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Topic Review
ORP5 and ORP8
Oxysterol binding related proteins 5 and 8 (ORP5 and ORP8) are two close homologs of the larger oxysterol binding protein (OSBP) family of sterol sensors and lipid transfer proteins (LTP). Early studies indicated these transmembrane proteins, anchored to the endoplasmic reticulum (ER), bound and sensed cholesterol and oxysterols. They were identified as important for diverse cellular functions including sterol homeostasis, vesicular trafficking, proliferation and migration. In addition, they were implicated in lipid-related diseases such as atherosclerosis and diabetes, but also cancer, although their mechanisms of action remained poorly understood. Then, alongside the increasing recognition that membrane contact sites (MCS) serve as hubs for non-vesicular lipid transfer, added to their structural similarity to other LTPs, came discoveries showing that ORP5 and 8 were in fact phospholipid transfer proteins that rather sense and exchange phosphatidylserine (PS) for phosphoinositides, including phosphatidylinositol-4-phosphate (PI(4)P) and potentially phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2). Evidence now points to their action at MCS between the ER and various organelles including the plasma membrane, lysosomes, mitochondria, and lipid droplets. Dissecting exactly how this unexpected phospholipid transfer function connects with sterol regulation in health or disease remains a challenge for future studies.
  • 491
  • 15 Jul 2021
Topic Review
Inflammaging of Hematopoietic Stem Cells
Hematopoietic stem cells (HSCs) sustain the lifelong production of all blood cell lineages. The functioning of aged HSCs is impaired, including a declined repopulation capacity and myeloid and platelet-restricted differentiation. Both cell-intrinsic and microenvironmental extrinsic factors contribute to HSC aging. Recent studies highlight the emerging role of inflammation in contributing to HSC aging. 
  • 490
  • 13 Sep 2021
Topic Review
Akhirin
The structure of AKH comprises two von Willebrand factor-A (vWF-A) domains and one Limulus factor C, Coch-5b2 and Lgl1 (LCCL) domain. The chick AKH has an open reading frame of 748 amino acid residues, and the mouse AKH has an open reading frame of 650 amino acid residues (A). AKH has relatively high homology to vitrinand cochlin.
  • 490
  • 22 Sep 2021
Topic Review
IIIG9 in Cancer and Other Pathologies
The identification of new proteins that regulate the function of one of the main cellular phosphatases, protein phosphatase 1 (PP1), is essential to find possible pharmacological targets to alter phosphatase function in various cellular processes, including the initiation and development of multiple diseases. IIIG9 is a regulatory subunit of PP1 initially identified in highly polarized ciliated cells. In addition to its ciliary location in ependymal cells, researchers showed that IIIG9 has extraciliary functions that regulate the integrity of adherens junctions.
  • 490
  • 01 Dec 2022
Topic Review
ZBP1-Mediated Necroptosis
Cell death is a fundamental pathophysiological process in human disease. The discovery of necroptosis, a form of regulated necrosis that is induced by the activation of death receptors and formation of necrosome, represents a major breakthrough in the field of cell death in the past decade. Z-DNA-binding protein (ZBP1) is an interferon (IFN)-inducing protein, initially reported as a double-stranded DNA (dsDNA) sensor, which induces an innate inflammatory response. ZBP1 was identified as an important sensor of necroptosis during virus infection. It connects viral nucleic acid and receptor-interacting protein kinase 3 (RIPK3) via two domains and induces the formation of a necrosome. 
  • 490
  • 03 Jan 2023
Topic Review
AKR1B10 in Physiology and Pathophysiology
AKR1B10 is a human nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase belonging to the aldo-keto reductase (AKR) 1B subfamily. It catalyzes the reduction of aldehydes, some ketones and quinones, and interacts with acetyl-CoA carboxylase and heat shock protein 90α. The enzyme is highly expressed in epithelial cells of the stomach and intestine, but down-regulated in gastrointestinal cancers and inflammatory bowel diseases. In contrast, AKR1B10 expression is low in other tissues, where the enzyme is upregulated in cancers, as well as in non-alcoholic fatty liver disease and several skin diseases. In addition, the enzyme’s expression is elevated in cancer cells resistant to clinical anti-cancer drugs. Thus, growing evidence supports AKR1B10 as a potential target for diagnosing and treating these diseases. Herein, we reviewed the literature on the roles of AKR1B10 in a healthy gastrointestinal tract, the development and progression of cancers and acquired chemoresistance, in addition to its gene regulation, functions, and inhibitors.
  • 489
  • 24 Jun 2021
Topic Review
CFTR Lifecycle Map
Cystic Fibrosis (CF) is one of the most common genetic diseases prevalent among the Caucasian population and is caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. To date, several hundred disease-causing mutations are known, resulting in a vast range of geno- and phenotypes, which makes the development of therapeutics especially challenging. To support the development of novel therapeutics, systems biological disease maps can be used. Disease maps represent existing knowledge on disease mechanisms in a computationally readable and comprehensive manner so they can then be used by clinicians and experimental scientists as well as computational scientists for different purposes, such as structuring high-throughput data, identifying disease biomarkers, developing better diagnostics and also identifying potential drug targets and drug repositioning. The CFTR Lifecycle Map in particular details the biogenesis of CFTR in cells to support ongoing drug discovery endeavours in CF research.
  • 489
  • 22 Nov 2021
Topic Review
In Vitro Models of Immune Dysfunction in Space
Spaceflight affects the body on every level. Reports on astronaut health identify bone marrow remodelling and dysfunction of the innate immune system as significant health risks of long-term habitation in space. Microgravity-induced alterations of the bone marrow induce physical changes to the bone marrow stem cell niche. Downstream effects on innate immunity are expected due to impaired hematopoiesis and myelopoiesis. To date, few studies have investigated these effects in real microgravity and the sparsely available literature often reports contrasting results. This emphasizes a need for the development of physiologically relevant in vitro models of the bone marrow stem cell niche, capable of delivering appropriate sample sizes for robust statistics.
  • 489
  • 07 Apr 2022
Topic Review
Mesenchymal Stem Cells in Infectious Diseases
Mesenchymal stem cells (MSCs) are attractive in various fields of regenerative medicine due to their therapeutic potential and complex unique properties. Basic stem cell research and the global COVID-19 pandemic have given impetus to the development of cell therapy for infectious diseases. 
  • 489
  • 22 Nov 2022
Topic Review
MicroRNA-502-3p and Human Diseases: Focus on Alzheimer's Disease
The microRNA-500’s family has five different genotypes: microRNA-362, microRNA-500a, microRNA-500b, microRNA-501, and microRNA-502 (Genesnames.org). All the forms of miR-500 family members are expressed in humans and different animal species. The miR-502-3p sequence is 22 nucleotides long and is found in Homo sapiens (Has-miR-502-3p) as annotated by 7 gene databases such as MalaCards, miRBase, GeneCards, TarBase, ENA, RefSeq, and LncBase. The miR-502 were also found to be conserved in seven different animal species such as Cow (Bos taurus) Bta-miR-502a; Dog (Canis lupus familiaris) Cfa-miR-502; Horse (Equus caballus) Eca-miR-502-3p; Gorilla (Gorilla gorilla) Ggo-miR-502a; Rhesus monkey (Macaca mulatta) Mml-miR-502-3p); Rabbit (Oryctolagus cuniculus) Ocu-miR-502-3p; and Bornean orangutan (Pongo pygmaeus) Ppy-miR-502-3p (https://rnacentral.org/rna) (accessed on 26 February 2023). The miR-502-3p is encoded by the MIR502 gene (ENSG00000272080) which is composed of an 86 base-pairs genomic sequence, a plus stranded RNA orientation starting from 50,014,598, and ending at 50,014,683. The MiR502 gene is located at the Chromosome X genomic location: 50,014,598-50,014,683 forward strands.
  • 489
  • 13 Apr 2023
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