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Sökning: WFRF:(Persson Anders) > Umeå universitet

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11.
  • Brännström, Kristoffer, et al. (författare)
  • Ca2+ enhances Aβ polymerization rate and fibrillar stability in a dynamic manner
  • 2013
  • Ingår i: Biochemical Journal. - : Portland Press. - 0264-6021 .- 1470-8728. ; 450, s. 189-197
  • Tidskriftsartikel (refereegranskat)abstract
    • Identifying factors that affect the self-assembly of the amyloid-β peptide (Aβ) is of utmost importance in the quest to understand the molecular mechanisms causing Alzheimer's disease (AD). Ca2+ has previously been shown to accelerate both Aβ fibril nucleation and maturation, and a dysregulated Ca2+ homeostasis frequently correlates with development of AD. The mechanisms regarding Ca2+ binding as well as its effect on fibril kinetics are not fully understood. Using a polymerization assay we show that Ca2+ in a dynamic and reversible manner enhances both the elongation rate and fibrillar stability, where specifically the "dock and lock" phase mechanism is enhanced. Through NMR analysis we found that Ca2+ affects the fibrillar architecture. In addition, and unexpectedly, we found that Ca2+ does not bind the free Aβ monomer. This implies that Ca2+ binding requires an architecture adopted by assembled peptides, and consequently is mediated through intermolecular interactions between adjacent peptides. This gives a mechanistic explanation to the enhancing effect on fibril maturation and indicates structural similarities between prefibrillar structures and mature amyloid. Taken together we expose how Ca2+ levels affect the delicate equilibrium between the monomeric and assembled Aβ and how fluctuations in vivo may contribute to development and progression of the disease.
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12.
  • Ericsson, Philip, et al. (författare)
  • Personality-dependent inter- and intraspecific foraging competition in the invasive round goby, Neogobius melanostomus
  • 2021
  • Ingår i: Journal of Fish Biology. - : Wiley-Blackwell. - 0022-1112 .- 1095-8649. ; 98:5, s. 1234-1241
  • Tidskriftsartikel (refereegranskat)abstract
    • This study examines the impact of boldness on foraging competition of the highly invasive round goby Neogobius melanostomus Pallas 1815. Individual risk tolerance, or boldness, was measured as the time to resume movement after a simulated predation strike. Fish that resumed movement faster were categorized as "bold," fish that took more time to resume movement were categorized as "shy" and those that fell in between these two categories were determined to have "intermediate" boldness. Competitive impacts of boldness in N. melanostomus were determined in a laboratory foraging experiment in which interspecific (juvenile Atlantic cod Gadus morhua Linnaeus 1758) and intraspecific (intermediate N. melanostomus) individuals were exposed to either bold or shy N. melanostomus competitors. G. morhua consumed fewer prey when competing with bold N. melanostomus than when competing with shy N. melanostomus, whereas intermediately bold N. melanostomus foraging was not affected by competitor boldness. Bold and shy N. melanostomus consumed similar amounts of prey, and the number of interactions between paired fish did not vary depending on the personality of N. melanostomus individuals. Therefore, intraspecific foraging competition was not found to be personality dependent. This study provides evidence that individual differences in boldness can mediate competitive interactions in N. melanostomus; nonetheless, results also show that competition is also governed by other mechanisms that require further study.
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13.
  • Eriksson, Anders, et al. (författare)
  • Diagnostic accuracy of postmortem imaging vs autopsy : a systematic review
  • 2017
  • Ingår i: European Journal of Radiology. - : ELSEVIER IRELAND LTD. - 0720-048X .- 1872-7727. ; 89, s. 249-269
  • Forskningsöversikt (refereegranskat)abstract
    • Background Postmortem imaging has been used for more than a century as a complement to medico-legal autopsies. The technique has also emerged as a possible alternative to compensate for the continuous decline in the number of clinical autopsies. To evaluate the diagnostic accuracy of postmortem imaging for various types of findings, we performed this systematic literature review. Data sources The literature search was performed in the databases PubMed, Embase and Cochrane Library through January 7, 2015. Relevant publications were assessed for risk of bias using the QUADAS tool and were classified as low, moderate or high risk of bias according to pre-defined criteria. Autopsy and/or histopathology were used as reference standard. Findings The search generated 2600 abstracts, of which 340 were assessed as possibly relevant and read in full-text. After further evaluation 71 studies were finally included, of which 49 were assessed as having high risk of bias and 22 as moderate risk of bias. Due to considerable heterogeneity - in populations, techniques, analyses and reporting - of included studies it was impossible to combine data to get a summary estimate of the diagnostic accuracy of the various findings. Individual studies indicate, however, that imaging techniques might be useful for determining organ weights, and that the techniques seem superior to autopsy for detecting gas Conclusions and Implications In general, based on the current scientific literature, it was not possible to determine the diagnostic accuracy of postmortem imaging and its usefulness in conjunction with, or as an alternative to autopsy. To correctly determine the usefulness of postmortem imaging, future studies need improved planning, improved methodological quality and larger materials, preferentially obtained from multi-center studies.
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14.
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15.
  • Lind, Lars, et al. (författare)
  • Obesity is associated with coronary artery stenosis independently of metabolic risk factors : the population-based SCAPIS study
  • 2022
  • Ingår i: Atherosclerosis. - : Elsevier. - 0021-9150 .- 1879-1484. ; 362, s. 1-10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and aims: Previous studies reported divergent results on whether metabolically healthy obesity is associated with increased coronary artery calcium and carotid plaques. We investigated this in a cross-sectional fashion in a large, well-defined, middle-aged population using coronary CT angiography (CCTA) and carotid ultrasound. Methods: In the SCAPIS study (50–65 years, 51% female), CCTA and carotid artery ultrasound were performed in 23,674 individuals without clinical atherosclerotic disease. These subjects were divided into six groups according to BMI (normal weight, overweight, obese) and the presence of metabolic syndrome (MetS) according to the NCEP consensus criteria. Results: The severity of coronary artery stenosis was increased in individuals with obesity without MetS compared to normal-weight individuals without MetS (OR 1.47, 95%CI 1.34–1.62; p < 0.0001), even after adjusting for non-HDL-cholesterol and several lifestyle factors. Such difference was not observed for the presence of carotid artery plaques (OR 0.94, 95%CI 0.87–1.02; p = 0.11). Obese or overweight individuals without any MetS criteria (except the waist criterion) showed significantly more pronounced stenosis in the coronary arteries as compared to the normal-weight individuals, while one criterion was needed to show increased plaque prevalence in the carotid arteries. High blood pressure was the most important single criterion for increased atherosclerosis in this respect. Conclusions: Individuals with obesity without MetS showed increased severity of coronary artery stenosis, but no increased occurrence of carotid artery plaques compared to normal-weight individuals without MetS, further emphasizing that obesity is not a benign condition even in the absence of MetS.
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16.
  • Olofsson, Anders, et al. (författare)
  • Amide solvent protection analysis demonstrates that amyloid-beta(1-40) and amyloid-beta(1-42) form different fibrillar structures under identical conditions.
  • 2007
  • Ingår i: Biochem J. - 1470-8728. ; 404:1, s. 63-70
  • Tidskriftsartikel (refereegranskat)abstract
    • AD (Alzheimer's disease) is a neurodegenerative disorder characterized by self-assembly and amyloid formation of the 39–43 residue long Ab (amyloid-b)-peptide. The most abundant species, Ab(1–40) and Ab(1–42), are both present within senile plaques, but Ab(1–42) peptides are considerably more prone to self-aggregation and are also essential for the development of AD. To understand the molecular and pathological mechanisms behind AD, a detailed knowledge of the amyloid structures of Ab-peptides is vital. In the present study we have used quenched hydrogen/deuterium-exchange NMR experiments to probe the structure of Ab(1–40) fibrils. The fibrils were prepared and analysed identically as in our previous study on Ab(1–42) fibrils, allowing a direct comparison of the two fibrillar structures. The solvent protection pattern of Ab(1–40) fibrils revealed two well-protected regions, consistent with a structural arrangement of two b-strands connected with a bend. This protection pattern partly resembles the pattern found in Ab(1–42) fibrils, but the Ab(1–40) fibrils display a significantly increased protection for the N-terminal residues Phe4–His14, suggesting that additional secondary structure is formed in this region. In contrast, the C-terminal residues Gly37–Val40 show a reduced protection that suggests a loss of secondary structure in this region and an altered filament assembly. The differences between the present study and other similar investigations suggest that subtle variations in fibril-preparation conditions may significantly affect the fibrillar architecture.
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17.
  • Olofsson, Anders, et al. (författare)
  • Quenched hydrogen/deuterium exchange NMR characterization of amyloid-β peptide aggregates formed in the presence of Cu2+ or Zn2
  • 2009
  • Ingår i: The FEBS Journal. - : Wiley InterScience. - 1742-464X .- 1742-4658. ; 276:15, s. 4051-4060
  • Tidskriftsartikel (refereegranskat)abstract
    • Alzheimer's disease, a neurodegenerative disorder causing synaptic impairment and neuronal cell death, is strongly correlated with aggregation of the amyloid-β peptide (Aβ). Divalent metal ions such as Cu2+ and Zn2+ are known to significantly affect the rate of aggregation and morphology of Aβ assemblies in vitro and are also found at elevated levels within cerebral plaques in vivo. The present investigation characterized the architecture of the aggregated forms of Aβ(1–40) and Aβ(1–42) in the presence or absence of either Cu2+ or Zn2+ using quenched hydrogen/deuterium exchange combined with solution NMR spectroscopy. The NMR analyses provide a quantitative and residue-specific structural characterization of metal-induced Aβ aggregates, showing that both the peptide sequence and the type of metal ion exert an impact on the final architecture. Common features among the metal-complexed peptide aggregates are two solvent-protected regions with an intervening minimum centered at Asn27, and a solvent-accessible N-terminal region, Asp1–Lys16. Our results suggest that Aβ in complex with either Cu2+ or Zn2+ can attain an aggregation-prone β-strand–turn–β-strand motif, similar to the motif found in fibrils, but where the metal binding to the N-terminal region guides the peptide into an assembly distinctly different from the fibril form.
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18.
  • Peters, Björn, et al. (författare)
  • Dynamics of urine proteomics biomarker and disease progression in patients with IgA nephropathy
  • 2023
  • Ingår i: Nephrology, Dialysis and Transplantation. - : Oxford University Press. - 0931-0509 .- 1460-2385. ; 38:12, s. 2826-2834
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Immunoglobulin A nephropathy (IgAN) frequently leads to kidney failure. The urinary proteomics-based classifier IgAN237 may predict disease progression at the time of kidney biopsy. We studied whether IgAN237 also predicts progression later in the course of IgAN.Methods: Urine from patients with biopsy-proven IgAN was analyzed using capillary electrophoresis-mass spectrometry at baseline (IgAN237-1, n = 103) and at follow-up (IgAN237-2, n = 89). Patients were categorized as "non-progressors" (IgAN237 ≤0.38) and "progressors" (IgAN237 >0.38). Estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio slopes were calculated.Results: Median age at biopsy was 44 years, interval between biopsy and IgAN237-1 was 65 months and interval between IgAN237-1 and IgAN237-2 was 258 days (interquartile range 71-531). IgAN237-1 and IgAN237-2 values did not differ significantly and were correlated (rho = 0.44, P < .001). Twenty-eight percent and 26% of patients were progressors based on IgAN237-1 and IgAN237-2, respectively. IgAN237 inversely correlated with chronic eGFR slopes (rho = -0.278, P = .02 for score-1; rho = -0.409, P = .002 for score-2) and with ±180 days eGFR slopes (rho = -0.31, P = .009 and rho = -0.439, P = .001, respectively). The ±180 days eGFR slopes were worse for progressors than for non-progressors (median -5.98 versus -1.22 mL/min/1.73 m2 per year for IgAN237-1, P < .001; -3.02 vs 1.08 mL/min/1.73 m2 per year for IgAN237-2, P = .0047). In multiple regression analysis baseline progressor/non-progressor according to IgAN237 was an independent predictor of eGFR180days-slope (P = .001).Conclusion: The urinary IgAN237 classifier represents a risk stratification tool in IgAN also later in the course of the dynamic disease. It may guide patient management in an individualized manner.
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19.
  • Tieva, Åse, et al. (författare)
  • Effect on energy and macronutrient intake with partial replacement of external food supply by in-house cooking at a nursing home for older people in Sweden
  • 2015
  • Ingår i: International Journal of Consumer Studies. - : Wiley. - 1470-6423 .- 1470-6431. ; 39:4, s. 369-379
  • Tidskriftsartikel (refereegranskat)abstract
    • An increased awareness of the importance of nutrition for older people's health and quality of life has underpinned projects and quality improvements for the meal situation in care establishments. The present study took place in a nursing home in a village outside an average-sized town situated in mid-Sweden. Care staff had initiated a change from external catered meals to purchase the food and cook the main meals themselves. The intention was to increase flexibility in accommodating the requests and needs of the elderly and, in doing so, to achieve increased professional pride and satisfaction. To ensure that no negative effects resulted for the residents in the nursing home, outcomes were evaluated through the present intervention study. The objective was to investigate whether and, if so, how their energy and nutrient intake and weight were affected. At the start, only one main hot meal was exchanged for home cooking to avoid work load problems as no increased costs were allowed and no extra staff were to be recruited. The study population consisted of 21 residents, aged 69-97 years. Weight, energy and nutrient intake were recorded before and during the intervention by 3-day food records validated by Goldberg's cutoff method. The same 3 days of the weekSunday to Tuesdayand the same menus were used for both measurement periods. At group level, the energy intake corresponded to the estimated energy requirements, both at baseline and at follow-up, although the intervention resulted in a significantly higher energy intake from the meals cooked in the ward kitchens. Two-thirds of the residents (n=13) slightly increased in weight from baseline to follow-up, while two participants (with body mass index 27.5 kg/m(2) and 33.5 kg/m(2), respectively) lost 5.0 kg and 6.9 kg, respectively. The total protein intake was insufficient both at baseline and follow-up and only met the participants' needs to 8122% and 83 +/- 26%, respectively. In conclusion, the intervention resulted in no adverse consequences for participants in terms of energy and nutrient intake. Most participants were weight stable or had small increases in weight, and the greatest weight gain was observed in the lighter clients. The low protein intake at both time points causes concern and suggests the need for further nutritional interventions to optimize older people's protein intake.
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20.
  • Torén, Kjell, 1952, et al. (författare)
  • Chronic airflow limitation and its relation to respiratory symptoms among ever-smokers and never-smokers: a cross-sectional study
  • 2020
  • Ingår i: Bmj Open Respiratory Research. - : BMJ. - 2052-4439. ; 7:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Background The diagnosis of chronic obstructive pulmonary disease is based on the presence of persistent respiratory symptoms and chronic airflow limitation (CAL). CAL is based on the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1:FVC) after bronchodilation, and FEV1:FVC less than the fifth percentile is often used as a cut-off for CAL. The aim was to investigate if increasing percentiles of FEV1:FVC were associated withany respiratory symptom(cough with phlegm, dyspnoea or wheezing) in a general population sample of never-smokers and ever-smokers. Methods In a cross-sectional study comprising 15 128 adults (50-64 years), 7120 never-smokers and 8008 ever-smokers completed a respiratory questionnaire and performed FEV(1)and FVC after bronchodilation. We calculated theirz-scores for FEV1:FVC and defined the fifth percentile using the Global Lung Function Initiative (GLI) reference value, GLI(5)and increasing percentiles up to GLI(25). We analysed the associations between different strata of percentiles and prevalence ofany respiratory symptomusing multivariable logistic regression for estimation of OR. Results Among all subjects, regardless of smoking habits, the odds ofany respiratory symptomwere elevated up to the GLI(15-20)strata. Among never-smokers, the odds ofany respiratory symptomwere elevated at GLI(<5)(OR 3.57, 95% CI 2.43 to 5.23) and at GLI(5-10)(OR 2.57, 95% CI 1.69 to 3.91), but not at higher percentiles. Among ever-smokers, the odds ofany respiratory symptomwere elevated from GLI(<5)(OR 4.64, 95% CI 3.79 to 5.68) up to GLI(>= 25)(OR 1.33, 95% CI 1.00 to 1.75). Conclusions The association between percentages of FEV1:FVC and respiratory symptoms differed depending on smoking history. Our results support a higher percentile cut-off for FEV1:FVC for never-smokers and, in particular, for ever-smokers.
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