bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating individuals’ genetic and non-genetic effects underlying infectious disease transmission from temporal epidemic data
Authors: Pooley Christopher M. , Marion Glenn , Bishop Stephen C. , Bailey Richard I. , Doeschl-Wilson Andrea B. 
Published: April 2019

AbstractIndividuals differ widely in their contribution to the spread of infection within and across populations. Three key epidemiological host traits affect infectious disease spread: susceptibility (propensity to acquire infection), infectivity (propensity to transmit infection to others) and recoverability (propensity to recover quickly). Interventions aiming to reduce disease spread may target improvement in any one of these traits, but the necessary statistical methods for obtaining risk estimates are lacking. In this paper we introduce a novel software tool calledSIRE(standing for “Susceptibility, Infectivity and Recoverability Estimation”), which allows simultaneous estimation of the genetic effect of a single nucleotide polymorphism (SNP), as well as non-genetic influences on these three unobservable host traits. SIRE implements a flexible Bayesian algorithm which accommodates a wide range of disease surveillance data comprising any combination of recorded individual infection and/or recovery times, or disease status measurements. Different genetic and non-genetic regulations and data scenarios (representing realistic recording schemes) were simulated to validate SIRE and to assess their impact on the precision, accuracy and bias of parameter estimates. This analysis revealed that with few exceptions, SIRE provides unbiased, accurate parameter estimates associated with all three host traits. For most scenarios, SNP effects associated with recoverability can be estimated with highest precision, followed by susceptibility. For infectivity, many epidemics with few individuals give substantially more statistical power to identify SNP effects than the reverse. Importantly, precise estimates of SNP and other effects could be obtained even in the case of incomplete, censored and relatively infrequent measurements of individuals’ infection or survival status, albeit requiring more individuals to yield equivalent precision. SIRE represents a new tool for analysing a wide range of experimental and field disease data with the aim of discovering and validating SNPs and other factors controlling infectious disease transmission.
CRK2 and C-terminal phosphorylation of NADPH oxidase RBOHD regulate ROS production in Arabidopsis
Authors: Kimura Sachie , Hunter Kerri , Vaahtera Lauri , Tran Huy Cuong , Citterico Matteo , Vaattovaara Aleksia , Rokka Anne , Stolze Sara Christina , Harzen Anne , Meißner Lena , Wilkens Maya Melina Tabea , Hamann Thorsten , Toyota Masatsugu , Nakagami Hirofumi , Wrzaczek Michael 
Published: April 2019

ABSTRACTReactive oxygen species (ROS) are important messengers in eukaryotic organisms and their production is tightly controlled. Active extracellular ROS production by NADPH oxidases in plants is triggered by receptor-like protein kinase (RLK)-dependent signaling networks. Here we show that the cysteine-rich RLK CRK2 kinase activity is required for plant growth and CRK2 exists in a preformed complex with the NADPH oxidase RBOHD in Arabidopsis. Functional CRK2 is required for the full elicitor-induced ROS burst and consequently the crk2 mutant is impaired in defense against the bacterial pathogen Pseudomonas syringae pv. tomato DC3000. Our work demonstrates that CRK2 regulates plant innate immunity. We identified in vitro CRK2-dependent phosphorylation sites in the C-terminal region of RBOHD. Phosphorylation of S703 RBOHD is enhanced upon flg22 treatment and substitution of S703 with alanine reduced ROS production in Arabidopsis. Phylogenetic analysis suggests that phospho-sites in C-terminal region of RBOHD are conserved throughout the plant lineage and between animals and plants. We propose that regulation of NADPH oxidase activity by phosphorylation of the C-terminal region might be an ancient mechanism and that CRK2 is an important element in regulating MAMP-triggered ROS production.One-sentence summaryCRK2 associates with and activates RBOHD to trigger MAMP-induced ROS production and reveals a novel regulatory mechanism for plant NADPH oxidases through phosphorylation of the C-terminus.
Co-infections by non-interacting pathogens are not independent & require new tests of interaction
Authors: Hamelin Frédéric M. , Allen Linda J.S. , Bokil Vrushali A. , Gross Louis J. , Hilker Frank M. , Jeger Michael J. , Manore Carrie A. , Power Alison G. , Rúa Megan A. , Cunniffe Nik J. 
Published: April 2019

AbstractIf pathogen species, strains or clones do not interact, intuition suggests the proportion of co-infected hosts should be the product of the individual prevalences. Independence consequently underpins the wide range of methods for detecting pathogen interactions from cross-sectional survey data. However, the very simplest of epidemiological models challenge the underlying assumption of statistical independence. Even if pathogens do not interact, death of co-infected hosts causes net prevalences of individual pathogens to decrease simultaneously. The induced positive correlation between prevalences means the proportion of co-infected hosts is expected to be higher than multiplication would suggest. By modeling the dynamics of multiple non-interacting pathogens, we develop a pair of novel tests of interaction that properly account for non-independence. Our tests allow us to reinterpret data from previous studies including pathogens of humans, plants, and animals. Our work demonstrates how methods to identify interactions between pathogens can be updated using simple epidemic models.
Geographic variation in the genetic basis of resistance to leaf rust between locally adapted ecotypes of the biofuel crop switchgrass (Panicum virgatum)
Authors: VanWallendael Acer , Bonnette Jason , Juenger Thomas E. , Fritschi Felix B. , Fay Philip A. , Mitchell Robert B. , Lloyd-Reilley John , Rouquette Francis M. , Bergstrom Gary C. , Lowry David B. 
Published: April 2019

SummaryLocal adaptation is an important process in plant evolution, which can be impacted by differential pathogen pressures along environmental gradients. However, the degree to which pathogen resistance loci vary in effect across space and time is incompletely described.To understand how the genetic architecture of resistance varies across time and geographic space, we quantified rust (Puccinia spp.) severity in switchgrass (Panicum virgatum) plantings at eight locations across the central United States for three years and conducted quantitative trait locus (QTL) mapping for rust progression.We mapped several variable QTLs, but two large-effect QTLs which we have namedPrr1andPrr2were consistently associated with rust severity in multiple sites and years, particularly in northern sites. In contrast, there were numerous small-effect QTLs at southern sites, indicating a genotype-by-environment interaction in rust resistance loci. Interestingly,Prr1andPrr2had a strong epistatic interaction, which also varied in strength and direction of effect across space.Our results suggest that abiotic factors covarying with latitude interact with the genetic loci underlying plant resistance to control rust infection severity. Further, our results indicate that segregating genetic variation in epistatically interacting loci may play a key role in determining response to infection across geographic space.
REMoDNaV: Robust Eye-Movement Classification for Dynamic Stimulation
Authors: Dar Asim H. , Wagner Adina S. , Hanke Michael 
Published: April 2019

AbstractTracking of eye movements is an established measurement for many types of experimental paradigms. More complex and more prolonged visual stimuli have made algorithmic approaches to eye movement event classification the most pragmatic option. A recent analysis revealed that many current algorithms are lackluster when it comes to data from viewing dynamic stimuli such as video sequences. Here we present an event classification algorithm—built on an existing velocity-based approach—that is suitable for both static and dynamic stimulation, and is capable of classifying saccades, post-saccadic oscillations, fixations, and smooth pursuit events. We validated classification performance and robustness on three public datasets: 1) manually annotated, trial-based gaze trajectories for viewing static images, moving dots, and short video sequences, 2) lab-quality gaze recordings for a feature length movie, and 3) gaze recordings acquired under suboptimal lighting conditions inside the bore of a magnetic resonance imaging (MRI) scanner for the same full-length movie. We found that the proposed algorithm performs on par or better compared to state-of-the-art alternatives for static stimulation. Moreover, it yields eye movement events with biologically plausible characteristics on prolonged dynamic recordings. Lastly, algorithm performance is robust on data acquired under suboptimal conditions that exhibit a temporally varying noise level. These results indicate that the proposed algorithm is a robust tool with improved classification accuracy across a range of use cases. The algorithm is cross-platform compatible, implemented using the Python programming language, and readily available as free and open source software from public sources.
Brain BOLD MRI O2and CO2stress testing: Implications for perioperative neurocognitive disorder following surgery
Authors: Mutch W. Alan C. , El-Gabalawy Renée , Ryner Lawrence , Puig Josep , Essig Marco , Kilborn Kayla , Fidler Kelsi , Graham M. Ruth 
Published: April 2019

AbstractRespiratory end-tidal (ET) gas control is fundamental to anaesthetic management. The range of ET O2and CO2during the conduct of anaesthesia can significantly deviate from values in the awake state. Recent work shows ET CO2influences the incidence of perioperative neurocognitive disorder (POND). We examine the effects of controlled alterations in both ET O2and CO2on cerebral blood flow (CBF) in awake adults using BOLD MRI. Twelve healthy adults had BOLD and CBF responses measured to alterations in ET CO2and O2in various combinations commonly observed under anaesthesia. Dynamic alterations in regional BOLD and CBF were seen in all subjects with expected and inverse responses to both stimuli. These effects were incremental and rapid (within seconds). The most dramatic effects were seen with combined hyperoxia and hypocapnia. Inverse responses increased with age. Here we show that human brain CBF responds dramatically to alterations in ET respiratory gas tensions commonly seen during anaesthesia. Such alterations may impact the observed incidence of POND following surgery and intensive care, and is an important area for further investigation.
Modeling the Switching behavior of Functional Connectivity Microstates (FCμstates) as a Novel Biomarker for Mild Cognitive Impairment
Authors: Dimitriadis SI , López María Eugenia , Maestu Fernando , Pereda Ernesto 
Published: April 2019

AbstractIt is evident the need for designing and validating novel biomarkers for the detection of mild cognitive impairment (MCI). MCI patients have a high risk of developing Alzheimer’s disease (AD), and for that reason the introduction of novel and reliable biomarkers is of significant clinical importance. Motivated by recent findings about the rich information of dynamic functional connectivity graphs (DFCGs) about brain (dys)function, we introduced a novel approach of identifying MCI based on magnetoencephalographic (MEG) resting state recordings.The activity of different brain rhythms {δ, θ, α1, α2, β1, β2, γ1, γ2} was first beamformed with linear constrained minimum norm variance in the MEG data to determine ninety anatomical regions of interest (ROIs). A dynamic functional connectivity graph (DFCG) was then estimated using the imaginary part of phase lag value (iPLV) for both intra-frequency coupling (8) and also cross-frequency coupling pairs (28). We analyzed DFCG profiles of neuromagnetic resting state recordings of 18 Mild Cognitive Impairment (MCI) patients and 20 healthy controls. We followed our model of identifying the dominant intrinsic coupling mode (DICM) across MEG sources and temporal segments that further leads to the construction of an integrated DFCG (iDFCG). We then filtered statistically and topologically every snapshot of the iDFCG with data-driven approaches. Estimation of the normalized Laplacian transformation for every temporal segment of the iDFCG and the related eigenvalues created a 2D map based on the network metric time series of the eigenvalues (NMTSeigs). NMTSeigs preserves the non-stationarity of the fluctuated synchronizability of iDCFG for each subject. Employing the initial set of 20 healthy elders and 20 MCI patients, as training set, we built an overcomplete dictionary set of network microstates (nμstates). Afterward, we tested the whole procedure in an extra blind set of 20 subjects for external validation.We succeeded a high classification accuracy on the blind dataset (85 %) which further supports the proposed Markovian modeling of the evolution of brain states. The adaptation of appropriate neuroinformatic tools that combine advanced signal processing and network neuroscience tools could manipulate properly the non-stationarity of time-resolved FC patterns revealing a robust biomarker for MCI.
Mutual Information Analysis of Neural Representations of Speech in Noise in the Aging Midbrain
Authors: Zan Peng , Presacco Alessandro , Anderson Samira , Simon Jonathan Z. 
Published: April 2019

AbstractYounger adults with normal hearing can typically understand speech in the presence of a competing speaker without much effort, but this ability to understand speech in challenging conditions deteriorates with age. Older adults, even with clinically normal hearing, often have problems understanding speech in noise. Earlier auditory studies using the frequency-following response (FFR), primarily believed generated by the midbrain, have demonstrated age-related neural deficits when analyzed using traditional measures. Here we use a mutual information paradigm to analyze the FFR to speech (masked by a competing speech signal) by estimating the amount of stimulus information contained in the FFR. Our results show, first, a broad-band informational loss associated with aging for both FFR amplitude and phase. Second, this age-related loss of information is more severe in higher frequency FFR bands (several hundred Hz). Third, the mutual information between the FFR and the stimulus decreases as noise level increases for both age groups. Fourth, older adults benefit neurally, i.e., show a reduction in loss of information, when the speech masker is changed from meaningful (talker speaking a language that they can comprehend, such as English) to meaningless (talker speaking a language that they cannot comprehend, such as Dutch). This benefit is not seen in younger listeners, which suggests age-related informational loss may be more severe when the speech masker is meaningful than when it is meaningless. In summary, as a method, mutual information analysis can unveil new results that traditional measures may not have enough statistical power to assess.New & NoteworthyOlder adults, even with clinically normal hearing, often have problems understanding speech in noise. Auditory studies using the frequency-following response (FFR) have demonstrated age-related neural deficits using traditional methods. Here we use a mutual information paradigm to analyze the FFR to speech masked by competing speech. Results confirm those using traditional analysis, but additionally show that older adults benefit neurally when the masker changes from a language that they comprehend to a language they cannot.
Efficient treatment of a preclinical inflammatory bowel disease model with engineered bacteria
Authors: Ferenczi Szilamer , Horváth István , Szeőcs Natália , Grózer Zsuzsanna , Kuti Dániel , Juhász Balázs , Winkler Zsuzsanna , Pankotai Tibor , Sükösd Farkas , Kovács Krisztina J. , Szallasi Zoltan 
Published: April 2019

AbstractWe developed an engineered bacterium based, RNA interference mediated therapeutic method to significantly reduce the symptoms in the most frequently used animal model of inflammatory bowel disease. This transkingdom RNA interference strategy was based on the non-pathogenic E. coli MDS42 strain, which was engineered to constitutively produce invasin and histeriolysin cytolysin. These proteins enabled the bacteria first to invade the colon epithelium and then degrade in the phagosome. This allowed the delivery of a plasmid encoding shRNA targeting TNF alpha into the cytoplasm of the target cells. The expression levels of TNF alpha and other cytokines significantly decreased and the inflammatory symptoms were significantly reduced. With further safety modifications this method could serve as a safe and side-effect free alternative to biologicals targeting TNF-alpha.
Adapterama II: Universal amplicon sequencing on Illumina platforms (TaggiMatrix)
Authors: Glenn Travis C. , Pierson Todd W. , Bayona-Vásquez Natalia J. , Kieran Troy J. , Hoffberg Sandra L. , Thomas Jesse C. , Lefever Daniel E. , Finger John W. , Gao Bei , Bian Xiaoming , Louha Swarnali , Kolli Ramya T. , Bentley Kerin , Rushmore Julie , Wong Kelvin , Shaw Timothy I. , Rothrock Michael J. , McKee Anna M. , Guo Tai L. , Mauricio Rodney , Molina Marirosa , Cummings Brian S. , Lash Lawrence H. , Lu Kun , Gilbert Gregory S. , Hubbell Stephen P. , Faircloth Brant C. 
Published: April 2019

AbstractNext-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. Most NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5’ end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (eight forward primers + 12 reverse primers yield 8 × 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy.
N-WASP regulates the mobility of the B cell receptor and co-receptors during signaling activation
Authors: Rey-Suarez Ivan , Wheatley Brittany , Koo Peter , Shu Zhou , Mochrie Simon , Song Wenxia , Shroff Hari , Upadhyaya Arpita 
Published: April 2019

AbstractRegulation of membrane receptor mobility is important in tuning the cell’s response to external signals. This is particularly relevant in the context of immune receptor signaling. The binding of B cell receptors (BCR) to antigen induces B cell receptor activation. While actin dynamics and BCR signaling are known to be linked, the role of actin dynamics in modulating receptor mobility is not well understood. Here, we use single molecule imaging to examine BCR movement during signaling activation and examine the role of actin dynamics on BCR mobility. We use a novel machine learning based method to classify BCR trajectories into distinct diffusive states and show that the actin regulatory protein N-WASP regulates receptor mobility. Constitutive loss or acute inhibition of N-WASP, which is associated with enhanced signaling, leads to a predominance of BCR trajectories with lower diffusivity and is correlated with a decrease in actin dynamics. Furthermore, loss of N-WASP reduces diffusivity of CD19, a stimulatory co-receptor of the BCR but not that of unstimulated FcγRIIB, an inhibitory co-receptor. The effect of N-WASP is mirrored by inhibition of the Arp2/3 complex and formins. Our results implicate the dynamic actin network in fine-tuning receptor mobility and receptor-ligand interactions, thereby modulating B cell signaling.
An Optimized Registration Workflow and Standard Geometric Space for Small Animal Brain Imaging
Authors: Ioanas Horea-Ioan , Marks Markus , Zerbi Valerio , Yanik Mehmet Fatih , Rudin Markus 
Published: April 2019

AbstractThe reliability of scientific results critically depends on reproducible and transparent data processing. Cross-subject and cross-study comparability of imaging data in general, and magnetic resonance imaging (MRI) data in particular, is contingent on the quality of registration to a standard reference space. In small animal MRI this is not adequately provided by currently used processing workflows, which utilize high-level scripts optimized for human data, and adapt animal data to fit the scripts, rather than vice-versa. In this fully reproducible article we showcase a generic workflow optimized for the mouse brain, alongside a standard reference space suited to harmonize data between analysis and operation. We introduce four separate metrics for automated quality control (QC), and a visualization method to aid operator inspection. Benchmarking this workflow against common legacy practices reveals that it performs more consistently, better preserves variance across subjects while minimizing variance across sessions, and improves both volume and smoothness conservation RMSE approximately 2-fold. We propose this open source workflow and the QC metrics as a new standard for small animal MRI registration, ensuring workflow robustness, data comparability, and region assignment validity, all of which are indispensable prerequisites for the comparability of scientific results across experiments and centers.
Immunodietica: A data-driven approach to investigate interactions between diet and autoimmune disorders
Authors: Gershteyn Iosif M. , Ferreira Leonardo M.R. 
Published: April 2019

AbstractAutoimmunity is on the rise around the globe. Diet has been proposed as a risk factor for autoimmunity and shown to modulate the severity of several autoimmune disorders. Yet, the interaction between diet and autoimmunity in humans remains largely unstudied. Here, we systematically interrogated commonly consumed animals and plants for peptide epitopes previously implicated in human autoimmune disease. A total of fourteen species investigated could be divided into three broad categories regarding their content in human autoimmune epitopes, which we represented using a new metric, the Gershteyn-Ferreira index (GF index). Strikingly, pig contains a disproportionately high number of unique autoimmune epitopes compared to all other species analyzed. This work uncovers a potential new link between pork consumption and autoimmunity in humans and lays the foundation for future studies on the impact of diet on the pathogenesis and progression of autoimmune disorders.