Seasonal physiological responses of Argania spinosa tree from Mediterranean to semi-arid climate

Argania spinosa (the argan tree) is a slow-growing tree endemic of Morocco, growing on semi-arid areas where no other tree species can live. With the aim of predicting temporal changes in A. spinosa woodlands under a probable increase in aridity, we set off to investigate these questions: how do A. spinosa physiological attributes respond to variations in climatic conditions and seasonality, and which is the set of attributes that most affects tree response to environmental conditions? In three study sites, Beni Snassen (North), High-Atlas (Mountain) and Admine Forest in Agadir (Coastal), gas exchange measurements, photochemical efficiency, leaf water potential and different leaf attributes were monitored in February, July and November of 2006. The Mountain site presents the most continental climate. Trees in this site were the most stressed in summer, having the lowest midday leaf water potential values, photochemical efficiency and assimilation rates. We found a Ψ_md threshold around -4 MPa, below which stomatal conductance responds linearly to Ψ_md. Plants from the North area never reached this threshold during the study period. Although leaf pigments presented a clear seasonal pattern, leaves from Coastal trees exhibit the highest content for each season. The three study sites were separated by two discriminate functions obtained by canonical discriminant analysis. In summer, the Mountain population is separated from the other sites mainly by assimilation rate and F_v/F_m, while in winter transpiration rates and chlorophyll content are the main discriminant variables. Our study shows that A. spinosa trees adjust their physiological status and leaf attributes to environmental conditions allowing plants to thrive under a dry climate. Under a scenario of global change, the distribution of the argan tree likely shifts to milder areas.     

Novel Tools to Analyze the Function of Salmonella Effectors Show That SvpB Ectopic Expression Induces Cell Cycle Arrest in Tumor Cells

In order to further characterize its role in pathogenesis and to establish whether its overproduction can lead to eukaryotic tumor cell death, Salmonella strains able to express its virulence factor SpvB (an ADP-ribosyl transferase enzyme) in a salicylate-inducible way have been constructed and analyzed in different eukaryotic tumor cell lines. To do so, the bacterial strains bearing the expression system have been constructed in a ∆purD background, which allows control of bacterial proliferation inside the eukaryotic cell. In the absence of bacterial proliferation, salicylate-induced SpvB production resulted in activation of caspases 3 and 7 and apoptotic cell death. The results clearly indicated that controlled SpvB production leads to F-actin depolimerization and either G1/S or G2/M phase arrest in all cell lines tested, thus shedding light on the function of SpvB in Salmonella pathogenesis. In the first place, the combined control of protein production by salicylate regulated vectors and bacterial growth by adenine concentration offers the possibility to study the role of Salmonella effectors during eukaryotic cells infection. In the second place, the salicylate-controlled expression of SpvB by the bacterium provides a way to evaluate the potential of other homologous or heterologous proteins as antitumor agents, and, eventually to construct novel potential tools for cancer therapy, given that Salmonella preferentially proliferates in tumors.     

Zero‐modified Poisson model: Bayesian approach,influence diagnostics,and an application to a Brazilian leptospirosis notification data

In this paper, a Bayesian method for inference is developed for the zero‐modified Poisson (ZMP) regression model. This model is very flexible for analyzing count data without requiring any information about inflation or deflation of zeros in the sample. A general class of prior densities based on an information matrix is considered for the model parameters. A sensitivity study to detect influential cases that can change the results is performed based on the Kullback–Leibler divergence. Simulation studies are presented in order to illustrate the performance of the developed methodology. Two real datasets on leptospirosis notification in Bahia State (Brazil) are analyzed using the proposed methodology for the ZMP model.     

PARP-1 Regulates Metastatic Melanoma through Modulation of Vimentin-induced Malignant Transformation

PARP inhibition can induce anti-neoplastic effects when used as monotherapy or in combination with chemo- or radiotherapy in various tumor settings; however, the basis for the anti-metastasic activities resulting from PARP inhibition remains unknown. PARP inhibitors may also act as modulators of tumor angiogenesis. Proteomic analysis of endothelial cells revealed that vimentin, an intermediary filament involved in angiogenesis and a specific hallmark of EndoMT (endothelial to mesenchymal transition) transformation, was down-regulated following loss of PARP-1 function in endothelial cells. VE-cadherin, an endothelial marker of vascular normalization, was up-regulated in HUVEC treated with PARP inhibitors or following PARP-1 silencing; vimentin over-expression was sufficient to drive to an EndoMT phenotype. In melanoma cells, PARP inhibition reduced pro-metastatic markers, including vasculogenic mimicry. We also demonstrated that vimentin expression was sufficient to induce increased mesenchymal/pro-metastasic phenotypic changes in melanoma cells, including ILK/GSK3-β-dependent E-cadherin down-regulation, Snail1 activation and increased cell motility and migration. In a murine model of metastatic melanoma, PARP inhibition counteracted the ability of melanoma cells to metastasize to the lung. These results suggest that inhibition of PARP interferes with key metastasis-promoting processes, leading to suppression of invasion and colonization of distal organs by aggressive metastatic cells.     

JmjC-KDMs KDM3A and KDM6B modulate radioresistance under hypoxic conditions in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC), the most frequent esophageal cancer (EC) subtype, entails dismal prognosis. Hypoxia, a common feature of advanced ESCC, is involved in resistance to radiotherapy (RT). RT response in hypoxia might be modulated through epigenetic mechanisms, constituting novel targets to improve patient outcome. Post-translational methylation in histone can be partially modulated by histone lysine demethylases (KDMs), which specifically removes methyl groups in certain lysine residues. KDMs deregulation was associated with tumor aggressiveness and therapy failure. Thus, we sought to unveil the role of Jumonji C domain histone lysine demethylases (JmjC-KDMs) in ESCC radioresistance acquisition. The effectiveness of RT upon ESCC cells under hypoxic conditions was assessed by colony formation assay. KDM3A/KDM6B expression, and respective H3K9me2 and H3K27me3 target marks, were evaluated by RT-qPCR, Western blot, and immunofluorescence. Effect of JmjC-KDM inhibitor IOX1, as well as KDM3A knockdown, in in vitro functional cell behavior and RT response was assessed in ESCC under hypoxic conditions. In vivo effect of combined IOX1 and ionizing radiation treatment was evaluated in ESCC cells using CAM assay. KDM3A, KDM6B, HIF-1α, and CAIX immunoexpression was assessed in primary ESCC and normal esophagus. Herein, we found that hypoxia promoted ESCC radioresistance through increased KDM3A/KDM6B expression, enhancing cell survival and migration and decreasing DNA damage and apoptosis, in vitro. Exposure to IOX1 reverted these features, increasing ESCC radiosensitivity and decreasing ESCC microtumors size, in vivo. KDM3A was upregulated in ESCC tissues compared to the normal esophagus, associating and colocalizing with hypoxic markers (HIF-1α and CAIX). Therefore, KDM3A upregulation in ESCC cell lines and primary tumors associated with hypoxia, playing a critical role in EC aggressiveness and radioresistance. KDM3A targeting, concomitant with conventional RT, constitutes a promising strategy to improve ESCC patients’ survival.Subject terms: Predictive markers, Cancer     

Synchrotron X-ray imaging via ultra-small-angle scattering: principles of quantitative analysis and application in studying bone integration to synthetic grafting materials

Optimized experimental conditions for extracting accurate information at subpixel length scales from analyzer-based X-ray imaging were obtained and applied to investigate bone regeneration by means of synthetic β-TCP grafting materials in a rat calvaria model. The results showed a 30% growth in the particulate size due to bone ongrowth/ingrowth within the critical size defect over a 1-month healing period.     

Incorporation and toxicity of 32P-orthophosphate and occurrence of polyphosphate in Entamoeba trophozoites

We explored the requirements of inorganic phosphate (Pi), the incorporation of 32P-orthophosphate (32Pi), and the occurrence of inorganic polyphosphate (polyP) in axenic Entamoeba cultures. Maximal population densities and growth rates of Entamoeba histolytica trophozoites were attained in complete TP-S-1 medium. As 32Pi concentration was increased in the medium, its own incorporation and the culture growth rate were progressively inhibited, especially in Pi-deficient medium. PolyP grains were found in the cytoplasm and occasionally in the nuclear membrane of E. histolytica-like, E. invadens, and E. moshkovskii trophozoites.