bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic Preictal Discharges in Patients With Mesial Temporal Lobe Epilepsy
Authors: Chen Jia , Li Liping , Wu Dongyan , Li Xiaoxuan , Xue Qing , Wang Liying , Du Jialin , Wang Di , Hu Minjing , Ren Liankun , Wang Yuping 
Published: May 2018

Purpose:
It has been challenging to detect early changes preceding seizure onset in patients with epilepsy. This study investigated the preictal discharges (PIDs) by intracranial electroencephalogram of 11 seizures from 7 patients with mesial temporal lobe epilepsy.

Methods:
The EEG segments consisting of 30 seconds before ictal onset and 5 seconds after ictal onset were selected for analysis. After PID detection, the amplitude and interval were measured. According to the timing of PID onset, the 30-second period preceding seizure onset was divided into two stages: before PID stage and PID stage. The autocorrelation coefficients during the two stages were calculated and compared.

Results:
Preictal discharge amplitude progressively increased, while PID interval gradually decreased toward seizure onset. The autocorrelation coefficients of PID channels were significantly higher during PID stage than before PID stage. There was an overlap between channels with PIDs and seizure onset channels (80.77%).

Conclusions:
Preictal discharges emerge prior to ictal event, with a dynamic change and a spatial correlation with seizure onset zone. These findings deepen our understanding of seizure generation and help early prediction and localization of seizure onset zone.
Determination of sulfonamides in milk by capillary electrophoresis with PEG@MoS
2
as a dispersive solid-phase extraction sorbent
Authors: An Jianxin , Wang Xuan , Ming Meiting , Li Jian , Ye Nengsheng 
Published: May 2018

A synthetic polyethylene glycol-molybdenum disulfide (PEG@MoS
2
) composite was prepared using a simple method, and the application of this material in dispersive solid-phase extraction (DSPE) was investigated for the enrichment of eight sulfonamides (SAs) in milk samples. The composite was characterized by energy dispersive spectroscopy, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and Brunauer–Emmett–Teller measurements. The results showed that the MoS
2
synthesized in the presence of PEG has the advantage of a larger surface area and that the adsorption effect of this MoS
2
was enhanced. After extraction, the eight SAs were separated by capillary zone electrophoresis with a good linear relationship (
R
2
> 0.9902) in the range of 0.3–30 µg ml
−1
and good precision (between 0.32% and 9.83%). Additionally, good recoveries (between 60.52% and 110.91%) were obtained for the SAs in the milk samples. The developed PEG@MoS
2
-based DSPE method could be applied for the enrichment of SAs in real milk samples.
Subset-Based Analysis using Gene-Environment Interactions for Discovery of Genetic Associations across Multiple Studies or Phenotypes
Authors: Yu Youfei , Xia Lu , Lee Seunggeun , Zhou Xiang , Stringham Heather M , Boehnke Michael , Mukherjee Bhramar 
Published: May 2018

AbstractObjectivesClassical methods for combining summary data from genome-wide association studies (GWAS) only use marginal genetic effects and power can be compromised in the presence of heterogeneity. We aim to enhance the discovery of novel associated loci in the presence of heterogeneity of genetic effects in sub-groups defined by an environmental factor.MethodsWe present a p-value Assisted Subset Testing for Associations (pASTA) framework that generalizes the previously proposedassociation analysis based on subsets (ASSET) method by incorporating gene-environment (G-E) interactions into the testing procedure. We conduct simulation studies and provide two data examples.ResultsSimulation studies show that our proposal is more powerful than methods based on marginal associations in the presence of G-E interactions and maintains comparable power even in their absence. Both data examples demonstrate that our method can increase power to detect overall genetic associations and identify novel studies/phenotypes that contribute to the association.ConclusionsOur proposed method can be a useful screening tool to identify candidate single nucleotide polymorphisms (SNPs) that are potentially associated with the trait(s) of interest for further validation. It also allows researchers to determine the most probable subset of traits that exhibit genetic associations in addition to the enhancement of power.
The RNA demethylase FTO targets m6Am in snRNA to establish distinct methyl isoforms that influence splicing
Authors: Mauer Jan , Sindelar Miriam , Guez Théo , Vasseur Jean-Jacques , Rentmeister Andrea , Gross Steven S. , Pellizzoni Livio , Debart Françoise , Goodarzi Hani , Jaffrey Samie R. 
Published: May 2018

SummarySmall nuclear RNAs (snRNAs) are core spliceosome components and mediate pre-mRNA splicing. During their biogenesis, snRNAs acquire several constitutive nucleotide modifications. Here we show that snRNAs also contain a regulated and reversible nucleotide modification causing them to exist as two different methyl isoforms, m1 and m2, reflecting the methylation state of the adenosine adjacent to the snRNA cap. We find that snRNA biogenesis involves the formation of an initial m1-isoform with a single-methylated adenosine (2’-O-methyladenosine, Am), which is then converted to a dimethylated m2-isoform (N6,2’-O-dimethyladenosine, m6Am). The relative m1- and m2-isoform levels are determined by the RNA demethylase FTO, which selectively demethylates the m2-isoform. We show FTO is inhibited by endogenous metabolites, resulting in increased m2-snRNA levels. Furthermore, cells that exhibit high m2-snRNA levels show altered patterns of alternative splicing. Together, these data reveal that FTO has a central role in snRNA biogenesis and controls a previously unknown step of snRNA processing involving reversible methylation, thereby providing a potential link between reversible RNA modifications and mRNA splicing.
A tail of two sides: Artificially doubled false positive rates in neuroimaging due to the sidedness choice with t-tests
Authors: Chen Gang , Cox Robert W. , Glen Daniel R. , Rajendra Justin K. , Reynolds Richard C. , Taylor Paul A. 
Published: May 2018

ABSTRACTOne-sided t-tests are widely used in neuroimaging data analysis. While such a test may be applicable when investigating specific regions and prior information about directionality is present, we argue here that it is often mis-applied, with severe consequences for false positive rate (FPR) control. Conceptually, a pair of one-sided t-tests conducted in tandem (e.g., to test separately for both positive and negative effects), effectively amounts to a two-sided t-test. However, replacing the two-sided test with a pair of one-sided tests without multiple comparisons correction essentially doubles the intended FPR of statements made about the same study; that is, the actual family-wise error (FWE) of results at the whole brain level would be 10% instead of the 5% intended by the researcher. Therefore, we strongly recommend that, unless otherwise explicitly justified, two-sided t-tests be applied instead of two simultaneous one-sided t-tests.
The timing and direction of introgression under the multispecies network coalescent
Authors: Hibbins Mark S. , Hahn Matthew W. 
Published: May 2018

AbstractIntrogression is a pervasive biological process, and many statistical methods have been developed to infer its presence from genomic data. However, many of the consequences and genomic signatures of introgression remain unexplored from a methodological standpoint. Here, we develop a model for the timing and direction of introgression based on the multispecies network coalescent, and from it suggest new approaches for testing introgression hypotheses. We suggest two new statistics,D1andD2, which can be used in conjunction with other information to test hypotheses relating to the timing and direction of introgression, respectively.D1may find use in evaluating cases of homoploid hybrid speciation, whileD2provides a four-taxon test for polarizing introgression. Although analytical expectations for our statistics require a number of assumptions to be met, we show how simulations can be used to test hypotheses about introgression when these assumptions are violated. We apply theD1statistic to genomic data from the wild yeastSaccharomyces paradoxus, a proposed example of homoploid hybrid speciation, demonstrating its use as a test of this model. These methods provide new and powerful ways to address questions relating to the timing and direction of introgression.
The y-ome defines the thirty-four percent ofEscherichia coligenes that lack experimental evidence of function
Authors: Ghatak Sankha , King Zachary A. , Sastry Anand , Palsson Bernhard O. 
Published: May 2018

AbstractExperimental studies ofEscherichia coliK-12 MG1655 often implicate poorly annotated genes in cellular phenotypes. However, we lack a systematic understanding of these genes. How many are there? What informationisavailable for them? And what features do they share that could explain the gap in our understanding? Efforts to build predictive, whole-cell models ofE. coliinevitably face this knowledge gap. We approached these questions systematically by assembling annotations from the knowledge bases EcoCyc, EcoGene, UniProt, RefSeq, and RegulonDB. We identified the genes that lack direct experimental evidence of function (the “y-ome”) which include 1563 of 4653 unique genes (34%), of which 131 have absolutely no evidence of function. An additional 304 genes (6.6%) are pseudogenes or phantom genes. y-ome genes tend to have lower expression levels and are enriched in the termination region of theE. colichromosome. Where evidence is available for y-ome genes, it most often points to them being membrane proteins and transporters. We resolve the misconception that a gene inE. coliwhose primary name starts with “y” is unannotated, and we discuss the value of the y-ome for systematic improvement ofE. coliknowledge bases and its extension to other organisms.
Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts
Authors: Pascalis Chiara De , Pérez-González Carlos , Seetharaman Shailaja , Boëda Batiste , Vianay Benoit , Burute Mithila , Leduc Cécile , Borghi Nicolas , Trepat Xavier , Etienne-Manneville Sandrine 
Published: May 2018

AbstractMesenchymal cell migration relies on the coordinated regulation of the actin and microtubule networks which participate in polarised cell protrusion, adhesion and contraction. During collective migration, most of the traction forces are generated by the acto-myosin network linked to focal adhesions at the front of leader cells, which transmit these pulling forces to the followers. Here, using an in vitro wound healing assay to induce polarisation and collective directed migration of primary astrocytes, we show that the intermediate filament (IF) network composed of vimentin, GFAP and nestin contributes to directed collective movement by controlling the distribution of forces in the migrating cell monolayer. Together with the cytoskeletal linker plectin, these IFs control the organisation and dynamics of the acto-myosin network, promoting the actin-driven treadmilling of adherens junctions, thereby facilitating the polarisation of leader cells. Independently of their effect on adherens junctions, IFs influence the dynamics and localisation of focal adhesions and limit their mechanical coupling to the acto-myosin network. We thus conclude that IFs promote collective directed migration by restricting the generation of traction forces to the front of leader cells, preventing aberrant tractions in the followers and by contributing to the maintenance of lateral cell-cell interactions.
Integrated accounts of behavioral and neuroimaging data using flexible recurrent neural network models
Authors: Dezfouli Amir , Morris Richard , Ramos Fabio , Dayan Peter , Balleine Bernard W. 
Published: May 2018

AbstractNeuroscience studies of human decision-making abilities commonly involve sub-jects completing a decision-making task while BOLD signals are recorded using fMRI. Hypotheses are tested about which brain regions mediate the effect of past experience, such as rewards, on future actions. One standard approach to this is model-based fMRI data analysis, in which a model is fitted to the behavioral data, i.e., a subject’s choices, and then the neural data are parsed to find brain regions whose BOLD signals are related to the model’s internal signals. However, the internal mechanics of such purely behavioral models are not constrained by the neural data, and therefore might miss or mischaracterize aspects of the brain. To address this limitation, we introduce a new method using recurrent neural network models that are flexible enough to be jointly fitted to the behavioral and neural data. We trained a model so that its internal states were suitably related to neural activity during the task, while at the same time its output predicted the next action a subject would execute. We then used the fitted model to create a novel visualization of the relationship between the activity in brain regions at different times following a reward and the choices the subject subsequently made. Finally, we validated our method using a previously published dataset. We found that the model was able to recover the underlying neural substrates that were discovered by explicit model engineering in the previous work, and also derived new results regarding the temporal pattern of brain activity.
Exploratory noise governs both flexibility and spontaneous errors and is regulated by cocaine
Authors: Ebitz R. Becket , Sleezer Brianna J. , Jedema Hank P. , Bradberry Charles W. , Hayden Benjamin Y. 
Published: May 2018

SUMMARYIn many cognitive processes, lapses (spontaneous errors) are attributed to nuisance processes like sensorimotor noise or disengagement. However, some lapses could also be caused by exploratory noise: behavioral randomness that facilitates learning in changing environments. If so, strategic processes would need only up-regulate (rather than generate) exploration to adapt to a changing environment. This view predicts that lapse rates should be correlated with flexibility because they share a common cause. We report that when macaques performed a set-shifting task, lapse rates were negatively correlated with perseverative error frequency. Furthermore, chronic exposure to cocaine, which impairs cognitive flexibility, increased perseverative errors, but, surprisingly, improved overall performance by reducing lapse rates. We reconcile these results with a model in which cocaine decreased exploration by deepening attractor basins corresponding to rules. These results support the idea that exploratory noise contributes to lapses, meaning that it affects rule-based decision-making even when it has no strategic value.
Heterogeneous Impacts of Protein-Stabilizing Osmolytes on Hydrophobic Interaction
Authors: Mukherjee Mrinmoy , Mondal Jagannath 
Published: May 2018

AbstractOsmolytes’ mechanism of protecting proteins against denaturation is a longstanding puzzle, further complicated by the complex diversities inherent in protein sequences. An emergent approach in understanding osmolytes’ mechanism of action towards biopolymer has been to investigate osmolytes’ interplay with hydrophobic interaction, the major driving force of protein folding. However, the crucial question is whether all these protein-stabilizing osmolytes display asingle unifiedmechanism towards hydrophobic interactions. By simulating the hydrophobic collapse of a macromolecule in aqueous solutions of two such osmoprotectants, Glycine and Trimethyl N-oxide (TMAO), both of which are known to stabilize protein’s folded conformation, we here demonstrate that these two osmolytes can impart mutually contrasting effects towards hydrophobic interaction. While TMAO preserves its protectant nature across diverse range of polymer-osmolyte interactions, glycine is found to display an interesting cross-over from being a protectant at weaker polymer-osmolyte interaction to a denaturant of hydrophobicity at stronger polymer-osmolyte interactions. A preferential-interaction analysis reveals that a subtle balance ofconformation-dependentexclusion/binding of osmolyte molecules from/to the macromolecule holds the key to overall heterogenous behavior. Specifically, TMAO’s consistent stabilization of collapsed configuration of macromolecule is found to be a result of TMAO’s preferential binding to polymer via hydrophobic methyl groups. However, polar Glycine’s cross-over from being a protectant to denaturant across polymer-osmolyte interaction is rooted in its switch from preferential exclusion to preferential binding to the polymer with increasing interaction. Overall, by highlighting the complex interplay of osmolytes with hydrophobic interaction, this work puts forward the necessity of quantitative categorization of osmolytes’ action in protein.
The human cytomegalovirus ER resident glycoprotein UL148 activates the unfolded protein response
Authors: Siddiquey Mohammed N.A. , Zhang Hongbo , Nguyen Christopher C. , Domma Anthony J. , Kamil Jeremy P. 
Published: May 2018

ABSTRACTEukaryotic cells are equipped with three sensors that respond to the accumulation of misfolded proteins within the lumen of the endoplasmic reticulum (ER) by activating the unfolded protein response (UPR), which functions to resolve proteotoxic stresses involving the secretory pathway. Here, we identify UL148, a viral ER resident glycoprotein from human cytomegalovirus (HCMV), as an inducer of the UPR. Metabolic labeling results indicate that global mRNA translation is markedly decreased when UL148 expression is induced in uninfected cells. Further, we find evidence suggesting that ectopic expression of UL148 is sufficient to activate at least two UPR sensors: the inositol requiring enzyme-1 (IRE1), as indicated by splicing ofXbp1mRNA, and the PKR-like ER kinase (PERK), as indicated by phosphorylation of eIF2αand accumulation of ATF4 protein. During wild-type HCMV infection,Xbp-1splicing, eIF2αphosphorylation and ATF4 accumulation neatly accompanied the onset of UL148 expression. However, the appearance of these UPR indicators was either markedly delayed or absent duringUL148-null infections. siRNA depletion of PERK dampened the extent of eIF2αphosphorylation and ATF4 induction observed during wild-type infection, implicating PERK as opposed to other eIF2αkinases. A virus disrupted forUL148showed statistically significant 2- to 4-fold decreases during infection in the levels of transcripts canonically regulated by PERK/ATF4 and by the ATF6 pathway.Taken together, our results argue that UL148 is sufficient to activate the UPR when expressed ectopically and that UL148 is an important cause of UPR activation in the context of the HCMV infected cell.IMPORTANCEThe unfolded protein response (UPR) is an ancient cellular response to ER stress of broad importance to viruses. Certain consequences of the UPR, including mRNA degradation and translational shut-off, would presumably be disadvantageous to viruses, while other attributes of the UPR, such as ER expansion and upregulation of protein folding chaperones, might enhance viral replication. Although HCMV is estimated to express at least 200 distinct viral proteins, we show that the HCMV ER resident glycoprotein UL148 contributes substantially to the UPR during infection, and moreover is sufficient to activate the UPR in non-infected cells. Experimental activation of the UPR in mammalian cells is difficult to achieve without the use of toxins. Therefore, UL148 may provide a new tool to investigate fundamental aspects of the UPR. Furthermore, our findings may have implications for understanding the mechanisms underlying the effects of UL148 on HCMV cell tropism and evasion of cell mediated immunity.
The contribution of melanization toDrosophilasurvival changes withEnterococcus faecalisV583 genomic content
Authors: Teixeira Neuza , Jacinto António , Silva Lopes Maria de Fátima 
Published: May 2018

ABSTRACTEnterococcus faecalisis a human opportunist pathogen able to infect and killDrosophila. Previous studies proved thatE. faecaliscarrying the Fsr quorum sensing system are extremely virulent. Fsr is the regulator of two important virulence factors, gelatinase and serine protease, which cause death ofDrosophilaadult flies by decreasing its tolerance to infection. The exact mechanism underlying the toxicity of theseE. faecalisvirulence factors is nevertheless not known, in particular the way they interfere with the host immune response. In the present study, we investigated the influence of Fsr-GelE-SprE bacterial factors on different immunity responses, namely antimicrobial peptide production, phagocytosis and melanization. UsingE. faecalisV583 wild type andE. faecalisV583 ΔfsrBΔgelEΔsprEmutant we showed that both drosomycin production and phagocytosis were activated to similar levels by the two bacterial strains. However, fly pupae infected with the mutant strain showed less melanization and higher survival rates when compared to pupae infected with wild type bacteria. Using adult flies carrying thePPO1ΔPPO2Δmutation, we found that absence of melanization had a different impact in survival of the flies when infected with the twoE. faecalisstrains.PPO1Δ,PPO2Δmutant flies were more tolerant toE. faecalisdeprived of its major virulence factors. By showing that the presence of theE. faecalisproteases completely alters the impact of melanization activation onDrosophilatolerance, this study provides new clues on the interactions betweenE. faecalisvirulence factors and the fly´s immune system. Future studies onDrosophilaimmunity should consider the pathogen genomic content.
A particle-filter framework for robust cryoEM 3D reconstruction
Authors: Hu Mingxu , Yu Hongkun , Gu Kai , Wang Kunpeng , Ren Siyuan , Li Bing , Gan Lin , Xu Shizhen , Yang Guangwen , Shen Yuan , Li Xueming 
Published: May 2018

AbstractElectron cryo-microscopy (cryoEM) is now a powerful tool in determining atomic structures of biological macromolecules under nearly natural conditions. The major task of single-particle cryoEM is to estimate a set of parameters for each input particle image to reconstruct the three-dimensional structure of the macromolecules. As future large-scale applications require increasingly higher resolution and automation, robust high-dimensional parameter estimation algorithms need to be developed in the presence of various image qualities. In this paper, we introduced a particle-filter algorithm for cryoEM, which was a sequential Monte Carlo method for robust and fast high-dimensional parameter estimation. The cryoEM parameter estimation problem was described by a probability density function of the estimated parameters. The particle filter uses a set of random and weighted support points to represent such a probability density function. The statistical properties of the support points not only enhance the parameter estimation with self-adaptive accuracy but also provide the belief of estimated parameters, which is essential for the reconstruction phase. The implementation of these features showed strong tolerance to bad particles and enabled robust defocus refinement, demonstrated by the remarkable resolution improvement at the atomic level.