Detecting one's own errors and appropriately correcting behavior are crucial for efficient goal-directed performance. A correlate of rapid evaluation of behavioral outcomes is the error-related negativity (Ne/ERN) which emerges at the time of the erroneous response over frontal brain areas. However, whether the error monitoring system's ability to distinguish between errors and correct responses at this early time point is a necessary precondition for the subsequent emergence of error awareness remains unclear. The present study investigated this question using error-related brain activity and vocal error signaling responses in seven human patients with lesions in the rostral anterior cingulate cortex (rACC) and adjoining ventromedial prefrontal cortex, while they performed a flanker task. The difference between errors and correct responses was severely attenuated in these patients indicating impaired rapid error monitong, but they showed no impairment in error signaling. However, impaired rapid error monitoring coincided with a failure to increase response accuracy on trials following errors. These results demonstrate that the error monitoring system's ability to distinguish between errors and correct responses at the time of the response is crucial for adaptive post-error adjustments, but not a necessary precondition for error awareness.

Apicomplexan parasites such as Toxoplasma gondii rely on actin-based motility to cross biological barriers and invade host cells. Key structural and biochemical differences in host and parasite actins make this an attractive target for small-molecule inhibitors. Here we took advantage of recent advances in the synthesis of cyclic depsipeptide compounds that stabilize filamentous actin to test the ability of chondramides to disrupt growth of T. gondii in vitro. Structural modeling of chondramide A (2) binding to an actin filament model revealed variations in the binding site between host and parasite actins. A series of 10 previously synthesized analogues (2b-k) with substitutions in the β-tyrosine moiety blocked parasite growth on host cell monolayers with EC₅₀ values that ranged from 0.3 to 1.3 μM. In vitro polymerization assays using highly purified recombinant actin from T. gondii verified that synthetic and natural product chondramides target the actin cytoskeleton. Consistent with this, chondramide treatment blocked parasite invasion into host cells and was more rapidly effective than pyrimethamine, a standard therapeutic agent. Although the current compounds lack specificity for parasite vs host actin, these studies provide a platform for the future design and synthesis of synthetic cyclic peptide inhibitors that selectively disrupt actin dynamics in parasites.

The present study investigated adjustments of selective attention following errors and their relation to the error-related negativity (Ne/ERN), a correlate of errors in event-related potentials. We hypothesized that, if post-error adjustments reflect an adaptive mechanism that should prevent the occurrence of further errors, then adjustments of attentional selectivity should be observed only following errors due to insufficient selective attention. To test this, a four-choice flanker task was used in which errors due to insufficient selective attention (flanker errors) and other errors (nonflanker errors) could be distinguished. We found strong adjustments of selective attention following flanker errors but not following nonflanker errors. Moreover, the Ne/ERN amplitude was correlated with adjustments of selective attention on a trial-by-trial basis. The results provide support for the notion that the Ne/ERN is a correlate of adaptive adjustments following errors.

Violations of outcome expectancies have been proposed to account for error-related brain activity in the medial prefrontal cortex. The present study investigated whether early error monitoring processes are sensitive only to the expectancy of errors, or whether these processes also evaluate the significance of errors. To this end, we considered the error-related negativity (Ne/ERN), an electrophysiological marker of early error monitoring, in a modified flanker task in which errors could occur because participants responded to the flankers instead of the target (flanker error) or because a response unrelated to the stimulus was given (nonflanker error). By manipulating the onset of the flankers relative to the target, we manipulated two variables: the probability (and thus the expectancy) of flanker errors and the proportion of significant attention errors among each error type. Contrary to the predictions of outcome expectancy accounts, we found that the Ne/ERN was larger for flanker errors than for nonflanker errors only in the condition in which flanker errors were particularly frequent. Consistent with the error significance account, however, Ne/ERN amplitude mirrored the estimated proportion of significant attention errors as estimated by multinomial modeling. These results provide support for the idea that early performance monitoring as reflected by the Ne/ERN involves an evaluation of error significance.

Is confidence in perceptual decisions generated by the same brain processes as decision itself, or does confidence require metacognitive processes following up on the decision? In a masked orientation task with varying stimulus-onset-asynchrony, we used EEG and cognitive modelling to trace the timing of the neural correlates of confidence. Confidence reported by human observers increased with stimulus-onset-asynchrony in correct and to a lesser degree in incorrect trials, a pattern incompatible with established models of confidence. Electrophysiological activity was associated with confidence in two different time periods, namely 350-500 ​ms after stimulus onset and 250-350 ​ms after the response. Cognitive modelling revealed that only the activity following on the stimulus exhibited the same statistical regularities as confidence, while the statistical pattern of the activity following the response was incompatible with confidence. It is argued that electrophysiological markers of confidence and error awareness are at least in parts distinct.

Error-related brain activity has been linked to error detection enabling adaptive behavioral adjustments. However, it is still unclear which role error awareness plays in this process. Here, we show that the error-related negativity (Ne/ERN), an event-related potential reflecting early error monitoring, is dissociable from the degree of error awareness. Participants responded to a target while ignoring two different incongruent distractors. After responding, they indicated whether they had committed an error, and if so, whether they had responded to one or to the other distractor. This error classification paradigm allowed distinguishing partially aware errors, (i.e., errors that were noticed but misclassified) and fully aware errors (i.e., errors that were correctly classified). The Ne/ERN was larger for partially aware errors than for fully aware errors. Whereas this speaks against the idea that the Ne/ERN foreshadows the degree of error awareness, it confirms the prediction of a computational model, which relates the Ne/ERN to post-response conflict. This model predicts that stronger distractor processing - a prerequisite of error classification in our paradigm - leads to lower post-response conflict and thus a smaller Ne/ERN. This implies that the relationship between Ne/ERN and error awareness depends on how error awareness is related to response conflict in a specific task. Our results further indicate that the Ne/ERN but not the degree of error awareness determines adaptive performance adjustments. Taken together, we conclude that the Ne/ERN is dissociable from error awareness and foreshadows adaptive performance adjustments. Our results suggest that the relationship between the Ne/ERN and error awareness is correlative and mediated by response conflict.

Adjusting behavior following errors is essential for successful goal-directed performance. Error-related pupil dilation indicates increased autonomic arousal and has been shown to predict adaptive adjustments of post-error behavior. Because different types of errors may require different behavioral adjustments, we investigated whether this process is also sensitive to the evaluation of different types of errors. We used a four-choice flanker task where errors occur either by pressing a button associated with the distractors (flanker errors), or by pressing a button not associated with the stimulus at all (nonflanker errors). Flanker errors imply suboptimal selective attention to the target and are therefore of increased significance for successful performance. Pupil dilation was larger for flanker errors than nonflanker errors, and only pupil dilation on flanker errors predicted a decrease of error probability on the next trial. Moreover, the error-related negativity, an electrophysiological marker of early error monitoring in the medial frontal cortex, was larger on flanker errors anticipating the effect of error type on pupil dilation. These results show that error-related pupil dilation is sensitive to the type and significance of errors and correlates with adaptive behavioral adjustments accordingly. This suggests that mechanisms underlying error-related pupil dilation receive inputs from error evaluation mechanisms in the medial frontal cortex.

High per- and polyfluorinated alkyl substance (PFAS) concentrations have been detected in agricultural soils in Southwest Germany. Discharges of PFAS-contaminated paper sludge and compost are suspected to be the cause of the contamination. Perfluorinated carboxylic acids (PFCAs) have been detected also in groundwater, drinking water, and plants in this area. Recently, previously unknown compounds have been identified by high-resolution mass spectrometry (HRMS). Major contaminants were polyfluorinated dialkylated phosphate esters (diPAPs) and N-ethyl perfluorooctane sulfonamide ethanol-based phosphate diester (diSAmPAP). In this study, HRMS screening for PFAS was applied to 14 soil samples from the contaminated area and 14 impregnated paper samples which were from a similar period than the contamination. The paper samples were characterized by diPAPs (from 4:2/6:2 to 12:2/12:2), fluorotelomer mercapto alkyl phosphates (FTMAPs; 6:2/6:2 to 10:2/10:2), and diSAmPAP. In soil samples, diPAPs and their transformation products (TPs) were the major contaminants, but also FTMAPs, diSAmPAP, and their TPs occurred. The distribution patterns of the carbon chain lengths of the precursor PFAS in soil samples were shown to resemble those in paper samples. This supports the hypothesis that paper sludge is a major source of contamination. The presence of major degradation products like PFCAs, FTSAs, or PFOS and their distribution of carbon chain lengths indicate the activity of biotic or abiotic degradation processes and selective leaching processes from the upper soil horizons.

Reaction of triglycerides with trimethyl orthoformate in presence of camphorsulfonic acid (CSA) gave the fatty acid methyl esters (FAMEs, 4) in good yield. However, under these conditions, the protected glycerol could not be obtained. Formation of orthoesters 9 was possible in a separate reaction using very weak acidic conditions, namely catalytic amounts of pyridinium para-toluenesulfonate (PPTS). Subjecting the orthoesters 9 to thermolysis at 270 °C gave allyl alcohol (11) with good efficiency.

Biodegradable polymers, especially poly(lactide-co-glycolide) (PLGA), have good biocompatibility and toxicological properties. In combination with active ingredients, a specialized drug delivery system can be generated. The aim of the present study was to develop a drug delivery system consisting of PLGA microspheres loaded with the natural active ingredient totarol, which has several antimicrobial mechanisms. Totarol, isolated from the Podocarpus totara tree, was purified using column chromatography, and the eluate was checked for purity using thin layer chromatography. The spherically shaped microspheres with mean diameters of 147.21±3.45 µm and 131.14±3.69 µm (totarol-loaded and -unloaded microspheres, respectively) were created using the single emulsion evaporation method. Furthermore, the encapsulation efficiency, in a range of 84.72%±6.68% to 92.36%±0.99%, was measured via UV/vis spectroscopy. In a 90-day in vitro drug release study, the release of totarol was investigated by UV/vis spectroscopy as well, showing a release of 53.76%. The toxicity on cells was determined using BJ fibroblasts or Human Embryonic Kidney cells and an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, which showed no influence on the cell growth. The minimal inhibitory concentration was ascertained. A totarol concentration between 64 µg/mL and 128 µg/mL was necessary to inhibit the bacterial growth over a period of 24 hours. Biofilm formation on the surface of totarol-loaded microspheres was determined using transmission electron microscopy. No biofilm formation could be detected, even if the totarol concentration was below the minimal inhibitory concentration. The hemocompatibility investigations on various markers with fresh heparinized blood (1.5 IU/mL) showed that totarol and totarol-loaded microspheres have no influence on different blood parameters. The PLGA microspheres characterized by slow release of totarol and great entrapment efficiency represent a novel drug delivery system, which may be highly beneficial for the long-term therapy of bacterial infections.