Abstract
PANTHER (Protein Analysis Through Evolutionary Relationships, http://www.pantherdb.org) is a resource for the evolutionary and functional classification of protein-coding genes from all ...domains of life. The evolutionary classification is based on a library of over 15,000 phylogenetic trees, and the functional classifications include Gene Ontology terms and pathways. Here, we analyze the current coverage of genes from genomes in different taxonomic groups, so that users can better understand what to expect when analyzing a gene list using PANTHER tools. We also describe extensive improvements to PANTHER made in the past two years. The PANTHER Protein Class ontology has been completely refactored, and 6101 PANTHER families have been manually assigned to a Protein Class, providing a high level classification of protein families and their genes. Users can access the TreeGrafter tool to add their own protein sequences to the reference phylogenetic trees in PANTHER, to infer evolutionary context as well as fine-grained annotations. We have added human enhancer-gene links that associate non-coding regions with the annotated human genes in PANTHER. We have also expanded the available services for programmatic access to PANTHER tools and data via application programming interfaces (APIs). Other improvements include additional plant genomes and an updated PANTHER GO-slim.
The PANTHER database (Protein ANalysis THrough Evolutionary Relationships, http://pantherdb.org) contains comprehensive information on the evolution and function of protein-coding genes from 104 ...completely sequenced genomes. PANTHER software tools allow users to classify new protein sequences, and to analyze gene lists obtained from large-scale genomics experiments. In the past year, major improvements include a large expansion of classification information available in PANTHER, as well as significant enhancements to the analysis tools. Protein subfamily functional classifications have more than doubled due to progress of the Gene Ontology Phylogenetic Annotation Project. For human genes (as well as a few other organisms), PANTHER now also supports enrichment analysis using pathway classifications from the Reactome resource. The gene list enrichment tools include a new 'hierarchical view' of results, enabling users to leverage the structure of the classifications/ontologies; the tools also allow users to upload genetic variant data directly, rather than requiring prior conversion to a gene list. The updated coding single-nucleotide polymorphisms (SNP) scoring tool uses an improved algorithm. The hidden Markov model (HMM) search tools now use HMMER3, dramatically reducing search times and improving accuracy of E-value statistics. Finally, the PANTHER Tree-Attribute Viewer has been implemented in JavaScript, with new views for exploring protein sequence evolution.
Despite the ubiquitous nature of boredom, the definition, function, and correlates of boredom are still poorly understood. In this review, we summarize the “known” (consistent evidence) and “unknown” ...(inconsistent evidence) correlates of boredom. We show that boredom is consistently related to negative affect, task-unrelated thought, over-estimation of elapsed time, reduced agency, as well as to over- and under-stimulation. Activation of the default mode network was consistent across the few available fMRI studies, while the recruitment of other brain areas such as the hippocampus and anterior insular cortex, was a notable but less consistent correlate of boredom. Other less consistent correlates of boredom are also reviewed, such as the level of arousal and the mental attributions given to fluctuations of attention. Finally, we identify two critical factors that may contribute to current inconsistencies in the literature and may hamper further progress in the field. First, there is relatively little consistency in the way in which boredom has been operationalized across studies to date, with operationalizations of boredom ranging from negative affect paired with under-stimulation, over-stimulation, to negative affect paired with a lack of goal-directed actions. Second, preliminary evidence suggests the existence of distinct types of boredom (e.g., searching vs. apathetic) that may have different and sometimes even opposing correlates. Adopting a more precise and consistent way of operationalizing boredom, and arriving at an empirically validated taxonomy of different types of boredom, could serve to overcome the current roadblocks to facilitate further progress in our scientific understanding of boredom.
The Autobiographical Emotional Memory Task (AEMT), which involves recalling and writing about intense emotional experiences, is a widely used method to experimentally induce emotions. The validity of ...this method depends upon the extent to which it can induce specific desired emotions (intended emotions), while not inducing any other (incidental) emotions at different levels across one (or more) conditions. A review of recent studies that used this method indicated that most studies exclusively monitor post-writing ratings of the intended emotions, without assessing the possibility that the method may have differentially induced other incidental emotions as well. We investigated the extent of this issue by collecting both pre- and post-writing ratings of incidental emotions in addition to the intended emotions. Using methods largely adapted from previous studies, participants were assigned to write about a profound experience of anger or fear (Experiment 1) or happiness or sadness (Experiment 2). In line with previous research, results indicated that intended emotions (anger and fear) were successfully induced in the respective conditions in Experiment 1. However, disgust and sadness were also induced while writing about an angry experience compared to a fearful experience. Similarly, although happiness and sadness were induced in the appropriate conditions, Experiment 2 indicated that writing about a sad experience also induced disgust, fear, and anger, compared to writing about a happy experience. Possible resolutions to avoid the limitations of the AEMT to induce specific discrete emotions are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The frontoparietal control network (FPCN) plays a central role in executive control. It has been predominantly viewed as a unitary domain general system. Here, we examined patterns of FPCN functional ...connectivity (FC) across multiple conditions of varying cognitive demands, to test for FPCN heterogeneity. We identified two distinct subsystems within the FPCN based on hierarchical clustering and machine learning classification analyses of within-FPCN FC patterns. These two FPCN subsystems exhibited distinct patterns of FC with the default network (DN) and the dorsal attention network (DAN). FPCNA exhibited stronger connectivity with the DN than the DAN, whereas FPCNB exhibited the opposite pattern. This twofold FPCN differentiation was observed across four independent datasets, across nine different conditions (rest and eight tasks), at the level of individual-participant data, as well as in meta-analytic coactivation patterns. Notably, the extent of FPCN differentiation varied across conditions, suggesting flexible adaptation to task demands. Finally, we used meta-analytic tools to identify several functional domains associated with the DN and DAN that differentially predict activation in the FPCN subsystems. These findings reveal a flexible and heterogeneous FPCN organization that may in part emerge from separable DN and DAN processing streams. We propose that FPCNA may be preferentially involved in the regulation of introspective processes, whereas FPCNB may be preferentially involved in the regulation of visuospatial perceptual attention.
Contemporary investigations regard creativity as a dynamic form of cognition that involves movement between the dissociable stages of creative generation and creative evaluation. Our recently ...proposed Dynamic Framework of Thought (Christoff et al., 2016) offered a conceptualization of these stages in terms of an interplay between sources of constraint and variability on thought. This initial conceptualization, however, has yet to be fully explicated and given targeted discussion. Here, we refine this framework’s account of creativity by highlighting the dynamic nature of creative thought, both within and between the stages of creative generation and evaluation. In particular, we emphasize that creative generation in particular is best regarded as a product of multiple, varying mental states, rather than being a singular mental state in and of itself. We also propose that the psychedelic state is a mental state with high potential for facilitating creative generation and update the Dynamic Framework of Thought to incorporate this state. This paper seeks to highlight the dynamic nature of the neurocognitive processes underlying creative thinking and to draw attention to the potential utility of psychedelic substances as experimental tools in the neuroscience of creativity.
•Creativity involves the dynamic traversal of varying neurocognitive states•Creative generation can occur in a number of distinct states•The psychedelic state may facilitate creative generation•Psychedelics may be a useful tool in the neuroscience of creativity
Cyclin-dependent kinase 7 (CDK7) regulates both cell cycle and transcription, but its precise role remains elusive. We previously described THZ1, a CDK7 inhibitor, which dramatically inhibits ...superenhancer-associated gene expression. However, potent CDK12/13 off-target activity obscured CDK7s contribution to this phenotype. Here, we describe the discovery of a highly selective covalent CDK7 inhibitor. YKL-5-124 causes arrest at the G
/S transition and inhibition of E2F-driven gene expression; these effects are rescued by a CDK7 mutant unable to covalently engage YKL-5-124, demonstrating on-target specificity. Unlike THZ1, treatment with YKL-5-124 resulted in no change to RNA polymerase II C-terminal domain phosphorylation; however, inhibition could be reconstituted by combining YKL-5-124 and THZ531, a selective CDK12/13 inhibitor, revealing potential redundancies in CDK control of gene transcription. These findings highlight the importance of CDK7/12/13 polypharmacology for anti-cancer activity of THZ1 and posit that selective inhibition of CDK7 may be useful for treatment of cancers marked by E2F misregulation.
•The vast majority of research currently defines mind wandering as off-task thought.•Freedom of movement in thought is introduced as a new dimension of mind wandering.•Freedom of movement in thought ...is only weakly correlated to being off-task.•40% of thoughts were misclassified if off-task thought is assumed to be freely-moving.
Mind wandering is frequently defined as task-unrelated or perceptually decoupled thought. However, these definitions may not capture the dynamic features of a wandering mind, such as its tendency to ‘move freely’. Here we test the relationship between three theoretically dissociable dimensions of thought: freedom of movement in thought, task-relatedness, and perceptual decoupling (i.e., lack of awareness of surroundings). Using everyday life experience sampling, thought probes were randomly delivered to participants’ phones for ten days. Results revealed weak intra-individual correlations between freedom of movement in thought and task-unrelatedness, as well as perceptual decoupling. Within our dataset, over 40% of thoughts would have been misclassified under the assumption that off-task thought is inherently freely moving. Overall, freedom of movement appears to be an independent dimension of thought that is not captured by the two most common measures of mind wandering. Future work focusing on the dynamics of thought may be crucial for improving our understanding of the wandering mind.
Despite a surge of empirical work on student participation in online learning environments, the causal links between the learning-related factors and processes with the desired learning outcomes ...remain unexplored. This study presents a systematic literature review of approaches to model learning in Massive Open Online Courses offering an analysis of learning-related constructs used in the prediction and measurement of student engagement and learning outcome. Based on our literature review, we identify current gaps in the research, including a lack of solid frameworks to explain learning in open online setting. Finally, we put forward a novel framework suitable for open online contexts based on a well-established model of student engagement. Our model is intended to guide future work studying the association between contextual factors (i.e., demographic, classroom, and individual needs), student engagement (i.e., academic, behavioral, cognitive, and affective engagement metrics), and learning outcomes (i.e., academic, social, and affective). The proposed model affords further interstudy comparisons as well as comparative studies with more traditional education models.
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