Schroedersmall5037

The neuromuscular junction (NMJ) is the peripheral synapse formed between a motor neuron axon terminal and a muscle fibre. NMJs are thought to be the primary site of peripheral pathology in many neuromuscular diseases, but innervation/denervation status is often assessed qualitatively with poor systematic criteria across studies, and separately from 3D morphological structure. Here, we describe the development of 'NMJ-Analyser', to comprehensively screen the morphology of NMJs and their corresponding innervation status automatically. NMJ-Analyser generates 29 biologically relevant features to quantitatively define healthy and aberrant neuromuscular synapses and applies machine learning to diagnose NMJ degeneration. We validated this framework in longitudinal analyses of wildtype mice, as well as in four different neuromuscular disease models three for amyotrophic lateral sclerosis (ALS) and one for peripheral neuropathy. EGFR inhibitor We showed that structural changes at the NMJ initially occur in the nerve terminal of mutant TDP43 and FUS ALS models. Using a machine learning algorithm, healthy and aberrant neuromuscular synapses are identified with 95% accuracy, with 88% sensitivity and 97% specificity. Our results validate NMJ-Analyser as a robust platform for systematic and structural screening of NMJs, and pave the way for transferrable, and cross-comparison and high-throughput studies in neuromuscular diseases.Metastasis is the process of cancer cell dissemination from primary tumors to different organs being the bone the preferred site for metastatic homing of prostate cancer (PCa) cells. Prostate tumorigenesis is a multi-stage process that ultimately tends to advance to become metastatic PCa. Once PCa patients develop skeletal metastases, they eventually succumb to the disease. Therefore, it is imperative to identify essential molecular drivers of this process to develop new therapeutic alternatives for the treatment of this devastating disease. Here, we have identified MAP4K4 as a relevant gene for metastasis in PCa. Our work shows that genetic deletion of MAP4K4 or pharmacological inhibition of its encoded kinase, HGK, inhibits metastatic PCa cells migration and clonogenic properties. Hence, MAP4K4 might promote metastasis and tumor growth. Mechanistically, our results indicate that HGK depleted cells exhibit profound differences in F-actin organization, increasing cell spreading and focal adhesion stability. Additionally, HGK depleted cells fails to respond to TNF-α stimulation and chemoattractant action. Moreover, here we show that HGK upregulation in PCa samples from TCGA and other databases correlates with a poor prognosis of the disease. Hence, we suggest that it could be used as prognostic biomarker to predict the appearance of an aggressive phenotype of PCa tumors and ultimately, the appearance of metastasis. In summary, our results highlight an essential role for HGK in the dissemination of PCa cells and its potential use as prognostic biomarker.Minerals play an important role in animal metabolism. Knowledge of mineral requirements allows well-formulated diets to be provided, which is the main factor that affects performance. To determine the macromineral and trace element requirements for growth and maintenance, thirty-eight 2-month-old Santa Ines lambs with initial body weight (BW) of 13.0 ± 1.49 kg were distributed in a factorial design with feeding levels (ad libitum, 30% and 60% feed restriction) and sex classes [castrated (CM) and intact males (IM)]. The net mineral requirements for gain were higher (P  0.05) the maintenance requirement of the trace elements Co, Cu, Zn and Cr which were 0.0015, 0.037, 0.698, and 0.0055 (mg/kg EBW0.75), respectively. Our study indicated that the Santa Ines net mineral requirements are different from the main nutritional requirements established by committees for sheep, which may result in unbalanced diets.The structural morphology of coronary stents (e.g. stent expansion, lumen scaffolding, strut apposition, tissue protrusion, side branch jailing, strut fracture), and the local hemodynamic environment after stent deployment are key determinants of procedural success and subsequent clinical outcomes. High-resolution intracoronary imaging has the potential to enable the geometrically accurate three-dimensional (3D) reconstruction of coronary stents. The aim of this work was to present a novel algorithm for 3D stent reconstruction of coronary artery stents based on optical coherence tomography (OCT) and angiography, and test experimentally its accuracy, reproducibility, clinical feasibility, and ability to perform computational fluid dynamics (CFD) studies. Our method has the following steps 3D lumen reconstruction based on OCT and angiography, stent strut segmentation in OCT images, packaging, rotation and straightening of the segmented struts, planar unrolling of the segmented struts, planar stent wireframe recew stent scaffolds and stenting techniques.Although the application of sub-sensory mechanical noise to the soles of the feet has been shown to enhance balance, there has been no study on how the bandwidth of the noise affects balance. Here, we report a single-blind randomized controlled study on the effects of a narrow and wide bandwidth mechanical noise on healthy young subjects' sway during quiet standing on firm and compliant surfaces. For the firm surface, there was no improvement in balance for both bandwidths-this may be because the young subjects could already balance near-optimally or optimally on the surface by themselves. For the compliant surface, balance improved with the introduction of wide but not narrow bandwidth noise, and balance is improved for wide compared to narrow bandwidth noise. This could be explained using a simple model, which suggests that adding noise to a sub-threshold pressure stimulus results in markedly different frequency of nerve impulse transmitted to the brain for the narrow and wide bandwidth noise-the frequency is negligible for the former but significantly higher for the latter. Our results suggest that if a person's standing balance is not optimal (for example, due to aging), it could be improved by applying a wide bandwidth noise to the feet.