bluuebunny/crossref_metadata_2025_split huggingface dataset:
Application of High-Speed T1 Sequences for High-Quality Hepatic Arterial Phase Magnetic Resonance Imaging
Authors: Park Yang Shin , Lee Chang Hee , Kim Jeong Woo , Lee Young-Sun , Paek MunYoung , Kim Kyeong Ah 
Published: April 2017

Purpose
The aim of this study was to compare intraindividual single and multiple arterial phase acquisitions and evaluate which acquisition method was more advantageous for obtaining high-quality hepatic arterial phase in gadoxetic acid–enhanced liver magnetic resonance imaging (MRI).

Materials and Methods
Sixty-seven patients who underwent gadoxetic acid–enhanced liver MRIs and had all 3 kinds of acquisitions (single, dual, and triple arterial phases) were retrospectively included. For hepatic arterial phase imaging, controlled aliasing in parallel imaging results in higher acceleration (CAIPIRINHA) with or without time-resolved imaging with interleaved stochastic trajectories (TWIST) was used. The adequacy of optimal hepatic arterial timing was assessed and respiratory motion artifacts were rated using a 5-point scale, with the highest score indicating the worst image quality. Optimal timing and respiratory motion artifacts among 3 different acquisitions were compared using Fisher exact test and repeated measures one-way analysis of variance with multiple comparisons.

Results
Optimal timing of hepatic arterial phase was observed in 89.6% (60/67) of single arterial phase acquisitions and 98.5% (66/67) of both dual and triple arterial phase acquisitions (P = 0.015). Respiratory motion artifact was significantly lower in single and dual arterial acquisitions than in triple arterial acquisition (mean score, 1.70 vs 1.90 vs 2.49; P < 0.001), although there was no significant difference between single and dual arterial acquisitions (P = 0.091).

Conclusions
A 15-second breath-hold dual arterial phase acquisition during gadoxetic acid–enhanced MRI reliably offers well-timed hepatic arterial phase with less respiratory motion artifact. However, a 13-second breath-hold single arterial phase acquisition was most effective in reducing respiratory motion artifact.
Conservation, development and the management of infectious disease: avian influenza in China, 2004–2012
Authors: Wu Tong , Perrings Charles 
Published: April 2017

There is growing evidence that wildlife conservation measures have mixed effects on the emergence and spread of zoonotic disease. Wildlife conservation has been found to have both positive (dilution) and negative (contagion) effects. In the case of avian influenza H5N1 in China, the focus has been on negative effects. Lakes and wetlands attracting migrating waterfowl have been argued to be disease hotspots. We consider the implications of waterfowl conservation for H5N1 infections in both poultry and humans between 2004 and 2012. We model both environmental and economic risk factors. Environmental risk factors comprise the conditions that structure interaction between wild and domesticated birds. Economic risk factors comprise the cost of disease, biosecurity measures and disease risk mitigation. We find that H5N1 outbreaks in poultry populations are indeed sensitive to the existence of wild-domesticated bird mixing zones, but not in the way we would expect from the literature. We find that risk is decreasing in protected migratory bird habitat. Since the number of human cases is increasing in the number of poultry outbreaks, as expected, the implication is that the protection of wetlands important for migratory birds offers unexpected human health benefits.This article is part of the themed issue ‘Conservation, biodiversity and infectious disease: scientific evidence and policy implications’.
Draft genome sequence of aCandidatusBrocadia bacterium enriched from tropical-climate activated sludge
Authors: Liu Xianghui , Arumugam Krithika , Natarajan Gayathri , Seviour Thomas W. , Drautz-Moses Daniela I. , Wuertz Stefan , Law Yingyu , Williams Rohan B. H. 
Published: April 2017

AbstractWe present the draft genome of an anaerobic ammonium-oxidizing (anammox) bacterium, cluster IIICandidatusBrocadia, which was enriched in an anammox reactor. A 3.2 Mb genome sequence comprising 168 contigs was assembled, in which 2,765 gene-coding regions, 47 tRNAs, and 5S, 16S and 23S ribosomal RNAs were annotated. No evidence for the presence of a nitric oxide-forming nitrite reductase was found.
Gestational age at birth and risk of intellectual disability without a common genetic cause: findings from the Stockholm Youth Cohort
Authors: Heuvelman Hein , Abel Kathryn , Wicks Susanne , Gardner Renee , Johnstone Edward , Lee Brian , Magnusson Cecilia , Dalman Christina , Rai Dheeraj 
Published: April 2017

AbstractBackgroundPreterm birth is linked to intellectual disability and there is evidence to suggest post-term birth may also incur risk. However, these associations have not yet been investigated in the absence of common genetic causes of intellectual disability (where risk associated with late delivery may be preventable) or with methods allowing stronger causal inference from non-experimental data. We aimed to examine risk of intellectual disability without a common genetic cause across the entire range of gestation, using a matched-sibling design to account for unmeasured confounding by shared familial factors.Methods and FindingsWe conducted a population-based retrospective study using data from the Stockholm Youth Cohort (n=499,621) and examined associations in a nested cohort of matched siblings (n=8,034). Children born at non-optimal gestational duration (before/after 40 weeks 3 days) were at greater risk of intellectual disability. Risk was greatest among those born extremely early (adjusted OR24 weeks=14.54 [95% CI 11.46–18.44]), lessening with advancing gestational age toward term (aOR32 weeks=3.59 [3.22–4.01]; aOR37 weeks=1.50 [1.38–1.63]); aOR38 weeks=1.26 [1.16-1.37]; aOR39weeks=1.10 [1.04-1.17]) and increasing with advancing gestational age post-term (aOR42 weeks=1.16 [1.08–1.25]; aOR42 weeks=1.41 [1.21–1.64]; aOR44 weeks=1.71 [1.34–2.18]; aOR45 weeks=2.07 [1.47–2.92]). Associations persisted in a nested cohort of matched outcome-discordant siblings suggesting they were robust against confounding from shared genetic or environmental traits, although there may have been residual confounding by unobserved non-shared characteristics. Risk of intellectual disability was greatest among children showing evidence of fetal growth restriction, especially when birth occurred before or after term.ConclusionsBirth at non-optimal gestational duration may be linked causally with greater risk of intellectual disability. The mechanisms underlying these associations need to be elucidated as they will be relevant to clinical practice concerning elective delivery within the term period and the mitigation of risk in children who are born post-term.
The neural circuitry of emotion-induced distortions of trust
Authors: Engelmann Jan B. , Meyer Friederike , Ruff Christian C. , Fehr Ernst 
Published: April 2017

AbstractAversive emotions are likely to be a key source of irrational human decision-making but still little is known about the neural circuitry underlying emotion-cognition interactions during social behavior. Here, we show that incidental aversive emotions distort trust decisions and cause significant changes in the associated neural circuitry. Experimentally-induced negative affect reduced trust, suppressed trust-specific activity in left temporoparietal junction (TPJ), and reduced functional connectivity between TPJ and emotion-related regions such as the amygdala. The posterior superior temporal sulcus (pSTS) seems to play a key role in mediating the impact of emotion on behavior: Functional connectivity of this brain area with left TPJ was associated with trust in the absence of negative emotions, but aversive emotions disrupted this association between TPJ-pSTS connectivity and behavioral trust. Our findings may be useful for a better understanding of the neural circuitry of affective distortions and may help identify the neural bases of psychiatric diseases that are associated with emotion-related psychological and behavioral dysfunctions.
Synaptophysin is a β-Amyloid Target that Regulates Synaptic Plasticity and Seizure Susceptibility in an Alzhiemer’s Model
Authors: Adams Daniel J. , Shen Chong , Levenga Josien , Basta Tamara , Eisenberg Stephen P. , Mapes James , Hampton Lukas , Grounds Kelly , Hoeffer Charles A. , Stowell Michael H. B. 
Published: April 2017

Intro/abstractAlzheimer’s disease (AD), a condition characterized by cognitive deficits and progressive loss of memory, is causally linked to the short amyloid peptide Aβ42, which disrupts normal neurotransmission1,2. Neurotransmitter (NT) release from synaptic vesicles (SV) requires coordinated binding of the conserved core secretory machinery comprised of the soluble NSF attachment protein receptor (vSNARE) synaptobrevin 2 (VAMP2) on the SV and the cognate tSNAREs on the plasma membrane. Synaptophysin (SYP) is the most abundant SV protein3and the major pre-fusion binding partner of VAMP24. A major challenge in understanding the etiology and prevention of AD is determining the proteins directly targeted by Aβ42 and elucidating if these targets mediate disease phenotypes. Here we demonstrate that Aβ42 binds to SYP with picomolar affinity and disrupts the SYP/VAMP2 complex resulting in inhibition of both neurotransmitter release and synaptic plasticity. While functionally redundant paralogs of SYP have masked its critical activity in knockout studies5,6, we now demonstrate a profound seizure susceptibility phenotype in SYP knockout mice that is recapitulated in an AD model mouse. Our studies imply a subtle yet critical role for SYP in the synaptic vesicle cycle and the etiology of AD.
Disease mechanism, drug-target and biomarker prediction software: Application on prostate cancer and validation
Authors: Altay Gokmen , Nurmemmedov Elmar , Kesari Santosh , Neal David E. 
Published: April 2017

AbstractWe present an R software package that performs at genome-wide level differential network analysis and infers only disease-specific molecular interactions between two different cell conditions. This helps revealing the disease mechanism and predicting most influential genes as potential drug targets or biomarkers of the disease condition of interest. As an exemplary analysis, we performed an application of the software over LNCaP datasets and, out of approximately 25000 genes, predicted CXCR7 and CXCR4 together as drug targets of LNCaP prostate cancer dataset. We further successfully validated them with our initial wet-lab experiments. The introduced software can be applied to all the diseases, especially cancer, with gene expression data of two different conditions (e.g. tumor vs normal) and thus has the potential of a global benefit. As a distinct remark, our software provide the causal disease mechanism with multiple potential drug-targets rather than a single independent target prediction.AvailabilityThe introduced R software package for the analysis is available in CRAN athttps://cran.r-project.org/web/packages/dc3netand also athttps://github.com/altayg/dc3net
Position Effect Variegation in natural populations not explained by common variation in known modifiers
Authors: Kelsey Keegan J. P. , Clark Andrew G. 
Published: April 2017

ABSTRACTChanges in chromatin state may drive changes in gene expression, and it is of growing interest to understand the population genetic forces that drive differences in chromatin state. Here, we use the phenomenon of position effect variegation (PEV), a well-studied proxy for chromatin state, to explore the genetic architecture of natural variation in factors that modify chromatin state. While previous mutation screens have identified over 150 suppressors and enhancers of PEV, it remains unknown to what extent allelic variation in these modifiers mediates inter-individual variation in chromatin state. Is natural variation in PEV mediated by segregating variation in known Su(var) and E(var) genes, or is the trait polygenic, with many variants mapping elsewhere in the genome? We designed a mapping study that directly answers this question and suggests that the bulk of the variance in PEV does not map to genes with prior annotated impact to PEV. Instead, we find enrichment of topP-value ranked associations that suggest impact to active promoter and transcription start site proximal regions. This work provides a quantitative view of the role naturally segregating autosomal variants play in modifying PEV, a phenomenon that continues to shape our understanding of chromatin state and epigenetics.
Late Bayesian inference in sensorimotor behavior
Authors: Remington Evan , Jazayeri Mehrdad 
Published: April 2017

AbstractSensorimotor skills rely on performing noisy sensorimotor computations on noisy sensory measurements. Bayesian models suggest that humans compensate for measurement noise and reduce behavioral variability by biasing perception toward prior expectations. Whether the same holds for noise in sensorimotor computations is not known. Testing human subjects in tasks with different levels of sensorimotor complexity, we found a similar bias-variance tradeoff associated with increased sensorimotor noise. This result was accurately captured by a model which implements Bayesian inference after – not before – sensorimotor transformation. These results indicate that humans perform “late inference” downstream of sensorimotor computations rather than, or in addition to, “early inference” in the perceptual domain. The brain thus possesses internal models of noise in both sensory measurements and sensorimotor computations.
Reassessment of lesion-associated gene and variant pathogenicity in focal human epilepsies
Authors: Neupert Lisa M. , Nothnagel Michael , May Patrick , Palotie Aarno , Daly Mark , Nürnberg Peter , Blümcke Ingmar , Lal Dennis 
Published: April 2017

PurposeIncreasing availability of surgically resected brain tissue from Focal Cortical Dysplasia and low-grade epilepsy-associated tumor patients fostered large-scale genetic examination. However, assessment of germline and somatic variant pathogenicity remains difficult.MethodsHere, we critically reevaluated the pathogenicity for all neuropathology-associated variants reported to date in the PubMed and ClinVar databases, including 12 disease-related genes and 88 neuropathology-associated missense variants. We (1) assessed evolutionary gene constraint using thepLIand missensezscores, (2) applied guidelines by the American College of Medical Genetics and Genomics (ACMG), and (3) predicted pathogenicity by using PolyPhen-2, CADD, and GERP.ResultsConstraint analysis classified only seven out of 12 genes to be likely disease-associated, while 35 (40%) of those 88 variants were classified as being variants of unknown significance (VUS) and 53 (60%) as being likely pathogenic (LPII). Pathogenicity prediction yielded discrimination between neuropathology-associated variants (LPII and VUS) and rare variant scores obtained from individuals present in the Genome Aggregation Database (gnomAD).ConclusionWe conclude that several VUS are likely disease-associated and will be reclassified by future molecular evidence. In summary, interpretation of lesion-associated gene variants remains complex while the application of current ACMG guidelines including bioinformatic pathogenicity prediction will help improving interpretation and prediction.
A computational study about the mechanism of action of metformin on hepatic gluconeogenesis, focused on its ability to create stable pseudo-aromatic copper complexes
Authors: Rebecchi Fabio 
Published: April 2017

AbstractMetformin is the best therapeutic choice for treating type 2 Diabetes.Despite this, and the fact it has been prescribed worldwide for decades, its mechanism of gluconeogenesis inhibition is still unknown.In the following work a novel mechanism of inhibition is suggested: that metformin performs its action on the target enzyme not as a pure molecule but, after sequestering endogenous cellular copper, as a copper complex.This result was obtained using chemoinformatics methods including homology modeling for the creation of the target enzyme’s tridimensional virtual structure, molecular docking for both the determination of the movement of the prosthetic group inside its cavity and for the identification of the best ligand poses for the metformin copper complexes, and eventually pharmacophore modeling and virtual screening to find alternative virtual leads that could achieve similar effects.The simulations show the complex binding as a non competitive inhibitor to the large exit of the mitochondrial glycerophosphate dehydrogenase enzyme’s FAD cavity, preventing FAD movement inside the cavity and/or quinone interaction and therefore its electron transfer function.The proposed mechanism seems to be successful at explaining a wide range of existing experimental results, both regarding measurements of metformin non-competitive inhibition of GPD2 and the role of copper and pH in its action.The virtual screening outcome of at least two similarly active purchasable molecule hints to an easy way to experimentally test the proposed mechanisms.In fact, the virtual leads are very similar to the copper complex but quite different from metformin alone, and a laboratory confirmation of their activity should plausibly imply that metformin acts in synergy with copper, giving us the ability to design new antidiabetic drugs in a novel and more rational fashion, with significant savings in research costs and efforts.
A minority-ruled population coding of kinematics in the striatum
Authors: Taouali Wahiba , Rueda-Orozco Pavel E. , Robbe David 
Published: April 2017

AbstractThe structure of population activity in the dorsolateral striatum during the performance of motor sequences has not been characterized and it is unclear if striatal ensembles encode (predict) kinematic parameters defining how sequences are executed. Here we analyzed hundreds of striatal spike trains from naive and trained rats performing a running sequence. We found that the population response was composed of a diversity of phasic modulations covering the entire sequence. The accuracy of kinematics encoding by single neurons was around chance level but improved when neuronal ensembles were considered. The distribution of single-neuron contributions to ensemble encoding was highly skewed with a minority of neurons responsible for most of the encoding accuracy. Importantly, running speed ensemble encoding improved after learning. We propose that during motor learning, striatal ensembles adjust their task representation by tuning the activity of a minority of neurons to the kinematic parameters most relevant to motor performance.
The neural representational space of social memory
Authors: Dziura Sarah L. , Thompson James C. 
Published: April 2017

AbstractSocial functioning involves learning about the social networks in which we live and interact; knowing not just our friends, but also who is friends with our friends. Here we utilized a novel incidental learning paradigm and representational similarity analysis (RSA), a functional MRI multivariate pattern analysis technique, to examine the relationship between learning social networks and the brain's response to the faces within the networks. We found that accuracy of learning face pair relationships through observation is correlated with neural similarity patterns to those pairs in the left temporoparietal junction (TPJ), the left fusiform gyrus, and the subcallosal ventromedial prefrontal cortex (vmPFC), all areas previously implicated in social cognition. This model was also significant in portions of the cerebellum and thalamus. These results show that the similarity of neural patterns represent how accurately we understand the closeness of any two faces within a network, regardless of their true relationship. Our findings indicate that these areas of the brain not only process knowledge and understanding of others, but also support learning relations between individuals in groups.Significance StatementKnowledge of the relationships between people is an important skill that helps us interact in a highly social world. While much is known about how the human brain represents the identity, goals, and intentions of others, less is known about how we represent knowledge about social relationships between others. In this study, we used functional neuroimaging to demonstrate that patterns in human brain activity represent memory for recently learned social connections.
Characterisation of an antimicrobial and phytotoxic ribonuclease secreted by the fungal wheat pathogenZymoseptoria tritici
Authors: Kettles Graeme J. , Bayon Carlos , Sparks Caroline A. , Canning Gail , Kanyuka Kostya , Rudd Jason J. 
Published: April 2017

Abstract-The fungusZymoseptoria triticiis the causal agent of Septoria Tritici Blotch (STB) disease of wheat leaves.Z. triticisecretes many functionally uncharacterised effector proteins during infection. Here we characterised a secreted ribonuclease (Zt6) with an unusual biphasic expression pattern.-Transient expression systems were used to characterise Zt6, and mutants thereof, in both host and non-host plants. Cell-free protein expression systems monitored impact of Zt6 protein on functional ribosomes, andin vitroassays of cells treated with recombinant Zt6 determined toxicity against bacteria, yeasts and filamentous fungi.-We demonstrated that Zt6 is a functional ribonuclease and that phytotoxicity is dependent on both the presence of a 22-amino acid N-terminal “loop” region and its catalytic activity. Zt6 selectively cleaves both plant and animal rRNA species, and is toxic to wheat, tobacco, bacterial and yeast cells but not toZ. triticiitself.-Zt6 is the firstZ. triticieffector demonstrated to have a likely dual functionality. The expression pattern of Zt6 and potent toxicity towards microorganisms suggests that whilst it may contribute to the execution of wheat cell death, it is also likely to have an important secondary function in antimicrobial competition and niche protection.
Statistically robust methylation calling for whole-transcriptome bisulfite sequencing reveals distinct methylation patterns for mouse RNAs
Authors: Legrand Carine , Tuorto Francesca , Hartmann Mark , Liebers Reinhard , Jacob Dominik , Helm Mark , Lyko Frank 
Published: April 2017

AbstractCytosine-5 RNA methylation plays an important role in several biologically and pathologically relevant processes. However, owing to methodological limitations, the transcriptome-wide distribution of this mark has remained largely unknown. We previously established RNA bisulfite sequencing as a method for the analysis of RNA cytosine-5 methylation patterns at single-base resolution. More recently, next-generation sequencing has provided opportunities to establish transcriptome-wide maps of this modification. Here we present a computational approach that integrates tailored filtering and data-driven statistical modeling to eliminate many of the artifacts that are known to be associated with bisulfite sequencing. Using RNAs from mouse embryonic stem cells we performed a comprehensive methylation analysis of mouse tRNAs, rRNAs and mRNAs. Our approach identified all known methylation marks in tRNA and two previously unknown but evolutionary conserved marks in 28S rRNA. In addition, mRNAs were found to be very sparsely methylated or not methylated at all. Finally, the tRNA-specific activity of the DNMT2 methyltransferase could be resolved at single-base resolution, which provided important further validation. Our approach can be used to profile cytosine-5 RNA methylation patterns in many experimental contexts and will be important for understanding the function of cytosine-5 RNA methylation in RNA biology and in human disease.