scholarly journals Quantification and Mapping of DNA Modifications

2021 ◽  
Author(s):  
Yi Dai ◽  
Bi-Feng Yuan ◽  
Yu-Qi Feng
Keyword(s):  
Biological Processes ◽  
Dna Molecules ◽  
Substantial Evidence ◽  
Dna Modifications ◽  
Reversible Modification

Apart from the four canonical nucleobases, DNA molecules carry a number of natural modifications. Substantial evidence shows DNA modifications can regulate diverse biological processes. Dynamic and reversible modification of DNA...

scholarly journals Roles of G Protein-Coupled Receptors (GPCRs) in Gastrointestinal Cancers: Focus on Sphingosine 1-Shosphate Receptors, Angiotensin II Receptors, and Estrogen-Related GPCRs

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 2988
Author(s):  
Zhen Zeng ◽  
Chunxiang Ma ◽  
Kexin Chen ◽  
Mingshan Jiang ◽  
Reshma Vasu ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
G Protein ◽  
G Protein Coupled Receptors ◽  
Angiotensin Ii Receptors ◽  
Biological Processes ◽  
Substantial Evidence ◽  
Sphingosine 1 Phosphate ◽  
Gi Cancers ◽  
G Protein Coupled ◽  
Made In

It is well established that gastrointestinal (GI) cancers are common and devastating diseases around the world. Despite the significant progress that has been made in the treatment of GI cancers, the mortality rates remain high, indicating a real need to explore the complex pathogenesis and develop more effective therapeutics for GI cancers. G protein-coupled receptors (GPCRs) are critical signaling molecules involved in various biological processes including cell growth, proliferation, and death, as well as immune responses and inflammation regulation. Substantial evidence has demonstrated crucial roles of GPCRs in the development of GI cancers, which provided an impetus for further research regarding the pathophysiological mechanisms and drug discovery of GI cancers. In this review, we mainly discuss the roles of sphingosine 1-phosphate receptors (S1PRs), angiotensin II receptors, estrogen-related GPCRs, and some other important GPCRs in the development of colorectal, gastric, and esophageal cancer, and explore the potential of GPCRs as therapeutic targets.

scholarly journals The role of vitamin C in epigenetic regulation

2017 ◽  
Vol 71 (1) ◽  
pp. 0-0 ◽  
Author(s):  
Jolanta Guz ◽  
Ryszard Oliński
Keyword(s):  
Vitamin C ◽  
Epigenetic Regulation ◽  
Cultured Cells ◽  
Chromatin Modification ◽  
Enzymatic Reactions ◽  
Biological Processes ◽  
Oxidation Reactions ◽  
Dna Modifications ◽  
Almost All

Vitamin C (L-ascorbic acid) is a micronutrient best known for its anti-scurvy activity in humans. Vitamin C is involved in many biological processes involving enzymatic reactions that are catalyzed by members of dioxygenases which use Fe(II) and 2-oxoglutarate as a co-substrate.The article reviews recent data that suggest the involvement of ascorbate in dioxygenases catalyzed chromatin and DNA modifications which thereby contribute to epigenetic regulation. Concerning chromatin modification, the dioxygenases are involved in distinct demethylation reactions with varying specificity for the position of the lysine on the target histone. TET hydroxylases catalyse the oxidation of methyl groups in the 5 position of cytosine in DNA yielding 5-hydroxymethylcytosine, while further iterative oxidation reactions results in the formation of 5-formylcytosine and 5-carboxylcytosine. A few previous studies demonstrated that ascorbate may enhance generation of 5-hydroxymethylcytosine in cultured cells, probably acting as a cofactor of TETs during hydroxylation of 5-methylcytosine. Physiological concentrations of ascorbate in human serum (10-100 μM) may guarantee stable level of 5-hydroxymethylcytosine, a modification necessary for epigenetic function of the cell. 5-Hydroxymethylcytosine level is substantially decreased in almost all investigated cancers, what may be linked with cancer development. Therefore, it is possible that supplementation with ascorbate could contribute to better management of individual cancer patient. This issue is also discussed in our paper.

scholarly journals Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA

2018 ◽  
Vol 116 (2) ◽  
pp. 641-649 ◽  
Author(s):  
Lee Serpas ◽  
Rebecca W. Y. Chan ◽  
Peiyong Jiang ◽  
Meng Ni ◽  
Kun Sun ◽  
...  
Keyword(s):  
Systemic Circulation ◽  
Biological Processes ◽  
Dna Molecules ◽  
Plasma Dna ◽  
Partial Restoration ◽  
Fetal Dna ◽  
Physical Form ◽  
Circulating Fetal Dna ◽  
Antibody Levels

Circulating DNA in plasma consists of short DNA fragments. The biological processes generating such fragments are not well understood. DNASE1L3 is a secreted DNASE1-like nuclease capable of digesting DNA in chromatin, and its absence causes anti-DNA responses and autoimmunity in humans and mice. We found that the deletion of Dnase1l3 in mice resulted in aberrations in the fragmentation of plasma DNA. Such aberrations included an increase in short DNA molecules below 120 bp, which was positively correlated with anti-DNA antibody levels. We also observed an increase in long, multinucleosomal DNA molecules and decreased frequencies of the most common end motifs found in plasma DNA. These aberrations were independent of anti-DNA response, suggesting that they represented a primary effect of DNASE1L3 loss. Pregnant Dnase1l3−/− mice carrying Dnase1l3+/− fetuses showed a partial restoration of normal frequencies of plasma DNA end motifs, suggesting that DNASE1L3 from Dnase1l3-proficient fetuses could enter maternal systemic circulation and affect both fetal and maternal DNA fragmentation in a systemic as well as local manner. However, the observed shortening of circulating fetal DNA relative to maternal DNA was not affected by the deletion of Dnase1l3. Collectively, our findings demonstrate that DNASE1L3 plays a role in circulating plasma DNA homeostasis by enhancing fragmentation and influencing end-motif frequencies. These results support a distinct role of DNASE1L3 as a regulator of the physical form and availability of cell-free DNA and may have important implications for the mechanism whereby this enzyme prevents autoimmunity.

scholarly journals Large-scale trans-eQTLs affect hundreds of transcripts and mediate patterns of transcriptional co-regulation Short: trans-eQTLs reveal patterns of transcriptional co-regulation

2016 ◽  
Author(s):  
Boel Brynedal ◽  
JinMyung Choi ◽  
Towfique Raj ◽  
Robert Bjornson ◽  
Barbara E Stranger ◽  
...  
Keyword(s):  
Multiple Testing ◽  
Large Scale ◽  
Biological Processes ◽  
Confidence Set ◽  
Substantial Evidence ◽  
Limited Sample ◽  
Phenotypic Differences ◽  
Multiple Transcripts ◽  
A Cell ◽  
Variance Explained

AbstractGenetic variation affecting gene regulation is a driver of phenotypic differences between individuals and can be used to uncover how biological processes are organized in a cell. Although detecting cis-eQTLs is now routine, trans-eQTLs have proven more challenging to find due to the modest variance explained and the multiple testing burden when comparing millions of SNPs for association to thousands of transcripts. Here, we provide evidence for the existence of trans-eQTLs by looking for SNPs associated with the expression of multiple genes simultaneously. We find substantial evidence of trans-eQTLs, with an 1.8-fold enrichment in nominally significant markers in all three populations and significant overlap between results across the populations. These trans-eQTLs target the same genes and show the same direction of effect across populations. We define a high-confidence set of eight independent trans-eQTLs which are associated to multiple transcripts in all three populations, and affect the same targets in all three populations with the same direction of effect. We then show that target transcripts of trans-eQTLs encode proteins that interact more frequently than expected by chance, and are enriched for pathway annotations indicative of roles in basic cell homeostasis. Thus, we have demonstrated that trans-eQTLs can be accurately identified even in studies of limited sample size.

scholarly journals iDNA-MT: Identification DNA Modification Sites in Multiple Species by Using Multi-Task Learning Based a Neural Network Tool

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiao Yang ◽  
Xiucai Ye ◽  
Xuehong Li ◽  
Lesong Wei
Keyword(s):  
State Of The Art ◽  
Computational Method ◽  
Biological Processes ◽  
Accurate Identification ◽  
Task Learning ◽  
Dna Modifications ◽  
Benchmark Datasets ◽  
Comparative Results ◽  
Multiple Species ◽  
Gated Recurrent Units

MotivationDNA N4-methylcytosine (4mC) and N6-methyladenine (6mA) are two important DNA modifications and play crucial roles in a variety of biological processes. Accurate identification of the modifications is essential to better understand their biological functions and mechanisms. However, existing methods to identify 4mA or 6mC sites are all single tasks, which demonstrates that they can identify only a certain modification in one species. Therefore, it is desirable to develop a novel computational method to identify the modification sites in multiple species simultaneously.ResultsIn this study, we proposed a computational method, called iDNA-MT, to identify 4mC sites and 6mA sites in multiple species, respectively. The proposed iDNA-MT mainly employed multi-task learning coupled with the bidirectional gated recurrent units (BGRU) to capture the sharing information among different species directly from DNA primary sequences. Experimental comparative results on two benchmark datasets, containing different species respectively, show that either for identifying 4mA or for 6mC site in multiple species, the proposed iDNA-MT outperforms other state-of-the-art single-task methods. The promising results have demonstrated that iDNA-MT has great potential to be a powerful and practically useful tool to accurately identify DNA modifications.

Replication of Bacteriophage 186 DNA

1972 ◽  
Vol 30 ◽  
pp. 194-195
Author(s):  
Dhruba K. Chattoraj ◽  
Ross B. Inman
Keyword(s):  
Electron Microscopy ◽  
Dna Replication ◽  
Frame Of Reference ◽  
Dna Molecules ◽  
E Coli ◽  
Phage Dna ◽  
Partial Denaturation

Electron microscopy of replicating intermediates has been quite useful in understanding the mechanism of DNA replication in DNA molecules of bacteriophage, mitochondria and plasmids. The use of partial denaturation mapping has made the tool more powerful by providing a frame of reference by which the position of the replicating forks in bacteriophage DNA can be determined on the circular replicating molecules. This provided an easy means to find the origin and direction of replication in λ and P2 phage DNA molecules. DNA of temperate E. coli phage 186 was found to have an unique denaturation map and encouraged us to look into its mode of replication.

Synchrony of Digestion of SV40 DNA by Exonuclease III Determined by EM

1975 ◽  
Vol 33 ◽  
pp. 674-675
Author(s):  
Ray Wu ◽  
G. Ruben ◽  
B. Siegel ◽  
P. Spielman ◽  
E. Jay
Keyword(s):  
Dark Field ◽  
Uranyl Acetate ◽  
Enzyme Digestion ◽  
Dna Molecules ◽  
Exonuclease Iii ◽  
Aluminum Films ◽  
Double Stranded Dna ◽  
Before And After ◽  
Exo Iii ◽  
Sv40 Dna

A method for determining long nucleotide sequences of double-stranded DNA is being developed. It involves (a) the synchronous digestion of the DNA from the 3' ends with EL coli exonuclease III (Exo III) followed by (b) resynthesis with labeled nucleotides and DNA polymerase. A crucial factor in the success of this method is the degree to which the enzyme digestion proceeds synchronously under proper conditions of incubation (step a). Dark field EM is used to obtain accurate measurements on the lengths and distribution of the DNA molecules before and after digestion with Exo III, while gel electrophoresis is used in parallel to obtain a mean length for these molecules. It is the measurements on a large enough sample of individual molecules by EM that provides the information on how synchronously the digestion proceeds. For length measurements, the DNA molecules were picked up on 20-30 Å thick carbon-aluminum films, using the aqueous Kleinschmidt technique and stained with 7.5 x 10-5M uranyl acetate in 90% ethanol for 3 minutes.

Ultrasturcture of cerebellar cells and neuropil in rats subjected to partial global cerebral ischemia

1986 ◽  
Vol 44 ◽  
pp. 126-127
Author(s):  
R.V.W. Dimlich ◽  
M.H. Biros
Keyword(s):  
Purkinje Cells ◽  
Glial Cells ◽  
Granule Cells ◽  
Molecular Layer ◽  
Cell Types ◽  
Primary Objective ◽  
Global Cerebral Ischemia ◽  
Forebrain Ischemia ◽  
Substantial Evidence ◽  
Cerebellar Cells

Although a previous study in this laboratory determined that Purkinje cells of the rat cerebellum did not appear to be damaged following 30 min of forebrain ischemia followed by 30 min of reperfusion, it was suggested that an increase in rough endoplasmic reticulum (RER) and/or polysomes had occurred in these cells. The primary objective of the present study was to morphometrically determine whether or not this increase had occurred. In addition, since there is substantial evidence that glial cells may be affected by ischemia earlier than other cell types, glial cells also were examined. To ascertain possible effects on other cerebellar components, granule cells and neuropil near Purkinje cells as well as neuropil in the molecular layer also were evaluated in this investigation.

Fluorescent potentiometric dyes for membrane-potential imaging

1994 ◽  
Vol 52 ◽  
pp. 166-167
Author(s):  
Leslie M. Loew
Keyword(s):  
Membrane Potential ◽  
Single Cells ◽  
Quantitative Imaging ◽  
Optical Recording ◽  
Biological Processes ◽  
Major Focus ◽  
The Past ◽  
Excitable Systems ◽  
Major Application ◽  
The Impact

A major application of potentiometric dyes has been the multisite optical recording of electrical activity in excitable systems. After being championed by L.B. Cohen and his colleagues for the past 20 years, the impact of this technology is rapidly being felt and is spreading to an increasing number of neuroscience laboratories. A second class of experiments involves using dyes to image membrane potential distributions in single cells by digital imaging microscopy - a major focus of this lab. These studies usually do not require the temporal resolution of multisite optical recording, being primarily focussed on slow cell biological processes, and therefore can achieve much higher spatial resolution. We have developed 2 methods for quantitative imaging of membrane potential. One method uses dual wavelength imaging of membrane-staining dyes and the other uses quantitative 3D imaging of a fluorescent lipophilic cation; the dyes used in each case were synthesized for this purpose in this laboratory.

Apoptosis and development

2003 ◽  
Vol 39 ◽  
pp. 11-24 ◽  
Author(s):  
Justin V McCarthy
Keyword(s):  
Drosophila Melanogaster ◽  
Mammalian Cells ◽  
Cell Number ◽  
Model Organisms ◽  
Biological Processes ◽  
Nematode Caenorhabditis Elegans ◽  
Apoptotic Pathway ◽  
Genetic Pathways ◽  
Evolutionarily Conserved ◽  
Multicellular Organisms

Apoptosis is an evolutionarily conserved process used by multicellular organisms to developmentally regulate cell number or to eliminate cells that are potentially detrimental to the organism. The large diversity of regulators of apoptosis in mammalian cells and their numerous interactions complicate the analysis of their individual functions, particularly in development. The remarkable conservation of apoptotic mechanisms across species has allowed the genetic pathways of apoptosis determined in lower species, such as the nematode Caenorhabditis elegans and the fruitfly Drosophila melanogaster, to act as models for understanding the biology of apoptosis in mammalian cells. Though many components of the apoptotic pathway are conserved between species, the use of additional model organisms has revealed several important differences and supports the use of model organisms in deciphering complex biological processes such as apoptosis.

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