TIMELESS

Summary

Gene Symbol: TIMELESS
Description: timeless circadian regulator
Alias: TIM, TIM1, hTIM, protein timeless homolog, Tof1 homolog, timeless circadian clock 1, timeless homolog
Species: human
Products:     TIMELESS

Top Publications

  1. Zylka M, Shearman L, Levine J, Jin X, Weaver D, Reppert S. Molecular analysis of mammalian timeless. Neuron. 1998;21:1115-22 pubmed
    We cloned the mouse cDNA of a mammalian homolog of the Drosophila timeless (tim) gene and designated it mTim. The mTim protein shows five homologous regions with Drosophila TIM...
  2. Kume K, Zylka M, Sriram S, Shearman L, Weaver D, Jin X, et al. mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell. 1999;98:193-205 pubmed
    ..Luciferase reporter gene assays show that mCRY1 or mCRY2 alone abrogates CLOCK:BMAL1-E box-mediated transcription. The mPER and mCRY proteins appear to inhibit the transcriptional complex differentially. ..
  3. Yoshizawa Sugata N, Masai H. Human Tim/Timeless-interacting protein, Tipin, is required for efficient progression of S phase and DNA replication checkpoint. J Biol Chem. 2007;282:2729-40 pubmed
    Tipin was originally isolated as a protein interacting with Timeless/Tim1/Tim (Tim), which is known to be involved in both circadian rhythm and cell cycle checkpoint regulation...
  4. Chou D, Elledge S. Tipin and Timeless form a mutually protective complex required for genotoxic stress resistance and checkpoint function. Proc Natl Acad Sci U S A. 2006;103:18143-7 pubmed
    Tipin is a mammalian protein that interacts with Timeless, which plays a role in DNA damage checkpoint responses...
  5. Yang X, Wood P, Hrushesky W. Mammalian TIMELESS is required for ATM-dependent CHK2 activation and G2/M checkpoint control. J Biol Chem. 2010;285:3030-4 pubmed publisher
    b>Timeless (Tim), a core circadian clock gene in Drosophila, is retained in mammals but has no apparent mammalian circadian clock function. Mammalian TIM is essential for ATR-dependent Chk1 activation and S-phase arrest...
  6. Dheekollu J, Wiedmer A, Hayden J, Speicher D, Gotter A, Yen T, et al. Timeless links replication termination to mitotic kinase activation. PLoS ONE. 2011;6:e19596 pubmed publisher
    ..The human Timeless protein (Tim) associates with S phase replication checkpoint proteins Claspin and Tipin, and plays an important ..
  7. Unsal Kaçmaz K, Mullen T, Kaufmann W, Sancar A. Coupling of human circadian and cell cycles by the timeless protein. Mol Cell Biol. 2005;25:3109-16 pubmed
    The Timeless protein is essential for circadian rhythm in Drosophila. The Timeless orthologue in mice is essential for viability and appears to be required for the maintenance of a robust circadian rhythm as well...
  8. Mansour H, Wood J, Logue T, Chowdari K, Dayal M, Kupfer D, et al. Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia. Genes Brain Behav. 2006;5:150-7 pubmed
    ..Modest associations with SNPs at ARNTL (BmaL1) and TIMELESS genes were observed in the BD1 samples...
  9. Unsal Kaçmaz K, Chastain P, Qu P, Minoo P, Cordeiro Stone M, Sancar A, et al. The human Tim/Tipin complex coordinates an Intra-S checkpoint response to UV that slows replication fork displacement. Mol Cell Biol. 2007;27:3131-42 pubmed
    ..and activates the transducer kinase Chk1 through interactions with the mediator proteins TopBP1, Claspin, and Timeless (Tim)...

More Information

Publications125 found, 100 shown here

  1. Shi J, Wittke Thompson J, Badner J, Hattori E, Potash J, Willour V, et al. Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm. Am J Med Genet B Neuropsychiatr Genet. 2008;147B:1047-55 pubmed publisher
    ..We conducted an association study of five circadian genes (CRY2, PER1-3, and TIMELESS) in a family collection of 36 trios and 79 quads (Sample I), and 10 circadian genes (ARNTL, ARNTL2, BHLHB2, ..
  2. Lavebratt C, Sjöholm L, Partonen T, Schalling M, Forsell Y. PER2 variantion is associated with depression vulnerability. Am J Med Genet B Neuropsychiatr Genet. 2010;153B:570-581 pubmed publisher
    ..In conclusion, genetic variation in PER2 is associated with depression vulnerability a Swedish population-based sample. More studies are needed to determine if this is the case also for NPAS2, ARNTL, and RORA. ..
  3. Leman A, Noguchi C, Lee C, Noguchi E. Human Timeless and Tipin stabilize replication forks and facilitate sister-chromatid cohesion. J Cell Sci. 2010;123:660-70 pubmed publisher
    The Timeless-Tipin protein complex has been reported to be important for replication checkpoint and normal DNA replication processes. However, the precise mechanisms by which Timeless-Tipin preserves genomic integrity are largely unclear...
  4. Fu A, Leaderer D, Zheng T, Hoffman A, Stevens R, Zhu Y. Genetic and epigenetic associations of circadian gene TIMELESS and breast cancer risk. Mol Carcinog. 2012;51:923-9 pubmed publisher
    ..evaluate this hypothesis, we conducted a genetic and epigenetic association study of the circadian regulator TIMELESS in breast carcinogenesis...
  5. Sangoram A, Saez L, Antoch M, Gekakis N, Staknis D, Whiteley A, et al. Mammalian circadian autoregulatory loop: a timeless ortholog and mPer1 interact and negatively regulate CLOCK-BMAL1-induced transcription. Neuron. 1998;21:1101-13 pubmed
    We report the cloning and mapping of mouse (mTim) and human (hTIM) orthologs of the Drosophila timeless (dtim) gene...
  6. Gotter A. Tipin, a novel timeless-interacting protein, is developmentally co-expressed with timeless and disrupts its self-association. J Mol Biol. 2003;331:167-76 pubmed
    The mouse Timeless gene (mTim) was identified originally on the basis of its similarity to a Drosophila circadian gene, but has no substantiated role in the circadian clock mechanism...
  7. Gotter A, Suppa C, Emanuel B. Mammalian TIMELESS and Tipin are evolutionarily conserved replication fork-associated factors. J Mol Biol. 2007;366:36-52 pubmed
    The function of the mammalian TIMELESS protein (TIM) has been enigmatic. TIM is essential for early embryonic development, but little is known regarding its biochemical and cellular function...
  8. Mordas A, Tokatlidis K. The MIA pathway: a key regulator of mitochondrial oxidative protein folding and biogenesis. Acc Chem Res. 2015;48:2191-9 pubmed publisher
    ..concept of the oxidative folding pathway was first proposed on the basis of folding and import data for the small Tim proteins that have conserved cysteine motifs and must adopt intramolecular disulfides after import so that they are ..
  9. Kristensen B. Regulatory B and T cell responses in patients with autoimmune thyroid disease and healthy controls. Dan Med J. 2016;63: pubmed
    ..Several phenotypes have been associated with B10 cells such as CD5+, CD25+, TIM-1+, CD24hiCD38hi and CD27+CD43+...
  10. Fan C, Zhang Y, Zhou Y, Li B, He Y, Guo Y, et al. Up-regulation of A20/ABIN1 contributes to inefficient M1 macrophage polarization during Hepatitis C virus infection. Virol J. 2015;12:147 pubmed publisher
    ..For instance, HCV antigens impact macrophage PD-1 and Tim-3 expression, and contribute to impaired viral clearance...
  11. Hamel R, Dejarnac O, Wichit S, Ekchariyawat P, Neyret A, Luplertlop N, et al. Biology of Zika Virus Infection in Human Skin Cells. J Virol. 2015;89:8880-96 pubmed publisher
    ..Several entry and/or adhesion factors, including DC-SIGN, AXL, Tyro3, and, to a lesser extent, TIM-1, permitted ZIKV entry, with a major role for the TAM receptor AXL...
  12. Vivas Ruiz D, Gonzalez Kozlova E, Delgadillo J, Palermo P, Sandoval G, Lazo F, et al. Biochemical and molecular characterization of the hyaluronidase from Bothrops atrox Peruvian snake venom. Biochimie. 2019;162:33-45 pubmed publisher
    ..Spatial modeling of Hyal-Ba displayed a TIM-Barrel (α/β) fold and an EGF-like domain in the C-terminal portion...
  13. Magnuson A, Fouts J, Regan D, Booth A, Dow S, Foster M. Adipose tissue extrinsic factor: Obesity-induced inflammation and the role of the visceral lymph node. Physiol Behav. 2018;190:71-81 pubmed publisher
    ..The research of Tim Bartness greatly enhanced the understanding of adipose tissue regulation...
  14. Khan A, Srivastava R, Chentoufi A, Geertsema R, Thai N, Dasgupta G, et al. Therapeutic immunization with a mixture of herpes simplex virus 1 glycoprotein D-derived “asymptomatic” human CD8+ T-cell epitopes decreases spontaneous ocular shedding in latently infected HLA transgenic rabbits: association with low frequency of lo. J Virol. 2015;89:6619-32 pubmed
    ..lymph nodes (DLN), conjunctiva, and TG, and (iv) was associated with fewer exhausted HSV-1 gD-specific PD-1(+) TIM-3+ CD8(+) T cells...
  15. Srivastava R, Roy S, Coulon P, Vahed H, Prakash S, Dhanushkodi N, et al. Therapeutic Mucosal Vaccination of Herpes Simplex Virus 2-Infected Guinea Pigs with Ribonucleotide Reductase 2 (RR2) Protein Boosts Antiviral Neutralizing Antibodies and Local Tissue-Resident CD4+ and CD8+ TRM Cells Associated with Protection against. J Virol. 2019;93: pubmed publisher
    ..and CRTAM+ CFSE+ CD8+ TRM cells, which express low levels of PD-1 and TIM-3 exhaustion markers and were localized to healed sites of the vaginal mucocutaneous (VM) tissues...
  16. Theurl I, Hilgendorf I, Nairz M, Tymoszuk P, Haschka D, Asshoff M, et al. On-demand erythrocyte disposal and iron recycling requires transient macrophages in the liver. Nat Med. 2016;22:945-51 pubmed publisher
    ..Monocyte-derived FPN1(+)Tim-4(neg) macrophages are transient, reside alongside embryonically derived T cell immunoglobulin and mucin domain ..
  17. Mami Chouaib F, Blanc C, Corgnac S, Hans S, Malenica I, Granier C, et al. Resident memory T cells, critical components in tumor immunology. J Immunother Cancer. 2018;6:87 pubmed publisher
    ..TRM cells also predominantly express checkpoint receptors such as PD-1, CTLA-4 and Tim-3...
  18. Liu Y, Ji H, Zhang Y, Shen X, Gao F, Nguyen T, et al. Negative CD4 + TIM-3 signaling confers resistance against cold preservation damage in mouse liver transplantation. Am J Transplant. 2015;15:954-964 pubmed publisher
    ..T cell immunoglobulin and mucin domain (TIM-3)-Galectin-9 (Gal-9) signaling regulates CD4+ Th1 immune responses...
  19. Liu Z, Xie L, Bian T, Qi G, Wang Z. (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one reduces lipoteichoic acid-induced damage in rat cardiomyoblast cells. Anatol J Cardiol. 2018;19:198-204 pubmed publisher
    ..This study aimed to investigate if the new compound (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) isolated from Alpinia katsumadai Hayata could provide protection against lipoteichoic acid (LTA)-induced cell ..
  20. Hitakarun A, Tan ariya P, Siripattanapipong S, Mungthin M, Piyaraj P, Naaglor T, et al. Comparison of PCR methods for detection of Leishmania siamensis infection. Parasit Vectors. 2014;7:458 pubmed publisher
    ..b (cyt b), heat shock protein 70 (hsp70), the spliced leader mini-exon, and the triose-phosphate isomerase (tim) genes were compared. Both the ITS1-PCR and the SSU rRNA-PCR could detect promastigote of L...
  21. Lind L, Ärnlöv J, Lindahl B, Siegbahn A, Sundström J, Ingelsson E. Use of a proximity extension assay proteomics chip to discover new biomarkers for human atherosclerosis. Atherosclerosis. 2015;242:205-10 pubmed publisher
    ..arteries affected by plaques in sex-adjusted models (osteoprotegrin, T-cell immunoglobulin and mucin domain (TIM)-1, growth/differentiation factor 15 (GDF-15), matrix metalloprotease-12 (MMP-12), renin, tumor necrosis factor ..
  22. Holowka D, Baird B. Roles for lipid heterogeneity in immunoreceptor signaling. Biochim Biophys Acta. 2016;1861:830-836 pubmed publisher
    ..This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.
  23. Nakane S, Wakamatsu T, Masui R, Kuramitsu S, Fukui K. In vivo, in vitro, and x-ray crystallographic analyses suggest the involvement of an uncharacterized triose-phosphate isomerase (TIM) barrel protein in protection against oxidative stress. J Biol Chem. 2011;286:41636-46 pubmed publisher
    ..Our results suggest that TTHB071 protects the cell from oxidative stress, through controlling the metabolism of FMN, pyridoxal phosphate, or an analogous compound. ..
  24. Satyanarayanan S, Chien Y, Chang J, Huang S, Guu T, Su H, et al. Melatonergic agonist regulates circadian clock genes and peripheral inflammatory and neuroplasticity markers in patients with depression and anxiety. Brain Behav Immun. 2019;: pubmed publisher
    ..treatment and alterations of the nine core circadian genes (CLOCK, PER1, PER2, CRY1, CRY2, NR1D1, NR1D2, DEC1 and TIMELESS) in the patient group when compared with the control group (p ≤ 0.05)...
  25. Bashi T, Shovman O, Fridkin M, Volkov A, Barshack I, Blank M, et al. Novel therapeutic compound tuftsin-phosphorylcholine attenuates collagen-induced arthritis. Clin Exp Immunol. 2016;184:19-28 pubmed publisher
    ..box protein 3 (FoxP3(+) ) Treg cells and CD19(+) IL-10(+) CD5(high) CD1d(high) T cell immunoglobulin mucin-1 (TIM-1(+) ) Breg cell phenotypes (P < 0.0001) in treated mice...
  26. Ferluga J, Kouser L, Murugaiah V, Sim R, Kishore U. Potential influences of complement factor H in autoimmune inflammatory and thrombotic disorders. Mol Immunol. 2017;84:84-106 pubmed publisher
    ..There may be co-operation with other phagocytic receptors, such as complement C1q receptors, and the Tim glycoprotein family, which specifically bind phosphatidylserine expressed on the apoptotic cell surface...
  27. Ascierto P, Agarwala S, Botti G, Cesano A, Ciliberto G, Davies M, et al. Future perspectives in melanoma research : Meeting report from the "Melanoma Bridge". Napoli, December 1st-4th 2015. J Transl Med. 2016;14:313 pubmed
    ..Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g...
  28. Yeim S, Boudebesse C, Etain B, Belliviera F. [Circadian markers and genes in bipolar disorder]. Encephale. 2015;41:S38-44 pubmed publisher
    ..between multiple circadian genes and bipolar disorder, such as CLOCK, ARTNL1, GSK3β, PER3, NPAS2, NR1D1, TIMELESS, RORA, RORB, and CSNK1ε...
  29. Hao H, He M, Li J, Zhou Y, Dang J, Li F, et al. Upregulation of the Tim-3/Gal-9 pathway and correlation with the development of preeclampsia. Eur J Obstet Gynecol Reprod Biol. 2015;194:85-91 pubmed publisher
    ..However, the mechanisms underlying immune tolerance during preeclampsia are still poorly understood. Tim-3, a Th1-specific cell surface molecule, is a relatively newly described molecule with important immunological ..
  30. Fam H, Choi K, Fougner L, Lim C, Boerkoel C. Reactive oxygen species stress increases accumulation of tyrosyl-DNA phsosphodiesterase 1 within mitochondria. Sci Rep. 2018;8:4304 pubmed publisher
    ..oxidant-responsive kinases P38 and ERK1, and the translocation of Tdp1 from the nucleus to the mitochondria via the TIM/TOM complex. This translocation occurred independently of mtDNA...
  31. Heon E, Wulan H, Macdonald L, Malek A, Braunstein G, Eaves C, et al. IL-15 induces strong but short-lived tumor-infiltrating CD8 T cell responses through the regulation of Tim-3 in breast cancer. Biochem Biophys Res Commun. 2015;464:360-6 pubmed publisher
    ..We did not observe increased IL-10 or PD-1 upregulation, but we have found an increase of Tim-3 upregulation on IL-15-, but not IL-2-stimulated cells...
  32. Jagannathan P, Lutwama F, Boyle M, Nankya F, Farrington L, McIntyre T, et al. Vδ2+ T cell response to malaria correlates with protection from infection but is attenuated with repeated exposure. Sci Rep. 2017;7:11487 pubmed publisher
    ..Microscopic parasitemia and expression of the immunoregulatory markers Tim-3 and CD57 were associated with diminished Vδ2+ T cell pro-inflammatory cytokine production...
  33. Rossdale P. A true moderniser of equine practice. Vet Rec. 2017;181:i-ii pubmed publisher
    b>Peter Rossdale recently celebrated his 90th birthday. Tim Greet describes the career of this pioneering equine vet.
  34. Wang X, Shen H, Zhangyuan G, Huang R, Zhang W, He Q, et al. 14-3-3ζ delivered by hepatocellular carcinoma-derived exosomes impaired anti-tumor function of tumor-infiltrating T lymphocytes. Cell Death Dis. 2018;9:159 pubmed publisher
    ..ones exhibited higher frequency of exhausted phenotypes as measured by inhibitory receptors such as PD-1, TIM-3, LAG3, and CTLA-4...
  35. Lu N, Li Y, Zhang Z, Xing J, Sun Y, Yao S, et al. Human Semaphorin-4A drives Th2 responses by binding to receptor ILT-4. Nat Commun. 2018;9:742 pubmed publisher
    ..cells and drives Th1 immune responses by binding to the receptor T-cell immunoglobulin and mucin domain protein 2 (Tim-2) in mice...
  36. Brito A, Tremblay G, Bertrand A, Castonguay Y, Belanger G, Michaud R, et al. Performance and nitrogen use efficiency in mid-lactation dairy cows fed timothy cut in the afternoon or morning. J Dairy Sci. 2016;99:5445-5460 pubmed publisher
    ..m.-cut TIM), a total mixed ration containing timothy baleage and silage cut in the afternoon (p.m...
  37. Nejatbakhsh F, Karegar Borzi H, Amin G, Eslaminejad A, Hosseini M, Bozorgi M, et al. Squill Oxymel, a traditional formulation from Drimia Maritima (L.) Stearn, as an add-on treatment in patients with moderate to severe persistent asthma: A pilot, triple-blind, randomized clinical trial. J Ethnopharmacol. 2017;196:186-192 pubmed publisher
    In Traditional Iranian Medicine (TIM), Squill (Drimia maritima (L.) Stearn) Oxymel was utilized in the treatment of asthma...
  38. Devrukhakar P, M S, G S, R S. Proposal of degradation pathway with toxicity prediction for hydrolytic and photolytic degradation products of timolol. J Pharm Biomed Anal. 2018;154:7-15 pubmed publisher
    Timolol (TIM) is a potent ?-adrenergic blocker, useful in treatment of ocular hypertension or open-angle glaucoma. Development and validation of stability indicating LCMS assay method for TIM was accomplished coherent with ICH guideline...
  39. Allebrandt K, Teder Laving M, Akyol M, Pichler I, Muller Myhsok B, Pramstaller P, et al. CLOCK gene variants associate with sleep duration in two independent populations. Biol Psychiatry. 2010;67:1040-7 pubmed publisher
    ..This adds another putative function for CLOCK besides its possible involvement in circadian timing, depression, obesity, and personality. ..
  40. Ogawara D, Soda H, Iwasaki K, Suyama T, Taniguchi H, Fukuda Y, et al. Remarkable response of nivolumab-refractory lung cancer to salvage chemotherapy. Thorac Cancer. 2017;: pubmed publisher
    ..Immunosuppressive regulatory T cells and cells positive for TIM-3 were also observed...
  41. Fischer M, Gouëzel C, Fradin S, Saplacan V, Gerard J, Fellahi J, et al. Assessment of changes in blood glucose concentration with intravascular microdialysis. J Clin Monit Comput. 2018;32:1135-1142 pubmed publisher
    ..Changes in blood glucose measurement were evaluated by four-quadrant plot and trend interchangeability methods (TIM). In the 23 patients analyzed, the CVC was used as part of standard care with no complications...
  42. Kikushige Y, Miyamoto T. Identification of TIM-3 as a Leukemic Stem Cell Surface Molecule in Primary Acute Myeloid Leukemia. Oncology. 2015;89 Suppl 1:28-32 pubmed publisher
    ..T-cell immunoglobulin mucin-3 (TIM-3) is expressed in most types of AML LSCs, but not in normal hematopoietic stem cells (HSCs); therefore, TIM-3 ..
  43. Dai C, Lin F, Geng R, Ge X, Tang W, Chang J, et al. Implication of combined PD-L1/PD-1 blockade with cytokine-induced killer cells as a synergistic immunotherapy for gastrointestinal cancer. Oncotarget. 2016;7:10332-44 pubmed publisher
    ..Initially, phenotypic analysis was performed to document CD3, CD56, NKG2D, DNAM-1, PD-L1, PD-1, CTLA-4, TIM-3, 2B4, and LAG-3 on CIK cells...
  44. Yang Y, Chen Z, Hurlburt B, Li G, Zhang Y, Fei D, et al. Identification of triosephosphate isomerase as a novel allergen in Octopus fangsiao. Mol Immunol. 2017;85:35-46 pubmed publisher
    ..weight of 28kDa protein was purified from octopus (Octopus fangsiao) and identified as triosephosphate isomerase (TIM) by mass spectrometry...
  45. Engelen E, Janssens R, Yagita K, Smits V, van der Horst G, Tamanini F. Mammalian TIMELESS is involved in period determination and DNA damage-dependent phase advancing of the circadian clock. PLoS ONE. 2013;8:e56623 pubmed publisher
    ..Interestingly, the animal circadian clock proteins CRYPTOCHROME (CRY), PERIOD (PER) and TIMELESS (TIM) are strongly conserved at the amino acid level through evolution...
  46. Schalbetter S, Mansoubi S, Chambers A, Downs J, Baxter J. Fork rotation and DNA precatenation are restricted during DNA replication to prevent chromosomal instability. Proc Natl Acad Sci U S A. 2015;112:E4565-70 pubmed publisher
    ..However, generally, fork rotation and precatenation are actively inhibited by Timeless/Tof1 and Tipin/Csm3...
  47. Webster J. Animal Welfare: Freedoms, Dominions and "A Life Worth Living". Animals (Basel). 2016;6: pubmed publisher
    ..achieve an overall picture of mental state and welfare status, but the principles upon which they are based are timeless. Their aim is to be no more than a memorable set of signposts to right action...
  48. Zhang Y, Zhang X, Xia Y, Jia X, Li H, Zhang Y, et al. CD19+ Tim-1+ B cells are decreased and negatively correlated with disease severity in Myasthenia Gravis patients. Immunol Res. 2016;64:1216-1224 pubmed
    T cell immunoglobulin mucin domain-1(Tim-1) was recently identified to be critical and essential for optimal regulatory B cells function in maintaining immune tolerance...
  49. Benmoussa A, Lee C, Laffont B, Savard P, Laugier J, Boilard E, et al. Commercial Dairy Cow Milk microRNAs Resist Digestion under Simulated Gastrointestinal Tract Conditions. J Nutr. 2016;146:2206-2215 pubmed
    ..We used a computer-controlled, in vitro, gastrointestinal model TNO intestinal model-1 (TIM-1) and analyzed, by quantitative polymerase chain reaction, the concentration of 2 microRNAs within ..
  50. Soares da Costa T, Patel M, Desbois S, Gupta R, Faou P, Perugini M. Identification of a dimeric KDG aldolase from Agrobacterium tumefaciens. Proteins. 2017;85:2058-2065 pubmed publisher
    ..The results show that DapA5 (1) adopts an ?/? structure consistent with the TIM-barrel fold of KDG aldolases, (2) possesses KDG aldolase enzyme activity, and (3) exists as a tight dimer in ..
  51. Ding Q, Mohib K, Kuchroo V, Rothstein D. TIM-4 Identifies IFN-?-Expressing Proinflammatory B Effector 1 Cells That Promote Tumor and Allograft Rejection. J Immunol. 2017;199:2585-2595 pubmed publisher
    ..Although T cell Ig and mucin domain-containing molecule (TIM)-1 broadly identifies IL-10+ regulatory B cells, no similar markers for Be1 cells have been described...
  52. Sharma K, Dhillon A, Goyal A. Insights into Structure and Reaction Mechanism of &#946;-Mannanases. Curr Protein Pept Sci. 2018;19:34-47 pubmed publisher
    ..Structural survey of ?- mannanases of GH5 and GH26, suggests that both families contain similar TIM barrel fold. In addition, they also share common catalytic residues and their location in the structure...
  53. Song B, Zhen S, Meng F. T cell inflammation profile after surgical resection may predict tumor recurrence in HBV-related hepatocellular carcinoma. Int Immunopharmacol. 2016;41:35-41 pubmed publisher
    ..The peripheral blood and tumor-infiltrating T cells from patients with recurrent HCC also presented higher PD-1 and TIM-3 expression than patients without recurrent HCC...
  54. Hsein H, Garrait G, Tamani F, Beyssac E, Hoffart V. Denatured Whey Protein Powder as a New Matrix Excipient: Design and Evaluation of Mucoadhesive Tablets for Sustained Drug Release Applications. Pharm Res. 2017;34:365-377 pubmed publisher
    ..Finally, release and absorption were studied in the artificial digestive system (TIM 1). Tablets based on DWP and containing 300 mg of theophylline were obtained by direct compression...
  55. Xu L, Ye Z, Wang B, Huang Y, Zhou L, Liu C, et al. Tim-4 expression increases in ischemic stroke patients and is associated with poor outcome. J Neuroimmunol. 2017;: pubmed publisher
    T cell immunoglobin and mucin domain (Tim)-4 on monocytes is involved in immune regulation. Here, we investigated Tim-4 expression on circulating monocytes and in plasma of ischemic stroke...
  56. Wang Z, Liu X, Wang X, Chong T, Lin S, Wang M, et al. Polymorphisms in TIM-3 and breast cancer susceptibility in Chinese women: A case-control study. Oncotarget. 2016;7:43703-43712 pubmed publisher
    Previous studies have found associations between polymorphisms in T cell immunoglobulin and mucin domain 3 (TIM-3) and increased risks of various cancers...
  57. Li J, Xu D, Li H. Evaluation of failed immunotherapy among patients with negative APLA recurrent spontaneous abortion by serum anticardiolipin antibodies and mononuclear cell of Tim-1. Eur Rev Med Pharmacol Sci. 2017;21:908-912 pubmed
    ..The present study is aimed to analyze the expression of serum anticardiolipin antibody (ACA) and mononuclear cells of Tim-1 among the patients with negative anti paternal lymphocyte antibody (APLA) recurrent spontaneous abortion ..
  58. Wu Q, Zhu X, Wang Y, Fu X, Yang J, Cao Z. [Expression of Tim-3 on peripheral blood CD4+ T cells and its correlation with liver function damage parameters in advanced schistosomiasis patients]. Zhongguo Xue Xi Chong Bing Fang Zhi Za Zhi. 2015;27:470-3, 496 pubmed
    To explore the expression levels of T cell immunoglobulin and mucin domain protein 3 (Tim-3) on peripheral blood CD4+ T cells and its correlation with liver function damage parameters in advanced schistosomiasis patients...
  59. Baba S, Vishwakarma R, Ashraf N. Functional Characterization of CsBGlu12, a β-Glucosidase from Crocus sativus, Provides Insights into Its Role in Abiotic Stress through Accumulation of Antioxidant Flavonols. J Biol Chem. 2017;292:4700-4713 pubmed publisher
    ..CsBGlu12 has a characteristic glucoside hydrolase 1 family (α/β)8 triose-phosphate isomerase (TIM) barrel structure with a highly conserved active site...
  60. Parekh V, Pabbisetty S, Wu L, Sebzda E, Martinez J, Zhang J, et al. Autophagy-related protein Vps34 controls the homeostasis and function of antigen cross-presenting CD8?+ dendritic cells. Proc Natl Acad Sci U S A. 2017;114:E6371-E6380 pubmed publisher
    ..to MHC class I-restricted T cells, a property that was associated with defective expression of the T-cell Ig mucin (TIM)-4 receptor...
  61. Rovituso D, Scheffler L, Wunsch M, Kleinschnitz C, Dörck S, Ulzheimer J, et al. CEACAM1 mediates B cell aggregation in central nervous system autoimmunity. Sci Rep. 2016;6:29847 pubmed publisher
    ..CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain -3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells...
  62. Perrigault M, Tran D. Identification of the Molecular Clockwork of the Oyster Crassostrea gigas. PLoS ONE. 2017;12:e0169790 pubmed publisher
    ..Results provided the characterization of most of canonical clock gene including clock, bmal/cycle, period, timeless, vertebrate-type cry, rev-erb, ror as well as other members of the cryptochrome/photolyase family (plant-like cry,..
  63. Xu L, Huang Y, Tan L, Yu W, Chen D, Lu C, et al. Increased Tim-3 expression in peripheral NK cells predicts a poorer prognosis and Tim-3 blockade improves NK cell-mediated cytotoxicity in human lung adenocarcinoma. Int Immunopharmacol. 2015;29:635-641 pubmed publisher
    T cell immunoglobulin- and mucin-domain-containing molecule-3 (Tim-3) has been shown to play an important role in mediating NK-cell function in human diseases...
  64. Tallerico R, Cristiani C, Staaf E, Garofalo C, Sottile R, Capone M, et al. IL-15, TIM-3 and NK cells subsets predict responsiveness to anti-CTLA-4 treatment in melanoma patients. Oncoimmunology. 2017;6:e1261242 pubmed publisher
    ..Survival correlated with low expression of the inhibitory receptor TIM-3 on circulating T and NK cells prior to and during treatment and with the increased frequency of mature ..
  65. Della Corte C, Viscardi G, Di Liello R, Fasano M, Martinelli E, Troiani T, et al. Role and targeting of anaplastic lymphoma kinase in cancer. Mol Cancer. 2018;17:30 pubmed publisher
    ..inflammatory myofibroblastic tumors and neuroblastoma, as a consequence of fusion with other oncogenes (NPM, EML4, TIM, etc) or gene amplification, mutation or protein overexpression...
  66. Sada Ovalle I, Ocaña Guzman R, Pérez Patrigeón S, Chávez Galán L, Sierra Madero J, Torre Bouscoulet L, et al. Tim-3 blocking rescue macrophage and T cell function against Mycobacterium tuberculosis infection in HIV+ patients. J Int AIDS Soc. 2015;18:20078 pubmed publisher
    T cell immunoglobulin and mucin domain (Tim) 3 and programmed death 1 (PD-1) are co-inhibitory receptors involved in the so-called T cell exhaustion, and in vivo blockade of these molecules restores T cell dysfunction...
  67. Deng H, Vedad J, Desamero R, Callender R. Difference FTIR Studies of Substrate Distribution in Triosephosphate Isomerase. J Phys Chem B. 2017;121:10036-10045 pubmed publisher
    Triosephosphate isomerase (TIM) catalyzes the interconversion between dihydroxyacetone phosphate (DHAP) and d-glyceraldehyde 3-phosphate (GAP), via an enediol(ate) intermediate...
  68. Porada S, Schipper F, Aslan M, Antonietti M, Presser V, Fellinger T. Capacitive Deionization using Biomass-based Microporous Salt-Templated Heteroatom-Doped Carbons. ChemSusChem. 2015;8:1823 pubmed publisher
    Invited for this month's cover are the groups of Tim-Patrick Fellinger (MPI Potsdam) and Volker Presser (INM Saarbrücken and Saarland University)...
  69. González Gugel E, Saxena M, Bhardwaj N. Modulation of innate immunity in the tumor microenvironment. Cancer Immunol Immunother. 2016;65:1261-8 pubmed publisher
    ..We identified the expression of Tim-3 as one of the factors responsible for NK cell exhaustion and showed that anti-Tim3 antibodies partially reversed ..
  70. Liu L, Jiang G, Peng Z, Li Y, Li J, Zou L, et al. The effect of high fat diet on daily rhythm of the core clock genes and muscle functional genes in the skeletal muscle of Chinese soft-shelled turtle (Trionyx sinensis). Comp Biochem Physiol B Biochem Mol Biol. 2017;213:17-27 pubmed publisher
    ..feeding trial experiment, we measured the daily expression levels of 17 core clock genes (Clock, Bmal1/2, NPAS2, Tim, Cry1/2, Per1/2, DBP, AANAT, NIFL3, BHLHE40, NR1D2, RORA, RORB, RORC) and 12 muscle functional genes (FBXO32, MBNL1,..
  71. Englund A, Kovanen L, Saarikoski S, Haukka J, Reunanen A, Aromaa A, et al. NPAS2 and PER2 are linked to risk factors of the metabolic syndrome. J Circadian Rhythms. 2009;7:5 pubmed publisher
    ..049). Our findings support the view that relevant relationships between circadian clocks and the metabolic syndrome in humans exist. ..
  72. Mijusković M, Stanojević I, Milovic N, Cerovic S, Petrovic D, Maksić D, et al. Tissue and urinary KIM-1 relate to tumor characteristics in patients with clear renal cell carcinoma. Int Urol Nephrol. 2018;50:63-70 pubmed publisher
    ..Urinary KIM-1 was determined by ELISA TIM-1/KIM-1 kit and normalized by urinary creatinine...
  73. Isshiki T, Akiba H, Nakayama M, Harada N, Okumura K, Homma S, et al. Cutting Edge: Anti-TIM-3 Treatment Exacerbates Pulmonary Inflammation and Fibrosis in Mice. J Immunol. 2017;199:3733-3737 pubmed publisher
    ..T cell Ig and mucin domain (TIM)-3 is a new candidate immune checkpoint molecule; however, the potential toxicity associated with anti-TIM-3 ..
  74. Zhu Y, Stevens R, Hoffman A, FitzGerald L, Kwon E, Ostrander E, et al. Testing the circadian gene hypothesis in prostate cancer: a population-based case-control study. Cancer Res. 2009;69:9315-22 pubmed publisher
  75. Vilgelm A, Johnson D, Richmond A. Combinatorial approach to cancer immunotherapy: strength in numbers. J Leukoc Biol. 2016;100:275-90 pubmed publisher
    ..the immune-checkpoint blockade include therapeutics targeting additional inhibitory receptors of T cells, such as TIM-3, LAG-3, TIGIT, and BTLA, and agonists of T cell costimulatory receptors 4-1BB, OX40, and GITR, as well as agents ..
  76. Penaloza MacMaster P, Alayo Q, Ra J, Provine N, Larocca R, Lee B, et al. Inhibitory receptor expression on memory CD8 T cells following Ad vector immunization. Vaccine. 2016;34:4955-4963 pubmed publisher
    ..CD8 T cells induced by Ad5 exhibited increased expression of the inhibitory receptor Tim-3 and showed decreased central memory differentiation as compared with alternative serotype Ad vectors, even a year ..
  77. Handa R, Territo P, Blomgren P, Persohn S, Lin C, Johnson C, et al. Development of a novel magnetic resonance imaging acquisition and analysis workflow for the quantification of shock wave lithotripsy-induced renal hemorrhagic injury. Urolithiasis. 2017;45:507-513 pubmed publisher
    ..T1 weighted (T1W) and T2 weighted (T2W) images were acquired on a Siemens 3T Tim Trio MRI scanner...
  78. Dong J, Yang X, Wang L, Wei X, Wang A, Hao C, et al. Modulation of Tim-3 Expression by Antigen-Dependent and -Independent Factors on T Cells from Patients with Chronic Hepatitis B Virus Infection. Front Cell Infect Microbiol. 2017;7:98 pubmed publisher
    T-cell immunoglobulin domain and mucin domain-containing molecule-3 (Tim-3) was up-regulated on viral specific T cells and contributed to T cells exhaustion during chronic hepatitis B virus (HBV) infection...
  79. Milano G. Resistance to immunotherapy: clouds in a bright sky. Invest New Drugs. 2017;35:649-654 pubmed publisher
    ..Upregulation of T cell immunoglobulin mucin domain 3 (TIM-3) in CD8+ T-cells has been reported in patients developing acquired resistance to anti-PD-1 treatment...
  80. Liu S, Lin H, Lin C, Sun X, Ye L, Qiu F, et al. TIMELESS confers cisplatin resistance in nasopharyngeal carcinoma by activating the Wnt/β-catenin signaling pathway and promoting the epithelial mesenchymal transition. Cancer Lett. 2017;402:117-130 pubmed publisher
    This study investigated the expression, clinicopathological significance and mechanism of action of TIMELESS, a mammalian homolog of a Drosophila circadian rhythm gene, in nasopharyngeal carcinoma...
  81. Zhang C, Zhang Z, Wang L, Han J, Li F, Shen C, et al. Pseudomonas aeruginosa-mannose sensitive hemagglutinin injection treated cytokine-induced killer cells combined with chemotherapy in the treatment of malignancies. Int Immunopharmacol. 2017;51:57-65 pubmed publisher
    ..CIK cells exhibited enhanced proliferation but decreased expression of inhibitory cell surface markers such as Tim-3 and PD-1. Particularly in CIK cells, PA-MSHA promoted the extrusion of pro-inflammatory cytokines like IFN-γ...
  82. Qian Y, Qiao S, Dai Y, Xu G, Dai B, Lu L, et al. Molecular-Targeted Immunotherapeutic Strategy for Melanoma via Dual-Targeting Nanoparticles Delivering Small Interfering RNA to Tumor-Associated Macrophages. ACS Nano. 2017;11:9536-9549 pubmed publisher
    ..Moreover, the siRNA-carrying M2NPs down-regulated expression of the exhaustion markers (PD-1 and Tim-3) on the infiltrating CD8+ T cells and stimulated their IFN-γ secretion (6...
  83. Tayi L, Kumar S, Nathawat R, Haque A, Maku R, Patel H, et al. A mutation in an exoglucanase of Xanthomonas oryzae pv. oryzae that confers an endo mode of activity affects bacterial virulence but not the induction of immune responses in rice. Mol Plant Pathol. 2017;: pubmed publisher
    ..86Å. The core structure of CbsA shows a central distorted TIM barrel made up of eight ? strands with N and C-terminal loops enclosing the active site which is a characteristic ..
  84. Somyajit K, Gupta R, Sedlackova H, Neelsen K, Ochs F, Rask M, et al. Redox-sensitive alteration of replisome architecture safeguards genome integrity. Science. 2017;358:797-802 pubmed publisher
    ..In the oligomeric state, PRDX2 forms a replisome-associated ROS sensor, which binds the fork accelerator TIMELESS when exposed to low levels of ROS...
  85. Collins B, Kaplan H, Cavey M, Lelito K, Bahle A, Zhu Z, et al. Differentially timed extracellular signals synchronize pacemaker neuron clocks. PLoS Biol. 2014;12:e1001959 pubmed publisher
    ..Because simultaneously reducing Pdfr and mGluRA expression in LNvs severely dampened Timeless clock protein oscillations, we conclude that the master pacemaker LNvs require extracellular signals to function ..
  86. Kim J, Patel M, Mangraviti A, Kim E, Theodros D, Velarde E, et al. Combination Therapy with Anti-PD-1, Anti-TIM-3, and Focal Radiation Results in Regression of Murine Gliomas. Clin Cancer Res. 2017;23:124-136 pubmed publisher
    Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme...
  87. Johnson B, Midura E, Prakash P, Rice T, Kunz N, Kalies K, et al. Neutrophil derived microparticles increase mortality and the counter-inflammatory response in a murine model of sepsis. Biochim Biophys Acta Mol Basis Dis. 2017;1863:2554-2563 pubmed publisher
    ..Furthermore, the NDMPs express phosphatidylserine and are ingested by F4/80 macrophages via a Tim-4 and MFG-E8 dependent mechanism...
  88. Fusetto R, Denecke S, Perry T, O Hair R, Batterham P. Partitioning the roles of CYP6G1 and gut microbes in the metabolism of the insecticide imidacloprid in Drosophila melanogaster. Sci Rep. 2017;7:11339 pubmed publisher
    ..tools of gene overexpression and CRISPR gene knock-out with the mass spectrometric technique, the Twin-Ion Method (TIM). Analysing axenic larvae indicated that microbes living within D...
  89. Tremiño L, Forcada Nadal A, Contreras A, Rubio V. Studies on cyanobacterial protein PipY shed light on structure, potential functions, and vitamin B6 -dependent epilepsy. FEBS Lett. 2017;591:3431-3442 pubmed publisher
    ..PipY crystal structures with and without PLP reveal a single-domain monomer folded as the TIM barrel of type-III fold PLP enzymes, with PLP highly exposed, fitting a role for PipY in PLP homeostasis...
  90. Over H, Cook R. Where do spontaneous first impressions of faces come from?. Cognition. 2018;170:190-200 pubmed publisher
    ..Our TIM framework has both theoretical and substantive implications, and can be extended to trait inferences from non-..
  91. Lin H, Yang B, Teng M. T-cell immunoglobulin mucin-3 as a potential inducer of the epithelial-mesenchymal transition in hepatocellular carcinoma. Oncol Lett. 2017;14:5899-5905 pubmed publisher
    T-cell immunoglobulin mucin (TIM)-3 is an important member of the TIM gene family, which was thought to contribute to the progression of numerous types of cancer, including hepatocellular carcinoma (HCC); however, the mechanism ..
  92. Yi E, Xu F, Li P. (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one alleviates lipoteichoic acid-induced photoreceptor cell damage. Cutan Ocul Toxicol. 2017;:1-17 pubmed publisher
    ..In this study, the protective effects of (3R)-5,6,7-trihydroxy-3-isopropyl-3-methylisochroman-1-one (TIM) against the lipoteichoic acid (LTA)-induced cell damage in mouse photoreceptor-derived 661W cells were ..