bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ecological interventions to prevent and manage zoonotic pathogen spillover
Authors: Sokolow Susanne H. , Nova Nicole , Pepin Kim M. , Peel Alison J. , Pulliam Juliet R. C. , Manlove Kezia , Cross Paul C. , Becker Daniel J. , Plowright Raina K. , McCallum Hamish , De Leo Giulio A. 
Published: August 2019

Spillover of a pathogen from a wildlife reservoir into a human or livestock host requires the pathogen to overcome a hierarchical series of barriers. Interventions aimed at one or more of these barriers may be able to prevent the occurrence of spillover. Here, we demonstrate how interventions that target the ecological context in which spillover occurs (i.e. ecological interventions) can complement conventional approaches like vaccination, treatment, disinfection and chemical control. Accelerating spillover owing to environmental change requires effective, affordable, durable and scalable solutions that fully harness the complex processes involved in cross-species pathogen spillover.
This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Epidemic growth rates and host movement patterns shape management performance for pathogen spillover at the wildlife–livestock interface
Authors: Manlove Kezia R. , Sampson Laura M. , Borremans Benny , Cassirer E. Frances , Miller Ryan S. , Pepin Kim M. , Besser Thomas E. , Cross Paul C. 
Published: August 2019

Managing pathogen spillover at the wildlife–livestock interface is a key step towards improving global animal health, food security and wildlife conservation. However, predicting the effectiveness of management actions across host–pathogen systems with different life histories is an on-going challenge since data on intervention effectiveness are expensive to collect and results are system-specific. We developed a simulation model to explore how the efficacies of different management strategies vary according to host movement patterns and epidemic growth rates. The model suggested that fast-growing, fast-moving epidemics like avian influenza were best-managed with actions like biosecurity or containment, which limited and localized overall spillover risk. For fast-growing, slower-moving diseases like foot-and-mouth disease, depopulation or prophylactic vaccination were competitive management options. Many actions performed competitively when epidemics grew slowly and host movements were limited, and how management efficacy related to epidemic growth rate or host movement propensity depended on what objective was used to evaluate management performance. This framework offers one means of classifying and prioritizing responses to novel pathogen spillover threats, and evaluating current management actions for pathogens emerging at the wildlife–livestock interface.
This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Onward transmission of viruses: how do viruses emerge to cause epidemics after spillover?
Authors: Wasik Brian R. , de Wit Emmie , Munster Vincent , Lloyd-Smith James O. , Martinez-Sobrido Luis , Parrish Colin R. 
Published: August 2019

The critical step in the emergence of a new epidemic or pandemic viral pathogen occurs after it infects the initial spillover host and then is successfully transmitted onwards, causing an outbreak chain of transmission within that new host population. Crossing these choke points sets a pathogen on the pathway to epidemic emergence. While many viruses spill over to infect new or alternative hosts, only a few accomplish this transition—and the reasons for the success of those pathogens are still unclear. Here, we consider this issue related to the emergence of animal viruses, where factors involved likely include the ability to efficiently infect the new animal host, the demographic features of the initial population that favour onward transmission, the level of shedding and degree of susceptibility of individuals of that population, along with pathogen evolution favouring increased replication and more efficient transmission among the new host individuals. A related form of emergence involves mutations that increased spread or virulence of an already-known virus within its usual host. In all of these cases, emergence may be due to altered viral properties, changes in the size or structure of the host populations, ease of transport, climate change or, in the case of arboviruses, to the expansion of the arthropod vectors. Here, we focus on three examples of viruses that have gained efficient onward transmission after spillover: influenza A viruses that are respiratory transmitted, HIV, a retrovirus, that is mostly blood or mucosal transmitted, and canine parvovirus that is faecal:oral transmitted. We describe our current understanding of the changes in the viruses that allowed them to overcome the barriers that prevented efficient replication and spread in their new hosts. We also briefly outline how we could gain a better understanding of the mechanisms and variability in order to better anticipate these events in the future.
This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Host phylogenetic distance drives trends in virus virulence and transmissibility across the animal–human interface
Authors: Guth Sarah , Visher Elisa , Boots Mike , Brook Cara E. 
Published: August 2019

Historically, efforts to assess ‘zoonotic risk’ have focused mainly on quantifying the potential for cross-species emergence of viruses from animal hosts. However, viruses clearly differ in relative burden, both in terms of morbidity and mortality (virulence) incurred and the capacity for sustained human-to-human transmission. Extending previously published databases, we delineated host and viral traits predictive of human mortality associated with viral spillover, viral capacity to transmit between humans following spillover and the probability of a given virus being zoonotic. We demonstrate that increasing host phylogenetic distance from humans positively correlates with human mortality but negatively correlates with human transmissibility, suggesting that the virulence induced by viruses emerging from hosts at high phylogenetic distance may limit capacity for human transmission. Our key result is that hosts most closely related to humans harbour zoonoses of lower impact in terms of morbidity and mortality, while the most distantly related hosts—in particular, order Chiroptera (bats)—harbour highly virulent zoonoses with a lower capacity for endemic establishment in human hosts. As a whole, our results emphasize the importance of understanding how zoonoses manifest in the human population and also highlight potential risks associated with multi-host transmission chains in spillover.
This article is part of the theme issue ‘Dynamic and integrative approaches to understanding pathogen spillover’.
Design of Epitope Based Peptide Vaccine Against Pseudomonas Aeruginosa Fructose Bisphosphate Aldolase Protein using Immunoinformatics
Authors: Elhag Mustafa , Alaagib Ruaa Mohamed , Ahmed Nagla Mohamed , Abubaker Mustafa , Haroun Esraa Musa , Obi Sahar , Hassan Mohammed A. 
Published: August 2019

AbstractPseudomonas aeruginosais common pathogen that is responsible of serious illnesses hospital acquired infection as ventilator associated pneumonia and various sepsis syndrome. Also it is a multidrug resistant pathogen recognized for its ubiquity, its intrinsically advanced antibiotic resistant mechanisms. generally affects the immuonocompromised but can also infect the immunocompetent as in hot tub folliculitis. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against Fructose bisphosphate aladolase (FBA) ofPseudomonas aeruginosausing immunoinformatics tools. The sequences were obtained from NCBI and prediction tests took place to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility and hydrophilicity tests. Six MHC I epitopes were the most promising, while four from MHC II. Nineteen epitopes were shared between MHC I and II. For the population coverage, the epitopes covered 95.62% of the alleles worldwide excluding certain MHC II alleles. We recommend invivo and invitro studies to prove it’s effectiveness.
Olfactory receptor subgenome and expression in a highly olfactory procellariiform seabird
Authors: Sin Simon Yung Wa , Cloutier Alison , Nevitt Gabrielle , Edwards Scott V. 
Published: August 2019

AbstractProcellariiform seabirds are known for their well-developed olfactory capabilities, reflected by their large olfactory bulb to brain ratio and olfactory-mediated behaviors. Many species in this clade use olfactory cues for foraging and navigation, and some species can recognize individual-specific odors. Their genomes and transcriptomes may yield important clues about how the olfactory receptor (OR) subgenome was shaped by natural and sexual selection. In this study, we assembled a high-quality Leach’s storm petrel (Oceanodroma leucorhoa) genome to facilitate characterization of the OR repertoire. We also surveyed expressed OR genes through transcriptome analysis of the olfactory epithelium - to our knowledge, the first avian study to interrogate OR diversity in this way. We detected a large number (∼61) of intact OR genes, and identified OR genes under positive selection. In addition, we estimated that this species has the lowest proportion (∼60%) of pseudogenes compared to other waterbirds studied thus far. We show that the traditional annotation-based genome mining method underestimates OR gene number (214) as compared to copy number analysis using depth-of-coverage analysis, which estimated a total of 492 OR genes. By examining OR expression pattern in this species, we identified highly expressed OR genes, and OR genes that were differentially expressed between age groups, providing valuable insight into the development of olfactory capabilities in this and other avian species. Our genomic evidence is consistent with the Leach’s storm petrel’s well-developed olfactory sense, a key sensory foundation for its pelagic lifestyle and behavioral ecology.
It takes two vanilloid ligand bindings per channel to transduce painful capsaicin stimuli
Authors: Liu Ting-Yi , Chu Ying , Mei Hao-Ruei , Chang Dennis S. , Chuang Huai-Hu 
Published: August 2019

AbstractThe capsaicin receptor TRPV1 in mammals evolved the capability of integrating pain arising from combinations of noxious temperature or chemical irritants. Four-fold repetition of TRPV1 subunits makes an ion channel endowed with excellent sensitivity for pain detection, assisting this ionotropic receptor to differentiate graded injuries. We manipulated the stoichiometry and relative steric coordination of capsaicin binding at the molecular level, explicating rules with which a receptor codes pain within a broad range of intensity. The first ligand binding delivers small but clear initiation of channel activation. Maximal agonist action has already been reached in a receptor-in-tandem containing two or three wild-type receptor units, displaying activity comparable to the full liganded all-wild-type tandem tetramers. When the binding sites outnumbered ligands, independent action dominates in each channel. The non-vanilloid agonist 2-APB differs from capsaicin by adopting a distinct open mechanism since it does not demand a vanilloid group to activate. The sharing of the same pore greatly simplifies synergism to transduce relevant inputs by summation for pain signaling. And questions the need to explore deeper into other aspects of nociception.
A prospective role for the rumen in generating antibiotic resistance
Authors: Strachan Cameron R. , Mueller Anna J. , Ghanbari Mahdi , Neubauer Viktoria , Zwirzitz Benjamin , Thalguter Sarah , Dziecol Monika , Wetzels Stefanie U. , Zanghellini Jürgen , Wagner Martin , Schmitz-Esser Stephan , Mann Evelyne 
Published: August 2019

ABSTRACTAntibiotics were a revolutionary discovery of the 20th century, but the ability of bacteria to spread the genetic determinants of resistance via horizontal gene transfer (HGT) has quickly endangered their use1. Indeed, there is a global network of microbial gene exchange, the analysis of which has revealed particularly frequent transfer of resistance determinants between farm animals and human-associated bacteria2. Here, we leverage the recent release of a rumen microbial genome reference set and show that the wide-spread resistance gene cluster aadE-sat4-aphA-3 is harboured in ruminal Bacteroidetes. While this cluster appears to have been recently transferred between commensal bacteria in the rumen and many diverse animal and human pathogens, comparative analysis suggests that the cluster stabilized in the pathogens. Then, focusing on streptomycin resistance, it was found that homologues from the rumen span much of the known diversity of aminoglycoside O-nucleotidyltransferases (AadEs) and that distinct variants of the enzyme are present in a single rumen bacterial genome. Notably, a second variant of AadE has also been recently transferred, albeit more often as a single gene, throughout a different set of animal and human associated bacteria. By examining the synteny of AadE orthologues in various bacterial genomes and analyzing corresponding gene trees in an environmental context, we speculate that the ruminant associated microbiome has a salient role in the emergence of specific resistance variants and clusters. In light of the recent literature on the evolutionary origin of antibiotic resistance, we further suggest that the rumen provides a possible route of dissemination of resistance genes from soil resistomes, throughout the farm, and to human pathogens3.
Systematic search for schizophrenia pathways sensitive to perturbation by immune activation
Authors: Gao Yue , Liang Xiaozhen , Ren Zhonglu , Li Yanjun , Yang Xinping 
Published: August 2019

AbstractImmune activation has been recently found to play a large part in the development of schizophrenia, but the underlying mechanism remains largely unknown. Here, we report the construction of a high-quality protein interaction network for schizophrenia (SCZ Network) using a “neighborhood walking” approach to searching across human interactome network for disease-related neighborhoods. The spatiotemporal expression pattern of the immune genes in the SCZ Network demonstrates that this disease network is sensitive to the perturbation of immune activation during mid- to late fetal development and adolescence. The immune genes in the network are involved in pathways regulating the formation, structure and function of synapses and neural connections. Using single-cell transcriptome sequencing on the brains of immune-activated mice, we found that immune activation disturbed the SCZ network in the major brain cell types and the dysregulated pathways were also involved in synapse regulation, demonstrating that our “neighborhood walking” approach enables biological discovery in complex disorders.
LIBR Methamphetamine and Opioid Cue Database (LIBR MOCD): Development and Validation
Authors: Ekhtiari Hamed , Kuplicki Rayus , Pruthi Asheema , Paulus Martin 
Published: August 2019

AbstractIntroductionDrug cue reactivity (DCR) is widely used in experimental settings for both assessment and intervention. There is no validated database of pictorial cues available for methamphetamine and opioids.Methods360 images in three-groups (methamphetamine, opioid and neutral (control)) matched for their content (objects, hands, faces and actions) were selected in an initial development phase. 28 participants with a history of both methamphetamine and opioid use (37.1 ± 8.11 years old, 12 female) with over six months of abstinence were asked to rate images for craving, valence, arousal, typicality and relatedness.ResultsAll drug images were differentiated from neutral images. Drug related images received higher arousal and lower valence ratings compared to neutral images (craving (0-100) for neutral (11.5±21.9), opioid (87.7±18.5), and methamphetamine (88±18), arousal (1-9) for neutral (2.4±1.9), opioid (4.6±2.7), and methamphetamine (4.6±2.6), and valence (1-9) for neutral (4.8±1.3), opioid (4.4±1.9), and methamphetamine (4.4±1.8)). There is no difference between methamphetamine and opioid images in craving, arousal and valence. There is a significant positive relationship between the amount of time that participants spent on drug-related images and the craving they reported for the image. Every 10 points of craving were associated with an increased response time of 383millisecond. Three image sets were automatically selected for equivalent fMRI tasks (methamphetamine and opioids) from the database (tasks are available at github).ConclusionLIBR MOCD provides a resource of validated images/tasks for future DCR studies. Additionally, researchers can select several sets of unique but equivalent images based-on their psychological/physical characteristics for multiple assessments/interventions.
Methodological Challenges in Translational Drug Response Modeling in Cancer
Authors: Schätzle Lisa-Katrin , Esfahani Ali Hadizadeh , Schuppert Andreas 
Published: August 2019

AbstractTranslational models directly relating drug response-specific processes observed in vitro to their in vivo role in cancer patients constitute a crucial part of the development of personalized medication. Unfortunately, ongoing research is often confined by the irreproducibility of the results in other contexts. While the inconsistency of pharmacological data has received great attention recently, the computational aspect of this crisis still deserves closer examination. Notably, studies often focus only on isolated model characteristics instead of examining the overall workflow and the interplay of individual model components. Here, we present a systematic investigation of translational models using the R-package FORESEE. Our findings confirm that with the current exploitation of the available data and the prevailing trend of optimizing methods to only one specific use case, modeling solutions will continue to suffer from non-transferability. Instead, the conduct of developing translational approaches urgently needs to change to retrieve clinical relevance in the future.
openTSNE: a modular Python library for t-SNE dimensionality reduction and embedding
Authors: Poličar Pavlin G. , Stražar Martin , Zupan Blaž 
Published: August 2019

AbstractSummaryPoint-based visualisations of large, multi-dimensional data from molecular biology can reveal meaningful clusters. One of the most popular techniques to construct such visualisations is t-distributed stochastic neighbor embedding (t-SNE), for which a number of extensions have recently been proposed to address issues of scalability and the quality of the resulting visualisations. We introduce openTSNE, a modular Python library that implements the core t-SNE algorithm and its extensions. The library is orders of magnitude faster than existing popular implementations, including those from scikit-learn. Unique to openTSNE is also the mapping of new data to existing embeddings, which can surprisingly assist in solving batch effects.AvailabilityopenTSNE is available at https://github.com/pavlin-policar/openTSNE.Contactpavlin.policar@fri.uni-lj.si, blaz.zupan@fri.uni-lj.si
Cytosine but not adenine base editor generates mutations in mice
Authors: Lee Hye Kyung , Smith Harold E. , Liu Chengyu , Willi Michaela , Hennighausen Lothar 
Published: August 2019

ABSTRACTDeaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms and its ultimate success therapeutically depends on its accuracy. Here we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editor (ABE) in mouse embryos using unbiased whole genome sequencing of a family-based trio cohort. We demonstrate that BE4-edited mice carry an excess of single-nucleotide variants and deletions compared to ABE-edited mice and controls.
The structure ofMycobacterium tuberculosisheme-degrading protein, MhuD, in complex with product
Authors: Chao Alex , Burley Kalistyn H. , Sieminski Paul J. , Mobley David L. , Goulding Celia W. 
Published: August 2019

AbstractMycobacterium tuberculosis(Mtb), the causative agent of tuberculosis, requires iron for survival. In Mtb, MhuD is the cytosolic protein that degrades imported heme. MhuD is distinct, both in sequence and structure, from canonical heme oxygenases (HOs) but homologous with IsdG-type proteins. Canonical HO is found mainly in eukaryotes, while IsdG-type proteins are predominantly found in prokaryotes including pathogens. While there are several published structures of MhuD and other IsdG-type proteins in complex with heme substrate, no structures have been reported of IsdG-type proteins in complex with product, unlike HOs. We recently showed that the Mtb variant MhuD-R26S produces biliverdin IXα (αBV) rather than the wild-type (WT) mycobilin isomers as product. Given that mycobilin and other IsdG-type protein products like staphylobilin are difficult to isolate in quantities sufficient for structure determination, here we use the MhuD-R26S variant and its product αBV as a proxy to study the IsdG-type protein/product complex. First we show that αBV has nanomolar affinity for MhuD and the R26S variant. Second we determined the MhuD-R26S-αBV complex structure to 2.5 Å, which reveals two notable features (1) two αBV molecules bound per active site and (2) a new α-helix (α3) as compared with the MhuD-heme structure. Finally, by molecular dynamics simulations we show that α3 is stable with the proximal αBV alone. MhuD’s high affinity for its product and structural and electrostatic changes that accompany substrate turnover suggest that there is an unidentified protein that is responsible for product extraction from MhuD and other IsdG-type proteins.
Can individual and integrated water, sanitation, and handwashing interventions reduce fecal contamination in the household environment? Evidence from the WASH Benefits cluster-randomized trial in rural Kenya
Authors: Pickering Amy J. , Swarthout Jenna , Mureithi MaryAnne , Mboya John , Arnold Benjamin F. , Wolfe Marlene , Dentz Holly N. , Lin Audrie , Arnold Charles D. , Rao Gouthami , Stewart Christine P. , Ram Pavani K. , Clasen Thomas , Colford John M. , Null Clair 
Published: August 2019

AbstractCombined water, sanitation, and handwashing (WSH) interventions have the potential to reduce fecal pathogens along more transmission pathways than single interventions alone. We measuredEscherichia colilevels in 3909 drinking water samples, 2691 child hand rinses, and 2422 toy ball rinses collected from households enrolled in a two-year cluster-randomized controlled trial evaluating single and combined WSH interventions. Water treatment alone reducedE. coliin drinking water, while a combined WSH intervention improved water quality by the same magnitude but did not affect levels of fecal indicator bacteria on child hands or toy balls. The failure of the WSH interventions to reduceE. colialong important child exposure pathways is consistent with the lack of a protective effect from the interventions on child diarrhea or child growth during the trial. Our results have important implications for WSH program design; the sanitation and handwashing interventions implemented in this trial should not be expected to reduce child exposure to fecal contamination in other similar settings.