Acanthamoeba castellanii induces host cell death via a phosphatidylinositol 3-kinase-dependent mechanism

Granulomatous amoebic encephalitis due to Acanthamoeba castellanii is a serious human infection with fatal consequences, but it is not clear how the circulating amoebae interact with the blood-brain barrier and transmigrate into the central nervous system. We studied the effects of an Acanthamoeba encephalitis isolate belonging to the T1 genotype on human brain microvascular endothelial cells, which constitute the blood-brain barrier. Using an apoptosis-specific enzyme-linked immunosorbent assay, we showed that Acanthamoeba induces programmed cell death in brain microvascular endothelial cells. Next, we observed that Acanthamoeba specifically activates phosphatidylinositol 3-kinase. Acanthamoeba-mediated brain endothelial cell death was abolished using LY294002, a phosphatidylinositol 3-kinase inhibitor. These results were further confirmed using brain microvascular endothelial cells expressing dominant negative forms of phosphatidylinositol 3-kinase. This is the first demonstration that Acanthamoeba-mediated brain microvascular endothelial cell death is dependent on phosphatidylinositol 3-kinase

Patterns of postural sway in high anxious children

This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Magnetoencephalographic Signals Identify Stages in Real-Life Decision Processes

We used magnetoencephalography (MEG) to study the dynamics of neural responses in eight subjects engaged in shopping for day-to-day items from supermarket shelves. This behavior not only has personal and economic importance but also provides an example of an experience that is both personal and shared between individuals. The shopping experience enables the exploration of neural mechanisms underlying choice based on complex memories. Choosing among different brands of closely related products activated a robust sequence of signals within the first second after the presentation of the choice images. This sequence engaged first the visual cortex (80-100 ms), then as the images were analyzed, predominantly the left temporal regions (310-340 ms). At longer latency, characteristic neural activetion was found in motor speech areas (500-520 ms) for images requiring low salience choices with respect to previous (brand) memory, and in right parietal cortex for high salience choices (850-920 ms). We argue that the neural processes associated with the particular brand-choice stimulus can be separated into identifiable stages through observation of MEG responses and knowledge of functional anatomy

Citrulline protects mice from experimental cerebral malaria by ameliorating hypoargininemia, urea cycle changes and vascular leak

© 2019 Gramaglia et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Clinical and model studies indicate that low nitric oxide (NO) bioavailability due in part to profound hypoargininemia contributes to cerebral malaria (CM) pathogenesis. Protection against CM pathogenesis may be achieved by altering the diet before infection with Plasmodium falcIParum infection (nutraceutical) or by administering adjunctive therapy that decreases CM mortality (adjunctive therapy). This hypothesis was tested by administering citrulline or arginine in experimental CM (eCM). We report that citrulline injected as prophylaxis immediately post infection (PI) protected virtually all mice by ameliorating (i) hypoargininemia, (ii) urea cycle impairment, and (iii) disruption of blood brain barrier. Citrulline prophylaxis inhibited plasma arginase activity. Parasitemia was similar in citrulline- And vehicle control-groups, indicating that protection from pathogenesis was not due to decreased parasitemia. Both citrulline and arginine administered from day 1 PI in the drinking water significantly protected mice from eCM. These observations collectively indicate that increasing dietary citrulline or arginine decreases eCM mortality. Citrulline injected IP on day 4 PI with quinine-injected IP on day 6 PI partially protected mice from eCM; citrulline plus scavenging of superoxide with pegylated superoxide dismutase and pegylated catalase protected all recIPients from eCM. These findings indicate that ameliorating hypoargininemia with citrulline plus superoxide scavenging decreases eCM mortality

Conditional accuracy in response interference tasks: Evidence from the Eriksen flanker task and the spatial conflict task

Two well-known response interference tasks are the Eriksen flanker task and the spatial conflict task. The tasks are logically equivalent, and comparable effects of current and previous stimulus type (congruent or incongruent) have been shown with regard to reaction time (RT). Here, we investigated whether interference and sequential trial effects also had comparable effects on accuracy. We specifically tested whether these effects interacted with the speed of responding using conditional accuracy functions (CAFs). The CAFs revealed that in both tasks congruency and sequential trial effects on accuracy are found only in trials with fast responses (< 600 ms). Sequential trial effects on accuracy were weaker for the flanker task than for the spatial conflict task. In very fast trials (< 400 ms) response activation by distracting flankers led to below-chance performance in the flanker task, but response activation by incongruent spatial location did not lead to below-chance performance in the spatial conflict task. The pattern of results hints at subtle differences in processing architecture between the tasks

Effects of affective picture viewing on postural control

<p>Abstract</p> <p>Background</p> <p>Emotion theory holds that unpleasant events prime withdrawal actions, whereas pleasant events prime approach actions. Recent studies have suggested that passive viewing of emotion eliciting images results in postural adjustments, which become manifest as changes in body center of pressure (COP) trajectories. From those studies it appears that posture is modulated most when viewing pictures with negative valence. The present experiment was conducted to test the hypothesis that pictures with negative valence have a greater impact on postural control than neutral or positive ones. Thirty-four healthy subjects passively viewed a series of emotion eliciting images, while standing either in a bipedal or unipedal stance on a force plate. The images were adopted from the International Affective Picture System (IAPS). We analysed mean and variability of the COP and the length of the associated sway path as a function of emotion.</p> <p>Results</p> <p>The mean position of the COP was unaffected by emotion, but unipedal stance resulted in overall greater body sway than bipedal stance. We found a modest effect of emotion on COP: viewing pictures of mutilation resulted in a smaller sway path, but only in unipedal stance. We obtained valence and arousal ratings of the images with an independent sample of viewers. These subjects rated the unpleasant images as significantly less pleasant than neutral images, and the pleasant images as significantly more pleasant than neutral images. However, the subjects rated the images as overall less pleasant and less arousing than viewers in a closely comparable American study, pointing to unknown differences in viewer characteristics.</p> <p>Conclusion</p> <p>Overall, viewing emotion eliciting images had little effect on body sway. Our finding of a reduction in sway path length when viewing pictures of mutilation was indicative of a freezing strategy, i.e. fear bradycardia. The results are consistent with current knowledge about the neuroanatomical organization of the emotion system and the neural control of behavior.</p

Human blood-brain barrier receptors for Alzheimer's amyloid-beta 1- 40. Asymmetrical binding, endocytosis, and transcytosis at the apical side of brain microvascular endothelial cell monolayer.

This is the published version. Copyright 1998 by American Society for Clinical Investigation.A soluble monomeric form of Alzheimer's amyloid-beta (1-40) peptide (sAbeta1-40) is present in the circulation and could contribute to neurotoxicity if it crosses the brain capillary endothelium, which comprises the blood-brain barrier (BBB) in vivo. This study characterizes endothelial binding and transcytosis of a synthetic peptide homologous to human sAbeta1-40 using an in vitro model of human BBB. 125I-sAbeta1-40 binding to the brain microvascular endothelial cell monolayer was time dependent, polarized to the apical side, and saturable with high- and low-affinity dissociation constants of 7.8+/-1.2 and 52.8+/-6.2 nM, respectively. Binding of 125I-sAbeta1-40 was inhibited by anti-RAGE (receptor for advanced glycation end products) antibody (63%) and by acetylated low density lipoproteins (33%). Consistent with these data, transfected cultured cells overexpressing RAGE or macrophage scavenger receptor (SR), type A, displayed binding and internalization of 125I-sAbeta1-40. The internalized peptide remains intact > 94%. Transcytosis of 125I-sAbeta1-40 was time and temperature dependent, asymmetrical from the apical to basolateral side, saturable with a Michaelis constant of 45+/-9 nM, and partially sensitive to RAGE blockade (36%) but not to SR blockade. We conclude that RAGE and SR mediate binding of sAbeta1-40 at the apical side of human BBB, and that RAGE is also involved in sAbeta1-40 transcytosis

Examining links between anxiety, reinvestment and walking when talking by older adults during adaptive gait

Falls by older adults often result in reduced quality of life and debilitating fear of further falls. Stopping walking when talking (SWWT) is a significant predictor of future falls by older adults and is thought to reflect age-related increases in attentional demands of walking. We examine whether SWWT is associated with use of explicit movement cues during locomotion, and evaluate if conscious control (i.e., movement specific reinvestment) is causally linked to falls-related anxiety during a complex walking task. We observed whether twenty-four older adults stopped walking when talking when asked a question during an adaptive gait task. After certain trials, participants completed a visual-spatial recall task regarding walkway features, or answered questions about their movements during the walk. In a subsequent experimental condition, participants completed the walking task under conditions of raised postural threat. Compared to a control group, participants who SWWT reported higher scores for aspects of reinvestment relating to conscious motor processing but not movement self-consciousness. The higher scores for conscious motor processing were preserved when scores representing cognitive function were included as a covariate. There were no group differences in measures of general cognitive function, visual spatial working memory or balance confidence. However, the SWWT group reported higher scores on a test of external awareness when walking, indicating allocation of attention away from task-relevant environmental features. Under conditions of increased threat, participants self-reported significantly greater state anxiety and reinvestment and displayed more accurate responses about their movements during the task. SWWT is not associated solely with age-related cognitive decline or generic increases in age-related attentional demands of walking. SWWT may be caused by competition for phonological resources of working memory associated with consciously processing motor actions and appears to be causally linked with fall-related anxiety and increased vigilance.This research was supported by The Royal Society (IE131576) and British Academy (SG132820)

Posture as Index for Approach-Avoidance Behavior

Approach and avoidance are two behavioral responses that make people tend to approach positive and avoid negative situations. This study examines whether postural behavior is influenced by the affective state of pictures. While standing on the Wii™ Balance Board, participants viewed pleasant, neutral, and unpleasant pictures (passively viewing phase). Then they had to move their body to the left or the right (lateral movement phase) to make the next picture appear. We recorded movements in the anterior-posterior direction to examine approach and avoidant behavior. During passively viewing, people approached pleasant pictures. They avoided unpleasant ones while they made a lateral movement. These findings provide support for the idea that we tend to approach positive and avoid negative situations

Contribution of Each Leg to the Control of Unperturbed Bipedal Stance in Lower Limb Amputees: New Insights Using Entropy

The present study was designed to assess the relative contribution of each leg to unperturbed bipedal posture in lower limb amputees. To achieve this goal, eight unilateral traumatic trans-femoral amputees (TFA) were asked to stand as still as possible on a plantar pressure data acquisition system with their eyes closed. Four dependent variables were computed to describe the subject's postural behavior: (1) body weight distribution, (2) amplitude, (3) velocity and (4) regularity of centre of foot pressure (CoP) trajectories under the amputated (A) leg and the non-amputated (NA) leg. Results showed a larger body weight distribution applied to the NA leg than to the A leg and a more regular CoP profiles (lower sample entropy values) with greater amplitude and velocity under the NA leg than under the A leg. Taken together, these findings suggest that the NA leg and the A leg do not equally contribute to the control of unperturbed bipedal posture in TFA. The observation that TFA do actively control unperturbed bipedal posture with their NA leg could be viewed as an adaptive process to the loss of the lower leg afferents and efferents because of the unilateral lower-limb amputation. From a methodological point of view, these results demonstrate the suitability of computing bilateral CoP trajectories regularity for the assessment of lateralized postural control under pathological conditions