Effects of 60-day bed rest with and without exercise on cellular and humoral immunological parameters

Exercise at regular intervals is assumed to have a positive effect on immune functions. Conversely, after spaceflight and under simulated weightlessness (e.g., bed rest), immune functions can be suppressed. We aimed to assess the effects of simulated weightlessness (Second Berlin BedRest Study; BBR2-2) on immunological parameters and to investigate the effect of exercise (resistive exercise with and without vibration) on these changes. Twenty-four physically and mentally healthy male volunteers (20-45 years) performed resistive vibration exercise (n=7), resistance exercise without vibration (n=8) or no exercise (n=9) within 60 days of bed rest. Blood samples were taken 2 days before bed rest, on days 19 and 60 of bed rest. Composition of immune cells was analyzed by flow cytometry. Cytokines and neuroendocrine parameters were analyzed by Luminex technology and ELISA/RIA in plasma. General changes over time were identified by paired t-test, and exercise-dependent effects by pairwise repeated measurements (analysis of variance (ANOVA)). With all subjects pooled, the number of granulocytes, natural killer T cells, hematopoietic stem cells and CD45RA and CD25 co-expressing T cells increased and the number of monocytes decreased significantly during the study; the concentration of eotaxin decreased significantly. Different impacts of exercise were seen for lymphocytes, B cells, especially the IgD(+) subpopulation of B cells and the concentrations of IP-10, RANTES and DHEA-S. We conclude that prolonged bed rest significantly impacts immune cell populations and cytokine concentrations. Exercise was able to specifically influence different immunological parameters. In summary, our data fit the hypothesis of immunoprotection by exercise and may point toward even superior effects by resistive vibration exercise.Cellular & Molecular Immunology advance online publication, 10 November 2014; doi:10.1038/cmi.2014.106.

Occupant behaviour simulation for cellular offices in early design stages - Architectural and modelling considerations

Building simulation is most useful and most difficult in early design stages. Most useful since the optimisation potential is large and most difficult because input data are often not available at the level of resolution required for simulation software. The aim of this paper is to addresses this difficulty, by analysing the predominantly qualitative information in early stages of an architectural design process in search for indicators towards quantitative simulation input. The discussion in this paper is focused on cellular offices. Parameters related to occupancy, the use of office equipment, night ventilation, the use of lights and blinds are reviewed based on simulation input requirements, architectural considerations in early design stages and occupant behaviour considerations in operational stages. A worst and ideal case scenario is suggested as a generic approach to model occupant behaviour in early design stages when more detailed information is not available. Without actually predicting specific occupant behaviour, this approach highlights the magnitude of impact that occupants can have on comfort and building energy performance and it matches the level of resolution of available architectural information in early design stages. This can be sufficient for building designers to compare the magnitude of impact of occupants with other parameters in order to inform design decisions. Potential indicators in early design stages towards the ideal or worst case scenario are discussed.

Cellular localization and associations of the major lipolytic proteins in human skeletal muscle at rest and during exercise

Lipolysis involves the sequential breakdown of fatty acids from triacylglycerol and is increased during energy stress such as exercise. Adipose triglyceride lipase (ATGL) is a key regulator of skeletal muscle lipolysis and perilipin (PLIN) 5 is postulated to be an important regulator of ATGL action of muscle lipolysis. Hence, we hypothesized that non-genomic regulation such as cellular localization and the interaction of these key proteins modulate muscle lipolysis during exercise. PLIN5, ATGL and CGI-58 were highly (>60%) colocated with Oil Red O (ORO) stained lipid droplets. PLIN5 was significantly colocated with ATGL, mitochondria and CGI-58, indicating a close association between the key lipolytic effectors in resting skeletal muscle. The colocation of the lipolytic proteins, their independent association with ORO and the PLIN5/ORO colocation were not altered after 60 min of moderate intensity exercise. Further experiments in cultured human myocytes showed that PLIN5 colocation with ORO or mitochondria is unaffected by pharmacological activation of lipolytic pathways. Together, these data suggest that the major lipolytic proteins are highly expressed at the lipid droplet and colocate in resting skeletal muscle, that their localization and interactions appear to remain unchanged during prolonged exercise, and, accordingly, that other post-translational mechanisms are likely regulators of skeletal muscle lipolysis.

The deleterious effects of oxidative and nitrosative stress on palmitoylation, membrane lipid rafts and lipid-based cellular signalling : new drug targets in neuroimmune disorders

Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer’s and Parkinson’s disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.

A fluorescent histone deacetylase (HDAC) inhibitor for cellular imaging

Fluorescence microscopy studies using 4-morpholinoscriptaid (4MS) demonstrated rapid cellular uptake of this scriptaid analogue into the cytoplasm but no nuclear penetration. As 4MS and scriptaid have the same in vitro activity against HDACs and KASUMI-1 cells; 4MS exemplifies a rational approach to subtly modify ‘profluorogenic’ substrates for intracellular studies.

Vitamin C and E supplementation prevents some of the cellular adaptations to endurance-training in humans

BACKGROUND: It is clear that reactive oxygen species (ROS) produced during skeletal muscle contraction have a regulatory role in skeletal muscle adaptation to endurance exercise. However, there is much controversy in the literature regarding whether attenuation of ROS by antioxidant supplementation can prevent these cellular adaptations. Therefore, the aim of this study was to determine whether vitamin C and E supplementation attenuates performance and cellular adaptations following acute endurance exercise and endurance training. METHODS: A double-blinded, placebo-controlled randomized control trial was conducted in eleven healthy young males. Participants were matched for peak oxygen consumption (VO2peak) and randomly allocated to placebo or antioxidant (vitamin C (2×500mg/day) and E (400IU/day)) groups. Following a four-week supplement loading period, participants completed acute exercise (10×4min cycling at 90% VO2peak, 2min active recovery). Vastus lateralis muscle samples were collected pre-, immediately-post- and 3h-post-exercise. Participants then completed four weeks of training (3 days/week) using the aforementioned exercise protocol while continuing supplementation. Following exercise training, participants again completed an acute exercise bout with muscle biopsies. RESULTS: Acute exercise tended to increase skeletal muscle oxidative stress as measured by oxidized glutathione (GSSG) (P=0.058) and F2-isoprostanes (P=0.056), with no significant effect of supplementation. Acute exercise significantly increased mRNA levels of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), mitochondrial transcription factor A (TFAM) and PGC related coactivator (PRC), with no effect of supplementation. Following endurance training, supplementation did not prevent significantly increased VO2peak, skeletal muscle levels of citrate synthase activity or mRNA or protein abundance of cytochrome oxidase subunit 4 (COX IV) (P<0.05). However, following training, vitamin C and E supplementation significantly attenuated increased skeletal muscle superoxide dismutase (SOD) activity and protein abundance of SOD2 and TFAM. CONCLUSION: Following acute exercise, supplementation with vitamin C and E did not attenuate skeletal muscle oxidative stress or increased gene expression of mitochondrial biogenesis markers. However, supplementation attenuated some (SOD, TFAM) of the increased skeletal muscle adaptations following training in healthy young men.