bluuebunny/crossref_metadata_2025_split huggingface dataset:
Domain-relevant auditory expertise modulates the additivity of neural mismatch responses in humans
Authors: Hansen Niels Chr. , Højlund Andreas , Møller Cecilie , Pearce Marcus , Vuust Peter 
Published: February 2019

AbstractIt is unknown whether domain-relevant expertise is associated with more independent or more dependent predictive processing of acoustic features. Here, mismatch negativity (MMNm) was recorded with magnetoencephalography (MEG) from 25 musicians and 25 non-musicians, exposed to complex musical multi-feature and simple oddball control paradigms. Deviants differed in frequency (F), intensity (I), perceived location (L), or any combination of these (FI, IL, LF, FIL). Neural processing overlap was assessed through MMNm additivity by comparing double- and triple-deviant MMNms (“empirical”) to summed constituent single-deviant MMNms (“modelled”). Significantly greater subadditivity was present in musicians compared to non-musicians, specifically for frequency-related deviants in complex contexts. Despite using identical sounds, expertise effects were absent from the simple paradigm. This novel finding supports thedependent processing hypothesiswhereby experts recruit overlapping neural resources facilitating more integrative representations of domain-relevant stimuli. Such specialized predictive processing may enable experts such as musicians to capitalise on complex acoustic cues.
Luliconazole, a New Antifungal, vs Amphotericin B, Voriconazole, Posaconazole and Caspofungin against Clinical and EnvironmentalAspergillusNigri Complex
Authors: Hivary Sahar , Fatahinia Mahnaz , Halvaeezadeh Marzieh , Mahmoudabadi Ali Zarei 
Published: February 2019

ABSTRACTBlack Aspergilli are,the most causes of aspergillosis andAspergillus niger and A. tubingensis are two more frequently isolates. Although, amphotericin B was a gold standard for the treatment of invasive fungal infection for several decades, it replaced by several new antifungals. Furthermore, a novel antifungal, luliconazole, appears to offer the potential for improved therapy for aspergillosis. The aim of the present study was to compare the effect of a novel antifungal agent, luliconazole, with classical antifungalagainst clinical and environmental strains of black Aspergilli. Sixty seven strains of black Aspergilli were identified using morphological and molecular tests (β-Tubulin gene). Antifungal susceptibility test was applied according to CLSI M38 A2. The results were reported as MIC range, MIC50, MIC90and MICGM. In the present study,A. nigerwas the common isolate followed by,A. tubingensisand 54.1% (clinical) and 30% (environmental) of isolates were resistant to caspofungin. The highest resistant rate was found in amphotericin B for both clinical (86.5%) and environmental (96.7%) strains. Clinical strains ofAspergilluswere more sensitive to voriconazole (86.7%) than environmental strains (70.3%). On the other hand, 83.8% of clinical and 70% of environmental isolates were resistant to posaconazole, respectively. It is found that the lowest MIC range, MIC50, MIC90, and MICGMwas attributed to luliconazole in clinical strains. In conclusion, luliconazole vs. routine antifungal is a potent antifungal forA. nigercomplexin vitro. The MIC range, MIC50, MIC90and MICGMof luliconazole against black Aspergilli were the lowest among the representative tested antifungals.
Selectivity of Guanine Nucleotide Exchange Factor-mediated Cdc42 activation in primary human endothelial cells
Authors: Reinhard Nathalie R. , der Niet Sanne van , Chertkova Anna , Postma Marten , Hordijk Peter L. , Gadella Theodorus W.J. , Goedhart Joachim 
Published: February 2019

AbstractThe Rho GTPase family is involved in actin dynamics and regulates the barrier function of the endothelium. One of the main barrier-promoting Rho GTPases is Cdc42, also known as cell division control protein 42 homolog. Currently, regulation of Cdc42-based signaling networks in endothelial cells (ECs) lack molecular details. To examine these, we focused on a subset of 15 Rho guanine nucleotide exchange factors (GEFs), which are expressed in the endothelium. By performing single cell FRET measurements with Rho GTPase biosensors in primary human ECs, we monitored GEF efficiency towards Cdc42 and Rac1. A new, single cell-based analysis was developed and used to enable the quantitative comparison of cellular activities of the full-length GEFs. Our data reveal a specific GEF dependent activation profile, with most efficient Cdc42 activation induced by PLEKHG2, FGD1, PLEKHG1 and pRex1 and the highest selectivity for FGD1. Additionally, we generated truncated GEF constructs that comprise only the catalytic dbl homology (DH) domain or together with the adjacent pleckstrin homology domain (DHPH). The DH domain by itself did not activate Cdc42, whereas the DHPH domain of ITSN1, ITSN2 and PLEKHG1 showed activity towards Cdc42. Together, our study characterized endothelial GEFs that may activate Cdc42, which will be of great value for the field of vascular biology.Abstract FigureGraphical Abstract
The mechanistic basis for chromatin invasion and remodeling by the yeast pioneer transcription factor Rap1
Authors: Mivelaz Maxime , Cao Anne-Marinette , Kubik Slawomir , Zencir Sevil , Hovius Ruud , Boichenko Iuliia , Stachowicz Anna Maria , Kurat Christoph F. , Shore David , Fierz Beat 
Published: February 2019

ABSTRACTPioneer transcription factors (pTFs) bind to target sites within compact chromatin initiating chromatin remodeling and controlling the recruitment of downstream factors. The mechanisms by which pTFs overcome the chromatin barrier are not well understood. Here we reveal, using single-molecule fluorescence approaches, how the yeast transcription factor Rap1 invades and remodels chromatin. Using a reconstituted chromatin system replicating yeast promoter architecture we demonstrate that Rap1 can bind nucleosomal DNA within a chromatin fiber, but with shortened dwell times compared to naked DNA. Moreover, we show that Rap1 binding opens chromatin fiber structure by inhibiting nucleosome-nucleosome contacts. Finally, we reveal that Rap1 collaborates with the chromatin remodeler RSC to destabilize promoter nucleosomes, paving the way to form long-lived bound states on now exposed DNA. Together, our results provide a mechanistic view of how Rap1 gains access and opens chromatin, thereby establishing an active promoter architecture and controlling gene expression.
Molecular mechanism of the chitinolytic monocopper peroxygenase reaction
Authors: Bissaro Bastien , Streit Bennett , Isaksen Ingvild , Eijsink Vincent G.H. , Beckham Gregg T. , DuBois Jennifer , Røhr Åsmund K. 
Published: February 2019

ABSTRACTLytic polysaccharide monooxygenases (LPMOs) are a recently discovered class of monocopper enzymes, broadly distributed across the Tree of Life. We recently reported that LPMOs can use H2O2 as an oxidant, revealing a novel reaction pathway. Here, we aimed to elucidate the H2O2-mediated reaction mechanism with experimental and computational approaches. In silico studies suggest that a network of hydrogen bonds, involving both the enzyme and the substrate, brings H2O2 into a strained reactive conformation, and guides the derived hydroxyl radical towards formation of a copper-oxyl intermediate. The initial H2O2 homolytic cleavage and subsequent hydrogen atom abstraction from chitin by the copper-oxyl intermediate are suggested to be the main energy barriers. Under single turnover conditions, stopped-flow fluorimetry demonstrates that LPMO-Cu(II) reduction to Cu(I) is a fast process compared to the re-oxidation reactions. We found that re-oxidation of LPMO-Cu(I) is 2000-fold faster with H2O2 than with O2, the latter being several orders of magnitude slower than rates reported for other monooxygenases. In agreement with the notion of ternary complex formation, when chitin is added, re-oxidation by H2O2 is accelerated whereas that by O2 slows. Simulations indicated that Glu60, a highly-conserved residue, gates the access to the confined active site and constrains H2O2 during catalysis, and Glu60 mutations significantly decreased the enzyme performance. By providing molecular and kinetic insights into the peroxygenase activity of chitinolytic LPMOs, this study will aid the development of applications of enzymatic and synthetic copper catalysis and contribute to understanding pathogenesis, notably chitinolytic plant defenses against fungi and insects.
The effect of stimulus envelope shape on the auditory steady-state response
Authors: Van Canneyt Jana , Hofmann Michael , Wouters Jan , Francart Tom 
Published: February 2019

AbstractAuditory steady-state responses (ASSRs) are auditory evoked potentials that reflect phase-locked neural activity to periodic stimuli. ASSRs are often evoked by tones with a modulated envelope, with sinusoidal envelopes being most common. However, it is unclear if and how the shape of the envelope affects ASSR responses. In this study, we used various trapezoidal modulated tones to evoke ASSRs (modulation frequency = 40 Hz) and studied the effect of four envelope parameters: attack time, hold time, decay time and off time. ASSR measurements in 20 normal hearing subjects showed that envelope shape significantly influenced responses: increased off time and/or increased decay time led to responses with a larger signal-to-noise-ratio (SNR). Response phase delay was significantly influenced by attack time and to a lesser degree by off time. We also simulated neural population responses that approximate ASSRs with a model of the auditory periphery (Bruce et al. 2018). The modulation depth of the simulated responses, i.e. the difference between maximum and minimum firing rate, correlated highly with the response SNRs found in the ASSR measurements. Longer decay time and off time enhanced the modulation depth both by decreasing the minimum firing rate and by increasing the maximum firing rate. In conclusion, custom envelopes with long decay and off time provide larger response SNRs and the benefit over the commonly used sinusoidal envelope was in the range of several dB.
Comparative transcriptome analysis of Powdery mildew Resistance between two Melon (Cucumis melo L) with Different Thickness Peel
Authors: Hong Cheng , Wei-ping Kong , Jun-Feng Lü 
Published: February 2019

AbstractMelon (Cucumis melo L.) is wildly planted in the world and China is a major producer of muskmelon. Powdery mildew is one of the most common fungal diseases in the world and this disease frequently affects melon (Cucumis melo L.) and due to the reduction of melon yield. In this study, one material GanTianmi with thin peel and another material XueLianHua with thick peel were selected. After inoculating the powdery mildew, both materials were used to do the RNA-Seq. In total two RNA-seq libraries were constructed and sequenced separately. The reads per kilobase per Million mapped reads (RPKM) values of all the genes in the two materials were calculated and there were 13828 genes were expressed in the material G and 13944 genes were expressed in the material S (RPKM>1). The differentially expression gene (DEG) analysis result suggested that total 769 the DEGs between the two materials were identified. All the DEGs were annotated with several database and the transcript factors (TFs) that related to disease resistance such as MYB, ERF and WRKY among the DEGs were also identified. This research could not only provide the information about understanding the mechanism of powdery mildew infection but also help researchers breed the varieties with powdery mildew resistance.
The landscape of the alternatively spliced transcriptome remains stable during aging across different species and tissues
Authors: Sieber Patricia , Barth Emanuel , Marz Manja 
Published: February 2019

ABSTRACTAging is characterized by a decline of cellular homeostasis over time, leading to various severe disorders and death. Alternative splicing is an important regulatory level of gene expression and thus takes on a key role in the maintenance of accurate cell and tissue function. Missplicing of certain genes has already been linked to several age-associated diseases, such as progeria, Alzheimer’s disease, Parkinson’s disease and cancer. Nevertheless, many studies focus only on transcriptional variations of single genes or the expression changes of spliceosomal genes, coding for the proteins that aggregate to the spliceosomal machinery. Little is known on the general change of present and switching isoforms in different tissues over time. In this descriptive RNA-Seq study, we report differences and commonalities of isoform usage during aging among different tissues within one species and compare changes of alternative splicing among different, evolutionarily distinct species. Although we identified a multitude of differntially spliced genes among different time points, we observed little to no general changes in the transcriptomic landscape of the investigated samples. Although there is undoubtedly considerable influence of specifically spliced genes on certain age-associated processes, this work shows that alternative splicing remains stable for the majority of genes with aging.
Contextual effects on binocular matching are evident in primary visual cortex
Authors: Rideaux Reuben , Welchman Andrew E 
Published: February 2019

ABSTRACTGlobal context can dramatically influence local visual perception. This phenomenon is well-documented for monocular features, e.g., the Kanizsa triangle. It has been demonstrated for binocular matching: the disambiguation of the Wallpaper Illusion (Brewster, 1844) via the luminance of the background (Anderson & Nakayama, 1994). For monocular features, there is evidence that global context can influence neuronal responses as early as V1 (Muckli et al., 2015). However, for binocular matching, the activity in this area of the visual cortex is thought to represent local processing, suggesting that the influence of global context may occur at later stages of cortical processing. Here we sought to test if binocular matching is influenced by contextual effects in V1, using fMRI to measure brain activity while participants viewed perceptually ambiguous “wallpaper” stereograms whose depth was disambiguated by the luminance of the surrounding region. We localized voxels in V1 corresponding to the ambiguous region of the pattern, i.e., where the signal received from the eyes was not predictive of depth, and despite the ambiguity of the input signal, using multi-voxel pattern analysis we were able to reliably decode perceived (near/far) depth from the activity of these voxels. These findings indicate that stereoscopic related neural activity is influenced by global context as early as V1.
Ligand dependent gene regulation by transient ERα clustered enhancers
Authors: Saravanan Bharath , Soota Deepanshu , Islam Zubairul , Jayani Ranveer , Mann Rajat , Farooq Umer , Meel Sweety , Walavalkar Kaivalya , Gayen Srimonta , Singh Anurag Kumar , Hannenhalli Sridhar , Notani Dimple 
Published: February 2019

AbstractUnliganded nuclear receptors have been implicated in ligand-dependent gene regulation. However, the underlying mechanisms are not fully understood. Here we demonstrate that unliganded ERα binds to specific sites in the genome thereby pre-marking them as future functional enhancers. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, or persistent, ERα-bound sites. Interestingly, the persistent sites interact extensively, via chromatin looping, with the proximal transiently bound sites forming ERα clustered enhancers in 3D. CRISPR-based deletion of TFF1 persistent site disrupts the formation of its clustered enhancer resulting in the loss of E2-dependent induced expression of TFF1 and its neighboring genes within the same cluster. The clustered enhancers overlap with nuclear ERα puncta that coalesce in a ligand-dependent manner. Furthermore, formation of clustered enhancers, as well as puncta, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish the role of persistent unliganded ERα binding in priming enhancer clusters in 3D that drive transient, but robust, gene expression in a ligand-dependent fashion.
The functional landscape of the human phosphoproteome
Authors: Ochoa David , Jarnuczak Andrew F. , Gehre Maja , Soucheray Margaret , Kleefeldt Askar A. , Viéitez Cristina , Hill Anthony , Garcia-Alonso Luz , Swaney Danielle L. , Vizcaíno Juan Antonio , Noh Kyung-Min , Beltrao Pedro 
Published: February 2019

AbstractProtein phosphorylation is a key post-translational modification regulating protein function in almost all cellular processes. While tens of thousands of phosphorylation sites have been identified in human cells to date, the extent and functional importance of the phosphoproteome remains largely unknown. Here, we have analyzed 6,801 publicly available phospho-enriched mass spectrometry proteomics experiments, creating a state-of-the-art phosphoproteome containing 119,809 human phosphosites. To prioritize functional sites, 59 features indicative of proteomic, structural, regulatory or evolutionary relevance were integrated into a single functional score using machine learning. We demonstrate how this prioritization identifies regulatory phosphosites across different molecular mechanisms and pinpoint genetic susceptibilities at a genomic scale. Several novel regulatory phosphosites were experimentally validated including a role in neuronal differentiation for phosphosites present in the SWI/SNF SMARCC2 complex member. The scored reference phosphoproteome and its annotations identify the most relevant phosphorylations for a given process or disease addressing a major bottleneck in cell signaling studies.
Manganese-induced Parkinsonism in mice is reduced using a novel contaminated water sediment exposure model
Authors: Freeman Dana M. , O’Neal Rachel , Zhang Qiang , Bouwer Edward J. , Wang Zhibin 
Published: February 2019

AbstractThe effects of heavy metals on human health have become an important area of study. For instance, acute manganese toxicity is known to induce Parkinsonism. Heavy metals including manganese enter the aquatic environment from both anthropogenic and natural processes. These metals accumulate within water sediments and their behavior is then dependent upon the sediment composition and phase. These metal-sediment interactions remain to be explored within in-vivo animal studies. To study the effect of these interactions, herein we successfully developed an exposure model in mice that encapsulates the aquatic microenvironment of heavy metals before exposure. Male and female C57/BL6 mice were exposed to manganese contaminated sediment via their drinking water (Sed_Mn) or to manganese placed directly into their drinking water with no prior sediment interaction (Mn) for six weeks. Sediment interaction did not alter total manganese in drinking water (mg/L) or weekly manganese consumption (mg) in males (54.9±1.5 mg) or females (44.6±1.0 mg) over the six-week exposure period. We analyzed motor impairment, a common feature in Parkinson’s disease, using the beam traversal, cylinder, and accelerating rotarod behavioral tests. We observed Parkinson’s like deficits in motor control in both treatment groups as early as four weeks of exposure in males but not in females. Intriguingly, mice given water incubated with manganese spiked sediment (Sed_Mn) performed better overall compared to mice given manganese directly in water (Mn) despite having similar exposure in males and females. Male Sed_Mn mice compared to Mn mice had a 146% reduction in time to cross the beam traversal test (p<0.05), a 10% increase in rearing activity in the cylinder test (p<0.05), and a 14% increase in time remaining on the rotarod (not significant). Female Sed_Mn mice compared to Mn mice had no change in the time to cross the beam traversal test, a 36% increase in rearing activity in the cylinder test (p<0.05), and a 35% increase in time on the rotarod (p<0.05). Our study indicates that metal-sediment interactions may alter metal toxicity in mammals and introduces a new exposure model to test the toxicity of metal contaminants of drinking water.
Characterization of the workplace chemical exposome using untargeted LC-MS/MS: a case study
Authors: McCall Laura-Isobel , Anderson Victoria M. , Fogle Robert S. , Haffner Jacob J. , Hossain Ekram , Liu Renmeng , Ly Anita H. , Ma Hongyan , Nadeem Maham , Yao Songyuan 
Published: February 2019

AbstractWestern people now spend close to 90% of their time indoors, one-quarter of which occurs at their place of employment. As such, interactions between employees and the workplace built environment have significant potential impact on employee health and safety. However, the range of workers’ daily chemical exposures is still poorly understood. Likewise, the influence of workers themselves and of worker behavior on the chemical composition of the workplace is still unknown. In this case study, we used untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) to compare the chemical signatures of three different types of workplaces: scientific research buildings, office buildings, and one mixed-purpose building. Our results identified differential signatures of public building surfaces based on building purpose, sampling location and surface materials. Overall, these results are helping define the influence of human behavior on the workplace chemical environment and identify the chemical hazards to which people are exposed throughout their workday.HighlightsImplementation of untargeted liquid chromatography-tandem mass spectrometry to study workplace chemical exposures.Shared chemical signatures were identified based on building purpose.Differential chemical signatures were identified based on surface material and sampling location.Annotated molecules include pharmaceuticals, illicit drugs, food chemicals, constituents of paints and stains, and cleaning products.
SNIPE score can capture prodromal Alzheimer’s in cognitively normal subjects
Authors: Zandifar Azar , Fonov Vladimir , Potvin Olivier , Duchesne Simon , Collins D. Louis ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2019

AbstractCapturing early changes in the brain related to Alzheimer’s disease may lead to models that successfully predict cognitive decline and the eventual onset of dementia, well ahead of onset of clinical symptoms. In this study we used both hippocampal volume and our hippocampal driven SNIPE score to show which marker better captures Alzheimer’s related changes in a large dataset of normal controls (N=515) from the ADNI study, comparing controls that remain cognitively stable and controls that progress to either MCI or Alzheimer’s dementia during 10 years of follow-up (median follow-up: 30 months). We measured hippocampal volume and SNIPE score and found that the effect size to differentiate between stable and progressor groups was significantly larger for SNIPE score than for volume. Our results also show that there is a significant age-related difference between groups for both markers, and the difference is greater with the SNIPE score. Our experiments show that considering high sensitivity of our SNIPE score regarding to early AD-related brain changes, this marker is a better candidate in comparison to hippocampal volume for predicting the future onset of dementia.