ABSTRACT
BACKGROUND: The nuclear lamina links the nuclear membrane to chromosomes and plays a crucial role in regulating chromatin states and gene expression. However, current knowledge of nuclear lamina in plants is limited compared to animals and humans. RESULTS: This study mainly focused on elucidating the mechanism through which the putative nuclear lamina component protein KAKU4 regulates chromatin states and gene expression in Arabidopsis leaves. Thus, we constructed a network using the association proteins of lamin-like proteins, revealing that KAKU4 is strongly associated with chromatin or epigenetic modifiers. Then, we conducted ChIP-seq technology to generate global epigenomic profiles of H3K4me3, H3K27me3, and H3K9me2 in Arabidopsis leaves for mutant (kaku4-2) and wild-type (WT) plants alongside RNA-seq method to generate gene expression profiles. The comprehensive chromatin state-based analyses indicate that the knockdown of KAKU4 has the strongest effect on H3K27me3, followed by H3K9me2, and the least impact on H3K4me3, leading to significant changes in chromatin states in the Arabidopsis genome. We discovered that the knockdown of the KAKU4 gene caused a transition between two types of repressive epigenetics marks, H3K9me2 and H3K27me3, in some specific PLAD regions. The combination analyses of epigenomic and transcriptomic data between the kaku4-2 mutant and WT suggested that KAKU4 may regulate key biological processes, such as programmed cell death and hormone signaling pathways, by affecting H3K27me3 modification in Arabidopsis leaves. CONCLUSIONS: In summary, our results indicated that KAKU4 is directly and/or indirectly associated with chromatin/epigenetic modifiers and demonstrated the essential roles of KAKU4 in regulating chromatin states, transcriptional regulation, and diverse biological processes in Arabidopsis.
Subject(s)
Arabidopsis , Chromatin , Animals , Humans , Chromatin/genetics , Histones , Arabidopsis/genetics , Nuclear Lamina , Gene Expression Regulation , Nuclear ProteinsABSTRACT
Lamins are the major components of the nuclear lamina, which regulate chromatin structure and gene expression. KAKU4 is a unique nuclear lamina component in the nuclear periphery, modulates nuclear shape and size in Arabidopsis. The knowledge about the regulatory role of KAKU4 in leaf development remains limited. Here we found that knockdown of KAKU4 resulted in an accelerated leaf senescence phenotype, with elevated levels of H2O2 and hormones, particularly SA, JA, and ABA. Our results demonstrated the importance of KAKU4 as a potential negative regulator in age-triggered leaf senescence in Arabidopsis. Furthermore, we conducted combination analyses of transcriptomic and epigenomic data for the kaku4 mutant and WT leaves. The knockdown of KAKU4 lowered H3K27me3 deposition in the up-regulated genes associated with hormone pathways, programmed cell death, and leaf senescence, including SARD1, SAG113/HAI1, PR2, and so forth. In addition, we found the functional crosstalks between KAKU4 and its associated proteins (CRWN1/4, PNET2, GBPL3, etc.) through comparing multiple transcriptome datasets. Overall, our results indicated that KAKU4 may inhibit the expression of a series of genes related to hormone signals and H2O2 metabolism by affecting the deposition of H3K27me3, thereby suppressing leaf senescence.
Subject(s)
Arabidopsis , Arabidopsis/genetics , Histones , Hydrogen Peroxide , Plant Senescence , HormonesABSTRACT
Bacterial diseases are one of the most common issues that result in crop loss worldwide, and the increasing usage of chemical pesticides has caused the occurrence of resistance in pathogenic bacteria and environmental pollution problems. Nanomaterial mediated gene silencing is starting to display powerful efficiency and environmental friendliness for improving plant disease resistance. However, the internalization of nanomaterials and the physiological mechanisms behind nano-improved plant disease resistance are still rarely understood. We engineered the polyethyleneimine (PEI) functionalized gold nanoparticles (PEI-AuNPs) with fluorescent properties and ROS scavenging activity to act as siRNA delivery platforms. Besides the loading, protection, and delivery of nucleic acid molecules in plant mature leaf cells by PEI-AuNPs, its fluorescent property further enables the traceability of the distribution of the loaded nucleic acid molecules in cells. Additionally, the PEI-AuNPs-based RNAi delivery system successfully mediated the silencing of defense-regulated gene AtWRKY1. Compared to control plants, the silenced plants performed better resistance to Pseudomonas syringae, showing a reduced bacterial number, decreased ROS content, increased antioxidant enzyme activities, and improved chlorophyll fluorescence performance. Our results showed the advantages of AuNP-based RNAi technology in improving plant disease resistance, as well as the potential of plant nanobiotechnology to protect agricultural production.
Subject(s)
Disease Resistance , Gold , Metal Nanoparticles , Plant Diseases , Pseudomonas syringae , RNA, Small Interfering , Reactive Oxygen Species , Gold/chemistry , Metal Nanoparticles/chemistry , Reactive Oxygen Species/metabolism , Plant Diseases/microbiology , Polyethyleneimine/chemistry , Gene Silencing , Arabidopsis/geneticsABSTRACT
With the accumulation of massive data sets from high-throughput experiments and the rapid emergence of new types of omics data, gene sets have become more diverse and essential for the refinement of gene annotation at multidimensional levels. Accordingly, we collected and defined 236 007 gene sets across different categories for 44 plant species in the Plant Gene Set Annotation Database (PlantGSAD). These gene sets were divided into nine main categories covering many functional subcategories, such as trait ontology, co-expression modules, chromatin states, and liquid-liquid phase separation. The annotations from the collected gene sets covered all of the genes in the Brassicaceae species Arabidopsis and Poaceae species Oryza sativa. Several GSEA tools are implemented in PlantGSAD to improve the efficiency of the analysis, including custom SEA for a flexible strategy based on customized annotations, SEACOMPARE for the cross-comparison of SEA results, and integrated visualization features for ontological analysis that intuitively reflects their parent-child relationships. In summary, PlantGSAD provides numerous gene sets for multiple plant species and highly efficient analysis tools. We believe that PlantGSAD will become a multifunctional analysis platform that can be used to predict and elucidate the functions and mechanisms of genes of interest. PlantGSAD is publicly available at http://systemsbiology.cau.edu.cn/PlantGSEAv2/.
Subject(s)
Databases, Genetic , Molecular Sequence Annotation , Plants/classification , Software , Chromatin/genetics , Plants/geneticsABSTRACT
Plant Knotted1-like homeobox (KNOX) genes encode homeodomain-containing transcription factors. In rice (Oryza sativa L.), little is known about the downstream target genes of KNOX Class II subfamily proteins. Here we generated chromatin immunoprecipitation (ChIP)-sequencing datasets for HOS59, a member of the rice KNOX Class II subfamily, and characterized the genome-wide binding sites of HOS59. We conducted trait ontology (TO) analysis of 9705 identified downstream target genes, and found that multiple TO terms are related to plant structure morphology and stress traits. ChIP-quantitative PCR (qPCR) was conducted to validate some key target genes. Meanwhile, our IP-MS datasets showed that HOS59 was closely associated with BELL family proteins, some grain size regulators (OsSPL13, OsSPL16, OsSPL18, SLG, etc.), and some epigenetic modification factors such as OsAGO4α and OsAGO4ß, proteins involved in small interfering RNA-mediated gene silencing. Furthermore, we employed CRISPR/Cas9 editing and transgenic approaches to generate hos59 mutants and overexpression lines, respectively. Compared with wild-type plants, the hos59 mutants have longer grains and increased glume cell length, a loose plant architecture, and drooping leaves, while the overexpression lines showed smaller grain size, erect leaves, and lower plant height. The qRT-PCR results showed that mutation of the HOS59 gene led to upregulation of some grain size-related genes such as OsSPL13, OsSPL18, and PGL2. In summary, our results indicate that HOS59 may be a repressor of the downstream target genes, negatively regulating glume cell length, rice grain size, plant architecture, etc. The identified downstream target genes and possible interaction proteins of HOS59 improve our understanding of the KNOX regulatory networks.
Subject(s)
Oryza , Edible Grain/genetics , Edible Grain/metabolism , Gene Expression Regulation, Plant/genetics , Oryza/genetics , Oryza/metabolism , Plant Leaves/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism , Transcription Factors/genetics , Transcription Factors/metabolismABSTRACT
Insulators characterized in Drosophila and mammals have been shown to play a key role in the restriction of promiscuous enhancer-promoter interactions, as well as reshaping the topological landscape of chromosomes. Yet the role of insulators in plants remains poorly understood, in large part because of a lack of well-characterized insulators and binding factor(s). In this study, we isolated a 1.2-kb RS2-9 insulator from the Oryza sativa (rice) genome that can, when interposed between an enhancer and promoter, efficiently block the activation function of both constitutive and floral organ-specific enhancers in transgenic Arabidopsis and Nicotiana tabacum (tobacco). In the rice genome, the genes flanking RS2-9 exhibit an absence of mutual transcriptional interactions, as well as a lack of histone modification spread. We further determined that O. sativa Homeobox 1 (OSH1) bound two regions of RS2-9, as well as over 50 000 additional sites in the rice genome, the majority of which resided in intergenic regions. Mutation of one of the two OSH1-binding sites in RS2-9 impaired insulation activity by up to 60%, whereas the mutation of both binding sites virtually abolished insulator function. We also demonstrated that OSH1 binding sites were associated with 72% of the boundaries of topologically associated domains (TADs) identified in the rice genome, which is comparable to the 77% of TAD boundaries bound by the insulator CCCTC-binding factor (CTCF) in mammals. Taken together, our findings indicate that OSH1-RS2-9 acts as a true insulator in plants, and highlight a potential role for OSH1 in gene insulation and topological organization in plant genomes.
Subject(s)
Enhancer Elements, Genetic/physiology , Oryza/genetics , Oryza/metabolism , Promoter Regions, Genetic/physiology , Repressor Proteins/genetics , Repressor Proteins/metabolism , Crops, Agricultural/genetics , Crops, Agricultural/metabolism , Gene Expression Regulation, Plant , Genes, Plant , Transcription Factors/physiologyABSTRACT
This paper is concerned with the distributed generalized Nash equilibrium (GNE) tracking problem of noncooperative games in dynamic environments, where the cost function and/or the coupled constraint function are time-varying and revealed to each agent after it makes a decision. We first consider the case without coupled constraints and propose a distributed inertial online game (D-IOG) algorithm based on the mirror descent method. The proposed algorithm is capable of tracking Nash equilibrium (NE) through a time-varying communication graph and has the potential of achieving a low average regret. With an appropriate non-increasing stepsize sequence and an inertial parameter, the regrets can grow sublinearly if the deviation of the NE sequence grows sublinearly. Second, the time-varying coupled constraints are further investigated, and a modified D-IOG algorithm for tracking GNE is proposed based on the primal-dual and mirror descent methods. Then, the upper bounds of regrets and constraint violation are derived. Moreover, inertia and two information transmission modes are discussed. Finally, two simulation examples are provided to illustrate the effectiveness of the D-IOG algorithms.
ABSTRACT
Arabidopsis PHO1;H10 is a member of the PHO1 gene family with SPX and EXS domains, and its functions remain largely unknown. As shown in PCSD database, the upstream region of PHO1;H10 gene is in the active chromatin states, with high DHS accessibility and binding sites of multiple transcription factors, especially ABI5, SPCH and HY5. Co-expression network and data-mining analyses showed PHO1;H10 and co-expression genes were with activation under high light stress. We did wet-lab experiments, and found that the detached leaves of PHO1;H10 overexpression lines accumulated more anthocyanin than those of WT and mutant under high light treatment. RNA-seq results showed overexpression of PHO1;H10 up-regulated many anthocyanin biosynthetic genes. The GSEA analysis result showed that the functional module related to anthocyanin pathway was significantly enriched. In summary, we conducted systems biology approach, combining dry- and wet-lab analyses, and discovered that PHO1;H10 might play an essential role during modulating high light-induced anthocyanin accumulation in the Arabidopsis detached leaves.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/metabolism , Anthocyanins , Systems Biology , Plant Leaves/genetics , Plant Leaves/metabolism , Gene Expression Regulation, PlantABSTRACT
Subtilases (SBTs), which belong to the serine peptidases, control plant development by regulating cell wall properties and the activity of extracellular signaling molecules, and affect all stages of the life cycle, such as seed development and germination, and responses to biotic and abiotic environments. In this study, 146 Gossypium hirsutum, 138 Gossypium barbadense, 89 Gossypium arboreum and 84 Gossypium raimondii SBTs were identified and divided into six subfamilies. Cotton SBTs are unevenly distributed on chromosomes. Synteny analysis showed that the members of SBT1 and SBT4 were expanded in cotton compared to Arabidopsis thaliana. Co-expression network analysis showed that six Gossypium arboreum SBT gene family members were in a network, among which five SBT1 genes and their Gossypium hirsutum and Arabidopsis thaliana direct homologues were down-regulated by salt treatment, indicating that the co-expression network might share conserved functions. Through co-expression network and annotation analysis, these SBTs may be involved in the biological processes of auxin transport, ABA signal transduction, cell wall repair and root tissue development. In summary, this study provides valuable information for the study of SBT genes in cotton and excavates SBT genes in response to salt stress, which provides ideas for cotton breeding for salinity resistance.
Subject(s)
Arabidopsis , Gossypium , Gossypium/metabolism , Multigene Family , Arabidopsis/genetics , Plant Breeding , Genome, Plant , Phylogeny , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Stress, Physiological/geneticsABSTRACT
Insulators in vertebrates play a role in genome architecture and orchestrate temporo-spatial enhancer-promoter interactions. In plants, insulators and their associated binding factors have not been documented as of yet, largely as a result of a lack of characterized insulators. In this study, we took a comprehensive strategy to identify and validate the enhancer-blocking insulator CW198. We show that a 1.08-kb CW198 fragment from Arabidopsis can, when interposed between an enhancer and a promoter, efficiently abrogate the activation function of both constitutive and floral organ-specific enhancers in transgenic Arabidopsis and tobacco plants. In plants, both transcriptional crosstalk and spreading of histone modifications were rarely detectable across CW198, which resembles the insulation property observed across the CTCF insulator in the mammalian genome. Taken together, our findings support that CW198 acts as an enhancer-blocking insulator in both Arabidopsis and tobacco. The significance of the present findings and their relevance to the mitigation of mutual interference between enhancers and promoters, as well as multiple promoters in transgenes, is discussed.
Subject(s)
Arabidopsis , Insulator Elements , Animals , Insulator Elements/genetics , Enhancer Elements, Genetic/genetics , Arabidopsis/genetics , Promoter Regions, Genetic/genetics , Transgenes/genetics , Nicotiana/genetics , Mammals/geneticsABSTRACT
BACKGROUND: The early clinical diagnosis of spinal infections in elderly patients with recessive or atypical symptoms is difficult. Klebsiella aerogenes is a common opportunistic bacterium that can infect the respiratory tract, urinary tract, and even the central nervous system. However, whether it can infect the lumbar spine has not been previously described. CASE PRESENTATION: In this paper, we report the case of a 69-year-old female patient with osteoporosis who was initially diagnosed with hemolytic anemia. Later, she was diagnosed with K. aerogenes infection of the lumbar spine based on imaging combined with blood culture and metagenome next-generation sequencing (mNGS) detection. After precise medication, the lumbar degeneration was improved. CONCLUSIONS: Bacterial infection should therefore be considered in cases of lumbar degenerative disease in middle-aged and elderly patients.
Subject(s)
Enterobacter aerogenes , Klebsiella Infections , Aged , Female , High-Throughput Nucleotide Sequencing/methods , Humans , Klebsiella Infections/diagnosis , Lumbar Vertebrae , Metagenome , Middle AgedABSTRACT
DIRIGENT (DIR) genes play important roles in regulating plant growth and development and have been studied in many plant species. However, information on DIR genes in soybean is limited. Here, we identified and characterized 54 GmDIRs and studied the characteristics of GmDIRs. Most of the GmDIRs contained a classical gene structure, one exon; 26 conserved motifs were found among these GmDIRs. The GmDIRs were grouped into four subfamilies, DIR-a, DIR-b, DIR-e and DIR-f, based on a phylogenetic analysis, and 24 duplicated gene pairs were identified. Differences in the cis-acting elements in the GmDIR promoter regions might result in distinct expression patterns of GmDIRs in different tissues. In addition, GmDIR27 had a close relationship with the pod dehiscence gene GmPdh1, and overexpression of GmDIR27 increased pod dehiscence by affecting several pod dehiscence-related gene expressions. Generally, our results provide essential information that aids future efforts to functionally characterize soybean GmDIR genes.
Subject(s)
Gene Expression Regulation, Developmental , Genes, Plant , Glycine max/genetics , Seeds/genetics , Gene Duplication , Gene Expression Regulation, Plant , Seeds/growth & development , Glycine max/growth & development , Glycine max/metabolismABSTRACT
Daytime napping is common in many regions around the world and has been an important part of people's daily life. Daytime napping has attracted increasing attention in recent years. Thus, we conducted a meta-analysis to evaluate the relationship between daytime napping and stroke, and help reduce the risk of stroke by improving living habits. The Embase, PubMed, Web of Science and PsycINFO databases were searched for cohort studies published before October 2020 and eight eligible studies with 524,408 participants and 5,875 stroke cases were included in the final analysis. The pooled relative risk (RR) of stroke was 1.47 (95% confidence interval [CI]: 1.24-1.74; p < .001) with significant heterogeneity (I2 = 58%, p for heterogeneity = 0.02). However, the heterogeneity decreased when the study in which adjusting for sleep duration and stratifying the results based on sleep duration was not performed was excluded (RR: 1.38; 95% CI: 1.19-1.60, I2 = 44%, p for heterogeneity = 0.10). In dose-response analysis, the linear trend indicated that for every 10-min increase in daytime napping, the risk of stroke increased by 3%. Further well-designed large studies are needed to explore the effects of daytime napping on stroke and the underlying biological mechanisms.
Subject(s)
Sleep , Stroke , Cohort Studies , Habits , Humans , Risk Factors , Stroke/epidemiologyABSTRACT
A total of 115 convalescent inpatients with COVID-19 were enrolled. According to the results of scans of lung lesions via computed tomography (CT), the patients were divided into mild, moderate, and severe groups. The clinical data of the patients were collected, including age, gender, finger pulse oxygen pressure, ventricular rate, body temperature, etc. The correlation between the clinical indicators and the lesions of high-resolution CT (HRCT) and bronchiectasis was analyzed. Among the 115 patients, 82 had no bronchiectasis and 33 had bronchiectasis. The bronchodilation-prone layers mainly included the left and right lower lobe of the lung. The probability of branching in the inflamed area was greater than that in the noninflamed area in patients with COVID-19. There were significant differences in gender, CT lesion range, and number of incidents of bronchiectasis between noninflamed and inflamed areas (P < 0.05). Moreover, there were significant differences in age, total proportion of CT lesions, volume of CT lesions, and total number of patients with bronchiectasis among the three groups (P < 0.05). CT lesion range was positively correlated with the total number of patients with bronchiectasis and patient age (respectively, r = 0.186, P < 0.05; r = 0.029, P < 0.05). The lesion range in HRCT images of lungs in patients with COVID-19 is correlated with bronchodilation. The larger the lesion, the higher the probability of bronchiectasis and the more incidents of bronchiectasis.
Subject(s)
Bronchiectasis/pathology , Bronchiectasis/virology , COVID-19/pathology , COVID-19/virology , Lung/pathology , Lung/virology , Pneumonia/pathology , Pneumonia/virology , Adult , Female , Humans , Male , Retrospective Studies , SARS-CoV-2/pathogenicity , Severity of Illness Index , Tomography, X-Ray Computed/methodsABSTRACT
INTRODUCTION: Globus pallidus internus (GPi) deep brain stimulation (DBS) combined with anterior capsulotomy offers a promising treatment option for severe medication-refractory cases of Tourette's syndrome (TS) with psychiatric comorbidities. Several patients treated with this combined surgery experienced sustained relief after discontinuation of stimulation over the course of treatment. METHODS: Retrospectively, the medical records and clinical outcomes were reviewed of 8 patients (6 men; 2 women with mean age of 20.3 years) who had undergone bilateral GPi-DBS combined with anterior capsulotomy for medically intractable TS and psychiatric comorbidities. All patients had experienced an accidental interruption or intentional withdrawal of pallidal stimulation during treatment. RESULTS: The widespread clinical benefits achieved during the combined treatment were fully maintained after intentional or accidental DBS discontinuation. The improvement in overall tic symptoms achieved was on average 78% at the follow-up or close to the DBS discontinuation, while it was 83% at last follow-up (LFU). At LFU, most patients had functionally recovered; exhibited only mild tics; displayed minor or no obsessive-compulsive disorder symptoms, anxiety, or depression; and experienced a much better quality of life. CONCLUSION: Bilateral GPi-DBS combined with anterior capsulotomy appears to result in marked and sustained improvements in TS symptoms and psychiatric comorbidities, which are fully maintained over time, even without pallidal stimulation.
Subject(s)
Deep Brain Stimulation , Tourette Syndrome , Adult , Female , Globus Pallidus , Humans , Male , Quality of Life , Retrospective Studies , Tourette Syndrome/surgery , Young AdultABSTRACT
Flowering time has a critically important effect on the reproduction of plants, and many components involved in flowering-time regulation have been identified in multiple plant species. However, studies of the flowering-time genes in mungbean (Vigna radiata) have been limited. Here, we characterized a novel mungbean gene, VrLELP, involved in flowering-time regulation in transgenic Arabidopsis. Subcellular localization analysis revealed that VrLELP was localized in the membrane, cytoplasm and nucleus and the nucleus and membrane contained higher signal than cytoplasm, similar to the empty vector control. The expression of VrLELP was higher in leaves and pods and lower in nodule roots relative to other tissues. The expression of VrLELP varied during flower development. The expression of VrLELP also varied during the day, reaching a peak after 12 h of illumination under long-day conditions. In contrast, under short-day conditions, the abundance of VrLELP transcripts changed little throughout the day. In addition, VrLELP delayed flowering time in transgenic Arabidopsis plants by suppressing the expression of the flowering-time genes CO and FT under short-day conditions. However, VrLELP did not affect flowering time under long-day conditions in Arabidopsis. Our study provides essential information for future studies of the molecular mechanisms of the flowering-time regulation system in mungbean.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Flowers/genetics , Flowers/metabolism , Gene Expression Regulation, Plant , Photoperiod , Plants, Genetically Modified/metabolism , ReproductionABSTRACT
Lonicera japonica Thunb., a traditional Chinese herb, has been used for treating human diseases for thousands of years. Recently, the genome of L. japonica has been decoded, providing valuable information for research into gene function. However, no comprehensive database for gene functional analysis and mining is available for L. japonica. We therefore constructed LjaFGD (www.gzybioinformatics.cn/LjaFGD and bioinformatics.cau.edu.cn/LjaFGD), a database for analyzing and comparing gene function in L. japonica. We constructed a gene co-expression network based on 77 RNA-seq samples, and then annotated genes of L. japonica by alignment against protein sequences from public databases. We also introduced several tools for gene functional analysis, including Blast, motif analysis, gene set enrichment analysis, heatmap analysis, and JBrowse. Our co-expression network revealed that MYB and WRKY transcription factor family genes were co-expressed with genes encoding key enzymes in the biosynthesis of chlorogenic acid and luteolin in L. japonica. We used flavonol synthase 1 (LjFLS1) as an example to show the reliability and applicability of our database. LjaFGD and its various associated tools will provide researchers with an accessible platform for retrieving functional information on L. japonica genes to further biological discovery.
Subject(s)
Databases, Genetic , Genomics , Lonicera/genetics , Base Sequence , Biosynthetic Pathways , Chlorogenic Acid/metabolism , Gene Expression Regulation, Plant , Gene Regulatory Networks , Luteolin/biosynthesis , Molecular Sequence AnnotationABSTRACT
OBJECTIVE: To evaluate the short-term and long-term clinical effectiveness and safety of subthalamic nucleus deep brain stimulation (STN-DBS) for medically intractable pediatric isolated dystonia. METHODS: Using a longitudinal retrospective design, we assessed the clinical outcomes of nine patients who underwent STN-DBS for treatment-refractory pediatric isolated dystonia one decade ago (mean age at surgery: 15.9 ± 4.5 years). The primary clinical outcome used was assessed by retrospective video analyses of patients' dystonia symptoms using the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). Clinical assessments were performed at baseline, 1-year follow-up (1-yr FU), and 10-year follow-up (10-yr FU). Adverse side effects, including surgery-related, device-related, and stimulation-related effects, were also documented. RESULTS: After STN-DBS surgery, the mean improvement in the BFMDRS motor score was 77.1 ± 26.6% at 1-yr FU and 90.4 ± 10.4% at 10-yr FU. Similarly, the mean BFMDRS disability score was improved by 69.5 ± 13.6% at 1-yr FU and by 86.5 ± 13.9% at 10-yr FU. The clinical improvements gained at 10-yr FU were significantly larger than those observed at 1-yr FU. Negative correlations were found between the duration of disease to age at surgery ratio (DD/AS) and the improvements in the BFMDRS motor score and total score at 1-yr FU and 10-yr FU. CONCLUSION: To our knowledge, this study provides the first clinical evidence for the short- and long-term effectiveness and safety of STN-DBS for pediatric isolated dystonia. Additionally, putative evidence is provided that earlier STN-DBS intervention in patients with refractory pediatric isolated dystonia may improve short- and long-term clinical outcomes.
Subject(s)
Deep Brain Stimulation/methods , Dystonia/therapy , Subthalamic Nucleus , Adolescent , Child , Dystonia/physiopathology , Female , Humans , Longitudinal Studies , Male , Retrospective Studies , Severity of Illness Index , Treatment Outcome , Young AdultABSTRACT
Genome-wide maps of chromatin states have become a powerful representation of genome annotation and regulatory activity. We collected public and in-house plant epigenomic data sets and applied a Hidden Markov Model to define chromatin states, which included 290 553 (36 chromatin states), 831 235 (38 chromatin states) and 3 936 844 (26 chromatin states) segments across the whole genome of Arabidopsis thaliana, Oryza sativa and Zea mays, respectively. We constructed a Plant Chromatin State Database (PCSD, http://systemsbiology.cau.edu.cn/chromstates) to integrate detailed information about chromatin states, including the features and distribution of states, segments in states and related genes with segments. The self-organization mapping (SOM) results for these different chromatin signatures and UCSC Genome Browser for visualization were also integrated into the PCSD database. We further provided differential SOM maps between two epigenetic marks for chromatin state comparison and custom tools for new data analysis. The segments and related genes in SOM maps can be searched and used for motif and GO analysis, respectively. In addition, multi-species integration can be used to discover conserved features at the epigenomic level. In summary, our PCSD database integrated the identified chromatin states with epigenetic features and may be beneficial for communities to discover causal functions hidden in plant chromatin.
Subject(s)
Arabidopsis/genetics , Chromatin/genetics , Databases, Genetic , Oryza/genetics , Zea mays/genetics , Epigenesis, Genetic , Genome, Plant , Markov Chains , Software , User-Computer InterfaceABSTRACT
By putting heterologous genomic regulatory systems into contact, chromosome addition lines derived from interspecific or intergeneric crosses allow the investigation of transcriptional regulation in new genomic environments. Here, we report the transcriptional and epigenetic adaptation of stably inherited alien maize chromosomes in two oat-maize addition (OMA) lines. We found that the majority of maize genes displayed maize-specific transcription in the oat genomic environment. Nevertheless, a quarter of the expressed genes encoded by the two maize chromosomes were differentially expressed genes (DEGs). Notably, highly conserved orthologs were more severely differentially expressed in OMAs than less conserved orthologs. Additionally, syntenic genes and highly abundant genes were over-represented among DEGs. Gene suppression was more common than activation among the DEGs; however, the genes in the former maize pericentromere, which expanded to become the new centromere in OMAs, were activated. Histone modifications (H3K4me3, H3K9ac and H3K27me3) were consistent with these transcriptome results. We expect that cis regulation is responsible for unchanged expression in OMA versus maize; and trans regulation is the predominant mechanism behind DEGs. The genome interaction identified here reveals the important consequences of interspecific/intergeneric crosses and potential mechanisms of plant evolution when genomic environments interact.