OXR1A, a Coactivator of PRMT5 Regulating Histone Arginine Methylation

Oxidation resistance gene 1 (OXR1) protects cells against oxidative stress. We find that male mice with brain-specific isoform A knockout (Oxr1A−/−) develop fatty liver. RNA sequencing of male Oxr1A−/− liver indicates decreased growth hormone (GH) signaling, which is known to affect liver metabolism. Indeed, Gh expression is reduced in male mice Oxr1A−/− pituitary gland and in rat Oxr1A−/− pituitary adenoma cell-line GH3. Oxr1A−/− male mice show reduced fasting-blood GH levels. Pull-down and proximity ligation assays reveal that OXR1A is associated with arginine methyl transferase PRMT5. OXR1A-depleted GH3 cells show reduced symmetrical dimethylation of histone H3 arginine 2 (H3R2me2s), a product of PRMT5 catalyzed methylation, and chromatin immunoprecipitation (ChIP) of H3R2me2s shows reduced Gh promoter enrichment. Finally, we demonstrate with purified proteins that OXR1A stimulates PRMT5/MEP50-catalyzed H3R2me2s. Our data suggest that OXR1A is a coactivator of PRMT5, regulating histone arginine methylation and thereby GH production within the pituitary gland.publishedVersio

Health and welfare of Atlantic salmon in FishGLOBE V5 -a novel closed containment system at sea

Closed-containment (CCS) systems offer several advantages in controlling the production environment for Atlantic salmon (Salmo salar) aquaculture, especially at sea, where fish are more exposed to challenging environmental conditions. Here, we report the health and welfare of Atlantic salmon in FishGLOBE V5, a 3500 m3 semi-closed containment system. A group of 200,000 post-smolts was followed from a recirculating aquaculture system (RAS) facility, then for three and a half months in FishGLOBE V5, and three months after release in net pens. Fish samples were collected at four time points during the production period, while water quality was evaluated when the fish were in FishGLOBE V5. The water quality in FishGLOBE V5 was within the recommended range for salmon post-smolts. The mortality rate was 1.4% in FishGLOBE V5 and 4.9% in net pens. There was an increase in the prevalence of eye, snout and dorsal fin damages before the fish left the FishGLOBE V5 phase. The plasma level of magnesium was slightly elevated during this phase as well, indicating osmotic imbalance and stress. Histological evaluation of skin and gills showed sporadic cases of non-specific pathologies. In particular, the transitory stay in FishGLOBE V5 partially improved skin health, but not gill health. Gene expression profiling of some biomarkers showed that rearing fish in FishGLOBE V5 could influence the expression of genes involved in stress response, mucus production, and epithelial integrity. This study documented that rearing salmon for a certain period in FishGLOBE V5 during production affected different health and welfare indicators. These changes should be taken into consideration for the improvement of FishGLOBE V5 as a viable technology for post-smolt production at sea.Health and welfare of Atlantic salmon in FishGLOBE V5 -a novel closed containment system at seapublishedVersio

NLRP3 inflammasome promotes myocardial remodeling during diet-induced obesity

Background: Obesity is an increasingly prevalent metabolic disorder in the modern world and is associated with structural and functional changes in the heart. The NLRP3 inflammasome is an innate immune sensor that can be activated in response to endogenous danger signals and triggers activation of interleukin (IL)-1β and IL-18. Increasing evidence points to the involvement of the NLRP3 inflammasome in obesity-induced inflammation and insulin resistance, and we hypothesized that it also could play a role in the development of obesity induced cardiac alterations. Methods and Results: WT, Nlrp3−/−, and ASC−/− (Pycard−/−) male mice were exposed to high fat diet (HFD; 60 cal% fat) or control diet for 52 weeks. Cardiac structure and function were evaluated by echocardiography and magnetic resonance imaging, respectively. Whereas, NLRP3 and ASC deficiency did not affect the cardiac hypertrophic response to obesity, it was preventive against left ventricle concentric remodeling and impairment of diastolic function. Furthermore, whereas NLRP3 and ASC deficiency attenuated systemic inflammation in HFD fed mice; long-term HFD did not induce significant cardiac fibrosis or inflammation, suggesting that the beneficial effects of NLRP3 inflammasome deficiency on myocardial remodeling at least partly reflect systemic mechanisms. Nlrp3 and ASC (Pycard) deficient mice were also protected against obesity-induced systemic metabolic dysregulation, as well as lipid accumulation and impaired insulin signaling in hepatic and cardiac tissues. Conclusions: Our data indicate that the NLRP3 inflammasome modulates cardiac concentric remodeling in obesity through effects on systemic inflammation and metabolic disturbances, with effect on insulin signaling as a potential mediator within the myocardium.publishedVersio

Marine bioaktive fiskepeptider for forebygging av overvekt og mikrobiotarelaterte sykdommer i mennesker og dyr

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Marine bioaktive fiskepeptider for forebygging av overvekt og mikrobiotarelaterte sykdommer i mennesker og dyr

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Humoral immunity to SARS-CoV-2 mRNA vaccination in multiple sclerosis: the relevance of time since last rituximab infusion and first experience from sporadic revaccinations

Introduction The effect of disease-modifying therapies (DMT) on vaccine responses is largely unknown. Understanding the development of protective immunity is of paramount importance to fight the COVID-19 pandemic. Objective To characterise humoral immunity after mRNA-COVID-19 vaccination of people with multiple sclerosis (pwMS). Methods All pwMS in Norway fully vaccinated against SARS-CoV-2 were invited to a national screening study. Humoral immunity was assessed by measuring anti-SARS-CoV-2 SPIKE RBD IgG response 3–12 weeks after full vaccination, and compared with healthy subjects. Results 528 pwMS and 627 healthy subjects were included. Reduced humoral immunity (anti-SARS-CoV-2 IgG <70 arbitrary units) was present in 82% and 80% of all pwMS treated with fingolimod and rituximab, respectively, while patients treated with other DMT showed similar rates as healthy subjects and untreated pwMS. We found a significant correlation between time since the last rituximab dose and the development of humoral immunity. Revaccination in two seronegative patients induced a weak antibody response. Conclusions Patients treated with fingolimod or rituximab should be informed about the risk of reduced humoral immunity and vaccinations should be timed carefully in rituximab patients. Our results identify the need for studies regarding the durability of vaccine responses, the role of cellular immunity and revaccinations. This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.publishedVersio

Report from a krill focused survey with RV Kronprins Haakon and land-based predator work in Antarctica during 2018/2019

The primary objective for this krill research activity was twofold 1) to conduct a survey that provides updated estimates of the biomass and distribution of krill which are used in models to estimate sustainable yield in CCAMLR Area 48 and 2) to develop knowledge on the marine environment essential for the implementation of a Feed-Back Management (FBM) system. The survey follows a similar design as a survey initiated by CCAMLR in year 2000 for comparative purposes, but in addition focuses on high krill-density areas, contains state-of-the art methods and employs modern technology for the research topics currently in focus. In terms of FBM, Marine Protected Area (MPA) development in CCAMLR Planning Domain 1 encompasses the major krill fishing grounds. Thus, data supporting FBM are critical if the fishery is to be managed by an empirical understanding of krill density, distribution, availability and predator needs as opposed to purely conservation-based measures. A future developed FBM system, requires acoustic data to be collected, processed and reported continuously during the fishing season as a measure of the available prey field. This information can be integrated with finer-scale knowledge of krill predator feeding strategies and updated through specific scientific studies at regular (multiyear) intervals. The survey and coupled FBM process studies took place during the Austral summer 2018-2019. The work was coordinated by Norway and involved collaborative international efforts as well as vessels from Norway, Association of Responsible Krill fishing companies (ARK) and the Norwegian fishing company Aker BioMarine AS, China, Korea, Ukraine and United Kingdom. This report presents preliminary results from the survey performed with the Norwegian RV Kronprins Haakon during 08th January – 24th February 2019 and the land-based predator research carried out between 21st November 2018 and 20th February 2019.publishedVersio

Still Arctic? — The changing Barents Sea

The Barents Sea is one of the Polar regions where current climate and ecosystem change is most pronounced. Here we review the current state of knowledge of the physical, chemical and biological systems in the Barents Sea. Physical conditions in this area are characterized by large seasonal contrasts between partial sea-ice cover in winter and spring versus predominantly open water in summer and autumn. Observations over recent decades show that surface air and ocean temperatures have increased, sea-ice extent has decreased, ocean stratification has weakened, and water chemistry and ecosystem components have changed, the latter in a direction often described as “Atlantification” or “borealisation,” with a less “Arctic” appearance. Temporal and spatial changes in the Barents Sea have a wider relevance, both in the context of large-scale climatic (air, water mass and sea-ice) transport processes and in comparison to other Arctic regions. These observed changes also have socioeconomic consequences, including for fisheries and other human activities. While several of the ongoing changes are monitored and quantified, observation and knowledge gaps remain, especially for winter months when field observations and sample collections are still sparse. Knowledge of the interplay of physical and biogeochemical drivers and ecosystem responses, including complex feedback processes, needs further development.Still Arctic? — The changing Barents SeapublishedVersio

SpeB of Streptococcus pyogenes Differentially Modulates Antibacterial and Receptor Activating Properties of Human Chemokines

BACKGROUND: CXC chemokines are induced by inflammatory stimuli in epithelial cells and some, like MIG/CXCL9, IP-10/CXCL10 and I-TAC/CXCL11, are antibacterial for Streptococcus pyogenes. METHODOLOGY/PRINCIPAL FINDINGS: SpeB from S. pyogenes degrades a wide range of chemokines (i.e. IP10/CXCL10, I-TAC/CXCL11, PF4/CXCL4, GROalpha/CXCL1, GRObeta/CXCL2, GROgamma/CXCL3, ENA78/CXCL5, GCP-2/CXCL6, NAP-2/CXCL7, SDF-1/CXCL12, BCA-1/CXCL13, BRAK/CXCL14, SRPSOX/CXCL16, MIP-3alpha/CCL20, Lymphotactin/XCL1, and Fractalkine/CX3CL1), has no activity on IL-8/CXCL8 and RANTES/CCL5, partly degrades SRPSOX/CXCL16 and MIP-3alpha/CCL20, and releases a 6 kDa CXCL9 fragment. CXCL10 and CXCL11 loose receptor activating and antibacterial activities, while the CXCL9 fragment does not activate the receptor CXCR3 but retains its antibacterial activity. CONCLUSIONS/SIGNIFICANCE: SpeB destroys most of the signaling and antibacterial properties of chemokines expressed by an inflamed epithelium. The exception is CXCL9 that preserves its antibacterial activity after hydrolysis, emphasizing its role as a major antimicrobial on inflamed epithelium