摘要：
In conditions of proteasomal impairment, the damaged or misfolded proteins, collectively known as aggresome, can accumulate in the perinuclear space and be subsequently eliminated by autophagy. Abnormal aggregation of microtubule-associated protein tau in the cytoplasm is a common neuropathological feature of tauopathies. The deficiency in ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), a proteasomal deubiquitinating enzyme, is closely related to tau aggregation; however, the associated mechanisms remain unclear. Here, we showed that UCH-L1 inhibition interrupts proteasomal impairment-induced tau aggresome formation. By reducing the production of lysine (K63)-linked ubiquitin chains, UCH-L1 inhibition decreases HDAC6 deacetylase activity and attenuates the interaction of HDAC6 and tau protein, finally leading to tau aggresome formation impairment. All these results indicated that UCH-L1 plays a key role in the process of tau aggresome formation by regulating HDAC6 deacetylase activity and implied that UCH-L1 may act as a signaling molecule to coordinate the effects of the ubiquitin-proteasome system and the autophagy-lysosome pathway, which mediate protein aggregates degradation in the cytoplasm.
摘要：
Diverse stimuli induce stomatal closure by triggering the efflux of osmotic anions, which is mainly mediated by the main anion channel SLAC1 in plants, and the anion permeability and selectivity of SLAC1 channels from several plant species have been reported to be variable. However, the genetic identity as well as the anion permeability and selectivity of the main S-type anion channel ZmSLAC1 in maize are still unknown. In this study, we identified GRMZM2G106921 as the gene encoding ZmSLAC1 in maize, and the maize mutants zmslac1-1 and zmslac1-2 harboring a mutator (Mu) transposon in ZmSLAC1 exhibited strong insensitive phenotypes of stomatal closure in response to diverse stimuli. We further found that ZmSLAC1 functions as a nitrate-selective anion channel without obvious permeability to chloride, sulfate and malate, clearly different from SLAC1 channels of Arabidopsis thaliana, Brassica rapa ssp. chinensis and Solanum lycopersicum L. Further experimental data show that the expression of ZmSLAC1 successfully rescued the stomatal movement phenotypes of the Arabidopsis double mutant atslac1-3atslah3-2 by mainly restoring nitrate-carried anion channel currents of guard cells. Together, these findings demonstrate that ZmSLAC1 is involved in stomatal closure mainly by mediating the efflux of nitrate in maize.
作者机构：
[Cheng, Mengrong; Zhang, Manling; Zhou, Qian; Huang, Qingyang; Mei, Bing; Huang, Han; Han, Lanchun] Cent China Normal Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China.
通讯机构：
[Huang, Qingyang] C;Cent China Normal Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China.
关键词：
Obesity;Genome-wide association studies;Single nucleotide polymorphisms;MicroRNAs;Phosphorylation;Transcription factors;Gene expression;Protein-protein interactions
摘要：
OBJECTIVES: Genome-wide association studies (GWASs) have discovered associations of numerous SNPs and genes with obesity. However, the underlying molecular mechanisms through which these SNPs and genes affect the predisposition to obesity remain not fully understood. Aims of our study are to comprehensively characterize obesity GWAS SNPs and genes through computational approaches. METHODS: For obesity GWAS identified SNPs, functional annotation, effects on miRNAs binding and impact on protein phosphorylation were performed via RegulomeDB and 3DSNP, miRNASNP, and the PhosSNP 1.0 database, respectively. For obesity associated genes, protein-protein interaction network construction, gene ontology and pathway enrichment analyses were performed by STRING, PANTHER and STRING, respectively. RESULTS: A total of 445 SNPs are significantly associated with obesity related phenotypes at threshold P < 5x10-8. A number of SNPs were eQTLs for obesity associated genes, some SNPs located at binding sites of obesity related transcription factors. SNPs that might affect miRNAs binding and protein phosphorylation were identified. Protein-protein interaction network analysis identified the highly-interconnected "hub" genes. Obesity associated genes mainly involved in metabolic process and catalytic activity, and significantly enriched in 15 signal pathways. CONCLUSIONS: Our results provided the targets for follow-up experimental testing and further shed new light on obesity pathophysiology.
作者机构：
[Li, Bo; Bi, Liyan; Wang, Huimei; Yang, Ying; Jen, Philip H. -S.; Shen, Shuang; Yang, Y; Jen, PHS; Zheng, Tihua] Binzhou Med Coll, Coll Special Educ, Yantai, Shandong, Peoples R China.;[Wang, Xin] Cent China Normal Univ, Coll Life Sci, Wuhan, Hubei, Peoples R China.;[Jen, Philip H. -S.] Univ Missouri Columbia, Div Biol Sci, Columbia, MO USA.
通讯机构：
[Yang, Y; Jen, PHS] B;Binzhou Med Coll, Coll Special Educ, Yantai, Shandong, Peoples R China.
关键词：
dorsal nucleus of the lateral lemniscus;facilitation;inferior colliculus;inhibition;mice;modulation of auditory signal processing
摘要：
In the ascending auditory pathway, the central nucleus of the inferior colliculus (IC) receives and integrates excitatory and inhibitory inputs from many bilateral lower auditory nuclei, intrinsic projections within the IC, contralateral IC through the commissure of the IC and from the auditory cortex. All these presynaptic excitatory and inhibitory inputs dynamically shape and modulate the auditory response properties of individual IC neurons. For this reason, acoustic response properties vary among individual IC neurons due to different activity pattern of presynaptic inputs. The present study examines modulation of auditory response properties of IC neurons by combining sound stimulation with focal electrical stimulation of the contralateral dorsal nucleus of the lateral lemniscus (referred to as ESDNLL) in the albino mouse. Brief ESDNLL produces variation (increase or decrease) in the number of impulses, response latency and discharge duration of modulated IC neurons. Additionally, 30-minute short-term ESDNLL alone produces variation in the best frequency (BF) and minimum threshold (MT) of modulated IC neurons. These varied response parameters recover in different manner and time course among individual modulated IC neurons. Possible pathways and neural mechanisms underlying these findings are discussed. (C) 2018 IBRO. Published by Elsevier Ltd. All rights reserved.
摘要：
Ovomermis sinensis is a potentially-valuable nematode for controlling insect pests. The parasitic stage of the nematode absorbs nutrients in its host’s hemolymph to maintain its growth development and then kills the host when it emerges. At present, little known about its reproductive development, particularly the responsible molecular mechanism. More detailed research on the genes of reproductive development will not only help us understand the mechanisms underlying sex differentiation in the nematode, but would also be valuable for successfully cultivating them in vitro and using them for biocontrol. In this study, we used the homology cloning method to clone the full-length cDNA of a DEAD-box family gene (Oslaf-1) from O. sinensis. Then, using qRT-PCR technology to detect the expression pattern of the Oslaf-1 gene at different development stages and tissues, the gene was found to be highly expressed in the post-parasitic stage (P < 0.01) and ovarian (P < 0.05) of O. sinensis. Western blot analysis showed the same result that the gene is associated with gonadal development and function, but is not gonad-specific. In situ hybridization further demonstrated that the gene is widely expressed in early embryos and is mainly distributed in the gonadal area. However, the signal was mainly concentrated in the reproductive primordia in pre-parasitic juveniles. RNA interference (RNAi) studies revealed that the sex ratio of O. sinensis soaked in dsRNA of Oslaf-1 was not statistically different than the gfp dsRNA treated groups. Our results suggest that Oslaf-1 may play a vital role in the reproductive systems of the nematode. In addition, we speculate that the Oslaf-1 gene plays an important role during embryonic development and that it occurs and develops in the gonads of pre-parasitic juveniles of O. sinensis.
作者机构：
[Tong, Zhiqian; Tan, Tao] Capital Med Univ, Beijing Inst Brain Disorders, Alzheimers Dis Ctr, Beijing 100069, Peoples R China.;[Tan, Tao] Sichuan Prov Hosp Women & Children, Chengdu, Sichuan, Peoples R China.;[Song, Weihong; Zhang, Yun] Univ British Columbia, Dept Psychiat, Townsend Family Labs, Vancouver, BC, Canada.;[Luo, Hongjun; Li, Hui; Luo, Wenhong] Shantou Univ, Cent Lab, Med Coll, Shantou, Guangdong, Peoples R China.;[Lv, Jihui] Beijing Geriatr Hosp, Beijing, Peoples R China.
通讯机构：
[Tong, Zhiqian] C;[Song, Weihong] U;Capital Med Univ, Beijing Inst Brain Disorders, Alzheimers Dis Ctr, Beijing 100069, Peoples R China.;Univ British Columbia, 2255 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
关键词：
ALDH2;hyperglycemia;dementia;Alzheimer
摘要：
Patients with type 2 diabetes mellitus (T2DM) often develop cognitive impairments and have an increased risk of developing Alzheimer's disease. Hyperglycemia is a major characteristic of T2DM, but how elevated glucose levels lead to cognitive decline remains elusive. Here, we report that patients with T2DM and mutations in the formaldehyde (FA)-degrading enzyme aldehyde dehydrogenase 2 (ALDH2) gene had higher levels of FA and more severe dementia. Injection of FA induced hyperglycemia and cognitive deficits in rats. Ablation of gene expression of ALDH2, the main enzyme to oxidize FA, resulted in abnormally high levels of hippocampal FA, leading to hyperglycemia and cognitive impairments as well as potentiating streptozotocin-induced diabetes development in ALDH2 knockout mice. We found that FA interacts with insulin to form FA-insulin adducts, and these FA-insulin adducts caused insulin deficiency, contributing to memory decline in diabetic rodent models. Reduction of FA by transgenic overexpression of human ALDH2 attenuates hyperglycemia and alleviates cognitive deficits in diabetic mouse models. These findings suggest that excess FA plays a critical role in mediating diabetes-related dementia. Targeting FA and its metabolizing enzyme ALDH2 may be a valid approach for preventing and treating dementia in diabetes mellitus.Tan, T., Zhang, Y., Luo, W., Lv, J., Han, C., Hamlin, J. N. R., Luo, H., Li, H., Wan, Y., Yang, X., Song, W., Tong, Z. Formaldehyde induces diabetes-associated cognitive impairments.
期刊：
PROTEIN JOURNAL,2018年37(6):531-538 ISSN：1572-3887
通讯作者：
Liu, Yanli
作者机构：
[Liu, Jinlin; Liang, Xiao; Yang, Xiajie; Gong, Siying; Li, Fangzhou; Qi, Chao; Lei, Ming; Liu, Ke; Li, Bing; Liu, Yanli; Zhou, Mengqi] Cent China Normal Univ, Hubei Key Lab Genet Regulat & Integrat Biol, Sch Life Sci, Wuhan 430079, Hubei, Peoples R China.;[Cao, Yu] Cent China Normal Univ, Key Lab Pesticide & Chem Biol, Minist Educ, Coll Chem, Wuhan 430079, Hubei, Peoples R China.
通讯机构：
[Liu, Yanli] C;Cent China Normal Univ, Hubei Key Lab Genet Regulat & Integrat Biol, Sch Life Sci, Wuhan 430079, Hubei, Peoples R China.
关键词：
AL protein;PHD domain;Histone binding
摘要：
Alfin1-like (AL) is a family of proteins homologous to the alfalfa Alfin1 in plant and bears an Alfin domain and a PHD domain at their N- and C-terminus, respectively. There are 7 AL proteins in Arabidopsis, and the PHD domains of most AL proteins are reported to bind to histone H3K4me3. Here we reported gene cloning, protein expression and purification of the PHD domains of all the AL family proteins in Arabidopsis. We then systematically characterized their histone binding abilities by quantitative isothermal titration calorimetry and fluorescence polarization binding assays. Our binding results indicate that all the PHD domains of the AL proteins bind to the histone H3K4me3 peptide with varying methylation state preference and binding affinities. Our study presented here provides the foundation for further studies of the peptide state-specific recognition by PHD domains of AL proteins.
