bluuebunny/crossref_metadata_2025_split huggingface dataset:
Time-dependent competition between habitual and goal-directed response preparation
Authors: Hardwick Robert M , Forrence Alexander D , Krakauer John W , Haith Adrian M 
Published: October 2017

AbstractConverging evidence indicates that separate goal-directed and habitual systems compete to control behavior1. However, it has proven difficult to reliably induce habitual behavior in human participants2–4. We reasoned that habits may be present in the form of habitually prepared responses, but are overridden by goal-directed processes, preventing their overt expression. Here we show that latent habits can be unmasked by limiting the time participants have to respond to a stimulus. Participants trained for 4 days on a visuomotor association task. By continuously varying the time allowed to prepare responses, we found that the probability of expressing a learned habit followed a stereotyped time course, peaking 300-600ms after stimulus presentation. This time course was captured by a computational model of response preparation in which habitual responses are automatically prepared at short latency, but are replaced by goal-directed responses at longer latency. A more extensive period of practice (20 days) led to increased habit expression by reducing the average time of movement initiation. These findings refine our understanding of habits, and show that practice can influence habitual behavior in distinct ways: by promoting habit formation, and by modulating the likelihood of habit expression.
APC/C-Vihar regulates centrosome activity and stability in theDrosophilagermline
Authors: Braun A. L. , Meghini F. , Villa-Fombuena G. , Guermont M. , Fernandez-Martinez E. , Glover D.M. , Martín-Bermudo M. D. , González-Reyes A. , Kimata Y. 
Published: October 2017

AbstractA universal feature of metazoan reproduction is the elimination of the maternal centrosomes prior to the end of oogenesis. In animals that have a syncytial cyst stage of oocyte development, includingDrosophilaand mouse, the germline centrosomes undergo a migration to all reside within the oocyte. However, the functional significance of centrosome transport within the female germline and the mechanism orchestrating this event are still a mystery. The Anaphase Promoting Complex/Cyclosome (APC/C) is a multi-subunit ubiquitin ligase (E3) that temporally regulates progression of the cell cycle as well as the centrosome cycle. By altering the negative regulation of the cooperating ubiquitin conjugating enzyme (E2), Vihar/Ube2c, we show that temporal control of APC/C activity ensures centrosome stability and migration during earlyDrosophilaoogenesis. When there is perduring APC/C activity, Polo kinase is precociously targeted for destruction, which results in centriole instability and decreased centrosome transport to the oocyte. We show that decreased centrosome transport correlates with a decreased accumulation of pericentriolar material (PCM) proteins on the oocyte nucleus, which results in a weakening of the structural integrity of the egg chamber and loss of oocyte fate – the overall consequence being a reduction in female fertility. Considering the conserved roles of the APC/C and Polo kinase throughout the animal kingdom and the fact that many animals have a syncytial stage of egg development, our results provide insight into the general necessity of gametic centrosome transport for female fertility.
Contact inhibitory Eph signaling suppresses EGF-promoted cell migration by decoupling EGFR activity from vesicular recycling
Authors: Stallaert Wayne , Sabet Ola , Brüggemann Yannick , Baak Lisa , Bastiaens Philippe I.H. 
Published: October 2017

AbstractThe ability of cells to adapt their behavior to growth factors in relation to their environment is an essential aspect of tissue development and homeostasis. Here we show that Eph receptor signaling from cell-cell contacts changes the cellular response to EGFR activation by altering its vesicular trafficking. Eph receptor activation traps EGFR in Rab5-positive early endosomes through an inhibition of Akt-dependent vesicular recycling. By altering the spatial distribution of EGFR activity during EGF stimulation, Eph receptor activation selectively suppresses migratory Akt signaling from the plasma membrane, while preserving proliferative ERK signaling from endosomes. We also show that soluble extracellular signals engaging the G-protein coupled receptor Kiss1 similarly suppress vesicular recycling to alter EGFR signaling. The cellular environment can thus modulate EGFR vesicular trafficking dynamics to generate context-dependent responses to EGF stimulation.SummaryEph receptor activation generates context-dependent cellular responses to EGFR activation by altering its vesicular trafficking dynamics.
Reconstitution of Helical Soluble α-Synuclein through Transient Interaction with Lipid Interfaces
Authors: Rovere Matteo , Sanderson John B. , Fonseca-Ornelas Luis , Bartels Tim 
Published: October 2017

Abstractα-synuclein (αSyn) is one of the key players in the pathogenesis of Parkinson’s disease (PD) and other synucleinopathies. Its misfolding and subsequent aggregation into intracellular inclusions are the pathological hallmark of these diseases and may also play a central role in the molecular cascade leading to neurodegeneration. In this work, we report the existence of a novel soluble α-helical conformer of αSyn, an archetypal “intrinsically disordered protein” (IDP), obtained through transient interaction with lipid interfaces. We describe how the stability of this conformer is highly dependent on the continuous, dynamic oligomerization of the folded species. The conformational space of αSyn appears to be highly context-dependent, and lipid bilayers might play crucial roles as molecular chaperones for cytosolic species in a cellular environment, as they do in the case of this previously unreported structure.Significance StatementBoth genetic and histopathologic evidence tie α-synuclein (αSyn) to the pathogenesis of Parkinson’s disease (PD), a widespread neurodegenerative disorder. Lipids play a central role in the dynamics of αSyn in physiology and disease. αSyn undergoes a coil-to-helix transition when binding to lipid vesicles and it is involved in the regulation of synaptic vesicle trafficking. Furthermore, recently discovered α-helical, aggregation-resistant “multimers” of αSyn could constitute a protective conformational pathway. We report the existence of a folded, lipid-unbound αSyn conformer that forms upon transient interaction with lipids and is stabilized by dynamic homooligomerization, suggesting that synaptic activity could modulate resistance towards aggregation. Our results are therefore important both for the molecular pathology of PD and the structural biology of intrinsically disordered proteins.
Decisions are expedited through multiple neural adjustments spanning the sensorimotor hierarchy
Authors: Steinemann Natalie A. , O’Connell Redmond G. , Kelly Simon P. 
Published: October 2017

AbstractWhen decision makers prioritize speed over accuracy, neural activity is elevated in brain circuits involved in preparing actions. Such “urgency” signal components, defined by their independence from sensory evidence, are observed even before evidence is presented and can grow dynamically during decision formation. Is urgency applied globally, or are there adjustments of a distinct nature applied at different processing levels? Using a novel multi-level recording paradigm, we show that dynamic urgency impacting cortical action-preparation signals is echoed downstream in electromyographic indices of muscle activation, but does not directly influence upstream cortical levels. A motor-independent representation of cumulative evidence reached lower pre-response levels under conditions of greater motor-level urgency, paralleling a decline in choice accuracy. At the sensory level itself, we find a boost in differential evidence, which is correlated with changes in pupil size and acts to alleviate, rather than contribute to, the overall accuracy cost under speed pressure.
Genome-wide and high-density CRISPR-Cas9 screens identify point mutations inPARP1causing PARP inhibitor resistance
Authors: Pettitt Stephen J. , Krastev Dragomir B. , Brandsma Inger , Drean Amy , Song Feifei , Aleksandrov Radoslav , Harrell Maria I. , Menon Malini , Brough Rachel , Campbell James , Frankum Jessica , Ranes Michael , Pemberton Helen N. , Rafiq Rumana , Fenwick Kerry , Swain Amanda , Guettler Sebastian , Lee Jung-Min , Swisher Elizabeth M. , Stoynov Stoyno , Yusa Kosuke , Ashworth Alan , Lord Christopher J. 
Published: October 2017

AbstractPARP inhibitors (PARPi) target homologous recombination defective tumour cells via synthetic lethality. Genome-wide and high-density CRISPR-Cas9 “tag, mutate and enrich” mutagenesis screens identified single amino acid mutations in PARP1 that cause profound PARPi-resistance. These included PARP1 mutations outside of the DNA interacting regions of the protein, such as mutations in solvent exposed regions of the catalytic domain and clusters of mutations around points of contact between ZnF, WGR and HD domains. These mutations altered PARP1 trapping, as did a mutation found in a clinical case of PARPi resistance. These genetic studies reinforce the importance of trapped PARP1 as a key cytotoxic DNA lesion and suggest that interactions between non-DNA binding domains of PARP1 influence cytotoxicity. Finally, different mechanisms of PARPi resistance (BRCA1reversion,PARP1,53BP1,REV7mutation) had differing effects on chemotherapy sensitivity, suggesting that the underlying mechanism of PARPi resistance likely influences the success of subsequent therapies.
Cell-specific modulation of nuclear pore complexes controls cell cycle entry during asymmetric division
Authors: Kumar Arun , Sharma Priyanka , Shcheprova Zhanna , Daulny Anne , Sanmartín Trinidad , Matucci Irene , Funaya Charlotta , Beato Miguel , Mendoza Manuel 
Published: October 2017

SummaryThe acquisition of cellular identity is coupled to changes in the nuclear periphery and nuclear pore complexes (NPCs). Whether and how these changes determine cell fate remains unclear. We have uncovered a mechanism regulating NPC acetylation to direct cell fate after asymmetric division in budding yeast. The lysine deacetylase Hos3 associates specifically with daughter cell NPCs during mitosis to delay cell cycle entry (Start). Hos3-dependent deacetylation of nuclear basket and central channel nucleoporins establishes daughter cell-specific nuclear accumulation of the transcriptional repressor Whi5 during anaphase and perinuclear silencing of the CLN2 gene in the following G1 phase. Hos3-dependent coordination of both events restrains Start in daughter but not in mother cells. We propose that deacetylation modulates transport-dependent and - independent functions of NPCs, leading to differential cell cycle progression in mother and daughter cells. Similar mechanisms might regulate NPC functions in specific cell types and/or cell cycle stages in multicellular organisms.
Polygenic risk scores applied to a single cohort reveal pleiotropy among hundreds of human phenotypes
Authors: Socrates Adam , Bond Tom , Karhunen Ville , Auvinen Juha , Rietveld Cornelius A. , Veijola Juha , Jarvelin Marjo-Riitta , O’Reilly Paul F. 
Published: October 2017

AbstractBackgroundThere is now convincing evidence that pleiotropy across the genome contributes to the correlation between human traits and comorbidity of diseases. The recent availability of genome-wide association study (GWAS) results have made the polygenic risk score (PRS) approach a powerful way to perform genetic prediction and identify genetic overlap among phenotypes.Methods and findingsHere we use the PRS method to assess evidence for shared genetic aetiology across hundreds of traits within a single epidemiological study – the Northern Finland Birth Cohort 1966 (NFBC1966). We replicate numerous recent findings, such as a genetic association between Alzheimer’s disease and lipid levels, while the depth of phenotyping in the NFBC1966 highlights a range of novel significant genetic associations between traits.ConclusionsThis study illustrates the power in taking a hypothesis-free approach to the study of shared genetic aetiology between human traits and diseases. It also demonstrates the potential of the PRS method to provide important biological insights using only a single well-phenotyped epidemiological study of moderate sample size (~5k), with important advantages over evaluating genetic correlations from GWAS summary statistics only.
The genomics of local adaptation in trees: Are we out of the woods yet?
Authors: Lind Brandon M. , Menon Mitra , Bolte Constance E. , Faske Trevor M. , Eckert Andrew J. 
Published: October 2017

AbstractThere is substantial interest in uncovering the genetic basis of the traits underlying adaptive responses in tree species, as this information will ultimately aid conservation and industrial endeavors across populations, generations, and environments. Fundamentally, the characterization of such genetic bases is within the context of a genetic architecture, which describes the mutlidimensional relationship between genotype and phenotype through the identification of causative variants, their relative location within a genome, expression, pleiotropic effect, environmental influence, and degree of dominance, epistasis, and additivity. Here, we review theory related to polygenic local adaptation and contextualize these expectations with methods often used to uncover the genetic basis of traits important to tree conservation and industry. A broad literature survey suggests that most tree traits generally exhibit considerable heritability, that underlying quantitative genetic variation (QST) is structured more so across populations than neutral expectations (FST) in 69% of comparisons across the literature, and that single-locus associations often exhibit small estimated per-locus effects. Together, these results suggest differential selection across populations often acts on tree phenotypes underlain by polygenic architectures consisting of numerous small to moderate effect loci. Using this synthesis, we highlight the limits of using solely single-locus approaches to describe underlying genetic architectures and close by addressing hurdles and promising alternatives towards such goals, remark upon the current state of tree genomics, and identify future directions for this field. Importantly, we argue, the success of future endeavors should not be predicated on the shortcomings of past studies and will instead be dependent upon the application of theory to empiricism, standardized reporting, centralized open-access databases, and continual input and review of the community’s research.
Awake fMRI Reveals Covert Arousal in Aggressive Dogs Under Social Resource Threat
Authors: Cook Peter , Prichard Ashley , Spivak Mark , Berns Gregory S. 
Published: October 2017

AbstractDomestic dogs are highly social, and have been shown sensitive not only to the actions of humans and other dogs but to the interactions between them. To examine the canine neurobiological response to observed interactions between a human and another dog, we collected fMRI data from dogs while they watched their owner feed a realistic fake dog or deposit food in a bucket. Given the likelyihood that arousal and affective state may contribute to responses to observed social situations, we examined the relationship between amygdala activation in these two conditions and an independent measure of aggressive temperament from the C-BARQ scale. Dogs rated more aggressive showed significantly higher activation in the fake-dog versus bucket condition. This finding suggests a neurobiological mechanism mediated by the amygdala for dog-directed aggression, especially when their owner interacts with another dog. Such a mechanism may have some parallels to human jealousy. Further, it adds to a growing body of evidence that specific neurobiological responses correlate with canine temperament and can be a predictor of future behavior. We also found evidence that the amygdala response habituates with repeated observed interactions. This suggests value in exposure-based interventions for potentially aggressive dogs.
Single-cell transcriptional dynamics of flavivirus infection
Authors: Zanini Fabio , Pu Szu-Yuan , Bekerman Elena , Einav Shirit , Quake Stephen R. 
Published: October 2017

ABSTRACTDengue and Zika viral infections affect millions of people annually and can be complicated by hemorrhage or neurological manifestations, respectively. However, a thorough understanding of the host response to these viruses is lacking, partly because conventional approaches ignore heterogeneity in virus abundance across cells. We present viscRNA-Seq (virus-inclusive single cell RNA-Seq), an approach to probe the host transcriptome together with intracellular viral RNA at the single cell level. We applied viscRNA-Seq to monitor dengue and Zika virus infection in cultured cells and discovered extreme heterogeneity in virus abundance. We exploited this variation to identify host factors that show complex dynamics and a high degree of specificity for either virus, including proteins involved in the endoplasmic reticulum translocon, signal peptide processing, and membrane trafficking. We validated the viscRNA-Seq hits and discovered novel proviral and antiviral factors. viscRNA-Seq is a powerful approach to assess the genome-wide virus-host dynamics at single cell level.
Relevance of host cell surface glycan structure for cell specificity of influenza A virus
Authors: Kastner Markus , Karner Andreas , Zhu Rong , Huang Qiang , Zhang Dandan , Liu Jianping , Geissner Andreas , Sadewasser Anne , Lesch Markus , Wörmann Xenia , Karlas Alexander , Seeberger Peter , Wolff Thorsten , Hinterdorfer Peter , Herrmann Andreas , Sieben Christian 
Published: October 2017

AbstractInfluenza A viruses (IAV) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycan receptors on host cells. HAs receptor specificity towards sialic acid (SA) is well studied and clearly critical for virus infection, but the contribution of the highly complex cellular plasma membrane to the cellular specificity remains elusive. In addition, some studies indicated that other host cell factors such as the epidermal growth factor receptor might contribute to the initial virus-cell contact and further downstream signaling1.Here we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS) to compare influenza virus receptor specificity with actual host cell binding. Unexpectedly, our study reveals that HAs receptor binding preference does not necessarily reflect virus-cell specificity. We propose SVFS as a tool to elucidate the cell binding preference of IAV thereby including the complex environment of sialylated receptors within the plasma membrane of living cells.
Transcriptome analysis reveals the differences between cellular response to ribosomal stress and translational stress
Authors: Shamsuzzaman Md , Gregory Brian , Bruno Vincent , Lindahl Lasse 
Published: October 2017

AbstractRibosome biogenesis is an essential metabolic process of a growing cell. Cells need to continuously synthesize new ribosomes in order to make new proteins than can support building biomass and cell division. It is obvious that in the absence of ribosome biogenesis, cell growth will stop and cell division will stall. However, it is not clear whether cell growth stops due to reduced protein synthesis capacity (translational stress) or due to activation of signaling specific to ribosome biogenesis abnormalities (ribosomal stress). To understand the signaling pathways leading to cell cycle arrest under ribosomal and translational stress conditions, we performed time series RNA-seq experiments of cells at different time of ribosomal and translational stress. We found that expression of ribosomal protein genes follow different course over the time of these two stress types. In addition, ribosomal stress is sensed early in the cell, as early as 2hr. Up-regulation of genes responsive to oxidative stress and over representation of mRNAs for transcription factors responsive to stress was detected in cell at 2hr of ribosomal protein depletion. Even though, we detected phenotypic similarities in terms of cell separation and accumulation in G1 phase cells during inhibition of ribosome formation and ribosome function, different gene expression patterns underlie these phenotypes, indicating a difference in causalities of these phenotypes. Both ribosomal and translational stress show common increased expression of stress responsive gene expression, like Crz1 target gene expression, signature of oxidative stress response and finally membrane or cell wall instability. We speculate that cell membrane and cell wall acts as major stress sensor in the cell and adjust cellular metabolism accordingly. Any change in membrane lipid composition, or membrane protein oxidation, or decrease or increase in intracellular turgor pressure causes stress in cell membrane. Cell membrane or cell wall stress activates and/or inactivates specific signaling pathway which triggers stress responsive gene expression and adaptation of cellular behavior accordingly.
Employee feedback orientation: a paternalistic leadership perspective
Authors: Hawass Hisham Hamid 
Published: October 2017

Purpose
The purpose of this study is to examine the direct effect of paternalistic leadership on the employee’s feedback orientation in the Egyptian public sector. It also investigates the mediating effect of the employee’s workplace well-being on the relationship between paternalistic leadership and feedback orientation.

Design/methodology/approach
The study uses a questionnaire that consists of measures adopted from existing and tested scales. A mediation analysis is conducted using structure equation modelling to examine the hypothesized relationships.

Findings
The findings reveal that paternalistic leadership is positively associated with feedback utility, accountability, awareness and self-efficacy. Moreover, the employee’s workplace well-being significantly mediates the proposed relationship between paternalistic leadership and the aforementioned dimensions of feedback orientation.

Originality/value
The relationship between paternalistic leadership and feedback orientation has received an extremely limited academic attention. This study hypothesizes a mediation model which investigates the leadership, well-being and feedback associations in the traditionally under-researched Egyptian context.