Posture and hand load alter muscular response to sudden elbow perturbations

Joint stiffness and stability are reliant on coordinated muscle activity which may differ depending on initial posture and loading during sudden perturbations. This study investigated the effects of arm posture and hand load on muscle activity during perturbations of the arm. Fifteen male participants experienced perturbations to the wrist causing elbow extension using a combination of three body postures (standing, supine, sitting) and three hand load conditions (no, solid, and fluid loads), with known and unknown timing. Surface EMG was collected from eight muscles of the right upper extremity. The response to sudden loading was examined using muscle activities pre (baseline) and post (reflex) perturbation. During the baseline period, known perturbation timing resulted in greater muscular activity than for unknown timing, while the opposite was found for the reflex period. During the reflex period with fluid load, biceps brachii and brachioradialis demonstrated increased activity of 2.4% and 4.0% of maximum respectively, from supine to standing. During the reflex period, the fluid load resulted in forearm co-contraction 23% and 47% greater than the solid and no load conditions. Body orientation and hand loading influenced muscular response to elbow perturbations. Muscle co-contraction at the elbow during known timing suggests a contribution to elbow joint stability that may reduce injury risk caused by sudden elbow loading.     

Crosstalk in surface electromyography of the proximal forearm during gripping tasks.

Electromyographic (EMG) crosstalk was systematically analyzed to evaluate the magnitude of common signal present between electrode pairs around the forearm. Surface EMG was recorded and analyzed from seven electrode pairs placed circumferentially around the proximal forearm in six healthy individuals. The cross-correlation function was used to determine the amount of common signal, which was found to decrease as the distance between electrode pairs increased, but was not significantly altered by forearm posture (pronation, neutral, supination). Overall, approximately 40% common signal was detected between adjacent electrode pairs (3 cm apart), dropping to about 10% at 6 cm spacing and 2.5% at 9 cm. The magnitude of common signal approached 50% between adjacent electrode pairs over the extensor muscles, while over 60% was observed between neighbouring sites on the flexor aspect of the forearm. Although flexor and extensor EMG amplitude was similar, less than 2% common signal was present between flexor and extensor electrode pairs during both pinch and grasp tasks. Maximum grip force production was not affected by forearm rotation for pinch, but reduced 18% from neutral (mid-prone) to pronation during grasp (p=0.01). In spite of differences in grip force, mean muscle activity did not vary between the three forearm postures during maximum pinch or grasp trials. While this study improved our knowledge of crosstalk and electrode spacing issues, further examination of forearm EMG is required to improve understanding of muscle loading, EMG properties and motor control during gripping tasks.     

IFN-alpha secretion by type 2 predendritic cells up-regulates MHC class I in the HIV-1-infected thymus.

The ability of HIV-1 to evade the host immune response leads to the establishment of chronic infection. HIV-1 has been reported to up-regulate MHC I molecules on the surface of thymocytes from HIV-1-infected thymus. We demonstrate in this study that HIV-1 up-regulates MHC I on both HIV-1-infected and uninfected thymocytes in a manner that is independent of Nef, proportional to viral replication, and entirely mediated by IFN-alpha. IL-3Ralpha+ type 2 predendritic cells (preDC2) resident in the thymic medulla secrete IFN-alpha, which acts on IFN-alphabetaR-expressing immature thymocytes to induce MHC I expression. Furthermore, thymic preDC2 are permissive for HIV-1 infection and positive for intracellular p24. These data demonstrate the ability of IFN-alpha secreted by preDC2 to induce MHC I up-regulation in the HIV-1-infected human thymus.     

V3 spinal neurons establish a robust and balanced locomotor rhythm during walking

A robust and well-organized rhythm is a key feature of many neuronal networks, including those that regulate essential behaviors such as circadian rhythmogenesis, breathing, and locomotion. Here we show that excitatory V3-derived neurons are necessary for a robust and organized locomotor rhythm during walking. When V3-mediated neurotransmission is selectively blocked by the expression of the tetanus toxin light chain subunit (TeNT), the regularity and robustness of the locomotor rhythm is severely perturbed. A similar degeneration in the locomotor rhythm occurs when the excitability of V3-derived neurons is reduced acutely by ligand-induced activation of the allatostatin receptor. The V3-derived neurons additionally function to balance the locomotor output between both halves of the spinal cord, thereby ensuring a symmetrical pattern of locomotor activity during walking. We propose that the V3 neurons establish a regular and balanced motor rhythm by distributing excitatory drive between both halves of the spinal cord.     

Programmed death 1 ligand (PD-L) 1 and PD-L2 limit autoimmune kidney disease: distinct roles

The programmed death 1/programmed death 1 ligand (PD-L) pathway is instrumental in peripheral tolerance. Blocking this pathway exacerbates experimental autoimmune diseases, but its role in autoimmune kidney disease has not been explored. Therefore, we tested the hypothesis that the programmed death 1 ligands (PD-L1 and PD-L2), provide a protective barrier during T cell- and macrophage (Mphi)-dependent autoimmune kidney disease. For this purpose, we compared nephrotoxic serum nephritis (NSN) in mice lacking PD-L1 (PD-L1(-/-)), PD-L2 (PD-L2(-/-)), or both (PD-L1/L2(-/-)) to wild-type (WT) C57BL/6 mice. Kidney pathology, loss of renal function, and intrarenal leukocyte infiltrates were increased in each PD-L(-/-) strain as compared with WT mice. Although the magnitude of renal pathology was similar in PD-L1(-/-) and PD-L2(-/-) mice, our findings suggest that kidney disease in each strain is regulated by distinct mechanisms. Specifically, we detected increased CD68(+) cells along with elevated circulating IgG and IgG deposits in glomeruli in PD-L2(-/-) mice, but not PD-L1(-/-) mice. In contrast, we detected a rise in activated CD8(+) T cells in PD-L1(-/-) mice, but not PD-L2(-/-) mice. Furthermore, since PD-L1 is expressed by parenchymal and hemopoietic cells in WT kidneys, we explored the differential impact of PD-L1 expression on these cell types by inducing NSN in bone marrow chimeric mice. Our results indicate that PD-L1 expression on hemopoietic cells, and not parenchymal cells, is primarily responsible for limiting leukocyte infiltration during NSN. Taken together, our findings indicate that PD-L1 and PD-L2 provide distinct negative regulatory checkpoints poised to suppress autoimmune renal disease.     

Evaluation of the carpal tunnel based on 3-D reconstruction from MRI

While deviated wrist postures have been linked to the development of carpal tunnel syndrome, the relative contributions of posture-related changes in size, shape and volume of the carpal tunnel contribute to median nerve compression are unclear. The purpose of this study was two-fold: (1) to reconstruct the carpal tunnel from MRI data in neutral and non-neutral (30 degrees extension, 30 degrees flexion) wrist postures, and (2) to evaluate errors associated with off-axis imaging. Three-dimensional reconstruction of the carpal tunnels of 8 volunteers from the university community revealed that the orientation of the carpal tunnel was not directly explained by external wrist angle. The average orientation of the carpal tunnel was extended in all postures, ranging from 25 degrees +/-9 degrees in extension, 13 degrees +/-5 degrees in neutral and 4 degrees +/-4 degrees in the flexed wrist. Changing the orientation of the imaging plane to be perpendicular to the reconstructed carpal tunnel revealed that axial images overestimated cross-sectional area by an average of nearly 10% in extension, 4% in neutral and less than 1% in flexion. Similarly, adjusting the imaging plane to be perpendicular to external wrist angle overestimated cross-sectional area by an average of 2% in extension, 4% in neutral and 24% in flexion. Distortion of the carpal tunnel shape also became evident with rotation of the imaging plane. The data suggest that correction for the orientation of the carpal tunnel itself to be more appropriate than relying on external wrist angle. Computerized reconstruction provided detailed anatomic visualization of the carpal tunnel, and has created the framework to develop a biomechanical model of the carpal tunnel. Similar reconstruction of the tissue structures passing through (median nerve and flexor tendons) and entering the carpal tunnel (muscle tissue) will enable evaluation and partitioning of median nerve injury mechanisms.