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Gene Review

TOX  -  thymocyte selection-associated high...

Homo sapiens

Synonyms: KIAA0808, TOX1, Thymocyte selection-associated high mobility group box protein TOX, Thymus high mobility group box protein TOX
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Disease relevance of TOX

  • Toxicity mediated by reactive oxygen species (ROS-TOX) was detected in the OxyR(-) assay using cells sensitive to oxidative stress due to a deficiency in the OxyR function [1].
  • Mean TOX in the two groups were similarly close except when considering alopecia as a relevant toxic event [2].
  • Multicenter evaluation of the Clostridium difficile TOX A/B TEST [3].
  • Infant birth weight ratio (IBR) was lower in +TOX women (0.84 vs. 0.90, p = 0.003). +TOX women were twice as likely to have small-for-gestational-age (IBR < 0.85) neonates than were -TOX [4].

High impact information on TOX

  • TOX expression is up-regulated by both pre-TCR and TCR activation of immature thymocytes but not by TCR activation of mature naïve T cells [5].
  • TOX provides a link between calcineurin activation and CD8 lineage commitment [6].
  • We further demonstrate that up-regulation of TOX in double positive thymocytes is calcineurin dependent, linking this critical signaling pathway to nuclear changes during positive selection [6].
  • Strong ROS-TOX required a pyrogallol arrangement (exifone; 2,3,4-trihydroxybenzophenone, 1; baicalein) or a 2-aminoresorcinol sequence (3-amino-2,4-dihydroxybenzophenone, 4) [1].
  • The average time spent in these health states (TOX, CT, TWiST and REL, respectively) were then weighted by utility coefficients reflecting relative QoL value according to that of TWiST and summed up giving the so-called Q-TWiST [2].

Chemical compound and disease context of TOX

  • The detection of faecal cytotoxicity using tissue culture was compared with three commercial Clostridium difficile enzyme immunoassay (EIA) kits; Premier C difficile toxin A (Meridian Diagnostic, Inc.); CD-TOX C difficile toxin A (Porton Cambridge); and Cytoclone A+B EIA (Cambridge Biotech Corporation) [7].

Biological context of TOX

  • Three other human and murine predicted proteins are identified that share a common HMG-box domain with TOX, as well as other features [8].
  • We show here that expression of the HMG box protein TOX is sufficient to induce changes in coreceptor gene expression associated with beta-selection, including CD8 gene demethylation [6].
  • The average instantaneous TOX concentration for chlorine dioxide, chloramine, and chlorine disinfection after 30 min contact time increased by 60, 92, and 238 micrograms/L, respectively, from a nondisinfected concentration of 25 micrograms/L [9].
  • STUDY DESIGN: Using urine toxicology data at delivery, subjects were classified drug positive (+TOX) (n = 53) or negative (-TOX) (n = 159) [4].

Anatomical context of TOX

  • We recently identified an HMG-box protein involved in T cell development, designated TOX, which is highly conserved in humans and mice [8].
  • OBJECTIVE: To develop methods for using a DNA-specific dye to discriminate between motile and nonmotile sperm and static particulate matter in fresh and diluted semen, using computer-assisted sperm analysis (CASA) with the Hamilton Thorne IVOS, TOX version (Hamilton-Thorne Research, Beverly, MA) [10].
  • The aim of these investigations was to establish a model for the study of neutrophil (NEU) and monocyte (MO) mediated cytotoxicity (TOX), and to study the protective actions of model protease inhibitor, peroxide scavengers and glucocorticoids in this model [11].

Associations of TOX with chemical compounds

  • However, TOX concentrations decreased substantially with increasing initial iodide concentrations [12].
  • Phenol structures in natural fulvic acids in DOM isolated from groundwater produced significant trihalomethanes (THM) and total organic halogen (TOX) yields upon chlorination, and these structures also were responsible for the enhanced SUVA and specific fluorescence characteristics relative to DOM in reclaimed water [13].
  • The same happened for organic chlorine (TOX) conversion into inorganic chloride, i.e. 100%, after 3 h at 70 degrees C, and 87%, after 27 h at 25 degrees C. As the recorded trends of CMP removal and chloride formation were basically the same, hydroxy substitution (ipso-substitution) was hypothesised as one likely mechanism of CMP degradation [14].
  • Of 160 faecal samples examined by all four methods, 52 (32.5%) were cytotoxic, 44 (27.5%) were positive by Premier, 48 (30%) by CD-TOX EIA, and 50 (31.3%) with Cytoclone [7].
  • The TOX method is moderately sensitive to nitrate rinse volume [15].

Other interactions of TOX

  • Herbicide decay, corresponding evolutions of TOC, TOX and chloride ion release were regularly monitored throughout the reactions [16].

Analytical, diagnostic and therapeutic context of TOX

  • RESULTS: We show here that based on sequence alignment, TOX best fits into the sequence-independent HMG-box family [8].
  • In this study, we evaluated the TOX A/B TEST, a new 1-h enzyme immunoassay (EIA) that detects toxins A and B. We compared the test with the tissue culture assay, which is recognized as the "gold standard" for C. difficile testing [3].
  • Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools [17].
  • However, after resolution of six discrepants using another ELISA for toxin A detection the sensitivity, specificity, positive and negative predictive values for the TOX A/B test are as follows: 94.5%; 100%; 100%; 98.8% [17].
  • TOX-ACLS: toxicologic-oriented advanced cardiac life support [18].


  1. A convenient approach for evaluating the toxicity profiles of in vitro neuroprotective alkylaminophenol derivatives. Urios, A., Largeron, M., Fleury, M.B., Blanco, M. Free Radic. Biol. Med. (2006) [Pubmed]
  2. Evaluating treatment strategies in advanced Waldenström macroglobulinemia: use of quality-adjusted survival analysis. Lévy, V., Porcher, R., Leblond, V., Fermand, J.P., Cazin, B., Maloisel, F., Harousseau, J.L., Remenieras, L., Guibon, O., Chevret, S. Leukemia (2001) [Pubmed]
  3. Multicenter evaluation of the Clostridium difficile TOX A/B TEST. Lyerly, D.M., Neville, L.M., Evans, D.T., Fill, J., Allen, S., Greene, W., Sautter, R., Hnatuck, P., Torpey, D.J., Schwalbe, R. J. Clin. Microbiol. (1998) [Pubmed]
  4. Smoking and illicit drug use during pregnancy: impact on neonatal outcome. Miles, D.R., Lanni, S., Jansson, L., Svikis, D. The Journal of reproductive medicine. (2006) [Pubmed]
  5. TOX: an HMG box protein implicated in the regulation of thymocyte selection. Wilkinson, B., Chen, J.Y., Han, P., Rufner, K.M., Goularte, O.D., Kaye, J. Nat. Immunol. (2002) [Pubmed]
  6. TOX provides a link between calcineurin activation and CD8 lineage commitment. Aliahmad, P., O'Flaherty, E., Han, P., Goularte, O.D., Wilkinson, B., Satake, M., Molkentin, J.D., Kaye, J. J. Exp. Med. (2004) [Pubmed]
  7. Evaluation of three commercial enzyme immunoassay kits for detecting faecal Clostridium difficile toxins. Arrow, S.A., Croese, L., Bowman, R.A., Riley, T.V. J. Clin. Pathol. (1994) [Pubmed]
  8. TOX defines a conserved subfamily of HMG-box proteins. O'Flaherty, E., Kaye, J. BMC Genomics (2003) [Pubmed]
  9. Products identified at an alternative disinfection pilot plant. Lykins, B.W., Koffskey, W. Environ. Health Perspect. (1986) [Pubmed]
  10. Motility and other characteristics of human sperm can be measured by computer-assisted sperm analysis of samples stained with Hoechst 33342. Farrell, P.B., Foote, R.H., Zinaman, M.J. Fertil. Steril. (1996) [Pubmed]
  11. Cytotoxicity of human phagocytes studied in vitro in a novel model based on neutral red absorbtion. Brattsand, R., Delander, E.L., Peterson, C., Wieslander, E. Agents Actions (1991) [Pubmed]
  12. Effect of bromide and iodide ions on the formation and speciation of disinfection byproducts during chlorination. Hua, G., Reckhow, D.A., Kim, J. Environ. Sci. Technol. (2006) [Pubmed]
  13. Nature and chlorine reactivity of organic constituents from reclaimed water in groundwater, Los Angeles County, California. Leenheer, J.A., Rostad, C.E., Barber, L.B., Schroeder, R.A., Anders, R., Davisson, M.L. Environ. Sci. Technol. (2001) [Pubmed]
  14. Temperature activated degradation (mineralization) of 4-chloro-3-methyl phenol by Fenton's reagent. Lopez, A., Mascolo, G., Detomaso, A., Lovecchio, G., Villani, G. Chemosphere (2005) [Pubmed]
  15. Determination of TOCl, TOBr and TOI in drinking water by pyrolysis and off-line ion chromatography. Hua, G., Reckhow, D.A. Analytical and bioanalytical chemistry. (2006) [Pubmed]
  16. Chlorinated herbicide (triallate) dehalogenation by iron powder. Volpe, A., Lopez, A., Mascolo, G., Detomaso, A. Chemosphere (2004) [Pubmed]
  17. Comparison of the TOX A/B test to a cell culture cytotoxicity assay for the detection of Clostridium difficile in stools. Aldeen, W.E., Bingham, M., Aiderzada, A., Kucera, J., Jense, S., Carroll, K.C. Diagn. Microbiol. Infect. Dis. (2000) [Pubmed]
  18. TOX-ACLS: toxicologic-oriented advanced cardiac life support. Albertson, T.E., Dawson, A., de Latorre, F., Hoffman, R.S., Hollander, J.E., Jaeger, A., Kerns, W.R., Martin, T.G., Ross, M.P. Annals of emergency medicine. (2001) [Pubmed]
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