Ping pong for health: the meaning of space in a sport based health intervention at the workplace.

Purpose: This is a study on a sport-based intervention, with a focus on physical activity, social relations, and learning, to promote health and well-being in the workplace lived space. Lived space is situated and associated with social and cultural conventions which affect the quality of the perceived space at work. The aim of the paper is to elucidate the participant's experiences of the intervention and how health and well-being were affected. Methods: The intervention was conducted with employees from the warehouse of a company within the retail sector. The design consisted of one initial workshop as a baseline, a sport-based intervention, three group interviews, and a final workshop. A hermeneutic phenomenological analysis focused on experiences of the intervention and the meaning of the workplace as the lived space. Results: Three themes emerged in the analysis; Expressing positive individual effects, Expressing improved work environment and The meaning of the workplace as lived space. The themes are discussed in relation to three basic health foci: physical activity, social relations and learning. Conclusion: The workplace as a lived space offers a valuable opportunity for sport-based interventions that improve health and well-being through physical activity, social relations, and learning.

Specific uptake of an amyloid-ß protofibril-binding antibody-tracer in AßPP transgenic mouse brain.

Evidence suggests that amyloid-ß (Aß) protofibrils/oligomers are pathogenic agents in Alzheimer's disease (AD). Unfortunately, techniques enabling quantitative estimates of these species in patients or patient samples are still rather limited. Here we describe the in vitro and ex vivo characteristics of a new antibody-based radioactive ligand, [125I]mAb158, which binds to Aß protofibrils with high affinity. [125I]mAb158 was specifically taken up in brain of transgenic mice expressing amyloid-ß protein precursor (AßPP) as shown ex vivo. This was in contrast to [125I]mAb-Ly128 which does not bind to Aß. The uptake of intraperitoneally-administered [125I]mAb158 into the brain was age- and time-dependent, and saturable in AßPP transgenic mice with modest Aß deposition. Brain uptake was also found in young AßPP transgenic mice that were devoid of Aß deposits, suggesting that [125I]mAb158 targets soluble Aß protofibrils. The radioligand was diffusely located in the parenchyma, sometimes around senile plaques and only occasionally colocalized with cerebral amyloid angiopathy. A refined iodine-124-labeled version of mAb158 with much improved blood-brain barrier passage and a shorter plasma half-life might be useful for PET imaging of Aß protofibrils.

Monoclonal antibodies selective for α-synuclein oligomers/protofibrils recognize brain pathology in Lewy body disorders and α-synuclein transgenic mice with the disease-causing A30P mutation.

Inclusions of intraneuronal alpha-synuclein (α-synuclein) can be detected in brains of patients with Parkinson's disease and dementia with Lewy bodies. The aggregation of α-synuclein is a central feature of the disease pathogenesis. Among the different α-synuclein species, large oligomers/protofibrils have particular neurotoxic properties and should therefore be suitable as both therapeutic and diagnostic targets. Two monoclonal antibodies, mAb38F and mAb38E2, with high affinity and strong selectivity for large α-synuclein oligomers were generated. These antibodies, which do not bind amyloid-beta or tau, recognize Lewy body pathology in brains from patients with Parkinson's disease and dementia with Lewy bodies and detect pathology earlier in α-synuclein transgenic mice than linear epitope antibodies. An oligomer-selective sandwich ELISA, based on mAb38F, was set up to analyze brain extracts of the transgenic mice. The overall levels of α-synuclein oligomers/protofibrils were found to increase with age in these mice, although the levels displayed a large interindividual variation. Upon subcellular fractionation, higher levels of α-synuclein oligomers/protofibrils could be detected in the endoplasmic reticulum around the age when behavioral disturbances develop. In summary, our novel oligomer-selective α-synuclein antibodies recognize relevant pathology and should be important tools to further explore the pathogenic mechanisms in Lewy body disorders. Moreover, they could be potential candidates both for immunotherapy and as reagents in an assay to assess a potential disease biomarker.

Focusing mutations into the P. fluorescens esterase binding site increases enantioselectivity more effectively than distant mutations.

Rational design of enzymes with improved properties, such as enantioselectivity, usually focuses mutations within the substrate binding site. On the other hand, directed evolution of enzymes usually targets the entire protein and discovers beneficial mutations far from the substrate binding site. In this paper, we propose an explanation for this discrepancy and show that a combined approach--random mutagenesis within the substrate binding site--is better. To increase the enantioselectivity (E) of a Pseudomonas fluorescens esterase (PFE) toward methyl 3-bromo-2-methylpropionate, we focused mutagenesis into the substrate binding site at Trp28, Val121, Phe198, and Val225. Five of the catalytically active mutants (13%) showed better enantioselectivity than wild-type PFE. The increases in enantioselectivity were higher (up to 5-fold, reaching E = 61) than with mutants identified by random mutagenesis of the entire enzyme.