458 research outputs found
Increased CO<sub>2</sub> loss from vegetated drained lake tundra ecosystems due to flooding
Tundra ecosystems are especially sensitive to climate change, which is particularly rapid in high northern latitudes resulting in significant alterations in temperature and soil moisture. Numerous studies have demonstrated that soil drying increases the respiration loss from wet Arctic tundra. And, warming and drying of tundra soils are assumed to increase CO2 emissions from the Arctic. However, in this water table manipulation experiment (i.e., flooding experiment), we show that flooding of wet tundra can also lead to increased CO2 loss. Standing water increased heat conduction into the soil, leading to higher soil temperature, deeper thaw and, surprisingly, to higher CO2 loss in the most anaerobic of the experimental areas. The study site is located in a drained lake basin, and the soils are characterized by wetter conditions than upland tundra. In experimentally flooded areas, high wind speeds (greater than ~4 m s−1) increased CO2 emission rates, sometimes overwhelming the photosynthetic uptake, even during daytime. This suggests that CO2 efflux from C rich soils and surface waters can be limited by surface exchange processes. The comparison of the CO2 and CH4 emission in an anaerobic soil incubation experiment showed that in this ecosystem, CO2 production is an order of magnitude higher than CH4 production. Future increases in surface water ponding, linked to surface subsidence and thermokarst erosion, and concomitant increases in soil warming, can increase net C efflux from these arctic ecosystems
Effects of etelcalcetide on fibroblast growth factor 23 in patients with secondary hyperparathyroidism receiving hemodialysis
Background:
Etelcalcetide is an intravenous calcimimetic approved for treatment of secondary hyperparathyroidism (sHPT) in patients receiving hemodialysis. Besides lowering parathyroid hormone (PTH), etelcalcetide also significantly reduces fibroblast growth factor 23 (FGF23), but the mechanisms are unknown.
Methods:
To investigate potential mediators of etelcalcetide-induced FGF23 reduction, we performed secondary analyses of the 26-week randomized trials that compared the effects on PTH of etelcalcetide (n = 509) versus placebo (n = 514) and etelcalcetide (n = 340) versus cinacalcet (n = 343) in adults with sHPT receiving hemodialysis. We analyzed changes in FGF23 in relation to changes in PTH, calcium, phosphate and bone turnover markers. We also investigated how concomitant treatments aimed at mitigating hypocalcemia altered the FGF23-lowering effects of etelcalcetide.
Results:
Etelcalcetide reduced FGF23 [median % change (quartile 1-quartile 3)] from baseline to the end of the trial significantly more than placebo [-56% (-85 to -7) versus +2% (-40 to +65); P < 0.001] and cinacalcet [-68% (-87 to -26) versus -41% (-76 to +25); P < 0.001]. Reductions in FGF23 correlated strongly with reductions in calcium and phosphate, but not with PTH; correlations with bone turnover markers were inconsistent and of borderline significance. Increases in concomitant vitamin D administration partially attenuated the FGF23-lowering effect of etelcalcetide, but increased dialysate calcium concentration versus no increase and increased dose of calcium supplementation versus no increase did not attenuate the FGF23-lowering effects of etelcalcetide.
Conclusion:
These data suggest that etelcalcetide potently lowers FGF23 in patients with sHPT receiving hemodialysis and that the effect remains detectable among patients who receive concomitant treatments aimed at mitigating treatment-associated decreases in serum calcium
Engineered Phage Endolysin Eliminates Gardnerella Biofilm without Damaging Beneficial Bacteria in Bacterial Vaginosis Ex Vivo.
Bacterial vaginosis is characterized by an imbalance of the vaginal microbiome and a characteristic biofilm formed on the vaginal epithelium, which is initiated and dominated by Gardnerella bacteria, and is frequently refractory to antibiotic treatment. We investigated endolysins of the type 1,4-beta-N-acetylmuramidase encoded on Gardnerella prophages as an alternative treatment. When recombinantly expressed, these proteins demonstrated strong bactericidal activity against four different Gardnerella species. By domain shuffling, we generated several engineered endolysins with 10-fold higher bactericidal activity than any wild-type enzyme. When tested against a panel of 20 Gardnerella strains, the most active endolysin, called PM-477, showed minimum inhibitory concentrations of 0.13-8 µg/mL. PM-477 had no effect on beneficial lactobacilli or other species of vaginal bacteria. Furthermore, the efficacy of PM-477 was tested by fluorescence in situ hybridization on vaginal samples of fifteen patients with either first time or recurring bacterial vaginosis. In thirteen cases, PM-477 killed the Gardnerella bacteria and physically dissolved the biofilms without affecting the remaining vaginal microbiome. The high selectivity and effectiveness in eliminating Gardnerella, both in cultures of isolated strains as well as in clinically derived samples of natural polymicrobial biofilms, makes PM-477 a promising alternative to antibiotics for the treatment of bacterial vaginosis, especially in patients with frequent recurrence
International Veterinary Epilepsy Task Force consensus report on epilepsy definition, classification and terminology in companion animals
Dogs with epilepsy are among the commonest neurological patients in veterinary practice and therefore have historically attracted much attention with regard to definitions, clinical approach and management. A number of classification proposals for canine epilepsy have been published during the years reflecting always in parts the current proposals coming from the human epilepsy organisation the International League Against Epilepsy (ILAE). It has however not been possible to gain agreed consensus, “a common language”, for the classification and terminology used between veterinary and human neurologists and neuroscientists, practitioners, neuropharmacologists and neuropathologists. This has led to an unfortunate situation where different veterinary publications and textbook chapters on epilepsy merely reflect individual author preferences with respect to terminology, which can be confusing to the readers and influence the definition and diagnosis of epilepsy in first line practice and research studies.
In this document the International Veterinary Epilepsy Task Force (IVETF) discusses current understanding of canine epilepsy and presents our 2015 proposal for terminology and classification of epilepsy and epileptic seizures. We propose a classification system which reflects new thoughts from the human ILAE but also roots in former well accepted terminology. We think that this classification system can be used by all stakeholders
Validation of a Chromosome 14 Risk Haplotype for Idiopathic Epilepsy in the Belgian Shepherd Dog Found to Be Associated with an Insertion in the RAPGEF5 Gene
An idiopathic epilepsy (IE) risk haplotype on canine chromosome (CFA) 14 has been reported to interact with the CFA37 common risk haplotype in the Belgian shepherd (BS). Additional IE cases and control dogs were genotyped for the risk haplotypes to validate these previous findings. In the new cohort, the interaction between the two regions significantly elevated IE risk. When the haplotypes were analyzed individually, particular haplotypes on both CFA14 (ACTG) and 37 (GG) were associated with elevated IE risk, though only the CFA37 AA was significantly associated (p < 0.003) with reduced risk in the new cohort. However, the CFA14 ACTG risk was statistically significant when the new and previous cohort data were combined. The frequency of the ACTG haplotype was four-fold higher in BS dogs than in other breeds. Whole genome sequence analysis revealed that a 3-base pair predicted disruptive insertion in the RAPGEF5 gene, which is adjacent to the CFA14 risk haplotype. RAPGEF5 is involved in the Wnt-β-catenin signaling pathway that is crucial for normal brain function. Although this risk variant does not fully predict the likelihood of a BS developing IE, the association with a variant in a candidate gene may provide insight into the genetic control of canine IE
Comparative analysis of photosynthetic light environments within the crowns of juvenile rain forest trees
Median total daily quantum flux densities for saplings of both species were less than 2% of full sun and did not differ significantly. More than 90% of the measurements within the crowns of these saplings were less than 25 pmol mm2 s-'. Spatial variability of photon flux densities within sapling crowns was similar for the two species despite differences in leaf display patterns. In saplings of both species, photon flux densities varied significantly over the relatively short distances within crowns and from day to day. Height growth of both species was significantly correlated with total daily photon flux densities and with percentage of full sun. However, only the tolerant species, Minquurtia, showed a significant correlation between diameter growth and crown light environment
Warming experiments elucidate the drivers of observed directional changes in tundra vegetation
Few studies have clearly linked long-term monitoring with insitu experiments to clarify potential drivers of observed change at a given site. This is especially necessary when findings from a site are applied to a much broader geographic area. Here, we document vegetation change at Barrow and Atqasuk, Alaska, occurring naturally and due to experimental warming over nearly two decades. An examination of plant cover, canopy height, and community indices showed more significant differences between years than due to experimental warming. However, changes with warming were more consistent than changes between years and were cumulative in many cases. Most cases of directional change observed in the control plots over time corresponded with a directional change in response to experimental warming. These included increases in canopy height and decreases in lichen cover. Experimental warming resulted in additional increases in evergreen shrub cover and decreases in diversity and bryophyte cover. This study suggests that the directional changes occurring at the sites are primarily due to warming and indicates that further changes are likely in the next two decades if the regional warming trend continues. These findings provide an example of the utility of coupling insitu experiments with long-term monitoring to accurately document vegetation change in response to global change and to identify the underlying mechanisms driving observed changes
A luciferase-based quick potency assay to predict chondrogenic differentiation.
Chondrogenic differentiation of adipose derived stem cells (ASC) is challenging but highly promising for cartilage repair. Large donor variability of chondrogenic differentiation potential raises the risk for transplantation of cells with reduced efficacy and a low chondrogenic potential. Therefore quick potency assays are required in order to control the potency of the isolated cells before cell transplantation. Current in vitro methods to analyze the differentiation potential are time consuming and thus, a novel enhancer and tissue-specific promoter combination was employed for the detection of chondrogenic differentiation of ASC in a novel quick potency bioassay. Human primary ASC were co-transfected with the Metridia luciferase based collagen type II reporter gene pCMVE_ACDCII-MetLuc together with a Renilla control plasmid and analyzed for their chondrogenic potential. On day 3 after chondrogenic induction, the luciferase activity was induced in all tested donors under three dimensional (3D) culture conditions and in a second approach also under 2D culture conditions. With our newly developed quick potency bioassay we can determine chondrogenic potential already after 3 days of chondrogenic induction and under 2D culture conditions. This will enhance the efficiency of testing cell functionality, which should allow in the future to predict the suitability of cells derived from individual patients for cell therapies, in a very short time and at low costs
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