• Env is a viral gene that encodes the protein forming the viral envelope. (wikipedia.org)
  • This gene encodes a mitochondrial solute carrier protein family member. (nih.gov)
  • The Mucin 1 (MUC1) gene encodes a membrane bound glycosylated phosphoprotein, belonging to the family of mucins which are heavily glycosylated proteins. (sigmaaldrich.com)
  • This gene encodes soluble NSF attachment protein gamma. (antibodies-online.com)
  • MFN2 encodes an outer mitochondrial membrane protein that is important in the regulation of fusion of the mitochondria. (neuroophthalmology.ca)
  • The neuraminidase (NA) gene encodes the other surface protein of the virus. (cdc.gov)
  • Mutation of this gene results in neuropathy and optic atrophy. (nih.gov)
  • Interestingly, MFN2 shows functional overlap with the OPA1 gene, the protein underlying the most common form of autosomal dominant optic atrophy. (neuroophthalmology.ca)
  • The most relevant proteins involved in the mitochondrial fusion process are three GTPase dynamin-like proteins: mitofusin 1 (MFN1) and 2 (MFN2), located in the outer mitochondrial membrane, and optic atrophy protein 1 (OPA1), in the inner membrane. (centrodinoferrari.com)
  • An expanding number of degenerative disorders are associated with mutations in the genes encoding MFN2 and OPA1, including Charcot-Marie-Tooth disease type 2A and autosomal dominant optic atrophy. (centrodinoferrari.com)
  • In recent years, our understanding of genetic predisposition to PD has advanced vastly, including causative mutations in the genes encoding α-synuclein, LRRK2, parkin, PINK1, and DJ-1 just to name a few 5 . (nature.com)
  • The role of the mitochondrial outer membrane protein SLC25A46 in mitochondrial fission and fusion. (nih.gov)
  • Depolarized mitochondria recruit Parkin to the outer mitochondrial membrane, triggering autophagosome formation, rapid lysosomal fusion, and Parkin redistribution," the team noted. (genengnews.com)
  • Both genes have complementary functions in the fusion of mitochondrial membranes. (neuroophthalmology.ca)
  • Alterations in mitochondrial dynamics due to mutations in proteins involved in the fusion-fission machinery represent an important pathogenic mechanism of human diseases. (centrodinoferrari.com)
  • This review provides an overview of the basic molecular mechanisms involved in mitochondrial fusion and focuses on the alteration in mitochondrial DNA amount resulting from impairment of mitochondrial dynamics. (centrodinoferrari.com)
  • We also review the literature describing the main disorders associated with the disruption of mitochondrial fusion. (centrodinoferrari.com)
  • Mitochondrial fusion and fission are fundamental processes underlying cellular dynamics [1]. (centrodinoferrari.com)
  • Fusion of the outer mitochondrial membrane depends on two GTPase family members: mitofusin 1 (MFN1) and mitofusin 2 (MFN2). (centrodinoferrari.com)
  • The expression of the env gene enables retroviruses to target and attach to specific cell types, and to infiltrate the target cell membrane. (wikipedia.org)
  • Env expression is regulated by the gene product of rev. (wikipedia.org)
  • Moreover, we identified that PARIS actively modulates expression of PPARγ target genes by physically binding to the promoter regions. (nature.com)
  • The dominant discovery in these experiments indicates that there is a heterologous expression of certain genes in plants that can regulate cell death. (essaywriter.org)
  • Most maize CDPK genes exhibited different expression levels in different tissues and developmental stages. (biomedcentral.com)
  • Expression analyses suggested that maize CDPK genes are important components of maize development and multiple transduction pathways. (biomedcentral.com)
  • We observed a downregulation in the expression of genes involved in host response, such as TNF signaling, IL-1β production, and phagosome formation in Mφ, and phosphatidylinositol signaling and TNF signaling in PMNs, being in line with the ability of the pathogen to survive within phagocytes. (frontiersin.org)
  • Furthermore, monitoring QS signaling gene expression revealed that AHL synthases LasI/RhlI and QS transcriptional regulators LasR/RhlR genes were inhibited and antagonized, respectively, by cerPAC. (nature.com)
  • Fusion gene: a 320-kb large interstitial deletion within the pseudoautosomal region 1 (PAR1) on chromosome X [del(X)(p22.33p22.33)] and chromosome Y [del(Y)(p11.32p11.32)] results in juxtaposition of the first non-encoding exon of P2RY8 to the CRLF2 coding region to form P2RY8-CRLF2 fusion which leads to over-expression of full-length CRLF2. (atlasgeneticsoncology.org)
  • Using retroviral expression screening for transforming genes in biphenotypic acute leukaemia, P2RY8 has been confirmed to have oncogenic potential (Fujiwara et al. (atlasgeneticsoncology.org)
  • An interstitial deletion of the pseudoautosomal region 1 (PAR1) of either of the sex chromosomes results in juxtaposition of the first noncoding exon of the P2RY8 gene to the first exon of CRLF2, such that CRLF2 expression from this chimeric locus is driven by the P2RY8 promoter. (atlasgeneticsoncology.org)
  • The responses attributed to TNFa are not a direct result of TNFa, but rather its ability to regulate the expression of TNFa responsive genes whose products directly mediate the response. (cdc.gov)
  • DNA array or real-time PCR techniques were used to evaluate gene expression induced by TNFa in myoblast cultures. (cdc.gov)
  • Myoblasts from TNFR1 and TNFR2 deficient mice demonstrated that TNFa induced gene expression in primary myoblasts is dependent on both receptors. (cdc.gov)
  • In the current study, we cloned and expressed the gene encoding silkworm SP2 ( sp2 ) both in a prokaryotic expression system and a silkworm baculovirus system. (hindawi.com)
  • The coiled-coil domain is a structural motif found in proteins that are involved in a diverse array of biological functions such as the regulation of gene expression, cell division, membrane fusion and drug extrusion and delivery. (antikoerper-online.de)
  • Treatment of cells with IFNalpha results in an antiviral state against HSV-1 which has been attributed to reduced viral IE gene expression. (gla.ac.uk)
  • NCBI Gene Expression Omnibus, GSE134202. (elifesciences.org)
  • Gene expression patterns, assayed by RNA sequencing, show that tethering induces global supercoiling changes, which are likely incompatible with replication initiation. (nih.gov)
  • Treatment with NMT inhibitor IMP-1088 potently abrogated VACV infection, while VACV gene expression, DNA replication, morphogenesis and EV formation remained unaffected. (cdc.gov)
  • Following removal of the outer membrane, the scFvs displayed on the inner membrane are panned against a target antigen immobilized on magnetic beads to isolate scFvs that bind to the target antigen. (jove.com)
  • Kar2p is localized to the luminal (i.e., noncytoplasmic) face of the ER membrane, yet nuclear fusion must initiate from the cytosolic side of the outer nuclear membrane or the ER membrane with which it is contiguous. (rupress.org)
  • Initially, the dimerization of mitofusins results in the tethering of the outer membranes of adjoining mitochondria. (centrodinoferrari.com)
  • Before fusion, curving of the outer membranes is promoted by the phospholipase D-dependent hydrolysis of cardiolipin. (centrodinoferrari.com)
  • NSF and SNAPs appear to be general components of the intracellular membrane fusion apparatus, and their action at specific sites of fusion must be controlled by SNAP receptors particular to the membranes being fused. (antibodies-online.com)
  • The protein encoded by P2RY8 gene is composed of 359-amino acids and belongs to the P2Y family of G-protein coupled receptors that are preferentially activated by adenosine and uridine nucleotides. (atlasgeneticsoncology.org)
  • TNFa delivers its signals to target cells by binding to specific cell surface membrane receptors (TNFR1 and TNFR2). (cdc.gov)
  • A(H5) viruses in HA clade 2.3.4.4b and lacked amino acid changes that improve recognition of mammalian receptors or fusion of the viral membrane with the host endosomal membranes. (cdc.gov)
  • Analysis of this HA gene shows that it is closely related to avian A(H5) viruses in HA clade 2.3.4.4b and lacked amino acid changes that improve recognition of mammalian receptors or fusion of the viral membrane with the host endosomal membranes. (cdc.gov)
  • The fusion peptide inserts itself in the host cell membrane and brings the host cell membrane very close to the viral membrane to facilitate membrane fusion. (wikipedia.org)
  • The mature product of the env gene is the viral spike protein, which has two main parts: the surface protein (SU) and the transmembrane protein (TM). (wikipedia.org)
  • It is responsible for binding to new host cells and mediating fusion between the viral membrane, and the target cell membrane. (scienceblogs.com)
  • To keep using HIV-1 as an example, this precursor protein gets chopped in two, into a t rans m embrane gp41, which stays anchored in the viral membrane, and a s ub u nit gp120, which is noncovalently attached to gp41 like a lolly-pop. (scienceblogs.com)
  • A particle according to any one of the preceding claims, wherein heterologous polypeptide sterically hinders fusion of an enveloped viral particle with an eukaryotic cell to which it is bound. (sumobrain.com)
  • Following fusion of the virus envelope with the cell membrane Vmw65 is released into the cell and forms a complex with cellular factors which bind to TAATGARAT (where R is a purine) elements upstream of the viral immediate early (IE) genes. (gla.ac.uk)
  • Studies headed by researchers at the Gladstone Institutes have generated new insights into the role played by genes known as PINK1 and Parkin, which are associated with Parkinson's disease, in the recycling of energy-generating mitochondria in brain cells. (genengnews.com)
  • Mitochondria are highly dynamic, complex organelles that continuously alter their shape, ranging between two opposite processes, fission and fusion, in response to several stimuli and the metabolic demands of the cell. (centrodinoferrari.com)
  • Fusion allows the exchange of contents, DNA, and metabolites between neighboring mitochondria, including damaged or senescent mitochondria, promoting their survival [2, 3]. (centrodinoferrari.com)
  • IRE uses HVEPs to cause cell death by inducing membrane disruption, and it is primarily used as a radical ablative therapy in the treatment of soft-tissue tumors in the liver, kidney, prostate, and pancreas. (rsna.org)
  • Disruption of the genes encoding other Sec63p-associated proteins (Sec71p and Sec72p) also results in karyogamy defects. (rupress.org)
  • However, we recently learned that this disruption library contains within the T-DNA an AP3 gene and, as a consequence, approximately 15% of the lines show lethality. (purdue.edu)
  • We decided not to use these lines because of our inability to determine whether a rat phenotype would be caused by the T-DNA disruption or a combination of the disruption and the effects of the AP3 gene. (purdue.edu)
  • We provide a method to simultaneously screen a library of antibody fragments for binding affinity and cytoplasmic solubility by using the Escherichia coli twin-arginine translocation pathway, which has an inherent quality control mechanism for intracellular protein folding, to display the antibody fragments on the inner membrane. (jove.com)
  • The method harnesses the intrinsic intracellular folding quality control mechanism of the Escherichia coli twin-arginine translocation (Tat) pathway to display an scFv library on the E. coli inner membrane. (jove.com)
  • Upregulation of this gene, abnormal intracellular localization and varied glycosylation of Muc1 has been associated with carcinomas. (sigmaaldrich.com)
  • SCGN interacts with the SNARE complex, which is required for vesicle fusion with the plasma membrane. (elifesciences.org)
  • RNA-guided Gene Regulation: Structure and. (hhmi.org)
  • The MUC1 gene is mapped to human chromosome 1q22. (sigmaaldrich.com)
  • The AGPS gene is found on chromosome 2 . (medlineplus.gov)
  • Schematic diagram of the human X chromosome indicating the location of the P2RY8 gene. (atlasgeneticsoncology.org)
  • The P2RY8 gene is located on both chromosomes X and Y. It was discovered by Cantagrel and co-workers while investigating a pericentric inversion on the X chromosome, inv(X)(p22.3 q13.2), in a family with mental retardation. (atlasgeneticsoncology.org)
  • The GNPAT gene is found on chromosome 1 . (medlineplus.gov)
  • We report that a localized inducible protein tether between the chromosome and cell membrane in E. coli cells imparts a rapid and complete block to replication initiation. (nih.gov)
  • Type 1 fusion machines initially bind a receptor on the target cell surface, which triggers a conformational change, allowing for binding of the fusion protein. (wikipedia.org)
  • This oligomerization has also been implicated in fusion initiation with the membrane of the target cell. (wikipedia.org)
  • The env gene codes for the gp160 protein which forms a homotrimer, and is cleaved into gp120 and gp41 by the host cell protease, furin. (wikipedia.org)
  • Although this gene was isolated as a transforming gene from a melanoma cell line, no linkage between MEL and malignant melanoma has been demonstrable. (nih.gov)
  • Virus-mediated gene therapy has the potential to deliver exogenous genetic material into specific cell types to promote survival and counteract disease. (frontiersin.org)
  • Gene therapy viruses are non-replicating, but still hijack host cell machinery to express transgenes of interest in the nucleus. (frontiersin.org)
  • Therefore, there is need for fundamental distinction between the different types and functions of genes that are involved in anti-cell death in plants. (essaywriter.org)
  • The main aim of this paper is to review the pathways that lead to cell death in plants with a purpose of identifying the anti-cell death genes. (essaywriter.org)
  • At the end of the discussion, significant insights will be developed to paint a picture of the emerging trends in plant development with respect to the topical research on anti-cell death genes. (essaywriter.org)
  • We identified 24 common genes that were significantly altered in both PMNs and PBMCs, including genes involved in IFN signaling that were downregulated after treatment in both cell populations, and IL1R1 that was upregulated. (frontiersin.org)
  • Many TPs function as gateways or "loading docks" to deny or permit the transport of specific substances across the biological membrane, to get into the cell, or out of the cell as in the case of waste byproducts. (wn.com)
  • These molecules are found in cell membranes throughout the body. (medlineplus.gov)
  • Plasmalogens may also play important roles in interactions between lipids and proteins, the transmission of chemical signals in cells, and the fusion of cell membranes. (medlineplus.gov)
  • Cell membrane. (atlasgeneticsoncology.org)
  • After fusion of the two plasma membranes of the mating cells, a dinucleated cell forms initially in which the two haploid nuclei then rapidly fuse to form a single diploid nucleus. (rupress.org)
  • Subcellular localization results showed that SP2 is located mainly on the cell membrane. (hindawi.com)
  • Indeed, a number of genes identified as potential manipulators of the host cell phenotype are absent from the T . equi genome. (biomedcentral.com)
  • T . equi has lost the putative genes for host cell transformation, or the genes were acquired by T . parva and T . annulata after divergence from T . equi . (biomedcentral.com)
  • Translocation carcinoma is a renal cell carcinoma (RCC) subtype that harbors a translocation involving a member of the microphthalmia transcription factor gene family. (medscape.com)
  • Importantly, we observed that loss of N-myristoylation resulted in greatly reduced infectivity of assembled mature virus particles, characterized by significantly reduced host cell entry and a decline in membrane fusion activity of progeny virus. (cdc.gov)
  • The sphingomyelin that accumulates in the lysosomes of Niemann-Pick disease-affected cells is thought to arise from the degradation of the cells and their organelles because it is a major component of all mammalian cell membranes. (medscape.com)
  • A membrane receptor reagent and assay is disclosed in which liposomes are bound to an evanescent wave emitting surface. (google.com)
  • Despite this, we are not aware of any reports of HSMN, type VI associated with mutations in the OPA1 gene. (neuroophthalmology.ca)
  • The RAS-related proteins of the RAB/YPT family may play a role in the transport of proteins from the endoplasmic reticulum to the Golgi and the plasma membrane. (nih.gov)
  • Upon maturation, the rate of endocytosis is reduced, and a cAMP-dependent neuronal signal triggers the transport of PLP from LEs/Ls to the plasma membrane. (rupress.org)
  • They are integral membrane zinc metaloprotease that cleave transmembrane domains in proteins. (tcdb.org)
  • All transmembrane proteins are integral membrane proteins (IMPs), but not all IMPs are transmembrane proteins. (wn.com)
  • 2020). Functional Characterization of TMEM127 Variants Reveals Novel Insights into Its Membrane Topology and Trafficking. (tcdb.org)
  • Membrane Trafficking, Fusion, and Synaptic. (hhmi.org)
  • In this study, we show that neurons regulate myelin membrane trafficking in oligodendrocytes. (rupress.org)
  • The Tat pathway ensures that only soluble, well-folded proteins are transported out of the cytoplasm and displayed on the inner membrane, thereby eliminating poorly folded scFvs prior to interrogation for antigen-binding. (jove.com)
  • After 2 plamaphareses a renal biopsy showed: Light: endothelial swelling, thickening of glomerular basement membranes,with double contours & intraluminal thrombi. (asn-online.org)
  • The α-5 (IV) chain of collagen is 1,685 amino acids in length and is expressed at 225 locations in the human glomerular basement membrane, retinal pigment layer, main visual cortex, and cochlea. (researchsquare.com)
  • A similar expansion of genes encoding an antagonist of a host innate immune protein has been observed in the genome of vaccinia virus (discussed on TWiV #198 ). (virology.ws)
  • In this study, we performed a bioinformatics analysis of the entire maize genome and identified 40 CDPK genes. (biomedcentral.com)
  • Here, we present a genome-wide analysis of the CDPK gene family in maize for the first time, and this genomic analysis of maize CDPK genes provides the first step towards a functional study of this gene family in maize. (biomedcentral.com)
  • The gene product is a 6,657 base pair mRNA with 41 predicted exons in the human gene. (wn.com)
  • The gene is composed of 4 exons and the promoter region contains the regulatory transcription factor binding sites for CREB, POU3F1 and deltaCREB. (atlasgeneticsoncology.org)
  • The COL4A5, COL4A3, and COL4A4 genes have 53, 52, and 48 exons, respectively, and it is estimated that only 10% of all possible pathogenic COL4A5 variants have been reported (Gubler et al. (researchsquare.com)
  • Structural membrane biochemistry and method. (hhmi.org)
  • During vertebrate brain development, axons are enwrapped by myelin, an insulating membrane produced by oligodendrocytes. (rupress.org)
  • In the absence of neurons, the major myelin membrane protein, the proteolipid protein (PLP), is internalized and stored in late endosomes/lysosomes (LEs/Ls) by a cholesterol-dependent and clathrin-independent endocytosis pathway that requires actin and the RhoA guanosine triphosphatase. (rupress.org)
  • Therefore comparative genomic analysis of T . equi was undertaken to: 1) identify genes contributing to immune evasion and persistence in equid hosts, 2) identify genes involved in PBMC infection biology and 3) define the phylogenetic position of T . equi relative to sequenced apicomplexan parasites. (biomedcentral.com)
  • Comparative genomic analysis of T . equi revealed the phylogenetic positioning relative to seven apicomplexan parasites using deduced amino acid sequences from 150 genes placed it as a sister taxon to Theileria spp . (biomedcentral.com)
  • Etherphospholipid biosynthesis and dihydroxyactetone-phosphate acyltransferase: resolution of the genomic organization of the human gnpat gene and its use in the identification of novel mutations. (medlineplus.gov)
  • As a response to the shape of certain molecules these "freight handling" TPs may have special ways of folding up or bending that will move a substance through the biological membrane. (wn.com)
  • The soluble NSF attachment proteins (SNAPs) enable N-ethyl-maleimide-sensitive fusion protein (NSF) to bind to target membranes. (antibodies-online.com)
  • Our analysis identified 50 genes that will be useful for definitive phylogenetic classification of T . equi and closely related organisms. (biomedcentral.com)
  • Microarray analysis of cells infected with non-pathogenic m. smegmatis revealed that a number of genes were up-regulated, most strikingly TNFa and Rab proteins involved in membrane fusion, in comparison to control un-infected cells. (europa.eu)
  • There is both genetic and biochemical evidence that Kar2p interacts with Sec63p, an ER membrane protein containing both luminal and cytosolic domains that is involved in protein translocation across the membrane. (rupress.org)
  • Some gene knockouts produce infertile phenotypes with obviously missing, specific activities that affect acrosome biogenesis during spermatogenesis or interfere with acrosome function in mature sperm. (nih.gov)
  • Taken together, these results suggest a direct role for Sec63p, Sec71p, and Sec72p in nuclear membrane fusion and argue against the alternative interpretation that the karyogamy defects result as an indirect consequence of the impaired membrane translocation of another component(s) required for the process. (rupress.org)
  • The hemagglutinin (HA) gene codes for one of the two surface glycoproteins and is central to species speci city because it is responsible for virus attachment and fusion with host cells. (cdc.gov)
  • This CD4-independence is associated with spontaneous mutation in the env gene. (wikipedia.org)
  • Purpose We report a novel gene mutation in a female patient with Alport syndrome who was planning to undergo assisted reproduction to achieve pregnancy. (researchsquare.com)
  • Conclusion Genetic testing prior to pregnancy is recommended in Alport syndrome patients or family members prior to pregnancy to determine the specific location of the gene mutation. (researchsquare.com)
  • 1. Identification and characterization of Arabidopsis rat mutants and molecular cloning of RAT genes (Gelvin, Citovsky, Hohn, and Ziemienowicz laboratories, with help from undergraduate students at Tuskegee University). (purdue.edu)
  • Recently, mutations in the mitofusin 2 (MFN2) gene have been associated with HSMN, type 6. (neuroophthalmology.ca)
  • reviewed in Roll and Reuther, 2010), as well as mutations of the lymphoid transcription factor gene IKZF1 (IKAROS) (Harvey et al. (atlasgeneticsoncology.org)
  • Firstly, the regulatory region controlling transcription of the gene encoding the IE protein Vmwl 10 has been replaced by the Moloney murine leukaemia virus (MMLV) enhancer. (gla.ac.uk)
  • Tethers, composed of a trans-membrane and transcription repressor fusion protein bound to an array of operator sequences, can be placed up to 1 Mb from the origin with no loss of penetrance. (nih.gov)
  • In this study, the sp2 gene was cloned and expressed in Escherichia coli to produce a 6xHis-tagged fusion protein, which was then used to generate a polyclonal antibody. (hindawi.com)
  • In this review article, we outline key characteristics of major gene therapy viruses-adenovirus, adeno-associated virus (AAV), and lentivirus-and summarize the mechanisms regulating important steps in the virus journey from binding at peripheral nerve terminals to nuclear delivery. (frontiersin.org)
  • Molecular Mechanisms of Membrane Transporter. (hhmi.org)
  • Administration of gene therapy viruses into skeletal muscle, where distal terminals of motor and sensory neurons reside, has been shown to result in extensive transduction of cells within the spinal cord, brainstem, and sensory ganglia. (frontiersin.org)
  • Together, our work revealed how PARIS drives adverse effects on modulation of PPAR-γ associated gene clusters in DA neurons. (nature.com)
  • Previous studies examining the structure of in820 in the in vitro latency system showed that the thymidine kinaase (TK) gene is not bound by nucleosomes with regular spacing. (gla.ac.uk)
  • Abnormal α-chain structures destroy the integrity of the basement membrane, which initially leads to hematuria and later develops into moderate-to-severe proteinuria, progressive renal failure, high-pitched sensorineural hearing impairment, and eye disease. (researchsquare.com)
  • A transmembrane protein (TP) is a type of membrane protein spanning the entirety of the biological membrane to which it is permanently attached . (wn.com)
  • That is, transmembrane proteins span from one side of a membrane through to the other side of the membrane. (wn.com)
  • Transmembrane protein 131 (TMEM131) is a protein that is encoded by the TMEM131 gene in humans. (wn.com)
  • The authors believe that one copy of this gene was duplicated repeatedly as more of the encoded protein was needed to replicate in host cells. (virology.ws)
  • Monoclonal Anti-MUC1 (mouse IgG1 isotype) is derived from the hybridoma 1D1 produced by the fusion of mouse myeloma cells and splenocytes from BALB/c mice immunized with semi-purified MUC1 from pleural effusion of a breast cancer patient. (sigmaaldrich.com)
  • Theyre coated in the membranes of the cells they budded off of. (scienceblogs.com)
  • HVEPs increase the membrane permeability of cells, a phenomenon known as electroporation. (rsna.org)
  • The study reported here also showed the absence of a regular chromatin structure on the TK gene and furthermore that the nature of the inhibitor of DNA replication used to prevent the spread of nonlatent virus was not a significant variable. (gla.ac.uk)
  • In the second step, fusion of the inner membranes requires a motor-like process driven by OPA1 and coordinated by various other proteins, including the prohibitins. (centrodinoferrari.com)
  • Peptidase processing of bacteriocins is known in some cases to occur during transport, and the peptidase and transporter presumably form a complex in the membrane. (tcdb.org)
  • While there are significant differences in sequence of the env gene between retroviruses, the gene is always located downstream of gag, pro, and pol. (wikipedia.org)
  • The protein encoded by this gene is a member of the RAS superfamily which are small GTP/GDP-binding proteins with an average size of 200 amino acids. (nih.gov)
  • With thousands of clinical trials to date, gene therapy is a flourishing strategy with great promise for the treatment of diseases impacting the nervous system. (frontiersin.org)