Reactive oxygen species (ROS) such as hydrogen peroxide and superoxide anions significantly accumulate during biotic and abiotic stress and cause oxidative damage and eventually cell death. There is ...accumulating evidence that ROS are also involved in regulating beneficial plant-microbe interactions, signal transduction and plant growth and development. Due to the relevance of ROS throughout the life cycle and for interaction with the multifactorial environment, the physiological phenotyping of the mechanisms controlling ROS homeostasis is of general importance.
In this study, we have developed a robust and resource-efficient experimental platform that allows the determination of the activities of the nine key ROS scavenging enzymes from a single extraction that integrates posttranscriptional and posttranslational regulations. The assays were optimized and adapted for a semi-high throughput 96-well assay format. In a case study, we have analyzed tobacco leaves challenged by pathogen infection, drought and salt stress. The three stress factors resulted in distinct activity signatures with differential temporal dynamics.
This experimental platform proved to be suitable to determine the antioxidant enzyme activity signature in different tissues of monocotyledonous and dicotyledonous model and crop plants. The universal enzymatic extraction procedure combined with the 96-well assay format demonstrated to be a simple, fast and semi-high throughput experimental platform for the precise and robust fingerprinting of nine key antioxidant enzymatic activities in plants.
The paper tests the pollution haven hypothesis in the context of three economies on the borders of the European Union in the Mediterranean Basin: Greece, Italy, and Turkey. Large differences in soft ...and hard aspects of green behaviour are revealed. Multinational firms are found to be more likely to use ‘soft talk’ strategies across the three economies. Yet the research also reveals that the multinationals are often more energy-intensive. Data for electricity consumption (where the largest regulatory differences exist across the EU border) show that there is a difference in the energy intensity of foreign and domestic firms in Turkey. At prices 45% lower than the unweighted EU average, the paper documents a 114% difference in electricity consumption by ownership. This difference in the difference between foreign and domestic firms' green behaviour across the three economies studied provides strong validation for the pollution haven hypothesis.
Pollution haven hypothesis, Green behaviour, Local and foreign firms, EU Internal Market regulations, Mediterranean Basin
Vitamin D has been hypothesized to reduce risk of pregnancy complications such as preeclampsia, gestational diabetes mellitus, and preterm delivery. However, many of these outcomes are rare and ...require a large sample size to study, representing a challenge for cohorts with a limited number of preserved samples. The aims of this study were to (1) identify predictors of serum 25-hydroxy-vitamin D (25(OH)D) among pregnant women in a subsample (N = 1494) of the Danish National Birth Cohort (DNBC) and (2) develop and validate a score predicting 25(OH)D-status in order to explore associations between vitamin D and maternal and offspring health outcomes in the DNBC. In our study sample, 42.3% of the population had deficient levels of vitamin D (<50 nmol/L 25(OH)D) and average levels of 25(OH)D-status were 56.7(s.d. 24.6) nmol/L. A prediction model consisting of intake of vitamin D from diet and supplements, outdoor physical activity, tanning bed use, smoking, and month of blood draw explained 40.1% of the variance in 25(OH)D and mean measured 25(OH)D-level increased linearly by decile of predicted 25(OH)D-score. In total 32.2% of the women were placed in the same quintile by both measured and predicted 25(OH)D-values and 69.9% were placed in the same or adjacent quintile by both methods. Cohen's weighted kappa coefficient (Κ = 0.3) reflected fair agreement between measured 25(OH)D-levels and predicted 25(OH)D-score. These results are comparable to other settings in which vitamin D scores have shown similar associations with disease outcomes as measured 25(OH)D-levels. Our findings suggest that predicted 25(OH)D-scores may be a useful alternative to measured 25(OH)D for examining associations between vitamin D and disease outcomes in the DNBC cohort, but cannot substitute for measured 25(OH)D-levels for estimates of prevalence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Continuous flow analysis (CFA) has become widely used for the measurement of aerosol-derived impurities in ice-core samples, resulting in high-resolution data sets of past aerosol deposition. Here, ...we present first results from coupling an inductively coupled plasma time-of-flight mass spectrometer (TOFMS) to a traditional CFA system. This setup enables the measurement of exactly coregistered elemental concentrations over the full mass range without degradation of sensitivity with an increasing number of analytes. The resulting total elemental concentration records have similar or better resolution than the established spectrophotometric methods. The unique capability of a TOFMS to measure fast transient signals and to still cover the full mass range furthermore enables the detection of the ionization of individual insoluble particles entering the plasma. The resulting mass spectra of the particles can be used to investigate the relative elemental composition of the mineral dust particles preserved in ice. The presented analysis of iron-bearing particles indicates that most of the particulate iron in Greenland ice is associated with Mg and Al and is likely part of clay minerals such as illite.
Evolutionary ecology often studies how environmental factors define optimal phenotypes without considering the bodily mechanisms involved in their regulation. Here we used a dynamic optimisation ...model to investigate optimally concerted hormonal control of the phenotype. We studied a semi‐realistic situation where hormonal control of appetite, metabolism and growth acts to prepare juvenile fish for an uncertain future with regard to food availability. We found a bottom–up effect in that hormone levels varied across environments and affected a range of phenotypic changes. We also describe a top–down effect as natural selection varied across environments, which affected evolutionary optimisation of hormone levels. These combined top–down and bottom–up effects produced a hormone‐regulated phenotype that adjusted its foraging intensity and risk‐taking in adaptive ways depending on the differences between current and expected long‐term environmental conditions. Hence, understanding the response of these fish to their current conditions also requires an understanding of their future expectations. We found that when food availability was low, it was optimal for the juvenile fish to have low growth hormone, thyroid hormone and orexin levels, contrary to when food availability was high when these levels were higher. Individual variation emerged from the individually experienced food availability trajectories: Those that on average experienced higher food availability grew faster and had higher short‐term mortality risk. They also had higher survival probability throughout the growth period. The opposite was true for individuals experiencing lower food availability. Hormonal mechanisms that often are overlooked by ecologists are thus important in the ultimate adaptive control of both behaviour and physiology, thereby impacting fitness through growth and survival.
The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn's disease (CD).
Using Danish national registries, this ...nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015-2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression.
Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.
When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 95% confidence interval: 1.57; 2.60) and CD patients (1.85 1.52; 2.24). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 0.29-0.89), and for CD patients, although not significantly (0.58 0.32-1.03). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics.
More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.
Key summary
Several biologic therapies are available in the treatment of ulcerative colitis and Crohn's disease.
Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.
Drug utilization studies comparing biologic therapies head-to-head are sparse.
In Denmark, during 2015-2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.
One in four patients experienced more than one biologic during the study period.
The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.
Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.
Abstract
Introduction
A family history of inflammatory bowel disease IBD is the strongest risk factor for disease. However, some first-degree relatives (FDRs) will develop disease, while others will ...not.
Methods
Using the nationwide Danish National Patient Register, we examined risk factors in families with two or more affected FDRs. First, we compared exposures between siblings with and without IBD within the same family within-family analysis. Second, we compared exposures between individuals with and without IBD across all families across-family analysis. Exposures included sex, birth order, mode of delivery, antibiotics, personal and family history of immune-mediated diseases, gastrointestinal infections, and surgical history preceding diagnosis. Uni- and multivariable conditional logistic regression analyses were conducted.
Results
In the ‘within-family analysis’, 1669 families were included 1732 cases, 2447 controls. Female sex (adjusted odds ratio aOR: 1.40, 95% confidence interval CI 1.23, 1.59), history of ankylosing spondylitis aOR: 2.88, 95% CI 1.05, 7.91 and exposure to antibiotics aOR: 1.28, 95% CI 1.02, 1.61 increased the risk for IBD. In the ‘across-family analysis’, 1254 cases and 37 584 controls were included, confirming an association with prior ankylosing spondylitis aOR: 3.92, 95% CI 1.38, 11.12 and exposure to antibiotics aOR: 1.29, 95% CI 1.04, 1.60. Having two or more relatives aOR: 6.26, 95% CI 1.34, 29.29 or a sibling with IBD aOR: 1.36, 95% CI 1.18, 1.57 increased the risk of IBD. Appendectomy reduced the risk of ulcerative colitis aOR: 0.32, 95% CI 0.14, 0.72.
Conclusion
In families with IBD, we identified risk factors for the unaffected FDR to develop disease. These findings provide an opportunity for counselling IBD relatives.
Background
Metformin has pleiotropic effects including anti-inflammatory properties and effects on the gut microbiome. It is primarily used in the older population, where the occurrence of ...inflammatory bowel disease (IBD) is increasing. The aim of this study was to examine whether metformin protects against development of IBD.
Methods
In the setting of a Danish nationwide population-based cohort, we conducted a nested case–control study using a new-user active comparator design. For each patient with IBD, we selected 10 IBD-free individuals matched on age, sex, and duration of follow-up. Conditional logistic regression was used to estimate odds ratios (ORs) of IBD. Adjustment included educational level, other immune-mediated inflammatory diseases, and use of dipeptidyl peptidase (DPP)-4 inhibitors and statins.
Results
Among 302,863 IBD-free new users of oral glucose-lowering drugs, we identified 1271 patients who developed IBD and 12,676 matched IBD-free individuals. Mean age at IBD diagnosis was 66 (SD, 11) years. We found no association between ever use of metformin and risk of IBD, Crohn’s disease or ulcerative colitis, adjusted OR 0.95 (95% CI 0.78–1.15), 0.87 (95% CI 0.60–1.26), and 1.04 (95% CI 0.83–1.31), respectively. Neither was the cumulative dose of metformin or the treatment duration with metformin associated with risk of IBD.
Conclusions
In this population-based study, we report that despite anti-inflammatory effects and a notable impact on the gut microbiome, metformin use is not associated with reduced risk of older onset IBD.
Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface clusters in the soma and proximal dendrites as ...well as in the axon initial segment (AIS). Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching imaging, mutagenesis, and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted and clustered localization in the AIS. These results indicate that neurons can regulate the expression and clustering of Kv2.1 in different membrane domains independently by using two distinct localization mechanisms, which would allow neurons to precisely control local membrane excitability.
Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including putative phosphorylation sites, that is important for the AIS localization. This raises the possibility that the destination of a channel protein can be dynamically regulated via changes in post-translational modification, which would impact the excitability of specific membrane compartments.
Background and Aims.
Lowering the blood concentration of low-density lipoprotein cholesterol (LDL-C), is a cornerstone in preventing atherosclerotic cardiovascular disease (ASCVD). Current European ...guidelines recommends LDL-C < 1.4 mmol/L for secondary prevention in high-risk patients. The aim of this study is to investigate monitoring and treatment of hypercholesterolemia one year after a ASCVD event.
Danish patients with hypercholesterolemia and an incident ASCVD event from 2015 to 2020 were included in this nationwide cohort study. Patients' LDL-C measurements and lipid-lowering treatment were followed for one year after ASCVD event, or until death or migration. Imputation was used to estimate absolute LDL-values when patients were unmeasured.
A total of 139,043 patients were included in the study with a mean follow-up time of 10.4 months. During the one-year period, 120,020 (86%) patients had their LDL-C measured at least once, 83,723 (60%) patients were measured at least twice. During the period one to six months after ASCVD event 25,999 (19%) achieved an LDL-C < 1.4 mmol/L, 93,349 (67%) failed to achieve an LDL-C < 1.4 mmol/L, and 196,950 (14%) had died or migrated. Missing LDL-C values were estimated via imputation. At the end of month twelve, 60,583 (44%) patients were in statin monotherapy, 2926 (2%) were treated with other lipid-lowering treatment, 42,869 (31%) were in no treatment, and 32,665 (23%) had died or migrated.
Many Danish patients are not appropriately followed-up with LDL-C measurements, and a substantial number of patients are not in lipid-lowering treatment one year after an ASCVD event.
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•One year after an atherosclerotic CVD event 14% of Danish patients does not have an LDL-C measurement.•Only 19% of Danish patients achieve an LDL-C under <1.4 mmol/L one to six months after an atherosclerotic CVD event.•One year after atherosclerotic CVD event 31% of Danes with hypercholesterolemia were not in any lipid lowering treatment.
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