scholarly journals Reprogrammable Recognition Codes in Bicoid Homeodomain-DNA Interaction

2000 ◽  
Vol 20 (20) ◽  
pp. 7673-7684 ◽  
Author(s):  
Vrushank Dave ◽  
Chen Zhao ◽  
Fan Yang ◽  
Chang-Shung Tung ◽  
Jun Ma
Keyword(s):  
Dna Sequences ◽  
Human Disease ◽  
Dna Recognition ◽  
Dna Interaction ◽  
Morphogenetic Protein ◽  
Different Types ◽  
Disease Protein

ABSTRACT We describe experiments to determine how the homeodomain of the Drosophila morphogenetic protein Bicoid recognizes different types of DNA sequences found in natural enhancers. Our chemical footprint analyses reveal that the Bicoid homeodomain makes both shared and distinct contacts with a consensus site A1 (TAATCC) and a nonconsensus site X1 (TAAGCT). In particular, the guanine of X1 at position 4 (TAAGCT) is protected by Bicoid homeodomain. We provide further evidence suggesting that the unique arginine at position 54 (Arg 54) of the Bicoid homeodomain enables the protein to recognize X1 by specifically interacting with this position 4 guanine. We also describe experiments to analyze the contribution of artificially introduced Arg 54 to DNA recognition by other Bicoid-related homeodomains, including that from the human disease protein Pitx2. Our experiments demonstrate that the role of Arg 54 varies depending on the exact homeodomain framework and DNA sequences. Together, our results suggest that Bicoid and its related homeodomains utilize distinct recognition codes to interact with different DNA sequences, underscoring the need to study DNA recognition by Bicoid-class homeodomains in an individualized manner.

scholarly journals The N-Terminal Helix-Turn-Helix Motif of Transcription Factors MarA and Rob Drives DNA Recognition

2020 ◽  
Author(s):  
Marina Corbella ◽  
Qinghua Liao ◽  
Peter M. Kasson ◽  
Shina Caroline Lynn Kamerlin
Keyword(s):  
Transcription Factors ◽  
Dna Binding ◽  
Dna Sequences ◽  
Dynamical Behavior ◽  
Dna Recognition ◽  
Tight Binding ◽  
Binding Mode ◽  
Efficient Design ◽  
Terminal Loop

<div> <div> <div> <p>DNA-binding proteins play an important role in gene regulation and cellular function. The transcription factors MarA and Rob are two homologous members of the AraC/XylS family that regulate multidrug resistance. They share a common DNA-binding domain, and Rob possesses an additional C-terminal domain that permits binding of low-molecular weight effectors. Both proteins possess two helix-turn- helix (HTH) motifs capable of binding DNA; however, while MarA interacts with its promoter through both HTH-motifs, prior studies indicate that Rob binding to DNA via a single HTH-motif is sufficient for tight binding. In the present work, we perform microsecond time scale all-atom simulations of the binding of both transcription factors to different DNA sequences to understand the determinants of DNA recognition and binding. Our simulations characterize sequence-specific changes in the dynamical behavior upon DNA binding, showcasing the role of Arg40 of the N-terminal HTH-motif in allowing for specific tight binding. Finally, our simulations explain how an acidic C-terminal loop of Rob can control DNA binding mode. In doing so, we provide detailed molecular insight into DNA binding and recognition by these proteins, which in turn is an important step towards the efficient design of anti-virulence agents that target these proteins. </p> </div> </div> </div>

Animal Models of Peripheral Neuropathy and Neuropathic Pain

2017 ◽  
Author(s):  
Katelyn Donaldson ◽  
Ahmet Höke
Keyword(s):  
Neuropathic Pain ◽  
Peripheral Neuropathy ◽  
Animal Models ◽  
Human Disease ◽  
New Drugs ◽  
Molecular Pathways ◽  
Peripheral Neuropathies ◽  
Different Types

There are numerous types of peripheral neuropathies and conditions that cause neuropathic pain with varying symptoms and different mechanisms of pathogenesis. Therefore, it is not surprising that many different animal models of peripheral neuropathies and neuropathic pain have been developed with varying degrees of fidelity to recapitulate the human disease. Nevertheless, these models are useful in a deconstructive manner to examine role of specific molecular pathways in pathogenesis of different types of peripheral neuropathies and test potential new drugs.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

Potential Uses of Vinegar as a Medicine and Related in vivo Mechanisms

2016 ◽  
Vol 86 (3-4) ◽  
pp. 127-151 ◽  
Author(s):  
Zeshan Ali ◽  
Zhenbin Wang ◽  
Rai Muhammad Amir ◽  
Shoaib Younas ◽  
Asif Wali ◽  
...  
Keyword(s):  
Chemical Structure ◽  
Review Paper ◽  
Heart Diseases ◽  
Folk Medicine ◽  
Active Role ◽  
Current Review ◽  
Different Types ◽  
Positive Effect

While the use of vinegar to fi ght against infections and other crucial conditions dates back to Hippocrates, recent research has found that vinegar consumption has a positive effect on biomarkers for diabetes, cancer, and heart diseases. Different types of vinegar have been used in the world during different time periods. Vinegar is produced by a fermentation process. Foods with a high content of carbohydrates are a good source of vinegar. Review of the results of different studies performed on vinegar components reveals that the daily use of these components has a healthy impact on the physiological and chemical structure of the human body. During the era of Hippocrates, people used vinegar as a medicine to treat wounds, which means that vinegar is one of the ancient foods used as folk medicine. The purpose of the current review paper is to provide a detailed summary of the outcome of previous studies emphasizing the role of vinegar in treatment of different diseases both in acute and chronic conditions, its in vivo mechanism and the active role of different bacteria.

The Diagnosis of Lupus Anticoagulants by the Activated Partial Thromboplastin Time - The Central Role of Phosphatidyl Serine

1984 ◽  
Vol 52 (02) ◽  
pp. 172-175 ◽  
Author(s):  
P R Kelsey ◽  
K J Stevenson ◽  
L Poller
Keyword(s):  
Screening Method ◽  
Coagulation Factors ◽  
Phosphatidyl Serine ◽  
Test System ◽  
Specific Factor ◽  
Marginal Effect ◽  
Constant Composition ◽  
Lupus Anticoagulants ◽  
Different Types

SummaryLiposomes of pure phospholipids were used in a modified APTT test system and the role of phosphatidyl serine (PS) in determining the sensitivity of the test system to the presence of lupus anticoagulants was assessed. Six consecutive patients with lupus anticoagulants and seven haemophiliacs with anticoagulants directed at specific coagulation factors, were studied. Increasing the concentration of phospholipid in the test system markedly reduced the sensitivity to lupus anticoagulants but had marginal effect on the specific factor inhibitors. The same effect was achieved when the content of PS alone was increased in a vehicle liposome of constant composition.The results suggest that the lupus anticoagulants can best be detected by a screening method using an APTT test with a reagent of low PS content. The use of a reagent rich in PS will largely abolish the lupus anticoagulant’s effect on the APTT. An approach using the two different types of reagent may facilitate differentiation of lupus inhibitors from other types of anticoagulant.

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.

The Role of Evaluative Tools in the Creation of the Memorial Media Portrait of Jacques Chirac (1932—2019)

2020 ◽  
pp. 97-110
Author(s):  
E. N. Mikhailova ◽  
V. A. Telegina
Keyword(s):  
Print Media ◽  
Political Elite ◽  
Systematic Analysis ◽  
Research Material ◽  
Political Orientations ◽  
Different Types ◽  
The Media ◽  
The Creation ◽  
Entire Text

The article is devoted to the study of evaluative tools used in modern French media in order to form the media image of a representative of the political elite. The techniques used in the creation of a memorial media portrait of Jacques Chirac (1932—2019), President of France from 1995 to 2007 are considered. The research material was the most prestigious French print media of various political orientations, published in late September — early October 2019 in connection with the death of the ex-President of the French Republic. The relevance of the research topic is dictated by the close attention of modern linguistics to axiological phenomena, differently presented in different types of discursive practices. The novelty of the study is due to the appeal to the analysis of the complex of evaluation tools used in the French print media when characterizing the former leader of the state during the nation’s farewell period. The estimated potential of the title of the article and its influence on the formation of the estimated vector of the entire text of the publication are shown. A systematic analysis of the assessment expression means, reflected in the memorial media portrait of the politician, is given. The factors that influenced the peculiarities of their use in this type of media portrait are revealed.

The influence of information relevance on the continued influence effect of misinformation

2020 ◽  
Author(s):  
Hua Jin ◽  
Lina Jia ◽  
Xiaojuan Yin ◽  
Shilin Wei ◽  
Guiping Xu
Keyword(s):  
Experimental Study ◽  
Questionnaire Survey ◽  
Personal Involvement ◽  
Influence Effect ◽  
Information Relevance ◽  
Different Types ◽  
Role Of Information

Misinformation often continues to influence people’s cognition even after corrected (the ‘continued influence effect of misinformation’, the CIEM). This study investigated the role of information relevance in the CIEM by questionnaire survey and experimental study. The results showed that information with higher relevance to the individuals had a larger CIEM, indicating a role of information relevance in the CIEM. Personal involvement might explain the effects of information relevance on the CIEM. This study provides insightful clues for reducing the CIEM in different types of misinformation and misinformation with varying relevance.

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