Systematic characterization of protein structural features of alternative splicing isoforms using AlphaFold 2.

Alternative splicing is an important cellular process in eukaryotes, altering pre-mRNA to yield multiple protein isoforms from a single gene. However, our understanding of the impact of alternative splicing events on protein structures is currently constrained by a lack of sufficient protein structural data. To address this limitation, we employed AlphaFold 2, a cutting-edge protein structure prediction tool, to conduct a comprehensive analysis of alternative splicing for approximately 3,000 human genes, providing valuable insights into its impact on the protein structural. Our investigation employed state of the art high-performance computing infrastructure to systematically characterize structural features in alternatively spliced regions and identified changes in protein structure following alternative splicing events. Notably, we found that alternative splicing tends to alter the structure of residues primarily located in coils and beta-sheets. Our research highlighted a significant enrichment of loops and highly exposed residues within human alternatively spliced regions. Specifically, our examination of the Septin-9 protein revealed potential associations between loops and alternative splicing, providing insights into its evolutionary role. Furthermore, our analysis uncovered two missense mutations in the Tau protein that could influence alternative splicing, potentially contributing to the pathogenesis of Alzheimer's disease. In summary, our work, through a thorough statistical analysis of extensive protein structural data, sheds new light on the intricate relationship between alternative splicing, evolution, and human disease.

Optimizing Input for Gesture Recognition using Convolutional Networks on HD-sEMG Instantaneous Images.

Hand gesture recognition using high-density surface electromyography (HD-sEMG) has gained increasing attention recently due its advantages of high spatio-temporal resolution. Convolutional neural networks (CNN) have also recently been implemented to learn the spatio-temporal features from the instantaneous samples of HD-sEMG signals. While the CNN itself learns the features from the input signal it has not been considered whether certain pre-processing techniques can further improve the classification accuracies established by previous studies. Therefore, common pre-processing techniques were applied to a benchmark HD-sEMG dataset (CapgMyo DB-a) and their validation accuracies were compared. Monopolar, bipolar, rectified, common-average referenced, and Laplacian spatial filtered configurations of the HD-sEMG signals were evaluated. Results showed that the baseline monopolar HD-sEMG signals maintained higher prediction accuracies versus the other signal configurations. The results of this study discourage the use of extra pre-processing steps when using convolutional networks to classify the instantaneous samples of HD-sEMG for gesture recognition.

Thermosensitive and Conductive Hybrid Polymer for Real-Time Monitoring of Spheroid Growth and Drug Responses.

Three-dimensional (3D) cell culture based on polymer scaffold provides a promising tool to mimic a physiological microenvironment for drug testing; however, the next-generation cell activity monitoring technology for 3D cell culture is still challenging. Conventionally, drug efficacy evaluation and cell growth heavily rely on cell staining assays, using optical devices or flow cytometry. Here, we report a dual-function polymer scaffold (DFPS) composed of thermosensitive, silver flake- and gold nanoparticle-decorated polymers, enabling conductance change upon cell proliferation or death for in situ cell activity monitoring and drug screening. The cell activity can be quantitatively monitored via measuring the conductance change induced by polymeric network swelling or shrinkage. This novel dual-function system (1) provides a 3D microenvironment to enable the formation and growth of tumor spheroid in vitro and streamlines the harvesting of tumor spheroids through the thermosensitive scaffold and (2) offers a simple and direct quantitative method to monitor 3D cell culture in situ for drug responses. As a proof of concept, we demonstrated that a breast cancer stem cell line MDA-MB-436 was able to form cell spheroids in the scaffold, and the conductance change of the sensor exhibited a linear relationship with cell concentration. To examine its potential in drug screening, cancer spheroids in the cell sensor were treated with paclitaxel (PTX) and docetaxel (DTX), and predicted quantitative evaluation of the cytotoxic effect of drugs was established. Our results indicated that this cell sensing system may hold promising potential in expanding into an array device for high-throughput drug screening.