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Disturbance of the cholinergic system plays a crucial role in the pathological progression of neurological diseases that cause dyskinesia-like behaviors. However, the molecular mechanisms underlying this disturbance remain elusive. Here, we showed that cyclin-dependent kinase 5 (Cdk5) was reduced in cholinergic neurons of midbrain according to the single-nucleus RNA sequencing analysis. Serum levels of CDK5 also decreased in patients with Parkinson’s disease accompanied by motor symptoms. Moreover, Cdk5 deficiency in cholinergic neurons triggered paw tremors, abnormal motor coordination, and motor balance deficits in mice. These symptoms occurred along with cholinergic neuron hyperexcitability and increases in the current density of large-conductance Ca2+-activated K+ channels (BK channels). Pharmacological inhibition of BK channels restrained the excessive intrinsic excitability of striatal cholinergic neurons in Cdk5-deficient mice. Furthermore, CDK5 interacted with BK channels and negatively regulated BK channel activity via phosphorylation of threonine-908. Restoration of CDK5 expression in striatal cholinergic neurons reduced dyskinesia-like behaviors in ChAT-Cre;Cdk5f/f mice. Together, these findings indicate that CDK5-induced phosphorylation of BK channels involves in cholinergic-neuron-mediated motor function, providing a potential new therapeutic target for treating dyskinesia-like behaviors arising from neurological diseases.

In this paper, a direct numerical simulation (DNS) of dielectric fluid flow subjected to unipolar injection under an alternating current (AC) electric field is carried out. The effect of frequency f of pulsed direct current (PDC) and AC on the transient evolution of electroconvection and their subcritical bifurcations are investigated in details. Electroconvection under PDC or AC tends to exhibit oscillating flow due to the periodic boundary condition of charge density and potential compared to the direct current (DC) case. The results demonstrate that under the PDC field, the linear criterion Tc decreases with increasing frequency, while the nonlinear stability criterion Tf is hardly affected. Under the AC field, a critical frequency fc = 0.0316 is found, which separates electroconvection into two typical flow regimes—periodic flow regime (f

DNA G-quadruplexes occur in oncologically relevant regions, thus are interesting targets for cancer research and treatment. Here, the authors solved the 1:1 and 4:2 (ligand/DNA) NMR structures of human telomeric DNA in complex with platinum(II)-tripod ligand and show that the binding is dynamic.

In this study, sodium alginate (SA), dimethyl dodecyl betaine (BS), and chitosan (CS) were used for single, binary, and ternary modifications on the surface of semi-carbonized fibers (Sf) prepared using acrylic fiber. Batch method was used to investigate the adsorption characteristic of oxytetracycline (OTC) on the tested materials, and the effects of pH, temperature, and ionic strength on oxytetracycline adsorption were compared. The structural particularities of the tested materials was studied using scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR). Results showed that: (1) Langmuir model can better fitted the adsorption isotherms of OTC than Henry and Freundlich models, with the maximum adsorption capacity (qm) maintained at 16.11– 65.25 mmol/kg. The qm of oxytetracycline presented the trend of ternary > binary > single modification. (2) In the pH range of 1–9 and ionic strength range of 0.01–0.5 mol/L, the adsorption amount of OTC on different modified Sfs increased first and then decreased with increasing pH and ionic strength, reaching the maximum value at pH 5 and ionic strength of 0.1 mol/L. (3) OTC adsorption on different modified Sfs increased with the increase in temperature, and the adsorption was a spontaneous, endothermic, and entropy-increasing process, which conformed to the pseudo-second-order kinetic equation. (4) SEM and FTIR results proved that the modifiers were modified on the surface and that they changed the surface properties of Sf. The adsorption amount of OTC on 100SA/BS/ CS-Sf still reached about 50% of the original material after three times of regeneration. [ABSTRACT FROM AUTHOR]