Twenty-four subjects walked at different, freely chosen speeds (V) ranging from 0.4 to 2.6 m s-1, while the motion and the ground reaction forces were recorded in three-dimensional space. We considered the time course of the changes of the angles of elevation of the trunk, pelvis, thigh, shank, and foot in the sagittal plane. These angles specify the orientation of each segment with respect to the vertical and to the direction of forward progression. The changes of the trunk and pelvis angles are of limited amplitude and reflect the dynamics of both right and left lower limbs. The changes of the thigh, shank, and foot elevation are ample, and they are coupled tightly among each other. When these angles are plotted one versus the others, they describe regular loops constrained on a plane. The plane of angular covariation rotates, slightly but systematically, along the long axis of the gait loop with increasing V. The rotation, quantified by the change of the direction cosine of the normal to the plane with the thigh axis (u3t), is related to a progressive phase shift between the foot elevation and the shank elevation with increasing V. As a next step in the analysis, we computed the mass-specific mean absolute power (Pu) to obtain a global estimate of the rate at which mechanical work is performed during the gait cycle. When plotted on logarithmic coordinates, Pu increases linearly with V. The slope of this relationship varies considerably across subjects, spanning a threefold range. We found that, at any given V > 1 m s-1, the value of the plane orientation (u3t) is correlated with the corresponding value of the net mechanical power (Pu). On the average, the progressive rotation of the plane with increasing V is associated with a reduction of the increment of Pu that would occur if u3t remained constant at the value characteristic of low V. The specific orientation of the plane at any given speed is not the same in all subjects, but there is an orderly shift of the plane orientation that correlates with the net power expended by each subject. In general, smaller values of u3t tend to be associated with smaller values of Pu and vice versa. We conclude that the parametric tuning of the plane of angular covariation is a reliable predictor of the mechanical energy expenditure of each subject and could be used by the nervous system for limiting the overall energy expenditure.

The tyrosine kinase Src is frequently activated in advanced human prostate carcinomas and its activation correlates with tyrosine phosphorylation of the RNAbinding protein Sam68. Herein, we have investigated the expression and function of Sam68 in human prostate cancer cells. Analysis of specimens obtained from 20 patients revealed that Sam68 is upregulated at the protein level in 35% of the samples. Real-time polymerase chain reaction confirmed the results at the mRNA level in most patients. Downregulation of Sam68 by RNAi in LNCaP prostate cancer cells delayed cell cycle progression and reduced the proliferation rate. Moreover, depletion of Sam68 sensitized cells to apoptosis induced by DNAdamaging agents. Similarly, stable cell lines expressing a truncated GFP-Sam68 GSG protein displayed reduced growth rates and higher sensitivity to cisplatin-induced apoptosis. Microarray analyses revealed that a subset of genes involved in proliferation and apoptosis were altered when Sam68 was knocked down in LNCaP cells. Our results indicate that Sam68 expression supports prostate cancer cells proliferation and survival to cytotoxic agents.

To identify differentially expressed genes in multiple sclerosis, microarrays were used in a stringent experimental setting-leukapheresis from disease-discordant monozygotic twins and gene expression profiling in CD4(+) and CD8(+) T-cell subsets. Disease-related differences emerged only in the CD8(+) T-cell subset. The five differentially expressed genes identified included killer cell lectin-like receptor subfamily B, member 1, also known as natural killer receptor protein 1a/CD161, presented by the International Multiple Sclerosis Genetics Consortium as one of the non-MHC candidate loci. Flow cytometric analysis on peripheral blood of healthy donors and patients with multiple sclerosis and rheumatoid arthritis confirmed an upregulation of CD161 at the protein level, showing also a significant excess of CD161(high)CD8(+) T cells in multiple sclerosis. This subset prevalently included chemokine (C-C motif) receptor 6(+), cytokine-producing, effector-memory T cells with proinflammatory profiles. It also included all circulating interleukin-17(+)CD8(+) T cells. In the CD161(high)CD8(+) subset, interleukin-12 facilitated proliferation and interferon-γ production, with CD161 acting as a co-stimulatory receptor. CD161(+)CD8(+)CD3(+) T cells producing interferon-γ were part of intralesional immune infiltrates and ectopic B cell follicles in autopsy multiple sclerosis brains. Variations of CD161 expression on CD8(+) T cells identify a subset of lymphocytes with proinflammatory characteristics that have not been previously reported in multiple sclerosis and are likely to contribute to disease immunopathology.

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