bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systems genetics approach reveals environment-dependent associations between SNPs, protein co-expression and drought-related traits in maize
Authors: Blein-Nicolas Mélisande , Negro Sandra Sylvia , Balliau Thierry , Welcker Claude , Bosquet Llorenç Cabrera , Nicolas Stéphane Dimitri , Charcosset Alain , Zivy Michel 
Published: May 2019

ABSTRACTThe effect of drought on maize yield is of particular concern in the context of climate change and human population growth. However, the complexity of drought-response mechanisms make the design of new drought-tolerant varieties a difficult task that would greatly benefit from a better understanding of the genotype-phenotype relationship. To provide novel insight into this relationship, we applied a systems genetics approach integrating high-throughput phenotypic, proteomic and genomic data acquired from 254 maize hybrids grown under two watering conditions. Using association genetics and protein co-expression analysis, we detected more than 22,000 pQTLs across the two conditions and confidently identified fifteen loci with potential pleiotropic effects on the proteome. We showed that even mild water deficit induced a profound remodeling of the proteome, which affected the structure of the protein co-expression network, and a reprogramming of the genetic control of the abundance of many proteins, notably those involved in stress response. Co-localizations between pQTLs and QTLs for ecophysiological traits, found mostly in the water deficit condition, indicated that this reprogramming may also affect the phenotypic level. Finally, we identified several candidate genes that are potentially responsible for both the co-expression of stress response proteins and the variations of ecophysiological traits under water deficit. Taken together, our findings provide novel insights into the molecular mechanisms of drought tolerance and suggest some pathways for further research and breeding.
Hitting a moving target: Microbial evolutionary strategies in a dynamic ocean
Authors: Walworth Nathan G. , Zakem Emily J. , Dunne John P. , Collins Sinéad , Levine Naomi M. 
Published: May 2019

AbstractMarine microbes form the base of ocean food webs and drive ocean biogeochemical cycling. Yet little is known about how microbial populations will evolve due to global change-driven shifts in ocean dynamics. Understanding adaptive timescales is critical where long-term trends (e.g. warming) are coupled to shorter-term advection dynamics that move organisms rapidly between ecoregions. Here we investigated the interplay between physical and biological timescales using a model of adaptation and an eddy-resolving ocean circulation climate model. Two criteria (α and β) were identified that relate physical and biological timescales and determine the timing and nature of adaptation. Genetic adaptation was impeded in highly variable regimes (α<1) but promoted in more stable environments (α>1). An evolutionary trade-off emerged where greater short-term transgenerational effects (low-β-strategy) enabled rapid responses to environmental fluctuations but delayed genetic adaptation, while fewer short-term transgenerational effects (high-β-strategy) allowed faster genetic adaptation but inhibited short-term responses. Our results suggest that organisms with faster growth rates are better positioned to adapt to rapidly changing ocean conditions and that more variable environments will favor a bet-hedging, low-β-strategy. Understanding the relationship between evolutionary and physical timescales is critical for robust predictions of future microbial dynamics.
Identification of microRNA-target interactions for antioxidant defense response under drought stress by high-throughput sequencing in Zanthoxylum bungeanum Maxim
Authors: Fei Xitong , Hu Haichao , Li Jingmiao , Liu Yulin , Wei Anzhi 
Published: May 2019

ABSTRACTWhen the plant is in an unfavorable environment such as drought or high temperature, it will accumulate a large amount of active oxygen, which will seriously affect the normal growth and development of the plant. The antioxidant system can remove the reactive oxygen species produced under drought conditions and so mitigate oxidative damage. We examined the trends of antioxidant enzymes, miRNAs and their target genes in Zanthoxylum bungeanum under drought stress. According to the changes of antioxidant enzymes, miRNAs and their target genes expression patterns of Zanthoxylum bungeanum under drought stress, an interaction model was constructed to provide a reference for further understanding of plant antioxidant mechanism. The results indicate that under drought stress, POD, CAT, APX, proline, MDA and related genes all show positive responses to drought, while SOD and its genes showed a negative response. It is speculated that in the antioxidant process of Zanthoxylum bungeanum, POD, CAT, and APX play a major role, and SOD plays a supporting role. In addition, the expression levels of miRANs and their target genes were basically negatively correlated, indicating that miRNAs are involved in the regulation of the antioxidant system of Zanthoxylum bungeanum.
Antibiotics can be used to contain drug-resistant bacteria by maintaining sufficiently large sensitive populations
Authors: Hansen Elsa , Karslake Jason , Woods Robert J. , Read Andrew F. , Wood Kevin B. 
Published: May 2019

AbstractStandard infectious disease practice calls for aggressive drug treatment that rapidly eliminates the pathogen population before resistance can emerge. When resistance is absent, this elimination strategy can lead to complete cure. However, it also removes drug-sensitive cells as quickly as possible, removing competitive barriers that may slow the growth of resistant cells. In contrast to the elimination strategy, the containment strategy aims to maintain the maximum tolerable number of pathogens, exploiting competitive suppression to achieve chronic control. Here we combine in vitro experiments in computer-controlled bioreactors with mathematical modeling to investigate whether containment strategies can delay failure of antibiotic treatment regimens. To do so, we measured the “escape time” required for drug-resistant E. coli populations to eclipse a threshold density maintained by adaptive antibiotic dosing. Populations containing only resistant cells rapidly escape containment, but we found that matched populations with the maximum possible number of sensitive cells could be contained for significantly longer. The increase in escape time occurs only when the threshold density–the acceptable bacterial burden–is sufficiently high, an effect that mathematical models attribute to increased competition. The findings provide decisive experimental confirmation that maintaining the maximum number of sensitive cells can be used to contain resistance when the size of the population is sufficiently large.
Genome replication dynamics of a bacteriophage and its satellite reveal strategies for parasitism and viral restriction
Authors: Barth Zachary K , Silvas Tania V , Angermeyer Angus , Seed Kimberley D 
Published: May 2019

ABSTRACTPhage-inducible chromosomal island-like elements (PLEs) are bacteriophage satellites found inVibrio cholerae. PLEs parasitize the lytic phage ICP1, excising from the bacterial chromosome, replicating, and mobilizing to new host cells following cell lysis. PLEs protect their host cell populations by completely restricting the production of ICP1 progeny. Previously, it was found that ICP1 replication was reduced during PLE(+) infection. Despite robustly replicating its genome, PLE produces relatively few transducing units, leading us to investigate if PLE DNA replication itself is antagonistic to ICP1 replication. Here we identify key constituents of PLE replication and assess their role in interference of ICP1. PLE encodes a RepA_N initiation factor that is sufficient to drive replication from the PLE origin of replication during ICP1 infection. In contrast to previously characterized bacteriophage satellites, expression of the PLE initiation factor was not sufficient for PLE replication in the absence of phage. Replication of PLE was necessary for interference of ICP1 DNA replication, but replication of a minimalized PLE replicon was not sufficient for ICP1 DNA replication interference. Despite restoration of ICP1 DNA replication, non-replicating PLE remained broadly inhibitory against ICP1. These results suggest that PLE DNA replication is one of multiple mechanisms contributing to ICP1 restriction.
Novel strategy for treating neurotropic viral infections using hypolipidemic drug Atorvastatin
Authors: Mallick Suvadip , Chakraborty Surajit , Hazra Bibhabasu , Dev Sujata , Mukherjee Sriparna , Wani Masood Ahmad , Basu Anirban 
Published: May 2019

AbstractChandipura virus (CHPV) and Japanese Encephalitis Virus (JEV) are known to infect neurons followed by their successful propagation. Increased incidences of central nervous system invasion by the abovementioned viruses have been reported in case of children and elderly thus culminating into severe neurological damage. Literature suggests induction of endoplasmic reticulum (ER)-stress related proteins upon CHPV and JEV infection which help promote viral reproduction. Since earlier studies underscore the pleotropic role of atorvastatin (AT) in neuroprotection against flaviviruses like Hepatitis C and dengue, it was hypothesized that AT might also act as a neuroprotective agent against RNA viruses like CHPV and JEV. AT-mediated antiviral activity was evaluated by assessing survivability of virus-infected mouse pups treated with the drug. Balb C mice were used for in vivo experiments. Neuro2A cell line was used as the model for in vitro experiments. Cells subjected to AT treatment were infected by CHPV and JEV followed by evaluation of ER stress-related and apoptosis-related proteins by immunoblotting technique and immunofluorescence microscopy. Interaction of host protein with viral genome was assessed by RNA-Co-IP. AT treatment exhibited significant anti-viral activity against CHPV and JEV infections via hnRNPC-dependent manner. Viral genome-hnRNPC interaction was found to be abrogated upon AT action. AT was also observed to reduce secretion of proinflammatory cytokines by the neurons in response to viral infection. Moreover, AT treatment was also demonstrated to reduce neuronal death by abrogating virus-induced miR-21 upregulation in hnRNPC-dependent fashion. This study thus suggests probable candidature of AT as antiviral against CHPV and JEV infections.
www.Malaria.tools - comparative genomic and transcriptomic database for Plasmodium species
Authors: Tan Qiao Wen , Mutwil Marek 
Published: May 2019

ABSTRACTMalaria is a tropical parasitic disease caused by the Plasmodium genus, which resulted in an estimated 219 million cases of malaria and 435,000 malaria-related deaths in 2017. Despite the availability of the P. falciparum genome since 2002, almost 50% of the genes remain unannotated. To remedy this paucity of functional information, we used transcriptomic data to build gene co-expression networks for two Plasmodium species (P. falciparum and P. berghei), and included genomic data of four other Plasmodium species, P. yoleii, P. knowlesi, P. vivax and P. cynomolgi, as well as two non-Plasmodium species from the Apicomplexa, Toxoplasma gondii and Theileria parva. The database is preloaded with tools that allow the identification and cross-species comparison of co-expressed gene neighborhoods, clusters, and life stage-specific expression, thus providing sophisticated tools to predict gene function. Moreover, we exemplify how the tools can be used to easily identify genes relevant for pathogenicity and various life stages of the malaria parasite. The database is freely available at www.malaria.tools.
Feasibility of a surface-coated lung model for the quantification of active agent deposition for preclinical studies
Authors: Dörner Philipp , Müller Philipp M. , Reiter Jana , Gruhlke Martin C. , Slusarenko Alan J. , Schröder Wolfgang , Klaas Michael 
Published: May 2019

AbstractMultiple drug resistance (MDR) of a growing number of bacterial pathogens represents an increasing challenge in conventional curative treatments of infectious diseases. However, the development and testing of new antibiotics is associated with a high number of animal experiments. A symmetrical parametrized lung test rig allowing the exposure of air-passage surfaces to antibiotics was designed and tested to demonstrate proof-of-principle with aerosols containing allicin, which is an antimicrobial natural product from garlic. An artificial lung surface is coated with bacteria embedded in a hydrogel and growth inhibition is visualized by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), that is reduced from colourless to the dark blue formazan in the presence of metabolically active, living cells. A nebulizer is used to generate the aerosols. The results show that allicin has an antibiotic effect as an aerosol and that the deposition pattern of the active agent occurred mainly around the carinal regions. The model represents an integral system for continuous, spatial detection of aerosol deposition and allows the analysis of bacterial behaviour and the toxicity of the active agent. In this way the deposition of antimicrobial aerosols on the bronchial surfaces is characterized in preliminary tests without any animal experiments.
Neural oscillations while remembering traumatic memories in PTSD
Authors: Reuveni Inbal , Herz Noa , Bonne Omer , Peri Tuvia , Schreiber Shaul , Harpaz Yuval , Goldstein Abraham 
Published: May 2019

AbstractBackgroundIn posttraumatic stress disorder (PTSD), the traumatic event is often re-experienced through vivid sensory fragments of the traumatic experience. Though the sensory phenomenology of traumatic memories is well established, neural indications for this qualitative experience are lacking. The current study aimed at monitoring the oscillatory brain activity of PTSD patients during directed and imaginal exposure to the traumatic memory using magnetoencephalography (MEG), in a paradigm resembling exposure therapy.MethodsBrain activity of healthy trauma-exposed controls and PTSD participants was measured with MEG as they listened to individualized trauma narratives as well as to a neutral narrative and as they imagined the narrative in detail. Source localization analysis on varied frequency bands was conducted in order to map neural generators of altered oscillatory activity.ResultsPTSD patients exhibited increased power of high-frequency bands over visual areas and increased delta and theta power over auditory areas in response to trauma recollection compared to neutral recollection, while controls did not show such differential activation. PTSD participants also showed abnormal modulation of lower frequencies in the medial prefrontal cortex.ConclusionsElicitation of traumatic memories results in a distinct neural pattern in PTSD patients compared to healthy trauma-exposed individuals. Investigating the oscillatory neural dynamics of PTSD patients can help us better understand the processes underlying trauma re-experiencing.
Identification of aNidoviralesOrf1a N7-guanine cap Methyltransferase signature-sequence as a genetic marker of large genomeTobaniviridae
Authors: Ferron François , Debat Humberto Julio , Decroly Etienne , Canard Bruno 
Published: May 2019

AbstractMembers of theNidoviralesorder have (+)RNA genomes amongst the largest in size in the RNA virus world. Expression of their genes is promoted through reading of genomic RNA and mRNA transcripts by the ribosome of the infected cell. The 5’-end of these RNAs is supposedly protected by an RNA-cap structure (m7GpppNm) whose most synthesis steps remain elusive. In Eukaryotes, the RNA-cap structure is methylated by RNA methyltransferases (MTases) at the RNA-cap N7-guanine position as well as the 2’-O methyl position of the first transcribed nucleotide. InCoronaviridae, two separate enzymes (nsp14 and nsp16) perform the N7-guanine and the 2’-OH methylation, respectively. One salient feature of theNidoviralesN7-guanine MTase nsp14 is that it is the only example of non-Rossman fold viral MTase known so far. Conversely, all otherNidoviralesnsp16-like MTases have a canonical Rossman fold. ManyNidoviralesmembers lack either any RNA MTase signature sequence (e.g.,Arteriviridae), or lack a N7-guanine MTase signature sequence (e.g.,Tobaniviridae,Euroniviridae,Roniviridae,Medioniviridae). Both nsp14-and nsp16-like enzyme genes are usually located in Orf1b encoding for the replication machinery. Here, we report the discovery of a putative Rossman fold RNA MTase in the Orf1a of tenTobaniviridaemembers. Multiple sequence alignments and structural analyses identify this novel gene as a typical RNA-cap N7-guanine MTase with substrate specificity and active-site organization similar to the canonical eukaryotic RNA-cap N7-guanine MTase.
Dissociable effects of visual crowding on the perception of colour and motion
Authors: Greenwood John A. , Parsons Michael J. 
Published: May 2019

AbstractOur ability to recognise objects in peripheral vision is fundamentally limited by crowding, the deleterious effect of clutter that disrupts the recognition of features ranging from orientation and colour to motion and depth. Prior research is equivocal on whether this reflects a singular process that disrupts all features simultaneously or multiple processes that affect each independently. We examined crowding for motion and colour, two features that allow a strong test of feature independence. ‘Cowhide’ stimuli were presented 15 degrees in peripheral vision, either in isolation or surrounded by flankers to give crowding. Observers reported either the target direction (clockwise/counterclockwise from upwards) or its hue (blue/purple). We first established that both features show systematic crowded errors (predominantly biased towards the flanker identities) and selectivity for target-flanker similarity (with reduced crowding for dissimilar target/flanker elements). The multiplicity of crowding was then tested with observers identifying both features: a singular object-selective mechanism predicts that when crowding is weak for one feature and strong for the other that crowding should be all-or-none for both. In contrast, when crowding was weak for colour and strong for motion, errors were reduced for colour but remained for motion, and vice versa with weak motion and strong colour crowding. This double dissociation reveals that crowding disrupts certain combinations of visual features in a feature-specific manner, ruling out a singular object-selective mechanism. The ability to recognise one aspect of a cluttered scene, like colour, thus offers no guarantees for the correct recognition of other aspects, like motion.Significance statementOur peripheral vision is primarily limited by crowding, the disruption to object recognition that arises in clutter. Crowding is widely assumed to be a singular process, affecting all of the features (orientation, motion, colour, etc.) within an object simultaneously. In contrast, we observe a double dissociation whereby observers make errors regarding the colour of a crowded object whilst correctly judging its direction, and vice versa. This dissociation can be reproduced by a population-coding model where the direction and hue of target/flanker elements are pooled independently. The selective disruption of some object features independently of others rules out a singular crowding mechanism, posing problems for high-level crowding theories, and suggesting that the underlying mechanisms may be distributed throughout the visual system.
Disruption of the CSF-1-CSF-1R axis alters cerebellar microglia and is associated with motor and social interaction defects
Authors: Kana Veronika , Desland Fiona A. , Casanova-Acebes Maria , Ayata Pinar , Badimon Ana , Nabel Elisa , Yamamuro Kazuhiko , Sneeboer Marjolein , Tan I-Li , Flanigan Meghan E. , Rose Samuel A. , Chang Christie , Leader Andrew , Bouris Hortense Le , Sweet Eric , Tung Navpreet , Wroblewska Aleksandra , Lavin Yonit , See Peter , Baccarini Alessia , Ginhoux Florent , Chitu Violeta , Stanley E. Richard , Russo Scott J. , Yue Zhenyu , Brown Brian D. , Joyner Alexandra L. , De Witte Lotje , Morishita Hirofumi , Schaefer Anne , Merad Miriam 
Published: May 2019

AbstractMicroglia, the brain resident macrophages, critically shape forebrain neuronal circuits. However, their precise function in the cerebellum is unknown. Here we show that human and mouse cerebellar microglia express a unique molecular program distinct from forebrain microglia. Cerebellar microglial identity was driven by the CSF-1R ligand CSF-1, independently of the alternate CSF-1R ligand, IL-34. Accordingly, CSF-1 depletion from Nestin+cells led to severe depletion and transcriptional alterations of cerebellar microglia, while microglia in the forebrain remained intact. Strikingly, CSF-1 deficiency and alteration of cerebellar microglia were associated with reduced Purkinje cells, altered neuronal function, and defects in motor learning and social novelty interactions. These findings reveal a novel CSF-1-CSF-1R signaling-mediated mechanism that contributes to motor function and social behavior.SummaryMicroglia are a heterogeneous population whose identity and function are dictated by signals from their microenvironment. Kana et al. show that CSF-1 signaling is critical for maintaining cerebellar microglial transcriptional identity and homeostasis, and that altering the CSF-1 – CSF-1R axis leads to motor and behavioral defects.
Genetic risk underlying psychiatric and cognitive symptoms in Huntington’s Disease
Authors: Ellis Natalie , Tee Amelia , McAllister Branduff , Massey Thomas , McLauchlan Duncan , Stone Timothy , Correia Kevin , Loupe Jacob , Kim Kyung-Hee , Barker Douglas , Hong Eun Pyo , Chao Michael J. , Long Jeffrey D. , Lucente Diane , Vonsattel Jean Paul G. , Pinto Ricardo Mouro , Elneel Kawther Abu , Ramos Eliana Marisa , Mysore Jayalakshmi Srinidhi , Gillis Tammy , Wheeler Vanessa C. , Medway Christopher , Hall Lynsey , Kwak Seung , Sampaio Cristina , Ciosi Marc , Maxwell Alastair , Chatzi Afroditi , Monckton Darren G. , Orth Michael , Landwehrmeyer G. Bernhard , Paulsen Jane S. , Shoulson Ira , Myers Richard H. , van Duijn Erik , Rickards Hugh , MacDonald Marcy E. , Lee Jong-min , Gusella James F. , Jones Lesley , Holmans Peter 
Published: May 2019

AbstractHuntington’s disease (HD) is an inherited neurodegenerative disorder caused by an expanded CAG repeat in the HTT gene. It is diagnosed following a standardized exam of motor control and often presents with cognitive decline and psychiatric symptoms. Recent studies have detected genetic loci modifying the age at onset of motor symptoms in HD, but genetic factors influencing cognitive and psychiatric presentations are unknown. We tested the hypothesis that psychiatric and cognitive symptoms in HD are influenced by the same common genetic variation as in the general population by constructing polygenic risk scores from large genome-wide association studies of psychiatric and neurodegenerative disorders, and of intelligence, and testing for correlation with the presence of psychiatric and cognitive symptoms in a large sample (n=5160) of HD patients. Polygenic risk score for major depression was associated specifically with increased risk of depression in HD, as was schizophrenia risk score with psychosis and irritability. Cognitive impairment and apathy were associated with reduced polygenic risk score for intelligence. In general, polygenic risk scores for psychiatric disorders, particularly depression and schizophrenia, are associated with increased risk of the corresponding psychiatric symptoms in HD, suggesting a common genetic liability. However, the genetic liability to cognitive impairment and apathy appears to be distinct from other psychiatric symptoms in HD. No associations were observed between HD symptoms and risk scores for other neurodegenerative disorders. These data provide a rationale for treatments effective in depression and schizophrenia to be used to treat depression and psychotic symptoms in HD.