Coupling between muscle activities and muscle torques during horizontal-planar arm movements with direction reversal.

In this study we investigated the hypothesis that the simple set of rules used to explain the modulation of muscle activities during single-joint movements could also be applied for reversal movements of the shoulder and elbow joints. The muscle torques of both joints were characterized by a triphasic impulse. The first impulse of each joint accelerated the limb to the target and was generated by an initial burst of the muscles activated first (primary mover). The second impulse decelerated the limb to the target, reversed movement direction and accelerated the limb back to the initial position, and was generated by an initial burst of the muscles activated second (secondary movers). A third impulse, in each joint, decelerated the limb to the initial position due to the generation of a second burst of the primary movers. The first burst of the primary mover decreased abruptly, and the latency between the activation of the primary and secondary movers varied in proportion with target distances for the elbow, but not for the shoulder muscles. All impulses and bursts increased with target distances and were well coupled. Therefore, as predicted, the bursts of muscle activities were modulated to generate the appropriate level of muscle torque.     

Age causes a redistribution of joint torques and powers during gait.

At self-selected walking speeds, elderly compared with young adults generate decreased joint torques and powers in the lower extremity. These differences may be actual gait-limiting factors and neuromuscular adaptations with age or simply a consciously selected motor pattern to produce a slower gait. The purpose of the study was to compare joint torques and powers of young and elderly adults walking at the same speed. Twelve elderly and fourteen young adults (ages 69 and 21 yr) walked at 1.48 m/s over a force platform while being videotaped. Hip, knee, and ankle torques and powers were calculated from the reaction force and kinematic data. A support torque was calculated as the sum of the three joint torques. Extensor angular impulse during stance and positive work at each joint were derived from the torques and powers. Step length was 4% shorter and cadence was 4% higher in elderly adults (both P < 0.05) compared with young adults. Support angular impulse was nearly identical between groups, but elderly adults had 58% greater angular impulse and 279% more work at the hip, 50% less angular impulse and 39% less work at the knee, and 23% less angular impulse and 29% less work at the ankle compared with young adults (t-test, all P < 0.05). Age caused a redistribution of joint torques and powers, with the elderly using their hip extensors more and their knee extensors and ankle plantar flexors less than young adults when walking at the same speed. Along with a reduction in motor and sensory functions, the natural history of aging causes a shift in the locus of function in motor performance.     

Sarcoidosis is not associated with a generalized defect in T cell suppressor function

In pulmonary sarcoidosis, the marked expansion of CD4+ (helper/inducer) T cells in the alveolar structures of the lung is maintained by local IL-2 release by activated CD4+ HLA-DR+ T cells without concomitant expansion and activation of CD8+ (suppressor/cytotoxic) T cells, suggesting that sarcoid may be associated with a generalized abnormality of CD8+ T cells. Consistent with this concept, evaluation of the expression of the IL-2R on fresh lung T cells from individuals with active sarcoidosis demonstrated that 7 +/- 1% of sarcoid lung CD4+ T cells are spontaneously expressing the IL-2R compared with only 1 +/- 1% lung CD8+ T cells (p less than 0.01). However, stimulation of purified sarcoid blood CD8+ T cells with the anti-T3/TCR complex mAb OKT3 was followed by the normal expression of IL-2R (p greater than 0.1) and proliferation (p greater than 0.1). In addition, lung sarcoid CD8+ T cells responded to OKT3 similarly to normal lung CD8+ T cells and to autologous blood CD8+ T cells as regards expression of IL-2R (p greater than 0.1) and proliferation (p greater than 0.1). Finally, using CD4+ cells activated with allogenic Ag to induce, in coculture, fresh autologous CD8+ cells to suppress proliferation of fresh autologous CD4+ cells to the same Ag, sarcoid CD8+ T cells suppressed CD4+ cell proliferation in a normal fashion (p greater than 0.1). These results demonstrate that sarcoid CD8+ (suppressor/cytotoxic) T cells are competent to respond to a proliferation signal normally and can be induced to normally suppress CD4+ T cell proliferation to Ag, suggesting that the expansion of activated CD4+ T cells in pulmonary sarcoidosis is not due to a generalized abnormality of CD8+ T cells or of their suppressor T cell function.     

The time-dependent distribution of phosphorylated intermediates in native sarcoplasmic reticulum Ca2+-ATPase from skeletal muscle is not compatible with a linear kinetic model

Quenched-flow mixing was used to characterize the kinetic behavior of the intermediate reactions of the skeletal muscle sarcoplasmic reticulum (SR) Ca-ATPase (SERCA1) at 2 and 21 degrees C. At 2 degrees C, phosphorylation of SR Ca-ATPase with 100 microM ATP labeled one-half of the catalytic sites with a biphasic time dependence [Mahaney, J. E., Froehlich, J. P., and Thomas, D. D. (1995) Biochemistry 34, 4864-4879]. Chasing the phosphoenzyme (EP) with 1.66 mM ADP 10 ms after the start of phosphorylation revealed mostly ADP-insensitive E2P (95% of EP(total)), consistent with its rapid formation from ADP-sensitive E1P. The consecutive relationship of the phosphorylated intermediates predicts a decrease in the proportion of E1P ([E1P]/[EP(total)]) with increasing phosphorylation time. Instead, after 10 ms the proportion of E1P increased and that of E2P decreased until they reached a constant 1:1 stoichiometry ([E1P]:[E2P] approximately 1). At 21 degrees C, phosphorylation displayed a transient overshoot associated with an inorganic phosphate (P(i)) burst, reflecting increased turnover of E2P at the higher temperature. The P(i) burst exceeded the decay of the EP overshoot, suggesting that rephosphorylation of the enzyme occurs before the recycling step (E2 --> E1). This behavior and the reversed order of accumulation of phosphorylated intermediates at 2 degrees C are not compatible with the conventional linear consecutive reaction mechanism: E1 + ATP --> E1.ATP --> E1P + ADP --> E2P --> E2.P(i) --> E1 + P(i). Solubilization of the Ca-ATPase into monomers using the nonionic detergent C(12)E(8) gave a pattern of phosphorylation in which E1P and E2P behave like consecutive intermediates. Kinetic modeling of the C(12)E(8)-solubilized SR Ca-ATPase showed that it behaves according to the conventional Ca-ATPase reaction mechanism, consistent with monomeric catalytic function. We conclude that the nonconforming features of native SERCA1 arise from oligomeric protein conformational interactions that constrain the subunits to a staggered or out-of-phase mode of operation.     

JNK1 is not essential for TNF-mediated joint disease

Tumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central importance. Herein, we investigate the role in vivo of TNF-α signalling through c-Jun N-terminal kinase (JNK)1 in destructive arthritis. Human TNF transgenic (hTNFtg) mice, which develop inflammatory arthritis, were intercrossed with JNK1-deficient (JNK1 ^-/-) mice. Animals (n = 35) of all four genotypes (wild-type, JNK1 ^-/-, hTNFtg, JNK1 ^-/-hTNFtg) were assessed for clinical and histological signs of arthritis. Clinical features of arthritis (swelling and decreased grip strength) developed equally in hTNFtg and JNK1 ^-/-hTNFtg mice. Histological analyses revealed no differences in the quantity of synovial inflammation and bone erosions or in the cellular composition of the synovial infiltrate. Bone destruction and osteoclast formation were observed to a similar degree in hTNFtg and JNK1 ^-/-hTNFtg animals. Moreover, cartilage damage, as indicated by proteoglycan loss in the articular cartilage, was comparable in the two strains. Intact phosphorylation of JNK and c-Jun as well as expression of JNK2 in the synovial tissue of JNK1 ^-/-hTNFtg mice suggests that signalling through JNK2 may compensate for the deficiency in JNK1. Thus, JNK1 activation does not seem to be essential for TNF-mediated arthritis.     

JNK1 is not essential for TNF-mediated joint disease

Tumour necrosis factor (TNF) signalling molecules are considered as promising therapeutic targets of antirheumatic therapy. Among them, mitogen-activated protein kinases are thought to be of central importance. Herein, we investigate the role in vivo of TNF-alpha signalling through c-Jun N-terminal kinase (JNK)1 in destructive arthritis. Human TNF transgenic (hTNFtg) mice, which develop inflammatory arthritis, were intercrossed with JNK1-deficient (JNK1-/-) mice. Animals (n = 35) of all four genotypes (wild-type, JNK1-/-, hTNFtg, JNK1-/-hTNFtg) were assessed for clinical and histological signs of arthritis. Clinical features of arthritis (swelling and decreased grip strength) developed equally in hTNFtg and JNK1-/-hTNFtg mice. Histological analyses revealed no differences in the quantity of synovial inflammation and bone erosions or in the cellular composition of the synovial infiltrate. Bone destruction and osteoclast formation were observed to a similar degree in hTNFtg and JNK1-/-hTNFtg animals. Moreover, cartilage damage, as indicated by proteoglycan loss in the articular cartilage, was comparable in the two strains. Intact phosphorylation of JNK and c-Jun as well as expression of JNK2 in the synovial tissue of JNK1-/-hTNFtg mice suggests that signalling through JNK2 may compensate for the deficiency in JNK1. Thus, JNK1 activation does not seem to be essential for TNF-mediated arthritis.     

The influence of soft tissue movement on ground reaction forces, joint torques and joint reaction forces in drop landings

The aim of this study was to determine the effects that soft tissue motion has on ground reaction forces, joint torques and joint reaction forces in drop landings. To this end a four body-segment wobbling mass model was developed to reproduce the vertical ground reaction force curve for the first 100 ms of landing. Particular attention was paid to the passive impact phase, while selecting most model parameters a priori, thus permitting examination of the rigid body assumption on system kinetics. A two-dimensional wobbling mass model was developed in DADS (version 9.00, CADSI) to simulate landing from a drop of 43 cm. Subject-specific inertia parameters were calculated for both the rigid links and the wobbling masses. The magnitude and frequency response of the soft tissue of the subject to impulsive loading was measured and used as a criterion for assessing the wobbling mass motion. The model successfully reproduced the vertical ground reaction force for the first 100 ms of the landing with a peak vertical ground reaction force error of 1.2% and root mean square errors of 5% for the first 15 ms and 12% for the first 40 ms. The resultant joint forces and torques were lower for the wobbling mass model compared with a rigid body model, up to nearly 50% lower, indicating the important contribution of the wobbling masses on reducing system loading.     

Impaired muscle glycogen resynthesis after a marathon is not caused by decreased muscle GLUT-4 content

Asp, Sven, Thomas Rohde, and Erik A. Richter. Impairedmuscle glycogen resynthesis after a marathon is not caused by decreasedmuscle GLUT-4 content. J. Appl.Physiol. 83(5): 1482-1485, 1997.Our purpose wasto investigate whether the slow rate of muscle glycogen resynthesisafter a competitive marathon is associated with a decrease in the totalmuscle content of the muscle glucose transporter (GLUT-4). Sevenwell-trained marathon runners participated in the study, and musclebiopsies were obtained from the lateral head of the gastrocnemiusmuscle before, immediately after, and 1, 2, and 7 days after themarathon, as were venous blood samples. Muscle GLUT-4 content wasunaltered over the experimental period. Muscle glycogen concentrationwas 758 ± 53 mmol/kg dry weight before the marathon anddecreased to 148 ± 39 mmol/kg dry weight immediately afterward.Despite a carbohydrate-rich diet (containing at least 7 gcarbohydrate · kg bodymass¹ · day¹),the muscle glycogen concentration remained 30% lower than before-race values 2 days after the race, whereas it had returned to before-race levels 7 days after the race. We conclude that the total GLUT-4 proteincontent is unaltered in the lateral gastrocnemius after a competitivemarathon and that the slow recovery of muscle glycogen after the raceapparently involves factors other than changes in the total content ofthis protein.

     

The use of generalized linear models and generalized estimating equations in bioarchaeological studies

The current article explores whether the application of generalized linear models (GLM) and generalized estimating equations (GEE) can be used in place of conventional statistical analyses in the study of ordinal data that code an underlying continuous variable, like entheseal changes. The analysis of artificial data and ordinal data expressing entheseal changes in archaeological North African populations gave the following results. Parametric and nonparametric tests give convergent results particularly for P values <0.1, irrespective of whether the underlying variable is normally distributed or not under the condition that the samples involved in the tests exhibit approximately equal sizes. If this prerequisite is valid and provided that the samples are of equal variances, analysis of covariance may be adopted. GLM are not subject to constraints and give results that converge to those obtained from all nonparametric tests. Therefore, they can be used instead of traditional tests as they give the same amount of information as them, but with the advantage of allowing the study of the simultaneous impact of multiple predictors and their interactions and the modeling of the experimental data. However, GLM should be replaced by GEE for the study of bilateral asymmetry and in general when paired samples are tested, because GEE are appropriate for correlated data. Am J Phys Anthropol 153:473–483, 2014. © 2013 Wiley Periodicals, Inc.     

The cell adhesion molecule M-cadherin is not essential for muscle development and regeneration

M-cadherin is a classical calcium-dependent cell adhesion molecule that is highly expressed in developing skeletal muscle, satellite cells, and cerebellum. Based on its expression pattern and observations in cell culture, it has been postulated that M-cadherin may be important for the fusion of myoblasts to form myotubes, the correct localization and function of satellite cells during muscle regeneration, and the specialized architecture of adhering junctions in granule cells of cerebellar glomeruli. In order to investigate the potential roles of M-cadherin in vivo, we generated a null mutation in mice. Mutant mice were viable and fertile and showed no gross developmental defects. In particular, the skeletal musculature appeared essentially normal. Moreover, muscle lesions induced by necrosis were efficiently repaired in mutant mice, suggesting that satellite cells are present, can be activated, and are able to form new myofibers. This was also confirmed by normal growth and fusion potential of mutant satellite cells cultured in vitro. In the cerebellum of M-cadherin-lacking mutants, typical contactus adherens junctions were present and similar in size and numbers to the equivalent junctions in wild-type animals. However, the adhesion plaques in the cerebellum of these mutants appeared to contain elevated levels of N-cadherin compared to wild-type animals. Taken together, these observations suggest that M-cadherin in the mouse serves no absolutely required function during muscle development and regeneration and is not essential for the formation of specialized cell contacts in the cerebellum. It seems that N-cadherin or other cadherins can largely compensate for the lack of M-cadherin.     

The muscle chloride channel ClC-1 is not directly regulated by intracellular ATP

ClC-1 belongs to the gene family of CLC Cl(-) channels and Cl(-)/H(+) antiporters. It is the major skeletal muscle chloride channel and is mutated in dominant and recessive myotonia. In addition to the membrane-embedded part, all mammalian CLC proteins possess a large cytoplasmic C-terminal domain that bears two so-called CBS (from cystathionine-beta-synthase) domains. Several studies indicate that these domains might be involved in nucleotide binding and regulation. In particular, Bennetts et al. (J. Biol. Chem. 2005. 280:32452-32458) reported that the voltage dependence of hClC-1 expressed in HEK cells is regulated by intracellular ATP and other nucleotides. Moreover, very recently, Bennetts et al. (J. Biol. Chem. 2007. 282:32780-32791) and Tseng et al. (J. Gen. Physiol. 2007. 130:217-221) reported that the ATP effect was enhanced by intracellular acidification. Here, we show that in striking contrast with these findings, human ClC-1, expressed in Xenopus oocytes and studied with the inside-out configuration of the patch-clamp technique, is completely insensitive to intracellular ATP at concentrations up to 10 mM, at neutral pH (pH 7.3) as well as at slightly acidic pH (pH 6.2). These results have implications for a general understanding of nucleotide regulation of CLC proteins and for the physiological role of ClC-1 in muscle excitation.