Internal Representations of Temporal Statistics and Feedback Calibrate Motor-Sensory Interval Timing

Humans have been shown to adapt to the temporal statistics of timing tasks so as to optimize the accuracy of their responses, in agreement with the predictions of Bayesian integration. This suggests that they build an internal representation of both the experimentally imposed distribution of time intervals (the prior) and of the error (the loss function). The responses of a Bayesian ideal observer depend crucially on these internal representations, which have only been previously studied for simple distributions. To study the nature of these representations we asked subjects to reproduce time intervals drawn from underlying temporal distributions of varying complexity, from uniform to highly skewed or bimodal while also varying the error mapping that determined the performance feedback. Interval reproduction times were affected by both the distribution and feedback, in good agreement with a performance-optimizing Bayesian observer and actor model. Bayesian model comparison highlighted that subjects were integrating the provided feedback and represented the experimental distribution with a smoothed approximation. A nonparametric reconstruction of the subjective priors from the data shows that they are generally in agreement with the true distributions up to third-order moments, but with systematically heavier tails. In particular, higher-order statistical features (kurtosis, multimodality) seem much harder to acquire. Our findings suggest that humans have only minor constraints on learning lower-order statistical properties of unimodal (including peaked and skewed) distributions of time intervals under the guidance of corrective feedback, and that their behavior is well explained by Bayesian decision theory.     

Identification, sequencing and mutagenesis of the gene for a d-carbamoylase from Agrobacterium radiobacter

Abstract A clone positive for d-carbamoylase activity (2.7 kb Hin dIII- Bam H1 DNA fragment) was obtained by screening a genomic library of Agrobacterium radiobacter in Escherichia coli . This DNA fragment contains an open reading frame of 912 bp which is predicted to encode a peptide of 304 amino acids with a calculated molecular mass of 34247 Da. The d-carbamoylase gene. named cauA , was placed under the control of T7 RNA-dependent promoter and expressed in E. coli BL21 (DE3). After induction with isopropyl-thio-β-d-galactopyranoside, the synthesis of d-carbamoylase in E. coli reached about 40% of the total protein. The expressed protein was shown to possess a molecular mass, on SDS-PAGE, of 36 kDa and showed an enhanced allowed us to establish that a Pro¹⁴→Leu¹⁴ exchange leads to an inactive enzyme species, while a Cys²⁷⁹→Ser²⁷⁹ exchange did not impair the functional properties of the enxyme.     

The kinetics of methotrexate polyglutamation in human breast cancer cells

The polyglutamation kinetics of methotrexate (MTX) in MCF-7 human breast cancer cells have been formulated mathematically. The model takes account of glutamation and hydrolysis kinetics up through the pentaglutamate level, increased synthesis of dihydrofolate reductase following exposure to drug, reversible tight-binding to reductase, and membrane transport of polyglutamates. The glutamation, hydrolysis, and efflux parameters have been determined from fits to experimental MTX polyglutamate uptake and efflux data. The preferred substrate for folypolyglutamyl synthase in the intact cell appears to be MTX diglutamate, on average being two to three times as reactive as either the parent drug or the triglutamate. Hydrolysis rate constants range from 0.03 to 0.19 h-1, but no clear trend with chain length is observable given the large uncertainty of each parameter estimate. However, the efflux of MTX polyglutamates from MCF-7 cells does show a trend with chain length decreasing with increasing length as expected. The best characteristic time of MTX diglutamate efflux is 4.1 h, about one-third that of the higher polyglutamate species, in agreement with observations on the MDA.MB.436 breast cancer cell line. The model shows quantitative agreement with the fraction of MTX polyglutamates found still to be bound to reductase in MCF-7 cells following 24 h of efflux, and qualitative agreement with the time dependence of bound MTX-polyglutamate concentration profiles obtained on the ZR-75 breast cancer line.     

Binding of azide and thiocyanate ligands to copper(II) model complexes

Summary Binding of azide to a series of copper(II) complexes has been investigated by absorption, CD and EPR spectroscopy. Axial binding of azide to Cu(II) can be differentiated from equatorial binding through the lower intensity and lack of optical activity of the LMCT band. The affinity of azide for Cu(II) increases with the overall positive charge of the complex. The preliminary data on thiocyanate binding to Cu(II) seem to agree with the trends observed for the corresponding azide adducts.     

Voltammetric studies on the electrochemical behaviour of membrane-entrapped hemes

Summary The electrochemical behaviour of Fe(III)-protoporphyrin IX entrapped into a cellulose triacetate membrane has been investigated by cyclic voltammetry. The physical entrapment into a solid matrix does not modify the redox properties of the entrapped berries, which also act as efficient promoters in the electrochemistry of cytochromec. Such a system represents a promising example of a simple solid-state promoter, and stimulates further investigations in order to obtain more complex systems that may be of significance for basic and applied bioelectrochemistry.