Lokomat guided gait in hemiparetic stroke patients:the effects of training parameters on muscle activity and temporal symmetry

Purpose: The Lokomat is a commercially available robotic gait trainer, applied for gait rehabilitation in post-stroke hemiparetic patients. Selective and well-dosed clinical use of the Lokomat training parameters, i.e. guidance, speed and bodyweight support, requires a good understanding of how these parameters affect the neuromuscular control of post-stroke hemiparetic gait. Materials and methods: Ten stroke patients (unilateral paresis, 7 females, 64.5 ± 6.4 years, >3months post-stroke, FAC scores 2–4)) walked in the Lokomat under varying parameter settings: 50% or 100% guidance, 0.28 or 0.56m/s, 0% or 50% bodyweight support. Electromyography was recorded bilaterally from Gluteus Medius, Biceps Femoris, Vastus Lateralis, Medial Gastrocnemius, and Tibialis Anterior. Pressure sensors placed under the feet were used to determine the level of temporal gait symmetry. Results: Varying guidance and bodyweight support had little effect on muscle activity, but increasing treadmill speed led to increased activity in both the affected (Biceps Femoris, Medial Gastrocnemius, Tibialis Anterior) and unaffected leg (all muscles). The level of temporal symmetry was unaffected by the parameter settings. Conclusions: The Lokomat training parameters are generally ineffective in shaping short term muscle activity and step symmetry patients with hemiparetic stroke, as speed is the only parameter that significantly affects muscular amplitude. Trial Registration: d.n.a.IMPLICATIONS FOR REHABILITATIONThe Lokomat is a commercially available gait trainer that can be used for gait rehabilitation in post-stroke hemiparetic patients.This study shows that muscle amplitude is generally low during Lokomat guided walking, and that treadmill Speed is the main training parameter to influence muscular output in stroke patients during Lokomat walking.Varying Guidance and Bodyweight Support within a clinical relevant range barely affected muscle activity, and temporal step symmetry was unaffected by variation in any of the training parameters.Based on the findings it is advised to increase speed as early as possible during Lokomat therapy, or use other means (e.g. feedback or instructions) to stimulate active involvement of patients during training. The Lokomat is a commercially available gait trainer that can be used for gait rehabilitation in post-stroke hemiparetic patients. This study shows that muscle amplitude is generally low during Lokomat guided walking, and that treadmill Speed is the main training parameter to influence muscular output in stroke patients during Lokomat walking. Varying Guidance and Bodyweight Support within a clinical relevant range barely affected muscle activity, and temporal step symmetry was unaffected by variation in any of the training parameters. Based on the findings it is advised to increase speed as early as possible during Lokomat therapy, or use other means (e.g. feedback or instructions) to stimulate active involvement of patients during training.</p

Справа Івана Дзюби

У статті автор, використовуючи документи Галузевого державного архіву СБ України, досліджує постать видатного літературознавця, громадського діяча Івана Дзюби у контексті боротьби співробітників органів держбезпеки УРСР з «українським буржуазним націоналізмом».В статье автор, используя документы Отраслевого государственного архива СБ Украины, исследует личность выдающегося литературоведа, общественного деятеля Ивана Дзюбы в контексте борьбы сотрудников органов госбезопасности УССР с «украинским буржуазным национализмом».Using the documents of State branch archive of State Security of Ukraine, the author investigates the personality of Ivan Dzyuba during the struggle of KGB of the UkSSR against the «Ukrainian bourgeois nationalism»

Regulated Membrane Localization of Tiam1, Mediated by the NH2-terminal Pleckstrin Homology Domain, Is Required for Rac-dependent Membrane Ruffling and C-Jun NH2-terminal Kinase Activation

Rho-like GTPases, including Cdc42, Rac, and Rho, regulate signaling pathways that control actin cytoskeletal structures and transcriptional activation. The Tiam1 gene encodes an activator of Rac1, and similarly to constitutively activated (V12)Rac1, overexpression of Tiam1 in fibroblasts induces the formation of membrane ruffles. Tiam1 contains a Dbl homology (DH) domain and adjacent pleckstrin homology (PH) domain, hallmarks for activators of Rho-like GTPases. Unique for Tiam1 are an additional PH domain and a Discs-large homology region in the NH2-terminal part of the protein. Here we show that both in fibroblasts and COS cells, membrane localization of Tiam1 is required for the induction of membrane ruffling. A detailed mutational analysis, in combination with confocal laser scanning microscopy and immunoelectron microscopy, demonstrates that the NH2-terminal PH domain of Tiam1, but not the DH-adjacent PH domain, is essential for membrane association. This NH2-terminal PH domain of Tiam1 can be functionally replaced by the myristoylated membrane localization domain of c-Src, indicating that the primary function of this PH domain is to localize the protein at the membrane. After serum starvation, both membrane association of Tiam1 and ruffling can be induced by serum, suggesting that receptor stimulation induces membrane translocation of Tiam1. Similar to V12Rac1, Tiam1 stimulates the activity of the c-Jun NH2-terminal kinase (JNK). This Rac-dependent stimulation of JNK also requires membrane association of Tiam1. We conclude that the regulated membrane localization of Tiam1 through its NH2-terminal PH domain determines the activation of distinct Rac-mediated signaling pathways

The Rac activator Tiam1 is required for α3β1-mediated laminin-5 deposition, cell spreading, and cell migration

The Rho-like guanosine triphosphatase Rac1 regulates various signaling pathways, including integrin-mediated adhesion and migration of cells. However, the mechanisms by which integrins signal toward Rac are poorly understood. We show that the Rac-specific guanine nucleotide exchange factor Tiam1 (T-lymphoma invasion and metastasis 1) is required for the integrin-mediated laminin (LN)-5 deposition, spreading, and migration of keratinocytes. In contrast to wild-type keratinocytes, Tiam1-deficient (Tiam1−/−) keratinocytes are unable to adhere to and spread on a glass substrate because they are unable to deposit their own LN5 substrate. Both Tiam1 and V12Rac1 can rescue the defects of Tiam1−/− keratinocytes, indicating that these deficiencies are caused by impaired Tiam1-mediated Rac activation. Tiam1−/− cells are unable to activate Rac upon α3β1-mediated adhesion to an exogenous LN5 substrate. Moreover, Tiam1 deficiency impairs keratinocyte migration in vitro and reepithelialization of excision wounds in mouse skin. Our studies indicate that Tiam1 is a key molecule in α3β1-mediated activation of Rac, which is essential for proper production and secretion of LN5, a requirement for the spreading and migration of keratinocytes

Knockout of the Arp2/3 complex in epidermis causes a psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2

Arp2/3 complex assembles branched actin filaments key to many cellular processes, but its organismal roles remain poorly understood. Here we employed conditional arpc4 knockout mice to study the function of the Arp2/3 complex in the epidermis. We found that depletion of the Arp2/3 complex by knockout of arpc4 results in skin abnormalities at birth that evolve into a severe psoriasis-like disease hallmarked by hyperactivation of transcription factor Nrf2. Knockout of arpc4 in cultured keratinocytes was sufficient to induce nuclear accumulation of Nrf2, upregulation of Nrf2-target genes and decreased filamentous actin levels. Furthermore, pharmacological inhibition of the Arp2/3 complex unmasked the role of branched actin filaments in Nrf2 regulation. Consistently, we unveiled that Nrf2 associates with the actin cytoskeleton in cells and binds to filamentous actin in vitro. Finally, we discovered that Arpc4 is downregulated in both human and mouse psoriatic epidermis. Thus, the Arp2/3 complex affects keratinocytes' shape and transcriptome through an actin-based cell-autonomous mechanism that influences epidermal morphogenesis and homeostasis