bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homeostatic plasticity rules control the wiring of axo-axonic synapses at the axon initial segment
Authors: Pan-Vazquez Alejandro , Wefelmeyer Winnie , Sabater Victoria Gonzalez , Burrone Juan 
Published: October 2018

AbstractGABAergic interneurons are chiefly responsible for controlling the activity of local circuits in the cortex1,2. However, the rules that govern the wiring of interneurons are not well understood3. Chandelier cells (ChCs) are a type of GABAergic interneuron that control the output of hundreds of neighbouring pyramidal cells through axo-axonic synapses which target the axon initial segment (AIS)4. Despite their importance in modulating circuit activity, our knowledge of the development and function of axo-axonic synapses remains elusive. In this study, we investigated the role of activity in the formation and plasticity of ChC synapses. In vivo imaging of ChCs during development uncovered a narrow window (P12-P18) over which axons arborized and formed connections. We found that increases in the activity of either pyramidal cells or individual ChCs during this temporal window resulted in a reversible decrease in axo-axonic connections. Voltage imaging of GABAergic transmission at the AIS showed that axo-axonic synapses were depolarising during this period. Identical manipulations of network activity in older mice (P40-P46), when ChC synapses are inhibitory, resulted in an increase in axo-axonic synapses. We propose that the direction of ChC plasticity follows homeostatic rules that depend on the polarity of axo-axonic synapses.
The BRadykinesia Akinesia INcoordination (BRAIN) tap test: capturing the sequence effect
Authors: Hasan Hasan , Burrows Maggie , Athauda Dilan S. , Hellman Bruce , James Ben , Warner Tom , Foltynie Thomas , Giovannoni Gavin , Lees Andrew J. , Noyce Alastair J. 
Published: October 2018

AbstractBackgroundThe BRAIN tap test is an online keyboard tapping task that has been previously validated to assess upper limb motor function in Parkinson’s disease (PD).ObjectivesTo develop a new parameter which detects a sequence effect and to reliably distinguish between PD patients ‘on’ and ‘off’ medication. Alongside, we sought to validate a mobile version of the test for use on smartphones and tablet devices.MethodsBRAIN test scores in 61 patients with PD and 93 healthy controls were compared. A range of established parameters captured speed and accuracy of alternate taps. The new VS (Velocity Score) recorded the inter-tap speed. Decrement in the VS was used as a marker for the sequence effect. In the validation phase, 19 PD patients and 19 controls were tested using multiple types of hardware platforms including smart devices.ResultsQuantified slopes from the VS demonstrated bradykinesia (sequence effect) in PD patients (slope cut-off −0.002) with sensitivity of 58% and specificity of 81% (discovery phase of the study) and sensitivity of 65% and specificity of 88% (validation phase). All BRAIN test parameters differentiated between ‘on’ medication and ‘off’ medication states in PD. Most BRAIN tap test parameters had high test-retest reliability values (ICC>0.75). Differentiation between PD patients and controls was possible on all hardware versions of the test.ConclusionThe BRAIN tap test is a simple, user-friendly and free-to-use tool for assessment of upper limb motor dysfunction in PD, which now includes a measure of bradykinesia.
Association between chronic hepatitis C virus infection and myocardial infarction in people living with HIV in the United States
Authors: Williams-Nguyen Jessica , Hawes Stephen E , Nance Robin M , Lindström Sara , Heckbert Susan R , Kim H Nina , Mathews W Chris , Cachay Edward R , Budoff Matt , Hurt Christopher B , Hunt Peter W , Geng Elvin , Moore Richard D , Mugavero Michael J , Peter Inga , Kitahata Mari M , Saag Michael S , Crane Heidi M , Delaney Joseph A 
Published: October 2018

AbstractHepatitis C virus (HCV) is common among people living with HIV (PLWH). The potential for extrahepatic manifestations of HCV, including myocardial infarction (MI), is a topic of active research. MI is classified into types, predominantly atheroembolic Type 1 MI (T1MI) and supply-demand mismatch Type 2 MI (T2MI). We examined the association between HCV and MI in the CFAR Network of Integrated Clinical Systems (CNICS), a multi-center clinical cohort of PLWH. MIs were centrally adjudicated and categorized by type using the Universal MI definition. We estimated the association between chronic HCV (RNA+) and time to MI adjusting for demographic characteristics, cardiovascular risk factors, clinical characteristics and substance use. Among 24,755 PLWH aged ≥18, there were 336 T1MI and 330 T2MI during a median of 4.2 years of follow-up. HCV was associated with a 68% greater risk of T2MI (adjusted hazard ratio (aHR) 1.68, 95% CI: 1.22, 2.30) but not T1MI (aHR 0.96, 95% CI: 0.63, 1.45). In a cause-specific analysis of T2MI, HCV was associated with a 2-fold greater risk of T2MI attributed to sepsis (aHR 2.26, 95% CI: 1.34, 3.81). Extrahepatic manifestations of HCV in this high-risk population are an important area for continued research.
NanoMEA: a versatile platform for high-throughput analysis of structure-function relationships in human stem cell-derived excitable cells and tissues
Authors: Smith Alec S.T. , Choi Eunpyo , Gray Kevin , Macadangdang Jesse , Ahn Eun Hyun , Clark Elisa C. , Tyler Phillip , Laflamme Michael A. , Tung Leslie , Wu Joseph C. , Murry Charles E. , Kim Deok-Ho 
Published: October 2018

AbstractSomatic cells derived from human pluripotent stem cell (hPSC) sources hold significant potential as a means to improve current in vitro screening assays. However, their inconsistent ability to recapitulate the structural and functional characteristics of native cells has raised questions regarding their ability to accurately predict the functional behavior of human tissues when exposed to chemical or pathological insults. In addition, the lack of cytoskeletal organization within conventional culture platforms prevents analysis of how structural changes in human tissues affect functional performance. Using cation-permeable hydrogels, we describe the production of multiwell nanotopographically-patterned microelectrode arrays (nanoMEAs) for studying the effect of structural organization on hPSC-derived cardiomyocyte and neuronal function in vitro. We demonstrate that nanoscale topographic substrate cues promote the development of more ordered cardiac and neuronal monolayers while simultaneously enhancing cytoskeletal organization, protein expression patterns, and electrophysiological function in these cells. We then show that these phenotypic improvements act to alter the sensitivity of hPSC-derived cardiomyocytes to treatment with arrhythmogenic and conduction-blocking compounds that target structural features of the cardiomyocyte. Similarly, we demonstrate that neuron sensitivity to synaptic blockers is increased when cells are maintained on nanotopographically-patterned Nafion surfaces. The improved structural and functional capacity of hPSC-derived cardiomyocyte and neuronal populations maintained on nanoMEAs may have important implications for improving the predictive capabilities of cell-based electrophysiological assays used in preclinical screening applications.
Identification ofSlit3as a locus affecting nicotine preference in zebrafish and human smoking behaviour
Authors: García-González Judit , Brock Alistair J. , Parker Matthew O. , Riley Riva , Jolliffe David , Sudwarts Ari , Teh Muy-Teck , Busch-Nentwich Elisabeth M. , Stemple Derek L. , Martineau Adrian R. , Kaprio Jaakko , Palviainen Teemu , Kuan Valerie , Walton Robert T. , Brennan Caroline H. 
Published: October 2018

ABSTRACTTo facilitate smoking genetics research we determined whether a screen of mutagenized zebrafish for nicotine preference could predict loci affecting smoking behaviour. Of 30 ENU mutagenized families screened, two showed increased or decreased nicotine preference. Out of 25 inactivating mutations in the families, one in theslit3gene segregated with increased nicotine preference in heterozygous individuals. Focussed SNP analysis of the humanSLIT3locus in cohorts from UK (n=863) and Finland (n=1715) identified two variants that predict cigarette consumption and likelihood of cessation. Characterisation ofslit3mutant larvae and adult fish revealed decreased sensitivity to the dopaminergic and serotonergic antagonist amisulpride, known to affect startle reflex that is correlated with addiction in humans, and increasedhtr1aamRNA expression in mutant larvae. No effect on neuronal pathfinding was detected. These findings reveal a role for SLIT3 in development of pathways affecting responses to nicotine in zebrafish and smoking in humans.
ebayGSEA: An improved Gene Set Enrichment Analysis method for Epigenome-Wide-Association Studies
Authors: Dong Danyue , Yuan Tian , Zheng Shijie C. , Teschendorff Andrew E. 
Published: October 2018

AbstractMotivationThe biological interpretation of differentially methylated sites derived from Epigenome-Wide-Association Studies remains a significant challenge. Gene Set Enrichment Analysis (GSEA) is a general tool to help aid biological interpretation, yet its correct and unbiased implementation in the EWAS context is difficult due to the differential probe representation of Illumina Infinium DNA methylation beadchips.ResultsWe present a novel GSEA method, called ebayGSEA, which ranks genes, not CpGs, according to the overall level of differential methylation, as assessed using all the probes mapping to the given gene. Applied on simulated and real EWAS data, we show how ebayGSEA may exhibit higher sensitivity and specificity than the current state-of-the-art, whilst also avoiding differential probe representation bias. Thus, ebayGSEA will be a useful additional tool to aid the interpretation of EWAS data.Availability and implementationebayGSEA is available from https://github.com/aet21/ebayGSEA, and has been incorporated into the ChAMP Bioconductor package (https://www.bioconductor.org).
Proximity RNA labeling by APEX-Seq Reveals the Organization of Translation Initiation Complexes and Repressive RNA Granules
Authors: Padròn Alejandro , Iwasaki Shintaro , Ingolia Nicholas T. 
Published: October 2018

AbstractDiverse ribonucleoprotein complexes control messenger RNA processing, translation, and decay. Transcripts in these complexes localize to specific regions of the cell and can condense into non-membrane-bound structures such as stress granules. It has proven challenging to map the RNA composition of these large and dynamic structures, however. We therefore developed an RNA proximity labeling technique, APEX-Seq, which uses the ascorbate peroxidase APEX2 to probe the spatial organization of the transcriptome. We show that APEX-Seq can resolve the localization of RNAs within the cell and determine their enrichment or depletion near key RNA-binding proteins. Matching the spatial transcriptome, as revealed by APEX-Seq, with the spatial proteome determined by APEX-mass spectrometry (APEX-MS) provides new insights into the organization of translation initiation complexes on active mRNAs, as well as exposing unanticipated complexity in stress granule composition, and provides a powerful and general approach to explore the spatial environment of macromolecules.
Exonuclease III (XthA) enforcesin vivoDNA cloning ofEscherichia colito create cohesive ends
Authors: Nozaki Shingo , Niki Hironori 
Published: October 2018

AbstractEscherichia colihas an ability to assemble DNA fragments with homologous overlapping sequences of 15-40 bp at each end. Several modified protocols have already been reported to improve this simple and useful DNA-cloning technology. However, the molecular mechanism by whichE. coliaccomplishes such cloning is still unknown. In this study, we provide evidence that thein vivocloning ofE. coliis independent of both RecA and RecET recombinase, but is dependent on XthA, a 3’ to 5’ exonuclease. Here, in vivocloning ofE. coliby XthA is referred to as iVEC (in vivo E. colicloning). Next, we show that the iVEC activity is reduced by deletion of the C-terminal domain of DNA polymerase I (PolA). Collectively, these results suggest the following mechanism of iVEC. First, XthA resects the 3′ ends of linear DNA fragments that are introduced intoE. colicells, resulting in exposure of the single-stranded 5′ overhangs. Then, the complementary single-stranded DNA ends hybridize each other, and gaps are filled by DNA polymerase I. Elucidation of the iVEC mechanism at the molecular level would further advance the development ofin vivoDNA-cloning technology. Already we have successfully demonstrated multiple-fragment assembly of up to seven fragments in combination with an effortless transformation procedure using a modified host strain for iVEC.ImportanceCloning of a DNA fragment into a vector is one of the fundamental techniques in recombinant DNA technology. Recently,in vitrorecombination of DNA fragments effectively joins multiple DNA fragments in place of the canonical method. Interestingly,E. colican take up linear double-stranded vectors, insert DNA fragments and assemble themin vivo.Thein vivocloning have realized a high level of usability comparable to that byin vitrorecombination reaction, since now it is only necessary to introduce PCR products intoE. colifor thein vivocloning. However, the mechanism ofin vivocloning is highly controversial. Here we clarified the fundamental mechanism underlyingin vivocloning of E. coli and also constructed anE. colistrain that was optimized forin vivocloning.
Nearest-neighbor parameter for inosine-cytosine pairs through a combined experimental and computational approach
Authors: Sakuraba Shun , Iwakiri Junichi , Hamada Michiaki , Kameda Tomoshi , Tsuji Genichiro , Kimura Yasuaki , Abe Hiroshi , Asai Kiyoshi 
Published: October 2018

AbstractIn RNA secondary structure prediction, nearest-neighbor parameters are used to determine the stability of a given structure. We derived the nearest-neighbor parameters for RNAs containing inosine-cytosine pairs. For parameter derivation, we developed a method that combines UV adsorption measurement experiments with free-energy calculations using molecular dynamics simulations. The method provides fast drop-in parameters for modified bases. Derived parameters were compared and found to be consistent with existing parameters for canonical RNAs. A duplex with an internal inosine-cytosine pair is 0.9 kcal/mol more unstable than the same duplex with an internal guanine-cytosine pair, and is as stable as the one with an internal adenine-uracil pair (only 0.1 kcal/mol more stable) on average.
WHATEVER YOU WANT: INCONSISTENT RESULTS IS THE RULE, NOT THE EXCEPTION, IN THE STUDY OF PRIMATE BRAIN EVOLUTION
Authors: Wartel Andreas , Lindenfors Patrik , Lind Johan 
Published: October 2018

AbstractPrimate brains differ in size and architecture. Hypotheses to explain this variation are numerous and many tests have been carried out. However, after body size has been accounted for there is little left to explain. The proposed explanatory variables for the residual variation are many and covary, both with each other and with body size. Further, the data sets used in analyses have been small, especially in light of the many proposed predictors. Here we report the complete list of models that results from exhaustively combining six commonly used predictors of brain and neocortex size. This provides an overview of how the output from standard statistical analyses changes when the inclusion of different predictors is altered. By using both the most commonly tested brain data set and a new, larger data set, we show that the choice of included variables fundamentally changes the conclusions as to what drives primate brain evolution. Our analyses thus reveal why studies have had troubles replicating earlier results and instead have come to such different conclusions. Although our results are somewhat disheartening, they highlight the importance of scientific rigor when trying to answer difficult questions. It is our position that there is currently no empirical justification to highlight any particular hypotheses, of those adaptive hypotheses we have examined here, as the main determinant of primate brain evolution.
Subthalamic nucleus local field potentials recordings reveal subtle effects of promised reward during conflict resolution in Parkinson’s disease
Authors: Duprez Joan , Houvenaghel Jean-François , Dondaine Thibaut , Péron Julie , Haegelen Claire , Drapier Sophie , Modolo Julien , Jannin Pierre , Vérin Marc , Sauleau Paul 
Published: October 2018

AbstractCognitive action control depends on cortical-subcortical circuits, involving notably the subthalamic nucleus (STN), as evidenced by local field potentials recordings (LFPs) studies. The STN consistently shows an increase in theta oscillations power during conflict resolution. Some studies have shown that cognitive action control in Parkinson’s disease (PD) could be influenced by the occurrence of monetary reward. In this study, we investigated whether incentive motivation could modulate STN activity, and notably STN theta activity, during response conflict resolution. To achieve this objective, we recorded STN LFPs during a motivated Simon task in PD patients who had undergone deep brain stimulation surgery. Behavioral results revealed that promised rewards increased the difficulty in resolving conflict situations, thus replicating previous findings. Signal analyses locked on the imperative stimulus onset revealed the typical pattern of increased theta power in a conflict situation. However, this conflict-related modulation of theta power was not influenced by the size of the reward cued. We nonetheless identified a significant effect of the reward size on local functional organization (indexed by inter-trial phase clustering) of theta oscillations, with higher organization associated with high rewards while resolving conflict. When focusing on the period following the onset of the reward cue, we unveiled a stronger beta power decrease in higher reward conditions. However, these LFPs results were not correlated to behavioral results. Our study suggests that the STN is involved in how reward information can influence computations during conflict resolution. However, considering recent studies as well as the present results, we suspect that these effects are subtle.
Computer vision and deep learning automates nocturnal rainforest ant tracking to provide insight into behavior and disease risk
Authors: Imirzian Natalie , Zhang Yizhe , Kurze Christoph , Loreto Raquel G. , Chen Danny Z. , Hughes David P. 
Published: October 2018

AbstractDetermining how ant colonies optimize foraging while mitigating disease risk provides insight into how the ants have achieved ecological success. Fungal infected cadavers surround the main foraging trails of the carpenter antCamponotus rufipes, offering a system to study how foragers behave given the persistent occurrence of disease threats. Studies on social insect foraging behavior typically require many hours of human labor due to the high density of individuals. To overcome this, we developed deep learning based computer vision algorithms to track foraging ants, frame-by-frame, from video footage. We found foragers can be divided into behavioral categories based on how straight they walk across the trail. Eighty percent of ants walk directly across the trail, while 20% wander or circle when crossing the trail. Departure from the main trail encourages exploration of new areas and could enhance discovery of new food resources. Conversely, results from our agent-based model simulations suggest deviation from a straight path exposes foragers to more infectious fungal spores. Consistency in walking behavior may protect most ants from infection, while the foragers with increased exposure due to their mode of walking could be a sufficient number of new hosts to sustain disease in this environment.
Increasing phylogenetic stochasticity at high elevations on summits across a remote North American wilderness
Authors: Marx Hannah E. , Richards Melissa , Johnson Grahm M. , Tank David C. 
Published: October 2018

ABSTRACTPREMISE OF THE STUDY:At the intersection of ecology and evolutionary biology, community phylogenetics can provide insights into overarching biodiversity patterns, particularly in remote and understudied ecosystems. To understand community assembly of the high-alpine flora of the Sawtooth National Forest, USA, we analyzed phylogenetic structure within and between nine summit communities.METHODS:We used high-throughput sequencing to supplement existing data and infer a nearly completely sampled community phylogeny of the alpine vascular flora. We calculated mean nearest taxon distance (MNTD) and mean pairwise distance (MPD) to quantify phylogenetic divergence within summits, and assed how maximum elevation explains phylogenetic structure. To evaluate similarities between summits we quantified phylogenetic turnover, taking into consideration micro-habitats (talus vs. meadows).KEY RESULTS:We found different patterns of community phylogenetic structure within the six most species-rich orders, but across all vascular plants phylogenetic structure was largely no different from random. There was a significant negative correlation between elevation and tree-wide phylogenetic diversity (MPD) within summits: significant overdispersion degraded as elevation increased. Between summits we found high phylogenetic turnover, which was driven by greater niche heterogeneity on summits with alpine meadows.CONCLUSIONS:This study provides further evidence that stochastic processes shape the assembly of vascular plant communities in the high-alpine at regional scales. However, order-specific patterns suggest adaptations may be important for assembly of specific sectors of the plant tree of life. Further studies quantifying functional diversity will be important to disentangle the interplay of eco-evolutionary processes that likely shape broad community phylogenetic patterns in extreme environments.
The metaefficiency of trade shows: a benchmarking analysis by sector
Authors: Alberca Pilar , Parte Laura , Rodríguez Ainhoa 
Published: October 2018

Purpose
The purpose of this paper is to analyze the efficiency of trade shows and provide insights for trade show exhibitors using data envelopment analysis (DEA). The paper also offers a benchmarking analysis of the business factors for the most efficient trade shows in each sector.

Design/methodology/approach
The paper uses the metafrontier DEA methodology and identifies several frontiers according to the sector in which the trade show operates since different sectors could not share homogeneous production technology for exhibitor firms.

Findings
The main findings reveal different profiles of individual sectors. The investment sector presents a more homogenous profile than either the consumer goods or the services sector. The consumer goods sector is more heterogeneous but it is also possible to find common characteristics for the most efficient trade shows. The service sector is characterized by a high variability and as such it is more difficult to identify benchmarking elements for the most efficient trade shows.

Research limitations/implications
The main limitation of the study is that the sample only includes audited trade shows. Future studies could extend the period under study in order to obtain a more complete picture on the evolution of trade show efficiency.

Originality/value
This paper extends the DEA results by profiling the most efficient trade shows in each sector so that this information can be used as a benchmarking tool to define exhibitors’ strategic decision making.