| 1. |
- Flowers, Sarah A., et al.
(författare)
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Decrease of core 2 O-glycans on synovial lubricin in osteoarthritis reduces galectin-3 mediated crosslinking
- 2020
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 295:47, s. 16023-16036
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Tidskriftsartikel (refereegranskat)abstract
- The synovial fluid glycoprotein lubricin (also known as proteoglycan 4) is a mucin-type O-linked glycosylated biological lubricant implicated to be involved in osteoarthritis (OA) development. Lubricin's ability to reduce friction is related to its glycosylation consisting of sialylated and unsialylated Tn-antigens and core 1 and core 2 structures. The glycans on lubricin have also been suggested to be involved in crosslinking and stabilization of the lubricating superficial layer of cartilage by mediating interaction between lubricin and galectin-3. However, with the spectrum of glycans being found on lubricin, the glycan candidates involved in this interaction were unknown. Here, we confirm that the core 2 O-linked glycans mediate this lubricin-galectin-3 interaction, shown by surface plasmon resonance data indicating that recombinant lubricin (rhPRG4) devoid of core 2 structures did not bind to recombinant galectin-3. Conversely, transfection of Chinese hamster ovary cells with the core 2 GlcNAc transferase acting on a mucin-type O-glycoprotein displayed increased galectin-3 binding. Both the level of galectin-3 and the galectin-3 interactions with synovial lubricin were found to be decreased in late-stage OA patients, coinciding with an increase in unsialylated core 1 O-glycans (T-antigens) and Tn-antigens. These data suggest a defect in crosslinking of surface-active molecules in OA and provide novel insights into OA molecular pathology.
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| 2. |
- Hagberg, Cecilia, et al.
(författare)
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Att bygga för grisproduktion på Gotland - en vägledning
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Gotland Slagteri AB jointly with pig producers experienced that several construction projects of pig facilities were delayed or hindered due to insufficient locally established advisory services, specifically with competence in construction of pig facilities and the associated growth process. In corporation with the unit of Agriculture and Horticulture at Research Institutes of Sweden (RISE) and the farm advisory service, Gård och Djurhälsan, a project was carried out with the aim to write a handbook about the construction and growth process. One of the objectives with the handbook was to serve as a manual in which a pig producer could get more information about a specific topic relevant in the process. The handbook is composed of shorter texts in addition to checklists, "step by step", templates, forms and calculation tools. The project group has had several, so-called dialogue meetings, where specific topics, relevant to the construction and growth process, have been discussed within the group or with the participation of experts. The purpose of these meetings has been to retrieve deeper knowledge of specific topics, e.g., pig production planning, bank and finances, disease control and organic production. All these dialogue meetings have resulted in various chapters in this handbook. Additionally, there are a stand-alone template about writing a work environment plan for construction sites, several calculation tools for the operational phases in pig production, a template for ventilation and heat demand in pig units, a construction investment calculation tool and a time planning tool, i.e., a Gantt chart. The guidance focuses on the administration of a construction project and the growth process related to it. This guide does not contain topics related to e.g., crop production, feed production or manure handling. Neither such administration as required during the actual operational phase of the pig facility, such as systematic work environment plan or systematic fire protection plan. Additionally, the project group went on a study tour to Bornholm, Denmark, to discuss pros and cons operating an abattoir or pig production on an island (Grisproduktion på Bornholm – reseberättelse från studieresa i projektet ”Utökad grisproduktion på Gotland”, RISE report 2021:114).
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| 3. |
- Hagberg, Cecilia, et al.
(författare)
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Grisproduktion på Bornholm – reseberättelse från studieresa i projektet”Utökad grisproduktion på Gotland”
- 2021
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Pig production on Bornholm – a travelogue about pig production on Bornholm carried out in the project “Growing pig businesses on Gotland” Both Bornholm (Denmark) and Gotland (Sweden) are islands located in the Baltic Sea. Gotland is about five times as large in comparison with Bornholm, but the number of pig producers is twice as many on Bornholm. For both Bornholm and Gotland, pig production is important. Without pig production, a local abattoir would not be operating on the islands. A closure of the local abattoir would result in the loss of 150– 200 jobs. Such closure would affect the whole society. In addition, animal transports to slaughter would be significantly longer. In 2014 there was an imminent threat that the local abattoir on Bornholm would be closed due to profitability issues. With joint efforts the abattoir was rescued, and the production volumes are now expected to be 545,000 slaughtered pigs in 2021/2022. The density of pig herds on Bornholm is a raising concern among veterinarians and pig producers due to the spreading of diseases among the herds. For instance, there is a concern about the spreading of Porcine reproductive and respiratory syndrome (PRRS), which is not found in Sweden. PRRS was discovered in Sweden in 2007, but the affected pig herds were eliminated and the disease was eradicated. For both Denmark and Sweden there is another imminent threat in African swine fever (ASF), which is found in several countries in Europe. Denmark took measures to hinder the propagation of wild boars in the country, diminishing the risk of the spread of ASF. In Sweden, the wild boar population was established in the 80´s and has grown since then, increasing the risk of bringing ASF into the country. Thus, Gotland has an advantage with no wild boar population established on the island. In general, the surrounding water barrier on an island may be a natural barrier to hinder the introduction and spreading of diseases. In both Danish and Swedish pig production, there are difficulties finding staff. Between 50–70% of the staff in Danish pig production are foreigners. This proportion is significantly lower on Bornholm. So far, there is a market for agricultural properties on Bornholm, but as many pig producers approach retirement, the future situation is uncertain. It is becoming more common for employees to purchase farms in Bornholm when no relatives are interested to take over the business. For both Bornholm and Gotland, it is challenging for younger people to purchase farms due to the large investments. The process also takes many years. Developments towards more automation and digitalization in pig production became clear during the study trip to Bornholm. Danish Crown A/S has developed a mobile application in which the pig producers can report animals for slaughter. On the study tour the project group visited a pig farm with 600 sows and 20 000 fatteners. The pig farmer had invested in several automaton techniques to reduce operating costs for labor. The pig producers on Bornholm use production follow-up programs (corresponding to WinPig in Sweden) to a large extent. In addition, advisers are hired frequently. At Danish Crown A/S, there is an "owner service" that pig producers can join. In the owner service, the abattoir's consultants offer advices of interests for the pig producer. There is also a farm advisory service on Bornholm, namely Bornholms Landbrug och Fødevarer (BLF). BLF administrates several experience groups and on Bornholm there are as many as 17–18 (!) for pig producers and their staff. The intention of the groups is to exchange knowledge between pig producers. Many of the groups are aimed for the staff and are held in the pig barns. In addition, pig producers on Bornholm have a long and appreciated experience of benchmarking. The purpose of benchmarking is to compare the own business results to other pig producer’s. In Denmark, the pig veterinarian visits pig farms continuously, approximately every month. Visits by the pig veterinarian provide additional advices and follow-ups for the pig producer.
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| 4. |
- Heldin, Johan, et al.
(författare)
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Dynamin inhibitors impair platelet-derived growth factor beta-receptor dimerization and signaling
- 2019
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Ingår i: Experimental Cell Research. - : ELSEVIER INC. - 0014-4827 .- 1090-2422. ; 380:1, s. 69-79
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Tidskriftsartikel (refereegranskat)abstract
- The role of plasma membrane composition and dynamics in the activation process of receptor tyrosine kinases (RTKs) is still poorly understood. In this study we have investigated how signaling via the RTK, platelet-derived growth factor beta-receptor (PDGFR-beta) is affected by Dynasore or Dyngo-4a, which are commonly used dynamin inhibitors. PDGFR-beta preferentially internalizes via clathrin-coated pits and in this pathway, Dynamin II has a major role in the formation and release of vesicles from the plasma membrane by performing the membrane scission. We have found that dynamin inhibitors impedes the activation of PDGFR-beta by impairing ligand-induced dimerization of the receptor monomers, which leads to a subsequent lack of phosphorylation and activation both of receptors and downstream effectors, such as ERK1/2 and AKT. In contrast, dynamin inhibitors did not affect epidermal growth factor receptor (EGFR) dimerization and phosphorylation. Our findings suggest that there is a link between plasma membrane dynamics and PDGFR-beta activation, and that this link is not shared with the epidermal growth factor receptor.
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| 5. |
- Huang, Shan, et al.
(författare)
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Cathepsin g Degrades Both Glycosylated and Unglycosylated Regions of Lubricin, a Synovial Mucin
- 2020
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- Lubricin (PRG4) is a mucin type protein that plays an important role in maintaining normal joint function by providing lubrication and chondroprotection. Improper lubricin modification and degradation has been observed in idiopathic osteoarthritis (OA), while the detailed mechanism still remains unknown. We hypothesized that the protease cathepsin G (CG) may participate in degrading lubricin in synovial fluid (SF). The presence of endogenous CG in SF was confirmed in 16 patients with knee OA. Recombinant human lubricin (rhPRG4) and native lubricin purified from the SF of patients were incubated with exogenous CG and lubricin degradation was monitored using western blot, staining by Coomassie or Periodic Acid-Schiff base in gels, and with proteomics. Full length lubricin (∼300 kDa), was efficiently digested with CG generating a 25-kDa protein fragment, originating from the densely glycosylated mucin domain (∼250 kDa). The 25-kDa fragment was present in the SF from OA patients, and the amount was increased after incubation with CG. A CG digest of rhPRG4 revealed 135 peptides and 72 glycopeptides, and confirmed that the protease could cleave in all domains of lubricin, including the mucin domain. Our results suggest that synovial CG may take part in the degradation of lubricin, which could affect the pathological decrease of the lubrication in degenerative joint disease. © 2020, The Author(s).
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| 6. |
- Huang, Shan, et al.
(författare)
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Truncated lubricin glycans in osteoarthritis stimulate the synoviocyte secretion of VEGFA, IL-8, and MIP-1α : Interplay between O-linked glycosylation and inflammatory cytokines
- 2022
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- The primary aim of the study was to identify inflammatory markers relevant for osteoarthritis (OA)-related systemic (plasma) and local (synovial fluid, SF) inflammation. From this, we looked for inflammatory markers that coincided with the increased amount of O-linked Tn antigen (GalNAcα1-Ser/Thr) glycan on SF lubricin. Inflammatory markers in plasma and SF in OA patients and controls were measured using a 44-multiplex immunoassay. We found consistently 29 markers detected in both plasma and SF. The difference in their concentration and the low correlation when comparing SF and plasma suggests an independent inflammatory environment in the two biofluids. Only plasma MCP-4 and TARC increased in our patient cohort compared to control plasma. To address the second task, we concluded that plasma markers were irrelevant for a direct connection with SF glycosylation. Hence, we correlated the SF-inflammatory marker concentrations with the level of altered glycosylation of SF-lubricin. We found that the level of SF-IL-8 and SF-MIP-1α and SF-VEGFA in OA patients displayed a positive correlation with the altered lubricin glycosylation. Furthermore, when exposing fibroblast-like synoviocytes from both controls and OA patients to glycovariants of recombinant lubricin, the secretion of IL-8 and MIP-1α and VEGFA were elevated using lubricin with Tn antigens, while lubricin with sialylated and nonsialylated T antigens had less or no measurable effect. These data suggest that truncated glycans of lubricin, as found in OA, promote synovial proinflammatory cytokine production and exacerbate local synovial inflammation.
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| 7. |
- Thomsson, Ola, et al.
(författare)
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Aggression and cortisol levels in three different group housing routines for lactating sows
- 2015
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 57
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Tidskriftsartikel (refereegranskat)abstract
- Background: Lactating sows in Swedish organic piglet production are commonly group-housed with piglets in a multi-suckling pen within 14 days after farrowing. Nursing behaviour may be disturbed when lactating sows are moved to a new environment and mixed with other sows, as they spend more time fighting with other sows and exploring the new surroundings. This can disrupt the inhibitory effect of suckling on ovarian activity and increase the risk of lactational oestrus, making efficient reproductive management difficult. Therefore this study evaluated aggression and levels of the stress hormone cortisol in lactating sows group-housed together with their piglets at one (W1), two (W2) or three (W3) weeks post farrowing.Results: There was no significant difference (P > 0.05) between the three management routines (W1, W2, W3) regarding number of attacks initiated or received in the mixed group. After mixing, W2 sows had a lower number of shoulder scratches (P < 0.05) than W3 sows. Among the W3 sows, there was a lower (P < 0.01) cortisol concentration in saliva when sows were group housed compared to when they were individually housed. The cortisol response, measured as variation in cortisol concentration in saliva, was also lower (P < 0.05) in group-housed W3 sows compared with W1 sows. For all management routines, sows already living in the new environment (resident sows) initiated more attacks (P < 0.001) and received fewer attacks (P < 0.01) than sows entering the new environment (intruder sows). Overall, multiparous sows initiated more attacks and received fewer attacks than primiparous sows (P < 0.001).Conclusions: Overall, the results suggest that mixing and group housing sows at three weeks post farrowing is less stressful than mixing and group housing sows at one week post farrowing. The results also indicate that parity and whether a sow is a resident or intruder in the group housing environment may have an effect on aggression levels when sows are group-housed.
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| 8. |
- Thomsson, Ola, et al.
(författare)
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Consequences for Piglet Performance of Group Housing Lactating Sows at One, Two, or Three Weeks Post-Farrowing
- 2016
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Housing lactating sows with piglets in a multi-suckling pen from around 14 days post-farrowing is common practice in Swedish organic piglet production. However, nursing-suckling interaction is less frequent in multi-suckling pens than in individual farrowing pens, thus affecting piglet performance, e.g., piglet growth. Moreover, piglet mortality is higher in systems using multi-suckling pens. Three management routines whereby lactating sows with piglets were moved from individual farrowing pens to multi-suckling pens at one, two, or three weeks post-farrowing were compared in terms of nursing-suckling interaction and piglet performance. Correlations between nursing-suckling interaction, piglet performance, and piglet mortality were also examined. In total, 43 Yorkshire sows with piglets were included in the study. Nursing-suckling interaction and all piglet performance parameters except piglet mortality did not differ between management routines. Piglet mortality in the individual farrowing pens did not differ between management routines, but piglet mortality in the multi-suckling pen was lower (P<0.05) when piglets were group housed at three weeks compared with one week post-farrowing. Overall piglet mortality was positively correlated with mortality in the multi-suckling pen for piglets group housed at one week (r = 0.61: P<0.05) and at two weeks post-farrowing (r = 0.62: P<0.05) but not for piglets group housed at three weeks post-farrowing. In conclusion, overall piglet mortality could be reduced if sows and piglets are group housed at three weeks post-farrowing and piglet survival the first week post-farrowing is improved.
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| 9. |
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| 10. |
- Thomsson, Ola, et al.
(författare)
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Sow performance in multi-suckling pens with different management routines
- 2018
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Ingår i: Acta Veterinaria Scandinavica. - : Springer Science and Business Media LLC. - 0044-605X .- 1751-0147. ; 60
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Tidskriftsartikel (refereegranskat)abstract
- Production systems with group housing of sows during a part of the lactation are used in certified organic production and can increase the occurrence of lactational estrus thus making batch-wise breeding difficult. The aim of this study was to investigate the occurrence of lactational estrus and time at return to estrus after weaning by following the performance of the sow (change in body weight, back fat and litter size) in three different management routines. The sows and their litters were moved from individual to multi-suckling pen at one (W1; n = 14), two (W2; n = 13), or 3 weeks (W3; n = 16) post farrowing. All sows had a total lactation of 6 weeks. Ovulation was monitored by analysis of fecal progesterone metabolites. Only one sow (W3) ovulated during lactation. Sows in the W2 and W3 groups had a shorter weaning-to-standing estrus interval than W1-sows (2.6 +/- 0.3; 2.7 +/- 0.2 and 4.0 +/- 0.3 days respectively, P < 0.001). The W1-sows and piglets might have kept their nursing bond more intact all through the group housing since the piglets were completely dependent on the nursing at the time of their move to the group pen, thereby staying in lactational anestrus and retaining standard weaning-estrous interval. There was no difference in litter size at grouping or at weaning between management routines and parities. Third and later parity sows had significantly thicker back fat at farrowing and at weaning than 1st and 2nd parity sows (P < 0.05). In conclusion, the occurrence of lactational estrus can be low in a multi-suckling pen and the interval between farrowing and move to a multi-suckling pen can affect the weaning to estrus interval. The short weaning-to-standing estrus interval seen in W2 and W3 suggests that estrus detection should start immediately post weaning for sows kept in multi-suckling pens.
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