Topology and Dynamics of Transcriptome (Dys)Regulation.

RNA transcripts play a crucial role as witnesses of gene expression health. Identifying disruptive short sequences in RNA transcription and regulation is essential for potentially treating diseases. Let us delve into the mathematical intricacies of these sequences. We have previously devised a mathematical approach for defining a "healthy" sequence. This sequence is characterized by having at most four distinct nucleotides (denoted as nt≤4). It serves as the generator of a group denoted as fp. The desired properties of this sequence are as follows: fp should be close to a free group of rank nt-1, it must be aperiodic, and fp should not have isolated singularities within its SL2(C) character variety (specifically within the corresponding Groebner basis). Now, let us explore the concept of singularities. There are cubic surfaces associated with the character variety of a four-punctured sphere denoted as S24. When we encounter these singularities, we find ourselves dealing with some algebraic solutions of a dynamical second-order differential (and transcendental) equation known as the Painlevé VI Equation. In certain cases, S24 degenerates, in the sense that two punctures collapse, resulting in a "wild" dynamics governed by the Painlevé equations of an index lower than VI. In our paper, we provide examples of these fascinating mathematical structures within the context of miRNAs. Specifically, we find a clear relationship between decorated character varieties of Painlevé equations and the character variety calculated from the seed of oncomirs. These findings should find many applications including cancer research and the investigation of neurodegenative diseases.

Aggression by omission: Redefining and measuring an understudied construct.

Researchers of aggression have classically focused on what has been previously called active aggression-the deliberate infliction of harm through the direct application of deleterious consequences. However, the counterpart to this, what was originally called passive aggression, has gone understudied, and its definition has mutated beyond its original conceptualization. The present two studies (N's 196 and 220, respectively) attempted to examine passive aggression as originally defined-the deliberate withholding of behavior to ensure that a target is harmed-and renaming it aggression by omission (ABO), in contrast to aggression by commission (ABC). These studies found that both fit within a similar nomological network of antagonism, Sadism, and trait aggression. Study 2 additionally found that both were equally affected by provocation and were considered equally harmful. These findings encourage further research into ABO to capture this construct concretely, especially in the context of common paradigms (e.g., the Taylor Aggression Paradigm, Hot Sauce, Point-Subtraction Aggression Paradigm), and trait aggression scales, which typically measure ABC.

Interactive effects of mindfulness and negative urgency on intimate partner aggression perpetration.

Intimate partner aggression (IPA) is a costly and incompletely understood phenomenon. Negative urgency, the tendency to act impulsively in response to negative affect, is predictive of IPA perpetration. Mindfulness, by virtue of its emphasis on nonreactivity to negative affect, is an opposing force to urgent tendencies that may mitigate the negative urgency-IPA link. Yet, no research to date investigates the interactive effects of negative urgency and mindfulness on IPA perpetration. Two studies were conducted that measured and manipulated multiple facets of mindfulness alongside measures of negative urgency and tendencies of IPA perpetration (combined N = 508 undergraduate students in monogamous intimate relationships). Counter to our preregistered predictions, we found that negative urgency's association with greater IPA perpetration increased at higher levels of mindfulness. These findings suggest that mindfulness may not be a protective factor against IPA perpetration for individuals higher in negative urgency, but rather may serve as a risk factor.

The structure of aggressive personality.

OBJECTIVE: We sought to factor analyze a broad array of aggression measures to identify a comprehensive, coherent factor structure for this construct. BACKGROUND: Measures and models of trait aggression have multiplied to the point of incoherence. METHOD: In Study 1, a diverse sample of 922 undergraduates completed a battery of items acquired from 42 self-report aggression questionnaires. In Study 2, we administered a curated item pool to another diverse sample of 1447 undergraduates, alongside criterion measures. RESULTS: We curated an initial item pool of 734 items down to 289 items that exhibited sufficient variability, were not redundant with other items, and possessed strong loadings onto a central 'trait aggression' factor. These remaining items were best characterized by a six-factor structure, which captured relational, angry, violent, retaliatory, intimate partner, and alcohol forms of aggression. We estimated their hierarchical structure, correlations with their original aggression scales, Five Factor Model trait dimensions, impulsivity facets, and found them to be robust to gender composition and the inclusion of alcohol-naive and intimate-partner-naive participants. CONCLUSIONS: This factor structure mostly supported widely-accepted models of aggressive personality that focus on its overt and relational forms and reactive functions, though proactive aggression only loosely emerged as a distinct entity. We retained the final items as the Comprehensive Aggression Scale (CAS).

Inside the mindful moment: The effects of brief mindfulness practice on large-scale network organization and intimate partner aggression.

Mindfulness can produce neuroplastic changes that support adaptive cognitive and emotional functioning. Recently interest in single-exercise mindfulness instruction has grown considerably because of the advent of mobile health technology. Accordingly, the current study sought to extend neural models of mindfulness by investigating transient states of mindfulness during single-dose exposure to focused attention meditation. Specifically, we examined the ability of a brief mindfulness induction to attenuate intimate partner aggression via adaptive changes to intrinsic functional brain networks. We employed a dual-regression approach to examine a large-scale functional network organization in 50 intimate partner dyads (total n = 100) while they received either mindfulness (n = 50) or relaxation (n = 50) instruction. Mindfulness instruction reduced coherence within the Default Mode Network and increased functional connectivity within the Frontoparietal Control and Salience Networks. Additionally, mindfulness decoupled primary visual and attention-linked networks. Yet, this induction was unable to elicit changes in subsequent intimate partner aggression, and such aggression was broadly unassociated with any of our network indices. These findings suggest that minimal doses of focused attention-based mindfulness can promote transient changes in large-scale brain networks that have uncertain implications for aggressive behavior.

Structures of the Insecticidal Toxin Complex Subunit XptA2 Highlight Roles for Flexible Domains.

The Toxin Complex (Tc) superfamily consists of toxin translocases that contribute to the targeting, delivery, and cytotoxicity of certain pathogenic Gram-negative bacteria. Membrane receptor targeting is driven by the A-subunit (TcA), which comprises IgG-like receptor binding domains (RBDs) at the surface. To better understand XptA2, an insect specific TcA secreted by the symbiont X. nematophilus from the intestine of entomopathogenic nematodes, we determined structures by X-ray crystallography and cryo-EM. Contrary to a previous report, XptA2 is pentameric. RBD-B exhibits an indentation from crystal packing that indicates loose association with the shell and a hotspot for possible receptor binding or a trigger for conformational dynamics. A two-fragment XptA2 lacking an intact linker achieved the folded pre-pore state like wild type (wt), revealing no requirement of the linker for protein folding. The linker is disordered in all structures, and we propose it plays a role in dynamics downstream of the initial pre-pore state.

Development of a measure of aggressive behavior expectancies in adults: The Aggression Expectancy Questionnaire.

According to sociocognitive theories, aggression is learned and elicited through a series of cognitive processes, such as expectancies, or the various consequences that an individual considers more or less likely following aggressive behavior. The current manuscript describes a measurement development project that ultimately yielded a 16-item measure of positive and negative aggression expectancies suitable for use in adult populations. Across two content generation surveys, two preliminary item refinement studies, and three full studies, we took an iterative approach and administered large item pools to several samples and refined item content through a combination of empirical (i.e., factor loadings, model fit) and conceptual (i.e., content breadth, non-redundancy) considerations. The Aggression Expectancy Questionnaire displays a four-factor structure, as well as evidence of convergent and divergent validity with self-reported aggression and relevant basic (e.g., antagonism, anger) and complex (e.g., psychopathy) personality variables. It is posited that this type of cognitive mechanism may serve as an intermediary link between distal characterological predictors of aggression and its proximal manifestation, which is in line with several prominent theories of personality and may ultimately hold clinical utility by providing a framework for aggression interventions.

DNA Sequence and Structure under the Prism of Group Theory and Algebraic Surfaces.

Taking a DNA sequence, a word with letters/bases A, T, G and C, as the relation between the generators of an infinite group π, one can discriminate between two important families: (i) the cardinality structure for conjugacy classes of subgroups of π is that of a free group on one to four bases, and the DNA word, viewed as a substitution sequence, is aperiodic; (ii) the cardinality structure for conjugacy classes of subgroups of π is not that of a free group, the sequence is generally not aperiodic and topological properties of π have to be determined differently. The two cases rely on DNA conformations such as A-DNA, B-DNA, Z-DNA, G-quadruplexes, etc. We found a few salient results: Z-DNA, when involved in transcription, replication and regulation in a healthy situation, implies (i). The sequence of telomeric repeats comprising three distinct bases most of the time satisfies (i). For two-base sequences in the free case (i) or non-free case (ii), the topology of π may be found in terms of the SL(2,C) character variety of π and the attached algebraic surfaces. The linking of two unknotted curves-the Hopf link-may occur in the topology of π in cases of biological importance, in telomeres, G-quadruplexes, hairpins and junctions, a feature that we already found in the context of models of topological quantum computing. For three- and four-base sequences, other knotting configurations are noticed and a building block of the topology is the four-punctured sphere. Our methods have the potential to discriminate between potential diseases associated to the sequences.

Neural mechanisms of intergroup exclusion and retaliatory aggression.

Aggression occurs frequently and severely between rival groups. Although there has been much study into the psychological and socio-ecological determinants of intergroup aggression, the neuroscience of this phenomenon remains incomplete. To examine the neural correlates of aggression directed at outgroup (versus ingroup) targets, we recruited 35 healthy young male participants who were current or former students of the same university. While undergoing functional MRI, participants completed an aggression task against both an ingroup and an outgroup opponent in which their opponents repeatedly provoked them at varying levels and then participants could retaliate. Participants were then socially included and then excluded by two outgroup members and then completed the same aggression task against the same two opponents. Both before and after outgroup exclusion, aggression toward outgroup members was positively associated with activity in the ventral striatum during decisions about how aggressive to be toward their outgroup opponent. Aggression toward outgroup members was also linked to greater post-exclusion activity in the rostral and dorsal medial prefrontal cortex during provocation from their outgroup opponent. These altered patterns of brain activity suggest that frontostriatal mechanisms may play a significant role in motivating aggression toward outgroup members.

Group Theory of Syntactical Freedom in DNA Transcription and Genome Decoding.

Transcription factors (TFs) are proteins that recognize specific DNA fragments in order to decode the genome and ensure its optimal functioning. TFs work at the local and global scales by specifying cell type, cell growth and death, cell migration, organization and timely tasks. We investigate the structure of DNA-binding motifs with the theory of finitely generated groups. The DNA 'word' in the binding domain-the motif-may be seen as the generator of a finitely generated group Fdna on four letters, the bases A, T, G and C. It is shown that, most of the time, the DNA-binding motifs have subgroup structures close to free groups of rank three or less, a property that we call 'syntactical freedom'. Such a property is associated with the aperiodicity of the motif when it is seen as a substitution sequence. Examples are provided for the major families of TFs, such as leucine zipper factors, zinc finger factors, homeo-domain factors, etc. We also discuss the exceptions to the existence of such DNA syntactical rules and their functional roles. This includes the TATA box in the promoter region of some genes, the single-nucleotide markers (SNP) and the motifs of some genes of ubiquitous roles in transcription and regulation.

An empirically based power primer for laboratory aggression research.

Recent reviews suggest that, like much of the psychological literature, research studies using laboratory aggression paradigms tend to be underpowered to reliably locate commonly observed effect sizes (e.g., r = ~.10-.20, Cohen's d = ~0.20-0.40). In an effort to counter this trend, we provide a "power primer" that laboratory aggression researchers can use as a resource when planning studies using this methodology. Using simulation-based power analyses and effect size estimates derived from recent literature reviews, we provide sample size recommendations based on type of research question (e.g., main effect vs. two-way vs. three-way interactions) and correlations among predictors. Results highlight the large number of participants that must be recruited to reach acceptable (~80%) power, especially for tests of interactions where the recommended sample sizes far exceed those typically employed in this literature. These discrepancies are so substantial that we urge laboratory aggression researchers to consider a moratorium on tests of three-way interactions. Although our results use estimates from the laboratory aggression literature, we believe they are generalizable to other lines of research using behavioral tasks, as well as psychological science more broadly. We close by offering a series of best practice recommendations and reiterating long-standing calls for attention to statistical power as a basic element of study planning.

The tangled webs we wreak: Examining the structure of aggressive personality using psychometric networks.

OBJECTIVE: Trait aggression is a prominent construct in the psychological literature, yet little work has sought to situate trait aggression among broader frameworks of personality. Initial evidence suggests that trait aggression may be best couched within the nomological network of the Five-Factor Model (FFM). The current work sought to locate the most appropriate home for trait aggression among the FFM. METHOD: We applied a preregistered regimen of psychometric network analyses to three datasets (combined N = 2927) that contained self-reports of trait aggression and the FFM traits. RESULTS: Trait aggression was highly central in the factor-level networks, which contained associations consistent with the conceptualization of this construct as a lower-order component of low agreeableness. The facet-level networks revealed that the behavioral facets of trait aggression reflected low agreeableness, but that the anger and hostility facets reflected high neuroticism. The item-level network suggested that the intent to initiate aggressive encounters was the primary bridge that empirically linked trait aggression to agreeableness. CONCLUSIONS: Our results indicate that trait aggression is primarily a lower-order facet of agreeableness, advance our understanding of trait aggression, integrate it with broader frameworks of personality, and suggest future directions to refine this complex dispositional tendency.

Measurement Invariance and Item Response Theory Analysis of the Taylor Aggression Paradigm.

The Taylor Aggression Paradigm (TAP) is a widely used laboratory aggression task, yet item response theory analyses of this task are nonexistent. To estimate these aspects of the TAP, we combined data from nine laboratory studies that employed the 25-trial version of the TAP (combined N = 1,856). One- and four-factor solutions for the TAP data exhibited evidence of measurement invariance across gender (men vs. women) and experimental provocation (negative vs. positive social feedback), as well as negligible instances of differential item functioning. As such, psychometric properties of the TAP were invariant across binary representations of gender and experimental provocation. Furthermore, trials following low and high provocation were the least informative and those following moderate provocation were the most informative. Scoring approaches to the TAP may benefit from giving greater weight to trials following moderate provocation. Overall, we find great utility in applying item response theory approaches to behavioral laboratory tasks.

Neural mechanisms of intimate partner aggression.

People sometimes hurt those they profess to love; yet our understanding of intimate partner aggression (IPA) and its causes remains incomplete. We examined brain activity using functional magnetic resonance imaging (fMRI) in an ethnically and racially diverse sample of 50 female-male, monogamous romantic couples as they completed an aggression task against their intimate partner, a close friend, and a different-sex stranger. Laboratory and real-world IPA were uniquely associated with altered activity within and connectivity between cortical midline structures that subserve social cognition and the computation of value. Men's IPA most corresponded to lower posterior cingulate reactivity during provocation and women's IPA most corresponded to lower ventromedial prefrontal cortex activity during IPA itself. Actor-partner independence modeling suggested women's IPA may correspond to their male partner's neural reactivity to provocation. Broadly, these findings highlight the importance of self-regulatory functions of the medial cortex and away from effortful inhibition subserved by dorsolateral cortices.

Punishment on Pause: Preliminary Evidence That Mindfulness Training Modifies Neural Responses in a Reactive Aggression Task.

Reactive aggression, a hostile retaliatory response to perceived threat, has been attributed to failures in emotion regulation. Interventions for reactive aggression have largely focused on cognitive control training, which target top-down emotion regulation mechanisms to inhibit aggressive impulses. Recent theory suggests that mindfulness training (MT) improves emotion regulation via both top-down and bottom-up neural mechanisms and has thus been proposed as an alternative treatment for aggression. Using this framework, the current pilot study examined how MT impacts functional brain physiology in the regulation of reactive aggression. Participants were randomly assigned to 2 weeks of MT (n = 11) or structurally equivalent active coping training (CT) that emphasizes cognitive control (n = 12). Following training, participants underwent functional magnetic resonance imaging (fMRI) during a retaliatory aggression task, a 16-trial game in which participants could respond to provocation by choosing whether or not to retaliate in the next round. Training groups did not differ in levels of aggression displayed. However, participants assigned to MT exhibited enhanced ventromedial prefrontal cortex (vmPFC) recruitment during punishment events (i.e., the aversive consequence of losing) relative to those receiving active CT. Conversely, the active coping group demonstrated greater dorsomedial prefrontal cortex (dmPFC) activation when deciding how much to retaliate, in line with a bolstered top-down behavior monitoring function. The findings suggest that mindfulness and cognitive control training may regulate aggression via different neural circuits and at different temporal stages of the provocation-aggression cycle. Trial Registration: identification no. NCT03485807.

Construct Validation of Experimental Manipulations in Social Psychology: Current Practices and Recommendations for the Future.

Experimental manipulations in social psychology must exhibit construct validity by influencing their intended psychological constructs. Yet how do experimenters in social psychology attempt to establish the construct validity of their manipulations? Following a preregistered plan, we coded 348 experimental manipulations from the 2017 issues of the Journal of Personality and Social Psychology. Representing a reliance on "on-the-fly" experimentation, the vast majority of these manipulations were created ad hoc for a given study and were not previously validated before implementation. A minority of manipulations had their construct validity evaluated by pilot testing before implementation or via a manipulation check. Of the manipulation checks administered, most were face valid, single-item self-reports, and only a few met criteria for "true" validation. In aggregate, roughly two fifths of manipulations relied solely on face validity. To the extent that they are representative of the field, these results suggest that best practices for validating manipulations are not commonplace-a potential contributor to replicability issues. These issues can be remedied by validating manipulations before implementation using validated manipulation checks, standardizing manipulation protocols, estimating the size and duration of manipulations' effects, and estimating each manipulation's effects on multiple constructs within the target nomological network.

The flux, pulse, and spin of aggression-related affect.

Aggression is an affect-laden behavior. The within-person variability of affective states that immediately precede, accompany, and follow aggression-and their links to between-person variability in aggressive behavior and traits-remain incompletely understood. To address this gap in our understanding, we examined 8 studies in which 2,173 participants reported the negative and positive affect they experienced before, during, and after a laboratory or online aggression task. We quantified the within-person variability within (flux) and across (pulse) negative and positive affect intensity, as well as the variability in oscillations between negative and positive affect (spin). Internal meta-analyses revealed an association between aggressive behavior and traits and flux in positive affect (against our preregistered predictions). Probing this effect with piecewise growth models showed that less aggressive individuals exhibited a pronounced decrease in positive affect during aggression, as compared to before and after the act. This downward fluctuation in positive affect was attenuated among aggressive individuals, who exhibited relatively stable levels of positive aggression-related affect. Thus, stable positive affect surrounding an aggressive act and higher positive affect during the act may buttress and promote aggressive tendencies. These findings support a reinforcement model of aggressive behavior, contrast with the aggression literature's conventional focus on negative affect and the instability thereof, and point to the utility of dynamic measures of moment-to-moment affect in understanding human social behavior. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

What makes a "successful" psychopath? Longitudinal trajectories of offenders' antisocial behavior and impulse control as a function of psychopathy.

Psychopathy is a considerable risk factor for violent behavior. However, many psychopathic individuals refrain from antisocial and criminal acts. The mechanisms underlying the formation of this "successful" phenotype are uncertain. We tested a compensatory model of "successful" psychopathy, which posits that relatively "successful" psychopathic individuals develop greater conscientious traits that serve to inhibit their heightened antisocial impulses. To test this model, we examined the 7-year longitudinal Research on Pathways to Desistance study of 1,354 adjudicated adolescents. Higher initial psychopathy was associated with steeper increases in general inhibitory control and the inhibition of aggression over time. This effect was magnified among "successful" offenders (i.e., those who reoffended less). These findings support our compensatory model, suggesting that psychopathic individuals who develop greater self-regulatory control over their antisocial impulses become relatively more "successful" than their less regulated counterparts. Moreover, our results speak of the importance of the five-factor model for understanding psychopathy and the crucial role of conscientiousness in the form that psychopathic individuals take. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

p-Curve analysis of the Taylor Aggression Paradigm: Estimating evidentiary value and statistical power across 50 years of research.

The overall reliability or evidentiary value of any body of literature is established in part by ruling out publication bias for any observed effects. Questionable research practices have potentially undermined the evidentiary value of commonly used research paradigms in psychological science. Subsequently, the evidentiary value of these common methodologies remains uncertain. To quantify the severity of these issues in the literature, we selected the Taylor Aggression Paradigm (TAP) as a case study and submitted 170 hypothesis tests spanning over 50 years of research to a preregistered p-curve analysis. The TAP literature (N = 24,685) demonstrated significant evidentiary value but yielded a small average effect size (d = 0.29) and inadequate power (38%). The main effects demonstrated greater evidentiary value, power, and effect sizes than interactions. Studies that tested the effects of measured traits did not differ in evidentiary value or power to those that tested the effects of experimentally manipulated states. Exploratory analyses revealed that evidentiary value, statistical power, and effect sizes have improved over time. We provide recommendations for researchers who seek to maximize the evidentiary value of their psychological measures.

Trait Aggression is Primarily a Facet of Antagonism: Evidence from Dominance, Latent Correlational, and Item-Level Analyses.

Trait aggression has been studied for decades and yet remains adrift from broader frameworks of personality such as the Five Factor Model. Across two datasets from undergraduate participants (Study 1: N = 359; Study 2; N = 620), we observed strong manifest and latent correlations between trait aggression and lower agreeableness (i.e., greater antagonism). Trait aggression was also linked to greater neuroticism and lower conscientiousness, but their effect sizes fell beneath our preregistered threshold. Subsequent item-level analyses were unable to articulate trait aggression and agreeableness items into separate factors using the IPIP-NEO, but not the Big Five Inventory. Our findings suggest that trait aggression is accurately characterized as primarily a facet of antagonism, while also reflecting other personality dimensions.