| 41. |
- Berg, Ina, 1982-
(författare)
-
Modeling Amyloid Disease in Drosophila melanogaster
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Amyloid diseases are caused by protein misfolding and aggregation. To date there are 27 known proteins causing amyloid disorders involving brain and peripheral protein deposition. The proteins involved in this mechanism do not share sequence homology, but the amyloid fibrils share biophysical properties and possibly a common pathogenic mechanism. Amyloid deposits are known to be involved in a broad range of neurodegenerative diseases, such as Alzheimer’s disease and Creutzfeldt-Jakob disease, as well as in non-neuropathic diseases, such as senile systemic amyloidosis and type II diabetes.During the last decade the fruit fly, Drosophila melanogaster (Drosophila), have increasingly been used as a model for neurodegenerative disease, such as Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis, and familial amyloidotic polyneuropathy. The advantages of using the Drosophila model are the well-defined genetic characteristics, the quantity, short life span, simplicity in genetic manipulation and the powerful binary UAS-Gal4 transgenic system. The UAS-Gal4 system allows for rapid generation of individual strains in which expression of a specific gene of interest can be directed to different tissues or cell types. The system allows the target gene to be activated in different cell- and tissue-types by altering the activator-expressing lines.This thesis has been focused on modeling amyloid diseases in Drosophila. This has been performed by:Creating new model systems of senile systemic amyloidosis and familial amyloidotic polyneuropathy in DrosophilaDeveloping a new staining protocol for detection of amyloid in DrosophilaInitiate a compound screen of Alzheimer’s disease modeled in Drosophila
|
|
| 42. |
- Berg, Ina, et al.
(författare)
-
Modeling Familial Amyloidotic Polyneuropathy (Transthyretin V30M) in Drosophila melanogaster
- 2009
-
Ingår i: NEURODEGENERATIVE DISEASES. - : S. Karger AG. - 1660-2854 .- 1660-2862. ; 6:3, s. 127-138
-
Tidskriftsartikel (refereegranskat)abstract
- Background/Aims: Transthyretin (TTR) is a prevalent plasma and cerebrospinal fluid protein associated with sporadic and heritable amyloidosis. TTR amyloidosis is linked to a vast number of mutations with varying phenotype, tissue distribution and age of onset. The most prevalent mutation associated with familial amyloidotic polyneuropathy (FAP) is the V30M mutation. Studies of transgenic mouse models of TTR V30M FAP have been hampered by variable phenotype, low disease penetrance, and slow onset. Methods/Results: To model TTR-associated amyloid disease in the Drosophila model system, transgenic Drosophila were generated, expressing wild-type (wt) TTR or TTR V30M, associated with sporadic senile systemic amyloidosis (SSA) and inherited FAP, respectively. We found that expression of FAP-associated TTR V30M mutant in the nervous system resulted in reduced lifespan and in reduced climbing ability indicating neurological impairment, whereas expression of TTR wt showed a milder phenotype. Congo red staining of the Drosophila brain shows positive amyloid binding in the aged TTR V30M flies. Extensive brain vacuole formation was evident for the aged TTR V30M flies, whereas a milder phenotype was shown by the TTR wt flies. In addition, expression of TTR V30M in the eye leads to tissue damage, including rough eye, morphological changes and fibrous deposition. Conclusion: Our results suggest that Drosophila is a promising complementary system for studies of TTR-associated amyloid diseases.
|
|
| 43. |
- Björk, Linnea, et al.
(författare)
-
Amino-Acid Side-Chain Nanoarchitectonics for Tuning the Chiroptical Properties and Supramolecular Structure of Pentameric Oligothiophenes
- 2024
-
Ingår i: ChemPhotoChem. - : WILEY-V C H VERLAG GMBH. - 2367-0932.
-
Tidskriftsartikel (refereegranskat)abstract
- Oligothiophenes with specific photophysical properties and molecular organization are of great interest, since this class of materials are used in organic electronics and bioelectronics, as well as biosensing. Herein, 8 different pentameric oligothiophenes, denoted proteophenes, with different amino acid substitution patterns at distinct positions along the thiophene backbone were investigated. Spectroscopic and microscopic studies of the ligands revealed the formation of optically active self-assembled materials under acidic or basic conditions. The distinct photophysical characteristics, including induced circular dichroism, as well as the supramolecular structures of the assemblies deduced from light scattering and transmission electron microscopy, were highly influenced by the positioning of distinct amino acid moieties along the thiophene backbone. Proteophenes functionalized with only glutamate residues or these functionalities in combination with hydrophobic valine moieties formed fibrillar structures with excellent chiroptical properties under acidic conditions. In addition, the amino acid functionality at the beta-position of distinct thiophene moieties influenced the induced circular dichroism pattern observed from the proteophenes. Overall, the obtained results demonstrate how changes in the position of various amino acid functionalities, as well as the chemical nature of the amino acid side chain functionality greatly affect the optical properties as well as the architecture of the self-assembled materials. Self-assembled Proteophenes. Oligothiophenes with distinct amino acid side-chain functionalities along the conjugated backbone displayed distinct chiroptical and structural properties in acidic or alkaline solutions. The distinct photophysical characteristics, as well as the supramolecular structures of the assemblies were highly influenced by the chemical nature of the amino acid, as well as the positioning of distinct amino acid moieties along the thiophene backbone.image
|
|
| 44. |
- Björkman, Andrea, et al.
(författare)
-
Aberrant recombination and repair during immunoglobulin class switching in BRCA1-deficient human B cells.
- 2015
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 112:7, s. 2157-2162
-
Tidskriftsartikel (refereegranskat)abstract
- Breast cancer type 1 susceptibility protein (BRCA1) has a multitude of functions that contribute to genome integrity and tumor suppression. Its participation in the repair of DNA double-strand breaks (DSBs) during homologous recombination (HR) is well recognized, whereas its involvement in the second major DSB repair pathway, nonhomologous end-joining (NHEJ), remains controversial. Here we have studied the role of BRCA1 in the repair of DSBs in switch (S) regions during immunoglobulin class switch recombination, a physiological, deletion/recombination process that relies on the classical NHEJ machinery. A shift to the use of microhomology-based, alternative end-joining (A-EJ) and increased frequencies of intra-S region deletions as well as insertions of inverted S sequences were observed at the recombination junctions amplified from BRCA1-deficient human B cells. Furthermore, increased use of long microhomologies was found at recombination junctions derived from E3 ubiquitin-protein ligase RNF168-deficient, Fanconi anemia group J protein (FACJ, BRIP1)-deficient, or DNA endonuclease RBBP8 (CtIP)-compromised cells, whereas an increased frequency of S-region inversions was observed in breast cancer type 2 susceptibility protein (BRCA2)-deficient cells. Thus, BRCA1, together with its interaction partners, seems to play an important role in repairing DSBs generated during class switch recombination by promoting the classical NHEJ pathway. This may not only provide a general mechanism underlying BRCA1's function in maintaining genome stability and tumor suppression but may also point to a previously unrecognized role of BRCA1 in B-cell lymphomagenesis.
|
|
| 45. |
- Bohlin, Anna, et al.
(författare)
-
Perceived gender inequality in the couple relationship and musculoskeletal pain in middle-aged women and men
- 2013
-
Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 41:8, s. 825-831
-
Tidskriftsartikel (refereegranskat)abstract
- Aims: Musculoskeletal pain is a major health problem, especially in women, and is partially determined by psychosocial factors. The aim of the present study was to investigate whether gender inequality in the couple relationship was related to musculoskeletal pain. Methods: Participants (n=721; 364 women and 357 men) were all individuals living in a couple relationship in the Northern Swedish Cohort, a 26-year Swedish cohort study. Self-administered questionnaire data at age 42 years comprised perceived gender inequality in the couple relationship and musculoskeletal pain (in three locations, summarised into one score and median-split), concurrent demographic factors, psychological distress, and previous musculoskeletal pain at age 30 years. Associations were examined using logistic regression. Results: Gender inequality was positively associated with symptoms of musculoskeletal pain in the total sample, remaining significant after addition of possible confounders and of previous musculoskeletal pain. Separate adjustment for concurrent psychological distress attenuated the association but not below significance. The association was present and of comparable strength in both women and men. Conclusions: Gender inequality in the couple relationship might contribute to the experience of musculoskeletal pain in both women and men. The results highlight the potential adverse bodily consequences of living in unequal relationships.
|
|
| 46. |
- Brydsten, Anna, et al.
(författare)
-
Does contextual unemployment matter for health status across the life course?
- 2016
-
Ingår i: European Journal of Public Health. - : Oxford University Press. - 1101-1262 .- 1464-360X. ; 26:Suppl 1, s. 142-142
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Individual health is affected by one’s individual life conditionsand by the context in which individuals live, interact anddevelop. Research shows that living in a neighbourhood withhigh levels of unemployment might affect residents’ health, atleast partially independent of own labour market status.However, how such contextual-individual transactions playout across the life course is unknown. The present study aims:(i) to examine whether neighbourhood unemployment isrelated to health status across the life course independently ofthe individual employment from adolescence to middle age(age 16 to 42); and (ii) to analyse whether this relationship isobservable at four specific life course periods from adolescenceto middle age (age 16, 21, 30 and 42).Methods: A 26-year prospective Swedish cohort (n = 1010), linked toregister data on neighbourhood unemployment. Individualemployment and functional somatic symptoms were measuredby self-reported questionnaire data. Two models of hierarchallinear regressions were built: a longitudinal analysis, and a setof age-specific cross-sectional analyses at each age.Results: The longitudinal analysis showed an independent contributionof neighbourhood unemployment and individual employmenton FSS across the life course. The cross-sectional analysisshowed an association at age 30, when accounting forindividual employment, but no association was found at age21 and 42.Conclusions: Neighbourhood unemployment has a significant relationshipwith functional somatic symptoms across the life course. Thereseems to be an age-specific pattern where neighbourhoodunemployment may have stronger implications in earlyadulthood than in other phases of the life courseKey messages:High neighbourhood unemployment predicts higher levelsof individual FSS across the life course, independently ofown labour market position, socioeconomic status andeducationThese findings stress the importance of neighbourhoodunemployment for current health status as well as development of health status across the life course, particular duringearly adulthood
|
|
| 47. |
- Brydsten, Anna, et al.
(författare)
-
Does contextual unemployment matter for health status across the life course? A longitudinal multilevel study exploring the link between neighbourhood unemployment and functional somatic symptoms
- 2017
-
Ingår i: Health and Place. - : Elsevier BV. - 1353-8292 .- 1873-2054. ; 43, s. 113-120
-
Tidskriftsartikel (refereegranskat)abstract
- This study examines whether neighbourhood unemployment is related to functional somatic symptoms, independently of the individual employment, across the life course and at four specific life course periods (age 16, 21, 30 and 42). Self-reported questioner data was used from a 26-year prospective Swedish cohort (n=1010) with complementary neighbourhood register data. A longitudinal and a set of age-specific cross-sectional hierarchal linear regressions was carried out. The results suggest that living in a neighbourhood with high unemployment has implications for residents' level of functional somatic symptoms, regardless of their own unemployment across time, particularly at age 30.
|
|
| 48. |
- Brydsten, Anna, 1984-
(författare)
-
Yesterday once more? Unemployment and health inequalities across the life course in northern Sweden
- 2017
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- AbstractBackground. It is relatively well established in previous research that unemployment has direct health consequences in terms of mental and physical ill health. Recently, knowledge has emerged indicating that unemployment can lead to economic consequences that remain long after re-establishment in the labour market. However, few empirical studies have been able to apply a life course perspective asking whether there are also long-term health consequences of unemployment, and, when and in which context unemployment may affect the individual health status across the life course. The aim of this thesis was to analyse the relationship between unemployment and illness across the life course, and how it relates to individual and structural factors in the geographical setting of northern Sweden. In particular, three main areas have been explored: youth unemployment and illness in adulthood (Paper I and Paper II), contextual unemployment of national unemployment rate and neighbourhood unemployment (Paper II and Paper III) and lastly, social determinants of health inequality between employment statuses (Paper IV).Methods. This thesis is positioned in Sweden between the early 1980s and the mid-2010s, following two comparable cohorts sampled from northern Sweden (26 and 19 years follow-up time respectively from youth to midlife) and a cross-sectional sample from 2014 of the four northernmost counties in Sweden. The two longitudinal cohorts comprised the Northern Swedish Cohort and the Younger Northern Swedish Cohort, consisting of all pupils in the 9th grade of compulsory school in Luleå municipality in 1981 and 1989. The participants responded to an extensive questionnaire on socioeconomic factors, work and health, in 5 and 2 waves respectively of data collections. Neighbourhood register data from Statistics Sweden was also collected for all participants in the Northern Sweden Cohort. At the latest data collection, 94.3% (n=1010) participated in the Northern Sweden Cohort and 85.6% (n=686) in the Younger Northern Sweden Cohort. The cross-sectional study Health on Equal Terms is a national study, administered by the Public Health Agency together with Statistics Sweden and county councils with the aim of mapping public health and living conditions in the country over time. In this thesis, material from 2014 has been used for northern Sweden with a response rate of around 50% (effective sample n=12769). The statistical analyses used were linear regression, multilevel analysis and difference-in-difference analysis to estimate the concurrent and long-term health consequences of unemployment, and a decomposition analysis to disentangle the inequality in health between different labour market positions. The health outcomes in focus were functional somatic symptoms (the occurrence of relatively common physical illnesses such as head, muscle and stomach ache, insomnia and palpitation) and psychological distress.Results. Among men only, as little as one month of youth unemployment was related to increased levels of functional somatic symptoms in midlife, regardless of previous ill health or unemployment later in life, although only during relatively low national unemployment (pre-recession) when comparing with youth unemployment during high national unemployment (recession). This was explained by the health promoting effect of more time spent in higher education during the recession period. Furthermore, the health impact of neighbourhood unemployment highlights the importance of the contextual setting for individuals’ health both across the life course and at specific periods of life. Lastly, employment-related mental health inequalities exist for both men and women in all life phases (youth, adulthood and midlife). Economic and social deprivation related to unemployment and illness varied across different phases in life and across genders.Conclusion. The key findings of this thesis paint a rather pessimistic vision of the future: one’s own and others’ unemployment may cause not only ill health today but also ill health later in life. Importantly, the responsibility of unemployment and the associated ill health should not be placed on the already marginalised individuals and communities. Instead, the responsibility should be directed towards the structural aspects of society and the political choices that shape these. In other words, health inequality manifested by the position in the labour market is socially produced, unfair and changeable through political decisions. The results of this study therefore cannot contribute to any simple or concrete solutions to the concurrent or long-term health consequences of individual or contextual unemployment, as the solution is beyond the areas of responsibility and abilities of research. However, if there are long-term health consequences of one’s own and other people’s unemployment, labour market and public health policies should be initiated from a young age and continue throughout the life course to reduce individual suffering and future costs of social insurance, sick-leave and unemployment benefits.
|
|
| 49. |
- Byhamre, Marja Lisa, et al.
(författare)
-
Snus use during the life-course and risk of the metabolic syndrome and its components
- 2017
-
Ingår i: Scandinavian Journal of Public Health. - : Sage Publications. - 1403-4948 .- 1651-1905. ; 45:8, s. 733-740
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: We aimed to investigate the association between life-course exposure to snus and prevalence of the metabolic syndrome and its components in adulthood.Design and method: Tobacco habits at baseline (age 16) and three follow-ups (ages 21, 30 and 43) were assessed among 880 participants in a population-based cohort in Northern Sweden. Presence of the metabolic syndrome at age 43 was ascertained using the International Diabetes Federation criteria. Odds ratios and CIs for risk of the metabolic syndrome and its components by snus use at 16, 21, 30 and 43 years were calculated using logistic regression. Cumulative snus use was defined as number of life periods (1-4) with current snus use.Results: At age 43, 164 participants (18.6%) were current snus users. We found no association between exclusive snus use at the ages of 16, 21, 30 and 43 years and the metabolic syndrome at age 43 years. Snus use (among non-smokers) was associated with raised triglycerides and high blood pressure in crude analysis, but not in multivariable models. There was no association between cumulative snus use and risk of the metabolic syndrome. Cumulative snus use was associated with central obesity, raised triglycerides and impaired fasting glucose/diabetes mellitus type 2 in crude analyses, but not after adjustments.Conclusion: The health consequences of snus exposure from adolescence to mid-adulthood do not seem to include increased risk of the metabolic syndrome or its components. The cardio-metabolic risk of dual exposure to snus and cigarettes may warrant further attention.
|
|
| 50. |
- Bäck, Marcus, et al.
(författare)
-
Tyrosine Side-Chain Functionalities at Distinct Positions Determine the Chirooptical Properties and Supramolecular Structures of Pentameric Oligothiophenes
- 2020
-
Ingår i: ChemistryOpen. - : Wiley. - 2191-1363. ; 9:11, s. 1100-1108
-
Tidskriftsartikel (refereegranskat)abstract
- Control over the photophysical properties and molecular organization of pi-conjugated oligothiophenes is essential to their use in organic electronics. Herein we synthesized and characterized a variety of anionic pentameric oligothiophenes with different substitution patterns of L- or D-tyrosine at distinct positions along the thiophene backbone. Spectroscopic, microscopic, and theoretical studies of L- or D-tyrosine substituted pentameric oligothiophene conjugates revealed the formation of optically active pi-stacked self-assembled aggregates under acid conditions. The distinct photophysical characteristics, as well as the supramolecular structures of the assemblies, were highly influenced by the positioning of the L- or D-tyrosine moieties along the thiophene backbone. Overall, the obtained results clearly demonstrate how fundamental changes in the position of the enantiomeric side-chain functionalities greatly affect the optical properties as well as the architecture of the self-assembled supramolecular structures.
|
|
