Crystal and Electronic Structures of Alluaudite-Type Double Molybdates of Scandium and Indium

Double molybdates of indium and scandium with alluaudite structure are prepared by the solid-phase synthesis method. The crystal structure of the indium containing compound is refined and optical characteristics of Na5R(Mo04)4(R = Sc, In) are determined. Electronic structures of Na5R(Mo04)4(R = Sc, In) molybdates are studied within the ab initio method taking account of Na/Sc(In) positional disordering. Calculations of the imaginary part of dielectric function predict the optical gap of ~3.8 eV, in accordance with absorption spectroscopy data. It is established that formation energy of sodium vacancies strongly depends on sodium position and Sc(In) concentration. As a result, various diffusion mechanisms may be activated in alluaudite-type compounds with high and low contents of metal R. © 2019, Pleiades Publishing, Ltd

Vaccine antigens modulate the innate response of monocytes to Al(OH)3.

Aluminum-based adjuvants have widely been used in human vaccines since 1926. In the absence of antigens, aluminum-based adjuvants can initiate the inflammatory preparedness of innate cells, yet the impact of antigens on this response has not been investigated so far. In this study, we address the modulating effect of vaccine antigens on the monocyte-derived innate response by comparing processes initiated by Al(OH)3 and by Infanrix, an Al(OH)3-adjuvanted trivalent combination vaccine (DTaP), containing diphtheria toxoid (D), tetanus toxoid (T) and acellular pertussis (aP) vaccine antigens. A systems-wide analysis of stimulated monocytes was performed in which full proteome analysis was combined with targeted transcriptome analysis and cytokine analysis. This comprehensive study revealed four major differences in the monocyte response, between plain Al(OH)3 and DTaP stimulation conditions: (I) DTaP increased the anti-inflammatory cytokine IL-10, whereas Al(OH)3 did not; (II) Al(OH)3 increased the gene expression of IFNγ, IL-2 and IL-17a in contrast to the limited induction or even downregulation by DTaP; (III) increased expression of type I interferons-induced proteins was not observed upon DTaP stimulation, but was observed upon Al(OH)3 stimulation; (IV) opposing regulation of protein localization pathways was observed for Al(OH)3 and DTaP stimulation, related to the induction of exocytosis by Al(OH)3 alone. This study highlights that vaccine antigens can antagonize Al(OH)3-induced programming of the innate immune responses at the monocyte level

Experimental detection of short regulatory motifs in eukaryotic proteins: tips for good practice as well as for bad

It has become clear in outline though not yet in detail how cellular regulatory and signalling systems are constructed. The essential machines are protein complexes that effect regulatory decisions by undergoing internal changes of state. Subcomponents of these cellular complexes are assembled into molecular switches. Many of these switches employ one or more short peptide motifs as toggles that can move between one or more sites within the switch system, the simplest being on-off switches. Paradoxically, these motif modules (termed short linear motifs or SLiMs) are both hugely abundant but difficult to research. So despite the many successes in identifying short regulatory protein motifs, it is thought that only the “tip of the iceberg” has been exposed. Experimental and bioinformatic motif discovery remain challenging and error prone. The advice presented in this article is aimed at helping researchers to uncover genuine protein motifs, whilst avoiding the pitfalls that lead to reports of false discovery. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12964-015-0121-y) contains supplementary material, which is available to authorized users

Mobilise-D insights to estimate real-world walking speed in multiple conditions with a wearable device

This study aimed to validate a wearable device’s walking speed estimation pipeline, considering complexity, speed, and walking bout duration. The goal was to provide recommendations on the use of wearable devices for real-world mobility analysis. Participants with Parkinson’s Disease, Multiple Sclerosis, Proximal Femoral Fracture, Chronic Obstructive Pulmonary Disease, Congestive Heart Failure, and healthy older adults (n = 97) were monitored in the laboratory and the real-world (2.5 h), using a lower back wearable device. Two walking speed estimation pipelines were validated across 4408/1298 (2.5 h/laboratory) detected walking bouts, compared to 4620/1365 bouts detected by a multi-sensor reference system. In the laboratory, the mean absolute error (MAE) and mean relative error (MRE) for walking speed estimation ranged from 0.06 to 0.12 m/s and − 2.1 to 14.4%, with ICCs (Intraclass correlation coefficients) between good (0.79) and excellent (0.91). Real-world MAE ranged from 0.09 to 0.13, MARE from 1.3 to 22.7%, with ICCs indicating moderate (0.57) to good (0.88) agreement. Lower errors were observed for cohorts without major gait impairments, less complex tasks, and longer walking bouts. The analytical pipelines demonstrated moderate to good accuracy in estimating walking speed. Accuracy depended on confounding factors, emphasizing the need for robust technical validation before clinical application. Trial registration: ISRCTN – 12246987

Salt-induced formation of the A-state of ferricytochrome c--effect of the anion charge on protein structure

Structural information on partially folded forms is important for a deeper understanding of the folding mechanism(s) and the factors affecting protein stabilization. The non-native compact state of equine cytochrome c stabilized by salts in an acidic environment (pH 2.0-2.2), called the A-state, is considered a suitable model for the molten globule of cytochrome c, as it possesses a native-like alpha-helix conformation but a fluctuating tertiary structure. In this article, we extend our knowledge on anion-induced protein stabilization by determining the effect of anions carrying a double negative charge; unlike monovalent anions (which are thought to exert an 'ionic atmosphere' effect on the macromolecule), divalent anions are thought to bind to the protein at specific surface sites. Our data indicate that divalent anions, in comparison to monovalent ions, have a greater tendency to stabilize the native-like M-Fe(III)-H coordinated state of the protein. The possibility that divalent anions may bind to the protein at the same sites previously identified for polyvalent anions was evaluated. To investigate this issue, the behavior of the K88E, K88E/T89K and K13N mutants was investigated. The data obtained indicate that the mutated residues, which contribute to form the binding sites of polyanions, are important for stabilization of the native conformation; the mutants investigated, in fact, all show an increased amount of the misligated H-Fe(III)-H state and, with respect to wild-type cytochrome c, appear to be less sensitive to the presence of the anion. These residues also modulate the conformation of unfolded cytochrome c, influencing its spin state and the coordination to the prosthetic group