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Topic Review
Tumor Necrosis Factor -Related Apoptosis-Inducing Ligand Signaling Pathways
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a type II transmembrane protein that undergoes proteolytic cleavage to produce an extracellular ligand. TRAIL can bind to decoy receptor 1 (DcR1) which lacks a death domain (DD) altogether, and DcR2 which has a truncated DD. These decoy receptors are unable to induce DISC (death-inducing signaling complex) formation and act as negative regulators of the apoptotic signaling by competitively binding TRAIL. The canonical TRAIL-induced apoptotic signaling pathway is an example of apoptosis mediated through the extrinsic death pathway, which entails activation of cell-surface receptors by a ligand to induce activation of downstream caspases.
  • 1.9K
  • 30 Nov 2022
Topic Review
Histone Modifications Involved in E–P Interactions
The physical interactions between enhancers and promoters create chromatin conformations involved in gene regulation.  Although it is not entirely comprehensive how chromatin-mediated enhancer–promoter (E–P) interactions with various histone marks can affect gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential to control gene expression.
  • 1.9K
  • 21 Nov 2022
Topic Review
Molecular Mechanisms of Parthanatos
Differential evolution of apoptosis, programmed necrosis, and autophagy, parthanatos is a form of cell death mediated by poly(ADP-ribose) polymerase 1 (PARP1), which is caused by DNA damage. PARP1 hyper-activation stimulates apoptosis-inducing factor (AIF) nucleus translocation, and accelerates nicotinamide adenine dinucleotide (NAD+) and adenosine triphosphate (ATP) depletion, leading to DNA fragmentation. The mechanisms of parthanatos mainly include DNA damage, PARP1 hyper-activation, PAR accumulation, NAD+ and ATP depletion, and AIF nucleus translocation. Parthanatos, a kind of new programmed death mode, has been put forward by Professors Ted and Valina Dawson to indicate a caspase-independent cell death subroutine that critically relies on the hyper-activation of poly(ADP-ribose) polymerase 1 (PARP1).
  • 1.9K
  • 18 Jul 2022
Topic Review
Circular Bacterial Chromosome
A circular bacterial chromosome is a bacterial chromosome in the form of a molecule of circular DNA. Unlike the linear DNA of most eukaryotes, typical bacterial chromosomes are circular. Most bacterial chromosomes contain a circular DNA molecule – there are no free ends to the DNA. Free ends would otherwise create significant challenges to cells with respect to DNA replication and stability. Cells that do contain chromosomes with DNA ends, or telomeres (most eukaryotes), have acquired elaborate mechanisms to overcome these challenges. However, a circular chromosome can provide other challenges for cells. After replication, the two progeny circular chromosomes can sometimes remain interlinked or tangled, and they must be resolved so that each cell inherits one complete copy of the chromosome during cell division.
  • 1.9K
  • 25 Nov 2022
Topic Review
Neutrophil Apoptosis as A Powerful Anti-Inflammatory Signal
Neutrophils are highly abundant circulating leukocytes that are amongst the first cells to be recruited to sites of infection or sterile injury. Their ability to generate and release powerful cytotoxic products ties with their role in host defence from bacterial and fungal infections. Neutrophilic inflammation is tightly regulated to limit the amount of ‘bystander injury’ caused. Neutrophils were in the past regarded as short-lived, indiscriminate killers of invading microorganisms. Neutrophils are recognised to also have important anti-inflammatory functions that are critical for the resolution of inflammation and return to homeostasis.
  • 1.9K
  • 30 Dec 2022
Topic Review
Minor Intron Splicing
Pre-mRNA splicing is an essential step in gene expression and is catalyzed by two machineries in eukaryotes: the major (U2 type) and minor (U12 type) spliceosomes. While the majority of introns in humans are U2 type, less than 0.4% are U12 type, also known as minor introns (mi-INTs), and require a specialized spliceosome composed of U11, U12, U4atac, U5, and U6atac snRNPs. The high evolutionary conservation and apparent splicing inefficiency of U12 introns have set them apart from their major counterparts and led to speculations on the purpose for their existence.
  • 1.9K
  • 21 Jun 2021
Topic Review
C. albicans
Candida albicans is a major fungal pathogen of humans, accounting for 15% of nosocomial infections with an estimated attributable mortality of 47%. C. albicans is usually a benign member of the human microbiome in healthy people.
  • 1.9K
  • 12 Aug 2021
Topic Review
Female Germ Cell Development
In the present era, infertility is one of the major issues which restricts many couples to have their own children. Infertility is the inability to achieve a clinical pregnancy after regular unprotected sexual intercourse for the period of one year or more. Various factors including defective male or female germ cell development, unhealthy and improper lifestyles, diseases like cancer and associated chemo-or-radiation therapies, congenital disorders, etc., may be responsible for infertility. Therefore, it is highly important to understand the basic concepts of germ cell development including primordial germ cell (PGC) formation, specification, migration, entry to genital ridges and their molecular mechanisms, activated pathways, paracrine and autocrine signaling, along with possible alteration which can hamper germ cell development and can cause adversities like cancer progression and infertility. Knowing all these aspects in a proper way can be very much helpful in improving our understanding about gametogenesis and finding possible ways to cure related disorders. 
  • 1.9K
  • 10 Jun 2021
Topic Review
Transcriptionally Active Chromatin Structure
Chromatin structure can either positively or negatively regulates transcription and plays an essential role in eukaryotic gene expression and cell identity. 
  • 1.9K
  • 13 May 2021
Topic Review
Bisphenol A-Induced Male Infertility
Bisphenol A (BPA) is a well-known endocrine disruptor present in epoxy resins and polycarbonate plastics, which negatively disturbs the male reproductive system affecting male fertility. In vivo studies showed that BPA exposure has deleterious effects on spermatogenesis by disturbing the hypothalamic-pituitary-gonadal axis and inducing oxidative stress in the testis. This compound seems to disrupt hormone signalling even at low concentrations, modifying the levels of inhibin B, oestradiol, and testosterone. The adverse effects on seminal parameters are mainly supported by studies based on urinary BPA concentration, showing a negative association between BPA levels and sperm concentration, motility, normal morphology and sperm DNA damage.
  • 1.9K
  • 01 Apr 2021
Topic Review
Intracellular Signalling in Wound Healing
The cells response to injury is initiated by growth factors and cytokines that play a key role in wound restoration, and their biological action is achieved via signal transduction. Growth factors and cytokines play distinct roles through all phases of wound healing. In response to injury, they can trigger several strategic signalling transduction pathways that are mostly activated during embryonic skin development. Extracellular signal-regulated kinases (ERKs) and calcium (Ca2+) are the first intracellular signalling molecules for tissue repair response. These signalling molecules regulate several biological activities including cellular migration, proliferation, contractility, survival and many more related to different transcription factors that are usually induced by several other intracellular signalling pathways. This phenomenon makes it difficult to link a specific signalling response to injury.
  • 1.8K
  • 28 Apr 2022
Topic Review
Cardiovascular Diseases and Stem Cells
This entry provides an update on previous and current research in the field of Cardiovascular diseases (CVDs), a class of disorders affecting the heart or blood vessels. Despite progress in clinical research and therapy, CVDs still represent the leading cause of mortality and morbidity worldwide. The hallmarks of cardiac diseases include inflammation, fibrosis, scar tissue, hyperplasia, hypertrophy, abnormal ventricular remodeling, and cardiomyocyte death, which is an irreversible process that induces heart failure with progressive and dramatic consequences. Both genetic and environmental factors pathologically contribute to the development of CVDs, but the precise causes that trigger cardiac diseases and their progression are still largely unknown. In this scenario, the possibility to generate patient-specific cardiac cells from induced pluripotent stem cells (iPSCs) represents a powerful platform for the investigation of these life-threatening disorders.
  • 1.8K
  • 26 Oct 2020
Topic Review
Endoplasmic Reticulum-Related Protein Targeting and Protein Transport
Cells use an impressive array of components to enable the safe transport of protein cargo from the cytosolic ribosomes to the endoplasmic reticulum. Safety during the transit is warranted by the interplay of cytosolic chaperones, membrane receptors, and protein translocases that together form functional networks and serve as protein targeting and translocation routes. While two targeting routes to the endoplasmic reticulum, SRP (signal recognition particle) and GET (guided entry of tail-anchored proteins), prefer targeting determinants at the N- and C-terminus of the cargo polypeptide, respectively, the discovered SND (SRP-independent) route seems to preferentially cater for cargos with non-generic targeting signals that are less hydrophobic or more distant from the termini. 
  • 1.8K
  • 19 Mar 2022
Topic Review
Redox Homeostasis in Muscular Dystrophies
Reactive oxygen species are (ROS) are signaling molecules moderately and continuously produced by skeletal muscles as a consequence of their contractile activity and high mitochondrial oxygen consumption. The main source of ROS production is located in the cytosol through the activity of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (NOX enzymes), xanthine oxidase (XO), and nitric oxide synthase (NOS), and by the mitochondrial electron transport chain. When ROS exceed the antioxidant buffering capacity of tissues, oxidative stress occurs.
  • 1.8K
  • 15 Jun 2021
Topic Review
Misregulation of Wnt Signaling Pathways
Wnt signaling pathways constitute a group of signal transduction pathways that direct many physiological processes, such as development, growth, and differentiation. Dysregulation of these pathways is thus associated with many pathological processes, including neurodegenerative diseases, metabolic disorders, and cancer. At the same time, alterations are observed in plasma membrane compositions, lipid organizations, and ordered membrane domains in brain and metabolic diseases that are associated with Wnt signaling pathway activation.
  • 1.8K
  • 03 Nov 2021
Topic Review
GRKs
G protein-coupled receptor (GPCR) kinases (GRKs) play an important role in the regulation of signaling of GPCRs that bind neurotransmitters. The canonical model of GPCR desensitization posits that GRKs phosphorylate ligand-activated GPCRs, and this phosphorylation prepares receptors for the high-affinity binding of arrestin proteins. Arrestin binding prevents further G protein coupling, promotes receptor internalization, and initiates and/or facilitates specific branches of signaling. Existing data suggest that the role of GPCR phosphorylation by GRKs is distinct in different receptors. The relationship between G protein- and arrestin-mediated signaling on the one hand, and therapeutic and side effects of drugs on the other, is more complex than is widely believed. Also, the relationship between rapid (minutes to hours) GRK/arrestin-mediated regulation and long-term (days to weeks) neural plasticity remains to be elucidated. 
  • 1.8K
  • 19 Jan 2021
Topic Review
The ROR Pathway
The WNT pathway is one of the major signaling cascades frequently deregulated in human cancer. Binding of WNT ligands to their respective receptors can trigger various downstream signaling cascades centered around cell proliferation, survival or migration. In particular, WNT signaling via the receptor tyrosine kinase-like orphan receptors (RORs) has gained increasing attention in cancer research due to their overexpression in a multitude of tumor entities.
  • 1.8K
  • 19 Feb 2021
Topic Review
Medical Applications of Senescence-Associated β-Galactosidase Assay
β-galactosidase is a lysosomal hydrolase, which cleaves terminal β-d-galactose residues. Senescence-associated β-galactosidase (SA-β-gal) assay found its place in the routine work of thousands of biological laboratories. There is a bulk of evidence that supports the future implementation of β-galactosidase detection as a prognostic marker in medical practice as well.
  • 1.8K
  • 11 Oct 2022
Topic Review
MicroRNAs in Regulation of Melanogenesis
Melanogenesis is the process leading to the synthesis of melanin, the main substance that influences skin color and plays a pivotal role against UV damage. Altered melanogenesis is observed in several pigmentation disorders. Melanogenesis occurs in specialized cells called melanocytes, physically and functionally related by means of autocrine and paracrine interplay to other skin cell types. Several external and internal factors control melanin biosynthesis and operate through different intracellular signaling pathways, which finally leads to the regulation of microphthalmia-associated transcription factor (MITF), the key transcription factor involved in melanogenesis and the expression of the main melanogenic enzymes, including TYR, TYRP-1, and TYRP-2. Epigenetic factors, including microRNAs (miRNAs), are involved in melanogenesis regulation. miRNAs are small, single-stranded, non-coding RNAs, of approximately 22 nucleotides in length, which control cell behavior by regulating gene expression, mainly by binding the 3′ untranslated region (3′-UTR) of target mRNAs.
  • 1.8K
  • 17 Jun 2021
Topic Review
The B-cell Activating Factor/A Proliferation-Inducing Ligand System
It cannot present MZ B-cell populations without discussing the B-cell Activating Factor/A Proliferation-Inducing Ligand System (BAFF/APRIL) system. Without a doubt, one of the most important molecules for the survival and differentiation of B-cells is BAFF. BAFF, also known as B lymphocyte stimulator (BLyS), is part of the tumor necrosis factor (TNF) family and is encoded by the TNFSF13B gene.
  • 1.8K
  • 18 Apr 2022
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