| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Adner, Mikael, et al.
(författare)
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Contractile endothelin-B (ETB) receptors in human small bronchi
- 1996
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 1399-3003 .- 0903-1936. ; 9:2, s. 351-355
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Tidskriftsartikel (refereegranskat)abstract
- Endothelins (ETs) are a family of novel regulatory peptides and various lines of evidence suggest an important role for ETs in regulating pulmonary function. Two receptors for endothelin, ETA and ETB, have been found in the human lung, and according to recent studies a non-ETA receptor seems to mediate the contraction of large sized human bronchi. Several studies have emphasized the importance of small bronchi in the pathogenesis of airway disease. In the present paper, improved methodology was used which enables in vitro studies of small human bronchi down to a diameter of 0.5-1.0 mm. Using the new methodology we have tried to further characterize this receptor. Small bronchi from the distal parts of the bronchial tree were obtained from pulmonary tissue removed from 15 patients with lung cancer. They were dissected and cut into ring segments, in which isometric tension was recorded. ET-1, ET-2 and ET-3 elicited strong concentration-dependent contractions of the human small bronchus. Basically, the three peptides were equipotent with about the same maximal response. Upon reapplication, they all showed the same tachyphylaxis pattern, reaching half the initial contraction. Comparative analysis of IRL 1620, a selective ETB receptor agonist, revealed that the effect of the ETB agonist was, in all respects, similar to the responses induced by the ETs. PD 145065, a combined ETA/ETB receptor antagonist competitively inhibited the contractions induced by IRL 1620, whereas FR139317, a selective ETA receptor antagonist, was without effect. In conclusion, the present study shows that accurate measurements can be made in vitro on small human bronchi and all present data are in favour of an ETB receptor mediating endothelin-induced contraction of human bronchi smaller than 1.0 mm.
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| 3. |
- Circiumaru, Alexandra, et al.
(författare)
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Anti-Citrullinated Protein Antibody Reactivity towards Neutrophil-Derived Antigens : Clonal Diversity and Inter-Individual Variation
- 2023
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Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Why the adaptive immune system turns against citrullinated antigens in rheumatoid arthritis (RA) and whether anti-citrullinated protein antibodies (ACPAs) contribute to pathogenesis are questions that have triggered intense research, but still are not fully answered. Neutrophils may be crucial in this context, both as sources of citrullinated antigens and also as targets of ACPAs. To better understand how ACPAs and neutrophils contribute to RA, we studied the reactivity of a broad spectrum of RA patient-derived ACPA clones to activated or resting neutrophils, and we also compared neutrophil binding using polyclonal ACPAs from different patients.Methods: Neutrophils were activated by Ca2+ ionophore, PMA, nigericin, zymosan or IL-8, and ACPA binding was studied using flow cytometry and confocal microscopy. The roles of PAD2 and PAD4 were studied using PAD-deficient mice or the PAD4 inhibitor BMS-P5.Results: ACPAs broadly targeted NET-like structures, but did not bind to intact cells or influence NETosis. We observed high clonal diversity in ACPA binding to neutrophil-derived antigens. PAD2 was dispensable, but most ACPA clones required PAD4 for neutrophil binding. Using ACPA preparations from different patients, we observed high patient-to-patient variability in targeting neutrophil-derived antigens and similarly in another cellular effect of ACPAs, the stimulation of osteoclast differentiation.Conclusions: Neutrophils can be important sources of citrullinated antigens under conditions that lead to PAD4 activation, NETosis and the extrusion of intracellular material. A substantial clonal diversity in targeting neutrophils and a high variability among individuals in neutrophil binding and osteoclast stimulation suggest that ACPAs may influence RA-related symptoms with high patient-to-patient variability.
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| 4. |
- Enarsson, Lars-Erik, et al.
(författare)
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Tailoring the chemistry of polyelectrolytes to control their adsorption on cellulosic surfaces
- 2009
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Ingår i: Colloids and Surfaces A. - : Elsevier BV. - 0927-7757 .- 1873-4359. ; 340:1-3, s. 135-142
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Tidskriftsartikel (refereegranskat)abstract
- The adsorption of two types of cationic polyacrylamides in the presence of a background electrolyte was studied on substrates including silicon oxide, kraft pulp fibres and thin films of regenerated cellulose. One of the polyelectrolytes was a conventional cationic polyacrylamide (MeCPAM) and the other was a benzyl-containing derivative of cationic polyacrylamide (BzCPAM). It was found that the aromatic substituents of BzCPAM strongly enhanced the adsorption on substrates of hydrophobically modified silicon oxide when a background electrolyte was present. A similar effect was also seen in the case of BzCPAM adsorption on unbleached pulp fibres, but in this case MeCPAM also exhibited a strong adsorption at high background electrolyte concentrations. On bleached pulp fibres, BzCPAM maintained a high adsorption up to a concentration of 100 mM NaCl whereas MeCPAM adsorption showed a significant decrease at this salt concentration. On model cellulose films, the adsorption of BzCPAM was similar to that of MeCPAM and the non-ionic interactions with cellulose appeared weak, since there was no adsorption of either polyelectrolyte in 300 mM NaCl.
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| 5. |
- Johannsson, Gudmundur, 1960, et al.
(författare)
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Growth hormone treatment of abdominally obese men reduces abdominal fat mass, improves glucose and lipoprotein metabolism, and reduces diastolic blood pressure.
- 1997
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 82:3, s. 727-34
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Tidskriftsartikel (refereegranskat)abstract
- The most central findings in both GH deficiency in adults and the metabolic syndrome are abdominal/visceral obesity and insulin resistance. Abdominal obesity is associated with blunted GH secretion and low serum insulin-like growth factor-I concentrations. GH treatment in GH-deficient adults has demonstrated favorable effects on most of the features of GH deficiency in adults, but it is not known whether GH can improve some of the metabolic aberrations observed in abdominal/visceral obesity. Thirty men, 48-66 yr old, with abdominal/visceral obesity were treated with recombinant human GH (rhGH) in a 9-month randomized, double-blind, placebo-controlled trial. The daily dose of rhGH was 9.5 micrograms/kg. Body fat was assessed from total body potassium, and abdominal sc and visceral adipose tissue was measured using computed tomography. The glucose disposal rate (GDR) was measured during an euglycemic, hyperinsulinemic glucose clamp. In response to the rhGH treatment, total body fat and abdominal sc and visceral adipose tissue decreased by 9.2 +/- 2.4%, 6.1 +/- 3.2%, and 18.1 +/- 7.6%, respectively. After an initial decrease in the GDR at 6 weeks, the GDR increased in the rhGH-treated group as compared with the placebo-treated one (P < 0.05). The mean serum concentrations of total cholesterol (P < 0.01) and triglyceride (P < 0.05) decreased, whereas blood glucose and serum insulin concentrations were unaffected by the rhGH treatment. Furthermore, diastolic blood pressure decreased and systolic blood pressure was unchanged in response to rhGH treatment. This trial has demonstrated that GH can favorably affect some of the multiple perturbations associated with abdominal/visceral obesity. This includes a reduction in abdominal/visceral obesity, an improved insulin sensitivity, and favorable effects on lipoprotein metabolism and diastolic blood pressure.
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| 6. |
- Lönn, Lars, 1956, et al.
(författare)
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Body weight and body composition changes after treatment of hyperthyroidism.
- 1998
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Ingår i: The Journal of clinical endocrinology and metabolism. - : The Endocrine Society. - 0021-972X. ; 83:12, s. 4269-73
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Tidskriftsartikel (refereegranskat)abstract
- Body composition changes in nine adults with hyperthyroidism were determined with dual energy x-ray absorptiometry and computed tomography at diagnosis and after 3 and 12 months of euthyroidism achieved by surgery, antithyroid drugs, or treatment with radioiodine. Mean body weight was 67.6 kg at diagnosis and increased 2.7 kg (P=0.06) and 8.7 kg (P < 0.001) after 3 and 12 months of euthyroidism, respectively. Basal metabolic rate decreased from 2087 Cal/24 h at diagnosis to 1601 Cal/24 h at 12 months (P=0.001), whereas reported energy intake dropped from 3244 to 2436 Cal/24 h (P=0.01). According to dual energy x-ray absorptiometry, body fat was unchanged at 3 months, but increased by 5.3 kg (P < 0.0001) at 12 months. Fat-free mass increased 2.7 kg (P=0.003) at 3 months and 3.5 kg (P < 0.0001) at 12 months. Changes in bone mineral content and density did not reach significance. According to computed tomography, skeletal muscle plus skin areas increased by 11% (trunk) and 18% (thigh) at 3 months and by 17% (trunk) and 25% (thigh) at 12 months. There was no increase in sc adipose tissue (AT) at 3 months, but at 12 months this AT depot increased by 15% (thigh) and 33% (trunk). Intraperitoneal AT showed a borderline significant increase by 28% (P=0.08) at 3 months and by 40% (P=0.015) at 12 months. Areas of visceral organs and bone tissue of femur did not change significantly during the study. It is concluded that during early recovery from hyperthyroidism, priority is given to the replenishment of skeletal muscles and ip AT, whereas sc AT is increased at a later stage.
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| 7. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae
- 2006
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Ingår i: YSBN Meeting Nov. 14-16, 2006- Vienna- Austria.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Robustness analysis of HOG pathway genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening method that allows the investigation of the upper limit copy number of genes, and thereby the upper permissible range of gene expression level. This method is based on a 2-micron plasmid vector containing the leu2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2ura3 deletion yeast cells transformed with pTOW plasmid are cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to compensate for the lack of leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth or has a toxic effect when a certain copy number is exceeded (it reaches to its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will be concentrated. In this study we have applied the gTOW method on 29 HOG pathway related genes in Saccharomyces cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition and consists of two branches that activate a MAPK (Hog1) via a MAPKK (Pbs2) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes and the quantitative data provided by the gTOW method collating with the existing computational models could be used to analyze the robustness and fragility of the pathway. 1. Hisao Moriya, Yuki Shimizu-Yoshida and Hiroaki Kitano, 2006, PLoS Genetics, 2:7
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| 8. |
- Ahmadpour, Doryaneh, 1973, et al.
(författare)
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Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae
- 2007
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Ingår i: FEBS-SysBio March 10-16, 2007- Gosau, Austria.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Robustness analysis of HOG pathway related genes in Saccharomyces cerevisiae Doryaneh Ahmadpour1, Lars-Göran Ottosson1, Markus Krantz2, Jonas Warringer1, Anders Blomberg1 and Stefan Hohmann1* 1Department of Cell and Molecular Biology/Microbiology, Göteborg University, S-405 30 Göteborg, Sweden 2 The Systems Biology Institute (SBI), Shibuya, Tokyo, Japan E-mail: doryaneh.ahmadpour@gmm.gu.se Robustness is a fundamental property of biological systems and crucial for their effective function under internal or external perturbations. For instance, it has been proposed that internal parameters such as gene expression have been optimized during evolution such that a given system has the observed robustness. The permissible ranges of internal parameters in the cells are not comprehensively understood since there has not been a technique to measure such parameters. “Genetic tug-of-war” (gTOW) [1] is a genetic screening approach that allows the determination of the upper limit copy number of genes, and thereby the upper permissible range of the level of gene expression. This method is based on a 2-micron plasmid vector containing the LEU2d allele with a very weak complementation activity and the gene of interest inserted as target gene. When the leu2 ura3 mutant yeast transformed with pTOW plasmids is cultured under leucine-limiting conditions, there will be a bias toward increasing the plasmid copy number to satisfy the requirement for leucine. On the other hand there will be an opposing bias toward decreasing the plasmid copy number if the target gene inhibits growth when a certain copy number is exceeded (i.e. it reaches its upper limit). Eventually as a result of the “tug-of-war” between these two selection biases cells with optimized plasmid copy number will accumulate. In this study we have applied the gTOW method on 29 HOG pathway genes in S. cerevisiae. The high osmolarity glycerol (HOG) MAPK pathway is essential for yeast survival in high osmolarity condition [2]. It consists of two branches that activate a MAPK (Hog1) to orchestrate part of the transcriptional response. The HOG pathway is the best understood osmoresponsive system in eukaryotes. The quantitative data provided by the gTOW method collating with the existing computational models [3] could be used to analyze the robustness and fragility of the pathway. 1. Moriya H, et al., (2006), PLoS Genet 2(7): e111 2. Hohmann S (2002), Microbiol Mol Biol Rev 66:300 3. Klipp E, et al., (2005), Nat Biotechnol 23:975
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| 9. |
- Arnegård, Johan, 1958-
(författare)
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Upplevelser och lärande i äventyrssport och skola
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The physicality of sports and outdoor life offers great opportunities for intensive experiences – participants ”feel” the happening in their bodies. As well as looking upon physical activity mainly as something instrumental, as for example in competitive sports and exercise culture, other aspects can also be central, for instance the pure joy of movement. The existential or expressive side of physical activity is examined in this doctoral thesis.In order to study such experiential quality more thoroughly, the author’s attention turns to adventure sports participants, as they appear to have a capacity for becoming highly involved and seeking very intense experiences. Who is involved in adventure sports? Why are they engaged in a sport that demands such great hardships and risk-taking? What do they get out of it? The overall objective of the thesis is to shed light on adventure sports as a practice and to discuss the educational significance of flow and other experiential qualities in adventure sports and in schools.The analyses are based on three empirical sub-studies. The first began with a questionnaire that 161 adventure sports participants responded to. This was followed by an interview study of eleven men and three women, all of whom had extensive experience in adventure sports. The categories of sport were evenly divided between climbing, off-piste skiing and hang gliding.In the second sub-study a detailed investigation of climbing was carried out. A notable sportification has brought about a very clear and interesting change in parts of this activity. Six traditional/adventure climbers and six sport climbers were interviewed, of which half were men and half women. All the climbers were experienced and very much involved in their sport.The aim of the third sub-study was to seek an answer as to whether pupils have experiences in their daily school life that are similar to those of adventure sports participants. An ESM (Experience Sampling Method) investigation was carried out with 60 pupils in compulsory school year nine (corresponding to UK schools’ year eleven) from four different schools. The pupils’ parents answered a special parent questionnaire including questions about academic and professional backgrounds, living conditions, habits, interests, attitudes and leisure time activities.The results were analysed taking into consideration the phenomenological perspective and structuralistic or more correctly expressed the cultural sociological perspective. Mihály Csikszentmihályi’s theoretical argument on optimal experiences, which in turn is based on the flow concept, constitutes the phenomenological foundation. Pierre Bourdieu’s concept apparatus and theories were used to closely examine the participants’ backgrounds, life histories and current living situations.The study shows that a preference for adventure sports is clearly linked to the participants’ backgrounds and earlier life experiences. A behavioural pattern is incorporated and developed into an embodied capacity to master a practice, a result of a long learning process. Participants were clearly concordant in these respects. Participants emphasise the abundant opportunities for intensive experiences that arise from adventure sports. It is a matter of something multidimentional: the active body, outdoor life in natural surroundings, exacting and clear goals, total focus, and about exercising control. This approach presents a model for identification of content qualities, which together create the dynamics that form the meaningful rewards that result from participation in adventure sports. The dimensions include flow experiences, but also go beyond them.The deep sense of presence, the physical involvement, the fact that they can choose the path and increase the degree of difficulty themselves – and simultaneously counter this new challenge with increased capacity so that they are engaged at the ”right level” – also provide favourable conditions for a stimulating and successful learning experience.The observation was made that it was primarily in the practical and aesthetic subjects that school pupils had the same deep feeling of presence together with a meaningful and pleasurable holistic experience as the adventure sports participants had. Here they were actively involved with their hands or with their whole bodies, and they could make their own choices and be in control of the activity, which for most pupils led to a strong feeling of satisfaction.
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| 10. |
- Behrenz, Lars, et al.
(författare)
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Arbetsgivares perspektiv på subventionerade anställningar : en kartläggning
- 2015
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Trots en kraftig ökning av antalet subventionerade anställningar från mitten av 2000-talet är det ett stort antal arbetsgivare som inte använder sig av lönesubventioner. Denna rapport har försökt att kartlägga och analysera arbetsgivares perspektiv på lönekostnadssubventioner. När det gäller analyser som berör de arbetsgivare som använt sig av lönesubventioner är den viktigaste förklaringsfaktorn att man använt sig av subventioner tidigare. Våra intervjuer visar också att de arbetsgivare som använder sig av lönesubventioner ofta har ett socialt ansvarstagande. Ett av huvudresultaten med följande studie är att 95 procent av de som använder sig av subventioner är nöjda. Omfattningen i pengar och personens kvalifikationer var mest avgörande för anställningsbeslutet. Av de som inte använt sig av lönesubventioner är det 20 procent som inte känt till att möjligheten finns. Intervjuer med arbetsgivare utan erfarenhet av att anställa med lönesubventioner visar att de är skeptiska att hitta lämplig personal genom att anställa med lönesubventioner. När vi ställer en hypotetisk fråga till samtliga arbetsgivare om vad som skulle kunna få dem att anställa med en subvention framkommer möjligheten att få pröva aktuell person som den klart viktigaste faktorn. Utifrån våra resultat föreslår vi bl.a. att Arbetsförmedlingen, i ett försöksupplägg, ska ges möjlighet att agera bemanningsföretag och vi föreslår också att man ska genomföra en omfattande informationskampanj till arbetsgivare.
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| 11. |
- Bendre, Ameya, et al.
(författare)
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Growth failure in aggrecan haploinsufficiency is due to a decrease in growth plate matrix volume and hypertrophic cell size
- 2023
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 96:Suppl. 4, s. 40-41
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Heterozygous loss-of-function mutations in the aggrecan gene (ACAN) cause autosomal dominant short stature with advanced bone age, early-onset osteoarthritis and intervertebral disc disease (SSOAOD; OMIM#165800). ACAN mutations is a relatively common finding in idiopathic short stature (ISS) and has been reported to be the cause of growth failure in approximately 2% of children with ISS. However, the underlying cellular and molecular mechanisms by which ACAN mutations cause growth failure in SSOAOD have not been elucidated.Objective: To investigate the underlying cellular and molecular mechanisms of growth failure using a mouse model of SSOAOD.Methods: Cartilage matrix deficiency mouse (Acan cmd) has a naturally occurring 7 bp micro-deletion in aggrecan gene. Heterozygous Acancmd and wild-type (WT) male and female mice were assessed for skeletal and body growth at 1,3,6,12 and 24 weeks of age. Histomorphometric analysis was performed on Masson-Trichrome stained proximal tibial and distal femoral growth plates. Cell proliferation was assessed by EdU incorporation. Quantification of percentage matrix area was performed using Image J. Single-cell RNA sequencing was carried out on chondro-cytes isolated from 18 day old WT and Acan cmd female mice according to 3’ gene expression protocol (10X Genomics).Results: Heterozygous Acancmd mice were born at a normal size and similar to humans with SSOAOD but showed decreased postnatal growth resulting in a gradually worsening dwarfism with reduced total body length and tibial and femoral lengths (p<0.0001). In the growth plates, chondrocytes were found to be more tightly packed with reduced matrix area (p<0.0001) and increased column density in Acan cmd mice compared to WT mice. Growth plate height (p<0.0001), heights of the individual zones (p<0.001), the number of resting zone chondrocytes (p<0.01), proliferative cells per column (p<0.0001), and the size of terminal hypertrophic chondrocytes (p<0.001) were slightly reduced in both male and female Acan cmd mice, especially at 1 week of age. Interestingly, chondrocyte proliferation was similar in Acan cmd and WT mice at all time-points assessed (p=0.90). Female Acan cmd mice exhibited a more pronounced phenotype than male mice.Conclusions: Similar to children with heterozygous ACAN mutations, heterozygous Acancmd mice exhibit a growth pattern with postnatal growth failure resulting in adult short stature. The growth failure is primarily caused by decreased matrix production and hypertrophic cell size, whereas chondrocyte proliferation is normal. Single-cell RNA sequencing of growth plate chondrocytes is ongoing and will identify the underlying pathogenic mechanisms and might also identify compensatory mechanisms limiting the effects of aggrecan haploinsufficiency.
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| 12. |
- Bendre, Ameya, et al.
(författare)
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Postnatal growth failure of aggrecan deficient mice is due to impaired growth plate chondrogenesis
- 2022
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Ingår i: Hormone Research in Paediatrics. - : S. Karger. - 1663-2818 .- 1663-2826. ; 95:Suppl. 2, s. 294-294
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Heterozygous Aggrecan (Acan) mutations cause autosomal short stature (ISS) with advanced bone age, early-onset osteoarthritis and intervertebral disc disease (OMIM#165800) in humans. Cartilage matrix deficiency mouse (Acancmd) has a naturally occurring 7 bp micro-deletion in aggrecan gene. Heterozygous Acancmd mice develop postnatal dwarfism with progressing age. However, the underlying cellular and molecular mechanisms causing the growth failure have not been characterized in detail.Objective: To investigate the molecular mechanism of proportionate dwarfism in heterozygous Acan cmd mouse.Methods: Heterozygous Acancmd and wild-type (WT) male and female mice were assessed for skeletal and body growth, at 1, 3, 6, 12 and 24 weeks of age. Histomorphometric analysis was performed on Masson-Trichrome stained proximal tibial and femoral growth plates. Cell proliferation was assessed by EdU incorpora-tion and assessed by confocal microscopy. Quantification of percentage matrix area was performed using Image J image analysis software.Results: Heterozygous Acancmd mice were born with a normal body size. However, postnatal growth was reduced resulting in a gradually worsening dwarfism with reduced total body length (p <0.0001) as well as shorter tibial length (p<0.0001) and femoral length (p<0.0001) than their wild-type littermates. Histomorphometric analyses revealed that growth plate chondrocytes were more tightly packed with reduced matrix area (p<0.001) and increased proliferative column density in Acancmd mice compared to wild-type mice. Interestingly, the number of resting zone chondrocytes, proliferative cells per column and hypertropic cells per column were reduced at 1 week of age. In contrast, the size of terminal hypertrophic chondrocytes were normal during early postnatal growth, but reduced at 12 and 24 weeks of age. Despite the differences in growth plate morphology, chondrocyte proliferation was similar in Acan cmd and WT mice. Interestingly, female mice exhibited a more pronounced growth phenotype than the males.Conclusions: Heterozygous Acan cmd mice have a growth disorder that is similar to that in children with heterozygous ACAN mutations in terms of progression with age as well as in magnitude (10-15% smaller). Histomorphometric analyses suggest that the growth failure of aggrecan deficient mice is due to a combination of reduced matrix production and decreased size of the terminal hypertrophic chondrocytes. Further studies will elucidate the pathogenic mechanisms as well as the effect of estrogen on growth in aggrecan haploinsufficiency.
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| 13. |
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| 14. |
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| 15. |
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| 16. |
- Chau, Michael, et al.
(författare)
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The synovial microenvironment suppresses chondrocyte hypertrophy and promotes articular chondrocyte differentiation
- 2022
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Ingår i: NPJ Regenerative medicine. - : Nature Publishing Group. - 2057-3995. ; 7:1
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Tidskriftsartikel (refereegranskat)abstract
- During the development of the appendicular skeleton, the cartilaginous templates undergo hypertrophic differentiation and remodels into bone, except for the cartilage most adjacent to joint cavities where hypertrophic differentiation and endochondral bone formation are prevented, and chondrocytes instead form articular cartilage. The mechanisms that prevent hypertrophic differentiation and endochondral bone formation of the articular cartilage have not been elucidated. To explore the role of the synovial microenvironment in chondrocyte differentiation, osteochondral allografts consisting of articular cartilage, epiphyseal bone, and growth plate cartilage from distal femoral epiphyses of inbred Lewis rats expressing enhanced green fluorescent protein from a ubiquitous promoter were transplanted either in inverted or original (control) orientation to matching sites in wildtype littermates, thereby allowing for tracing of transplanted cells and their progenies. We found that no hypertrophic differentiation occurred in the growth plate cartilage ectopically placed at the joint surface. Instead, the transplanted growth plate cartilage, with time, remodeled into articular cartilage. This finding suggests that the microenvironment at the articular surface inhibits hypertrophic differentiation and supports articular cartilage formation. To explore this hypothesis, rat chondrocyte pellets were cultured with and without synoviocyte-conditioned media. Consistent with the hypothesis, hypertrophic differentiation was inhibited and expression of the articular surface marker lubricin (Prg4) was dramatically induced when chondrocyte pellets were exposed to synovium- or synoviocyte-conditioned media, but not to chondrocyte- or osteoblast-conditioned media. Taken together, we present evidence for a novel mechanism by which synoviocytes, through the secretion of a factor or factors, act directly on chondrocytes to inhibit hypertrophic differentiation and endochondral bone formation and promote articular cartilage formation. This mechanism may have important implications for articular cartilage development, maintenance, and regeneration.
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| 17. |
- Dekkers, Koen, et al.
(författare)
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An online atlas of human plasma metabolite signatures of gut microbiome composition.
- 2022
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Human gut microbiota produce a variety of molecules, some of which enter the bloodstream and impact health. Conversely, dietary or pharmacological compounds may affect the microbiota before entering the circulation. Characterization of these interactions is an important step towards understanding the effects of the gut microbiota on health. In this cross-sectional study, we used deep metagenomic sequencing and ultra-high-performance liquid chromatography linked to mass spectrometry for a detailed characterization of the gut microbiota and plasma metabolome, respectively, of 8583 participants invited at age 50 to 64 from the population-based Swedish CArdioPulmonary bioImage Study. Here, we find that the gut microbiota explain up to 58% of the variance of individual plasma metabolites and we present 997 associations between alpha diversity and plasma metabolites and 546,819 associations between specific gut metagenomic species and plasma metabolites in an online atlas ( https://gutsyatlas.serve.scilifelab.se/ ). We exemplify the potential of this resource by presenting novel associations between dietary factors and oral medication with the gut microbiome, and microbial species strongly associated with the uremic toxin p-cresol sulfate. This resource can be used as the basis for targeted studies of perturbation of specific metabolites and for identification of candidate plasma biomarkers of gut microbiota composition.
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| 18. |
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| 19. |
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| 20. |
- Dou, Zelong, et al.
(författare)
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Rat perichondrium transplanted to articular cartilage defects forms articular-like, hyaline cartilage
- 2021
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Ingår i: Bone. - : Elsevier. - 8756-3282 .- 1873-2763. ; 151
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Perichondrium autotransplants have been used to reconstruct articular surfaces destroyed by infection or trauma. However, the role of the transplanted perichondrium in the healing of resurfaced joints have not been investigated.DESIGN: Perichondrial and periosteal tissues were harvested from rats hemizygous for a ubiquitously expressed enhanced green fluorescent protein (EGFP) transgene and transplanted into full-thickness articular cartilage defects at the trochlear groove of distal femur in wild-type littermates. As an additional control, cartilage defects were left without a transplant (no transplant control). Distal femurs were collected 3, 14, 56, 112 days after surgery.RESULTS: Tracing of transplanted cells showed that both perichondrium and periosteum transplant-derived cells made up the large majority of the cells in the regenerated joint surfaces. Perichondrium transplants contained SOX9 positive cells and with time differentiated into a hyaline cartilage that expanded and filled out the defects with Col2a1-positive and Col1a1-negative chondrocytes and a matrix rich in proteoglycans. At later timepoints the cartilaginous perichondrium transplants were actively remodeled into bone at the transplant-bone interface and at post-surgery day 112 EGFP-positive perichondrium cells at the articular surface were positive for Prg4. Periosteum transplants initially lacked SOX9 expression and despite a transient increase in SOX9 expression and chondrogenic differentiation, remained Col1a1 positive, and were continuously thinning as periosteum-derived cells were incorporated into the subchondral compartment.CONCLUSIONS: Perichondrium and periosteum transplanted to articular cartilage defects did not just stimulate regeneration but were themselves transformed into cartilaginous articular surfaces. Perichondrium transplants developed into an articular-like, hyaline cartilage, whereas periosteum transplants appeared to produce a less resilient fibro-cartilage.
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| 22. |
- Eklöf, Anders, 1956-, et al.
(författare)
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Instructions, independence, and uncertainty : student framing in self-regulated project work
- 2014
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Ingår i: European Educational Research Journal (online). - 1474-9041 .- 1474-9041. ; 13:6, s. 646-660
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Tidskriftsartikel (refereegranskat)abstract
- This study presents an approach to student interaction in self-regulated project work. By combining frame analysis and socio-cultural risk theory, the authors explore the importance of students' framing activities as a basis for their understanding of tasks. The increase in self-regulated work in Swedish schools can be seen as being in line with developments in Europe towards more individualisation. The authors argue that their data provide examples of how the global discourse imposes itself on local discourses. This mode of work, as it appears in the material presented in this article, exemplifies how complex assessment ideas have penetrated the school context. The authors emphasise the concepts of uncertainty, risk and complexity in analysing the framing process, and claim that the focus on these concepts is essential in analysing self-regulated work, contributing to better understanding of self-regulated learning processes.
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| 23. |
- Eklöf, Anders, et al.
(författare)
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Instructions, independence, and uncertainty : student framing in self-regulated project work
- 2014
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Ingår i: European Educational Research Journal (online). - : SAGE Publications. - 1474-9041. ; 13:6, s. 646-660
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Tidskriftsartikel (refereegranskat)abstract
- This study presents an approach to student interaction in self-regulated project work. By combining frame analysis and socio-cultural risk theory, the authors explore the importance of students' framing activities as a basis for their understanding of tasks. The increase in self-regulated work in Swedish schools can be seen as being in line with developments in Europe towards more individualisation. The authors argue that their data provide examples of how the global discourse imposes itself on local discourses. This mode of work, as it appears in the material presented in this article, exemplifies how complex assessment ideas have penetrated the school context. The authors emphasise the concepts of uncertainty, risk and complexity in analysing the framing process, and claim that the focus on these concepts is essential in analysing self-regulated work, contributing to better understanding of self-regulated learning processes.
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| 24. |
- Eklöf, Anders, 1956-
(författare)
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Project work, independence and critical thinking
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis studies how students do projects in a Swedish upper secondaryschool. The students have to produce products and at the same time provethem self as independent in relation to the teachers, and negotiate therequirements of the project setting and the written instructions within thegroup. The study focuses on what comes out as problematic for the students,how they solve these dilemma situations and what resources are used in orderto do so.A choice was made only to analyse student group interaction in parts ofthe project process where the teachers were not physically present thus fillinga research gap.The empirical material was collected during three years in sex secondaryschool classes through filmed sessions of groups or pairs working with theirproject.Each of the four articles primarily focuses a special dilemma; structure,independence, instructions and critical thinking. By combining Goffman’sframe analysis with the concepts of risk and uncertainty from a Risk – societyperspective, issues related to what it means to do project work asindependent, critical 21st-century learner are illustrated and discussed.The choice to look only at situations in which students have to managewithout the aid of a physically present teacher illuminates several practicalconsequences like an unwillingness to go to the teacher and ask questions andan increased concentration on and interpretation of the written instructions. Adevelopment of Miller and Parlett’s (1974) discussion of student approach tocues are suggested. The concept of the cue choosing student are constructedin order to better respond to demands from an individualised interactionsociety. The study also emphasises how the students have to balance differentframeworks in order to be both authors and assessed students. Byimplementing a risk society perspective new ways of analysing andunderstanding independence and classroom interaction is suggested and arecontextualization of critical thinking proposed.
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| 25. |
- Eklöf, Anders
(författare)
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Project work, independence and critical thinking
- 2014
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Doktorsavhandling (populärvet., debatt m.m.)abstract
- This thesis studies how students do projects in a Swedish upper secondaryschool. The students have to produce products and at the same time provethem self as independent in relation to the teachers, and negotiate therequirements of the project setting and the written instructions within thegroup. The study focuses on what comes out as problematic for the students,how they solve these dilemma situations and what resources are used in orderto do so.A choice was made only to analyse student group interaction in parts ofthe project process where the teachers were not physically present thus fillinga research gap.The empirical material was collected during three years in sex secondaryschool classes through filmed sessions of groups or pairs working with theirproject.Each of the four articles primarily focuses a special dilemma; structure,independence, instructions and critical thinking. By combining Goffman’sframe analysis with the concepts of risk and uncertainty from a Risk – societyperspective, issues related to what it means to do project work asindependent, critical 21st-century learner are illustrated and discussed.The choice to look only at situations in which students have to managewithout the aid of a physically present teacher illuminates several practicalconsequences like an unwillingness to go to the teacher and ask questions andan increased concentration on and interpretation of the written instructions. Adevelopment of Miller and Parlett’s (1974) discussion of student approach tocues are suggested. The concept of the cue choosing student are constructedin order to better respond to demands from an individualised interactionsociety. The study also emphasises how the students have to balance differentframeworks in order to be both authors and assessed students. Byimplementing a risk society perspective new ways of analysing andunderstanding independence and classroom interaction is suggested and arecontextualization of critical thinking proposed.
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