Long noncoding RNA lncMREF promotes myogenic differentiation and muscle regeneration by interacting with the Smarca5/p300 complex

Long noncoding RNAs (lncRNAs) play important roles in the spatial and temporal regulation of muscle development and regeneration. Nevertheless, the determination of their biological functions and mechanisms underlying muscle regeneration remains challenging. Here, we identified a lncRNA named lncMREF (lncRNA muscle regeneration enhancement factor) as a conserved positive regulator of muscle regeneration among mice, pigs and humans. Functional studies demonstrated that lncMREF, which is mainly expressed in differentiated muscle satellite cells, promotes myogenic differentiation and muscle regeneration. Mechanistically, lncMREF interacts with Smarca5 to promote chromatin accessibility when muscle satellite cells are activated and start to differentiate, thereby facilitating genomic binding of p300/CBP/H3K27ac to upregulate the expression of myogenic regulators, such as MyoD and cell differentiation. Our results unravel a novel temporal-specific epigenetic regulation during muscle regeneration and reveal that lncMREF/Smarca5-mediated epigenetic programming is responsible for muscle cell differentiation, which provides new insights into the regulatory mechanism of muscle regeneration.     

The Heterogeneity in the Landscape of Gene Dominance in Maize is Accompanied by Unique Chromatin Environments

Subgenome dominance after whole-genome duplication (WGD) has been observed in many plant species. However, the degree to which the chromatin environment affects this bias has not been explored. Here, we compared the dominant subgenome (maize1) and the recessive subgenome (maize2) with respect to patterns of sequence substitutions, genes expression, transposable element accumulation, small interfering RNAs, DNA methylation, histone modifications, and accessible chromatin regions (ACRs). Our data show that the degree of bias between subgenomes for all the measured variables does not vary significantly when both of the WGD genes are located in pericentromeric regions. Our data further indicate that the location of maize1 genes in chromosomal arms is pivotal for maize1 to maintain its dominance, but location has a less effect on maize2 homoeologs. In addition to homoeologous genes, we compared ACRs, which often harbor cis-regulatory elements, between the two subgenomes and demonstrate that maize1 ACRs have a higher level of chromatin accessibility, a lower level of sequence substitution, and are enriched in chromosomal arms. Furthermore, we find that a loss of maize1 ACRs near their nearby genes is associated with a reduction in purifying selection and expression of maize1 genes relative to their maize2 homoeologs. Taken together, our data suggest that chromatin environment and cis-regulatory elements are important determinants shaping the divergence and evolution of duplicated genes.     

DNASE1L3 inhibits proliferation,invasion and metastasis of hepatocellular carcinoma by interacting with β‐catenin to promote its ubiquitin degradation pathway

As a member of the deoxyribonuclease 1 family, DNASE1L3 plays a significant role both inside and outside the cell. However, the role of DNASE1L3 in hepatocellular carcinoma (HCC) and its molecular basis remains to be further investigated. In this study, we report that DNASE1L3 is downregulated in clinical HCC samples and evaluate the relationship between its expression and HCC clinical features. In vivo and in vitro experiments showed that DNASE1L3 negatively regulates the proliferation, invasion and metastasis of HCC cells. Mechanistic studies showed that DNASE1L3 recruits components of the cytoplasmic β‐catenin destruction complex (GSK‐3β and Axin), promotes the ubiquitination degradation of β‐catenin, and inhibits its nuclear transfer, thus, decreasing c‐Myc, P21 and P27 level. Ultimately, cell cycle and EMT signals are restrained. In general, this study provides new insight into the mechanism for HCC and suggests that DNASE1L3 can become a considerable target for HCC.

Decreased expression of DNASE1L3 is associated with poor prognosis in patients with HCC DNASE1L3 inhibits the proliferation and cell cycle of HCC cells in vitro and promotes the invasion and metastasis of HCC cells DNASE1L3 inhibits the tumorigenicity and metastasis of HCC cells in vivo DNASE1L3 interacts with β‐catenin and promotes its binding to the β‐catenin destroying complex DNASE1L3 interacts with P21 and stabilizes P21 by mediating the deubiquitin activity     

An insight into planarian regeneration

BackgroundPlanarian has attracted increasing attentions in the regeneration field for its usefulness as an important biological model organism attributing to its strong regeneration ability. Both the complexity of multiple regulatory networks and their coordinate functions contribute to the maintenance of normal cellular homeostasis and the process of regeneration in planarian. The polarity, size, location and number of regeneration tissues are regulated by diverse mechanisms. In this review we summarize the recent advances about the importance genetic and molecular mechanisms for regeneration control on various tissues in planarian.MethodsA comprehensive literature search of original articles published in recent years was performed in regards to the molecular mechanism of each cell types during the planarian regeneration, including neoblast, nerve system, eye spot, excretory system and epidermal.ResultsAvailable molecular mechanisms gave us an overview of regeneration process in every tissue. The sense of injuries and initiation of regeneration is regulated by diverse genes like follistatin and ERK signaling. The Neoblasts differentiate into tissue progenitors under the regulation of genes such as egfr‐3. The regeneration polarity is controlled by Wnt pathway, BMP pathway and bioelectric signals. The neoblast within the blastema differentiate into desired cell types and regenerate the missing tissues. Those tissue specific genes regulate the tissue progenitor cells to differentiate into desired cell types to complete the regeneration process.ConclusionAll tissue types in planarian participate in the regeneration process regulated by distinct molecular factors and cellular signaling pathways. The neoblasts play vital roles in tissue regeneration and morphology maintenance. These studies provide new insights into the molecular mechanisms for regulating planarian regeneration.

Genetic and molecular mechanisms for regeneration control on various tissues in planarian.     

Identification of core genes in prefrontal cortex and hippocampus of Alzheimer's disease based on mRNA‐miRNA network

Alzheimer''s disease (AD) is a neurodegenerative disorder with cognitive impairment and abnormal mental behaviour. There is currently no effective cure. The development of early diagnostic markers and the mining of potential therapeutic targets are one of the important strategies. This study aimed to explore potential biomarkers or therapeutic targets related to AD in the hippocampus and prefrontal cortex, two brain regions highly related to AD. Differentially expressed genes and miRNAs between AD patients and healthy controls were obtained from the Gene Expression Omnibus database. The mRNA‐miRNA network was constructed and key genes involved in AD were screened out by protein–protein interaction analysis, and were subsequently verified by independent datasets and qPCR in an AD mouse model. Our findings showed that six hub genes including CALN1, TRPM7, ATR, SOCS3, MOB3A and OGDH were believed to be involved in the pathogenesis of AD. Western blot analysis further determined that CALN1, ATR and OGDH were the possible biomarkers and therapeutic targets for AD. In addition, 6 possible miRNAs biomarkers have also been verified by qPCR on AD animal models. Our findings may benefit clinical diagnosis and early prevention of AD.     

温度诱导Targetron系统用于大肠杆菌高效基因失活

构建基于Te I3c/4c嗜热二型内含子的温度诱导Targetron基因失活系统(Thermotargetron),并应用于中温微生物基因编辑。在大肠杆菌HMS174(DE3)基因组中,选择Subunitofflagellum基因(fliC)和C4dicarboxylate orotate:H+symporter基因(dctA)为靶基因。根据Te I3c/4c DNA识别规则,在fliC和dctA基因中选择fliC489a、fliC828s、fliC1038s和dctA2a位点为基因打靶位点。使用重叠延伸PCR方法,基于pHK-TT1A质粒构建打靶载体。打靶载体转化HMS174菌株,对数期转化子培养液48℃热激1h后涂布于氯霉素抗性LB平板上。使用菌落PCR和DNA测序检测突变株并计算基因失活效率。获得突变株后,通过琼脂穿刺和碳源代谢实验,鉴定ΔfliC、ΔdctA突变株表型变化。菌落PCR测序结果表明,Te I3c/4c插入到fliC和dctA基因设计位点,且打靶效率高达100%。突变株表型验证实验表明,ΔfliC突变株运动能力显著下降,ΔdctA突变株苹果酸代谢能力缺失。综上所述,...     

A baseline epidemiological study of the co-infection of enteric protozoans with human immunodeficiency virus among men who have sex with men from Northeast China

BackgroundHuman immunodeficiency virus (HIV) and enteric parasite co-infection not only aggravates the clinical symptoms of parasites but also accelerates acquired immunodeficiency syndrome (AIDS) progression. However, co-infection research on men who have sex with men (MSM), the predominant high-risk population of HIV/AIDS in China, is still limited. In this study, we investigated the epidemiology of enteric parasites, risk factors, and associations with clinical significance in an MSM HIV/AIDS population in Heilongjiang Province, northeast China.MethodsWe recruited 308 MSMs HIV/AIDS patients and 199 HIV-negative individuals in two designated AIDS hospitals in Heilongjiang between April 2016 and July 2017. Fresh stool samples were collected. DNA extraction, molecular identification, and genotyping of Cryptosporidium species, Entamoeba histolytica, Cyclospora cayetanensis, Enterocytozoon bieneusi, and Blastocystis hominis were performed. Fourteen diarrhea-related pathogens were examined to exclude the influence of other bacterial pathogens on diarrhea incidence.Results31.5% of MSM HIV/AIDS participants were infected with at least one parasite species, a significantly higher proportion than that found in the HIV-negative individuals (2.5%). E. bieneusi presented the highest prevalence, followed by B. hominis, E. histolytica, Cryptosporidium spp., and C. cayetanensis. Warm seasons were the risk factor for parasitic infections in this population [odds ratio (OR) = 2.6, 95% CI: 1.47–4.57]. In addition, these individuals showed a higher proportion (35.8%) of present diarrhea (PD) compared with men who have sex with women (MSW) with HIV/AIDS (16.7%). The infection proportions of both Cryptosporidium spp. and E. histolytica were significantly higher in the PD. E. bieneusi infection was more prevalent in the historic diarrhea (HD) group. CD4⁺ T cell counts in the MSM patients with the above three parasites were significantly lower. New species and genotypes were found, and MSM patients had a wider range of species or genotypes.ConclusionsEnteric parasitic infection was prevalent in the MSM HIV/AIDS population, especially in patients with present diarrhea during warm seasons. E. histolytica and B. hominis should also be considered high-risk parasites for opportunistic infections in AIDS patients in addition to Cryptosporidium spp.     

“互联网+”教育在生物化学课程中应用的分析与思考

在"互联网+"教育的大力推广之下,微课、慕课、翻转课堂、手机课堂等多种教学模式应运而生。通过在生物化学课程中运用"互联网+"教学模式:教师课前准备并向学生发布相关学习资源、学生预习情况和预习效果的评价、学生成绩量化标准,取得了初步的成效。本文从我国"互联网+生物化学"教育现状、"互联网+"教育在生物化学课程中的应用以及生物化学课程与"互联网+"教育结合的未来发展等三个方面进行了阐述。