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The concept of Data Transportability (DT) of Confined Field Testing (CFT) to support the Environmental Risk Assessment (ERA) of Genetically Modified (GM) plants was first introduced in the literature by Garcia-Alonso et al., in 2014. Since then, DT has been discussed in many countries and regions as a concept to prevent duplication of regulatory studies without compromising quality of the ERA. However, despite its usefulness and scientific justification, DT is not well adopted at this time and many regulatory agencies around the world require additional in-country CFT be conducted before approving GM plants. Based on the current circumstances, the authors organized a parallel session entitled "Introduction and Scientific Justification of DT for CFT for the ERA of GM plants" at 16th ISBR (the International Society for Biosafety Research). This session mainly consisted of the following three parts. The first two speakers, Andrew Roberts and Abigail Simmons provided an overview of DT and examples of conditions for the transportability of field data/conclusions advocated in the peer-reviewed scientific journals. Next, the current status of DT adoption in some countries/regions such as Japan and Africa, and a theoretical case study for Argentina were introduced by Kazuyuki Hiratsuka, Douglas Miano, and Facundo Vesprini, respectively. Lastly, a risk hypothesis-based approach for DT which was developed in advance by the five speakers of this parallel session, was introduced. During the discussion, there was a common understanding that transition to the risk hypothesis-based approach for DT was scientifically appropriate, considering the accumulated evidences that several countries have conducted confirmatory local CFT for more than 20 years but they have not detected any differences related to the ERA assessment endpoints in GM crops. The risk hypothesis-based approach for DT introduced here is expected to play an important role in discussions on the implementation of DT in various parts of the world in the future.
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Local immune memory develops at the site of antigen exposure and facilitates a rapid and strong local adaptive defense upon re-exposure. Resident memory T (TRM) cells play a role in local immune memory, and their cell-surface molecules CD69 and CD103 promote their tissue residency. However, the contribution of these molecules to skin immune memory remains unclear. In this study, by inducing contact hypersensitivity (CHS) in CD69KO (CD69-deficient) and CD103-deficient mice, where different degrees of TRM cell contribution are observed by repeated challenges on the right ear and a single challenge on the left ear, we found that the deficiency of CD69 but not CD103 leads to impaired CHS upon repeated antigen challenges, even although TRM cells-like CD8 T cells developed at the challenged site of CD69KO. CHS responses in both ears were diminished in CD69KO by FTY720 or CD8 neutralization, suggesting that CHS in CD69KO is ascribed to circulating CD8 T cells and that the developed TRM cell-like CD8 T cells do not behave as TRM cells. The infiltration of macrophages was reduced in the rechallenged site of CD69KO, along with the downregulation of Cxcl1 and Cxcl2. Thus, CD69 is considered essential for an effective recall response, involving the development of functional TRM cells and the recruitment of macrophages.
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Field trials were conducted in Japan under different growing conditions to better understand seed production of wild soybean (Glycine soja Seib. et Zucc.). The objectives of these trials were to evaluate yield and yield components of wild soybean: (1) across 11 diverse populations grown under favorable conditions to assess seed production potential, (2) under different planting densities (112, 208, 416, and 832 plants/m2) to assess intra-specific competition, and (3) across growing conditions (favorable, ruderal, and natural) to assess the impacts of environmental stress and inter-specific competition. Significant differences in yield and seed number observed among the evaluated wild soybean populations were predominantly due to environmental effects and genetic by environmental interaction. Seed production was impacted by both intra- and inter-specific competition. Wild soybean grown without plant competition had 51-fold and 247-fold higher yield compared to when grown in ruderal and natural environments, respectively. Under favorable growing conditions, wild soybean had substantial yield potential due to the ability to produce a high number of seeds. In nature, yield potential is severely limited because of plant competition and other environmental stressors. The results of this research are useful to inform environmental risk assessment when considering the potential impact of soybean biotechnology traits that increase or protect yield. If such traits were to be inadvertently transferred from imported soybean into wild soybean, this research indicates that the effects would likely have little overall impact on wild soybean seed production.
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Fabaceae , Glycine max , Clima , Glicina , SemillasRESUMEN
Cutaneous T-cell lymphoma (CTCL) is a heterogeneous group of non-Hodgkin lymphoma, including various clinical manifestations, such as mycosis fungoides (MF) and Sézary syndrome (SS). CTCL mostly develops from CD4 T cells with the skin-tropic memory phenotype. Malignant T cells in MF lesions show the phenotype of skin resident memory T cells (TRM), which reside in the peripheral tissues for long periods and do not recirculate. On the other hand, malignant T cells in SS represent the phenotype of central memory T cells (TCM), which are characterized by recirculation to and from the blood and lymphoid tissues. The kinetics and the functional characteristics of malignant cells in CTCL are still unclear due, in part, to the fact that both the malignant cells and the T cells exerting anti-tumor activity possess the same characteristics as T cells. Capturing the features of both the malignant and the benign T cells is necessary for understanding the pathogenesis of CTCL and would lead to new therapeutic strategies specifically targeting the skin malignant T cells or benign T cells.
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Linfoma Cutáneo de Células T/inmunología , Células T de Memoria/patología , Piel/inmunología , Animales , Humanos , Piel/patología , Microambiente TumoralRESUMEN
Nonsmall cell lung cancer (NSCLC) is one of the most common histologically deï¬ned subtypes of lung cancer. To identify a promising molecular target for NSCLC therapy, we performed gene expression analysis at the exon level using postoperative specimens of NSCLC patients. Exon array and realtime PCR analyses revealed that an alternative splicing variant of solute carrier organic anion transporter family member 1B3 (SLCO1B3) called cancer typeSLCO1B3 (CtSLCO1B3) was signiï¬cantly upregulated in the NSCLC samples. SLCO1B3 expressed in the liver [liver type (Lt)SLCO1B3] was found to be localised in the cell membrane, whereas CtSLCO1B3 was detected in the cytoplasm of NSCLC cells. RNAimediated knockdown of CtSLCO1B3 inhibited in vitro anchorageindependent cell growth, cell migration, and in vivo tumour growth of A549 cells. Overexpression of CtSLCO1B3 but not LtSLCO1B3 upregulated anchorageindependent cell growth and cell migration of NCIH23 cells. Mechanistically, CtSLCO1B3 was found to regulate the expression of epithelialmesenchymal transition (EMT)related genes. The upregulation of Ecadherin was discovered to be especially pivotal to phenotypes of CtSLCO1B3suppressed A549 cells. These ï¬ndings suggest that CtSLCO1B3 functions as a tumourpromoting factor via regulating EMTrelated factors in NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas/patología , Transición Epitelial-Mesenquimal , Neoplasias Pulmonares/patología , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/fisiología , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/etiología , Movimiento Celular , Proliferación Celular , Humanos , Neoplasias Pulmonares/etiología , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
An expanding trend for genetically engineered (GE) crops is to cultivate varieties in which two or more single trait products have been combined using conventional breeding to produce a stacked trait product that provides a useful grouping of traits. Here, we report results from compositional analysis of several GE stacked trait products from maize and soybean. The results demonstrate that these products are each compositionally equivalent to a relevant non-GE comparator variety, except for predictable shifts in the fatty acid profile in the case of stacked trait products that contain a trait, MON 87705, that confers a high-oleic-acid phenotype in soybean. In each case, the conclusion on compositional equivalence for the stacked trait product reflects the conclusions obtained for the single trait products. These results provide strong support for conducting a reassessment of those regulatory guidelines that mandate explicit characterization of stacked trait products produced through conventional breeding.
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Glycine max/química , Plantas Modificadas Genéticamente/química , Zea mays/química , Aminoácidos/química , Cruzamiento , Ácidos Grasos/química , Alimentos Modificados Genéticamente , Ingeniería Genética , Proteínas de Plantas/química , Plantas Modificadas Genéticamente/genética , Plantas Modificadas Genéticamente/metabolismo , Glycine max/genética , Glycine max/metabolismo , Zea mays/genética , Zea mays/metabolismoRESUMEN
Requirement of in-country confined field trials for genetically modified (GM) crops prior to unrestricted release is well-established among countries with domestic regulations for the cultivation approval of GM crops. However, the requirement of in-country confined field trials is not common in countries where the scope of the application does not include cultivation. Nonetheless, Japan and China request in-country confined field trials for GM crops which are intended only for use as food, feed and processing. This paper considers the transportability of confined field trial data from cultivation countries (e.g. United States, Canada, and South American countries) to import countries like Japan for the environmental risk assessment of GM crops by reviewing: (1) the purpose of confined field trial assessment, (2) weediness potential, defined as "an ability to establish and persist in an unmanaged area that is frequently disturbed by human activity", of host crops, and (3) reliability of the confined field trial data obtained from cultivation countries. To review the reliability of the confined field data obtained in the US, this paper describes actual examples of three confined field trials of approved GM corn events conducted both in the US and Japan. Based on the above considerations, this paper concludes that confined field data of GM corn and cotton is transportable from cultivation countries to importing countries (e.g. from the US to Japan), regardless of the characteristics of the inserted gene(s). In addition, this paper advocates harmonization of protocols for confined field trials to facilitate more efficient data transportability across different geographies.
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Productos Agrícolas/genética , Exposición a Riesgos Ambientales/prevención & control , Plantas Modificadas Genéticamente/efectos adversos , Medición de Riesgo , Estadística como Asunto , Seguridad de Productos para el Consumidor , HumanosRESUMEN
Tobacco cytochrome P450 (CYP) 71AH11 metabolized the herbicide chlorotoluron, and its mRNA level was increased in tobacco culture cells by the treatment of 2,4-D. In order to clarify molecular mechanisms of induced gene expression of CYP71AH11 by herbicide treatment, a 1574-bp 5'-flanking region of CYP71AH11 was cloned, ligated to the reporter ß-glucuronidase (GUS) gene, and then transformed into tobacco plants. The GUS activity in the transgenic tobacco plants was highly induced by bromoxynil treatment, followed by 2,4-D. Chlorotoluron was slightly increased the GUS activity. The bromoxynil-increased GUS activity was partially repressed by the antioxidants, suggesting that reactive oxygen species may be involved in activation of the 5'-flanking region of CYP71AH11 by bromoxynil treatment. Deletion and mutation assays showed that the region CD (-1281 to -770bp from the start codon of CYP71AH11) was important, but not sufficient, for response to bromoxynil. Electrophoretic mobility shift assays and southwestern blotting revealed that the sequences AAAAAG, and GAACAAAC and GAAAATTC in the CD region were important for interaction to the nuclear proteins of <30 and ≈75 kDa, respectively. Particularly, interaction between AAAAAG and <30 kDa proteins was increased by bromoxynil treatment. These results gave a cue for understanding the bromoxynil-induced gene expression of CYP71AH11, which may contribute to herbicide tolerance and selectivity in crop plants.