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Vogel S.E.,University of Western Ontario | Vogel S.E.,Georg August University Go Ttingen | Remark A.,University of Western Ontario | Ansari D.,University of Western Ontario
Journal of Experimental Child Psychology | Year: 2014

A growing body of evidence has indicated a link between individual differences in children's symbolic numerical magnitude discrimination (e.g., judging which of two numbers is numerically larger) and their arithmetic achievement. In contrast, relatively little is known about the processing of numerical order (e.g., deciding whether two numbers are in ascending or descending numerical order) and whether individual differences in judging numerical order are related to the processing of numerical magnitude and arithmetic achievement. In view of this, we investigated the relationships among symbolic numerical magnitude comparison, symbolic order judgments, and mathematical achievement. Data were collected from a group of 61 first-grade children who completed a magnitude comparison task, an order judgment task, and two standardized tests of arithmetic achievement. Results indicated a numerical distance effect (NDE) in both the symbolic numerical magnitude discrimination and the numerical order judgment condition. However, correlation analyses demonstrated that although individual differences in magnitude comparison correlated significantly with arithmetic achievement, performance on the order judgment task did not. Moreover, the NDE of the magnitude and order comparison performance was also found to be uncorrelated. These findings suggest that order and numerical magnitude processing may be underpinned by different processes and relate differentially to arithmetic achievement in young children. © 2014 Elsevier Inc. Source

Siewert I.,Georg August University Go Ttingen | Gallezowska J.,Wroclaw Medical University
Chemistry - A European Journal | Year: 2015

Herein, we report the synthesis, the thermochemical data, and the catalytic reactivity of a new mononuclear cobalt complex, which has four NH protons in the ligand sphere. The combination of the redox-active metal ion and NH units enabled the coupling of proton and electron-transfer steps, which we exploited in the electrocatalytic water oxidation. Proton-coupled electron transfer: A cobalt complex with four NH protons in the ligand sphere was utilised as a water-oxidising electrocatalyst. We demonstrated that the combination of the redox-active metal ion and NH units enabled the coupling of proton- and electron-transfer steps (see figure). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Source

Kumar J.,Tata Institute of Fundamental Research | Choudhary B.C.,Tata Institute of Fundamental Research | Metpally R.,Tata Institute of Fundamental Research | Metpally R.,University of Iowa | And 6 more authors.
PLoS Genetics | Year: 2010

UNC-104/KIF1A is a Kinesin-3 motor that transports synaptic vesicles from the cell body towards the synapse by binding to PI(4,5)P2 through its PH domain. The fate of the motor upon reaching the synapse is not known. We found that wild-type UNC-104 is degraded at synaptic regions through the ubiquitin pathway and is not retrogradely transported back to the cell body. As a possible means to regulate the motor, we tested the effect of cargo binding on UNC-104 levels. The unc-104(e1265) allele carries a point mutation (D1497N) in the PI(4,5)P2 binding pocket of the PH domain, resulting in greatly reduced preferential binding to PI(4,5)P2 in vitro and presence of very few motors on pre-synaptic vesicles in vivo. unc-104(e1265) animals have poor locomotion irrespective of in vivo PI(4,5)P2 levels due to reduced anterograde transport. Moreover, they show highly reduced levels of UNC-104 in vivo. To confirm that loss of cargo binding specificity reduces motor levels, we isolated two intragenic suppressors with compensatory mutations within the PH domain. These show partial restoration of in vitro preferential PI(4,5)P2 binding and presence of more motors on pre-synaptic vesicles in vivo. These animals show improved locomotion dependent on in vivo PI(4,5)P2 levels, increased anterograde transport, and partial restoration of UNC-104 protein levels in vivo. For further proof, we mutated a conserved residue in one suppressor background. The PH domain in this triple mutant lacked in vitro PI(4,5)P2 binding specificity, and the animals again showed locomotory defects and reduced motor levels. All allelic variants show increased UNC-104 levels upon blocking the ubiquitin pathway. These data show that inability to bind cargo can target motors for degradation. In view of the observed degradation of the motor in synaptic regions, this further suggests that UNC-104 may get degraded at synapses upon release of cargo. © 2010 Kumar et al. Source

Dohler F.,University of Hamburg | Sepulveda-Falla D.,University of Hamburg | Krasemann S.,University of Hamburg | Altmeppen H.,University of Hamburg | And 5 more authors.
Brain | Year: 2014

Alzheimer's disease is the most common form of dementia and the generation of oligomeric species of amyloid-β is causal to the initiation and progression of it. Amyloid-β oligomers bind to the N-terminus of plasma membrane-bound cellular prion protein (PrPC) initiating a series of events leading to synaptic degeneration. Composition of bound amyloid-β oligomers, binding regions within PrPC, binding affinities and modifiers of this interaction have been almost exclusively studied in cell culture or murine models of Alzheimer's disease and our knowledge on PrP C-amyloid-β interaction in patients with Alzheimer's disease is limited regarding occurrence, binding regions in PrPC, and size of bound amyloid-β oligomers. Here we employed a PrPC-amyloid- β binding assay and size exclusion chromatography on neuropathologically characterized Alzheimer's disease and non-demented control brains (n = 15, seven female, eight male, average age: 79.2 years for Alzheimer's disease and n = 10, three female, seven male, average age: 66.4 years for controls) to investigate amyloid-β-PrPC interaction. PrPC-amyloid-β binding always occurred in Alzheimer's disease brains and was never detected in non-demented controls. Neither expression level of PrPC nor known genetic modifiers of Alzheimer's disease, such as the PrPC codon 129 polymorphism, influenced this interaction. In Alzheimer's disease brains, binding of amyloid-β to PrPC occurred via the PrPC N-terminus. For synthetic amyloid-β42, small oligomeric species showed prominent binding to PrPC, whereas in Alzheimer's disease brains larger protein assemblies containing amyloid-β42 bound efficiently to PrPC. These data confirm Alzheimer's disease specificity of binding of amyloid-β to PrPC via its N-terminus in a large cohort of Alzheimer's disease/control brains. Differences in sizes of separated protein fractions between synthetic and brain-derived amyloid-β binding to PrPC suggest that larger assemblies of amyloid-β or additional non-amyloid-β components may play a role in binding of amyloid-β42 to PrPC in Alzheimer's disease. © 2014 The Author . Source

Bechdolf A.,University of Cologne | Muller H.,University of Cologne | Stutzer H.,University of Cologne | Wagner M.,University of Bonn | And 15 more authors.
Schizophrenia Bulletin | Year: 2011

Antipsychotics, cognitive behavioral therapy (CBT), and omega-3-fatty acids have been found superior to control conditions as regards prevention of psychosis in people at-risk of first-episode psychosis. However, no large-scale trial evaluating the differential efficacy of CBT and antipsychotics has been performed yet. In PREVENT, we evaluate CBT, aripiprazole, and clinical management (CM) as well as placebo and CM for the prevention of psychosis in a randomized, double-blind, placebo-controlled trial with regard to the antipsychotic intervention and a randomized controlled trial with regard to the CBT intervention with blinded ratings. The hypotheses are first that CBT and aripiprazole and CM are superior to placebo and CM and second that CBT is not inferior to aripiprazole and CM combined. The primary outcome is transition to psychosis. By November 2010, 156 patients were recruited into the trial. The subjects were substantially functionally compromised (Social and Occupational Functioning Assessment Scale mean score 52.5) and 78.3% presented with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition axis I comorbid diagnosis. Prior to randomization, 51.5% of the participants preferred to be randomized into the CBT arm, whereas only 12.9% preferred pharmacological treatment. First, assessments of audiotaped treatment sessions confirmed the application of CBT-specific skills in the CBT condition and the absence of those in CM. The overall quality rating of the CBT techniques applied in the CBT condition was good. When the final results of the trial are available, PREVENT will substantially expand the current limited evidence base for best clinical practice in people at-risk (prodromal) of first-episode psychosis. © 2011 The Author. Source

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