| 1. |
- Abadpour, Shadab, et al.
(författare)
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Glial cell-line derived neurotrophic factor protects human islets from nutrient deprivation and endoplasmic reticulum stress induced apoptosis
- 2017
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- One of the key limitations to successful human islet transplantation is loss of islets due to stress responses pre- and post-transplantation. Nutrient deprivation and ER stress have been identified as important mechanisms leading to apoptosis. Glial Cell-line Derived Neurotrophic Factor (GDNF) has recently been found to promote islet survival after isolation. However, whether GDNF could rescue human islets from nutrient deprivation and ER stress-mediated apoptosis is unknown. Herein, by mimicking those conditions in vitro, we have shown that GDNF significantly improved glucose stimulated insulin secretion, reduced apoptosis and proinsulin: insulin ratio in nutrient deprived human islets. Furthermore, GDNF alleviated thapsigargin-induced ER stress evidenced by reduced expressions of IRE1 alpha and BiP and consequently apoptosis. Importantly, this was associated with an increase in phosphorylation of PI3K/AKT and GSK3B signaling pathway. Transplantation of ER stressed human islets pre- treated with GDNF under kidney capsule of diabetic mice resulted in reduced expressions of IRE1 alpha and BiP in human islet grafts with improved grafts function shown by higher levels of human C-peptide post-transplantation. We suggest that GDNF has protective and anti-apoptotic effects on nutrient deprived and ER stress activated human islets and could play a significant role in rescuing human islets from stress responses.
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| 2. |
- Abreu, Murilo S., et al.
(författare)
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Monoaminergic levels at the forebrain and diencephalon signal for the occurrence of mutualistic and conspecific engagement in client reef fish
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Social interactions are commonly found among fish as in mammals and birds. While most animals interact socially with conspecifics some however are also frequently and repeatedly observed to interact with other species (i.e. mutualistic interactions). This is the case of the (so-called) fish clients that seek to be cleaned by other fish (the cleaners). Clients face an interesting challenge: they raise enough motivation to suspend their daily activities as to selectively visit and engage in interactions with cleaners. Here we aimed, for the first time, to investigate the region-specific brain monoaminergic level differences arising from individual client fish when facing a cleaner (interspecific context) compared to those introduced to another conspecific (socio-conspecific context). We show that monoaminergic activity differences occurring at two main brain regions, the diencephalon and the forebrain, are associated with fish clients' social and mutualistic activities. Our results are the first demonstration that monoaminergic mechanisms underlie client fish mutualistic engagement with cleanerfish. These pathways should function as a pre-requisite for cleaning to occur, providing to clients the cognitive and physiological tools to seek to be cleaned.
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| 3. |
- Abu Hamdeh, Sami, et al.
(författare)
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Proteomic differences between focal and diffuse traumatic brain injury in human brain tissue
- 2018
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- The early molecular response to severe traumatic brain injury (TBI) was evaluated using biopsies of structurally normal-appearing cortex, obtained at location for intracranial pressure (ICP) monitoring, from 16 severe TBI patients. Mass spectrometry (MS; label free and stable isotope dimethyl labeling) quantitation proteomics showed a strikingly different molecular pattern in TBI in comparison to cortical biopsies from 11 idiopathic normal pressure hydrocephalus patients. Diffuse TBI showed increased expression of peptides related to neurodegeneration (Tau and Fascin, p < 0.05), reduced expression related to antioxidant defense (Glutathione S-transferase Mu 3, Peroxiredoxin-6, Thioredoxin-dependent peroxide reductase; p < 0.05) and increased expression of potential biomarkers (e.g. Neurogranin, Fatty acid-binding protein, heart p < 0.05) compared to focal TBI. Proteomics of human brain biopsies displayed considerable molecular heterogeneity among the different TBI subtypes with consequences for the pathophysiology and development of targeted treatments for TBI.
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| 4. |
- Accordini, Simone, et al.
(författare)
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Incidence trends of airflow obstruction among European adults without asthma : a 20-year cohort study
- 2020
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Investigating COPD trends may help healthcare providers to forecast future disease burden. We estimated sex- and smoking-specific incidence trends of pre-bronchodilator airflow obstruction (AO) among adults without asthma from 11 European countries within a 20-year follow-up (ECRHS and SAPALDIA cohorts). We also quantified the extent of misclassification in the definition based on pre-bronchodilator spirometry (using post-bronchodilator measurements from a subsample of subjects) and we used this information to estimate the incidence of post-bronchodilator AO (AO(post-BD)), which is the primary characteristic of COPD. AO incidence was 4.4 (95% CI: 3.5-5.3) male and 3.8 (3.1-4.6) female cases/1,000/year. Among ever smokers (median pack-years: 20, males; 12, females), AO incidence significantly increased with ageing in men only [incidence rate ratio (IRR), 1-year increase: 1.05 (1.03-1.07)]. A strong exposure-response relationship with smoking was found both in males [IRR, 1-pack-year increase: 1.03 (1.02-1.04)] and females [1.03 (1.02-1.05)]. The positive predictive value of AO for AO(post-BD) was 59.1% (52.0-66.2%) in men and 42.6% (35.1-50.1%) in women. AO(post-BD) incidence was 2.6 (1.7-3.4) male and 1.6 (1.0-2.2) female cases/1,000/year. AO incidence was considerable in Europe and the sex-specific ageing-related increase among ever smokers was strongly related to cumulative tobacco exposure. AO(post-BD) incidence is expected to be half of AO incidence.
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| 5. |
- Adamik, Peter, et al.
(författare)
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Barrier crossing in small avian migrants : individual tracking reveals prolonged nocturnal flights into the day as a common migratory strategy
- 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
- Over decades it has been unclear how individual migratory songbirds cross large ecological barriers such as seas or deserts. By deploying light-level geolocators on four songbird species weighing only about 12 g, we found that these otherwise mainly nocturnal migrants seem to regularly extend their nocturnal flights into the day when crossing the Sahara Desert and the Mediterranean Sea. The proportion of the proposed diurnally flying birds gradually declined over the day with similar landing patterns in autumn and spring. The prolonged flights were slightly more frequent in spring than in autumn, suggesting tighter migratory schedules when returning to breeding sites. Often we found several patterns for barrier crossing for the same individual in autumn compared to the spring journey. As only a small proportion of the birds flew strictly during the night and even some individuals might have flown non-stop, we suggest that prolonged endurance flights are not an exception even in small migratory species. We emphasise an individual’s ability to perform both diurnal and nocturnal migration when facing the challenge of crossing a large ecological barrier to successfully complete a migratory journey.
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| 6. |
- Agić, Heda, 1989-, et al.
(författare)
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Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic. Cyathinema digermulense gen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration. C. digermulense shares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity, C. digermulense was a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstatten.
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| 7. |
- Ahi, Ehsan Pashay, et al.
(författare)
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Gene expression profiling suggests differences in molecular mechanisms of fin elongation between cichlid species
- 2019
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Comparative analyses of gene regulation inform about the molecular basis of phenotypic trait evolution. Here, we address a fin shape phenotype that evolved multiple times independently across teleost fish, including several species within the family Cichlidae. In a previous study, we proposed a gene regulatory network (GRN) involved in the formation and regeneration of conspicuous filamentous elongations adorning the unpaired fins of the Neolamprologus brichardi. Here, we tested the members of this network in the blockhead cichlid, Steatocranus casuarius, which displays conspicuously elongated dorsal and moderately elongated anal fins. Our study provided evidence for differences in the anatomy of fin elongation and suggested gene regulatory divergence between the two cichlid species. Only a subset of the 20 genes tested in S. casuarius showed the qPCR expression patterns predicted from the GRN identified in N. brichardi, and several of the gene-by-gene expression correlations differed between the two cichlid species. In comparison to N. brichardi, gene expression patterns in S. casuarius were in better (but not full) agreement with gene regulatory interactions inferred in zebrafish. Within S. casuarius, the dorsoventral asymmetry in ornament expression was accompanied by differences in gene expression patterns, including potential regulatory differentiation, between the anal and dorsal fin.
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| 8. |
- Ahi, Ehsan Pashay, et al.
(författare)
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Transcriptional study of appetite regulating genes in the brain of zebrafish (Danio rerio) with impaired leptin signalling
- 2019
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The hormone leptin is a key regulator of body weight, food intake and metabolism. In mammals, leptin acts as an anorexigen and inhibits food intake centrally by affecting the appetite centres in the hypothalamus. In teleost fish, the regulatory connections between leptin and other appetite-regulating genes are largely unknown. In the present study, we used a zebrafish mutant with a loss of function leptin receptor to investigate brain expression patterns of 12 orexigenic and 24 anorexigenic genes under different feeding conditions (normal feeding, 7-day fasting, 2 and 6-hours refeeding). Expression patterns were compared to wild-type zebrafish, in order to identify leptin-dependent differentially expressed genes under different feeding conditions. We provide evidence that the transcription of certain orexigenic and anorexigenic genes is influenced by leptin signalling in the zebrafish brain. We found that the expression of orexigenic genes was not affected by impaired leptin signalling under normal feeding conditions; however, several orexigenic genes showed increased transcription during fasting and refeeding, including agrp, apln, galr1a and cnr1. This suggests an inhibitory effect of leptin signal on the transcription of these orexigenic genes during short-term fasting and refeeding in functional zebrafish. Most pronounced effects were observed in the group of anorexigenic genes, where the impairment of leptin signalling resulted in reduced gene expression in several genes, including cart family, crhb, gnrh2, mc4r, pomc and spx, in the control group. This suggests a stimulatory effect of leptin signal on the transcription of these anorexigenic genes under normal feeding condition. In addition, we found multiple gain and loss in expression correlations between the appetite-regulating genes, in zebrafish with impaired leptin signal, suggesting the presence of gene regulatory networks downstream of leptin signal in zebrafish brain. The results provide the first evidence for the effects of leptin signal on the transcription of various appetite-regulating genes in zebrafish brain, under different feeding conditions. Altogether, these transcriptional changes suggest an anorexigenic role for leptin signal, which is likely to be mediated through distinct set of appetite-regulating genes under different feeding conditions.
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| 9. |
- Ahlstrom, Christina A., et al.
(författare)
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Acquisition and dissemination of cephalosporin-resistant E.coli in migratory birds sampled at an Alaska landfill as inferred through genomic analysis
- 2018
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Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Antimicrobial resistance (AMR) in bacterial pathogens threatens global health, though the spread of AMR bacteria and AMR genes between humans, animals, and the environment is still largely unknown. Here, we investigated the role of wild birds in the epidemiology of AMR Escherichia coli. Using next-generation sequencing, we characterized cephalosporin-resistant E. coli cultured from sympatric gulls and bald eagles inhabiting a landfill habitat in Alaska to identify genetic determinants conferring AMR, explore potential transmission pathways of AMR bacteria and genes at this site, and investigate how their genetic diversity compares to isolates reported in other taxa. We found genetically diverse E. coli isolates with sequence types previously associated with human infections and resistance genes of clinical importance, including blaCTX-M and blaCMY. Identical resistance profiles were observed in genetically unrelated E. coli isolates from both gulls and bald eagles. Conversely, isolates with indistinguishable core-genomes were found to have different resistance profiles. Our findings support complex epidemiological interactions including bacterial strain sharing between gulls and bald eagles and horizontal gene transfer among E. coli harboured by birds. Results suggest that landfills may serve as a source for AMR acquisition and/or maintenance, including bacterial sequence types and AMR genes relevant to human health.
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| 10. |
- Ahlström, Björn, et al.
(författare)
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A comparison of impact of comorbidities and demographics on 60-day mortality in ICU patients with COVID-19, sepsis and acute respiratory distress syndrome
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Severe Coronavirus disease 2019 (COVID-19) is associated with several pre-existing comorbidities and demographic factors. Similar factors are linked to critical sepsis and acute respiratory distress syndrome (ARDS). We hypothesized that age and comorbidities are more generically linked to critical illness mortality than a specific disease state. We used national databases to identify ICU patients and to retrieve comorbidities. The relative importance of risk factors for 60-day mortality was evaluated using the interaction with disease group (Sepsis, ARDS or COVID-19) in logistic regression models. We included 32,501 adult ICU patients. In the model on 60-day mortality in sepsis and COVID-19 there were significant interactions with disease group for age, sex and asthma. In the model on 60-day mortality in ARDS and COVID-19 significant interactions with cohort were found for acute disease severity, age and chronic renal failure. In conclusion, age and sex play particular roles in COVID-19 mortality during intensive care but the burden of comorbidity was similar between sepsis and COVID-19 and ARDS and COVID-19.
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