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Query: UNIPROT:P06889 (Mol)
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Small studies in human populations have suggested a correlation between the frequency of errors in antigen receptor gene assembly and lymphoid malignancy risk. In particular, agricultural workers exposed to pesticides have both an increased risk for lymphoma and an increased frequency of errors in antigen receptor gene assembly. In order to further investigate the potential of such errors to serve as a mechanistically based biomarker of lymphoid cancer risk, we have developed a sensitive PCR assay for quantifying errors of V(D)J recombination in the thymocytes of mice. This assay measures interlocus rearrangements between two T-cell receptor loci, V-gamma and J-beta, located on chromosomes 13 and 6, respectively. The baseline frequency in four strains of mice was determined at several ages (2-8 weeks of age) and was found to be stable at approximately 1.5 x 10(-5) per thymocyte. Strain AKR, which has a high susceptibility to T-cell lymphomas, did not show an elevated frequency of aberrant V(D)J events. We used this assay to examine the effects of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) on the frequency of these events. Female B6C3F1 mice, 27 days of age, were exposed to 2,4-D by gavage at doses of 0, 3, 10, 30, and 100 mg/kg/day for 4 successive days and sacrificed on day 5. Thymus DNA was isolated and examined for illegitimate V(D)J recombination-mediated gene rearrangements. In addition, pregnant mice were exposed to 2,4-D and thymocytes from the offspring examined at 2 weeks of age. No significant increase in aberrant V(D)J rearrangements was found, indicating that under these conditions 2,4-D does not appear to effect this important mechanism of carcinogenesis.
Environ Mol Mutagen 2003
PMID:Quantitation of aberrant interlocus T-cell receptor rearrangements in mouse thymocytes and the effect of the herbicide 2,4-dichlorophenoxyacetic acid. 1287 11

Thymus is the primary lymphoid organ involved in the development of thymocytes. Maturation related events of thymocytes within thymus, especially the widely discussed directional migration of thymocytes, is regulated by chemokines via chemokine receptors mediated signaling pathway. Multiple types of chemokines and chemokine receptors, as components of the network-interaction within thymic microenvironment, are involved in the thymopoiesis. It appears that these chemokines are functionally redundant and such phenomenon may be explained not only by the promiscuous, non-one-to-one matching between ligands-receptors within CXC or CC chemokine subfamily, but also by the various spatio-temporal expression patterns within different cell types and developmental stages. The redundancy and regulation of thymus expressed chemokines and chemokine receptors during thymocyte development are herein discussed.
Cell Mol Immunol 2004 Aug
PMID:Roles of chemokines in thymopoiesis: redundancy and regulation. 1622 69

Thymus, an important component of hematopoietic tissue, is a well-documented "target" of radiation carcinogenesis. Both acute and fractionated irradiation result in a high risk of leukemia and thymic lymphoma. However, the exact mechanisms underlying radiation-induced predisposition to leukemia and lymphoma are still unknown, and the contributions of genetic and epigenetic mechanisms in particular have yet to be defined. Global DNA hypomethylation is a well-known characteristic of cancer cells. Recent studies have also shown that tumor cells undergo prominent changes in histone methylation, particularly a substantial loss of trimethylation of histone H4-Lys20 and demethylation of genomic DNA. These losses are considered a universal marker of malignant transformation. In the present study, we investigated the effect of low-dose radiation exposure on the accumulation of DNA lesions and alterations of DNA methylation and histone H4-Lys20 trimethylation in the thymus tissue using an in vivo murine model. For the first time, we show that fractionated whole-body application of 0.5 Gy X-ray leads to decrease in histone H4-Lys20 trimethylation in the thymus. The loss of histone H4-Lys20 trimethylation was accompanied by a significant decrease in global DNA methylation as well as the accumulation of DNA damage as monitored by persistence of histone gammaH2AX foci in the thymus tissue of mice exposed to fractionated irradiation. Altered DNA methylation was associated with reduced expression of maintenance (DNMT1) and, to a lesser extent, de novo DNA methyltransferase DNMT3a in exposed animals. Expression of another de novo DNA methyltransferase DNMT3b was decreased only in males. Irradiation also resulted in approximately 20% reduction in the levels of methyl-binding proteins MeCP2 and MBD2. Our results show the involvement of epigenetic alterations in radiation-induced responses in vivo. These changes may play a role in genome destabilization that ultimately leads to cancer.
Mol Cancer Res 2005 Oct
PMID:Fractionated low-dose radiation exposure leads to accumulation of DNA damage and profound alterations in DNA and histone methylation in the murine thymus. 1625 89

Thymus and Activation-Regulated Chemokine (TARC) may be critical in Th2 cell recruitment in allergic inflammation; however, the mechanisms of allergen-induced TARC release are unclear. Since airway epithelium is the first line of defense to inhaled allergens, we questioned whether house dust mite allergen (Der p) can induce TARC expression in bronchial epithelial cells, how this is regulated at the molecular level, and if micro-environmental cytokines augment this effect. We examined the effects of Der p and the cytokines IL-4 and TGF-beta on TARC expression in 16HBE cells and primary bronchial asthma epithelium. Real-time PCR and immunofluorescence demonstrated that Der p induces TARC expression in bronchial epithelium. Supernatants from Der p-stimulated 16HBE cells were able to induce TARC-dependent T cell trafficking. IL-4 and TGF-beta cooperatively enhanced Der p-induced TARC expression in 16HBE cells. Specific inhibitors, immunodetection, and gel-shifts revealed that these effects are mediated by phosphorylation of the epidermal growth factor receptor (EGFR), mitogen-activated protein kinase (MAPK) signaling and subsequent nuclear factor (NF)-kappaB activation. A Disintegrin And Metalloproteinase (ADAM), a family of proteins involved in shedding of various growth factors, was shown to be responsible for EGFR activation. The increase in TARC production by direct interaction of Der p with the bronchial epithelium may be an important initial step in the generation of allergic inflammation, which is further potentiated by micro-environmental cytokines. Interference with ADAM or EGFR activity may be a novel promising target to prevent TARC release and subsequent allergic inflammation.
Am J Respir Cell Mol Biol 2007 Mar
PMID:Der p, IL-4, and TGF-beta cooperatively induce EGFR-dependent TARC expression in airway epithelium. 1702 89

Thymus development was studied in the cynomolgus monkey from day 35 of gestation (gd 35) to the stage of advanced involution in a 21-year-old monkey. Special emphasis was placed on thymus cell generation and cellular pattern formation. At gd 35, the epithelial bud of the thymus was visible in a sagittal position at the level of the thoracic aperture. At gd 50, first lymphocyte-like cells and few Human Leukocyte Antigen-D Region (HLA-DR) immunoreactive cells appeared. The cortico-medullary differentiation, Hassall's body precursors and faint immunoreactivity for T-lymphocytes (CD 3-positive) were detected from gd 60 onwards. First macrophages (CD 68 positive) were apparent at day 70, first CD 20 immunoreactive cells (B-lymphocyte-like cells) at gd 85, and natural killer cells (M1014 immunoreactive) at gd 100. At gd 100 all evaluated cell populations present in the adult cynomolgus monkey thymus were in place, whereas no B- and T-cell precursors or (CD 34 and CD 117, respectively) dendritic cells (CD 35 positive cells) were present. All these immunopositive cells persisted, partly with changing distribution patterns, until the advanced age of 21 years with the exception of natural killer cells, which were present only until adult ages (evaluation at 4-7 years). The rationale of this study was to analyse thymic development in the cynomolgus monkey and to evaluate the relevance of the development of thymus in non-human primate as a model for corresponding human targeted toxicological research.
J Mol Histol 2006 May
PMID:Thymus development in Macaca fascicularis (Cynomolgus monkey): an approach for toxicology and embryology. 1704 75

Thymus is a primary lymphoid organ, able to generate mature T cells that eventually colonize secondary lymphoid organs, and is therefore essential for peripheral T cell renewal. Recent data showed that normal thymocyte export can be altered by several influence factors including several chemokines, sphingosine1-phosphate (S1P), transcription factors such as Foxj1, Kruppel-like transcription factor 2 (KLF2) and antigen stimulation, etc. In this review, we summarized the recent reports about study strategies, influence factors and possible molecular mechanisms in thymic output.
Cell Mol Immunol 2006 Oct
PMID:Thymic output: influence factors and molecular mechanism. 1709 31

Thymus-independent type 2 (TI-2) antigens occasionally induce long-lasting IgM memory, but do not prime for typical secondary IgG responses. However, contrary to current understanding, we detected several TI-2-induced long-term memory effects in subsequent thymus-dependent (TD) responses to the hapten 2-phenyloxazolone coupled to a protein carrier. The early primary TD response, even 3 months after TI-2 immunization, included non-mutated IgM as well as IgG antibodies exhibiting higher affinities than the Ox1 idiotype which dominates and has highest affinity in sole TD responses. The secondary exclusive IgG response 8 weeks later contained major hitherto non-observed clones. Somatic hypermutation on the normally dominant V(H)Ox1 gene was largely silenced while the associated VkappaOx1 exhibited the classical affinity-enhancing mutations, thus suggesting a separate regulation of this process for V(H) and V(L) genes. Mutations accumulated in genes which normally are rarely or non-expressed or non-mutating. First evidence is presented that receptor revision by V(H) replacement may occur during immune maturation in genetically non-engineered wildtype mice. We conclude that the TI-2 antigen-induced altered selection of TD Ag-inducible clones and its severe gene-specific influence on further somatic mutations and affinity maturation represents a network memory, which we hypothesize to be mediated by anti-idiotypic regulatory T cells.
Mol Immunol 2008 May
PMID:Thymus-independent type 2 antigen induces a long-term IgG-related network memory. 1832 1

Interaction of chiral Ru(II) salen complexes (S)-1 and (R)-1 with Calf Thymus DNA (CT-DNA) was studied by absorption spectroscopy, competitive binding study, viscosity measurements, CD measurements, thermal denaturation study and cleavage studies by agarose gel electrophoresis. The DNA binding affinity of (S)-1 (6.25 x 10(3)M(-1)) was found to be greater than (R)-1 (3.0 x 10(3)M(-1)). The antimicrobial studies of these complexes on five different gram (+)/(-) bacteria and three different fungal organisms showed selective inhibition of the growth of gram (+) bacteria and were not affective against gram (-) and fungal organisms. Further, the (S)-1 enantiomer inhibited the growth of organisms to a greater extent as compared to (R)-1 enantiomer.
Spectrochim Acta A Mol Biomol Spectrosc 2009 Sep 15
PMID:Synthesis, characterization, DNA binding and cleavage studies of chiral Ru(II) salen complexes. 1952 73

Although the subfamily Nepetoideae (Lamiaceae) is considered to be monophyletic, relationships between tribes, subtribes and genera within the subfamily are poorly understood as complex and possibly homoplasious morphological characters make taxa difficult to delimit. DNA sequence data from three regions (chloroplast: trnK intron; trnL-F; nuclear: ITS) in total including 278 accessions, representing 38 out of 40 genera of subtribe Menthinae and 11 outgroup genera, were used to reconstruct the evolutionary history, test previous hypotheses of classification, explain biogeographic patterns and elucidate character evolution. Using maximum parsimony (MP) and Bayesian analysis phylogenetic reconstructions based on nuclear and chloroplast sequence data were incongruent, consequently the data were analyzed separately. Both nuclear and chloroplast datasets provide strong support for three major lineages: the "Satureja", "Micromeria" and "Clinopodium" group. The first contains members of Satureja and Gontscharovia. In the second lineage Micromeria s.str. and Origanum were resolved as monophyletic, Pentapleura and Zataria indicated as sister groups. Thymbra includes two species of Satureja turning the latter genus polyphyletic. Thymus is revealed as paraphyletic with respect to Argantoniella and Saccocalyx in both and Origanum in the plastid dataset only. In the third lineage, the Clinopodium-group, branching pattern is highly incongruent among datasets and possibly influenced by recent and ancient hybridization, chloroplast capture and incomplete lineage sorting. However, identical terminal groups are inferred in both analyses. A Madagascan lineage of "Micromeria", sister to the recently described South African Killickia, is suggested to represent a new genus. The Himalayan Clinopodium nepalense group and the tropical African C. abyssinicum alliance are monophyletic but indicated in different positions. Both groups appear in the ITS phylogeny in a clade with Cyclotrichium and Mentha, relationships not suggested previously. The enigmatic Micromeria cymuligera is close to Mentha and possibly is a representative of this genus. Species of Acinos, now regarded as part of Clinopodium, are mixed up with species of Ziziphora, questioning either the inclusion of Acinos in Clinopodium or generic distinctness of Ziziphora. All data sets suggest a monophyly of the New World taxa and argue for long distance dispersal from the Old World, rather than a vicariance explanation. Bystropogon marks the split up between the two lineages. Inclusion of 22 genera intermixed with Clinopodium spp. in the New World clade provides evidence that the current circumscription of the genus is highly unnatural. Low sequence divergence resulting in low phylogenetic resolution especially at the base of the clade indicate a rapid radiation accompanied by considerable ecological diversification and speciation.
Mol Phylogenet Evol 2010 May
PMID:Molecular phylogeny of Menthinae (Lamiaceae, Nepetoideae, Mentheae)--Taxonomy, biogeography and conflicts. 2015 13

Failure to repair DNA double-strand breaks (DSBs) can lead to cell death or cancer. Although nonhomologous end joining (NHEJ) has been studied extensively in mammals, little is known about it in primary tissues. Using oligomeric DNA mimicking endogenous DSBs, NHEJ in cell-free extracts of rat tissues were studied. Results show that efficiency of NHEJ is highest in lungs compared to other somatic tissues. DSBs with compatible and blunt ends joined without modifications, while noncompatible ends joined with minimal alterations in lungs and testes. Thymus exhibited elevated joining, followed by brain and spleen, which could be correlated with NHEJ gene expression. However, NHEJ efficiency was poor in terminally differentiated organs like heart, kidney and liver. Strikingly, NHEJ junctions from these tissues also showed extensive deletions and insertions. Hence, for the first time, we show that despite mode of joining being generally comparable, efficiency of NHEJ varies among primary tissues of mammals.
Cell Mol Life Sci 2011 Feb
PMID:Efficiency of nonhomologous DNA end joining varies among somatic tissues, despite similarity in mechanism. 2068 Mar 88


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