Nitrogen balance and fate in a heavily impacted watershed (Oglio River, Northern Italy): in quest of the missing sources and sinks

We present data from a comprehensive investigation carried out from 2007 to 2010, focussing on nitrogen pollution in the Oglio River basin (3800 km², Po Plain, Northern Italy). Nitrogen mass balances, computed for the whole basin with 2000 and 2008 data, suggest a large N surplus in this area, over 40 000 t N yr⁻¹, and increasing between 2000 and 2008. Calculations indicate a very large impact of animal husbandry and agricultural activities in this watershed, with livestock manure and synthetic fertilizers contributing 85% of total N inputs (about 100 000 t N yr⁻¹) and largely exceeding crop uptake and other N losses (about 60 000 t N yr⁻¹). Nitrogen from domestic and industrial origin is estimated as about 5800 and 7200 t N yr⁻¹, respectively, although these loads are overestimated, as denitrification in treatment plants is not considered; nonetheless, they represent a minor term of the N budget. Annual export of nitrogen from the basin, calculated from flow data and water chemistry at the mouth of the Oglio River, is estimated at 13 000 t N yr⁻¹, and represents a relatively small fraction of N inputs and surplus (∼12% and 34%, respectively). After considering N sinks in crop uptake, soil denitrification and volatilization, a large excess remains unaccounted (∼26 000 t N yr⁻¹) in unknown temporary or permanent N sinks. Nitrogen removal via denitrification was evaluated in the Oglio riverbed with stable isotope techniques (δ¹⁵N and δ¹⁸O in nitrate). The downstream final segment of the river displays an enriched nitrate stable isotope composition but calculations suggest a N removal corresponding to at most 20% of the unaccounted for N amount. Denitrification was also evaluated in riverine wetlands with the isotope pairing technique. Areal rates are elevated but overall N removal is low (about 1% of the missing N amount), due to small wetland surfaces and limited lateral connectivity. The secondary drainage channel network has a much higher potential for nitrogen removal via denitrification, due to its great linear development, estimated in over 12 500 km, and its capillary distribution in the watershed. In particular, we estimated a maximum N loss up to 8500 t N yr⁻¹, which represents up to 33% of the unaccounted for N amount in the basin. Overall, denitrification in surface aquatic habitats within this basin can be responsible for the permanent removal of about 12 000 t N yr⁻¹; but the fate of some 14 000 t remains unknown. Available data on nitrate concentration in wells suggest that in the central part of the watershed groundwater accumulates nitrogen. Simultaneously, we provide evidences that part of the stored nitrate can be substantially recycled via springs and can pollute surface waters via river-groundwater interactions. This probably explains the ten fold increase of nitrate concentration in a reach of the Oglio River where no point pollutions sources are present

Nitrogen balance and fate in a heavily impacted watershed (Oglio River, Northern Italy): in quest of the missing sources and sinks

Abstract. We present data from a comprehensive investigation carried out from 2007 to 2010, focussing on nitrogen pollution in the Oglio River basin (3800 km2, Po Plain, Northern Italy). Nitrogen mass balances, computed for the whole basin with 2000 and 2008 data, suggest a large N surplus in this area, over 40 000 t N yr−1, and increasing between 2000 and 2008. Calculations indicate a very large impact of animal husbandry and agricultural activities in this watershed, with livestock manure and synthetic fertilizers contributing 85% of total N inputs (about 100 000 t N yr−1) and largely exceeding crop uptake and other N losses (about 60 000 t N yr−1). Nitrogen from domestic and industrial origin is estimated as about 5800 and 7200 t N yr−1, respectively, although these loads are overestimated, as denitrification in treatment plants is not considered; nonetheless, they represent a minor term of the N budget. Annual export of nitrogen from the basin, calculated from flow data and water chemistry at the mouth of the Oglio River, is estimated at 13 000 t N yr−1, and represents a relatively small fraction of N inputs and surplus (∼12% and 34%, respectively). After considering N sinks in crop uptake, soil denitrification and volatilization, a large excess remains unaccounted (∼26 000 t N yr−1) in unknown temporary or permanent N sinks. Nitrogen removal via denitrification was evaluated in the Oglio riverbed with stable isotope techniques (δ15N and δ18O in nitrate). The downstream final segment of the river displays an enriched nitrate stable isotope composition but calculations suggest a N removal corresponding to at most 20% of the unaccounted for N amount. Denitrification was also evaluated in riverine wetlands with the isotope pairing technique. Areal rates are elevated but overall N removal is low (about 1% of the missing N amount), due to small wetland surfaces and limited lateral connectivity. The secondary drainage channel network has a much higher potential for nitrogen removal via denitrification, due to its great linear development, estimated in over 12 500 km, and its capillary distribution in the watershed. In particular, we estimated a maximum N loss up to 8500 t N yr−1, which represents up to 33% of the unaccounted for N amount in the basin. Overall, denitrification in surface aquatic habitats within this basin can be responsible for the permanent removal of about 12 000 t N yr−1; but the fate of some 14 000 t remains unknown. Available data on nitrate concentration in wells suggest that in the central part of the watershed groundwater accumulates nitrogen. Simultaneously, we provide evidences that part of the stored nitrate can be substantially recycled via springs and can pollute surface waters via river-groundwater interactions. This probably explains the ten fold increase of nitrate concentration in a reach of the Oglio River where no point pollutions sources are present

Wet deposition at the base of Mt Everest: Seasonal evolution of the chemistry and isotopic composition

The chemistry of wet deposition was investigated during 2012–2014 at the Pyramid International Laboratory in the Upper Khumbu Valley, Nepal, at 5050 m a.s.l., within the Global Atmosphere Watch (GAW) programme. The main hydro-chemical species and stable isotopes of the water molecule were determined for monsoon rain (July–September) and snow samples (October–June). To evaluate the synoptic-scale variability of air masses reaching the measurement site, 5 day back-trajectories were computed for the sampling period. Ion concentrations in precipitation during the monsoon were low suggesting that they represent global regional background concentrations. The associations between ions suggested that the principal sources of chemical species were marine aerosols, rock and soil dust, and fossil fuel combustion. Most chemical species exhibited a pattern during the monsoon, with maxima at the beginning and at the end of the season, partially correlated with the precipitation amount. Snow samples exhibited significantly higher concentrations of chemical species, compared to the monsoon rainfall observations. Particularly during 2013, elevated concentrations of NO3−, SO42− and NH4+ were measured in the first winter snow event, and in May at the end of the pre-monsoon season. The analysis of large-scale circulation and wind regimes as well as atmospheric composition observations in the region indicates the transport of polluted air masses from the Himalayan foothills and Indian sub-continent up to the Himalaya region. During the summer monsoon onset period, the greater values of pollutants can be attributed to air-mass transport from the planetary boundary layer (PBL) of the Indo-Gangetic plains. Isotopic data confirm that during the monsoon period, precipitation occurred from water vapor that originated from the Indian Ocean and the Bay of Bengal; by contrast during the non-monsoon period, an isotopic signature of more continental origin appeared, indicating that the higher recorded NO3− and SO42− concentrations could be ascribed to a change in air circulation patterns. A comparison of recent monsoon deposition chemistry with data from the 1990's shows similar levels of contaminants in the rainfall. However, non-monsoon deposition can be significant, as it largely contributed to the ion wet deposition fluxes for all analyzed species in 2013

CIS is a potent checkpoint in NK cell-mediated tumor immunity

The detection of aberrant cells by natural killer (NK) cells is controlled by the integration of signals from activating and inhibitory ligands and from cytokines such as IL-15. We identified cytokine-inducible SH2-containing protein (CIS, encoded by Cish) as a critical negative regulator of IL-15 signaling in NK cells. Cish was rapidly induced in response to IL-15, and deletion of Cish rendered NK cells hypersensitive to IL-15, as evidenced by enhanced proliferation, survival, IFN-γ production and cytotoxicity toward tumors. This was associated with increased JAK-STAT signaling in NK cells in which Cish was deleted. Correspondingly, CIS interacted with the tyrosine kinase JAK1, inhibiting its enzymatic activity and targeting JAK for proteasomal degradation. Cish -/- mice were resistant to melanoma, prostate and breast cancer metastasis in vivo, and this was intrinsic to NK cell activity. Our data uncover a potent intracellular checkpoint in NK cell-mediated tumor immunity and suggest possibilities for new cancer immunotherapies directed at blocking CIS function

Early expression of the fractalkine receptor CX3CR1 in pancreatic carcinogenesis

Background:In pancreatic ductal adenocarcinoma (PDAC), fractalkine receptor CX3CR1 contributes to perineural invasion (PNI). We investigated whether CX3CR1 expression occurs early in PDAC and correlates with tumour features other than PNI.Methods:We studied CX3CR1 and CX3CL1 expression by immunohistochemistry in 104 human PDAC and coexisting Pancreatic Intraepithelial Neoplasia (PanIN), and in PdxCre/LSL-KrasG12D mouse model of PDAC. CX3CR1 expression in vitro was studied by a spheroid model, and in vivo by syngenic mouse graft of tumour cells.Results:In total, 56 (53.9%) PDAC expressed CX3CR1, 70 (67.3%) CX3CL1, and 45 (43.3%) both. CX3CR1 expression was independently associated with tumour glandular differentiation (P=0.005) and PNI (P=0.01). Pancreatic Intraepithelial Neoplasias were more frequently CX3CR1+ (80.3%, P<0.001) and CX3CL1+ (86.8%, P=0.002) than matched cancers. The survival of PDAC patients was better in those with CX3CR1+ tumour (P=0.05). Mouse PanINs were also CX3CR1+ and -CL1+. In vitro, cytokines significantly increased CX3CL1 but not CX3CR1 expression. Differently, CX3CR1 was upregulated in tumour spheroids, and in vivo only in well-differentiated tumours.Conclusion:Tumour differentiation, rather than inflammatory signalling, modulates CX3CR1 expression in PanINs and PDAC. CX3CR1 expression pattern suggests its early involvement in PDAC progression, outlining a potential target for interfering with the PanIN transition to invasive cance

Design strategies to improve patient motivation during robot-aided rehabilitation

BACKGROUND: Motivation is an important factor in rehabilitation and frequently used as a determinant of rehabilitation outcome. Several factors can influence patient motivation and so improve exercise adherence. This paper presents the design of two robot devices for use in the rehabilitation of upper limb movements, that can motivate patients during the execution of the assigned motor tasks by enhancing the gaming aspects of rehabilitation. In addition, a regular review of the obtained performance can reinforce in patients' minds the importance of exercising and encourage them to continue, so improving their motivation and consequently adherence to the program. In view of this, we also developed an evaluation metric that could characterize the rate of improvement and quantify the changes in the obtained performance. METHODS: Two groups (G1, n = 8 and G2, n = 12) of patients with chronic stroke were enrolled in a 3-week rehabilitation program including standard physical therapy (45 min. daily) plus treatment by means of robot devices (40 min., twice daily) respectively for wrist (G1) and elbow-shoulder movements (G2). Both groups were evaluated by means of standard clinical assessment scales and the new robot measured evaluation metric. Patients' motivation was assessed in 9/12 G2 patients by means of the Intrinsic Motivation Inventory (IMI) questionnaire. RESULTS: Both groups reduced their motor deficit and showed a significant improvement in clinical scales and the robot measured parameters. The IMI assessed in G2 patients showed high scores for interest, usefulness and importance subscales and low values for tension and pain subscales. CONCLUSION: Thanks to the design features of the two robot devices the therapist could easily adapt training to the individual by selecting different difficulty levels of the motor task tailored to each patient's disability. The gaming aspects incorporated in the two rehabilitation robots helped maintain patients' interest high during execution of the assigned tasks by providing feedback on performance. The evaluation metric gave a precise measure of patients' performance and thus provides a tool to help therapists promote patient motivation and hence adherence to the training program

Bcl11b sets pro-T cell fate by site-specific cofactor recruitment and by repressing Id2 and Zbtb16

Multipotent progenitor cells confirm their T cell–lineage identity in the CD4^–CD8^– double-negative (DN) pro-T cell DN2 stages, when expression of the essential transcription factor Bcl11b begins. In vivo and in vitro stage-specific deletions globally identified Bcl11b-controlled target genes in pro-T cells. Proteomics analysis revealed that Bcl11b associated with multiple cofactors and that its direct action was needed to recruit those cofactors to selective target sites. Regions near functionally regulated target genes showed enrichment for those sites of Bcl11b-dependent recruitment of cofactors, and deletion of individual cofactors relieved the repression of many genes normally repressed by Bcl11b. Runx1 collaborated with Bcl11b most frequently for both activation and repression. In parallel, Bcl11b indirectly regulated a subset of target genes by a gene network circuit via the transcription inhibitor Id2 (encoded by Id2) and transcription factor PLZF (encoded by Zbtb16); Id2 and Zbtb16 were directly repressed by Bcl11b, and Id2 and PLZF controlled distinct alternative programs. Thus, our study defines the molecular basis of direct and indirect Bcl11b actions that promote T cell identity and block alternative potentials