Disease relevance of T

• CONCLUSION: Low intravenous doses of FGF1 or FGF2 appear to protect bone marrow from the toxic effects of radiation without increasing the rates of tumor growth or metastases or decreasing the radiosensitivity of tumors [1].
• Expression of the Brachyury gene during mesoderm development in differentiating embryonal carcinoma cell cultures [2].
• We demonstrate that hypoxia accelerates the expression of Brachyury (a mesoderm-specific transcription factor), BMP4 (a mesoderm-promoting growth factor) and FLK1 (a marker of hemangioblasts, the bipotential progenitor of endothelial and hematopoietic cells) in differentiating ES cell cultures [3].
• Using the inhibitor of de novo pyrimidine biosynthesis, phosphonoacetyl-L-aspartate (PALA), as selective agent we found that PALA resistant cells arise with a frequency of about 5 x 10(-5) and that the interaction of polyomavirus large T protein with the retinoblastoma protein or another related pocket protein is important for this to occur [4].
• Association between historically high frequencies of neural tube defects and the human T homologue of mouse T (Brachyury) [5].

Psychiatry related information on T

• BACKGROUND: Low doses of the N-methyl-D-aspartate receptor (NMDAR) antagonist MK-801 (dizocilpine) or ethanol increase locomotor activity to a lesser extent in long-sleep (LS), than in short-sleep (SS), mice [6].
• RESULTS: Low doses and high doses of celecoxib significantly lengthened the tumor latency period (P<.03 and P<.003, respectively) and reduced tumor multiplicity (P<.005 and P<.001, respectively) compared with controls [7].
• BACKGROUND: Low-dose ethanol-induced activation (LDA) and initial sensitivity to alcohol are both predictors of alcohol abuse in human populations [8].
• We have also developed replicate lines of mice selectively bred for high (High Exploratory Behavior: HEB) or low (Low Exploratory Behavior: LEB) head dipping on a hole-board and evaluated the effects of diazepam and methamphetamine on hole-board behaviors in these mice [9].

High impact information on T

• It takes advantage of the properties of a cell line, 15P-1, established from testicular cells of transgenic mice that express the large T protein of polyoma virus in the seminiferous epithelium [10].
• The Brachyury (T) gene is required for mesoderm formation in the mouse [11].
• The expression of complexed middle T protein in both tumorigenic endothelial cells and unperturbed testes implies that endothelial cells may be particularly susceptible to the action of the middle T oncogene [12].
• Transgene RNAs and protein are present in both hemangiomas and the testes of these mice, and the Py middle T protein in both tissues is complexed to a cellular tyrosine kinase [12].
• Upon microinjection into fertilized mouse eggs of circular molecules of plasmid pPyLT1 carrying the gene encoding the large T protein of polyoma virus within bacterial vector sequences, autonomous circular plasmids were stably maintained in low copy numbers in transgenic strains [13].

Chemical compound and disease context of T

• CONCLUSIONS: Low-dose atorvastatin cholesterol-dependently reduces lesion progression in the aortic root but shows antiinflammatory vascular activity and tends to retard atherogenesis in the aortic arch beyond its cholesterol-lowering effect [14].
• OBJECTIVE: Low-dose methotrexate (MTX), a mainstay in the treatment of rheumatoid arthritis, is effective in only 60-70% of patients, a finding mirrored by poor antiinflammatory efficacy in some animal models, most notably collagen-induced arthritis [15].
• (1) Low urinary citrate is a risk factor for the development of kidney stones [16].
• CONCLUSIONS: Low dose suramin enhanced the in vitro and in vivo activity of subtherapeutic and therapeutic MMC without enhancing host toxicity, thus, providing proof of concept for evaluating low dose suramin as a chemosensitizer with MMC in bladder cancer [17].
• RESULTS: Low oxygen pressure exposure and hypoxia mimics treatments were associated with increased glucose consumption and release of lactate in differentiated 3T3-F442A adipocytes [18].

Biological context of T

• However, the enhancement of the T/+ phenotype in compound mutant mice (Sp5(lacZ)/Sp5(lacZ), T/+) indicates a genetic interaction between Sp5 and Brachyury [19].
• Mutations induced by N-ethyl-N-nitrosourea (ENU) at the Brachyury (T), quaking (qk), and tufted (tf) loci of the mouse tw5 haplotype have now allowed the analysis of crossovers between two complete t haplotypes [20].
• In Brachyury curtailed homozygotes, the expression of Sax-1 was found to be reduced during neurulation and even lost at day 9.0 pc [21].
• Homozygotes for this mutation show a short tail phenotype and, moreover, this mutation causes the tailless character by interacting with the T (brachyury) gene on Chromosome (Chr) 17 [22].
• Alterations in gene expression during mesoderm formation and axial patterning in Brachyury (T) embryos [23].

Anatomical context of T

• They consist of misfolded ectodermal and endodermal cell layers, do not form a primitive streak or any detectable mesodermal cells and fail to express the developmental marker genes Bra (T), Bmp-2/4 and Shh [24].
• Brachyury is required for elongation and vasculogenesis in the murine allantois [25].
• Within the caudal notochord, developing floorplate, and hindgut, HNF3alpha, HNF3beta, Shh, and Brachyury expression domains correlate directly with known genetic roles and predicted tissue interdependence during induction and differentiation of these structures [26].
• Brachyury homozygotes fail to make posterior somites, notochord, floor plate, and a placental connection, resulting in death by 10.5 days of development [27].
• In embryos dissected between 5.5 and 6.5 dpc, Brachyury is first expressed in the distal extra-embryonic ectoderm and subsequently on one side of the epiblast [28].

Associations of T with chemical compounds

• BMP Stimulation of Alkaline Phosphatase Activity in Pluripotent Mouse C2C12 Cells is Inhibited by Dermatopontin, One of the Most Abundant Low Molecular Weight Proteins in Demineralized Bone Matrix [29].
• The expression of Brachyury is not affected by DMSO but is induced by cell aggregation, which requires extracellular calcium [2].
• They express large T protein, present the phenotype of differentiated luminal prostatic cells (positive with antibodies to cytokeratin 18, 19, weakly positive for prostatic acid phosphatase and prostatic specific antigen, negative with anticytokeratin 14 and KL2 antibody) [30].
• In contrast, retinoic acid blocks the expression of the mesodermal genes Brachyury, cardiac actin, and zeta-globin [31].
• For Treatment 3 (T3) oocytes were matured in the portable incubator without CO(2) equilibration, in tubes containing HEPES buffered TCM 199 supplemented as in T1 [32].

Physical interactions of T

• Isoforms with an intact T-box bound specifically to DNA sites resembling the consensus brachyury half site, although with less avidity compared with the related factor, Tbx5 [33].
• Mga binds the preferred Brachyury-binding sequence and represses transcription of reporter genes containing promoter-proximal Brachyury-binding sites [34].

Regulatory relationships of T

• Here we show that Brachyury is specifically down-regulated in Wnt3a mutants in cells fated to form paraxial mesoderm [35].
• Reduction of MACF1 in Wnt-1-expressing P19 cells resulted in decreased T (Brachyury) gene expression, a DNA-binding transcription factor that is a direct target of Wnt/beta-catenin signaling and required for mesoderm formation [36].
• The presence (or absence) of E-cadherin regulates the expression of the transcription factor T-brachyury, indicating that cadherins play a role in linking cell surface receptors and gene expression [37].
• ES cells thus deprived of LIF/DIA differentiate spontaneously to a cell type that expresses Brachyury (T), a marker of early mesoderm [38].
• Here, we show that Nanog expression is up-regulated in mouse ES cells by the binding of T (Brachyury) and STAT3 to an enhancer element in the mouse Nanog gene [39].

Other interactions of T

• T1, T2, and the unlinked t-int are distinct and unrelated loci, and mutations in these genes do not complement one another genetically [40].
• An allele of the mouse brachyury locus, T22H, had been shown previously to involve a deletion of several markers in the proximal part of chromosome 17, and almost certainly includes deletion of the t-complex distorter gene Tcd-1 [41].
• We have compared the expression pattern of myogenic markers and markers for the hypaxial muscle precursors in the mutants Brachyury curtailed, truncate, Danforth's short tail and Pintail [42].
• In vitro, DNA binding studies show that it binds to the GC box, a DNA motif present in the promoter of a very large number of genes, including Brachyury, and recognised by members of the Sp1 family [19].
• T (Brachyury) is a direct target of Wnt3a during paraxial mesoderm specification [35].

Analytical, diagnostic and therapeutic context of T

• The existence of a second gene mapping near Brachyury and affecting the same developmental processes was alluded to over 50 years ago and has been debated ever since [27].
• Whole mount in situ hybridization of Pax6 revealed a normal pattern while staining by sonic hedgehog (shh) and Brachyury (T) exhibited abnormal patterns in the anterior-posterior (A-P) direction at both mesencephalic and thoracic levels [43].
• (1) A cDNA fragment encoding 212 amino acids of the rabbit Brachyury gene was cloned by RT-PCR and used as a molecular marker for mesoderm progenitors [44].
• CONCLUSION: Low-dose radiosensitization of actively dividing tumor cells by PARP-1 inhibitors suggests that they may have a role in enhancing the efficacy of ultrafractionated or low-dose-rate radiotherapy regimens [45].
• CONCLUSIONS: Low AR expression and maintained stroma IGF-1 synthesis may result in limited tumor cell death after castration therapy [46].

References