Hippocampal CA3 Transcriptional Modules Associated with Granule Cell Alterations and Cognitive Impairment in Refractory Mesial Temporal Lobe Epilepsy Patients

Abstract In about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules’ main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.

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Hippocampal CA3 transcriptional modules associated with granule cell alterations and cognitive impairment in refractory mesial temporal lobe epilepsy patients

Scientific Reports ◽

10.1038/s41598-021-89802-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Silvia Yumi Bando ◽

Fernanda Bernardi Bertonha ◽

Luciana Ramalho Pimentel-Silva ◽

João Gabriel Mansano de Oliveira ◽

Marco Antonio Duarte Carneiro ◽

...

Keyword(s):

Granule Cell ◽

Functional Characterization ◽

Disease Onset ◽

Enrichment Analysis ◽

Mesial Temporal Lobe Epilepsy ◽

Hippocampal Ca3 ◽

High Gene ◽

Cell Alterations ◽

Highly Correlated ◽

Patients With Epilepsy

AbstractIn about a third of the patients with epilepsy the seizures are not drug-controlled. The current limitation of the antiepileptic drug therapy derives from an insufficient understanding of epilepsy pathophysiology. In order to overcome this situation, it is necessary to consider epilepsy as a disturbed network of interactions, instead of just looking for changes in single molecular components. Here, we studied CA3 transcriptional signatures and dentate gyrus histopathologic alterations in hippocampal explants surgically obtained from 57 RMTLE patients submitted to corticoamygdalohippocampectomy. By adopting a systems biology approach, integrating clinical, histopathological, and transcriptomic data (weighted gene co-expression network analysis), we were able to identify transcriptional modules highly correlated with age of disease onset, cognitive dysfunctions, and granule cell alterations. The enrichment analysis of transcriptional modules and the functional characterization of the highly connected genes in each trait-correlated module allowed us to unveil the modules’ main biological functions, paving the way for further investigations on their roles in RMTLE pathophysiology. Moreover, we found 15 genes with high gene significance values which have the potential to become novel biomarkers and/or therapeutic targets in RMTLE.

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Preferential Ribosome Loading on the Stress-Upregulated mRNA Pool Shapes the Selective Translation under Stress Conditions

Plants ◽

10.3390/plants10020304 ◽

2021 ◽

Vol 10 (2) ◽

pp. 304

Author(s):

Yan Chen ◽

Min Liu ◽

Zhicheng Dong

Keyword(s):

Enrichment Analysis ◽

Close Correlation ◽

Stress Conditions ◽

Functional Categories ◽

Molecular Pattern ◽

Mrna Pool ◽

Selective Translation ◽

Stress Responsive Genes ◽

Highly Correlated ◽

Response To Water

The reprogramming of gene expression is one of the key responses to environmental stimuli, whereas changes in mRNA do not necessarily bring forth corresponding changes of the protein, which seems partially due to the stress-induced selective translation. To address this issue, we systematically compared the transcriptome and translatome using self-produced and publicly available datasets to decipher how and to what extent the coordination and discordance between transcription and translation came to be in response to wounding (self-produced), dark to light transition, heat, hypoxia, Pi starvation and the pathogen-associated molecular pattern (elf18) in Arabidopsis. We found that changes in total mRNAs (transcriptome) and ribosome-protected fragments (translatome) are highly correlated upon dark to light transition or heat stress. However, this close correlation was generally lost under other four stresses analyzed in this study, especially during immune response, which suggests that transcription and translation are differentially coordinated under distinct stress conditions. Moreover, Gene Ontology (GO) enrichment analysis showed that typical stress responsive genes were upregulated at both transcriptional and translational levels, while non-stress-specific responsive genes were changed solely at either level or downregulated at both levels. Taking wounding responsive genes for example, typical stress responsive genes are generally involved in functional categories related to dealing with the deleterious effects caused by the imposed wounding stress, such as response to wounding, response to water deprivation and response to jasmonic acid, whereas non-stress-specific responsive genes are often enriched in functional categories like S-glycoside biosynthetic process, photosynthesis and DNA-templated transcription. Collectively, our results revealed the differential as well as targeted coordination between transcriptome and translatome in response to diverse stresses, thus suggesting a potential model wherein preferential ribosome loading onto the stress-upregulated mRNA pool could be a pacing factor for selective translation.

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Hippocampal CA3 Transcriptome Signature Correlates with Initial Precipitating Injury in Refractory Mesial Temporal Lobe Epilepsy

PLoS ONE ◽

10.1371/journal.pone.0026268 ◽

2011 ◽

Vol 6 (10) ◽

pp. e26268 ◽

Cited By ~ 15

Author(s):

Silvia Y. Bando ◽

Maryana C. Alegro ◽

Edson Amaro ◽

Alexandre V. Silva ◽

Luiz H. M. Castro ◽

...

Keyword(s):

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Mesial Temporal Lobe Epilepsy ◽

Hippocampal Ca3 ◽

Mesial Temporal Lobe ◽

Transcriptome Signature

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NPF genes excavation and their expression response to vernalization and nitrogen deficiency in allotetraploid rapeseed

10.21203/rs.3.rs-236072/v1 ◽

2021 ◽

Author(s):

Hongbo Chao ◽

Jianjie He ◽

Weiguo Zhao ◽

Hong Fu ◽

Yingpeng Hua ◽

...

Keyword(s):

Expression Patterns ◽

Functional Characterization ◽

Nitrogen Deficiency ◽

Enrichment Analysis ◽

Functional Differentiation ◽

Peptide Transporter ◽

Peptide Transporters ◽

Transporter Family ◽

Expression Response ◽

Metabolite Content

Abstract Background The NITRATE TRANSPORTER 1/PEPTIDE TRANSPORTER FAMILY (NPF) genes, initially characterized as nitrate or peptide transporters in plants, involve in the transport of a large variety of substrates including amino acids, nitrate, auxin (IAA), jasmonates (JAs), abscisic acid (ABA) and gibberellins (GAs) and glucosinolates. The evolution and expression diversification of genes determine their functional differentiation in polyploid species. Results Among 169 NPF genes excavated in Brassica napus, 97 B. napus NPF (BnaNPF) genes evolved from B. rapa, and 72 BnaNPF genes from B. olereaca. They unevenly distributed on B. napus genome and exhibited obvious synteny with NPF genes in Arabidopsis thaliana, B. rapa and B. olereaca. BnaNPF genes were identified to show diversified expression patterns in 90 different organs or tissues based on transcriptome profile data. Besides, they exhibited complex expression changes in the development process of leaves, silique wall and seeds, which indicated that the expression of BnaNPF genes maybe respond to altered phytohormone and secondary metabolite content through combining with promoter elements enrichment analysis. Furthermore, many BnaNPF genes were detected to response to vernalization with two different patterns and 20 BnaNPF genes responded to nitrate deficiency. Conclusion The evolution of BnaNPF genes and their expression pattern including response to vernalization and nitrogen deficiency were characterized and provide valuable information for further functional characterization in rapeseed.

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An angiogenesis-related long noncoding RNA signature correlates with prognosis in patients with hepatocellular carcinoma

Bioscience Reports ◽

10.1042/bsr20204442 ◽

2021 ◽

Vol 41 (4) ◽

Author(s):

Dengliang Lei ◽

Yue Chen ◽

Yang Zhou ◽

Gangli Hu ◽

Fang Luo

Keyword(s):

Hepatocellular Carcinoma ◽

Liver Cancer ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Enrichment Analysis ◽

Clinical Information ◽

Roc Curves ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Highly Correlated

Abstract Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide. Neovascularization is closely related to the malignancy of tumors. We constructed a signature of angiogenesis-related long noncoding RNA (lncRNA) to predict the prognosis of patients with HCC. The lncRNA expression matrix of 424 HCC patients was downloaded from The Cancer Genome Atlas (TCGA). First, gene set enrichment analysis (GSEA) was used to distinguish the differentially expressed genes of the angiogenesis genes in liver cancer and adjacent tissues. Next, a signature of angiogenesis-related lncRNAs was constructed using univariate and multivariate analyses, and receiver operating characteristic (ROC) curves were used to assess the accuracy. The signature and relevant clinical information were used to construct the nomogram. A 5-lncRNA signature was highly correlated with overall survival (OS) in HCC patients and performed well in evaluations using the C-index, areas under the curve, and calibration curves. In summary, the 5-lncRNA model can serve as an accurate signature to predict the prognosis of patients with liver cancer, but its mechanism of action must be further elucidated by experiments.

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Microbe-set enrichment analysis facilitates functional interpretation of microbiome profiling data

Scientific Reports ◽

10.1038/s41598-020-78511-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Yan Kou ◽

Xiaomin Xu ◽

Zhengnong Zhu ◽

Lei Dai ◽

Yan Tan

Keyword(s):

Statistical Significance ◽

Functional Characterization ◽

Enrichment Analysis ◽

Underlying Mechanism ◽

Functional Interpretation ◽

Useful Knowledge ◽

Knowledge Based ◽

Disease Associations ◽

Differential Abundance Analysis ◽

Microbiome Profiling

AbstractThe commensal microbiome is known to influence a variety of host phenotypes. Microbiome profiling followed by differential abundance analysis has been established as an effective approach to study the mechanisms of host-microbiome interactions. However, it is challenging to interpret the collective functions of the resultant microbe-sets due to the lack of well-organized functional characterization of commensal microbiome. We developed microbe-set enrichment analysis (MSEA) to enable the functional interpretation of microbe-sets by examining the statistical significance of their overlaps with annotated groups of microbes that share common attributes such as biological function or phylogenetic similarity. We then constructed microbe-set libraries by query PubMed to find microbe-mammalian gene associations and disease associations by parsing the Disbiome database. To demonstrate the utility of our novel MSEA methodology, we carried out three case studies using publicly available curated knowledge resource and microbiome profiling datasets focusing on human diseases. We found MSEA not only yields consistent findings with the original studies, but also recovers insights about disease mechanisms that are supported by the literature. Overall, MSEA is a useful knowledge-based computational approach to interpret the functions of microbes, which can be integrated with microbiome profiling pipelines to help reveal the underlying mechanism of host-microbiome interactions.

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Regulatory protein genes and microRNAs in response to selenium stimuli in Pueraria lobata (Willd.) Ohwi

Metallomics ◽

10.1093/mtomcs/mfaa004 ◽

2020 ◽

Author(s):

Yanni Li ◽

Meijun He ◽

Jishuang Li ◽

Yiwei Yao ◽

Li Zhu ◽

...

Keyword(s):

Structural Gene ◽

Target Genes ◽

Regulatory Protein ◽

Enrichment Analysis ◽

Regulation Of Transcription ◽

Pueraria Lobata ◽

Ros Scavenging ◽

Edible Plant ◽

Go Enrichment ◽

Highly Correlated

Abstract Regulatory protein genes and microRNAs (miRNAs) play important roles in response to abiotic and biotic stress, and the biosynthesis of secondary metabolites in plants. However, their responses to selenium (Se) stimuli have not been comprehensively studied in Pueraria lobata (Willd.) Ohwi, a Selenocompound-rich medicinal and edible plant. In this study, we identified a total of 436/556/1161/624 transcription factors (TFs), 134/157/308/172 transcriptional regulators (TRs) and 341/456/250/518 protein kinases (PKs), which were coexpressed with at least one Selenocompound-related structural gene/sulfate transporter or phosphate transporter/ROS scavenging structural gene/isoflavone-related structural gene, respectively. Then, we identified a total of 87 expressed miRNAs by Se disposure, in which 11 miRNAs, including miR171f-3p, miR390b-3P, miR-N111b, miR-N118, miR-N30, miR-N38-3P, miR-N61a, miR-N61b, miR-N80-3p, miR-N84-3P and miR-N90.2-3P were significantly up-regulated. We also identified a total of 1172 target genes for the 87 expressed miRNAs. Go enrichment analysis of these target genes showed that terms of regulation of transcription, DNA-templated, integral component of membrane, nucleus, ATP binding and plasma membrane are the top five subclassifications. Finally, we revealed that 5 miRNAs targeted 10 regulatory protein genes, which are highly correlated with at least one Selenocompound-related structural gene or transporter gene; 5 miRNAs targeted 10 regulatory protein genes, which are highly correlated with at least one ROS scavenging structural gene; 5 miRNAs targeted 9 regulatory protein genes, which are potentially involved in the isoflavone biosynthesis. Overall, the study provides us the comprehensive insight of the roles of regulatory proteins and miRNAs in response to Se stimuli in P. lobata.

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TMEA: A Thermodynamically Motivated Framework for Functional Characterization of Biological Responses to System Acclimation

Entropy ◽

10.3390/e22091030 ◽

2020 ◽

Vol 22 (9) ◽

pp. 1030

Author(s):

Kevin Schneider ◽

Benedikt Venn ◽

Timo Mühlhaus

Keyword(s):

Free Energy ◽

Functional Characterization ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

Enrichment Score ◽

Energy Investment ◽

Biological Responses ◽

Novel Approach ◽

Biological Studies

The objective of gene set enrichment analysis (GSEA) in modern biological studies is to identify functional profiles in huge sets of biomolecules generated by high-throughput measurements of genes, transcripts, metabolites, and proteins. GSEA is based on a two-stage process using classical statistical analysis to score the input data and subsequent testing for overrepresentation of the enrichment score within a given functional coherent set. However, enrichment scores computed by different methods are merely statistically motivated and often elusive to direct biological interpretation. Here, we propose a novel approach, called Thermodynamically Motivated Enrichment Analysis (TMEA), to account for the energy investment in biological relevant processes. Therefore, TMEA is based on surprisal analysis, which offers a thermodynamic-free energy-based representation of the biological steady state and of the biological change. The contribution of each biomolecule underlying the changes in free energy is used in a Monte Carlo resampling procedure resulting in a functional characterization directly coupled to the thermodynamic characterization of biological responses to system perturbations. To illustrate the utility of our method on real experimental data, we benchmark our approach on plant acclimation to high light and compare the performance of TMEA with the most frequently used method for GSEA.

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P5398CircRNAs deregulation in heart failure patients

European Heart Journal ◽

10.1093/eurheartj/ehz746.0358 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

S Greco ◽

A Made' ◽

M Longo ◽

R Tikhomirov ◽

S Castelvecchio ◽

...

Keyword(s):

Molecular Mechanisms ◽

Rna Binding ◽

Rna Binding Proteins ◽

Functional Characterization ◽

Enrichment Analysis ◽

Host Gene ◽

Circular Rnas ◽

Amplification Efficiency ◽

Rna Seq ◽

Bioinformatics Pipeline

Abstract Background Circular RNAs (circRNAs) are an emerging class of noncoding RNAs stemming from the splicing and circularization of pre-mRNAs exons. CircRNAs can regulate transcription and splicing, sequester microRNAs acting as “sponge” and inducing the respective targets, and bind to RNA binding proteins. Recently, they have been found deregulated in dilated cardiomyopathies (DCM), one of the cardiovascular diseases with the worst rate of morbidity and mortality, and whose molecular mechanisms are only partially known. Purpose Therein, we will evaluate in ischemic DCM patients the modulation of 17 circRNAs, 14 out of them obtained from literature data on DCM ischemic or not, while the other 3 were circRNAs not characterized in the heart previously. The study aims to identify circRNAs candidates for further functional characterization in DCM. In addition, as differential expression (DE) analysis is not easily performed for circRNAs in RNA-seq datasets, the validated circRNAs will be used to set up the most specific and sensitive bioinformatics pipeline for circRNA-DE analysis. Methods We designed divergent and convergent specific primers for 17 circRNAs and their host gene, respectively, and their amplification efficiency was measured by RT-qPCR. Transcripts expression was measured in left ventricle biopsies of 12 patients affected by non end-stage ischemic HF and of 12 matched controls. Results We identified cPVT1, cANKRD17, cBPTF as DE, and validated the modulation of 5 out of the 14 DCM-related circRNAs (cHIPK3, cALPK2, cPCMTD1, cNEBL, cSLC8A1), while cPDRM5, cTTN1 showed opposite modulation, which may be due to the specific disease condition. All of them were modulated differently from the respective host gene. CircRNA/miRNA interactions were predicted using Starbase 3.0. Next, mRNAs-targets of the identified miRNAs were predicted by mirDIP 4.1 and intersected with gene expression datasets of the same patients, previously obtained by microarray analysis. We found that cBPTF and cANKRD17 might sponge 12 and 2 miRNAs, respectively. Enrichment analysis of the relevant targets identified several important pathways implicated in DCM, such as MAPK, FoxO, EGFR, VEGF and Insulin/IGF pathways. In addition, deep RNA-Seq analysis that is currently ongoing and the validated circRNAs will be used to optimize the bioinformatics pipeline for circRNA DE analysis. Conclusions We identified a subset of circRNAs deregulated in ischemic HF potentially implicated in HF pathogenesis.

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Stereotactic laser ablation of amygdala and hippocampus using a Leksell stereotactic frame

Neurosurgical FOCUS ◽

10.3171/2018.4.focusvid.17712 ◽

2018 ◽

Vol 44 (videosuppl2) ◽

pp. V1 ◽

Cited By ~ 1

Author(s):

Ahmed J. Awad ◽

Ha S. Nguyen ◽

Elsa Arocho-Quinones ◽

Ninh Doan ◽

Wade Mueller ◽

...

Keyword(s):

Laser Ablation ◽

Temporal Lobe Epilepsy ◽

Temporal Lobe ◽

Perioperative Complications ◽

Mesial Temporal Lobe Epilepsy ◽

Stereotactic Frame ◽

History Of ◽

Mesial Temporal Lobe ◽

Invasive Techniques ◽

Patients With Epilepsy

Approximately one-third of patients with epilepsy are resistant to medical therapy, particularly in those with mesial temporal lobe epilepsy. While there are several surgical modalities, efforts have been focused on developing safer and minimally invasive techniques. In this video, the authors present the case of a 45-year-old woman with a 2-year history of refractory left mesial temporal lobe epilepsy who underwent MRI-guided laser ablation of amygdala and hippocampus. There were no perioperative complications.The video can be found here: https://youtu.be/XFHt2jTdE_4.

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