bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insect societies fight back: the evolution of defensive traits against social parasites
Authors: Grüter Christoph , Jongepier Evelien , Foitzik Susanne 
Published: June 2018

Insect societies face many social parasites that exploit their altruistic behaviours or their resources. Due to the fitness costs these social parasites incur, hosts have evolved various behavioural, chemical, architectural and morphological defence traits. Similar to bacteria infecting multicellular hosts, social parasites have to successfully go through several steps to exploit their hosts. Here, we review how social insects try to interrupt this sequence of events. They can avoid parasite contact by choosing to nest in parasite-free locales or evade attacks by adapting their colony structure. Once social parasites attack, hosts attempt to detect them, which can be facilitated by adjustments in colony odour. If social parasites enter the nest, hosts can either aggressively defend their colony or take their young and flee. Nest structures are often shaped to prevent social parasite invasion or to safeguard host resources. Finally, if social parasites successfully establish themselves in host nests, hosts can rebel by killing the parasite brood or by reproducing in the parasites' presence. Hosts of social parasites can therefore develop multiple traits, leading to the evolution of complex defence portfolios of co-dependent traits. Social parasites can respond to these multi-level defences with counter-adaptations, potentially leading to geographical mosaics of coevolution.
This article is part of the Theo Murphy meeting issue ‘Evolution of pathogen and parasite avoidance behaviours’.
Parasite avoidance behaviours in aquatic environments
Authors: Behringer Donald C. , Karvonen Anssi , Bojko Jamie 
Published: June 2018

Parasites, including macroparasites, protists, fungi, bacteria and viruses, can impose a heavy burden upon host animals. However, hosts are not without defences. One aspect of host defence, behavioural avoidance, has been studied in the terrestrial realm for over 50 years, but was first reported from the aquatic environment approximately 20 years ago. Evidence has mounted on the importance of parasite avoidance behaviours and it is increasingly apparent that there are core similarities in the function and benefit of this defence mechanism between terrestrial and aquatic systems. However, there are also stark differences driven by the unique biotic and abiotic characteristics of terrestrial and aquatic (marine and freshwater) environments. Here, we review avoidance behaviours in a comparative framework and highlight the characteristics of each environment that drive differences in the suite of mechanisms and cues that animals use to avoid parasites. We then explore trade-offs, potential negative effects of avoidance behaviour and the influence of human activities on avoidance behaviours. We conclude that avoidance behaviours are understudied in aquatic environments but can have significant implications for disease ecology and epidemiology, especially considering the accelerating emergence and re-emergence of parasites.This article is part of the Theo Murphy meeting issue ‘Evolution of pathogen and parasite avoidance behaviours'.
Tripal Developer Toolkit
Authors: Condon Bradford , Almsaeed Abdullah , Chen Ming , West Joe , Staton Margaret 
Published: June 2018

AbstractTripal is an open-source biological community database construction toolkit utilizing the content management system Drupal. Tripal is used to make biological, genetic and genomic data more discoverable, shareable, searchable, and standardized. As funding for community level genomics databases declines, Tripal’s open source codebase provides a means for sites to be built and maintained with a minimal investment in staff and new development. Tripal is ultimately as strong as the community of sites and developers that use it. We present a set of developer tools that will make building and maintaining Tripal 3 sites easier for new and returning users. These tools break down barriers to entry such as setting up developer and testing environments, acquiring and loading test datasets, working with controlled vocabulary terms, and writing new Drupal classes.
Identification and quantification of Lyme pathogen strains by deep sequencing of outer surface protein C (ospC) amplicons
Authors: Di Lia , Wan Zhenmao , Akther Saymon , Ying Chunxiao , Larracuente Amanda , Li Li , Di Chong , Nunez Roy , Cucura D. Moses , Goddard Noel L. , Krampis Konstantino , Qiu Wei-gang 
Published: June 2018

AbstractMixed infection of a single tick or host by Lyme disease spirochetes is common and a unique challenge for diagnosis, treatment, and surveillance of Lyme disease. Here we describe a novel protocol for differentiating Lyme strains based on deep sequencing of the hypervariable outer-surface protein C locus (ospC). Improving upon the traditional DNA-DNA hybridization method, the next-generation sequencing-based protocol is high-throughput, quantitative, and able to detect new pathogen strains. We applied the method to over one hundred infectedIxodes scapularisticks collected from New York State, USA in 2015 and 2016. Analysis of strain distributions within individual ticks suggests an overabundance of multiple infections by five or more strains, inhibitory interactions among co-infecting strains, and presence of a new strain closely related toBorreliella bissettiae. A supporting bioinformatics pipeline has been developed. With the newly designed pair of universalospCprimers targeting intergenic sequences conserved among all known Lyme pathogens, the protocol could be used for culture-free identification and quantification of Lyme pathogens in wildlife and clinical specimens across the globe.
The Evolution of Bequeathal in Stable Habitats
Authors: Clarke Parry M.R. , Mcelreath Mary Brooke , Barrett Brendan J. , Mabry Karen E. , Mcelreath Richard 
Published: June 2018

ABSTRACTAdults sometimes disperse while philopatric offspring inherit the natal site, a pattern known asbequeathal. Despite a decades-old empirical literature, little theoretical work has explored when natural selection may favor bequeathal. We present a simple mathematical model of the evolution of bequeathal in a stable environment, under both global and local dispersal. We find that natural selection favors bequeathal when adults are competitively advantaged over juveniles, baseline mortality is high, the environment is unsaturated, and when juveniles experience high dispersal mortality. However, frequently bequeathal may not evolve, because the fitness cost for the adult is too large relative to inclusive fitness benefits. Additionally, there are many situations for which bequeathal is an ESS, yet cannot invade the population. As bequeathal in real populations appears to be facultative, yet-to-be-modeled factors like timing of birth in the breeding season may strongly influence the patterns seen in natural populations.
Diagnostic algorithms to study post-concussion syndrome using electronic health records: validating a method to capture an important patient population
Authors: Dennis Jessica , Yengo-Kahn Aaron M. , Kirby Paul , Solomon Gary S. , Cox Nancy J. , Zuckerman Scott L. 
Published: June 2018

AbstractIntroductionPost-concussion syndrome (PCS) is characterized by persistent cognitive, somatic, and emotional symptoms after a mild traumatic brain injury (mTBI). Genetic and other biological variables may contribute to PCS etiology, and the emergence of biobanks linked to electronic health records (EHR) offers new opportunities for research on PCS. We sought to validate the use of EHR data of PCS patients by comparing two diagnostic algorithms.MethodsVanderbilt University Medical Center curates a de-identified database of 2.8 million patient EHR. We developed two EHR-based algorithmic approaches that identified individuals with PCS by: (i) natural language processing (NLP) of narrative text in the EHR combined with structured demographic, diagnostic, and encounter data; or (ii) coded billing and procedure data. The predictive value of each algorithm was assessed, and cases and controls identified by each approach were compared on demographic and medical characteristics.ResultsFirst, the NLP algorithm identified 507 cases and 10,857 controls. The positive predictive value (PPV) in the cases was 82% and the negative predictive value in the controls was 78%. Second, the coded algorithm identified 1,142 patients with two or more PCS billing codes and had a PPV of 76%. Comparisons of PCS controls to both case groups recovered known epidemiology of PCS: cases were more likely than controls to be female and to have pre-morbid diagnoses of anxiety, migraine, and PTSD. In contrast, controls and cases were equally likely to have ADHD and learning disabilities, in accordance with the findings of recent systematic reviews of PCS risk factors.ConclusionsEHR are a valuable research tool for PCS. Ascertainment based on coded data alone had a predictive value comparable to an NLP algorithm, recovered known PCS risk factors, and maximized the number of included patients.
Enterobacter cloacae complex ST-171 Isolates Expressing KPC-4 Carbapenemase Recovered from Canine Patients in Ohio, USA
Authors: Daniels Joshua B. , Chen Liang , Grooters Susan V. , Mollenkopf Dixie F. , Mathys Dimitria A. , Kreiswirth Barry N. , Wittum Thomas E. 
Published: June 2018

ABSTRACTCarbapenem resistant Enterobacteriaceae (CRE) have emerged as a critical public health threat. Organisms expressing the Klebsiella pneumoniae carbapenemase (KPC) were first recognized in the US in the late 1990s and continue to be the predominant CRE genotype reported in clinical isolates. Strains harboring blaKPC alleles have been observed in multiple species of Enterobacteriaceae, including the Enterobacter cloacae complex. A major E. cloacae clone, Enterobacter xiangfangensis ST171, has emerged as an important cause of hospital associated infections (HAI) and has been shown to carry different alleles of KPC in the context of Tn4401, residing on plasmids of multiple incompatibility groups. While CRE are commonly isolated from infected humans, their recovery from animals has been rare, particularly from companion animals. In the US, only six CRE have been reported from companion animals, and one from livestock, none of which were blaKPC. This report describes two E. xiangfangensis sequence type ST171 isolates each with a large IncHI2 plasmid bearing blaKPC-4 recovered from dogs with infections at the Ohio State University Veterinary Medical Center. Our phylogenetic comparison of these canine isolates with available sequences from clinical human isolates of KPC-4 identified in ST171 suggest an epidemiologically significant clonal strain.
Discovery of glycerol phosphate modification on streptococcal rhamnose polysaccharides
Authors: Edgar Rebecca J. , Hensbergen Vincent P. van , Ruda Alessandro , Turner Andrew G. , Deng Pan , Breton Yoann Le , El-Sayed Najib M. , Belew Ashton T. , McIver Kevin S. , McEwan Alastair G. , Morris Andrew J. , Lambeau Gérard , Walker Mark J. , Rush Jeffrey S. , Korotkov Konstantin V. , Widmalm Göran , Sorge Nina M. van , Korotkova Natalia 
Published: June 2018

AbstractCell wall glycopolymers on the surface of Gram-positive bacteria are fundamental to bacterial physiology and infection biology. These structures have also gained interest as vaccine antigens, in particular for the human pathogens Group AStreptococcus(GAS) andStreptococcus mutans. Streptococcal cell wall glycopolymers are considered to be functional homologues of wall teichoic acids but surprisingly lack the biologically-relevant and characteristic anionic charge. Here we identifygacH, a gene of unknown function in the GAS Group A Carbohydrate (GAC) biosynthetic cluster, in two independent transposon library screens for its ability to confer resistance to zinc and susceptibility to the bactericidal enzyme human group IIA secreted phospholipase A2. To understand the underlying mechanism of these phenotypes, we determined the structure of the extracellular domain of GacH and discover that it represents a new family of glycerol phosphate (GroP) transferases. Importantly, we demonstrate the presence of GroP in both the GAC and the homologous SerotypecCarbohydrate (SCC) fromS. mutans,which is conferred bygacHandsccHproducts, respectively. NMR analysis of GAC released from cell wall by non-destructive methods reveals that approximately 30% of the GAC GlcNAc side-chains are modified by GroP at the C6 hydroxyl group. This previously unrecognized structural modification impacts host-pathogen interaction and has implications for vaccine design.Graphical abstract
Genetic determinants of penicillin tolerance inVibrio cholerae
Authors: Weaver Anna I. , Murphy Shannon G. , Umans Benjamin , Tallavajhala Srikar , Onyekwere Ikenna , Wittels Stephen , Shin Jung-Ho , VanNieuwenhze Michael , Waldor Matthew K. , Dörr Tobias 
Published: June 2018

AbstractMany bacteria are resistant to killing (“tolerant”) by typically bactericidal antibiotics due to their ability to counteract drug-induced cell damage.Vibrio cholerae, the cholera agent, displays an unusually high tolerance to diverse inhibitors of cell wall synthesis. Exposure to these agents, which in other bacteria leads to lysis and death, results in a breakdown of the cell wall and subsequent sphere formation inV. cholerae. Spheres readily recover to rod-shaped cells upon antibiotic removal, but the mechanisms mediating the recovery process are not well-characterized. Here, we found that the mechanisms of recovery are dependent on environmental conditions. Interestingly, on agarose pads, spheres undergo characteristic stages during the restoration of rod shape. Drug inhibition and microscopy experiments suggest that class A Penicillin Binding Proteins (aPBPs) play a more active role than the Rod system, especially early in sphere recovery. TnSeq analyses revealed that LPS and cell wall biogenesis genes as well as the sigma E cell envelope stress response were particularly critical for recovery. LPS core and O-antigen appear to be more critical for sphere formation/integrity and viability than Lipid A modifications. Overall, our findings demonstrate that the outer membrane is a key contributor to beta lactam tolerance and suggest a role for aPBPs in cell wall biogenesis in the absence of rod-shape cues. Factors required for post-antibiotic recovery could serve as targets for antibiotic adjuvants that enhance the efficacy of antibiotics that inhibit cell wall biogenesis.
Crystal structure of the MBD domain of MBD3 in complex with methylated CG DNA
Authors: Liu Ke , Lei Ming , Gan Bing , Cheng Harry , Li Yanjun , Min Jinrong 
Published: June 2018

ABSTRACTMBD3 is a core subunit of the Mi-2/NuRD complex, and has been previously reported to lack methyl-CpG binding ability. However, recent reports show that MBD3 recognizes both mCG and hmCG DNA with a preference for hmCG, and is required for the normal expression of hmCG marked genes in ES cells. Nevertheless, it is not clear how MBD3 recognizes the methylated DNA. In this study, we carried out structural analysis coupled with isothermal titration calorimetry (ITC) binding assay and mutagenesis studies to address the structural basis for the mCG DNA binding ability of the MBD3 MBD domain. We found that the MBD3 MBD domain prefers binding mCG over hmCG through the conserved arginine fingers, and this MBD domain as well as other mCG binding MBD domains can recognize the mCG duplex without orientation selectivity. Furthermore, we found that the tyrosine-to-phenylalanine substitution at Phe34 of MBD3 is responsible for its weaker mCG DNA binding ability compared to other mCG binding MBD domains. In summary, our study demonstrates that the MBD3 MBD domain is a mCG binder, and also illustrates its binding mechanism to the methylated CG DNA.
Molecular and functional heterogeneity of cerebellar granule cell terminals expands temporal coding in molecular layer interneurons
Authors: Dorgans Kevin , Demais Valérie , Bailly Yannick , Poulain Bernard , Isope Philippe , Doussau Frédéric 
Published: June 2018

AbstractIn the cerebellum, molecular layer interneurons (MLIs) play an essential role in motor behavior by exerting precise temporal control of Purkinje cells, the sole output of the cerebellar cortex. The recruitment of MLIs is tightly controlled by the release of glutamate from granule cells (GCs) during high-frequency activities. Here we study how single MLIs are recruited by their distinct unitary GC inputs during burst of GC stimulations. Stimulation of individual GC-MLI synapses revealed four classes of connections segregated by their profile of short-term plasticity. Each class of connection differentially drives MLI recruitment. Molecular and ultrastructural analyses revealed that GC-MLI synaptic diversity is underlain by heterogeneous expression of synapsin II at individual GC terminals. In synapsin II knock-out mice, the number of classes is reduced to profiles associated with slow MLI recruitment. Our study reveals that molecular diversity across GC terminals enables diversity in temporal coding by MLIs and thereby influences the processing of sensory information by cerebellar networks.
Functionally distinct ERAP1 and ERAP2 are a hallmark of HLA-A29-(Birdshot) Uveitis
Authors: Kuiper Jonas J.W. , van Setten Jessica , Devall Matthew , Cretu-Stancu Mircea , Hiddingh Sanne , Ophoff Roel A. , Missotten Tom O.A.R. , van Velthoven Mirjam , Den Hollander Anneke I , Hoyng Carel B , James Edward , Reeves Emma , Cordero-Coma Miguel , Fonollosa Alejandro , Adán Alfredo , Martín Javier , Koeleman Bobby P.C. , de Boer Joke H. , Pulit Sara L. , Márquez Ana , Radstake Timothy R. D. J. 
Published: June 2018

AbstractBirdshot Uveitis (Birdshot) is a rare eye condition that affects HLA-A29-positive individuals and could be considered a prototypic member of the recently proposed “MHC-I-opathy” family. Genetic studies have pinpointed the ERAP1 and ERAP2 genes as shared associations across MHC-I-opathies, which suggests ERAP dysfunction may be a root cause for MHC-I-opathies. We mapped the ERAP1 and ERAP2 haplotypes in 84 Dutch cases and 890 controls. We identified association at variant rs10044354, which mediated a marked increase in ERAP2 expression. We also identified and cloned an independently associated ERAP1 haplotype (tagged by rs2287987) present in more than half of the cases; this ERAP1 haplotype is also the primary risk and protective haplotype for other MHC-I-opathies. We show that the risk ERAP1 haplotype conferred significantly altered expression of ERAP1 isoforms in transcriptomic data (n=360), resulting in lowered protein expression and distinct enzymatic activity. Both the association for rs10044354 (meta-analysis: OR[95% CI]=2.07[1.58-2.71], p=1.24 × 10(−7)) and rs2287987 (OR[95% CI]: =2.01 [1.51-2.67], p=1.41 × 10(−6)) replicated and showed consistent direction of effect in an independent Spanish cohort of 46 cases and 2,103 controls. In both cohorts, the combined rs2287987-rs10044354 haplotype associated with Birdshot more strongly than either SNP alone (meta-analysis: p=3.9 × 10(−9)). Finally, we observed that ERAP2 protein expression is dependent on the ERAP1 background across three European populations (n=3,353). In conclusion, a functionally distinct combination of ERAP1 and ERAP2 are a hallmark of Birdshot and provide rationale for strategies designed to correct ERAP function for treatment of Birdshot and MHC-I-opathies more broadly.
Application of adaptive-network-based fuzzy inference systems to the parameter optimization of a biochemical rule-based model
Authors: Hoard Brittany R. 
Published: June 2018

Our main contribution is an efficient machine learning approach to fitting parameters of a biological model. We study the binding of the shrimp protein Pen a 1 with antibody-receptor complexes because this process is important in understanding the allergic response. Previously, we developed a BioNetGen model that simulates this process. We previously developed a method for encoding steric effects via the optimization of two parameters: the cutoff distance and the rule rate. We optimized these two parameters by fitting the output to that generated by a 3D robotics-inspired Monte Carlo simulation that explicitly represents molecular geometry.In this work, we aim to optimize the parameters for our BioNetGen model using an efficient method: an adaptive-network-based fuzzy inference system implemented in MAT-LAB. We want to develop fuzzy systems that can accurately predict the rule binding rate and cutoff distance given a residual-sum-of-squares value or a probability distribution. We construct the fuzzy systems using fuzzy c-means clustering with existing data from BioNetGen model parameter scans as the training data. We create and test fuzzy systems with various input data and number of clusters, and analyze their performance with regard to the effective optimization of our rule-based model. We find that the fuzzy system that uses a residual-sum-of-squares value as the input value performs acceptably well. However, the performance of the fuzzy systems that use probabilities as their input values perform inconsistently in our tests.The results of this study suggest that the system that uses a residual-sum-of-squares value as the input value could potentially be used to find an adequate fit for our biochemical model. However, the systems that use probabilities as their input values need further development to improve the consistency and reliability of their output. Testing more values for other clustering parameters other than the number of clusters may accomplish this. Further research could also include similar studies using other training or clustering algorithms. This methodology could be modified for use with fitting other biological models.
Unsupervized Quantification of Demographic Structure for Single-copy Alignments
Authors: Rohrlach AB , Bean Nigel , Glonek Gary , Holland Barbara , Tobler Ray , Tuke Jonathan , Cooper Alan 
Published: June 2018

AbstractSingle-copy sequence alignments have been a valuable source of information for genetic studies; their lack of recombination makes phylogenetic analyses tractable [1]. Specifically, mitochondrial DNA will continue to play an important role in genetic studies due to its high mutation rate and high copy per cell count of the molecule [2]. In this paper we develop a new method for the analysis of single-copy sequence data that simultaneously considers the relationships between sequenced individuals and positions of interest in the genome. We then show that tests for relationships between genetic information and qualitative and quantitative characteristics can be calculated. We motivate the use of our method with examples from empirical data.