Activated sputum eosinophils associated with exacerbations in children on mepolizumab.

BACKGROUND: MUPPITS-2 was a randomized, placebo-controlled clinical trial that demonstrated mepolizumab (anti-IL-5) reduced exacerbations and blood and airway eosinophils in urban children with severe eosinophilic asthma. Despite this reduction in eosinophilia, exacerbation risk persisted in certain patients treated with mepolizumab. This raises the possibility that subpopulations of airway eosinophils exist that contribute to breakthrough exacerbations. OBJECTIVE: We aimed to determine the effect of mepolizumab on airway eosinophils in childhood asthma. METHODS: Sputum samples were obtained from 53 MUPPITS-2 participants. Airway eosinophils were characterized using mass cytometry and grouped into subpopulations using unsupervised clustering analyses of 38 surface and intracellular markers. Differences in frequency and immunophenotype of sputum eosinophil subpopulations were assessed based on treatment arm and frequency of exacerbations. RESULTS: Median sputum eosinophils were significantly lower among participants treated with mepolizumab compared with placebo (58% lower, 0.35% difference [95% CI 0.01, 0.74], P = .04). Clustering analysis identified 3 subpopulations of sputum eosinophils with varied expression of CD62L. CD62Lint and CD62Lhi eosinophils exhibited significantly elevated activation marker and eosinophil peroxidase expression, respectively. In mepolizumab-treated participants, CD62Lint and CD62Lhi eosinophils were more abundant in participants who experienced exacerbations than in those who did not (100% higher for CD62Lint, 0.04% difference [95% CI 0.0, 0.13], P = .04; 93% higher for CD62Lhi, 0.21% difference [95% CI 0.0, 0.77], P = .04). CONCLUSIONS: Children with eosinophilic asthma treated with mepolizumab had significantly lower sputum eosinophils. However, CD62Lint and CD62Lhi eosinophils were significantly elevated in children on mepolizumab who had exacerbations, suggesting that eosinophil subpopulations exist that contribute to exacerbations despite anti-IL-5 treatment.

The nuclear matrix protein CIZ1 facilitates localization of Xist RNA to the inactive X-chromosome territory.

The nuclear matrix protein Cip1-interacting zinc finger protein 1 (CIZ1) promotes DNA replication in association with cyclins and has been linked to adult and pediatric cancers. Here we show that CIZ1 is highly enriched on the inactive X chromosome (Xi) in mouse and human female cells and is retained by interaction with the RNA-dependent nuclear matrix. CIZ1 is recruited to Xi in response to expression of X inactive-specific transcript (Xist) RNA during the earliest stages of X inactivation in embryonic stem cells and is dependent on the C-terminal nuclear matrix anchor domain of CIZ1 and the E repeats of Xist CIZ1-null mice, although viable, display fully penetrant female-specific lymphoproliferative disorder. Interestingly, in mouse embryonic fibroblast cells derived from CIZ1-null embryos, Xist RNA localization is disrupted, being highly dispersed through the nucleoplasm rather than focal. Focal localization is reinstated following re-expression of CIZ1. Focal localization of Xist RNA is also disrupted in activated B and T cells isolated from CIZ1-null animals, suggesting a possible explanation for female-specific lymphoproliferative disorder. Together, these findings suggest that CIZ1 has an essential role in anchoring Xist to the nuclear matrix in specific somatic lineages.

A simple optical flow model explains why certain object viewpoints are special.

A core challenge in perception is recognizing objects across the highly variable retinal input that occurs when objects are viewed from different directions (e.g. front versus side views). It has long been known that certain views are of particular importance, but it remains unclear why. We reasoned that characterizing the computations underlying visual comparisons between objects could explain the privileged status of certain qualitatively special views. We measured pose discrimination for a wide range of objects, finding large variations in performance depending on the object and the viewing angle, with front and back views yielding particularly good discrimination. Strikingly, a simple and biologically plausible computational model based on measuring the projected three-dimensional optical flow between views of objects accurately predicted both successes and failures of discrimination performance. This provides a computational account of why certain views have a privileged status.

Influence of fecal microbial transplant (FMT) between male and female rats on methamphetamine-induced hyperthermia.

OBJECTIVE: To investigate the effect of bidirectional fecal microbial transplant (FMT) between male and female rats on methamphetamine (MA)-induced hyperthermia. METHODS: FMT was performed between male and female rats prior to MA (10 mg/kg, sc) treatment. Core body temperature, plasma drug and norepinephrine (NE) levels were measured and compared between treatment groups. 16S rRNA gene sequencing of bacterial communities between male and female rats was performed. RESULTS: MA treatment resulted in significantly higher core body temperatures in male groups (control and FMT-treated) compared to MA-treated female groups (control and FMT-treated). Plasma concentrations of MA and amphetamine were higher in females than males. Whereas, plasma norepinephrine (NE) levels were not different between male and female rats 90 minutes after MA treatment. At the phyla level, the microbiome of male and female control rats were dominated by Firmicutes and Bacteroidetes. Males had a higher relative abundance of Firmicutes and lower relative abundances of Bacteroidetes than females. The FMT procedure changed the recipient group towards their donor with males getting closer to their donors than females. In the control groups following MA treatment, Firmicutes increased and Bacteroides decreased in females and males. Conversely, in the FMT treatment groups following MA treatment, Firmicutes decreased while Bacteroidetes increased in females and males. CONCLUSIONS: Although definite differences in the structure and diversity of the gut microbiome were observed using 16S rRNA gene sequencing of bacterial communities between male and female rats, these differences do not seem to contribute to the sex-based differences in MA-induced hyperthermia.

Early childhood impulsivity and parenting predict children's development of externalizing psychopathology.

Parenting and child impulsivity are consistent predictors of children's externalizing symptoms; however, the role of the range of parenting (i.e., variation in parenting across contexts), and its interactions with child impulsivity, are poorly understood. We examined whether characteristic parenting practices and parenting range predicted the course of externalizing symptoms in 409 children (Mage = 3.43 years at baseline, 208 girls) across ages 3, 5, 8, and 11. We assessed parent positive affectivity (PPA), hostility, and parenting structure at child age 3 using three behavioral tasks that varied in context, examining range by modeling a latent difference score for each parenting dimension. Greater PPA range, mean structure, and parenting structure range all predicted fewer symptoms at age 3 for children with higher impulsivity. Lower mean hostility predicted fewer symptoms at age 3 for children with lower impulsivity. Greater PPA, and smaller PPA range, predicted a decrease in symptoms for children higher in impulsivity. Lower hostility range predicted a decrease in symptoms for children with lower impulsivity but predicted maintaining symptoms for children with higher impulsivity. Results demonstrate the differential roles average parenting practices and parenting range play in the development of child externalizing psychopathology, especially in the context of child impulsivity.

Exploring the Interplay Between Message Format, Need for Cognition and Personal Relevance on Processing Messages About Physical Activity: a Two-Arm Randomized Experimental Trial.

BACKGROUND: According to the Elaboration Likelihood Model, persuasion can occur via two different routes (the central route and peripheral route), with the route utilized dependent on factors associated with motivation and ability. This study aimed to explore the moderating role of need for cognition (NFC) and perceived relevance on the processing of physical activity messages designed to persuade via either the central route or the peripheral route. METHOD: Participants (N = 50) were randomized to receive messages optimized for central route processing or messages optimized for peripheral route processing. Eye-tracking devices were used to assess attention, which was the primary outcome. Message perceptions and the extent of persuasion (changes in physical activity determinants) were also assessed via self-report as secondary outcomes. Moderator effects were examined using interaction terms within mixed effects models and linear regression models. RESULTS: There were no detected interactions between condition and NFC for any of the study outcomes (all ps > .05). Main effects of personal relevance were observed for some self-report outcomes, with increased relevance associated with better processing outcomes. An interaction between need for cognition and personal relevance was observed for perceived behavioral control (p = 0.002); greater relevance was associated with greater perceived behavioral control for those with a higher need for cognition. CONCLUSION: Matching physical activity messages based on NFC may not increase intervention efficacy. Relevance of materials is associated with greater change in physical activity determinants and may be more so among those with a higher NFC.

A Network of Sputum MicroRNAs Is Associated with Neutrophilic Airway Inflammation in Asthma.

Rationale: MicroRNAs are potent regulators of biologic systems that are critical to tissue homeostasis. Individual microRNAs have been identified in airway samples. However, a systems analysis of the microRNA-mRNA networks present in the sputum that contribute to airway inflammation in asthma has not been published.Objectives: Identify microRNA and mRNA networks in the sputum of patients with asthma.Methods: We conducted a genome-wide analysis of microRNA and mRNA in the sputum from patients with asthma and correlated expression with clinical phenotypes. Weighted gene correlation network analysis was implemented to identify microRNA networks (modules) that significantly correlate with clinical features of asthma and mRNA expression networks. MicroRNA expression in peripheral blood neutrophils and lymphocytes and in situ hybridization of the sputum were used to identify the cellular sources of microRNAs. MicroRNA expression obtained before and after ozone exposure was also used to identify changes associated with neutrophil counts in the airway.Measurements and Main Results: Six microRNA modules were associated with clinical features of asthma. A single module (nely) was associated with a history of hospitalizations, lung function impairment, and numbers of neutrophils and lymphocytes in the sputum. Of the 12 microRNAs in the nely module, hsa-miR-223-3p was the highest expressed microRNA in neutrophils and was associated with increased neutrophil counts in the sputum in response to ozone exposure. Multiple microRNAs in the nely module correlated with two mRNA modules enriched for TLR (Toll-like receptor) and T-helper cell type 17 (Th17) signaling and endoplasmic reticulum stress. hsa-miR-223-3p was a key regulator of the TLR and Th17 pathways in the sputum of subjects with asthma.Conclusions: This study of sputum microRNA and mRNA expression from patients with asthma demonstrates the existence of microRNA networks and genes that are associated with features of asthma severity. Among these, hsa-miR-223-3p, a neutrophil-derived microRNA, regulates TLR/Th17 signaling and endoplasmic reticulum stress.

Global Rating Scales for the Assessment of Arthroscopic Surgical Skills: A Systematic Review.

PURPOSE: To evaluate whether sufficient validity and reliability evidence exists to support the use of global rating scales (GRS) as evaluation tools in both formative assessment and competency assessment of arthroscopic procedures. METHODS: A search of PubMed, Embase, and Scopus was conducted for articles published between 1990 and 2018. Studies reporting measures of validity and reliability of GRS relating to arthroscopic skills were included. Procedural checklists and other assessment tools were excluded. RESULTS: A total of 39 articles met the inclusion criteria. In total, 7 de novo GRS specific for arthroscopic education and 3 pre-existing GRS repurposed 4 times for arthroscopic education were identified in the literature. The 11 GRS were used to assess 1175 surgeons 3890 times. Three GRS tools explicitly defined an arbitrary minimum competency threshold, 6 of 11 tools demonstrated construct validity-the ability to significantly discriminate between groups of differing experience-and 5 of 11 tools assessed inter-rater reliability, but only the Arthroscopic Surgical Skills Evaluation Tool demonstrated excellent inter-rater reliability. The Arthroscopic Surgical Skills Evaluation Tool was validated by 16 articles for a total of 537 surgeons for hip, knee, shoulder, and ankle arthroscopy in both simulated and clinical environments but was found to be invalid in wrist arthroscopy. The Basic Arthroscopic Knee Skill Scoring System was validated by 15 articles for a total of 497 surgeons for knee, hip, and shoulder in both clinical and simulated environments. The remaining 9 GRS were validated by 2 or fewer studies. CONCLUSIONS: Overall, GRS have contributed to training, feedback, and formative assessment practices. The GRS reviewed demonstrate both construct and concurrent validity as well as reliability in multiple arthroscopic procedures in multiple joints. Currently, there is sufficient evidence to use GRS as a feedback tool. However, there is insufficient evidence for its use in high-stakes examinations or as a minimum competency assessment. LEVEL OF EVIDENCE: Level III, systematic review of level I to III studies.

Insecurity about getting old: age-contingent self-worth, attentional bias, and well-being.

Objectives: Older adulthood has often been recognized as a time of increased well-being and positive cognitive biases. However, older adults can also experience many social and identity challenges. We sought to investigate which older adults might be most vulnerable to these difficulties. We propose that to the extent an older adult has age-related contingent self-esteem they will be at risk for lower well-being and negative attentional biases.Methods: Across three studies, we measured older adults' self-reported aging self-worth contingencies, as well as various measures of well-being including subjective stress. We then had participants complete a cued-dot probe task, where each trial either began with an aging threat or not.Results: In an initial pilot study, we found that older adults reporting specific cognitive decline contingencies held an attentional bias toward rejection, primarily when cued with the word senile. In Study 1, we found general aging contingencies to be associated with lower well-being and a rejection bias when cued with old. In Study 2, we found that a stronger rejection bias, particularly when cued with old, was associated with greater stress.Conclusions: These findings demonstrate that older adults who are insecure about aging may have lower well-being and negatively biased social cognitive patterns. Negatively biased attentional patterns may play a key role in maintaining feelings of insecurity. Importantly, our research sheds light on those older adults who may not experience a positivity effect.

A review of interactions between peripheral and foveal vision.

Visual processing varies dramatically across the visual field. These differences start in the retina and continue all the way to the visual cortex. Despite these differences in processing, the perceptual experience of humans is remarkably stable and continuous across the visual field. Research in the last decade has shown that processing in peripheral and foveal vision is not independent, but is more directly connected than previously thought. We address three core questions on how peripheral and foveal vision interact, and review recent findings on potentially related phenomena that could provide answers to these questions. First, how is the processing of peripheral and foveal signals related during fixation? Peripheral signals seem to be processed in foveal retinotopic areas to facilitate peripheral object recognition, and foveal information seems to be extrapolated toward the periphery to generate a homogeneous representation of the environment. Second, how are peripheral and foveal signals re-calibrated? Transsaccadic changes in object features lead to a reduction in the discrepancy between peripheral and foveal appearance. Third, how is peripheral and foveal information stitched together across saccades? Peripheral and foveal signals are integrated across saccadic eye movements to average percepts and to reduce uncertainty. Together, these findings illustrate that peripheral and foveal processing are closely connected, mastering the compromise between a large peripheral visual field and high resolution at the fovea.

Stronger saccadic suppression of displacement and blanking effect in children.

Humans do not notice small displacements to objects that occur during saccades, termed saccadic suppression of displacement (SSD), and this effect is reduced when a blank is introduced between the pre- and postsaccadic stimulus (Bridgeman, Hendry, & Stark, 1975; Deubel, Schneider, & Bridgeman, 1996). While these effects have been studied extensively in adults, it is unclear how these phenomena are characterized in children. A potentially related mechanism, saccadic suppression of contrast sensitivity-a prerequisite to achieve a stable percept-is stronger for children (Bruno, Brambati, Perani, & Morrone, 2006). However, the evidence for how transsaccadic stimulus displacements may be suppressed or integrated is mixed. While they can integrate basic visual feature information from an early age, they cannot integrate multisensory information (Gori, Viva, Sandini, & Burr, 2008; Nardini, Jones, Bedford, & Braddick, 2008), suggesting a failure in the ability to integrate more complex sensory information. We tested children 7 to 12 years old and adults 19 to 23 years old on their ability to perceive intrasaccadic stimulus displacements, with and without a postsaccadic blank. Results showed that children had stronger SSD than adults and a larger blanking effect. Children also had larger undershoots and more variability in their initial saccade endpoints, indicating greater intrinsic uncertainty, and they were faster in executing corrective saccades to account for these errors. Together, these results suggest that children may have a greater internal expectation or prediction of saccade error than adults; thus, the stronger SSD in children may be due to higher intrinsic uncertainty in target localization or saccade execution.

Transsaccadic integration benefits are not limited to the saccade target.

Across saccades, humans can integrate the low-resolution presaccadic information of an upcoming saccade target with the high-resolution postsaccadic information. There is converging evidence to suggest that transsaccadic integration occurs at the saccade target. However, given divergent evidence on the spatial specificity of related mechanisms such as attention, visual working memory, and remapping, it is unclear whether integration is also possible at locations other than the saccade target. We tested the spatial profile of transsaccadic integration, by testing perceptual performance at six locations around the saccade target and between the saccade target and initial fixation. Results show that integration benefits do not differ between the saccade target and surrounding locations. Transsaccadic integration benefits are not specific to the saccade target and can occur at other locations when they are behaviorally relevant, although there is a trend for worse performance for the location above initial fixation compared with those in the direction of the saccade. This suggests that transsaccadic integration may be a more general mechanism used to reconcile task-relevant pre- and postsaccadic information at attended locations other than the saccade target.NEW & NOTEWORTHY This study shows that integration of pre- and postsaccadic information across saccades is not restricted to the saccade target. We found performance benefits of transsaccadic integration at attended locations other than the saccade target, and these benefits did not differ from those found at the saccade target. This suggests that transsaccadic integration may be a more general mechanism used to reconcile pre- and postsaccadic information at task-relevant locations.

Transsaccadic integration is dominated by early, independent noise.

Humans are able to integrate pre- and postsaccadic percepts of an object across saccades to maintain perceptual stability. Previous studies have used Maximum Likelihood Estimation (MLE) to determine that integration occurs in a near-optimal manner. Here, we compared three different models to investigate the mechanism of integration in more detail: an early noise model, where noise is added to the pre- and postsaccadic signals before integration occurs; a late-noise model, where noise is added to the integrated signal after integration occurs; and a temporal summation model, where integration benefits arise from the longer transsaccadic presentation duration compared to pre- and postsaccadic presentation only. We also measured spatiotemporal aspects of integration to determine whether integration can occur for very brief stimulus durations, across two hemifields, and in spatiotopic and retinotopic coordinates. Pre-, post-, and transsaccadic performance was measured at different stimulus presentation durations, both at the saccade target and a location where the pre- and postsaccadic stimuli were presented in different hemifields across the saccade. Results showed that for both within- and between-hemifields conditions, integration could occur when pre- and postsaccadic stimuli were presented only briefly, and that the pattern of integration followed an early noise model. Whereas integration occurred when the pre- and post-saccadic stimuli were presented in the same spatiotopic coordinates, there was no integration when they were presented in the same retinotopic coordinates. This contrast suggests that transsaccadic integration is limited by early, independent, sensory noise acting separately on pre- and postsaccadic signals.

The spatial and temporal properties of attentional selectivity for saccades and reaches.

The preparation and execution of saccades and goal-directed movements elicits an accompanying shift in attention at the locus of the impending movement. However, some key aspects of the spatiotemporal profile of this attentional shift between eye and hand movements are not resolved. While there is evidence that attention is improved at the target location when making a reach, it is not clear how attention shifts over space and time around the movement target as a saccade and a reach are made to that target. Determining this spread of attention is an important aspect in understanding how attentional resources are used in relation to movement planning and guidance in real world tasks. We compared performance on a perceptual discrimination paradigm during a saccade-alone task, reach-alone task, and a saccade-plus-reach task to map the temporal profile of the premotor attentional shift at the goal of the movement and at three surrounding locations. We measured performance relative to a valid baseline level to determine whether motor planning induces additional attentional facilitation compared to mere covert attention. Sensitivity increased relative to movement onset at the target and at the surrounding locations, for both the saccade-alone and saccade-plus-reach conditions. The results suggest that the temporal profile of the attentional shift is similar for the two tasks involving saccades (saccade-alone and saccade-plus-reach tasks), but is very different when the influence of the saccade is removed. In this case, performance in the saccade-plus-reach task reflects the lower sensitivity observed when a reach-alone task is being conducted. In addition, the spatial profile of this spread of attention is not symmetrical around the target. This suggests that when a saccade and reach are being planned together, the saccade drives the attentional shift, and the reach-alone carries little attentional weight.

The spatiotemporal characteristics of the attentional shift relative to a reach.

While the attentional shift preceding a saccadic eye movement has been well documented, the mechanisms surrounding the attentional shift preceding a reach are not well understood. It is unknown whether these mechanisms may be the same as those used in perceptual tasks, or those used in the planning of a saccade. We mapped the spatiotemporal properties of attention relative to a reach to determine the time course of attentional facilitation for hand movements alone. Participants had to reach toward a target and during the reach a perceptual probe could appear at one of six locations around the target, and at nine temporal offsets relative to the cue. Results showed a consistent pattern of facilitation in the planning stages of the reach, with attention increasing and then reaching a plateau during the completion of the movement before dropping off. These results demonstrate that planning a hand movement necessitates a shift in attention across the visual field around 150 ms before the onset of a reach. While these results are broadly consistent with the results of experiments mapping attentional shifts for saccades, the spatiotemporal profile of facilitation found shows that reaching without a concurrent eye movement also causes shifts in attention across the visual field. These results also suggest that the profile of the attentional shift preceding and during a hand movement is different at different locations across the visual field.

Latent structure and measurement invariance of the Depression Self-Rating Scale for Children across sex and age.

Measurement tools from which valid interpretations can be made are critical for assessing early emerging depressive symptoms, as depressive symptoms in childhood are associated with increased risk for early-onset depressive disorder, recurrence, suicidality, and other psychopathology. The Depression Self-Rating Scale for Children (DSRS) is a widely used self-report scale assessing youth depressive symptoms. The relatively few studies investigating the DSRS' latent structure have yielded mixed results, and measurement invariance (MI) based on sex and age has not been examined. We examined the factor structure and MI of the DSRS across sex and age in a community sample of 6-9-year-olds (N = 352; Mage = 7.57 years, SD = .70). Consistent with the largest prior structural study of the DSRS, a two-factor structure, with factors reflecting elevated negative affect (NA) and low positive affect (PA), showed strong model fit. Although this structure was consistent across sex and age (i.e., configural invariance), loadings of DSRS items varied across sex and age (i.e., metric noninvariance). Allowing the loadings of items contributing to noninvariance to vary across groups improved model fit. Implications for the clinical and research utility of the DSRS and suggestions for future research are discussed. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A genome-wide cytotoxicity screen of cluster F1 mycobacteriophage Girr reveals novel inhibitors of Mycobacterium smegmatis growth.

Over the past decade, thousands of bacteriophage genomes have been sequenced and annotated. A striking observation from this work is that known structural features and functions cannot be assigned for >65% of the encoded proteins. One approach to begin experimentally elucidating the function of these uncharacterized gene products is genome-wide screening to identify phage genes that confer phenotypes of interest like inhibition of host growth. This study describes the results of a screen evaluating the effects of overexpressing each gene encoded by the temperate Cluster F1 mycobacteriophage Girr on the growth of the host bacterium Mycobacterium smegmatis. Overexpression of 29 of the 102 Girr genes (~28% of the genome) resulted in mild to severe cytotoxicity. Of the 29 toxic genes described, 12 have no known function and are predominately small proteins of <125 amino acids. Overexpression of the majority of these 12 cytotoxic no known functions proteins resulted in moderate to severe growth reduction and represent novel antimicrobial products. The remaining 17 toxic genes have predicted functions, encoding products involved in phage structure, DNA replication/modification, DNA binding/gene regulation, or other enzymatic activity. Comparison of this dataset with prior genome-wide cytotoxicity screens of mycobacteriophages Waterfoul and Hammy reveals some common functional themes, though several of the predicted Girr functions associated with cytotoxicity in our report, including genes involved in lysogeny, have not been described previously. This study, completed as part of the HHMI-supported SEA-GENES project, highlights the power of parallel, genome-wide overexpression screens to identify novel interactions between phages and their hosts.

Critical assessment of the spectroscopic activity assay for monitoring trypsin activity in organic-aqueous solvent.

Solvent-assisted protein digestion involves enzymatic hydrolysis in mixed aqueous-organic solvents. With trypsin, acetonitrile is the modifying solvent of choice, recommended at concentrations from 10 to 80% to improve protein sequence coverage in mass spectrometry. Spectroscopic activity assays employing substrate mimics such as N-benzoyl arginine ethyl ester (BAEE) appear to show a relative enhancement of trypsin activity in mixed solvent systems. However, as reported here, the changing solvent polarity induces bias in the absorbance measurement, lending upward of 35% error in the apparent trypsin activity as the acetonitrile is raised to 70%. Furthermore, time-dependent spectroscopic and mass spectrometric measurements reveal a progressive deactivation of trypsin over a 5- to 10-min period in as little as 30% acetonitrile.

The eyes anticipate where objects will move based on their shape.

Imagine staring into a clear river, starving, desperately searching for a fish to spear and cook. You see a dark shape lurking beneath the surface. It doesn't resemble any sort of fish you've encountered before - but you're hungry. To catch it, you need to anticipate which way it will move when you lunge for it, to compensate for your own sensory and motor processing delays1,2,3. Yet you know nothing about the behaviour of this creature, and do not know in which direction it will try to escape. What cues do you then use to drive such anticipatory responses? Fortunately, many species4, including humans, have the remarkable ability to predict the directionality of objects based on their shape - even if they are unfamiliar and so we cannot rely on semantic knowledge about their movements5. While it is known that such directional inferences can guide attention5, we do not yet fully understand how such causal inferences are made, or the extent to which they enable anticipatory behaviours. Does the oculomotor system, which moves our eyes to optimise visual input, use directional inferences from shape to anticipate upcoming motion direction? Such anticipation is necessary to stabilise the moving object on the high-resolution fovea of the retina while tracking the shape, a primary goal of the oculomotor system6, and to guide any future interactions7,8. Here, we leveraged a well-known behaviour of the oculomotor system: anticipatory smooth eye movements (ASEM), where an increase in eye velocity is observed in the direction of a stimulus' expected motion, before the stimulus actually moves3, to show that the oculomotor system extracts directional information from shape, and uses this inference to predict and anticipate upcoming motion.