Publications by authors named "Martin E Maier"

82 Publications

Cognitive modelling reveals distinct electrophysiological markers of decision confidence and error monitoring.

Neuroimage 2020 09 24;218:116963. Epub 2020 May 24.

Katholische Universität Eichstätt-Ingolstadt, Fakultät für Psychologie und Pädagogik, Lehrstuhl für Allgemeine Psychologie, Eichstätt, Germany.

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.
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http://dx.doi.org/10.1016/j.neuroimage.2020.116963DOI Listing
September 2020

Total Synthesis of the Plant Growth Promoter Auxofuran Featuring a Gold(I) Catalyzed Furan Formation.

J Org Chem 2020 06 4;85(12):8203-8208. Epub 2020 Jun 4.

Institut für Organische Chemie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany.

A concise synthesis of auxofuran () was developed. Starting with a Sonogashira cross-coupling reaction, enynol () was prepared. A gold(I) catalyzed cycloisomerization led to disubstituted furan . Via an intramolecular Friedel-Crafts cyclization, a dihydrobenzofuranone was obtained. Functional group manipulations, including benzylic oxidation, led to the target molecule.
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http://dx.doi.org/10.1021/acs.joc.0c00408DOI Listing
June 2020

Are errors detected before they occur? Early error sensations revealed by metacognitive judgments on the timing of error awareness.

Conscious Cogn 2020 01 11;77:102857. Epub 2019 Dec 11.

Department of Psychology, Catholic University of Eichstätt-Ingolstadt, Germany.

Errors in choice tasks are not only detected fast and reliably, participants often report that they knew that an error occurred already before a response was produced. These early error sensations stand in contrast with evidence suggesting that the earliest neural correlates of error awareness emerge around 300 ms after erroneous responses. The present study aimed to investigate whether anecdotal evidence for early error sensations can be corroborated in a controlled study in which participants provide metacognitive judgments on the subjective timing of error awareness. In Experiment 1, participants had to report whether they became aware of their errors before or after the response. In Experiment 2, wemeasured confidence in these metacognitive judgments. Our data show that participants report early error sensations with high confidence in the majority of error trials across paradigms and experiments. These results provide first evidence for early error sensations, informing theories of error awareness.
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http://dx.doi.org/10.1016/j.concog.2019.102857DOI Listing
January 2020

Error-related pupil dilation is sensitive to the evaluation of different error types.

Biol Psychol 2019 02 29;141:25-34. Epub 2018 Dec 29.

Catholic University of Eichstätt-Ingolstadt, Ostenstraße 25, D-85072, Eichstätt, Germany.

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.
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http://dx.doi.org/10.1016/j.biopsycho.2018.12.013DOI Listing
February 2019

Total Synthesis of Biselyngbyolide B and Its C21-C22 Z-Isomer.

J Org Chem 2018 04 3;83(8):4554-4567. Epub 2018 Apr 3.

Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18 , 72076 Tübingen , Germany.

Investigations toward the synthesis of the 18-membered macrolactone biselyngbyolide B (2) from a C1-C13 and a C14-C23 fragment are described. As a key reaction in the synthesis of the C1-C13 fragment, we used an asymmetric propargylation of chiral vinylketene silyl N, O-acetal 12. Access to a C14-C23 fragment featuring a skipped diene and a sensitive allyl alcohol function was initially attempted via reductive fragmentation of a pyran template. However, this ring opening on iodide 32 with t-BuLi led to dienynol 33 with a 21 Z double bond. With a silyl protecting group at 3-OH and by implementing an intramolecular Stille coupling for macrolactonization, the 21 Z-isomer of biselyngbyolide B (47) was obtained. For preparation of a C14-C23 fragment with the 21 E-configuration, a cross-coupling of vinylstannane 48 with 4-bromocrotonate (49) set the configuration of the two double bonds. Biselyngbyolide B (2) was then accessed by an intramolecular Heck coupling. In preliminary biological cytotoxicity assays, 2 turned out to be active, whereas the 21 Z-isomer 47 was much less active. The 3-OMEM analogue 40 was devoid of activity. These results support the notion that the side chain with the correct configuration is relevant for binding to the Ca-ATPase and the biological activity.
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http://dx.doi.org/10.1021/acs.joc.8b00298DOI Listing
April 2018

Errors can elicit an error positivity in the absence of an error negativity: Evidence for independent systems of human error monitoring.

Neuroimage 2018 05 1;172:427-436. Epub 2018 Feb 1.

Catholic University of Eichstätt-Ingolstadt, 85072, Eichstätt, Germany.

Errors in human behavior elicit a cascade of brain activity related to performance monitoring and error detection. Whereas the early error-related negativity (Ne/ERN) has been assumed to reflect a fast mismatch or prediction error signal in the medial frontal cortex, the later error positivity (Pe) is viewed as a correlate of conscious error processing. A still open question is whether these components represent two independent systems of error monitoring that rely on different types of information to detect an error. Here, we investigated the prediction that the Ne/ERN but not the Pe requires a representation of the correct response to emerge. To this end, we created a condition in which no information about the correct response was available while error detection was still possible. We hypothesized that a Pe, but no Ne/ERN should be obtained in this case. Participants had to classify targets but ignore flankers that were always associated with an incorrect response. Targets but not flankers were masked with varying target-masking intervals. Crucially, on some trials no target at all was presented, thus preventing the representation of a correct response and the emergence of an Ne/ERN. However, because flankers were easily visible and responses to the flankers were always incorrect, detection of these flanker errors was still possible. In line with predictions of a multiple-systems account, we observed a robust Pe in the absence of an Ne/ERN for these errors. Moreover, this Pe relied on the same neural activity as that on trials with a visible target, as revealed by multivariate pattern analysis. These findings demonstrate that the mechanisms reflected by the two components use different types of information to detect errors, providing evidence for independent systems of human error monitoring.
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http://dx.doi.org/10.1016/j.neuroimage.2018.01.081DOI Listing
May 2018

Rhodomyrtone (Rom) is a membrane-active compound.

Biochim Biophys Acta Biomembr 2018 May 6;1860(5):1114-1124. Epub 2018 Jan 6.

Microbial Genetics, Interfaculty Institute of Microbiology and Infection Medicine Tübingen (IMIT), University of Tübingen, Tübingen, Germany. Electronic address:

Particularly in Asia medicinal plants with antimicrobial activity are used for therapeutic purpose. One such plant-derived antibiotic is rhodomyrtone (Rom) isolated from Rhodomyrtus tomentosa leaves. Rom shows high antibacterial activity against a wide range of Gram-positive bacteria, however, its mode of action is still unclear. Reporter gene assays and proteomic profiling experiments in Bacillus subtilis indicate that Rom does not address classical antibiotic targets like translation, transcription or DNA replication, but acts at the cytoplasmic membrane. In Staphylococcus aureus, Rom decreases the membrane potential within seconds and at low doses, causes release of ATP and even the excretion of cytoplasmic proteins (ECP), but does not induce pore-formation as for example nisin. Lipid staining revealed that Rom induces local membrane damage. Rom's antimicrobial activity can be antagonized in the presence of a very narrow spectrum of saturated fatty acids (C15:0, C16:0, or C18:0) that most likely contribute to counteract the membrane damage. Gram-negative bacteria are resistant to Rom, presumably due to reduced penetration through the outer membrane and its neutralization by LPS. Rom is cytotoxic for many eukaryotic cells and studies with human erythrocytes showed that Rom induces eryptosis accompanied by erythrocyte shrinkage, cell membrane blebbing, and membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Rom's distinctive interaction with the cytoplasmic membrane reminds on the amphipathic, alpha-helical peptides, the phenol-soluble modulins (PSMs), and renders Rom an important tool for the investigation of membrane physiology.
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http://dx.doi.org/10.1016/j.bbamem.2018.01.011DOI Listing
May 2018

Intramolecular Diels-Alder Reactions of Tethered Enoate Substituted Furans Induced by Dialkylaluminum Chloride.

J Org Chem 2017 12 13;82(23):12798-12805. Epub 2017 Nov 13.

Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18, 72076 Tübingen, Germany.

Gold(I)-catalyzed cycloisomerization of enynols 11 and 17, obtained by Sonogashira coupling, led to the tethered enoate-substituted furans 14 and 19. While attempts at thermal and several Lewis acid induced intramolecular Diels-Alder reactions remained fruitless, dialkylaluminum chloride led to the formation of hexahydroindene and octahydronaphthalene derivatives 20-23. Their formation can be explained by Lewis acid induced opening of the epoxy bridge with transfer of one alkyl group to the intermediate cycloadduct.
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http://dx.doi.org/10.1021/acs.joc.7b02117DOI Listing
December 2017

Neural correlates of reconfiguration failure reveal the time course of task-set reconfiguration.

Neuropsychologia 2017 Nov 20;106:100-111. Epub 2017 Sep 20.

Department of Psychology, Catholic University of Eichstätt-Ingolstadt, Germany.

The ability to actively prepare for new tasks is crucial for achieving goal-directed behavior. The task-switching paradigm is frequently used to investigate this task-set reconfiguration. In the present study, we adopted a novel approach to identify a neural signature of reconfiguration in event-related potentials. Our method was to isolate neural correlates of reconfiguration failure and to use these correlates to reveal the time course of reconfiguration in task switches and task repetitions. We employed a task-switching paradigm in which two types of errors could be distinguished: task errors (the incorrect task was applied) and response errors (an incorrect response for the correct task was provided). Because differential activity between both error types distinguishes successful and failed reconfiguration, this activity could be used as a neural signature of the reconfiguration process. We found that, whereas reconfiguration takes place on task repetitions and task switches, it occurred earlier in the former than in the latter. Single-trial analysis revealed that the same activity predicted the amplitude of error-related brain activity, providing further support that this preparatory activity reflects reconfiguration. Our results implicate that reconfiguration is not switch-specific but that task switches and task repetitions differ with respect to the time course of reconfiguration. Furthermore, this study demonstrates that considering neural correlates of failure is a promising approach to link cognitive mechanisms to specific neural processes.
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http://dx.doi.org/10.1016/j.neuropsychologia.2017.09.018DOI Listing
November 2017

A Radical-Based Synthesis of Lingzhiol.

J Org Chem 2017 09 29;82(18):9844-9850. Epub 2017 Aug 29.

Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18, 72076 Tübingen, Germany.

The polycyclic natural product lingzhiol [(±)-1] was synthesized from dimethoxytetralone 8 via cyclization of an intermediate benzylic radical, generated from spiroepoxide 14, onto an alkynyl substituent generating tetracyclic compound 13 with an exocyclic double bond. After oxidative cleavage of the double bond of 13 and reduction of the keto function of 23, the correct diastereomer, 12-syn, was converted to lingzhiol (1) via known steps. In a similar manner, lingzhiol analogue 39 was synthesized from 5-methoxy-1-tetralone (27).
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http://dx.doi.org/10.1021/acs.joc.7b01416DOI Listing
September 2017

Working memory load impairs the evaluation of behavioral errors in the medial frontal cortex.

Psychophysiology 2017 Oct 30;54(10):1472-1482. Epub 2017 May 30.

Department of Psychology, Catholic University of Eichstätt-Ingolstadt, Eichstätt, Germany.

Early error monitoring in the medial frontal cortex enables error detection and the evaluation of error significance, which helps prioritize adaptive control. This ability has been assumed to be independent from central capacity, a limited pool of resources assumed to be involved in cognitive control. The present study investigated whether error evaluation depends on central capacity by measuring the error-related negativity (Ne/ERN) in a flanker paradigm while working memory load was varied on two levels. We used a four-choice flanker paradigm in which participants had to classify targets while ignoring flankers. Errors could be due to responding either to the flankers (flanker errors) or to none of the stimulus elements (nonflanker errors). With low load, the Ne/ERN was larger for flanker errors than for nonflanker errors-an effect that has previously been interpreted as reflecting differential significance of these error types. With high load, no such effect of error type on the Ne/ERN was observable. Our findings suggest that working memory load does not impair the generation of an Ne/ERN per se but rather impairs the evaluation of error significance. They demonstrate that error monitoring is composed of capacity-dependent and capacity-independent mechanisms.
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http://dx.doi.org/10.1111/psyp.12899DOI Listing
October 2017

Neural signatures of adaptive post-error adjustments in visual search.

Neuroimage 2017 04 22;150:270-278. Epub 2017 Feb 22.

Catholic University of Eichstätt-Ingolstadt, Germany.

Errors in speeded choice tasks can lead to post-error adjustments both on the behavioral and on the neural level. There is an ongoing debate whether such adjustments result from adaptive processes that serve to optimize performance or whether they reflect interference from error monitoring or attentional orientation. The present study aimed at identifying adaptive adjustments in a two-stage visual search task, in which participants had to select and subsequently identify a target stimulus presented to the left or right visual hemifield. Target selection and identification can be measured by two distinct event-related potentials, the N2pc and the SPCN. Using a decoder analysis based on multivariate pattern analysis, we were able to isolate the processing stages related to error sources and post-error adjustments. Whereas errors were linked to deviations in the N2pc and the SPCN, only for the N2pc we identified a post-error adjustment, which exhibits key features of source-specific adaptivity. While errors were associated with an increased N2pc, post-error adjustments consisted in an N2pc decrease. We interpret this as an adaptive adjustment of target selection to prevent errors due to disproportionate processing of the task-irrelevant target location. Our study thus provides evidence for adaptive post-error adjustments in visual search.
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http://dx.doi.org/10.1016/j.neuroimage.2017.02.059DOI Listing
April 2017

Mediofrontal Negativity Signals Unexpected Timing of Salient Outcomes.

J Cogn Neurosci 2017 Apr 29;29(4):718-727. Epub 2016 Nov 29.

University of Bologna.

The medial prefrontal cortex (mPFC) and ACC have been consistently implicated in learning predictions of future outcomes and signaling prediction errors (i.e., unexpected deviations from such predictions). A computational model of ACC/mPFC posits that these prediction errors should be modulated by outcomes occurring at unexpected times, even if the outcomes themselves are predicted. However, unexpectedness per se is not the only variable that modulates ACC/mPFC activity, as studies reported its sensitivity to the salience of outcomes. In this study, mediofrontal negativity, a component of the event-related brain potential generated in ACC/mPFC and coding for prediction errors, was measured in 48 participants performing a Pavlovian aversive conditioning task, during which aversive (thus salient) and neutral outcomes were unexpectedly shifted (i.e., anticipated or delayed) in time. Mediofrontal ERP signals of prediction error were observed for outcomes occurring at unexpected times but were specific for salient (shock-associated), as compared with neutral, outcomes. These findings have important implications for the theoretical accounts of ACC/mPFC and suggest a critical role of timing and salience information in prediction error signaling.
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http://dx.doi.org/10.1162/jocn_a_01074DOI Listing
April 2017

Formal Total Synthesis of Amphidinolide Q.

J Org Chem 2016 10 29;81(20):9728-9737. Epub 2016 Sep 29.

Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18, 72076 Tübingen, Germany.

With the preparation of macrolactone 33a we describe a formal total synthesis of amphidinolide Q. The corresponding seco acid 32 originated from an aldol reaction between methyl ketone 6 and methyl (E)-3-methyl-4-oxobut-2-enoate (5). The synthesis of ketone 6 (C5-C16 fragment) started with desymmetrized meso-diol 9. Chain extension reactions involving cyanide, lithium trimethylsilylacetylide, and a Wittig reaction led to aldehyde 22. The two additional stereocenters at C11 and C13 were set by a Noyori transfer hydrogenation on alkynone 14 and a Feringa-Minnaard methyl cuprate addition on enoate 21. The but-1-ene-2-yl subunit on the side chain terminus was created from an unsaturated aldehyde by a substitution reaction on a derived allylic tosylate.
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http://dx.doi.org/10.1021/acs.joc.6b01806DOI Listing
October 2016

Development and in vitro characterization of poly(lactide--glycolide) microspheres loaded with an antibacterial natural drug for the treatment of long-term bacterial infections.

Drug Des Devel Ther 2016;10:2823-2832. Epub 2016 Sep 7.

Department of Thoracic, Cardiac and Vascular Surgery, University Hospital Tuebingen, Tuebingen.

Biodegradable polymers, especially poly(lactide--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 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.
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http://dx.doi.org/10.2147/DDDT.S105367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019313PMC
September 2016

Error monitoring is related to processing internal affective states.

Cogn Affect Behav Neurosci 2016 12;16(6):1050-1062

Center for Studies and Research in Cognitive Neuroscience Cesena, Cesena, Italy.

Detecting behavioral errors is critical for optimizing performance. Here, we tested whether error monitoring is enhanced in emotional task contexts, and whether this enhancement depends on processing internal affective states. Event-related potentials were recorded in individuals with low and high levels of alexithymia-that is, individuals with difficulties identifying and describing their feelings. We administered a face word Stroop paradigm (Egner, Etkin, Gale, & Hirsch, 2008) in which the task was to classify emotional faces either with respect to their expression (happy or fearful; emotional task set) or with respect to their gender (female or male; neutral task set). The error-related negativity, a marker of rapid error monitoring, was enhanced in individuals with low alexithymia when they adopted the emotional task set. By contrast, individuals with high alexithymia did not show such an enhancement. Moreover, in the high-alexithymia group, the difference in the error-related negativities between the emotional and neutral task sets correlated negatively with difficulties identifying their own feelings, as measured by the Toronto Alexithymia Scale. These results show that error-monitoring activity is stronger in emotional task contexts and that this enhancement depends on processing internal affective states.
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http://dx.doi.org/10.3758/s13415-016-0452-1DOI Listing
December 2016

Error-related brain activity and error awareness in an error classification paradigm.

Neuroimage 2016 Oct 11;139:202-210. Epub 2016 Jun 11.

Catholic University of Eichstätt-Ingolstadt, Germany; Centro Studi e Ricerche in Neuroscienze Cognitive, Cesena, Italy.

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.
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http://dx.doi.org/10.1016/j.neuroimage.2016.05.074DOI Listing
October 2016

Toward Leiodermatolide: Synthesis of the Core Structure.

Org Lett 2016 07 9;18(13):3146-9. Epub 2016 Jun 9.

Institut für Organische Chemie, Eberhard Karls Universität Tübingen , Auf der Morgenstelle 18, 72076 Tübingen, Germany.

The macrocyclic core (35) of the marine natural product leiodermatolide (1) was synthesized from two key fragments, vinyl iodide 23 (C1-C11 part) and vinyl stannane 31 (C12-C18 part). A Stille coupling led to conjugated Z,Z-diene 32. The derived seco acid 34 was cyclized using a Yamaguchi macrolactonization. Key steps in the assembly of vinyl iodide 23 were a Paterson aldol reaction, and a Kumada coupling on a triflate derivative to create the C4-C5 trisubstituted double bond. The two stereocenters in fragment 31 were established by a Marshall-Tamaru reaction. The longest linear sequence comprises 20 steps.
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http://dx.doi.org/10.1021/acs.orglett.6b01355DOI Listing
July 2016

Error significance but not error expectancy predicts error-related negativities for different error types.

Behav Brain Res 2016 Jan 23;297:259-67. Epub 2015 Oct 23.

Catholic University of Eichstätt-Ingolstadt, Ostenstraße 25, D-85072 Eichstätt, Germany.

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.
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http://dx.doi.org/10.1016/j.bbr.2015.10.031DOI Listing
January 2016

Multisensory stimulation in hemianopic patients boosts orienting responses to the hemianopic field and reduces attentional resources to the intact field.

Restor Neurol Neurosci 2015 ;33(4):405-19

Department of Psychology, University of Bologna, Bologna, Italy.

Purpose: Lateralised lesions can disrupt inhibitory cross-callosal fibres which maintain interhemispheric equilibrium in attention networks, with a consequent attentional bias towards the ipsilesional field. Some evidence of this imbalance has also been found in hemianopic patients (Tant et al., 2002). The aim of the present study was to reduce this attentional bias in hemianopic patients by using multisensory stimulation capable of activating subcortical structures responsible for orienting attention, such as the superior colliculus.

Methods: Eight hemianopic patients underwent a course of multisensory stimulation treatment for two weeks and their behavioural and electrophysiological performance was tested at three time intervals: baseline 1 (before treatment), control baseline 2 (two weeks after baseline 1 and immediately before treatment as a control for practice effects) and finally after treatment.

Results: The results show improvements on various clinical measures, on orienting responses in the hemianopic field, and a reduction of electrophysiological activity (P3 amplitude) in response to stimuli presented in the intact visual field.

Conclusions: These results suggest that the primary visual deficit in hemianopic patients might be accompanied by an ipsilesional attentional bias which might be reduced by multisensory stimulation.
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http://dx.doi.org/10.3233/RNN-140457DOI Listing
June 2016

Impaired rapid error monitoring but intact error signaling following rostral anterior cingulate cortex lesions in humans.

Front Hum Neurosci 2015 17;9:339. Epub 2015 Jun 17.

Centro Studi e Ricerche in Neuroscienze Cognitive, Polo Scientifico-Didattico di Cesena, Alma Mater Studiorum Università di Bologna Cesena, Italy ; Dipartimento di Psicologia, Alma Mater Studiorum Università di Bologna Bologna, Italy.

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.
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http://dx.doi.org/10.3389/fnhum.2015.00339DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469832PMC
July 2015

Design and synthesis of analogues of natural products.

Authors:
Martin E Maier

Org Biomol Chem 2015 May;13(19):5302-43

Institut für Organische Chemie, Eberhard Karls Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen, Germany.

In this article strategies for the design and synthesis of natural product analogues are summarized and illustrated with some selected examples. Proven strategies include diverted total synthesis (DTS), function-oriented synthesis (FOS), biology-oriented synthesis (BIOS), complexity to diversity (CtD), hybrid molecules, and biosynthesis inspired synthesis. The latter includes mutasynthesis, the synthesis of natural products encoded by silent genes, and propionate scanning. Most of the examples from our group fall in the quite general concept of DTS. Thus, in case an efficient strategy to a natural product is at hand, modifications are possible at almost any stage of a synthesis. However, even for compounds of moderate complexity, organic synthesis remains a bottle neck. Unless some method for predicting the biological activity of a designed molecule becomes available, the design and synthesis of natural product analogues will remain what it is now, namely it will largely rely on trial and error.
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http://dx.doi.org/10.1039/c5ob00169bDOI Listing
May 2015

Synthesis and Characterization of a Biotinylated Multivalent Targeted Contrast Agent.

Chempluschem 2015 Mar 12;80(3):612-622. Epub 2014 Dec 12.

MR Neuroimaging Agents Group, Max Planck Institute for Biological Cybernetics, 72076 Tübingen (Germany).

A new bimodal and multivalent dendritic contrast agent (CA) that targets the protein avidin was prepared and characterized. The tripartite lysine core was used to link the ligand biotin, the fluorescent dye, and the dendron carrying GdDOTA (DOTA=1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) chelates for amplification of the magnetic resonance imaging (MRI) signal. The longitudinal relaxivity of this dendrimeric CA was greater than those of its GdDOTA chelate and most of the common commercial agents at the investigated high magnetic field (7 T). The capacity of the dendrimeric CA to bind to the target protein was confirmed by fluorescence measurements upon its treatment with NeutrAvidin-agarose gel or NeutrAvidin-coated microspheres and the results were compared with those of its monomeric analogue. The fluorescence intensity of monomer-treated targets was found to be greater than that from those treated with dendrimeric CA; however, a several-fold increase in the MRI signal was observed on the same samples treated with the dendrimeric CA. The inductively coupled plasma mass spectrometry analysis of the digested samples indicated somewhat higher Gd content and hence slightly better binding of monomeric versus dendrimeric CA. This bimodal and multivalent targeted probe opens an avenue for the preparation of new nanosized CAs that allow high-resolution MRI of various targets, such as cellular receptors or specific cellular populations.
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http://dx.doi.org/10.1002/cplu.201402329DOI Listing
March 2015

Emotional and movement-related body postures modulate visual processing.

Soc Cogn Affect Neurosci 2015 Aug 1;10(8):1092-101. Epub 2015 Jan 1.

Department of Psychology, University of Bologna, 40126 Bologna, Italy, CSRNC, Centre for Studies and Research in Cognitive Neuroscience, Cesena Campus, University of Bologna, 47521 Cesena, Italy,

Human body postures convey useful information for understanding others' emotions and intentions. To investigate at which stage of visual processing emotional and movement-related information conveyed by bodies is discriminated, we examined event-related potentials elicited by laterally presented images of bodies with static postures and implied-motion body images with neutral, fearful or happy expressions. At the early stage of visual structural encoding (N190), we found a difference in the sensitivity of the two hemispheres to observed body postures. Specifically, the right hemisphere showed a N190 modulation both for the motion content (i.e. all the observed postures implying body movements elicited greater N190 amplitudes compared with static postures) and for the emotional content (i.e. fearful postures elicited the largest N190 amplitude), while the left hemisphere showed a modulation only for the motion content. In contrast, at a later stage of perceptual representation, reflecting selective attention to salient stimuli, an increased early posterior negativity was observed for fearful stimuli in both hemispheres, suggesting an enhanced processing of motivationally relevant stimuli. The observed modulations, both at the early stage of structural encoding and at the later processing stage, suggest the existence of a specialized perceptual mechanism tuned to emotion- and action-related information conveyed by human body postures.
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http://dx.doi.org/10.1093/scan/nsu167DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4526487PMC
August 2015

Mediofrontal negativity signals unexpected omission of aversive events.

Sci Rep 2014 Apr 28;4:4816. Epub 2014 Apr 28.

Center for Studies and Research in Cognitive Neuroscience, University of Bologna, Italy.

Research based on event-related potential (ERP) reported mediofrontal negativities following unexpected negative feedback or performance error. Some authors proposed that these signals reflect reward prediction error for worse than expected outcomes, while others suggested that mediofrontal negativities express medial prefrontal cortex coding for unexpected non-occurrence of a predicted outcome, whether worse or better than expected. Many studies found mediofrontal negativities coding for unexpected negative outcomes; however, few studies found them after unexpected positive outcomes. The present study investigated ERP and skin conductance response (SCR) to the unexpected omission of electric shocks during Pavlovian aversive conditioning. To manipulate expectancies, participants were presented with visual stimuli paired with electric shock on either 80% (CS+1) or 20% (CS+2) of trials. SCR analysis confirmed higher shock-delivery expectancy for CS+1, relative to CS+2. ERP analysis evidenced a stronger negative frontocentral ERP component after unexpected, relative to expected, shock-omission. Methodological and theoretical implications are discussed.
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http://dx.doi.org/10.1038/srep04816DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4104829PMC
April 2014

Mechanistic study of gold(I)-catalyzed hydroamination of alkynes: outer or inner sphere mechanism?

Angew Chem Int Ed Engl 2014 Jul 12;53(30):7760-4. Epub 2014 Jun 12.

Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen (Germany).

An experimental mechanistic study of the gold(I)-catalyzed hydroamination shows the formation of conformationally flexible auro-iminium salts Au-Im, which originate from the protonation of a vinyl gold species. Rotation around the C-CAu bond is the reason for the loss of stereospecificity of protodeauration, which explains the stereochemical result of the Stradiotto reaction. The ambiguity about inner or outer sphere mechanism is thus resolved in favor of the outer sphere mechanism.
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http://dx.doi.org/10.1002/anie.201402557DOI Listing
July 2014

Unseen fearful faces influence face encoding: evidence from ERPs in hemianopic patients.

J Cogn Neurosci 2014 Nov 4;26(11):2564-77. Epub 2014 Jun 4.

Università of Bologna, Bologna, Italy.

Visual threat-related signals are not only processed via a cortical geniculo-striatal pathway to the amygdala but also via a subcortical colliculo-pulvinar-amygdala pathway, which presumably mediates implicit processing of fearful stimuli. Indeed, hemianopic patients with unilateral damage to the geniculo-striatal pathway have been shown to respond faster to seen happy faces in their intact visual field when unseen fearful faces were concurrently presented in their blind field [Bertini, C., Cecere, R., & Làdavas, E. I am blind, but I "see" fear. Cortex, 49, 985-993, 2013]. This behavioral facilitation in the presence of unseen fear might reflect enhanced processing of consciously perceived faces because of early activation of the subcortical pathway for implicit fear perception, which possibly leads to a modulation of cortical activity. To test this hypothesis, we examined ERPs elicited by fearful and happy faces presented to the intact visual field of right and left hemianopic patients, whereas fearful, happy, or neutral faces were concurrently presented in their blind field. Results showed that the amplitude of the N170 elicited by seen happy faces was selectively increased when an unseen fearful face was concurrently presented in the blind field of right hemianopic patients. These results suggest that when the geniculo-striate visual pathway is lesioned, the rapid and implicit processing of threat signals can enhance facial encoding. Notably, the N170 modulation was only observed in left-lesioned patients, favoring the hypothesis that implicit subcortical processing of fearful signals can influence face encoding only when the right hemisphere is intact.
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http://dx.doi.org/10.1162/jocn_a_00671DOI Listing
November 2014

Inhibition by cellular vacuolar ATPase impairs human papillomavirus uncoating and infection.

Antimicrob Agents Chemother 2014 May 10;58(5):2905-11. Epub 2014 Mar 10.

Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, Luxembourg, Luxembourg.

Several viruses, including human papillomaviruses, depend on endosomal acidification for successful infection. Hence, the multisubunit enzyme vacuolar ATPase (V-ATPase), which is mainly responsible for endosome acidification in the cell, represents an attractive target for antiviral strategies. In the present study, we show that V-ATPase is required for human papillomavirus (HPV) infection and that uncoating/disassembly but not endocytosis is affected by V-ATPase inhibition. The infection inhibitory potencies of saliphenylhalamide, a proven V-ATPase inhibitor, and its derivatives, as well as those of other V-ATPase inhibitors, were analyzed on different HPV types in relevant cell lines. Variation in the selectivity indices among V-ATPase inhibitors was high, while variation for the same inhibitor against different HPV subtypes was low, indicating that broad-spectrum anti-HPV activity can be provided.
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http://dx.doi.org/10.1128/AAC.02284-13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3993236PMC
May 2014

The mechanism of gold(I)-catalyzed hydroalkoxylation of alkynes: an extensive experimental study.

Chemistry 2014 Feb 8;20(7):1918-30. Epub 2014 Jan 8.

Institut für Organische Chemie, Universität Tübingen, Auf der Morgenstelle 18, 72076 Tübingen (Germany), Fax: (+49) 7071-295137.

An extensive experimental study of the mechanism of gold(I)-catalyzed hydroalkoxylation of internal alkynes has been conducted by using NMR spectroscopy. This study was focused on the organogold intermediates, observations of actual catalytic intermediates in situ, and the reaction kinetics that are involved in this reaction. Based on the experimental results, a complete mechanistic picture was established, including on- and off-cycle processes that explain the role of diaurated species. We have shown that gold-catalyzed hydroalkoxylation of internal alkynes is a reaction that requires only one gold atom for the catalytic cycle, disproving a recent hypothesis regarding the involvement of cooperative gold catalysis.
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http://dx.doi.org/10.1002/chem.201303795DOI Listing
February 2014

New calcium-selective smart contrast agents for magnetic resonance imaging.

Chemistry 2013 Dec 7;19(52):18011-26. Epub 2013 Nov 7.

Max Planck Institute for Biological Cybernetics, Dept. of Physiology of Cognitive Processes, 72076 Tübingen (Germany); Present address: Case NFCR Center for Imaging Research, Dept. of Radiology, Case Western Reserve University, Cleveland, OH (USA).

Calcium plays a vital role in the human body and especially in the central nervous system. Precise maintenance of Ca(2+) levels is very crucial for normal cell physiology and health. The deregulation of calcium homeostasis can lead to neuronal cell death and brain damage. To study this functional role played by Ca(2+) in the brain noninvasively by using magnetic resonance imaging, we have synthesized a new set of Ca(2+) -sensitive smart contrast agents (CAs). The agents were found to be highly selective to Ca(2+) in the presence of other competitive anions and cations in buffer and in physiological fluids. The structure of CAs comprises Gd(3+)-DO3A (DO3A=1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane) coupled to a Ca(2+) chelator o-amino phenol-N,N,O-triacetate (APTRA). The agents are designed to sense Ca(2+) present in extracellular fluid of the brain where its concentration is relatively high, that is, 1.2-0.8 mM. The determined dissociation constant of the CAs to Ca(2+) falls in the range required to sense and report changes in extracellular Ca(2+) levels followed by an increase in neural activity. In buffer, with the addition of Ca(2+) the increase in relaxivity ranged from 100-157%, the highest ever known for any T1-based Ca(2+)-sensitive smart CA. The CAs were analyzed extensively by the measurement of luminescence lifetime measurement on Tb(3+) analogues, nuclear magnetic relaxation dispersion (NMRD), and (17)O NMR transverse relaxation and shift experiments. The results obtained confirmed that the large relaxivity enhancement observed upon Ca(2+) addition is due to the increase of the hydration state of the complexes together with the slowing down of the molecular rotation and the retention of a significant contribution of the water molecules of the second sphere of hydration.
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http://dx.doi.org/10.1002/chem.201300169DOI Listing
December 2013