bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virion-associated spermidine transmits with Rift Valley fever virus particles to maintain infectivity
Authors: Mastrodomenico Vincent , Esin Jeremy J. , Qazi Shefah , Omoba Oreoluwa S. , Fung Brittany L. , Khomutov Maxim A. , Ivanov Alexander V. , Mukhopadhyay Suchetana , Mounce Bryan C. 
Published: January 2020

AbstractViruses require host cell metabolites to productively infect, and the mechanisms by which viruses usurp these molecules is diverse. One group of cellular metabolites important in virus infection is the polyamines, small positively-charged molecules involved in cell cycle, translation, and nucleic acid synthesis, among other cellular functions. Polyamines also support replication of diverse viruses, and they are important for processes such as transcription, translation, and viral protein enzymatic activity. Rift Valley fever virus (RVFV) is a negative-sense RNA virus that requires polyamines to produce infectious particles. In polyamine depleted conditions, noninfectious particles are produced that interfere with virus replication and stimulate immune signaling. Here, we find that RVFV relies on virion-associated polyamines to maintain infectivity. We show that RVFV replication is facilitated by any of the three biogenic polyamines; however, we specifically find spermidine associated with purified virions. Using a panel of polyamine homologs, we observe that virions can also associate with (R)-3-methylspermidine and norspermidine, though not with other less homologous molecules. Using polyamine reporter cells, we demonstrate that virion-associated polyamines transmit from one infected cell to another. Finally, we find that virions devoid of polyamines are unstable and cannot be supplemented with exogenous polyamines to regain stability or infectivity. These data highlight a unique role for polyamines, and spermidine in particular, in maintaining virus infectivity, a function not previously appreciated. Further, these studies are the first to identify polyamines associated with RVFV virions. Targeting polyamines represents a promising antiviral strategy, and this work highlights a new mechanism by which we can inhibit virus replication through FDA-approved polyamine depleting pharmaceuticals.
The effects of cannabidiol on cue- and stress-induced reinstatement of cocaine seeking behavior in mice are reverted by the CB1 receptor antagonist AM4113
Authors: Luján Miguel Ángel , Alegre-Zurano Laia , Martín-Sánchez Ana , Valverde Olga 
Published: January 2020

ABSTRACTCocaine addiction is a brain disorder characterized by the consumption of the drug despite harmful consequences, the loss of control over drug intake and increased risk of relapse. Albeit prolonged research efforts, there is no available medication approved for the treatment of cocaine addiction. In the last decade, cannabinoid-based compounds have drawn increased interest for its potential therapeutic applications in various psychiatric conditions. Cannabidiol, a non-psychotomimetic constituent of theC. sativaplant, shows promising results in rodent models of anxiety, schizophrenia, depression and drug addiction. However, the specific effects and mechanisms of action of cannabidiol in a rodent model of extinction-based abstinence and drug seeking relapse remain unclear. Here, we administered cannabidiol (20 mg/kg) to male CD-1 mice trained to self-administer cocaine (0.75 mg/kg/inf) during extinction training (8–12 days). Then, we evaluated the reinstatement of cocaine seeking induced by cues, stress and drug priming. To ascertain the participation of CB1 receptors in these behavioral responses, we systemically administered the neutral cannabinoid antagonist AM4113 (5 mg/kg) before each reinstatement session. The results document that cannabidiol (20 mg/kg) does not modulate extinction training but attenuates ‘extinction burst’ responding after one cannabidiol injection. Furthermore, cannabidiol specifically blocked the reinstatement of cocaine seeking triggered by a cue presentation, an effect prevented by AM4113 (5 mg/kg). Unexpectedly, cannabidiol facilitated stress-induced reinstatement of cocaine seeking behavior, also by a CB1-dependent mechanism. Finally, cannabidiol did not affect cocaine-primed (10 mg/kg) precipitation of cocaine seeking. Our results reveal a series of complex changes induced by cannabidiol treatment with opposite implications for the reinstatement of cocaine seeking behavior that may limit therapeutic opportunities. The activity of CB1 receptors seems to play a crucial role in the expression of cannabidiol-induced neuroplasticity underlying both the desirable and undesirable reinstatement effects here detailed.
Vast diversity of anti-CRISPR proteins predicted with a machine-learning approach
Authors: Gussow Ayal B. , Shmakov Sergey A. , Makarova Kira S. , Wolf Yuri I. , Bondy-Denomy Joseph , Koonin Eugene V. 
Published: January 2020

AbstractBacteria and archaea evolve under constant pressure from numerous, diverse viruses and thus have evolved multiple defense systems. The CRISPR-Cas are adaptive immunity systems that have been harnessed for the development of the new generation of genome editing and engineering tools. In the incessant host-parasite arms race, viruses evolved multiple anti-defense mechanisms including numerous, diverse anti-CRISPR proteins (Acrs) that can inhibit CRISPR-Cas and therefore have enormous potential for application as modulators of genome editing tools. Most Acrs are small, highly variable proteins which makes their prediction a formidable task. We developed a machine learning approach for comprehensive Acr prediction. The model showed high predictive power when tested against an unseen test set that included several families of recently discovered Acrs and was employed to predict 2,500 novel candidate Acr families. An examination of the top candidates confirms that they possess typical Acr features. One of the top candidates was independently tested and found to possess anti-CRISPR activity (AcrIIA12). We provide a web resource (http://acrcatalog.pythonanywhere.com/) to access the predicted Acrs sequences and annotation. The results of this analysis expand the repertoire of predicted Acrs almost by two orders of magnitude and provide a rich resource for experimental Acr discovery.
Distribution of genetic diversity reveals colonization and philopatry of the loggerhead sea turtles across geographic scales
Authors: Baltazar-Soares Miguel , Klein Juliana L. , Correia Sandra M. , Reischig Thomas , Taxonera Amoros Albert , Monteiro Roque Silvana , Dos Passos Leno , Jandira Durão , João Pina Lomba , Dinis Herculano , Cameron Sahmorie J.K. , Stiebens Victor A. , Eizaguirre Christophe 
Published: January 2020

AbstractAimUnderstanding the processes that underlie the distribution of genetic diversity in endangered species is a goal of modern conservation biology. Specifically, how population structure affects genetic diversity and contributes to a species’ adaptive potential remain elusive. The loggerhead sea turtle (Caretta caretta) faces multiple conservation challenges due to its migratory nature and philopatric behaviour.LocationsAtlantic Ocean, Cabo Verde, island of BoavistaMethodsHere, using 4207 mtDNA sequences, we analysed the colonisation patterns and distribution of genetic diversity within a major ocean basin (the Atlantic), a regional rookery (Cabo Verde Archipelago) and a local island (Island of Boavista, Cabo Verde).ResultsHypothesis-driven population genetic models suggest the colonization of the Atlantic has occurred in two distinct waves, each corresponding to major mtDNA lineages. We propose the oldest lineage entered the basin via the isthmus of Panama and sequentially established aggregations in Brazil, Cabo Verde and in the area of USA and Mexico. The second lineage entered the Atlantic via the Cape of Good Hope, establishing colonies in the Mediterranean Sea, and from then on, re-colonized the already existing rookeries of the Atlantic. At the Cabo Verde level, we reveal an asymmetric gene flow maintaining links across nesting groups despite significant genetic structure amongst nesting groups. This structure stems from female philopatric behaviour which could further be detected by weak but significant structure amongst beaches separated by only a few kilometres on the island of Boavista.Main conclusionTo explore demographic processes at diverse geographic scales improves understanding the complex evolutionary history of highly migratory philopatric species. Unveiling the past facilitates the design of conservation programmes targeting the right management scale to maintain a species’ adaptive potential and putative response to human-induced selection.
Finer Metagenomic Reconstruction via Biodiversity Optimization
Authors: Foucart Simon , Koslicki David 
Published: January 2020

AbstractWhen analyzing communities of microorganisms from their sequenced DNA, an important task is taxonomic profiling: enumerating the presence and relative abundance of all organisms, or merely of all taxa, contained in the sample. This task can be tackled via compressive-sensing-based approaches, which favor communities featuring the fewest organisms among those consistent with the observed DNA data. Despite their successes, these parsimonious approaches sometimes conflict with biological realism by overlooking organism similarities. Here, we leverage a recently developed notion of biological diversity that simultaneously accounts for organism similarities and retains the optimization strategy underlying compressive-sensing-based approaches. We demonstrate that minimizing biological diversity still produces sparse taxonomic profiles and we experimentally validate superiority to existing compressive-sensing-based approaches. Despite showing that the objective function is almost never convex and often concave, generally yielding NP-hard problems, we exhibit ways of representing organism similarities for which minimizing diversity can be performed via a sequence of linear programs guaranteed to decrease diversity. Better yet, when biological similarity is quantified byk-mer co-occurrence (a popular notion in bioinformatics), minimizing diversity actually reduces to one linear program that can utilize multiplek-mer sizes to enhance performance. In proof-of-concept experiments, we verify that the latter procedure can lead to significant gains when taxonomically profiling a metagenomic sample, both in terms of reconstruction accuracy and computational performance. Reproducible code is available athttps://github.com/dkoslicki/MinimizeBiologicalDiversity.
Heparan sulfate structure is influenced by the ER-Golgi dynamics of its modifying enzymes
Authors: Meneghetti Maria Cecília Zorél , Deboni Paula , Palomino Carlos Modesto Vera , Braga Luiz Patekoski , Cavalheiro Renan Pelluzzi , Viana Gustavo Monteiro , Yates Edwin A. , Nader Helena B. , Lima Marcelo A. 
Published: January 2020

AbstractThe cell surface and extracellular matrix polysaccharide, heparan sulfate (HS) conveys chemical information to control or influence crucial biological processes. Attempts to describe its structure-function relationships with HS binding proteins in a classical ‘lock and key’ type manner, however, have been unsuccessful. HS chains are synthesized in a non-template driven process in the ER and Golgi apparatus, involving a large number of enzymes capable of fine-tuning structures. Changes in the localization of HS-modifying enzymes throughout the Golgi, rather than protein expression levels, were found to correlate with changes in the structure of HS. Following brefeldin A treatment, the HS-modifying enzymes localized preferentially in COPII vesicles and at the trans-Golgi. Further, shortly after treatment with heparin, the HS-modifying enzyme moved from cis to trans-Golgi, which coincided with increased HS trisulfated disaccharide content. Finally, it was shown that COPI subunits and Sec24 gene expression changed. Collectively, these findings highlight that the ER-Golgi dynamics of HS-modifying enzymes via vesicular trafficking processes are critical prerequisite for the complete delineation of HS biosynthesis.
A metabolomics study of ascorbic acid-inducedin situfreezing tolerance in spinach (Spinacia oleraceaL.)
Authors: Min Kyungwon , Chen Keting , Arora Rajeev 
Published: January 2020

AbstractFreeze-thaw stress is one of the major environmental constraints that limit plant growth and reduces productivity and quality. Plants exhibit a variety of cellular dysfunction following freeze-thaw stress, including accumulation of reactive oxygen species (ROS). This means that enhancement of antioxidant capacity by exogenous application of antioxidants could potentially be one of major strategies for improving freezing tolerance (FT) of plants. Exogenous application of ascorbic acid (AsA), as an antioxidant, has been shown to improve plant tolerance against abiotic stresses but its effect on FT has not been investigated. We evaluated the effect of AsA-feeding on FT of spinach (Spinacia oleraceaL.) at whole-plant and excised leaf level, and conducted metabolite profiling of leaves before and after AsA-treatment to explore metabolic explanation for change in FT. AsA-application did not impede leaf-growth; instead slightly promoted it. Temperature-controlled freeze-thaw tests revealed AsA-fed plants were more freezing tolerant as indicated by: 1) less visual damage/mortality; 2) lower ion-leakage; and 3) less oxidative-injury, lower abundance of free radicals (O2•−and H2O2). Comparative leaf metabolic profiling revealed clear separation of metabolic phenotypes for controlvs. AsA-fed leaves. Specifically, AsA-fed leaves had greater abundance of antioxidants (AsA, glutathione, alpha-& gamma-tocopherol) and compatible solutes (proline, galactinol, myo-inositol). AsA-fed leaves also had higher activity of antioxidant enzymes (superoxide dismutase, ascorbate peroxidase, catalase). These changes, together, may improve FT via alleviating freeze-induced oxidative stress as well as protecting membranes from freeze-desiccation. Additionally, improved FT by AsA-feeding may potentially include enhanced cell wall/lignin augmentation and bolstered secondary metabolism as indicated by diminished level of phenylalanine and increased abundance of branched amino acids, respectively.
Disruption of cross-feeding interactions by invading taxa can cause invasional meltdown in microbial communities
Authors: Herren Cristina M. 
Published: January 2020

AbstractThe strength of biotic interactions within an ecological community affects the susceptibility of the community to invasion by introduced taxa. In microbial communities, cross-feeding is a widespread type of biotic interaction that has the potential to affect community assembly and stability. Yet, there is little understanding of how the presence of cross-feeding within a community affects invasion risk. Here, I develop a metabolite-explicit model where native microbial taxa interact through both cross-feeding and competition for metabolites. I use this model to study how the strength of biotic interactions, especially cross-feeding, influence whether an introduced taxon can join the community. I found that stronger cross-feeding and competition led to much lower invasion risk, as both types of biotic interactions lead to greater metabolite scarcity for the invader. I also evaluated the impact of a successful invader on community composition and structure. The effect of invaders on the native community was greatest at intermediate levels of cross-feeding; at this “critical” level of cross-feeding, successful invaders generally causing decreased diversity, decreased productivity, greater metabolite availability, and decreased quantities of metabolites exchanged among taxa. Furthermore, these changes resulting from a successful primary invader made communities further susceptible to future invaders. The increase in invasion risk was greatest when the network of metabolite exchange between taxa was minimally redundant. Thus, this model demonstrates a case of invasional meltdown that is mediated by initial invaders disrupting the metabolite exchange networks of the native community.
Dugesia japonicais the best suited of three planarian species for high-throughput toxicology screening
Authors: Ireland Danielle , Bochenek Veronica , Chaiken Daniel , Rabeler Christina , Onoe Sumi , Soni Ameet , Collins Eva-Maria S. 
Published: January 2020

AbstractHigh-throughput screening (HTS) using new approach methods is revolutionizing toxicology. Asexual freshwater planarians are a promising invertebrate model for neurotoxicity HTS because their diverse behaviors can be used as quantitative readouts of neuronal function. Currently, three planarian species are commonly used in toxicology research:Dugesia japonica,Schmidtea mediterranea, andGirardia tigrina. However, onlyD. japonicahas been demonstrated to be suitable for HTS. Here, we assess the two other species for HTS suitability by direct comparison withD. japonica. Through quantitative assessments of morphology and multiple behaviors, we assayed the effects of 4 common solvents (DMSO, ethanol, methanol, ethyl acetate) and a negative control (sorbitol) on neurodevelopment. Each chemical was screened blind at 5 concentrations at two time points over a twelve-day period. We obtained two main results: First,G. tigrinaandS. mediterraneaplanarians showed significantly reduced movement compared toD. japonicaunder HTS conditions, due to decreased health over time and lack of movement under red lighting, respectively. This made it difficult to obtain meaningful readouts from these species. Second, we observed species differences in sensitivity to the solvents, suggesting that care must be taken when extrapolating chemical effects across planarian species. Overall, our data show thatD. japonicais best suited for behavioral HTS given the limitations of the other species. Standardizing which planarian species is used in neurotoxicity screening will facilitate data comparisons across research groups and accelerate the application of this promising invertebrate system for first-tier chemical HTS, helping streamline toxicology testing.
Entropy of city street networks linked to future spatial navigation ability
Authors: Coutrot A. , Manley E. , Goodroe S. , Gahnstrom C. , Filomena G. , Yesiltepe D. , Dalton R.C. , Wiener J. M. , Hölscher C. , Hornberger M. , Spiers H. J. 
Published: January 2020

AbstractCultural and geographical properties of the environment have been shown to deeply influence cognition and mental health[1–6]. While living near green spaces has been found to be strongly beneficial [7–11], urban residence has been associated with a higher risk of some psychiatric disorders [12–14] (although see [15]). However, how the environment one grew up in impacts later cognitive abilities remains poorly understood. Here, we used a cognitive task embedded in a video game[16] to measure non-verbal spatial navigation ability in 397,162 people from 38 countries across the world. Overall, we found that people who grew up outside cities are better at navigation. More specifically, people were better at navigating in environments topologically similar to where they grew up. Growing up in cities with low Street Network Entropy (e.g. Chicago) led to better results at video game levels with a regular layout, while growing up outside cities or in cities with higher Street Network Entropy (e.g. Prague) led to better results at more entropic video game levels. This evidences the impact of the environment on human cognition on a global scale, and highlights the importance of urban design on human cognition and brain function.
An information-theoretic approach for measuring the distance of organ tissue samples using their transcriptomic signatures
Authors: Manatakis Dimitris V. , VanDevender Aaron , Manolakos Elias S. 
Published: January 2020

AbstractMotivationRecapitulating aspects of human organ functions using in-vitro (e.g., plates, transwells, etc.), in-vivo (e.g., mouse, rat, etc.), or ex-vivo (e.g., organ chips, 3D systems, etc.) organ models are of paramount importance for precision medicine and drug discovery. It will allow us to identify potential side effects and test the effectiveness of therapeutic approaches early in their design phase and will inform the development of accurate disease models. Developing mathematical methods to reliably compare the “distance/similarity” of organ models from/to the real human organ they represent is an understudied problem with important applications in biomedicine and tissue engineering.ResultsWe introduce the Transctiptomic Signature Distance,TSD, an information-theoretic distance for assessing the transcriptomic similarity of two tissue samples, or two groups of tissue samples. In developingTSD, we are leveraging next-generation sequencing data and information retrieved from well-curated databases providing signature gene sets characteristic for human organs. We present the justification and mathematical development of the new distance and demonstrate its effectiveness in different scenarios of practical importance using several publicly available RNA-seq datasets.Contactdimitris.manatakis@emulatebio.comSupplementary informationSupplementary data are available atbioRxiv.
Pattern of early human-to-human transmission of Wuhan 2019-nCoV
Authors: Riou Julien , Althaus Christian L. 
Published: January 2020

ABSTRACTOn December 31, 2019, the World Health Organization was notified about a cluster of pneumonia of unknown aetiology in the city of Wuhan, China. Chinese authorities later identified a new coronavirus (2019-nCoV) as the causative agent of the outbreak. As of January 23, 2020, 655 cases have been confirmed in China and several other countries. Understanding the transmission characteristics and the potential for sustained human-to-human transmission of 2019-nCoV is critically important for coordinating current screening and containment strategies, and determining whether the outbreak constitutes a public health emergency of international concern (PHEIC). We performed stochastic simulations of early outbreak trajectories that are consistent with the epidemiological findings to date. We found the basic reproduction number,R0, to be around 2.2 (90% high density interval 1.4—3.8), indicating the potential for sustained human-to-human transmission. Transmission characteristics appear to be of a similar magnitude to severe acute respiratory syndrome-related coronavirus (SARS-CoV) and the 1918 pandemic influenza. These findings underline the importance of heightened screening, surveillance and control efforts, particularly at airports and other travel hubs, in order to prevent further international spread of 2019-nCoV.