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Genetics and exercise: an introduction
Published in Adam P. Sharples, James P. Morton, Henning Wackerhage, Molecular Exercise Physiology, 2022
Claude Bouchard, Henning Wackerhage
Only one DNA strand of the double helix is transcribed into an RNA. Noncoding intron regions copied from the DNA are cut (spliced) out of the RNA and the exons fused together during its processing from “pre-RNA” to mature mRNA. Transcription begins at an initiation site along the DNA strand termed a promoter. Other regulatory DNA sequences are enhancer and silencer sequences. Enhancers are short DNA sequences that are activated when bound by proteins resulting in an increase in transcription (gene turned on). A gene sequence includes variable numbers of enhancers, and there is a relation between the number of activated enhancers and the rate of transcription and resultant amount of mRNA for that gene. In contrast, silencer sequences can bind repressor proteins that attenuate or suppress (silence) the transcription of a gene. Silencers just like enhancers are often located upstream of the gene-coding sequence, but they are also found downstream or far away from the gene. The latter can still impact the rate of transcription because the looping of the DNA within the nucleus brings the enhancer or silencer sites in close proximity to promoter(s).
ChIP-seq analysis
Published in Altuna Akalin, Computational Genomics with R, 2020
One of the first next steps after you have your peaks is to find out what kind of genes they might be associated with. This is very similar to the gene set analysis we introduced for RNA-seq in Chapter 8. The same tools, such as gProfileR package, can be used on the genes associated with the peaks. However, associating peaks to genes is not always trivial due to long-range gene regulation. Many enhancers can regulate genes that are far away and their targets are not always the nearest gene. However, associating peaks to nearest genes is a generally practiced strategy in ChIP-seq analysis. We have introduced how to find the nearest genes in Chapter 6. There are also other R packages that will do the association to genes and the gene set analysis in a single workflow. One such package is rGREAT from Bioconductor. This package relies on a web-based tool called GREAT2.
Disease Prediction and Drug Development
Published in Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam, Introduction to Computational Health Informatics, 2019
Arvind Kumar Bansal, Javed Iqbal Khan, S. Kaisar Alam
Enhancers promote the binding of transcription-factors to the promoters to start transcription. With eukaryotes, the corresponding enhancer could be both upstream (occurring before) or downstream (occurring after) the coding-region. However, in a bacterial gene, the corresponding enhancer always occurs upstream. The coding-region of the eukaryotic genes is a repeated sequence of (exon, intron) pairs, and there can be one or more such pairs.
Developments in the discovery and design of intranasal antidepressants
Published in Expert Opinion on Drug Discovery, 2020
Małgorzata Panek, Paweł Kawalec, Andrzej Pilc, Władysław Lasoń
Apart from new formulations of drug delivery, also some enhancers could be applied to increase the penetration of drugs through the nasal mucosa. In general, enhancers could improve drug absorption by inhibition of enzymatic activity, reduction of mucosal viscosity or elasticity, decrease of mucociliary clearance, opening of the tight junction, as well as drug solubilization or stabilization. Surfactants, fatty acid salts, bile salts, phospholipids, chelators, glycyrrhetinic acid derivatives, cyclodextrins, and glycols are examples of penetration enhancers that were tested for organic drugs [101]. However, the use of enhancers in clinical practice must be careful and requires strict control of critical parameters such as toxicity, variability between patients, or unintentional transport of other molecules [102].
A Woman with Missing Hb A2 Due to a Novel (εγ)δβ0-Thalassemia and a Novel δ-Globin Variant Hb A2-Gebenstorf (HBD: c.209G>A)
Published in Hemoglobin, 2020
Elisabeth Saller, Jeroen Knijnenburg, Cornelis L. Harteveld, Fabrizio Dutly
The human β-globin gene cluster consists of five genes arranged in chromosome 11 in the same order in which they are expressed during development: 5′-ε-, Gγ-, Aγ-, δ- and β-globin gene [Human Genome Variation Society (HGVS): 5′-HBE-HBG2-HBG1-HBD-HBB] [1]. Hb A2, which makes up for 2.5% of the total Hb in adults, is composed of two α- and two δ-globin chains (α2δ2) and can be detected only after birth, when the δ-globin gene expression is increasing and Hb A2 synthesis occurs. The ‘fetal to adult Hb switch’ takes place shortly before birth replacing Hb F (α2γ2) for Hb A (α2β2) as β chain production augments. This is controlled by enhancer-gene promoter interaction that results in recruitment of transcription factors that trigger gene expression. The β-locus control region (β-LCR) enhancer is located 50 kb upstream of the β-globin gene and consists of hypersensitive sites (HS) 1–5 [2]. A phenotypic β-thalassemia (β-thal) minor can be caused by mutation of the β gene, of a regulator such as BCL11A [3] or by deletion of the LCR enhancer itself.
Permeation enhancers in transdermal drug delivery: benefits and limitations
Published in Expert Opinion on Drug Delivery, 2020
Andrej Kováčik, Monika Kopečná, Kateřina Vávrová
To date, hundreds of molecules have been identified to facilitate drug delivery through the skin barrier; some examples illustrating the enhancer chemical heterogeneity are shown in Figure 3. Enhancers can be classified according to various principles. Enhancers could be of natural [11,62,69–75], synthetic [51,64,76,77] or semi-synthetic origin [59,66,73,78–80] (Table 2). According to their general chemical properties, most enhancers can be classified as small solvents [11,56,71,76,81–83], amphiphiles [11,51,59,62,69,70,72,74,76,84] (this includes surfactants [66,85–88] that have been extensively reviewed elsewhere [85]), and peptides [75,89] (Table 2). Next, we suggest a chemical classification using the main functional group; thus, the enhancers include hydrocarbons [62,69,90,91], alcohols [69–71,81,83,92], acetals [85,93], amines [77,94], carboxylic acids [70,72,86,92], esters [11,59,64,66,84,86–88], amides [51,74–76,95,96], and sulfoxides [56,71] (Table 2). We intentionally do not create separate groups for surfactants (all surfactants are amphiphiles, either synthetic or semi-synthetic, and have various functional groups) or terpenes. Individual enhancers of each class including examples of their action are discussed elsewhere [11,16,19,54].