Effects of Elevated H\u3csup\u3e+\u3c/sup\u3e And P\u3csub\u3ei\u3c/sub\u3e on The Contractile Mechanics of Skeletal Muscle Fibres From Young and Old Men: Implications for Muscle Fatigue in Humans

The present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole‐muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73–89 years, n = 6) compared to young men (20–29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7‐fold greater with age and strongly associated with reductions in the electrically‐evoked contractile properties. To test whether cross‐bridge mechanisms could explain age‐related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H+) (pH 6.2) and inorganic phosphate (Pi) (30 mm). The fatigue‐mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low‐ to high‐force state of the cross‐bridge cycle, confirming findings from non‐human studies that these ions act synergistically to impair cross‐bridge function. Other than severe age‐related atrophy of fast fibres (−55%), contractile function and the depressive effects of the fatigue‐mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age‐related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age‐related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age‐related increased fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi

In-vitro resistance of cloned human glioma cells to natural killer activity of allogeneic peripheral lymphocytes.

Cells from an established culture of a human astrocytoma were incubated with normal allogeneic peripheral lymphocytes (PBL) in order to study the natural killer (NK) sensitivity of the in vitro propagated cell line. A proportion of cells in culture formed halos, into which lymphocytes did not penetrate. These cells were successfully cloned and showed a decreased susceptibility to NK cytolysis compared with the parent line. Both cell lines could be transplanted into athymic nude mice. The cloned NK-resistant cells underwent a frequent spontaneous regression in nu/nu mice, despite the fact that when used as targets for nu/nu NK cells in vitro they were only moderately susceptible. Phase-contrast microscopy of the mass-cultured cells co-cultivated with lymphocytes suggested that their morphology and ability to form inpenetrable translucent halos might influence their susceptibility to NK lysis. Experiments performed on this assumption revealed that quiescent and halo forming tumour cells were not the primary targets for NK lysis. Cells in mass culture, although tumorigenic, were thus heterogeneous in respect of susceptibility to NK attack. These findings might be relevant to the mechanism of immune escape and tumour heterogeneity in respect of spontaneous cell-mediated lysis

Shearing a Glassy Material: Numerical Tests of Nonequilibrium Mode-Coupling Approaches and Experimental Proposals

The predictions of a nonequilibrium schematic mode-coupling theory developed to describe the nonlinear rheology of soft glassy materials have been numerically challenged in a sheared binary Lennard-Jones mixture. The theory gives an excellent description of the stress/temperature `jamming phase diagram' of the system. In the present paper, we focus on the issue of an effective temperature Teff for the slow modes of the fluid, as defined from a generalized fluctuation-dissipation theorem. As predicted theoretically, many different observables are found to lead to the same value of Teff, suggesting several experimental procedures to measure Teff. New, simple experimental protocols to access Teff from a generalized equipartition theorem are also proposed, and one such experiment is numerically performed. These results give strong support to the thermodynamic interpretation of Teff and make it experimentally accessible in a very direct way.Comment: Version accepted for publication - Physical Review Letter

Modeling mycorrhizal fungi dispersal by the mycophagous swamp wallaby (Wallabia bicolor)

Despite the importance of mammal-fungal interactions, tools to estimate the mammal-assisted dispersal distances of fungi are lacking. Many mammals actively consume fungal fruiting bodies, the spores of which remain viable after passage through their digestive tract. Many of these fungi form symbiotic relationships with trees and provide an array of other key ecosystem functions. We present a flexible, general model to predict the distance a mycophagous mammal would disperse fungal spores. We modelled the probability of spore dispersal by combining animal movement data from GPS-telemetry with data on spore gut-retention time. We test this model using an exemplar generalist mycophagist, the swamp wallaby (Wallabia bicolor). We show that swamp wallabies disperse fungal spores hundreds of metres—and occasionally up to 1265 m—from the point of consumption, distances that are ecologically significant for many mycorrhizal fungi. In addition to highlighting the ecological importance of swamp wallabies as dispersers of mycorrhizal fungi in eastern Australia, our simple modelling approach provides a novel and effective way of empirically describing spore dispersal by a mycophagous animal. This approach is applicable to the study of other animal-fungi interactions in other ecosystems.Funding provided by: Hermon Slade FoundationCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100001109Award Number: HSF08-6Funding provided by: Australian Research CouncilCrossref Funder Registry ID: http://dx.doi.org/10.13039/501100000923Award Number: DP0557022Methods are described in the published article

Shear-Induced Stress Relaxation in a Two-Dimensional Wet Foam

We report on experimental measurements of the flow behavior of a wet, two-dimensional foam under conditions of slow, steady shear. The initial response of the foam is elastic. Above the yield strain, the foam begins to flow. The flow consists of irregular intervals of elastic stretch followed by sudden reductions of the stress, i.e. stress drops. We report on the distribution of the stress drops as a function of the applied shear rate. We also comment on our results in the context of various two-dimensional models of foams

Low Magnesium Concentration Enforces Bone Calcium Deposition Irrespective of 1,25-Dihydroxyvitamin D3 Concentration

Efficient coordination between Mg2+ and vitamin D maintains adequate Ca2+ levels during lactation. This study explored the possible interaction between Mg2+ (0.3, 0.8, and 3 mM) and 1,25-dihydroxyvitamin D3 (1,25D; 0.05 and 5 nM) during osteogenesis using bovine mesenchymal stem cells. After 21 days, differentiated osteocytes were subjected to OsteoImage analysis, alkaline phosphatase (ALP) activity measurements, and immunocytochemistry of NT5E, ENG (endoglin), SP7 (osterix), SPP1 (osteopontin), and the BGLAP gene product osteocalcin. The mRNA expression of NT5E, THY1, ENG, SP7, BGLAP, CYP24A1, VDR, SLC41A1, SLC41A2, SLC41A3, TRPM6, TRPM7, and NIPA1 was also assessed. Reducing the Mg2+ concentration in the medium increased the accumulation of mineral hydroxyapatite and ALP activity. There was no change in the immunocytochemical localization of stem cell markers. Expression of CYP24A1 was higher in all groups receiving 5 nM 1,25D. There were tendencies for higher mRNA abundance of THY1, BGLAP, and NIPA1 in cells receiving 0.3 mM Mg2+ and 5 nM 1,25D. In conclusion, low levels of Mg2+ greatly enhanced the deposition of bone hydroxyapatite matrix. The effect of Mg2+ was not modulated by 1,25D, although the expression of certain genes (including BGLAP) tended to be increased by the combination of low Mg2+ and high 1,25D concentrations

Longitudinal Atomic Beam Spin Echo Experiments: A possible way to study Parity Violation in Hydrogen

We discuss the propagation of hydrogen atoms in static electric and magnetic fields in a longitudinal atomic beam spin echo (lABSE) apparatus. Depending on the choice of the external fields the atoms may acquire both dynamical and geometrical quantum mechanical phases. As an example of the former, we show first in-beam spin rotation measurements on atomic hydrogen, which are in excellent agreement with theory. Additional calculations of the behaviour of the metastable 2S states of hydrogen reveal that the geometrical phases may exhibit the signature of parity-(P-)violation. This invites for possible future lABSE experiments, focusing on P-violating geometrical phases in the lightest of all atoms.Comment: 6 pages, 4 figure

Jamming transition in emulsions and granular materials

We investigate the jamming transition in packings of emulsions and granular materials via molecular dynamics simulations. The emulsion model is composed of frictionless droplets interacting via nonlinear normal forces obtained using experimental data acquired by confocal microscopy of compressed emulsions systems. Granular materials are modeled by Hertz-Mindlin deformable spherical grains with Coulomb friction. In both cases, we find power-law scaling for the vanishing of pressure and excess number of contacts as the system approaches the jamming transition from high volume fractions. We find that the construction history parametrized by the compression rate during the preparation protocol has a strong effect on the micromechanical properties of granular materials but not on emulsions. This leads the granular system to jam at different volume fractions depending on the histories. Isostaticity is found in the packings close to the jamming transition in emulsions and in granular materials at slow compression rates and infinite friction. Heterogeneity of interparticle forces increases as the packings approach the jamming transition which is demonstrated by the exponential tail in force distributions and the small values of the participation number measuring spatial localization of the forces. However, no signatures of the jamming transition are observed in structural properties, like the radial distribution functions and the distributions of contacts.Comment: Submitted to PR