bluuebunny/crossref_metadata_2025_split huggingface dataset:
EEG-based Prediction of Cognitive Load in Intelligence Tests
Authors: Friedman Nir , Fekete Tomer , Gal Ya’akov (Kobi) , Shriki Oren 
Published: February 2019

ABSTRACTMeasuring and assessing the cognitive load associated with different tasks is crucial for many applications, from the design of instructional materials to monitoring the mental wellbeing of aircraft pilots. The goal of this paper is to utilize EEG to infer the cognitive workload of subjects during intelligence tests. We chose the well established advanced progressive matrices test, an ideal work-frame because it presents problems at increasing levels of difficulty, and has been rigorously validated in past experiments. We train classic machine learning models using basic EEG measures as well as measures of network connectivity and signal complexity. Our findings demonstrate that cognitive load can be well predicted using these features, even for a low number of channels. We show that by creating an individually tuned neural network for each subject, we can improve prediction compared to a general model and that such models are robust to decreasing the number of available channels as well.
GWAS hints at pleiotropic roles forFLOWERING LOCUS Tin flowering time and yield-related traits in canola
Authors: Raman Harsh , Raman Rosy , Qiu Yu , Yadav Avilash Singh , Sureshkumar Sridevi , Borg Lauren , Maheswaran Rohan , Wheeler David , Owens Ollie , Menz Ian , Balasubramanian Sureshkumar 
Published: February 2019

AbstractTransition to flowering at the right time is critical for local adaptation and to maximize seed yield in canola, which is an important oilseed crop. There is extensive variation among canola varieties in flowering time. However, our understanding of underlying genes and their role in canola productivity is still limited. We reveal natural variation in flowering time and response to photoperiod in a diverse GWAS panel (up to 368 accessions) of canola and identify associated SNPs across multiple experiments. Complementary QTL and eQTL mapping studies were also conducted in an Australian doubled haploid (DH) population for flowering time and other grain yield related traits. We show that several associations that were repeatedly detected across experiments map in the vicinity ofFLOWERING LOCUS T(FT) paralogues and its known transcriptional regulators. QTL mapping study in a DH population detected consistent genomic regions close toFTparalogs.FTsequences vary between accessions andFTexpression in field and controlled environment grown plants was correlated with flowering time.FTparalogs displayed association not only with flowering time, but also with plant emergence, shoot biomass and grain yield. Our findings suggest thatFTparalogs not only modulate flowering time but also modulate yield-related productivity traits in canola.HighlightThe genetic association, eQTL and expression analyses suggest thatFTparalogs have multifaceted roles in canola flowering time, plant development and productivity traits.
Early migration of precursor neurons initiates cellular and functional regeneration after spinal cord injury in zebrafish
Authors: Vandestadt Celia , Vanwalleghem Gilles C. , Castillo Hozana Andrade , Li Mei , Schulze Keith , Khabooshan Mitra , Don Emily , Anko Minna-Liisa , Scott Ethan K. , Kaslin Jan 
Published: February 2019

AbstractZebrafish have a remarkable capacity to regenerate following spinal cord (SC) injury but the responsible cellular events are not well understood. We used in vivo imaging and genetics to pin-point specific cellular processes controlling SC regeneration in zebrafish. We identified two temporally and mechanistically distinct phases of cellular regeneration in the SC. The initial phase relies on migration of precursor neurons to the injury, enabling rapid functional recovery, and activation of quiescent neural progenitor cells (NPCs). A second phase of regenerative neurogenesis compensates for both the lost tissue and cells depleted due to precursor neuron migration. We propose a critical role of precursor neurons recruitment in initiating neuronal circuit recovery and buying sufficient time for regenerative neurogenesis to take place. Taken together, our data suggests an unanticipated role of precursor cell recruitment in driving neural repair and functional recovery during the regenerative response.Graphical Abstract
NMR Mapping of Disordered Segments from a Viral Scaffolding Protein Encapsulated in a 23 MDa Procapsid Complex
Authors: Whitehead Richard D. , Teschke Carolyn M. , Alexandrescu Andrei T. 
Published: February 2019

SummaryScaffolding proteins are requisite for the capsid shell assembly of many tailed dsDNA bacteriophages, some archaeal viruses, herpesviruses, and adenoviruses. Despite their importance, no high-resolution structural information is available for scaffolding proteins within capsids. Here we use the inherent size limit of NMR to identify mobile segments of the phage P22 scaffolding protein in solution and when incorporated into a ~23 MDa procapsid complex. Free scaffolding protein gives NMR signals from both the N and C-terminus. When scaffolding protein is incorporated into P22 procapsids, NMR signals from the C-terminal helix-turn-helix (HTH) domain disappear due to binding to the procapsid interior. Signals from the N-terminal domain persist, indicating this segment retains flexibility when bound to procapsids. The unstructured character of the N-terminus coupled with its high content of negative charges, is likely important for the dissociation and release of scaffolding protein, during the genome packaging step accompanying phage maturation.Graphical AbstractScaffolding protein (SP) nucleates the assembly of phage P22 coat proteins into an icosahedral capsid structure that envelops the viral genome. NMR spectra of free SP show signals from the N-terminus (red) and a helix-turn-helix domain at the C-terminus (blue). When SP is incorporated into empty phage P22 procapsids to form a 23 MDa complex, the subset of signals from the N-terminal 40 residues persist indicating this segment is disordered. The unfolded nature of the N-terminus coupled with its negatively charged character, is important for the functional requirement of SP to exit the capsid as it becomes packaged with its genome.
Cell non-autonomous interactions during non-immune stromal progression in the breast tumor microenvironment
Authors: Utama Raditya , Bastian Anja , Sadagopan Narayanan , Jin Ying , Antoniou Eric , Gao Qing , Huang Yinghui J. , Gopalakrishna-Pillai Sailesh , Lee Peter P. , Atwal Gurinder S. 
Published: February 2019

SummaryThe breast tumor microenvironment of primary and metastatic sites is a complex milieu of differing cell populations, consisting of tumor cells and the surrounding stroma. Despite recent progress in delineating the immune component of the stroma, the genomic expression landscape of the non-immune stroma (NIS) population and their role in mediating cancer progression and informing effective therapies are not well understood. Here we obtained 52 cell-sorted NIS and epithelial tissue samples across 37 patients from i) normal breast, ii) normal breast adjacent to primary tumor, iii) primary tumor, and iv) metastatic tumor sites. Deep RNA-seq revealed diverging gene expression profiles as the NIS evolves from normal to metastatic tumor tissue, with intra-patient normal-primary variation comparable to inter-patient variation. Significant expression changes between normal and adjacent normal tissue support the notion of a cancer field effect, but extended out to the NIS. Most differentially expressed protein-coding genes and lncRNAs were found to be associated with pattern formation, embryogenesis, and the epithelial-mesenchymal transition. We validated the protein expression changes of a novel candidate gene, C2orf88, by immunohistochemistry staining of representative tissues. Significant mutual information between epithelial ligand and NIS receptor gene expression, across primary and metastatic tissue, suggests a unidirectional model of molecular signaling between the two tissues. Furthermore, survival analyses of 827 luminal breast tumor samples demonstrated the predictive power of the NIS gene expression to inform clinical outcomes. Together, these results highlight the evolution of NIS gene expression in breast tumors and suggest novel therapeutic strategies targeting the microenvironment.
Nutrient transporter translocation to the plasma membrane via a Golgi-independent unconventional route
Authors: Bouris Vangelis , Martzoukou Olga , Amillis Sotiris , Diallinas George 
Published: February 2019

AbstractNutrient transporters are believed to traffic from their site of synthesis, the ER, to the plasma membrane, through the Golgi, using the conventional vesicular trafficking pathway. However, here we report that the UapA purine transporter in Aspergillus nidulans, follows a Golgi-independent, unconventional new route, which does not involve key Rab GTPases, AP adaptors, microtubules or endosomes, but is dependent on functional COPII, clathrin heavy chain (ClaH) and actin. The role of ClaH in transporter secretion is shown to be unrelated to that performing, together with Rab11/AP-1, at the Golgi, and is seemingly due to an effect in actin network functioning. Our findings are discussed within the frame of a model that rationalizes why the trafficking mechanism uncovered herein might hold true for transporters in higher organisms.One Sentence SummaryFungal transporters use a non-polar, COPII- and actin-dependent, route for subcellular traffic to the cell membrane.
Functional analysis of evolutionary human methylated regions in schizophrenia patients
Authors: Banerjee Niladri , Polushina Tatiana , Stavrum Anne-Kristin , Steen Vidar Martin , Le Hellard Stephanie 
Published: February 2019

AbstractBackgroundRecent studies have implicated variations in DNA methylation in the aetiology of schizophrenia. Genome-wide scans in both brain and blood report differential methylated regions (DMRs) and positions (DMPs) between patients with schizophrenia and healthy controls. Previously, we reported that DMRs where human specific methylation (hDMR) has occurred over evolutionary time are enriched for schizophrenia-associated markers (SCZ_hDMR). However, it is unknown whether these human specific DMRs show variable methylation in patients with schizophrenia.MethodsUsing publicly available data, we investigate if human specific DMRs that harbour genetic variants associated with schizophrenia are differentially methylated between cases and controls.ResultsWe find statistically significant (p < 1e-4) methylation difference in schizophrenia associated human specific DMRs (SCZ hDMR) between brain samples of cases and controls. However, we fail to find evidence of similar differences in methylation in blood samples.ConclusionRegions that are evolutionarily important for human species and that are associated with schizophrenia, also show difference in methylation variation in the brain in patients with schizophrenia.
Microtubules stabilize intercellular contractile force transmission during tissue folding
Authors: Ko Clint S. , Tserunyan Vardges , Martin Adam C. 
Published: February 2019

AbstractDuring development, forces transmitted between cells are critical for sculpting epithelial tissues. Actomyosin contractility in the middle of the cell apex (medioapical) can change cell shape (e.g., apical constriction), but can also result in force transmission between cells via attachments to adherens junctions. How actomyosin networks maintain attachments to adherens junctions under tension is poorly understood. Here, we discovered that microtubules stabilize actomyosin intercellular attachments in epithelia duringDrosophilamesoderm invagination. First, we used live imaging to show a novel arrangement of the microtubule cytoskeleton during apical constriction: medioapical, non-centrosomal Patronin (CAMSAP) foci formed by actomyosin contraction organizes an apical microtubule network. Microtubules were required for mesoderm invagination but were not necessary for apical contractility or adherens junction assembly. Instead, microtubules promoted the stable connection between medioapical actomyosin and adherens junctions. These results define a role for coordination between actin and microtubule cytoskeletal systems in intercellular force transmission and tissue morphogenesis.
Machine-learning to Improve Prediction of Mortality following Acute Myocardial Infarction: An Assessment in the NCDR-Chest Pain-Myocardial Infarction Registry
Authors: Khera Rohan , Haimovich Julian , Hurley Nate , McNamara Robert , Spertus John A , Desai Nihar , Masoudi Frederick A. , Huang Chenxi , Normand Sharon-Lise , Mortazavi Bobak J. , Krumholz Harlan M 
Published: February 2019

ABSTRACTIntroductionAccurate prediction of risk of death following acute myocardial infarction (AMI) can guide the triage of care services and shared decision-making. Contemporary machine-learning may improve risk-prediction by identifying complex relationships between predictors and outcomes.Methods and ResultsWe studied 993,905 patients in the American College of Cardiology Chest Pain-MI Registry hospitalized with AMI (mean age 64 ± 13 years, 34% women) between January 2011 and December 2016. We developed and validated three machine learning models to predict in-hospital mortality and compared the performance characteristics with a logistic regression model. In an independent validation cohort, we compared logistic regression with lasso regularization (c-statistic, 0.891 [95% CI, 0.890-0.892]), gradient descent boosting (c-statistic, 0.902 [0.901-0.903]), and meta-classification that combined gradient descent boosting with a neural network (c-statistic, 0.904 [0.903-0.905]) with traditional logistic regression (c-statistic, 0.882 [0.881-0.883]). There were improvements in classification of individuals across the spectrum of patient risk with each of the three methods; the meta-classifier model – our best performing model - reclassified 20.9% of individuals deemed high-risk for mortality in logistic regression appropriately as low-to-moderate risk, and 8.2% of deemed low-risk to moderate-to-high risk based consistent with the actual event rates.ConclusionsMachine-learning methods improved the prediction of in-hospital mortality for AMI compared with logistic regression. Machine learning methods enhance the utility of risk models developed using traditional statistical approaches through additional exploration of the relationship between variables and outcomes.
Determinants of Self-referral among Outpatients at Referral Hospitals in East Wollega, Western Ethiopia
Authors: Geta Edosa Tesfaye , Belete Yibeltal Siraneh , Yesuf Elias Ali 
Published: February 2019

BackgroundPatient self-referral is a condition when patients refer themselves to higher level health facilities without having to see anyone else first or without being told to refer themselves by health professional. Despite the expansion in the number of health facilities, it has been seen when patients routinely accessed referral hospitals. The study aims to determine the magnitude and identify determinants of outpatient self-referral at referral hospitals.MethodsFacility based cross sectional study design was used to collect data from December 01- 30; 2017.The sample size was determined by using single population proportion formula. Data entry and analysis were made using SPSS version 20. Descriptive statistics of frequency, bivariate and multivariate logistic regression were performed.ResultsA total of 404 outpatients were included making response rate 96.8%. Among 391 outpatients interviewed 330(84.4%) were self-referred.The factors significantly associated with outpatient self-referral were referral information (AOR and 95%CI=0.324(0.150-0.696), illness severity (AOR and 95% CI=3.496(1.473-8.297), confidence of patients to get providers (AOR and 95 CI=3.027(1.510-6.070), availability of laboratory (AOR and 95%CI=4.966(2.199-11.216) and drugs (AOR and 95%CI=2.366(1.013-5.526) and quality of services (AOR and 95%CI=2.996(1.418-6.328).ConclusionThe proportion of outpatients’ self-referral was high and that associated with referral information, patient confidence to get health care providers, severity of illness, availability of laboratory and drugs, and quality of services. There should be monitoring system of referral linkage of health facilities at all levels and the health facilities should create awareness in the community about referral linkages of health facilities.
Characteristics of executive control network function based on a lateralized version of the ANT-R test in athletes from open skill sports: An fNIRS study
Authors: Yu Miao , Liu Yi B. , Yang Guang 
Published: February 2019

AbstractThe purpose of the study was to investigate the executive control network function characteristics of interceptive and strategic sports athletes from open skill sports. In order to do so, we used a revised lateralized attention network task to measure executive control efficiency and activation related to flanker interference changes on the right frontoparietal network using functional near-infrared spectroscopy in athletes from different sport sub-categories. Strategic athletes had higher accuracy and lower flanker conflict effects on accuracy, as well as longer reaction time and stronger conflict effects under the valid cue and invalid cue conditions. This was accompanied by higher activity in the right inferior frontal gyrus. These results extend the evidence suggesting that differences among interceptive sports and strategic sports athletes are due to the former using higher velocities to solve conflicts, and the latter using higher accuracy in the same tasks. These effects are attributed to differences in the right frontoparietal network.
PKA and HOG signaling contribute separable roles to anaerobic xylose fermentation in yeast engineered for biofuel production
Authors: Wagner Ellen R. , Myers Kevin S. , Riley Nicholas M. , Coon Joshua J. , Gasch Audrey P. 
Published: February 2019

AbstractLignocellulosic biomass offers a sustainable source for biofuel production that does not compete with food-based cropping systems. Importantly, two critical bottlenecks prevent economic adoption: many industrially relevant microorganisms cannot ferment pentose sugars prevalent in lignocellulosic medium, leaving a significant amount of carbon unutilized. Furthermore, chemical biomass pretreatment required to release fermentable sugars generates a variety of toxins, which inhibit microbial growth and metabolism, specifically limiting pentose utilization in engineered strains. Here we dissected genetic determinants of anaerobic xylose fermentation and stress tolerance in chemically pretreated corn stover biomass, called hydrolysate. We previously revealed that loss-of-function mutations in the stress-responsive MAP kinaseHOG1and negative regulator of the RAS/Protein Kinase A (PKA) pathway,IRA2, enhances anaerobic xylose fermentation. However, these mutations likely reduce cells’ ability to tolerate the toxins present in lignocellulosic hydrolysate, making the strain especially vulnerable to it. We tested the contributions of Hog1 and PKA signaling via IRA2 or PKA negative regulatory subunit BCY1 to metabolism, growth, and stress tolerance in corn stover hydrolysate and laboratory medium with mixed sugars. We found mutations causing upregulated PKA activity increase growth rate and glucose consumption in various media but do not have a specific impact on xylose fermentation. In contrast, mutation ofHOG1specifically increased xylose usage. We hypothesized improving stress tolerance would enhance the rate of xylose consumption in hydrolysate. Surprisingly, increasing stress tolerance did not augment xylose fermentation in lignocellulosic medium in this strain background, suggesting other mechanisms besides cellular stress limit this strain’s ability for anaerobic xylose fermentation in hydrolysate.
TIMP-1 attenuates the development of cutaneous inflammation-induced evoked and ongoing pain through receptor-mediated cell signaling
Authors: B.E. Knight , N. Kozlowski , J. Havelin , T. King , S.J. Crocker , E.E. Young , K.M. Baumbauer 
Published: February 2019

ABSTRACTUnresolved inflammation is a significant predictor for developing chronic pain, and targeting the mechanisms underlying inflammation offers opportunities for therapeutic intervention. During inflammation, matrix metalloproteinase (MMP) activity contributes to tissue remodeling and inflammatory signaling through proteolytic maturation of cytokines. MMP activity is regulated by tissue inhibitors of metalloproteinases (TIMPs) 1-4. TIMP-1 and −2 have known roles in pain, but only in the context of MMP inhibition. However, TIMP-1 also has receptor-mediated cell signaling functions that are not well understood. Here, we examined how TIMP-1-dependent cell signaling impacted inflammatory hypersensitivity and ongoing pain. We found that hindpaw injection of complete Freund’s adjuvant (CFA) increased keratinocyte-derived TIMP-1 that peaked 3 days following inflammation, when mechanical hypersensitivity began to emerge in WT mice. These data suggest that TIMP-1 expression inhibits the development of inflammatory hypersensitivity. To examine this possibility, we injected TIMP-1 knockout (T1KO) mice with a diluted CFA mixture to examine how subtle cutaneous inflammation affected behavioral hypersensitivity. T1KO mice exhibited rapid onset thermal and mechanical hypersensitivity at the site of inflammation that was absent or attenuated in WT controls. We also found that T1KO mice exhibited hypersensitivity in adjacent tissues innervated by different sets of afferents, and skin contralateral to the site of inflammation. Replacement of recombinant murine (rm)TIMP-1 alleviated hypersensitivity when administered at the site and time of inflammation. To examine the MMP-dependent and -independent mechanisms of rmTIMP-1, T1KO mice were administered full-length rmTIMP-1, the N-terminal region (TIMP-1(N)) with MMP-inhibitory properties, or the C-terminal region (TIMP-1(C)) that retains receptor signaling function. Each of the peptides prevented inflammatory hypersensitivity, suggesting that rmTIMP-1 acts through mechanisms that also include receptor-mediated cell signaling. We also found that hypersensitivity was neither due to genotype-specific differences in MMP-9 activity or expression, nor to differences in cytokine expression. Finally, to evaluate the potential clinical utility of TIMP-1, we administered rmTIMP-1 to WT mice and found that rmTIMP-1 prevented clonidine-induced conditioned place preference (e.g., ongoing pain) and inflammatory mechanical hypersensitivity. Collectively, our data suggest a novel role for TIMP-1 in the attenuation of inflammatory pain that occurs through previously uncharacterized cell signaling mechanisms.