Calmodulin triggers activity-dependent rRNA biogenesis via interaction with DDX21.

Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and memory formation. However, the signaling cascades that couple neuronal activity to the translational events remains elusive. In this study, we identified the role of calmodulin (CaM), a conserved Ca2+-binding protein, in rRNA biogenesis in neurons. We found the CaM-regulated rRNA synthesis is Ca2+-dependent and necessary for nascent protein synthesis and axon growth in hippocampal neurons. Mechanistically, CaM interacts with nucleolar DDX21 in a Ca2+-dependent manner to regulate nascent rRNA transcription within nucleoli. We further found CaM alters the conformation of DDX21 to liberate the DDX21-sequestered RPA194, the catalytic subunit of RNA polymerase I, to facilitate transcription of rDNA. Using high-throughput screening, we identified the small molecules Batefenterol and Indacaterol that attenuate the CaM-DDX21 interaction and suppress nascent rRNA synthesis and axon growth in hippocampal neurons. These results unveiled the previously unrecognized role of CaM as a messenger to link the activity-induced Ca2+ influx to the nucleolar events essential for protein synthesis. We thus identified the ability of CaM to transmit information to the nucleoli of neurons in response to stimulation.Significance statement Protein synthesis in response to neuronal activity, known as activity-dependent translation, is critical for synaptic plasticity and long-term memory formation. In this study, we identify the novel role of calmodulin (CaM), a highly conserved Ca2+-binding protein, which is well-known by regulating myriad vital biological processes, in activity-dependent translation by regulating rRNA synthesis in neurons. We find that CaM can shuttle into the nucleolus upon depolarization and modulate the activity-induced de novo rRNA biogenesis, which is associated with ribosome assembly and protein synthesis in neurons. Mechanistically, CaM interacts with DDX21, an RNA helicase directly associated with Pol I subunit, to regulate the transcription of rDNA. Our study demonstrates CaM as a messenger linking neuronal activity to ribosome-dependent protein biosynthesis.

Detection of TERC gene amplification by fluorescence in-situ hybridization in cervical intraepithelial lesions / 中华病理学杂志

<p><b>OBJECTIVE</b>To explore the feasibility and practical value of fluorescence in situ hybridization (FISH) detection of TERC gene amplification in cervical intraepithelial lesions (CIN) and squamous cell carcinoma (SCC).</p><p><b>METHODS</b>Tissue microarray was constructed to cover 150 cases of various cervical conditions, including 24 cases of normal cervical mucosa, 78 cases of CINs (CINI, 25 cases; CINII, 21 cases and CINIII, 32 cases) and 48 cases of SCC. FISH was used to detect TERC gene amplification.</p><p><b>RESULTS</b>TERC gene amplification was detected in 8% (2/25) CINI, 47.6% (10/21) CINII, 71.9% (23/32) CINIII and 87.5% (42/48) SCC. There were significant differences among these groups (P < 0.05). The amplification rates of TERC gene in SCC, CINIII and CINII were significantly higher than those of normal cervical epithelium and CINI (P < 0.05). Significant differences were also observed among CINI and CINII, CINIII and SCC (P < 0.05), and between CINII and SCC (P < 0.05). There were no significant differences between normal cervical epithelium and CINI, CINII and CIN III, and between CINIII and SCC (P > 0.05). FISH detection of amplification of TERC gene in CINI and CINII-III demonstrated the following statistics: sensitivity of 62.3%, specificity of 92.0%, accuracy of 71.8%, positive and negative predictive values of 94.3% and 53.5%, respectively.</p><p><b>CONCLUSIONS</b>FISH detection is a reliable method in detecting TERC gene amplification using paraffin tissue sections. When histological evaluation becomes difficult, TERC amplification detectable by FISH may offer a diagnostic distinction of CINI from CINII. Moreover, TERC amplification may be used as a biomarker in predicting CIN progression to invasive cancer.</p>

Using three different screening methods to study overweight and simple obesity among children under age 7 in Ningbo city / 中华流行病学杂志

Objective To investigate the occurrence of simple obesity among children under age 7 in Ningbo and to analyze the data regarding body mass index (BMI) from overweight screening under different standards. Methods Randomized cluster sampling was adopted and 64 038 children under 7 years old in Ningho were chosen and their length/height and weight were measured but pathological and secondary obesity cases were excluded. According to the Standardized Height and Weight set by WHO, more than 10% referring to overweight and more than 20% referring to obesity. Moreover, results of this study were compared with growth standards with WHO' s 2006 and IOTF standards. Results According to the Standardized Height and Weight set by WHO, the prevalence rates of overweight and obesity of children under age 7 were 4.25% and 2.88%. The ratio for boys were 4.45% and 3.01%, while for girls as 3.86% and 2.56%, with significant difference (P<0.01). Data showed that the rates for overweight and obesity increased along with age, reaching 11.84% and 9.68% for boys and 10.14% and 9.46% for girls at the age of 6. The ratios of overweight/obesity among different age groups and sex were 1.15-1.94:1. The critical value for P85, P95 were lower than the standards set by WHO and IOTE The rates for overweight and obesity for latter were 9.72%, 2.83% and 6.11%, 0.55% respectively. Conclusion Early childhood is the key period for obesity prevention, with boys in particular. Prevention and control for childhood obesity should be included in the programs for children' s health. Value of classification standards for the BMI screening of overweight and obesity for children under age 7 should be established in no time.

Research on the growth references of height, weight and body mass index for children under 7 years old / 中华流行病学杂志

Objective To understand the varying features and the trend of length/height-for-age,weight-for-age and body masa index(BMI)-for-age of children under six years old in Ningbo city,Zhejiang province.Methods By random clustered sampling,64 038 healthy children under six years old in Ningbo were chosen and their length/height and weight measured.Means,standard deviation and percentiles of length/height-for-age,weight-for-age and BMI were calculated by SAS systems.Results of this study were compared with growth standards from WHO 2006 and nine urban areas of China,in 2005.Results Data from our study showed that the annual growth rates were basically the same in boys and girls.All these indicators increased along with age but the younger the age,the faster the growth rate appeared.There were notable differences seen between genders and urban-rural distribution.BMIs were also varied with age and sex.BMI reached peak between 4 to 6 months,then dropped slowly when age increased.Conclusion The means of length/height-for-age,weight-for-age in Ningbo city had exceeded the WHO standards,and the growth by year under six year-olds in Ningbo was close to the data from nine urban areas of China in 2005.