scholarly journals Fine mapping of a thrips resistance QTL in Capsicum and the role of diterpene glycosides in the underlying mechanism

2021 ◽  
Author(s):  
Pauline van Haperen ◽  
Roeland E. Voorrips ◽  
Martijn van Kaauwen ◽  
Henriëtte D. L. M. van Eekelen ◽  
Ric C. H. de Vos ◽  
...  
Keyword(s):  
Gene Expression ◽  
Underlying Mechanism ◽  
Chromosome 6 ◽  
Susceptibility Allele ◽  
Homozygous State ◽  
Resistance Qtl ◽  
Carnitine Transporter ◽  
Important Trait ◽  
Underlying Mechanisms

Abstract Key message A major thrips resistance QTL in Capsicum was fine-mapped to a region of 0.4 Mbp, and a multidisciplinary approach has been used to study putative underlying mechanisms. Abstract Resistance to thrips is an important trait for pepper growers. These insects can cause extensive damage to fruits, flowers and leaves on field and greenhouse grown plants worldwide. Two independent studies in Capsicum identified diterpene glycosides as metabolites that are correlated with thrips resistance. In this study, we fine-mapped a previously defined thrips resistance QTL on chromosome 6, to a region of 0.4 Mbp harbouring 15 genes. Two of these 15 candidate genes showed differences in gene expression upon thrips induction, when comparing plants carrying the resistance allele in homozygous state to plants with the susceptibility allele in homozygous state for the QTL region. Three genes, including the two genes that showed difference in gene expression, contained a SNP that was predicted to lead to changes in protein structure. Therefore, these three genes, i.e. an acid phosphatase 1 (APS1), an organic cation/carnitine transporter 7 (OCT7) and an uncharacterized locus LOC107874801, are the most likely candidates for playing a role in thrips resistance and are a first step in elucidating the genetic basis of thrips resistance in Capsicum. In addition, we show that the diterpene glycoside profiles did not differ between plants with the resistance and susceptibility allele for the chromosome 6 QTL, suggesting that these compounds do not play a role in the resistance conferred by the genes located in the major thrips resistance QTL studied.

scholarly journals An Evidence for a Novel Antiviral Mechanism of Teleost Fish: Serum-Derived Exosomes Inhibit Virus Replication Through Incorporating Mx1 Protein

2021 ◽  
Author(s):  
Changjun Guo ◽  
Jian He ◽  
Zhi-Min Li ◽  
Yuanyuan Wang ◽  
Chen nan nan ◽  
...  
Keyword(s):  
Cancer Progression ◽  
Teleost Fish ◽  
Protein Composition ◽  
Underlying Mechanism ◽  
Antiviral Effect ◽  
Mandarin Fish ◽  
Underlying Mechanisms ◽  
Antiviral Mechanism ◽  
Fish Serum

Exosomes are associated with cancer progression, pregnancy, cardiovascular diseases, central nervous system–related diseases, immune responses and viral pathogenicity. However, study on the role of exosomes in the immune response of teleost fish, especially antiviral immunity, is limited. Herein, serum-derived exosomes from mandarin fish were used to investigate antiviral effect for the exosomes of teleost fish. Exosomes were isolated from mandarin fish serum by ultracentrifugation could internalize into Mandarin fish fry (MFF-1) cells and inhibited Infectious spleen and kidney necrosis virus (ISKNV) infection. To further investigated the underlying mechanisms of exosomes in inhibiting ISKNV infection. The protein composition of serum-derived exosomes was by analysis mass spectrometry and found that myxovirus resistance 1 (Mx1) was incorporated in the exosomes. Furthermore, the scMx1 protein was proved transferred to the recipient cells though the exosomes. Our results found that the serum-derived exosomes from mandarin fish could inhibit ISKNV replication and suggested an underlying mechanism of the serum-derived exosomes antivirus is that serum-derived exosomes incorporation of the Mx1 protein into exosomes and delivery into recipient cells. This study provided an evidence for the important antiviral role of exosomes in the immune system of teleost fish.

scholarly journals Critical Role of cRel Subunit of NF-κB in Sepsis Survival

2011 ◽  
Vol 79 (5) ◽  
pp. 1848-1854 ◽  
Author(s):  
Emilie Courtine ◽  
Frédéric Pène ◽  
Nicolas Cagnard ◽  
Julie Toubiana ◽  
Catherine Fitting ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Profiles ◽  
Critical Role ◽  
Cecal Ligation ◽  
Gene Expression Profiles ◽  
Severe Infection ◽  
A Genome ◽  
Underlying Mechanisms ◽  
Pathogen Clearance

ABSTRACTNF-κB is a critical regulator of gene expression during severe infections. NF-κB comprises homo- and heterodimers of proteins from the Rel family. Among them, p50 and p65 have been clearly implicated in the pathophysiology of sepsis. In contrast, the role of cRel in sepsis is still controversial and has been poorly studied in single-pathogen infections. We aimed to investigate the consequences of cRel deficiency in a cecal ligation and puncture (CLP) model of sepsis. We have approached the underlying mechanisms of host defense by analyzing bacterial clearance, systemic inflammation, and the distribution of spleen dendritic cell subsets. Moreover, by using a genome-wide technology, we have also analyzed the CLP-induced modifications in gene expression profiles both in wild-type (wt) and inrel−/−mice. The absence of cRel enhances mortality due to polymicrobial sepsis. Despite normal pathogen clearance, cRel deficiency leads to an altered systemic inflammatory response associated with a sustained loss of the spleen lymphoid dendritic cells. Furthermore, a whole-blood microarray study reveals that the differential outcome between wt andrel−/−mice during sepsis is preceded by remarkable changes in the expression of hundreds of genes involved in aspects of host-pathogen interaction, such as host survival and lipid metabolism. In conclusion, cRel is a key NF-κB member required for host antimicrobial defenses and a regulatory transcription subunit that controls the inflammatory and immune responses in severe infection.

scholarly journals Inhibition of SIRT2 suppresses hepatic fibrosis

2016 ◽  
Vol 310 (11) ◽  
pp. G1155-G1168 ◽  
Author(s):  
Maribel Arteaga ◽  
Na Shang ◽  
Xianzhong Ding ◽  
Sherri Yong ◽  
Scott J. Cotler ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Fibrosis ◽  
Hepatic Fibrosis ◽  
Hepatic Stellate Cells ◽  
Histone Deacetylases ◽  
Critical Role ◽  
Stellate Cells ◽  
Novel Strategy ◽  
Underlying Mechanisms

Liver fibrosis can progress to cirrhosis and result in serious complications of liver disease. The pathogenesis of liver fibrosis involves the activation of hepatic stellate cells (HSCs), the underlying mechanisms of which are not fully known. Emerging evidence suggests that the classic histone deacetylases play a role in liver fibrosis, but the role of another subfamily of histone deacetylases, the sirtuins, in the development of hepatic fibrosis remains unknown. In this study, we found that blocking the activity of sirtuin 2 (SIRT2) by using inhibitors or shRNAs significantly suppressed fibrogenic gene expression in HSCs. We further demonstrated that inhibition of SIRT2 results in the degradation of c-MYC, which is important for HSC activation. In addition, we discovered that inhibition of SIRT2 suppresses the phosphorylation of ERK, which is critical for the stabilization of c-MYC. Moreover, we found that Sirt2 deficiency attenuates the hepatic fibrosis induced by carbon tetrachloride (CCl4) and thioacetamide (TAA). Furthermore, we showed that SIRT2, p-ERK, and c-MYC proteins are all overexpressed in human hepatic fibrotic tissues. These data suggest a critical role for the SIRT2/ERK/c-MYC axis in promoting hepatic fibrogenesis. Inhibition of the SIRT2/ERK/c-MYC axis represents a novel strategy to prevent and to potentially treat liver fibrosis and cirrhosis.

scholarly journals Snail modulates JNK-mediated cell death in Drosophila

2019 ◽  
Vol 10 (12) ◽  
Author(s):  
Chenxi Wu ◽  
Zhuojie Li ◽  
Xiang Ding ◽  
Xiaowei Guo ◽  
Ying Sun ◽  
...  
Keyword(s):  
Cell Death ◽  
Transcriptional Activation ◽  
Underlying Mechanism ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Animal Development ◽  
Genetic Epistasis ◽  
Underlying Mechanisms ◽  
Promote Cell Death

AbstractCell death plays a pivotal role in animal development and tissue homeostasis. Dysregulation of this process is associated with a wide variety of human diseases, including developmental and immunological disorders, neurodegenerative diseases and tumors. While the fundamental role of JNK pathway in cell death has been extensively studied, its down-stream regulators and the underlying mechanisms remain largely elusive. From a Drosophila genetic screen, we identified Snail (Sna), a Zinc-finger transcription factor, as a novel modulator of ectopic Egr-induced JNK-mediated cell death. In addition, sna is essential for the physiological function of JNK signaling in development. Our genetic epistasis data suggest that Sna acts downstream of JNK to promote cell death. Mechanistically, JNK signaling triggers dFoxO-dependent transcriptional activation of sna. Thus, our findings not only reveal a novel function and the underlying mechanism of Sna in modulating JNK-mediated cell death, but also provide a potential drug target and therapeutic strategies for JNK signaling-related diseases.

scholarly journals Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation

2021 ◽  
Vol 22 (12) ◽  
pp. 6259
Author(s):  
Amany Tawfik ◽  
Nehal M. Elsherbiny ◽  
Yusra Zaidi ◽  
Pragya Rajpurohit
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Barrier Function ◽  
Underlying Mechanism ◽  
Age Related Macular Degeneration ◽  
Barrier Dysfunction ◽  
Age Related ◽  
The Central Nervous System ◽  
Underlying Mechanisms

Hyperhomocysteinemia (HHcy) is remarkably common among the aging population. The relation between HHcy and the development of neurodegenerative diseases, such as Alzheimer’s disease (AD) and eye diseases, and age-related macular degeneration (AMD) and diabetic retinopathy (DR) in elderly people, has been established. Disruption of the blood barrier function of the brain and retina is one of the most important underlying mechanisms associated with HHcy-induced neurodegenerative and retinal disorders. Impairment of the barrier function triggers inflammatory events that worsen disease pathology. Studies have shown that AD patients also suffer from visual impairments. As an extension of the central nervous system, the retina has been suggested as a prominent site of AD pathology. This review highlights inflammation as a possible underlying mechanism of HHcy-induced barrier dysfunction and neurovascular injury in aging diseases accompanied by HHcy, focusing on AD.

scholarly journals Zoledronic acid promotes osteoclasts ferroptosis by inhibiting FBXO9-mediated p53 ubiquitination and degradation

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12510
Author(s):  
Xingzhou Qu ◽  
Zhaoqi Sun ◽  
Yang Wang ◽  
Hui Shan Ong
Keyword(s):  
Gene Expression ◽  
Zoledronic Acid ◽  
Cell Viability ◽  
Cell Model ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Underlying Mechanism ◽  
Cell Counting ◽  
Venn Diagram

Bisphosphonates (BPs)-related osteonecrosis of jaw (BRONJ) is a severe complication of the long-term administration of BPs. The development of BRONJ is associated with the cell death of osteoclasts, but the underlying mechanism remains unclear. In the current study, the role of Zoledronic acid (ZA), a kind of bisphosphonates, in suppressing the growth of osteoclasts was investigated and its underlying mechanism was explored. The role of ZA in regulating osteoclasts function was evaluated in the RANKL-induced cell model. Cell viability was assessed by cell counting kit-8 (CCK-8) assay and fluorescein diacetate (FDA)-staining. We confirmed that ZA treatment suppressed cell viability of osteoclasts. Furthermore, ZA treatment led to osteoclasts death by facilitating osteoclasts ferroptosis, as evidenced by increased Fe2+, ROS, and malonyldialdehyde (MDA) level, and decreased glutathione peroxidase 4 (GPX4) and glutathione (GSH) level. Next, the gene expression profiles of alendronate- and risedronate-treated osteoclasts were obtained from Gene Expression Omnibus (GEO) dataset, and 18 differentially expressed genes were identified using venn diagram analysis. Among these 18 genes, the expression of F-box protein 9 (FBXO9) was inhibited by ZA treatment. Knockdown of FBXO9 resulted in osteoclasts ferroptosis. More important, FBXO9 overexpression repressed the effect of ZA on regulating osteoclasts ferroptosis. Mechanistically, FBXO9 interacted with p53 and decreased the protein stability of p53. Collectively, our study showed that ZA induced osteoclast cells ferroptosis by triggering FBXO9-mediated p53 ubiquitination and degradation.

scholarly journals The hourglass model of evolutionary conservation during embryogenesis extends to developmental enhancers with signatures of positive selection

2020 ◽  
Author(s):  
Jialin Liu ◽  
Rebecca R. Viales ◽  
Pierre Khoueiry ◽  
James P. Reddington ◽  
Charles Girardot ◽  
...  
Keyword(s):  
Gene Expression ◽  
Positive Selection ◽  
Evolutionary Conservation ◽  
Animal Evolution ◽  
Species Comparisons ◽  
Underlying Mechanisms ◽  
Hourglass Model ◽  
Late Stages ◽  
Developmental Hourglass

Inter-species comparisons of both morphology and gene expression within a phylum have revealed a period in the middle of embryogenesis with more similarity between species compared to earlier and later time-points. This developmental hourglass pattern has been observed in many phyla, yet the evolutionary constraints on gene expression, and underlying mechanisms of how this is regulated, remains elusive. Moreover, the role of positive selection on gene regulation in the more diverged earlier and later stages of embryogenesis remains unknown. Here, using DNase-seq to identify regulatory regions in two distant Drosophila species (D. melanogaster and D. virilis), we assessed the evolutionary conservation and adaptive evolution of enhancers throughout multiple stages of embryogenesis. This revealed a higher proportion of conserved enhancers at the phylotypic period, providing a regulatory basis for the hourglass expression pattern. Using an in silico mutagenesis approach, we detect signatures of positive selection on developmental enhancers at early and late stages of embryogenesis, with a depletion at the phylotypic period, suggesting positive selection as one evolutionary mechanism underlying the hourglass pattern of animal evolution.

scholarly journals Ligand dependent gene regulation by transient ERα clustered enhancers

2019 ◽  
Author(s):  
Bharath Saravanan ◽  
Deepanshu Soota ◽  
Zubairul Islam ◽  
Ranveer Jayani ◽  
Rajat Mann ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Nuclear Receptors ◽  
Active Phase ◽  
Dependent Manner ◽  
Induced Expression ◽  
Chromatin Looping ◽  
Underlying Mechanisms

AbstractUnliganded nuclear receptors have been implicated in ligand-dependent gene regulation. However, the underlying mechanisms are not fully understood. Here we demonstrate that unliganded ERα binds to specific sites in the genome thereby pre-marking them as future functional enhancers. Upon ligand exposure, ERα binds to several EREs relatively proximal to the pre-marked, or persistent, ERα-bound sites. Interestingly, the persistent sites interact extensively, via chromatin looping, with the proximal transiently bound sites forming ERα clustered enhancers in 3D. CRISPR-based deletion of TFF1 persistent site disrupts the formation of its clustered enhancer resulting in the loss of E2-dependent induced expression of TFF1 and its neighboring genes within the same cluster. The clustered enhancers overlap with nuclear ERα puncta that coalesce in a ligand-dependent manner. Furthermore, formation of clustered enhancers, as well as puncta, coincide with the active phase of signaling and their later disappearance results in the loss of gene expression even though persistent sites remain bound by ERα. Our results establish the role of persistent unliganded ERα binding in priming enhancer clusters in 3D that drive transient, but robust, gene expression in a ligand-dependent fashion.

The histone methyltransferase MLL is an upstream regulator of endothelial-cell sprout formation

Blood ◽  
2006 ◽  
Vol 109 (4) ◽  
pp. 1472-1478 ◽  
Author(s):  
Florian Diehl ◽  
Lothar Rössig ◽  
Andreas M. Zeiher ◽  
Stefanie Dimmeler ◽  
Carmen Urbich
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Umbilical Vein ◽  
Underlying Mechanism ◽  
Endothelial Cell Migration ◽  
Cell Functions ◽  
Sprout Formation

Abstract Posttranslational histone modification by acetylation or methylation regulates gene expression. Here, we investigated the role of the histone lysine methyltransferase MLL for angiogenic functions in human umbilical vein endothelial cells. Suppression of MLL expression by siRNA or incubation with the pharmacologic methyltransferase inhibitor 5′-deoxy-5′-(methylthio)adenosine significantly decreased endothelial-cell migration and capillary sprout formation, indicating that methyltransferase activity is required for proangiogenic endothelial-cell functions. Because the expression of homeodomain transcription factors (Hox) is regulated by MLL, we elucidated the role of Hox gene expression. MLL silencing was associated with reduced mRNA and protein expression of HoxA9 and HoxD3, whereas HoxB3, HoxB4, HoxB5, and HoxB9 were not altered. Overexpression of HoxA9 or HoxD3 partially compensated for impaired migration in MLL siRNA-transfected endothelial cells, suggesting that HoxA9 and HoxD3 both contribute to MLL-dependent migration. As a potential underlying mechanism, MLL siRNA down-regulated mRNA and protein levels of the HoxA9-dependent axon guidance factor EphB4. In contrast, MLL knockdown effects on capillary sprouting were not rescued by HoxA9 or HoxD3 overexpression, indicating that MLL affects additional targets required for 3-dimensional sprout formation. We conclude that MLL regulates endothelial-cell migration via HoxA9 and EphB4, whereas sprout formation requires MLL-dependent signals beyond HoxA9 and HoxD3.

scholarly journals EZH2 abnormalities in lymphoid malignancies: underlying mechanisms and therapeutic implications

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Boheng Li ◽  
Wee-Joo Chng
Keyword(s):  
Gene Expression ◽  
Essential Role ◽  
Histone H3 ◽  
Epigenetic Silencing ◽  
Post Translational Modifications ◽  
Therapeutic Implications ◽  
Polycomb Repressive Complex 2 ◽  
Lymphoid Malignancies ◽  
Underlying Mechanisms

AbstractEZH2 is the catalytic subunit of the polycomb repressive complex 2 (PRC2), which along with other PRC2 components mediates gene expression suppression via the methylation of Histone H3 at lysine 27. Recent studies have revealed a dichotomous role of EZH2 in physiology and in the pathogenesis of cancer. While it plays an essential role in the development of the lymphoid system, its deregulation, whether due to genetic or non-genetic causes, promotes B cell- and T cell-related lymphoma or leukemia. These findings triggered a boom in the development of therapeutic EZH2 inhibitors in recent years. Here, we discuss physiologic and pathogenic function of EZH2 in lymphoid context, various internal causes of EZH2 aberrance and how EZH2 modulates lymphomagenesis through epigenetic silencing, post-translational modifications (PTMs), orchestrating with surrounding tumor micro-environment and associating with RNA or viral partners. We also summarize different strategies to directly inhibit PRC2-EZH2 or to intervene EZH2 upstream signaling.

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