Rate and duration of hospitalisation for acute pulmonary embolism in the real-world clinical practice of different countries : Analysis from the RIETE registry

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Expression of MALT1 oncogene in hematopoietic stem/progenitor cells recapitulates the pathogenesis of human lymphoma in mice

Chromosomal translocations involving the MALT1 gene are hallmarks of mucosa-associated lymphoid tissue (MALT) lymphoma. To date, targeting these translocations to mouse B cells has failed to reproduce human disease. Here, we induced MALT1 expression in mouse Sca1(+)Lin(-) hematopoietic stem/progenitor cells, which showed NF-κB activation and early lymphoid priming, being selectively skewed toward B-cell differentiation. These cells accumulated in extranodal tissues and gave rise to clonal tumors recapitulating the principal clinical, biological, and molecular genetic features of MALT lymphoma. Deletion of p53 gene accelerated tumor onset and induced transformation of MALT lymphoma to activated B-cell diffuse large-cell lymphoma (ABC-DLBCL). Treatment of MALT1-induced lymphomas with a specific inhibitor of MALT1 proteolytic activity decreased cell viability, indicating that endogenous Malt1 signaling was required for tumor cell survival. Our study shows that human-like lymphomas can be modeled in mice by targeting MALT1 expression to hematopoietic stem/progenitor cells, demonstrating the oncogenic role of MALT1 in lymphomagenesis. Furthermore, this work establishes a molecular link between MALT lymphoma and ABC-DLBCL, and provides mouse models to test MALT1 inhibitors. Finally, our results suggest that hematopoietic stem/progenitor cells may be involved in the pathogenesis of human mature B-cell lymphomas

Tree water uptake in a tropical plantation varying in tree diversity: interspecific differences, seasonal shifts and complementarity

Westudied tree water uptake patterns, tested for complementary water use among species and analysed controlling factors in a tropical tree diversity experiment. The water uptake depth of five species was investigated across seasons and diversity levels using the natural abundance of water isotopes (δ2H, δ18O) and modelling. Three distinct water acquisition strategies were found for trees growing inmonocultures during the dry season: strong reliance (>70%) on soil water fromthe upper layer (0–30 cm) (Cedrela odorata), uptake from the upper and deeper layers (>30cm) in equal proportions (Hura crepitans, Anacardium excelsum and Luehea seemannii) and water uptake predominately from deeper layers (Tabebuia rosea). Seasonal shifts in water uptake were most pronounced for T. rosea. The water uptake pattern of a given species was independent of the diversity level underlining the importance of species identity and species characteristics in spatial and temporal tree water use. Statistics did not show a significant effect of diversity on source water fractions, but we did see some evidence for complementary water resource utilization in mixed species plots, especially in the dry season. Our results also demonstrated that the depth of soil water uptake was related to leaf phenology and tree transpiration rates. A higher proportion of water obtained from deeper soil layers was associated with a high percentage foliage cover in the dry season, which explained the higher transpiration rates

Carbon isotope composition and the NDVI as phenotyping approaches for drought adaptation in durum wheat: Beyond trait selection

High-throughput phenotyping platforms provide valuable opportunities to investigate biomass and drought-adaptive traits. We explored the capacity of traits associated with drought adaptation such as aerial measurements of the Normalized Difference Vegetation Index (NDVI) and carbon isotope composition (\u3b413C) determined at the leaf level to predict genetic variation in biomass. A panel of 248 elite durum wheat accessions was grown at the Maricopa Phenotyping platform (US) under well-watered conditions until anthesis, and then irrigation was stopped and plot biomass was harvested about three weeks later. Globally, the \u3b413C values increased from the first to the second sampling date, in keeping with the imposition of progressive water stress. Additionally, \u3b413C was negatively correlated with final biomass, and the correlation increased at the second sampling, suggesting that accessions with lower water-use efficiency maintained better water status and, thus, performed better. Flowering time affected NDVI predictions of biomass, revealing the importance of developmental stage when measuring the NDVI and the effect that phenology has on its accuracy when monitoring genotypic adaptation to specific environments. The results indicate that in addition to choosing the optimal phenotypic traits, the time at which they are assessed, and avoiding a wide genotypic range in phenology is crucial

Contribution of the ear and the flag leaf to grain filling in durum wheat inferred from the carbon isotope signature Genotypic and growing conditions effects

The ear, together with the flag leaf, is believed to play a major role as a source of assimilates during grain filling in C3 cereals. However, the intrusive nature of most of the available methodologies prevents reaching conclusive results in this regard. This study compares the carbon isotope composition (δ13C) in its natural abundance in the water-soluble fractions of the flag leaf blade and the ear with the δ13C of mature kernels to assess the relative contribution of both organs to grain filling in durum wheat (Triticum turgidum L. var. durum). The relative contribution of the ear was higher in landraces compared to modern cultivars, as well as in response to nitrogen fertilization and water stress. Such genotypic and environmentally driven differences were associated with changes in harvest index (HI), with the relative contribution of the ear being negatively associated with HI. In the case of the genotypic differences, the lower relative contribution of the ear in modern cultivars compared with landraces is probably associated with the appearance in the former of a certain amount of source limitation driven by a higher HI. In fact, the relative contribution of the ear was far more responsive to changes in HI in modern cultivars compared with landraces. © 2013 Institute of Botany, Chinese Academy of Sciences

Intravenous immunoglobulin promotes antitumor responses by modulating macrophage polarization

et al.Intravenous Igs (IVIg) therapy is widely used as an immunomodulatory strategy in inflammatory pathologies and is suggested to promote cancer regression. Because progression of tumors depends on their ability to redirect the polarization state of tumorassociated macrophages (from M1/immunogenic/proinflammatory to M2/anti-inflammatory), we have evaluated whether IVIg limits tumor progression and dissemination through modulation of macrophage polarization. In vitro, IVIg inhibited proinflammatory cytokine production from M1 macrophages and induced a M2-To-M1 polarization switch on human and murine M2 macrophages. In vivo, IVIg modified the polarization of tumor-associated myeloid cells in a Fcεr1γ chain-dependent manner, modulated cytokine blood levels in tumor-bearing animals, and impaired tumor progression via FcγRIII (CD16), FcγRIV, and FcRγ engagement, the latter two effects being macrophage mediated. Therefore, IVIg immunomodulatory activity is dependent on the polarization state of the responding macrophages, and its ability to trigger a M2-To-M1 macrophage polarization switch might be therapeutically useful in cancer, in which proinflammatory or immunogenic functions should be promoted.This work was supported by grants from Ministerio de Economía y Competitividad (SAF2011-23801), Genoma España (Mecanismos moleculares en enfermedades inflamatorias crónicas y autoinmunes project), Instituto de Salud Carlos III (Red de Investigación en Enfermedades Reumáticas), and Comunidad Autónoma de Madrid/Fondo Europeo de Desarrollo Regional (Rheumatoid Arthritis: Physiopathology Mechanisms Program) (to A.L.C.), and Ministerio de Economía y Competitividad Grant SAF2010-15106 (to M.L.T.). M.d.l.C.-E. is supported by a Formación de Personal Investigador predoctoral fellowship (BES-2009-021465) from Ministerio de Economía y Competitividad.Peer Reviewe