GLI2-Mediated Melanoma Invasion and Metastasis

Background The transforming growth factor-β (TGF-β) pathway, which has both tumor suppressor and pro-oncogenic activities, is often constitutively active in melanoma and is a marker of poor prognosis. Recently, we identified GLI2, a mediator of the hedgehog pathway, as a transcriptional target of TGF-β signaling. Methods We used real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blotting to determine GLI2 expression in human melanoma cell lines and subsequently classified them as GLI2high or as GLI2low according to their relative GLI2 mRNA and protein expression levels. GLI2 expression was reduced in a GLI2high cell line with lentiviral expression of short hairpin RNA targeting GLI2. We assessed the role of GLI2 in melanoma cell invasiveness in Matrigel assays. We measured secretion of matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography and expression of E-cadherin by western blotting and RT-PCR. The role of GLI2 in development of bone metastases was determined following intracardiac injection of melanoma cells in immunocompromised mice (n = 5-13). Human melanoma samples (n = 79) at various stages of disease progression were analyzed for GLI2 and E-cadherin expression by immunohistochemistry, in situ hybridization, or RT-PCR. All statistical tests were two-sided. Results Among melanoma cell lines, increased GLI2 expression was associated with loss of E-cadherin expression and with increased capacity to invade Matrigel and to form bone metastases in mice (mean osteolytic tumor area: GLI2high vs GLI2low, 2.81 vs 0.93 mm2, difference = 1.88 mm2, 95% confidence interval [CI] = 1.16 to 2.60, P < .001). Reduction of GLI2 expression in melanoma cells that had expressed high levels of GLI2 substantially inhibited both basal and TGF-β-induced cell migration, invasion (mean number of Matrigel invading cells: shGLI2 vs shCtrl (control), 52.6 vs 100, difference = 47.4, 95% CI = 37.0 to 57.8, P = .024; for shGLI2 + TGF-β vs shCtrl + TGF-β, 31.0 vs 161.9, difference = −130.9, 95% CI = −96.2 to −165.5, P = .002), and MMP secretion in vitro and the development of experimental bone metastases in mice. Within human melanoma lesions, GLI2 expression was heterogeneous, associated with tumor regions in which E-cadherin was lost and increased in the most aggressive tumors. Conclusion GLI2 was directly involved in driving melanoma invasion and metastasis in this preclinical stud

The Expanding Menagerie of Prunus-Infecting Luteoviruses

Members of the genus Luteovirus are responsible for economically destructive plant diseases worldwide. Over the past few years, three luteoviruses infecting Prunus trees have been characterized. However, the biological properties, prevalence, and genetic diversity of those viruses have not yet been studied. High-throughput sequencing of samples of various wild, cultivated, and ornamental Prunus species enabled the identification of four novel species in the genus Luteovirus for which we obtained complete or nearly complete genomes. Additionally, we identified another new putative species recovered from Sequence Read Archive data. Furthermore, we conducted a survey on peach-infecting luteoviruses in eight European countries. Analyses of 350 leaf samples collected from germplasm, production orchards, and private gardens showed that peach-associated luteovirus (PaLV), nectarine stem pitting-associated virus (NSPaV), and a novel luteovirus, peach-associated luteovirus 2 (PaLV2), are present in all countries; the most prevalent virus was NSPaV, followed by PaLV. The genetic diversity of these viruses was also analyzed. Moreover, the biological indexing on GF305 peach indicator plants demonstrated that PaLV and PaLV2, like NSPaV, are transmitted by graft at relatively low rates. No clear viral symptoms have been observed in either graft-inoculated GF305 indicators or different peach tree varieties observed in an orchard. The data generated during this study provide a broader overview of the genetic diversity, geographical distribution, and prevalence of peach-infecting luteoviruses and suggest that these viruses are likely asymptomatic in peach under most circumstances.This study was funded by the European Union through the Horizon 2020 Marie Skłodowska-Curie Actions Innovative Training Network (H2020 MSCA-60 ITN) project “INEXTVIR” (grant agreement number 813542). The ChLVA research part was financed by the Academy of Sciences of the Czech Republic (RVO60077344). The plant indexing biological tests conducted by CTIFL were funded by INTERFEL (fresh fruit and vegetable interprofessional association). D. Safarova and M. Navratil received support from the Ministry of Agriculture of the Czech Republic, National Agency for Agricultural Research (project QK1920124). M. Glasa and D. Mihálik received support from the Slovak Research & Development Agency (project APVV-18-0005)Peer reviewe

Chimie de la neige et de la fonte printaniere au Casset (Alpes du Sud). Influence des poussieres minerales

SIGLEAvailable from INIST (FR), Document Supply Service, under shelf-number : T 82313 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Molecular and cellular basis of depigmentation in vitiligo patients

---International audienceVitiligo is a chronic skin disease characterized by the appearance of zones of depigmentation. It is mostly described as an autoimmune disease in which the immune system destroys the melanocytes. Consistent with this origin, genetic studies have implicated genes encoding proteins mediating the immune response targeting melanocytes in the etiology of this disease, together with proteins specific to these cells. However, the destruction of melanocytes by the immune system is neither global nor complete, because the patients do not display total depigmentation. The etiopathology of vitiligo is clearly complex and cannot be simply reduced to an autoimmune reaction directed against pigmented cells. Intrinsic changes have beenobserved in the melanocytes, keratinocytes and dermal cells of vitiligo patients. Identification of the molecular and cellular changes occurring in normally pigmented skin in vitiligo patients, and an understanding of these changes, are essential to improve the definition of trigger events for this disease, with a view to developing treatments with long-term efficacy. This review focuses on the early events identified to date in the non-lesional regions of the skin in vitiligo patients, and discusses the process of repigmentation from melanocyte stem cells

C57BL/6 congenic mouse NRAS Q61K melanoma cell lines are highly sensitive to the combination of MEK and AKT inhibitors in vitro and in vivo

International audienc

Regional strategies and cross-border co-operation to control ozone pollution

In many European cities, air pollution is currently perceived as a local problem mainly related to road transport and certain industrial processes. However, some of the air pollution problems that UK local authorities are currently facing are related to air pollutants formed outside their geographical boundaries. For example, ground-level ozone episodes occurring in Sussex and Kent are often attributed to emission sources in continental Europe. Although there are international agreements in place for transboundary pollutants like ozone, relevant regional control strategies are lacking. A number of studies have recently focused on the formation, trends and spatial patterns of ozone pollution in different geographical areas making use of photochemical grid and/or trajectory models, emission inventories and field observations. Some of these tools may be applicable to the Trans Manche region. An analysis of monitoring data from five stations in England showed decreasing numbers of ozone episodes, but persistently high background levels, with some of the highest values observed at rural locations near the south east coast. Ozone concentrations in coastal areas on both sides of the Channel were highly correlated during recent episodes, probably due to the common origin of the sampled air masses. For this reason, co-operation between UK and French authorities is needed in order to optimise strategies for controlling regional ozone pollution.</p

Melanoblast proliferation dynamics during mouse embryonic development: Modeling and validation

International audienceIn this paper, we are looking for mathematical modeling of mouse embryonic melanoblast proliferation dynamics, taking into account, the expression level of β-catenin. This protein plays an important role into the whole signal pathway process. Different assumptions on some unobservable features lead to different candidate models. From real data measured, from biological experiments and from a priori biological knowledge, it was able to validate or invalidate some of the candidate models. Data assimilation and parameter identification allowed us to derive a mathematical model that is in very good agreement with biological data. As a result, the produced model can give tracks for biologists into their biological investigations and experimental evidence. Another interest is the use of this model for robust hidden parameter identification like double times or number of founder melanoblasts