ALBERT

Beschreibung: The objective of this work was to study the effect of root and foliar application of two commercial products containing amino acids from plant and animal origin on iron (Fe) nutrition of tomato seedlings cultivated in two nutrient media: lime and normal nutrient solutions. In the foliar-application experiment, each product was sprayed with 0.5 and 0.7 mL L –1 2, 7, 12, and 17 d after transplanting. In the root application experiment, 0.1 and 0.2 mL L –1 of amino acids products were added to the nutrient solutions. In both experiments, untreated control plants were included as well. Foliar and root application of the product containing amino acids from animal origin caused severe plant-growth depression and nonpositive effects on Fe nutrition were found. In contrast, the application of the product from plant origin stimulated plant growth. Furthermore, significantly enhanced root and leaf Fe III -chelate reductase activity, chlorophyll concentration, leaf Fe concentration, and Fe II : Fe ratio were found in tomato seedlings treated with the product from plant origin, especially when the amino acids were directly applied to the roots. These effects were more evident in plants developed under lime-induced Fe deficiency. The positive results on Fe uptake may be related to the action of glutamic acid, the most abundant amino acid in the formulation of the product from plant origin.

Beschreibung: p18INK4c is a cyclin-dependent kinase (CDK) inhibitor that interferes with the Rb-kinase activity of CDK6/CDK4. Disruption of p18INK4c in mice impairs B-cell terminal differentiation and confers increased susceptibility to tumor development; however, alterations of p18INK4c in human tumors have rarely been described. We used a tissue-microarray approach to analyze p18INK4c expression in 316 Hodgkin lymphomas (HLs). Nearly half of the HL cases showed absence of p18INK4c protein expression by Reed-Sternberg (RS) cells, in contrast with the regular expression of p18INK4c in normal germinal center cells. To investigate the cause of p18INK4c repression in RS cells, the methylation status of the p18INK4c promoter was analyzed by methylation-specific polymerase chain reaction (PCR) and bisulfite sequencing. Hypermethylation of the p18INK4c promoter was detected in 2 of 4 HL-derived cell lines, but in none of 7 non-Hodgkin lymphoma (NHL)–derived cell lines. We also detected p18INK4c hypermethylation, associated with absence of protein expression, in 5 of 26 HL tumors. The correlation of p18INK4c immunostaining with the follow-up of the patients showed shorter overall survival in negative cases, independent of the International Prognostic Score. These findings suggest that p18INK4c may function as a tumor suppressor gene in HL, and its inactivation may contribute to the cell cycle deregulation and defective terminal differentiation characteristic of the RS cells.

Beschreibung: Abstract 4942 INTRODUCTION. Patients with Mantle cell lymphoma (MCL) have an adverse outcome after relapse due to chemorefractory disease with conventional treatments. Bendamustine, a nitrogen mustard compound chemically related to the alkylating agents, has demonstrated high efficacy with a low toxicity profile in reported clinical trials. AIM. To analyze the Spanish experience in patients with relapsed/refractory MCL treated with Bendamustine. METHODS. Retrospective analysis of spanish experience in relapsed/refractory MCL treated with Bendamustine alone or in combination. This study has been approved by local ethical committees. RESULTS. Currently, there are 36 patients registered and 28 are available for this analysis. Patients'characteristics: 69% male, median age 65 years old (range 41–81), 87% ECOG≤ 1, 83% Ann Arbor stage IV, 37% high risk MIPI and 9% blastic variant. Previous regimens were CHOP or CHOP like ± R in 42.5%, HyperCVAD/MtxAraC ± R in 42.5%, R-CVP in 9% and other regimens in 6%. Median number of previous treatments were 2.6 (range 1–6), all patients had received prior Rituximab and 73% had chemosensitive disease to the last treatment. Bendamustine regimen was R-B (R-375mg/m2 D1, B-90 mg/m2 D1-2) in 78% patients, R-B with B-70 mg/m2 in 8%, B alone in 3%, R-B-Bortezomib in 3% and R-B plus consolidation (SCT, Y90Ibritumomab-tiuxetan) in 8%. Median number of cycles was 4.61 (range 1–7). G- CSF support was administered in 43% of cycles. Response: Overall response rate was 73%, with 43% CR & uCR and 30% PR. Survival: Median overall survival from diagnosis is 8,26 years (range: 1.6–11,6 years) without plateau. Median progression free survival (PFS) after Bendamustine treatment was 16 months (95% CI: 11.7–20.4), data that compares favourably with patients' PFS to previous therapy (12 months, 95% CI: 6.5–17.5). Median PFS for patients who achieved CR/uCR is 32.6 months (95% CI: 19.9–45.4) versus 11 months in patients with PR (95% CI: 3.9–18.8). With a median follow-up for surviving patients of 12 months since Bendamustine treatment, the estimated OS at 3 years is 47% (+ SD 14%). Toxicity: No treatment related mortality has been described so far. Over 152 cycles, only 10 hospitalizations due to febrile neutropenia were reported. No one case of lysis tumoral syndrome has been reported. CONCLUSION. Bendamustine plus Rituximab is a good rescue treatment in non selected pretreated patients with mantle cell lymphoma. CR rate and duration of response seem to reproduce in current clinical practice the good data reported in previous clinical trials and compares favourably with other available treatments. Disclosures: No relevant conflicts of interest to declare.

Beschreibung: The stem cell factor c-kit signaling pathway (SCF/c-kit) has been previously implicated in normal hematopoiesis, melanogenesis, and gametogenesis through the formation and migration of c-kit+ cells. These biologic functions are also determinants in epithelial–mesenchymal transitions during embryonic development governed by the Snail family of transcription factors. Here we show that the activation of c-kit by SCF specifically induces the expression of Slug, a Snail family member. Slug mutant mice have a cell-intrinsic defect with pigment deficiency, gonadal defect, and impairment of hematopoiesis. Kit+ cells derived from Slug mutant mice exhibit migratory defects similar to those of c-kit+ cells derived from SCF and c-kit mutant mice. Endogenous Slug is expressed in migratory c-kit+ cells purified from control mice but is not present in c-kit+cells derived from SCF mutant mice or in bone marrow cells from W/Wv mice, though Slug is present in spleen c-kit+ cells of W/Wv (mutants expressing c-kit with reduced surface expression and activity). SCF-induced migration was affected in primary c-kit+ cells purified from Slug−/− mice, providing evidence for a role of Slug in the acquisition of c-kit+ cells with ability to migrate. Slug may thus be considered a molecular target that contributes to the biologic specificity to the SCF/c-kit signaling pathway, opening up new avenues for stem cell mobilization.

Beschreibung: Monocytes are versatile cells that can express different functional programs in response to microenvironmental signals. We show that primary blood monocytes secrete the CXCL12 chemokine, and express the CXCR4 and CXCR7 receptors, leading to an autocrine/paracrine loop that contribute to shape monocyte differentiation to a distinct type of macrophages, with an enhanced expression of CD4, CD14, and CD163, or dendritic cells, with a reduced functional ability to stimulate antigen-specific T-lymphocyte responses. The in vivo relevance of CXCL12 production by mononuclear phagocytes was studied in metastatic melanoma tissues by a thoroughly immunofluorescence phenotyping of CXCL12high expressing cells, which were CD45+, coexpressed the macrophage antigens CD68, CD163, and CD209 and constituted the 60%-90% of tumor-associated macrophages. Microarray analysis of primary monocytes revealed that the vascular endothelial growth factor and the angiogenic chemokine CCL1 mRNA levels were up-regulated in response to CXCL12, leading to enhanced expression of both proteins. In addition, we found that CXCL12 autocrine/paracrine signaling down-regulates the expression of the transcription factor RUNX3 and contributes to maintain the long-term CD4 and CD14 expression in monocytes/macrophages. Together, these results suggest that autocrine CXCL12 production modulates differentiation of monocytes toward a distinct program with proangiogenic and immunosuppressive functions.

Beschreibung: Bacillus thuringiensis Cry3Aa toxin is a coleopteran specific toxin highly active against Colorado Potato Beetle (CPB).We have recently shown thatCry3Aa toxin is proteolytically cleaved by CPBmidgut membrane associated metalloproteases and that this cleavage is inhibited by ADAMmetalloprotease inhibitors. In the present study, we investigated whether the Cry3Aa toxin is a calmodulin (CaM) binding protein, as it is the case of several different ADAMshedding substrates. In pull-down assays using agarose beads conjugated with CaM, we demonstrated that Cry3Aa toxin specifically binds to CaMin a calcium-independent manner. Furthermore, we used gel shift assays and 1 H NMRspectra to demonstrate that CaMbinds to a 16-amino acid synthetic peptide corresponding to residues N256-V271 within the domain I of Cry3Aa toxin. Finally, to investigate whether CaM has any effect on Cry3Aa toxin CPBmidgut membrane associated proteolysis, cleavage assays were performed in the presence of the CaM-specific inhibitor trifluoperazine. We showed that trifluoperazine significantly increased Cry3Aa toxin proteolysis and also decreased Cry3Aa larval toxicity.

Beschreibung: Time series collected in the Camarinal and Espartel sills, the two main sills of the Strait of Gibraltar, have been analyzed to assess the first transformation of the Mediterranean outflow. In Espartel, west of Camarinal sill, the outflow has been estimated from a 6 year long time series of acoustic Doppler current profiler observations. The near bottom water flowing out at Espartel is around 0.1 units saltier and 0.1°C warmer than at Camarinal, which is explained by entrainment and mixing of Atlantic water by the outflow inside the basin bounded by both sills. The constancy of heat and salinity transport implies an Atlantic water entrainment of 0.03 Sv, which is about 4% of the outflow observed at Espartel (0.77 Sv) and a flow of 0.74 Sv at Camarinal (96% of the flow at Espartel). It is also shown that the high energy dissipation rate associated with internal tides is enough to sustain the entrainment and a thorough mixing of the entrained water.

Beschreibung: Aerosols play a significant yet complex and central role in the Earth´s radiation budget, and knowledge of long-term changes in the atmospheric turbidity induced by aerosols is therefore fundamental for a better understanding of climate change. However, there is little available information on changes in aerosol concentration in the atmosphere, especially prior to the 1980s. The present paper reviews publications reporting the suitability of sunshine duration records with regard to detecting changes in atmospheric aerosols. Some of the studies reviewed propose methods for estimating aerosol-related magnitudes, such as turbidity, from sunshine deficit at approximately sunrise and sunset, when the impact of aerosols on the solar beam is more easily observed. In addition, there is abundant evidence that one cause of the decadal changes observed in sunshine duration records involves variations in atmospheric aerosol loading. Possible directions for future research are also suggested: in particular, detailed studies of the burn (not only its length but also its width) registered by means of Campbell-Stokes sunshine recorders may provide a way of creating time series of atmospheric aerosol loading metrics dating back to over 120 years from the present.

Beschreibung: The aim of this study was to evaluate the biomass production potential for the Spanish Iberian Peninsula using the Populus spp. ‘I-214’ clone under several management regimes and land availability scenarios, and to determine its future contribution to Spanish energy demands. Empirical models were fitted to the data from a network of 144 plots located at 12 sites in the continental Mediterranean climatic regions of the Iberian Peninsula, in which yield was related to climate and soil, as well as to plantation management variables. Four models were developed considering average maximum temperature of the hottest month ( T MAXH , °C), length of drought ( A, months), intensity of drought ( K, unitless) and soil pH. Predictions were made for the irrigated agricultural land (IAL), where the value of the independent variables were within the validity range, and for two management scenarios. Energy production capacity was evaluated by considering the alternatives for transforming poplar SRC biomass: heat, bio-ethanol and electricity. The results indicated a mean productivity for the Spanish Iberian peninsula of between 15.3 and 10.9 Mg ha −1  yr −1 for the standard management scenario and the poorly irrigated and weeded management scenario respectively. Two IAL scenarios were considered for the calculation of biomass production potential: all IAL for which it was possible to make predictions is made available for poplar SRC (TP, maximum hypothetical production capacity), and another in which only unproductive IAL is available for poplar SRC (RP, production capacity without constricting agricultural production). The TP scenario contributes up to 6.8–9.6% of total energy demands, and the RP scenario 0.7–0.9%, depending on plantation management.