| 1. |
|
|
| 2. |
- Agardh, Carl-David, et al.
(författare)
-
Clinical evidence for the safety of GAD65 immunomodulation in adult-onset autoimmune diabetes.
- 2005
-
Ingår i: Journal of Diabetes and its Complications. - : Elsevier BV. - 1873-460X .- 1056-8727. ; 19:4, s. 238-246
-
Tidskriftsartikel (refereegranskat)abstract
- The purpose of this Phase II study was to evaluate if alum-formulated human recombinant GAD65 is safe and does not compromise beta cell function. The study was conducted as a randomized, double blind, placebo-controlled, dose-escalation clinical trial in a total of 47 Latent Autoimmune Diabetes in Adults (LADA) patients who received either placebo or 4, 20, 100, or 500 μg Diamyd subcutaneously at Weeks 1 and 4. Safety evaluations, including neurology, beta cell function tests, diabetes status assessment, hematology, biochemistry, and cellular and humoral immunological markers, were repeatedly assessed over 24 weeks. None of the patients had significant study-related adverse events (AE). Fasting c-peptide levels at 24 weeks were increased compared with placebo (P=.0015) in the 20 μg but not in the other dose groups. In addition, both fasting (P=.0081) and stimulated (P=.0236) c-peptide levels increased from baseline to 24 weeks in the 20 μg dose group. GADA log levels clearly increased (P=.0002) in response to 500 μg Diamyd. The CD4+CD25+/CD4+CD25− cell ratio increased (P=.0128) at 24 weeks in the 20 μg group. No sudden increase in HbA1c or plasma glucose or decrease in beta cell function was observed in any of the dose groups. These positive findings for clinical safety further support the clinical development of Diamyd as a therapeutic to prevent autoimmune diabetes.
|
|
| 3. |
- Bengtsson, Ylva, et al.
(författare)
-
Ulriksdals slott under 350 år
- 1995
-
Rapport (populärvet., debatt m.m.)abstract
- Studierna har utgått från Ulriksdals slott, uppfört av Jacob De la Gardie för 350 år sedan. Som kungligt slott har Ulriksdal genomgått ombyggnader under 1600 - och 1700-talet, men präglas idag mest av Karl XVs omfattande omdaning på 1850-talet och Gustav VI Adolfs lika genomgripande förändringar på 1920-talet.Slottet har bjudit på rika studiemöjligheter av stilideal, planlösning, interiörgestaltning, snickerikultur och stormtekniska system från hela 350-årsperioden. Genom noggranna uppmätningar och inventeringar på plats kopplade till arkivstudier har slottets komplicerade förändringshistoria kunnat analyseras,
|
|
| 4. |
- Borenäs, Marcus, et al.
(författare)
-
ALK signaling primes the DNA damage response sensitizing ALK-driven neuroblastoma to therapeutic ATR inhibition
- 2024
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - 1091-6490. ; 121:1
-
Tidskriftsartikel (refereegranskat)abstract
- High-risk neuroblastoma (NB) is a significant clinical challenge. MYCN and Anaplastic Lymphoma Kinase (ALK), which are often involved in high-risk NB, lead to increased replication stress in cancer cells, suggesting therapeutic strategies. We previously identified an ATR (ataxia telangiectasia and Rad3-related)/ALK inhibitor (ATRi/ALKi) combination as such a strategy in two independent genetically modified mouse NB models. Here, we identify an underlying molecular mechanism, in which ALK signaling leads to phosphorylation of ATR and CHK1, supporting an effective DNA damage response. The importance of ALK inhibition is supported by mouse data, in which ATRi monotreatment resulted in a robust initial response, but subsequent relapse, in contrast to a 14-d ALKi/ATRi combination treatment that resulted in a robust and sustained response. Finally, we show that the remarkable response to the 14-d combined ATR/ALK inhibition protocol reflects a robust differentiation response, reprogramming tumor cells to a neuronal/Schwann cell lineage identity. Our results identify an ability of ATR inhibition to promote NB differentiation and underscore the importance of further exploring combined ALK/ATR inhibition in NB, particularly in high-risk patient groups with oncogene-induced replication stress.
|
|
| 5. |
- Borin, Lars, et al.
(författare)
-
Swe-Clarin : Language Resources and Technology for Digital Humanities
- 2016
-
Ingår i: <em>Extended Papers of the International Symposium on Digital Humanities</em>. - : CEUR. ; , s. 29-51, s. 29-51
-
Konferensbidrag (refereegranskat)abstract
- CLARIN is a European Research Infrastructure Consortium (ERIC), which aims at (a) making extensive language-based materials available as primary research data to the humanities and social sciences (HSS); and (b) offering state-of-the-art language technology (LT) as an eresearch tool for this purpose, positioning CLARIN centrally in what is often referred to as the digital humanities (DH). The Swedish CLARIN node Swe-Clarin was established in 2015 with funding from the Swedish Research Council.In this paper, we describe the composition and activities of Swe-Clarin, aiming at meeting the requirements of all HSS and other researchers whose research involves using text and speech as primary research data, and spreading the awareness of what Swe-Clarin can offer these research communities. We focus on one of the central means for doing this: pilot projects conducted in collaboration between HSS researchers and Swe-Clarin, together formulating a research question, the addressing of which requires working with large language-based materials. Four such pilot projects are described in more detail, illustrating research on rhetorical history, second-language acquisition, literature, and political science. A common thread to these projects is an aspiration to meet the challenge of conducting research on the basis of very large amounts of textual data in a consistent way without losing sight of the individual cases making up the mass of data, i.e., to be able to move between Moretti’s “distant” and “close reading” modes.While the pilot projects clearly make substantial contributions to DH, they also reveal some needs for more development, and in particular a need for document-level access to the text materials. As a consequence of this, work has now been initiated in Swe-Clarin to meet this need, so that Swe-Clarin together with HSS scholars investigating intricate research questions can take on the methodological challenges of big-data language-based digital humanities.
|
|
| 6. |
- Borin, Lars, 1957, et al.
(författare)
-
Swe-Clarin: Language resources and technology for Digital Humanities
- 2017
-
Ingår i: Digital Humanities 2016. Extended Papers of the International Symposium on Digital Humanities (DH 2016) Växjö, Sweden, November, 7-8, 2016. Edited by Koraljka Golub, Marcelo Milra. Vol-2021. - Aachen : M. Jeusfeld c/o Redaktion Sun SITE, Informatik V, RWTH Aachen.. - 1613-0073.
-
Konferensbidrag (refereegranskat)abstract
- CLARIN is a European Research Infrastructure Consortium (ERIC), which aims at (a) making extensive language-based materials available as primary research data to the humanities and social sciences (HSS); and (b) offering state-of-the-art language technology (LT) as an e-research tool for this purpose, positioning CLARIN centrally in what is often referred to as the digital humanities (DH). The Swedish CLARIN node Swe-Clarin was established in 2015 with funding from the Swedish Research Council. In this paper, we describe the composition and activities of Swe-Clarin, aiming at meeting the requirements of all HSS and other researchers whose research involves using text and speech as primary research data, and spreading the awareness of what Swe-Clarin can offer these research communities. We focus on one of the central means for doing this: pilot projects conducted in collaboration between HSS researchers and Swe-Clarin, together formulating a research question, the addressing of which requires working with large language-based materials. Four such pilot projects are described in more detail, illustrating research on rhetorical history, second-language acquisition, literature, and political science. A common thread to these projects is an aspiration to meet the challenge of conducting research on the basis of very large amounts of textual data in a consistent way without losing sight of the individual cases making up the mass of data, i.e., to be able to move between Moretti’s “distant” and “close reading” modes. While the pilot projects clearly make substantial contributions to DH, they also reveal some needs for more development, and in particular a need for document-level access to the text materials. As a consequence of this, work has now been initiated in Swe-Clarin to meet this need, so that Swe-Clarin together with HSS scholars investigating intricate research questions can take on the methodological challenges of big-data language-based digital humanities.
|
|
| 7. |
- Borin, Lars, 1957, et al.
(författare)
-
Swe-Clarin: Language resources and technology for digital humanities
- 2016
-
Ingår i: CEUR Workshop Proceedings. - 1613-0073. ; 2021, s. 29-51
-
Konferensbidrag (refereegranskat)abstract
- CLARIN is a European Research Infrastructure Consortium (ERIC), which aims at (a) making extensive language-based materials available as primary research data to the humanities and social sciences (HSS); and (b) offering state-of-the-art language technology (LT) as an e-research tool for this purpose, positioning CLARIN centrally in what is often referred to as the digital humanities (DH). The Swedish CLARIN node Swe-Clarin was established in 2015 with funding from the Swedish Research Council. In this paper, we describe the composition and activities of Swe-Clarin, aiming at meeting the requirements of all HSS and other researchers whose research involves using text and speech as primary research data, and spreading the awareness of what Swe-Clarin can offer these research communities. We focus on one of the central means for doing this: pilot projects conducted in collaboration between HSS researchers and Swe-Clarin, together formulating a research question, the addressing of which requires working with large language-based materials. Four such pilot projects are described in more detail, illustrating research on rhetorical history, second-language acquisition, literature, and political science. A common thread to these projects is an aspiration to meet the challenge of conducting research on the basis of very large amounts of textual data in a consistent way without losing sight of the individual cases making up the mass of data, i.e., to be able to move between Moretti’s “distant” and “close reading” modes.
|
|
| 8. |
- Cervantes-Madrid, Diana Lizeth, 1987, et al.
(författare)
-
Repotrectinib (TPX-0005), effectively reduces growth of ALK driven neuroblastoma cells.
- 2019
-
Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Neuroblastoma is the most commonly diagnosed extracranial tumor in the first year of life. Approximately 9% of neuroblastoma patients present germline or somatic aberrations in the gene encoding for anaplastic lymphoma kinase (ALK). This increases in high-risk neuroblastomas, which have a 14% frequency of ALK aberrations at the time of diagnosis and show increasing numbers at relapse. Abrogating ALK activity with kinase inhibitors is employed as clinical therapy in malignancies such as non-small cell lung cancer and has shown good results in pediatric inflammatory myofibroblastic tumors and anaplastic large cell lymphomas. A phase I clinical trial of the first generation ALK inhibitor, crizotinib, in neuroblastoma patients showed modest results and suggested that further investigation was needed. Continuous development of ALK inhibitors has resulted in the third generation inhibitor repotrectinib (TPX-0005), which targets the active kinase conformations of ALK, ROS1 and TRK receptors. In the present study we investigated the effects of repotrectinib in a neuroblastoma setting in vitro and in vivo. Neuroblastoma cell lines were treated with repotrectinib to investigate inhibition of ALK and to determine its effect on proliferation. PC12 cells transfected with different ALK mutant variants were used to study the efficacy of repotrectinib to block ALK activation/signaling. The in vivo effect of repotrectinib was also analyzed in a neuroblastoma xenograft model. Our results show that repotrectinib is capable of inhibiting signaling activity of a range of ALK mutant variants found in neuroblastoma patients and importantly it exhibits strong antitumor effects in a xenograft model of neuroblastoma.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
- Gubrianska, Danica, et al.
(författare)
-
Bone and hormonal status 10 years post-allogeneic bone marrow transplantation
- 2019
-
Ingår i: Clinical Transplantation. - : WILEY. - 0902-0063 .- 1399-0012. ; 33:12
-
Tidskriftsartikel (refereegranskat)abstract
- Bone loss and endocrine dysfunction are potential late complications of allogeneic stem cell transplant (allo-SCT); however, scant information concerning the long-term effects in SCT adult patients is available. In the present study, we evaluated bone status, expressed as bone mineral density (BMD), and endocrine functions including PTH, TSH, free T4, testosterone, SHBG, FSH, LH, and IGF-1, in 20 adult leukemia patients >10 years after allo-SCT. A low BMD (Z score <-2.0) was observed in two patients; two patients had osteoporotic fractures, and two had a unilateral avascular necrosis of the femoral head. Elevated PTH was observed in 30% of patients, and 25-hydroxy vitamin D (25(OH)D) was low (<50 nmol/L) in 45% of the patients. The majority of the patients had thyroid tests within the reference range, while elevated FSH values were present in 8 of 12 males. We conclude that adult leukemia patients have relatively well-preserved BMD >10 years post-allo-SCT. Prophylactic treatment of osteoporosis should be individualized, but control of BMD is necessary for long-term follow-up. Control of PTH and vitamin D levels before and after allo-SCT is recommended, and vitamin D supplementation should be considered if indicated. Estrogen replacement therapy is a routine treatment in females, whereas gonadal function in males requires further investigation.
|
|
| 12. |
- Gustafsson, Björn, 1948, et al.
(författare)
-
The welfare of Sweden's old-age pensioners in times of bust and boom from 1990
- 2009
-
Ingår i: Ageing & Society. - 0144-686X .- 1469-1779. ; 29:4, s. 539-561
-
Tidskriftsartikel (refereegranskat)abstract
- This study analyses the development of the economic wellbeing of Swedes aged 65 years and older from 1990. This period was characterised by Sweden's deepest and most prolonged recession since the Great Depression, but was then followed by buoyant growth. In a series of interventions from 1991 through to 1998, pensions were cut and their full price indexation abandoned. In spite of these dramatic measures, this study shows that pensioners fared better than the working-age population, but also that poverty among older Swedes increased in absolute terms. During the following years of rapid economic growth, in contrast, the growth in pensioners' income fell behind that of workers and their relative poverty increased. The analysis shows that the limited resources of many older Swedes put them close to a Social poverty line. The study also shows that income inequality among older Swedes has grown with the increasing importance of capital income for the better off We conclude that the increasing gap between better-off and worse-off older people raises issues about the future provision of expenditures on public services for them. The paper concludes that, overall, poverty among older people in Sweden remains low by international standards and that the Swedish welfare state has maintained its resilience.
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
- Leander, Jacob, 1987, et al.
(författare)
-
A stochastic mixed effects model to assess treatment effects and fluctuations in home-measured peak expiratory flow and the association with exacerbation risk in asthma
- 2022
-
Ingår i: Cpt-Pharmacometrics & Systems Pharmacology. - : Wiley. - 2163-8306. ; 11:2, s. 212-224
-
Tidskriftsartikel (refereegranskat)abstract
- Home-based measures of lung function, inflammation, symptoms, and medication use are frequently collected in respiratory clinical trials. However, new statistical approaches are needed to make better use of the information contained in these data-rich variables. In this work, we use data from two phase III asthma clinical trials demonstrating the benefit of benralizumab treatment to develop a novel longitudinal mixed effects model of peak expiratory flow (PEF), a lung function measure easily captured at home using a hand-held device. The model is based on an extension of the mixed effects modeling framework to incorporate stochastic differential equations and allows for quantification of several statistical properties of a patient's PEF data: the longitudinal trend, long-term fluctuations, and day-to-day variability. These properties are compared between treatment groups and related to a patient's exacerbation risk using a repeated time-to-event model. The mixed effects model adequately described the observed data from the two clinical trials, and model parameters were accurately estimated. Benralizumab treatment was shown to improve a patient's average PEF level and reduce long-term fluctuations. Both of these effects were shown to be associated with a lower exacerbation risk. The day-to-day variability was neither significantly affected by treatment nor associated with exacerbation risk. Our work shows the potential of a stochastic model-based analysis of home-based lung function measures to support better estimation and understanding of treatment effects and disease stability. The proposed analysis can serve as a complement to descriptive statistics of home-based measures in the reporting of respiratory clinical trials.
|
|
| 16. |
- Mendoza, Patricia, et al.
(författare)
-
DamID transcriptional profiling identifies the Snail/Scratch transcription factor Kahuli as an Alk target in the Drosophila visceral mesoderm
- 2021
-
Ingår i: Development. - : The Company of Biologists. - 0950-1991 .- 1477-9129. ; 148:23
-
Tidskriftsartikel (refereegranskat)abstract
- Development of the Drosophila visceral muscle depends on Anaplastic Lymphoma Kinase (Alk) receptor tyrosine kinase (RTK) signaling, which specifies founder cells (FCs) in the circular visceral mesoderm (VM). Although Alk activation by its ligand Jelly Belly (Jeb) is well characterized, few target molecules have been identified. Here, we used targeted DamID (TaDa) to identify Alk targets in embryos overexpressing Jeb versus embryos with abrogated Alk activity, revealing differentially expressed genes, including the Snail/Scratch family transcription factor Kahuli (Kah). We confirmed Kah mRNA and protein expression in the VM, and identified midgut constriction defects in Kah mutants similar to those of pointed (pnt). ChIP and RNA-Seq data analysis defined a Kah target-binding site similar to that of Snail, and identified a set of common target genes putatively regulated by Kah and Pnt during midgut constriction. Taken together, we report a rich dataset of Alk-responsive loci in the embryonic VM and functionally characterize the role of Kah in the regulation of embryonic midgut morphogenesis.
|
|
| 17. |
- Palmér, Anne, 1961-
(författare)
-
Samspel och solostämmor : Om muntlig kommunikation i gymnasieskolan
- 2008
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The dissertation investigates oral communication from a language development perspective. The overall aim is to study the oral communication that is part of the learning process for Swedish as a subject and for vocational courses in the upper secondary schools. The focus is specifically on learning that incorporates reasoning and prepared speech.The method used is derived from ethnography and Conversation Analysis. The material consists of fieldnotes, video and audio recordings of lessons from two different classes. The dissertation is theoretically linked to “New Literacy Studies”; the oral prac¬tices and oral cultures involved in the instruction of Swedish are described and viewed as part of school literacy. The concept ‘elaborated topic’ is used to analyse the extent to which students and teachers develop reasoning.The results show that instruction in vocational training programmes can provide students with different conditions for oral language development. Students in the nursing programme took part in more varied communication than students in the technically/practically-oriented programme. The different oral cultures in the two classes could be described in terms of patterns for reasoning and prepared speech, knowledge ideology and power relations. The oral cultures of the classes investigated are reflected in the way they performed in the national test. The students’ ability to develop a sufficiently extensive line of reasoning for the test’s prepared speech did not correspond to how well they developed each topic of discus¬sion.The dissertation emphasises the importance of dialogically organised instruction with students in every upper secondary programme being encour¬aged in their reasoning and prepared speech. It highlights language and communication in and of itself as important content in the instruction of Swedish. Finally, it argues that each subject is responsible for contributing to the language development of students.
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
- Palmér, Sandra, et al.
(författare)
-
Branding in a university: creating value or problems
- 2009
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Business related aspects of branding have long been a subject both in businesses and amongst researchers. In Europe the Bologna process has pushed universities to become unique and to attract staff and students in a more deregulated market. To handle this, several universities have started to work with branding. The phenomenon of branding in a university setting has not previously been extensively researched and we need more studies on what branding may result in. Is it a risky and expensive venture or is it a road to success? This article studies the relationship between how an agreement of brand identity and brand image affects outcomes (commitment, retention, satisfaction and performance) for students and staff. The study was conducted at a university in northern Sweden which has worked intensely with its brand for the past few years. The results, using multiple hierarchical regression, indicate that branding has been successful to a certain extent. Identification with the universities communicated identity is linked to lower propensity to leave and higher commitment as well as higher job satisfaction. This also means that non-identification is linked to the opposite. Thus, this study shows that branding in a university setting works as a magnet and attracts those who concur with the brand and repels those who disagree with the brand. This underlines that the content of the identity is crucial. The people whom are in agreement with this identity must be individuals that the university wants to attract and retain. If this is not the case, branding is counter-productive.
|
|
| 21. |
- Palmér, Sofia, 1987-, et al.
(författare)
-
Validation of primary and outcome data quality in a Swedish population-based breast cancer quality registry
- 2024
-
Ingår i: BMC Cancer. - : BioMed Central (BMC). - 1471-2407. ; 24:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based cancer quality registries are of great importance for the improvement of cancer care. However, little is known about the quality of recurrence data in cancer quality registries. The aim of this study was to evaluate data quality in the regional Breast Cancer Quality Registry of Central Sweden, with emphasis on the validity of recorded information on recurrence.Methods: Validation by re-abstraction was performed on a random sample of 800 women with primary invasive breast cancer stage I-III diagnosed between 1993 and 2010, of which 400 had at least one registered recurrence and 400 had no registered recurrence. Registry data were compared with data from medical records. Exact agreement, correlation and kappa values, sensitivity and specificity were calculated.Results: Seven hundred forty-seven women (93%) were available for analysis. Exact agreement was high for diagnostics, tumor characteristics, surgery, and adjuvant oncological treatment (90% or more for most variables). The registry’s sensitivity was low for regional recurrence (47%), but higher for local and distant recurrence (80% and 75%) ,whereas specificity was overall high (≥ 95%). Combining all recurrence categories irrespective of localization improved sensitivity to 90% with a specificity of 91%. In 87% of women, the date of first recurrence according to medical records fell within ± 90 days of the date recorded in the registry.Conclusions: While the quality of data in the regional Breast Cancer Quality Registry was generally high, data accuracy on recurrences was lower. The overall precision of identifying any recurrence, irrespective of localization, was high. However, the accuracy of classification of recurrences (local, regional or distant) was lower, with evidence of underreporting for each of the recurrence categories. Given the importance of recurrence-related outcomes in the assessment of quality of care, efforts should be made to improve the reporting of recurrences.
|
|
| 22. |
- Pfeifer, Kathrin, et al.
(författare)
-
Patient-associated mutations in Drosophila Alk perturb neuronal differentiation and promote survival.
- 2022
-
Ingår i: Disease models & mechanisms. - : The Company of Biologists. - 1754-8411 .- 1754-8403. ; 15:8
-
Tidskriftsartikel (refereegranskat)abstract
- Activating anaplastic lymphoma kinase (ALK) receptor tyrosine kinase (RTK) mutations occur in pediatric neuroblastoma and are associated with poor prognosis. To study ALK-activating mutations in a genetically controllable system, we employed CRIPSR/Cas9, incorporating orthologs of the human oncogenic mutations ALKF1174L and ALKY1278S in the Drosophila Alk locus. AlkF1251L and AlkY1355S mutant Drosophila exhibited enhanced Alk signaling phenotypes, but unexpectedly depended on the Jelly belly (Jeb) ligand for activation. Both AlkF1251L and AlkY1355S mutant larval brains displayed hyperplasia, represented by increased numbers of Alk-positive neurons. Despite this hyperplasic phenotype, no brain tumors were observed in mutant animals. We showed that hyperplasia in Alk mutants was not caused by significantly increased rates of proliferation, but rather by decreased levels of apoptosis in the larval brain. Using single-cell RNA sequencing, we identified perturbations during temporal fate specification in AlkY1355S mutant mushroom body lineages. These findings shed light on the role of Alk in neurodevelopmental processes and highlight the potential of Alk-activating mutations to perturb specification and promote survival in neuronal lineages. This article has an associated First Person interview with the first author of the paper.
|
|
| 23. |
- Rana, Brinda K., et al.
(författare)
-
Natural variation within the neuronal nicotinic acetylcholine receptor cluster on human chromosome 15q24 : influence on heritable autonomic traits in twin pairs
- 2009
-
Ingår i: Journal of Pharmacology and Experimental Therapeutics. - : American Society for Pharmacology & Experimental Therapeutics (ASPET). - 0022-3565 .- 1521-0103. ; 331:2, s. 419-428
-
Tidskriftsartikel (refereegranskat)abstract
- Nicotinic acetylcholine receptors (nAChRs) are combinations of subunits arranged as pentamers encircling a central cation channel. At least nine α and four β subunits are expressed in the central and peripheral nervous systems; their presence in autonomic ganglia, the adrenal medulla, and central nervous system, with accompanying responses elicited by nicotinic agonists, point to their involvement in cardiovascular homeostasis. nAChRs formed by α3, α5, and β4 subunits may regulate blood pressure (BP) by mediating release of catestatin, the endogenous nicotinic antagonist fragment of chromogranin A (CHGA) and potent inhibitor of catecholamine secretion. Genes encoding these subunits (CHRNA3, CHRNA5, and CHRNB4) are clustered on human chromosome 15q24. Because variation in this cluster may alter autonomic regulation of BP, we sequenced ∼15 kilobase pairs in 15q24 containing their coding and 5′- and 3′-untranslated regions in 80 individuals. We identified 63 variants: 25 in coding regions of CHRNA3, CHRNA5, and CHRNB4 and 48 noncoding single-nucleotide polymorphisms (SNPs). Haplotype frequencies varied across ethnic populations. We assessed the contribution of six SNPs in the putative catestatin binding region of CHRNA3 and CHRNB4 to autonomic traits. In twins, catestatin and BP were heritable. CHRNA3 SNPs and haplotypes containing K95K (G285A) associated with circulating plasma catestatin, epinephrine levels, as well as systolic BP, suggesting altered coupling of the nAChRs to BP. Studies of chromaffin cells in vitro reveal that nicotinic agonist stimulation releases catecholamines and CHGA, a process augmented by overexpression of CHRNA3 and blocked by catestatin. These cellular events suggest a homeostatic mechanism underlying the pleiotropic actions of CHRNA3 genetic variation on autonomic function observed in twins.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Wiklund, Peder, 1985-
(författare)
-
Adipose tissue, the skeleton and cardiovascular disease
- 2011
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Cardiovascular disease (CVD) is the leading cause of death in the Western World, although the incidence of myocardial infarction (MI) has declined over the last decades. However, obesity, which is one of the most important risk factors for CVD, is increasingly common. Osteoporosis is also on the rise because of an aging population. Based on considerable overlap in the prevalence of CVD and osteoporosis, a shared etiology has been proposed. Furthermore, the possibility of interplay between the skeleton and adipose tissue has received increasing attention the last few years with the discovery that leptin can influence bone metabolism and that osteocalcin can influence adipose tissue. A main aim of this thesis was to investigate the effects of fat mass distribution and bone mineral density on the risk of MI. Using dual-energy x-ray absorptiometry (DEXA) we measured 592 men and women for regional fat mass in study I. In study II this was expanded to include 3258 men and women. In study III 6872 men and women had their bone mineral density measured in the total hip and femoral neck using DEXA. We found that a fat mass distribution with a higher proportion of abdominal fat mass was associated with both an adverse risk factor profile and an increased risk of MI. In contrast, a higher gynoid fat mass distribution was associated with a more favorable risk factor profile and a decreased risk of MI, highlighting the different properties of abdominal and gynoid fat depots (study I-II). In study III, we investigated the association of bone mineral density and risk factors shared between CVD and osteoporosis, and risk of MI. We found that lower bone mineral density was associated with hypertension, and also tended to be associated to other CVD risk factors. Low bone mineral density was associated with an increased risk of MI in both men and women, apparently independently of the risk factors studied (study III). In study IV, we investigated 50 healthy, young men to determine if a high-impact loading intervention in the form of a series of jumps would lead to changes in glucose and lipid metabolism. We found that the intervention group had significantly lowered serum glucose levels compared to the control group. Changes in all metabolic parameters favored the intervention group with an increase in lipolysis from baseline and a decrease in cholesterol. In summary, the proportion of abdominal and gynoid fat mass displayed contrasting associations to both CVD risk factors and MI risk. Abdominal fat mass was associated with a higher risk while a high proportion of gynoid fat mass was associated with a lower risk. Bone mineral density displayed an inverse association with MI risk, seemingly independently of CVD risk factors, suggesting other explanations to a shared pathogenesis. Finally, high impact loading on the skeleton in young, healthy men decreased serum glucose levels and tended to improve other metabolic parameters, suggesting that the skeleton can affect energy metabolism.
|
|
