Postural and respiratory activation of the trunk muscles changes with mode and speed of locomotion

Despite the importance of the deep intrinsic spinal muscles for trunk control, few studies have investigated their activity during human locomotion or how this may change with speed and mode of locomotion. Furthermore, it has not been determined whether the postural and respiratory functions, of which these muscles take part, can be coordinated when locomotor demands are increased. EMG recordings of abdominal and paraspinal muscles were made in seven healthy subjects using fine-wire and surface electrodes. Measurements were also made of respiration and gait parameters. Recordings were made for 10s as subjects walked on a treadmill at 1 and 2 ms(-1) and ran at 2, 3, 4 and 5 ms(-1). Unlike the superficial muscles, transversus abdominis was active tonically throughout the gait cycle with all tasks, except running at speeds of 3 ms(-1) and greater. All other muscles were recruited in a phasic manner. The relative duration of these bursts of activity was influenced by speed and/or mode of locomotion. Activity of all abdominal muscles, except rectus abdominis (RA), was modulated both for respiration and locomotor-related functions but this activity was affected by the speed and mode of locomotion. This study provides evidence that the deep abdominal muscles are controlled independently of the other trunk muscles. Furthermore, the pattern of recruitment of the trunk muscles and their respiratory and postural coordination is dependent on the speed and mode of locomotion. (C) 2003 Published by Elsevier B.V.

Analysis of the effect of different NKT cell subpopulations on the activation of CD4 and CD8 T cells, NK cells, and B cells

Objective. NKT cells have diverse immune regulatory functions including activation of cells involved in Th1- and Th2-type immune activities. Most previous studies have investigated the functions of NKT cells as a single family but more recent evidence indicates the distinct functional properties of NKT cell subpopulation. This study aims to determine whether NKT cell subpopulations have different stimulatory activities on other immune cells that may affect the outcome of NKT cell-based immunotherapy. Methods. NKT cells and NKT cell subpopulations (CD4(+)CD8(-), CD4(-)CD8(+), CD4(-)CD8(+)) were cocultured with PBMC and their activities on immune cells including CD4(+) and CD8(+) T cells, NK cells, and B cells were assessed by flow cytometry. The production of cytokines in culture was measured by enzyme-linked immunsorbent assay. Results. The CD4(+)CD8(-) NKT cells demonstrated substantially greater stimulatory activities on CD4(+) T cells, NK cells, and B cells than other NKT cell subsets. The CD4(-)CD8(+) NKT cells showed the greatest activity on CD8(+) T cells, and were the only NKT cell subset that activated these immune cells. The CD4(-)CD8(-) NKT cells showed moderate stimulatory activity on CD4(+) T cells and the least activity on other immune cells. Conclusion. The results here suggest that NKT cell subpopulations differ in their abilities to stimulate other immune cells. This highlights the potential importance of manipulating specific NKT cell subpopulations for particular therapeutic situations and of evaluating subpopulations, rather than NKT cells as a group, during investigation of a possible role of NKT cells in various disease settings. (c) 2006 International Society for Experimental Hematology. Published by Elsevier Inc.

Complex numbers and symmetries in quantum mechanics, and a nonlinear superposition principle for Wigner functions

Complex numbers appear in the Hilbert space formulation of quantum mechanics, but not in the formulation in phase space. Quantum symmetries are described by complex, unitary or antiunitary operators defining ray representations in Hilbert space, whereas in phase space they are described by real, true representations. Equivalence of the formulations requires that the former representations can be obtained from the latter and vice versa. Examples are given. Equivalence of the two formulations also requires that complex superpositions of state vectors can be described in the phase space formulation, and it is shown that this leads to a nonlinear superposition principle for orthogonal, pure-state Wigner functions. It is concluded that the use of complex numbers in quantum mechanics can be regarded as a computational device to simplify calculations, as in all other applications of mathematics to physical phenomena.

C-terminal charged cluster of MscL, RKKEE, functions as a pH sensor

The RKKEE cluster of charged residues located within the cytoplasmic helix of the bacterial mechanosensitive channel, MscL, is essential for the channel function. The structure of MscL determined by x-ray crystallography and electron paramagnetic resonance spectroscopy has revealed discrepancies toward the C-terminus suggesting that the structure of the C-terminal helical bundle differs depending on the pH of the cytoplasm. In this study we examined the effect of pH as well as charge reversal and residue substitution within the RKKEE cluster on the mechanosensitivity of Escherichia coli MscL reconstituted into liposomes using the patch-clamp technique. Protonation of either positively or negatively charged residues within the cluster, achieved by changing the experimental pH or residue substitution within the RKKEE cluster, significantly increased the free energy of activation for the MscL channel due to an increase in activation pressure. Our data suggest that the orientation of the C-terminal helices relative to the aqueous medium is pH dependent, indicating that the RKKEE cluster functions as a proton sensor by adjusting the channel sensitivity to membrane tension in a pH-dependent fashion. A possible implication of our results for the physiology of bacterial cells is briefly discussed.

Patched1 functions as a gatekeeper by promoting cell cycle progression

Mutations in the Hedgehog receptor, Patched 1 (Ptch1), have been linked to both familial and sporadic forms of basal cell carcinoma (BCC), leading to the hypothesis that loss of Ptch1 function is sufficient for tumor progression. By combining conditional knockout technology with the inducible activity of the Keratin6 promoter, we provide in vivo evidence that loss of Ptch1 function from the basal cell population of mouse skin is sufficient to induce rapid skin tumor formation, reminiscent of human BCC. Elimination of Ptch1 does not promote the nuclear translocation of beta-catenin and does not induce ectopic activation or expression of Notch pathway constituents. In the absence of Ptch1, however, a large proportion of basal cells exhibit nuclear accumulation of the cell cycle regulators cyclin D1 and B1. Collectively, our data suggest that Ptch1 likely functions as a tumor suppressor by inhibiting G(1)-S phase and G(2)-M phase cell cycle progression, and the rapid onset of tumor progression clearly indicates Ptch1 functions as a gatekeeper. In addition, we note the high frequency and rapid onset of tumors in this mouse model makes it an ideal system for testing therapeutic strategies, such as Patched pathway inhibitors.

Protein kinase C activation and its role in kidney disease

Protein kinase C (PKC) comprises a superfamily of isoenzymes, many of which are activated by cofactors such as diacylglycerol and phosphatidylserine. In order to be capable of activation, PKC must first undergo a series of phosphorylations. In turn, activated PKC phosphorylates a wide variety of intracellular target proteins and has multiple functions in signal transduced cellular regulation. A role for PKC activation had been noted in several renal diseases, but two that have had most investigation are diabetic nephropathy and kidney cancer. In diabetic nephropathy, an elevation in diacylglycerol and/or other cofactor stimulants leads to an increase in activity of certain PKC isoforms, changes that are linked to the development of dysfunctional vasculature. The ability of isoform-specific PKC inhibitors to antagonize diabetes-induced vascular disease is a new avenue for treatment of this disorder. In the development and progressive invasiveness of kidney cancer, increased activity of several specific isoforms of PKC has been noted. It is thought that this may promote the kidney cancer's inherent resistance to apoptosis, in natural regression or after treatments, or it may promote the invasiveness of renal cancers via cellular differentiation pathways. In general, however, a more complete understanding of the functions of individual PKC isoforms in the kidney, and development or recognition of specific inhibitors or promoters of their activation, will be necessary to apply this knowledge for treatment of cellular dysregulation in renal disease.