bluuebunny/crossref_metadata_2025_split huggingface dataset:
The fate of hippocampal synapses depends on the sequence of plasticity-inducing events
Authors: Wiegert J. Simon , Pulin Mauro , Gee Christine E. , Oertner Thomas G. 
Published: May 2018

AbstractSynapses change their strength in response to specific activity patterns. This functional plasticity is assumed to be the brain’s primary mechanism for information storage. We used optogenetic stimulation of rat hippocampal slice cultures to induce long-term potentiation (LTP), long-term depression (LTD), or both forms of plasticity in sequence. Two-photon imaging of spine calcium signals allowed us to identify stimulated synapses and to follow their fate for the next 7 days. We found that plasticity-inducing protocols affected the synapse’s chance for survival: LTP increased synaptic stability, LTD destabilized synapses, and the effect of the last stimulation protocol was dominant over earlier stimulations. Interestingly, most potentiated synapses were resistant to depression-inducing protocols delivered 24 hours later. Our findings suggest that activity-dependent changes in the transmission strength of individual synapses are transient, but have long-lasting consequences for synaptic lifetime.
Using the Wax moth larvaGalleria mellonellainfection model to detect emerging bacterial pathogens
Authors: Hernandez Rafael J. , Hesse Elze , Dowling Andrea J. , Coyle Nicola M. , Feil Edward J. , Gaze Will H. , Vos Michiel 
Published: May 2018

AbstractClimate change, changing farming practices, social and demographic changes and rising levels of antibiotic resistance are likely to lead to future increases in opportunistic bacterial infections that are more difficult to treat. Uncovering the prevalence and identity of pathogenic bacteria in the environment is key to assessing transmission risks. We describe the first use of the Wax moth larvaGalleria mellonella, a well-established model for the mammalian innate immune system, to selectively enrich and characterize pathogens from coastal environments in the South West of the U.K. Whole-genome sequencing of highly virulent isolates revealed amongst others aProteus mirabilisstrain carrying theSalmonellaSGI1 genomic island not reported from the U.K. before and the recently described speciesVibrio injenensishitherto only reported from human patients in Korea. Our novel method has the power to detect novel bacterial pathogens in the environment that potentially pose a serious risk to public health.
Extended haplotype phasing of de novo genome assemblies with FALCON-Phase
Authors: Kronenberg Zev N. , Rhie Arang , Koren Sergey , Concepcion Gregory T. , Peluso Paul , Munson Katherine M. , Hiendleder Stefan , Fedrigo Olivier , Jarvis Erich D. , Phillippy Adam M. , Eichler Evan E. , Williams John L. , Smith Tim P.L. , Hall Richard J. , Sullivan Shawn T. , Kingan Sarah B. 
Published: May 2018

ABSTRACTHaplotype-resolved genome assemblies are important for understanding how combinations of variants impact phenotypes. These assemblies can be created in various ways, such as use of tissues that contain single-haplotype (haploid) genomes, or by co-sequencing of parental genomes, but these approaches can be impractical in many situations. We present FALCON-Phase, which integrates long-read sequencing data and ultra-long-range Hi-C chromatin interaction data of a diploid individual to create high-quality, phased diploid genome assemblies. The method was evaluated by application to three datasets, including human, cattle, and zebra finch, for which high-quality, fully haplotype resolved assemblies were available for benchmarking. Phasing algorithm accuracy was affected by heterozygosity of the individual sequenced, with higher accuracy for cattle and zebra finch (>97%) compared to human (82%). In addition, scaffolding with the same Hi-C chromatin contact data resulted in phased chromosome-scale scaffolds.
Growth zone segmentation in the milkweed bug Oncopeltus fasciatus sheds light on the evolution of insect segmentation
Authors: Auman Tzach , Chipman Ariel D. 
Published: May 2018

AbstractOne of the best studied developmental processes is the Drosophila segmentation cascade. However, this cascade is generally considered to be highly derived and unusual. We present a detailed analysis of the sequential segmentation cascade of the milkweed bug Oncopletus fasciatus, as a comparison to Drosophila, with the aim of reconstructing the evolution of insect segmentation. We analyzed the expression of 12 genes, representing different phases during segmentation. We reconstruct the spatio-temporal relationships among these genes And their roles and position in the cascade. We conclude that sequential segmentation in the Oncopeltus germband includes three phases: Primary pair-rule genes generate segmental gene expression in the anterior growth zone, followed by secondary pair-rule genes, expressed in the transition between the growth zone and the segmented germband. Segment polarity genes are expressed in the segmented germband. This process generates a single-segment periodicity, and does not have a double-segment pattern at any stage.
Infections patterns and fitness effects ofRickettsiaandSodalissymbionts in the green lacewingChrysoperla carnea
Authors: Sontowski Rebekka , Gerth Michael , Richter Sandy , Gruppe Axel , Schlegel Martin , van Dam Nicole , Bleidorn Christoph 
Published: May 2018

AbstractEndosymbionts are wide-spread among insects and can play an essential role in host ecology. The common green lacewing (Chrysoperla carneas. str.) is a neuropteran insect species which is widely used as a biological pest control. We screened for endosymbionts in natural and laboratory populations of the green lacewing using diagnostic PCR amplicons. We found the endosymbiontRickettsiato be very common in all screened populations, whereas a so far uncharacterizedSodalisstrain was solely found in laboratory populations. The newSodalisstrain was characterized using a whole genome shotgun approach. Its draft genome revealed an approximate genome size of 4.3 Mbp and the presence of 5213 coding sequences. Phylogenomic analyses indicated that this bacterium is the sister taxon ofS. praecaptivus. In an experimental approach, we found a negative impact ofSodalison the reproduction success of the green lacewing. Co-infections withRickettsiaandSodaliscaused an even higher decrease of reproductive success than singleSodalisinfections. In contrast, no significant fitness differences were found inRickettsiainfected green lacewings compared to uninfected lacewings. TheRickettsia/Sodalis/Ch. carneasystem presents a promising model to study evolutionary endosymbiont-host interactions in Neuroptera and endosymbiont-endosymbiont interactions in general. The economic and ecological importance of green lacewings in biological pest control warrants a more profound understanding of its biology, which might be strongly influenced by symbionts.
The connexin 43 regulator Rotigaptide reduces cytokine-induced cell death in human islets
Authors: Ghiasi Seyed Mojtaba , Hansen Jakob Bondo , Christensen Dan Ploug , Mandrup-Poulsen Thomas 
Published: May 2018

AbstarctBackgroundIntercellular communication mediated by cationic fluxes through the Connexin-family of gap-junctions regulates glucose-stimulated insulin-secretion and beta-cell defense against inflammatory stress. Rotigaptide (RG, ZP123) is a peptide analog that increases intercellular conductance in cardiac muscle-cells by prevention of dephosphorylation and thereby uncoupling of Connexin-43 (Cx43), possibly via action on unidentified protein phosphatases. For this reason, it is being studied in human arrhythmias. It is unknown if RG protects beta-cell function and viability against inflammatory or metabolic stress, a question of considerable translational interest for the treatment of beta-cell failure in diabetes.MethodsApoptosis was measured in human islets known to express Cx43, treated with RG or the control peptide ZP119 and exposed to glucolipotoxicity or IL-1b + IFNg. INS-1 cells shown to lack Cx43 were used to verify if RG protected human islet-cells via Cx43-coupling. To study mechanisms of action of Cx43-independent effects of RG, NO, IkBa degradation, mitochondrial activity, ROS and insulin mRNA levels were determined.ResultsRG reduced cytokine-induced apoptosis ~40% in human islets. In Cx43-deficient INS-1 cells this protective effect was markedly blunted as expected, but unexpectedly RG still modestly reduced apoptosis, and improved mitochondrial function, insulin-2 gene levels and accumulated insulin release. RG reduced NO production in Cx43-deficient INS-1 cells associated with reduced iNOS-expression, suggesting that RG blunts cytokine-induced NF-kB signaling in insulin-producing cells in a Cx43-independent manner.ConclusionRG reduces cytokine-induced cell-death in human islets. The protective action in Cx43-deficient INS-1 cells suggests a novel inhibitory mechanism of action of RG on NF-kB signaling.
Photodynamic therapy effect on the ultrastructure of Trichomonas vaginalis trophozoites and their effectiveness in experimentally infected animals
Authors: Fonseca Thaisa H.S. , Gomes Jessica M.S. , Alacoque Marina , Vannier-Santos Marcos A. , Gomes Maria A. , Busatti Haendel G.N.O. 
Published: May 2018

AbstractBackgroundTrichomonas vaginalis is an amitochondrial parasitic that causes human trichomoniasis, the most common non-viral sexually transmitted infection in the world. The therapy of choice is metronidazole (MTZ). Despite MTZ effectiveness, resistant cases are becoming more frequent. Another point to emphasize are the side effects that may result in treatment discontinuation, leading to further spread of infection and emergence of resistant strains. This scenario reveals the need to develop new therapeutic options. Photodynamic therapy (PDT) is an experimental treatment that involves the activation of photosensitive substances and the generation of cytotoxic oxygen species and free radicals to promote the selective destruction of target tissues. A previous study, from our group, identified an excellent in vitro PDT activity using methylene blue and light emitting diode against MTZ sensitive and resistant strains of T. vaginalis. The aim of this study was to evaluate the efficacy of PDT in vivo and clarify its high trichomonicidal potential by evaluating its action upon T. vaginalis trophozoites through transmission electron microscopy (TEM).MethodologySeven-week-old female Balb/c mice were infected intravaginally with T. vaginalis trophozoites. On the third day of infection, methylene blue was introduced into the vaginal canal of the animals, which then received 68.1 J / cm2 of radiation for 35.6 sec. Control groups without infection and infected, treated with metronidazole were also included for comparison. Twenty-four hours after treatment the vaginal canal of the animals was scraped and the samples processed by the immunocytochemistry technique.
After in vitro photodynamic treatment, T. vaginalis trophozoites were processed for TEM. Ultrathin sections were collected in 400-mesh copper grids, contrasted with 5% uranyl acetate and 3% lead citrate, in aqueous solutions for 20 and 5 min., respectively and observed in a Jeol JEM 230 transmission electron microscope.ResultsTEM showed morphological changes such as centripetal displacement of organelles, cannibalism, hydrogenosomal damage, intense cytoplasmic vacuolization, dilated endoplasmic reticulum cisternae and membrane discontinuity, in both resistant and sensitive strains, suggesting that trichomonicidal activity is mainly due to necrosis.PDT significantly reduced infection in animals treated with a single therapy session, compared to control groups, being statistically as efficient as MTZ.ConclusionsOur results demonstrated high trichomonicidal activity of PDT with morphological alterations compatible with necrosis. Therefore these results indicate that PDT represents not only an alternative therapy for refractory trichomoniasis, but also routinely for this important neglected parasitic disease.
Reconstruction of consensus tissue-specific metabolic models
Authors: Correia Sara , Costa Bruno , Rocha Miguel 
Published: May 2018

AbstractGenome-Scale Metabolic Models have shown promising results in biomedical applications, such as understanding cancer metabolism and drug discovery. However, to take full advantage of these models there is the need to address the representation and simulation of the metabolic phenotypes of distinct cell types. With this aim, several algorithms have been recently proposed to reconstruct tissue-specific metabolic models based on available data. Here, the most promising were implemented and used to reconstruct models for two case studies, using omics data from distinct sources. The set of obtained models were compared and analyzed, being shown they are highly variable and that no combination of algorithm and data source can achieve models with acceptable phenotype predictions. We propose an algorithm to achieve a consensus model from the set of models available for a given tissue/cell line, and to improve it given functional data (e.g. known metabolic tasks). The results show that the resulting models are more accurate, both considering the prediction of known metabolic phenotypes and of experimental data not used in the model construction. Two case studies used for model validation consider healthy hepatocytes and a glioblastoma cell line. The open-source implementation of the algorithms is provided, together with the models built, in a software container, allowing full reproducibility, and representing by itself a contribution for the community.
Self-organising coordinate transformation with peaked and monotonic gain modulation in the primate dorsal visual pathway
Authors: Navarro Daniel M. , Mender Bedeho M. W. , Smithson Hannah E. , Stringer Simon M. 
Published: May 2018

AbstractWe study a self-organising neural network model of how visual representations in the primate dorsal visual pathway are transformed from an eye-centred to head-centred frame of reference. The model has previously been shown to robustly develop head-centred output neurons with a standard trace learning rule [1], but only under limited conditions. Specifically it fails when incorporating visual input neurons with monotonic gain modulation by eye-position. Since eye-centred neurons with monotonic gain modulation are so common in the dorsal visual pathway, it is an important challenge to show how efferent synaptic connections from these neurons may self-organise to produce head-centred responses in a subpopulation of postsynaptic neurons. We show for the first time how a variety of modified, yet still biologically plausible, versions of the standard trace learning rule enable the model to perform a coordinate transformation from eye-centred to head-centred reference frames when the visual input neurons have monotonic gain modulation by eye-position.
Healthy Ageing and Sentence Production: Disrupted Lexical Access in the Context of Intact Syntactic Planning
Authors: Hardy Sophie M. , Segaert Katrien , Wheeldon Linda 
Published: May 2018

AbstractHealthy ageing does not affect all features of language processing equally. In this study, we investigated the effects of ageing on different processes involved in fluent sentence production, a complex task that requires the successful execution and coordination of multiple processes. In Experiment 1, we investigated age-related effects on the speed of syntax selection using a syntactic priming paradigm. Both young and older adults produced target sentences quicker following syntactically related primes compared to unrelated primes, indicating that syntactic facilitation effects are preserved with age. In Experiment 2, we investigated age-related effects in syntactic planning and lexical retrieval using a planning scope paradigm: participants described moving picture displays designed to elicit sentences with either initial coordinate or simple noun phrases and, on half of the trials, the second picture was previewed. Without preview, both age groups were slower to initiate sentences with larger coordinate phrases, suggesting a similar phrasal planning scope. However, age-related differences did emerge relating to the preview manipulation: while young adults displayed speed benefits of preview in both phrase conditions, older adults only displayed speed preview benefits within the initial phrase (coordinate condition). Moreover, preview outside the initial phrase (simple condition) caused older adults to become significantly more error-prone. Thus, while syntactic planning scope appears unaffected by ageing, older adults do appear to encounter problems with managing the activation and integration of lexical items into syntactic structures. Taken together, our findings indicate that healthy ageing disrupts the lexical, but not the syntactic, processes involved in sentence production.
PROTEOME-WIDE ANALYSIS OF CD8+ T CELL RESPONSES TO EBV REVEALS DIFFERENCES BETWEEN PRIMARY AND PERSISTENT INFECTION
Authors: Forrest Calum , Hislop Andrew D. , Rickinson Alan B , Zuo Jianmin 
Published: May 2018

ABSTRACT (286 words)Human herpesviruses are antigenically rich agents that induce strong CD8+T cell responses in primary infection yet persist for life, continually challenging T cell memory through recurrent lytic replication and potentially influencing the spectrum of antigen-specific responses. Here we describe the first lytic proteome-wide analysis of CD8+ T cell responses to the Epstein-Barr gamma1-herpesvirus (EBV), and the first such proteome-wide analysis of primary versus memory CD8 responses to any human herpesvirus. Primary effector preparations were generated directly from activated CD8+ T cells in the blood of infectious mononucleosis (IM) patients by in vitro mitogenic expansion. For memory preparations, EBV-specific cells in the blood of long-term virus carriers were first re-stimulated in vitro by autologous dendritic cells loaded with a lysate of lytically-infected cells, then expanded as for IM cells. Preparations from 7 donors of each type were screened against each of 70 EBV lytic cycle proteins in combination with the donor’s individual HLA class I alleles. Multiple reactivities against immediate early (IE), early (E) and late (L) lytic cycle proteins, including many hitherto unrecognised targets, were detected in both contexts. Interestingly however, the two donor cohorts showed a different balance between IE, E and L reactivities. Primary responses targeted IE and a small group of E proteins preferentially, seemingly in line with their better presentation on the infected cell surface before later-expressed viral evasins take full hold. By contrast, target choice equilibrates in virus carriage with responses to key IE and E antigens still present but with responses to a select subset of L proteins now often prominent. We infer that, for EBV at least, long-term virus carriage with its low level virus replication and lytic antigen release is associated with a re-shaping of the virus-specific response.
Extracellular Electron Transfer by Shewanella oneidensis Controls Pd Nanoparticle Phenotype
Authors: Dundas Christopher M. , Graham Austin J. , Romanovicz Dwight K. , Keitz Benjamin K. 
Published: May 2018

AbstarctBiological production of inorganic materials is impeded by relatively few organisms possessing genetic and metabolic linkage to material properties. The physiology of electroactive bacteria is intimately tied to inorganic transformations, which makes genetically tractable and well-studied electrogens, such as Shewanella oneidensis, attractive hosts for material synthesis. Notably, this species is capable of reducing a variety of transition-metal ions into functional nanoparticles, but exact mechanisms of nanoparticle biosynthesis remain ill-defined. We report two key factors of extracellular electron transfer by S. oneidensis, the outer membrane cytochrome, MtrC, and soluble redox shuttles (flavins), that affect Pd nanoparticle formation. Changes in the expression and availability of these electron transfer components drastically modulated particle phenotype, including particle synthesis rate, structure, and cellular localization. These relationships may serve as the basis for biologically tailoring Pd nanoparticle catalysts and could potentially be used to direct the biogenesis of other metal nanomaterials.
StomataCounter: a neural network for automatic stomata identification and counting
Authors: Fetter Karl C. , Eberhardt Sven , Barclay Rich S. , Wing Scott , Keller Stephen R. 
Published: May 2018

ABSTRACTStomata regulate important physiological processes in plants and are often phenotyped by researchers in diverse fields of plant biology. Currently, there are no user friendly, fully-automated methods to perform the task of identifying and counting stomata, and stomata density is generally estimated by manually counting stomata.We introduce StomataCounter, an automated stomata counting system using a deep convolutional neural network to identify stomata in a variety of different microscopic images. We use a human-in-the-loop approach to train and refine a neural network on a taxonomically diverse collection of microscopic images.Our network achieves 98.1% identification accuracy on Ginkgo SEM micrographs, and 94.2% transfer accuracy when tested on untrained species.To facilitate adoption of the method, we provide the method in a publicly available website at http://www.stomata.science/.
Identification and quantification of modified nucleosides inSaccharomyces cerevisiaemRNAs
Authors: Tardu Mehmet , Lin Qishan , Koutmou Kristin S. 
Published: May 2018

ABSTRACTPost-transcriptional nucleoside modifications have long been recognized as key modulators of non-coding RNA structure and function. There is an emerging appreciation that the chemical modification of protein-coding messenger RNAs (mRNAs) also plays critical roles in the cell. Although there are over 100 known RNA modifications found in biology only a handful have been identified in mRNAs. We sought to identify and quantify modifications present in the mRNAs of yeast cells using a high throughput ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method that measures the levels of 36 types of RNA nucleosides in parallel. We detected the presence of six modified nucleosides in mRNAs at relatively high abundances: N7-methylguanosine, N6-methyladenosine, 2’-O-methylguanosine, 2’-O-methylcytosine, N4-acetylcytidine and 5-formylcytidine. Additionally, we investigated how the levels of mRNA modifications vary in response to cellular stress. We find that the concentrations of mRNA modifications including N6-methyladenosine and N4-acetylcytidine change in response to heat stress, glucose starvation and/or oxidative stress. This work expands the repertoire of potential chemical modifications in mRNAs, and utilizes a high-throughput approach to search for modifications that highlights the value of integrating mass-spectrometry tools in the mRNA modification discovery and characterization pipeline.
Incorporating Context into Language Encoding Models for fMRI
Authors: Jain Shailee , Huth Alexander G 
Published: May 2018

AbstractLanguage encoding models help explain language processing in the human brain by learning functions that predict brain responses from the language stimuli that elicited them. Current word embedding-based approaches treat each stimulus word independently and thus ignore the influence of context on language understanding. In this work, we instead build encoding models using rich contextual representations derived from an LSTM language model. Our models show a significant improvement in encoding performance relative to state-of-the-art embeddings in nearly every brain area. By varying the amount of context used in the models and providing the models with distorted context, we show that this improvement is due to a combination of better word embeddings learned by the LSTM language model and contextual information. We are also able to use our models to map context sensitivity across the cortex. These results suggest that LSTM language models learn high-level representations that are related to representations in the human brain.