ALBERT

Description: When children grow up, the first word or first step in walking is always a significant event [...]

Description: To build a representation of what we see, the human brain recruits regions throughout the visual cortex in cascading sequence. Recently, an approach was proposed to evaluate the dynamics of visual perception in high spatiotemporal resolution at the scale of the whole brain. This method combined functional magnetic resonance imaging (fMRI) data with magnetoencephalography (MEG) data using representational similarity analysis and revealed a hierarchical progression from primary visual cortex through the dorsal and ventral streams. To assess the replicability of this method, we here present the results of a visual recognition neuro-imaging fusion experiment and compare them within and across experimental settings. We evaluated the reliability of this method by assessing the consistency of the results under similar test conditions, showing high agreement within participants. We then generalized these results to a separate group of individuals and visual input by comparing them to the fMRI-MEG fusion data of Cichy et al (2016), revealing a highly similar temporal progression recruiting both the dorsal and ventral streams. Together these results are a testament to the reproducibility of the fMRI-MEG fusion approach and allows for the interpretation of these spatiotemporal dynamic in a broader context.

Description: An inhibitory aftermath of orienting, inhibition of return (IOR), has intrigued scholars since its discovery about 40 years ago. Since then, the phenomenon has been subjected to a wide range of neuroscientific methods and the results of these are reviewed in this paper. These include direct manipulations of brain structures (which occur naturally in brain damage and disease or experimentally as in TMS and lesion studies) and measurements of brain activity (in humans using EEG and fMRI and in animals using single unit recording). A variety of less direct methods (e.g., computational modeling, developmental studies, etc.) have also been used. The findings from this wide range of methods support the critical role of subcortical and cortical oculomotor pathways in the generation and nature of IOR.

Description: Current evidence supports the view that the visual pulvinar of primates consists of at least five nuclei, with two large nuclei, lateral pulvinar ventrolateral (PLvl) and central lateral nucleus of the inferior pulvinar (PIcl), contributing mainly to the ventral stream of cortical processing for perception, and three smaller nuclei, posterior nucleus of the inferior pulvinar (PIp), medial nucleus of the inferior pulvinar (PIm), and central medial nucleus of the inferior pulvinar (PIcm), projecting to dorsal stream visual areas for visually directed actions. In primates, both cortical streams are highly dependent on visual information distributed from primary visual cortex (V1). This area is so vital to vision that patients with V1 lesions are considered “cortically blind”. When the V1 inputs to dorsal stream area middle temporal visual area (MT) are absent, other dorsal stream areas receive visual information relayed from the superior colliculus via PIp and PIcm, thereby preserving some dorsal stream functions, a phenomenon called “blind sight”. Non-primate mammals do not have a dorsal stream area MT with V1 inputs, but superior colliculus inputs to temporal cortex can be more significant and more visual functions are preserved when V1 input is disrupted. The current review will discuss how the different visual streams, especially the dorsal stream, have changed during primate evolution and we propose which features are retained from the common ancestor of primates and their close relatives.

Description: The sources of the reduced fixation stability exhibited by patients with central vision loss in the light are relatively well understood, but we have no information on how they control eye position in complete darkness, in the absence of visual error signals. We therefore explored the effect of visual feedback on eye position stability by testing patients with age-related macular degeneration (AMD) and controls with normal vision in the light and in complete darkness. Nine patients (ages 67 to 92 years) and 16 controls (ages 16 to 74 years) were tested binocularly in the light and in complete darkness while remembering the location of a now invisible target. Binocular eye position was recorded with a video-based eye tracker. Results show that eye position stability both in the light and in the dark is worse for patients than for controls and that, for the two groups, eye position stability in the dark is, on average, 5.9 times worse than in the light. Large instability of fixation in patients with AMD was found even in absolute darkness when the scotoma cannot impair vision. These data reflect permanent changes in the oculomotor reference of patients with AMD.

Description: In this paper, a range of open-source tools, datasets, and software that have been developed for quantitative and in-depth evaluation of eye gaze data quality are presented. Eye tracking systems in contemporary vision research and applications face major challenges due to variable operating conditions such as user distance, head pose, and movements of the eye tracker platform. However, there is a lack of open-source tools and datasets that could be used for quantitatively evaluating an eye tracker’s data quality, comparing performance of multiple trackers, or studying the impact of various operating conditions on a tracker’s accuracy. To address these issues, an open-source code repository named GazeVisual-Lib is developed that contains a number of algorithms, visualizations, and software tools for detailed and quantitative analysis of an eye tracker’s performance and data quality. In addition, a new labelled eye gaze dataset that is collected from multiple user platforms and operating conditions is presented in an open data repository for benchmark comparison of gaze data from different eye tracking systems. The paper presents the concept, development, and organization of these two repositories that are envisioned to improve the performance analysis and reliability of eye tracking systems.

Description: The horizontal raphe (HR) as a demarcation line dividing the retina and choroid into separate vascular hemispheres is well established, but its development has never been discussed in the context of new findings of the last decades. Although factors for axon guidance are established (e.g., slit-robo pathway, ephrin-protein-receptor pathway) they do not explain HR formation. Early morphological organization, too, fails to establish a HR. The development of the HR is most likely induced by the long posterior ciliary arteries which form a horizontal line prior to retinal organization. The maintenance might then be supported by several biochemical factors. The circulation separate superior and inferior vascular hemispheres communicates across the HR only through their anastomosing capillary beds resulting in watershed zones on either side of the HR. Visual field changes along the HR could clearly be demonstrated in vascular occlusive diseases affecting the optic nerve head, the retina or the choroid. The watershed zone of the HR is ideally protective for central visual acuity in vascular occlusive diseases but can lead to distinct pathological features.

Description: The seminal model by Laurent Itti and Cristoph Koch demonstrated that we can compute the entire flow of visual processing from input to resulting fixations. Despite many replications and follow-ups, few have matched the impact of the original model—so what made this model so groundbreaking? We have selected five key contributions that distinguish the original salience model by Itti and Koch; namely, its contribution to our theoretical, neural, and computational understanding of visual processing, as well as the spatial and temporal predictions for fixation distributions. During the last 20 years, advances in the field have brought up various techniques and approaches to salience modelling, many of which tried to improve or add to the initial Itti and Koch model. One of the most recent trends has been to adopt the computational power of deep learning neural networks; however, this has also shifted their primary focus to spatial classification. We present a review of recent approaches to modelling salience, starting from direct variations of the Itti and Koch salience model to sophisticated deep-learning architectures, and discuss the models from the point of view of their contribution to computational cognitive neuroscience.

Description: Purpose: To access retinal straylight in a Brazilian sample and to compare it with European norms. Methods: Absolute Straylight was assessed using C-Quant that uses an adaptive staircase based on a 2-Alternated Forced Choice task. A young (22.2 ± 2.4 yrs, n = 20) and an old group (53.8 ± 7.4 yrs, n = 21) of subjects were tested. All refractive errors were corrected in the C-Quant device, and no subjects had ocular diseases or vision-threatening conditions (e.g., diabetes, unregulated blood pressure, high intraocular pressure, visible cataract). Eighty-five percent of all subjects in each age group had dark-pigmented eyes. Each eye was tested 3 times, yielding 6 straylight values (s). Only data fulfilling C-Quant reliability criteria were included. Results: There were no statistical differences between the three attempts on each eye (ANOVA, F = 0.993, p 〉 0.936) and between the two groups (ANOVA, F = 0.893, p 〉 0.725). Straylight values (s) were fit with an empirical equation to compare to European norms. There were no statistical differences between Brazilian straylight values and European norms for either young or old age groups (ANOVA, F = 5.114, p 〉 0.993). However, there was a tendency for our s values to be higher than the European norms, consistent with young Brazilian eyes having more light-scattering than age-matched European eyes. Conclusions: Consistent with European norms, light-scattering increases with age in the Brazilian sample. This increase is thought to be due, in large part, to age-related changes in lens structure and density. Although the differences between the populations are not significant, the tendency for Brazilian data to have higher s values than European values, especially at young subjects, is in the opposite direction from that expected from a dark-eyed population. This suggests the hypothesis that latitude-dependent (Sao Paulo, latitude 23° S, European latitudes between 40° N to 55° N) differences in the light environment could be associated with differences in s values.

Description: Rigorous peer-review is the corner-stone of high-quality academic publishing [...]

Description: Existing research has found that spatial attention alters how various stimulus properties are perceived (e.g., luminance, saturation), but few have explored whether it improves the accuracy of perception. To address this question, we performed two experiments using modified Posner cueing tasks, wherein participants made speeded detection responses to peripheral colour targets and then indicated their perceived colours on a colour wheel. In E1, cues were central and endogenous (i.e., prompted voluntary attention) and the interval between cues and targets (stimulus onset asynchrony, or SOA) was always 800 ms. In E2, cues were peripheral and exogenous (i.e., captured attention involuntarily) and the SOA varied between short (100 ms) and long (800 ms). A Bayesian mixed-model analysis was used to isolate the effects of attention on the probability and the fidelity of colour encoding. Both endogenous and short-SOA exogenous spatial cueing improved the probability of encoding the colour of targets. Improved fidelity of encoding was observed in the endogenous but not in the exogenous cueing paradigm. With exogenous cues, inhibition of return (IOR) was observed in both RT and probability at the long SOA. Overall, our findings reinforce the utility of continuous response variables in the research of attention.

Description: The key determinants of the range of clear focus in pre-presbyopes and their relative contributions to the difference between subjective range of focus and objective accommodation assessments have not been previously quantified. Fifty participants (aged 33.0 ± 6.4 years) underwent simultaneous monocular subjective (visual acuity measured with an electronic test-chart) and objective (dynamic accommodation measured with an Aston open-field aberrometer) defocus curve testing for lenses between +2.00 to -10.00 DS in +0.50 DS steps in a randomized order. Pupil diameter and ocular aberrations (converted to visual metrics normalized for pupil size) at each level of blur were measured. The difference between objective range over which the power of the crystalline lens changes and the subjective range of clear focus was quantified and the results modelled using pupil size, refractive error, tolerance to blur, and ocular aberrations. The subjective range of clear focus was principally accounted for by age (46.4%) and pupil size (19.3%). The objectively assessed accommodative range was also principally accounted for by age (27.6%) and pupil size (15.4%). Over one-quarter (26.0%) of the difference between objective accommodation and subjective range of clear focus was accounted for by age (14.0%) and spherical aberration at maximum accommodation (12.0%). There was no significant change in the objective accommodative response (F=1.426, p=0.229) or pupil size (F=0.799, p=0.554) of participants for levels of defocus above their amplitude of accommodation. Pre-presbyopes benefit from an increased subjective range of clear vision beyond their objective accommodation due in part to neural factors, resulting in a measured depth-of-focus of, on average, 1.0D.

Description: Ocular equivocation was the term given by Brewster in 1844 to binocular contour rivalry seen with Wheatstone’s stereoscope. The rivalries between Wheatstone and Brewster were personal as well as perceptual. In the 1830s, both Wheatstone and Brewster came to stereoscopic vision armed with their individual histories of research on vision. Brewster was an authority on physical optics and had devised the kaleidoscope; Wheatstone extended his research on audition to render acoustic patterns visible with his kaleidophone or phonic kaleidoscope. Both had written on subjective visual phenomena, a topic upon which they first clashed at the inaugural meeting of the British Association for the Advancement of Science in 1832 (the year Wheatstone made the first stereoscopes). Wheatstone published his account of the mirror stereoscope in 1838; Brewster’s initial reception of it was glowing but he later questioned Wheatstone’s priority. They both described investigations of binocular contour rivalry but their interpretations diverged. As was the case for stereoscopic vision, Wheatstone argued for central processing whereas Brewster’s analysis was peripheral and based on visible direction. Brewster’s lenticular stereoscope and binocular camera were described in 1849. They later clashed over Brewster’s claim that the Chimenti drawings were made for a 16th-century stereoscope. The rivalry between Wheatstone and Brewster is illustrated with anaglyphs that can be viewed with red/cyan glasses and in Universal Freeview format; they include rivalling ‘perceptual portraits’ as well as examples of the stimuli used to study ocular equivocation.

Description: A brief tribute to Bela Julesz (1928–2003) is made in words and images. In addition to a conventional stereophotographic portrait, his major contributions to vision research are commemorated by two ‘perceptual portraits’, which try to capture the spirit of his main accomplishments in stereopsis and the perception of texture.

Description: Decisions about where to fixate are highly variable and often inefficient. In the current study, we investigated whether such decisions would improve with increased motivation. Participants had to detect a discrimination target, which would appear in one of two boxes, but only after they chose a location to fixate. The distance between boxes determines which location to fixate to maximise the probability of being able to see the target: participants should fixate between the two boxes when they are close together, and on one of the two boxes when they are far apart. We “gamified” this task, giving participants easy-to-track rewards that were contingent on discrimination accuracy. Their decisions and performance were compared to previous results that were gathered in the absence of this additional motivation. We used a Bayesian beta regression model to estimate the size of the effect and associated variance. The results demonstrate that discrimination accuracy does indeed improve in the presence of performance-related rewards. However, there was no difference in eye movement strategy between the two groups, suggesting this improvement in accuracy was not due to the participants making more optimal eye movement decisions. Instead, the motivation encouraged participants to expend more effort on other aspects of the task, such as paying more attention to the boxes and making fewer response errors.

Description: Perception of a complex visual scene requires that important regions be prioritized and attentionally selected for processing. What is the basis for this selection? Although much research has focused on image salience as an important factor guiding attention, relatively little work has focused on semantic salience. To address this imbalance, we have recently developed a new method for measuring, representing, and evaluating the role of meaning in scenes. In this method, the spatial distribution of semantic features in a scene is represented as a meaning map. Meaning maps are generated from crowd-sourced responses given by naïve subjects who rate the meaningfulness of a large number of scene patches drawn from each scene. Meaning maps are coded in the same format as traditional image saliency maps, and therefore both types of maps can be directly evaluated against each other and against maps of the spatial distribution of attention derived from viewers’ eye fixations. In this review we describe our work focusing on comparing the influences of meaning and image salience on attentional guidance in real-world scenes across a variety of viewing tasks that we have investigated, including memorization, aesthetic judgment, scene description, and saliency search and judgment. Overall, we have found that both meaning and salience predict the spatial distribution of attention in a scene, but that when the correlation between meaning and salience is statistically controlled, only meaning uniquely accounts for variance in attention.

Description: The use of eye movements to explore scene processing has exploded over the last decade. Eye movements provide distinct advantages when examining scene processing because they are both fast and spatially measurable. By using eye movements, researchers have investigated many questions about scene processing. Our review will focus on research performed in the last decade examining: (1) attention and eye movements; (2) where you look; (3) influence of task; (4) memory and scene representations; and (5) dynamic scenes and eye movements. Although typically addressed as separate issues, we argue that these distinctions are now holding back research progress. Instead, it is time to examine the intersections of these seemingly separate influences and examine the intersectionality of how these influences interact to more completely understand what eye movements can tell us about scene processing.

Description: This paper reconstructs the “Arnheim’s puzzle” over the psychology of art. It is argued that the long-established psychological theories of art do not account properly for the observable variability of art, which provide the phenomena of interest whose psychological factors need to be discovered. The general purpose principles of such theories, the ensuing selective sample of art phenomena, and assumption of conventional properties of aesthetic experience make the predictions and the findings of the theories unrepresentative of art. From the discussion of examples drawn from contemporary visual arts and the presentation of the debate on the emergence of the cognitive capacities of art in paleoanthropology, a construct is presented on the specificity of the cognitive capacities of art and its anchoring to perception, which solves the puzzle and has implications for research and teaching psychology of art.

Description: The binocular viewing of a fronto-parallel pendulum with a reduced luminance in one eye results in the illusory tridimensional percept of the pendulum following an elliptical orbit in depth, the so-called Pulfrich phenomenon. A small percentage of mild anisometropic amblyopes who have rudimentary stereo are known to experience a spontaneous Pulfrich phenomenon, which posits a delay in the cortical processing of information involving their amblyopic eye. The purpose of this study is to characterize this spontaneous Pulfrich phenomenon in the mild amblyopic population. In order to assess this posited delay, we used a paradigm where a cylinder rotating in depth, defined by moving Gabor patches at different disparities (i.e., at different interocular phases), generates a strong to ambiguous depth percept. This paradigm allows one to accurately measure a spontaneous Pulfrich phenomenon and to determine how it depends on the spatio-temporal properties of stimulus. We observed a spontaneous Pulfrich phenomenon in anisometropic, strabismic, and mixed amblyopia, which is posited to be due to an interocular delay associated with amblyopic processing. Surprisingly, the posited delay was not always observed in the amblyopic eye, was not a consequence of the reduced contrast sensitivity of the amblyopic eye, and displayed a large variability across amblyopic observers. Increasing the density, decreasing the spatial frequency, or increasing the speed of the stimulus tended to reduce the observed delay. The spontaneous Pulfrich phenomenon seen by some amblyopes was variable and depended on the spatio-temporal properties of the stimulus. We suggest it could involve two conflicting components: an amblyopic delay and a blur-based acceleration.

Description: We investigated contrast processing in relation to visual comfort from coloured light in individuals with migraine. In Experiment 1, 24 individuals who experienced migraine with aura (MA), 15 migraine without aura (MO), and 23 healthy controls, identified which of four patterns, one in each quadrant, had the greatest contrast. Although there were no significant differences between groups, contrast discrimination was superior in the visual field affected by aura in all eight participants in whom the aura was consistently lateralised. In Experiment 2, 20 participants without aura and 20 controls selected comfortable light with a chromaticity close to the daylight (Planckian) locus, whilst 20 individuals with aura chose more strongly saturated colours, mostly distant from the locus. In Experiment 3, nine participants with consistently unilateral aura undertook the contrast discrimination task wearing (a) lenses that provided a comfortable colour of light and (b) grey lenses of similar transmission. With grey lenses, seven of the nine individuals with unilateral aura showed a superior performance in the affected field, as before. With lenses providing a comfortable colour, however, the performance was relatively poor for the nine individuals with unilateral aura, but not for the 10 controls. This was the case in both visual fields. The cortical hyper-responsiveness with which migraine is associated may improve the perception of contrast. The perception is poorer (and more normal) with ophthalmic lenses having a comfortable colour.

Description: Attention is a process that alters how cognitive resources are allocated, and it allows individuals to efficiently process information at the attended location. The presence of visual or auditory cues in the environment can direct the focus of attention toward certain stimuli even if the cued stimuli are not the individual’s primary target. Samson et al. demonstrated that seeing another person in the scene (i.e., a person-like cue) caused a delay in responding to target stimuli not visible to that person: “alter-centric intrusion.” This phenomenon, they argue, is dependent upon the fact that the cue used resembled a person as opposed to a more generic directional indicator. The characteristics of the cue are the core of the debate of this special issue. Some maintain that the perceptual-directional characteristics of the cue are sufficient to generate the bias while others argue that the cuing is stronger when the cue has social characteristics (relates to what another individual can perceive). The research contained in this issue confirms that human attention is biased by the presence of a directional cue. We discuss and compare the different studies. The pattern that emerges seems to suggest that the social relevance of the cue is necessary in some contexts but not in others, depending on the cognitive demand of the experimental task. One possibility is that the social mechanisms are involved in perspective taking when the task is cognitively demanding, while they may not play a role in automatic attention allocation.

Description: Currently there are several computational models of eye movement control that provide a good account of oculomotor behavior during reading of English and other alphabetic languages. I will provide an overview of two dominant models: E-Z Reader and SWIFT, as well as a recently proposed model: OB1-Reader. I will evaluate a critical issue of controversy among models, namely, whether words are lexically processed serially or in parallel. I will then consider reading in Chinese, a character-based, unspaced language with ambiguous word boundaries. Finally, I will evaluate the concepts of serialism and parallelism of process central to these models, and how these models might function in relation to lexical processing that is operationalized over parafoveal multi-constituent units.

Description: Visual tests can be used as noninvasive tools to test models of the pathophysiology underlying neurological conditions, such as migraine. They may also be used to track changes in performance that vary with the migraine cycle or can track the efficacy of prophylactic treatments. This article reviews the literature on performance differences on two visual tasks, global motion discrimination and orientation, which, of the many visual tasks that have been used to compare differences between migraine and control groups, have yielded the most consistent patterns of group differences. The implications for understanding the underlying pathophysiology in migraine are discussed, but the main focus is on bringing together disparate areas of research and suggesting those that can reveal practical uses of visual tests to treat and manage migraine.

Description: We review all published eye-tracking studies to date that have used eye movements to examine multiple object (MOT) or multiple identity tracking (MIT). In both tasks, observers dynamically track multiple moving objects. In MOT the objects are identical, whereas in MIT they have distinct identities. In MOT, observers prefer to fixate on blank space, which is often the center of gravity formed by the moving targets (centroid). In contrast, in MIT observers have a strong preference for the target-switching strategy, presumably to refresh and maintain identity-location bindings for the targets. To account for the qualitative differences between MOT and MIT, two mechanisms have been posited, a position tracking (MOT) and an identity tracking (MOT & MIT) mechanism. Eye-tracking studies of MOT have also demonstrated that observers execute rescue saccades toward targets in danger of becoming occluded or are about to change direction after a collision. Crowding attracts the eyes close to it in order to increase visual acuity for the crowded objects to prevent target loss. It is suggested that future studies should concentrate more on MIT, as MIT more closely resembles tracking in the real world.

Description: Pulvino-cortical (PC) projections are a major source of extrinsic input to early visual areas in the macaque. From bulk injections of anterograde tracers, these are known to terminate in layer 1 of V1 and densely in the middle cortical layers of extrastriate areas. Finer, single axon analysis, as reviewed here for projections from the lateral pulvinar (PL) in two macaque monkeys (n = 25 axons), demonstrates that PL axons have multiple arbors in V2 and V4, and that these are spatially separate and offset in different layers. In contrast, feedforward cortical axons, another major source of extrinsic input to extrastriate areas, are less spatially divergent and more typically terminate in layer 4. Functional implications are briefly discussed, including comparisons with the better investigated rodent brain.

Description: In motor imagery (MI), internal models may predict the action effects. A mismatch between predicted and intended action effects may result in error detection. To compare error detection in MI and motor execution (ME), ten-finger typists and hunt-and-peck typists performed a copy-typing task. Visibility of the screen and visibility of the keyboard were manipulated. Participants reported what type of error occurred and by which sources they detected the error. With covered screen, fewer errors were reported, showing the importance of distal action effects for error detection. With covered screen, the number of reported higher-order planning errors did not significantly differ between MI and ME. However, the number of reported motor command errors was lower in MI than in ME. Hence, only errors that occur in advance to internal modeling are equally observed in MI and ME. MI may require more attention than ME, leaving fewer resources to monitor motor command errors in MI. In comparison to hunt-and-peck typists, ten-finger typists detected more higher-order planning errors by kinesthesis/touch and fewer motor command errors by vision of the keyboard. The use of sources for error detection did not significantly differ between MI and ME, indicating similar mechanisms.

Description: Change blindness is a striking shortcoming of our visual system which is exploited in the popular `Spot the difference’ game, as it makes us unable to notice large visual changes happening right before our eyes. Change blindness illustrates the fact that we see much less than we think we do. In this paper, we introduce a fully automated model to predict colour change blindness in cartoon images based on image complexity, change magnitude and observer experience. Using linear regression with only three parameters, the predictions of the proposed model correlate significantly with measured detection times. We also demonstrate the efficacy of the model to classify stimuli in terms of difficulty.

Description: The purpose of the present study is to investigate the effect of congruence between music and paintings on the aesthetic preference of paintings. Congruence was specified as the similarity in perceived regularity and the complexity of jazz compositions and abstract paintings (the ratings of regularity and complexity in both sets of stimuli were obtained in the pilot study). In the main experiment, 32 participants rated the aesthetic pleasantness of paintings with congruent, incongruent, and no music background. In addition, they rated the music-paintings matching (how well the music goes with the painting). The results show no effect of congruence on aesthetic pleasantness ratings. The effect on the perceived matching was significant; matching is higher in the congruent compared to the incongruent condition. These findings suggest that congruency has a strong effect on the perceptual aspect of the music-paintings compatibility (visuo-auditory similarity) and no effect on the aesthetic aspect (liking).

Description: Like many predators, humans have forward-facing eyes that are set a short distance apart so that an extensive region of the visual field is seen from two different points of view. The human visual system can establish a three-dimensional (3D) percept from the projection of images into the left and right eye. How the visual system integrates local motion and binocular depth in order to accomplish 3D motion perception is still under investigation. Here, we propose a geometric-statistical model that combines noisy velocity constraints with a spherical motion prior to solve the aperture problem in 3D. In two psychophysical experiments, it is shown that instantiations of this model can explain how human observers disambiguate 3D line motion direction behind a circular aperture. We discuss the implications of our results for the processing of motion and dynamic depth in the visual system.

Description: Across saccades, small displacements of a visual target are harder to detect and their directions more difficult to discriminate than during steady fixation. Prominent theories of this effect, known as saccadic suppression of displacement, propose that it is due to a bias to assume object stability across saccades. Recent studies comparing the saccadic effect to masking effects suggest that suppression of displacement is not saccade-specific. Further evidence for this account is presented from two experiments where participants judged the size of displacements on a continuous scale in saccade and mask conditions, with and without blanking. Saccades and masks both reduced the proportion of correctly perceived displacements and increased the proportion of missed displacements. Blanking improved performance in both conditions by reducing the proportion of missed displacements. Thus, if suppression of displacement reflects a bias for stability, it is not a saccade-specific bias, but a more general stability assumption revealed under conditions of impoverished vision. Specifically, I discuss the potentially decisive role of motion or other transient signals for displacement perception. Without transients or motion, the quality of relative position signals is poor, and saccadic and mask-induced suppression of displacement reflects performance when the decision has to be made on these signals alone. Blanking may improve those position signals by providing a transient onset or a longer time to encode the pre-saccadic target position.

Description: We developed a temporal population receptive field model to differentiate the neural and hemodynamic response functions (HRF) in the human lateral geniculate nucleus (LGN). The HRF in the human LGN is dominated by the richly vascularized hilum, a structure that serves as a point of entry for blood vessels entering the LGN and supplying the substrates of central vision. The location of the hilum along the ventral surface of the LGN and the resulting gradient in the amplitude of the HRF across the extent of the LGN have made it difficult to segment the human LGN into its more interesting magnocellular and parvocellular regions that represent two distinct visual processing streams. Here, we show that an intrinsic clustering of the LGN responses to a variety of visual inputs reveals the hilum, and further, that this clustering is dominated by the amplitude of the HRF. We introduced a temporal population receptive field model that includes separate sustained and transient temporal impulse response functions that vary on a much short timescale than the HRF. When we account for the HRF amplitude, we demonstrate that this temporal response model is able to functionally segregate the residual responses according to their temporal properties.

Description: Mental imagery is the ability to generate images in the mind in the absence of sensory input. Both perceptual visual processing and internally generated imagery engage large, overlapping networks of brain regions. However, it is unclear whether they are characterized by similar temporal dynamics. Recent magnetoencephalography work has shown that object category information was decodable from brain activity during mental imagery, but the timing was delayed relative to perception. The current study builds on these findings, using electroencephalography to investigate the dynamics of mental imagery. Sixteen participants viewed two images of the Sydney Harbour Bridge and two images of Santa Claus. On each trial, they viewed a sequence of the four images and were asked to imagine one of them, which was cued retroactively by its temporal location in the sequence. Time-resolved multivariate pattern analysis was used to decode the viewed and imagined stimuli. Although category and exemplar information was decodable for viewed stimuli, there were no informative patterns of activity during mental imagery. The current findings suggest stimulus complexity, task design and individual differences may influence the ability to successfully decode imagined images. We discuss the implications of these results in the context of prior findings of mental imagery.

Description: We report two psychophysical experiments that investigate a visual illusion that is considered common knowledge among type designers, but has never been studied scientifically. Specifically, the thickness of a horizontal line is overestimated in relation to that of a vertical line. Experiment 1 confirmed the existence of the illusion. In Experiment 2, we replicated the effect and showed that the illusion is closely related to the vertical-horizontal illusion, in which the length of a vertical line is overestimated in comparison to a horizontal one. Both the overestimation of thickness and length is larger when the stimulus is surrounded by a horizontally elongated frame, as opposed to a vertically elongated frame. We discuss potential explanations for the thickness illusion and its relation to the vertical-horizontal illusion.

Description: According to theories of anticipatory behavior control, actions are initiated by predicting their sensory outcomes. From the perspective of event-predictive cognition and active inference, predictive processes activate currently desired events and event boundaries, as well as the expected sensorimotor mappings necessary to realize them, dependent on the involved predicted uncertainties before actual motor control unfolds. Accordingly, we asked whether peripersonal hand space is remapped in an uncertainty anticipating manner while grasping and placing bottles in a virtual reality (VR) setup. To investigate, we combined the crossmodal congruency paradigm with virtual object interactions in two experiments. As expected, an anticipatory crossmodal congruency effect (aCCE) at the future finger position on the bottle was detected. Moreover, a manipulation of the visuo-motor mapping of the participants’ virtual hand while approaching the bottle selectively reduced the aCCE at movement onset. Our results support theories of event-predictive, anticipatory behavior control and active inference, showing that expected uncertainties in movement control indeed influence anticipatory stimulus processing.

Description: Interocular suppression plays an important role in the visual deficits experienced by individuals with amblyopia. Most neurophysiological and functional MRI studies of suppression in amblyopia have used dichoptic stimuli that overlap within the visual field. However, suppression of the amblyopic eye also occurs when the dichoptic stimuli do not overlap, a phenomenon we refer to as long-range suppression. We used functional MRI to test the hypothesis that long-range suppression reduces neural activity in V1, V2 and V3 in adults with amblyopia, indicative of an early, active inhibition mechanism. Five adults with amblyopia and five controls viewed monocular and dichoptic quadrant stimuli during fMRI. Three of five participants with amblyopia experienced complete perceptual suppression of the quadrants presented to their amblyopic eye under dichoptic viewing. The blood oxygen level dependant (BOLD) responses within retinotopic regions corresponding to amblyopic and fellow eye stimuli were analyzed for response magnitude, time to peak, effective connectivity and stimulus classification. Dichoptic viewing slightly reduced the BOLD response magnitude in amblyopic eye retinotopic regions in V1 and reduced the time to peak response; however, the same effects were also present in the non-dominant eye of controls. Effective connectivity was unaffected by suppression, and the results of a classification analysis did not differ significantly between the control and amblyopia groups. Overall, we did not observe a neural signature of long-range amblyopic eye suppression in V1, V2 or V3 using functional MRI in this initial study. This type of suppression may involve higher level processing areas within the brain.

Description: When dissimilar images are presented to each eye, the images will alternate every few seconds in a phenomenon known as binocular rivalry. Recent research has found evidence of a bias towards one image at the initial ‘onset’ period of rivalry that varies across the peripheral visual field. To determine the role that visual field location plays in and around the fovea at onset, trained observers were presented small orthogonal achromatic grating patches at various locations across the central 3° of visual space for 1-s and 60-s intervals. Results reveal stronger bias at onset than during continuous rivalry, and evidence of temporal hemifield dominance across observers, however, the nature of the hemifield effects differed between individuals and interacted with overall eye dominance. Despite using small grating patches, a high proportion of mixed percept was still reported, with more mixed percept at onset along the vertical midline, in general, and in increasing proportions with eccentricity in the lateral hemifields. Results show that even within the foveal range, onset rivalry bias varies across visual space, and differs in degree and sensitivity to biases in average dominance over continuous viewing.

Description: Readers occasionally move their eyes to prior text. We distinguish two types of these movements (regressions). One type consists of relatively large regressions that seek to re-process prior text and to revise represented linguistic content to improve comprehension. The other consists of relatively small regressions that seek to correct inaccurate or premature oculomotor programming to improve visual word recognition. Large regressions are guided by spatial and linguistic knowledge, while small regressions appear to be exclusively guided by knowledge of spatial location. There are substantial individual differences in the use of regressions, and college-level readers often do not regress even when this would improve sentence comprehension.

Description: This paper presents a new mathematical model along with a measurement platform for accurate detection and monitoring of various visual distortions (VD) caused by macular disorders such as central serous chorioretinopathy (CSR) and age-related macular degeneration (AMD). This platform projects a series of graphical patterns on the patient’s retina and calculates the severity of VDs accordingly. The accuracy of this technique relies on the accurate detection of distorted lines by the patient. We also propose a simple mathematical model to evaluate the VD created by CSR. The model is used as a control for the test results achieved from the proposed platform. The proposed platform consists of the required hardware and software for the generation and projection of patterns along with the collection and processing of patients against their standard optical coherence tomography (OCT) images. Based on these results, the OCT images agree with the VD test results, and the proposed platform can be used as an alternative home monitoring method for various macular disorders.

Description: Processing of both a word’s orthography (its printed form) and phonology (its associated speech sounds) are critical for lexical identification during reading, both in beginning and skilled readers. Theories of learning to read typically posit a developmental change, from early readers’ reliance on phonology to more skilled readers’ development of direct orthographic-semantic links. Specifically, in becoming a skilled reader, the extent to which an individual processes phonology during lexical identification is thought to decrease. Recent data from eye movement research suggests, however, that the developmental change in phonological processing is somewhat more nuanced than this. Such studies show that phonology influences lexical identification in beginning and skilled readers in both typically and atypically developing populations. These data indicate, therefore, that the developmental change might better be characterised as a transition from overt decoding to abstract, covert recoding. We do not stop processing phonology as we become more skilled at reading; rather, the nature of that processing changes.

Description: The dynamic nature of the real world poses challenges for predicting where best to allocate gaze during object interactions. The same object may require different visual guidance depending on its current or upcoming state. Here, we explore how object properties (the material and shape of objects) and object state (whether it is full of liquid, or to be set down in a crowded location) influence visual supervision while setting objects down, which is an element of object interaction that has been relatively neglected in the literature. In a liquid pouring task, we asked participants to move empty glasses to a filling station; to leave them empty, half fill, or completely fill them with water; and then move them again to a tray. During the first putdown (when the glasses were all empty), visual guidance was determined only by the type of glass being set down—with more unwieldy champagne flutes being more likely to be guided than other types of glasses. However, when the glasses were then filled, glass type no longer mattered, with the material and fill level predicting whether the glasses were set down with visual supervision: full, glass material containers were more likely to be guided than empty, plastic ones. The key finding from this research is that the visual system responds flexibly to dynamic changes in object properties, likely based on predictions of risk associated with setting-down the object unsupervised by vision. The factors that govern these mechanisms can vary within the same object as it changes state.

Description: Two major uses of linear perspective are in planar paintings—the flat canvas is incongruent with the painted 3-D scene—and in forced perspectives, such as theater stages that are concave truncated pyramids, where the physical geometry and the depicted scene are congruent. Patrick Hughes pioneered a third major art form, the reverse perspective, where the depicted scene opposes the physical geometry. Reverse perspectives comprise solid forms composed of multiple planar surfaces (truncated pyramids and prisms) jutting toward the viewer, thus forming concave spaces between the solids. The solids are painted in reverse perspective: as an example, the left and right trapezoids of a truncated pyramid are painted as rows of houses; the bottom trapezoid is painted as the road between them and the top forms the sky. This elicits the percept of a street receding away, even though it physically juts toward the viewer. Under this illusion, the concave void spaces between the solids are transformed into convex volumes. This depth inversion creates a concomitant motion illusion: when a viewer moves in front of the art piece, the scene appears to move vividly. Two additional contributions by the artist are discussed, in which he combines reverse-perspective parts with forced and planar-perspective parts on the same art piece. The effect is spectacular, creating objects on the same planar surface that move in different directions, thus “breaking” the surface apart, demonstrating the superiority of objects over surfaces. We conclude with a discussion on the value of these art pieces in vision science.

Description: Saccadic eye movements are simple, visually guided actions. Operant conditioning of specific saccade directions can reduce the latency of eye movements in the conditioned direction. However, it is not clear to what extent this learning transfers from the conditioned task to novel tasks. The purpose of this study was to investigate whether the effects of operant conditioning of prosaccades to specific spatial locations would transfer to more complex oculomotor behaviours, specifically, prosaccades made in the presence of a distractor (Experiment 1) and antisaccades (Experiment 2). In part 1 of each experiment, participants were rewarded for making a saccade to one hemifield. In both experiments, the reward produced a significant facilitation of saccadic latency for prosaccades directed to the rewarded hemifield. In part 2, rewards were withdrawn, and the participant made a prosaccade to targets that were accompanied by a contralateral distractor (Experiment 1) or an antisaccade (Experiment 2). There were no hemifield-specific effects of the reward on saccade latency on the remote distractor effect or antisaccades, although the reward was associated with an overall slowing of saccade latency in Experiment 1. These data indicate that operant conditioning of saccadic eye movements does not transfer to similar but untrained tasks. We conclude that rewarding specific spatial locations is unlikely to induce long-term, systemic changes to the human oculomotor system.

Description: Geometric differences between the images seen by each eye enable the perception of depth. Additionally, depth is produced in the absence of geometric disparities with binocular disparities in either the average luminance or contrast, which is known as the Venetian blind effect. The temporal dynamics of the Venetian blind effect are much slower (1.3 Hz) than those for geometric binocular disparities (4–5 Hz). Sine-wave modulations of luminance and contrast disparity, however, can be discriminated from square-wave modulations at 1 Hz, which suggests a non-linearity. To measure this non-linearity, a luminance or contrast disparity modulation was presented at a particular frequency and paired with a geometric disparity modulation that cancelled the perceived rotation induced by the luminance or contrast modulation. Phases between the luminance or contrast and the geometric modulation varied in 50 ms increments from −200 and 200 ms. When phases were aligned, observers perceived little or no rotation. When not aligned, a perceived rotation was induced by a contrast or luminance disparity that was then cancelled by the geometric disparity. This causes the perception of a slight jump. The Generalized Difference Model, which is linear in time, predicted a minimal probability in cases when luminance or contrast disparities occurred before the geometric disparities due to the slower dynamics of the Venetian blind effect. The Gated Generalized Difference Model, which is non-linear in time, predicted a minimal probability for offsets of 0 ms. Results followed the Gated model, which further suggests a non-linearity in time for the Venetian blind effect.

Description: Attention is classically classified according to mode of engagement into voluntary and reflexive, and type of operation into covert and overt. The first distinguishes whether attention is elicited intentionally or by unexpected events; the second, whether attention is directed with or without eye movements. Recently, this taxonomy has been expanded to include automated orienting engaged by overlearned symbols and combined attention engaged by a combination of several modes of function. However, so far, combined effects were demonstrated in covert conditions only, and, thus, here we examined if attentional modes combined in overt responses as well. To do so, we elicited automated, voluntary, and combined orienting in covert, i.e., when participants responded manually and maintained central fixation, and overt cases, i.e., when they responded by looking. The data indicated typical effects for automated and voluntary conditions in both covert and overt data, with the magnitudes of the combined effect larger than the magnitude of each mode alone as well as their additive sum. No differences in the combined effects emerged across covert and overt conditions. As such, these results show that attentional systems combine similarly in covert and overt responses and highlight attention’s dynamic flexibility in facilitating human behavior.

Description: Illusory line motion (ILM) refers to the perception of motion in a line that is, in fact, presented in full at one time. One form of this illusion (flashILM) occurs when the line is presented between two objects following a brief luminance change in one of them and flashILM is thought to result from exogenous attention being captured by the flash. Exogenous attention fades with increasing delays, which predicts that flashILM should show a similar temporal pattern. Exogenous attention appears to follow flashILM to become more or less equally distributed along the line.The current study examines flashILM in order to test these predictions derived from the attentional explanation for flashILM and the results were consistent with them. The discussion then concludes with an exploratory analysis approach concerning states of consciousness and decision making and suggests a possible role for attention.

Description: The majority of eye tracking studies in reading are on issues dealing with word level or sentence level comprehension. By comparison, relatively few eye tracking studies of reading examine questions related to higher level comprehension in processing of longer texts. We present data from an eye tracking study of anaphor resolution in order to examine specific issues related to this discourse phenomenon and to raise more general methodological and theoretical issues in eye tracking studies of discourse processing. This includes matters related to the design of materials as well as the interpretation of measures with regard to underlying comprehension processes. In addition, we provide several examples from eye tracking studies of discourse to demonstrate the kinds of questions that may be addressed with this methodology, particularly with respect to the temporality of processing in higher level comprehension and how such questions correspond to recent theoretical arguments in the field.

Description: Inhibition of return is characterized by delayed responses to previously attended locations when the cue-target onset asynchrony (CTOA) is long enough. However, when cues are predictive of a target’s location, faster reaction times to cued as compared to uncued targets are normally observed. In this series of experiments investigating saccadic reaction times, we manipulated the cue predictability to 25% (counterpredictive), 50% (nonpredictive), and 75% (predictive) to investigate the interaction between predictive endogenous facilitatory (FCEs) and inhibitory cueing effects (ICEs). Overall, larger ICEs were seen in the counterpredictive condition than in the nonpredictive condition, and no ICE was found in the predictive condition. Based on the hypothesized additivity of FCEs and ICEs, we reasoned that the null ICEs observed in the predictive condition are the result of two opposing mechanisms balancing each other out, and the large ICEs observed with counterpredictive cueing can be attributed to the combination of endogenous facilitation at uncued locations with inhibition at cued locations. Our findings suggest that the endogenous activity contributed by cue predictability can reduce the overall inhibition observed when the mechanisms occur at the same location, or enhance behavioral inhibition when the mechanisms occur at opposite locations.

Description: Ganel, Freud, Chajut, and Algom (2012) demonstrated that maximum grip apertures (MGAs) differ significantly when grasping perceptually identical objects. From this finding they concluded that the visual size information used by the motor system is more accurate than the visual size information available to the perceptual system. A direct comparison between the accuracy in the perception and the action system is, however, problematic, given that accuracy in the perceptual task is measured using a dichotomous variable, while accuracy in the visuomotor task is determined using a continuous variable. We addressed this problem by dichotomizing the visuomotor measures. Using this approach, our results show that size discrimination in grasping is in fact inferior to perceptual discrimination therefore contradicting the original suggestion put forward by Ganel and colleagues.

Description: Visual search is a popular tool for studying a range of questions about perception and attention, thanks to the ease with which the basic paradigm can be controlled and manipulated. While often thought of as a sub-field of vision science, search tasks are significantly more complex than most other perceptual tasks, with strategy and decision playing an essential, but neglected, role. In this review, we briefly describe some of the important theoretical advances about perception and attention that have been gained from studying visual search within the signal detection and guided search frameworks. Under most circumstances, search also involves executing a series of eye movements. We argue that understanding the contribution of biases, routines and strategies to visual search performance over multiple fixations will lead to new insights about these decision-related processes and how they interact with perception and attention. We also highlight the neglected potential for variability, both within and between searchers, to contribute to our understanding of visual search. The exciting challenge will be to account for variations in search performance caused by these numerous factors and their interactions. We conclude the review with some recommendations for ways future research can tackle these challenges to move the field forward.

Description: Recent advances of computerized graphical methods have received significant attention for detection and home monitoring of various visual distortions caused by macular disorders such as macular edema, central serous chorioretinopathy, and age-related macular degeneration. After a brief review of macular disorders and their conventional diagnostic methods, this paper reviews such graphical interface methods including computerized Amsler Grid, Preferential Hyperacuity Perimeter, and Three-dimensional Computer-automated Threshold Amsler Grid. Thereafter, the challenges of these computerized methods for accurate and rapid detection of macular disorders are discussed. The early detection and progress assessment of macular disorders can significantly enhance the required clinical procedure for the diagnosis and treatment of macular disorders.

Description: The Irish Astronomical Tract is a 14th–15th century Gaelic document, based mainly on a Latin translation of the eighth-century Jewish astronomer Messahala. It contains a passage about the sun illusion—the apparent enlargement of celestial bodies when near the horizon compared to higher in the sky. This passage occurs in a chapter concerned with proving that the Earth is a globe rather than flat. Here the author denies that the change in size is caused by a change in the sun’s distance, and instead ascribes it (incorrectly) to magnification by atmospheric vapours, likening it to the bending of light when looking from air to water or through glass spectacles. This section does not occur in the Latin version of Messahala. The Irish author may have based the vapour account on Aristotle, Ptolemy or Cleomedes, or on later authors that relied on them. He seems to have been unaware of alternative perceptual explanations. The refraction explanation persists today in folk science.

Description: Autism spectrum disorder (ASD) is neurodevelopmental condition principally characterised by impairments in social interaction and communication, and repetitive behaviours and interests. This article reviews the eye movement studies designed to investigate the underlying sampling or processing differences that might account for the principal characteristics of autism. Following a brief summary of a previous review chapter by one of the authors of the current paper, a detailed review of eye movement studies investigating various aspects of processing in autism over the last decade will be presented. The literature will be organised into sections covering different cognitive components, including language and social communication and interaction studies. The aim of the review will be to show how eye movement studies provide a very useful on-line processing measure, allowing us to account for observed differences in behavioural data (accuracy and reaction times). The subtle processing differences that eye movement data reveal in both language and social processing have the potential to impact in the everyday communication domain in autism.

Description: Social attention describes how observers orient to social information and exhibit behaviors such as gaze following. These behaviors are examples of how attentional orienting may differ when in the presence of other people, although they have typically been studied without actual social presence. In the present study we ask whether orienting, as measured by head and eye movements, will change when participants are trying to mislead or hide their attention from a bystander. In two experiments, observers performed a preference task while being video-recorded, and subsequent participants were asked to guess the response of the participant based on a video of the head and upper body. In a second condition, observers were told to try to mislead the “guesser”. The results showed that participants’ preference responses could be guessed from videos of the head and, critically, that participants spontaneously changed their orienting behavior in order to mislead by reducing the rate at which they made large head movements. Masking the eyes with sunglasses suggested that head movements were most important in our setup. This indicates that head and eye movements can be used flexibly according to the socio-communicative context.

Description: When the head is tilted, an objectively vertical line viewed in isolation is typically perceived as tilted. We explored whether this shift also occurs when viewing global motion displays perceived as either object-motion or self-motion. Observers stood and lay left side down while viewing (1) a static line, (2) a random-dot display of 2-D (planar) motion or (3) a random-dot display of 3-D (volumetric) global motion. On each trial, the line orientation or motion direction were tilted from the gravitational vertical and observers indicated whether the tilt was clockwise or counter-clockwise from the perceived vertical. Psychometric functions were fit to the data and shifts in the point of subjective verticality (PSV) were measured. When the whole body was tilted, the perceived tilt of both a static line and the direction of optic flow were biased in the direction of the body tilt, demonstrating the so-called A-effect. However, we found significantly larger shifts for the static line than volumetric global motion as well as larger shifts for volumetric displays than planar displays. The A-effect was larger when the motion was experienced as self-motion compared to when it was experienced as object-motion. Discrimination thresholds were also more precise in the self-motion compared to object-motion conditions. Different magnitude A-effects for the line and motion conditions—and for object and self-motion—may be due to differences in combining of idiotropic (body) and vestibular signals, particularly so in the case of vection which occurs despite visual-vestibular conflict.

Description: Performance on random-dot global motion tasks may reach adult-like levels before 4 or as late as 16 years of age, depending on the specific parameters used to create the stimuli. Later maturation has been found for slower speeds, smaller spatial displacements, and sparser dot arrays. This protracted development on global motion tasks may depend on limitations specific to spatial aspects of a motion stimulus rather than to motion mechanisms per se. The current study investigated the impact of varying stimulus area (9, 36, and 81 deg2) on the global motion coherence thresholds of children 4–6 years old and adults for three signal dot displacements (∆x = 1, 5, and 30 arcmin). We aimed to determine whether children could achieve mature performance for the smallest displacements, a condition previously found to show late maturation, when a larger stimulus area was used. Coherence thresholds were higher in children compared to adults in the 1 and 5 arcmin displacement conditions, as reported previously, and this did not change as a function of stimulus area. However, both children and adults performed better with a larger stimulus area in the 30 arcmin displacement condition only. This suggests that immature spatial integration, as measured by stimulus area, cannot account for immaturities in global motion perception.

Description: There has been an increasing drive to understand failures in searches for weapons and explosives in X-ray baggage screening. Tracking eye movements during the search has produced new insights into the guidance of attention during the search, and the identification of targets once they are fixated. Here, we review the eye-movement literature that has emerged on this front over the last fifteen years, including a discussion of the problems that real-world searchers face when trying to detect targets that could do serious harm to people and infrastructure.

Description: In grapheme-color synesthesia, letters and numbers evoke abnormal colored perceptions. Although the underlying mechanisms are not known, it is largely thought that the synesthetic brain is characterized by atypical connectivity throughout various brain regions, including the visual areas. To study the putative impact of synesthesia on the visual brain, we assessed lateral interactions (i.e., local functional connectivity between neighboring neurons in the visual cortex) by recording steady-state visual evoked potentials (ssVEPs) over the occipital region in color-grapheme synesthetes (n = 6) and controls (n = 21) using the windmill/dartboard paradigm. Discrete Fourier Transform analysis was conducted to extract the fundamental frequency and the second harmonics of ssVEP responses from contrast-reversing stimuli presented at 4.27 Hz. Lateral interactions were assessed using two amplitude-based indices: Short-range and long-range lateral interactions. Results indicated that synesthetes had a statistically weaker signal coherence of the fundamental frequency component compared to the controls, but no group differences were observed on lateral interaction indices. However, a significant correlation was found between long-range lateral interactions and the type of synesthesia experience (projector versus associator). We conclude that the occipital activity related to lateral interactions in synesthetes does not substantially differ from that observed in controls. Further investigation is needed to understand the impact of synesthesia on visual processing, specifically in relation to subjective experiences of synesthete individuals.

Description: The eye movements of experts, reading medical images, have been studied for many years. Unlike topics such as face perception, medical image perception research needs to cope with substantial, qualitative changes in the stimuli under study due to dramatic advances in medical imaging technology. For example, little is known about how radiologists search through 3D volumes of image data because they simply did not exist when earlier eye tracking studies were performed. Moreover, improvements in the affordability and portability of modern eye trackers make other, new studies practical. Here, we review some uses of eye movements in the study of medical image perception with an emphasis on newer work. We ask how basic research on scene perception relates to studies of medical ‘scenes’ and we discuss how tracking experts’ eyes may provide useful insights for medical education and screening efficiency.

Description: Facial recognition is widely thought to involve a holistic perceptual process, and optimal recognition performance can be rapidly achieved within two fixations. However, is facial identity encoding likewise holistic and rapid, and how do gaze dynamics during encoding relate to recognition? While having eye movements tracked, participants completed an encoding (“study”) phase and subsequent recognition (“test”) phase, each divided into blocks of one- or five-second stimulus presentation time conditions to distinguish the influences of experimental phase (encoding/recognition) and stimulus presentation time (short/long). Within the first two fixations, several differences between encoding and recognition were evident in the temporal and spatial dynamics of the eye-movements. Most importantly, in behavior, the long study phase presentation time alone caused improved recognition performance (i.e., longer time at recognition did not improve performance), revealing that encoding is not as rapid as recognition, since longer sequences of eye-movements are functionally required to achieve optimal encoding than to achieve optimal recognition. Together, these results are inconsistent with a scan path replay hypothesis. Rather, feature information seems to have been gradually integrated over many fixations during encoding, enabling recognition that could subsequently occur rapidly and holistically within a small number of fixations.

Description: Under optimal conditions, just 3–6 ms of visual stimulation suffices for humans to see motion. Motion perception on this timescale implies that the visual system under these conditions reliably encodes, transmits, and processes neural signals with near-millisecond precision. Motivated by in vitro evidence for high temporal precision of motion signals in the primate retina, we investigated how neuronal and perceptual limits of motion encoding relate. Specifically, we examined the correspondence between the time scale at which cat retinal ganglion cells in vivo represent motion information and temporal thresholds for human motion discrimination. The timescale for motion encoding by ganglion cells ranged from 4.6 to 91 ms, and depended non-linearly on temporal frequency, but not on contrast. Human psychophysics revealed that minimal stimulus durations required for perceiving motion direction were similarly brief, 5.6–65 ms, and similarly depended on temporal frequency but, above ~10%, not on contrast. Notably, physiological and psychophysical measurements corresponded closely throughout (r = 0.99), despite more than a 20-fold variation in both human thresholds and optimal timescales for motion encoding in the retina. The match in absolute values of the neurophysiological and psychophysical data may be taken to indicate that from the lateral geniculate nucleus (LGN) through to the level of perception little temporal precision is lost. However, we also show that integrating responses from multiple neurons can improve temporal resolution, and this potential trade-off between spatial and temporal resolution would allow for loss of temporal resolution after the LGN. While the extent of neuronal integration cannot be determined from either our human psychophysical or neurophysiological experiments and its contribution to the measured temporal resolution is unknown, our results demonstrate a striking similarity in stimulus dependence between the temporal fidelity established in the retina and the temporal limits of human motion discrimination.

Description: Research suggests that pattern complexity (number of strokes) limits the visual span for Chinese characters, and that this may have important consequences for reading. With the present research, we investigated age differences in the visual span for Chinese characters by presenting trigrams of low, medium or high complexity at various locations relative to a central point to young (18–30 years) and older (60+ years) adults. A sentence reading task was used to assess their reading speed. The results showed that span size was smaller for high complexity stimuli compared to low and medium complexity stimuli for both age groups, replicating previous findings with young adult participants. Our results additionally showed that this influence of pattern complexity was greater for the older than younger adults, such that while there was little age difference in span size for low and medium complexity stimuli, span size for high complexity stimuli was almost halved in size for the older compared to the young adults. Finally, our results showed that span size correlated with sentence reading speed, confirming previous findings taken as evidence that the visual span imposes perceptual limits on reading speed. We discuss these findings in relation to age-related difficulty reading Chinese.

Description: The formation of structure in the visual system, that is, of the connections between cellswithin neural populations, is by and large an unsupervised learning process. In the primary visualcortex of mammals, for example, one can observe during development the formation of cells selectiveto localized, oriented features, which results in the development of a representation in area V1 ofimages’ edges. This can be modeled using a sparse Hebbian learning algorithms which alternatea coding step to encode the information with a learning step to find the proper encoder. A majordifficulty of such algorithms is the joint problem of finding a good representation while knowingimmature encoders, and to learn good encoders with a nonoptimal representation. To solve thisproblem, this work introduces a new regulation process between learning and coding which ismotivated by the homeostasis processes observed in biology. Such an optimal homeostasis ruleis implemented by including an adaptation mechanism based on nonlinear functions that balancethe antagonistic processes that occur at the coding and learning time scales. It is compatible witha neuromimetic architecture and allows for a more efficient emergence of localized filters sensitiveto orientation. In addition, this homeostasis rule is simplified by implementing a simple heuristicon the probability of activation of neurons. Compared to the optimal homeostasis rule, numericalsimulations show that this heuristic allows to implement a faster unsupervised learning algorithmwhile retaining much of its effectiveness. These results demonstrate the potential application of sucha strategy in machine learning and this is illustrated by showing the effect of homeostasis in theemergence of edge-like filters for a convolutional neural network.

Description: A simple and reliable analytical method for the simultaneous determination of alternariol (AOH), altenuene (ALT), tentoxin (TEN), altenusin (ALS), tenuazonic acid (TeA), and alternariol monomethyl ether (AME) in grapes was developed by ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS). A modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) procedure with the extraction by acetonitrile and purification by sodium chloride (0.5 g) and anhydrous magnesium sulfate (0.5 g) was established to recover the six Alternaria toxins. After validation by determining the linearity (R2 〉 0.99), recovery (77.8–101.6%), sensitivity (limit of detection in the range of 0.03–0.21 μg kg−1, and limit of quantification in the range of 0.09–0.48 μg kg−1), and precision (relative standard deviation (RSD) ≤ 12.9%), the analytical method was successfully applied to reveal the contamination state of Alternaria toxins in grapes. Among 56 grape samples, 40 (incidence of 71.4%) were contaminated with Alternaria toxins. TEN was the most frequently found mycotoxin (37.5%), with a concentration range of 0.10–1.64 μg kg−1, followed by TeA (28.6%) and AOH (26.8%). ALT (10.7%), AME (3.6%), and ALS (5.4%) were also detected in some samples. To the best of our knowledge, this is the first report about the Alternaria toxins contamination in grapes in China.

Description: Vascular diseases are multifactorial, often requiring multiple challenges, or ‘hits’, for their initiation. Intra-vascular hemolysis illustrates well the multiple-hit theory where a first event lyses red blood cells, releasing hemolysis-derived products, in particular cell-free heme which is highly toxic for the endothelium. Physiologically, hemolysis derived-products are rapidly neutralized by numerous defense systems, including haptoglobin and hemopexin which scavenge hemoglobin and heme, respectively. Likewise, cellular defense mechanisms are involved, including heme-oxygenase 1 upregulation which metabolizes heme. However, in cases of intra-vascular hemolysis, those systems are overwhelmed. Heme exerts toxic effects by acting as a damage-associated molecular pattern and promoting, together with hemoglobin, nitric oxide scavenging and ROS production. In addition, it activates the complement and the coagulation systems. Together, these processes lead to endothelial cell injury which triggers pro-thrombotic and pro-inflammatory phenotypes. Moreover, among endothelial cells, glomerular ones display a particular susceptibility explained by a weaker capacity to counteract hemolysis injury. In this review, we illustrate the ‘multiple-hit’ theory through the example of intra-vascular hemolysis, with a particular focus on cell-free heme, and we advance hypotheses explaining the glomerular susceptibility observed in hemolytic diseases. Finally, we describe therapeutic options for reducing endothelial injury in hemolytic diseases.

Description: Helicobacter pylori colonizes the gastric epithelial cells of at least half of the world’s population, and it is the strongest risk factor for developing gastric complications like chronic gastritis, ulcer diseases, and gastric cancer. To successfully colonize and establish a persistent infection, the bacteria must overcome harsh gastric conditions. H. pylori has a well-developed mechanism by which it can survive in a very acidic niche. Despite bacterial factors, gastric environmental factors and host genetic constituents together play a co-operative role for gastric pathogenicity. The virulence factors include bacterial colonization factors BabA, SabA, OipA, and HopQ, and the virulence factors necessary for gastric pathogenicity include the effector proteins like CagA, VacA, HtrA, and the outer membrane vesicles. Bacterial factors are considered more important. Here, we summarize the recent information to better understand several bacterial virulence factors and their role in the pathogenic mechanism.

Description: A comprehensive strategy combining a quantitative method for 28 mycotoxins and a post-target screening for other 245 fungal and bacterial metabolites in dry pet food samples were developed using an acetonitrile-based extraction and an ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) method. The proposed method showed satisfactory validation results according to Commission Decision 2002/657/EC. Average recoveries from 72 to 108% were obtained for all studied mycotoxins, and the intra-/inter-day precision were below 9 and 14%, respectively. Results showed mycotoxin contamination in 99% of pet food samples (n = 89) at concentrations of up to hundreds µg/kg, with emerging Fusarium mycotoxins being the most commonly detected mycotoxins. All positive samples showed co-occurrence of mycotoxins with the simultaneous presence of up to 16 analytes per sample. In the retrospective screening, up to 54 fungal metabolites were tentatively identified being cyclopiazonic acid, paspalitrem A, fusaric acid, and macrosporin, the most commonly detected analytes.

Description: Cyanobacteria and cyanotoxins constitute a serious environmental and human health problem. Moreover, concerns are raised with the use of contaminated water in agriculture and vegetable production as this can lead to food contamination and human exposure to toxins as well as impairment in crop development and productivity. The objective of this work was to assess the susceptibility of two green vegetables, spinach and lettuce, to the cyanotoxins microcystin (MC) and cylindrospermopsin (CYN), individually and in mixture. The study consisted of growing both vegetables in hydroponics, under controlled conditions, for 21 days in nutrient medium doped with MC or CYN at 10 μg/L and 50 μg/L, or CYN/MC mixture at 5 + 5 μg/L and 25 + 25 μg/L. Extracts from M. aeruginosa and C. ovalisporum were used as sources of toxins. The study revealed growth inhibition of the aerial part (Leaves) in both species when treated with 50µg/L of MC, CYN and CYN/MC mixture. MC showed to be more harmful to plant growth than CYN. Moreover spinach leaves growth was inhibited by both 5 + 5 and 25 + 25 µg/L CYN/MC mixtures, whereas lettuce leaves growth was inhibited only by 25 + 25 µg/L CYN/MC mixture. Overall, growth data evidence increased sensitivity of spinach to cyanotoxins in comparison to lettuce. On the other hand, plants exposed to CYN/MC mixture showed differential accumulation of CYN and MC. In addition, CYN, but not MC, was translocated from the roots to the leaves. CYN and MC affected the levels of minerals particularly in plant roots. The elements most affected were Ca, K and Mg. However, in leaves K was the mineral that was affected by exposure to cyanotoxins.

Description: A knowledge, attitude and practice (KAP) study was conducted in three districts of Malawi to test whether the training had resulted in increased knowledge and adoption of recommended pre- and post-harvest crop management practices, and their contribution to reducing aflatoxin contamination in groundnut, maize and sorghum. The study was conducted with 900 farmers at the baseline and 624 farmers at the end-line, while 726 and 696 harvested crop samples were collected for aflatoxin testing at the baseline and end-line, respectively. Results show that the knowledge and practice of pre- and post-harvest crop management for mitigating aflatoxin were inadequate among the farmers at the baseline but somewhat improved after the training as shown at the end-line. As a result, despite unfavorable weather, the mean aflatoxin contamination level in their grain samples decreased from 83.6 to 55.8 ppb (p 〈 0.001). However, it was also noted that increased knowledge did not significantly change farmers’ attitude toward not consuming grade-outs because of economic incentive incompatibility, leaving potential for improving the practices further. This existing gap in the adoption of aflatoxin mitigation practices calls for approaches that take into account farmers’ needs and incentives to attain sustainable behavioral change.

Description: The deliberate release of biological agents with terrorist or criminal intent continues to pose concerns in the current geopolitical situation. Therefore, attention is still needed to ensure preparedness against the potential use of pathogens as unconventional weapons. Botulinum neurotoxin (BoNT) is one such biological threat, characterized by an extremely low lethal dose, high morbidity and mortality when appropriately disseminated, and the capacity to cause panic and social disruption. This paper addresses the risks of a potential release of the botulinum neurotoxin and summarizes the relevant aspects of the threat.

Description: Tetanus and botulinum neurotoxins are the most poisonous substances known, so much so as to be considered for a possible terrorist use. At the same time, botulinum neurotoxin type A1 is successfully used to treat a variety of human syndromes characterized by hyperactive cholinergic nerve terminals. The extreme toxicity of these neurotoxins is due to their neurospecificity and to their metalloprotease activity, which results in the deadly paralysis of tetanus and botulism. Recently, many novel botulinum neurotoxins and some botulinum-like toxins have been discovered. This large number of toxins differs in terms of toxicity and biological activity, providing a potential goldmine for novel therapeutics and for new molecular tools to dissect vesicular trafficking, fusion, and exocytosis. The scattered data on toxicity present in the literature require a systematic organization to be usable by scientists and clinicians. We have assembled here the data available in the literature on the toxicity of these toxins in different animal species. The internal comparison of these data provides insights on the biological activity of these toxins.

Description: The fumonisins producing fungi, Fusarium spp., are ubiquitous in nature and contaminate several food matrices that pose detrimental health hazards on humans as well as on animals. This has necessitated profound research for the control and management of the toxins to guarantee better health of consumers. This review highlights the chemistry and biosynthesis process of the fumonisins, their occurrence, effect on agriculture and food, along with their associated health issues. In addition, the focus has been put on the detection and management of fumonisins to ensure safe and healthy food. The main focus of the review is to provide insights to the readers regarding their health-associated food consumption and possible outbreaks. Furthermore, the consumers’ knowledge and an attempt will ensure food safety and security and the farmers’ knowledge for healthy agricultural practices, processing, and management, important to reduce the mycotoxin outbreaks due to fumonisins.

Description: Chronic Migraine (CM) is a disabling neurologic condition with a severe impact on functioning and quality of life. Successful therapeutic management of patients with CM is complex, and differences in therapeutic response could be attributable to genetically determined factors, sensitivity to pharmacological treatment, psychosocial and relational factors affecting the patient’s compliance and approach on the therapeutic treatment. The aim of this prospective observational study was to explore self-efficacy, coping strategies, psychological distress and headache-related disability in a cohort of 40 patients with CM (mean age: 46.73; standard deviation 13.75) treated with OnabotulinumtoxinA and the relationship between these clinical and psychological aspects and acute medication consumption during OnabotulinumtoxinA prophylactic treatment. Patients presented an overall significant reduction in the Headache Index (HI) (p 〈 0.001), HI with severe intensity (p = 0.009), and total analgesic consumption (p = 0.003) after the prophylactic treatment. These results are in line with the literature. Despite this, higher nonsteroidal anti-inflammatory drugs consumption was associated with higher psychological distress, higher HI with severe and moderate intensity, and worse quality of life. Conversely, triptans consumption was correlated with HI of mild intensity, and problem-focused coping strategies. To conclude, the psychological profile, and in particular, the psychological distress and specific coping strategies might influence the self-management of acute medication.

Description: Acute hepatopancreatic necrosis disease (AHPND), a newly emergent farmed penaeid shrimp bacterial disease originally known as early mortality syndrome (EMS), is causing havoc in the shrimp industry. The causative agent of AHPND was found to be a specific strain of bacteria, e.g., Vibrio and Shewanella sps., that contains pVA1 plasmid (63–70 kb) encoding the binary PirAVP and PirBVP toxins. The PirABVP and toxins are the primary virulence factors of AHPND-causing bacteria that mediates AHPND and mortality in shrimp. Hence, in this study using a germ-free brine shrimp model system, we evaluated the PirABVP toxin-mediated infection process at cellular level, including toxin attachment and subsequent toxin-induced damage to the digestive tract. The results showed that, PirABVP toxin binds to epithelial cells of the digestive tract of brine shrimp larvae and produces characteristic symptoms of AHPND. In the PirABVP-challenged brine shrimp larvae, shedding or sloughing of enterocytes in the midgut and hindgut regions was regularly visualized, and the intestinal lumen was filled with moderately electron-dense cells of variable shapes and sizes. In addition, the observed cellular debris in the intestinal lumen of the digestive tract was found to be of epithelial cell origin. The detailed morphology of the digestive tract demonstrates further that the PirABVP toxin challenge produces focal to extensive necrosis and damages epithelial cells in the midgut and hindgut regions, resulting in pyknosis, cell vacuolisation, and mitochondrial and rough endoplasmic reticulum (RER) damage to different degrees. Taken together, our study provides substantial evidence that PirABVP toxins bind to the digestive tract of brine shrimp larvae and seem to be responsible for generating characteristic AHPND lesions and damaging enterocytes in the midgut and hindgut regions.

Description: Venoms are one of the most convergent of animal traits known, and encompass a much greater taxonomic and functional diversity than is commonly appreciated. This knowledge gap limits the potential of venom as a model trait in evolutionary biology. Here, we summarize the taxonomic and functional diversity of animal venoms and relate this to what is known about venom system morphology, venom modulation, and venom pharmacology, with the aim of drawing attention to the importance of these largely neglected aspects of venom research. We find that animals have evolved venoms at least 101 independent times and that venoms play at least 11 distinct ecological roles in addition to predation, defense, and feeding. Comparisons of different venom systems suggest that morphology strongly influences how venoms achieve these functions, and hence is an important consideration for understanding the molecular evolution of venoms and their toxins. Our findings also highlight the need for more holistic studies of venom systems and the toxins they contain. Greater knowledge of behavior, morphology, and ecologically relevant toxin pharmacology will improve our understanding of the evolution of venoms and their toxins, and likely facilitate exploration of their potential as sources of molecular tools and therapeutic and agrochemical lead compounds.

Description: Trimethylamine-N-oxide (TMAO) has been suggested as a marker and mediator of cardiovascular diseases. However, data are contradictory, and the mechanisms are obscure. Strikingly, the role of the TMAO precursor trimethylamine (TMA) has not drawn attention in cardiovascular studies even though toxic effects of TMA were proposed several decades ago. We assessed plasma TMA and TMAO levels in healthy humans (HH) and cardiovascular patients qualified for aortic valve replacement (CP). The cytotoxicity of TMA and TMAO in rat cardiomyocytes was evaluated using an MTT test. The effects of TMA and TMAO on albumin and lactate dehydrogenase (LDH) were assessed using fluorescence correlation spectroscopy. In comparison to HH, CP had a two-fold higher plasma TMA (p 〈 0.001) and a trend towards higher plasma TMAO (p = 0.07). In CP plasma, TMA was inversely correlated with an estimated glomerular filtration rate (eGFR, p = 0.002). TMA but not TMAO reduced cardiomyocytes viability. Incubation with TMA but not TMAO resulted in the degradation of the protein structure of LDH and albumin. In conclusion, CP show increased plasma TMA, which is inversely correlated with eGFR. TMA but not TMAO exerts negative effects on cardiomyocytes, likely due to its disturbing effect on proteins. Therefore, TMA but not TMAO may be a toxin and a marker of cardiovascular risk.

Description: Cereals are prone to fungal infection during growth, harvesting, transportation, and/or storage. As a result, cereals such as wheat grains and wheat-derived products may be contaminated with mycotoxins leading to acute and chronic health exposure. The current study investigated the presence of the mycotoxins: ochratoxin A (OTA), ochratoxin B (OTB), T-2, and HT-2 toxins in samples of wheat grains (n = 50), wheat flour (n = 50), and bread (n = 37) from the main mills in Lebanon using LC-MS/MS. Accuracy ranged from 98–100%, recoveries from 93–105%, and intraday and interday precision were 5–7% and 9–12%, respectively. The tested wheat grains, wheat flour, and bread samples did not contain detectable levels of T-2 and HT-2 toxins and OTB. Four wheat flour samples (8% of flour samples) showed positive OTA levels ranging from 0.6–3.4 μg·kg−1 with an arithmetic mean of 1.9 ± 0.2 μg·kg−1. Only one sample contained an OTA concentration greater than the limit set by the European Union (3 μg·kg−1) for wheat-derived products. This study suggests that mycotoxin contamination of wheat grains, wheat flour, and bread in Lebanon is currently not a serious public health concern. However, surveillance strategies and monitoring programs must be routinely implemented to ensure minimal mycotoxin contamination of wheat-based products.

Description: T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.

Description: Staphylococcus aureus colonizes epithelial surfaces, but it can also cause severe infections. The aim of this work was to investigate whether bacterial virulence correlates with defined types of tissue infections. For this, we collected 10–12 clinical S. aureus strains each from nasal colonization, and from patients with endoprosthesis infection, hematogenous osteomyelitis, and sepsis. All strains were characterized by genotypic analysis, and by the expression of virulence factors. The host–pathogen interaction was studied through several functional assays in osteoblast cultures. Additionally, selected strains were tested in a murine sepsis/osteomyelitis model. We did not find characteristic bacterial features for the defined infection types; rather, a wide range in all strain collections regarding cytotoxicity and invasiveness was observed. Interestingly, all strains were able to persist and to form small colony variants (SCVs). However, the low-cytotoxicity strains survived in higher numbers, and were less efficiently cleared by the host than the highly cytotoxic strains. In summary, our results indicate that not only destructive, but also low-cytotoxicity strains are able to induce infections. The low-cytotoxicity strains can successfully survive, and are less efficiently cleared from the host than the highly cytotoxic strains, which represent a source for chronic infections. The understanding of this interplay/evolution between the host and the pathogen during infection, with specific attention towards low-cytotoxicity isolates, will help to optimize treatment strategies for invasive and therapy-refractory infection courses.

Description: Snake venoms contain an astounding variety of different proteins. Among them are numerous C-type lectin family members, which are grouped into classical Ca2+- and sugar-binding lectins and the non-sugar-binding snake venom C-type lectin-related proteins (SV-CLRPs), also called snaclecs. Both groups share the robust C-type lectin domain (CTLD) fold but differ in a long loop, which either contributes to a sugar-binding site or is expanded into a loop-swapping heterodimerization domain between two CLRP subunits. Most C-type lectin (-related) proteins assemble in ordered supramolecular complexes with a high versatility of subunit numbers and geometric arrays. Similarly versatile is their ability to inhibit or block their target molecules as well as to agonistically stimulate or antagonistically blunt a cellular reaction triggered by their target receptor. By utilizing distinct interaction sites differentially, SV-CLRPs target a plethora of molecules, such as distinct coagulation factors and receptors of platelets and endothelial cells that are involved in hemostasis, thrombus formation, inflammation and hematogenous metastasis. Because of their robust structure and their high affinity towards their clinically relevant targets, SV-CLRPs are and will potentially be valuable prototypes to develop new diagnostic and therapeutic tools in medicine, provided that the molecular mechanisms underlying their versatility are disclosed.

Description: Milk is an important commodity in Kenya; the country has the largest dairy herd and highest per capita milk consumption in East Africa. As such, hazards in milk are of concern. Aflatoxin M1 (AFM1) is a toxic metabolite of aflatoxin B1 (AFB1) excreted in milk by lactating animals after ingesting AFB1-contaminated feeds. This metabolite is injurious to human health, but there is little information on the risk to human health posed by AFM1 in milk in rural Kenya. To fill this gap, a quantitative risk assessment (QRA) applying probabilistic statistical tools to quantify risks was conducted. This assessed the risk of liver cancer posed by AFM1 in milk, assuming 10-fold lower carcinogenicity than AFB1. Data from four agro–ecological zones in Kenya (semi-arid, temperate, sub-humid and humid) were used. We estimated that people were exposed to between 0.3 and 1 ng AFM1 per kg body weight per day through the consumption of milk. The annual incidence rates of cancer attributed to the consumption of AFM1 in milk were 3.5 × 10−3 (95% CI: 3 × 10−3–3.9 × 10−3), 2.9 × 10−3 (95% CI: 2.5 × 10−3–3.3 × 10−3), 1.4 × 10−3 (95% CI: 1.2 × 10−3–1.5 × 10−3) and 2.7 × 10−3 (95% CI: 2.3 × 10−3–3 × 10−3) cancers per 100,000 in adult females, adult males, children 6–18 years old, and in children less than five years old, respectively. Our results show that aflatoxin exposure from milk contributes relatively little to the incidence of liver cancer. Nonetheless, risk managers should take action based on cumulative exposure from all sources of aflatoxins.

Description: Mycotoxins contaminating animal feed can exert toxic effects in animals and be transferred into animal products. Therefore, mycotoxin occurrence in feed should be monitored. To this end, we performed a large-scale global survey of mycotoxin contamination in feed and assessed regional differences and year-to-year variation of mycotoxin occurrence. Concentrations of aflatoxin B1, zearalenone, fumonisins, ochratoxin A, deoxynivalenol, and T-2 toxin were analyzed in 74,821 samples of feed and feed raw materials (e.g., maize, wheat, soybean) collected from 100 countries from 2008 to 2017. In total, 88% of the samples were contaminated with at least one mycotoxin. Mycotoxin occurrence showed distinct regional trends and climate was a key determinant governing these trends. In most regions, the majority of samples complied with maximum levels and guidance values for mycotoxins in animal feed that are in effect in the European Union. However, 41.1%, 38.5%, and 20.9% of samples from South Asia, Sub-Saharan Africa, and Southeast Asia, respectively, exceeded the maximum level for aflatoxin B1 (20 µg/kg). In several regions, mycotoxin concentrations in maize showed a pronounced year-to-year variation that could be explained by rainfall or temperature during sensitive periods of grain development. A large fraction of samples (64%) was co-contaminated with ≥ 2 mycotoxins. Most frequently observed mycotoxin mixtures were combinations of deoxynivalenol, zearalenone, and fumonisins, as well as fumonisins and aflatoxin B1. Deoxynivalenol and zearalenone concentrations were correlated in maize and wheat. In conclusion, according to an extensive global survey, mycotoxin (co-)contamination of animal feed is common, shows regional trends, and is governed in part by climate and weather.

Description: Snakebite envenoming (SBE) is a priority neglected tropical disease, which kills in excess of 100,000 people per year. Additionally, many millions of survivors also suffer through disabilities and long-term health consequences. The only treatment for SBE, antivenom, has a number of major associated problems, not least, adverse reactions and limited availability. This emphasises the necessity for urgent improvements to the management of this disease. Administration of antivenom is too frequently based on symptomatology, which results in wasting crucial time. The majority of SBE-affected regions rely on broad-spectrum polyvalent antivenoms that have a low content of case-specific efficacious immunoglobulins. Research into small molecular therapeutics such as varespladib/methyl-varespladib (PLA2 inhibitors) and batimastat/marimastat (metalloprotease inhibitors) suggest that such adjunctive treatments could be hugely beneficial to victims. Progress into toxin-specific monoclonal antibodies as well as alternative binding scaffolds such as aptamers hold much promise for future treatment strategies. SBE is not implicit during snakebite, due to venom metering. Thus, the delay between bite and symptom presentation is critical and when symptoms appear it may often already be too late to effectively treat SBE. The development of reliable diagnostical tools could therefore initiate a paradigm shift in the treatment of SBE. While the complete eradication of SBE is an impossibility, mitigation is in the pipeline, with new treatments and diagnostics rapidly emerging. Here we critically review the urgent necessity for the development of diagnostic tools and improved therapeutics to mitigate the deaths and disabilities caused by SBE.

Description: Crotamine is a single-chain polypeptide with cell-penetrating properties, which is considered a promising molecule for clinical use. Nevertheless, its biosafety data are still scarce. Herein, we assessed the in vivo proinflammatory properties of crotamine, including its local effect and systemic serum parameters. Sixty male Wistar rats were intradermically injected with 200, 400 and 800 µg crotamine and analyzed after 1, 3 and 7 days. Local effect of crotamine was assessed by determination of MPO and NAG activities, NO levels and angiogenesis. Systemic inflammatory response was assessed by determination of IL-10, TNF-α, CRP, NO, TBARS and SH groups. Crotamine induced macrophages and neutrophils chemotaxis as evidenced by the upregulation of both NAG (0.5–0.6 OD/mg) and MPO (0.1–0.2 OD/mg) activities, on the first and third day of analysis, respectively. High levels of NO were observed for all concentrations and time-points. Moreover, 800 μg crotamine resulted in serum NO (64.7 μM) and local tissue NO (58.5 μM) levels higher or equivalent to those recorded for their respective histamine controls (55.7 μM and 59.0 μM). Crotamine also induced a significant angiogenic response compared to histamine. Systemically, crotamine induced a progressive increase in serum CRP levels up to the third day of analysis (22.4–45.8 mg/mL), which was significantly greater than control values. Crotamine (400 μg) also caused an increase in serum TNF-α, in the first day of analysis (1095.4 pg/mL), however a significant increase in IL-10 (122.2 pg/mL) was also recorded for the same time-point, suggesting the induction of an anti-inflammatory effect. Finally, crotamine changed the systemic redox state by inducing gradual increase in serum levels of TBARS (1.0–1.8 μM/mL) and decrease in SH levels (124.7–19.5 μM/mL) throughout the experimental period of analysis. In summary, rats intradermally injected with crotamine presented local and systemic acute inflammatory responses similarly to histamine, which limits crotamine therapeutic use on its original form.

Description: Shiga toxin-producing Escherichia coli (STEC) isolates (N = 38) that were incriminated in human disease from 2006 to 2013 in South Africa were characterized by serotype, virulence-associated genes, antimicrobial resistance and pulsed-field gel electrophoresis (PFGE). The isolates belonged to 11 O:H serotypes. STEC O26:H11 (24%) was the most frequent serotype associated with human disease, followed by O111:H8 (16%), O157:H7 (13%) and O117:H7 (13%). The majority of isolates were positive for key virulence-associated genes including stx1 (84%), eaeA (61%), ehxA (68.4%) and espP (55%), but lacked stx2 (29%), katP (42%), etpD (16%), saa (16%) and subA (3%). stx2 positive isolates carried stx2c (26%) and/or stx2d (26%) subtypes. All pathogenicity island encoded virulence marker genes were detected in all (100%) isolates except nleA (47%), nleC (84%) and nleD (76%). Multidrug resistance was observed in 89% of isolates. PFGE revealed 34 profiles with eight distinct clusters that shared ≥80% intra-serotype similarity, regardless of the year of isolation. In conclusion, STEC isolates that were implicated in human disease between 2006 and 2013 in South Africa were mainly non-O157 strains which possessed virulence genes and markers commonly associated with STEC strains that have been incriminated in mild to severe human disease worldwide. Improved STEC monitoring and surveillance programs are needed in South Africa to control and prevent STEC disease in humans.

Description: Ochratoxin A (OTA) is a widespread mycotoxin produced by several species of the genera Aspergillus and Penicillium. OTA exists in a variety of foods, including rice, oats, and coffee and is hepatotoxic, with a similar mode of action as aflatoxin B1. The precise mechanism of cytotoxicity is not yet known, but oxidative damage is suspected to contribute to its cytotoxic effects. In this study, human hepatocyte HepG2 cells were treated with various concentrations of OTA (5–500 nM) for 48 h. OTA triggered oxidative stress as demonstrated by glutathione depletion and increased reactive oxygen species, malondialdehyde level, and nitric oxide production. Apoptosis was observed with 500 nM OTA treatment. OTA increased both the mRNA and protein expression of phase I and II enzymes. The same results were observed in an in vivo study using ICR mice. Furthermore, the relationship between phase I and II enzymes was demonstrated by the knockdown of the aryl hydrocarbon receptor (AhR) and NF-E2-related factor 2 (Nrf2) with siRNA. Taken together, our results show that OTA induces oxidative stress through the phase I reaction regulated by AhR and induces apoptosis, and that the phase II reaction is activated by Nrf2 in the presence of oxidative stress.

Description: This study aims to evaluate the prevalence of mycotoxins in industry-submitted cool-season barley and wheat grown under low heat unit climate conditions. Seventy-two barley samples and 83 wheat samples were submitted by producers and industry from May 2016 to May 2017. The concentrations of twelve common mycotoxins, including nivalenol (NIV), deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), ochratoxin A (OTA), zearalenone (ZEN), α-zearalenol (α-ZAL), β-zearalenol (β-ZAL), diacetoxyscirpenol (DAS), T-2 toxin (T-2), HT-2 toxin (HT-2), and aflatoxin B1 (AFB1), were determined using the liquid chromatography/tandem mass spectrometry method. Mycotoxins were detected in 40 barley (56%) and 35 wheat (42%) samples submitted by producers and industry. DON showed the highest incidence in barley (44%) and wheat (33%). None of the barley samples contained detectable DAS and no wheat samples tested positive for α-ZAL, DAS, T-2, or AFB1. Co-occurrence of DON and other mycotoxins was frequently observed. Among the mycotoxin-positive samples, 70% of barley samples and 54% of wheat samples were co-contaminated with at least two mycotoxins. Four barley (6%) and five wheat (6%) samples contained levels of DON above 1000 μg/kg (regulatory level in diets for lactating dairy animals) and HT-2 content in five barley (7%) and four wheat (5%) samples exceeded 100 μg/kg (regulatory level in diets for cattle and poultry). Overall, contamination of these mycotoxins was more frequent and more severe in barley in comparison with wheat that was submitted by producers and industry. Comprehensive strategies, including the prevention of Fusarium toxins contamination, the routine monitoring of their prevalence, the detoxification of them in feed and food, as well as the inhibition of their absorption in the gastrointestinal tract, are highly required. A rapid detection method needs to be developed to screen mycotoxins in industry-submitted cool-season cereal grains.

Description: Toxins can function both as a harmful and therapeutic molecule, depending on their concentrations. The diversity in their function allows us to ask some very pertinent questions related to their origin and roles: (a) What makes them such effective molecules? (b) Are there evolutionary features encoded within the structures of the toxins for their function? (c) Is structural hierarchy in the toxins important for maintaining their structure and function? (d) Do protein dynamics play a role in the function of toxins? and (e) Do the evolutionary connections to these unique features and functions provide the fundamental points in driving evolution? In light of the growing evidence in structural biology, it would be appropriate to suggest that protein dynamics and flexibility play a much bigger role in the function of the toxin than the structure itself. Discovery of IDPs (intrinsically disorder proteins), multifunctionality, and the concept of native aggregation are shaking the paradigm of the requirement of a fixed three-dimensional structure for the protein’s function. Growing evidence supporting the above concepts allow us to redesign the structure-function aspects of the protein molecules. An evolutionary model is necessary and needs to be developed to study these important aspects. The criteria for a well-defined model would be: (a) diversity in structure and function, (b) unique functionality, and (c) must belong to a family to define the evolutionary relationships. All these characteristics are largely fulfilled by bacterial toxins. Bacterial toxins are diverse and widely distributed in all three forms of life (Bacteria, Archaea and Eukaryotes). Some of the unique characteristics include structural folding, sequence and functional combination of domains, targeting a cellular process to execute their function, and most importantly their flexibility and dynamics. In this work, we summarize certain unique aspects of bacterial toxins, including role of structure in defining toxin function, uniqueness in their enzymatic function, and interaction with their substrates and other proteins. Finally, we have discussed the evolutionary aspects of toxins in detail, which will help us rethink the current evolutionary theories. A careful study, and appropriate interpretations, will provide answers to several questions related to the structure-function relationship of proteins, in general. Additionally, this will also allow us to refine the current evolution theories.

Description: The Cytolethal Distending Toxin (CDT) is a bacterial virulence factor produced by several Gram-negative pathogenic bacteria. These bacteria, found in distinct niches, cause diverse infectious diseases and produce CDTs differing in sequence and structure. CDTs have been involved in the pathogenicity of the associated bacteria by promoting persistent infection. At the host-cell level, CDTs cause cell distension, cell cycle block and DNA damage, eventually leading to cell death. All these effects are attributable to the catalytic CdtB subunit, but its exact mode of action is only beginning to be unraveled. Sequence and 3D structure analyses revealed similarities with better characterized proteins, such as nucleases or phosphatases, and it has been hypothesized that CdtB exerts a biochemical activity close to those enzymes. Here, we review the relationships that have been established between CdtB structure and function, particularly by mutation experiments on predicted key residues in different experimental systems. We discuss the relevance of these approaches and underline the importance of further study in the molecular mechanisms of CDT toxicity, particularly in the context of different pathological conditions.

Description: A toxin is a poisonous substance produced within living cells or organisms. One of the most potent groups of toxins currently known are the Botulinum Neurotoxins (BoNTs). These are so deadly that as little as 62 ng could kill an average human; to put this into context that is approximately 200,000 × less than the weight of a grain of sand. The extreme toxicity of BoNTs leads to the need for methods of determining their concentration at very low levels of sensitivity. Currently the mouse bioassay is the most widely used detection method monitoring the activity of the toxin; however, this assay is not only lengthy, it also has both cost and ethical issues due to the use of live animals. This review focuses on detection methods both existing and emerging that remove the need for the use of animals and will look at three areas; speed of detection, sensitivity of detection and finally cost. The assays will have wide reaching interest, ranging from the pharmaceutical/clinical industry for production quality management or as a point of care sensor in suspected cases of botulism, the food industry as a quality control measure, to the military, detecting BoNT that has been potentially used as a bio warfare agent.

Description: Ulcers due to infections with Mycobacterium ulcerans are characterized by complete lack of wound healing processes, painless, an underlying bed of host dead cells and undermined edges due to necrosis. Mycolactone, a macrolide produced by the mycobacterium, is believed to be the toxin responsible. Of interest and relevance is the knowledge that Buruli ulcer (BU) patients remember experiencing trauma previously at the site of the ulcers, suggesting an impairment of wound healing processes, the plausible effect due to the toxin. Wound healing processes involve activation of the blood platelets to release the contents of the dense granules mainly serotonin, calcium ions, and ADP/ATP by exocytosis into the bloodstream. The serotonin release results in attracting more platelets and mast cells to the wound site, with the mast cells also undergoing degranulation, releasing compounds into the bloodstream by exocytosis. Recent work has identified interference in the co-translational translocation of many secreted proteins via the endoplasmic reticulum and cell death involving Wiskott-Aldrich syndrome protein (WASP), Sec61, and angiotensin II receptors (AT2R). We hypothesized that mycolactone by being lipophilic, passively crosses cell membranes and binds to key proteins that are involved in exocytosis by platelets and mast cells, thus inhibiting the initiation of wound healing processes. Based on this, molecular docking studies were performed with mycolactone against key soluble n-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins and regulators, namely Vesicle-associated membrane protein (VAMP8), Synaptosomal-associated protein (SNAP23, syntaxin 11, Munc13-4 (its isoform Munc13-1 was used), and Munc18b; and also against known mycolactone targets (Sec61, AT2R, and WASP). Munc18b was shown to be a plausible mycolactone target after the molecular docking studies with binding affinity of −8.5 kcal/mol. Structural studies and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) binding energy calculations of the mycolactone and Munc18b complex was done with 100 ns molecular dynamics simulations using GROMACS. Mycolactone binds strongly to Munc18b with an average binding energy of −247.571 ± 37.471 kJ/mol, and its presence elicits changes in the structural conformation of the protein. Analysis of the binding interactions also shows that mycolactone interacts with Arg405, which is an important residue of Munc18b, whose mutation could result in impaired granule exocytosis. These findings consolidate the possibility that Munc18b could be a target of mycolactone. The implication of the interaction can be experimentally evaluated to further understand its role in granule exocytosis impairment in Buruli ulcer.

Description: This study explored the probable in vivo cardiac and renal toxicities together with in silico approaches for predicting the apoptogenic potential of Euphorbia peplus methanolic extract (EPME) in rats. Cardiac and renal injury biomarkers were estimated with histopathological and immunohistochemical evaluations of both kidney and heart. The probable underlying mechanism of E. peplus compounds to potentiate p53 activity is examined using Molecular Operating Environment (MOE) docking software and validated experimentally by immunohistochemical localization of p53 protein in the kidney and heart tissues. The gas chromatography/mass spectrometry analysis of E. peplus revealed the presence of nine different compounds dominated by di-(2-ethylhexyl) phthalate (DEHP). Significant elevations of troponin, creatine phosphokinase, creatine kinase–myocardium bound, lactate dehydrogenase, aspartate transaminase, alkaline phosphatase, urea, creatinine, and uric acid were evident in the EPME treated rats. The EPME treated rats showed strong renal and cardiac p53 expression and moderate cardiac TNF-α expression. Further, our in silico results predicted the higher affinity and good inhibition of DEHP, glyceryl linolenate, and lucenin 2 to the MDM2-p53 interface compared to the standard reference 15 a compound. Conclusively, EPME long-term exposure could adversely affect the cardiac and renal tissues probably due to their inflammatory and apoptotic activity. Moreover, the in silico study hypothesizes that EPME inhibits MDM2-mediated degradation of p53 suggesting possible anticancer potentials which confirmed experimental by strong p53 expression in renal and cardiac tissues.

Description: In this study, magnetic graphene nanocomposite Fe3O4/rGO was synthesized by facile one-pot solvothermal method. The nanocomposite was successfully used as magnetic solid phase extraction (MSPE) adsorbents for the determination of aflatoxins in edible vegetable oils through the π–π stacking interactions. MSPE parameters including the amount of adsorbents, extraction and desorption time, washing conditions, and the type and volume of desorption solvent were optimized. Under optimal conditions, good linear relationships were achieved. Limits of detection of this method were as low as 0.02 µg/kg and 0.01 µg/kg for aflatoxin B1 and B2, respectively. Finally, the magnetic graphene nanocomposite was successfully applied to aflatoxin analysis in vegetable oils. The results indicated that the recoveries of the B-group aflatoxins ranged from 80.4% to 106.0%, whereas the relative standard deviations (RSDs) were less than 8.1%. Owing to the simplicity, rapidity and efficiency, Fe3O4/rGO magnetic solid phase extraction coupled with high-performance liquid chromatography fluorescence with post-column photochemical derivatization (Fe3O4/rGO MSPE-HPLC-PCD-FLD) is a promising analytical method for routine and accurate determination of aflatoxins in lipid matrices.

Description: Pertussis, caused by respiratory tract infection with the bacterial pathogen Bordetella pertussis, has long been considered to be a toxin-mediated disease. Bacteria adhere and multiply extracellularly in the airways and release several toxins, which have a variety of effects on the host, both local and systemic. Predominant among these toxins is pertussis toxin (PT), a multi-subunit protein toxin that inhibits signaling through a subset of G protein-coupled receptors in mammalian cells. PT activity has been linked with severe and lethal pertussis disease in young infants and a detoxified version of PT is a common component of all licensed acellular pertussis vaccines. The role of PT in typical pertussis disease in other individuals is less clear, but significant evidence supporting its contribution to pathogenesis has been accumulated from animal model studies. In this review we discuss the evidence indicating a role for PT in pertussis disease, focusing on its contribution to severe pertussis in infants, modulation of immune and inflammatory responses to infection, and the characteristic paroxysmal cough of pertussis.

Description: In this review, we discuss the role of the endocannabinoid (eCB) system in regulating energy and metabolic homeostasis. Endocannabinoids, via activating the cannabinoid type-1 receptor (CB1R), are commonly known as mediators of the thrifty phenotype hypothesis due to their activity in the central nervous system, which in turn regulates food intake and underlies the development of metabolic syndrome. Indeed, these findings led to the clinical testing of globally acting CB1R blockers for obesity and various metabolic complications. However, their therapeutic potential was halted due to centrally mediated adverse effects. Recent observations that highlighted the key role of the peripheral eCB system in metabolic regulation led to the preclinical development of various novel compounds that block CB1R only in peripheral organs with very limited brain penetration and without causing behavioral side effects. These unique molecules, which effectively ameliorate obesity, type II diabetes, fatty liver, insulin resistance, and chronic kidney disease in several animal models, are likely to be further developed in the clinic and may revive the therapeutic potential of blocking CB1R once again.

Description: Cardiotoxins (CTXs) are suggested to exert their cytotoxicity through cell membrane damage. Other studies show that penetration of CTXs into cells elicits mitochondrial fragmentation or lysosome disruption, leading to cell death. Considering the role of AMPK-activated protein kinase (AMPK) in mitochondrial biogenesis and lysosomal biogenesis, we aimed to investigate whether the AMPK-mediated pathway modulated Naja atra (Taiwan cobra) CTX3 cytotoxicity in U937 human leukemia cells. Our results showed that CTX3 induced autophagy and apoptosis in U937 cells, whereas autophagic inhibitors suppressed CTX3-induced apoptosis. CTX3 treatment elicited Ca2+-dependent degradation of the protein phosphatase 2A (PP2A) catalytic subunit (PP2Acα) and phosphorylation of AMPKα. Overexpression of PP2Acα mitigated the CTX3-induced AMPKα phosphorylation. CTX3-induced autophagy was via AMPK-mediated suppression of the Akt/mTOR pathway. Removal of Ca2+ or suppression of AMPKα phosphorylation inhibited the CTX3-induced cell death. CTX3 was unable to induce autophagy and apoptosis in U937 cells expressing constitutively active Akt. Met-modified CTX3 retained its membrane-perturbing activity, however, it did not induce AMPK activation and death of U937 cells. These results conclusively indicate that CTX3 induces autophagy and apoptosis in U937 cells via the Ca2+/PP2A/AMPK axis, and suggest that the membrane-perturbing activity of CTX3 is not crucial for the cell death signaling pathway induction.

Description: Trichothecenes are sesquiterpenoid mycotoxins produced by fungi from the order Hypocreales, including members of the Fusarium genus that infect cereal grain crops. Different trichothecene-producing Fusarium species and strains have different trichothecene chemotypes belonging to the Type A and B class. These fungi cause a disease of small grain cereals, called Fusarium head blight, and their toxins contaminate host tissues. As potent inhibitors of eukaryotic protein synthesis, trichothecenes pose a health risk to human and animal consumers of infected cereal grains. In 2009, Foroud and Eudes published a review of trichothecenes in cereal grains for human consumption. As an update to this review, the work herein provides a comprehensive and multi-disciplinary review of the Fusarium trichothecenes covering topics in chemistry and biochemistry, pathogen biology, trichothecene toxicity, molecular mechanisms of resistance or detoxification, genetics of resistance and breeding strategies to reduce their contamination of wheat and barley.

Description: The injection of botulinum toxin type A (BoNT/A) in the masticatory muscles, to cause its temporary paralysis, is a widely used intervention for clinical disorders such as oromandibular dystonia, sleep bruxism, and aesthetics (i.e., masseteric hypertrophy). Considering that muscle contraction is required for mechano-transduction to maintain bone homeostasis, it is relevant to address the bone adverse effects associated with muscle condition after this intervention. Our aim is to condense the current and relevant literature about mandibular bone loss in fully mature mammals after BoNT/A intervention in the masticatory muscles. Here, we compile evidence from animal models (mice, rats, and rabbits) to clinical studies, demonstrating that BoNT/A-induced masticatory muscle atrophy promotes mandibular bone loss. Mandibular bone-related adverse effects involve cellular and metabolic changes, microstructure degradation, and morphological alterations. While bone loss has been detected at the mandibular condyle or alveolar bone, cellular and molecular mechanisms involved in this process must still be elucidated. Further basic research could provide evidence for designing strategies to control the undesired effects on bone during the therapeutic use of BoNT/A. However, in the meantime, we consider it essential that patients treated with BoNT/A in the masticatory muscles be warned about a putative collateral mandibular bone damage.

Description: Mycotoxins are produced by a number of fungal genera spp., for example, Aspergillus, Penicillium, Alternaria, Fusarium, and Claviceps. Beauvericin (BEA) and Ochratoxin A (OTA) are present in various cereal crops and processed grains. This goal of this study was to determine their combination effect in HepG2 cells, presented for the first time. In this study, the type of interaction among BEA and OTA through an isobologram method, cell cycle disturbance by flow cytometry, and genotoxic potential by in vitro micronucleus (MN) assay following the TG 487 (OECD, 2016) of BEA and OTA individually and combined in HepG2 cells are presented. Cytotoxic concentration ranges studied by the MTT assay over 24, 48, and 72 h were from 0 to 25 µM for BEA and from 0 to 100 µM for OTA, while BEA + OTA combinations were at a 1:10 ratio from 3.4 to 27.5 µM. The toxicity observed for BEA was higher than for OTA at all times assayed; additive and synergistic effects were detected for their mixtures. Cell cycle arrest in the G0/G1 phase was detected for OTA and BEA + OTA treatments in HepG2 cells. Genotoxicity revealed significant effects for BEA, OTA, and in combinations underlining the importance of studying real exposure scenarios of chronic exposure to mycotoxins.

Description: A teratogenic agent or teratogen can disturb the development of an embryo or a fetus. Fumonisin B1 (FB1), produced by Fusarium verticillioides and F. proliferatum, is among the most commonly seen mycotoxins and contaminants from stale maize and other farm products. It may cause physical or functional defects in embryos or fetuses, if the pregnant animal is exposed to mycotoxin FB1. Due to its high similarity in chemical structure with lipid sphinganine (Sa) and sphingosine (So), the primary component of sphingolipids, FB1 plays a role in competitively inhibiting Sa and So, which are key enzymes in de novo ceramide synthase in the sphingolipid biosynthetic pathway. Therefore, it causes growth retardation and developmental abnormalities to the embryos of hamsters, rats, mice, and chickens. Moreover, maternal FB1 toxicity can be passed onto the embryo or fetus, leading to mortality. FB1 also disrupts folate metabolism via the high-affinity folate transporter that can then result in folate insufficiency. The deficiencies are closely linked to incidences of neural tube defects (NTDs) in mice or humans. The purpose of this review is to understand the toxicity and mechanisms of mycotoxin FB1 on the development of embryos or fetuses.