Seasonal characterization of the nutrients state in Oualidia Lagoon (Moroccan Atlantic coast)

The nutrient cycle in Oualidia lagoon, on the Atlantic Moroccan coast, was studied at both spatial and temporal scales, covering spring and summer conditions. Water samples were collected bimonthly at high tide from March to August during years 2011 and 2012 at six stations distributed throughout the lagoon. The physico- chemistry (temperature, salinity, dissolved O2) and nutrient enrichment of the lagoon surface water were monitored. The average nutrient concentration of surface water were 14.4 μmol.l-1 and 28.1 μmol.l-1 for NH4+, 20.4 μmol.l-1 and 19.9 μmol.l-1 for PO43- and 3.7 μmol.l-1 and 7.6 μmol.l-1 for NO2- in 2011 and 2012, respectively. Strong seasonal differences of nutrient distribution at the different stations were noticed. Temperature, salinity and dissolved O2 were correlated with nutrient concentrations, all parameters showing low spatial (inter-station) variability. Hydrological conditions exert a major control on the nutrient cycling in the lagoon. Results of this study are important to increase the richness on the scientific knowledge of nutrient dynamics along the Moroccan Atlantic coast, particularly in the semi-enclosed lagoons that are important transitional systems.Peer reviewe

Purinergic signalling and immune cells

This review article provides a historical perspective on the role of purinergic signalling in the regulation of various subsets of immune cells from early discoveries to current understanding. It is now recognised that adenosine 5'-triphosphate (ATP) and other nucleotides are released from cells following stress or injury. They can act on virtually all subsets of immune cells through a spectrum of P2X ligand-gated ion channels and G protein-coupled P2Y receptors. Furthermore, ATP is rapidly degraded into adenosine by ectonucleotidases such as CD39 and CD73, and adenosine exerts additional regulatory effects through its own receptors. The resulting effect ranges from stimulation to tolerance depending on the amount and time courses of nucleotides released, and the balance between ATP and adenosine. This review identifies the various receptors involved in the different subsets of immune cells and their effects on the function of these cells

Assessment of groundwater vulnerability to pollution of a wetland watershed : the case study of the Oualidia-Sidi Moussa wetland, Morocco

The susceptibility of wetlands to continental pollution is closely related to the vulnerability of their surface and sub-surface watersheds. Therefore, to help manage wetlands, especially those fed by groundwater, it can be useful to assess the vulnerability of their aquifers. This approach is illustrated by the case study of the wetland of Oualidia-Sidi Moussa. Firstly, the hydrogeological basin of the wetland was identified. Vulnerability mapping was then performed using the specific Susceptibility Index (SI) method. Results indicated that the natural protection against pollution of the watershed of the Oualidia-Sidi Moussa wetland was low, and that the system was indeed affected by anthropogenic pollution. Preservation of its ecological value requires urgent management actions

Adenosine receptor activation ameliorates type 1 diabetes

Growing evidence indicates that adenosine receptors could be promising therapeutic targets in autoimmune diseases. Here we studied the role of adenosine receptors in controlling the course of type 1 diabetes. Diabetes in CD-1 mice was induced by multiple-low-dose-streptozotocin (MLDS) treatment and in nonobese diabetic (NOD) mice by cyclophosphamide injection. The nonselective adenosine receptor agonist 5′-N-ethylcarboxamidoadenosine (NECA) prevented diabetes development in both MLDS-challenged mice and in cyclophosphamide-treated NOD mice. The effect of NECA was reversed by the selective A(2B) receptor antagonist N-(4-cyanophenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3-dipropyl-1H-purin-8-yl)phenoxy]acetamide (MRS 1754). The selective A(1) receptor agonist 2-chloro-N(6)-cyclopentyladenosine (CCPA) and A(3) receptor agonist N(6)-(3-iodobenzyl)-adenosine-5′-N-methyluronamide (IB-MECA) were less efficacious in ameliorating the course of diabetes. NECA inhibited diabetes in A(2A) receptor KO mice and the selective A(2A) receptor agonist 2-p-(2-carboxyethyl)phenethyl-amino-5′-N-ethyl-carboxamidoadenosine (CGS21680) had no effect in normal mice, indicating a lack of role of A(2A) receptors. NECA failed to prevent cytokine-induced β-cell death in vitro, but NECA strongly suppressed expression of the proinflammatory cytokines TNF-α, MIP-1α, IL-12, and IFN-γ in pancreata, endotoxin, or anti-CD3-stimulated splenic cells, and T helper 1 lymphocytes, indicating that the beneficial effect of NECA was due to immunomodulation. These results demonstrate that adenosine receptor ligands are potential candidates for the treatment of type 1 diabetes

Calcineurin-Inhibition Results in Upregulation of Local Renin and Subsequent Vascular Endothelial Growth Factor Production in Renal Collecting Ducts.

BACKGROUND: Tacrolimus (Tac) and Cyclosporine A (CyA) calcineurin inhibitors (CNIs) are 2 effective immunosuppressants which are essential to prevent allograft rejection. Calcineurin inhibitors are known to be nephrotoxic. However, the precise mechanism of nephrotoxicity is not fully understood. In this study, we investigated the in vivo effects of CNIs on the local renal renin-angiotensin system in the collecting duct (CD). METHODS: Three-week-old mice were treated with either vehicle, CyA (2 mg/kg per day), Tac (0.075 mg/kg per day), CyA + Aliskiren (25 mg/kg per day), or Tac + Aliskiren for 3 weeks. Serum creatinine was measured. Renin and vascular endothelial growth factor (VEGF) contents in CD were evaluated with flow cytometry and multiphoton microscopy. The diameter of vessels was assessed with multiphoton microscopy, and the amount of renal collagen was determined by real-time polymerase chain reaction and Masson staining. RESULTS: The elevated level of serum creatinine in CNI groups was abolished by Aliskiren. Flow cytometric analysis found elevated renin content in principal cells, which was prevented by Aliskiren. This result was further confirmed with multiphoton microscopy. The VEGF content in CD correlated with reduced capillary diameter and with the formation of fibrotic islands. CONCLUSIONS: Calcineurin inhibitors induce production of renin in the CD that may contribute to decreased renal blood flow. In turn, CD responds with increased VEGF production, resulting in disproportional vessel growth, further worsening the local hypoxia and striped fibrosis surrounding the CDs. Aliskiren, a direct renin inhibitor blocks these effects and improves CNI-induced nephropathy by decreasing renin production in the CDs. Our data suggest that Aliskiren may be used for the prevention of CNI nephrotoxicity

Comparative assessment of climate change and its impacts on three coastal aquifers in the Mediterranean

A comparative study on climate change and its impacts on coastal aquifers is performed for three Mediterranean areas. Common climate scenarios are developed for these areas using the ENSEMBLES projections that consider the A1b scenario. Temperature and precipitation data of three climate models are bias corrected with two different methods for a historic reference period, after which scenarios are created for 2020-2050 and 2069-2099 and used to calculate aquifer recharge for these periods based on two soil water budget methods. These multiple combinations of models and methods allow incorporating a level of uncertainty into the results. Groundwater flow models are developed for the three sites and then used to integrate future scenarios for three different parameters: (1) recharge, (2) crop water demand, and (3) sea level rise. Short-term predictions are marked by large ranges of predicted changes in recharge, only showing a consistent decrease at the Spanish site (mean 23 %), particularly due to a reduction in autumn rainfall. The latter is also expected to occur at the Portuguese site, resulting in a longer dry period. More frequent droughts are predicted at the Portuguese and Moroccan sites, but cannot be proven for the Spanish site. Toward the end of the century, results indicate a significant decrease (mean >25 %) in recharge in all areas, though most pronounced at the Portuguese site in absolute terms (mean 134 mm/year) and the Moroccan site in relative terms (mean 47 %). The models further predict a steady increase in crop water demand, causing 15-20 % additional evapotranspiration until 2100. Scenario modeling of groundwater flow shows its response to the predicted decreases in recharge and increases in pumping rates, with strongly reduced outflow into the coastal wetlands, whereas changes due to sea level rise are negligible

Adenosine A2A receptor activation protects CD4+ T lymphocytes against activation-induced cell death

Activation-induced cell death (AICD) is initiated by T-cell receptor (TCR) restimulation of already activated and expanded peripheral T cells and is mediated through Fas/Fas ligand (FasL) interactions. Adenosine is a purine nucleoside signaling molecule, and its immunomodulatory effects are mediated by 4 G-protein-coupled receptors: A1, A2A, A2B, and A3. In this study, we investigated the role of A2A receptors in regulating CD4+ T lymphocyte AICD. Our results showed that the selective A2A receptor agonist CGS21680 (EC50=15.2–32.6 nM) rescued mouse CD4+ hybridomas and human Jurkat cells from AICD and that this effect was reversed by the selective A2A receptor antagonist ZM241385 (EC50=2.3 nM). CGS21680 decreased phosphatidylserine exposure on the membrane, as well as the cleavage of caspase-3, caspase-8 and poly(ADP-ribose) polymerase indicating that A2A receptor stimulation blocks the extrinsic apoptotic pathway. In addition, CGS21680 attenuated both Fas and FasL mRNA expression. This decrease in FasL expression was associated with decreased activation of the transcription factor systems NF-κB, NF-ATp, early growth response (Egr)-1, and Egr-3. The antiapoptotic effect of A2A receptor stimulation was mediated by protein kinase A. Together, these results demonstrate that A2A receptor activation suppresses the AICD of peripheral T cells.—Himer, L., Csóka, B., Selmeczy, Z., Koscsó, B., Pócza, T., Pacher, P., Németh, Z. H., Deitch, E. A., Vizi, E. S., Cronstein, B. N., Haskó, G. Adenosine A2A receptor activation protects CD4+ T lymphocytes against activation-induced cell death

Comparative assessment of climate change and its impacts on three coastal aquifers in the Mediterranean

A comparative study on climate change and its impacts on coastal aquifers is performed for three Mediterranean areas. Common climate scenarios are developed for these areas using the ENSEMBLES projections that consider the A1b scenario. Temperature and precipitation data of three climate models are bias corrected with two different methods for a historic reference period, after which scenarios are created for 2020–2050 and 2069–2099 and used to calculate aquifer recharge for these periods based on two soil water budget methods. These multiple combinations of models and methods allow incorporating a level of uncertainty into the results. Groundwater flow models are developed for the three sites and then used to integrate future scenarios for three different parameters: (1) recharge, (2) crop water demand, and (3) sea level rise. Short-term predictions are marked by large ranges of predicted changes in recharge, only showing a consistent decrease at the Spanish site (mean 23 %), particularly due to a reduction in autumn rainfall. The latter is also expected to occur at the Portuguese site, resulting in a longer dry period. More frequent droughts are predicted at the Portuguese and Moroccan sites, but cannot be proven for the Spanish site. Toward the end of the century, results indicate a significant decrease (mean [25 %) in recharge in all areas, though most pronounced at the Portuguese site in absolute terms (mean 134 mm/year) and the Moroccan site in relative terms (mean 47 %). The models further predict a steady increase in crop water demand, causing 15–20 % additional evapotranspiration until 2100. Scenario modeling of groundwater flow shows its response to the predicted decreases in recharge and increases in pumping rates, with strongly reduced outflow into the coastal wetlands, whereas changes due to sea level rise are negligible

Development of highly selective casein kinase 1δ/1ε (CK1δ/ε) inhibitors with potent antiproliferative properties

The development of a series of potent and highly selective casein kinase 1δ/ε (CK1δ/ε) inhibitors is described. Starting from a purine scaffold inhibitor (SR-653234) identified by high throughput screening, we developed a series of potent and highly kinase selective inhibitors, including SR-2890 and SR-3029, which have IC(50) ≤ 50 nM versus CK1δ. The two lead compounds have ≤ 100 nM EC(50) values in MTT assays against the human A375 melanoma cell line and have physical, in vitro and in vivo PK properties suitable for use in proof of principle animal xenograft studies against human cancer cell lines