scholarly journals Mapping the dynamic transfer functions of epigenome editing

2021 ◽  
Author(s):  
Jessica B. Lee ◽  
Leandra M. Caywood ◽  
Jennifer Y. Lo ◽  
Nicholas Levering ◽  
Albert J. Keung
Keyword(s):  
Information Transfer ◽  
Transfer Functions ◽  
Stem Cell Differentiation ◽  
Biological Information ◽  
Fluorescent Reporter ◽  
Epigenome Editing ◽  
Eukaryotic Promoter ◽  
Physiological Processes ◽  
Signaling Components ◽  
Rich Content

AbstractBiological information can be encoded in the dynamics of signaling components which has been implicated in a broad range of physiological processes including stress response, oncogenesis, and stem cell differentiation. To study the complexity of information transfer across the eukaryotic promoter, we screened 119 dynamic conditions—modulating the frequency, intensity, and pulse width of light—regulating the binding of an epigenome editor to a fluorescent reporter. This system revealed highly tunable gene expression and filtering behaviors and provided the most comprehensive quantification to date of the maximum amount of information that can be reliably transferred across a promoter as ∼1.7 bits. Using a library of over 100 orthogonal epigenome editors, we further determined that chromatin state could be used to tune mutual information and expression levels, as well as completely alter the input-output transfer function of the promoter. This system unlocks the information-rich content of eukaryotic epigenome editing.

scholarly journals Assessing the measurement transfer function of single-cell RNA sequencing

2016 ◽  
Author(s):  
Hannah R. Dueck ◽  
Rizi Ai ◽  
Adrian Camarena ◽  
Bo Ding ◽  
Reymundo Dominguez ◽  
...  
Keyword(s):  
Transfer Function ◽  
Single Cell ◽  
Rna Sequencing ◽  
Large Scale ◽  
Transfer Functions ◽  
Single Cells ◽  
Biological Information ◽  
Gene Detection ◽  
Single Cell Rna Sequencing ◽  
Scale Control

AbstractRecently, measurement of RNA at single cell resolution has yielded surprising insights. Methods for single-cell RNA sequencing (scRNA-seq) have received considerable attention, but the broad reliability of single cell methods and the factors governing their performance are still poorly known. Here, we conducted a large-scale control experiment to assess the transfer function of three scRNA-seq methods and factors modulating the function. All three methods detected greater than 70% of the expected number of genes and had a 50% probability of detecting genes with abundance greater than 2 to 4 molecules. Despite the small number of molecules, sequencing depth significantly affected gene detection. While biases in detection and quantification were qualitatively similar across methods, the degree of bias differed, consistent with differences in molecular protocol. Measurement reliability increased with expression level for all methods and we conservatively estimate the measurement transfer functions to be linear above ~5-10 molecules. Based on these extensive control studies, we propose that RNA-seq of single cells has come of age, yielding quantitative biological information.

scholarly journals Biodiversity of CS–proteoglycan sulphation motifs: chemical messenger recognition modules with roles in information transfer, control of cellular behaviour and tissue morphogenesis

2018 ◽  
Vol 475 (3) ◽  
pp. 587-620 ◽  
Author(s):  
Anthony Hayes ◽  
Kazuyuki Sugahara ◽  
Brooke Farrugia ◽  
John M. Whitelock ◽  
Bruce Caterson ◽  
...  
Keyword(s):  
Information Transfer ◽  
Enzyme Inhibitors ◽  
Chondroitin Sulphate ◽  
Chain Structure ◽  
Bioactive Molecules ◽  
Biological Information ◽  
Extracellular Milieu ◽  
Overwhelming Evidence ◽  
Chemical Messenger ◽  
Cellular Behaviour

Chondroitin sulphate (CS) glycosaminoglycan chains on cell and extracellular matrix proteoglycans (PGs) can no longer be regarded as merely hydrodynamic space fillers. Overwhelming evidence over recent years indicates that sulphation motif sequences within the CS chain structure are a source of significant biological information to cells and their surrounding environment. CS sulphation motifs have been shown to interact with a wide variety of bioactive molecules, e.g. cytokines, growth factors, chemokines, morphogenetic proteins, enzymes and enzyme inhibitors, as well as structural components within the extracellular milieu. They are therefore capable of modulating a panoply of signalling pathways, thus controlling diverse cellular behaviours including proliferation, differentiation, migration and matrix synthesis. Consequently, through these motifs, CS PGs play significant roles in the maintenance of tissue homeostasis, morphogenesis, development, growth and disease. Here, we review (i) the biodiversity of CS PGs and their sulphation motif sequences and (ii) the current understanding of the signalling roles they play in regulating cellular behaviour during tissue development, growth, disease and repair.

scholarly journals Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells

2020 ◽  
Vol 21 (14) ◽  
pp. 5078 ◽  
Author(s):  
Walter J. Lukiw ◽  
Aileen I. Pogue
Keyword(s):  
Information Transfer ◽  
Biological Information ◽  
Messenger Rnas ◽  
Innate Immune Signaling ◽  
Cells Of Origin ◽  
Metabolic Products ◽  
Inflammatory Phenotype ◽  
The Central Nervous System ◽  
Neuro Inflammation ◽  
End Stage

Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30–1000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (Aβ) peptides. Brain microglia, for example, respond to both acute CNS injuries and degenerative diseases with complex reactions via the induction of a pro-inflammatory phenotype, and secrete EXs and EMVs enriched in selective pathogenic microRNAs (miRNAs) such as miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155, and others that are known to promote neuro-inflammation, induce complement activation, disrupt innate–immune signaling and deregulate the expression of neuron-specific phosphoproteins involved in neurotropism and synaptic signaling. This communication will review our current understanding of the trafficking of miRNA-containing EXs and EMVs from astrocytes and “activated pro-inflammatory” microglia to target neurons in neurodegenerative diseases with an emphasis on Alzheimer’s disease wherever possible.

scholarly journals A Multidisciplinary Review of the Roles of Cripto in the Scientific Literature Through a Bibliometric Analysis of its Biological Roles

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1480
Author(s):  
Elisa Rodrigues Sousa ◽  
Eugenio Zoni ◽  
Sofia Karkampouna ◽  
Federico La Manna ◽  
Peter C. Gray ◽  
...  
Keyword(s):  
Bibliometric Analysis ◽  
Scientific Literature ◽  
Stem Cell Differentiation ◽  
Tissue Growth ◽  
Growth And Remodeling ◽  
Comprehensive Overview ◽  
Critical Knowledge ◽  
Physiological Processes ◽  
First Time ◽  
Glucose Regulated Protein

Cripto is a small glycosylphosphatidylinisitol (GPI)-anchored and secreted oncofetal protein that plays important roles in regulating normal physiological processes, including stem cell differentiation, embryonal development, and tissue growth and remodeling, as well as pathological processes such as tumor initiation and progression. Cripto functions as a co-receptor for TGF-β ligands such as Nodal, GDF1, and GDF3. Soluble and secreted forms of Cripto also exhibit growth factor-like activity and activate SRC/MAPK/PI3K/AKT pathways. Glucose-Regulated Protein 78 kDa (GRP78) binds Cripto at the cell surface and has been shown to be required for Cripto signaling via both TGF-β and SRC/MAPK/PI3K/AKT pathways. To provide a comprehensive overview of the scientific literature related to Cripto, we performed, for the first time, a bibliometric analysis of the biological roles of Cripto as reported in the scientific literature covering the last 10 years. We present different fields of knowledge in comprehensive areas of research on Cripto, ranging from basic to translational research, using a keyword-driven approach. Our ultimate aim is to aid the scientific community in conducting targeted research by identifying areas where research has been conducted so far and, perhaps more importantly, where critical knowledge is still missing.

Exosomes: Applications in Respiratory Infectious Diseases and Prospects for Coronavirus Disease 2019 (COVID-19)

2020 ◽  
Vol 16 (4) ◽  
pp. 399-418
Author(s):  
Jia Feng ◽  
Ahmed Waqas ◽  
Zhihan Zhu ◽  
Lukui Chen
Keyword(s):  
Infectious Diseases ◽  
Immune Surveillance ◽  
Cell Communication ◽  
Stem Cell Differentiation ◽  
Target Cells ◽  
Physiological Processes ◽  
Global Pandemic ◽  
New Ideas ◽  
Respiratory Infectious Diseases ◽  
Almost All

Exosomes are small extracellular vesicles of 30–150 nm diameter secreted by almost all cells. In recent years, with continuous deeper understanding of exosomes physiological functions, different reports have proven that exosomes can facilitate cell-to-cell communication by binding to target cells and transferring their contents, together with RNAs, DNAs, proteins, and lipids between cells and tissues. With advantages that exosomes can be involved in various types of physiological processes, such as blood coagulation, cellular homeostasis, inflammation, immune surveillance, stem cell differentiation, neuroprotection, and tissue regeneration and angiogenesis. Exosomes have been demonstrated that they can be applied in identification and treatment of multiple disorders such as cancers, cerebral ischemia, and respiratory infectious diseases. Importantly, researchers utilize application of exosomes in the treatment of various respiratory infectious diseases that have made some breakthrough progress. However, with the global pandemic of Coronavirus Disease 2019 (COVID-19), we have focused on applications of exosomes in respiratory infectious diseases and their serious complications, including influenza, TB, ARDS and sepsis. In this review, we explain the use of exosomes in various respiratory infectious diseases and their serious complications, and hope to provide new ideas for the treatment of new coronavirus infections.

G-Protein-Coupled Receptors in Drug Discovery: Nanosizing Using Cell-Free Technologies and Molecular Biology Approaches

2005 ◽  
Vol 10 (8) ◽  
pp. 765-779 ◽  
Author(s):  
Wayne R. Leifert ◽  
Amanda L. Aloia ◽  
Olgatina Bucco ◽  
Richard V. Glatz ◽  
Edward J. McMurchie
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
Drug Targets ◽  
G Protein Coupled Receptors ◽  
Orphan Receptors ◽  
Molecular Switching ◽  
Physiological Processes ◽  
Current Cell ◽  
G Protein Coupled ◽  
Signaling Components

Signal transduction by G-protein-coupled receptors (GPCRs) underpins a multitude of physiological processes. Ligand recognition by the receptor leads to activation of a genericmolecular switch involving heterotrimeric G-proteins and guanine nucleotides. Signal transduction has been studied extensively with both cell-based systems and assays comprising isolated signaling components. Interest and commercial investment in GPCRs in areas such as drug targets, orphan receptors, highthroughput screening, biosensors, and so on will focus greater attention on assay development to allow for miniaturization, ultra-high throughput and, eventually, microarray/biochip assay formats. Although cell-based assays are adequate for many GPCRs, it is likely that these formatswill limit the development of higher density GPCRassay platforms mandatory for other applications. Stable, robust, cell-free signaling assemblies comprising receptor and appropriate molecular switching components will form the basis of future GPCR assay platforms adaptable for such applications as microarrays. The authors review current cell-free GPCR assay technologies and molecular biological approaches for construction of novel, functional GPCR assays.

scholarly journals Insuperable problems of the genetic code initially emerging in an RNA World

2017 ◽  
Author(s):  
Peter R Wills ◽  
Charles W Carter
Keyword(s):  
Protein Synthesis ◽  
Information Processing ◽  
Natural Selection ◽  
Information Transfer ◽  
Rna World ◽  
Biological Information ◽  
Universal System ◽  
Biological Information Processing ◽  
Relationship Of ◽  
The Relationship

AbstractDifferential equations for error-prone information transfer (template replication, transcription or translation) are developed in order to consider, within the theory of autocatalysis, the advent of coded protein synthesis. Variations of these equations furnish a basis for comparing the plausibility of contrasting scenarios for the emergence of tRNA aminoacylation, ultimately by enzymes, and the relationship of this process with the origin of the universal system of molecular biological information processing embodied in the Central Dogma. The hypothetical RNA World does not furnish an adequate basis for explaining how this system came into being, but principles of self-organisation that transcend Darwinian natural selection furnish an unexpectedly robust basis for a rapid, concerted transition to genetic coding from a peptide•RNA world.

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