Reduced motor planning underlying inhibition of prepotent responses in children with ADHD

To flexibly regulate their behavior, children’s ability to inhibit prepotent responses arises from cognitive and motor mechanisms that have an intertwined developmental trajectory. Subtle differences in planning and control can contribute to impulsive behaviors, which are common in Attention Deficit and Hyperactivity Disorder (ADHD) and difficult to be assessed and trained. We adapted a Go/No-Go task and employed a portable, low-cost kinematic sensor to explore the different strategies used by children with ADHD or typical development to provide a prepotent response (dominant condition) or inhibit the prepotent and select an alternative one (non-dominant condition). Although no group difference emerged on accuracy levels, the kinematic analysis of correct responses revealed that, unlike neurotypical children, those with ADHD did not show increased motor planning in non-dominant compared to dominant trials. Future studies should investigate whether motor control could help children with ADHD compensate for planning difficulties. This strategy might make inhibition harder in naturalistic situations that involve complex actions. Combining cognitive and kinematic measures is a potential innovative method for assessment and intervention of subtle differences in executive processes such as inhibition, going deeper than is possible based on accuracy outcomes alone

MXAN: a new software procedure to perform geometrical fitting of experimental XANES spectra.

A new software procedure, MXAN, to fit experimental XANES spectra is presented here. The method is based on the comparison between the experimental spectrum and several theoretical calculations generated by changing the relevant geometrical parameter of the site around the absorbing atom. The x-ray photoabsorption cross section is calculated using the general multiple-scattering scheme, utilizing a complex Hedin-Lunqvist energy-dependent potential to describe the exchange correlation interaction. Our method has been applied to the study of geometrical environment of the tetrahedral zinc site of the protein superoxide dismutase (SOD). The experimental Zn K-edge XANES spectrum has been fitted in the space of the first shell coordination parameters (ligand distances and angles) following the behavior of the chi-square as a function of the local distortion from the starting crystallographic structure. The recovered structure is found to be independent on the starting conditions, showing the theoretical uniqueness of the structural solution. Strengths and limitations of the application to real systems are also discussed

Iron and copper K-edge XAS study of serotransferrin and ovotransferrin.

The active metal site structure of transferrin with iron and copper atoms is investigated using metal K-XANES. Theoretical analysis of experimental data has been performed on the basis of full multiple-scattering theory. This approach made it possible to study the origin of XANES fine details and to investigate the local structure around active metal sites. A deep insight into the local structure and electronic subsystem of Fe, Cu transferrins is obtained. For example, in the case of Cu substitution of Fe in the active centre, the best fit of theoretical spectra to experiment has been obtained for distances 3% smaller between the Cu atom and the nearest neighbours

Structural determinants driving the binding process between PDZ domain of wild type human PALS1 protein and SLiM sequences of SARS-CoV E proteins

Short Linear Motifs (SLiMs) are functional protein microdomains that typically mediate interactions between a short linear region in one protein and a globular domain in another. Surface Plasmon Resonance assays have been performed to determine the binding affinity between PDZ domain of wild type human PALS1 protein and tetradecapeptides representing the SLiMs sequences of SARS-CoV-1 and SARS-CoV-2 E proteins (E-SLiMs). SARS-CoV-2 E-SLiM binds to the human target protein with a higher affinity compared to SARS-CoV-1, showing a difference significantly greater than previously reported using the F318W mutant of PALS1 protein and shorter target peptides. Moreover, molecular dynamics simulations have provided clear evidence of the structural determinants driving this binding process. Specifically, the Arginine 69 residue in the SARS-CoV-2 E-SLiM is the key residue able to both enhance the specific polar interaction with negatively charged pockets of the PALS1 PDZ domain and reduce significantly the mobility of the viral peptide. These experimental and computational data are reinforced by the comparison of the interaction between the PALS1 PDZ domain with the natural ligand CRB1, as well as the corresponding E-SLiMs of other coronavirus members such as MERS and OCF43. Our results provide a model at the molecular level of the strategies used to mimic the endogenous SLiM peptide in the binding of the tight junctions of the host cell, explaining one of the possible reasons of the severity of the infection and pulmonary inflammation by SARS-CoV-2

Spatial distribution of photoelectrons participating in formation of x-ray absorption spectra

Interpretation of x-ray absorption near-edge structure (XANES) experiments is often done via analyzing the role of particular atoms in the formation of specific peaks in the calculated spectrum. Typically, this is achieved by calculating the spectrum for a series of trial structures where various atoms are moved and/or removed. A more quantitative approach is presented here, based on comparing the probabilities that a XANES photoelectron of a given energy can be found near particular atoms. Such a photoelectron probability density can be consistently defined as a sum over squares of wave functions which describe participating photoelectron diffraction processes, weighted by their normalized cross sections. A fine structure in the energy dependence of these probabilities can be extracted and compared to XANES spectrum. As an illustration of this novel technique, we analyze the photoelectron probability density at the Ti K pre-edge of TiS2 and at the Ti K-edge of rutile TiO2.Comment: Journal abstract available on-line at http://link.aps.org/abstract/PRB/v65/e20511

Preconditioning-induced ischemic tolerance: a window into endogenous gearing for cerebroprotection

Ischemic tolerance defines transient resistance to lethal ischemia gained by a prior sublethal noxious stimulus (i.e., preconditioning). This adaptive response is thought to be an evolutionarily conserved defense mechanism, observed in a wide variety of species. Preconditioning confers ischemic tolerance if not in all, in most organ systems, including the heart, kidney, liver, and small intestine. Since the first landmark experimental demonstration of ischemic tolerance in the gerbil brain in early 1990's, basic scientific knowledge on the mechanisms of cerebral ischemic tolerance increased substantially. Various noxious stimuli can precondition the brain, presumably through a common mechanism, genomic reprogramming. Ischemic tolerance occurs in two temporally distinct windows. Early tolerance can be achieved within minutes, but wanes also rapidly, within hours. Delayed tolerance develops in hours and lasts for days. The main mechanism involved in early tolerance is adaptation of membrane receptors, whereas gene activation with subsequent de novo protein synthesis dominates delayed tolerance. Ischemic preconditioning is associated with robust cerebroprotection in animals. In humans, transient ischemic attacks may be the clinical correlate of preconditioning leading to ischemic tolerance. Mimicking the mechanisms of this unique endogenous protection process is therefore a potential strategy for stroke prevention. Perhaps new remedies for stroke are very close, right in our cells

Probing the active site in single-atom oxygen reduction catalysts via operando X-ray and electrochemical spectroscopy

[[abstract]]Nonnoble metal catalysts are low-cost alternatives to Pt for the oxygen reduction reactions (ORRs), which have been studied for various applications in electrocatalytic systems. Among them, transition metal complexes, characterized by a redox-active single-metal-atom with biomimetic ligands, such as pyrolyzed cobalt–nitrogen–carbon (Co–Nx/C), have attracted considerable attention. Therefore, we reported the ORR mechanism of pyrolyzed Vitamin B12 using operando X-ray absorption spectroscopy coupled with electrochemical impedance spectroscopy, which enables operando monitoring of the oxygen binding site on the metal center. Our results revealed the preferential adsorption of oxygen at the Co2+ center, with end-on coordination forming a Co2+-oxo species. Furthermore, the charge transfer mechanism between the catalyst and reactant enables further Co–O species formation. These experimental findings, corroborated with first-principle calculations, provide insight into metal active-site geometry and structural evolution during ORR, which could be used for developing material design strategies for high-performance electrocatalysts for fuel cell applications.[[notice]]補正完

Hemeproteins: Recent Advances in Quantitative XANES Analysis

Recently, we have shown that multiple scattering (MS) theory, via the MXAN package, is able to reproduce the experimental X-ray absorption near edge structure (XANES) data of biological samples, in particular hemeproteins, from the rising edge up to similar to 150-200 eV above the edge. In the present work, we illustrate how XANES can be used either as an independent tool to provide bond-lengths and bond-angles for a metalloprotein active site in solution, or in combination with X-ray Diffraction for structural determinations of ligand binding geometry of the same diffracting protein crystal, providing atomic precision even for crystallographic structures solved at > 1.2 angstrom resolution. At low temperature, XANES can be applied to provide the Fe-heme structure of trapped intermediate conformations; of fight triggered processes, and some aspects of the ligand binding dynamics. Very recently, XANES difference spectra have been analyzed to provide the Fe-heme structure of multiple intermediates of carbonmonoxy-myoglobin, obtained under different photolysis protocols in solution state