bluuebunny/crossref_metadata_2025_split huggingface dataset:
A synthetic morphogenic membrane system that responds with self-organized shape changes to local light cues
Authors: Gavriljuk Konstantin , Scocozza Bruno , Ghasemalizadeh Farid , Nandan Akhilesh P. , Medina Manuel Campos , Seidel Hans , Schmick Malte , Koseska Aneta , Bastiaens Philippe I. H. 
Published: November 2018

SUMMARYReconstitution of artificial cells capable of transducing extracellular signals into cytoskeletal changes is a challenge in synthetic biology that will reveal fundamental principles of non-equilibrium phenomena of cellular morphogenesis and information processing. Here, we generated a ‘life-like’ Synthetic Morphogenic Membrane System (SynMMS) by encapsulating a dynamic microtubule (MT) aster and a light-inducible signaling system driven by GTP/ATP chemical potential into cell-sized vesicles. The biomimetic design of the light-induced signaling system embodies the operational principle of morphogen induced Rho-GTPase signal transduction in cells. Activation of synthetic signaling promotes membrane-deforming growth of MT-filaments by dynamically elevating the membrane-proximal concentration of tubulin. The resulting membrane deformations enable the recursive coupling of the MT-aster with the signaling system, creating global self-organized morphologies that reorganize towards external light cues in dependence on prior sensory experience that is stored in the dynamically maintained morphology. SynMMS thereby signifies a step towards bio-inspired engineering of self-organized cellular morphogenesis.
Hfq CLASH uncovers sRNA-target interaction networks involved in adaptation to nutrient availability
Authors: Iosub Ira A. , Marchioretto Marta , Sy Brandon , McKellar Stuart , Nieken Karen J. , van Nues Rob W. , Tree Jai J. , Viero Gabriella , Granneman Sander 
Published: November 2018

AbstractBy shaping gene expression profiles, small RNAs (sRNAs) enable bacteria to very efficiently adapt to constant changes in their environment. To better understand howEscherichia coliacclimatizes to changes in nutrient availability, we performed UV cross-linking, ligation and sequencing of hybrids (CLASH) to uncover sRNA-target interactions. Strikingly, we uncovered hundreds of novel Hfq-mediated sRNA-target interactions at specific growth stages, involving many novel 3’UTR-derived sRNAs and a plethora of sRNA-sRNA interactions. We discovered sRNA-target interaction networks that play a role in adaptation to changes in nutrient availability. We characterized a novel 3’UTR-derived sRNA (MdoR), which is part of a regulatory cascade that enhances maltose uptake by (a) inactivating repressive pathways that block the accumulation of maltose transporters and (b) by reducing the flux of general porins to the outer membrane. Our work provides striking examples of how bacteria utilize sRNAs to integrate multiple regulatory pathways to enhance nutrient stress adaptation.
FDA-ARGOS: A Public Quality-Controlled Genome Database Resource for Infectious Disease Sequencing Diagnostics and Regulatory Science Research
Authors: Sichtig Heike , Minogue Timothy , Yan Yi , Stefan Christopher , Hall Adrienne , Tallon Luke , Sadzewicz Lisa , Nadendla Suvarna , Klimke William , Hatcher Eneida , Shumway Martin , Aldea Dayanara Lebron , Allen Jonathan , Koehler Jeffrey , Slezak Tom , Lovell Stephen , Schoepp Randal , Scherf Uwe 
Published: November 2018

ABSTRACTInfectious disease next generation sequencing (ID-NGS) diagnostics are on the cusp of revolutionizing the clinical market. To facilitate this transition, FDA proactively invested in tools to support innovation of emerging technologies. FDA and collaborators established a publicly available database, FDA dAtabase for Regulatory-Grade micrObial Sequences (FDA-ARGOS), as a tool to fill reference database gaps with quality-controlled genomes. This manuscript discusses quality control metrics for the proposed FDA-ARGOS genomic resource and outlines the need for quality-controlled genome gap filling in the public domain. Here, we also present three case studies showcasing potential applications for FDA-ARGOS in infectious disease diagnostics, specifically: assay design, reference database and in silico sequence comparison in combination with representative microbial organism wet lab testing; a novel composite validation strategy for ID-NGS diagnostics. The use of FDA-ARGOS as an in silico comparator tool could reduce the burden for completing ID-NGS clinical trials. In addition, use cases identifying Enterococcus avium and Ebola virus (Zaire ebolavirus variant Makona) demonstrate the utility of FDA-ARGOS as a reference database for independent performance validation of new tests and for documenting how one would use this database as an in silico sequence target comparator tool for ID-NGS validation, respectively.
Using expert driven machine learning to enhance dynamic metabolomics data analysis
Authors: Beirnaert Charlie , Peeters Laura , Meysman Pieter , Bittremieux Wout , Foubert Kenn , Custers Deborah , Van der Auwera Anastasia , Cuykx Matthias , Pieters Luc , Covaci Adrian , Laukens Kris 
Published: November 2018

AbstractData analysis for metabolomics is undergoing rapid progress thanks to the proliferation of novel tools and the standardization of existing workflows. However, as datasets and experiments continue to increase in size and complexity, standardized workflows are often not sufficient. In addition, as the ground truth for metabolomics experiments is intrinsically unknown, there is no way to critically evaluate the performance of tools. Here, we investigate the problem of dynamic multi-class metabolomics experiments using a simulated dataset with a known ground truth and evaluate the performance of tinderesting, a new and intuitive tool based on gathering expert knowledge to be used in machine learning, and compare it to EDGE, a statistical method for sequence data. This paper presents three novel outcomes. First we present a way to simulate dynamic metabolomics data with a known ground truth based on ordinary differential equations. This method is made available through the MetaboLouise R package. Second, we show that the EDGE tool, originally developed for genomics data analysis, is highly performant in analyzing dynamic case vs control metabolomics data. Last, we introduce the tinderesting method to analyse more complex dynamic metabolomics experiments that performs on par with statistical methods. This tool consists of a Shiny app for collecting expert knowledge, which in turn is used to train a machine learning model to emulate the decision process of the expert. This approach does not replace traditional data analysis workflows for metabolomics, but can provide additional information, improved performance or easier interpretation of results. The advantage is that the tool is agnostic to the complexity of the experiment, and thus is easier to use in advanced setups. All code for the presented analysis, MetaboLouise and tinderesting are freely available.
Functional disease architectures reveal unique biological role of transposable elements
Authors: Hormozdiari Farhad , Geijn Bryce van de , Nasser Joseph , Weissbrod Omer , Gazal Steven , Ju Chelsea J.-T. , O’Connor Luke , Hujoel Margaux Louise Anna , Engreitz Jesse , Hormozdiari Fereydoun , Price Alkes L. 
Published: November 2018

AbstractTransposable elements (TE) comprise roughly half of the human genome. Though initially derided as “junk DNA”, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases and complex traits remains unknown. Here, we analyze data from 41 independent diseases and complex traits (average N=320K) to draw three main conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39±2% of heritability; enrichment of 0.72±0.03; 0.38-1.23 enrichment across four main TE classes), TE explain substantially more heritability than expected based on their depletion for known functional annotations (expected enrichment of 0.35±0.03; 2.11x ratio of true vs. expected enrichment). This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function; SNPs inside the oldest 20% of TE explain 2.45x more heritability than SNPs inside the youngest 20% of TE. Third, Short Interspersed Nuclear Elements (SINE; one of the four main TE classes) are far more enriched for blood traits (2.05±0.30) than for other traits (0.96±0.09); this difference is far greater than expected based on the weaker depletion of SINEs for regulatory annotations in blood compared to other tissues. Our results elucidate the biological roles that TE play in the genetic architecture of diseases and complex traits.
APOE4is Associated with Differential Regional Vulnerability to Bioenergetic Deficits in AgedAPOEMice
Authors: Nuriel Tal , Larrea Delfina , Guilfoyle David N. , Pirhaji Leila , Shannon Kathleen , Arain Hirra , Ashok Archana , Pera Marta , Chen Qiuying , Dillman Allissa A. , Figueroa Helen Y. , Cookson Mark R. , Gross Steven S. , Fraenkel Ernest , Duff Karen E. , Area-Gomez Estela 
Published: November 2018

ABSTRACTThe ε4 allele of apolipoprotein E (APOE) is the dominant genetic risk factor for late-onset Alzheimer’s disease (AD). However, the reason for the association betweenAPOE4and AD remains unclear. While much of the research has focused on the ability of the apoE4 protein to increase the aggregation and decrease the clearance of Aβ, there is also an abundance of data showing thatAPOE4negatively impacts many additional processes in the brain, including bioenergetics. In order to gain a more comprehensive understanding of theAPOE4’s role in AD pathogenesis, we performed a multi-omic analysis ofAPOE4vs.APOE3expression in the entorhinal cortex (EC) and primary visual cortex (PVC) of agedAPOEmice. These studies revealed region-specific alterations in several bioenergetic pathways, including oxidative phosphorylation (OxPhos), the TCA-cycle and fatty acid metabolism. Follow-up analysis utilizing the Seahorse platform revealed decreased mitochondrial respiration in the hippocampus and cortex of agedAPOE4vs.APOE3mice, but not in the EC of these mice. Additional studies, as well as the original multi-omic data suggest that bioernergetic pathways in the EC of agedAPOEmice may be differentially regulated byAPOE4expression. Given the importance of the EC as one of the first regions to be affected by AD pathology in humans, this differential bionenergetic regulation observed in the EC vs. other brain regions of agedAPOE4mice may play an important role in the pathogenesis of AD, particularly amongAPOE4carriers.
Meiotic effects ofMSH4copy number variation support an adaptive role for post-polyploidy gene loss
Authors: Gonzalo Adrián , Lucas Marie-Odile , Marquis Catherine , Lloyd Andrew , Jenczewski Eric 
Published: November 2018

ABSTRACTMany eukaryotes descend from polyploid ancestors that experienced massive duplicate gene loss. This genomic erosion is particularly strong for duplicated (meiotic) recombination genes that return to a single copy more rapidly than genome average following polyploidy. To better understand the evolutionary forces underlying duplicate loss, we analysed how varying copy numbers ofMSH4, an essential meiotic recombination gene, influences crossover formation in allotetraploidBrassica napus. We show that faithful chromosome segregation and crossover frequencies between homologous chromosomes are unchanged withMSH4duplicate loss; by contrast, crossovers between homoeologous chromosomes (which result in genomic rearrangements) decrease with reductions inMSH4copy number. We also found that inter-homoeologue crossovers originate almost exclusively from the MSH4-dependent crossover pathway. Limiting the efficiency of this pathway by decreasing the copy number of key meiotic recombination genes could therefore contribute to adaptation to polyploidy, by promoting regular chromosome segregation and genomic stability.
Genotype network intersections promote evolutionary innovation
Authors: Bendixsen Devin P. , Collet James , Østman Bjørn , Hayden Eric J. 
Published: November 2018

AbstractEvolutionary innovations are qualitatively novel traits that emerge through evolution and increase biodiversity. The genetic mechanisms that lead to innovation remain poorly understood. A systems view of innovation requires the analysis of genotype networks – the vast networks of genetic variants that produce the same phenotype. Innovations can occur at the intersection of two different genotype networks. Here, we use high-throughput sequencing to study the fitness landscape at the intersection of the genotype networks of two catalytic RNA molecules (ribozymes). We determined the ability of numerous neighboring RNA sequences to catalyze two different chemical reactions. We find extensive functional overlap, and over half the genotypes can catalyze both functions to some extent. We demonstrate through evolutionary simulations that these numerous points of intersection facilitate the discovery of a new function. Our study reveals the properties of a fitness landscape where genotype networks intersect, and the consequences for evolutionary innovations.
Using subthreshold events to characterize the functional architecture of electrically coupled networks
Authors: Lefler Yaara , Amsalem Oren , Segev Idan , Yarom Yosef 
Published: November 2018

AbstractThe electrical connectivity in the inferior olive (IO) nucleus plays an important role in generating well-timed spiking activity. Here we combined electrophysiological and computational approaches to assess the functional organization of mice IO nucleus. Spontaneous fast and slow subthreshold events were commonly encountered during in vitro recordings. We show that the fast events represent a regenerative response in unique excitable spine-like structures in the axon hillock, whereas the slow events reflect the electrical connectivity between neurons (‘spikelets’). Recordings from cell pairs revealed the synchronized occurrence of distinct groups of spikelets; their rate and distribution enabled an accurate estimation of the number of connected cells and is suggestive of a clustered organization. This study thus provides a new perspective on the functional and structural organization of the olivary nucleus, insights into two different subthreshold non-synaptic events, and a novel experimental and theoretical approach to the study of electrically-coupled networks.
Flagellar stators stimulate c-di-GMP production by Pseudomonas aeruginosa
Authors: Baker Amy E. , Webster Shanice S. , Diepold Andreas , Kuchma Sherry L. , Bordeleau Eric , Armitage Judith P. , O’Toole George A. 
Published: November 2018

AbstractFlagellar motility is critical for surface attachment and biofilm formation in many bacteria. A key regulator of flagellar motility in Pseudomonas aeruginosa and other microbes is cyclic diguanylate (c-di-GMP). High levels of this second messenger repress motility and stimulate biofilm formation. C-di-GMP levels regulate motility in P. aeruginosa in part by influencing the localization of its two flagellar stator sets, MotAB and MotCD. Here we show that just as c-di-GMP can influence the stators, stators can impact c-di-GMP levels. We demonstrate that the swarming motility-driving stator MotC physically interacts with the transmembrane region of the diguanylate cyclase SadC. Furthermore, we demonstrate that this interaction is capable of stimulating SadC activity. We propose a model by which the MotCD stator set interacts with SadC to stimulate c-di-GMP production in conditions not permissive to motility. This regulation implies a positive feedback loop in which c-di-GMP signaling events cause MotCD stators to disengage from the motor; then disengaged stators stimulate c-di-GMP production to reinforce a biofilm mode of growth. Our studies help define the bidirectional interactions between c-di-GMP and the motility machinery.Importance.The ability of bacterial cells to control motility during early steps in biofilm formation is critical for the transition to a non-motile, biofilm lifestyle. Recent studies have clearly demonstrated the ability of c-di-GMP to control motility via a number of mechanisms, including through controlling transcription of motility-related genes and modulating motor function. Here we provide evidence that motor components can in turn impact c-di-GMP levels. We propose that communication between motor components and c-di-GMP synthesis machinery allows the cell to have a robust and sensitive switching mechanism to control motility during early events in biofilm formation.
Olfactory Spatial Attention: Neural Structural Connectivity Revealed
Authors: Elumalai Ganesh , Chatterjee Harshita , Syed Imran Shareef , Brown Valencia , Sober Lekesha Adele , Venkata Ghanta Nitya Akarsha Surya , Chandrasekhar Pradeep , Venkatesan Anbarasan , Sewram Nadira , Muthukumaran Nitesh Raj , Harkrishna Golla , Vamsi Nanduri Mojess , Team NeurON Nneoma Somtochukwu Osakwe , University Texila American 
Published: November 2018

AbstractDifferent aspects of spatial neglect, the disability to locate the position of the source of an external stimulus, has been studied frequently especially with regards to lack of response to visual stimuli. A modicum of papers fails to elaborate on that of the auditory field and even less conducted on the extraction of spatial information from olfactory stimuli. In this study we attempted to find a structural connection between the Olfactory Cortex (OC) and Temporoparietal Junction (TPJ), in order to suggest that processed olfactory information is carried from OC to TPJ, where the spatial information of the odor maybe acquired. Positive results were attained in all subjects with a lateralization observed in the right hemisphere.One Sentence SummaryExistence and hemispherical dominance.
Using EEG to characterise drowsiness during short duration exposure to elevated indoor Carbon Dioxide concentrations
Authors: Snow Stephen , Boyson Amy , Felipe-King Marco , Malik Obaid , Coutts Louise , Noakes Catherine J , Gough Hannah , Barlow Janet , schraefel m.c. 
Published: November 2018

AbstractDrowsiness which can affect work performance, is often elicited through self- reporting. This paper demonstrates the potential to use EEG to objectively quantify changes to drowsiness due to poor indoor air quality. Continuous EEG data was recorded from 23 treatment group participants subject to artificially raised indoor CO2 concentrations (average 2,700 ± 300 ppm) for approximately 10 minutes and 13 control group participants subject to the same protocol without additional CO2 (average 830 ± 70 ppm). EEG data were analysed for markers of drowsiness according neurophysiological methods at three stages of the experiment, Baseline, High CO2 and Post-Ventilation. Treatment group participants’ EEG data yielded a closer approximation to drowsiness than that of control group participants during the High CO2 condition, despite no significant group differences in self-reported sleepiness. Future work is required to determine the persistence of these changes to EEG over longer exposures and to better isolate the specific effect of CO2 on drowsiness compared to other environmental or physiological factors.Practical implicationsThis study introduces EEG as a potential objective indicator of the effect of indoor environmental conditions upon drowsinessParticipants exposed to 2,700 ppm for 10 minutes showed greater evidence of a progression towards drowsiness (as measured by EEG) than that of participants who received the same protocol without additional CO2 (mean 830 ± 70 ppm), despite similar ratings of subjective sleepiness.Subjective and objectively measured indications of drowsiness were reduced following ventilation of the room. Future work could explore the potential of regular ventilation episodes in knowledge work spaces to retain alertness.
First genome-wide association study of non-severe malaria in two birth cohorts in Benin
Authors: Milet Jacqueline , Boland Anne , Luisi Pierre , Sabbagh Audrey , Sadissou Ibrahim , Sonon Paulin , Domingo Nadia , Palstra Friso , Gineau Laure , Courtin David , Massougbodji Achille , Garcia André , Deleuze Jean-François , Perdry Hervé 
Published: November 2018

AbstractRecent research efforts to identify genes involved in malaria susceptibility using genome-wide approaches have focused on severe malaria. Here we present the first GWAS on non-severe malaria designed to identify genetic variants involved in innate immunity or innate resistance mechanisms. Our study was performed on two cohorts of infants from southern Benin (525 and 250 individuals respectively) closely followed from birth to 18-24 months of age, with an assessment of a space-and time-dependent environmental risk of exposure. Both the recurrence of mild malaria attacks and the recurrence of malaria infections as a whole (symptomatic and asymptomatic) were considered. Our study highlights a role ofPTPRT, a tyrosine phosphatase receptor involved in STAT3 pathway and several other genes whose biological functions are relevant in malaria infection. Results shows that GWAS on non-severe malaria can successfully identify new candidate genes and inform physiological mechanisms underlying natural protection against malaria.
The perceived influence of relationship quality on brand loyalty
Authors: Ledikwe Aobakwe , Roberts-Lombard Mornay , Klopper Hendrik Baltus 
Published: November 2018

PurposeThe purpose of this paper is to investigate the extent to which the attitudinal loyalty of customers of small and medium apparel businesses is influenced by their perceptions of trust, commitment and satisfaction. In turn, the influence of their attitudinal loyalty on future behavioural loyalty is established.Design/methodology/approachA quantitative descriptive research approach was employed and questionnaires were administered to customers of three selected small and medium enterprise (SME) brands in the metropolitan city of Gaborone, Botswana. A total of 260 questionnaires were suitable for data analysis. The interrelationship of the constructs was analysed via structural equation modelling. In addition, the measurement and structural models were assessed.FindingsTrust, commitment and satisfaction have a positive and significant influence on the attitudinal loyalty of SME customers, while attitudinal loyalty has a positive and significant influence on their behavioural loyalty.Research limitations/implicationsThe tested model confirms the hypothesised relationships between SME customers’ trust, commitment, satisfaction, attitudinal loyalty and behavioural loyalty. Attitudinal loyalty is linked to its three antecedents (trust, commitment and satisfaction) and its outcome, behavioural loyalty.Practical implicationsThe findings assist the management of SMEs in understanding how the cultivation of trust, commitment and satisfaction can foster attitudinal loyalty, ultimately leading to improved behavioural loyalty.Originality/valueThe current study contributes to new knowledge on the interrelationship of selected relationship quality dimensions, attitudinal loyalty and behavioural loyalty among SME customers in the apparel industry of Botswana. Few research studies have examined how attitudinal loyalty relates to its antecedents and outcome in Botswana, as an emerging African economy.