scholarly journals Simple post-translational circadian clock models from selective sequestration

2020 ◽  
Author(s):  
Mark Byrne
Keyword(s):  
Transcriptional Repression ◽  
Site Occupancy ◽  
Stable Limit Cycle ◽  
Cell Types ◽  
Test Tube ◽  
Fine Tuning ◽  
Stable Limit ◽  
Circadian Time ◽  
Molecular Components ◽  
Different Cell Types

AbstractIt is possible that there are post-translational circadian oscillators that continue functioning in the absence of negative feedback transcriptional repression in many cell types from diverse organisms. Apart from the KaiABC system from cyanobacteria, the minimal molecular components and interactions required to potentially create “test-tube” circadian oscillations in different cell types are currently unknown. Inspired by the KaiABC system, I provide proof-of-principle mathematical models that a protein with 2 (or more) modification sites which selectively sequesters an effector/cofactor molecule can function as a circadian time-keeper. The 2-site mechanism can be implemented using two relatively simple coupled non-linear ODEs in terms of site occupancy; the models do not require overly special fine-tuning of parameters for generating stable limit cycle oscillations.

scholarly journals MiR-7 in Cancer Development

Biomedicines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 325
Author(s):  
Petra Korać ◽  
Mariastefania Antica ◽  
Maja Matulić
Keyword(s):  
Cell Fate ◽  
Dominant Role ◽  
Tumor Development ◽  
Mrna Translation ◽  
Cell Types ◽  
Fine Tuning ◽  
Non Coding Rna ◽  
Tumor Types ◽  
Different Cell Types ◽  
The Brain

MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

Implications of microRNAs in the pathogenesis of atherosclerosis and prospects for therapy

2021 ◽  
Vol 22 ◽  
Author(s):  
Armita Mahdavi Gorabi ◽  
Mohsen Ghanbari ◽  
Thozhukat Sathyapalan ◽  
Tannaz Jamialahmadi ◽  
Amirhossein Sahebkar
Keyword(s):  
Immune Cell ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Fine Tuning ◽  
Lipid Uptake ◽  
Atherosclerosis Development ◽  
Signaling Receptors ◽  
Different Cell Types

MicroRNAs (miRNAs) are non-coding RNAs containing around 22 nucleotides, which are expressed in vertebrates and plants. They act as posttranscriptional gene expression regulators, fine-tuning various biological processes in different cell types. There is emerging evidence on their role in different stages of atherosclerosis. In addition to regulating the inflammatory cells involved in atherosclerosis, miRNAs play fundamental roles in the pathophysiology of atherosclerosis such as endothelial cell (EC) dysfunction, the aberrant function of the vascular smooth muscle cell (VSMC) and cholesterol metabolism. Moreover, miRNAs participate in several pathogenic pathways of atherosclerotic plaque development, including their effects on immune cell signaling receptors and lipid uptake. In this study, we review our current knowledge of the regulatory role of miRNAs in various pathogenic pathways underlying atherosclerosis development and also outline potential clinical applications of miRNAs in atherosclerosis.

Mutual desmosome formation between all binary combinations of human, bovine, canine, avian and amphibian cells: desmosome formation is not tissue- or species-specific

1985 ◽  
Vol 75 (1) ◽  
pp. 377-399 ◽  
Author(s):  
D.L. Mattey ◽  
D.R. Garrod
Keyword(s):  
Epithelial Cell ◽  
Corneal Epithelium ◽  
Fluorescent Antibody ◽  
Cell Types ◽  
Recognition Mechanism ◽  
Antibody Staining ◽  
Species Specific ◽  
Molecular Components ◽  
Different Cell Types ◽  
Darby Canine Kidney

Our previous work has suggested that the molecular components of desmosomes are highly conserved between different tissues and different vertebrate species. In order to determine whether the adhesion recognition mechanism of desmosomes is also conserved we have examined the specificity of desmosome formation between different epithelial cell types by co-culturing binary combinations of cells from different species and from epidermal and non-epidermal origin. The following cell types were used: human (HeLa, cervical carcinoma), bovine (Madin Darby bovine kidney, MDBK), canine (Madin Darby canine kidney, MDCK), avian (chick embryonic corneal epithelium) and amphibian (Rana pipiens, adult corneal epithelium). Different cells in co-culture were identified on the basis of at least one of the following criteria: (1) morphology by phase-contrast microscopy; (2) presence or absence of staining of cytokeratin with monoclonal antibody LE61; (3) morphology at the electron microscope level. Mutual desmosome formation between different cell types was assessed using fluorescent antibody staining with anti-desmoplakin antibodies and confirmed using electron microscopy. We have found that mutual desmosome formation occurred between all binary combinations of human, bovine, canine, avian and amphibian cells. Thus there is complete non-selectivity of desmosome formation between five different epithelial cell types from three vertebrate classes. Our results suggest that desmosome formation is not tissue- or species-specific and that the mechanism for intercellular binding involved in desmosomal adhesion is highly conserved.

scholarly journals Alternative Splicing Modulates Autoinhibition and SH3 Accessibility in the Src Kinase Fyn

2009 ◽  
Vol 29 (24) ◽  
pp. 6438-6448 ◽  
Author(s):  
C. Brignatz ◽  
M. P. Paronetto ◽  
S. Opi ◽  
M. Cappellari ◽  
S. Audebert ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Src Kinase ◽  
Cell Types ◽  
Site Directed Mutagenesis ◽  
Fine Tuning ◽  
Control Mechanisms ◽  
Molecular Control ◽  
Fyn Kinase ◽  
Functional Consequences ◽  
Different Cell Types

ABSTRACT Src family kinases are central regulators of a large number of signaling pathways. To adapt to the idiosyncrasies of different cell types, these kinases may need a fine-tuning of their intrinsic molecular control mechanisms. Here, we describe on a molecular level how the Fyn kinase uses alternative splicing to adapt to different cellular environments. Using structural analysis, site-directed mutagenesis, and functional analysis, we show how the inclusion of either exon 7A or 7B affects the autoinhibition of Fyn and how this changes the SH3-dependent interaction and tyrosine phosphorylation of Sam68, with functional consequences for the Sam68-regulated survival of epithelial cells. Our results illustrate a novel mechanism of evolution that may contribute to the complexity of Src kinase regulation.

scholarly journals TFregulomeR reveals transcription factors’ context-specific features and functions

2019 ◽  
Vol 48 (2) ◽  
pp. e10-e10 ◽  
Author(s):  
Quy Xiao Xuan Lin ◽  
Denis Thieffry ◽  
Sudhakar Jha ◽  
Touati Benoukraf
Keyword(s):  
Transcription Factors ◽  
Binding Sites ◽  
Leucine Zipper ◽  
Cell Types ◽  
Fine Tuning ◽  
A Cell ◽  
Context Specific ◽  
Gene Ontologies ◽  
Different Cell Types

Abstract Transcription factors (TFs) are sequence-specific DNA binding proteins, fine-tuning spatiotemporal gene expression. Since genomic occupancy of a TF is highly dynamic, it is crucial to study TF binding sites (TFBSs) in a cell-specific context. To date, thousands of ChIP-seq datasets have portrayed the genomic binding landscapes of numerous TFs in different cell types. Although these datasets can be browsed via several platforms, tools that can operate on that data flow are still lacking. Here, we introduce TFregulomeR (https://github.com/benoukraflab/TFregulomeR), an R-library linked to an up-to-date compendium of cistrome and methylome datasets, implemented with functionalities that facilitate integrative analyses. In particular, TFregulomeR enables the characterization of TF binding partners and cell-specific TFBSs, along with the study of TF’s functions in the context of different partnerships and DNA methylation levels. We demonstrated that TFs’ target gene ontologies can differ notably depending on their partners and, by re-analyzing well characterized TFs, we brought to light that numerous leucine zipper TFBSs derived from ChIP-seq experiments documented in current databases were inadequately characterized, due to the fact that their position weight matrices were assembled using a mixture of homodimer and heterodimer binding sites. Altogether, analyses of context-specific transcription regulation with TFregulomeR foster our understanding of regulatory network-dependent TF functions.

scholarly journals Single-Cell Entropy to Quantify the Cellular Order Parameter from Single-Cell RNA-Seq Data

2020 ◽  
Vol 15 (01) ◽  
pp. 35-49
Author(s):  
Jingxin Liu ◽  
You Song ◽  
Jinzhi Lei
Keyword(s):  
Single Cell ◽  
Order Parameter ◽  
Developmental Process ◽  
Cell Types ◽  
Gaussian Mixture ◽  
Cell Type ◽  
A Cell ◽  
Molecular Components ◽  
Different Cell Types ◽  
Type Classification

The cell is the basic functional and biological unit of life, and a complex system that contains a huge number of molecular components. How can we quantify the macroscopic state of a cell from the microscopic information of these molecular components? This is a fundamental question to increase the understanding of the human body. The recent maturation of single-cell RNA sequencing (scRNA-seq) technologies has allowed researchers to gain information on the transcriptomes of individual cells. Although considerable progress has been made in terms of cell-type clustering over the past few years, there is no strong consensus about how to define a cell state from scRNA-seq data. Here, we present single-cell entropy (scEntropy) as an order parameter for cellular transcriptome profiles from scRNA-seq data. scEntropy is a straightforward parameter with which to define the intrinsic transcriptional state of a cell that can provide a quantity to measure the developmental process and to distinguish different cell types. The proposed scEntropy followed by Gaussian mixture model (scEGMM) provides a coherent method of cell-type classification that is simple, includes no parameters or clustering and is comparable to existing machine learning-based methods in benchmarking studies. The results of cell-type classification based on scEGMM are robust and easy to biologically interpret.

Study of the Molecular Architecture of Keratin Filaments by Electron Microscopy

1982 ◽  
Vol 40 ◽  
pp. 118-119
Author(s):  
U. Aebi ◽  
P. Rew ◽  
T.-T. Sun
Keyword(s):  
Electron Microscopy ◽  
Structural Organization ◽  
Cell Types ◽  
Structural Features ◽  
Molecular Architecture ◽  
The Past ◽  
Keratin Filaments ◽  
Different Types ◽  
10 Nm Filaments ◽  
Different Cell Types

Various types of intermediate-sized (10-nm) filaments have been found and described in many different cell types during the past few years. Despite the differences in the chemical composition among the different types of filaments, they all yield common structural features: they are usually up to several microns long and have a diameter of 7 to 10 nm; there is evidence that they are made of several 2 to 3.5 nm wide protofilaments which are helically wound around each other; the secondary structure of the polypeptides constituting the filaments is rich in ∞-helix. However a detailed description of their structural organization is lacking to date.

Processing and Characterization of Recombinant von Willebrand Factor Expressed in Different Cell Types Using a Vaccinia Virus Vector

1992 ◽  
Vol 67 (01) ◽  
pp. 154-160 ◽  
Author(s):  
P Meulien ◽  
M Nishino ◽  
C Mazurier ◽  
K Dott ◽  
G Piétu ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Von Willebrand Factor ◽  
Human Fibroblasts ◽  
Active Form ◽  
Cell Types ◽  
Biologically Active ◽  
L Cells ◽  
Von Willebrand ◽  
Different Cell Types ◽  
Willebrand Factor

SummaryThe cloning of the cDNA encoding von Willebrand factor (vWF) has revealed that it is synthesized as a large precursor (pre-pro-vWF) molecule and it is now clear that the prosequence or vWAgll is responsible for the intracellular multimerization of vWF. We have cloned the complete vWF cDNA and expressed it using a recombinant vaccinia virus as vector. We have characterized the structure and function of the recombinant vWF (rvWF) secreted from five different cell types: baby hamster kidney (BHK), Chinese hamster ovary (CHO), human fibroblasts (143B), mouse fibroblasts (L) and primary embryonic chicken cells. Forty-eight hours after infection, the quantity of vWF antigen found in the cell supernatant varied from 3 to 12 U/dl depending on the cell type. By SDS-agarose gel electrophoresis, the percentage of high molecular weight forms of vWF varied from 39 to 49% relative to normal plasma for BHK, CHO, 143B and chicken cells but was less than 10% for L cells. In all cell types, the two anodic subbands of each multimer were missing. The two cathodic subbands were easily detected only in BHK and L cells. By SDS-PAGE of reduced samples, pro-vWF was present in similar quantity to the fully processed vWF subunit in L cells, present in moderate amounts in BHK and CHO and in very low amounts in 143B and chicken cells. rvWF from all cells bound to collagen and to platelets in the presence of ristocetin, the latter showing a high correlation between binding efficiency and degree of multimerization. rvWF from all cells was also shown to bind to purified FVIII and in this case binding appeared to be independent of the degree of multimerization. We conclude that whereas vWF is naturally synthesized only by endothelial cells and megakaryocytes, it can be expressed in a biologically active form from various other cell types.

Role of Transcriptional Read-Through in PRE Activity in Drosophila melanogaster

Acta Naturae ◽  
2016 ◽  
Vol 8 (2) ◽  
pp. 79-86 ◽  
Author(s):  
P. V. Elizar’ev ◽  
D. V. Lomaev ◽  
D. A. Chetverina ◽  
P. G. Georgiev ◽  
M. M. Erokhin
Keyword(s):  
Dna Sequences ◽  
Cell Types ◽  
Transcription Terminator ◽  
Response Elements ◽  
Polycomb Response Elements ◽  
The Individual ◽  
Multicellular Organisms ◽  
Different Cell Types ◽  
Main Factor

Maintenance of the individual patterns of gene expression in different cell types is required for the differentiation and development of multicellular organisms. Expression of many genes is controlled by Polycomb (PcG) and Trithorax (TrxG) group proteins that act through association with chromatin. PcG/TrxG are assembled on the DNA sequences termed PREs (Polycomb Response Elements), the activity of which can be modulated and switched from repression to activation. In this study, we analyzed the influence of transcriptional read-through on PRE activity switch mediated by the yeast activator GAL4. We show that a transcription terminator inserted between the promoter and PRE doesnt prevent switching of PRE activity from repression to activation. We demonstrate that, independently of PRE orientation, high levels of transcription fail to dislodge PcG/TrxG proteins from PRE in the absence of a terminator. Thus, transcription is not the main factor required for PRE activity switch.

MAPK: A Key Player in the Development and Progression of Stroke

2020 ◽  
Vol 19 (4) ◽  
pp. 248-256
Author(s):  
Yangmin Zheng ◽  
Ziping Han ◽  
Haiping Zhao ◽  
Yumin Luo
Keyword(s):  
Ischemic Stroke ◽  
Signaling Pathway ◽  
Complex Disease ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Effective Prevention ◽  
Prevention And Treatment ◽  
Different Cell Types

Conclusion: Stroke is a complex disease caused by genetic and environmental factors, and its etiological mechanism has not been fully clarified yet, which brings great challenges to its effective prevention and treatment. MAPK signaling pathway regulates gene expression of eukaryotic cells and basic cellular processes such as cell proliferation, differentiation, migration, metabolism and apoptosis, which are considered as therapeutic targets for many diseases. Up to now, mounting evidence has shown that MAPK signaling pathway is involved in the pathogenesis and development of ischemic stroke. However, the upstream kinase and downstream kinase of MAPK signaling pathway are complex and the influencing factors are numerous, the exact role of MAPK signaling pathway in the pathogenesis of ischemic stroke has not been fully elucidated. MAPK signaling molecules in different cell types in the brain respond variously after stroke injury, therefore, the present review article is committed to summarizing the pathological process of different cell types participating in stroke, discussed the mechanism of MAPK participating in stroke. We further elucidated that MAPK signaling pathway molecules can be used as therapeutic targets for stroke, thus promoting the prevention and treatment of stroke.

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