An Asian-centric human movement database capturing activities of daily living.

Assessment of human movement performance in activities of daily living (ADL) is a key component in clinical and rehabilitation settings. Motion capture technology is an effective method for objective assessment of human movement. Existing databases capture human movement and ADL performance primarily in the Western population, and there are no Asian databases to date. This is despite the fact that Asian anthropometrics influence movement kinematics and kinetics. This paper details the protocol in the first phase of the largest Asian normative human movement database. Data collection has commenced, and this paper reports 10 healthy participants. Twelve tasks were performed and data was collected using Qualisys motion capture system, force plates and instrumented table and chair. In phase two, human movement of individuals with stroke and knee osteoarthritis will be captured. This can have great potential for benchmarking with the normative human movement captured in phase one and predicting recovery and progression of movement for patients. With individualised progression, it will offer the development of personalised therapy protocols in rehabilitation.

Lats1/2 Sustain Intestinal Stem Cells and Wnt Activation through TEAD-Dependent and Independent Transcription.

Intestinal homeostasis is tightly regulated by complex yet poorly understood signaling networks. Here, we demonstrate that Lats1/2, the core Hippo kinases, are essential to maintain Wnt pathway activity and intestinal stem cells. Lats1/2 deletion leads to loss of intestinal stem cells but drives Wnt-uncoupled crypt expansion. To explore the function of downstream transcriptional enhanced associate domain (TEAD) transcription factors, we identified a selective small-molecule reversible inhibitor of TEAD auto-palmitoylation that directly occupies its lipid-binding site and inhibits TEAD-mediated transcription in vivo. Combining this chemical tool with genetic and proteomics approaches, we show that intestinal Wnt inhibition by Lats deletion is Yes-associated protein (YAP)/transcriptional activator with PDZ-binding domain (TAZ) dependent but TEAD independent. Mechanistically, nuclear YAP/TAZ interact with Groucho/Transducin-Like Enhancer of Split (TLE) to block Wnt/T-cell factor (TCF)-mediated transcription, and dual inhibition of TEAD and Lats suppresses Wnt-uncoupled Myc upregulation and epithelial over-proliferation in Adenomatous polyposis coli (APC)-mutated intestine. Our studies highlight a pharmacological approach to inhibit TEAD palmitoylation and have important implications for targeting Wnt and Hippo signaling in human malignancies.

Dual phosphorylation of Ric-8A enhances its ability to mediate G protein α subunit folding and to stimulate guanine nucleotide exchange.

Resistance to inhibitors of cholinesterase-8A (Ric-8A) and Ric-8B are essential biosynthetic chaperones for heterotrimeric G protein α subunits. We provide evidence for the direct regulation of Ric-8A cellular activity by dual phosphorylation. Using proteomics, Western blotting, and mutational analyses, we determined that Ric-8A was constitutively phosphorylated at five serines and threonines by the protein kinase CK2. Phosphorylation of Ser435 and Thr440 in rat Ric-8A (corresponding to Ser436 and Thr441 in human Ric-8A) was required for high-affinity binding to Gα subunits, efficient stimulation of Gα subunit guanine nucleotide exchange, and mediation of Gα subunit folding. The CK2 consensus sites that contain Ser435 and Thr440 are conserved in Ric-8 homologs from worms to mammals. We found that the homologous residues in mouse Ric-8B, Ser468 and Ser473, were also phosphorylated. Mutation of the genomic copy of ric-8 in Caenorhabditis elegans to encode alanine in the homologous sites resulted in characteristic ric-8 reduction-of-function phenotypes that are associated with defective Gq and Gs signaling, including reduced locomotion and defective egg laying. The C. elegans ric-8 phosphorylation site mutant phenotypes were partially rescued by chemical stimulation of Gq signaling. These results indicate that dual phosphorylation represents a critical form of conserved Ric-8 regulation and demonstrate that Ric-8 proteins are needed for effective Gα signaling. The position of the CK2-phosphorylated sites within a structural model of Ric-8A reveals that these sites contribute to a key acidic and negatively charged surface that may be important for its interactions with Gα subunits.

The repeatablity of spinal motion of normal and scoliotic adolescents during walking.

The main aim of this study was to assess the within-day repeatability of measuring trunk and spinal motion during walking using external markers and a motion analysis system. A secondary aim was to compare the repeatability of motion between the scoliotic and normal spine. The sagittal and coronal plane trunk and spinal motion, three-dimensional pelvic and shoulder motion of 9 normal and 19 scoliotic adolescents was assessed. Intra-subject within-day repeatability was evaluated using waveform similarity statistics. Trunk sagittal and coronal plane motion was fairly repeatable. Repeatability of spinal frontal plane motion was fair, but that of sagittal plane motion is poor. Pelvic coronal and transverse plane motion was very reproducible but pelvic sagittal plane motion was very variable. Shoulder motion in all three planes was found to have a poor level of repeatability. A relationship possibly exists between the range of motion and repeatability values. Although the scoliotic adolescents had less variable spinal motion, differences from the normal subjects were not statistically significant. However, the scoliotic subjects had significantly more repeatable sagittal and coronal plane pelvic motion and coronal plane shoulder motion. The results of this study suggest that trunk sagittal and coronal plane motion and spinal coronal plane motion of normal and scoliotic adolescents can be reliably measured within a single test session.