| 1. |
- Bisquert, Ricardo, et al.
(författare)
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The Role of the PAA1 Gene on Melatonin Biosynthesis in Saccharomyces cerevisiae: A Search of New Arylalkylamine N-Acetyltransferases
- 2023
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Ingår i: Microorganisms. - 2076-2607. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Recently, the presence of melatonin in fermented beverages has been correlated with yeast metabolism during alcoholic fermentation. Melatonin, originally considered a unique product of the pineal gland of vertebrates, has been also identified in a wide range of invertebrates, plants, bacteria, and fungi in the last two decades. These findings bring the challenge of studying the function of melatonin in yeasts and the mechanisms underlying its synthesis. However, the necessary information to improve the selection and production of this interesting molecule in fermented beverages is to disclose the genes involved in the metabolic pathway. So far, only one gene has been proposed as involved in melatonin production in Saccharomyces cerevisiae, PAA1, a polyamine acetyltransferase, a homolog of the vertebrate’s aralkylamine N-acetyltransferase (AANAT). In this study, we assessed the in vivo function of PAA1 by evaluating the bioconversion of the different possible substrates, such as 5-methoxytryptamine, tryptamine, and serotonin, using different protein expression platforms. Moreover, we expanded the search for new N-acetyltransferase candidates by combining a global transcriptome analysis and the use of powerful bioinformatic tools to predict similar domains to AANAT in S. cerevisiae. The AANAT activity of the candidate genes was validated by their overexpression in E. coli because, curiously, this system evidenced higher differences than the overexpression in their own host S. cerevisiae. Our results confirm that PAA1 possesses the ability to acetylate different aralkylamines, but AANAT activity does not seem to be the main acetylation activity. Moreover, we also prove that Paa1p is not the only enzyme with this AANAT activity. Our search of new genes detected HPA2 as a new arylalkylamine N-acetyltransferase in S. cerevisiae. This is the first report that clearly proves the involvement of this enzyme in AANAT activity.
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| 2. |
- Boström, Hanna L. B., et al.
(författare)
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How Reproducible is the Synthesis of Zr-Porphyrin Metal-Organic Frameworks? An Interlaboratory Study
- 2024
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Ingår i: Advanced Materials. - 0935-9648 .- 1521-4095. ; 36:15
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Tidskriftsartikel (refereegranskat)abstract
- Metal-organic frameworks (MOFs) are a rapidly growing class of materials that offer great promise in various applications. However, the synthesis remains challenging: for example, a range of crystal structures can often be accessed from the same building blocks, which complicates the phase selectivity. Likewise, the high sensitivity to slight changes in synthesis conditions may cause reproducibility issues. This is crucial, as it hampers the research and commercialization of affected MOFs. Here, it presents the first-ever interlaboratory study of the synthetic reproducibility of two Zr-porphyrin MOFs, PCN-222 and PCN-224, to investigate the scope of this problem. For PCN-222, only one sample out of ten was phase pure and of the correct symmetry, while for PCN-224, three are phase pure, although none of these show the spatial linker order characteristic of PCN-224. Instead, these samples resemble dPCN-224 (disordered PCN-224), which has recently been reported. The variability in thermal behavior, defect content, and surface area of the synthesised samples are also studied. The results have important ramifications for field of metal-organic frameworks and their crystallization, by highlighting the synthetic challenges associated with a multi-variable synthesis space and flat energy landscapes characteristic of MOFs. It performed an interlaboratory study of the synthesis of the metal-organic frameworks (MOFs) PCN-222 and PCN-224. Ten participants independently synthesized the two MOFs and the products are analyzed, primarily by X-ray diffraction. The success rates are low (one-three samples corresponding to a pure sample of the correct phase), thus highlighting the problems with irreproducibility in MOF synthesis. image
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| 3. |
- Jonkman, Nini H., et al.
(författare)
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Do self-management interventions work in patients with heart failure? An individual patient data meta-analysis
- 2016
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 133:12, s. 1189-1198
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: -Self-management interventions are widely implemented in care for patients with heart failure (HF). Trials however show inconsistent results and whether specific patient groups respond differently is unknown. This individual patient data meta-analysis assessed the effectiveness of self-management interventions in HF patients and whether subgroups of patients respond differently.METHODS AND RESULTS: -Systematic literature search identified randomized trials of self-management interventions. Data of twenty studies, representing 5624 patients, were included and analyzed using mixed effects models and Cox proportional-hazard models including interaction terms. Self-management interventions reduced risk of time to the combined endpoint HF-related hospitalization or all-cause death (hazard ratio [HR], 0.80; 95% confidence interval [CI], 0.71-0.89), time to HF-related hospitalization (HR, 0.80; 95%CI, 0.69-0.92), and improved 12-month HF-related quality of life (standardized mean difference 0.15; 95%CI, 0.00-0.30). Subgroup analysis revealed a protective effect of self-management on number of HF-related hospital days in patients <65 years (mean number of days 0.70 days vs. 5.35 days; interaction p=0.03). Patients without depression did not show an effect of self-management on survival (HR for all-cause mortality, 0.86; 95%CI, 0.69-1.06), while in patients with moderate/severe depression self-management reduced survival (HR, 1.39; 95%CI, 1.06-1.83, interaction p=0.01).CONCLUSIONS: -This study shows that self-management interventions had a beneficial effect on time to HF-related hospitalization or all-cause death, HF-related hospitalization alone, and elicited a small increase in HF-related quality of life. The findings do not endorse limiting self-management interventions to subgroups of HF patients, but increased mortality in depressed patients warrants caution in applying self-management strategies in these patients.
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| 4. |
- Jonkman, Nini H., et al.
(författare)
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What Are Effective Program Characteristics of Self-Management Interventions in Patients With Heart Failure? : An Individual Patient Data Meta-analysis
- 2016
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Ingår i: Journal of Cardiac Failure. - : Elsevier BV. - 1071-9164 .- 1532-8414. ; 22:11, s. 861-871
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Tidskriftsartikel (refereegranskat)abstract
- Background To identify those characteristics of self-management interventions in patients with heart failure (HF) that are effective in influencing health-related quality of life, mortality, and hospitalizations.Methods and Results Randomized trials on self-management interventions conducted between January 1985 and June 2013 were identified and individual patient data were requested for meta-analysis. Generalized mixed effects models and Cox proportional hazard models including frailty terms were used to assess the relation between characteristics of interventions and health-related outcomes. Twenty randomized trials (5624 patients) were included. Longer intervention duration reduced mortality risk (hazard ratio 0.99, 95% confidence interval [CI] 0.97–0.999 per month increase in duration), risk of HF-related hospitalization (hazard ratio 0.98, 95% CI 0.96–0.99), and HF-related hospitalization at 6 months (risk ratio 0.96, 95% CI 0.92–0.995). Although results were not consistent across outcomes, interventions comprising standardized training of interventionists, peer contact, log keeping, or goal-setting skills appeared less effective than interventions without these characteristics.Conclusion No specific program characteristics were consistently associated with better effects of self-management interventions, but longer duration seemed to improve the effect of self-management interventions on several outcomes. Future research using factorial trial designs and process evaluations is needed to understand the working mechanism of specific program characteristics of self-management interventions in HF patients.
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| 5. |
- Queipo, Francisco Javier, et al.
(författare)
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Immunohistochemistry subtyping of urothelial carcinoma is feasible in the daily practice
- 2022
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Ingår i: Virchows Archiv. - : Springer Science and Business Media LLC. - 0945-6317 .- 1432-2307. ; 481:2, s. 191-200
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Tidskriftsartikel (refereegranskat)abstract
- The preferred treatment of choice in muscle-invasive bladder cancer (MIBC) is usually transurethral resection followed by cystectomy, with neoadjuvant chemotherapy being a second option. As the treatment is associated with relevant side effects, a great effort is being made to improve the selection of patients, with molecular subtyping being one of the main strategies. Our aim was to develop an immunohistochemical algorithm for subtyping MIBCs. After a literature review, we have developed a simple algorithm to subtype MIBCs based on their morphology and three common antibodies: GATA3, CK5/6, and p16. We applied it to 113 muscle-invasive carcinomas. The positivity threshold for GATA3 and CK5/6 was 20% with at least moderate intensity, while p16 was 70% with moderate to intense nuclear and cytoplasmic staining. Cases GATA3 + CK5/6 − were considered luminal, while cases GATA3 − CK5/6 + were classified as nonluminal/basal squamous. Luminal p16 + cases were labeled as genomically unstable and luminal p16 − as Uro-like. Cases GATA3 + CK5/6 + with a predominantly basal pattern were labeled luminal, while diffuse cases were labeled nonluminal/basal squamous. All GATA3-CK5/6 − cases were considered nonluminal and were divided into mesenchymal-like or neuroendocrine, depending on the morphology. We were able to classify the 113 cases as: 82 (72.57%) were luminal, being 47 Uro-like (41.59%) and 35 (30.97%) genomically unstable; 31 (27.43%) were nonluminal, being 24 basal/squamous (21.24%), two (1.76%) mesenchymal-like, and five (4.42%) neuroendocrine like. We have achieved a feasible and cost-effective algorithm to subtype MIBCs from morphological features and the use of three common antibodies. Further studies in external cohorts are necessary to validate these results.
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| 6. |
- Taucher, Jan, et al.
(författare)
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Influence of ocean acidification and deep water upwelling on oligotrophic plankton communities in the subtropical North Atlantic : insights from an in situ mesocosm study
- 2017
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Ingår i: Frontiers in Marine Science. - : Frontiers Media S.A.. - 2296-7745. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Oceanic uptake of anthropogenic carbon dioxide (CO2) causes pronounced shifts in marine carbonate chemistry and a decrease in seawater pH. Increasing evidence indicates that these changes—summarized by the term ocean acidification (OA)—can significantly affect marine food webs and biogeochemical cycles. However, current scientific knowledge is largely based on laboratory experiments with single species and artificial boundary conditions, whereas studies of natural plankton communities are still relatively rare. Moreover, the few existing community-level studies were mostly conducted in rather eutrophic environments, while less attention has been paid to oligotrophic systems such as the subtropical ocean gyres. Here we report from a recent in situ mesocosm experiment off the coast of Gran Canaria in the eastern subtropical North Atlantic, where we investigated the influence of OA on the ecology and biogeochemistry of plankton communities in oligotrophic waters under close-to-natural conditions. This paper is the first in this Research Topic of Frontiers in Marine Biogeochemistry and provides (1) a detailed overview of the experimental design and important events during our mesocosm campaign, and (2) first insights into the ecological responses of plankton communities to simulated OA over the course of the 62-day experiment. One particular scientific objective of our mesocosm experiment was to investigate how OA impacts might differ between oligotrophic conditions and phases of high biological productivity, which regularly occur in response to upwelling of nutrient-rich deep water in the study region. Therefore, we specifically developed a deep water collection system that allowed us to obtain ~85 m3 of seawater from ~650 m depth. Thereby, we replaced ~20% of each mesocosm's volume with deep water and successfully simulated a deep water upwelling event that induced a pronounced plankton bloom. Our study revealed significant effects of OA on the entire food web, leading to a restructuring of plankton communities that emerged during the oligotrophic phase, and was further amplified during the bloom that developed in response to deep water addition. Such CO2-related shifts in plankton community composition could have consequences for ecosystem productivity, biomass transfer to higher trophic levels, and biogeochemical element cycling of oligotrophic ocean regions.
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| 7. |
- Wu, Yu-Tzu, et al.
(författare)
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Education and wealth inequalities in healthy ageing in eight harmonised cohorts in the ATHLOS consortium : a population-based study
- 2020
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Ingår i: The Lancet Public Health. - 2468-2667. ; 5:7, s. e386-e394
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The rapid growth of the size of the older population is having a substantial effect on health and social care services in many societies across the world. Maintaining health and functioning in older age is a key public health issue but few studies have examined factors associated with inequalities in trajectories of health and functioning across countries. The aim of this study was to investigate trajectories of healthy ageing in older men and women (aged ≥45 years) and the effect of education and wealth on these trajectories.METHODS: This population-based study is based on eight longitudinal cohorts from Australia, the USA, Japan, South Korea, Mexico, and Europe harmonised by the EU Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) consortium. We selected these studies from the repository of 17 ageing studies in the ATHLOS consortium because they reported at least three waves of collected data. We used multilevel modelling to investigate the effect of education and wealth on trajectories of healthy ageing scores, which incorporated 41 items of physical and cognitive functioning with a range between 0 (poor) and 100 (good), after adjustment for age, sex, and cohort study.FINDINGS: We used data from 141 214 participants, with a mean age of 62·9 years (SD 10·1) and an age range of 45-106 years, of whom 76 484 (54·2%) were women. The earliest year of baseline data was 1992 and the most recent last follow-up year was 2015. Education and wealth affected baseline scores of healthy ageing but had little effect on the rate of decrease in healthy ageing score thereafter. Compared with those with primary education or less, participants with tertiary education had higher baseline scores (adjusted difference in score of 10·54 points, 95% CI 10·31-10·77). The adjusted difference in healthy ageing score between lowest and highest quintiles of wealth was 8·98 points (95% CI 8·74-9·22). Among the eight cohorts, the strongest inequality gradient for both education and wealth was found in the Health Retirement Study from the USA.INTERPRETATION: The apparent difference in baseline healthy ageing scores between those with high versus low education levels and wealth suggests that cumulative disadvantage due to low education and wealth might have largely deteriorated health conditions in early life stages, leading to persistent differences throughout older age, but no further increase in ageing disparity after age 70 years. Future research should adopt a lifecourse approach to investigate mechanisms of health inequalities across education and wealth in different societies.FUNDING: European Union Horizon 2020 Research and Innovation Programme.
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| 8. |
- Wutke, Saskia, et al.
(författare)
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Spotted phenotypes in horses lost attractiveness in the Middle Ages
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Horses have been valued for their diversity of coat colour since prehistoric times; this is especially the case since their domestication in the Caspian steppe in ∼3,500 BC. Although we can assume that human preferences were not constant, we have only anecdotal information about how domestic horses were influenced by humans. Our results from genotype analyses show a significant increase in spotted coats in early domestic horses (Copper Age to Iron Age). In contrast, medieval horses carried significantly fewer alleles for these phenotypes, whereas solid phenotypes (i.e., chestnut) became dominant. This shift may have been supported because of (i) pleiotropic disadvantages, (ii) a reduced need to separate domestic horses from their wild counterparts, (iii) a lower religious prestige, or (iv) novel developments in weaponry. These scenarios may have acted alone or in combination. However, the dominance of chestnut is a remarkable feature of the medieval horse population.
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| 9. |
- Wutke, Saskia, et al.
(författare)
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The origin of ambling horses
- 2016
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Ingår i: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:15, s. 697-699
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Tidskriftsartikel (refereegranskat)abstract
- Horseback riding is the most fundamental use of domestic horses and has had a huge influence on the development of human societies for millennia. Over time, riding techniques and the style of riding improved. Therefore, horses with the ability to perform comfortable gaits (e.g. ambling or pacing), so-called ‘gaited’ horses, have been highly valued by humans, especially for long distance travel. Recently, the causative mutation for gaitedness in horses has been linked to a substitution causing a premature stop codon in the DMRT3 gene (DMRT3_Ser301STOP) [1]. In mice, Dmrt3 is expressed in spinal cord interneurons and plays an important role in the development of limb movement coordination [1]. Genotyping the position in 4396 modern horses from 141 breeds revealed that nowadays the mutated allele is distributed worldwide with an especially high frequency in gaited horses and breeds used for harness racing [2]. Here, we examine historic horse remains for the DMRT3 SNP, tracking the origin of gaitedness to Medieval England between 850 and 900 AD. The presence of the corresponding allele in Icelandic horses (9th–11th century) strongly suggests that ambling horses were brought from the British Isles to Iceland by Norse people. Considering the high frequency of the ambling allele in early Icelandic horses, we believe that Norse settlers selected for this comfortable mode of horse riding soon after arrival. The absence of the allele in samples from continental Europe (including Scandinavia) at this time implies that ambling horses may have spread from Iceland and maybe also the British Isles across the continent at a later date.
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