The leader RNA of SARS-CoV-2 sequesters polypyrimidine tract binding protein (PTBP1) and influences pre-mRNA splicing in infected cells.

The large amount of viral RNA produced during infections has the potential to interact with and effectively sequester cellular RNA binding proteins, thereby influencing aspects of post-transcriptional gene regulation in the infected cell. Here we demonstrate that the abundant 5' leader RNA region of SARS-CoV-2 viral RNAs can interact with the cellular polypyrimidine tract binding protein (PTBP1). Interestingly, the effect of a knockdown of PTBP1 protein on cellular gene expression is also mimicked during SARS-CoV-2 infection, suggesting that this protein may be functionally sequestered by viral RNAs. Consistent with this model, the alternative splicing of mRNAs that is normally controlled by PTBP1 is dysregulated during SARS-CoV-2 infection. Collectively, these data suggest that the SARS-CoV-2 leader RNA sequesters the cellular PTBP1 protein during infection, resulting in significant impacts on the RNA biology of the host cell. These alterations in post-transcriptional gene regulation may play a role in SARS-CoV-2 mediated molecular pathogenesis.

Periodic tapping mechanisms of skill learning in a fast-paced video game.

Timing plays a critical role when building up motor skill. In this study, we investigated and simulated human skill learning in a simplified variant of the Space Fortress video game named Auto Orbit with a strong timing component. Our principal aim was to test whether a computational model designed to simulate keypress actions repeated at rates slower than 500 ms (>500 ms) could also simulate human learning with repeated keypress actions taking place at very fast rates (≤500 ms). The main finding was that increasing speed stress forced human participants to qualitatively switch their behavior from a cognitively controlled strategy to an inherently rhythmic motor strategy. We show how the adaptive control of thought rational architecture's periodic tapping motor extension can replicate such rhythmic patterns of keypresses in two different computational models of human learning. The first model implements streamed motor actions across hands that are temporally decoupled, while the second model implements a coupled motor strategy in which actions from both hands are executed relative to the same periodic motor clock. Different subsets of subjects correspond to these two models. Our modeling simulations integrate previous psychological and motor control findings within a single cognitive architecture, and successfully replicate human behavioral patterns across a range of experimental measures at fast speed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

UV damage induces production of mitochondrial DNA fragments with specific length profiles.

UV light is a potent mutagen that induces bulky DNA damage in the form of cyclobutane pyrimidine dimers (CPDs). In eukaryotic cells, photodamage and other bulky lesions occurring in nuclear genomes (nucDNAs) can be repaired through nucleotide excision repair (NER), where dual incisions on both sides of a damaged site precede the removal of a single-stranded oligonucleotide containing the damage. Mitochondrial genomes (mtDNAs) are also susceptible to damage from UV light, but current views hold that the only way to eliminate bulky DNA damage in mtDNAs is through mtDNA degradation. Damage-containing oligonucleotides excised during NER can be captured with anti-damage antibodies and sequenced (XR-seq) to produce high resolution maps of active repair locations following UV exposure. We analyzed previously published datasets from Arabidopsis thaliana, Saccharomyces cerevisiae, and Drosophila melanogaster to identify reads originating from the mtDNA (and plastid genome in A. thaliana). In A. thaliana and S. cerevisiae, the mtDNA-mapping reads have unique length distributions compared to the nuclear-mapping reads. The dominant fragment size was 26 nt in S. cerevisiae and 28 nt in A. thaliana with distinct secondary peaks occurring in 2-nt (S. cerevisiae) or 4-nt (A. thaliana) intervals. These reads also show a nonrandom distribution of di-pyrimidines (the substrate for CPD formation) with TT enrichment at positions 7-8 of the reads. Therefore, UV damage to mtDNA appears to result in production of DNA fragments of characteristic lengths and positions relative to the damaged location. We hypothesize that these fragments may reflect the outcome of a previously uncharacterized mechanism of NER-like repair in mitochondria or a programmed mtDNA degradation pathway.

An Integrated Model of Collaborative Skill Acquisition: Anticipation, Control Tuning, and Role Adoption.

We studied collaborative skill acquisition in a dynamic setting with the game Co-op Space Fortress. While gaining expertise, the majority of subjects became increasingly consistent in the role they adopted without being able to communicate. Moreover, they acted in anticipation of the future task state. We constructed a collaborative skill acquisition model in the cognitive architecture ACT-R that reproduced subject skill acquisition trajectory. It modeled role adoption through reinforcement learning and predictive processes through motion extrapolation and learned relevant control parameters using both a reinforcement learning procedure and a new to ACT-R supervised learning procedure. This is the first integrated cognitive model of collaborative skill acquisition and, as such, gives us valuable insights into the multiple cognitive processes that are involved in learning to collaborate.

The environmental basis of memory.

Memory should make more available things that are more likely to be needed. Across multiple environmental domains, it has been shown that such a system would match qualitatively the memory effects involving repetition, delay, and spacing (Schooler & Anderson, 2017). To obtain data of sufficient size to study how detailed patterns of past appearance predict probability of being needed again, we examined the patterns with which words appear in large two data sets: tweets from popular sources and comments on popular subreddits. The two data sets show remarkably similar statistics, which are also consistent with earlier, smaller studies of environmental statistics. None of a candidate set of mathematical models of memory do well at predicting the observed patterns in these environments. A new model of human memory based on the environmental model proposed by Anderson and Milson (1989) did better at predicting the environmental data and a wide range of behavioral studies that measure memory availability by probability of recall and speed of retrieval. A critical variable in this model was range, the span of time over which an item occurs, which was discovered in mining the environmental data. These results suggest that theories of memory can be guided by mining of the statistical structure of the environment. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Contributions of CO2-Baited Malaise-Type Traps to the Knowledge of Hematophagous and Oestrid Flies (Diptera: Oestridae) Parasitizing Cervid Hosts.

This review describes an innovative and efficient modification of a type of Malaise trap meme overlooked in a recent review of such insect traps. It further identifies the large variety of dipteran parasites of vertebrates caught in the traps when CO2 was added as an attractant that otherwise rarely were caught in unbaited traps. Baited trap catches of parasitic flies mimicked those caught attacking cervid hosts. This review particularly focuses on comprehensive studies of: 1) several hematophagous species of largely unknown snipe flies (Diptera: Rhagionidae: Symphoromyia [Artiodactyla: Cervidae]) found host specific for Columbian black-tailed deer (Odocoileus hemionus columbianus Richardson), and 2) the biology of oestrid fly (Diptera: Oestridae) parasites of black-tailed deer and caribou/reindeer [Rangifer tarandus (L.) (Artiodactyla: Cervidae)], after it was discovered that the non-hematophagous females are guided to their vertebrate hosts by tracking a source of CO2, as done by many hematophagous flies.

A plant-infecting subviral RNA associated with poleroviruses produces a subgenomic RNA which resists exonuclease XRN1 in vitro.

Subviral agents are nucleic acids which lack the features for classification as a virus. Tombusvirus-like associated RNAs (tlaRNAs) are subviral positive-sense, single-stranded RNAs that replicate autonomously, yet depend on a coinfecting virus for encapsidation and transmission. TlaRNAs produce abundant subgenomic RNA (sgRNA) upon infection. Here, we investigate how the well-studied tlaRNA, ST9, produces sgRNA and its function. We found ST9 is a noncoding RNA, due to its lack of protein coding capacity. We used resistance assays with eukaryotic Exoribonuclease-1 (XRN1) to investigate sgRNA production via incomplete degradation of genomic RNA. The ST9 3' untranslated region stalled XRN1 very near the 5' sgRNA end. Thus, the XRN family of enzymes drives sgRNA accumulation in ST9-infected tissue by incomplete degradation of ST9 RNA. This work suggests tlaRNAs are not just parasites of viruses with compatible capsids, but also mutually beneficial partners that influence host cell RNA biology.

A decay-based account of learning and adaptation in complex skills.

How do humans adapt to parametric changes in a task without having to learn a new skill from scratch? Many studies of memory and sensorimotor adaptation have proposed theories that incorporate a decay on prior events, which leads the agent to eventually forget old experiences. This study investigates if a similar decay mechanism can account for human adaptation in complex skills that require the simultaneous integration of cognitive, motor, and perceptual processes. In 2 experiments, subjects learned to play a novel racing video game while adapting to parametric changes in the physics of the game's controls. Human learning and performance were modeled using the ACT-R cognitive architecture, which has been used successfully to model learning and fluency across a wide range of skills in prior research. Anderson et al. (2019) introduced the Controller module, a new component of the architecture that learns the setting of control parameters for actions and allows the agent to execute the rapid and precise actions that are necessary for good performance on complex tasks. Model simulations support including a moderate time-based decay on the weight of the experiences that the Controller uses. This is implemented in the Controller module by discounting the influence of older observations which helps the agent to focus on recent experiences that better reflect the current relationship between different settings of a control parameter and the rate of payoff from using that setting. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Discovering skill.

This paper shows how identical skills can emerge either from instruction or discovery when both result in an understanding of the causal structure of the task domain. The paper focuses on the discovery process, extending the skill acquisition model of Anderson et al. (2019) to address learning by discovery. The discovery process involves exploring the environment and developing associations between discontinuities in the task and events that precede them. The growth of associative strength in ACT-R serves to identify potential causal connections. The model can derive operators from these discovered causal relations just as does with the instructed causal information. Subjects were given a task of learning to play a video game either with a description of the game's causal structure (Instruction) or not (Discovery). The Instruction subjects learned faster, but successful Discovery subjects caught up. After 20 3-minute games the behavior of the successful subjects in the two groups was largely indistinguishable. The play of these Discovery subjects jumped in the same discrete way as did the behavior of simulated subjects in the model. These results show how implicit processes (associative learning, control tuning) and explicit processes (causal inference, planning) can combine to produce human learning in complex environments.

Aedes aegypti miRNA-33 modulates permethrin induced toxicity by regulating VGSC transcripts.

Aedes aegypti is a major vector of Zika, dengue, and other arboviruses. Permethrin adulticidal spraying, which targets the voltage-gated sodium channel (VGSC), is commonly done to reduce local mosquito populations and protect humans from exposure to arbovirus pathogens transmitted by this dangerous pest. Permethrin resistance, however, is a growing problem and understanding its underlying molecular basis may identify avenues to combat it. We identified a single G:C polymorphism in pre-miR-33 that was genetically associated with permethrin resistance; resulting isoforms had structural differences that may affect DICER-1/pre-miRNA processing rates. We then assessed the effects of overexpression of pre-miR-33 isoforms on permethrin toxicological phenotypes, VGSC transcript abundance and protein levels for two genetically related mosquito strains. One strain had its naturally high permethrin resistance levels maintained by periodic treatment, and the other was released from selection. VGSC protein levels were lower in the permethrin resistant strain than in the related permethrin-susceptible strain. Overexpression of the G-pre-miR-33 isoform reduced VGSC expression levels in both strains. To further elucidate changes in gene expression associated with permethrin resistance, exome-capture gDNA deep sequencing, genetic association mapping and subsequent gene set enrichment analysis revealed that transport genes, in particular, were selected in resistant versus susceptible mosquitoes. Collectively, these data indicate that miR-33 regulates VGSC expression as part of a nuanced system of neuronal regulation that contributes to a network of heritable features determining permethrin resistance.

Gordon H. Bower (1932-2020).

Memorializes Gordon H. Bower (1932-2020). One of the founders and leaders of cognitive science, Gordon was widely recognized for his contributions to science. He was elected to the National Academy of Sciences, the American Academy of Arts and Sciences, the Society of Experimental Psychologists, and the American Philosophical Society. Among his many awards were the Distinguished Scientific Contributions Award from the American Psychological Association in 1979 and the National Medal of Science in 2005 "for his unparalleled contributions to cognitive and mathematical psychology, for his lucid analysis of memory and learning, and for his important service to psychology and American science." Gordon was active both at Stanford University, serving as department chair and associate dean of humanities and sciences, and on the national stage, where he served as chief scientific adviser to the National Institute of Mental Health and was president of the Cognitive Science Society, the Psychonomic Society, and the Association for Psychological Science. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

The interface between coronaviruses and host cell RNA biology: Novel potential insights for future therapeutic intervention.

Coronaviruses, including SARS-Cov-2, are RNA-based pathogens that interface with a large variety of RNA-related cellular processes during infection. These processes include capping, polyadenylation, localization, RNA stability, translation, and regulation by RNA binding proteins or noncoding RNA effectors. The goal of this article is to provide an in-depth perspective on the current state of knowledge of how various coronaviruses interact with, usurp, and/or avoid aspects of these cellular RNA biology machineries. A thorough understanding of how coronaviruses interact with RNA-related posttranscriptional processes in the cell should allow for new insights into aspects of viral pathogenesis as well as identify new potential avenues for the development of anti-coronaviral therapeutics. This article is categorized under: RNA in Disease and Development > RNA in Disease.

Reconstructing fine-grained cognition from brain activity.

We describe the Sketch-and-Stitch method for bringing together a cognitive model and EEG to reconstruct the cognition of a subject. The method was tested in the context of a video game where the actions are highly interdependent and variable: simply changing whether a key was pressed or not for a 30th of a second can lead to a very different outcome. The Sketch level identifies the critical events in the game and the Stitch level fills in the detailed actions between these events. The critical events tend to produce robust EEG signals and the cognitive model provides probabilities of various transitions between critical events and the distribution of intervals between these events. This information can be combined in a hidden semi-Markov model that identifies the most probable sequence of critical events and when they happened. The Stitch level selects detailed actions from an extensive library of model games to produce these critical events. The decision about which sequence of actions to select from the library is made on the basis of how well they would produce weaker aspects of the EEG signal. The resulting approach can produce quite compelling replays of actual games from the EEG of a subject.

Spatiotemporal analysis of event-related fMRI to reveal cognitive states.

Cognitive science has a rich history of developing theories of processing that characterize the mental steps involved in performance of many tasks. Recent work in neuroimaging and machine learning has greatly improved our ability to link cognitive processes with what is happening in the brain. This article analyzes a hidden semi-Markov model-multivoxel pattern-analysis (HSMM-MVPA) methodology that we have developed for inferring the sequence of brain states one traverses in the performance of a cognitive task. The method is applied to a functional magnetic resonance imaging (fMRI) experiment where task boundaries are known that should separate states. The method is able to accurately identify those boundaries. Then, applying the method to synthetic data, we explore more fully those factors that influence performance of the method: signal-to-noise ratio, numbers of states, state sojourn times, and numbers of underlying experimental conditions. The results indicate the types of experimental tasks where applications of the HSMM-MVPA method are likely to yield accurate and insightful results.

Zika virus noncoding sfRNAs sequester multiple host-derived RNA-binding proteins and modulate mRNA decay and splicing during infection.

Insect-borne flaviviruses produce a 300-500-base long noncoding RNA, termed subgenomic flavivirus RNA (sfRNA), by stalling the cellular 5'-3'-exoribonuclease 1 (XRN1) via structures located in their 3' UTRs. In this study, we demonstrate that sfRNA production by Zika virus represses XRN1 analogous to what we have previously shown for other flaviviruses. Using protein-RNA reconstitution and a stringent RNA pulldown assay with human choriocarcinoma (JAR) cells, we demonstrate that the sfRNAs from both dengue type 2 and Zika viruses interact with a common set of 21 RNA-binding proteins that contribute to the regulation of post-transcriptional processes in the cell, including splicing, RNA stability, and translation. We found that four of these sfRNA-interacting host proteins, DEAD-box helicase 6 (DDX6) and enhancer of mRNA decapping 3 (EDC3) (two RNA decay factors), phosphorylated adaptor for RNA export (a regulator of the biogenesis of the splicing machinery), and apolipoprotein B mRNA-editing enzyme catalytic subunit 3C (APOBEC3C, a nucleic acid-editing deaminase), inherently restrict Zika virus infection. Furthermore, we demonstrate that the regulations of cellular mRNA decay and RNA splicing are compromised by Zika virus infection as well as by sfRNA alone. Collectively, these results reveal the large extent to which Zika virus-derived sfRNAs interact with cellular RNA-binding proteins and highlight the potential for widespread dysregulation of post-transcriptional control that likely limits the effective response of these cells to viral infection.

Learning rapid and precise skills.

A theory is presented about how instruction and experience combine to produce human fluency in a complex skill. The theory depends critically on 4 aspects of the ACT-R architecture. The first is the timing of various modules, particularly motor timing, which results in behavior that closely matches human behavior. The second is the ability to interpret declarative representations of instruction so that they lead to action. The third aspect concerns how practice converts this declarative knowledge into a procedural form so that appropriate actions can be quickly executed. The fourth component, newly added to the architecture, is a Controller module that learns the setting of control variables for actions. The overall theory is implemented in a computational model that is capable of simulating human learning. Its predictions are confirmed in a first experiment involving 2 games derived from the experimental video game Space Fortress. The second experiment tests predictions from the Controller module about lack of transfer between video games. Across the 2 experiments a single model, with the same parameter settings, is shown to simulate human learning of 3 video games. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Evaluation of a cognitive-behavioral intervention for high- and medium-risk probationers.

Reducing recidivism is a central goal of treatment programs for offenders. Preliminary evidence suggests that cognitive-behavioral group interventions based on the National Institute of Corrections curriculum (Bush, Glick, & Taymans, 1997) may be effective in reducing recidivism rates among adult probationers. We evaluated the effectiveness of a program based on this curriculum among 167 high- and medium-risk probationers assigned to this program and a comparison group of 120 high- and medium-risk probationers matched on age and number of prior criminal charges. Improvements over prior studies included use of survival analytic methods and propensity score matching, a longer follow-up interval, and examination of treatment effectiveness within ethnic groups. Relative to the comparison group, treatment group probationers were more likely to complete probation satisfactorily and survive longer before rearrest. Moreover, supplementary analyses suggested that ethnicity was associated with differences in intervention effectiveness. Treatment was predictive of lower recidivism rates among European Americans and African Americans but was less effective among Latino American probationers.

Psychopathy, self-identified race/ethnicity, and nonviolent recidivism: A longitudinal study.

Psychopathy has long been noted to play an important role in the prediction of criminal behavior and offending. Although many studies have demonstrated that psychopathic traits are predictive of violent recidivism among offenders, relatively few studies have examined the predictive validity of psychopathic traits for nonviolent recidivism and very few have examined this issue in a sample of offenders in the United States. To address this issue, we examined the predictive validity of psychopathy for both nonviolent and general recidivism using the Psychopathy Checklist-Revised (PCL-R) in a sample of 422 county jail inmates. We also examined whether ratings on Factors 1 and 2 differentially predicted nonviolent and general recidivism and whether predictive validity varied among European American, African American, and Latino American male offenders. Psychopathic traits were modestly predictive of nonviolent and general (total) recidivism. Factor 2 ratings were not more predictive of nonviolent recidivism than Factor 1 ratings in this sample, but the two factor scores also predicted nonviolent recidivism interactively. Psychopathic traits were also predictive of both outcomes in subsamples of European American and African American offenders, but not among Latino American offenders. Findings are consistent in magnitude and pattern with prior studies addressing the prediction of violence, and they show that the relationship between psychopathy and criminal conduct generalizes to the prediction of nonviolent crime in a United States offender sample. Results suggest potential differences between the predictive validity of psychopathy among Latino American offenders and other racial/ethnic groups, which suggest the need for additional research. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The Common Time Course of Memory Processes Revealed.

Magnetoencephalography (MEG) was used to compare memory processes in two experiments, one involving recognition of word pairs and the other involving recall of newly learned arithmetic facts. A combination of hidden semi-Markov models and multivariate pattern analysis was used to locate brief "bumps" in the sensor data that marked the onset of different stages of cognitive processing. These bumps identified a separation between a retrieval stage that identified relevant information in memory and a decision stage that determined what response was implied by that information. The encoding, retrieval, decision, and response stages displayed striking similarities across the two experiments in their duration and brain activation patterns. Retrieval and decision processes involve distinct brain activation patterns. We conclude that memory processes for two different tasks, associative recognition versus arithmetic retrieval, follow a common spatiotemporal neural pattern and that both tasks have distinct retrieval and decision stages.

Mapping working memory retrieval in space and in time: A combined electroencephalography and electrocorticography approach.

In this study, we investigated the time course and neural correlates of the retrieval process underlying visual working memory. We made use of a rare dataset in which the same task was recorded using both scalp electroencephalography (EEG) and Electrocorticography (ECoG), respectively. This allowed us to examine with great spatial and temporal detail how the retrieval process works, and in particular how the medial temporal lobe (MTL) is involved. In each trial, participants judged whether a probe face had been among a set of recently studied faces. With a method that combines hidden semi-Markov models and multivariate pattern analysis, the neural signal was decomposed into a sequence of latent cognitive stages with information about their durations on a trial-by-trial basis. Analyzed separately, EEG and ECoG data yielded converging results on discovered stages and their interpretation, which reflected 1) a brief pre-attention stage, 2) encoding the stimulus, 3) retrieving the studied set, and 4) making a decision. Combining these stages with the high spatial resolution of ECoG suggested that activity in the temporal cortex reflected item familiarity in the retrieval stage; and that once retrieval is complete, there is active maintenance of the studied face set in the decision stage in the MTL. During this same period, the frontal cortex guides the decision by means of theta coupling with the MTL. These observations generalize previous findings on the role of MTL theta from long-term memory tasks to short-term memory tasks.