Opposing Motor Memories in the Direct and Indirect Pathways of the Basal Ganglia.

Loss of dopamine neurons causes motor deterioration in Parkinson's disease patients. We have previously reported that in addition to acute motor impairment, the impaired motor behavior is encoded into long-term memory in an experience-dependent and task-specific manner, a phenomenon we refer to as aberrant inhibitory motor learning. Although normal motor learning and aberrant inhibitory learning oppose each other and this is manifested in apparent motor performance, in the present study, we found that normal motor memory acquired prior to aberrant inhibitory learning remains preserved in the brain, suggesting the existence of independent storage. To investigate the neuronal circuits underlying these two opposing memories, we took advantage of the RNA-binding protein YTHDF1, an m 6 A RNA methylation reader involved in the regulation of protein synthesis and learning/memory. Conditional deletion of Ythdf1 in either D1 or D2 receptor-expressing neurons revealed that normal motor memory is stored in the D1 (direct) pathway of the basal ganglia, while inhibitory memory is stored in the D2 (indirect) pathway. Furthermore, fiber photometry recordings of GCaMP signals from striatal D1 (dSPN) and D2 (iSPN) receptor-expressing neurons support the preservation of normal memory in the direct pathway after aberrant inhibitory learning, with activities of dSPN predictive of motor performance. Finally, a computational model based on activities of motor cortical neurons, dSPN and iSPN neurons, and their interactions through the basal ganglia loops supports the above observations. These findings have important implications for novel approaches in treating Parkinson's disease by reactivating preserved normal memory, and in treating hyperkinetic movement disorders such as chorea or tics by erasing aberrant motor memories.

Obstetric blood transfusion in placenta previa patients with prenatal anemia: a retrospective study.

BACKGROUND: The appropriate use of obstetric blood transfusion is crucial for patients with placenta previa and prenatal anemia. This retrospective study aims to explore the correlation between prenatal anemia and blood transfusion-related parameters in this population. METHODS: We retrieved the medical records of consecutive participants who were diagnosed with placenta previa and underwent cesarean section in our hospital. We compared the baseline demographics and clinical characteristics of patients with and without anemia. The correlation between prenatal anemia and obstetric blood transfusion-related parameters was evaluated using multivariate regression analysis. RESULTS: A total of 749 patients were enrolled, with a mean prenatal hemoglobin level of 10.87 ± 1.37 g/dL. Among them, 54.87% (391/749) were diagnosed with anemia. The rate of obstetric blood transfusion was significantly higher in the anemia group (79.54%) compared to the normal group (44.41%). The median allogeneic red blood cell transfusion volume in the anemia group was 4.00 U (IQR 2.00-6.00), while in the normal group, it was 0.00 U (IQR 0.00-4.00). The prenatal hemoglobin levels had a non-linear relationship with intraoperative allogeneic blood transfusion rate, massive blood transfusion rate, red blood cell transfusion units, and fresh plasma transfusion volume in patients with placenta previa, with a threshold of 12 g/dL. CONCLUSIONS: Our findings suggest that prenatal anemia is associated with a higher rate of blood transfusion-related parameters in women with placenta previa when the hemoglobin level is < 12 g/dL. These results highlight the importance of promoting prenatal care in placenta previa patients with a high requirement for blood transfusion.

Unraveling the underlying mechanism of good electrochemical performance of hard carbon in PC/EC-Based electrolyte.

Although hard carbon in propylene carbonate / ethylene carbonate (PC/EC)-based electrolytes possesses favorable electrochemical characteristics in rechargeable sodium-ion batteries, the underlying mechanism is still vague. Numerous hypotheses have been proposed to solve the puzzle, but none of them have satisfactorily unraveled the reason at the molecular-level. In this study, we firstly attempted to address this mystery through a profound insight into the disparity of the ion solvation/desolvation behavior in electrolyte. Combining the results of density functional theory (DFT) calculations and experiments, the work explains that compared to the sole PC-based electrolyte, Na+-EC4 molecules in the PC/EC-based electrolyte preferentially undergo reduction and contribute to the emergence of a more stable protective film on the surface of hard carbon, leading to the preferable durability and rate capability of the cell. Nevertheless, applying the ion solvation/desolvation model, it also reveals that Na+-(solvent)n molecules in the PC/EC-based electrolyte can achieve faster Na+ desolvation processes than in the PC-based electrolyte alone, contributing to the enhancement of charge transfer kinetics. This research holds great importance in uncovering the possible mechanism of the remarkable electrochemical- properties of hard carbon in PC/EC-based electrolytes, and advancing its practical utilization in future sodium-ion batteries.

Nanog induced intermediate state in regulating stem cell differentiation and reprogramming.

BACKGROUND: Heterogeneous gene expressions of cells are widely observed in self-renewing pluripotent stem cells, suggesting possible coexistence of multiple cellular states with distinct characteristics. Though the elements regulating cellular states have been identified, the underlying dynamic mechanisms and the significance of such cellular heterogeneity remain elusive. RESULTS: We present a gene regulatory network model to investigate the bimodal Nanog distribution in stem cells. Our model reveals a novel role of dynamic conversion between the cellular states of high and low Nanog levels. Model simulations demonstrate that the low-Nanog state benefits cell differentiation through serving as an intermediate state to reduce the barrier of transition. Interestingly, the existence of low-Nanog state dynamically slows down the reprogramming process, and additional Nanog activation is found to be essential to quickly attaining the fully reprogrammed cell state. CONCLUSIONS: Nanog has been recognized as a critical pluripotency gene in stem cell regulation. Our modeling results quantitatively show a dual role of Nanog during stem cell differentiation and reprogramming, and the importance of the intermediate state during cell state transitions. Our approach offers a general method for analyzing key regulatory factors controlling cell differentiation and reprogramming.