Foliar nutrient resorption patterns of four functional plants along a precipitation gradient on the Tibetan Changtang Plateau

Nutrient resorption from senesced leaves as a nutrient conservation strategy is important for plants to adapt to nutrient deficiency, particularly in alpine and arid environment. However, the leaf nutrient resorption patterns of different functional plants across environmental gradient remain unclear. In this study, we conducted a transect survey of 12 communities to address foliar nitrogen (N) and phosphorus (P) resorption strategies of four functional groups along an eastward increasing precipitation gradient in northern Tibetan Changtang Plateau. Soil nutrient availability, leaf nutrient concentration, and N:P ratio in green leaves ([N:P]g) were linearly correlated with precipitation. Nitrogen resorption efficiency decreased, whereas phosphorus resorption efficiency except for sedge increased with increasing precipitation, indicating a greater nutrient conservation in nutrient-poor environment. The surveyed alpine plants except for legume had obviously higher N and P resorption efficiencies than the world mean levels. Legumes had higher N concentrations in green and senesced leaves, but lowest resorption efficiency than nonlegumes. Sedge species had much lower P concentration in senesced leaves but highest P resorption efficiency, suggesting highly competitive P conservation. Leaf nutrient resorption efficiencies of N and P were largely controlled by soil and plant nutrient, and indirectly regulated by precipitation. Nutrient resorption efficiencies were more determined by soil nutrient availability, while resorption proficiencies were more controlled by leaf nutrient and N:P of green leaves. Overall, our results suggest strong internal nutrient cycling through foliar nutrient resorption in the alpine nutrient-poor ecosystems on the Plateau. The patterns of soil nutrient availability and resorption also imply a transit from more N limitation in the west to a more P limitation in the east Changtang. Our findings offer insights into understanding nutrient conservation strategy in the precipitation and its derived soil nutrient availability gradient

Burkitt lymphoma beyond MYC translocation: N-MYC and DNA methyltransferases dysregulation

Background: The oncogenic transcription factor MYC is pathologically activated in many human malignancies. A paradigm for MYC dysregulation is offered by Burkitt lymphoma, where chromosomal translocations leading to Immunoglobulin gene-MYC fusion are the crucial initiating oncogenic events. However, Burkitt lymphoma cases with no detectable MYC rearrangement but maintaining MYC expression have been identified and alternative mechanisms can be involved in MYC dysregulation in these cases. Methods: We studied the microRNA profile of MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases in order to uncover possible differences at the molecular level. Data was validated at the mRNA and protein level by quantitative Real-Time polymerase chain reaction and immunohistochemistry, respectively. Results: We identified four microRNAs differentially expressed between the two groups. The impact of these microRNAs on the expression of selected genes was then investigated. Interestingly, in MYC translocation-negative cases we found over-expression of DNA-methyl transferase family members, consistent to hypo-expression of the hsa-miR-29 family. This finding suggests an alternative way for the activation of lymphomagenesis in these cases, based on global changes in methylation landscape, aberrant DNA hypermethylation, lack of epigenetic control on transcription of targeted genes, and increase of genomic instability. In addition, we observed an over-expression of another MYC family gene member, MYCN that may therefore represent a cooperating mechanism of MYC in driving the malignant transformation in those cases lacking an identifiable MYC translocation but expressing the gene at the mRNA and protein levels. Conclusions: Collectively, our results showed that MYC translocation-positive and MYC translocation-negative Burkitt lymphoma cases are slightly different in terms of microRNA and gene expression. MYC translocation-negative Burkitt lymphoma, similarly to other aggressive B-cell non Hodgkin's lymphomas, may represent a model to understand the intricate molecular pathway responsible for MYC dysregulation in cancer

Macrophage MerTK promotes profibrogenic cross-talk with hepatic stellate cells via soluble mediators

Background & Aims: Activation of Kupffer cells and recruitment of monocytes are key events in fibrogenesis. These cells release soluble mediators which induce the activation of hepatic stellate cells (HSCs), the main fibrogenic cell type within the liver. Mer tyrosine kinase (MerTK) signaling regulates multiple processes in macrophages and has been implicated in the pathogenesis of non-alcoholic steatohepatitis-related fibrosis. In this study, we explored if MerTK activation in macrophages influences the profibrogenic phenotype of HSCs. Methods: Macrophages were derived from THP-1 cells or differentiated from peripheral blood monocytes towards MerTK+/CD206+/CD163+/CD209- macrophages. The role of MerTK was assessed by pharmacologic and genetic inhibition. HSC migration was determined in Boyden chambers, viability was measured by the MTT assay, and proliferation was evaluated by the BrdU incorporation assay. Results: Gas-6 induced MerTK phosphorylation and Akt activation in macrophages, and these effects were inhibited by UNC569. During polarization, MerTK+/CD206+/CD163+/CD209- macrophages exhibited activation of STAT3, ERK1/2, p38 and increased expression of VEGF-A. Activation of MerTK in THP-1 macrophages induced a secretome which promoted a significant increase in migration, proliferation, viability and expression of profibrogenic factors in HSCs. Similarly, conditioned medium from MerTK+ macrophages induced a significant increase in cell migration, proliferation, STAT3 and p38 phosphorylation and upregulation of IL-8 expression in HSCs. Moreover, conditioned medium from Gas-6-stimulated Kupffer cells induced a significant increase in HSC proliferation. These effects were specifically related to MerTK expression and activity in macrophages, as indicated by pharmacologic inhibition and knockdown experiments. Conclusions: MerTK activation in macrophages modifies the secretome to promote profibrogenic features in HSCs, implicating this receptor in the pathogenesis of hepatic fibrosis. Lay summary: Fibrosis represents the process of scarring occurring in patients with chronic liver diseases. This process depends on production of scar tissue components by a specific cell type, named hepatic stellate cells, and is regulated by interaction with other cells. Herein, we show that activation of MerTK, a receptor present in a population of macrophages, causes the production of factors that act on hepatic stellate cells, increasing their ability to produce scar tissue

Virus-encoded microRNA contributes to the molecular profile of EBV-positive Burkitt lymphomas

Burkitt lymphoma (BL) is an aggressive neoplasm characterized by consistent morphology and phenotype, typical clinical behavior and distinctive molecular profile. The latter is mostly driven by the MYC over-expression associated with the characteristic translocation (8;14) (q24; q32) or with variant lesions. Additional genetic events can contribute to Burkitt Lymphoma pathobiology and retain clinical significance. A pathogenetic role for Epstein-Barr virus infection in Burkitt lymphomagenesis has been suggested; however, the exact function of the virus is largely unknown.In this study, we investigated the molecular profiles (genes and microRNAs) of Epstein-Barr virus-positive and -negative BL, to identify specific patterns relying on the differential expression and role of Epstein-Barr virus-encoded microRNAs.First, we found significant differences in the expression of viral microRNAs and in selected target genes. Among others, we identified LIN28B, CGNL1, GCET2, MRAS, PLCD4, SEL1L, SXX1, and the tyrosine kinases encoding STK10/STK33, all provided with potential pathogenetic significance. GCET2, also validated by immunohistochemistry, appeared to be a useful marker for distinguishing EBV-positive and EBV-negative cases. Further, we provided solid evidences that the EBV-encoded microRNAs (e.g. BART6) significantly mold the transcriptional landscape of Burkitt Lymphoma clones.In conclusion, our data indicated significant differences in the transcriptional profiles of EBV-positive and EBV-negative BL and highlight the role of virus encoded miRNA

Current position of 5HT3 antagonists and the additional value of NK1 antagonists; a new class of antiemetics

The advent of the 5HT3 receptor antagonists (5HT3 antagonists) in the 1990s and the combination with dexamethasone has resulted in acute emesis protection in 70% of patients receiving highly emetogenic chemotherapy. Despite complete protection in the acute phase, however, 40% of patients as yet have symptoms in the delayed phase, 5HT3 antagonists and dexamethasone are only modestly effective in this delayed phase. Moreover, the antiemetic protection over repeated cycles is not sustained. Neurokinine 1 receptor antagonists (NK1 antagonists) belong to a new class of antiemetic agents that specifically target the NK1 receptor, which is involved in both the acute and, particularly, the delayed phase of emesis. Clinical studies have demonstrated that the addition of NK1 antagonists to dual therapy with a 5HT3 antagonist plus dexamethasone improves the acute emesis protection by a further 10-15%. In the delayed phase, the proportion of patients remaining free of emesis increases by even 20-30%. Since the effectiveness of this triplet combination was found to be sustained over six cycles of chemotherapy, the chance for an individual patient to remain completely protected during both the acute and the delayed phase over six chemotherapy cycles is nearly doubled

Constitutive psgl-1 correlates with cd30 and tcr pathways and represents a potential target for immunotherapy in anaplastic large t-cell lymphoma

Due to the high expression of P-selectin glycoprotein ligand-1 (PSGL-1) in lymphoprolif-erative disorders and in multiple myeloma, it has been considered as a potential target for humoral immunotherapy, as well as an immune checkpoint inhibitor in T-cells. By investigating the expression of SELPLG in 678 T-and B-cell samples by gene expression profiling (GEP), further supported by tissue microarray and immunohistochemical analysis, we identified anaplastic large T-cell lymphoma (ALCL) as constitutively expressing SELPLG at high levels. Moreover, GEP analysis in CD30+ ALCLs highlighted a positive correlation of SELPLG with TNFRSF8 (CD30-coding gene) and T-cell receptor (TCR)-signaling genes (LCK, LAT, SYK and JUN), suggesting that the common dysreg-ulation of TCR expression in ALCLs may be bypassed by the involvement of PSGL-1 in T-cell activation and survival. Finally, we evaluated the effects elicited by in vitro treatment with two anti-PSGL-1 antibodies (KPL-1 and TB5) on the activation of the complement system and induction of apoptosis in human ALCL cell lines. In conclusion, our data demonstrated that PSGL-1 is specifically enriched in ALCLs, altering cell motility and viability due to its involvement in CD30 and TCR signaling, and it might be considered as a promising candidate for novel immunotherapeutic approaches in ALCLs

The Land surface Data Toolkit (LDT v7.2) – a data fusion environment for land data assimilation systems

The effective applications of land surface models (LSMs) and hydrologic models pose a varied set of data input and processing needs, ranging from ensuring consistency checks to more derived data processing and analytics. This article describes the development of the Land surface Data Toolkit (LDT), which is an integrated framework designed specifically for processing input data to execute LSMs and hydrological models. LDT not only serves as a preprocessor to the NASA Land Information System (LIS), which is an integrated framework designed for multi-model LSM simulations and data assimilation (DA) integrations, but also as a land-surface-based observation and DA input processor. It offers a variety of user options and inputs to processing datasets for use within LIS and stand-alone models. The LDT design facilitates the use of common data formats and conventions. LDT is also capable of processing LSM initial conditions and meteorological boundary conditions and ensuring data quality for inputs to LSMs and DA routines. The machine learning layer in LDT facilitates the use of modern data science algorithms for developing data-driven predictive models. Through the use of an object-oriented framework design, LDT provides extensible features for the continued development of support for different types of observational datasets and data analytics algorithms to aid land surface modeling and data assimilation.</p