A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape.

Interferon-stimulated genes (ISGs) form the backbone of the innate immune system and are important for limiting intra- and intercellular viral replication and spread. We conducted a mass-spectrometry-based survey to understand the fundamental organization of the innate immune system and to explore the molecular functions of individual ISGs. We identified interactions between 104 ISGs and 1,401 cellular binding partners engaging in 2,734 high-confidence interactions. 90% of these interactions are unreported so far, and our survey therefore illuminates a far wider activity spectrum of ISGs than is currently known. Integration of the resulting ISG-interaction network with published datasets and functional studies allowed us to identify regulators of immunity and processes related to the immune system. Given the extraordinary robustness of the innate immune system, this ISG network may serve as a blueprint for therapeutic targeting of cellular systems to efficiently fight viral infections.

Eliminating first trimester combined testing: Consequences for early detection of significant fetal anomalies.

OBJECTIVE: To determine whether implementation of cell-free DNA (cfDNA) testing for aneuploidy as a first-tier test and subsequent abolition of first trimester combined testing (FCT) affected the first trimester detection (<14 weeks) of certain fetal anomalies. METHODS: We performed a geographical cohort study in two Fetal Medicine Units between 2011 and 2020, including 705 fetuses with prenatally detected severe brain, abdominal wall and congenital heart defects. Cases were divided into two groups: before (n = 396) and after (n = 309) cfDNA introduction. The primary outcome was the first trimester detection rate (<14 weeks) overall and for non-chromosomal anomalies solely. RESULTS: Overall, gastroschisis, AVSD and HLHS were detected more often in the first trimester in the before group compared to the after group, respectively 54.5% versus 18.5% (p = 0.004), 45.9% versus 26.9% (p = 0.008) and 30% versus 3.4% (p = 0.005). After exclusion of chromosomal anomalies identifiable through cfDNA testing, the detection of AVSD remained higher in the before group (43.3% vs. 9.5%, p = 0.02), leading to a possible earlier gestation at termination. The termination of pregnancy (TOP) rate did not differ among the groups. In the after group, referrals for suspected anomalies following a dating scan between 11 and 14 weeks significantly increased from 17.4% to 29.1% (p < 0.001). CONCLUSION: This study underscores the value of a scan dedicated to fetal anatomy in the first trimester as we observed a decline in the early detection of certain fetal anomalies (detectable in the first trimester) subsequent to the abolition of FCT.

Congenital small bowel obstruction: Prenatal detection and outcome.

OBJECTIVE: To evaluate and compare the outcome of fetuses and neonates with congenital small bowel obstructions (SBO), evaluate the screening performance of prenatal ultrasound for SBO and identify possible risk factors for adverse outcomes. METHODS: All cases referred to the Amsterdam University Medical Centers between 2007 and 2021 for a prenatal suspected SBO, supplemented by cases of postnatal diagnosis of SBO, were included. The primary outcome was survival after 24 weeks of gestation until the first year of life. RESULTS: 147 cases of SBO were included with a survival rate of 86.2% (119/138) after 24 weeks of gestation until the first year of age. Additional structural or chromosomal anomalies were found to have an increased risk of adverse outcomes. Intrauterine fetal demise occurred in 10/147 (6.8%) cases and 9/147 (6.1%) cases died during postnatal follow-up. The overall positive predictive value of all prenatally diagnosed cases was 91.5%. Surgical correction was performed in 123/128 (96.0%) of the live-born cases. CONCLUSIONS: Congenital SBO has an overall favorable prognosis, but the outcome is negatively impacted by the possible presence of additional structural or chromosomal anomalies. Fetal monitoring in the early third trimester should be considered, since all cases of Intrauterine fetal demise occurred between 30 and 35 weeks of gestation.

Individual motion perception parameters and motion sickness frequency sensitivity in fore-aft motion.

Previous literature suggests a relationship between individual characteristics of motion perception and the peak frequency of motion sickness sensitivity. Here, we used well-established paradigms to relate motion perception and motion sickness on an individual level. We recruited 23 participants to complete a two-part experiment. In the first part, we determined individual velocity storage time constants from perceived rotation in response to Earth Vertical Axis Rotation (EVAR) and subjective vertical time constants from perceived tilt in response to centrifugation. The cross-over frequency for resolution of the gravito-inertial ambiguity was derived from our data using the Multi Sensory Observer Model (MSOM). In the second part of the experiment, we determined individual motion sickness frequency responses. Participants were exposed to 30-minute sinusoidal fore-aft motions at frequencies of 0.15, 0.2, 0.3, 0.4 and 0.5 Hz, with a peak amplitude of 2 m/s2 in five separate sessions, approximately 1 week apart. Sickness responses were recorded using both the MIsery SCale (MISC) with 30 s intervals, and the Motion Sickness Assessment Questionnaire (MSAQ) at the end of the motion exposure. The average velocity storage and subjective vertical time constants were 17.2 s (STD = 6.8 s) and 9.2 s (STD = 7.17 s). The average cross-over frequency was 0.21 Hz (STD = 0.10 Hz). At the group level, there was no significant effect of frequency on motion sickness. However, considerable individual variability was observed in frequency sensitivities, with some participants being particularly sensitive to the lowest frequencies, whereas others were most sensitive to intermediate or higher frequencies. The frequency of peak sensitivity did not correlate with the velocity storage time constant (r = 0.32, p = 0.26) or the subjective vertical time constant (r = - 0.37, p = 0.29). Our prediction of a significant correlation between cross-over frequency and frequency sensitivity was not confirmed (r = 0.26, p = 0.44). However, we did observe a strong positive correlation between the subjective vertical time constant and general motion sickness sensitivity (r = 0.74, p = 0.0006). We conclude that frequency sensitivity is best considered a property unique to the individual. This has important consequences for existing models of motion sickness, which were fitted to group averaged sensitivities. The correlation between the subjective vertical time constant and motion sickness sensitivity supports the importance of verticality perception during exposure to translational sickness stimuli.

Adaptation aftereffects reveal representations for encoding of contingent social actions.

A hallmark of human social behavior is the effortless ability to relate one's own actions to that of the interaction partner, e.g., when stretching out one's arms to catch a tripping child. What are the behavioral properties of the neural substrates that support this indispensable human skill? Here we examined the processes underlying the ability to relate actions to each other, namely the recognition of spatiotemporal contingencies between actions (e.g., a "giving" that is followed by a "taking"). We used a behavioral adaptation paradigm to examine the response properties of perceptual mechanisms at a behavioral level. In contrast to the common view that action-sensitive units are primarily selective for one action (i.e., primary action, e.g., 'throwing"), we demonstrate that these processes also exhibit sensitivity to a matching contingent action (e.g., "catching"). Control experiments demonstrate that the sensitivity of action recognition processes to contingent actions cannot be explained by lower-level visual features or amodal semantic adaptation. Moreover, we show that action recognition processes are sensitive only to contingent actions, but not to noncontingent actions, demonstrating their selective sensitivity to contingent actions. Our findings show the selective coding mechanism for action contingencies by action-sensitive processes and demonstrate how the representations of individual actions in social interactions can be linked in a unified representation.

The role of acceleration and jerk in perception of above-threshold surge motion.

Inertial motions may be defined in terms of acceleration and jerk, the time-derivative of acceleration. We investigated the relative contributions of these characteristics to the perceived intensity of motions. Participants were seated on a high-fidelity motion platform, and presented with 25 above-threshold 1 s forward (surge) motions that had acceleration values ranging between 0.5 and 2.5 [Formula: see text] and jerks between 20 and 60 [Formula: see text], in five steps each. Participants performed two tasks: a magnitude estimation task, where they provided subjective ratings of motion intensity for each motion, and a two-interval forced choice task, where they provided judgments on which motion of a pair was more intense, for all possible combinations of the above motion profiles. Analysis of the data shows that responses on both tasks may be explained by a single model, and that this model should include acceleration only. The finding that perceived motion intensity depends on acceleration only appears inconsistent with previous findings. We show that this discrepancy can be explained by considering the frequency content of the motions, and demonstrate that a linear time-invariant systems model of the otoliths and subsequent processing can account for the present data as well as for previous findings.

Perceiving animacy purely from visual motion cues involves intraparietal sulcus.

Distinguishing animate from inanimate objects is fundamental for social perception in humans and animals. Visual motion cues indicative of self-propelled object motion are useful for animacy perception: they can be detected over a wide expanse of visual field, at distance and in low visibility conditions, can attract attention and provide clues about object behaviour. However, the neural correlates of animacy perception evoked exclusively by visual motion cues, i.e. not relying on form, background or visual context, are unclear. We aimed to address this question in four psychophysical experiments in humans, two of which performed during neuroimaging. The stimulus was a single dot with constant form that moved on a blank background and evoked controlled degrees of perceived animacy through parametric variations of self-propelled motion cues. BOLD signals reflecting perceived animacy in a graded manner irrespective of eye movements were found in one intraparietal region. Additional whole-brain and region-of-interest analyses revealed no comparable effects in brain regions associated with social processing or other areas. Our study shows that animacy perception evoked solely by visual motion cues, a basic perceptual process in social cognition, engages brain regions not primarily associated with social cognition.

Two Ways to Facial Expression Recognition? Motor and Visual Information Have Different Effects on Facial Expression Recognition.

Motor-based theories of facial expression recognition propose that the visual perception of facial expression is aided by sensorimotor processes that are also used for the production of the same expression. Accordingly, sensorimotor and visual processes should provide congruent emotional information about a facial expression. Here, we report evidence that challenges this view. Specifically, the repeated execution of facial expressions has the opposite effect on the recognition of a subsequent facial expression than the repeated viewing of facial expressions. Moreover, the findings of the motor condition, but not of the visual condition, were correlated with a nonsensory condition in which participants imagined an emotional situation. These results can be well accounted for by the idea that facial expression recognition is not always mediated by motor processes but can also be recognized on visual information alone.

Cue reactivity towards bodies in anorexia nervosa - common and differential effects in adolescents and adults.

BACKGROUND: Aberrant reward mechanisms with regard to slim body shapes are discussed in patients with anorexia nervosa (AN). The aim of the present study was to examine of cue reactivity toward body shapes in AN via the late positive potential (LPP), an event-related electroencephalography (EEG) component. By including adolescents and adults, aspects of development and chronification could be studied (2 × 2 design). METHODS: Thirty-two female AN patients (19 adolescents and 13 adults) and 37 control participants (16 adolescents and 21 adults) were included. Standardized photographic stimuli showing women's bodies in underwear from five body mass index (BMI) categories (extremely underweight to extremely overweight) were presented. During picture evaluation, EEG activity was recorded (10-20 system). The LPP was measured in two time windows characterized by different topographies (450-700 ms: posterior; 1000-1300 ms: central). RESULTS: Regarding the posterior component, LPP amplitudes were clearly reduced in adult but not in adolescent patients; for both time windows the LPP showed differential patterns over BMI categories for patients and controls. Regarding the central component, a highly significant linear decrease from extremely underweight to extremely overweight body shapes was revealed in patients and no significant modulation in control participants. CONCLUSIONS: Adolescent and adult patients show increased sustained attention toward extremely underweight bodies. In chronically ill patients, this bias appears to be accompanied by generally reduced automatic attention. The LPP findings provide a differentiated picture of aberrant cue reactivity which could be interpreted as motivated attention toward body shapes in AN.

More vection means more velocity storage activity: a factor in visually induced motion sickness?

Full-field visual rotation around the vertical axis induces a sense of self-motion (vection), optokinetic nystagmus (OKN), and, eventually, also motion sickness (MS). If the lights are then suddenly switched off, optokinetic afternystagmus (OKAN) occurs. This is due to the discharge of the velocity storage mechanism (VSM), a central integrative network that has been suggested to be involved in motion sickness. We previously showed that visually induced motion sickness (VIMS) following optokinetic stimulation is dependent on vection intensity. To shed light on this relationship, the current study investigated whether vection intensity is related to VSM activity, and thus, to the OKAN. In repetitive trials (eight per condition), 15 stationary participants were exposed to 120 s of visual yaw rotation (60°/s), followed by 90 s in darkness. The visual stimulus either induced strong vection (i.e., scene rotating normally) or weak vection (central and peripheral part moving in opposite directions). Eye movements and subjective vection intensity were continuously measured. Results showed that OKAN occurred less frequently and with lower initial magnitude in the weak-vection condition compared to the strong-vection condition. OKAN decay time constants were not significantly different. The results suggest that the stimuli that produced strong vection also enhanced the charging of the VSM. As VSM activity presumably is a factor in motion sickness, the enhanced VSM activity in our strong-vection condition hints at an involvement of the VSM in VIMS, and could explain why visual stimuli producing a strong sense of vection also elicit high levels of VIMS.

Body-relative horizontal-vertical anisotropy in human representations of traveled distances.

A growing number of studies investigated anisotropies in representations of horizontal and vertical spaces. In humans, compelling evidence for such anisotropies exists for representations of multi-floor buildings. In contrast, evidence regarding open spaces is indecisive. Our study aimed at further enhancing the understanding of horizontal and vertical spatial representations in open spaces utilizing a simple traveled distance estimation paradigm. Blindfolded participants were moved along various directions in the sagittal plane. Subsequently, participants passively reproduced the traveled distance from memory. Participants performed this task in an upright and in a 30° backward-pitch orientation. The accuracy of distance estimates in the upright orientation showed a horizontal-vertical anisotropy, with higher accuracy along the horizontal axis compared with the vertical axis. The backward-pitch orientation enabled us to investigate whether this anisotropy was body or earth-centered. The accuracy patterns of the upright condition were positively correlated with the body-relative (not the earth-relative) coordinate mapping of the backward-pitch condition, suggesting a body-centered anisotropy. Overall, this is consistent with findings on motion perception. It suggests that the distance estimation sub-process of path integration is subject to horizontal-vertical anisotropy. Based on the previous studies that showed isotropy in open spaces, we speculate that real physical self-movements or categorical versus isometric encoding are crucial factors for (an)isotropies in spatial representations.

Decoding visual roughness perception: an fMRI study.

The neural substrates of tactile roughness perception have been investigated by many neuroimaging studies, while relatively little effort has been devoted to the investigation of neural representations of visually perceived roughness. In this human fMRI study, we looked for neural activity patterns that could be attributed to five different roughness intensity levels when the stimuli were perceived visually, i.e., in absence of any tactile sensation. During functional image acquisition, participants viewed video clips displaying a right index fingertip actively exploring the sandpapers that had been used for the behavioural experiment. A whole brain multivariate pattern analysis found four brain regions in which visual roughness intensities could be decoded: the bilateral posterior parietal cortex (PPC), the primary somatosensory cortex (S1) extending to the primary motor cortex (M1) in the right hemisphere, and the inferior occipital gyrus (IOG). In a follow-up analysis, we tested for correlations between the decoding accuracies and the tactile roughness discriminability obtained from a preceding behavioural experiment. We could not find any correlation between both although, during scanning, participants were asked to recall the tactilely perceived roughness of the sandpapers. We presume that a better paradigm is needed to reveal any potential visuo-tactile convergence. However, the present study identified brain regions that may subserve the discrimination of different intensities of visual roughness. This finding may contribute to elucidate the neural mechanisms related to the visual roughness perception in the human brain.

No advantage for remembering horizontal over vertical spatial locations learned from a single viewpoint.

Previous behavioral and neurophysiological research has shown better memory for horizontal than for vertical locations. In these studies, participants navigated toward these locations. In the present study we investigated whether the orientation of the spatial plane per se was responsible for this difference. We thus had participants learn locations visually from a single perspective and retrieve them from multiple viewpoints. In three experiments, participants studied colored tags on a horizontally or vertically oriented board within a virtual room and recalled these locations with different layout orientations (Exp. 1) or from different room-based perspectives (Exps. 2 and 3). All experiments revealed evidence for equal recall performance in horizontal and vertical memory. In addition, the patterns for recall from different test orientations were rather similar. Consequently, our results suggest that memory is qualitatively similar for both vertical and horizontal two-dimensional locations, given that these locations are learned from a single viewpoint. Thus, prior differences in spatial memory may have originated from the structure of the space or the fact that participants navigated through it. Additionally, the strong performance advantages for perspective shifts (Exps. 2 and 3) relative to layout rotations (Exp. 1) suggest that configurational judgments are not only based on memory of the relations between target objects, but also encompass the relations between target objects and the surrounding room-for example, in the form of a memorized view.

Effects of visual stimulus characteristics and individual differences in heading estimation.

Visual heading estimation is subject to periodic patterns of constant (bias) and variable (noise) error. The nature of the errors, however, appears to differ between studies, showing underestimation in some, but overestimation in others. We investigated whether field of view (FOV), the availability of binocular disparity cues, motion profile, and visual scene layout can account for error characteristics, with a potential mediating effect of vection. Twenty participants (12 females) reported heading and rated vection for visual horizontal motion stimuli with headings ranging the full circle, while we systematically varied the above factors. Overall, the results show constant errors away from the fore-aft axis. Error magnitude was affected by FOV, disparity, and scene layout. Variable errors varied with heading angle, and depended on scene layout. Higher vection ratings were associated with smaller variable errors. Vection ratings depended on FOV, motion profile, and scene layout, with the highest ratings for a large FOV, cosine-bell velocity profile, and a ground plane scene rather than a dot cloud scene. Although the factors did affect error magnitude, differences in its direction were observed only between participants. We show that the observations are consistent with prior beliefs that headings align with the cardinal axes, where the attraction of each axis is an idiosyncratic property.

Auditory Task Irrelevance: A Basis for Inattentional Deafness.

Objective This study investigates the neural basis of inattentional deafness, which could result from task irrelevance in the auditory modality. Background Humans can fail to respond to auditory alarms under high workload situations. This failure, termed inattentional deafness, is often attributed to high workload in the visual modality, which reduces one's capacity for information processing. Besides this, our capacity for processing auditory information could also be selectively diminished if there is no obvious task relevance in the auditory channel. This could be another contributing factor given the rarity of auditory warnings. Method Forty-eight participants performed a visuomotor tracking task while auditory stimuli were presented: a frequent pure tone, an infrequent pure tone, and infrequent environmental sounds. Participants were required either to respond to the presentation of the infrequent pure tone (auditory task-relevant) or not (auditory task-irrelevant). We recorded and compared the event-related potentials (ERPs) that were generated by environmental sounds, which were always task-irrelevant for both groups. These ERPs served as an index for our participants' awareness of the task-irrelevant auditory scene. Results Manipulation of auditory task relevance influenced the brain's response to task-irrelevant environmental sounds. Specifically, the late novelty-P3 to irrelevant environmental sounds, which underlies working memory updating, was found to be selectively enhanced by auditory task relevance independent of visuomotor workload. Conclusion Task irrelevance in the auditory modality selectively reduces our brain's responses to unexpected and irrelevant sounds regardless of visuomotor workload. Application Presenting relevant auditory information more often could mitigate the risk of inattentional deafness.

Assortative Matching with Inequality in Voluntary Contribution Games.

Voluntary contribution games are a classic social dilemma in which the individually dominant strategies result in a poor performance of the population. However, the negative zero-contribution predictions from these types of social dilemma situations give way to more positive (near-)efficient ones when assortativity, instead of random mixing, governs the matching process in the population. Under assortative matching, agents contribute more than what would otherwise be strategically rational in order to be matched with others doing likewise. An open question has been the robustness of such predictions when heterogeneity in budgets amongst individuals is allowed. Here, we show analytically that the consequences of permitting heterogeneity depend crucially on the exact nature of the underlying public-good provision efficacy, but generally are rather devastating. Using computational methods, we quantify the loss resulting from heterogeneity vis-a-vis the homogeneous case as a function of (i) the public-good provision efficacy and (ii) the population inequality.

Response to Tyrosine Kinase Inhibitors in Myeloproliferative Neoplasia with 8p11 Translocation and CEP110-FGFR1 Rearrangement.

This brief communication reports on a patient with an exceedingly rare "8p11 (eight-p-eleven) myeloproliferative syndrome" (EMS) with CEP110-FGFR1 rearrangement who responded to treatment with the multi-tyrosine kinase inhibitor (TKI) dasatinib. Dasatinib improved quality of life substantially by increasing blood counts and reducing the need for transfusions. This report demonstrates that the second-generation TKI may provide a therapeutic option for elderly and frail EMS patients who cannot be offered aggressive therapy, including allogeneic hematopoietic cell transplantation. The Oncologist 2017;22:480-483.

Prenatal and adult androgen activities in alcohol dependence.

OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.

Abstract representations of associated emotions in the human brain.

Emotions can be aroused by various kinds of stimulus modalities. Recent neuroimaging studies indicate that several brain regions represent emotions at an abstract level, i.e., independently from the sensory cues from which they are perceived (e.g., face, body, or voice stimuli). If emotions are indeed represented at such an abstract level, then these abstract representations should also be activated by the memory of an emotional event. We tested this hypothesis by asking human participants to learn associations between emotional stimuli (videos of faces or bodies) and non-emotional stimuli (fractals). After successful learning, fMRI signals were recorded during the presentations of emotional stimuli and emotion-associated fractals. We tested whether emotions could be decoded from fMRI signals evoked by the fractal stimuli using a classifier trained on the responses to the emotional stimuli (and vice versa). This was implemented as a whole-brain searchlight, multivoxel activation pattern analysis, which revealed successful emotion decoding in four brain regions: posterior cingulate cortex (PCC), precuneus, MPFC, and angular gyrus. The same analysis run only on responses to emotional stimuli revealed clusters in PCC, precuneus, and MPFC. Multidimensional scaling analysis of the activation patterns revealed clear clustering of responses by emotion across stimulus types. Our results suggest that PCC, precuneus, and MPFC contain representations of emotions that can be evoked by stimuli that carry emotional information themselves or by stimuli that evoke memories of emotional stimuli, while angular gyrus is more likely to take part in emotional memory retrieval.