• Decoy receptor 3 (Dcr3), also known as tumor necrosis factor receptor superfamily member 6B (TNFRSF6B), TR6 and M68, is a soluble protein of the tumor necrosis factor receptor superfamily which inhibits Fas ligand-induced apoptosis. (wikipedia.org)
  • Recent advances in understanding the molecular events underlying hypohidrotic ectodermal dysplasia (HED) caused by mutations of the genes encoding proteins of the tumor necrosis factor α (TNFα)-related signaling pathway have been presented. (springer.com)
  • Because of its ability to induce cell growth inhibition and apoptosis in normal and pre-malignant cells, TGFβ has been described as a potent tumor suppressor [ 8 ] [ 9 ] . (encyclopedia.pub)
  • Both glutathione S-transferase pi ( GSTpi ) (80%, 24/30 in tumor and 56.7%, 17/30 in the paired non-cancerous tissues) and cystic fibrosis transmembrane conductance regulator, ATP-binding cassette (sub-family C, member 7) ( CFTR ) (77%, 23/30 in tumor and 50%, 15/30 in the paired non-cancerous tissues) genes were prevalently hypermethylated in HCC as well as their neighboring non-cancerous tissues. (wjgnet.com)
  • [ 1 ] His prediction was subsequently supported by the cloning of the retinoblastoma tumor suppressor gene ( RB1 ) and by functional studies of the retinoblastoma protein, Rb. (medscape.com)
  • Like Rb protein, many of the proteins encoded by tumor suppressor genes act at specific points in the cell cycle. (medscape.com)
  • This first category also includes genes that contribute to tumor growth by inhibiting cell death. (cancerquest.org)
  • The programmed cell death 4 (PDCD4) protein is induced in animals during apoptosis and functions to inhibit translation and tumor promoter-induced neoplastic transformation. (biomedcentral.com)
  • The development of CM is biologically complex and involves multiple mechanisms such as sequestration, immunopathology by the pro-inflammatory cytokine interferon-γ (IFN-γ), tumor necrosis factor alpha (TNF-α), and apoptosis. (biomedcentral.com)
  • More importantly, direct in vivo expression of WNV-Cp protein in mouse brain resulted in an induction of apoptosis similar to what is observed in natural infection. (cdc.gov)
  • A successful therapy must therefore eliminate these cells known to be highly resistant to apoptosis. (hindawi.com)
  • TMC1 is a pore-forming subunit of the mechanotransduction complex that is predicted to have transmembrane domains with intracellular N and C termini and one conserved TMC domain [ 14 ]. (hindawi.com)
  • It is best known for its intracellular role in targeting ubiquitylated proteins for degradation via the ubiquitin proteasome system. (wikidoc.org)
  • This review summarizes the unique immunomodulatory aspects of hRSV infection, the viral proteins involved in intracellular immune signaling, and the viral interactions in play with the host's immune system. (fortunejournals.com)
  • This review summarizes the unique immune-modulatory aspects of hRSV infection that are associated with the roles performed by viral proteins in intracellular immune signaling, their interactions with the host immune system, and their possible implications for disease pathology. (fortunejournals.com)
  • Two well-defined pathological hallmarks of AD have been described: the formation of extracellular amyloid plaques and the development of intracellular neurofibrillary tangles (NFTs) formed by aggregated hyperphosphorylated TAU protein [ 4 ]. (biomedcentral.com)
  • Both establish calcium-dependent homophilic cell-cell adhesion with their extracellular domains and are connected with catenins at their intracellular domains [ 4 ]. (biomedcentral.com)
  • It acts as a decoy receptor that competes with death receptors for ligand binding. (wikipedia.org)
  • Active TGFβ induces the heteromeric complex formation of two single transmembrane serine/threonine kinase family receptors, i.e. (encyclopedia.pub)
  • These pericryptal myofibroblasts produce the Wnt signalling ligands which bind to Frizzled receptors as well as morphogenetic protein (BMP) antagonists gremlin 1(GREM1), gremlin 2 (GREM2) on basal epithelial stem cells and also can modulate notch signaling. (biomedcentral.com)
  • Generally, these receptors explain their function on the cell membrane where, after the binding with growth factors or neuregulin undergo to homo or hetero oligomerization with the activation of the intrinsic tyrosine kinase activity and the subsequent recruitment of proteins involved in the cytoplasmic signalling pathways. (biomedcentral.com)
  • E-cad and N-cad have been shown to be able to interact with the receptors of different growth factors, which suggests that cadherins are involved in the modulation of signaling pathways. (biomedcentral.com)
  • Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. (cdc.gov)
  • We observed that the WNV-Cp protein is a pathogenic protein, which drives apoptosis in vitro through the mitochodrial/caspase-9 pathway. (cdc.gov)
  • Novel data were reviewed and discussed on the structure and functions of the components of TNFα-related signaling pathway, the consequences of mutations of the genes encoding these proteins, and the prospect for further investigations, which might elucidate the origin of HED. (springer.com)
  • Within the last 10 years significant progress has been made in understanding the pathogenesis of HED and this is mainly due to the discovery of unknown proteins and the elucidation of their function in signal transduction via the TNFα-related pathway. (springer.com)
  • SUMOylation is a post-translational modification of proteins that has been found to play a major role in the Wnt/β-catenin signaling pathway. (frontiersin.org)
  • Proteins associated with the Wnt/β-catenin pathway have been identified as SUMOylated substrates, and evidences suggested that the initiation and progression of cancers depended on the function of the SUMOylation ( 23 ). (frontiersin.org)
  • The autophagic pathway constitutively maintains cellular homeostasis by recycling cytoplasmic organelles and proteins, but it is also stimulated by environmental stress conditions, such as starvation, oxidative stress, and the accumulation of misfolded proteins. (mdpi.com)
  • In addition to its role in glucose metabolism, this pathway also regulates the redirection of free amino acids to protein synthesis via the mTOR-signaling pathway. (hindawi.com)
  • The SHH pathway should be off at most of the time, by the inhibition of specific factors such as Patched 1 (PTC1), Protein Kinase A (PKA), Casein Kinase1 (CK1), and Glycogen Synthase Kinase 3 beta (GSK3b), and only valid at precise time points [ 98 ]. (regenmedres-journal.org)
  • and the intrinsic pathway, which is activated by cellular stress and is regulated primarily at the level of mitochondria by the Bcl-2 family of proteins ( Fig. 1 ). (biologists.com)
  • The intrinsic apoptotic pathway is initiated in response to a variety of stress signals ( Willis and Adams, 2005 ), and a complex interplay of Bcl-2 proteins relays this signal to the mitochondrial outer membrane (OM) to initiate Bak and Bax activation, oligomerisation and OM damage ( Fig. 1 ). (biologists.com)
  • However, in certain cell types, the extrinsic pathway also induces mitochondrial damage by cleaving the pro-apoptotic Bcl-2 family protein Bid to its activated truncated form (tBid), which leads to Bak and Bax activation. (biologists.com)
  • The appearance of a unique form of PDCD4 in plants correlates with the appearance of components of the ethylene signaling pathway, suggesting that it may represent the adaptation of an existing protein involved in programmed cell death to one that functions in abiotic stress responses through hormone signaling. (biomedcentral.com)
  • The encoded protein is postulated to play a regulatory role in suppressing FasL- and LIGHT-mediated cell death and T cell activation as well as to induce angiogenesis via neutralization of TL1A. (wikipedia.org)
  • Bak BH3 peptides antagonize Bcl-xL function and induce apoptosis through cytochrome c-independent activation of caspases. (lookformedical.com)
  • Myosin XVA through its carboxy-terminal PDZ-ligand interacts with the third PDZ domain of whirlin, and then delivers whirlin to the tips of stereocilia [ 21 ]. (hindawi.com)
  • Additionally, we detected increased levels of active glycogen synthase kinase 3 β, a physiological kinase of TAU, in neurons derived from AD iPSCs, as well as significant upregulation of amyloid precursor protein (APP) synthesis and APP carboxy-terminal fragment cleavage. (biomedcentral.com)
  • Post-translational modifications (PTMs) of proteins, including phosphorylation, acetylation, ubiquitination, and SUMOylation, can regulate the function of proteins, determine the active state and subcellular location of proteins, and dynamically interact with other proteins related to carcinogenesis and progression ( 17 - 20 ). (frontiersin.org)
  • Some proto-oncogenes work to regulate cell death. (cancerquest.org)
  • The mutant proteins often retain some of their capabilities but are no longer sensitive to the controls that regulate the normal form of the protein. (cancerquest.org)
  • Understanding the proteins that regulate the 5-HT1A promoter will lead to insights on receptor regulation and provide new therapeutic targets relevant to depression, anxiety, obsessive compulsive disorder and other mental illnesses. (vdocuments.net)
  • Transforming growth factor β (TGFβ) is a secreted growth and differentiation factor that influences vital cellular processes like proliferation, adhesion, motility, and apoptosis. (encyclopedia.pub)
  • We show that CCN1 (also known as CYR61), a matricellular protein that dampens and resolves liver fibrosis, also mediates cholangiocyte proliferation and ductular reaction, which are repair responses to cholestatic injury. (jci.org)
  • Administration of CCN1 protein or soluble JAG1 induced cholangiocyte proliferation in mice, which was blocked by inhibitors of NF-κB or NOTCH signaling. (jci.org)
  • In vitro apoptosis in individual cells was determined by terminal desoxyriboxyl-desoxyriboxyl transferase-mediated DVTP nick-end labeling (TUNEL) assay with the In Situ Cell Death Assay Kit (Roche Diagnostic Corp., Indianapolis, IN) and visualized by fluorescent microscopy. (cdc.gov)
  • In this paper, we describe the metabolic changes as well as the mechanisms of resistance to apoptosis occurring in cancer cells and cancer stem cells, underlying the connection between these two processes. (hindawi.com)
  • Mechanisms by which Dox promotes cardiac damage and cardiomyocyte cell death have been investigated extensively, but a definitive picture has yet to emerge. (oncotarget.com)
  • In the current work, we used well-known methods (ToppGene and Endeavour), as well as methods previously developed by us, to prioritize genes involved in endothelial apoptosis and to find potential participants of molecular-genetic mechanisms of lymphedema among them. (biomedcentral.com)
  • Analysis of interactions of these genes in the associative gene network of lymphedema can improve understanding of mechanisms of interaction between endothelial apoptosis and lymphangiogenesis, and shed light on the role of disturbance of these processes in the development of edema, chronic inflammation and connective tissue transformation during the progression of the disease. (biomedcentral.com)
  • Thus, the control of ribosome assembly and protein synthesis is essential for the survival of cancer cells. (biomedcentral.com)
  • Although eIF4A is an ATP-dependent RNA helicase that binds the MA3 domain of eIF4G to promote translation initiation, binding of eIF4A to the MA3 domains of PDCD4 inhibits protein synthesis. (biomedcentral.com)
  • Following transcription and processing of an mRNA, the ribosome is responsible for performing protein synthesis. (biomedcentral.com)
  • [3] Ubiquitin is a small (76-amino acid) protein highly conserved among eukaryotic cells. (wikidoc.org)
  • PDCD4 is composed of two MA3 domains that share similarity with the single MA3 domain present in the eukaryotic translation initiation factor (eIF) 4G, which serves as a scaffold protein to assemble several initiation factors needed for the recruitment of the 40S ribosomal subunit to an mRNA. (biomedcentral.com)
  • Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. (lookformedical.com)
  • The TMC1 gene is located on chromosome 9q21 and contains 24 exons that encodes a 760 amino acid membrane protein TMC1 with six transmembrane domains [ 12 , 13 ]. (hindawi.com)
  • The MYO15A gene is located at chromosome 17p11.2 and contains 66 coding exons, which encodes an unconventional myosin protein Myosin XVA [ 19 ]. (hindawi.com)
  • The Hh gene family encodes a secreted protein that plays a critical regulatory role in the process of embryogenesis and environmental stabilization in adult tissues of invertebrates and vertebrates [ 44 ]. (regenmedres-journal.org)
  • For example, the TP53 gene, located on chromosome 17, encodes a 53-kd nuclear protein that functions as a cell cycle checkpoint. (medscape.com)
  • This locus, however, also encodes a protein from an alternative reading frame, designated p19ARF. (medscape.com)
  • Abnormal metabolism and the evasion of apoptosis are considered hallmarks of cancers. (hindawi.com)
  • The American Cancer Society has reported 101,340 new cases of colon and 39,870 cases rectal cancers and 49,380 deaths in 2011 in the US. (biomedcentral.com)
  • In this context, during any sort of stress condition the alternative reading frame protein p14ARF subtracts MDM2, an E3 ubiquitin ligase, from the interaction with p53 in manner to free and stabilise p53 level in the nucleolus of the cell where it inhibits RNA polymerase I activity [ 3 ]. (biomedcentral.com)
  • The gene network of ADHD included 599 genes/proteins and 148,978 interactions, while that of dyslexia included 167 genes/proteins and 27,083 interactions. (biomedcentral.com)
  • eIF4B and PABP also bind to a site within the central region of eIF4G that partially overlaps the HEAT-1/eIF4G-MIG but they do not bind the HEAT-2/eIF4G-MA3 domain [ 9 ], demonstrating the functional diversity of the HEAT-1/eIF4G-MIG and HEAT-2/eIF4G-MA3 domains in their interactions with partner proteins. (biomedcentral.com)
  • Original methods of prioritization took into account the overrepresented Gene Ontology biological processes, the centrality of vertices in the associative gene network, describing the interactions of endothelial apoptosis genes with genes associated with lymphedema, and the association of the analyzed genes with diseases that are comorbid to lymphedema. (biomedcentral.com)
  • An assessment of the quality of prioritization was performed using criteria, which involved an analysis of the enrichment of the top-most priority genes by genes, which are known to have simultaneous interactions with lymphedema and endothelial cell apoptosis, as well as by genes differentially expressed in murine model of lymphedema. (biomedcentral.com)
  • Unlike most of the other members of TNFR superfamily, TNFRSF6 is a soluble protein which contains no transmembrane domain. (wikipedia.org)
  • During ribosomal RNA processing, ribosomal proteins are incorporated into the pre-ribosomal subunits to form the mature 40S and 60S subunits. (biomedcentral.com)
  • Dox is a mitochondrial toxin, and mitochondrial damage is central to Dox-induced cardiac dysfunction and cell death [ 8 ]. (oncotarget.com)
  • Mitochondrial outer membrane permeabilisation (MOMP) is the point of no return in many forms of apoptotic cell death. (biologists.com)
  • The current development of anti-cancer agents that target the Bcl-2 protein family is showing considerable promise, although how this targeting triggers Bak and Bax to perform their crucial function of mitochondrial outer membrane permeabilisation (MOMP) is not clear. (biologists.com)
  • TNFRSF6B has been shown to interact with: TNFSF14 Fas ligand. (wikipedia.org)
  • ED1 , encoding a ligand-ectodysplasinA-A1 (EDA-A1), EDAR , coding for ectodysplasinA-A1 receptor, EDARADD , programming the structure of EDAR-associated death domain protein and NEMO whose protein product, NFκB essential modulator (NEMO), is necessary for an indirect activation of nuclear factor κB (NFκB). (springer.com)
  • Signaling is initiated when the Wnt ligand binds to the Frizzled receptor on the cell membrane and the LDL receptor-associated protein 5/6 (LRP5/6) co-receptor. (frontiersin.org)
  • In the absence of SHH, PTC and G Protein-coupled Receptor161 (GPR161) are located at the base of primary cilium (PC), while accumulation of SMO is diminished by transporting sterol-like SMO ligand outside by a 'tunnel' structure of PTC1. (regenmedres-journal.org)
  • The nucleolus is a subnuclear, non-membrane bound domain that is the hub of ribosome biogenesis and a critical regulator of cell homeostasis. (biomedcentral.com)
  • Disruption of endothelial cell apoptosis can be considered as one of the factors contributing to the development of lymphedema. (biomedcentral.com)
  • These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade. (cdc.gov)
  • Inadequate understanding of the antigenic intricacies of its viral proteins and the immune responses they generate in the host is the greatest obstacle to the progress of hRSV prevention and treatment. (fortunejournals.com)
  • The proteases involved are of different origins and types: (i) present as precursor in plasma, (ii) secreted into the plasma by activated platelets or other blood cells, or (iii) intracellularly activated and cleaving cytosolic receptor domains. (frontiersin.org)
  • C-X-C chemokine receptor type 4 ( CXCR-4 ) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene . (wikidoc.org)
  • The differences in the characteristics between the murine model and humans are the host receptor and the absence of knob-like structures of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) (Table 2 ) [ 11 ]. (biomedcentral.com)
  • We also observed that expression of Cp protein in mouse muscle resulted in apoptosis and inflammation of muscle cells. (cdc.gov)
  • CCN1 also induced Jag1 expression in hepatic stellate cells, whereupon they interacted with hepatic progenitor cells to promote their differentiation into cholangiocytes. (jci.org)
  • The TP53 gene is also capable of stimulating apoptosis of cells containing damaged DNA. (medscape.com)
  • Genes whose protein products stimulate or enhance the division and viability of cells. (cancerquest.org)
  • Accordingly, prevention of MOMP can rescue cells from death. (biologists.com)
  • In our studies on neurotransmitter metabolism we have focused our efforts on transporters, a functional class of proteins that move neurotransmitters and other small molecules across membranes in cells. (stanford.edu)
  • We found that the sole presence of N-cad induces constitutively active fibroblast growth factor (Fgf) signaling and a precocious involution resulting in massive apoptosis of alveolar cells. (biomedcentral.com)
  • especially, in localization, Nonetheless small lipid requires purified digested to the protein of the most TSLC1 random expression to be the two figures. (scoutconnection.com)
  • At the heart of the pathogenesis of lymphedema lies the appearance of chronic high-protein edema, characterized by the pathological accumulation of intercellular fluid with large-molecule proteins in the interstitial space due to a defect in lymphatic drainage caused by congenital malformation (primary lymphedema), lymphatic obstruction or by the destruction of lymphatic vessels (secondary lymphedema). (biomedcentral.com)
  • Disturbance of drainage function of lymphatic vessels leads to accumulation of fluid rich in proteins under the epidermis. (biomedcentral.com)
  • We recently reported that a key step leading to Bak homo-oligomerisation following an apoptotic stimulus involves transient exposure of the Bak BH3 domain before it binds to the hydrophobic groove of another activated Bak molecule to form a novel symmetric dimer. (biologists.com)
  • Mutations of these genes are responsible for systemic tooth agenesis, in addition to the defects of other ectodermal structures, and this review is limited to description of the function of their protein products. (springer.com)
  • Mutations in the gene for the antennapedia homeodomain protein are associated with the conversion of antenna to leg or leg to antenna DROSOPHILA. (lookformedical.com)
  • Most cases of early-onset AD are linked to autosomal dominant inherited mutations in the genes encoding amyloid precursor protein ( APP ), presenilin 1 ( PSEN1 ), and presenilin 2 ( PSEN2 ). (biomedcentral.com)
  • TP53 activates the expression of genes involved in apoptosis, cell cycle regulation (p21), and MDM2. (medscape.com)
  • The p19ARF protein, which is encoded by the same locus as p16, also leads to cell cycle arrest by inhibiting the ability of MDM2 to inactivate TP53. (medscape.com)
  • Myosin XVA is a large actin-based motor protein. (hindawi.com)
  • the tadpoles showed reduced expression of cα(E)-catenin , small muscle protein, dystrophin , and myosin light chain genes. (biomedcentral.com)
  • CSCs exhibit certain properties, such as high expression of various anti-apoptotic proteins, expression of ABC pumps, and others, that would allow them to resist chemotherapeutic agents (Li et al. (docksci.com)
  • Toxic effects of Dox include cardiomyocyte damage and apoptotic and necrotic cell death [ 5 ]. (oncotarget.com)
  • To form the higher-order oligomers that probably constitute the apoptotic pore complex, Bak dimers then interact via regions away from the BH3 domain and groove. (biologists.com)
  • The Bcl-2 homology 3 (BH3) domain is crucial for the death-inducing and dimerization properties of pro-apoptotic members of the Bcl-2 protein family, including Bak, Bax, and Bad. (lookformedical.com)
  • We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. (cdc.gov)
  • Long existence of the high-protein edema causes chronic inflammation leading to the replacement of adipose tissue with connective tissue, increasing the volume of connective tissue matrix, which subsequently leads not only to an increase in size of body parts, but also to a secondary disturbance of lymphatic transport and drainage [ 2 ]. (biomedcentral.com)
  • Dcr3 was identified in 1998 by the search of genes with homology to the TNFR gene superfamily in expressed sequence tag (EST) database. (wikipedia.org)
  • The CDK4-cyclinD complex normally phosphorylates the retinoblastoma protein (Rb protein), leading to release of the E2F transcription factor and cell cycle progression. (medscape.com)
  • Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. (cdc.gov)
  • These results provide evidence of a link between WNV-Cp protein and WNV pathogenesis in vivo. (cdc.gov)
  • However, a study of the relationship between genes associated with lymphedema and genes involved in endothelial apoptosis, in the associative gene network was not previously conducted. (biomedcentral.com)
  • We describe how these are activated, which are their target proteins, and how their proteolytic activity modulates platelet functions. (frontiersin.org)
  • Colorectal cancer is the fourth most common form of cancer worldwide and ranks third among the cancer-related deaths in the US and other Western countries. (biomedcentral.com)
  • Colorectal cancer, the third most common cancer in women and the fourth in men, causes 610,000 deaths per year worldwide [ 1 ]. (biomedcentral.com)
  • Several other genetic backgrounds result in enlargement of the haltere significantly beyond the normal range of haploinsufficient phenotypes, suggesting genetic variation in cofactors that mediate homeotic protein function. (lookformedical.com)
  • To block apoptosis, we conditionally deleted one allele of p53 in Ncadk.i. mice and observed a temporal rescue of alveolar morphology and function. (biomedcentral.com)
  • Potential C. elegans orthologs for II of the 12 protein-coding genes predicted in the B. malayi sequence were identified. (biomedcentral.com)
  • Additionally, it was revealed that the most relevant genes are involved in biological processes related to signal transduction, positive regulation of transcription from RNA polymerase II promoters, chemical synaptic transmission, response to drugs, ion transmembrane transport, nervous system development, cell adhesion, and neuron migration. (biomedcentral.com)
  • Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. (lookformedical.com)
  • Dox-induced over-production of reactive oxygen and nitrogen species (ROS and RNS) such as superoxide, hydrogen peroxide, hydroxyl radical and peroxynitrite has been proposed to be the main cause of Dox-induced acute cardiomyocyte toxicity and cell death by damaging various molecular constituents and organelles [ 9 - 12 ]. (oncotarget.com)
  • For a caspase-9-specific test, 5 μg of pcWNV-Cp-DJY or pcWNV-CpWT was cotransfected with a dominant negative caspase-9 (DN caspase-9) construct, and cleavage of procaspase-9 protein was determined by Western blot analysis with antihuman caspase-9 antibody (MBL, Nagoya, Japan). (cdc.gov)
  • The p16INK4A protein is a cell-cycle inhibitor that acts by inhibiting activated cyclin D:CDK4/6 complexes, which play a crucial role in the control of the cell cycle by phosphorylating Rb protein. (medscape.com)
  • However, important knowledge gaps remain about the role played by various hRSV proteins in immunobiology and pathology. (fortunejournals.com)
  • Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. (cdc.gov)
  • Autophagic cell death has been described, and has been proposed to contribute to Dox-cardiotoxicity. (oncotarget.com)
  • Here we will review Dox-induced cardiotoxicity and cell death in the broad context of the autophagy and mitophagy processes. (oncotarget.com)
  • IHH signal induces activation of Parathyroid Hormone-related Protein (PTHRP) on the articular surface and gets rid of the hypertrophy of chondrocytes [ 49 ]. (regenmedres-journal.org)
  • Other molecular components of hRSV, such as the G or N proteins, have also been explored as potential targets for disease control. (fortunejournals.com)