| 61. |
- Jerlström-Hultqvist, Jon, et al.
(författare)
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Genome analysis and comparative genomics of a Giardia intestinalis assemblage E isolate.
- 2010
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Ingår i: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 11, s. 543-
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Tidskriftsartikel (refereegranskat)abstract
- Background Giardia intestinalis is a protozoan parasite that causes diarrhea in a wide range of mammalian species. To further understand the genetic diversity between the Giardia intestinalis species, we have performed genome sequencing and analysis of a wild-type Giardia intestinalis sample from the assemblage E group, isolated from a pig. Results We identified 5012 protein coding genes, the majority of which are conserved compared to the previously sequenced genomes of the WB and GS strains in terms of microsynteny and sequence identity. Despite this, there is an unexpectedly large number of chromosomal rearrangements and several smaller structural changes that are present in all chromosomes. Novel members of the VSP, NEK Kinase and HCMP gene families were identified, which may reveal possible mechanisms for host specificity and new avenues for antigenic variation. We used comparative genomics of the three diverse Giardia intestinalis isolates P15, GS and WB to define a core proteome for this species complex and to identify lineage-specific genes. Extensive analyses of polymorphisms in the core proteome of Giardia revealed differential rates of divergence among cellular processes. Conclusions Our results indicate that despite a well conserved core of genes there is significant genome variation between Giardia isolates, both in terms of gene content, gene polymorphisms, structural chromosomal variations and surface molecule repertoires. This study improves the annotation of the Giardia genomes and enables the identification of functionally important variation.
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| 62. |
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| 63. |
- Kilbo Edlund, Karl, et al.
(författare)
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Occupational particle exposure and chronic kidney disease: a cohort study in Swedish construction workers.
- 2024
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Ingår i: Journal of Occupational and Environmental Medicine. - : BMJ Publishing Group Ltd. - 1351-0711 .- 1470-7926. ; 81:5, s. 238-243
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Tidskriftsartikel (refereegranskat)abstract
- Increasing epidemiological and experimental evidence suggests that particle exposure is an environmental risk factor for chronic kidney disease (CKD). However, only a few case-control studies have investigated this association in an occupational setting. Hence, our objective was to investigate associations between particle exposure and CKD in a large cohort of Swedish construction workers.We performed a retrospective cohort study in the Swedish Construction Workers' Cohort, recruited 1971-1993 (n=286089). A job-exposure matrix was used to identify workers exposed to nine different particulate exposures, which were combined into three main categories (inorganic dust and fumes, wood dust and fibres). Incident CKD and start of renal replacement therapy (RRT) were obtained from validated national registries until 2021 and analysed using adjusted Cox proportional hazards models.Exposure to inorganic dust and fumes was associated with an increased risk of CKD and RRT during working age (adjusted HR for CKD at age <65 years 1.15, 95%CI 1.05 to 1.26). The elevated risk did not persist after retirement age. Exposure to cement dust, concrete dust and diesel exhaust was associated with CKD. Elevated HRs were also found for quartz dust and welding fumes.Workers exposed to inorganic particles seem to be at elevated risk of CKD and RRT. Our results are in line with previous evidence of renal effects of ambient air pollution and warrant further efforts to reduce occupational and ambient particle exposure.
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| 64. |
- Kriit, Hedi Katre, et al.
(författare)
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Using Distributed Lag Non-Linear Models to Estimate Exposure Lag-Response Associations between Long-Term Air Pollution Exposure and Incidence of Cardiovascular Disease
- 2022
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 19:5
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Tidskriftsartikel (refereegranskat)abstract
- Long-term air pollution exposure increases the risk for cardiovascular disease, but little is known about the temporal relationships between exposure and health outcomes. This study aims to estimate the exposure-lag response between air pollution exposure and risk for ischemic heart disease (IHD) and stroke incidence by applying distributed lag non-linear models (DLNMs). Annual mean concentrations of particles with aerodynamic diameter less than 2.5 µm (PM2.5 ) and black carbon (BC) were estimated for participants in five Swedish cohorts using dispersion models. Simultaneous estimates of exposure lags 1–10 years using DLNMs were compared with separate year specific (single lag) estimates and estimates for lag 1–5-and 6–10-years using moving average exposure. The DLNM estimated no exposure lag-response between PM2.5 total, BC, and IHD. However, for PM2.5 from local sources, a 20% risk increase per 1 µg/m3 for 1-year lag was estimated. A risk increase for stroke was suggested in relation to lags 2–4-year PM2.5 and BC, and also lags 8–9-years BC. No associations were shown in single lag models. Increased risk estimates for stroke in relation to lag 1–5-and 6–10-years BC moving averages were observed. Estimates generally supported a greater contribution to increased risk from exposure windows closer in time to incident IHD and incident stroke. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
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| 65. |
- Larsson, Gerry, et al.
(författare)
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A comprehensive system for leader evaluation and development
- 2003
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Ingår i: Leadership & Organization Development Journal. - : Emerald. - 0143-7739 .- 1472-5347. ; 24:1, s. 16-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to describe the development of a theoretical model for leader evaluation and development, an instrument based on this model, and a strategy for large scale implementation in the Swedish armed forces. The model rests on an interactional person by situation paradigm. It emphasises “developmental leadership”, which is inspired by transformational and functionalistic leadership approaches. The developmental leadership questionnaire (DLQ) was operationalised from the model and refined through structural equation modelling. The model and the DLQ will be used for three purposes: yearly evaluation of all personnel in the Swedish armed forces; yearly planning dialogues between each employee and his or her nearest supervisor; and a tool for leadership training. The implementation strategy includes an initial course in developmental leadership for all colonels. This is followed by the selection and training of local trainers, who, in turn, initiate the comprehensive programme locally. The system should be fully implemented by 2005.
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| 66. |
- Larsson, Gerry, et al.
(författare)
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A Comprehensive system for leader evaluation and development
- 2002
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Ingår i: The Leadership & Organization Development Journal. - 0143-7739. ; 24:1, s. 16-25
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to describe the development of a theoretical model for leader evaluation and development, an instrument based on this model, and a strategy for large scale implementation in the Swedish armed forces. The model rests on an interactional person by situation paradigm. It emphasises "developmental leadership", which is inspired by transformational and functionalistic leadership approaches. The developmental leadership questionnaire (DLQ) was operationalised from the model and refined through structural equation modelling. The model and the DLQ will be used for three purposes: yearly evaluation of all personnel in the Swedish armed forces; yearly planning dialogues between each employee and his or her nearest supervisor; and a tool for leadership training. The implementation strategy includes an initial course in developmental leadership for all colonels. This is followed by the selection and training of local trainers, who, in turn, initiate the comprehensive programme locally. The system should be fully implemented by 2005.
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| 67. |
- Lind, Nina, 1989-, et al.
(författare)
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Comorbidity and multimorbidity of asthma and allergy and intolerance to chemicals and certain buildings
- 2017
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Ingår i: Journal of Occupational and Environmental Medicine. - 1076-2752 .- 1536-5948. ; 59:1, s. 80-84
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We tested the hypothesis of high comorbidity between asthma/allergy and chemical intolerance (CI) and between asthma/allergy and building intolerance (BI), and high multimorbidity between asthma/allergy, CI, and BI.Methods: Population-based questionnaire data were used from 530 participants with asthma/allergy (allergic asthma, nonallergic asthma, allergic rhinitis, and/or atopic dermatitis), 414 with self-reported and 112 with physician-diagnosed CI, and 165 with self-reported and 47 with physician-diagnosed BI. Separate reference groups were formed for each of the five case groups.Results: Adjusted odds ratios varied from 4.6 to 13.1 for comorbidity, and from 6.6 to 46.4 for multimorbidity.Conclusion: The large comorbidity and multimorbidity between asthma/allergy, CI, and BI evokes the question as to whether there are similarities in underlying mechanisms between these conditions.
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| 68. |
- Lundtoft, Christian, et al.
(författare)
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Complement C4 copy number variation is linked to SSA/Ro and SSB/La autoantibodies in systemic inflammatory autoimmune diseases.
- 2022
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Ingår i: Arthritis & rheumatology (Hoboken, N.J.). - : Wiley. - 2326-5205 .- 2326-5191. ; 74:8, s. 1440-1450
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. We asked if C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS) or myositis.Using targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterised Scandinavian patients with SLE, pSS or myositis, and 1,251 healthy controls.A prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the three diseases. The strongest association was detected for patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (OR=18.0; CI95% : 10.2-33.3), whereas a weaker association was seen for patients without SSA/SSB autoantibodies (OR=3.1; CI95% : 1.7-5.5). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals' capacity to deposit C4b on immune complexes.We show that a low C4A copy number more strongly is associated with the autoantibody repertoire than with the clinically defined disease entities. These results may have implication for understanding the aetiopathogenetic mechanisms of systemic inflammatory autoimmune diseases, and for patient stratification when taking the genetic profile into account. This article is protected by copyright. All rights reserved.
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| 69. |
- Löfqvist, Chatarina, 1964, et al.
(författare)
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Longitudinal Postnatal Weight and Insulin-like Growth Factor I Measurements in the Prediction of Retinopathy of Prematurity
- 2006
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Ingår i: Arch Ophthalmol. - : American Medical Association (AMA). ; 124:12, s. 1711-1718
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Tidskriftsartikel (refereegranskat)abstract
- Objective To investigate whether postnatal growth and development influence retinopathy of prematurity (ROP) and may be included in screening for ROP. Design We developed an algorithm to predict for individual infants the risk of later ROP development requiring treatment based on the postnatal longitudinal systemic factors of insulin-like growth factor I (IGF-I) level, IGF binding protein 3 level, and postnatal weight gain. We developed the algorithm based on 79 preterm infants considered at risk for ROP by standard criteria (gestational age, 23.6-31.7 weeks) in a longitudinal study measuring weight gain and serum IGF-I and IGF binding protein 3 levels weekly from birth until discharge from the hospital. We monitored deviations from reference models for weight and IGF-I level (preterm children who developed no or minimal ROP) to detect indications for treatable ROP by Early Treatment for Retinopathy of Prematurity study criteria. Results This monitoring method detected 6 (100%) of 6 infants in this cohort who required treatment for ROP with a warning signal at least 5 weeks before requiring treatment and at least 3 weeks before the onset of stage 3 ROP. The majority of infants (61/73 infants) requiring no treatment were also correctly identified. Conclusions Monitoring the postnatal factors of weight, IGF-I level, and IGF binding protein 3 level substantially enhances the clinician's ability to identify patients who will require treatment for ROP.
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| 70. |
- Mihalič, Filip, et al.
(författare)
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Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes
- 2024
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Ingår i: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 41:2
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Tidskriftsartikel (refereegranskat)abstract
- The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 mu M). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.
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