Soluble tumor necrosis factor receptor 1 and 2 predict outcomes in advanced chronic kidney disease : a prospective cohort study

Background : Soluble tumor necrosis factor receptors 1 (sTNFR1) and 2 (sTNFR2) have been associated to progression of renal failure, end stage renal disease and mortality in early stages of chronic kidney disease (CKD), mostly in the context of diabetic nephropathy. The predictive value of these markers in advanced stages of CKD irrespective of the specific causes of kidney disease has not yet been defined. In this study, the relationship between sTNFR1 and sTNFR2 and the risk for adverse cardiovascular events (CVE) and all-cause mortality was investigated in a population with CKD stage 4-5, not yet on dialysis, to minimize the confounding by renal function. Patients and methods : In 131 patients, CKD stage 4-5, sTNFR1, sTNFR2 were analysed for their association to a composite endpoint of all-cause mortality or first non-fatal CVE by univariate and multivariate Cox proportional hazards models. In the multivariate models, age, gender, CRP, eGFR and significant comorbidities were included as covariates. Results : During a median follow-up of 33 months, 40 events (30.5%) occurred of which 29 deaths (22.1%) and 11 (8.4%) first non-fatal CVE. In univariate analysis, the hazard ratios (HR) of sTNFR1 and sTNFR2 for negative outcome were 1.49 (95% confidence interval (CI): 1.28-1.75) and 1.13 (95% CI: 1.06-1.20) respectively. After adjustment for clinical covariables (age, CRP, diabetes and a history of cardiovascular disease) both sTNFRs remained independently associated to outcomes (HR: sTNFR1: 1.51, 95% CI: 1.30-1.77; sTNFR2: 1.13, 95% CI: 1.06-1.20). A subanalysis of the non-diabetic patients in the study population confirmed these findings, especially for sTNFR1. Conclusion : sTNFR1 and sTNFR2 are independently associated to all-cause mortality or an increased risk for cardiovascular events in advanced CKD irrespective of the cause of kidney disease

Soy protein–gum karaya conjugate: emulsifying activity and rheological behavior in aqueous system and oil in water emulsion

The main objective of this study is to investigate the effects of mixing and conjugation of soy protein isolate (SPI) with gum karaya on the characteristics of the hybrid polymer (protein–gum) in both aqueous systems and oil-in-water (O/W) emulsions. It was hypothesized that the covalent linkage of gum karaya with SPI would improve the emulsifying activity and rheological properties of both polymers. Conjugation occurred under controlled conditions (i.e., 60 °C and 75 % relative humidity, 3 days). The conjugated hybrid polymer produced smaller droplet with better uniformity, higher viscosity and stronger emulsifying activity than native gum karaya, suggesting the conjugated polymer provided a bulkier secondary layer with more efficient coverage around oil droplets, thereby inducing stronger resistance against droplet aggregation and flocculation. Emulsions containing the native gum karaya produced the largest droplet size among all prepared emulsions (D 3,2 = 8.6 μm; D 4,3 = 22.4 μm); while the emulsion containing protein–gum conjugate (1:1 g/g) had the smallest droplet size (D 3,2 = 0.2 μm; D 4,3 = 0.7 μm) with lower polydispersity. The protein–gum conjugate (1:1 g/g) also showed the highest elastic and viscous modulus, the lowest polydispersity (span) and the highest emulsifying activity among all native, mixed and conjugated polymers. Therefore, the percentage of gum karaya used for production of O/W emulsion can be decreased by partially replacing it with the conjugated gum

Impact of pollen on throughfall biochemistry in European temperate and boreal forests

Pollen is known to affect forest throughfall biochemistry, but underlying mechanisms are not fully understood. We used generalized additive mixed modelling to study the relationship between long-term series of measured throughfall fluxes in spring (April–June) at forest plots and corresponding airborne pollen concentrations (Seasonal Pollen Integral, SPIn) from nearby aerobiological monitoring stations. The forest plots were part of the intensive long term monitoring (Level II) network of the UNECE International Co-operative Programme on Assessment and Monitoring of Air Pollution Effects on Forests (ICP Forests) with dominant tree genera Fagus, Quercus, Pinus and Picea, and were distributed all across Europe. We also conducted a 7-day laboratory dissolution experiment with bud scales and flower stalks of European beech (Fagus sylvatica L.), pollen of beech, common oak (Quercus robur L.), silver birch (Betula pendula L.), Scots pine (Pinus sylvestris L.), Corsican pine (Pinus nigra Arnold ssp. laricio (Poiret) Maire), Norway spruce (Picea abies (L.) Karst.) and sterilized pollen of silver birch in a nitrate (NO3--N) solution (11.3 mg N L-1). Throughfall fluxes of potassium (K+), ammonium (NH4+-N), dissolved organic carbon (DOC) and dissolved organic nitrogen (DON) showed a positive relationship with SPIn whereas NO3--N fluxes showed a negative relationship with SPIn. In years with massive seed production of beech and oak SPIn and throughfall fluxes of K+ and DOC were higher, but fluxes of NO3--N were lower. The experiment broadly confirmed the findings based on field data. Within two hours, pollen released large quantities of K+, phosphate, DOC and DON, and lesser amounts of sulphate, sodium and calcium. After 24-48 hours, NO3--N started to disappear, predominantly in the treatments with broadleaved pollen, while concentrations of nitrite and NH4+-N increased. At the end of the experiment, the inorganic nitrogen (DIN) was reduced, presumably because it was lost as gaseous nitric oxide (NO). There was no difference for sterilized pollen, indicating that the involvement of microbial activity was limited in above N transformations. Our results show that pollen dispersal might be an overlooked factor in forest nutrient cycling and might induce complex canopy N transformations, although the net-impact on N throughfall fluxes is rather lo

Mesoscale weather systems and associated potential wind power variations in a midlatitude sea strait (Kattegat)

Mesoscale weather systems cause spatiotemporal variability in offshore wind power, and insight into their fluctuations can support grid operations. In this study, a 10-year model integration with the kilometre-scale atmospheric model COnsortium for Small-scale MOdelling – CLimate Mode (COSMO-CLM) provided a wind and potential power fluctuation analysis in the Kattegat, a midlatitude sea strait with a width of 130 km and an irregular coastline. The model agrees well with scatterometer data away from coasts and small islands, with a spatiotemporal root-mean square difference of 1.35 m s−1. A comparison of 10 min wind speed at about 100 m with lidar data for a 2-year period reveals very good performance, with a slight model overestimation of 0.08 m s−1 and a high value for the Perkins skill score (0.97). From periodograms made using the Welch's method, it was found that the wind speed variability on a sub-hourly timescale is higher in winter compared to summer. In contrast, the wind power varies more in summer when winds often drop below the rated power threshold. During winter, variability is largest in the northeastern part of the Kattegat due to a spatial spin-up of convective systems over the sea during the predominant southwesterly winds. Summer convective systems are found to develop over land, driving spatial variability in offshore winds during this season. On average over the 10 summers, the mesoscale wind speeds are up to 20 % larger than the synoptic background at 17:00 UTC with a clear diurnal cycle. The winter-averaged mesoscale wind component is up to 10 % larger, with negligible daily variation. Products with a lower resolution like ERA5 substantially underestimate this ratio between the mesoscale and synoptic wind speed. Moreover, taking into account mesoscale spatial variability is important for correctly representing temporal variability in power production. The root-mean square difference between two power output time series, one ignoring and one accounting for mesoscale spatial variability, is 14 % of the total power generation.</p

Carbon-nitrogen interactions in European forests and semi-natural vegetation - Part 2: Untangling climatic, edaphic, management and nitrogen deposition effects on carbon sequestration potentials

The effects of atmospheric nitrogen deposition (N$_{dep}$) on carbon (C) sequestration in forests have often been assessed by relating differences in productivity to spatial variations of N$_{dep}$ across a large geographic domain. These correlations generally suffer from covariation of other confounding variables related to climate and other growth-limiting factors, as well as large uncertainties in total (dry+wet) reactive nitrogen (N$_{r}$) deposition.We propose a methodology for untangling the effects of N$_{dep}$ from those of meteorological variables, soil water retention capacity and stand age, using a mechanistic forest growth model in combination with eddy covariance CO$_{2}$ exchange fluxes from a Europe-wide network of 22 forest flux towers. Total N$_{r}$ deposition rates were estimated from local measurements as far as possible. The forest data were compared with data from natural or semi-natural, non-woody vegetation sites. The response of forest net ecosystem productivity to nitrogen deposition (dNEP= dN$_{dep}$) was estimated after accounting for the effects on gross primary productivity (GPP) of the co-correlates by means of a meta-modelling standardization procedure, which resulted in a reduction by a factor of about 2 of the uncorrected, apparent dGPP/dN$_{dep}$ value. This model-enhanced analysis of the C and N$_{dep}$ flux observations at the scale of the European network suggests a mean overall dNEP/dN$_{dep}$ response of forest lifetime C sequestration to N$_{dep}$ of the order of 40–50 g C per g N, which is slightly larger but not significantly different from the range of estimates published in the most recent reviews. Importantly, patterns of gross primary and net ecosystem productivity versus N$_{dep}$ were non-linear, with no further growth responses at high N$_{dep}$ levels (N$_{dep}$ >2.5–3 gNm$^{-2}$ yr$^{-1}$) but accompanied by increasingly large ecosystem N losses by leaching and gaseous emissions. The reduced increase in productivity per unit N deposited at high N$_{dep}$ levels implies that the forecast increased N$_{r}$ emissions and increased Ndep levels in large areas of Asia may not positively impact the continent’s forest CO$_{2}$ sink. The large level of unexplained variability in observed carbon sequestration efficiency (CSE) across sites further adds to the uncertainty in the dC/dN response

Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice

The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus.BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus.Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic

Sublingual Immunization with a Live Attenuated Influenza A Virus Lacking the Nonstructural Protein 1 Induces Broad Protective Immunity in Mice

The nonstructural protein 1 (NS1) of influenza A virus (IAV) enables the virus to disarm the host cell type 1 IFN defense system. Mutation or deletion of the NS1 gene leads to attenuation of the virus and enhances host antiviral response making such live-attenuated influenza viruses attractive vaccine candidates. Sublingual (SL) immunization with live influenza virus has been found to be safe and effective for inducing protective immune responses in mucosal and systemic compartments. Here we demonstrate that SL immunization with NS1 deleted IAV (DeltaNS1 H1N1 or DeltaNS1 H5N1) induced protection against challenge with homologous as well as heterosubtypic influenza viruses. Protection was comparable with that induced by intranasal (IN) immunization and was associated with high levels of virus-specific antibodies (Abs). SL immunization with DeltaNS1 virus induced broad Ab responses in mucosal and systemic compartments and stimulated immune cells in mucosa-associated and systemic lymphoid organs. Thus, SL immunization with DeltaNS1 offers a novel potential vaccination strategy for the control of influenza outbreaks including pandemics

Potent Neutralization of Influenza A Virus by a Single-Domain Antibody Blocking M2 Ion Channel Protein

Influenza A virus poses serious health threat to humans. Neutralizing antibodies against the highly conserved M2 ion channel is thought to offer broad protection against influenza A viruses. Here, we screened synthetic Camel single-domain antibody (VHH) libraries against native M2 ion channel protein. One of the isolated VHHs, M2-7A, specifically bound to M2-expressed cell membrane as well as influenza A virion, inhibited replication of both amantadine-sensitive and resistant influenza A viruses in vitro, and protected mice from a lethal influenza virus challenge. Moreover, M2-7A showed blocking activity for proton influx through M2 ion channel. These pieces of evidence collectively demonstrate for the first time that a neutralizing antibody against M2 with broad specificity is achievable, and M2-7A may have potential for cross protection against a number of variants and subtypes of influenza A viruses