Mitochondrial function, fatty acid metabolism, and immune system are relevant features of pig adipose tissue development

The molecular mechanisms underlying the genetic control of fat development in humans and livestock species still require characterization. To gain insights on gene expression patterns associated with genetic propensity for adiposity, we compared subcutaneous adipose tissue (SCAT) transcriptomics profiles from two contrasted pig breeds for body fatness. Samples were obtained from Large White (LW; lean phenotype) and Basque pigs (B; low growth and high fat content) at 35 kg ( n = 5 per breed) or 145 kg body weight ( n = 10 per breed). Using a custom adipose tissue microarray, we found 271 genes to be differentially expressed between the two breeds at both stages, out of which 123 were highly expressed in LW pigs and 148 genes were highly expressed in B pigs. Functional enrichment analysis based on gene ontology (GO) terms highlighted gene groups corresponding to the mitochondrial energy metabolism in LW pigs, whereas immune response was found significantly enriched in B pigs. Genes associated with lipid metabolism, such as ELOVL6, a gene involved in fatty acid elongation, had a lower expression in B compared with LW pigs. Furthermore, despite enlarged adipocyte diameters and higher plasma leptin concentration, B pigs displayed reduced lipogenic enzyme activities compared with LW pigs at 145 kg. Altogether, our results suggest that the development of adiposity was associated with a progressive worsening of the metabolic status, leading to a low-grade inflammatory state, and may thus be of significant interest for both livestock production and human health.

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Systems Biology Approaches Reveal a Multi-stress Responsive WRKY Transcription Factor and Stress Associated Gene Co-expression Networks in Chickpea

Current Bioinformatics ◽

10.2174/1574893614666190204152500 ◽

2019 ◽

Vol 14 (7) ◽

pp. 591-601 ◽

Cited By ~ 1

Author(s):

Aravind K. Konda ◽

Parasappa R. Sabale ◽

Khela R. Soren ◽

Shanmugavadivel P. Subramaniam ◽

Pallavi Singh ◽

...

Keyword(s):

Expression Pattern ◽

Gene Networks ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Wrky Transcription Factor ◽

Functional Enrichment ◽

Differentially Expressed ◽

Callose Deposition ◽

Significant Probability

Background: Chickpea is a nutritional rich premier pulse crop but its production encounters setbacks due to various stresses and understanding of molecular mechanisms can be ascribed foremost importance. Objective: The investigation was carried out to identify the differentially expressed WRKY TFs in chickpea in response to herbicide stress and decipher their interacting partners. Methods: For this purpose, transcriptome wide identification of WRKY TFs in chickpea was done. Behavior of the differentially expressed TFs was compared between other stress conditions. Orthology based cofunctional gene networks were derived from Arabidopsis. Gene ontology and functional enrichment analysis was performed using Blast2GO and STRING software. Gene Coexpression Network (GCN) was constructed in chickpea using publicly available transcriptome data. Expression pattern of the identified gene network was studied in chickpea-Fusarium interactions. Results: A unique WRKY TF (Ca_08086) was found to be significantly (q value = 0.02) upregulated not only under herbicide stress but also in other stresses. Co-functional network of 14 genes, namely Ca_08086, Ca_19657, Ca_01317, Ca_20172, Ca_12226, Ca_15326, Ca_04218, Ca_07256, Ca_14620, Ca_12474, Ca_11595, Ca_15291, Ca_11762 and Ca_03543 were identified. GCN revealed 95 hub genes based on the significant probability scores. Functional annotation indicated role in callose deposition and response to chitin. Interestingly, contrasting expression pattern of the 14 network genes was observed in wilt resistant and susceptible chickpea genotypes, infected with Fusarium. Conclusion: This is the first report of identification of a multi-stress responsive WRKY TF and its associated GCN in chickpea.

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A Systematic Analysis of Candidate Genes Associated with Nicotine Addiction

BioMed Research International ◽

10.1155/2015/313709 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Meng Liu ◽

Xia Li ◽

Rui Fan ◽

Xinhua Liu ◽

Ju Wang

Keyword(s):

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Nicotine Addiction ◽

Clustering Coefficient ◽

Functional Enrichment ◽

Moderate Degree ◽

Cancer Genes ◽

Systematic Analysis ◽

The Central Nervous System

Nicotine, as the major psychoactive component of tobacco, has broad physiological effects within the central nervous system, but our understanding of the molecular mechanism underlying its neuronal effects remains incomplete. In this study, we performed a systematic analysis on a set of nicotine addiction-related genes to explore their characteristics at network levels. We found that NAGenes tended to have a more moderate degree and weaker clustering coefficient and to be less central in the network compared to alcohol addiction-related genes or cancer genes. Further, clustering of these genes resulted in six clusters with themes in synaptic transmission, signal transduction, metabolic process, and apoptosis, which provided an intuitional view on the major molecular functions of the genes. Moreover, functional enrichment analysis revealed that neurodevelopment, neurotransmission activity, and metabolism related biological processes were involved in nicotine addiction. In summary, by analyzing the overall characteristics of the nicotine addiction related genes, this study provided valuable information for understanding the molecular mechanisms underlying nicotine addiction.

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Identification of Key Genes and Pathways Associated with Differences of Subchondral Bone in Osteoarthritis

10.21203/rs.3.rs-51799/v1 ◽

2020 ◽

Author(s):

Yiyuan Zhang ◽

Rongguo Yu ◽

Jiayu Zhang ◽

Eryou Feng ◽

Haiyang Wang ◽

...

Keyword(s):

Subchondral Bone ◽

Molecular Mechanisms ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Hub Genes ◽

Common Chronic Disease ◽

Drug Candidates ◽

Therapeutic Modalities ◽

Pathogenic Genes

Abstract BackgroundOsteoarthritis (OA) is a common chronic disease worldwide. Subchondral bone is an important pathological change in OA and responds more rapidly to adverse loading and events compared to cartilage. However, the pathogenic genes and pathways of subchondral bone are largely unclear.ObjectiveThis study aimed to identify signature differences in genes involved in knee lateral tibial (LT) and medial tibial (MT) plateaus of subchondral bone tissue while exploring their potential molecular mechanisms via bioinformatics analysis.MethodsFirst, the gene expression data of GSE51588 was downloaded from the GEO database. Differentially expressed genes (DEGs) between knee LT and MT were identified, and functional enrichment analyses were performed. Then, a protein-protein interactive network was constructed in order to acquire the hub genes, and modules analysis was conducted using STRING and Cytoscape for further analysis. The enriched hub genes were queried in DGIdb database to find suitable drug candidates in OA.ResultsA total of 202 DEGs (112 upregulated genes and 84 downregulated genes) were determined. In the PPI network, ten hub genes were identified. Five significant modules were identified using the MCODE plugin unit. Functional enrichment analysis revealed the most important signaling pathways. Six of the ten hub genes were targetable by a total of 35 drugs, suggesting their possible therapeutic use for OA .ConclusionsThe identified hub genes and functional enrichment pathways were implicated in the development and progression of subchondral bone in OA, thus improving our understanding of OA and offering molecular targets for future therapeutic modalities.

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Identifcation of The Ferroptosis-Related Gene Signature In Placenta of Patients With Early-Onset Preeclampsia

10.21203/rs.3.rs-618453/v1 ◽

2021 ◽

Author(s):

Nana Yang ◽

Qianghua Wang ◽

Biao Ding ◽

Yinging Gong ◽

Yue Wu ◽

...

Keyword(s):

Iron Homeostasis ◽

Molecular Mechanisms ◽

Late Onset ◽

Expression Profiles ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Differentially Expressed ◽

Ppi Network ◽

Network Analyses

Abstract Background: The accumulation of ROS resulting from upregulated levels of oxidative stress is commonly implicated in preeclampsia (PE). Ferroptosis is a novel form of iron-dependent cell death instigated by lipid peroxidation likely plays important role in PE pathogenesis. This study aims to investigate expression profiles and functions of the ferroptosis-related genes (FRGs) in early- and late-onset preeclampsia.Methods: The gene expression data and clinical information were downloaded from GEO database. The “limma” R package was used for screening differentially expressed genes. GO(Gene Ontology), Kyoto Encyclopedia of Genes and Genomes(KEGG) and protein protein interaction (PPI) network analyses were conducted to investigate the bioinformatics functions and molecular interactions of significantly different FRGs. Quantitative real-time reverse transcriptase PCR was used to verify the expression of hub FRGs in PE.Results: A total number of 4,215 DEGs were identified between EOPE and preterm cases and 3,356 DEGs were found between EOPE and LOPE subtypes. 20 significantly different FRGs were identified in EOPE, while only 3 in LOPE. Functional enrichment analysis revealed that the differentially expressed FRGs was mainly involved in EOPE and enriched in hypoxia- and iron-related pathways, such as response to hypoxia, iron homeostasis and iron ion binding process. The PPI network analysis and verification by RT-qPCR resulted in the identification of the following six interesting FRGs: FTH1, HIF1A, FTL, IREB2, MAPK8 and PLIN2. Conclusions: EOPE and LOPE owned distinct underlying molecular mechanisms and ferroptosis may be mainly implicated in pathogenesis of EOPE. Further studies are necessary for deeper inquiry into placental ferroptosis and its role in the pathogenesis of EOPE.

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3131 ONCOSTREAMS: NOVEL DYNAMICS PATHOLOGICAL MULTICELLULAR STRUCTURES INVOLVED IN GLIOBLATOMA GROWTH AND INVASION

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.253 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 111-111 ◽

Cited By ~ 2

Author(s):

Andrea Comba ◽

Patrick Dunn ◽

Anna E Argento ◽

Padma Kadiyala ◽

Sebastien Motsch ◽

...

Keyword(s):

Extracellular Matrix ◽

Target Genes ◽

Collective Motion ◽

Malignant Tumors ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Genetically Engineered ◽

Functional Enrichment ◽

Low Grade ◽

Normal Brain

OBJECTIVES/SPECIFIC AIMS: Oncostreams represent a novel growth pattern of GBM. In this study we uncovered the cellular and molecular mechanism that regulates the oncostreams function in GBM growth and invasion. METHODS/STUDY POPULATION: We studied oncostreams organization and function using genetically engineered mouse gliomas models (GEMM), mouse primary patient derived GBM model and human glioma biopsies. We evaluated the molecular landscape of oncostreams by laser capture microdissection (LCM) followed by RNA-Sequencing and bioinformatics analysis. RESULTS/ANTICIPATED RESULTS: Oncostreams are multicellular structures of 10-20 cells wide and 2-400 μm long. They are distributed throughout the tumors in mouse and human GBM. Oncostreams are heterogeneous structures positive for GFAP, Nestin, Olig2 and Iba1 cells and negative for Neurofilament. Using GEMM we found a negative correlation between oncostream density and animal survival. Moreover, examination of patient’s glioma biopsies evidenced that oncostreams are present in high grade but no in low grade gliomas. This suggests that oncostreams may play a role in tumor malignancy. Our data also indicated that oncostreams aid local invasion of normal brain. Transcriptome analysis of oncostreams revealed 43 differentially expressed (DE) genes. Functional enrichment analysis of DE genes showed that “collagen catabolic processes”, “positive regulation of cell migration”, and “extracellular matrix organization” were the most over-represented GO biological process. Network analysis indicated that Col1a1, ACTA2, MMP9 and MMP10 are primary target genes. These genes were also overexpressed in more malignant tumors (WT-IDH) compared to the less malignant (IDH1- R132H) tumors. Confocal time lapse imagining of 3D tumor slices demonstrated that oncostreams display a collective motion pattern within gliomas that has not been seen before. DISCUSSION/SIGNIFICANCE OF IMPACT: In summary, oncostreams are anatomically and molecularly distinctive, regulate glioma growth and invasion, display collective motion and are regulated by the extracellular matrix. We propose oncostreams as novel pathological markers valuable for diagnosis, prognosis and designing therapeutics for GBM patients.

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Immunological pathways of macrophage response to Brucella ovis infection

Innate Immunity ◽

10.1177/1753425920958179 ◽

2020 ◽

Vol 26 (7) ◽

pp. 635-648

Author(s):

Zhixiong Zhou ◽

Guojing Gu ◽

Yichen Luo ◽

Wenjie Li ◽

Bowen Li ◽

...

Keyword(s):

Immune Response ◽

Molecular Mechanisms ◽

Group Versus ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Sequencing Data ◽

Brucella Ovis ◽

Qrt Pcr ◽

Raw264.7 Macrophage

As the molecular mechanisms of Brucella ovis pathogenicity are not completely clear, we have applied a transcriptome approach to identify the differentially expressed genes (DEGs) in RAW264.7 macrophage infected with B. ovis. The DEGs related to immune pathway were identified by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) functional enrichment analysis. Quantitative real-time PCR (qRT-PCR) was performed to validate the transcriptome sequencing data. In total, we identified 337 up-regulated and 264 down-regulated DEGs in B. ovis-infected group versus mock group. Top 20 pathways were enriched by KEGG analysis and 20 GO by functional enrichment analysis in DEGs involved in the molecular function, cellular component, and biological process and so on, which revealed multiple immunological pathways in RAW264.7 macrophage cells in response to B. ovis infection, including inflammatory response, immune system process, immune response, cytokine activity, chemotaxis, chemokine-mediated signaling pathway, chemokine activity, and CCR chemokine receptor binding. qRT-PCR results showed Ccl2 (ENSMUST00000000193), Ccl2 (ENSMUST00000124479), Ccl3 (ENSMUST00000001008), Hmox1 (ENSMUST00000005548), Hmox1 (ENSMUST00000159631), Cxcl2 (ENSMUST00000075433), Cxcl2 (ENSMUST00000200681), Cxcl2 (ENSMUST00000200919), and Cxcl2 (ENSMUST00000202317). Our findings firstly elucidate the pathways involved in B. ovis-induced host immune response, which may lay the foundation for revealing the bacteria–host interaction and demonstrating the pathogenic mechanism of B. ovis.

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Comparative Transcriptome Analysis Suggests Key Roles for 5-Hydroxytryptamlne Receptors in Control of Goose Egg Production

Genes ◽

10.3390/genes11040455 ◽

2020 ◽

Vol 11 (4) ◽

pp. 455 ◽

Cited By ~ 1

Author(s):

Qingyuan Ouyang ◽

Shenqiang Hu ◽

Guosong Wang ◽

Jiwei Hu ◽

Jiaman Zhang ◽

...

Keyword(s):

Egg Production ◽

Expression Profiles ◽

Expression Patterns ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Production Performance ◽

Functional Enrichment ◽

Differentially Expressed ◽

Receptor Interaction ◽

Anser Anser

To date, research on poultry egg production performance has only been conducted within inter or intra-breed groups, while those combining both inter- and intra-breed groups are lacking. Egg production performance is known to differ markedly between Sichuan white goose (Anser cygnoides) and Landes goose (Anser anser). In order to understand the mechanism of egg production performance in geese, we undertook this study. Here, 18 ovarian stromal samples from both Sichuan white goose and Landes goose at the age of 145 days (3 individuals before egg production initiation for each breed) and 730 days (3 high- and low egg production individuals during non-laying periods for each breed) were collected to reveal the genome-wide expression profiles of ovarian mRNAs and lncRNAs between these two geese breeds at different physiological stages. Briefly, 58, 347, 797, 777, and 881 differentially expressed genes (DEGs) and 56, 24, 154, 105, and 224 differentially expressed long non-coding RNAs (DElncRNAs) were found in LLD vs. HLD (low egg production Landes goose vs. high egg production Landes goose), LSC vs. HSC (low egg production Sichuan White goose vs. high egg production Sichuan white goose), YLD vs. YSC (young Landes goose vs. young Sichuan white goose), HLD vs. HSC (high egg production Landes goose vs. high egg production Sichuan white goose), and LLD vs. LSC (low egg production Landes goose vs. low egg production Sichuan white goose) groups, respectively. Functional enrichment analysis of these DEGs and DElncRNAs suggest that the “neuroactive ligand–receptor interaction pathway” is crucial for egg production, and particularly, members of the 5-hydroxytryptamine receptor (HTR) family affect egg production by regulating ovarian metabolic function. Furthermore, the big differences in the secondary structures among HTR1F and HTR1B, HTR2B, and HTR7 may lead to their different expression patterns in goose ovaries of both inter- and intra-breed groups. These results provide novel insights into the mechanisms regulating poultry egg production performance.

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Integrative Analysis Reveals Common and Unique Roles of Tetraspanins in Fibrosis and Emphysema

Frontiers in Genetics ◽

10.3389/fgene.2020.585998 ◽

2020 ◽

Vol 11 ◽

Author(s):

Lokesh P. Tripathi ◽

Mari N. Itoh ◽

Yoshito Takeda ◽

Kazuyuki Tsujino ◽

Yasushi Kondo ◽

...

Keyword(s):

Pulmonary Fibrosis ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Functional Enrichment ◽

Integrative Approach ◽

Chronic Obstructive ◽

Lung Pathology ◽

Obstructive Pulmonary Disease

While both chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are multifactorial disorders characterized by distinct clinical and pathological features, their commonalities and differences have not been fully elucidated. We sought to investigate the preventive roles of tetraspanins Cd151 and Cd9 -that are involved in diverse cellular processes in lung pathophysiology- in pulmonary fibrosis and emphysema, respectively, and to obtain a deeper understanding of their underlying molecular mechanisms toward facilitating improved therapeutic outcomes. Using an integrative approach, we examined the transcriptomic changes in the lungs of Cd151- and Cd9-deficient mice using functional-enrichment-analysis, pathway-perturbation-analysis and protein-protein-interaction (PPI) network analysis. Circadian-rhythm, extracellular-matrix (ECM), cell-adhesion and inflammatory responses and associated factors were prominently influenced by Cd151-deletion. Conversely, cellular-junctions, focal-adhesion, vascular-remodeling, and TNF-signaling were deeply impacted by Cd9-deletion. We also highlighted a “common core” of factors and signaling cascades that underlie the functions of both Cd151 and Cd9 in lung pathology. Circadian dysregulation following Cd151-deletion seemingly facilitated progressive fibrotic lung phenotype. Conversely, TGF-β signaling attenuation and TNF-signaling activation emerged as potentially novel functionaries of Cd9-deletion-induced emphysema. Our findings offer promising avenues for developing novel therapeutic treatments for pulmonary fibrosis and emphysema.

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Protein expression profiles in Meishan and Duroc sows during mid-gestation reveal differences affecting uterine capacity, endometrial receptivity, and the maternal–fetal Interface

BMC Genomics ◽

10.1186/s12864-019-6353-2 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Kejun Wang ◽

Kaijie Yang ◽

Qiao Xu ◽

Yufang Liu ◽

Wenting Li ◽

...

Keyword(s):

Protein Expression ◽

Expression Profiles ◽

Expression Patterns ◽

Enrichment Analysis ◽

Functional Enrichment Analysis ◽

Embryonic Mortality ◽

Functional Enrichment ◽

Matrix Remodeling ◽

Swine Industry ◽

Embryonic Loss

Abstract Background Embryonic mortality is a major concern in the commercial swine industry and primarily occurs early in gestation, but also during mid-gestation (~ days 50–70). Previous reports demonstrated that the embryonic loss rate was significant lower in Meishan than in commercial breeds (including Duroc). Most studies have focused on embryonic mortality in early gestation, but little is known about embryonic loss during mid-gestation. Results In this study, protein expression patterns in endometrial tissue from Meishan and Duroc sows were examined during mid-gestation. A total of 2170 proteins were identified in both breeds. After statistical analysis, 70 and 114 differentially expressed proteins (DEPs) were identified in Meishan and Duroc sows, respectively. Between Meishan and Duroc sows, 114 DEPs were detected at day 49, and 98 DEPs were detected at day 72. Functional enrichment analysis revealed differences in protein expression patterns in the two breeds. Around half of DEPs were more highly expressed in Duroc at day 49 (DUD49), relative to DUD72 and Meishan at day 49 (MSD49). Many DEPs appear to be involved in metabolic process such as arginine metabolism. Our results suggest that the differences in expression affect uterine capacity, endometrial matrix remodeling, and maternal-embryo cross-talk, and may be major factors influencing the differences in embryonic loss between Meishan and Duroc sows during mid-gestation. Conclusions Our data showed differential protein expression pattern in endometrium between Meishan and Duroc sows and provides insight into the development process of endometrium. These findings could help us further uncover the molecular mechanism involved in prolificacy.

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Exploring the Functional Disorder and Corresponding Key Transcription Factors in Intraductal Papillary Mucinous Neoplasms Progression

International Journal of Genomics ◽

10.1155/2015/197603 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Guiying Bai ◽

Chenxuan Wu ◽

Yingtang Gao ◽

Guiming Shu

Keyword(s):

Transcription Factors ◽

Ductal Carcinoma ◽

Expression Patterns ◽

Enrichment Analysis ◽

Microarray Dataset ◽

Functional Enrichment Analysis ◽

Mucinous Carcinoma ◽

Functional Enrichment ◽

Functional Disorder ◽

Similar Expression Pattern

This study has analyzed the gene expression patterns of an IPMN microarray dataset including normal pancreatic ductal tissue (NT), intraductal papillary mucinous adenoma (IPMA), intraductal papillary mucinous carcinoma (IPMC), and invasive ductal carcinoma (IDC) samples. And eight clusters of differentially expressed genes (DEGs) with similar expression pattern were detected byk-means clustering. Then a survey map of functional disorder in IPMN progression was established by functional enrichment analysis of these clusters. In addition, transcription factors (TFs) enrichment analysis was used to detect the key TFs in each cluster of DEGs, and three TFs (FLI1, ERG, and ESR1) were found to significantly regulate DEGs in cluster 1, and expression of these three TFs was validated by qRT-PCR. All these results indicated that these three TFs might play key roles in the early stages of IPMN progression.

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