bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal music perception engages motor prediction: a TMS study
Authors: Gordon Chelsea L. , Iacoboni Marco , Balasubramaniam Ramesh 
Published: June 2018

AbstractCortico-spinal excitability (CSE) in humans measured with Transcranial Magnetic Stimulation (TMS) is generally increased by the perception of other people’s actions. This perception can be unimodal (visual or auditory) or multimodal (visual and auditory). The increase in TMS-measured CSE is typically prominent for muscles involved in the perceived action (muscle specificity). There are two main classes of accounts for this phenomenon. One suggests that the motor system mirrors the actions that the observer perceives (the resonance account). The other suggests that the motor system predicts the actions that the observer perceives (the predictive account). To test these accounts (which need not be mutually exclusive), subjects were presented with four versions of three-note piano sequences: sound only, sight only, audiovisual, and audiovisual with sound lagging behind while CSE was measured in two hand muscles. Muscle specificity did not interact with modality in the flexor digiti minimi (FDM), but was reliably higher for the first dorsal interosseous (FDI) while subjects perceived the audiovisual version of the three-note piano sequences with sound lagging behind. Since this version of the three-note piano sequences is the only one that overtly violates experience-based expectations, this finding supports predictive coding accounts of motor facilitation during action perception.
Gene activation precedes DNA demethylation in response to infection in human dendritic cells
Authors: Pacis Alain , Mailhot-Léonard Florence , Tailleux Ludovic , Randolph Haley E , Yotova Vania , Dumaine Anne , Grenier Jean-Christophe , Barreiro Luis B 
Published: June 2018

ABSTRACTDNA methylation is considered to be a relatively stable epigenetic mark. Yet, a growing body of evidence indicates that DNA methylation levels can change rapidly, for example, in innate immune cells facing an infectious agent. Nevertheless, the causal relationship between changes in DNA methylation and gene expression during infection remains to be elucidated. Here, we generated time-course data on DNA methylation, gene expression, and chromatin accessibility patterns during infection of human dendritic cells with Mycobacterium tuberculosis. We found that the immune response to infection is accompanied by active demethylation of thousands of CpG sites overlapping distal enhancer elements. However, virtually all changes in gene expression in response to infection occur prior to detectable changes in DNA methylation, indicating that the observed losses in methylation are a downstream consequence of transcriptional activation. Footprinting analysis revealed that immune-related transcription factors (TF), such as NF-κB/Rel, are recruited to enhancer elements prior to the observed losses in methylation, suggesting that DNA demethylation is mediated by TF binding to cis-acting elements. Collectively, our results show that DNA demethylation is not required for the establishment of the core regulatory program engaged upon infection.
Robust and stable transcriptional repression inGiardiausing CRISPRi
Authors: McInally SG , Hagen KD , Nosala C , Williams J , Nguyen K , Booker J , Jones K , Scott C. Dawson 
Published: June 2018

AbstractGiardia lambliais a binucleate protistan parasite causing significant diarrheal disease worldwide. An inability to target Cas9 to both nuclei, combined with the lack of non-homologous end joining and markers for positive selection, has stalled the adaptation of CRISPR/Cas9-mediated genetic tools for this widespread parasite. CRISPR interference (CRISPRi) is a modification of the CRISPR/Cas9 system that directs catalytically inactive Cas9 (dCas9) to target loci for stable transcriptional repression. Using aGiardianuclear localization signal to target dCas9 to both nuclei, we developed efficient and stable CRISPRi-mediated transcriptional repression of exogenous and endogenous genes inGiardia. Specifically, CRISPRi knockdown of kinesin-2a and kinesin-13 causes severe flagellar length defects that mirror defects with morpholino knockdown. Knockdown of the ventral disc MBP protein also causes severe structural defects that are highly prevalent and persist in the population more than five days longer than transient morpholino-based knockdown. By expressing two gRNAs in tandem to simultaneously knock down kinesin-13 and MBP, we created a stable dual knockdown strain with both flagellar length and disc defects. The efficiency and simplicity of CRISPRi in polyploidGiardiaallows for rapid evaluation of knockdown phenotypes and highlights the utility of CRISPRi for emerging model systems.
Nested oscillatory dynamics in cortical organoids model early human brain network development
Authors: Trujillo Cleber A. , Gao Richard , Negraes Priscilla D. , Chaim Isaac A. , Domissy Alain , Vandenberghe Matthieu , Devor Anna , Yeo Gene W. , Voytek Bradley , Muotri Alysson R. 
Published: June 2018

SUMMARYStructural and transcriptional changes during early brain maturation follow fixed developmental programs defined by genetics. However, whether this is true for functional network activity remains unknown, primarily due to experimental inaccessibility of the initial stages of the living human brain. Here, we developed cortical organoids that spontaneously display periodic and regular oscillatory network events that are dependent on glutamatergic and GABAergic signaling. These nested oscillations exhibit cross-frequency coupling, proposed to coordinate neuronal computation and communication. As evidence of potential network maturation, oscillatory activity subsequently transitioned to more spatiotemporally irregular patterns, capturing features observed in preterm human electroencephalography (EEG). These results show that the development of structured network activity in the human neocortex may follow stable genetic programming, even in the absence of external or subcortical inputs. Our approach provides novel opportunities for investigating and manipulating the role of network activity in the developing human cortex.HIGHLIGHTSEarly development of human functional neural networks and oscillatory activity can be modeled in vitro.Cortical organoids exhibit phase-amplitude coupling between delta oscillation (2 Hz) and high-frequency activity (100-400 Hz) during network-synchronous events.Differential role of glutamate and GABA in initiating and maintaining oscillatory network activity.Developmental impairment of MECP2-KO cortical organoids impacts the emergence of oscillatory activity.Cortical organoid network electrophysiological signatures correlate with human preterm neonatal EEG features.eTOCBrain oscillations are a candidate mechanism for how neural populations are temporally organized to instantiate cognition and behavior. Cortical organoids initially exhibit periodic and highly regular nested oscillatory network events that eventually transition to more spatiotemporally complex activity, capturing features of late-stage preterm infant electroencephalography. Functional neural circuitry in cortical organoids exhibits emergence and development of oscillatory network dynamics similar to those found in the developing human brain.
Coopting the Lap system ofPseudomonas fluorescensto reversibly customize bacterial cell surfaces
Authors: Smith T. Jarrod , Sondermann Holger , O’Toole George A. 
Published: June 2018

AbstractInitialattachment to a surface is a key and highly regulated step in biofilm formation. In this study, we present a platform for reversibly functionalizing bacterial cell surfaces, with an emphasis on designing biofilms. We engineered the Lap system ofPseudomonas fluorescensPf0-1, which is normally used to regulate initial cell surface attachment, to display various protein cargo at the bacterial cell surface and control extracellular release of the cargo in response to changing levels of the second messenger cdi-GMP. To accomplish this goal, we fused the protein cargo between the N-terminal retention module and C-terminal secretion signal of LapA, and controlled surface localization of the cargo with natural signals known to stimulate or deplete c-di-GMP levels inP. fluorescensPf0-1. We show this system can tolerate large cargo in excess of 500 amino acids, directP. fluorescensPf0-1 to surfaces it does not typically colonize, and program this microbe to sequester the toxic medal cadmium.
Pre-stimulus oscillatory activity predicts successful episodic encoding for both young and older adults
Authors: Strunk Jon , Duarte Audrey 
Published: June 2018

AbstractHealthy aging is associated with declines in episodic memory performance that are due in part to deficits in encoding. Emerging results from young adult studies suggest that the neural activity during the time-period preceding stimulus presentation is sensitive to episodic memory performance. It is unknown whether age-related declines in episodic memory are due solely to changes in the recruitment of processes elicited by stimuli during encoding or also in processes recruited in anticipation of these stimuli. Here, we recorded oscillatory EEG while young and old participants encoded visual and auditory words that were preceded by cues indicating the stimulus modality. Alpha oscillatory activity preceding and following stimulus onset was predictive of subsequent memory accuracy similarly across age. Frontal beta oscillations linked to semantic elaboration during encoding were reduced by age. Post-stimulus theta power was positively predictive of episodic memory accuracy for old but not young adults, potentially reflecting older adults’ tendency to self-generate associations during encoding. Collectively, these results suggest that the preparatory mobilization of neural processes prior to encoding that benefits episodic memory performance is not affected by age.
Adjunct phage treatment enhances the effectiveness of low antibiotic concentration againstStaphylococcus aureusbiofilmsin vitro
Authors: Dickey James , Perrot Véronique 
Published: June 2018

AbstractPhage therapy is drawing more interest as antibiotic resistance becomes an ever more serious threat to public health. Bacterial biofilms represent a major obstacle in the fight against bacterial infections as they are inherently refractory to many types of antibiotics. Treating biofilms with phage has shown promise in a handful of experimental and case studies. However, quantification of the effect of phage combined with antibiotics is needed to pave the way for larger clinical trials. Here we explore the effect of using phage in combination with a total of nine antibiotics, applied simultaneously or as a pretreatment before antibiotics are applied to in vitro biofilms ofStaphylococcus aureus. Most antibiotics alone were ineffective at low concentration (2×MIC), but the addition of phage to treatment regimens led to substantial improvements in efficacy. At high concentration (10×MIC), antibiotics alone were effective, and in most cases the addition of phage to treatment regimens did not improve efficacy. Using phage with rifampin was also very effective at reducing the outgrowth of resistant strains during the course of treatment.
Peculiar features of the plastids of the colourless algaEuglena longaand photosynthetic euglenophytes unveiled by transcriptome analyses
Authors: Záhonová Kristína , Füssy Zoltán , Birčák Erik , Novák Vanclová Anna M. G. , Klimeš Vladimír , Vesteg Matej , Krajčovič Juraj , Oborník Miroslav , Eliáš Marek 
Published: June 2018

AbstractBackground:Euglenophytes are an interesting algal group that emerged within the ancestrally plastid-lacking Euglenozoa phylum by acquiring a plastid from a green algal donor. However, the knowledge of euglenophyte plastid biology and evolution is highly incomplete, partly because euglenophytes have so far been little studied on a genome- and transcriptome-wide scale. Transcriptome data from only a single species,Euglena gracilis, have been exploited to functional insights, but aspects of the plastid biology have been largely neglected.Results:To expand the resources for studying euglenophyte biology and to improve our knowledge of the euglenophyte plastid function and evolution, we sequenced and analysed the transcriptome of the non-photosynthetic speciesEuglena longa. The transcriptomic data confirmed the absence of genes for the photosynthetic machinery in this species, but provided a number of candidate plastid-localized proteins bearing the same type of N-terminal bipartite topogenic signals (BTSs) as known from the photosynthetic speciesE. gracilis. Further comparative analyses using transcriptome assemblies available forE. gracilisand two additional photosynthetic euglenophytes of the genusEutreptiellaenabled us to unveil several salient aspects of the basic plastid infrastructure in euglenophytes. First, a number of plastidial proteins seem to reach the organelle as C-terminal translational fusions with other BTS-bearing proteins. Second, the conventional eubacteria-derived plastidial ribosomal protein L24 is missing and seems to have been replaced by very different homologs of the archaeo-eukaryotic origin. Third, no homologs of any key component of the TOC/TIC system (translocon of the outer/inner chloroplast membrane) and the plastid division apparatus are discernible in euglenophytes, and the machinery for intraplastidial protein targeting has been simplified by the loss of the cpSRP/cpFtsY system and the SEC2 translocon. Lastly, euglenophytes proved to encode a plastid-targeted homolog of the termination factor Rho horizontally acquired from a Lambdaproteobacteria-related donor, suggesting an unprecedented modification of the transcription mechanism in their plastid.Conclusions:Our study suggests that the euglenophyte plastid has been substantially remodelled comparted to its green algal progenitor by both loss of original and acquisition of novel molecular components, making it a particularly interesting subject for further studies.
Seizures start as silent microseizures by neuronal ensembles
Authors: Wenzel Michael , Hamm Jordan P. , Peterka Darcy S. , Yuste Rafael MD 
Published: June 2018

AbstractUnderstanding seizure formation and spread remains a critical goal of epilepsy research. While many studies have documented seizure spread, it remains mysterious how they start. We used fast in-vivo two-photon calcium imaging to reconstruct, at cellular resolution, the dynamics of focal cortical seizures as they emerge in epileptic foci (intrafocal), and subsequently propagate (extrafocal). We find that seizures start as intrafocal coactivation of small numbers of neurons (ensembles), which are electrographically silent. These silent “microseizures” expand saltatorily until they break into neighboring cortex, where they progress smoothly and first become detectable by LFP. Surprisingly, we find spatially heterogeneous calcium dynamics of local PV interneuron sub-populations, which rules out a simple role of inhibitory neurons during seizures. We propose a two-step model for the circuit mechanisms of focal seizures, where neuronal ensembles first generate a silent microseizure, followed by widespread neural activation in a travelling wave, which is then detected electrophysiologically.
Transcriptomic analysis of fetal membranes reveals pathways involved in preterm birth
Authors: Pereyra Silvana , Sosa Claudio , Bertoni Bernardo , Sapiro Rossana 
Published: June 2018

AbstractPreterm birth (PTB), defined as infant delivery before 37 weeks of completed gestation, results of the interaction of both genetic and environmental components and constitutes a complex multifactorial syndrome. Transcriptome analysis of PTB has proved challenging because of the multiple causes of PTB and the numerous maternal and fetal gestational tissues that must interact to facilitate parturition. A common pathway of labor and PTB may be the activation of fetal membranes. In this work, chorioamnion membranes from severe preterm and term fetus were analyzed using RNA sequencing. A total of 270 genes were differentially expressed (DE): 252 were up-regulated and 18 were down-regulated in the severe preterm compared to the term births. We found great gene expression homogeneity in the control samples, and not in severe preterm samples. In this work, we identified up-regulated pathways that were previously suggested as leading to PTB like immunological and inflammatory paths. New pathways that were not identified in preterm like the hemopoietic path appeared up-regulated in preterm membranes. A group of 18 down-regulated genes discriminates between term and severe preterm cases. These genes potentially characterize a severe preterm transcriptome pattern and therefore are candidate genes for understanding the syndrome. Some of the down-regulated genes are involved in the nervous system, morphogenesis (WNT-1, DLX5, PAPPA2) and ion channel complexes (KCNJ16, KCNB1), making them good candidates as biomarkers of PTB.The identification of this DE gene pattern may help to develop a multi-gene disease classifier. These markers were generated in an admixtured South American population where PTB has a high incidence. Since genetic background may impact differentially in different populations it is mandatory to include populations like South American and African ones that are usually excluded from high throughput approaches. These classifiers should be compared to those in other populations to get a global landscape of PTB.
Visual signals suppress Alpha Power Increases & Frequency Decreases before and after a Mindfulness Meditation Intervention for Problem Gambling
Authors: Martin Kaili-Larissa , Jindani Farah , Turner Nigel , DeSouza Joseph FX 
Published: June 2018

AbstractThe use of mindfulness meditation (MM) in the treatment of problem gambling (PG), has been used effectively for over five years. However, the neural mechanisms responsible for the improvements are unknown. The literature describes healthy individuals with an increase in alpha power and a decrease in alpha frequency after eight weeks of mindfulness meditation, but it is unknown if changes are similar amongst individuals with PG. Using resting-state electroencephalography (rsEEG), we measured the changes in alpha oscillations before and after an eight-week mindfulness meditation intervention (MMi) and a pre/ post-five-minute mindfulness meditation body scan (MMb). For people with PG, we observed an increase in alpha power and decreased alpha peak frequency after the MMi, while the inverse was true for the MMb. The most considerable alpha rhythm changes occurred in the frontal and temporal lobes, areas sensitive to reward and sensory processing in PG. Our observed changes may reflect theories that MMi for PG may improve attentional control as hypothesized by previous research in alpha oscillations and cue-reward processing.
Neurobiological Basis of Brain Blood Oxygenation Responses Correlated with Cognitive Stroop Task Performance Before and After an Acute Bout of Aerobic Exercise
Authors: Pal Amrita 
Published: June 2018

ABSTRACTCardiovascular activities may increase the brain blood flow improving neural activities leading to improved cognition. Consequently, the effects of an acute bout of moderate intensity aerobic exercise on cortical brain blood oxygenation and its correlation with cognitive color-word Stroop task performance were tested. The Stroop tasks were congruent (color matches word) and incongruent (color does not match word). Prefrontal (PFC) and motor cortex (MC) blood flow was recorded by fNIRS (functional Near-Infrared Spectroscopy) while the human subjects performed the Stroop tasks before and after 30 minutes of exercise or equivalent time of rest (controlling for practice effect of repeating the Stroop task multiple times). It was predicted that PFC blood flow increase after exercise will correlate with increased Stroop interference and decreased cognitive flexibility after an acute bout of aerobic exercise at 70% of maximal Heart Rate (HR). We observed that Stroop interference in aerobic exercise and practice alone (rest) were not significantly (p>0.6) different indicating that exercise did not improve cognition above the learning effect. Increase in blood flow (both neurovascular and neurometabolic coupling) in previously deactivated PFC channels was positively correlated (p<0.05) to increased Stroop interference (worse cognitive speed and accuracy) after an acute bout of aerobic exercise.HighlightsDoes moderate intensity aerobic exercise improve cognition?Does prefrontal cortex oxygenation correlate with cognition changes after exercise?
Using LASSO in gene co-expression network for genome-wide identification of gene interactions responding to salt stress in rice
Authors: Du Qian , Campbell Malachy , Yu Huihui , Liu Kan , Walia Harkamal , Zhang Qi , Zhang Chi 
Published: June 2018

AbstractIn many applications, such as gene co-expression network analyses, data arises with a huge number of covariates while the size of sample is comparatively small. To improve the accuracy of prediction, variable selection is often used to get a sparse solution by forcing coefficients of variables contributing less to the observed response variable to zero. Various algorithms were developed for variable selection, but LASSO is well known for its statistical accuracy, computational feasibility and broad applicability to adaptation. In this project, we applied LASSO to the gene co-expression network of rice with salt stress to discover key gene interactions for salt-tolerance related phenotypes. The dataset we have is a high-dimensional one, having 50K genes from 100 samples, with the issue of multicollinearity for fitting linear regression - the expression level of genes in the same pathway tends to be highly correlated. The property of LASSO with sparse parameters is naturally suitable to identify gene interactions of interest in this dataset. After biologically functional modules in the co-expression network was identified, the major changed expression patterns were further selected by LASSO regression to establish a linear relationship between gene expression profiles and physiological responses, such as sodium/potassium condenses, with salt stress. Five modules of intensively co-expressed genes, from 45 to 291 genes, were identified by our method with significant P-values, which indicate these modules are significantly associated with physiological responses to stress. Genes in these modules have functions related to ion transport, osmotic adjustment, and oxidative tolerance. For example, LOC_Os7g47350 and LOC_Os07g37320 are co-expressed gene in the same module 15. Both are ion transporter genes and have higher gene expression levels for rice with low sodium levels with salt stress.
Non-enzymatic roles of human RAD51 at stalled replication forks
Authors: Mason Jennifer M. , Chan Yuen-Ling , Weichselbaum Ralph W. , Bishop Douglas K. 
Published: June 2018

ABSTRACTThe central recombination enzyme RAD51 has been implicated in replication fork processing and restart in response to replication stress. Here, we use a separation-of-function allele of RAD51 that retains DNA binding, but not strand exchange activity, to reveal mechanistic aspects of RAD51’s roles in the response to replication stress. We find that cells lacking RAD51 strand exchange activity protect replication forks from MRE11-dependent degradation, as expected from previous studies. Unexpectedly we find that RAD51’s strand exchange activity is not required to convert stalled forks to a form that can be degraded by DNA2. Such conversion was shown previously to require replication fork reversal, supporting a model in which fork reversal depends on a non-enzymatic function of RAD51. We also show RAD51 promotes replication restart by both strand exchange-dependent and strand exchange-independent mechanisms.