Effects of contusion load on cervical spinal cord:A finite element study

Injury of cervical spine is a common injury of locomotor system usually accompanied by spinal cord injury, however the injury mechanism of contusion load to the spinal cord is not clear. This study aims to investigate its injury mechanism associated with the contusion load, with different extents of spinal cord compression. A finite element model of cervical spinal cord was established and two scenarios of contusion injury loading conditions, i.e. back-to-front and front-to-back loads, were adopted. Four different compression displacements were applied to the middle section of the cervical spinal cord. The distributions of von Mises stress in middle transverse cross section were obtained from the finite element analysis. For the back-to-front loading scenario, the stress concentration was found in the area at and near the central canal and the damage may lead to the central canal syndrome from biomechanical point of view. With the front-to-back load, the maximum von Mises stress located in central canal area of gray matter when subject to 10% compression, whilst it appeared at the anterior horn when the compression increased. For the white matter, the maximum von Mises stress appeared in the area of the anterior funiculus. This leads to complicated symptoms given rise by damage to multiple locations in the cervical spinal cord. The illustrative results demonstrated the need of considering different loading scenarios in understanding the damage mechanisms of the cervical spinal cord, particularly when the loading conditions were given rise by different pathophysiological causes

Visualization of MG53-mediated Cell Membrane Repair Using in vivo and in vitro Systems

Repair of acute injury to the cell membrane is an elemental process of normal cellular physiology, and defective membrane repair has been linked to many degenerative human diseases. The recent discovery of MG53 as a key component of the membrane resealing machinery allows for a better molecular understanding of the basic biology of tissue repair, as well as for potential translational applications in regenerative medicine. Here we detail the experimental protocols for exploring the in vivo function of MG53 in repair of muscle injury using treadmill exercise protocols on mouse models, for testing the ex vivo membrane repair capacity by measuring dye entry into isolated muscle fibers, and for monitoring the dynamic process of MG53-mediated vesicle trafficking and cell membrane repair in cultured cells using live cell confocal microscopy

mTORC1 controls lysosomal Ca²⁺ release through the two-pore channel TPC2

The ion channel TPC2 is required for Ca 2+ mobilization from lysosomes in response to mTORC1 inhibition and to NAADP. </jats:p

An emerging role for NAADP-mediated Ca2+ signaling in the pancreatic beta-cell

Several recent reports, including one in this journal, have reignited the debate about whether the calcium-mobilizing messenger, nicotinic adenine nucleotide diphosphate (NAADP) plays a central role in the regulation of calcium signalling in pancreatic β-cell. These studies have highlighted a role for NAADP-induced Ca(2+) mobilization not only in mediating the effects of the incretin, GLP-1 and the autocrine proliferative effects of insulin, but also possibly a fundamental role in glucose-mediated insulin secretion in the pancreatic β-cell

CD151 Drives Cancer Progression Depending on Integrin α3β1 through EGFR Signaling in Non-Small Cell Lung Cancer

Background Tetraspanins CD151, a transmembrane 4 superfamily protein, has been identified participating in the initiation of a variety of cancers. However, the precise function of CD151 in non-small cell lung cancer (NSCLC) remains unclear. Here, we addressed the pro-tumoral role of CD151 in NSCLC by targeting EGFR/ErbB2 which favors tumor proliferation, migration and invasion. Methods First, the mRNA expression levels of CD151 in NSCLC tissues and cell lines were measured by RT-PCR. Meanwhile, CD151 and its associated proteins were analyzed by western blotting. The expression levels of CD151 in NSCLC samples and its paired adjacent lung tissues were then verified by Immunohistochemistry. The protein interactions are evaluated by co-immunoprecipitation. Flow cytometry was applied to cell cycle analysis. CCK-8, EdU Incorporation, and clonogenic assays were used to analyze cell viability. Wound healing, transwell migration, and matrigel invasion assays were utilized to assess the motility of tumor cells. To investigate the role of CD151 in vivo, lung carcinoma xenograft mouse model was applied. Results High CD151 expression was identified in NSCLC tissues and cell lines, and its high expression was significantly associated with poor prognosis of NSCLC patients. Further, knockdown of CD151 in vitro inhibited tumor proliferation, migration, and invasion. Besides, inoculation of nude mice with CD151-overexpressing tumor cells exhibited substantial tumor proliferation compared to that in control mice which inoculated with vector-transfected tumor cells. Noteworthy, we found that overexpression of CD151 conferred cell migration and invasion by interacting with integrins. We next sought to demonstrate that CD151 regulated downstream signaling pathways via activation of EGFR/ErbB2 in NSCLC cells. Therefore, we infer that CD151 probably affects the sensitivity of NSCLC in response to anti-cancer drugs. Conclusions Based on these results, we demonstrated a new mechanism of CD151-mediated tumor progression by targeting EGFR/ErbB2 signaling pathway, by which CD151 promotes NSCLC proliferation, migration, and invasion, which may considered as a potential target of NSCLC treatment

Toward 6G TKμ\mu Extreme Connectivity: Architecture, Key Technologies and Experiments

Sixth-generation (6G) networks are evolving towards new features and order-of-magnitude enhancement of systematic performance metrics compared to the current 5G. In particular, the 6G networks are expected to achieve extreme connectivity performance with Tbps-scale data rate, Kbps/Hz-scale spectral efficiency, and $\mu$s-scale latency. To this end, an original three-layer 6G network architecture is designed to realise uniform full-spectrum cell-free radio access and provide task-centric agile proximate support for diverse applications. The designed architecture is featured by super edge node (SEN) which integrates connectivity, computing, AI, data, etc. On this basis, a technological framework of pervasive multi-level (PML) AI is established in the centralised unit to enable task-centric near-real-time resource allocation and network automation. We then introduce a radio access network (RAN) architecture of full spectrum uniform cell-free networks, which is among the most attractive RAN candidates for 6G TK$\mu$ extreme connectivity. A few most promising key technologies, i.e., cell-free massive MIMO, photonics-assisted Terahertz wireless access and spatiotemporal two-dimensional channel coding are further discussed. A testbed is implemented and extensive trials are conducted to evaluate innovative technologies and methodologies. The proposed 6G network architecture and technological framework demonstrate exciting potentials for full-service and full-scenario applications.Comment: 15 pages, 12 figure

Modeling pedestrian safety at roundabouts

This study proposes a method for using a human participant in a field experiment to model pedestrian safety at roundabouts in the United States. Studies show that roundabouts are safer for vehicles, but are inconclusive as to whether pedestrians are at greater risk at roundabouts than at signalized intersections. Recent simulations, including virtual reality, can model pedestrian vehicle interaction, but the proposed technique could use real-world data to calibrate these models. Eight hours of video was made to gather data at a signalized intersection and a roundabout. A physical simulation was used to assess the pedestrian’s cross/don’t cross decision. Standard walking pace was simulated at 3.5 feet per second and a disabled pedestrian at half that pace. This study focused on factors such as signalization, approach streams, exit vs. entrance lanes, pace and direction to provide a realistic picture of the cross vs. don’t cross decision. Data showed that slow pedestrians had a significantly higher rate of don’t cross decisions at the roundabout. Roundabouts are thought to be safer for pedestrians than signalized intersections due to a lower number of conflict points, but the confusing multiple streams of roundabout traffic converging on exit lanes and the frames of approaching traffic at roundabout entrances may mean that another concept may be needed to fully capture pedestrian risks. The data on ‘relevant traffic’ showed that pedestrians had to be attentive to almost six times as many approach streams of traffic in the roundabout as in the signalized intersection. The value of this study is four-fold: 1) Future studies could revisit the conflict point at the core of Traffic Conflict Analysis and consider conflict streams as well; 2) Future studies could consider the cross/don’t cross decision as an important data point with which to evaluate the safety of roundabout crossings; 3) Slow pedestrians fared worse in their ability to cross at the roundabout than at the signalized intersection; 4) The human participant in a field experiment method can be a valuable source of data for calibrating pedestrian safety simulation systems

Enhancing Muscle Membrane Repair by Gene Delivery of MG53 Ameliorates Muscular Dystrophy and Heart Failure in δ-Sarcoglycan-deficient Hamsters

Muscular dystrophies (MDs) are caused by genetic mutations in over 30 different genes, many of which encode for proteins essential for the integrity of muscle cell structure and membrane. Their deficiencies cause the muscle vulnerable to mechanical and biochemical damages, leading to membrane leakage, dystrophic pathology, and eventual loss of muscle cells. Recent studies report that MG53, a muscle-specific TRIM-family protein, plays an essential role in sarcolemmal membrane repair. Here, we show that systemic delivery and muscle-specific overexpression of human MG53 gene by recombinant adeno-associated virus (AAV) vectors enhanced membrane repair, ameliorated pathology, and improved muscle and heart functions in δ-sarcoglycan (δ-SG)-deficient TO-2 hamsters, an animal model of MD and congestive heart failure. In addition, MG53 overexpression increased dysferlin level and facilitated its trafficking to muscle membrane through participation of caveolin-3. MG53 also protected muscle cells by activating cell survival kinases, such as Akt, extracellular signal-regulated kinases (ERK1/2), and glycogen synthase kinase-3β (GSK-3β) and inhibiting proapoptotic protein Bax. Our results suggest that enhancing the muscle membrane repair machinery could be a novel therapeutic approach for MD and cardiomyopathy, as demonstrated here in the limb girdle MD (LGMD) 2F model

TPCs: Endolysosomal channels for Ca2+ mobilization from acidic organelles triggered by NAADP

Two-pore channels (TPCs or TPCNs) are novel members of the large superfamily of voltage-gated cation channels with slightly higher sequence homology to the pore-forming subunits of voltage-gated Ca(2+) and Na(+) channels than most other members. Recent studies demonstrate that TPCs locate to endosomes and lysosomes and form Ca(2+) release channels that respond to activation by the Ca(2+) mobilizing messenger, nicotinic acid adenine dinucleotide phosphate (NAADP). With multiple endolysosomal targeted NAADP receptors now identified, important new insights into the regulation of endolysosomal function in health and disease will therefore be unveiled