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Sökning: WFRF:(Nyström T.) > (2010-2014)

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1.
  • Thompson, B.A., et al. (författare)
  • Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database
  • 2014
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 46:2, s. 107-115
  • Tidskriftsartikel (refereegranskat)abstract
    • The clinical classification of hereditary sequence variants identified in disease-related genes directly affects clinical management of patients and their relatives. The International Society for Gastrointestinal Hereditary Tumours (InSiGHT) undertook a collaborative effort to develop, test and apply a standardized classification scheme to constitutional variants in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2. Unpublished data submission was encouraged to assist in variant classification and was recognized through microattribution. The scheme was refined by multidisciplinary expert committee review of the clinical and functional data available for variants, applied to 2,360 sequence alterations, and disseminated online. Assessment using validated criteria altered classifications for 66% of 12,006 database entries. Clinical recommendations based on transparent evaluation are now possible for 1,370 variants that were not obviously protein truncating from nomenclature. This large-scale endeavor will facilitate the consistent management of families suspected to have Lynch syndrome and demonstrates the value of multidisciplinary collaboration in the curation and classification of variants in public locus-specific databases. © 2014 Nature America, Inc.
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2.
  • Gyllenberg, A, et al. (författare)
  • Variability in the CIITA gene interacts with HLA in multiple sclerosis.
  • 2014
  • Ingår i: Genes and immunity. - Stockholm : Springer Science and Business Media LLC. - 1476-5470 .- 1466-4879. ; 15, s. 162-167
  • Tidskriftsartikel (refereegranskat)abstract
    • The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.
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  • Al-Khalili, Lubna, et al. (författare)
  • Profiling of human myotubes reveals an intrinsic proteomic signature associated with type 2 diabetes
  • 2014
  • Ingår i: Translational Proteomics. - : Elsevier BV. - 2212-9634 .- 2212-9626. ; 2:1, s. 25-38
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of insulin resistance and type 2 diabetes (T2D) involves a complex array of metabolic defects in skeletal muscle. An in vitro cell culture system excludes the acute effects of external systemic factors existing in vivo. Thus, we aimed to determine whether intrinsic differences in the protein profile exist in cultured myotubes derived from T2D versus normal glucose tolerant (NGT) healthy people. Applying two dimensional difference gel electrophoresis technology (2-D DIGE), the abundance of 47 proteins differed in myotubes derived from T2D patients versus NGT donors. Proteins involved in fatty acid and amino acid metabolism, TCA cycle, mitochondrial function, mRNA processing, DNA repair and cell survival showed higher abundance, while proteins associated with redox signaling (PARK7; Parkinson disease 7), glutathione metabolism (glutathione S-transferase, GST, isoforms T1, P1 and M2), and protein dynamics (heat shock protein, HSP, isoform B1 and 90A) showed reduced abundance in myotubes derived from T2D versus NGT donors. Consistent with our proteome analysis results, the level of total glutathione was reduced in myotubes obtained from T2D versus NGT donors. Taken together, our data provide evidence for intrinsic differences in the profile of proteins involved in energy metabolism, cellular oxidative stress, protein dynamics and gene regulation in myotubes derived from T2D patients. These differences thereby suggest a genetic or epigenetic influence on protein content level, which can be further investigated to understand the molecular underpinnings of T2D progression and lead to new therapeutic approaches.
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  • Galaz, Victor, et al. (författare)
  • Can web crawlers revolutionize ecological monitoring?
  • 2010
  • Ingår i: Frontiers in ecology and the environment. - : Wiley. - 1540-9295. ; 8:2, s. 99-104
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite recent advances, ecosystem service monitoring is limited by insufficient data, the complexity of social–ecological systems, and poor integration of information that tracks changes in ecosystems and economic activities. However, new information and communication technologies are revolutionizing the generation of, and access to, such data. Can researchers who are interested in ecological monitoring tap into these increased flows of information by “mining” the internet to detect “early-warning” signs that may signal abrupt ecological changes? Here, we explore the possibility of using web crawlers and internet-based information to complement conventional ecological monitoring, with a special emphasis on the prospects for avoiding “late warnings”, that is, when ecosystems have already shifted to less desirable states. Using examples from coral reef ecosystems, we explore the untapped potential, as well as the limitations, of relying on web-based information to monitor ecosystem services and forewarn us of negative ecological shifts.
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10.
  • Hagman, Karl, et al. (författare)
  • On the potential roles of ticks and migrating birds in the ecology of West Nile virus
  • 2014
  • Ingår i: Infection Ecology & Epidemiology. - : Informa UK Limited. - 2000-8686. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Mosquitoes are the primary vectors of West Nile virus (WNV). Ticks have, however, been suggested to be potential reservoirs of WNV. In order to investigate their role in the spread of the virus, ticks, which had been collected from birds migrating northwards from Africa to Europe, were analyzed for the potential presence of WNV-RNA.METHODS: On the Mediterranean islands Capri and Antikythira a total of 14,824 birds were captured and investigated from which 747 ticks were collected.RESULTS AND CONCLUSION: Most of the identified ticks (93%) were nymphs and larvae of Hyalomma marginatum sensu lato, most of which were or appear to be Hyalomma rufipes. Of these ticks 729 were individually screened for WNV-RNA. None of the ticks was found to be WNV positive. Thus, there was no evidence that Hyalomma marginatum s.l. ticks play a role in the spread of WNV from Africa to Europe.
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11.
  • Khonsari, R H, et al. (författare)
  • Shape and volume of craniofacial cavities in intentional skull deformations
  • 2013
  • Ingår i: American Journal of Physical Anthropology. - : Wiley. - 0002-9483 .- 1096-8644. ; 151:1, s. 110-119
  • Tidskriftsartikel (refereegranskat)abstract
    • Intentional cranial deformations (ICD) have been observed worldwide but are especially prevalent in preColombian cultures. The purpose of this study was to assess the consequences of ICD on three cranial cavities (intracranial cavity, orbits, and maxillary sinuses) and on cranial vault thickness, in order to screen for morphological changes due to the external constraints exerted by the deformation device. We acquired CT-scans for 39 deformed and 19 control skulls. We studied the thickness of the skull vault using qualitative and quantitative methods. We computed the volumes of the orbits, of the maxillary sinuses, and of the intracranial cavity using haptic-aided semi-automatic segmentation. We finally defined 3D distances and angles within orbits and maxillary sinuses based on 27 anatomical landmarks and measured these features on the 58 skulls. Our results show specific bone thickness patterns in some types of ICD, with localized thinning in regions subjected to increased pressure and thickening in other regions. Our findings confirm that volumes of the cranial cavities are not affected by ICDs but that the shapes of the orbits and of the maxillary sinuses are modified in circumferential deformations. We conclude that ICDs can modify the shape of the cranial cavities and the thickness of their walls but conserve their volumes. These results provide new insights into the morphological effects associated with ICDs and call for similar investigations in subjects with deformational plagiocephalies and craniosynostoses.
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  • Nathanson, D., et al. (författare)
  • Plasma levels of glucagon like peptide-1 associate with diastolic function in elderly men
  • 2011
  • Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 28:3, s. 301-305
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Congestive heart failure is a major cause of morbidity and mortality in diabetes. Besides the glycaemic effects of glucagon-like peptide 1 (GLP-1) mimetics, their effects on the heart are of interest. Methods We aimed to investigate longitudinal relationships between plasma levels of fasting GLP-1 (fGLP-1), 60-min oral glucose tolerance test-stimulated GLP-1 levels (60GLP-1), and the dynamic GLP-1 response after oral glucose tolerance test (Delta GLP-1 = 60GLP-1 - fGLP-1) and incidence of hospitalized congestive heart failure, during a follow-up time of a maximum of 9.8 years in 71-year-old men. We also investigated, cross-sectionally, the association between GLP-1 and left ventricular function as estimated by echocardiography. Results During the follow-up period, 16 of 290 participants with normal glucose tolerance experienced a congestive heart failure event (rate 0.7/100 person-years at risk), as did eight of 136 participants (rate 0.8/100 person-years at risk) with impaired glucose tolerance and nine of 72 participants (rate 1.7/100 person-years at risk) with Type 2 diabetes mellitus. Although GLP-1 concentrations did not predict congestive heart failure (fGLP-1: HR 0.98, 95% CI 0.4-2.4; 60GLP-1: HR 1.1, 95% CI 0.4-2.6; Delta GLP-1: HR 0.9, 95% CI 0.3-2.3), there was an association between left ventricular diastolic function (E/A ratio) and fGLP-1 (r = 0.19, P = 0.001), 60GLP-1 (r = 0.20, P < 0.001) and Delta GLP-1 (r = 0.18, P = 0.004). There was a lack of differences in plasma levels of GLP-1 between the groups with Type 2 diabetes and normal glucose tolerance. Conclusions There were no longitudinal associations between GLP-1 levels and incidence of hospitalization for congestive heart failure. However, without any causality proven, GLP-1 levels did correlate, cross-sectionally, with left ventricular diastolic function in this cohort, suggesting that pathways including GLP-1 might be involved in the regulation of cardiac diastolic function.
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  • Nathanson, D, et al. (författare)
  • Reduced plasma levels of glucagon-like peptide-1 in elderly men are associated with impaired glucose tolerance but not with coronary heart disease
  • 2010
  • Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 53:2, s. 277-280
  • Tidskriftsartikel (refereegranskat)abstract
    • AIMS/HYPOTHESIS: Besides the insulinotropic effects of glucagon-like peptide-1 (GLP-1) mimetics, their effects on endothelial dysfunction and myocardial ischaemia are of interest. No previous study has investigated associations between plasma levels of GLP-1 and CHD. METHODS: We investigated longitudinal relationships of fasting GLP-1 with the dynamic GLP-1 response after OGTT (difference between 60 min OGTT-stimulated and fasting GLP-1 levels [DeltaGLP-1]) and CHD in a population-based cohort of 71-year-old men. In the same cohort, we also cross-sectionally investigated the association between stimulated GLP-1 levels and: (1) cardiovascular risk factors (blood pressure, lipids, urinary albumin, waist circumference and insulin sensitivity index [M/I] assessed by euglycaemic-hyperinsulinaemic clamp); and (2) impaired glucose tolerance (IGT) and type 2 diabetes mellitus. RESULTS: During the follow-up period (maximum 13.8 years), of 294 participants with normal glucose tolerance (NGT), 69 experienced a CHD event (13.8 years), as did 42 of 141 with IGT and 32 of 74 with type 2 diabetes mellitus. DeltaGLP-1 did not predict CHD (HR 1.0, 95% CI 0.52-2.28). The prevalence of IGT was associated with DeltaGLP-1, lowest vs highest quartile (OR 0.3, 95% CI 0.12-0.58), with no such association for type 2 diabetes mellitus (OR 1.0, 95% CI 0.38-2.86). M/I was significantly associated with DeltaGLP-1 in the type 2 diabetes mellitus group (r = 0.38, p < 0.01), but not in the IGT (r = 0.11, p = 0.28) or NGT (r = 0.10, p = 0.16) groups. CONCLUSIONS/INTERPRETATION: Impaired GLP-1 secretion is associated with IGT, but not with type 2 diabetes mellitus. This finding in the latter group might be confounded by oral glucose-lowering treatment. GLP-1 does not predict CHD. Although DeltaGLP-1 was associated with insulin sensitivity in the type 2 diabetes mellitus group, GLP-1 does not seem to be a predictor of CHD in insulin-resistant patients.
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14.
  • Nyholm, Dag, et al. (författare)
  • Frequent administration of levodopa/carbidopa microtablets vs levodopa/carbidopa/entacapone in healthy volunteers
  • 2013
  • Ingår i: Acta Neurologica Scandinavica. - : Hindawi Limited. - 0001-6314 .- 1600-0404. ; 127:2, s. 124-132
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES:An oral dispersible microtablet formulation of levodopa/carbidopa 5/1.25 mg (LC-5) was developed for individualized repeated dosing. The aim was to compare pharmacokinetic profiles of LC-5 and levodopa/carbidopa/entacapone (LCE).MATERIALS AND METHODS:A randomized, crossover study was carried out in 11 healthy subjects. Plasma concentrations of levodopa, carbidopa and 3-O-methyldopa were determined after intake of 300 mg levodopa during the day, either as three intakes of 100/25/200 mg LCE or as a morning dose of 75/18.25 mg followed by five repeated doses of 45/11.25 mg LC-5.RESULTS:Repeated dosing (2.4-hourly) with LC-5 microtablets compared to LCE (6-hourly) avoided long periods with low plasma levodopa levels. Time to maximum plasma concentrations was significantly shorter for LC-5. LC-5 showed lower fluctuation index (FI) in plasma compared to LCE (ANOVA P = 0.0028). FI for dose 2-5 was on average 1.26 for levodopa in LC-5, and 2.23 for dose 1-2 of LCE. The ratio between the two mean FI:s is 0.565; that is, LC-5 gave nearly half the FI as compared to LCE.CONCLUSIONS:Fractionation of levodopa with LC-5 into small, frequent administrations as compared to standard administrations of LCE decreased the FI in plasma for both levodopa and carbidopa by nearly half.
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  • Nyström, Markus B.T., et al. (författare)
  • Is Cognitive Functioning Important for Quality in Ageing?
  • 2014
  • Ingår i: Abstracts of the Psychonomic Society. ; , s. 87-87
  • Konferensbidrag (refereegranskat)abstract
    • Well-being and happiness are two important aspects of quality in ageing. By using a large scale memory data base (the Betula study) the importance of cognitive status (episodic memory) for an individual’s subjective notion of well-being and happiness were investigated, both among middle- and old aged individuals. When a number of factors where controlled for (e.g., physical health, psycho-social aspects), results indicated no relationships between cognitive status and well-being or happiness, in any age group. However, data suggested that subjective experience of memory capacity seems to play an important role. Further, being married, having low levels of stress, and not having sleeping problems, also seem to be associated with both well-being and happiness. The result suggests that other factors, rather than cognitive status, plays a substantial roll in the quality of ageing. Future studies would benefit from using longitudinal data to be able to investigate these relationships over time.
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  • Nyström, Markus B T, et al. (författare)
  • Psychopathy-Related Personality Traits and Shame Management Strategies in Adolescents
  • 2013
  • Ingår i: Journal of Interpersonal Violence. - : SAGE Publications. - 0886-2605 .- 1552-6518. ; 28:3, s. 519-537
  • Tidskriftsartikel (refereegranskat)abstract
    • The purpose of this study was to examine whether there is a correlation between the amount of psychopathy-related personality traits and the type of shame management in adolescents. Two hypotheses were examined; first, that there is a positive correlation between psychopathy-related personality traits and more unconscious and externalized shame management strategies, and second, that there is a negative correlation between psychopathy-related personality traits and more conscious and internalized shame management strategies. Gender differences were also examined. In total, 236 participants were available for the study. All were secondary-level students, aged 16 to 21 years. Of these, 196 were examined: 96 were male and 100 female. The study used two self-assessment forms-the Youth Psychopathic traits Inventory (YPI) and the Compass of Shame Scale (CoSS)-to measure the relevant personality characteristics. The results indicated gender differences, which led to all the analyses being conducted separately for males and females. Support was found for the study's first hypothesis, but not for the second, which was true for both males and females. Our results may have implications for the treatment of adolescents with a high percentage of psychopathy-related personality traits; they also indicate the need for more research on the association between psychopathy and shame management.
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  • Nyström, Magda, 1984, et al. (författare)
  • Numerical simulations of Boger fluids through different contraction configurations for the development of a measuring system for extensional viscosity
  • 2012
  • Ingår i: Rheologica Acta. - : Springer Science and Business Media LLC. - 1435-1528 .- 0035-4511. ; 51:8, s. 713-727
  • Tidskriftsartikel (refereegranskat)abstract
    • This paper reports the flow behaviour of Newtonian and Boger fluids through various axisymmetric contraction configurations by means of numerical predictions. A principal aim has been to evaluate the geometrical design choice of the hyperbolic contraction flow. The FENE-CR model has been used to reflect the behaviour of Boger fluids, with constant shear viscosity, finite (yet large) extensional viscosity and less than quadratic first normal stress difference. Numerical calculations have been performed on six different contraction configurations to evaluate an optimized geometry for measuring extensional viscosity in uniaxial extensional flow. The influence of a sharp or rounded recess-corner on the nozzle has also been investigated. Few commercial measuring systems are currently available for measurement of the extensional rheology of medium-viscosity fluids, such as foods and other biological systems. In this context, a technique based on the hyperbolic contraction flow would be a suitable alternative. The pressure drop, the velocity field, the first normal stress difference and the strain rate across the geometry have each been evaluated for Newtonian and Boger fluids. This numerical study has shown that the hyperbolic configuration is superior to the other geometry choices in achieving a constant extension rate. In this hyperbolic configuration, no vortices are formed, the measuring range is broader and the strain rate is constant throughout the geometric domain, unlike in the alternative configurations tested. The difference between sharp and rounded recess-corner configurations proved to be negligible and a rise in excess pressure drop (epd) for increasing deformation rates has been observed.
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  • Nyström, Olle, 1979, et al. (författare)
  • PHOCUS Radiometer Payload
  • 2011
  • Ingår i: Proceedings of the 22nd International Symposium on Space Terahertz Technology, Tucson, AZ, USA, April 26-28, 2011. ; , s. P-9
  • Konferensbidrag (refereegranskat)abstract
    • PHOCUS – Particles, Hydrogen and Oxygen Chemistry in the Upper Summer Mesosphere is a Swedish sounding rocket experiment with the main goal of investigating the upper atmosphere in the altitude range 50-110 km. This paper describes the radiometer instruments (SondRad) in the PHOCUS payload, which are intended to explore the water vapour concentration in connection with the appearance of noctilucent (night shining) clouds. The design of the radiometer system has been done in collaboration between Omnisys Instruments AB and the Group for Advanced Receiver Development (GARD) at Chalmers University of Technology where Omnisys was responsible for the design, implementation, and verification of the radiometers and backend and GARD was responsible for the optics and calibration systems. The radiometers cover the water absorption lines at 183 GHz and 557 GHz with 67 kHz backend resolution. The 183 GHz channel is a side-looking radiometer while the 557 GHz radiometer is placed along the rocket axis looking in the forward direction. Both channels employ sub-harmonically pumped Schottky mixers and FFT spectrometer back-ends. The 183 GHz channel employs a CW-pilot signal calibrating the entire receiving chain while the IF-chain of the 557 GHz channel is calibrated by injecting a signal from a calibrated noise source through a directional coupler. The instrument will collect complete spectra for both the 183 and 557 GHz with 300 Hz rate for the 183 GHz channel and 10 Hz for the 557 GHz channel for about 60 seconds reaching the apogee of the flight trajectory and 100 seconds after that. With lossless data compression using variable resolution over the spectrum, the data set is reduced to 2 x 12 MByte.
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  • Nyström, Sofia N., et al. (författare)
  • AA-Amyloid is cleared by endogenous immunological mechanisms
  • 2012
  • Ingår i: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 19:3, s. 138-145
  • Tidskriftsartikel (refereegranskat)abstract
    • Reactive amyloidosis is a complication to longstanding inflammatory diseases.Protein amyloid A (AA), an N-terminal fragment of the acute phase protein serumamyloid A, undergoes conformational changes and is deposited as amyloid in tissue.AA-amyloidosis is reversible and reduction of amyloid mass has been reported as theinflammation ceases. Not much is known about the endogenous factors thatcontribute to amyloid resolution. Herein, we describe the dynamics of amyloiddegradation in experimental murine AA-amyloidosis and show that amyloiddegradation depends on macrophages and antibody formation. AA-amyloidosis wasinduced in mice and resolution of amyloid was monitored over time by histologicaltechniques. Internalized amyloid was present in macrophages that appeared at siteof deposition. At 9 months, when virtually all amyloid was cleared, amyloidosis wasre-induced in one group of animals by a single silver nitrate injection. This causedeposition of excessive amounts of amyloid, and indicate that even thoughundetectable the amyloid reseed in the body and can there act as amyloid enhancingfactor. Antibodies directed against protein AA were detected in animals duringamyloid clearance by ELISA-technique. Passive immunization with an amyloidspecific monoclonal antibody, produced by a B-cell clone recovered from an animalwith advanced AA-amyloidosis, diminish amyloid deposits in murine AA-amyloidosis.Immunoglobulins co-localize with amyloid deposits and can contribute to amyloiddegradation by Fc-receptor mediated phagocytosis.
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22.
  • Sun, Chengjun, et al. (författare)
  • CRYAB-650 C>G (rs2234702) affects susceptibility to type 1 diabetes and IAA-positivity in Swedish population
  • 2012
  • Ingår i: Human Immunology. - : Elsevier. - 0198-8859 .- 1879-1166. ; 73:7, s. 759-766
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Single nucleotide polymorphisms (SNPs) in the promoter region of CRYAB gene have been associated with in multiple sclerosis. CRYAB gene, which encodes alpha B-crystallin (a member of small heat shock protein), was reported as a potential autoimmune target. In this study we investigated whether SNPs in the promoter region of CRYAB gene were also important in the etiology of Type 1 diabetes (T1D).METHODS: Genotyping of SNPs in the promoter region of CRYAB gene was performed in a Swedish cohort containing 444 T1D patients and 350 healthy controls. Three SNPs were included in this study: CRYAB-652 A>G (rs762550), -650 C>G (rs2234702) and -249 C > G (rs14133). Two SNPs (CRYAB-652 and -650) were not included in previous genome wide association studies.RESULTS: CRYAB-650 (rs2234702)*C allele was significantly more frequent in patients than in controls (OR = 1.48, Pc = 0.03). CRYAB-650*C allele was associated with IAA positivity (OR = 8.17, Pc < 0.0001) and IA-2A positivity (OR = 2.14, Pc = 0.005) in T1D patients. This association with IAA was amplified by high-risk HLA carrier state (OR = 10.6, P < 0.0001). No association was found between CRYAB-650 and other autoantibody positivity (GADA and ICA). CRYAB haplotypes were also associated with IAA and IA-2A positivity (highest OR = 2.07 and 2.11, respectively), these associations remain in high HLA-risk T1D patients.CONCLUSIONS: CRYAB-650 was associated with T1D in the Swedish cohort we studied. CRYAB-650*C allele might confers susceptibility to the development of T1D. CRYAB-650 was also associated with the development of IAA-positivity in T1D patients, especially in those carrying T1D high-risk HLA haplotypes.
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23.
  • Sundqvist, E., et al. (författare)
  • Cytomegalovirus seropositivity is negatively associated with multiple sclerosis
  • 2014
  • Ingår i: Multiple Sclerosis. - : SAGE Publications. - 1352-4585 .- 1477-0970. ; 20:2, s. 165-173
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Epidemiological data suggest a role for common viruses in the pathogenesis of multiple sclerosis (MS), and recent data showed a negative association of past cytomegalovirus (CMV) infection on pediatric MS risk. Objective: Our aim was to analyze the association of CMV infection with MS risk in an adult case-control material. A meta-analysis was performed to validate our findings. Methods: Epidemiological Investigation in MS (EIMS) is a case-control study with incident cases and population-based controls. Anti-CMV antibody titers were measured with ELISA, and HLA-A and DRB1 genotyping was performed with SSP-PCR, in 658 MS cases, who all fulfilled the McDonald criteria for MS, and 786 controls. Results: CMV seropositivity was associated with a decreased MS risk, OR = 0.73 (0.58-0.92 95% CI), p = 0.005, adjusted for index age, gender, smoking, sun exposure, EBNA1 IgG titer and HLA-A*02 and DRB1*15. When we removed all cases and controls younger than 18 years at index, the protective effect was still apparent. Conclusions: CMV is negatively associated with adult-onset MS pathology, consistent with results from a study on pediatric MS cases. It remains to be shown whether this negative association is due to a true protective effect of CMV infection on MS risk. © 2013 The Author(s).
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  • Wallmenius, Katarina, et al. (författare)
  • Spotted fever Rickettsia species in Hyalomma and Ixodes ticks infesting migratory birds in the European Mediterranean area
  • 2014
  • Ingår i: Parasites & Vectors. - : Springer Science and Business Media LLC. - 1756-3305. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: A few billion birds migrate annually between their breeding grounds in Europe and their wintering grounds in Africa. Many bird species are tick-infested, and as a result of their innate migratory behavior, they contribute significantly to the geographic distribution of pathogens, including spotted fever rickettsiae. The aim of the present study was to characterize, in samples from two consecutive years, the potential role of migrant birds captured in Europe as disseminators of Rickettsia-infected ticks. Methods: Ticks were collected from a total of 14,789 birds during their seasonal migration northwards in spring 2009 and 2010 at bird observatories on two Mediterranean islands: Capri and Antikythira. All ticks were subjected to RNA extraction followed by cDNA synthesis and individually assayed with a real-time PCR targeting the citrate synthase (gltA) gene. For species identification of Rickettsia, multiple genes were sequenced. Results: Three hundred and ninety-eight (2.7%) of all captured birds were tick-infested; some birds carried more than one tick. A total number of 734 ticks were analysed of which 353 +/- 1 (48%) were Rickettsia-positive; 96% were infected with Rickettsia aeschlimannii and 4% with Rickettsia africae or unidentified Rickettsia species. The predominant tick taxon, Hyalomma marginatum sensu lato constituted 90% (n = 658) of the ticks collected. The remaining ticks were Ixodes frontalis, Amblyomma sp., Haemaphysalis sp., Rhipicephalus sp. and unidentified ixodids. Most ticks were nymphs (66%) followed by larvae (27%) and adult female ticks (0.5%). The majority (65%) of ticks was engorged and nearly all ticks contained visible blood. Conclusions: Migratory birds appear to have a great impact on the dissemination of Rickettsia-infected ticks, some of which may originate from distant locations. The potential ecological, medical and veterinary implications of such Rickettsia infections need further examination.
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26.
  • Weinert, B. T., et al. (författare)
  • Acetyl-Phosphate Is a Critical Determinant of Lysine Acetylation in E. coli
  • 2013
  • Ingår i: Molecular Cell. - : Elsevier BV. - 1097-2765. ; 51:2, s. 265-272
  • Tidskriftsartikel (refereegranskat)abstract
    • Lysine acetylation is a frequently occurring post-translational modification in bacteria; however, little is known about its origin and regulation. Using the model bacterium Escherichia coil (E. coil), we found that most acetylation occurred at a low level and accumulated in growth-arrested cells in a manner that depended on the formation of acetyl-phosphate (AcP) through glycolysis. Mutant cells unable to produce AcP had significantly reduced acetylation levels, while mutant cells unable to convert AcP to acetate had significantly elevated acetylation levels. We showed that AcP can chemically acetylate lysine residues in vitro and that AcP levels are correlated with acetylation levels in vivo, suggesting that AcP may acetylate proteins nonenzymatically in cells. These results uncover a critical role for AcP in bacterial acetylation and indicate that most acetylation in E. coil occurs at a low level and is dynamically affected by metabolism and cell proliferation in a global, uniform manner.
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