37 research outputs found

    The teleost polymeric Ig receptor counterpart in ballan wrasse (Labrus bergylta) differs from pIgR in higher vertebrates

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    As mucosal barriers in fish are the main sites where pathogens are encountered, mucosal immunity is crucial to avoid infection in the aquatic environment. In teleost fish, immunoglobulins are present in gut, gill and skin mucus, although not in the same amounts as in higher vertebrates. In mammals, the poly-Ig receptor (pIgR) is synthesized in epithelial cells and mediates the active transport of poly-immunoglobulins (pIgs) across the epithelium. During transport, a component of the pIgR, the secretory component (SC), is covalently bound to pIgs secreted into the mucus providing protection against proteases and avoiding degradation. The teleost pIgR gene does not show synteny to higher vertebrates, the overall structure of the protein is different (comprising two Ig domains) and its functional mechanisms remain unclear. The J-chain which is essential for pIgR-mediated transport of IgA and IgM in higher vertebrates is absent in teleost fish. The aim of the present study was to characterize the ballan wrasse (Labrus bergylta) pIgR and use it as a marker for further studies of mucosal immunity in this species. The pIgR gene was unambiguously identified. Unexpectedly, reverse transcription real time PCR (RT-qPCR) revealed highest abundance of pIgR mRNA in liver and significantly lower expression in mucosal organs such as foregut, hindgut, and skin. In situ hybridization showed pIgR-positive cells dispersed in the lamina propria while it was undetectable in epithelial cells of foregut and hindgut of ballan wrasse. A similar pattern was observed in Atlantic salmon. Liquid Chromatography-Mass Spectrometry (LC-MS/MS) analysis of IgM enriched mucus samples from gut, gill, skin, and bile gave relatively few matches to wrasse pIgR. Notably, the matching peptides were from the transmembrane (TM) and cytoplasmatic (Cy) region as well as the putative SC, indicating leakage from lysed cells rather than covalent bonds between IgM and SC. Altogether, the results indicate that pIgR has another (or at least an additional) function in wrasse. Another pIgR-like molecule (pIgRL) in ballan wrasse (comprising three Ig domains) was analyzed to see if this could be an alternative functional pIgR homolog. However, the presence of pIgRL mRNA in blood leukocytes and a relatively high expression in immune organs like spleen and head kidney pointed to a receptor function on a circulating leukocyte population. As significant amounts of IgM were found in bile of ballan wrasse further studies should consider the hepato-biliary route regarding IgM delivery to the gut lumen.publishedVersio

    Physical and nutrient stimuli differentially modulate gut motility patterns, gut transit rate, and transcriptome in an agastric fish, the ballan wrasse

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    The effects of nutrient and mechanical sensing on gut motility and intestinal metabolism in lower vertebrates remains largely unknown. Here we present the transcriptome response to luminal stimulation by nutrients and an inert bolus on nutrient response pathways and also the response on gut motility in a stomachless fish with a short digestive tract; the ballan wrasse (Labrus berggylta). Using an in vitro model, we differentiate how signals initiated by physical stretch (cellulose and plastic beads) and nutrients (lipid and protein) modulate the gut evacuation rate, motility patterns and the transcriptome. Intestinal stretch generated by inert cellulose initiated a faster evacuation of digesta out of the anterior intestine compared to digestible protein and lipid. Stretch on the intestine upregulated genes associated with increased muscle activity, whereas nutrients stimulated increased expression of several neuropeptides and receptors which are directly involved in gut motility regulation. Although administration of protein and lipid resulted in similar bulbous evacuation times, differences in intestinal motility, transit between the segments and gene expression between the two were observed. Lipid induced increased frequency of ripples and standing contraction in the middle section of the intestine compared to the protein group. We suggest that this difference in motility was modulated by factors [prepronociceptin (pnoca), prodynorphin (pdyn) and neuromedin U (nmu), opioid neurotransmitters and peptides] that are known to inhibit gastrointestinal motility and were upregulated by protein and not lipid. Our findings show that physical pressure in the intestine initiate contractions propelling the bolus distally, directly towards the exit, whereas the stimuli from nutrients modulates the motility to prolong the residence time of digesta in the digestive tract for optimal digestion.publishedVersio

    The thymus and T-cell ontogeny in ballan wrasse (Labrus bergylta) is nutritionally modelled

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    Marine fish larvae often experience high mortality unrelated to predation during early life stages, and farmed ballan wrasse (Labrus bergylta) is no exception. Knowing when the adaptive immune system is developed and fully functional, and how nutrition may modulate these processes is therefore of importance to establish effective prophylactic measures and will also extend the relatively limited knowledge on the immune system in lower vertebrates. The thymus anlage of ballan wrasse was found to be histologically visible for the first time at larval stage 3 (20–30 days post hatch, dph) and becomes lymphoid at stage 5 (50–60 dph) correlating with an increase of T-cell marker transcripts. At this stage, a clear zonation into a RAG1+ cortex and a RAG1- CD3ϵ+ medulla was distinguished, indicating that T-cell maturation processes in ballan wrasse are similar to other teleosts. The higher abundance of CD4-1+ compared to CD8β+ cells in the thymus together with the apparent lack of CD8β+ cells in gill, gut, and pharynx, where CD4-1+ cells were identified, indicates that helper T-cells have a more prominent role during larval development compared to cytotoxic T-cells. As ballan wrasse lacks a stomach but has an exceptionally high IgM expression in the hindgut, we hypothesize that helper T-cells are crucial for activation and recruitment of IgM+ B-cells and possibly other leukocytes to the gut during early development. Nutritional factors such as DHA/EPA, Zn and Se may lead to an earlier expression of certain T-cell markers as well as a larger size of the thymus, indicating an earlier onset of adaptive immunity. Including live feeds that supplies the larva with higher amounts of these nutrients can therefore be beneficial for ballan wrasse farming.publishedVersio

    Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

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    Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference) and obesity (BMI >2 SD above the median). Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesit

    Worldwide trends in underweight and obesity from 1990 to 2022 : a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults

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    A list of authors and their affiliations appears online. A supplementary appendix is herewith attached.Background: Underweight and obesity are associated with adverse health outcomes throughout the life course. We estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from 1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories. Methods: We used data from 3663 population-based studies with 222 million participants that measured height and weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the individual and combined prevalence of underweight (BMI 2 SD above the median). Findings: From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in 11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and 140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%) with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and 42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents, the increases in double burden were driven by increases in obesity, and decreases in double burden by declining underweight or thinness. Interpretation: The combined burden of underweight and obesity has increased in most countries, driven by an increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of underweight while curbing and reversing the increase in obesity.peer-reviewe

    Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

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    Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

    Development of the adaptive immune system in ballan wrasse (Labrus bergylta) and the impact of different start-feed diets

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    Berggylt (Labrus bergylta) spiser hovedsakelig bløtdyr, pigghuder og krepsdyr, der også ektoparasitter som plukkes fra andre fisker kan nyttes. Denne egenskapen har ført til at berggylt nå er brukt som rensefisk innen lakseoppdrett for å begrense lakselus infestasjoner. Oppdrett av berggylt har imidlertid møtt på de samme utfordringene som ved oppdrett av andre marine arter, inkludert sen vekst og høy dødelighet i de tidlige livsstadiene. I disse larvestadiene er det adaptive immunsystemet underutviklet, og larvene er derfor mer mottakelige for infeksjoner. Denne studien har undersøkt utviklingen av de viktigste primære lymfoide organene, tymus og hodenyre, utviklingen av T- og B-celler, samt transporten av IgM til tarmlumen hos berggylt. Effekten av alternative næringskilder på disse parameterne ble også evaluert. Nyren viste seg å være det første lymfoide organet som ble utviklet, da den var til stede ved klekking, etterfulgt av tymus og milt som begge ble synlig ved stadium 3 (20-30 dager post klekking, dpk). Svært lave mRNA nivåer av gener relatert til adaptiv immunitet ble observert frem til larvestadium 5 (50 til 70 dpk). På dette stadiet ble en betydelig økning av RAG1 og RAG2, så vel som T-cellemarkørtranskripter (CD3ε, ZAP70, LCK, CD4-1 og CD8β), markører for antigenpresentasjon (MHC-IIα, CD74α) og B-cellemarkører (IgM, IgT og IgD) funnet, og lymfopoiesen starter derfor trolig på dette larvestadiet. Lokaliseringen av RAG1 i berggyltlarver viste dessuten en tydelig sonering av tymus, med en RAG1+ korteks og RAG1-CD3ε+ medulla. Det ble også observert RAG1+ immunceller samt et stort antall IgM+ celler i berggyltens eksokrine pankreas, noe som antyder at berggyltens B-celler også kan utvikles her. Effekten av to startfôrdietter på berggyltens lymfopoiese ble også evaluert, der larver av rur som er ansett som en mer optimal diett ble sammenlignet med en tradisjonell diett av rotatorier og Artemia. Høyere nivåer av omega-3 flerumettede fettsyrer (PUFA) og spesifikke mineraler ble observert når næringsinnholdet ble sammenlignet mellom disse to diettene. Disse forskjellene ble gjenspeilet i en moderat økning av visse T-cellemarkører samt en økning i tymus-størrelsen i berggylt som ble foret med rur. I fisk spiller mukosal immunitet en vital rolle, der slimhinnebarrierer med mukosa-assosierte lymfoide vev (MALT) fungerer som et primært sted for å fange opp eventuelle patogener. I berggyltlarver ble det funnet at IgM+ B-celler migrerte til tarmen tidligere enn hjelper T-celler, og disse tidlige mukosale B-cellene produserer derfor sannsynligvis naturlige antistoffer (det vil si B-celler som produserer IgM før eksponering for antigener). Disse naturlige antistoffene er trolig viktig for å beskytte larvens tarm i fravær av en funksjonell mage, som foreslått for voksen berggylt. Tilstedeværelsen av spesifikke immunglobuliner i tarmens, gjellenes og hudens slim er også avgjørende for en effektiv bekjempelse av patogener. Et molekyl kalt pIgR medierer aktiv transport av immunglobuliner over epitel hos høyerestående vertebrater, og pIgR er også identifisert i mange fiskearter. Men selv om berggyltens pIgR ble funnet å være strukturelt lik den hos andre teleoster, indikerte resultatene i denne studien på at IgM primært transporteres til tarmlumen via leverens galleganger eller gjennom bukspyttkjertelens utførselskanaler. Påvisning av IgM i berggyltegg, samt identifikasjon av sekretoriske IgT transkripter i berggyltlarver før første fôring (4 dpk), indikerer at maternal overføring av antistoffer er viktig for overlevelse av tidlige berggyltstadier. Den medfødte og adaptive delen av immunsystemet er imidlertid tett integrert. Fiskelarver er derfor avhengige av medfødte forsvarsstrategier før adaptiv immunitet modnes, og dette gjelder også for berggyltlarvene. Resultatene fra dette arbeidet indikerer når immunkompetanse tidligst kan være oppnådd under berggyltens utvikling (> 90-100 dph), noe som er viktig for å utvikle effektive vaksinasjonsstrategier. Resultatene indikerer dessuten at en startfôrdiett basert på rur kan være fordelaktig for en optimal T-celle modning i tidlige livsstadier.Ballan wrasse (Labrus bergylta) primarily feeds on molluscs, echinoderms, and crustaceans, while also targeting ectoparasites on other fish. The latter trait has made ballan wrasse the preferred cleaner fish for managing salmon lice infestations within salmonid aquaculture. Cultivating this species is relatively new and faces challenges common to other marine species, including slow growth and high early-life mortality. During early larval stages, the adaptive immune system remains underdeveloped, making larvae more susceptible to infections. The present study investigates the development of the main primary lymphoid organs, the thymus and head kidney, the emergence of T- and B-cells, and transport of IgM into the gut lumen of ballan wrasse. The effect of early nutrition on these parameters has also been investigated. The sequence of lymphoid organ appearance started with the kidney present at hatching, followed by thymus and spleen at stage 3 (20-30 days post-hatching, dph). Transcriptomic data revealed very low baseline expression levels of genes related to adaptive immunity until larval stage 5 (50 to 70 dph). At this stage, a significant increase of RAG1 and RAG2 transcripts, as well as transcripts that are T-cell markers (including CD3ε, ZAP70, LCK, CD4-1, and CD8β), markers of antigen presentation (MHC-IIα, CD74α), and B-cell markers (IgM, IgT, and IgD) appeared, indicating lymphoid activity at this stage. The localization of RAG1 mRNA in wrasse larvae revealed a clear corticomedullary structure in the thymus with a RAG1+ cortex and RAG1- CD3ε+ medulla. Interestingly, RAG1 was abundantly expressed in small cells within pancreatic tissue. This detected expression together with the identification of a high number of IgM+ cells in the exocrine pancreas strongly suggest that B-lymphopoiesis also occurs in pancreatic tissue of ballan wrasse. When analysing nutritional differences between two start-feed diets, one being a commonly used combination of rotifers and Artemia, and the other an experimental diet comprising barnacle nauplii, variations primarily existed in the levels of omega-3 poly-unsaturated fatty acids (PUFAs) and specific minerals. These differences were reflected in specific parameters of the adaptive immune system, including an increase of the level of specific T-cell marker transcripts and an enlarged thymus size in barnacle fed larvae. In fish, mucosal immunity plays a vital role with mucosal barriers, particularly mucosa-associated lymphoid tissues (MALTs), serving as primary sites for encountering pathogens. Through the examination of ballan wrasse lymphocyte migration to developing MALTs, it was found that IgM+ B-cells reached the gut before helper T-cells. This observation indicates that B-cells play an early role in protecting young larvae, possibly by generating natural antibodies (i.e., B-cells producing IgM prior to exposure of antigens). Natural antibodies are presumably important for protecting the gut of larvae in the absence of a functional stomach, as proposed for adult ballan wrasse. The presence of secreted immunoglobulins in the mucus of gut, gills, and skin, is essential for combating pathogens and maintaining homeostasis. A molecule named pIgR mediates active transport of immunoglobulins across the epithelium in higher vertebrates, and a teleost counterpart has been reported in many species. Although wrasse pIgR was found to be structurally similar to that in other teleosts, the present results indicate that IgM is primarily transported to the gut lumen through the hepato-biliary route involving the liver, or through the pancreatic route involving the exocrine pancreas. IgM was present in eggs of ballan wrasse and transcripts of sIgT were detected in larvae prior to first feeding (4 dph), indicating that maternal transfer also occurs in ballan wrasse. The innate and adaptive arms of the immune system are closely integrated, and an extremely complex interaction of players. Fish larvae rely on innate defensive mechanisms before adaptive immunity matures, and this is also the case for ballan wrasse. Results from this work indicate when immunocompetence might be achieved during ballan wrasse development (> 90-100 dph), which is important for developing efficient vaccination strategies. Furthermore, cultivation of ballan wrasse larvae might benefit from using a barnacle diet as start-diet.Doktorgradsavhandlin

    Dietary lipid modulation of intestinal serotonin in Ballan wrasse- Labrus bergylta – In vitro analyses

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    Salmon lice infections by Lepeophtheirus salmonis represent one of the biggest challenges for the salmon industry. Intensive use of chemical delousing methods has led to resistance in lice against several of the chemicals, this has sparked an interest for the use of cleaner fish as an efficient delousing solution. A goal for several salmon farmers is that farmed cleaner fish should replace wild catches, this has led to commercial farming of Ballan wrasse. In order to optimize the cultivation, knowledge about B. wrasse digestive physiology (normal functioning and regulation) and its nutritional requirements are equally important. Serotonin (5-HT) has been proposed to be an important molecule at regulating gut motility involved in digestion of nutrients as well as appetite regulation. Serotonin function in B. wrasse is unknown, elucidating its role might contribute to a better understanding of the gastrointestinal functionality that might help to overcome farming limitations of this cultured specie. There were two separate aims of this study. A transcriptomic part; revealing the expression of genes in the intestine regulated by lipid ingestion, emphasizing genes associated to lipid and 5-HT metabolism. Here, the aim was to observe the dietary lipid modulation of the gene expression over time (post prandial incubation time from 10m to 3 hours). In addition to this, my aim was to investigate the amount of 5-HT in the gut of Ballan wrasse from the same intestines to detect potential correlation to gene expressions involved in 5-HT metabolism. These investigations were done, in vitro on ex vivo intestines of Ballan wrasse, using a lipid diet (hydrolysed fish oil). Results showed significant response of only one gene involved in 5-HT metabolism (TPH2) and 3 genes involved in lipid metabolism after feeding (ELOVL1, PLIN2 and PPARG). Interestingly enough, 5-HT was observed to be present in the gut of Ballan wrasse with a tendency to increase 3 hours after feeding. Also, by analysing genome and transcriptomic data, I propose the presence of enterocromaffin cells (EC cells) in the gut of B. wrasse. EC cells theoretically, produce the majority of intestinal 5-HT synthesized through the enzyme TPH1. Unlike TPH1, its isoform TPH2 (exclusive to enteric neurons, another 5-HT producing cell) was observed to be significantly upregulated by feeding, suggesting an active role in nutrient sensing
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