Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL

Objective To investigate the effects of alcoholic extract of Hemerocallis citrina Baroni on the depressive-like behaviors in zebrafish larvae(Danio rerio)induced by reserpine.Methods Zebrafish larvae were divided into various groups:control(Con)group,reserpine group,fluoxetine group,H.citrina alcohol extract(HCE)low dose group(1.5 mg/L),HCE medium dose group(3 mg/L),and HCE high dose group(4.5 mg/L).Depressive-like behaviors were analyzed using sound and light stimulation.Real-time PCR was used to investigate the effects of HCE on depression related astrocyte markers(GFAP,C3,C4B,EMP-1,S100α-10)and the neurotrophic factor BDNF and its receptor genes(P75,TrkB).Results In comparison to the control group,the model group demonstrated significantly shorter movement distance and reduced movement time under sound and light stimulation(P＜0.05,P＜0.001,P＜0.0001).Following the administration of HCE,zebrafish larvae exhibited significantly heightened sensitivity to light and sound stimulation compared to the model group(P＜0.05,P＜0.0001).Astrocyte marker genes were up-regulated in the model group zebrafish brains compared to the control group(P＜0.0001).However,when the model group was administered HCE,the expression of astrocyte markers was significantly down-regulated compared to the model group(P＜0.0001).Neurotrophic factor and its receptor genes(BDNF,P75,TrkB)were down-regulated in zebrafish brains in the model group compared to those in the control group(P＜0.0001).However,in the group administered HCE,the expression of BDNF,P75,and TrkB was significantly up-regulated compared to that in the model group(P＜0.01,P＜0.0001).These findings suggest that HCE suppressed the inflammatory responses caused by astrocyte activation and promoted the production of neurotrophic factors and their receptor genes,thereby exerting an ameliorative effect on depression.Conclusions Alcoholic extracts of H.citrina can ameliorate the depression-like behavioral changes induced by reserpine in zebrafish larvae.They reduce the expression of astrocyte markers in the zebrafish brain and promote the production of neurotrophic factors and their receptor genes,playing an antidepressant role.

To evaluate five methods in the estimation on the rate of case fatality during the epidemics of diseases based on the summarizing data. Case fatality rates, derived from the simulation data, 2003 SARS epidemic data in Hong Kong, Singapore Beijing and the 2013 H7N9 epidemic data in mainland China were analyzed, using these 5 methods. Results from the simulation analysis discovered that the relative errors and the standard deviations of the Chen [7, 8] (method 3), Chen [9] (method 4)were minor with high accuracy. Data from the analysis on 2003 SARS epidemic was noticed that the estimation from method 3, 4 in Hong Kong and Singapore both showing high veracities. Since the case fatality rate reported in Beijing was not a constant value, method 5 showed low accuracy even though it was close to the final case fatality rate. Data from the 2013 H7N9 epidemic showed that the estimations of method 1, 2, 3, 4 were all higher than that in the method 5, suggesting that method 3, 4 could be used to estimate the case fatality rates of epidemics more precisely.
China ; epidemiology ; Hong Kong ; epidemiology ; Humans ; Influenza A Virus, H7N9 Subtype ; Influenza, Human ; mortality ; Regression Analysis ; Severe Acute Respiratory Syndrome ; mortality

To evaluate five methods in the estimation on the rate of case fatality during the epidemics of diseases based on the summarizing data. Case fatality rates,derived from the simulation data,2003 SARS epidemic data in Hong Kong,Singapore Beijing and the 2013 H7N9 epidemic data in mainland China were analyzed,using these 5 methods. Results from the simulation analysis discovered that the relative errors and the standard deviations of the Chen[7,8] (method 3),Chen[9] (method 4) were minor with high accuracy. Data from the analysis on 2003 SARS epidemic was noticed that the estimation from method 3,4 in Hong Kong and Singapore both showing high veracities. Since the case fatality rate reported in Beijing was not a constant value,method 5 showed low accuracy even though it was close to the final case fatality rate. Data from the 2013 H7N9 epidemic showed that the estimations of method 1,2,3,4 were all higher than that in the method 5, suggesting that method 3,4 could be used to estimate the case fatality rates of epidemics more precisely.