bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequencing reveals genetic diversity in Mycobacterium avium subspecies paratuberculosis population circulating in Irish cattle
Authors: Perets Viktor , Cassidy Sophie , Kenny Kevin , O'Connor Aoife , O'Mahony Jim , Crispell Joseph , Gordon Stephen 
Published: January 2020

Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne’s Disease (JD), a chronic enteritis, in cattle. Whole genome sequencing (WGS) has been applied to many pathogen systems, where its unprecedented resolution has greatly enhanced our understanding of the molecular epidemiology of pathogen transmission. However, WGS has seen limited application to MAP; understanding the transmission dynamics of MAP will inform control of JD. We report the first study into the application of WGS to MAP in Ireland.
DNA was extracted from 167 MAP isolates sourced from cattle across Ireland. Libraries were prepared and sequenced on an Illumina-NextSeq500 platform. Sequencing data were processed using an in-house bioinformatic pipeline, which trimmed reads, aligned them to the reference genome MAP K10, followed by variant calling, quality filtering and construction of a maximum-likelihood phylogeny. DNA extracts were also used for MIRU-VNTR typing.
The resulting phylogeny shows that the MAP population present in Irish cattle is genetically diverse, which may have resulted from importation of MAP strains from across Europe into Ireland. Similar diversity was observed in a WGS study that noted the impact of cattle imports on the Canadian MAP population. Some Irish isolates were genetically similar to European and Canadian isolates.
Comparing our WGS data with MIRU-VNTR indicates that MIRU-VNTR has limited resolution for discriminating MAP strains, and often does not distinguish isolates to sufficient resolution.
The genomic data presented here provide the first snapshot of genetic diversity of Irish MAP and a baseline for future studies into spread and persistence of MAP in Irish cattle.
Using metagenomics to investigate the impact of hospital stay and the ARK intervention on the human gut resistome
Authors: Yokoyama Maho , Peto Leon , Walker A. Sarah , Llewelyn Martin 
Published: January 2020

Antimicrobials are vital for modern medicine. Antimicrobial use selects for antimicrobial resistant bacteria, particularly among the gut microflora. Minimising antimicrobial resistance (AMR) selection by avoiding unnecessary antibiotic use helps combat AMR. Metagenomic analyses have the potential to provide accurate detection and quantification of AMR genes within an individual’s gut microbiome (gut ‘resistome’), allowing the impact of different types of antibiotic exposures to be evaluated and guide interventions to reduce AMR.
We have developed a short-read sequencing approach to characterise the gut ‘resistome’ and piloted this in two clinical sample sets.
The first consisted of paired stool samples from older hospitalised adults. 25 pairs of samples (1 to 50 days apart) showed a median AMR gene reads/kb/million total reads (RPKM) of 1841 (124 to 17,832), and a median AMR gene count of 55 (2 to 101).
The second consisted of faecal discards from Clostridium difficile testing at a hospital eleven months apart. In these samples (n=21) the median AMR gene read was 923 RPKM (240 to 19,475), and the median AMR gene count was 36 (9 to 82).
In both sample sets there was a trend towards an increase in AMR gene RPKM and number between the time points. dfrF, ErmB and tetW were the commonest AMR genes in both sample sets.
This approach is being applied to analyse the impact of an intervention (ARK-Hospital) designed to change antibiotic prescribing behaviour. The data will allow us to determine the patient-level impact of reduced antibiotic exposure on carried AMR.
The role of the cingulate cortex in the generation of motor tics and the experience of the premonitory urge-to-tic in Tourette syndrome
Authors: Jackson Stephen R. , Sigurdsson Hilmar P. , Dyke Katherine , Condon Maria , Jackson Georgina M. 
Published: January 2020

AbstractTourette syndrome (TS) is a neurological disorder of childhood onset that is characterised by the occurrence of motor and vocal tics. TS is associated with cortical-striatal-thalamic-cortical circuit [CSTC] dysfunction and hyper-excitability of cortical limbic and motor regions that are thought to lead to the occurrence of tics. Individuals with TS often report that their tics are preceded by ‘premonitory sensory/urge phenomena’ (PU) that are described as uncomfortable bodily sensations that precede the execution of a tic and are experienced as a strong urge for motor discharge. While the precise role played by PU in the occurrence of tics is largely unknown, they are nonetheless of considerable theoretical and clinical importance as they form a core component of many behavioural therapies used in the treatment of tic disorders. Recent evidence indicates that the cingulate cortex may play an important role in the generation of PU in TS, and in ‘urges-for-action’ more generally. In the current study we utilised voxel-based morphometry (VBM) techniques, together with ‘seed-to-voxel’ structural covariance network (SCN) mapping, to investigate the putative role played by the cingulate cortex in the generation of motor tics and the experience of PU in a relatively large group of young people with TS. Whole-brain VBM analysis revealed that TS was associated with clusters of significantly reduced grey matter volumes bilaterally within: the orbito-frontal cortex; the cerebellum; and the anterior and mid cingulate cortex. Similarly, analysis of SCNs associated with bilateral mid- and anterior-cingulate ‘seed’ regions demonstrated that TS is associated withincreasedstructural covariance primarily with the bilateral motor cerebellum; the inferior frontal cortex; and the posterior cingulate cortex.
The dynamics of the improvising brain: a study of musical creativity using jazz improvisation
Authors: Da Mota Patricia Alves , Fernandes Henrique M , Stark Eloise , Cabral Joana , Heggli Ole Adrian , Sousa Nuno , Kringelbach Morten L , Vuust Peter 
Published: January 2020

AbstractThe neuroscience of jazz improvisation has shown promising results for understanding domain-specific and domain-general processes of creativity. Here, we used fMRI to measure for the first time the dynamic neural substrates of musical creativity in 16 skilled jazz pianists while they played by memory, improvised freely (iFreely) and by melody (iMelody), and during resting-state. We used the Leading Eigenvector Dynamics Analysis (LEiDA) to examine how different modes of improvisation (musical creativity) evolve over time, and which cognitive mechanisms are responsible for different stages of musical creation. Our results reveal that a substate comprising auditory, sensorimotor and posterior salience networks had a significantly higher probability of occurrence (POc) in both modes of improvisation than in resting-state and play by memory. Another substate comprising the default mode (DMN), executive control (ECN) and language networks had significantly lower POc iniFreelythan in resting-state, withiMelodyhaving a higher POc thaniFreely.Such indicates thatiMelody,a more constrained form of creativity involves a higher recurrence of subsystems responsible for goal-directed cognition and cognitive control processes. On the other hand,iFreelyrecruits brain networks responsible for generation of spontaneous musical creativity. Overall, this study brings new insights into the large-scale brain mechanisms supporting and promoting the complex process of creativity, specifically in the context of jazz improvisation, as well as the relevance of different improvisation modes in creativity research.
Low contribution of rare species to resilience and adaptive capacity in novel spatial regimes arising from biome shifts caused by global change
Authors: Angeler David G. , Roberts Caleb P. , Twidwell Dirac , Allen Craig R. 
Published: January 2020

AbstractHuman activity causes biome shifts that alter biodiversity and spatial resilience patterns, ultimately challenging conservation. Rare species, often considered vulnerable to change and endangered, can be a critical element of resilience by providing adaptive capacity in response to disturbances. However, little is known about changes in rarity and dominance patterns of communities once a biome transitions into a novel spatial regime, and how this affects conservation. We used time series modeling to identify species rarity and dominance patterns in an expanding terrestrial (southern) spatial regime in the North American Great Plains and another (northern) regime that will become encroached by the southern regime in the near future. In this approach, presumably rare and abundant species show stochastic and deterministic dynamics, respectively. We specifically assessed how stochastic species of the northern spatial regime influence the resilience and adaptive capacity of a novel spatial regime once it has been encroached by the southern regime by either becoming deterministic or staying stochastic. Using 47 years (1968 – 2014) of breeding bird survey data and a space-for-time substitution, we found half of the stochastic species from the northern regime to be either deterministic or stochastic in the southern regime. However, the overall contribution of these species to the community of the southern regime was low, manifested in marginal contributions to resilience and adaptive capacity of this regime. Also, none of these species were of conservation concern, suggesting limited need for revised species conservation action in the novel spatial regime. From a systemic perspective our result suggest that while stochastic species can potentially compensate for the loss of dominant species after disturbances and maintain the system in its current regime, they may only marginally contribute to resilience and adaptive capacity in a new spatial regime after fundamental ecological changes have occurred.
Observed but Never Experienced – Vicarious Learning of Fear Under Ecological Conditions
Authors: Szczepanik Michał , Kaźmierowska Anna M. , Michałowski Jarosław M. , Wypych Marek , Olsson Andreas , Knapska Ewelina 
Published: January 2020

AbstractLearning to avoid threats often occurs by observing the behavior of others. Most previous research on observational fear learning in humans has used pre-recorded stimuli as social cues. Here, we aimed to enhance the ecological validity of the learning situation: the ‘observer’ watched their friend (‘demonstrator’) performing a differential fear-conditioning task in real time. During the task, one conditioned stimulus (CS+) was repeatedly linked with electric stimulation (US) while another one (CS-) was always safe. Subsequently, the observer was presented with the CS+ and CS- directly but without receiving any shocks. Skin conductance (SCR) and fear-potentiated startle (FPS) responses were measured in observers throughout the whole experiment. While the US applied to the demonstrator elicited strong SCR in the observers, subsequent differential SCR to CSs (CS+ vs. CS-) presented directly were dependent on declarative knowledge of the CS+/US contingency. Contingency-aware observers also showed elevated FPS during both CS+ and CS- compared to intertrial intervals. We conclude that observational fear learning involves two components: an automatic emotional reaction to the response of the demonstrator and learning to predict stimulus contingency (CS+/US pairing). Ecological modifications proposed offer new perspectives on studying social learning of emotions.
Interrogating surface versus intracellular transmembrane receptor populations using cell-impermeable SNAP-tag substrates
Authors: Poc Pascal , Gutzeit Vanessa A. , Ast Julia , Lee Joon , Jones Ben J. , D’Este Elisa , Mathes Bettina , Hodson David J. , Levitz Joshua , Broichhagen Johannes 
Published: January 2020

AbstractEmploying self-labelling protein tags for the attachment of fluorescent dyes has become a routine and powerful technique in optical microscopy to visualize and track fused proteins. However, membrane permeability of the dyes and the associated background signals can interfere with the analysis of extracellular labeling sites. Here we describe a novel approach to improve extracellular labeling by functionalizing the SNAP-tag substrate benzyl guanine (“BG”) with a charged sulfonate (“SBG”). This chemical manipulation improves solubility, reduces non-specific staining and renders the bioconjugation handle impermeable while leaving its cargo untouched. We report SBG-conjugated fluorophores across the visible spectrum, which cleanly label SNAP-fused proteins in the plasma membrane of living cells. We demonstrate the utility of SBG-conjugated fluorophores to interrogate class A, B and C G protein-coupled receptors (GPCRs) using a range of imaging approaches including nanoscopic super-resolution imaging, analysis of GPCR trafficking from intra- and extracellular pools,in vivolabelling in mouse brain and analysis of receptor stoichiometry using single molecule pull down.
A novel fibrinogen gamma-chain mutation, p. γAla327Val, causes structural abnormality of D region and ultimately leads to congenital dysfibrinogenemia
Authors: Wei Aiqiu , Wu Yangyang , Xiang Liqun , Yan Jie , Cheng Peng , Deng Donghong , Lin Faquan 
Published: January 2020

ABSTRACTCongenital dysfibrinogenemia (CD) is a coagulation disorder caused by mutations in the fibrinogen gene, which result in abnormal fibrinogen function. Many studies have confirmed that over half of dysfibrinogenemia cases are asymptomatic. In this study, we aimed to investigate the pathogenesis of CD caused by γ Ala327Val heterozygous mutation, a new mutation, by studying fibrinogen function. Blood samples of patients were collected and the coagulation function, fibrinogen (Fg) aggregation test, fibrin clot lysis test, and SDS-PAGE were performed. Coagulation was monitored using a thromboelastometer, and the fibrin clot network structure was observed by scanning electron microscopy. The effect of the mutation on fibrinogen structure and function was predicted by molecular modeling. The fibrinogen activity concentration in patients with CD was significantly lower than that in healthy individuals. Thromboelastography showed that the K value of patients with CD was higher than that for healthy individuals. The Angle values were also decreased. The function of fibrinogen in patients with CD was low. Compared to fibrinogen from healthy individuals, fibrin size was different, the fiber network structure was loose, the pore size was increased, and the fiber branch nodes were increased for fibrinogen isolated from the proband. The γ Ala327Val mutation led to changes in the structure of fibrinogen D region, affecting its structural stability. Ala327Val heterozygous missense mutation in exon 8 of FGG gene γ-chain thus leads to abnormal fibrinogen structure and impairs the aggregation function of fibrinogen. This mutation is reported here for the first time.
The Maryland Analysis of Developmental EEG (MADE) Pipeline
Authors: Debnath Ranjan , Buzzell George A. , Morales Santiago , Bowers Maureen E. , Leach Stephanie C. , Fox Nathan A. 
Published: January 2020

AbstractCompared to adult EEG, EEG signals recorded from pediatric populations have shorter recording periods and contain more artifact contamination. Therefore, pediatric EEG data necessitate specific preprocessing approaches in order to remove environmental noise and physiological artifacts without losing large amounts of data. However, there is presently a scarcity of standard automated preprocessing pipelines suitable for pediatric EEG.In an effort to achieve greater standardization of EEG preprocessing, and in particular for the analysis of pediatric data, we developed the Maryland Analysis of Developmental EEG (MADE) pipeline as an automated preprocessing pipeline compatible with EEG data recorded with different hardware systems, different populations, levels of artifact contamination, and length of recordings. MADE uses EEGLAB and functions from some EEGLAB plugins, and includes additional customizable features particularly useful for EEG data collected from pediatric populations.MADE processes event-related and resting state EEG from raw data files through a series of preprocessing steps and outputs processed clean data ready to be analyzed in time, frequency, or time-frequency domain. MADE provides a report file at the end of the preprocessing that describes a variety of features of the processed data to facilitate the assessment of the quality of processed data. In this paper we discuss some practical issues, which are specifically relevant to pediatric EEG preprocessing. We also provide custom-written scripts to address these practical issues.MADE is freely available under the terms of the GNU General Public License athttps://github.com/ChildDevLab/MADE-EEG-preprocessing-pipeline.
A Reporter Mouse forIn VivoDetection of DNA Damage in Embryonic Germ Cells
Authors: Bloom Jordana C. , Schimenti John C. 
Published: January 2020

AbstractMaintaining genome integrity in the germline is essential for survival and propagation of a species. In both mouse and human, germ cells originate during fetal development and are hypersensitive to both endogenous and exogenous DNA damaging agents. Currently, mechanistic understanding of how primordial germ cells respond to DNA damage is limited in part by the tools available to study these cells. We developed a mouse transgenic reporter strain expressing a 53BP1-mCherry fusion protein under the control of the Oct4ΔPE embryonic germ cell-specific promoter. This reporter binds sites of DNA double strand breaks (DSBs) on chromatin, forming foci. Using ionizing radiation as a DNA double strand break-inducing agent, we show that the transgenic reporter expresses specifically in the embryonic germ cells of both sexes and forms DNA damage induced foci in both a dose- and time-dependent manner. The dynamic time-sensitive and dose-sensitive DNA damage detection ability of this transgenic reporter, in combination with its specific expression in embryonic germ cells, makes it a versatile and valuable tool for increasing our understanding of DNA damage responses in these unique cells.
The proteasomal deubiquitinating enzyme PSMD14 regulates macroautophagy by controlling Golgi-to-ER retrograde transport
Authors: Bustamante HA , Cereceda K , González AE , Valenzuela GE , Cheuquemilla Y , Hernández S , Arias-Muñoz E , Cerda-Troncoso C , Bandau S , Soza A , Kausel G , Kerr B , Mardones GA , Cancino J , Hay RT , Rojas-Fernandez A , Burgos PV 
Published: January 2020

ABSTRACTUbiquitination regulates several biological processes. Here, we search for ubiquitin-related genes implicated in protein membrane trafficking performing a High-Content siRNA Screening including 1,187 genes of the human “ubiquitinome” using Amyloid Precursor Protein (APP) as a reporter. We identified the deubiquitinating enzyme PSMD14, a subunit of the 19S regulatory particle of the proteasome, specific for K63-Ub chains in cells, as a novel key regulator of Golgi-to-endoplasmic reticulum (ER) retrograde transport. Silencing or pharmacological inhibition of PSMD14 caused a robust and rapid inhibition of Golgi-to-ER retrograde transport which leads to a potent blockage of macroautophagy by a mechanism associated with the retention of Atg9A and Rab1A at the Golgi apparatus. Because pharmacological inhibition of the proteolytic core of the 20S proteasome did not recapitulate these effects, we concluded that PSMD14, and their K-63-Ub chains, act as a crucial regulator factor for macroautophagy by controlling Golgi-to-ER retrograde transport.
Near-atomic structures of the BBSome reveal a novel mechanism for transition zone crossing
Authors: Bahl Kriti , Yang Shuang , Chou Hui-Ting , Woodsmith Jonathan , Stelzl Ulrich , Walz Thomas , Nachury Maxence V. 
Published: January 2020

ABSTRACTThe BBSome is a complex of eight Bardet-Biedl Syndrome (BBS) proteins that removes signaling receptors from cilia. The GTPase ARL6/BBS3 recruits the BBSome to the ciliary membrane where the BBSome–ARL6GTPcomplex ferries G protein-coupled receptors (GPCRs) across the transition zone, a diffusion barrier at the base of cilia. Here, we find that the BBSome undergoes a conformational change upon recruitment to membranes by ARL6GTP. Modeling the binding of the BBSome to membranes and to the GPCR Smoothened (SMO) reveals that the amphipathic helix 8 of SMO must be released from the membrane for SMO to be recognized by the BBSome. Underscoring the functional importance of amphipathic helix extraction in TZ crossing, we find that exchanging the amphipathic helix of ARL6 for one that embeds deeper into the membrane blocks BBSome-mediated exit of GPCRs from cilia. We propose that the rigid curvature and dense lipid packing of the transition zone reject asymmetric insertions in the inner leaflet and that the BBSome licenses transition zone crossing by extracting bulky amphipathic helices from the inner leaflet.
Transposase assisted tagmentation of RNA/DNA hybrid duplexes
Authors: Lu Bo , Dong Liting , Yi Danyang , Zhu Chenxu , Zhang Meiling , Li Xiaoyu , Yi Chengqi 
Published: January 2020

AbstractTn5-mediated transposition of double-strand DNA has been widely utilized in various high-throughput sequencing applications. Here, we report that the Tn5 transposase is also capable of direct tagmentation of RNA/DNA hybridsin vitro. As a proof-of-concept application, we utilized this activity to replace the traditional library construction procedure of RNA sequencing, which contains many laborious and time-consuming processes. Results of activity of transposase assisted RNA/DNA hybrids co-tagmentation (termed “ATRAC-seq”) are comparable to traditional RNA-seq methods in terms of gene number, gene body coverage and gene expression analysis; at the meantime, ATRAC-seq enables a one-tube library construction protocol and hence is more rapid (within 8 h) and convenient. We expect this tagmentation activity on RNA/DNA hybrids to have broad potentials on RNA biology and chromatin research.
Using EEG to understand how our brain elaborate information in stated choice experiments: Easy versus hard tasks in the choice of vehicles
Authors: Cherchi Elisabetta , Vuong Quoc C , Stergiou Antonia 
Published: January 2020

ABSTRACTIn the current study, we aim to provide preliminary evidence that complex consumer choices depends on cognitive processes and executive functions that may not be fully captured by current stated choice (SC) approaches. To address this gap, here we combine the standard SC experiment with electroencephalogram (EEG) recordings while manipulating the cognitive demands of the task. Our study is applied to the choice context of a car purchase between a petrol and an electric vehicle. Respondents were asked to fill in a stated choice experiment online and a subsample of these respondents were then invited to participate in an EEG study during which they repeated the same SC experiment while we continuously recorded EEG signals from their scalp. We then modelled people’s choice behaviours in easy and hard decisions, and compared this analysis of their choice behaviour to their EEG responses in these two conditions. Our results confirm that hard decisions lead to higher cognitive demands and larger EEG responses in electrodes on the frontal part of the scalp and these demands can lead to choices inconsistent with the compensatory assumptions.