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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.
  • 1.4K
  • 10 Feb 2022
Topic Review
A Long-Lasting PARP1-Activation Mediates Signal-Induced Gene Expression
PolyADP-ribosylation is an evolutionary conserved, reversible post-translational modification of proteins. Numerous nuclear proteins act as substrates of the abundant nuclear polyADP-ribose polymerase 1 (PARP1). In this modification, negatively charged ADP-ribose chains constructed on chromatin-bound proteins, cause their repulsion from the negatively charged DNA. In accordance, polyADP-ribosylation is a post-translational modification of proteins that causes relaxation of the highly condensed structure of the chromatin. Histone H1, which is bound to the linker DNA, located between the nucleosomes, is a prominent substrate of PARP1.
  • 1.4K
  • 19 May 2022
Topic Review
Circadian Rhythms and Glioblastomas
Gliomas are solid tumors of the central nervous system (CNS) that originated from different glial cells. The World Health Organization (WHO) classifies these tumors into four groups (I–IV) with increasing malignancy. Glioblastoma (GBM) is the most common and aggressive type of brain tumor classified as grade IV. GBMs are resistant to conventional therapies with poor prognosis after diagnosis even when the Stupp protocol that combines surgery and radiochemotherapy is applied. Nowadays, few novel therapeutic strategies have been used to improve GBM treatment, looking for higher efficiency and lower side effects, but with relatively modest results. The circadian timing system temporally organizes the physiology and behavior of most organisms and daily regulates several cellular processes in organs, tissues, and even in individual cells, including tumor cells.
  • 1.4K
  • 15 Aug 2021
Topic Review
Sphingosine 1-phosphate
The breakdown of the endothelial cell (EC) barrier contributes significantly to sepsis mortality. Sphingosine 1-phosphate (S1P) is one of the most effective EC barrier-stabilizing signaling molecules. Stabilization is mainly transduced via the S1P receptor type 1 (S1PR1). Here, we demonstrate that S1P was autonomously produced by ECs. S1P secretion was significantly higher in primary human umbilical vein endothelial cells (HUVEC) compared to the endothelial cell line EA.hy926. Constitutive barrier stability of HUVEC, but not EA.hy926, was significantly compromised by the S1PR1 antagonist W146 and by the anti-S1P antibody Sphingomab. HUVEC and EA.hy926 differed in the expression of the S1P-transporter Spns2, which allowed HUVEC, but not EA.hy926, to secrete S1P into the extracellular space. Spns2 deficient mice showed increased serum albumin leakage in bronchoalveolar lavage fluid (BALF). Lung ECs isolated from Spns2 deficient mice revealed increased leakage of fluorescein isothiocyanate (FITC) labeled dextran and decreased resistance in electric cell-substrate impedance sensing (ECIS) measurements. Spns2 was down-regulated in HUVEC after stimulation with pro-inflammatory cytokines and lipopolysaccharides (LPS), which contributed to destabilization of the EC barrier. Our work suggests a new mechanism for barrier integrity maintenance. Secretion of S1P by EC via Spns2 contributed to constitutive EC barrier maintenance, which was disrupted under inflammatory conditions via the down-regulation of the S1P-transporter Spns2.
  • 1.4K
  • 30 Oct 2020
Topic Review
Cell-Penetrating Peptides
Cell-penetrating peptides (CPPs) comprise a class of short polypeptides that possess the ability to selectively interact with the cytoplasmic membrane of certain cell types, translocate across plasma membranes and accumulate in the cell cytoplasm, organelles (e.g., the nucleus and mitochondria), and other subcellular compartments. CPPs are either of natural origin or de novo designed and synthesized from segments and patches of larger proteins or designed by algorithms. With such intrinsic characteristics, along with membrane permeation, translocation, and cellular uptake properties, CPPs can intracellularly convey diverse substances and nanomaterials, such as hydrophilic organic compounds and drugs, macromolecules (nucleic acids and proteins), nanoparticles (nanocrystals and polyplexes), metals and radionuclides, which can be covalently attached via CPP N- and C-terminals or through the preparation of CPP complexes. A cumulative number of studies on animal toxins, primarily isolated from the venom of arthropods and snakes, have revealed the cell-penetrating activities of venom peptides and toxins, which can be harnessed for application in biomedicine and pharmaceutical biotechnology.
  • 1.4K
  • 12 Mar 2021
Topic Review
Regulated Cell Death Modes
Most animal cell types have the ability to undergo turnover at different rates throughout the organism's life span, dying either accidentally or in a deliberate manner. If a cell suffers from irreparable structural or organelle damage, it most likely passively disintegrates and dies. In this case, the plasma membrane ruptures and the noxious intracellular components are released into the extracellular matrix, where they trigger an inflammatory response. However, if a cell sustains non-fatal damage, or if it is too old, contains dysfunctional organelles, has suffered oxidative damage, etc, it is deliberately eliminated through an active, physiologically-regulated process of cell death termed regulated cell death (RCD), which is not accompanied by an inflammatory response. RCD plays beneficial physiological roles in development and in systems maintenance, but can become malignant and lead to pathological conditions when it is impaired, insufficient or in excess.  In the context of liver injury and disease, RCD is pivotal in directing the severity and outcome of the disease. Hepatocyte death is a critical event in the progression of disease due to resultant inflammation, which may lead to fibrosis, cirrhosis, and other morbidities if not treated in a timely manner.
  • 1.4K
  • 18 Feb 2021
Topic Review
DNA Manipulation and Single-Molecule Imaging
DNA replication, repair, and recombination in the cell play a significant role in the regulation of the inheritance, maintenance, and transfer of genetic information. To elucidate the biomolecular mechanism in the cell, some molecular models of DNA replication, repair, and recombination have been proposed. These biological studies have been conducted using bulk assays, such as gel electrophoresis. Because in bulk assays, several millions of biomolecules are subjected to analysis, the results of the biological analysis only reveal the average behavior of a large number of biomolecules. Therefore, revealing the elementary biological processes of a protein acting on DNA (e.g., the binding of protein to DNA, DNA synthesis, the pause of DNA synthesis, and the release of protein from DNA) is difficult. Single-molecule imaging allows the analysis of the dynamic behaviors of individual biomolecules that are hidden during bulk experiments. Thus, the methods for single-molecule imaging have provided new insights into almost all of the aspects of the elementary processes of DNA replication, repair, and recombination. However, in an aqueous solution, DNA molecules are in a randomly coiled state. Thus, the manipulation of the physical form of the single DNA molecules is important. 
  • 1.4K
  • 01 Apr 2021
Topic Review
Magnesium Deficiency and Cardiometabolic Disease
Magnesium (Mg2+) has many physiological functions within the body. These include important roles in maintaining cardiovascular functioning, where it contributes to the regulation of cardiac excitation–contraction coupling, endothelial functioning and haemostasis. The haemostatic roles of Mg2+ impact upon both the protein and cellular arms of coagulation. 
  • 1.4K
  • 26 Jul 2023
Topic Review
The Disease of Sympathetic Overdrive (DSO)
The sympathetic nervous system (SNS) is one of components of the autonomic system (ANS), whose overall ultimate function is to prepare the body for activities, which is a systemic response that affects many organs and systems. Accumulating evidence suggests that the SNS plays a crucial role in human numerous diseases. In the present article, we review the SNS dysfunction and even the disease of sympathetic overdrive (DSO) impact on cardiovascular, digestive, endocrine and metabolic as well as mental nervous system and various systems of the body. Despite the fact that the existence of this disease has not been truly recognized and confirmed. Here we proposed a hypothesis of the disease as DSO for the first time. The aim of the study is identifying the framework of the DSO, including the risk-factors, symptoms, end-points, mechanisms, and the strategies of management in order to improve both of the theory and clinical practice.As the hypothesis of DSO is novel born , the enrichment and improvement of hypothesis of the DSO are surely needed.
  • 1.4K
  • 25 Jul 2024
Topic Review
Ion Channels of Nociception
Acute pain plays the vital role protecting our health whereas chronic and pathological pain are debilitating conditions.  However molecular mechanisms of pain which are the keys for pain relief remain largely unaddressed. Nevertheless, new molecular actors with important roles in pain mechanisms are being characterized, such as the mechanosensitive Piezo ion channels. This study presents modern trends and promising advances in the field of molecular mechanisms of pain. 
  • 1.3K
  • 24 Mar 2021
Topic Review
Molecular Basis of Soybean Cold Tolerance
Cold stress is a major factor influencing the geographical distribution of soybean growth and causes immense losses in productivity. Understanding the molecular mechanisms that the soybean has undergone to survive cold temperatures will have immense value in improving soybean cold tolerance. Cold-tolerant quantitative trait loci (QTLs) were found to be overlapped with the genomic region of maturity loci of E1, E3, E4, pubescence color locus of T, stem growth habit gene locus of Dt1, and leaf shape locus of Ln, indicating that pleiotropic loci may control multiple traits, including cold tolerance. The C-repeat responsive element binding factors (CBFs) are evolutionarily conserved across species. The expression of most GmDREB1s was upregulated by cold stress and overexpression of GmDREB1B;1 in soybean protoplast, and transgenic Arabidopsis plants can increase the expression of genes with the DRE core motif in their promoter regions under cold stress. Other soybean cold-responsive regulators, such as GmMYBJ1, GmNEK1, GmZF1, GmbZIP, GmTCF1a, SCOF-1 and so on, enhance cold tolerance by regulating the expression of COR genes in transgenic Arabidopsis. CBF-dependent and CBF-independent pathways are cross-talking and work together to activate cold stress gene expression. 
  • 1.3K
  • 02 Feb 2023
Topic Review
Cardiac Autonomic Neuropathy
Cardiac autonomic neuropathy (CAN) is one of the earliest manifestations of type 2 diabetes (T2D). It constitutes the major cause of silent cardiovascular events in patients without overt cardiac disease. The high prevalence of CAN in patients newly diagnosed with T2D suggests that its pathophysiology is rooted in an earlier stage of metabolic derangement, possibly being prediabetes.
  • 1.3K
  • 11 Dec 2020
Topic Review
Histone-lysine N-methyltransferase Subclass Complexes
KMT2 (histone-lysine N-methyltransferase subclass 2) complexes methylate lysine 4 on the histone H3 tail at gene promoters and gene enhancers. H3K4 methylation mark allows to control gene transcription. The KMT2s function in large multi-subunit complexes, which, in vertebrates, are often referred to as COMPASS or COMPASS-like complexes (COMplex of Proteins ASsociated with Set1). These complexes contain an enzyme (KMT2A or KMT2B, KMT2C or KMT2D, KMT2F or KMT2G), common core subunits (WDR5, RBBP5, ASH2L, DPY30) and unique interacting proteins, which are different for each of the three KMT2 groups (A/B, C/D and F/G). Also, the KMT2 complexes dynamically interact with many transcription factors.
  • 1.3K
  • 23 Dec 2020
Topic Review Video
Transgenerational-Epigenetic Inheritance and Immune System
Epigenetic modifications cause heritable changes in gene expression which are not due to alterations in underlying DNA sequence. Inside the eukaryotic nucleus, there is condense packing of DNA around histone proteins to constitute chromatin structure. Epigenetic modifications are caused by factors that alter chromatin structure. Some epigenetic factors are enzymes that regulate DNA methylation and histone modifications, non-coding RNA, and prions. An offspring inherits parental epigenetic modifications but most of them are deleted and reset during early developmental stages. Some epigenetic modifications are retained and persist across multiple generations. If any epigenetic modification is the result of a stimulus or immune response in one generation, such that the modification continues to be inherited in subsequent generations which are not subjected to the stimulus; and the inheritance continues beyond the 3rd generation in the female germline and 2nd generation in male, then the phenomenon is called transgenerational epigenetic inheritance (TGEI). This entry is focused on a review which discusses some examples of TGEI that are reported in association with  immune system development and disorders.
  • 1.3K
  • 22 May 2021
Topic Review
Lysosomes Support DNA Replication
Lysosomes, acidic, membrane-bound organelles, are not only the core of the cellular recycling machinery, but they also serve as signaling hubs regulating various metabolic pathways. Lysosomes maintain energy homeostasis and provide pivotal substrates for anabolic processes, such as DNA replication. Every time the cell divides, its genome needs to be correctly duplicated; therefore, DNA replication requires rigorous regulation. Challenges that negatively affect DNA synthesis, such as nucleotide imbalance, result in replication stress with severe consequences for genome integrity. The lysosomal complex mTORC1 is directly involved in the synthesis of purines and pyrimidines to support DNA replication.
  • 1.3K
  • 25 May 2021
Topic Review
The Origin of Geranylgeraniol and Farnesol
Isoprenoids are the output of the polymerization of five-carbon, branched isoprenic chains derived from isopentenyl pyrophosphate (IPP) and its isomer, dimethylallyl pyrophosphate (DMAPP). Isoprene units are consecutively condensed to form longer structures such as farnesyl and geranylgeranyl pyrophosphate (FPP and GGPP, respectively), necessary for the biosynthesis of several metabolites. Polyprenyl transferases and synthases use polyprenyl pyrophosphates as their natural substrates; however, it is known that free polyprenols, such as farnesol (FOH), and geranylgeraniol (GGOH) can be incorporated into prenylated proteins, ubiquinone, cholesterol, and dolichols. Furthermore, FOH and GGOH have been shown to block the effects of isoprenoid biosynthesis inhibitors such as fosmidomycin, bisphosphonates, or statins in several organisms.
  • 1.3K
  • 13 Dec 2022
Topic Review
Endoplasmic Reticulum Stress
The endoplasmic reticulum (ER) is a principal subcellular organelle responsible for protein quality control in the secretory pathway, preventing protein misfolding and aggregation. Failure of protein quality control in the ER triggers several molecular mechanisms such as ER-associated degradation (ERAD), the unfolded protein response (UPR) or reticulophagy, which are activated upon ER stress (ERS) to re-establish protein homeostasis by transcriptionally and translationally regulated complex signalling pathways.
  • 1.3K
  • 13 Jun 2023
Topic Review
Mammalian Zona Pellucida Glycoproteins
Zona pellucida (ZP) plays an important role in the oocyte lifespan providing mechanical protection and defense against polyspermic fertilization by directly modulating sperm function.
  • 1.3K
  • 27 May 2021
Topic Review
Anti-Cancer Peptides as Immunomodulatory Agents
The usage of peptide-based drugs to combat cancer is gaining significance in the pharmaceutical industry. The collateral damage caused to normal cells due to the use of chemotherapy, radiotherapy, etc. has given an impetus to the search for alternative methods of cancer treatment.
  • 1.3K
  • 23 Dec 2022
Topic Review
Mycotoxins Beauvericin and Enniatins
Mycotoxins are a structurally diverse group of mostly low-molecular-weight compounds. Their structures range from single heterocyclic rings to irregularly arranged rings of six to eight members and their molecular weights are usually less than 1000 Da. Therefore, they do not induce any response in the human immune system.
  • 1.3K
  • 05 Feb 2021
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