Dual-task interference in action programming and action planning - Evidence from the end-state comfort effect

In the present study, we examined the extent of interference between a cognitive task (auditory n-back task) and different aspects of motor performance. Specifically, we wanted to find out whether such interference is more pronounced for aspects of planning as compared to programming. Here, motor planning is represented by a phenomenon called the end-state comfort effect , the fact that we tolerate uncomfortable initial postures in favour of a more comfortable final posture. We asked participants to grasp differently sized cylindrical objects and to place them on target platforms of varying height (grasp-and-place task), So, participants were required to (1) adjust their hand opening to the object width (action programming) and (2) to plan whether to grasp the object higher or lower in order to be able to place it comfortably onto the low or high target platform. We found that participants demonstrated the end-state comfort effect by anticipating the final posture und planning the movement accordingly with a higher object-grasp for low end-target position and lower object-grasp height for high end-target position, respectively. The auditory task was negatively affected by having to perform a visuomotor task in parallel, suggesting that the two tasks share cognitive and attentional resources. No significant impact from the auditory task on the motor tasks was found. Accordingly, it was not possible to determine which of the two motor aspects (programming or planning) contributed more towards the interference observed in the auditory task. To address this question, we carried out a second experiment. For this second experiment we focussed on the interference effects found in the auditory task and contrasted two versions of the grasp-and-place task. In the first version of the task, the height of the target-shelf varied from trial-to-trial but the width of the target object remained the same. We assumed that this version had high planning demands and low programming demands. In the second version the width of the target object varied and the target-shelf height remained constant. Presumably this increased programming demands but reduced planning demands. Significant interference with the auditory task was only found for the first version, supporting the hypothesis that motor planning requires more cognitive resources and thus creates higher multitasking costs

Geldpolitik mit optimaler Zinsstruktur

Aus den normativ gegebenen Zielen des gesamtwirtschaftlichen Gleichgewichts, die den Sollzustand eines Wirtschaftssystems beschreiben, werden mit Hilfe der goldenen Regel der Kapitalakkumulation von Allais und der Eigenzinstheorie von Keynes notwendige Bedingungen an die Zinsstruktur einer Marktwirtschaft auf einem optimalen Wachstumspfad mit maximalem Konsum und maximalen Gewinnen abgeleitet. Aus den Bedingungen für eine optimale Zinsstruktur wird eine neue Geldpolitik entwickelt, die Stabilität ohne Zinseszinseffekt, Wachstum ohne Zwang, Preisstabilität und eine aus Zinseinsparungen bezahlbare Vollbeschäftigung verspricht.Liquiditätsprämie, Liquiditätsfalle, Liquiditätsgebühr, Zinsstruktur, Eigenzins, Negativzins, Neutrale Liquidität, Optimale Liquidität, Neutrales Geld, Optimaler Wachstumspfad, Allais-Theorem, Goldene Regel der Kapitalakkumulation, Quantitätsgleichung, Umlaufsicherung, Preisstabilität, Geldpolitik, Geldordnungspolitik

Topologically protected colloidal transport above a square magnetic lattice

We theoretically study the motion of magnetic colloidal particles above a magnetic pattern and compare the predictions with Brownian dynamics simulations. The pattern consists of alternating square domains of positive and negative magnetization. The colloidal motion is driven by periodic modulation loops of an external magnetic field. There exist loops that induce topologically protected colloidal transport between two different unit cells of the pattern. The transport is very robust against internal and external perturbations. Theory and simulations are in perfect agreement

Grasping and perception are both affected by irrelevant information and secondary tasks : New evidence from the Garner paradigm

Funding: This work was supported by the DFG Priority Program SPP 1772 concerning multitasking “Human performance under multiple cognitive task requirements: From basic mechanisms to optimized task scheduling” (DFG/SCHE 735/2-1) awarded to Thomas Schenk. We would like to thank Laura Koroknai for her assistance with data collection.Peer reviewedPostprin

Methaemoglobin and COHb in patients with malaria

Background Haemolytic conditions may contribute to disease pathogenesis and severe clinical manifestations through the liberation of free haemoglobin (Hb) and production of toxic free haem. Thus, free Hb and haem should be associated with altered MetHb and COHb levels in malaria as in other conditions. Methods This study comprises data collected at three different sites: (i) a retrospective analysis of the first arterial blood gas result (ABGS) of any patient during 2010 at the University Hospital in Lisbon; (ii) a retrospective analysis of ABGS from patients with severe malaria admitted to the intensive care unit in Berlin, Germany; and (iii) a prospective study of non-invasive MetHb measurements in children with and without malaria in Lambaréné, Gabon. Results In Lisbon, the mean MetHb level was 1.4% (SD: 0.5) in a total of 17,834 ABGS. Only 11 of 98 samples with a MetHb level of >3.0 referred to infections. COHb levels showed no particular association with clinical conditions, including sepsis. In 13 patients with severe malaria in Berlin, the mean MetHb levels on admission was 1.29%, with 1.36% for cerebral malaria and 1.14% for non-cerebral malaria (P > 0.05). All COHb measurements were below 2.3%. In Lambaréné, Gabon, 132 healthy children had a mean MetHb level of 1.57%, as compared to 150 children with malaria, with a value of 1.77% and 2.05% in uncomplicated and complicated cases, respectively (P < 0.01). Conclusions The data appears consistent with the methaemoglobin/haem hypothesis in malaria and sepsis pathogenesis. However, although MetHb was significantly different between healthy controls and children with malaria in Africa, the difference was rather small, also when compared to previous studies. Still, non-invasive bedside MetHb testing may warrant further evaluation as it could be a simple adjuvant tool for prognosis in resource poor settings

Rapid high-resolution detection of colistin resistance in Gram-negative bacteria using flow cytometry: a comparison with broth microdilution, a commercial screening test and WGS

Background Even though both EUCAST and CLSI consider broth microdilution (BMD) as the reference method for antimicrobial susceptibility testing (AST) of colistin, the method exhibits potential flaws related to properties of the colistin molecule. Objectives To develop a flow cytometry method (FCM) for colistin AST and to validate it against BMD, a commercial screening test and WGS. Methods Colistin-mediated loss of membrane integrity in Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter spp. was detected with the fluorescent probe YoPro-1 by FCM. An international collection of 65 resistant and 109 susceptible isolates were analysed and the colistin concentration required to reach the EC50 was compared with the BMD MIC and the presence of genotypic resistance markers. Results The overall FCM sensitivity and specificity for colistin resistance was 89% and 94%, with E. coli > K. pneumoniae > P. aeruginosa, whereas the performance for Acinetobacter spp. was poor. All tested E. coli were correctly categorized. Three K. pneumoniae isolates with genotypic findings consistent with colistin resistance were detected by FCM but not BMD. Compared with BMD, FCM delivered AST results with a 75% reduction of time. Conclusions Here, we present a rapid FCM-based AST assay for qualitative and quantitative testing of colistin resistance in E. coli and K. pneumoniae. The assay revealed probable chromosomal colistin resistance in K. pneumoniae that was not detected by BMD. If confirmed, these results question the reliability of BMD for colistin testing.publishedVersio

Grasping discriminates between object sizes less not more accurately than the perceptual system

Funding: This work was supported by the DFG Priority Program SPP 1772 “Human performance under multiple cognitive task requirements: From basic mechanisms to optimized task scheduling” (DFG/SCHE 735/2-1) and also research funding from the following two projects: DFG/SCHE 735/3-1 und DFG/SCHE 735/4-1. Acknowledgments: We want to thank Lara Werner and Regina Härtl for help in data acquisition.Peer reviewedPublisher PD

The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63‐branched ubiquitin chains

The assembly of a specific polymeric ubiquitin chain on a target protein is a key event in the regulation of numerous cellular processes. Yet, the mechanisms that govern the selective synthesis of particular polyubiquitin signals remain enigmatic. The homologous ubiquitin-conjugating (E2) enzymes Ubc1 (budding yeast) and Ube2K (mammals) exclusively generate polyubiquitin linked through lysine 48 (K48). Uniquely among E2 enzymes, Ubc1 and Ube2K harbor a ubiquitin-binding UBA domain with unknown function. We found that this UBA domain preferentially interacts with ubiquitin chains linked through lysine 63 (K63). Based on structural modeling, in vitro ubiquitination experiments, and NMR studies, we propose that the UBA domain aligns Ubc1 with K63-linked polyubiquitin and facilitates the selective assembly of K48/K63-branched ubiquitin conjugates. Genetic and proteomics experiments link the activity of the UBA domain, and hence the formation of this unusual ubiquitin chain topology, to the maintenance of cellular proteostasis.Deutsche Forschungsgemeinschaft (DFG) http://dx.doi.org/10.13039/501100001659Max‐Planck‐Gesellschaft (MPG) http://dx.doi.org/10.13039/501100004189Peer Reviewe

Small-molecule sequestration of amyloid-β as a drug discovery strategy for Alzheimer's disease.

Disordered proteins are challenging therapeutic targets, and no drug is currently in clinical use that modifies the properties of their monomeric states. Here, we identify a small molecule (10074-G5) capable of binding and sequestering the intrinsically disordered amyloid-β (Aβ) peptide in its monomeric, soluble state. Our analysis reveals that this compound interacts with Aβ and inhibits both the primary and secondary nucleation pathways in its aggregation process. We characterize this interaction using biophysical experiments and integrative structural ensemble determination methods. We observe that this molecule increases the conformational entropy of monomeric Aβ while decreasing its hydrophobic surface area. We also show that it rescues a Caenorhabditis elegans model of Aβ-associated toxicity, consistent with the mechanism of action identified from the in silico and in vitro studies. These results illustrate the strategy of stabilizing the monomeric states of disordered proteins with small molecules to alter their behavior for therapeutic purposes