bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Impact of In-Scanner Head Motion on Structural Connectivity Derived from Diffusion Tensor Imaging
Authors: Baum Graham L. , Roalf David R. , Cook Philip A. , Ciric Rastko , Rosen Adon F.G. , Xia Cedric , Elliot Mark A. , Ruparel Kosha , Verma Ragini , Tunc Birkan , Gur Ruben C. , Gur Raquel E. , Bassett Danielle S. , Satterthwaite Theodore D. 
Published: September 2017

ABSTRACTMultiple studies have shown that data quality is a critical confound in the construction of brain networks derived from functional MRI. This problem is particularly relevant for studies of human brain development where important variables (such as participant age) are correlated with data quality. Nevertheless, the impact of head motion on estimates of structural connectivity derived from diffusion tractography methods remains poorly characterized. Here, we evaluated the impact of in-scanner head motion on structural connectivity using a sample of 949 participants (ages 8-23 years old) who passed a rigorous quality assessment protocol for diffusion tensor imaging (DTI) acquired as part of the Philadelphia Neurodevelopmental Cohort. Structural brain networks were constructed for each participant using both deterministic and probabilistic tractography. We hypothesized that subtle variation in head motion would systematically bias estimates of structural connectivity and confound developmental inference, as observed in previous studies of functional connectivity. Even following quality assurance and retrospective correction for head motion, eddy currents, and field distortions, in-scanner head motion significantly impacted the strength of structural connectivity in a consistency-and length-dependent manner. Specifically, increased head motion was associated with reduced estimates of structural connectivity for high-consistency network edges, which included both short-and long-range connections. In contrast, motion inflated estimates of structural connectivity for low-consistency network edges that were primarily shorter-range. Finally, we demonstrate that age-related differences in head motion can both inflate and obscure developmental inferences on structural connectivity. Taken together, these data delineate the systematic impact of head motion on structural connectivity, and provide a critical context for identifying motion-related confounds in studies of structural brain network development.
Genome-Wide Association Studies Identify 15 Genetic Markers Associated with Marmite Taste Preference
Authors: Roos Thomas R. , A. Kulemin Nikolay , I. Ahmetov Ildus , Lasarow Avi , Grimaldi Keith 
Published: September 2017

AbstractMarmite is a popular food eaten around the world, to which individuals have commonly considered themselves either “lovers” or “haters”. We aimed to determine whether this food preference has a genetic basis.Weperformed a genome-wide association study (GWAS) for Marmite taste preference using genotype and questionnaire data froma cohort of 261 healthy adults. We found 1 single nucleotide polymorphism (SNP) associated with Marmite taste preferencethat reached genome-wide significance (p<5x10-8) in our GWAS analyses. We found another 4 SNPsassociated with Marmite taste preference that reached genome-wide significance (p<5x10-8) in at leastoneGWAS and/or for at least one phenotype analysed. Moreover, we identified 10 additional SNPs potentially associated with Marmite taste preference through candidate gene analysis. Our results indicate that there is a genetic basis to Marmite taste preference and we have identified 15 genetic markers for this trait. Overall, we conclude that Marmite tastepreference is a complex human trait influenced by multiple genetic markers, as well as the environment.Summary of Main ResultsMarmite taste preference is a complex human trait with many factors influencing whether an individual loves or hates Marmite.The relative contribution of genetics versus environment (ie. heritability) for Marmite taste preference is unknown.The genetic contribution to Marmite taste preference involves multiple genetic markers each contributing a small amount (ie. the trait is polygenic). There is not one single Marmite gene with a large contribution like in thecase of theTAS2R38gene and bitter taste perception.We have found a total of 15 SNPs associated with Marmite taste preference: 5 SNPs by a genetic-association screen atgenome-wide significance, and 10 SNPs by a candidate gene approach at nominal significance.We did not find an association between theTAS2R38bitter taste receptor gene and Marmite taste preference.It is important to independently replicate the findings of this study in order to validate these genetic markers and get a more accurate idea of their true effect on Marmite taste preference.
Complex Models of Sequence Evolution Require Accurate Estimators as Exemplified with the Invariable Site plus Gamma Model
Authors: Nguyen Lam-Tung , von Haeseler Arndt , Quang Minh Bui 
Published: September 2017

ABSTRACTThe invariable site plus Γ model is widely used to model rate heterogeneity among alignment sites in maximum likelihood and Bayesian phylogenetic analyses. The proof that the invariable site plus continuous Γ model is identifiable (model parameters can be inferred correctly given enough data) has increased the creditability of its application to phylogeny reconstruction. However, most phylogenetic software implement the invariable site plus discrete Γ model, whose identifiability is likely but unproven. How well the parameters of the invariable site plus discrete Γ model are estimated is still disputed. Especially the correlation of the fraction of invariable sites with the fractions of sites with a slow evolutionary rate is discussed as being problematic. We show that optimization heuristics as implemented in frequently used phylogenetic software cannot always reliably estimate the shape parameter, the proportion of invariable sites and the tree length. Here, we propose an improved optimization heuristic that accurately estimates the three parameters. While research efforts mainly focus on tree search methods, our results signify the equal importance of verifying and developing effective estimation methods for complex models of sequence evolution.
A sequence-based, deep learning model accurately predicts RNA splicing branchpoints
Authors: Paggi Joseph M. , Bejerano Gill 
Published: September 2017

AbstractExperimental detection of RNA splicing branchpoints, the nucleotide serving as the nucleophile in the first catalytic step of splicing, is difficult. To date, annotations exist for only 16-21% of 3’ splice sites in the human genome and even these limited annotations have been shown to be plagued by noise. We develop a sequence-only, deep learning based branchpoint predictor, LaBranchoR, which we conclude predicts a correct branchpoint for over 90% of 3’ splice sites genome-wide. Our predicted branchpoints show large agreement with trends observed in the raw data, but analysis of conservation signatures and overlap with pathogenic variants reveal that our predicted branchpoints are generally more reliable than the raw data itself. We use our predicted branchpoints to identify a sequence element upstream of branchpoints consistent with extended U2 snRNA base pairing, show an association between weak branchpoints and alternative splicing, and explore the effects of variants on branchpoints.
Hsf1 phosphorylation generates cell-to-cell variation in Hsp90 levels and promotes phenotypic plasticity
Authors: Zheng Xu , Beyzavi Ali , Krakowiak Joanna , Patel Nikit , Khalil Ahmad S. , Pincus David 
Published: September 2017

ABSTRACTClonal populations of cells exhibit cell-to-cell variation in the transcription of individual genes. In addition to this “noise” in gene expression, heterogeneity in the proteome and the proteostasis network expands the phenotypic diversity of a population. Heat shock transcription factor (Hsf1) regulates chaperone gene expression, thereby coupling transcriptional noise to proteostasis. Here we show that cell-to-cell variation in Hsf1 activity is an important determinant of phenotypic plasticity. Budding yeast cells with high Hsf1 activity were enriched for the ability to acquire resistance to an antifungal drug, and this enrichment depended on Hsp90 – a known “phenotypic capacitor” and canonical Hsf1 target. We show that Hsf1 phosphorylation promotes cell-to-cell variation, and this variation – rather than absolute Hsf1 activity – promotes antifungal resistance. We propose that Hsf1 phosphorylation enables differential tuning of the proteostasis network in individual cells, allowing populations to access a wide range of phenotypic states.
Basolateral amygdala glutamatergic neurons maintain aversive emotional salience
Authors: Sengupta Auntora , Yau Joanna O.Y. , Bressel Philip Jean-Richard Dit , Liu Yu , Zayra Millan E. , Power John M. , McNally Gavan P. 
Published: September 2017

AbstractBasolateral amygdala (BLA) glutamatergic neurons serve a well-accepted role in fear conditioning and fear extinction. However, the specific learning processes related to their activity at different times during learning remain poorly understood. We addressed this using behavioral tasks isolating distinct aspects of fear learning in rats. We show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of aversive reinforcement or non-reinforcement causes reductions in the salience of conditioned stimuli, rendering these stimuli less able to be learned about and less able to control fear or safety behaviours. This salience reduction was stimulus-specific, long-lasting, and specific to aversive emotional states - precisely the goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition. They show that a primary function of BLA glutamatergic neurons is to maintain the salience of conditioned stimuli. This is a necessary precursor for these stimuli to gain and maintain control over fear and safety behavior.Significance statementThe amygdala is essential for learning to fear and learning to reduce fear. However, the specific roles served by activity of different amygdala neurons at different times during learning is poorly understood. We used behavioral tasks isolating distinct aspects of learning in rats to show that brief optogenetic inhibition of BLA glutamatergic neurons around moments of reinforcement or non-reinforcement disrupts maintenance of conditioned stimulus (CS) salience. This causes a stimulus-specific, long-lasting, and aversive emotion specific deficit in the ability of the CS to be learned about or control fear responses. These consequences are the precisely goals of therapeutic interventions in human anxiety disorders. Our findings identify a core learning process disrupted by brief BLA optogenetic inhibition.
Canadian immigrant guidelines on how to become productive members of society
Authors: Krysa Isabella M. , Mills Albert , Barragan Salvador 
Published: September 2017

PurposeThe purpose of this paper is to critically look at how immigrants to Canada are informed and educated about how to become productive members of society. The authors adopted a postcolonial framework to unveil the underlying assumptions embedded in the messages that are conveyed to “teach” and “prepare” immigrants for the Canadian workplace. In particular, the authors focus on non-white immigrants because they form the majority of immigrants to Canada and at the same time data show that they experience particular socio-economic obstacles in their settlement process that European immigrants did not.Design/methodology/approachThe authors apply postcolonialism as the theoretical framework. This approach allows the authors to analyze the relationship between the local subject and the encounter with the non-local other, in this case the immigrant who is from a non-European background. The authors conduct a Foucauldian critical discourse analysis on selected texts that serve as information sources for immigrants. These texts include government documents, immigrant information brochures, and workplace information books and booklets.FindingsThe analysis shows ideological positions that reveal discursive messages representing the non-white immigrant in binary terms. Such immigrants are represented in opposing (and inferior) terms to the local (largely white) Canadian citizen. By adopting a postcolonial lens, the analysis shows that the messages to acculturate immigrants reveal assimilationist features.Research limitations/implicationsThe authors acknowledge that the authors’ own personal socio-political, intellectual, and ideological locations influence the approach, logic, research process, and the interpretation of the findings. For future research, other textual sources should be analyzed with regard to the messages they convey to immigrants as a form of education to see what kind of acculturation is conveyed.Practical implicationsThis paper sheds light on the necessity to develop policies that not only aim to acculturate immigrants using integration strategies but also to carefully communicate and educate newcomers through messages that that do not stem from colonial assumptions.Originality/valueThis research points out the taken-for granted and oftentimes invisible forms of discriminatory practices in the workplace that appear non-discriminatory on the surface but are rooted in colonial thinking. Consequently, the authors challenge “mainstream” management theories concerning diversity in the workplace by questioning the underlying messages portrayed to immigrants.
The living wage as an income range for decent work and life
Authors: Yao Christian , Parker Jane , Arrowsmith James , Carr Stuart C. 
Published: September 2017

PurposeA “living” wage (LW) is conventionally defined as enabling meaningful participation in society above subsistence through, for example, recreation, supporting a family, and savings. There is increasing debate over LWs due to growing inequality, rising living costs and welfare reform but this remains largely framed by the econometric cost-benefit parameters that apply to minimum wage regulation. The capabilities approach advocated by Sen (1999) offers a different perspective that is inclusive of choice, contingencies and the inter-connections between quality of (paid) work and private life. The paper aims to discuss these issues.Design/methodology/approachThe paper adopts this framework and utilises a qualitative exploration of the narratives of 606 New Zealand employees to understand perceived wage effectiveness. The results suggest that a focus on a specific LW rate might be conceptually limiting, in comparison to a LW range.FindingsFirst, the findings indicate that there is a pivot range in which people move from self-assessed “survival” to “decent” income. Second, a LW may have more than a simply monetary effect in better meeting employees’ living costs; it can also improve well-being through subjective perceptions of valued freedoms to do with job satisfaction, equity and security.Originality/valueThe results thus draw attention to a wider notion of a LW in terms of personal and family well-being, utilising a capabilities approach, with implications for organisational practice, policy and theory concerning sustainable livelihood and the UN Sustainable Development Goals.
Living wages: a US perspective
Authors: Luce Stephanie 
Published: September 2017

Purpose
The purpose of this paper is to provide background on the US living wage movement, with particular attention to recent victories, and also the ways in which the US movement differs from living wage movements in other countries. It begins with some technical distinctions of terms, then analyzes the campaigns and movement for higher wages, and considers some of the challenges the campaigns have faced. It will conclude with some discussion about the future of the movement.

Design/methodology/approach
This is a general review of living wage campaigns in the USA. This is based on a review of existing literature and the author’s own prior research and participant observation.

Findings
The author argues that the initial living wage movement that began in the early 1990s was limited in scope but successful in building coalitions and political power to launch a much more expansive movement to raise wages in 2012.

Originality/value
This paper is a general summary of the last 20 years of living wage campaigns. It does not include new research.
Cerebral dopaminergic and glutamatergic transmission relate to different subjective responses of acute alcohol intake: an in vivo multimodal imaging study
Authors: Leurquin‐Sterk Gil , Ceccarini Jenny , Crunelle Cleo Lina , Weerasekera Akila , de Laat Bart , Himmelreich Uwe , Bormans Guy , Van Laere Koen 
Published: September 2017

AbstractConverging preclinical evidence links extrastriatal dopamine release and glutamatergic transmission via the metabotropic glutamate receptor 5 (mGluR5) to the rewarding properties of alcohol. To date, human evidence is lacking on how and where in the brain these processes occur. Mesocorticolimbic dopamine release upon intravenous alcohol administration and mGluR5 availability were measured in 11 moderate social drinkers by single‐session [18F]fallypride and [18F]FPEB positron emission tomography, respectively. Additionally, baseline and postalcohol glutamate and glutamine levels in the anterior cingulate cortex (ACC) were measured by using proton‐magnetic resonance spectroscopy. To investigate differences in reward domains linked to both neurotransmitters, regional imaging data were related to subjective alcohol responses. Alcohol induced significant [18F]fallypride displacement in the prefrontal cortex (PFC), temporal and parietal cortices and thalamus (P < 0.05, corrected for multiple comparisons). Dopamine release in the ACC and orbitofrontal and ventromedial PFCs were correlated with subjective ‘liking’ and ‘wanting’ effects (P < 0.05). In contrast, baseline mGluR5 availability was positively correlated with the ‘high’ effect of alcohol in dorsolateral, ventrolateral and ventromedial PFCs and in the medial temporal lobe, thalamus and caudate nucleus (P < 0.05). Although neither proton‐magnetic resonance spectroscopy glutamate nor glutamine levels were affected by alcohol, baseline ACC glutamate levels were negatively associated with the alcohol ‘liking’ effect (P < 0.003). These data reveal new mechanistic understanding and differential neurobiological underpinnings of the effects of acute alcohol consumption on human behavior. Specifically, prefrontal dopamine release may encode alcohol ‘liking’ and ‘wanting’ effects in specific areas underlying value processing and motivation, whereas mGluR5 availability in distinct prefrontal–temporal–subcortical regions is more related to the alcohol ‘high’ effect.
Phosphorylated SNAP25 in the CA1 regulates morphine‐associated contextual memory retrieval via increasing GluN2B‐NMDAR surface localization
Authors: Wang Xinjuan , Liu Yan , Jia Meng , Sun Xiaowei , Wang Na , Li Yijing , Cui Cailian 
Published: September 2017

AbstractAlthough our previous studies have demonstrated both protein kinase C (PKC) and GluN2B‐containing N‐methyl‐d‐aspartate receptor (GluN2B‐NMDAR) play crucial roles in morphine‐associated learning and memory, the relationship between them remains unexplored. In this study, we validated the enhanced PKC and membrane GluN2B protein expression in the hippocampal CA1 after morphine conditioned place preference (CPP) expression in rats. Interestingly, we also found that phosphorylation of SNAP25 at Ser187 (pSer187‐SNAP25), a PKC‐activated target, was significantly increased following morphine CPP expression. Blocking the pSer187‐SNAP25 by intra‐CA1 injection of an interfering peptide impaired morphine CPP expression and accompanied by the reduced ratio of GluN2B membrane/total in the CA1. In addition, intra‐CA1 blockade of pSer187‐SNAP25 did not affect natural learning and memory process as evidenced by intact sucrose‐induced CPP expression and normal locomotor activity in rats. Therefore, our results reveal that enhanced pSer187‐SNAP25 by PKC recruits GluN2B‐NMDAR to the membrane surface in the hippocampal CA1 and mediates context‐induced addiction memory retrieval. Our findings in this study fill in the missing link and provide better understanding of the molecular mechanisms involved in morphine‐associated contextual memory retrieval.
Hydroxycarbamide in children with sickle cell anaemia after first‐dose vs. chronic therapy: pharmacokinetics and predictive models for drug exposure
Authors: Estepp Jeremie H. , Wiczling Paweł , Moen Joseph , Kang Guolian , Mack Joana Marie , Liem Robert , Panepinto Julie A. , Garg Uttam , Kearns Gregory , Neville Kathleen A. 
Published: September 2017

AimsThe purposes of this work were to: (1) compare pharmacokinetic (PK) parameters for hydroxycarbamide in children receiving their first dose (HCnew) vs. those receiving chronic therapy (HCchronic), (2) assess the external validity of a published PK dosing strategy, and (3) explore the accuracy of dosing strategies based on a limited number of HC measurements.MethodsUtilizing data from two prospective, multicenter trials of hydroxycarbamide (Pharmacokinetics of Liquid Hydroxyurea in Pediatric Patients with Sickle Cell Anemia; NCT01506544 and Single‐Dose (SD) and Steady‐State (SS) Pharmacokinetics of Hydroxyurea in Children and Adolescents with Sickle Cell Disease), plasma drug concentration vs. time profiles were evaluated with a model independent approach in the HCnew and HCchronic groups. Various predictive scenarios were analysed to evaluate whether systemic exposure with hydroxycarbamide could be accurately predicted.ResultsAbsorption of hydroxycarbamide was rapid, variable and dose independent. Dose‐normalized peak plasma concentrations and drug exposure (AUC) were higher, and weight‐normalized apparent oral clearance was lower in the HCnew group. We assessed a PK‐guided dosing strategy along with other predictive scenarios and found that inclusion of plasma samples only slightly improved the accuracy of AUC predictions when compared to a population‐based method.ConclusionsChildren naïve to hydroxycarbamide exhibit a different PK profile compared to children receiving chronic therapy. Accuracy of population‐based dosing is sufficient to target AUCs in individual patients. Further clearance/bioavailability studies are needed to address the factors responsible for variability in the disposition of hydroxycarbamide.