scholarly journals Timing Embryo Segmentation: Dynamics and Regulatory Mechanisms of the Vertebrate Segmentation Clock

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tatiana P. Resende ◽  
Raquel P. Andrade ◽  
Isabel Palmeirim
Keyword(s):  
Molecular Clock ◽  
Molecular Mechanisms ◽  
Genetic Network ◽  
Regulatory Mechanisms ◽  
Internal Organs ◽  
Skeletal Malformations ◽  
Somite Formation ◽  
Efficient Protection ◽  
High Degree ◽  
Molecular Regulatory Mechanisms

All vertebrate species present a segmented body, easily observed in the vertebrate column and its associated components, which provides a high degree of motility to the adult body and efficient protection of the internal organs. The sequential formation of the segmented precursors of the vertebral column during embryonic development, the somites, is governed by an oscillating genetic network, the somitogenesis molecular clock. Herein, we provide an overview of the molecular clock operating during somite formation and its underlying molecular regulatory mechanisms. Human congenital vertebral malformations have been associated with perturbations in these oscillatory mechanisms. Thus, a better comprehension of the molecular mechanisms regulating somite formation is required in order to fully understand the origin of human skeletal malformations.

Tumor-Related Molecular Regulatory Mechanisms of Long Non-Coding RNA RMST: Recent Evidence

2021 ◽  
Vol 21 ◽  
Author(s):  
Xuhui Chen ◽  
Kai Liu ◽  
Wen Xu ◽  
Gang Zhou ◽  
Chengfu Yuan
Keyword(s):  
Molecular Mechanisms ◽  
Medullary Thyroid Cancer ◽  
Regulatory Mechanisms ◽  
Molecular Pathways ◽  
Medullary Thyroid ◽  
Disease States ◽  
Non Coding Rna ◽  
Carcinoma Colon ◽  
Molecular Regulatory Mechanisms ◽  
Long Non Coding Rna

Background: Long non-coding RNA rhabdomyosarcoma 2-associated transcript (LncRNA RMST) will affect every aspect of tumor progression, such as proliferation, translocation and apoptosis. As a result, RMST can be used as an attractive biomarker for early diagnosis and clinical therapies of different disease states. This article aims to review pathophysiological functions, molecular mechanisms as well as promising biotherapies of RMST in multiple tumors. Methods: Through the systematic induction and summary of 46 papers published in PubMed concerning this study, the molecular mechanisms of RMST in all kinds of tumors have been reviewed. Results: LncRNA RMST is a tumor-related regulatory mediator, aberrantly expressed in diverse tumors, regarding medullary thyroid cancer, hepatocellular carcinoma, endometrial carcinoma, colon cancer, pancreatic cancer, glioma, Wilm’s tumor and breast cancer. Furthermore, as a mechanism-based player, RMST probably guides the translation and post-translation modification, containing DNA methylation and SUMOylation. It is capable of regulating distinct tumor cells and stem cells of biological behaviors via various molecular pathways. Conclusion: LncRNA RMST, potentially as an original therapeutic target, is valuable in the occurrence, development and apoptosis of different tumors.

scholarly journals Molecular Mechanisms of lncRNAs in the Dependent Regulation of Cancer and Their Potential Therapeutic Use

2022 ◽  
Vol 23 (2) ◽  
pp. 764
Author(s):  
Carlos García-Padilla ◽  
Ángel Dueñas ◽  
Virginio García-López ◽  
Amelia Aránega ◽  
Diego Franco ◽  
...  
Keyword(s):  
Tumor Suppressor Genes ◽  
Gene Networks ◽  
Molecular Mechanisms ◽  
Genetic Alterations ◽  
Regulatory Mechanisms ◽  
Epigenetic Landscape ◽  
Cellular Processes ◽  
Non Coding Rna ◽  
Non Coding Rnas ◽  
Molecular Regulatory Mechanisms

Deep whole genome and transcriptome sequencing have highlighted the importance of an emerging class of non-coding RNA longer than 200 nucleotides (i.e., long non-coding RNAs (lncRNAs)) that are involved in multiple cellular processes such as cell differentiation, embryonic development, and tissue homeostasis. Cancer is a prime example derived from a loss of homeostasis, primarily caused by genetic alterations both in the genomic and epigenetic landscape, which results in deregulation of the gene networks. Deregulation of the expression of many lncRNAs in samples, tissues or patients has been pointed out as a molecular regulator in carcinogenesis, with them acting as oncogenes or tumor suppressor genes. Herein, we summarize the distinct molecular regulatory mechanisms described in literature in which lncRNAs modulate carcinogenesis, emphasizing epigenetic and genetic alterations in particular. Furthermore, we also reviewed the current strategies used to block lncRNA oncogenic functions and their usefulness as potential therapeutic targets in several carcinomas.

scholarly journals Regulatory Mechanisms of Anthocyanin Biosynthesis in Apple and Pear

2021 ◽  
Vol 22 (16) ◽  
pp. 8441
Author(s):  
Huimin Liu ◽  
Zijin Liu ◽  
Yu Wu ◽  
Lamei Zheng ◽  
Genfa Zhang
Keyword(s):  
Molecular Mechanisms ◽  
Anthocyanin Biosynthesis ◽  
Phenylpropanoid Pathway ◽  
Regulatory Mechanisms ◽  
Fruit Species ◽  
Great Progress ◽  
Model Plant Arabidopsis Thaliana ◽  
Specific Factors ◽  
Molecular Regulatory Mechanisms ◽  
Plant Arabidopsis Thaliana

Anthocyanins contribute to the quality and flavour of fruits. They are produced through the phenylpropanoid pathway, which is regulated by specific key genes that have been identified in many species. The dominant anthocyanin forms are reversibly transformed at different pH states, thus forming different colours in aqueous solutions. In plants, anthocyanins are controlled by specific factors of the biosynthetic pathway: light, temperature, phytohormones and transcription factors. Although great progress in research on anthocyanin structures and the regulation of anthocyanin biosynthesis has been made, the molecular regulatory mechanisms of anthocyanin biosynthesis in different plants remain less clear. In addition, the co-regulation of anthocyanin biosynthesis is poorly understood. In this review, we summarise previous findings on anthocyanin biosynthesis, including the biochemical and biological features of anthocyanins; differences in anthocyanin biosynthesis among fruit species, i.e., apple, red pear, and the model plant Arabidopsis thaliana; and the developmental and environmental regulation of anthocyanin accumulation. This review reveals the molecular mechanisms underlying anthocyanin biosynthesis in different plant species and provides valuable information for the development of anthocyanin-rich red-skinned and red-fleshed apple and pear varieties.

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

scholarly journals The Saccharomyces cerevisiae RAD6 Group Is Composed of an Error-Prone and Two Error-Free Postreplication Repair Pathways

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1633-1641 ◽  
Author(s):  
Wei Xiao ◽  
Barbara L Chow ◽  
Stacey Broomfield ◽  
Michelle Hanna
Keyword(s):  
Mammalian Cells ◽  
Molecular Mechanisms ◽  
Signal Transducer ◽  
Repair Pathway ◽  
Polyubiquitin Chain ◽  
Postreplication Repair ◽  
Translesion Dna Synthesis ◽  
Radiation Repair ◽  
Repair Pathways ◽  
High Degree

Abstract The RAD6 postreplication repair and mutagenesis pathway is the only major radiation repair pathway yet to be extensively characterized. It has been previously speculated that the RAD6 pathway consists of two parallel subpathways, one error free and another error prone (mutagenic). Here we show that the RAD6 group genes can be exclusively divided into three rather than two independent subpathways represented by the RAD5, POL30, and REV3 genes; the REV3 pathway is largely mutagenic, whereas the RAD5 and the POL30 pathways are deemed error free. Mutants carrying characteristic mutations in each of the three subpathways are phenotypically indistinguishable from a single mutant such as rad18, which is defective in the entire RAD6 postreplication repair/tolerance pathway. Furthermore, the rad18 mutation is epistatic to all single or combined mutations in any of the above three subpathways. Our data also suggest that MMS2 and UBC13 play a key role in coordinating the response of the error-free subpathways; Mms2 and Ubc13 form a complex required for a novel polyubiquitin chain assembly, which probably serves as a signal transducer to promote both RAD5 and POL30 error-free postreplication repair pathways. The model established by this study will facilitate further research into the molecular mechanisms of postreplication repair and translesion DNA synthesis. In view of the high degree of sequence conservation of the RAD6 pathway genes among all eukaryotes, the model presented in this study may also apply to mammalian cells and predicts links to human diseases.

The impact of Traditional Chinese Medicine on mitophagy in disease models

2021 ◽  
Vol 27 ◽  
Author(s):  
Li-Ping Yu ◽  
Ting-Ting Shi ◽  
Yan-Qin Li ◽  
Jian-Kang Mu ◽  
Ya-Qin Yang ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Human Diseases ◽  
Regulatory Mechanisms ◽  
Disease Models ◽  
Relationship Of ◽  
The Impact ◽  
The Relationship

: Mitophagy plays an important role in maintaining mitochondrial quality and cell homeostasis through the degradation of damaged, aged, and dysfunctional mitochondria and misfolded proteins. Many human diseases, particularly neurodegenerative diseases, are related to disorders of mitochondrial phagocytosis. Exploring the regulatory mechanisms of mitophagy is of great significance for revealing the molecular mechanisms underlying the related diseases. Herein, we summarize the major mechanisms of mitophagy, the relationship of mitophagy with human diseases, and the role of traditional Chinese medicine (TCM) in mitophagy. These discussions enhance our knowledge of mitophagy and its potential therapeutic targets using TCM.

scholarly journals Indirubin attenuates mouse psoriasis-like skin lesion in a CD274-dependent manner: an achievement of RNA sequencing

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Xiaochun Xue ◽  
Jianhua Wu ◽  
Junhui Li ◽  
Jianguo Xu ◽  
Haiying Dai ◽  
...  
Keyword(s):  
Network Analysis ◽  
Skin Lesion ◽  
Candidate Genes ◽  
Rna Sequencing ◽  
Molecular Mechanisms ◽  
Regulatory Mechanisms ◽  
Epidermal Keratinocytes ◽  
Dependent Manner ◽  
Human Epidermal Keratinocytes ◽  
Ifn Γ

It was previously reported that the expression of CD274 was down-regulated in psoriatic epidermis, leading to immune disorders of psoriasis. However, the regulatory mechanisms of CD274 were rarely elucidated. We aimed to explore the regulatory mechanisms of CD274. Skin samples were collected from 18 patients with psoriasis vulgaris and 9 healthy participants for RNA sequencing. Candidate genes were chosen based on degree and k-core difference of genes in the co-expression network. The relations between candidate genes and CD274 were validated by flow cytometry and real-time PCR in primary human epidermal keratinocytes. The therapeutic effect of indirubin was assessed in an imiquimod-treated mouse model. Interferon-γ (IFN-γ), cyclin-dependent kinase (CDK) 1, Toll-like receptor 3 (TLR3), TLR4 and interleukin (IL)-17A were considered as candidate genes. In primary human epidermal keratinocytes, the level of CD274 was obviously increased under the stimulation of IFN-γ and CDK1 inhibitor (indirubin), independent of TLR4, TLR3 or IL-17A. Indirubin alleviated the severity of psoriatic mice in a CD274-dependent manner. Co-expression network analysis served as an effective method for the exploration of molecular mechanisms. We demonstrated for the first time that CD274 was the regulator of indirubin-mediated effect on mouse psoriasis-like skin lesion based on co-expression network analysis, contributing to the alleviation of mouse psoriasis-like skin lesion.

scholarly journals Distinct Amino Acid Availability-Dependent Regulatory Mechanisms of MepS and MepM Levels in Escherichia coli

2021 ◽  
Vol 12 ◽  
Author(s):  
Yung Jae Kim ◽  
Byoung Jun Choi ◽  
Si Hyoung Park ◽  
Han Byeol Lee ◽  
Ji Eun Son ◽  
...  
Keyword(s):  
Amino Acid ◽  
Minimal Medium ◽  
Molecular Mechanisms ◽  
Aromatic Amino Acids ◽  
Normal Growth ◽  
Regulatory Mechanisms ◽  
Dependent Manner ◽  
Bacterial Physiology ◽  
Protein Levels ◽  
Amino Acid Availability

Peptidoglycan (PG) hydrolases play important roles in various aspects of bacterial physiology, including cytokinesis, PG synthesis, quality control of PG, PG recycling, and antibiotic resistance. However, the regulatory mechanisms of their expression are poorly understood. In this study, we have uncovered novel regulatory mechanisms of the protein levels of the synthetically lethal PG endopeptidases MepS and MepM, which are involved in PG synthesis. A mutant defective for both MepS and MepM was lethal in an amino acid-rich medium, whereas it exhibited almost normal growth in a minimal medium, suggesting the expendability of MepS and MepM in a minimal medium. Protein levels of MepS and MepM dramatically decreased in the minimal medium. Although MepM was revealed as a substrate of Prc, a periplasmic protease involved in the proteolysis of MepS, only the decrease in the MepS level in the minimal medium was affected by the prc depletion. Phenotypic and biochemical analyses showed that the presence of aromatic amino acids in the medium induced the accumulation of MepS, but not MepM, while the presence of glutamate increased the level of MepM, but not MepS. Together, these results demonstrate that the protein levels of the two major PG endopeptidases are regulated in an amino acid availability-dependent manner, but their molecular mechanisms and signaling are significantly distinct.

scholarly journals THIOZOLIDINEDIONES IN THE TREATMENT OF PATIENTS WITH EXTENSIVE PSORIASIS AND CONCOMITANT ALIMENTARY OBESITY

2020 ◽  
Vol 20 (4) ◽  
pp. 30-34
Author(s):  
Ya.O. Yemchenko ◽  
K.Ye. Ishcheikin ◽  
I.P. Kaidashev
Keyword(s):  
Systemic Inflammation ◽  
Molecular Mechanisms ◽  
Current Data ◽  
The Body ◽  
Internal Organs ◽  
Single View ◽  
Multifactorial Diseases ◽  
Alimentary Obesity ◽  
Inflammatory Processes

Psoriasis is one of the most common chronic recurrent systemic autoimmune multifactorial diseases, affected the skin, joints, internal organs and systems of the body. Despite the significant prevalence of psoriasis and a large number of studies devoted this problem there is still no single view on the pathogenesis of this dermatosis. To clear up the pathogenesis of psoriasis, it seems to be reasonable to focus on the common comorbidities or multimorbidities, which may occur in the course of psoriasis, as this issue is still insufficiently studied. Recent reports have proven the evidences of indisputable link between psoriasis and obesity. The scientific literature extensively covers the issues of identical pathogenetic mechanisms of inflammatory processes in psoriasis and obesity. Given the current data on the role of systemic inflammation underlying the development of both psoriasis and obesity, the study of molecular mechanisms of its development and in particularly the role of proinflammatory nuclear transcription factors, thiazolidinediones have been found out as pathogenetically justified medicine of choice for the therapy of these diseases. In this study, we determined the effectiveness of using 30 mg of pioglitazone daily for 6 months in the course of treatment for patients with extensive psoriasis vulgaris of moderate severity, who were also diagnosed as having concomitant grade І-ІІ alimentary obesity that was supported by clinical and immunological findings evidenced of systemic inflammation. Analyzing the results obtained, we have found out the prolonged therapy with pioglitazone leads to a decrease in systemic inflammation and contributes to a milder recurrent course of psoriasis.

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