bennett James E. M. , Philippides Andrew , Nowotny Thomas 
Published: September 2019

AbstractEffective decision making in a changing environment demands that accurate predictions are learned about decision outcomes. In Drosophila, such learning is or-chestrated in part by the mushroom body (MB), where dopamine neurons (DANs) signal reinforcing stimuli to modulate plasticity presynaptic to MB output neurons (MBONs). Here, we extend previous MB models, in which DANs signal absolute rewards, proposing instead that DANs signal reward prediction errors (RPEs) by utilising feedback reward predictions from MBONs. We formulate plasticity rules that minimise RPEs, and use simulations to verify that MBONs learn accurate reward predictions. We postulate as yet unobserved connectivity, which not only overcomes limitations in the experimentally constrained model, but also explains additional experimental observations that connect MB physiology to learning. The original, experimentally constrained model and the augmented model capture a broad range of established fly behaviours, and together make five predictions that can be tested using established experimental methods.
Big data and risk management in business processes: implications for corporate real estate
Authors: Battisti Enrico , Shams S.M. Riad , Sakka Georgia , Miglietta Nicola 
Published: September 2019

PurposeThe purpose of this paper is to improve understanding of the integration between big data (BD) and risk management (RM) in business processes (BPs), with special reference to corporate real estate (CRE).Design/methodology/approachThis conceptual study follows, methodologically, the structuring inter-textual coherence process – specifically, the synthesised coherence tactical approach. It draws heavily on theoretical evidence published, mainly, in the corporate finance and the business management literature.FindingsA new conceptual framework is presented for CRE to proactively develop insights into the potential benefits of using BD as a business strategy/instrument. The approach was found to strengthen decision-making processes and encourage better RM – with significant consequences, in particular, for business process management (BPM). Specifically, by recognising the potential uses of BD, it is also possible to redefine the processes with advantages in terms of RM.Originality/valueThis study contributes to the literature in the fields of real estate, RM, BPM and digital transformation. To the best knowledge of authors, although the literature has examined the concepts of BD, RM and BP, no prior studies have comprehensively examined these three elements and their conjoint contribution to CRE. In particular, the study highlights how the automation of data-intensive activities and the analysis of such data (in both structured and unstructured forms), as a means of supporting decision making, can lead to better efficiency in RM and optimisation of processes.
Exploring the impact of TMTs’ overseas experiences on innovation performance of Chinese enterprises
Authors: Yang Lin , Xu Chenwu , Wan Guoguang 
Published: September 2019

PurposeDrawing on the related insights from the upper echelon perspective, modern cognitive theory and path dependence theory, this paper aims to first integrate top management teams (TMTs) overseas experiences, research and development (R&D) strategic decision-making and innovation performance into a uniform theoretical framework and try to understand TMTs’ overseas experiences accounting for both the direct and indirect mechanisms of the variables involved within the transition economy of China.Design/methodology/approachThe paper adopts research sample from the listed companies on the Growth Enterprises Market Board (GEMB) of Shenzhen Stock Exchange of China due to their stronger innovation consciousness. The research data are mainly from the WIND database of China, as the data issued in this database must be checked and approved by China’s legal institutions including China Securities Regulatory Commission and its authorized agencies. The samples cover different types of ownership and the vast majority of industries of China, which makes the objects a wide range of coverage and representativeness. In addition, according to suggestions of Podsakoffet al.(2003), the authors design the controlling measures from two aspects of data collection and statistical analysis to reduce the homologous error as much as possible.FindingsEmpirical results show that innovation performance is positively affected by the centrality overseas functional experience and industrial experience but negatively affected by the heterogeneity of overseas functional experience of TMT. Meanwhile, R&D intensity and modes play partially mediating effect in the relationship between TMTs’ overseas functional experience centrality and industrial experience heterogeneity and innovation performance, but for the relationship between overseas functional experience heterogeneity and innovation performance, R&D intensity leads to fully mediating effect.Originality/valueThis study contributes toward filling the gaps by elucidating the effect of TMTs’ overseas experiences on the innovation performance, identifying the mediating role of R&D strategic decision-makings in this relationship and empirically examining the acting mechanisms and paths of the variables involved in the Chinese context. In addition, practitioners could use these findings to improve their selection and training processes regarding both the top management members and the designing of the R&D strategies.