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Beermann, F.

Publications and source records attributed to Beermann, F..

3 recordsLinked to original sources

The Human Rectus Femoris Muscle Receives an Independent Common Synaptic Input During Isometric Leg Extensions

The distribution of common synaptic inputs across spinal motor neuron pools within and across synergist muscles reveals direct insight in the neural control of movement. We previously documented two dominant common inputs in the human vastus lateralis (VL) and medialis (VM) muscle during isometric leg extensions. Whether these inputs are also shared with rectus femoris (RF), a synergist muscle that contributes substantially to leg extension but is biarticular, remains unknown. We simultaneously recorded motor unit activity from VM, RF, and VL using multiple targeted intramuscular electromyographic sensors during isometric knee extension. Decomposed motor unit spike trains were analyzed using discharge characteristics, pairwise correlation, spectral coherence, explained variance, and factor analysis to characterize the structure of common synaptic input within and across muscles. Despite their shared mechanical output via a common patellar tendon, the three muscles exhibited distinct patterns of neural organization. RF consistently received a strong, low-dimensional common input that was largely independent of the drive to VM and VL, as evidenced by elevated within-muscle correlation and coherence, low between-muscle coupling, and an invariant dedicated latent factor across all participants. VM and VL shared a substantial proportion of common synaptic input, but the degree of coupling and the underlying factor structure varied across individuals, ranging from a single shared factor to largely independent muscle-specific inputs. These findings indicate that the quadriceps are organized in a muscle- and subject-specific manner, with RF receiving a dedicated independent input.

neuroscience↗

Voluntary Dissociation of Motor Unit Activity in the Vastii Muscles

The CNS coordinates movement through consistent activation patterns across muscles and motor units, suggesting the presence of a relatively fixed and high-dimensional number of neural constraints on voluntary actions. In the human quadriceps, the vastus medialis (VM) and vastus lateralis (VL) control the knee extensor torque and are considered a synergistic pair largely activated by shared neural inputs. However, some evidence suggests that these muscles, or even subregions within them, can be controlled independently. In this study, we investigated whether humans can dissociate neural input to VM and VL during isometric contractions. Ten participants received real-time feedback from multiple intramuscular EMG electrodes that targeted different regions of the VM and VL while attempting to activate each muscle or sub-regions selectively. We found that nine out of ten subjects were able to clearly separate VM and VL activity based on the intramuscular EMG feedback. However, motor unit decomposition from the intramuscular EMGs revealed that selective recruitment of a unique set of motor units was possible only within the proximal region of VM. In contrast, VL and distal VM showed highly correlated activation, indicating tight functional coupling. Correlation analyses confirmed that the proximal VM exhibited distinct activation profiles compared with both distal VM and VL, supporting the existence of compartmentalized control within VM. These findings demonstrate that it is possible to dissociate the activation of motor units within this synergistic muscle group during low-force isometric contractions.

neuroscience↗

STAT3 promotes melanoma metastasis by CEBP-induced repression of the MITF pigmentation pathway

Metastatic melanoma is hallmarked by its ability to switch oncogenic MITF expression. Here we tested the impact of STAT3 on melanoma onset and progression in association with MITF expression levels. We established a mouse melanoma model for deleting Stat3 specifically in melanocytes with specific expression of human hyperactive NRASQ61K in an Ink4a deficient background. Mice with tissue specific Stat3 deletion showed an early onset of disease, but displayed significantly diminished lung metastases. Whole genome expression profiling also revealed a reduced invasion phenotype, which was functionally confirmed in 3D melanoma model systems. Notably, loss or knockdown of STAT3 in mouse or human cells resulted in up-regulation of MITF and induction of cell proliferation. Mechanistically we show that STAT3 induced CEBPa/b expression was sufficient to suppress MITF transcription. Epigenetic analysis by ATAC-seq confirmed that STAT3 enabled CEBPa/b binding to the MITF enhancer region thereby silencing it. We conclude that STAT3 is a metastasis driver in melanoma able to antagonize the MITF oncogene via direct induction of CEBP family member transcription facilitating RAS-RAF-driven melanoma metastasis.\n\nList of Abbreviations\n\nATAC-seq, Assay for Transposase-Accessible Chromatin using sequencing; CEBP, CAAT Box Enhancer Binding Protein; CRE, Cre recombinase; EGF, Epidermal Growth Factor; GEO, Gene Expression Omnibus; GSEA, Gene Set Enrichment Analysis; HSC70, Heat Shock 70 kDa protein; IHC, Immunohistochemistry; IL-6, Interleukin-6; JAK, Janus Kinase; MITF, Microphthalmia-Associated Transcription Factor; NSG, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice; OSM, Oncostatin M; PDGF, Platelet-Derived Growth Factor; pS, phosphoserine; pY, phosphotyrosine; RAS, Rat Sarcoma; RAF, Rapidly Accelerated Fibrosarcoma; RTK, Receptor Tyrosine Kinase; RT-PCR, Reverse Transcription Polymerase Chain Reaction; S100b, Calcium Binding Protein S100 beta; shRNA, short hairpin RNA; SOX10, Sex Determining Region Y-10; STAT, Signal Transducer and Activator of Transcription; TCGA, The Cancer Genome Atlas; TMA, Tissue Micro Array

cancer biology↗