bluuebunny/crossref_metadata_2025_split huggingface dataset:
Signal pathways involved in microbe–nematode interactions provide new insights into the biocontrol of plant-parasitic nematodes
Authors: Liang Lian-Ming , Zou Cheng-Gang , Xu Jianping , Zhang Ke-Qin 
Published: January 2019

Plant-parasitic nematodes (PPNs) cause severe damage to agricultural crops worldwide. As most chemical nematicides have negative environmental side effects, there is a pressing need for developing efficient biocontrol methods. Nematophagous microbes, the natural enemies of nematodes, are potential biocontrol agents against PPNs. These natural enemies include both bacteria and fungi and they use diverse methods to infect and kill nematodes. For instance, nematode-trapping fungi can sense host signals and produce special trapping devices to capture nematodes, whereas endo-parasitic fungi can kill nematodes by spore adhesion and invasive growth to break the nematode cuticle. By contrast, nematophagous bacteria can secrete virulence factors to kill nematodes. In addition, some bacteria can mobilize nematode-trapping fungi to kill nematodes. In response, nematodes can also sense and defend against the microbial pathogens using strategies such as producing anti-microbial peptides regulated by the innate immunity system. Recent progresses in our understanding of the signal pathways involved in microbe–nematode interactions are providing new insights in developing efficient biological control strategies against PPNs.
This article is part of the theme issue ‘Biotic signalling sheds light on smart pest management'.
A GWAS-Derived Polygenic Score for Interleukin-1β is Associated with Hippocampal Volume in Two Samples
Authors: Avinun Reut , Nevo Adam , Knodt Annchen R. , Elliott Maxwell L. , Hariri Ahmad R. 
Published: January 2019

AbstractAccumulating research suggests that the pro-inflammatory cytokine interleukin-1β (IL-1β) has a modulatory effect on the hippocampus, a brain structure important for learning and memory as well as linked with both psychiatric and neurodegenerative disorders. Here, we use an imaging genetics strategy to test an association between an IL-1β polygenic score, derived from summary statistics of a recent genome-wide association study (GWAS) of circulating cytokines, and hippocampal volume, in two independent samples. In the first sample of 512 non-Hispanic Caucasian university students (274 women, mean age 19.78 ± 1.24 years) from the Duke Neurogenetics Study, we identified a significant positive correlation between higher polygenic scores, which presumably reflect higher circulating IL-1β levels, and average hippocampal volume. This positive association was successfully replicated in a second sample of 7,960 white British volunteers (4,158 women, mean age 62.63±7.45 years) from the UK Biobank. Collectively, our results suggest that a functional GWAS-derived score of IL-1β blood circulating levels affects hippocampal volume, and lend further support in humans, to the link between IL-1β and the structure of the hippocampus.
Antitumor effects of Tv1 venom peptide in liver cancer
Authors: Anand Prachi , Filipenko Petr , Huaman Jeannette , Lyudmer Michael , Hossain Marouf , Santamaria Carolina , Huang Kelly , Ogunwobi Olorunseun O. , Holford Mandë 
Published: January 2019

AbstractA strategy for treating the most common type of liver cancer, hepatocellular carcinoma (HCC) applies a targeted therapy using venom peptides that are selective for ion channels and transporters overexpressed in tumor cells. Here, we report selective anti-HCC properties of Tv1, a venom peptide from the predatory marine terebrid snail,Terebra variegata.Tv1 was appliedin vitroto liver cancer cells and administeredin vivoto allograft tumor mouse models. Tv1 inhibited the proliferation of murine HCC cells via calcium dependent apoptosis resulting from down-regulation of the cyclooxygenase-2 (COX-2) pathway. Additionally, tumor sizes were significantly reduced in Tv1-treated syngeneic tumor-bearing mice. Tv1’s mechanism of action involves binding to specific transient receptor potential (TRP) cation channels that are overexpressed in HCC cell models. Our findings demonstrate the unique potential of venom peptides to function as tumor specific ligands in the quest for targeted cancer therapies.
Impairments in contractility and cytoskeletal organisation cause nuclear defects in nemaline myopathy
Authors: Ross Jacob A , Levy Yotam , Ripolone Michela , Kolb Justin S , Turmaine Mark , Holt Mark , Moggio Maurizio , Fiorillo Chiara , Lindqvist Johan , Figeac Nicolas , Zammit Peter S , Jungbluth Heinz , Vissing John , Witting Nanna , Granzier Henk , Zanoteli Edmar , Hardeman Edna C , Wallgren-Pettersson Carina , Ochala Julien 
Published: January 2019

AbstractNemaline myopathy (NM) is a genetically heterogeneous skeletal muscle disorder caused by mutations predominately affecting contractile filaments, in particular thin filament structure and/or regulation. The underlying cellular pathophysiology of this disease remains largely unclear. Here, we report novel pathological defects in skeletal muscle fibres of mice and patients with NM, including disrupted nuclear envelope, altered chromatin arrangement, and disorganisation of the cortical cytoskeleton. We demonstrate that such nuclear defects are caused by impairment of muscle fibre contractility, and that cytoskeletal organisation determines nuclear morphology. Our results overlap with findings in diseases caused by mutations in nuclear envelope or cytoskeletal proteins. Given the important role of nuclear shape and envelope in regulating gene expression, and the cytoskeleton in maintaining muscle fibre integrity, our findings are likely to underlie some of the hallmarks of NM, which include broad transcriptional alterations, arrested muscle fibre growth, contractile filament disarray and altered mechanical properties.
A novel blaSIM-1-carrying megaplasmid pSIM-1-BJ01 isolated from clinical Klebsiella pneumonia
Authors: Lü Yang , Liang Hui , Zhang Wei , Liu Jia , Wang Shiwei , Hu Hongyan 
Published: January 2019

ABSTRACTA rare carbapenem-resistant gene blaSIM-1 was found in a 316-kb megaplasmid designated pSIM-1-BJ01 isolated from a clinical strain Klebsiella pneumonia 13624. The plasmid pSIM-1-BJ01 was fully sequenced and analyzed. Its length is 316,557 bp and it has 342 putative open reading frames with two multidrug-resistant regions and a total of 19 resistant genes. Its backbone was highly homologous to the newly reported plasmid pRJA166a, which was isolated from a clinical third-generation cephalosporin-resistant hypervirulen strain K. pneumonia ST23. The plasmid pSIM-1-BJ01 was verified to be able to transfer to Escherichia coli. The emergency of the transferable blaSIM-1-carrying multidrug-resistant plasmid pSIM-1-BJ01 suggests the spread of blaSIM among Enterobacteriaceae is possible. Therefore, the data presented herein provided insights into the genomic diversity and evolution of blaSIM-carrying plasmids, as well as the dissemination and epidemiology of blaSIM among Enterobacteriaceae in public health system.
Semantic Integration of Clinical Laboratory Tests from Electronic Health Records for Deep Phenotyping and Biomarker Discovery
Authors: Zhang Xingmin Aaron , Yates Amy , Vasilevsky Nicole , Gourdine JP , Carmody Leigh C. , Danis Daniel , Joachimiak Marcin P. , Ravanmehr Vida , Pfaff Emily R. , Champion James , Robasky Kimberly , Xu Hao , Fecho Karamarie , Walton Nephi A. , Zhu Richard , Ramsdill Justin , Mungall Chris , Köhler Sebastian , Haendel Melissa A. , McDonald Clem , Vreeman Daniel J. , Peden David B. , Chute Christopher G. , Robinson Peter N. 
Published: January 2019

AbstractElectronic Health Record (EHR) systems typically define laboratory test results using the Laboratory Observation Identifier Names and Codes (LOINC) and can transmit them using Fast Healthcare Interoperability Resource (FHIR) standards. LOINC has not yet been semantically integrated with computational resources for phenotype analysis. Here, we provide a method for mapping LOINC-encoded laboratory test results transmitted in FHIR standards to the Human Phenotype Ontology (HPO) terms. We annotated the medical implications of 2421 commonly used laboratory tests with HPO terms. Using these annotations, a software assesses laboratory test results and converts each into an HPO term. We validated our approach with EHR data from 15,681 patients with respiratory complaints and identified known biomarkers for asthma. Finally, we provide a freely available SMART on FHIR application that can be used within EHR systems. Our approach allows reusing readily available laboratory tests in EHR for deep phenotyping and using the hierarchical structure of HPO for association studies with medical outcomes and genomics.One Sentence SummaryWe present an approach to semantically integrating LOINC-encoded laboratory data with the Human Phenotype Ontology and show that the integrated LOINC data can be used to identify biomarkers for asthma from electronic health record data.
A brainstem-central amygdala circuit underlies defensive responses to learned threats
Authors: Gu Yiran , Vazey Elena M. , Aston-Jones Gary , Lin Longnian , LeDoux Joseph E. , Sears Robert M 
Published: January 2019

AbstractNorepinephrine (NE) plays a central role in the acquisition of aversive learning via actions in the lateral nucleus of the amygdala (LA)1,2. However, the function of NE in expression of aversively-conditioned responses has not been established. Given the role of the central nucleus of the amygdala (CeA) in the expression of such behaviors3, and the presence of NE projections in this brain nucleus, we assessed the effects of NE activity in the CeA on behavioral expression using receptor-specific pharmacology and cell-and projection-specific chemogenetic manipulations. We found that inhibition and activation of locus coeruleus (LC) neurons decreases and increases freezing to aversively conditioned cues, respectively. We then show that locally inhibiting or activating LC terminals in CeA is sufficient to achieve this bidirectional modulation of defensive reactions. These findings support the hypothesis that LC projections to CeA are required for the expression of defensive responses elicited by conditioned threats.
Olfactory Co-Stimulation Influences Intranasal Somatosensory Perception
Authors: Karunanayaka Prasanna R. , Lu Jiaming , Yang Qing X. , Sathian K. 
Published: January 2019

ABSTRACTOlfactory sensitivity is influenced by intranasal trigeminal sensation. For instance, sniffing is central to how humans and animals perceive odorants. Here, we investigated the influence of olfactory co-stimulation on the perception of intranasal somatosensory stimulation. In this study, twenty-two healthy human subjects, with normal olfactory function, performed a localization task for weak air-puff stimuli, in the presence or absence of a pure odorant, phenyl ethyl alcohol (PEA; rose odor). Visual cues were used to inform participants to briefly hold their breath while weak, poorly localizable, air-puffs and/or PEA were delivered to either nostril. Although PEA alone could not be localized, when accompanied by a weak air-puff in the ipsilateral nostril, localization accuracy significantly improved, relative to presentation of the air-puff without the odorant. The enhancement of localization was absent when the air-puff and PEA were presented to opposite nostril. Since ipsilateral but not contralateral co-stimulation with PEA increased the accuracy of weak air-puff localization, the results argue against a non-specific alerting effect of PEA. These findings suggest an interaction between the olfactory and somatosensory trigeminal systems.
Foliar fungi alter reproductive timing and allocation in Arabidopsis under normal and water-stressed conditions
Authors: Zahn Geoffrey , Amend Anthony S. 
Published: January 2019

ABSTRACTMicrobes influence plant phenotypes but most known examples of this are from the study of below-ground microbes and plant disease modification. To examine the potential importance of phyllosphere microbes on non-disease related plant traits, we used sterile Arabidopsis clones to test the effects of foliar fungi on flowering phenology and reproductive allocation under conditions of varying water stress. We inoculated the sterile plants with fully-factorial combinations of four fungal isolates, then measured flowering time and reproductive allocation for each treatment group under normal and water-stressed conditions. All plants inoculated with foliar fungi had significantly later flowering and greater seed mass than the sterile control groups. The magnitude of this effect depended on the specific fungi present, but individual fungal effects diminished as inoculum richness increased. Above-ground microbes likely influence other plant traits as well and should be considered in any study measuring plant phenotypes.
In vitro and in silico identification of the mechanism of interaction of antimalarial drug – artemisinin with human serum albumin and genomic DNA
Authors: Ginosyan Siranush , Grabski Hovakim , Tiratsuyan Susanna 
Published: January 2019

AbstractArtemisinins are secondary metabolites of the medicinal plant Artemisia annua, which has been traditionally used in Chinese medicine. Artemisinins have anti-inflammatory, anticarcinogenic, immunomodulatory, antimicrobial, anthelmintic, antiviral, antioxidant, and other properties. Our preliminary reverse virtual screening demonstrated that the ligand-binding domain of the human glucocorticoid receptor (LBD of hGR) is the optimal target for artemisinin. At the same time, the binding sites for artemisinin with the ligand-binding domain of the human glucocorticoid receptor coincide with those of dexamethasone. However, the pharmacokinetics, pharmacodynamics, and exact molecular targets and mechanisms of action of artemisinin are not well known. In this work, the interaction of artemisinin with human serum albumin (HSA) was studied both in vitro and in silico. The results indicate that artemisinin leads to a decrease in optical absorption and quenching of fluorescence by a static mechanism, which is similar to the effect of dexamethasone. Artemisinin interacts with Drug site I on HSA and forms a hydrogen bond with arginine 218. Retardation of the genomic DNA of sarcoma S-180 cells show that artemisinin does not interact directly with DNA. On the basis of the obtained data, we proposed a hypothetical scheme of the mechanisms of action of artemisinin.HighlightsArtemisinin quenches the fluorescence of HSA by a static mechanism.Artemisinin quenches fluorescence of tryptophan.The optimized HSA structure was obtained through molecular dynamics simulations.Artemisinin binds with HSA in Drug site I and forms a hydrogen bond with Arg218.Dexamethasone binds with HSA in Drug site I and forms hydrogen bonds with Arg218, Arg222 and Va1343.A hypothetical scheme of the mechanism of action of Artemisinin was proposed.Graphical Abstract
Experimental and mathematical insights on the competition between poliovirus and a defective interfering genome
Authors: Shirogane Yuta , Rousseau Elsa , Voznica Jakub , Rouzine Igor M. , Bianco Simone , Andino Raul 
Published: January 2019

AbstractDuring replication, RNA virus populations accumulate genome alterations, such as mutations and deletions. The interactions between individual variants within the population can determine the fitness of the virus and, thus, the outcome of infection. We developed an ordinary differential equation model to infer the effect of the interaction between defective interfering (DI) replicons and wild-type (WT) poliovirus. We measure production of RNA and viral particles during a single infection cycle, and use these data to infer model parameters. We find that DI replicates faster than WT, but an equilibrium is established when both WT and DI compete for resources needed for RNA replication and genome encapsidation. In the presence of DI, the concentration of WT virions at cell lysis is suppressed by the factor of 5. Multiple generations within a single cell infection provide opportunities for significant inhibition of WT replication by competition with the faster replicating DI genomes.
Improved state change estimation in dynamic functional connectivity using hidden semi-Markov models
Authors: Shappell Heather , Caffo Brian S. , Pekar James J. , Lindquist Martin A. 
Published: January 2019

AbstractThe study of functional brain networks has grown rapidly over the past decade. While most functional connectivity (FC) analyses estimate one static network structure for the entire length of the functional magnetic resonance imaging (fMRI) time series, recently there has been increased interest in studying time-varying changes in FC. Hidden Markov models (HMMs) have proven to be a useful modeling approach for discovering repeating graphs of interacting brain regions (brain states). However, a limitation lies in HMMs assuming that the sojourn time, the number of consecutive time points in a state, is geometrically distributed. This may encourage inaccurate estimation of the time spent in a state before switching to another state. We propose a hidden semi-Markov model (HSMM) approach for inferring time-varying brain networks from fMRI data, which explicitly models the sojourn distribution. Specifically, we propose using HSMMs to find each subject’s most probable series of network states and the graphs associated with each state, while properly estimating and modeling the sojourn distribution for each state. We perform a simulation study, as well as an analysis on both task-based fMRI data from an anxiety-inducing experiment and resting-state fMRI data from the Human Connectome Project. Our results demonstrate the importance of model choice when estimating sojourn times and reveal their potential for understanding healthy and diseased brain mechanisms.
The regulatory function of dIno80 correlates with its DNA binding activity
Authors: Jain S , Maini J , Narang A , Maiti S , Brahmachari V 
Published: January 2019

ABSTRACTThe INO80 complex, including the Ino80 protein, forms a highly conserved canonical complex that remodels chromatin in the context of multiple cellular functions. TheDrosophilahomologue, dIno80, is involved in homeotic gene regulation during development as a canonical Pho-dIno80 complex. Previously, we found that dIno80 regulates homeotic genes by interacting with epigenetic regulators, such as polycomb and trithorax, suggesting the occurrence of non-canonical Ino80 complexes. Here using spectroscopic methods and gel retardation assays, we identified a set of consensus DNA sequences that DNA binding domain of dIno80 (DBINO) interacts with having differential affinity and high specificity. Testing these sequences in reporter assays, showed that this interaction can positively regulate transcription. These results suggest that, dIno80 has a sequence preference for interaction with DNA leading to transcriptional changes.SIGNIFICANCEThe chromatin remodeling proteins control gene expression by nucleosome sliding and exchange. They are known to function as multi-subunit complexes recruited to chromatin by transcription factors or histone modification readers. Here, we report a sequence specific binding potential for the chromatin remodeler, dIno80. We have carried outin vitrostudies with DNA binding domain of dIno80 to elucidate its sequence specific DNA binding. We have also showed that this binding can regulated reporter gene expression inDrosophilacells. Our results suggest a non-canonical role of Ino80 in transcriptional regulation.
Dynamics of chromosome replication and its relationship to predatory attack lifestyles in Bdellovibrio bacteriovorus
Authors: Makowski Łukasz , Trojanowski Damian , Till Rob , Lambert Carey , Lowry Rebecca , Sockett R. Elizabeth , Zakrzewska-Czerwińska Jolanta 
Published: January 2019

AbstractBdellovibrio bacteriovorus is a small Gram-negative, an obligate predatory bacterium that is largely found in wet, aerobic environments (i.e. soil). This bacterium attacks and invades other Gram-negative bacteria, including animal and plant pathogens. The intriguing life cycle of B. bacteriovorus consists of two phases: a free-living non-replicative attack phase wherein the predatory bacterium searches for its prey, and a reproductive phase, in which B. bacteriovorus degrades a host’s macromolecules and reuses them for its own growth and chromosome replication. Although the cell biology of this predatory bacterium has gained considerable interest in recent years, we know almost nothing about the dynamics of chromosome replication in B. bacteriovorus. Here, we performed a real-time investigation into the subcellular localization of the replisome(s) in single cells of B. bacteriovorus. Our results confirm that in B. bacteriovorus chromosome replication fires only during the reproductive phase, and show for the first time that this predatory bacterium exhibits a novel spatiotemporal arrangement of chromosome replication. The replication process starts at the invasive pole of the predatory bacterium inside the prey cell and proceeds until several copies of the chromosome have been completely synthesized. This chromosome replication is not coincident with the predator-cell division, and it terminates shortly before synchronous predator-filament septation occurs. In addition, we demonstrate that if this lifecycle fails in some cells of B. bacteriovorus, they can instead use two prey cells sequentially to complete their life cycle.ImportanceNew strategies are needed to combat multidrug-resistant bacterial infections. Application of the predatory bacterium, Bdellovibrio bacteriovorus, which kills other bacteria including pathogens, is considered promising for bacterial infections. The B. bacteriovorus life cycle consists of two phases, a free-living, invasive attack phase and an intracellular reproductive phase, in which this predatory bacterium degrades the host’s macromolecules and reuses them for its own growth. To understand the use of B. bacteriovorus as a ‘living antibiotic’, it is first necessary to dissect its life cycle including chromosome replication. Here, we present for the first time a real-time investigation into subcellular localization of chromosome replication in a single cells of B. bacteriovorus. This process initiates at the invasion pole of B. bacteriovorus and proceeds until several copies of the chromosome have been completely synthesized. Interestingly, we demonstrate that some cells of B. bacteriovorus require two prey cells sequentially to complete their life cycle.