Mesodermal genes. Medical search. Frequent questions

Both genes are expressed in the nascent mesoderm and neurectoderm , and morpholino knockdown of either causes defects in differentiation and morphogenesis of the mesoderm and neural plate . (xenbase.org)
Thus neurogenic gene functions appear to be required both for the normal segregation of founder cells and for muscle differentiation. (biologists.com)
Gene expression must be appropriately maintained to regulate development, differentiation, and proliferation of cells. (intechopen.com)
RA, produced by newly generated mesodermal cells, provides feedback that initiates NMP generation and induces neural differentiation, thereby coordinating the production of neural and mesodermal tissue. (mdc-berlin.de)
Therefore, gene activity is an important mechanism in embryonic development and adult stem cell differentiation. (edu.au)
HP1β is important for mesodermal differentiation of embryoid bodies. (biomedcentral.com)
Identification of genes involved in in vitro differentiation induction of embryonic stem cells (ESCs) into hematopoietic stem cells (HSCs) has been challenged during last decade. (ebiotrade.com)
Transduction of Lhx2 into ESC-derived mesodermal cells resulted in robust differentiation of c-Kit+/Sca-1+/Lineage- (KSL) cells in vitro. (ebiotrade.com)
Successful differentiation is guided in large part by epigenetic reprogramming and regulation of critical gene expression patterns. (biomedcentral.com)

Here, we identify and characterize the single Drosophila ortholog of the HB9/MNR2 gene family. (jneurosci.org)
Drosophila genes expressed specifically in all motoneurons have not been described, although a growing number of genes are known to be expressed in subsets of motoneurons. (jneurosci.org)
Migrating tracheal cells in Drosophila contact specific neural and glial cells as they navigate to precise targets in the CNS, and a novel tracheal gene called adrift is required for the process. (sdbonline.org)
Here we describe the function of a novel and essential Drosophila smORF gene named purriato (prto). (biomed.news)

Homozygous null embryos display extreme deformities with mesodermal development: the axis of the body is shortened, the notochord fails to form, and posterior somites never develop. (wikipedia.org)
At the molecular level, knockdown of PQBP1 in Xenopus animal cap explants inhibits target gene induction by FGF but not by BMP, Nodal or Wnt ligands, and knockdown of either PQBP1 or WBP11 in embryos inhibits expression of fgf4 and FGF4 -responsive cdx4 genes. (xenbase.org)
Founder cell segregation is deranged in embryos mutant for any of the neurogenic genes: enlarged clusters of cells expressing S59 or vestigial are detected at the sites where small numbers of founder cells segregate in the wild type. (biologists.com)
E2a Is Required for Subsets of Smad2/3 Binding and for Global Patterns of Smad2/3 Target Gene Expression (A) Smad2/3 targets 1,027 distinct genomic regions in control stage 10.5 embryos (yellow) and 1,671 regions in E2a -depleted embryos (blue). (xenbase.org)
D) Genes that retain Smad2/3 binding at the same genomic coordinates in E2a -depleted embryos (red box in B) are more likely to be downregulated by 2-fold or more in E2a -depleted embryos. (xenbase.org)
E and F) Significant overlap exists between genes that are Smad2/3 targets and genes that are downregulated in E2a -depleted embryos. (xenbase.org)
In Xenopus embryos, enforced expression of Tbx20a, but not Tbx20b, led to induction of mesodermal and endodermal lineage markers as well as cell migration, indicating that the long Tbx20a isoform uniquely bears functional domains that can alter gene expression and developmental behaviour in an in vivo context. (nih.gov)
This negative autoregulation is restricted to the mesodermal veg2 territory during the blastula stage as shown by WMISH analysis of MASO injected embryos. (caltech.edu)
We also demonstrated that ectopic expression of Nkx2.5 in chick embryos activates the hemoangiogenic gene expression program. (elifesciences.org)

Separately, E2a is necessary to drive transcription of Smad2 /3 target genes, including critical regulators of dorsal cell fate and morphogenesis. (xenbase.org)
2000 Right here we record that FoxD3 function in the Spemann organizer is vital for dorsal mesodermal advancement. (biopaqc.com)
FoxD3 functions like a transcriptional repressor to stimulate dorsal mesoderm and axis development and antagonism or knockdown of FoxD3 leads to severe axial problems and lack of dorsal mesodermal gene manifestation. (biopaqc.com)

Genome-wide ChIP-seq mapping showed that Brd4 and H4 acetylation are co-occupied in the genome, upstream of core pluripotency genes such as Oct4 and Nanog in ESCs and lineage-specific genes in embryoid bodies (EBs). (biomedcentral.com)

Tbx15 also down-regulates the mass of mitochondria and the rate of basal mitochondrial expression, with both decreasing significantly if the gene is overexpressed. (wikipedia.org)
Knockdown organisms show no change in white adipocytes, but do display reduced expression of the marker genes directly involved in brown adipocyte expression. (wikipedia.org)
Lentiviral (LV) vectors of the Retroviridae family show interesting properties for monogenic gene therapy, since they integrate into the host genome and allow long-lasting gene expression 22 . (nature.com)
The founder cells, characterised by the expression of genes encoding putative transcription factors such as S59 or vestigial , fuse with neighbouring myoblasts to form syncytial precursors of individual muscles. (biologists.com)
A tubal origin for high-grade serous ovarian cancer is supported by gene expression profiles of OSC that reveal that they are more similar to normal müllerian epithelium than the ovarian surface epithelium [ 7 ]. (hindawi.com)
In the vertebrate CNS, HB9/MNR2 transcription factors are specifically expressed in all somatic motoneurons and are necessary to distinguish motoneurons from interneurons, in part by repressing interneuron-specific gene expression. (jneurosci.org)
Relative levels of gene expression throughout development were determined by quantitative polymerase chain reaction (PCR) analysis and in cases where sufficient specific gene sequence was acquired, ribonucleic acid (RNA) probes were generated to evaluate the spatial expression patterns during the period of organogenesis. (europa.eu)
Spatial expression analysis of both genes revealed that Sof-RXR is expressed ubiquitously in all cells of the embryo, including the chondrocytes, whereas Sof-ALDH was expressed only in a sub-set of epithelial cells and no expression at the level of chondrocytes was observed. (europa.eu)
Here, we investigate how perturbation of the cofactor E2a affects global patterns of Smad2 /3 binding and gene expression during gastrulation. (xenbase.org)
This nucleoplasmic lamin A environment tends to be euchromatic, suggesting distinct roles of lamin A in the regulation of gene expression in peripheral and more central regions of the nucleus. (frontiersin.org)
Imbalances or disturbances in gene expression are sometimes deleterious for living things. (intechopen.com)
For example, steroid and thyroid hormones directly bind to nuclear receptors, which induce expression of specific genes. (intechopen.com)
In other words, expression of specific genes might have relevance to pathogenesis of diseases. (intechopen.com)
We described the early embryonic development of the loach, Misgurnus anguillicaudatus , based on morphological features and gene expression. (bioone.org)
The embryonic development of the loach resembled that of the zebrafish in terms of morphological change and gene expression. (bioone.org)
Tbx20 physically interacted with cardiac transcription factors Nkx2-5, GATA4, and GATA5, collaborating to synergistically activate cardiac gene expression. (nih.gov)
Branchless signaling also induces expression of genes, including pointed and DSRF, required for secondary and terminal branching in the leading cells of the primary branches. (sdbonline.org)
Expression of the gene is induced in the lead cell of the migrating ganglionic branch by the bnl FGF pathway, whereupon it promotes the switch from one neural substratum to another (Englund, 1999). (sdbonline.org)
These E-PZ-iPS-like cells with normal karyotype gained expression of pluripotent genes typical of iPS cells (Tra-1-81, SSEA-3, Nanog, Sox2, and Oct4) and lost gene expression characteristic of basal prostatic epithelial cells (CK5, CK14, and p63). (nih.gov)
The diverse cell types are genetically identical, but differ in their form and function due to differences in gene expression. (edu.au)
This regulatory module of the Spblimp1/krox gene, which lies immediately upstream of the transcription initiation site for Spblimp1/krox1a, directs expression with great accuracy to the midgut and hindgut of the postgastrular embryo. (caltech.edu)
RARÎ³ is required for mesodermal gene expression prior to gastrulation in Xenopus . (bvsalud.org)
Chemically induced gene expression changes were characterized by qRT-PCR, global run-on sequencing (GRO-seq) and immunoblotting, and the network of cooperative proteins of GATA4 and NKX2-5 were further explored by the examination of the GATA4 and NKX2-5 interactome by BioID. (biomedcentral.com)
Reporter gene assays were conducted to examine combinatorial effects of GATA-targeted compounds and bromodomain and extraterminal domain (BET) inhibition on chamber-specific gene expression. (biomedcentral.com)
GATA4-targeted compounds 3i-1000 and 3i-1103 were identified as differential modulators of atrial and ventricular gene expression. (biomedcentral.com)
In this line, reporter gene assays with combinatorial treatment of 3i-1000 and the BET bromodomain inhibitor (+)-JQ1 demonstrated the cooperative role of GATA4 and BRD4 in the modulation of chamber-specific cardiac gene expression. (biomedcentral.com)
ppGpp is an intracellular sensor that, in response to different types of stress, coordinates the rearrangement of the gene expression pattern of bacteria to promote adaptation and survival to new environmental conditions. (ibecbarcelona.eu)
First described to modulate metabolic adaptive responses, ppGpp modulates the expression of genes belonging to very diverse functional categories. (ibecbarcelona.eu)
Within the research in Molecular Biology, one important field along the years has been the analyses on how prokaryotes regulate the expression of their genes and what the consequences of these activities are. (ibecbarcelona.eu)
We show that expression of the cardiac transcription factor Nkx2.5 marks a mesodermal population outside of the cardiac crescent in the extraembryonic and lateral plate mesoderm, with characteristics of hemogenic angioblasts. (elifesciences.org)
Publicly available at the NCBI Gene Expression Omnibus (accession no: GSE65924). (elifesciences.org)
In this study, we simultaneously identified six lncRNA open reading frames (ORFs) with peptide-coding abilities including lysine-specific demethylase 4A antisense RNA 1 (KDM4A-AS1) ORF by combining weighted gene co-expression network analysis (WGCNA) for ESCC clinical samples, ribosome footprints, ORF prediction, mass spectrometry (MS) identification, and western blotting. (biomed.news)
Histone post-translational modifications (PTMs) modulate the chromatin landscape by changing overall charge and by recruiting chromatin modifier enzymes, thereby facilitating gene expression/repression and DNA repair. (biomedcentral.com)
1 In particular, morpholino oligonucleotides (MOs) have been used to block the expression of targeted genes in several invertebrate and vertebrate models. (cdc.gov)

In order to understand what a particular gene does, you have to understand what all the other genes do, as well as all the details of signaling and cell interactions that are going on, oh, and also, it's entire developmental history, since epigenetic interactions can shape the future behavior of a cell lineage. (scienceblogs.com)
C) DAVID clustering analysis shows enrichment for developmental (dev) terms in all Smad2/3-associated genes and for genes that have stable Smad2/3 binding when E2a is depleted (red box in B) but not other subcategories of Smad2/3 binding. (xenbase.org)
Pharmacological modulation of cell fate decisions and developmental gene regulatory networks holds promise for the treatment of heart failure. (biomedcentral.com)
a Relative fold change of developmental genes of the three germ layers in EBs derived from HP1α KO ESCs ( empty bars ) and EBs derived from HP1β KO ESCs ( filled bars ). (biomedcentral.com)
The histone demethylase KDM1A is a multi- faceted regulator of vital developmental processes, including mesodermal and cardiac tube formation during gastrulation. (ibecbarcelona.eu)

E-PZ-iPS-like cells demonstrated pluripotency by differentiating into ectodermal, mesodermal, and endodermal cells in vitro, although lack of teratoma formation in vivo and incomplete demethylation of pluripotency genes suggested only partial reprogramming. (nih.gov)

Gene therapy has been utilized successfully to repair or inactivate mutations in animal models of monogenic human diseases 19 as well as human in vitro cells 12 . (nature.com)
These are for the most part low-grade tumors that are characterized by a high frequency of mutations of KRAS , BRAF, ERBB2, CTNNB1 (the gene encoding beta catenin), and PIK3CA , low proliferation, and a 5-year survival of approximately 55% [ 2 ]. (hindawi.com)
They are characterized by a high frequency of mutations in TP53 , a tumor suppressor gene, and a high proliferative index. (hindawi.com)
Mutations in the gene adrift affect the first substratum switch causing failure of GBs to enter the CNS and misrouting along the ventral epidermis. (sdbonline.org)
Mutations in the ADAMTS10 and FBN1 genes can cause Weill-Marchesani syndrome. (medlineplus.gov)
Mutations in this gene disrupt the normal development of these structures, which leads to the specific features of Weill-Marchesani syndrome. (medlineplus.gov)
Autosomal recessive inheritance means both copies of the gene in each cell have mutations. (medlineplus.gov)
Mutations in this gene are associated with Hirschsprung disease/Mowat-Wilson syndrome. (beds.ac.uk)

Cancer-promoting genes MYC and TWIST1 co-opt immune system cells to enable cancer cells to spread, but blocking a key step in this process can help prevent the disease from developing. (news-medical.net)
These microenvironment changes are needed to enable mesodermal cells to migrate to their destination. (news-medical.net)
A critical bottleneck to the creation of specific cell types from stem cells (and related therapies) is our current inability to make cells execute complex multi-gene programs on command. (ca.gov)
We have learned that genes in mammalian cells are transcribed into messenger RNAs (mRNAs), which are to be translated into polypeptides (proteins). (intechopen.com)
bnl is expressed in discrete clusters of ectodermal and mesodermal cells arrayed around each tracheal sac. (sdbonline.org)
Transcription factor GATA4-targeted compounds that have previously shown in vivo efficacy in cardiac injury models were tested for stage-specific activation of atrial and ventricular reporter genes in differentiating pluripotent stem cells using a dual reporter assay. (biomedcentral.com)
Collectively, these results indicate the potential for therapeutic alteration of cell fate decisions and pathological gene regulatory networks by GATA4-targeted compounds modulating chamber-specific transcriptional programs in multipotent cardiac progenitor cells and cardiomyocytes. (biomedcentral.com)
Each cell type has the same genes, but they are expressed differently during development and in mature cells. (medicilon.com)
Carrying out research on human and mouse cells, the team found that the genes regulated by RSF1 overlapped greatly with those controlled by part of a complex that ubiquitinates H2A. (medicilon.com)
Knocking out RSF1 in cells derepressed the genes regulated by RSF1, and this was accompanied by changes in ubiquitinated H2A chromatin organization and release of linker histone H1. (medicilon.com)
In particular, the present invention provides neurogenesis inducing genes coding for Zic proteins, vectors containing such genes, host cells containing such vectors, proteins produced by such host cells, antibodies raised to such proteins, and therapeutic agents or agents for gene therapy for nervous diseases. (justia.com)

Failure of mesodermal induction has been suggested to cause Meckel-Gruber syndrome. (medscape.com)
The induction cascades of early morphogenesis involve numerous growth factors, homeobox genes, and paired domain genes. (medscape.com)
Patterning and induction from the mesodermal germ coating is an integral early stage of vertebrate embryogenesis. (biopaqc.com)

On the basis of recent vertebrate studies, the HB9/MNR2 gene family is a prime candidate for a general determinant of somatic motoneuron cell type. (jneurosci.org)
Thus, vertebrate HB9/MNR2 genes are expressed specifically in somatic motoneurons and are essential for distinguishing motoneuron/interneuron cell types. (jneurosci.org)
The critical factor that controls the outgrowth of primary branches is the product of the branchless ( bnl ) gene, a homolog of vertebrate FGFs (Sutherland, 1996). (sdbonline.org)

What you actually find in the genome are coding genes that produce proteins, coupled to regulatory elements that switch the coding genes off and on using a kind of sophisticated boolean logic. (scienceblogs.com)
The protein encoded by this gene is a member of the Zfh1 family of 2-handed zinc finger/homeodomain proteins. (beds.ac.uk)

pqbp1 and wbp11 genes are similarly expressed in mesoderm and neural tissues during Xenopus development. (xenbase.org)
It is not clear whether either of these requirements reflects an essential function for any or all of the neurogenic genes within the mesoderm itself. (biologists.com)

The splicing factor PQBP1 regulates mesodermal and neural development through FGF signaling. (xenbase.org)
Wnt signaling regulates β-catenin-mediated gene transcription and planar cell polarity (PCP). (silverchair.com)

To see if the two genes also contributed to metastases in humans, the scientists analyzed 10,000 samples of tumors collected from humans with 33 different types of cancer. (news-medical.net)
Type II tumors include high-grade serous carcinoma, malignant mixed mesodermal tumors, and undifferentiated carcinomas. (hindawi.com)
CpG methylation of the FHIT, FANCF, cyclin-D2, BRCA2 and RUNX3 genes in Granulosa cell tumors (GCTs) of ovarian origin. (cancercentrum.se)

Readout of multi-gene perturbation with single-cell RNA sequencing. (ca.gov)
Direct hiPSCs into a mesodermal progenitor state using simultaneous perturbation of multiple genes. (ca.gov)
Blimp1/Krox inputs expected from the perturbation analysis into other genes have been incorporated in our gene regulatory network. (caltech.edu)

This took place via a dysregulation of mesodermal cell fate specification. (medicilon.com)

I have a bit of a peeve with a common analogy for the human genome: that it is the blueprint of the body, and that we can find a mapping of genes to details of our morphological organization. (scienceblogs.com)
For instance, there is no code anywhere in the genome that commands the forelimbs to make five and only five digits: instead, a cascade of genes and cell movements produce a patterned tissue that in us contains sufficient mass and is of a size to generate five nuclei of condensing tissue that produce fingers. (scienceblogs.com)
The unfortunate consequence of those properties, though, is that you'll never be able to look at a single gene from the genome and sort out what it does in the embryo. (scienceblogs.com)
We discuss associated epigenetic and genome conformation changes elicited by the lamin A R482W mutation at the gene level. (frontiersin.org)

The absence of genomic resources renders the search for paralogous cuttlefish genes dependent upon the presence of highly conserved protein motifs within genes of interest, thus we used a degenerate primer strategy to isolate partial coding sequence from the conserved domains specific to these families. (europa.eu)

T-box transcription factor TBX15 is protein that is encoded in humans by the Tbx15 gene, mapped to Chromosome 3 in mice and Chromosome 1 in humans. (wikipedia.org)
Molecular characterization of the adrift gene demonstrates that it encodes a novel nuclear protein. (sdbonline.org)
The ADAMTS10 gene provides instructions for making a protein whose function is unknown. (medlineplus.gov)
The FBN1 gene provides instructions for making a protein called fibrillin-1. (medlineplus.gov)
Researchers at the University of Alabama (UAB) at Birmingham report the discovery of an important role for the RSF1, or remodeling and spacing factor 1, protein in silencing genes. (medicilon.com)
Smith UM, Consugar M, Tee LJ, McKee BM, Maina EN, Whelan S. The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. (medscape.com)
The present invention also relates to a gene which hybridizes with the neurogenesis inducing gene encoding for a protein comprising at least a portion of the amino acid sequence set forth in SEQ ID NO:2. (justia.com)

prto is dynamically expressed in mesodermal tissues and imaginal discs. (biomed.news)
In combination with transgenic organisms, such enzyme-actuated antisense tools will enable gene silencing in specific cell types, including tissues that are not amenable to optical targeting. (cdc.gov)

The stable nucleosome array leads to a chromatin architecture that is refractory to further remodeling required for ubiquitinated H2A target gene activation. (medicilon.com)
These ubiquitinated H2A nucleosomes are subjected to chromatin remodeling for gene activation. (medicilon.com)

Transcriptional activity is regulated by DNA binding transcription factors, but these typically act in more than one cell lineage activating different subsets of target genes in each. (edu.au)

Conventional MOs are typically used to constitutively disrupt targeted genes in an organism-wide manner. (cdc.gov)

Development of a machine-learning computational model for predicting target genes for multi-gene regulation. (ca.gov)
These genes maintain enrichment for DAVID terms associated with early development. (xenbase.org)

Histone H2AK119 ubiquitination (H2Aub), as mediated by Polycomb repressive complex 1 (PRC1), is a prevalent modification which has been linked to gene silencing. (medicilon.com)
We show that RSF1 is required both for H2Aub-target gene silencing and for maintaining stable nucleosome patterns at promoter regions. (medicilon.com)
This modification is linked to gene silencing, while removing ubiquitin from H2A leads to gene activation. (medicilon.com)
Dr. Wang and colleagues discovered that RSF1 mediates the gene-silencing function of ubiquitinated H2A. (medicilon.com)
In the PNAS paper, Dr. Wang and his group suggested a model for the action of RSF1 in gene silencing. (medicilon.com)
11 , 12 Light-dependent gene silencing can be achieved through whole-organism irradiation or the targeted illumination of specific cell populations. (cdc.gov)

Recent global analyses of gene transcripts revealed that specific transcription factors (TFs) and their networking systems physiologically correspond to the onset of human diseases, including cancer. (intechopen.com)

A CRISPR-based tool for simultaneous up- and downregulation of many (~5-20) genes, and a computational tool using scRNA-seq data to predict which genes to perturb for efficacious cell-type conversion. (ca.gov)

We and others have synthesized light-activatable cMOs that allow spatiotemporal control of RNA splicing or translation, complementing the use of conditional knockouts to study stage- and tissue-specific differences in gene function. (cdc.gov)
18 , 19 We surmised that cyclic cMOs containing an NfsB-cleavable linker could be used with analogous lines to knock down gene function in a tissue-specific manner (Figure 1 a). (cdc.gov)

Phosphorodiamidate morpholino oligonucleotides are widely used to interrogate gene function in whole organisms, and light-activatable derivatives can reveal spatial and temporal differences in gene activity. (cdc.gov)

onal repression by FoxD3 is necessary for mesodermal advancement. (biopaqc.com)

In another embodiment, the present invention relates to a gene comprising a DNA sequence having at least a portion of the nucleotide sequence set forth in SEQ ID NO: 1. (justia.com)

Histone acetylation is associated with gene activation [ 6 ]. (biomedcentral.com)

Understanding the mechanisms that turn sets of genes on or off is a fundamental quest in biology, and one that has clinical importance in diseases like cancer, where gene control goes awry. (medicilon.com)
Understanding how genes get turned on or off is critical for developing better therapies for diseases like cancer. (medicilon.com)

the same mutation of the Tbx15 gene is seen in both species. (wikipedia.org)
A mutation in the FBN1 gene has also been found to cause Weill-Marchesani syndrome. (medlineplus.gov)

Biallelic inactivating variants of the TBX15 gene can cause a recessively inherited condition called Cousin Syndrome. (wikipedia.org)
Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. (medscape.com)
Analysis of ZEB2 gene variation in two patients with Mowat-Wilson syndrome]. (beds.ac.uk)

Each cell carries this complex collection of regulated genes independently and identically, but the boolean logic circuits produce different outputs varying with the inputs from the environment and the diverging histories of each cell. (scienceblogs.com)

Due to cellular heterogeneity in the heart, the activation of gene programs representing specific atrial and ventricular cardiomyocyte subtypes would be highly desirable. (biomedcentral.com)

Biological processes where the bars in the graph go to the left of zero are those affected significantly by genes downregulated in HP1β −/− EBs, whereas the those where the bars go to the right of zero are those significantly affected by genes upregulated in HP1β −/− EBs. (biomedcentral.com)

Contributing to the interest of the present topic is the fact that modulation of gene activity involves the sensing of intra- and inter-cellular conditions, DNA binding and DNA dynamics, and interaction with the replication/transcription machinery of the cell. (ibecbarcelona.eu)

Identification of ZEB2 as an Immune-Associated Gene in Endometrial Carcinoma and Associated with Macrophage Infiltration by Bioinformatic Analysis. (beds.ac.uk)

Anatomy3

Organisms2

Chemicals and Drugs5

Phenomena and Processes3

Differentiation9

Drosophila4

Embryos9

Dorsal3

Embryoid bodies1

Expression34

Developmental5

Pluripotency genes1

Mutations8

Cells11

Induction3

Vertebrate3

Proteins2

Mesoderm2

Regulates2

Tumors3

Perturbation3

Specification1

Genome4

Genomic1

Protein7

Tissues2

Chromatin2

Subsets1

Disrupt1

Development2

Silencing6

Analyses1

CRISPR1

Tissue2

Spatial1

Repression1

Sequence1

Histone1

Diseases2

Mutation2

Syndrome3

Inputs1

Cardiomyocyte1

Significantly1

Modulation1

Identification1