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Topic Review
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Topic Review
Acyclic Nucleic Acids with Phosphodiester Linkages
The pseudo-rotational flexibility of the ribonucleotide is considerably limited due to the anomeric effect, and RNA/RNA and RNA/DNA duplexes are generally more thermally stable than DNA/DNA duplexes. The rigidity of the cyclic scaffold has been considered important for the formation of thermally stable duplexes, and the unexpectedly high thermal stability of duplexes formed with the participation of LNA oligomers could serve as an excellent justification for this point of view. However, this generalization is not consistent with the behavior of Peptide Nucleic Acids (PNA), in which the heterocyclic bases are attached to a linear peptide-like backbone, since duplexes composed of RNA or DNA and PNA strands are far more stable than RNA/RNA and DNA/DNA ones. This phenomenon may be attributed to the absence of a negative charge in the backbone, such that the absence of repulsive interactions balances the entropic cost of proper spatial organization of the flexible PNA scaffolds. Nonetheless, the widely accepted importance of the cyclic sugar components for the stability of the duplexes could be questioned. There is another perspective that can be applied to the acyclic analogs of nucleic acids that is related to the origin of life. The synthetic efforts on acyclic analogs of nucleic acids and provides information on the most interesting features of selected classes of such compounds, are here described. The selection includes the following types of analogs: Flexible (FNA), Unlocked (UNA), Glycol (GNA), Butyl (BuNA), Threoninol (TNA) and Serinol Nucleic Acids (SNA). These classes of analogs are discussed in terms of their synthetic methods, the thermal stability of their homo- and hetero-duplexes and their applicability in biological and biochemical research and nanotechnology.
664
10 Feb 2022
Topic Review
Acyl-CoA, Lysocardiolipin Acyltransferase 1 and Age-Related Diseases
Cardiolipin (CL) is a mitochondrial signature phospholipid that plays a pivotal role in mitochondrial dynamics, membrane structure, oxidative phosphorylation, mtDNA bioenergetics, and mitophagy. The depletion or abnormal acyl composition of CL causes mitochondrial dysfunction, which is implicated in the pathogenesis of aging and age-related disorders. However, the molecular mechanisms by which mitochondrial dysfunction causes age-related diseases remain poorly understood. Studies in the field has identified acyl-CoA: lysocardiolipin acyltransferase 1 (ALCAT1), an acyltransferase upregulated by oxidative stress, as a key enzyme that promotes mitochondrial dysfunction in age-related diseases. ALCAT1 catalyzes CL remodeling with very-long-chain polyunsaturated fatty acids, such as docosahexaenoic acid (DHA). Enrichment of DHA renders CL highly sensitive to oxidative damage by reactive oxygen species (ROS). Oxidized CL becomes a new source of ROS in the form of lipid peroxides, leading to a vicious cycle of oxidative stress, CL depletion, and mitochondrial dysfunction. Consequently, ablation or the pharmacological inhibition of ALCAT1 have been shown to mitigate obesity, type 2 diabetes, heart failure, cardiomyopathy, fatty liver diseases, neurodegenerative diseases, and cancer.
574
17 Jun 2022
Topic Review
ADA Gene
Adenosine deaminase
603
04 Jan 2021
Topic Review
ADAM Proteases
Limited proteolysis reactions by a disintegrin and metalloproteases (ADAMs) are key events in several paracrine signalling pathways. Therefore, ADAM proteases might also represent master-switches during hepatic fibrosis and other pathophysiologic events. Known and potential fibrosis-associated pathways regulated by ADAM proteases are discussed and the current knowledge on ADAM protease implication in several disease states is reviewed.
334
13 Jul 2023
Topic Review
ADAM9 in Cancers
ADAM9 plays an important role in tumor biology. It is overexpressed in several cancer types and is correlated with tumor aggressiveness and poor prognosis. Through either proteolytic or non-proteolytic pathways, ADAM9 promotes tumor progression, therapeutic resistance, and metastasis of cancers. Therefore, comprehensively understanding the mechanism of ADAM9 is crucial for the development of therapeutic anti-cancer strategies.
662
13 Jan 2021
Topic Review
Adams-Oliver Syndrome
Adams-Oliver syndrome is a rare condition that is present at birth. The primary features are an abnormality in skin development (called aplasia cutis congenita) and malformations of the limbs. A variety of other features can occur in people with Adams-Oliver syndrome.
863
04 Feb 2021
Topic Review
ADAMTS and Fertility in Females and Males
The ADAMTS (A Disintegrin and Metalloproteinase with Thrombospondin Motifs) family genes code for key metalloproteinases in the remodeling process of different ECM. Several genes of this family encode for proteins with important functions in reproductive processes; in particular, ADAMTS1, 4, 5 and 9 are genes that are differentially expressed in cell types and the physiological stages of reproductive tissues. ADAMTS enzymes degrade proteoglycans in the ECM of the follicles so that the oocytes can be released and regulate follicle development during folliculogenesis, favoring the action of essential growth factors, such as FGF-2, FGF-7 and GDF-9. The transcriptional regulation of ADAMTS1 and 9 in preovulatory follicles occurs because of the gonadotropin surge in preovulatory follicles, via the progesterone/progesterone receptor complex. In addition, in the case of ADAMTS1, pathways involving protein kinase A (PKA), extracellular signal regulated protein kinase (ERK1/2) and the epidermal growth factor receptor (EGFR) might contribute to ECM regulation. Different Omic studies indicate the importance of genes of the ADAMTS family from a reproductive aspect. ADAMTS genes could serve as biomarkers for genetic improvement and contribute to enhance fertility and animal reproduction.
209
11 Aug 2023
Topic Review
ADAMTS Proteins and Vascular Remodeling in Aortic Aneurysms
Extracellular matrix (ECM) undergoes remodeling processes to regulate vascular smooth muscle and endothelial cells’ proliferation, differentiation, and adhesion. Abnormalities affecting the ECM can lead to alteration in cellular behavior and from this, this can conduce to the development of pathologies. Metalloproteases play a key role in maintaining the homeostasis of ECM by mediating the cleavage of different ECM components. There are different types of metalloproteases: matrix metalloproteinases (MMPs), disintegrin and metalloproteinases (ADAMs), and ADAMs with thrombospondin motifs (ADAMTSs). ADAMTSs have been found to participate in cardiovascular physiology and diseases and specifically in aortic aneurysms. This entry aims to decipher the potential role of ADAMTS proteins in the physiopathologic development of Thoracic Aortic Aneurysms (TAA) and Abdominal Aortic Aneurysms (AAA).
597
12 Jan 2022
Topic Review
ADAMTSL4 Gene
ADAMTS like 4
414
05 Apr 2021
Topic Review
Adaptation of Seed Germination
Environmental conditions are the basis of plant reproduction and are the critical factors controlling seed dormancy and germination. Global climate change is currently affecting environmental conditions and changing the reproduction of plants from seeds. Disturbances in germination will cause disturbances in the diversity of plant communities. Models developed for climate change scenarios show that some species will face a significant decrease in suitable habitat area. Dormancy is an adaptive mechanism that affects the probability of survival of a species. The ability of seeds of many plant species to survive until dormancy recedes and meet the requirements for germination is an adaptive strategy that can act as a buffer against the negative effects of environmental heterogeneity. The influence of temperature and humidity on seed dormancy status underlines the need to understand how changing environmental conditions will affect seed germination patterns.
3.6K
06 Feb 2021
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