Brassington, A.-M. E., Sung, S. S., Toydemir, R. M., Le, T., Roeder, A. D., Rutherford, A. E., Whitby, F. G., Jorde, L. B., Bamshad, M. J. Tanteles, G. A., Nicolaou, N., Syrimis, A., Metaxa, R., Nicolaou, M., Christophidou-Anastasiadou, V., Skordis, N. Moskowitz, I. P. G., Kim, J. B., Moore, M. L., Wolf, C. M., Peterson, M. A., Shendure, J., Nobrega, M. A., Yokota, Y., Berul, C., Izumo, S., Seidman, J. G., Seidman, C. E. Murakami et al. (2005) found that TAZ (WWTR1; 300394) was a potent TBX5 transactivator. TAZ associated with TBX5 and stimulated TBX5-dependent promoters by interacting with the histone acetyltransferases p300 (EP300; 602700) and PCAF ( 602303). YAP ( 606608), a TAZ-related protein, also stimulated TBX5-dependent transcription. TBX5 with HOS-associated truncation mutations could not be stimulated by TAZ, but TBX5 with HOS-associated point mutations was unimpaired in its ability to respond to TAZ.

Li et al. (1997) pointed out that TBX3 may be a candidate gene for Noonan syndrome ( 163950) and ulnar-mammary syndrome (UMS; 181450). The latter possibility indeed proved to be the case; Bamshad et al. (1997) demonstrated mutations in TBX3 in 2 families with ulnar-mammary syndrome ( 602621.0001- 602621.0002). Each mutation was predicted to cause haploinsufficiency of TBX3, implying that critical levels of this transcription factor are required for morphogenesis of several organs. Limb abnormalities of ulnar-mammary syndrome involve posterior elements. Mutations in TBX5 cause anterior limb abnormalities in Holt-Oram syndrome. Because of similarities in structure and function of TBX3 and TBX5 and because of close linkage, Bamshad et al. (1997) proposed that these genes originated from a common ancestral gene, each having acquired specific complementary roles in patterning the mammalian upper limb. Methods: A549 cell was irradiated with carbon ion to establish the clone survival model and the transwell matrix assay was applied to measure the effect of carbon ion on cell viability, migration, and invasion, respectively. Normal human embryonic lung fibroblasts (WI-38) were irradiated with carbon ions of 0 and 2 Gy and then transferred to A549 cell co-culture medium for 24h. The migration and invasion of A549 cells were detected by the Transwell chamber. The analysis of metabonomic information in transfer medium by liquid phase mass spectrometry (LC-MS), The differential molecules were obtained by principal pomponent analysis (PCA) and the target proteins of significant differences ( p = 1.7 × 10 −3) obtained by combining with the STICH database. KEGG pathway was used to analyze the enrichment of the target protein pathway. In twin brothers and their father with ulnar-mammary syndrome, Tanteles et al. (2017) identified heterozygosity for a nonsense mutation in the TBX3 gene ( 601621.0006). Identification of TBX2 and TBX3 variants in patients with conotruncal heart defects by target sequencing. To understand better the role of TBX5 in forelimb and heart development, Basson et al. (1999) studied the clinical features of Holt-Oram syndrome caused by 10 different TBX5 mutations. Defects predicted to create null alleles caused substantial abnormalities in both limb and heart. In contrast, missense mutations produced distinct phenotypes: gly80-to-arg (601620.0004) caused significant cardiac malformations but only minor skeletal abnormalities, whereas arg237-to-gln (601620.0003) and arg237-to-trp (601620.0005) caused extensive upper limb malformations but less significant cardiac abnormalities. Amino acids altered by missense mutations were located on the 3-dimensional structure of a related T-box transcription factor, Xbra (of X. laevis), bound to DNA. Residue 80 is highly conserved within T-box sequences that interact with the major groove of target DNA; residue 237 is located in the T-box domain that selectively binds to the minor groove of DNA. These structural data, taken together with the predominant cardiac or skeletal phenotype produced by each missense mutation, suggested that organ-specific gene activation by TBX5 is predicated on biophysical interactions with different target DNA sequences.Where the benefit received is in the form of an asset, other than cash, and the ownership of that asset actually passes to the individual as opposed to an asset being made available for use which remains in the ownership of the provider. The amount or value of the benefit is likely to be determined by reference to the value of the asset at the point in time when it is received by the individual. In most cases this is likely to be similar to the approach that may be adopted for capital gains purposes where it may be appropriate to determine the open market acquisition value of the asset to the individual. Satisfying a debt

Wiese, C., Grieskamp, T., Airik, R., Mommersteeg, M. T. M., Gardiwal, A., de Gier-de Vries, C., Schuster-Gossler, K., Moorman, A. F. M., Kispert, A., Christoffels, V. M. Basson, C. T., Huang, T., Lin, R. C., Bachinsky, D. R., Weremowicz, S., Vaglio, A., Bruzzone, R., Quadrelli, R., Lerone, M., Romeo, G., Silengo, M., Pereira, A., Krieger, J., Mesquita, S. F., Kamisago, M., Morton, C. C., Pierpont, M. E. M., Muller, C. W., Seidman, J. G., Seidman, C. E. Yang et al. (2000) analyzed 11 Chinese patients with Holt-Oram syndrome using SSCP analysis of TBX5. The authors identified 3 novel mutations, including a frameshift mut Parking will be provided free to all outpatients who attend hospital for an appointment at least 3 times within a month and for an overall period of at least 3 months. A ‘month’ is defined as a period of 30 days. Garg et al. (2003) demonstrated that GATA4 ( 600576) interacts with TBX5 and showed that a missense mutation in GATA4, G296S ( 600576.0001), abrogated this interaction. Conversely, interaction of GATA4 and TBX5 was disrupted by specific human TBX5 missense mutations that cause similar cardiac septal defects. Garg et al. (2003) concluded that their results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5.The A549 cells were irradiated with different doses of carbon ions, and then Transwell was used to detect migration and invasion. Migration and invasion of A549 were detected by transwell chamber after carbon ion irradiation. The Transwell assay for the ability of invasion was performed as the following protocol: the polycarbonate membranes with an 8-μm pore (Corning, USA) were placed on 24-well Transwell plates (Corning, USA), The lower side of the filter was precoated with 10μg/mL collagen type I-C (Millpore, USA). After incubation for 3h, the number of cells that had migrated to the lower side was counted in five independent fields. These experiments were repeated a minimum of four times. The Transwell assay for the ability of migration was performed as the following protocol: Millpore filters with 8-lm pores (Millpore, USA) were precoated with 100ml of 0.1 μg/ml Matrigel (BD, USA). After incubation for 24h, the number of cells that had invaded to the lower side through the pores was counted in five independent fields. In both assays, FBS was used as a chemoattractant. These experiments were repeated a minimum of four times. The irradiated cells were prepared by trypsin digestion and cells (3 × 10 4) were resuspended in medium RPMI 1640 containing 1% (v/v) FBS and added to the top chamber. A culture medium containing 5% (v/v) FBS was then added to the bottom chamber. Meanwhile, for determining the influence of conditioned medium on the metastasis of bystander cells, medium of unirradiated cells in Transwells chamber was replaced with irradiation conditioned mediumn collected nonirradiated cells. For the controls in experiments, the irradiation conditioned mediumn were collected from a parallel culture that had not been irradiated. Other experimental conditions are the same as those for the detection of radiation-induced direct effects. Cell motility/migration was measured as the number of cells migrated from a defined area of the uncoated microfilter through micropores in the given time, 24h. The cells that migrated to the lower surface of the membrane were fixed with methanol for 10min and stained with 0.5% (w/v) crystal violet (BD Biosciences) for 30min. Metabonomics Analysis of RIBE Factors Bamshad, M., Lin, R. C., Law, D. J., Watkins, W. S., Krakowiak, P. A., Moore, M. E., Franceschini, P., Lala, R., Holmes, L. B., Gebuhr, T. C., Bruneau, B. G., Schinzel, A., Seidman, J. G., Seidman, C. E., Jorde, L. B. Borozdin, W., Bravo-Ferrer Acosta, A. M., Seemanova, E., Leipoldt, M., Bamshad, M. J., Unger, S., Kohlhase, J.

Basson, C. T., Bachinsky, D. R., Lin, R. C., Levi, T., Elkins, J. A., Soults, J., Grayzel, D., Kroumpouzou, E., Traill, T. A., Leblanc-Straceski, J., Renault, B., Kucherlapati, R., Seidman, J. G., Seidman, C. E. If the individual receiving a benefit makes any contribution towards that benefit, the contribution will normally be taken into account in determining the amount or value of the benefit. Zhen Yang 1† Qiuning Zhang 2,3† Hongtao Luo 2 Lihua Shao 3 Ruifeng Liu 2 Yarong Kong 2 Xueshan Zhao 4 Yichao Geng 4 Chengcheng Li 4 Xiaohu Wang 1,2,3,4* A dominant repression domain in Tbx3 mediates transcriptional repression and cell immortalization: relevance to mutations in Tbx3 that cause ulnar-mammary syndrome. In 2018, there were 18.1 million new cases of cancer worldwide, of which the incidence of lung cancer was 11.6% and the mortality rate was 18.4% ( 1). However, the metastasis of lung cancer is a major cause of treatment failure ( 2). Carbon ions with high LET rays ( 12C 6+) can inhibit the metastasis of tumor cells by their advantages in physics and biology ( 3, 4). Radiation induces bystander effect (RIBE) refers to the plethora of biological phenomena occurring in non-irradiated cells as a result of signal transmission from an irradiated cell ( 5). The study of proton targeting cancer cells and unirradiated normal fibroblasts also found an induced bi-directional bystander effect, and RIBE was detected in vitro, 3D tissues and mouse models ( 6).Growing evidence show that bystander responses can be regulated by four mechanisms-(i) gap junction intercellular communication (ii) communication of soluble factors released by irradiated cells or organs (iii) clastogenic factors and exosomes ( 7, 8).

Supplementary Material

Through this study, we prove the potential value of metabonomics after carbon ion radiation. The bystander effects induced by carbon ion radiation may change the non-irradiated tumor microenvironment, thus increasing or decreasing the corresponding metabolites. These metabolites can act on targeted molecules and finally show the ability of collective complex signal regulatory network to act on the metastasis and invasion of malignant tumor cells. The further study of radiation bystander effect and malignant tumor metastasis and its mechanism is expected to provide a scientific basis for the optimization of clinical tumor radiotherapy and radiation protection. A better understanding of the cellular and molecular mechanisms of the bystander phenomenon, together with evidence of their occurrence in vivo, will allow us to formulate a more accurate model in assessing the health effects of low doses of high LET radiation. Data Availability Statement In a Czech mother and 2 daughters who were diagnosed with Holt-Oram syndrome, Borozdin et al. (2006) identified a 2.19 to 2.27-Mb contiguous deletion encompassing the TBX5 and TBX3 genes. Clinical reexamination confirmed the presence of features of ulnar-mammary syndrome that were previously unrecognized. Borozdin et al. (2006) noted that the contiguous deletion also included the RBM19 gene (616444), but commented that it was unlikely to contribute to or modify the phenotype since all the anomalies present in the affected individuals could be explained by either TBX5 or TBX3 haploinsufficiency. Using SSCP analysis and direct sequencing of amplified products, Li et al. (1997) showed that the TBX5 gene was mutated in cases of familial and sporadic Holt-Oram syndrome (HOS; 142900) (see, e.g., 601620.0001).