Biology subjects

Oh, S.

Publications and source records attributed to Oh, S..

At least 55 records · Page 3Linked to original sources

bioRxiv2024

A transformer model for de novo sequencing of data-independent acquisition mass spectrometry data

A core computational challenge in the analysis of mass spectrometry data is the de novo sequencing problem, in which the generating amino acid sequence is inferred directly from an observed fragmentation spectrum without the use of a sequence database. Recently, deep learning models have made significant advances in de novo sequencing by learning from massive datasets of high-confidence labeled mass spectra. However, these methods are primarily designed for data-dependent acquisition (DDA) experiments. Over the past decade, the field of mass spectrometry has been moving toward using data-independent acquisition (DIA) protocols for the analysis of complex proteomic samples due to their superior specificity and reproducibility. Hence, we present a new de novo sequencing model called Cascadia, which uses a transformer architecture to handle the more complex data generated by DIA protocols. In comparisons with existing approaches for de novo sequencing of DIA data, Cascadia achieves state-of-the-art performance across a range of instruments and experimental protocols. Additionally, we demonstrate Cascadias ability to accurately discover de novo coding variants and peptides from the variable region of antibodies.

bioinformatics↗

bioRxiv2024

Epithelial tubule interconnection driven by HGF-Met signaling in the kidney

The formation of functional epithelial tubules is a central feature of many organ systems. Although the process of tubule formation by epithelial cells is well-studied, the way in which tubules connect with each other (i.e. anastomose) to form functional networks both in vivo and in vitro is not well understood. A key, unanswered question in the kidney is how the renal vesicles of the embryonic kidney connect with the nascent collecting ducts to form a continuous urinary system. We performed a ligand-receptor pair analysis on single cell RNA-seq data from embryonic mouse kidney tubules undergoing anastomosis to select candidates that might mediate this process in vivo. This analysis identified hepatocyte growth factor (HGF), which has known roles in cell proliferation, migration, and tubulogenesis, as one of several possible candidates. To test this possibility, we designed a novel assay to quantitatively examine epithelial tubule anastomosis in vitro using epithelial spheroids with fluorescently-tagged apical surfaces to enable direct visualization of anastomosis. This revealed that HGF is a potent inducer of tubule anastomosis. Tubule anastomosis occurs through a proliferation-independent mechanism that acts through the MAPK signaling cascade and matrix metalloproteinases (MMPs), the latter suggestive of a role in extracellular matrix turnover. Accordingly, treatment of explanted embryonic mouse kidneys with HGF and collagenase was sufficient to induce kidney tubule anastomosis. These results lay the groundwork for investigating how to promote functional interconnections between tubular epithelia, which have important clinical implications for utilizing in vitro grown kidney tissue in transplant medicine.

developmental biology↗

bioRxiv2024

Accounting for digestion enzyme bias in Casanovo

A key parameter of any proteomics mass spectrometry experiment is the identity of the enzyme that is used to digest proteins in the sample into peptides. The Casanovo de novo sequencing model was trained using data that was generated with trypsin digestion; consequently, the model prefers to predict peptides that end with the amino acids "K" or "R." This bias is desirable when the Casanovo is used to analyze data that was also generated using trypsin but can be problematic if the data was generated using some other digestion enzyme. In this work, we modify Casanovo to take as input the identify of the digestion enzyme, alongside each observed spectrum. We then train Casanovo with data generated using several different restriction enzymes, and we demonstrate that the resulting model successfully learns to capture enzyme-specific behavior. However, we find, surprisingly, that this new model does not yield a significant improvement in sequencing accuracy relative to a model trained without the enzyme information but using the same training set. This observation may have important implications for future attempts to make use of experimental metadata in de novo sequencing models.

bioinformatics↗

bioRxiv2024

Recruitment of CTCF to the SIRT1 promoter after Oxidative Stress mediates Cardioprotective Transcription

Because most DNA-binding transcription factors (dbTFs), including the architectural regulator CTCF, bind RNA and exhibit di-/multimerization, a central conundrum is whether these distinct properties are regulated post-transcriptionally to modulate transcriptional programs. Here, investigating stress-dependent activation of SIRT1, encoding an evolutionarily-conserved protein deacetylase, we show that induced phosphorylation of CTCF acts as a rheostat to permit CTCF occupancy of low-affinity promoter DNA sites to precisely the levels necessary. This CTCF recruitment to the SIRT1 promoter is eliciting a cardioprotective cardiomyocyte transcriptional activation program and provides resilience against the stress of the beating heart in vivo. Mice harboring a mutation in the conserved low-affinity CTCF promoter binding site exhibit an altered, cardiomyocyte-specific transcriptional program and a systolic heart failure phenotype. This transcriptional role for CTCF reveals that a covalent dbTF modification regulating signal-dependent transcription serves as a previously unsuspected component of the oxidative stress response.

cell biology↗

bioRxiv2024

Physiological Processing of Aversiveness in the Mind's Ear: Comparing Audiovisual, Auditory and Imagined Auditory Affective Stimuli

Understanding the somatovisceral responses to auditory affective imagery has important implications in disorders like misophonia. The current study compared physiological responses to aversive and nonaversive states across three modalities: audiovisual, auditory, and auditory imagery. Electromyographic activity over corrugator supercilii (EMGc) and zygomaticus major (EMGz), electrodermal activity (EDA), heart rate (HR), and finger skin temperature (SKT) were measured. There was significant differentiation in EMGc, EDA, and HR deceleration between aversive and nonaversive audiovisual stimuli. EMGc potentiation was the only physiological measure showing consistent differentiation across the three modalities. Cross-modal aversiveness classification results revealed a similar physiological response pattern between audiovisual and auditory modalities. The physiological response pattern during auditory affective imagery was useful for predicting the aversiveness in audiovisual modality but not the other way around. Vividness in auditory imagery correlated with subjective hedonic valence ratings, but not physiological responses. Taken together, the current data suggest that the aversiveness of auditory imagery is differentiable in subjective affective experience and facial muscle potentiation. These results of the physiological responses to imagined aversive sounds in nonclinical population would serve as a comparison baseline for the study of misophonia.

physiology↗

bioRxiv2024

Transcriptomic characterization of human lateral septum neurons reveals conserved and divergent marker genes across species

The lateral septum (LS) is a midline, subcortical structure, which regulates social behaviors that are frequently impaired in neurodevelopmental disorders including schizophrenia and autism spectrum disorder. Mouse studies have identified neuronal populations within the LS that express a variety of molecular markers, including vasopressin receptor, oxytocin receptor, and corticotropin releasing hormone receptor, which control specific facets of social behavior. Despite its critical role in regulating social behavior and notable gene expression patterns, comprehensive molecular profiling of the human LS has not been performed. Here, we conducted single nucleus RNA-sequencing (snRNA-seq) to generate the first transcriptomic profiles of the human LS using postmortem human brain tissue samples from 3 neurotypical donors. Our analysis identified 5 transcriptionally distinct neuronal cell types within the human LS that are enriched for TRPC4, the gene encoding Trp-related protein 4. Differential expression analysis revealed a distinct LS neuronal cell type that is enriched for OPRM1, the gene encoding the {micro}-opioid receptor. Leveraging recently generated mouse LS snRNA-seq datasets, we conducted a cross-species analysis. Our results demonstrate that TRPC4 enrichment in the LS is highly conserved between human and mouse, while FREM2, which encodes FRAS1 related extracellular matrix protein 2, is enriched only in the human LS. Together, these results highlight transcriptional heterogeneity of the human LS, and identify robust marker genes for the human LS.

neuroscience↗

bioRxiv2024

Orange Maker: a CRISPR/Cas9-mediated genome editing and screening project to generate orange-eyed DarkJedi GAL4 lines by undergraduate students

One of the greatest strengths of Drosophila genetics is its easily observable and selectable phenotypic markers. The mini-white marker has been widely used as a transgenic marker for Drosophila transgenesis. Flies carrying a mini-white construct can exhibit various eye colors ranging from pale orange to intense red, depending on the insertion site and gene dosage. Because the two copies of the mini-white marker show a stronger orange color, this is often used for selecting progenies carrying two transgenes together in a single chromosome after chromosomal recombination. However, some GAL4 lines available in the fly community originally have very strong red eyes. Without employing another marker, such as GFP, generating a recombinant chromosome with the strong red-eyed GAL4 and a desired UAS-transgene construct may be difficult. Therefore, we decided to change the red eyes of GAL4 lines to orange color. To change the eye color of the fly, we tested the CRISPR/Cas9 method with a guide RNA targeting the white gene with OK371-GAL4 and elav-GAL4. After a simple screening, we have successfully obtained multiple lines of orange-eyed OK371-GAL4 and elav-GAL4 that still maintain their original expression patterns. All of these simple experiments were performed by undergraduate students, allowing them to learn about a variety of different genetic experiments and genome editing while contributing to the fly research community by creating fruit fly lines that will be used in real-world research.

genetics↗

bioRxiv2024

A learned score function improves the power of mass spectrometry database search

One of the core problems in the analysis of protein tandem mass spectrometry data is the peptide assignment problem: determining, for each observed spectrum, the peptide sequence that was responsible for generating the spectrum. Two primary classes of methods are used to solve this problem: database search and de novo peptide sequencing. State-of-the-art methods for de novo sequencing employ machine learning methods, whereas most database search engines use hand-designed score functions to evaluate the quality of a match between an observed spectrum and a candidate peptide from the database. We hypothesize that machine learning models for de novo sequencing implicitly learn a score function that captures the relationship between peptides and spectra, and thus may be re-purposed as a score function for database search. Because this score function is trained from massive amounts of mass spectrometry data, it could potentially outperform existing, hand-designed database search tools. To test this hypothesis, we re-engineered Casanovo, which has been shown to provide state-of-the-art de novo sequencing capabilities, to assign scores to given peptide-spectrum pairs. We then evaluated the statistical power of this Casanovo score function, Casanovo-DB, to detect peptides on a benchmark of three mass spectrometry runs from three different species. Our results show that, at a 1% peptide-level false discovery rate threshold, Casanovo-DB outperforms existing hand-designed score functions by 35% to 88%. In addition, we show that re-scoring with the Percolator post-processor benefits Casanovo-DB more than other score functions, further increasing the number of detected peptides.

bioinformatics↗

bioRxiv2023

Sequential genetic, epigenetic alterations in human pluripotent stem cells for recurrent abnormality

Human embryonic stem cells (hESCs) are naturally equipped to maintain genome integrity to minimize genetic mutations during early embryo development. However, genetic aberration risks and subsequent cellular changes in hESCs during in vitro culture pose a significant threat to stem cell therapy. While a few studies have reported specific somatic mutations and copy number variations (CNVs), the molecular mechanisms underlying culture-adapted phenotype acquisitions of hESCs are largely unknown. Therefore, we conducted comprehensive genomic, single-cell transcriptomic, and single-cell ATAC-seq analyses of an isogenic hESC model displaying definitive culture-adapted phenotypes. Notably, hPSCs with a copy number gain of 20q11.21 during early passage did not present culture-adapted phenotypes nor BCL2L1 induction. Single-cell RNAseq and ATACseq analyses revealed active transcriptional regulation at 20q11.21 loci at late-passaged hESCs with the induced BCL2L1 and TPX2 to trigger culture-adapted phenotypes was associated with epigenetic changes facilitating TEA domain (TEAD) binding. These results suggest that copy number 20q11.21 gain and additional epigenetic changes are necessary for expressing culture-adapted phenotypes by activating gene transcription at this specific locus.

cell biology↗

bioRxiv2023

Aberrant Wnt activation in recurrent genetically variant human pluripotent stem cells impairs cardiomyocyte differentiation and phenotype

Human pluripotent stem cell (hPSC)-derived cardiomyocytes have emerged as powerful tools for disease modelling and cell therapy. The production of cardiomyocytes from hPSCs typically requires expanding large numbers of hPSCs and maintaining them in culture for extended periods of time. This in turn predisposes hPSCs to the acquisition of non-random genetic changes, including recurrent gains of chromosome 1q. Here, we show that gain of chromosome 1q in hPSCs affects both the efficiency of differentiation to cardiomyocytes and phenotype of the differentiated cells. Mechanistically, we show that aberrant activation of the Wnt signalling pathway underpins the skewed differentiation of variant 1q hPSCs. Collectively, our data demonstrates that the presence of genetically variant cells in cultures is a significant concern for production of hPSC-derived cardiomyocytes for research or clinical applications. Further, our results suggest new approaches for removing genetically variant cells for future clinical applications.

cell biology↗

bioRxiv2023

Membrane potential mediates an ancient mechano-transduction mechanism for multi-cellular homeostasis

Mechanical forces have been shown to influence cellular decisions to grow, die, or differentiate, through largely mysterious mechanisms. Separately, changes in resting membrane potential have been observed in development, differentiation, regeneration, and cancer. We now demonstrate that membrane potential is the central mediator of cellular response to mechanical pressure. We show that mechanical forces acting on the cell change cellular biomass density, which in turn alters membrane potential. Membrane potential then regulates cell number density in epithelia by controlling cell growth, proliferation, and cell elimination. Mechanistically, we show that changes in membrane potential control signaling through the Hippo and MAPK pathways, and potentially other signaling pathways that originate at the cell membrane. While many molecular interactions are known to affect Hippo signaling, the upstream signal that activates the canonical Hippo pathway at the membrane has previously been elusive. Our results establish membrane potential as a central regulator of growth and tissue homeostasis.

cell biology↗

bioRxiv2023

TBK1 is ubiquitinated by TRIM5alpha to assemble mitophagy machinery

Ubiquitination of mitochondrial proteins provides a basis for the downstream recruitment of mitophagy machinery, yet whether ubiquitination of the machinery itself contributes to mitophagy is unknown. Here, we show that K63-linked polyubiquitination of the key mitophagy regulator TBK1 is essential for its mitophagy functions. This modification is catalyzed by the ubiquitin ligase TRIM5. Mitochondrial damage triggers TRIM5s auto-ubiquitination and its interaction with ubiquitin-binding autophagy adaptors including NDP52, optineurin, and NBR1. Autophagy adaptors, along with TRIM27, enable TRIM5 to engage with TBK1. TRIM5 with intact ubiquitination function is required for the proper accumulation of active TBK1 on damaged mitochondria in Parkin-dependent and Parkin-independent mitophagy pathways. Additionally, we show that TRIM5 can directly recruit autophagy initiation machinery to damaged mitochondria. Our data support a model in which TRIM5 provides a self-amplifying, mitochondria-localized, ubiquitin-based, assembly platform for TBK1 and mitophagy adaptors that is ultimately required to recruit the core autophagy machinery.

cell biology↗

bioRxiv2023

Biomarker discovery in progressive supranuclear palsy from human cerebrospinal fluid using mass spectrometry-based proteomics

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder that is often misdiagnosed as Parkinsons Disease (PD) because of shared symptoms. PSP is characterized by the accumulation of tau protein in specific brain regions, which results in loss of balance, gaze impairment, and dementia. Diagnosing PSP is often challenging, and theres a significant demand for reliable biomarkers. However, existing biomarkers, including tau protein and neurofilament light chain (NfL) levels in cerebrospinal fluid (CSF), show inconsistencies in distinguishing PSP from other neurodegenerative disorders. To overcome these limitations, we conducted a comprehensive proteome analysis for CSF samples from 40 PSP, 40 PD, and healthy controls (HC) using the tandem mass tag-based quantification method, identifying 3,653 unique proteins. Our statistical analysis identified 190, 152, and 247 differentially expressed proteins when comparing PSP vs. HC, PSP vs. PD, and PSP against both PD and HC, respectively. Gene set enrichment analysis and interactome analysis conducted with the differentially expressed proteins in PSP CSF indicated that most of them were implicated in cell adhesion, cholesterol metabolism, and glycan biosynthesis. Cell-type enrichment analysis revealed that neuronally-derived proteins were predominant among the differentially expressed proteins. Potential biomarker classification performance showed that ATP6AP2 (reduced in PSP) had the highest AUC (0.922), followed by NEFM, EFEMP2, LAMP2, CHST12, FAT2, B4GALT1, LCAT, CBLN3, FSTL5, ATP6AP1, and GGH. This is the first large-scale mass spectrometry-based proteome analysis to discover CSF PSP biomarkers differentiating from both controls and PD, thereby laying a foundation for further development and validation.

systems biology↗

bioRxiv2023

The 21-base pair deletion mutant Calpain 3 does not inhibit wild-type Calpain 3 activity

IntroductionCalpain 3 is one of the calpain protease family members, which is a calcium-dependent proteolytic enzyme predominantly expressed in skeletal muscle. Loss-of-function mutations in the Calpain 3 gene have been related to autosomal recessive Limb-Girdle Muscular Dystrophy 1 (LGMDR1), a common form of muscular dystrophy. Recently, the heterozygous 21-bp deletion mutation of the Calpain 3 gene has been reported to cause autosomal dominant Limb-Girdle Muscular Dystrophy 4 (LGMDD4). According to its dominant inheritance pattern, it has been suggested that the deletion mutant proteins act in a dominant-negative manner. Therefore, we examined whether the mutant protein can suppress the activity of wild-type Calpain 3 and has any dominant toxicity in cell culture and in vivo Drosophila models. MethodsA human cell culture (HeLa cells) model with the transient transfection of human wild-type and mutant Calpain 3 and in vivo Drosophila models overexpressing wild-type and mutant Drosophila Calpain A and B were utilized in this study to assess dominant effects of Calpain 3 21-bp deletion mutant. Western blot analysis was used to determine protein stability and catalytic activity in cell culture. External eye morphology and muscle integrity were examined to observe dominant toxicity in Drosophila models. ResultsThe 21-bp deletion mutation of Calpain 3 resulted in catalytic inactivation, which did not inhibit wild-type Calpain 3 autolytic and catalytic activity against Calpastatin in HeLa cells. In addition, the mutant protein was normally processed by wild-type Calpain 3. Overexpression of wild-type and deletion mutant Calpain 3 in the Drosophila eye and muscles did not exhibit significant developmental and age-related dominant toxicity. DiscussionWe provide evidence that mutant Calpain 3 does not suppress wild-type Calpain 3 activity. Rather, it is a mutant lacking autocatalytic processing activity like many other loss-of-function Calpain 3 mutants causing LGMDR1. Our results implicate that the stability of the heteromeric mutant and wild-type Calpain 3 complexes may be affected without inhibiting the wild-type activity per se. However, a more thorough investigation is necessary to understand the molecular mechanism and dominant inheritance of the heterozygous 21-bp deletion mutation in LGMDD4.

cell biology↗

bioRxiv2023

A compact, ultrahigh-density headstage with high-fidelity hybrid integration for large-scale deep-brain opto-electrophysiology

Recent neuroscientific research seeks to comprehend the sophisticated deep-brain networks of neural circuits consisting of large scale neuronal ensembles across multiple brain regions. An ideal way to unveil the complex connectome might be stimulating individual neurons with high spatial resolution in a broad range of brain, while seamlessly monitoring the correspondent neuronal activities. Optogenetics is known as a key technology to enable such a goal thanks to its high spatial and temporal selectivity in neuromodulation. Existing silicon probe technologies have been able to partially achieve such a goal by recording broad region of brain activities through multiple electrodes per shank, but those cannot complete perfect coverage due to the limited channel counts for the optogenetic stimulation. Here, we present an high-channel-count optogenetic system with simultaneous 256 recoding and 128 optogenetic stimulation sites, exhibiting the highest channel density ever reported, enabled by a flexible polyimide cable-based hybrid-integration of a low-stimulation-artifact micro-LED ({micro}LED) opto-electrode with a low-power and -noise, area-efficient CMOS interfacing integrated-circuit (IC). The presented optogenetic system provides 256-neuron-size electrodes (11 x 15 {micro}m2) with a 40 {micro}m inter-electrode pitch for high spatial oversampling in recording and 128-soma-size {micro}LEDs (8 x 11 {micro}m2) with a 20 {micro}m inter-LED pitch for single-cell resolution in stimulation, resulting in a vertical span of 640 {micro}m and a horizontal span of 2,100 {micro}m with a total 8 shanks. For versatility in optogenetics-based experiments from small rodents to primates with user-preferable settings, the system base that provides programmability of recording and stimulation parameters and rest of signal processing, such as filtering, digitization, and data transmission including serial peripheral interface (SPI) has also been designed within small area of 23.8 x 28.8 mm2 with only 3.5-gram weight, resulting in the highest channel density both in size (0.56 channels/mm2) and weight (109.71 channels/gram) among the state-of-the-art optogenetics-based neuromodulation systems. To verify the system operation in vivo, a compact optogenetics headstage has been also fabricated. Using the prepared optogenetic headstage, 169 isolated neurons have been observed with various stimulation intensities. The results offered in this article indicate that the presented hybrid integrated ultrahigh-density, high-channel-count headstage can be used to realize the massive-scale in-depth brain studies with optogenetics.

bioengineering↗

bioRxiv2023

Cell wall fluidization by mechano-endopeptidases sets up a turgor-mediated volumetric pacemaker

The cell wall is an essential cellular component of bacteria and the target of many antibiotics. However, how bacteria regulate the rate of cell wall biosynthesis as growth rates change remains unresolved. In E. coli, cell wall growth was thought to proceed independently from turgor pressure1, the osmotic pressure that the cytoplasm exerts on the cell wall. Here, we uncover a striking increase of turgor pressure with growth rate. Modulating turgor pressure and measuring cell wall biosynthesis, we find that turgor pressure is directly controls the rate of cell wall biosynthesis. The picture that emerges is that turgor pressure is largely generated by counterions of negatively charged cellular biomass. The increase in turgor pressure with growth rates results from more ribosomes and therefore higher concentrations of negatively charged ribosomal RNA. Elegantly, the coupling between biomass composition, turgor pressure and cell wall biosynthesis simultaneously explains how bacteria achieve homeostasis of cytoplasmic crowding and how they regulate the rate of cell wall biosynthesis across growth rates.

microbiology↗

bioRxiv2023

Mesoscale DNA Features Impact APOBEC3A and APOBEC3B Deaminase Activity and Shape Tumor Mutational Landscapes

Antiviral DNA cytosine deaminases APOBEC3A and APOBEC3B are major sources of mutations in cancer by catalyzing cytosine-to-uracil deamination. APOBEC3A preferentially targets singlestranded DNAs, with a noted affinity for DNA regions that adopt stem-loop secondary structures. However, the detailed substrate preferences of APOBEC3A and APOBEC3B have been fully established, and the specific influence of the DNA sequence on APOBEC3A APOBEC3B deaminase activity remains to be investigated. Here, we find that APOBEC3B selectively targets DNA stem-loop structures, and they are distinct from those subjected deamination by APOBEC3A. We develop Oligo-seq, a novel in vitro sequencing-based to identify specific sequence contexts promoting APOBEC3A and APOBEC3B activity. Through this approach, we demonstrate that APOBEC3A an APOBEC3B deaminase activity is strongly regulated by specific sequences surrounding the targeted cytosine. Moreover, we identify structural features of APOBEC3B and APOBEC3A responsible for their substrate preferences. Importantly, we determine that APOBEC3B-induced mutations in hairpin-forming sequences within tumor genomes differ from the DNA stem-loop sequences mutated by APOBEC3A. Together, our study provides evidence that APOBEC3A and APOBEC3B can generate mutation landscapes in cancer genomes, driven by their unique substrate selectivity.

biochemistry↗

bioRxiv2023

Muscle Coordination Matters: Insights into Motor Planning using Corticospinal Responses during Functional Reaching

The central nervous system (CNS) moves the human body by forming a plan in the primary motor cortex and then executing this plan by activating the relevant muscles. It is possible to study motor planning by using noninvasive brain stimulation techniques to stimulate the motor cortex prior to a movement and examine the evoked responses. Studying the motor planning process can reveal useful information about the CNS, but previous studies have generally been limited to single degree of freedom movements (e.g., wrist flexion). It is currently unclear if findings in these studies generalize to multi-joint movements, which may be influenced by kinematic redundancy and muscle synergies. Here, our objective was to characterize motor planning in the cortex prior to a functional reach involving the upper extremity. We asked participants to reach for a cup placed in front of them when presented with a visual "Go Cue". Following the go cue, but prior to movement onset, we used transcranial magnetic stimulation (TMS) to stimulate the motor cortex and measured the changes in the magnitudes of evoked responses in several upper extremity muscles (MEPs). We varied each participants initial arm posture to examine the effect of muscle coordination on MEPs. Additionally, we varied the timing of the stimulation between the go cue and movement onset to examine the time course of changes in the MEPs. We found that the MEPs in all proximal (shoulder and elbow) muscles increased as the stimulation was delivered closer to movement onset, regardless of arm posture, but MEPs in the distal (wrist and finger) muscles were not facilitated or even inhibited. We also found that facilitation varied with arm posture in a manner that reflected the coordination of the subsequent reach. We believe that these findings provide useful insight into the way the CNS plans motor skills.

neuroscience↗