Six-well plate-based colony-forming efficacy assay and Co-Culture application to assess toxicity of metal oxide nanoparticles.

The development of a universal, label-free, and reliable in vitro toxicity testing method for nanoparticles is urgent because most nanoparticles can interfere with toxicity assays. In this regard, the colony-forming efficacy (CFE) assay has been suggested as a suitable in vitro toxicity assay for testing nanoparticles without such interference. Recently, the Organisation for Economic Co-operation and Development (OECD) developed a 60 × 15 mm Petri dish-based CFE assay for testing nanoparticles in MDCK-1 cells. However, further investigations are needed, including testing with other cell types, at a smaller scale for greater efficiency, and the application of the co-culture technique. In this study, we selected TiO2, CuO, CeO2, and SiO2 as test nanoparticles and successfully developed a 6-well plate-based CFE assay using HepG2 and A549 cells and a co-culture assay for combinations of HepG2 cells and THP-1 macrophages or A549 cells and THP-1 monocytes. The results suggest that the 6-wellplate-based CFE assay for HepG2 and A549 cells can be applied to nanoparticles, but the co-culture CFE assay has limitations in that it is not different from the single culture study, and it inhibits colony-formation by A549 cells in the presence of macrophages; this warrant further study.

Hidden osteonecrosis of the femoral head after healed femoral neck fractures: magnetic resonance imaging study of 58 consecutive patients.

INTRODUCTION: Several studies investigated the posttraumatic osteonecrosis of the femoral head (ONFH) after femoral neck fracture (FNF). However, no study has investigated the hidden ONFH after FNF, which is missed by simple radiographs, using magnetic resonance imaging (MRI). MATERIALS AND METHODS: This retrospective study involved 58 consecutive patients who underwent implant removal surgery after internal fixation due to FNF. MRI was used to investigate the incidence of hidden ONFHs, which were not initially revealed on plain radiographs. The comparisons between hidden ONFH and other groups were performed for patent demographics and clinical variables including ONFH location, lesion size, the progression rate of ONFH collapse, and end-stage arthroplasty conversion rate. RESULTS: Of the 58 patients, 38 exhibited no evidence of ONFH on plain radiograph screening. However, 13 of the 38 patients were confirmed of hidden ONFH via MRI. The collapse progressed in four of the 13 patients, and one of them underwent total hip arthroplasty surgery. No significant differences were found between the hidden and definite ONFH groups in demographics and clinical variables. However, a significant difference exists between the hidden ONFH and the normally healed FNF groups in terms of the Garden type (P < 0.001). CONCLUSIONS: A large number of cases with hidden ONFH were confirmed using MRI following healed FNF, and most of them were initially displaced FNF. Thus, the treatment method between internal fixation and hip arthroplasty should be carefully selected, particularly with displaced FNF.

OsCRP1, a Ribonucleoprotein Gene, Regulates Chloroplast mRNA Stability That Confers Drought and Cold Tolerance.

Chloroplast ribonucleoproteins (cpRNPs) are nuclear-encoded and highly abundant proteins that are proposed to function in chloroplast RNA metabolism. However, the molecular mechanisms underlying the regulation of chloroplast RNAs involved in stress tolerance are poorly understood. Here, we demonstrate that CHLOROPLAST RNA-BINDING PROTEIN 1 (OsCRP1), a rice (Oryza sativa) cpRNP gene, is essential for stabilization of RNAs from the NAD(P)H dehydrogenase (NDH) complex, which in turn enhances drought and cold stress tolerance. An RNA-immunoprecipitation assay revealed that OsCRP1 is associated with a set of chloroplast RNAs. Transcript profiling indicated that the mRNA levels of genes from the NDH complex significantly increased in the OsCRP1 overexpressing compared to non-transgenic plants, whereas the pattern in OsCRP1 RNAi plants were opposite. Importantly, the OsCRP1 overexpressing plants showed a higher cyclic electron transport (CET) activity, which is essential for elevated levels of ATP for photosynthesis. Additionally, overexpression of OsCRP1 resulted in significantly enhanced drought and cold stress tolerance with higher ATP levels compared to wild type. Thus, our findings suggest that overexpression of OsCRP1 stabilizes a set of mRNAs from genes of the NDH complex involved in increasing CET activity and production of ATP, which consequently confers enhanced drought and cold tolerance.

Anatomical locations of the motor endplates of sartorius muscle for botulinum toxin injections in treatment of muscle spasticity.

PURPOSE: This study aimed to detect the idyllic locations for botulinum neurotoxin injection by analyzing the intramuscular neural distributions of the sartorius muscles. METHODS: An altered Sihler's staining was conducted on sartorius muscles (15 specimens). The nerve entry points and intramuscular arborization areas were measured as a percentage of the total distance from the most prominent point of the anterior superior iliac spine (0%) to the medial femoral epicondyle (100%). RESULTS: Intramuscular neural distribution were densely detected at 20-40% and 60-80% for the sartorius muscles. The result suggests that the treatment of sartorius muscle spasticity requires botulinum neurotoxin injections in particular locations. CONCLUSIONS: These locations, corresponding to the locations of maximum arborization, are suggested as the most suggestive points for botulinum neurotoxin injection.

Carbon nanomaterial-derived lung burden analysis using UV-Vis spectrophotometry and proteinase K digestion.

BACKGROUND: The quantification of nanomaterials accumulated in various organs is crucial in studying their toxicity and toxicokinetics. However, some types of nanomaterials, including carbon nanomaterials (CNMs), are difficult to quantify in a biological matrix. Therefore, developing improved methodologies for quantification of CNMs in vital organs is instrumental in their continued modification and application. RESULTS: In this study, carbon black, nanodiamond, multi-walled carbon nanotube, carbon nanofiber, and graphene nanoplatelet were assembled and used as a panel of CNMs. All CNMs showed significant absorbance at 750 nm, while their bio-components showed minimal absorbance at this wavelength. Quantification of CNMs using their absorbance at 750 nm was shown to have more than 94% accuracy in all of the studied materials. Incubating proteinase K (PK) for 2 days with a mixture of lung tissue homogenates and CNMs showed an average recovery rate over 90%. The utility of this method was confirmed in a murine pharyngeal aspiration model using CNMs at 30 µg/mouse. CONCLUSIONS: We developed an improved lung burden assay for CNMs with an accuracy > 94% and a recovery rate > 90% using PK digestion and UV-Vis spectrophotometry. This method can be applied to any nanomaterial with sufficient absorbance in the near-infrared band and can differentiate nanomaterials from elements in the body, as well as the soluble fraction of the nanomaterial. Furthermore, a combination of PK digestion and other instrumental analysis specific to the nanomaterial can be applied to organ burden analysis.

Clinical validation of a nanodiamond-embedded thermoplastic biomaterial.

Detonation nanodiamonds (NDs) are promising drug delivery and imaging agents due to their uniquely faceted surfaces with diverse chemical groups, electrostatic properties, and biocompatibility. Based on the potential to harness ND properties to clinically address a broad range of disease indications, this work reports the in-human administration of NDs through the development of ND-embedded gutta percha (NDGP), a thermoplastic biomaterial that addresses reinfection and bone loss following root canal therapy (RCT). RCT served as the first clinical indication for NDs since the procedure sites involved nearby circulation, localized administration, and image-guided treatment progress monitoring, which are analogous to many clinical indications. This randomized, single-blind interventional treatment study evaluated NDGP equivalence with unmodified GP. This progress report assessed one control-arm and three treatment-arm patients. At 3-mo and 6-mo follow-up appointments, no adverse events were observed, and lesion healing was confirmed in the NDGP-treated patients. Therefore, this study is a foundation for the continued clinical translation of NDs and other nanomaterials for a broad spectrum of applications.

Reducing posttreatment relapse in cleft lip palatal expansion using an injectable estrogen-nanodiamond hydrogel.

Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17ß-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.

Bell-Type Correlation at Quantum Phase Transitions in Spin-1 Chain.

For the identification of non-trivial quantum phase, we exploit a Bell-type correlation that is applied to the one-dimensional spin-1 XXZ chain. It is found that our generalization of bipartite Bell correlation can take a decomposed form of transverse spin correlation together with high-order terms. The formulation of the density-matrix renormalisation group is utilized to obtain the ground state of a given Hamiltonian with non-trivial phase. Subsequently Bell-type correlation is evaluated through the analysis of the matrix product state. Diverse classes of quantum phase transitions in the spin-1 model are identified precisely through the evaluation of the first and the second moments of the generalized Bell correlations. The role of high-order terms in the criticality has been identified and their physical implications for the quantum phase have been revealed.

Cdk5 regulates N-cadherin-dependent neuronal migration during cortical development.

Cyclin-dependent kinase 5 (Cdk5) controls neuronal migration in the developing cortex when multipolar newborn neurons transform to become bipolar. However, by which mechanisms Cdk5 controls cell adhesion in migrating neurons are not fully understood. In this study, we examined the functional interaction between Cdk5 and N-cadherin (Ncad) in newborn neurons when they undergo the multipolar to bipolar transition in the intermediate zone (IZ). Detailed expression analysis revealed that both Cdk5 and Ncad were present in GFP-electroporated migrating neurons in the IZ. Misexpression of dominant negative Cdk5 into the embryonic brains stalled neuronal locomotion in the lower IZ in which arrested cells were round or multipolar. When Ncad was co-introduced with Cdk5DN, however, cells continue to migrate into the cortical plate (CP) and migrating neurons acquired typical bipolar morphology with a pia-directed leading process. Similarly, downregulation of CDK5 resulted in lesser aggregation ability, reversed by the expression of Ncad in vitro. Down-regulation of activity or protein level of CDK5 did not alter the total amount of NCAD proteins but lowered its surface expression in cells. Lastly, expression of CDK5 and NCAD overlapped in the IZ of the human fetal cortex, indicating that the role of Cdk5 and Ncad in neuronal migration is evolutionarily conserved.

Overexpression of OsTF1L, a rice HD-Zip transcription factor, promotes lignin biosynthesis and stomatal closure that improves drought tolerance.

Drought stress seriously impacts on plant development and productivity. Improvement of drought tolerance without yield penalty is a great challenge in crop biotechnology. Here, we report that the rice (Oryza sativa) homeodomain-leucine zipper transcription factor gene, OsTF1L (Oryza sativa transcription factor 1-like), is a key regulator of drought tolerance mechanisms. Overexpression of the OsTF1L in rice significantly increased drought tolerance at the vegetative stages of growth and promoted both effective photosynthesis and a reduction in the water loss rate under drought conditions. Importantly, the OsTF1L overexpressing plants showed a higher drought tolerance at the reproductive stage of growth with a higher grain yield than nontransgenic controls under field-drought conditions. Genomewide analysis of OsTF1L overexpression plants revealed up-regulation of drought-inducible, stomatal movement and lignin biosynthetic genes. Overexpression of OsTF1L promoted accumulation of lignin in shoots, whereas the RNAi lines showed opposite patterns of lignin accumulation. OsTF1L is mainly expressed in outer cell layers including the epidermis, and the vasculature of the shoots, which coincides with areas of lignification. In addition, OsTF1L overexpression enhances stomatal closure under drought conditions resulted in drought tolerance. More importantly, OsTF1L directly bound to the promoters of lignin biosynthesis and drought-related genes involving poxN/PRX38, Nodulin protein, DHHC4, CASPL5B1 and AAA-type ATPase. Collectively, our results provide a new insight into the role of OsTF1L in enhancing drought tolerance through lignin biosynthesis and stomatal closure in rice.

Allantoin accumulation through overexpression of ureide permease1 improves rice growth under limited nitrogen conditions.

In legumes, nitrogen (N) can be stored as ureide allantoin and transported by ureide permease (UPS) from nodules to leaves where it is catabolized to release ammonium and assimilation to amino acids. In non-leguminous plants especially rice, information on its roles in N metabolism is scarce. Here, we show that OsUPS1 is localized in plasma membranes and are highly expressed in vascular tissues of rice. We further evaluated an activation tagging rice overexpressing OsUPS1 (OsUPS1OX ) under several N regimes. Under normal field conditions, panicles from OsUPS1OX plants (14 days after flowering (DAF)) showed significant allantoin accumulation. Under hydroponic system at the vegetative stage, plants were exposed to N-starvation and measured the ammonium in roots after resupplying with ammonium sulphate. OsUPS1OX plants displayed higher ammonium uptake in roots compared to wild type (WT). When grown under low-N soil supplemented with different N-concentrations, OsUPS1OX exhibited better growth at 50% N showing higher chlorophyll, tiller number and at least 20% increase in shoot and root biomass relative to WT. To further confirm the effects of regulating the expression of OsUPS1, we evaluated whole-body-overexpressing plants driven by the GOS2 promoter (OsUPS1GOS2 ) as well as silencing plants (OsUPS1RNAi ). We found significant accumulation of allantoin in leaves, stems and roots of OsUPS1GOS2 while in OsUPS1RNAi allantoin was significantly accumulated in roots. We propose that OsUPS1 is responsible for allantoin partitioning in rice and its overexpression can support plant growth through accumulation of allantoin in sink tissues which can be utilized when N is limiting.

The rice OsNAC6 transcription factor orchestrates multiple molecular mechanisms involving root structural adaptions and nicotianamine biosynthesis for drought tolerance.

Drought has a serious impact on agriculture worldwide. A plant's ability to adapt to rhizosphere drought stress requires reprogramming of root growth and development. Although physiological studies have documented the root adaption for tolerance to the drought stress, underlying molecular mechanisms is still incomplete, which is essential for crop engineering. Here, we identified OsNAC6-mediated root structural adaptations, including increased root number and root diameter, which enhanced drought tolerance. Multiyear drought field tests demonstrated that the grain yield of OsNAC6 root-specific overexpressing transgenic rice lines was less affected by drought stress than were nontransgenic controls. Genome-wide analyses of loss- and gain-of-function mutants revealed that OsNAC6 up-regulates the expression of direct target genes involved in membrane modification, nicotianamine (NA) biosynthesis, glutathione relocation, 3'-phophoadenosine 5'-phosphosulphate accumulation and glycosylation, which represent multiple drought tolerance pathways. Moreover, overexpression of NICOTIANAMINE SYNTHASE genes, direct targets of OsNAC6, promoted the accumulation of the metal chelator NA and, consequently, drought tolerance. Collectively, OsNAC6 orchestrates novel molecular drought tolerance mechanisms and has potential for the biotechnological development of high-yielding crops under water-limiting conditions.

The Mobile bypass Signal Arrests Shoot Growth by Disrupting Shoot Apical Meristem Maintenance, Cytokinin Signaling, and WUS Transcription Factor Expression.

The bypass1 (bps1) mutant of Arabidopsis (Arabidopsis thaliana) produces a root-sourced compound (the bps signal) that moves to the shoot and is sufficient to arrest growth of a wild-type shoot; however, the mechanism of growth arrest is not understood. Here, we show that the earliest shoot defect arises during germination and is a failure of bps1 mutants to maintain their shoot apical meristem (SAM). This finding suggested that the bps signal might affect expression or function of SAM regulatory genes, and we found WUSCHEL (WUS) expression to be repressed in bps1 mutants. Repression appears to arise from the mobile bps signal, as the bps1 root was sufficient to rapidly down-regulate WUS expression in wild-type shoots. Normally, WUS is regulated by a balance between positive regulation by cytokinin (CK) and negative regulation by CLAVATA (CLV). In bps1, repression of WUS was independent of CLV, and, instead, the bps signal down-regulates CK responses. Cytokinin treatment of bps1 mutants restored both WUS expression and activity, but only in the rib meristem. How the bps signal down-regulates CK remains unknown, though the bps signal was sufficient to repress expression of one CK receptor (AHK4) and one response regulator (AHP6). Together, these data suggest that the bps signal pathway has the potential for long-distance regulation through modification of CK signaling and altering gene expression.

Overexpression of the OsERF71 Transcription Factor Alters Rice Root Structure and Drought Resistance.

Plant responses to drought stress require the regulation of transcriptional networks via drought-responsive transcription factors, which mediate a range of morphological and physiological changes. AP2/ERF transcription factors are known to act as key regulators of drought resistance transcriptional networks; however, little is known about the associated molecular mechanisms that give rise to specific morphological and physiological adaptations. In this study, we functionally characterized the rice (Oryza sativa) drought-responsive AP2/ERF transcription factor OsERF71, which is expressed predominantly in the root meristem, pericycle, and endodermis. Overexpression of OsERF71, either throughout the entire plant or specifically in roots, resulted in a drought resistance phenotype at the vegetative growth stage, indicating that overexpression in roots was sufficient to confer drought resistance. The root-specific overexpression was more effective in conferring drought resistance at the reproductive stage, such that grain yield was increased by 23% to 42% over wild-type plants or whole-body overexpressing transgenic lines under drought conditions. OsERF71 overexpression in roots elevated the expression levels of genes related to cell wall loosening and lignin biosynthetic genes, which correlated with changes in root structure, the formation of enlarged aerenchyma, and high lignification levels. Furthermore, OsERF71 was found to directly bind to the promoter of OsCINNAMOYL-COENZYME A REDUCTASE1, a key gene in lignin biosynthesis. These results indicate that the OsERF71-mediated drought resistance pathway recruits factors involved in cell wall modification to enable root morphological adaptations, thereby providing a mechanism for enhancing drought resistance.

Persistence Length and Cooperativity Estimation of Single Stranded DNA using FCS Combined with HYDRO Program.

Translational diffusion properties of single-stranded DNA (ssDNA) and G-quadruplexes were studied to determine the persistence length and cooperativity of G-quadruplex formation using FCS combined with HYDRO in which wormlike chain (WLC)-based Monte Carlo simulation are implemented. The presence of a guanine instead of a thymine shortened the contour length of nucleic acids and increased the vulnerability to ion screening. For cooperativity estimation, the telomeric sequence HT72 was assumed to undergo 27 intermediate states, which can be classified as ssDNA, single-G-quadruplex, double-G-quadruplex, and three consecutive G-quadruplexes. Each state type was modeled using a series of beads and appropriate bond lengths, which were obtained from the WLC model. Using the HYDRO program, we calculated diffusion times for each species, and these were used to calculate simulated HT72 diffusion times for mixtures of species in arbitrary KCl concentrations. By comparison between simulated and experimental diffusion properties, we obtained a positive cooperativity of C = 200 from FCS combined with HYDRO.

In the absence of BYPASS1-related gene function, the bps signal disrupts embryogenesis by an auxin-independent mechanism.

Development is often coordinated by biologically active mobile compounds that move between cells or organs. Arabidopsis mutants with defects in the BYPASS1 (BPS1) gene overproduce an active mobile compound that moves from the root to the shoot and inhibits growth. Here, we describe two related Arabidopsis genes, BPS2 and BPS3. Analyses of single, double and triple mutants revealed that all three genes regulate production of the same mobile compound, the bps signal, with BPS1 having the largest role. The triple mutant had a severe embryo defect, including the failure to properly establish provascular tissue, the shoot meristem and the root meristem. Aberrant expression of PINFORMED1, DR5, PLETHORA1, PLETHORA2 and WUSCHEL-LIKE HOMEOBOX5 were found in heart-stage bps triple-mutant embryos. However, auxin-induced gene expression, and localization of the PIN1 auxin efflux transporter, were intact in bps1 mutants, suggesting that the primary target of the bps signal is independent of auxin response. Thus, the bps signal identifies a novel signaling pathway that regulates patterning and growth in parallel with auxin signaling, in multiple tissues and at multiple developmental stages.

Investigation of the nanoviscosity effect of a G-quadruplex and single-strand DNA using fluorescence correlation spectroscopy.

Guanine (G)-quadruplexes are of interest because of their presence in the telomere sequence and the oncogene promoter region. Their diffusion and change of structure, especially in high viscosity solutions, are important for understanding their dynamics. G-quadruplexes may have less effective viscosity (nanoviscosity) when they are smaller than the solvent molecules. In this paper, we report the difference in the diffusion dynamics of the G-rich DNA sequences of single-strand DNA (ssDNA) and the G-quadruplex in aqueous, sucrose, and polyethylene glycol (PEG) solutions. From experiments with aqueous and sucrose solutions, we confirm that a simple diffusion model according to the viscosity is appropriate. In the PEG experiments, the nanoviscosity effect is observed according to PEG's molecular weight. In the PEG 200 solution, both the ssDNA and the G-quadruplex possess macroviscosity. In the PEG 10,000 solution, the G-quadruplex possesses nanoviscosity and the ssDNA possesses macroviscosity, whereas, in the PEG 35,000 solution, both ssDNA and the G-quadruplex possess nanoviscosity. The experimental results are consistent with the theoretical predictions.

Nanodiamond-mitoxantrone complexes enhance drug retention in chemoresistant breast cancer cells.

Chemoresistance is a prevalent issue that accounts for the vast majority of treatment failure outcomes in metastatic cancer. Among the mechanisms of resistance that markedly decrease treatment efficacy, the efflux of drug compounds by ATP-binding cassette (ABC) transporter proteins can impair adequate drug retention by cancer cells required for therapeutic cytotoxic activity. Of note, ABC transporters are capable of effluxing several classes of drugs that are clinical standards, including the anthracyclines such as doxorubicin, as well as anthracenediones such as mitoxantrone. To address this challenge, a spectrum of nanomaterials has been evaluated for improved drug retention and enhanced efficacy. Nanodiamonds (NDs) are emerging as a promising nanomaterial platform because they integrate several important properties into a single agent. These include a uniquely faceted truncated octahedral architecture that enables potent drug binding and dispersibility in water, scalably processed ND particles with uniform diameters of approximately 5 nm, and a demonstrated ability to improve drug tolerance while delaying tumor growth in multiple preclinical models, among others. This work describes a ND-mitoxantrone complex that can be rapidly synthesized and mediates marked improvements in drug efficacy. Comprehensive complex characterization reveals a complex with favorable drug delivery properties that is capable of improving drug retention and efficacy in an MDA-MB-231-luc-D3H2LN (MDA-MB-231) triple negative breast cancer cell line that was lentivirally transduced for resistance against mitoxantrone. Findings from this study support the further evaluation of ND-MTX in preclinical dose escalation and safety studies toward potentially clinical validation.

Transcriptional control of motor pool formation and motor circuit connectivity by the LIM-HD protein Isl2.

The fidelity of motor control requires the precise positional arrangement of motor pools and the establishment of synaptic connections between them. During neural development in the spinal cord, motor nerves project to specific target muscles and receive proprioceptive input from these muscles via the sensorimotor circuit. LIM-homeodomain transcription factors are known to play a crucial role in successively restricting specific motor neuronal fates. However, their exact contribution to limb-based motor pools and locomotor circuits has not been fully understood. To address this, we conducted an investigation into the role of Isl2, a LIM-homeodomain transcription factor, in motor pool organization. We found that deletion of Isl2 led to the dispersion of motor pools, primarily affecting the median motor column (MMC) and lateral motor column (LMC) populations. Additionally, hindlimb motor pools lacked Etv4 expression, and we observed reduced terminal axon branching and disorganized neuromuscular junctions in Isl2-deficient mice. Furthermore, we performed transcriptomic analysis on the spinal cords of Isl2-deficient mice and identified a variety of downregulated genes associated with motor neuron (MN) differentiation, axon development, and synapse organization in hindlimb motor pools. As a consequence of these disruptions, sensorimotor connectivity and hindlimb locomotion were impaired in Isl2-deficient mice. Taken together, our findings highlight the critical role of Isl2 in organizing motor pool position and sensorimotor circuits in hindlimb motor pools. This research provides valuable insights into the molecular mechanisms governing motor control and its potential implications for understanding motor-related disorders in humans.