Rehabilitation bei Menschen mit Behinderungen

Zeitschrift für Epileptologie - Nach dem 9. Sozialgesetzbuch (SGB) soll eine medizinische Rehabilitation (Reha) die Teilhabeeinschränkungen einer Behinderung mindern und eine...     

Classification and characterization of postural transitions using instrumented shoes

The frequency and quality of sit-to-stand and stand-to-sit postural transitions decrease with age and are highly relevant for fall risk assessment. Accurate classification and characterization of these transitions in daily life of older adults are therefore needed. In this study, we propose to use instrumented shoes for postural transition classification as well as transition duration estimation from insole force signals. In the first part, data were collected with 10 older adults and 10 young participants performing transitions in the laboratory while wearing the instrumented shoes, without arm assistance. A wavelet approach was used to transform the insole force data, and candidate events were selected for transition duration estimation. Transition durations were then validated against a model based on force plate reference. Vertical force estimation was also compared to force plate measurement. In the second part, postural transitions were classified in daily life using the instrumented shoes and validated against a highly accurate wearable system. Transition duration was estimated with an error ranging from 10 to 20% while the error for vertical force estimation was 7%. Postural transition classification was achieved with excellent sensitivity and precision exceeding 90%. In conclusion, the instrumented shoes are suitable for classifying and characterizing postural transitions in daily life conditions of healthy older adults.

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Graphical abstract “Experimental setup showing instrumented shoes, reference force plate, as well as IMUs used for postural transition classification and duration estimation comparison”

     

Differential global structural changes in the core particle of yeast and mouse proteasome induced by ligand binding

Two clusters of configurations of the main proteolytic subunit β5 were identified by principal component analysis of crystal structures of the yeast proteasome core particle (yCP). The apo-cluster encompasses unliganded species and complexes with nonpeptidic ligands, and the pep-cluster comprises complexes with peptidic ligands. The murine constitutive CP structures conform to the yeast system, with the apo-form settled in the apo-cluster and the PR-957 (a peptidic ligand) complex in the pep-cluster. In striking contrast, the murine immune CP classifies into the pep-cluster in both the apo and the PR-957–liganded species. The two clusters differ essentially by multiple small structural changes and a domain motion enabling enclosure of the peptidic ligand and formation of specific hydrogen bonds in the pep-cluster. The immune CP species is in optimal peptide binding configuration also in its apo form. This favors productive ligand binding and may help to explain the generally increased functional activity of the immunoproteasome. Molecular dynamics simulations of the representative murine species are consistent with the experimentally observed configurations. A comparison of all 28 subunits of the unliganded species with the peptidic liganded forms demonstrates a greatly enhanced plasticity of β5 and suggests specific signaling pathways to other subunits.Among the many factors involved in protein degradation through the ubiquitin-proteasome pathway, the core particle (CP) 20S proteasome plays the key role of the protease component. With the regulatory particle (RP), it forms a complex that selectively degrades ubiquitin-protein conjugates (1, 2). The CP in eukaryotes is a multisubunit complex composed of four stacked heptameric rings: two identical outer rings formed by seven different α subunits and two identical inner rings formed by seven different β subunits. The α_1–7β_1–7β_1–7α_1–7 organization defines a cylindrical structure (3). The α-rings control substrate entry into the lumen of the particle, where it is processed at the peptidolytic active centers, which are located at the inner walls of the β rings, specifically at subunits β1, β2, and β5. These active subunits are characterized by an N-terminal Thr residue. The other four β subunits have unprocessed N-terminal propeptides and are enzymatically inactive.All three active subunits share a common peptide hydrolyzing mechanism with two main steps (4): (i) the positioning of the substrate peptide in the active site by antiparallel alignment in between segments 47–49 and 21 of the active β subunits and (ii) peptide bond cleavage initiated by a nucleophilic attack of the hydroxyl group of the N-terminal Thr1 on the carbonyl carbon atom of the scissile peptide. Sequence diversity among β subunits endows them with distinctive structural features and different specificity pockets (S1, S2, S3, etc.) where the substrate side chains (P1, P2, P3, etc.) are bound (5). Consequently, the correlation of structural features of the S1 pockets with the distinctive cleavage products has led to the association of β1, β2, and β5 with caspase-like, trypsin-like, and chymotrypsin-like activities, respectively (6).The catalytically active subunits are substituted in immune cells of vertebrate organisms by the immune β-subunits β1i, β2i, and β5i as part of an adaptive immune response. These substitutions cause substantial functional differences between the constitutive (cCP) and immuno (iCP) species, reflected in higher yield of peptides that are recognized by the major histocompatibility complex (MHC) class I generated by iCP (7). Additionally, it has been observed that iCP achieves higher degradation rates than cCP, in both in vitro and cellular assays (8–13).Some sequence variations between the constitutive and immune subunits provide explanations to the observed catalytic differences. Most conspicuously, and first seen in the eukaryotic proteasome crystal structure from yeast (yCP) (3) and confirmed by the murine constitutive and immune CP structures (mcCP and miCP) (14), Arg45 of the β1 subunit, located at the base of the S1 pocket, is replaced by leucine in β1i, thereby causing a specific change of the electrostatic milieu, in line with the observed low postacidic activity of the iCP (15).Despite the high sequence similarity between β5 subunits of mcCP and miCP including identical active sites, a peptidic α-β-epoxyketone inhibitor, PR-957, showed higher affinity to iCP by one order of magnitude. The structural comparison of cCP and iCP in their apo and PR-957 liganded states suggested an explanation. On binding of PR-957, the cCP β5 backbone displays significant deformations, whereas the iCP β5 backbone remains unchanged. This observation, together with our experience in constructing β5 models for virtual screening purposes, prompted us to reinvestigate the vast amount of structural data for yCP by a procedure that facilitates discovery of global changes: principal component analysis (PCA).We focus our study on the β5 subunit, because β5 inactivation in yeast renders a lethal phenotype (16) and therefore β5 harbors an essential enzymatic activity, and because almost all crystallographically defined complexes are liganded at their β5 active site.Here we present a detailed investigation of the wealth of yeast and mouse proteasome ligand complex structures that led us to embark on structural comparisons beyond the immediate vicinity of the ligands to obtain a view of the global response of the core particle of yeast and mouse proteasome to complex formation. This study (i) is evidence of the structural plasticity of the β, specifically β5, subunits; (ii) offers perspectives for the analysis of the structure-function relationship of the CP; and (iii) provides an aid for the design and development of ligands as drugs for this intensively studied target for cancer and autoimmune diseases.     

Effects of Dietary Exposure to Zearalenone (ZEN) on Carp (Cyprinus carpio L.)

The mycotoxin zearalenone (ZEN) is frequently contaminating animal feeds including feed used in aquaculture. In the present study, the effects of dietary exposure to ZEN on carp (Cyprinus carpio L.) were investigated. ZEN at three different concentrations (low dose: 332 µg kg⁻¹, medium dose: 621 µg kg⁻¹ and high dose: 797 µg kg⁻¹ final feed, respectively) was administered to juvenile carp for four weeks. Additional groups received the mycotoxin for the same time period but were fed with the uncontaminated diet for two more weeks to examine the reversibility of the ZEN effects. No effects on growth were observed during the feeding trial, but effects on haematological parameters occurred. In addition, an influence on white blood cell counts was noted whereby granulocytes and monocytes were affected in fish treated with the medium and high dose ZEN diet. In muscle samples, marginal ZEN and α-zearalenol (α-ZEL) concentrations were detected. Furthermore, the genotoxic potential of ZEN was confirmed by analysing formation of micronuclei in erythrocytes. In contrast to previous reports on other fish species, estrogenic effects measured as vitellogenin concentrations in serum samples were not increased by dietary exposure to ZEN. This is probably due to the fact that ZEN is rapidly metabolized in carp.     

Effects of self-esteem and stress on self-assessed health: a Swiss study from adolescence to early adulthood

Purpose

A large literature shows important effects of self-esteem and stress on mental and physical health in young adulthood. Negative life events are one type of stressor associated with poor health, but it is less clear whether more neutral stressors are also associated with poor health. This study contributes to the existing literature by investigating the association between different types of stressful life events, self-esteem, and health during the transition from adolescence to early adulthood in Switzerland.

Methods

We draw on the “Transitions from Education to Employment” (TREE) panel study, a nationally representative longitudinal survey of a cohort of Swiss young adults, using logistic regression analysis. The study includes eight waves over a 10-year period, from 2001, average age 16, to 2010, average age 26. Our dependent variable is a dichotomized health self-assessment, and key independent variables include self-esteem and three measures of cumulative significant life events (SLEs): total cumulative SLEs, cumulative negative SLEs, and cumulative neutral SLEs.

Results

Self-esteem had a significant positive impact on health, whereas cumulative SLEs had a significant negative impact. Negative SLEs had a larger negative impact than total SLEs, and neutral SLEs had a smaller impact. Considered individually, negative SLEs were more likely to have a significant negative impact on health.

Conclusions

In addition to their known influence on mental health, stress and self-esteem are important factors influencing individuals’ general health, even in adolescence and young adulthood. While all types of stressors have a negative impact on health, the negative stressors seem to have more prominent effects than neutral stressors.