Importance of Mobile Genetic Elements and Conjugal Gene Transfer for Subsurface Microbial Community Adaptation to Biotransformation of Metals

The overall goal of this project is to investigate the effect of mobile genetic elements and conjugal gene transfer on subsurface microbial community adaptation to mercury and chromium stress and biotransformation. Our studies focus on the interaction between the fate of these metals in the subsurface and the microbial community structure and activity

Adaptation of subsurface microbial communities to mercury

This report gives information about the Adaptation of subsurface microbial communities to mercury

Use of on-line flow cytometry for the characterization of physiological behavior in stress conditions during the bioprocess

Peer reviewe

Effects of Water Stress, Defoliation and Crop Thinning on Vitis vinifera L. cv. Solaris Must and Wine Part II: 1HNMR Metabolomics

Proton nuclear magnetic resonance (1H NMR) metabolomics was employed to investigate the impact of water deficit, defoliation, and crop thinning on the chemical composition of must and wines from the cool-climate white grape variety Solaris. The obtained results show that viticultural practices (defoliation and crop thinning) affected the amino acid and sugar content of Solaris must and thereby the quality of the final wine—mainly in terms of compounds normally related to fruity aroma (i.e., isopentanol), non-sugar sweetness (i.e., proline and glycerol), and alcohol content. The content of tyrosol, a natural phenolic antioxidant with a high bioavailability, was increased in the final wine by a combination of defoliation and crop thinning. The results of the metabolomics analysis performed on the must and wine samples from the water stress experiment showed that short-term water deficit significantly affected the concentration of several flavor-related compounds, including glutamate, butyrate and propanol, of the organic acids lactate and fumarate, and of the phenolic compounds caffeic acid and p-coumaric acid. ANOVA simultaneous component analysis showed that the effect of water deficit accounted for 11% (p < 0.001) and 8% (p < 0.001) of the variability in the metabolite concentrations in must and wines, respectively, while viticultural practices accounted for 38% (p < 0.001) and 30% (p < 0.001) of the metabolite variability in must and wines, respectivelyinfo:eu-repo/semantics/publishedVersio

Scandiatransplant acceptable mismatch program-10 years with an effective strategy for transplanting highly sensitized patients

In March 2009, the Scandiatransplant acceptable mismatch program (STAMP) was introduced as a strategy toward improving kidney allocation to highly sensitized patients. Patients with a transplantability scorePeer reviewe

Characterization of Microfibrillar-associated Protein 4 (MFAP4) as a Tropoelastin- and Fibrillin-binding Protein Involved in Elastic Fiber Formation

MFAP4 (microfibrillar-associated protein 4) is an extracellular glycoprotein found in elastic fibers without a clearly defined role in elastic fiber assembly. In the present study, we characterized molecular interactions between MFAP4 and elastic fiber components. We established that MFAP4 primarily assembles into trimeric and hexameric structures of homodimers. Binding analysis revealed that MFAP4 specifically binds tropoelastin and fibrillin-1 and -2, as well as the elastin cross-linking amino acid desmosine, and that it co-localizes with fibrillin-1-positive fibers in vivo. Site-directed mutagenesis disclosed residues Phe(241) and Ser(203) in MFAP4 as being crucial for type I collagen, elastin, and tropoelastin binding. Furthermore, we found that MFAP4 actively promotes tropoelastin self-assembly. In conclusion, our data identify MFAP4 as a new ligand of microfibrils and tropoelastin involved in proper elastic fiber organization

Relative and absolute cancer risks among Nordic kidney transplant recipients-a population-based study

Kidney transplant recipients (KTRs) have an increased cancer risk compared to the general population, but absolute risks that better reflect the clinical impact of cancer are seldom estimated. All KTRs in Sweden, Norway, Denmark, and Finland, with a first transplantation between 1995 and 2011, were identified through national registries. Post-transplantation cancer occurrence was assessed through linkage with cancer registries. We estimated standardized incidence ratios (SIR), absolute excess risks (AER), and cumulative incidence of cancer in the presence of competing risks. Overall, 12 984 KTRs developed 2215 cancers. The incidence rate of cancer overall was threefold increased (SIR 3.3, 95% confidence interval [CI]: 3.2-3.4). The AER of any cancer was 1560 cases (95% CI: 1468-1656) per 100 000 person-years. The highest AERs were observed for nonmelanoma skin cancer (838, 95% CI: 778-901), non-Hodgkin lymphoma (145, 95% CI: 119-174), lung cancer (126, 95% CI: 98.2-149), and kidney cancer (122, 95% CI: 98.0-149). The five- and ten-year cumulative incidence of any cancer was 8.1% (95% CI: 7.6-8.6%) and 16.8% (95% CI: 16.0-17.6%), respectively. Excess cancer risks were observed among Nordic KTRs for a wide range of cancers. Overall, 1 in 6 patients developed cancer within ten years, supporting extensive post-transplantation cancer vigilance.Peer reviewe

Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN) : a double-blind, randomised, placebo-controlled phase 2b trial

Background IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy. Methods We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries. We recruited patients aged at least 18 years with biopsy-confirmed primary IgA nephropathy and persistent proteinuria despite optimised renin-angiotensin system (RAS) blockade. We randomly allocated patients with a computer algorithm, with a fixed block size of three, in a 1:1:1 ratio to 16 mg/day TRF-budesonide, 8 mg/day TRF-budesonide, or placebo, stratified by baseline urine protein creatinine ratio (UPCR). Patients self-administered masked capsules, once daily, 1 h before breakfast during the treatment phase. All patients continued optimised RAS blockade treatment throughout the trial. Our primary outcome was mean change from baseline in UPCR for the 9-month treatment phase, which was assessed in the full analysis set, defined as all randomised patients who took at least one dose of trial medication and had at least one post-dose efficacy measurement. Safety was assessed in all patients who received the intervention. This trial is registered with ClinicalTrials.gov, number NCT01738035. Findings Between Dec 11, 2012, and June 25, 2015, 150 randomised patients were treated (safety set) and 149 patients were eligible for the full analysis set. Overall, at 9 months TRF-budesonide (16 mg/day plus 8 mg/day) was associated with a 24.4% (SEM 7.7%) decrease from baseline in mean UPCR (change in UPCR vs placebo 0.74; 95% CI 0.59-0.94; p=0.0066). At 9 months, mean UPCR had decreased by 27.3% in 48 patients who received 16 mg/day (0.71; 0.53-0.94; p=0.0092) and 21.5% in the 51 patients who received 8 mg/day (0.76; 0.58-1.01; p=0.0290); 50 patients who received placebo had an increase in mean UPCR of 2.7%. The effect was sustained throughout followup. Incidence of adverse events was similar in all groups (43 [88%] of 49 in the TRF-budesonide 16 mg/day group, 48 [94%] of 51 in the TRF-budesonide 8 mg/day, and 42 [84%] of 50 controls). Two of 13 serious adverse events were possibly associated with TRF-budesonide-deep vein thrombosis (16 mg/day) and unexplained deterioration in renal function in follow-up (patients were tapered from 16 mg/day to 8 mg/day over 2 weeks and follow-up was assessed 4 weeks later). Interpretation TRF-budesonide 16 mg/day, added to optimised RAS blockade, reduced proteinuria in patients with IgA nephropathy. This effect is indicative of a reduced risk of future progression to end-stage renal disease. TRF-budesonide could become the first specific treatment for IgA nephropathy targeting intestinal mucosal immunity upstream of disease manifestation.Peer reviewe