Intramuscular pressures during exercise: an evaluation of a fiber optic transducer-tipped catheter system

The efficacy of a modified fibre optic transducer-tipped catheter system for measuring intramuscular pressures during exercise was determined. A microcapillary infusion technique using a catheter was employed as the standard of comparison due to its established dynamic properties. Pressures were measured in the tibialis anterior muscle of six healthy adults at rest before exercise, during isometric and concentric exercise, and at rest after exercise. The fibre optic system measured contraction pressures equal to the microcapillary infusion technique during all phases of the exercise protocols but recorded a lower relaxation pressure during isometric exercise and a lower rest pressure following 20 min of concentric exercise. Negative relaxation pressures were recorded by the fibre optic system for two subjects during continuous concentric exercise. It is hypothesized that a piston effect, due to the sliding of muscle fibres at the catheter tip following a contraction, rendered falsely low pressures during relaxation and that this artefact was reflected in the subsequent rest pressure following exercise. The larger volume (157 mm3) and area (3.49 mm2) of the fibre optic catheter in the muscle made it more prone to this effect than the conventional catheter (39 mm3 and 0.87 mm2, respectively). The fibre optic system may be preferred when recording the muscle contraction pressures during complex limb movements but should not be used when assessing the relaxation pressures or the pressure at rest following exercise.     

Interleukins 1α and 1β as regulators of steroidogenesis in human NCI-H295R adrenocortical cells

Inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) regulate the activity of the hypothalamo-pituitary-adrenal (HPA) axis at several levels. Although hypothalamic CRH secretion may be the primary mechanism by which these cytokines activate the HPA axis, IL-1 expression is increased within the adrenal glands in models for systemic inflammation, and IL-1 may augment adrenal glucocorticoid production. Our aim was to investigate the direct effects of IL-1α and IL-1β on adrenal steroidogenesis and expression of three key steroidogenic genes in human adrenocortical cells using the NCI-H295R cell line as a model. mRNAs encoding receptors for IL-1, TNF-α, and leukemia inhibitory factor (LIF) were detectable in the cell line (Affymetrix microarray analysis). Both IL-1α and IL-1β increased cortisol, androstenedione, dehydroepiandrosterone and dehydroepiandrosterone sulfate production, and the accumulation of mRNAs for steroidogenic acute regulatory protein (STAR), 17α-hydroxylase/17,20-lyase (CYP17A1) and 3β-hydroxysteroid dehydrogenase 2 (HSD3B2) in these cells (P<0.05 for all). Both ILs augmented TNF-α- and LIF-induced STAR and CYP17A1 mRNA accumulation, and TNF-α-induced cortisol production (P<0.05 for all). Both ILs also increased the apoptotic index of the cells (P<0.05), which was efficiently neutralized by their specific antibodies. The IL-induced changes in the STAR, HSD3B2, and CYP17A1 protein levels were not as evident as those in the respective mRNA levels. In conclusion, the combined effect of inflammatory cytokines at the adrenal level in acute or chronic inflammatory states could significantly stimulate glucocorticoid production, and thus explain the observed discrepancy between the cortisol and ACTH concentrations sometimes seen in sepsis and chronic inflammatory states.     

Responses of leaf photosynthesis,pigments and chlorophyll fluorescence within canopy position in a boreal grass (<Emphasis Type="Italic">Phalaris arundinacea</Emphasis> L.) to elevated temperature and CO<Subscript>2</Subscript> under varying water regimes

The effects of elevated growth temperature (ambient + 3.5°C) and CO₂ (700 μmol mol⁻¹) on leaf photosynthesis, pigments and chlorophyll fluorescence of a boreal perennial grass (Phalaris arundinacea L.) under different water regimes (well watered to water shortage) were investigated. Layer-specific measurements were conducted on the top (younger leaf) and low (older leaf) canopy positions of the plants after anthesis. During the early development stages, elevated temperature enhanced the maximum rate of photosynthesis (P _max) of the top layer leaves and the aboveground biomass, which resulted in earlier senescence and lower photosynthesis and biomass at the later periods. At the stage of plant maturity, the content of chlorophyll (Chl), leaf nitrogen (N_L), and light response of effective photochemical efficiency (Φ_PSII) and electron transport rate (ETR) was significantly lower under elevated temperature than ambient temperature in leaves at both layers. CO₂ enrichment enhanced the photosynthesis but led to a decline of N_L and Chl content, as well as lower fluorescence parameters of Φ_PSII and ETR in leaves at both layers. In addition, the down-regulation by CO₂ elevation was significant at the low canopy position. Regardless of climate treatment, the water shortage had a strongly negative effect on the photosynthesis, biomass growth, and fluorescence parameters, particularly in the leaves from the low canopy position. Elevated temperature exacerbated the impact of water shortage, while CO₂ enrichment slightly alleviated the drought-induced adverse effects on P _max. We suggest that the light response of Φ_PSII and ETR, being more sensitive to leaf-age classes, reflect the photosynthetic responses to climatic treatments and drought stress better than the fluorescence parameters under dark adaptation.     

No Serological Evidence of Influenza A H1N1pdm09 Virus Infection as a Contributing Factor in Childhood Narcolepsy after Pandemrix Vaccination Campaign in Finland

Background

Narcolepsy cataplexy syndrome, characterised by excessive daytime sleepiness and cataplexy, is strongly associated with a genetic marker, human leukocyte antigen (HLA) DQB1*06:02. A sudden increase in the incidence of childhood narcolepsy was observed after vaccination with AS03-adjuvanted Pandemrix influenza vaccine in Finland at the beginning of 2010. Here, we analysed whether the coinciding influenza A H1N1pdm pandemic contributed, together with the Pandemrix vaccination, to the increased incidence of childhood narcolepsy in 2010. The analysis was based on the presence or absence of antibody response against non-structural protein 1 (NS1) from H1N1pdm09 virus, which was not a component of Pandemrix vaccine.

Methods

Non-structural (NS) 1 proteins from recombinant influenza A/Udorn/72 (H3N2) and influenza A/Finland/554/09 (H1N1pdm09) viruses were purified and used in Western blot analysis to determine specific antibody responses in human sera. The sera were obtained from 45 patients who fell ill with narcolepsy after vaccination with AS03-adjuvanted Pandemrix at the end of 2009, and from controls.

Findings

Based on quantitative Western blot analysis, only two of the 45 (4.4%) Pandemrix-vaccinated narcoleptic patients showed specific antibody response against the NS1 protein from the H1N1pdm09 virus, indicating past infection with the H1N1pdm09 virus. Instead, paired serum samples from patients, who suffered from a laboratory confirmed H1N1pdm09 infection, showed high levels or diagnostic rises (96%) in H1N1pdm virus NS1-specific antibodies and very high cross-reactivity to H3N2 subtype influenza A virus NS1 protein.

Conclusion

Based on our findings, it is unlikely that H1N1pdm09 virus infection contributed to a sudden increase in the incidence of childhood narcolepsy observed in Finland in 2010 after AS03-adjuvanted Pandemrix vaccination.     

NETRIN-4 Protects Glioblastoma Cells FROM Temozolomide Induced Senescence

Glioblastoma multiforme is the most common primary tumor of the central nervous system. The drug temozolomide (TMZ) prolongs lifespan in many glioblastoma patients. The sensitivity of glioblastoma cells to TMZ is interfered by many factors, such as the expression of O-6-methylguanine-DNA methyltransferase (MGMT) and activation of AKT signaling. We have recently identified the interaction between netrin-4 (NTN4) and integrin beta-4 (ITGB4), which promotes glioblastoma cell proliferation via activating AKT-mTOR signaling pathway. In the current work we have explored the effect of NTN4/ITGB4 interaction on TMZ induced glioblastoma cell senescence. We report here that the suppression of either ITGB4 or NTN4 in glioblastoma cell lines significantly enhances cellular senescence. The sensitivity of GBM cells to TMZ was primarily determined by the expression of MGMT. To omit the effect of MGMT, we concentrated on the cell lines devoid of expression of MGMT. NTN4 partially inhibited TMZ induced cell senescence and rescued AKT from dephosphorylation in U251MG cells, a cell line bearing decent levels of ITGB4. However, addition of exogenous NTN4 displayed no significant effect on TMZ induced senescence rescue or AKT activation in U87MG cells, which expressed ITGB4 at low levels. Furthermore, overexpression of ITGB4 combined with exogenous NTN4 significantly attenuated U87MG cell senescence induced by TMZ. These data suggest that NTN4 protects glioblastoma cells from TMZ induced senescence, probably via rescuing TMZ triggered ITGB4 dependent AKT dephosphorylation. This suggests that interfering the interaction between NTN4 and ITGB4 or concomitant use of the inhibitors of the AKT pathway may improve the therapeutic efficiency of TMZ.     

Colonisation of ephemeral forest habitats by specialised species: beetles and bugs associated with recently dead aspen wood

The most appropriate strategy for preserving fragmented populations depends on a species’ ability to colonise distant habitat patches. Insects associated with early decay stages of dead wood are expected to have a high capacity to colonise new habitat patches. To study the dispersal ranges of beetles (Coleoptera) and flat bugs (Hemiptera: Aradidae) dependent on recently dead aspen (Populus tremula) wood in Finland, we set out 58 piles of recently cut aspen logs at various distances up to 1.6 km from forests that contained a high density of old aspen trees. We captured insects by trunk window-traps, and counted beetles’ exit holes. Habitat connectivity was measured in terms of the amount of suitable aspen-wood in the surrounding environment, with the closest dead wood items up-weighted by a negative-exponential function. The log-piles attracted many saproxylic insects including four red-listed aspen-specialist species. The exposure of log-piles to the sun, and high levels of habitat connectivity increased the species richness of aspen-specialists, whereas bark peeling by moose decreased richness. The spatial scale at which species richness had its strongest response to habitat was 93 m. Among individual species there was a wide variability in spatial scale of response. This study supports the view that conservation efforts in boreal forests should be concentrated on sites where colonisation by target species is most likely. Restoration of habitat by re-locating logs may be useful at localities with a rich and specialised fauna but which have too low rate of formation of dead wood by natural processes.     

SUMO wrestling in cell movement

Small ubiquitin-like modifier(SUMO)proteins 1,2 and 3 can be covalently conjugated to specific lysine residues on target proteins in a process dubbed SUMOylati...