Auditory stimulation improves motor function and caretaker burden in children with cerebral palsy- A randomized double blind study.

AIM: To investigate the impact of auditory stimulation on motor function in children with cerebral palsy (CP) and disabling hypertonia. METHOD: 9 matched pairs (age: 7y5m, SD 4y1m; 13 boys; gross-motor-functional-classification-scale: median 4; manual-ability-classification-system: median 4) were randomized to receive either auditory stimulation embedded in music (study, n = 9) or music alone (sham, control, n = 9) for at least 10 minutes 4 times a week for 4 weeks. Goal-Attainment-Scale, Care-and-Comfort-Hypertonicity-Questionnaire, Gross-Motor-Function-Measure and Quality-of-Upper-Extremity-Skills-Test (QUEST) were assessed before and 5 months following intervention. RESULT: Children receiving auditory stimulation attained more goals than children who listened to music alone (p = 0.002). Parents reported improved care and comfort in children in the study group compared to a slight deterioration in controls (p = 0.002). Upper extremity skills improved in the study group compared to controls (p = 0.006). Similar gross motor function changes were documented in both groups (p = 0.41). One participant reported increased seizure frequency; no other participants with epilepsy reported increased seizure frequency (n = 6/18) and no other adverse events were reported. INTERPRETATION: Auditory stimulation alleviated hypertonia and improved fine and gross motor functions

Myosin IIA Modulates T Cell Receptor Transport and CasL Phosphorylation during Early Immunological Synapse Formation

Activation of T cell receptor (TCR) by antigens occurs in concert with an elaborate multi-scale spatial reorganization of proteins at the immunological synapse, the junction between a T cell and an antigen-presenting cell (APC). The directed movement of molecules, which intrinsically requires physical forces, is known to modulate biochemical signaling. It remains unclear, however, if mechanical forces exert any direct influence on the signaling cascades. We use T cells from AND transgenic mice expressing TCRs specific to the moth cytochrome c 88–103 peptide, and replace the APC with a synthetic supported lipid membrane. Through a series of high spatiotemporal molecular tracking studies in live T cells, we demonstrate that the molecular motor, non-muscle myosin IIA, transiently drives TCR transport during the first one to two minutes of immunological synapse formation. Myosin inhibition reduces calcium influx and colocalization of active ZAP-70 (zeta-chain associated protein kinase 70) with TCR, revealing an influence on signaling activity. More tellingly, its inhibition also significantly reduces phosphorylation of the mechanosensing protein CasL (Crk-associated substrate the lymphocyte type), raising the possibility of a direct mechanical mechanism of signal modulation involving CasL

Requirement of Nck adaptors for actin dynamics and cell migration stimulated by platelet-derived growth factor B

The Nck family of Src homology (SH) 2/SH3 domain adaptors functions to link tyrosine phosphorylation induced by extracellular signals with downstream regulators of actin dynamics. We investigated the role of mammalian Nck adaptors in signaling from the activated platelet-derived growth factor (PDGF) receptor (PDGFβR) to the actin cytoskeleton. We report here that Nck adaptors are required for cytoskeletal reorganization and chemotaxis stimulated by PDGF-B. Analysis of tyrosine-phosphorylated proteins demonstrated that Crk-associated substrate (p130(Cas)), not the activated PDGFβR itself, is the major Nck SH2 domain-binding protein in PDGF-B-stimulated cells. Both Nck- and p130(Cas)-deficient cells fail to display cytoskeletal rearrangements, including the formation of membrane ruffles and the disassembly of actin bundles, typically shown by their WT counterparts in response to PDGF-B. Furthermore, Nck and p130(Cas) colocalize in phosphotyrosine-enriched membrane ruffles induced by PDGF-B in NIH 3T3 cells. These results suggest that Nck adaptors play an essential role in linking the activated PDGFβR with actin dynamics through a pathway that involves p130(Cas)