| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
- Wang, Li-San, et al.
(författare)
-
Rarity of the Alzheimer Disease-Protective APP A673T Variant in the United States.
- 2015
-
Ingår i: JAMA neurology. - : American Medical Association (AMA). - 2168-6157 .- 2168-6149. ; 72:2
-
Tidskriftsartikel (refereegranskat)abstract
- Recently, a rare variant in the amyloid precursor protein gene (APP) was described in a population from Iceland. This variant, in which alanine is replaced by threonine at position 673 (A673T), appears to protect against late-onset Alzheimer disease (AD). We evaluated the frequency of this variant in AD cases and cognitively normal controls to determine whether this variant will significantly contribute to risk assessment in individuals in the United States.
|
|
| 13. |
- Elsik, Christine G., et al.
(författare)
-
The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
-
Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
|
|
| 14. |
- Edelson, R. A., et al.
(författare)
-
Multiwavelength observations of short-timescale variability in NGC 4151. IV. Analysis of multiwavelength continuum variability
- 1996
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 470:1, s. 364-377377
-
Tidskriftsartikel (refereegranskat)abstract
- For pt.III see ibid., vol.470, no.1, p.349-63 (1996). Combines data from the three preceding papers in order to analyze the multi wave-band variability and spectral energy distribution of the Seyfert 1 galaxy NGC 4151 during the 1993 December monitoring campaign. The source, which was near its peak historical brightness, showed strong, correlated variability at X-ray, ultraviolet, and optical wavelengths. The strongest variations were seen in medium-energy (~1.5 keV) X-rays, with a normalized variability amplitude (NVA) of 24%. Weaker (NVA=6%) variations (uncorrelated with those at lower energies) were seen at soft gamma-ray energies of ~100 keV. No significant variability was seen in softer (0.1-1 keV) X-ray bands. In the ultraviolet/optical regime, the NVA decreased from 9% to 1% as the wavelength increased from 1275 to 6900 Aring. These data do not probe extreme ultraviolet (1200 Aring to 0.1 keV) or hard X-ray (250 keV) variability. The phase differences between variations in different bands were consistent with zero lag, with upper limits of lsim0.15 day between 1275 Aring and the other ultraviolet bands, lsim0.3 day between 1275 Aring and 1.5 keV, and lsim1 day between 1275 and 5125 Aring. These tight limits represent more than an order of magnitude improvement over those determined in previous multi-wave-band AGN monitoring campaigns. The ultraviolet fluctuation power spectra showed no evidence for periodicity, but were instead well fitted with a very steep, red power law (ales-2.5)
|
|
| 15. |
- Van Deerlin, Vivian M, et al.
(författare)
-
Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:3, s. 234-239
-
Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal lobar degeneration (FTLD) is the second most common cause of presenile dementia. The predominant neuropathology is FTLD with TAR DNA-binding protein (TDP-43) inclusions (FTLD-TDP). FTLD-TDP is frequently familial, resulting from mutations in GRN (which encodes progranulin). We assembled an international collaboration to identify susceptibility loci for FTLD-TDP through a genome-wide association study of 515 individuals with FTLD-TDP. We found that FTLD-TDP associates with multiple SNPs mapping to a single linkage disequilibrium block on 7p21 that contains TMEM106B. Three SNPs retained genome-wide significance following Bonferroni correction (top SNP rs1990622, P = 1.08 x 10(-11); odds ratio, minor allele (C) 0.61, 95% CI 0.53-0.71). The association replicated in 89 FTLD-TDP cases (rs1990622; P = 2 x 10(-4)). TMEM106B variants may confer risk of FTLD-TDP by increasing TMEM106B expression. TMEM106B variants also contribute to genetic risk for FTLD-TDP in individuals with mutations in GRN. Our data implicate variants in TMEM106B as a strong risk factor for FTLD-TDP, suggesting an underlying pathogenic mechanism.
|
|
| 16. |
- Crenshaw, D. M., et al.
(författare)
-
Multiwavelength observations of short-timescale variability in NGC 4151. I. Ultraviolet observations
- 1996
-
Ingår i: Astrophysical Journal. - : American Astronomical Society. - 0004-637X .- 1538-4357. ; 470:1, s. 322-335335
-
Tidskriftsartikel (refereegranskat)abstract
- Presents the results of an intensive ultraviolet monitoring campaign on the Seyfert 1 galaxy NGC 4151, as part of an effort to study its short-timescale variability over a broad range in wavelength. The nucleus of NGC 4151 was observed continuously with the International Ultraviolet Explorer for 9.3 days, yielding a pair of LWP and SWP spectra every ~70 minutes, and during 4 hr periods for 4 days prior to and 5 days after the continuous-monitoring period. The sampling frequency of the observations is an order of magnitude higher than that of any previous UV monitoring campaign on a Seyfert galaxy. The continuum fluxes in bands from 1275 to 2688 Aring went through four significant and well-defined ldquoeventsrdquo of duration 2-3 days during the continuous-monitoring period. The authors find that the amplitudes of the continuum variations decrease with increasing wavelength, which extends a general trend for this and other Seyfert galaxies to smaller timescales (i.e., a few days). The continuum variations in all the UV bands are simultaneous to within an accuracy of ~0.15 days, providing a strict constraint on continuum models. The emission-line light curves show only one major event during the continuous monitoring (a slow rise followed by a shallow dip) and do not correlate well with continuum light curves over the short duration of the campaign, because the timescale for continuum variations is apparently smaller than the response times of the emission lines
|
|
| 17. |
- Shah, MY, et al.
(författare)
-
Cancer-associated rs6983267 SNP and its accompanying long noncoding RNA CCAT2 induce myeloid malignancies via unique SNP-specific RNA mutations
- 2018
-
Ingår i: Genome research. - : Cold Spring Harbor Laboratory. - 1549-5469 .- 1088-9051. ; 28:4, s. 432-447
-
Tidskriftsartikel (refereegranskat)abstract
- The cancer-risk-associated rs6983267 single nucleotide polymorphism (SNP) and the accompanying long noncoding RNA CCAT2 in the highly amplified 8q24.21 region have been implicated in cancer predisposition, although causality has not been established. Here, using allele-specific CCAT2 transgenic mice, we demonstrate that CCAT2 overexpression leads to spontaneous myeloid malignancies. We further identified that CCAT2 is overexpressed in bone marrow and peripheral blood of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) patients. CCAT2 induces global deregulation of gene expression by down-regulating EZH2 in vitro and in vivo in an allele-specific manner. We also identified a novel non-APOBEC, non-ADAR, RNA editing at the SNP locus in MDS/MPN patients and CCAT2-transgenic mice. The RNA transcribed from the SNP locus in malignant hematopoietic cells have different allelic composition from the corresponding genomic DNA, a phenomenon rarely observed in normal cells. Our findings provide fundamental insights into the functional role of rs6983267 SNP and CCAT2 in myeloid malignancies.
|
|
| 18. |
- Clayton, A., et al.
(författare)
-
Considerations towards a roadmap for collection, handling and storage of blood extracellular vesicles
- 2019
-
Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 8:1
-
Tidskriftsartikel (refereegranskat)abstract
- There is an increasing interest in exploring clinically relevant information that is present in body fluids, and extracellular vesicles (EVs) are intrinsic components of body fluids ("liquid biopsies"). In this report, we will focus on blood. Blood contains not only EVs but also cells, and non-EV particles including lipoproteins. Due to the high concentration of soluble proteins and lipoproteins, blood, plasma and serum have a high viscosity and density, which hampers the concentration, isolation and detection of EVs. Because most if not all studies on EVs are single-centre studies, their clinical relevance remains limited. Therefore, there is an urgent need to improve standardization and reproducibility of EV research. As a first step, the International Society on Extracellular Vesicles organized a biomarker workshop in Birmingham (UK) in November 2017, and during that workshop several working groups were created to focus on a particular body fluid. This report is the first output of the blood EV work group and is based on responses by work group members to a questionnaire in order to discover the contours of a roadmap. From the answers it is clear that most respondents are in favour of evidence-based research, education, quality control procedures, and physical models to improve our understanding and comparison of concentration, isolation and detection methods. Since blood is such a complex body fluid, we assume that the outcome of the survey may also be valuable for exploring body fluids other than blood.
|
|
| 19. |
- Karlsson, Torbjörn, et al.
(författare)
-
Molecular interactions of the Src homology 2 domain protein Shb with phosphotyrosine residues, tyrosine kinase receptors and Src homology 3 domain proteins
- 1995
-
Ingår i: Oncogene. - 0950-9232 .- 1476-5594. ; 10:8, s. 1475-1483
-
Tidskriftsartikel (refereegranskat)abstract
- The molecular interactions of the Src homology 2 (SH2) domain and the N-terminal proline-rich sequence motifs (pro-1 to pro-5) of the SH2 protein Shb with other components were presently characterised. Using a degenerate phosphopeptide library the preferred binding site for the Shb SH2 domain was determined to pTyr-Thr/Val/Ile-X-Leu at positions +1 to +3 relative the phosphotyrosine residue. Experiments with competing peptides and platelet-derived growth factor (PDGF) beta-receptor mutants with Y to F substitutions in autophosphorylation sites revealed multiple binding sites for the Shb SH2 domain in the receptor. The Shb SH2 domain also binds to in vitro phosphorylated fibroblast growth factor receptor-1 (FGFR-1) mainly through position Y776. The receptor experiments suggest that other residues besides the +1 to +3 positions may also be of significance for Shb binding. The pro-4/pro-5 motif of Shb binds in vitro particularly well to the Src, p85 alpha PI3-kinase and Eps8 SH3 domains expressed as GST fusion proteins. However, the GST-SH3 domain fusion proteins tested bind in vitro to peptides corresponding to the pro-1 to pro-5 motifs of Shb with low affinity and selectivity, suggesting that sequences outside the core proline motif may also be important for Shb-SH3 domain interactions. In vivo association between Shb-SH3 domain proteins v-Src and Eps8 was detected by coimmunoprecipitation. PDGF treatment did not affect the association between Eps8 and Shb. The data suggest that Shb is an adaptor protein linking SH3 domain proteins to tyrosine kinases or other tyrosine phosphorylated proteins.
|
|
| 20. |
- Norton, Maria C, et al.
(författare)
-
Church attendance and new episodes of major depression in a community study of older adults: the Cache County Study.
- 2008
-
Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - 1079-5014. ; 63:3
-
Tidskriftsartikel (refereegranskat)abstract
- We examined the relation between church attendance, membership in the Church of Jesus Christ of Latter-Day Saints (LDS), and major depressive episode, in a population-based study of aging and dementia in Cache County, Utah. Participants included 2,989 nondemented individuals aged between 65 and 100 years who were interviewed initially in 1995 to 1996 and again in 1998 to 1999. LDS church members reported twice the rate of major depression that non-LDS members did (odds ratio = 2.56, 95% confidence interval = 1.07-6.08). Individuals attending church weekly or more often had a significantly lower risk for major depression. After controlling for demographic and health variables and the strongest predictor of future episodes of depression, a prior depression history, we found that church attendance more often than weekly remained a significant protectant (odds ratio = 0.51, 95% confidence interval = 0.28-0.92). Results suggest that there may be a threshold of church attendance that is necessary for a person to garner long-term protection from depression. We discuss sociological factors relevant to LDS culture.
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
- Norton, Maria C, et al.
(författare)
-
Three-year incidence of first-onset depressive syndrome in a population sample of older adults: the Cache County study.
- 2006
-
Ingår i: Am J Geriatr Psychiatry. - 1064-7481. ; 14:3, s. 237-45
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Estimates of incidence of late-life depression vary greatly with few studies excluding demented cases through in-depth evaluation and most studies failing to control for the effect of mortality and interval treatment. In a large population-based study, the authors examined the effect on incidence of first-onset depressive syndrome to determine whether any gender or age differences in incidence are attenuated with inclusion of these additional measures. METHOD: Incidence rates of depressive syndrome per 1,000 person-years are presented for 2,877 nondemented elderly (ages 65 to 100 years) residents of Cache County, Utah. Cases are identified by direct interview methods, by inference from prescription antidepressant medicine use, and by postmortem informant interview for decedents. RESULTS: In-person interviews yielded incidence rates of first-onset depressive disorder (any type) of 13.09 for men and 19.44 for women. Inclusion of antidepressant users increased these figures to 15.55 for men and 23.30 for women. Addition of postmortem interview data yielded rates of 20.66 for men and 26.29 for women. Individuals with no history of depression had rates for major depression of 7.88 for men and 8.75 for women; minor depression rates were 19.23 for men and 24.46 for women (p = 0.691; effect for minor depression p <0.0001). Age did not predict incidence. CONCLUSIONS: Incidence of first-onset major depression varies with data source and prior lifetime history of depression. Gender effects apparent in interview data are attenuated when postmortem information and pharmacotherapy were considered.
|
|
| 25. |
- Ohman, E. Magnus, et al.
(författare)
-
Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1) : a double-blind, multicentre, randomised trial
- 2017
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 389:10081, s. 1799-1808
-
Tidskriftsartikel (refereegranskat)abstract
- Background Dual antiplatelet therapy (DAPT), aspirin plus a P2Y12 inhibitor, is the standard antithrombotic treatment following acute coronary syndromes. The factor Xa inhibitor rivaroxaban reduced mortality and ischaemic events when added to DAPT, but caused increased bleeding. The safety of a dual pathway antithrombotic therapy approach combining low-dose rivaroxaban (in place of aspirin) with a P2Y12 inhibitor has not been assesssed in acute coronary syndromes. We aimed to assess rivaroxaban 2.5 mg twice daily versus aspirin 100 mg daily, in addition to clopidogrel or ticagrelor (chosen at investigator discretion before randomisation), for patients with acute coronary syndromes started within 10 days after presentation and continued for 6-12 months.Methods In this double-blind, multicentre, randomised trial (GEMINI-ACS-1) done at 371 clinical centres in 21 countries, eligible patients were older than 18 years with unstable angina, non-ST segment elevation myocardial infarction (NSTEMI) or ST segment elevation myocardial infarction (STEMI), with positive cardiac biomarkers and either ischaemic electrocardiographic changes or an atherosclerotic culprit lesion identified during angiography. Participants were randomly assigned (1: 1) within 10 days after admission for the index acute coronary syndromes event to either aspirin or rivaroxaban based on a computer-generated randomisation schedule. Randomisation was balanced by using randomly permuted blocks with size of four and was stratified based on the background P2Y12 inhibitor (clopidogrel or ticagrelor) intended to be used at the time of randomisation. Investigators and patients were masked to treatment assignment. Patients received a minimum of 180 days of double-blind treatment with rivaroxaban 2.5 mg twice daily or aspirin 100 mg daily. The choice of clopidogrel or ticagrelor during trial conduct was not randomised and was based on investigator preference. The primary endpoint was thrombolysis in myocardial infarction (TIMI) clinically significant bleeding not related to coronary artery bypass grafting (CABG; major, minor, or requiring medical attention) up to day 390. Primary analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT02293395.Findings Between April 22, 2015, and Oct 14, 2016, 3037 patients with acute coronary syndromes were randomly assigned; 1518 to receive aspirin and 1519 to receive rivaroxaban. 1704 patients (56%) were in the ticagrelor and 1333 (44%) in the clopidogrel strata. Median duration of treatment was 291 days (IQR 239-354). TIMI non-CABG clinically significant bleeding was similar with rivaroxaban versus aspirin therapy (total 154 patients [5%]; 80 participants [5%] of 1519 vs 74 participants [5%] of 1518; HR 1.09 [95% CI 0.80-1.50]; p=0.5840).Interpretation A dual pathway antithrombotic therapy approach combining low-dose rivaroxaban with a P2Y12 inhibitor for the treatment of patients with acute coronary syndromes had similar risk of clinically significant bleeding as aspirin and a P2Y12 inhibitor. A larger, adequately powered trial would be required to definitively assess the efficacy and safety of this approach.
|
|
| 26. |
- Povsic, Thomas J., et al.
(författare)
-
P2Y12 Inhibitor Switching in Response to Routine Notification of CYP2C19 Clopidogrel Metabolizer Status Following Acute Coronary Syndromes
- 2019
-
Ingår i: JAMA cardiology. - : AMER MEDICAL ASSOC. - 2380-6583 .- 2380-6591. ; 4:7, s. 680-684
-
Tidskriftsartikel (refereegranskat)abstract
- Importance Physician behavior in response to knowledge of a patient’s CYP2C19 clopidogrel metabolizer status is unknown.Objective To investigate the association of mandatory reporting of CYP2C19 pharmacogenomic testing, provided to investigators with no direct recommendations on how to use these results, with changes in P2Y12 inhibitor use, particularly clopidogrel, in the Randomized Trial to Compare the Safety of Rivaroxaban vs Aspirin in Addition to Either Clopidogrel or Ticagrelor in Acute Coronary Syndrome (GEMINI-ACS-1) clinical trial.Design, Setting, and Participants The GEMINI-ACS-1 trial compared rivaroxaban, 2.5 mg twice daily, with aspirin, 100 mg daily, plus open-label clopidogrel or ticagrelor (provided), in patients with recent acute coronary syndromes (ACS). The trial included 371 clinical centers in 21 countries and 3037 patients with ACS. Data were analyzed between May 2017 and February 2019.Interventions Investigators were required to prestipulate their planned response to CYP2C19 metabolizer status. In response to a regulatory mandate, results for all patients were reported to investigators approximately 1 week after randomization.Main Outcomes and Measures Reasons for switching P2Y12 inhibitors and occurrence of bleeding and ischemic events were collected.Results Of 3037 patients enrolled (mean [SD] age, 62.8 [9.0] years; 2275 men [74.9%], and 2824 white race/ethnicity [93.0%]), investigators initially treated 1704 (56.1%) with ticagrelor and 1333 (43.9%) with clopidogrel. Investigators prestipulated that they would use CYP2C19 metabolizer status to change P2Y12 inhibitor in 48.5% of genotyped clopidogrel-treated patients (n = 642 of 1324) and 5.5% of genotyped ticagrelor-treated patients (n = 93 of 1692). P2Y12 inhibitor switching for any reason occurred in 197 patients and was more common in patients treated with ticagrelor (146 of 1704 [8.6%]) compared with clopidogrel (51 of 1333 [3.8%]). Of patients initially treated with ticagrelor, only 1 (0.1% overall; 0.7% of all who switched) was switched based on CYP2C19 status. Of patients initially treated with clopidogrel, 23 (1.7% overall,;45.1% of all who switched) were switched owing to metabolizer status. Of 48 patients (3.6%) with reduced metabolizer status treated initially with clopidogrel, 15 (31.3%) were switched based on metabolizer status, including 48.1% (13 of 27) in which switching was prestipulated.Conclusions and Relevance Physicians were evenly split on how to respond to knowledge of CYP2C19 metabolizer status in clopidogrel-treated patients. Mandatory provision of this information rarely prompted P2Y12 inhibitor switching overall, including a minority of patients with reduced metabolizer status. These findings highlight the clinical equipoise among physicians regarding use of this information and the reluctance to use information from routine genotyping in the absence of definitive clinical trial data demonstrating the efficacy of this approach.
|
|
| 27. |
|
|
| 28. |
- Welsh, Joshua A., et al.
(författare)
-
Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches
- 2024
-
Ingår i: Journal of Extracellular Vesicles. - : John Wiley and Sons Inc. - 2001-3078. ; 13:2
-
Tidskriftsartikel (refereegranskat)abstract
- Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its ‘Minimal Information for Studies of Extracellular Vesicles’, which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly.
|
|
| 29. |
- Wengreen, H J, et al.
(författare)
-
Antioxidant intake and cognitive function of elderly men and women: the Cache County Study.
- 2007
-
Ingår i: The journal of nutrition, health & aging. - 1279-7707. ; 11:3, s. 230-7
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We prospectively examined associations between intakes of antioxidants (vitamins C, vitamin E, and carotene) and cognitive function and decline among elderly men and women of the Cache County Study on Memory and Aging in Utah. PARTICIPANTS AND DESIGN: In 1995, 3831 residents 65 years of age or older completed a baseline survey that included a food frequency questionnaire and cognitive assessment. Cognitive function was assessed using an adapted version of the Modified Mini-Mental State examination (3MS) at baseline and at three subsequent follow-up interviews spanning approximately 7 years. Multivariable-mixed models were used to estimate antioxidant nutrient effects on average 3MS score over time. RESULTS: Increasing quartiles of vitamin C intake alone and combined with vitamin E were associated with higher baseline average 3MS scores (p-trend = 0.013 and 0.02 respectively); this association appeared stronger for food sources compared to supplement or food and supplement sources combined. Study participants with lower levels of intake of vitamin C, vitamin E and carotene had a greater acceleration of the rate of 3MS decline over time compared to those with higher levels of intake. CONCLUSION: High antioxidant intake from food and supplement sources of vitamin C, vitamin E, and carotene may delay cognitive decline in the elderly.
|
|
| 30. |
- Zandi, Peter P, et al.
(författare)
-
Reduced risk of Alzheimer disease in users of antioxidant vitamin supplements: the Cache County Study.
- 2004
-
Ingår i: Archives of neurology. - : American Medical Association (AMA). - 0003-9942. ; 61:1, s. 82-8
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Antioxidants may protect the aging brain against oxidative damage associated with pathological changes of Alzheimer disease (AD). OBJECTIVE: To examine the relationship between antioxidant supplement use and risk of AD. DESIGN: Cross-sectional and prospective study of dementia. Elderly (65 years or older) county residents were assessed in 1995 to 1997 for prevalent dementia and AD, and again in 1998 to 2000 for incident illness. Supplement use was ascertained at the first contact. SETTING: Cache County, Utah. PARTICIPANTS: Among 4740 respondents (93%) with data sufficient to determine cognitive status at the initial assessment, we identified 200 prevalent cases of AD. Among 3227 survivors at risk, we identified 104 incident AD cases at follow-up. MAIN OUTCOME MEASURE: Diagnosis of AD by means of multistage assessment procedures. RESULTS: Analyses of prevalent and incident AD yielded similar results. Use of vitamin E and C (ascorbic acid) supplements in combination was associated with reduced AD prevalence (adjusted odds ratio, 0.22; 95% confidence interval, 0.05-0.60) and incidence (adjusted hazard ratio, 0.36; 95% confidence interval, 0.09-0.99). A trend toward lower AD risk was also evident in users of vitamin E and multivitamins containing vitamin C, but we saw no evidence of a protective effect with use of vitamin E or vitamin C supplements alone, with multivitamins alone, or with vitamin B-complex supplements. CONCLUSIONS: Use of vitamin E and vitamin C supplements in combination is associated with reduced prevalence and incidence of AD. Antioxidant supplements merit further study as agents for the primary prevention of AD.
|
|
| 31. |
- Clayton, Aled, et al.
(författare)
-
Summary of the ISEV workshop on extracellular vesicles as disease biomarkers, held in Birmingham, UK, during December 2017
- 2018
-
Ingår i: Journal of Extracellular Vesicles. - : Wiley. - 2001-3078. ; 7
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- © 2018 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. This report summarises the presentations and activities of the ISEV Workshop on extracellular vesicle biomarkers held in Birmingham, UK during December 2017. Among the key messages was broad agreement about the importance of biospecimen science. Much greater attention needs to be paid towards the provenance of collected samples. The workshop also highlighted clear gaps in our knowledge about pre-analytical factors that alter extracellular vesicles (EVs). The future utility of certified standards for credentialing of instruments and software, to analyse EV and for tracking the influence of isolation steps on the structure and content of EVs were also discussed. Several example studies were presented, demonstrating the potential utility for EVs in disease diagnosis, prognosis, longitudinal serial testing and stratification of patients. The conclusion of the workshop was that more effort focused on pre-analytical issues and benchmarking of isolation methods is needed to strengthen collaborations and advance more effective biomarkers.
|
|
| 32. |
- Goodwin, Graham C., et al.
(författare)
-
Robust Identification of Process Models from Plant Data
- 2008
-
Ingår i: Journal of Process Control. - : Elsevier. - 0959-1524. ; 18:9, s. 810-820
-
Tidskriftsartikel (refereegranskat)abstract
- A precursor to any advanced control solution is the step of obtaining an accurate model of the process. Suitable models can be obtained from phenomenological reasoning, analysis of plant data or a combination of both. Here, we will focus on the problem of estimating (or calibrating) models from plant data. A key goal is to achieve robust identification. By robust we mean that small errors in the hypotheses should lead to small errors in the estimated models. We argue that, in some circumstances, it is essential that special precautions, including discarding some part of the data, be taken to ensure that robustness is preserved. We present several practical case studies to illustrate the results.
|
|
| 33. |
|
|
| 34. |
- Hayden, Kathleen M, et al.
(författare)
-
Effects of family history and apolipoprotein E epsilon4 status on cognitive decline in the absence of Alzheimer dementia: the Cache County Study.
- 2009
-
Ingår i: Archives of neurology. - : American Medical Association (AMA). - 1538-3687 .- 0003-9942. ; 66:11, s. 1378-83
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To evaluate the influences of a family history of Alzheimer dementia (FHxAD) and the apolipoprotein E epsilon4 genotype (APOE epsilon4) on cognitive decline. DESIGN, SETTING, AND PARTICIPANTS: Residents of Cache County, Utah, aged 65 years or older, were invited to participate. At baseline, 2957 participants provided DNA for genotyping of APOE and a detailed FHxAD. They also completed the Modified Mini-Mental State Examination. Cognitive status was reexamined after 3 and 7 years. We used mixed-effects models to examine the association among FHxAD, APOE epsilon4, and cognitive trajectories. MAIN OUTCOME MEASURE: Modified Mini-Mental State Examination score trajectories over time. RESULTS: Compared with participants who did not have APOE epsilon4 or an FHxAD, those with APOE epsilon4 scored lower on the Modified Mini-Mental State Examination at baseline (-0.70 points; 95% confidence interval [CI], -1.15 to -0.24). Participants with an FHxAD and APOE epsilon4 differed less, if at all, in baseline score (-0.46 points; 95% CI, -1.09 to 0.16) but declined faster during the 7-year study (-9.75 points [95% CI, -10.82 to -8.67] vs -2.91 points [95% CI, -3.37 to -2.44]). After exclusion of participants who developed prodromal AD or incident dementia, the group with an FHxAD and APOE epsilon4 declined much less during the 7-year study (-1.54; 95% CI, -2.59 to -0.50). CONCLUSIONS: Much of the association among FHxAD, APOE epsilon4, and cognitive decline may be attributed to undetected incipient (latent) disease. In the absence of latent disease, the 2 factors do not appear individually to be associated with cognitive decline, although they may be additive.
|
|
| 35. |
- Hägerkvist, Robert, et al.
(författare)
-
Consequences of Shb and c-Abl interactions for cell death in response to various stress stimuli
- 2007
-
Ingår i: Experimental Cell Research. - : Elsevier BV. - 0014-4827 .- 1090-2422. ; 313:2, s. 284-291
-
Tidskriftsartikel (refereegranskat)abstract
- The adaptor protein Shb has previously been shown to regulate apoptosis in response to cytokines and inhibitors of angiogenesis although the mechanisms governing these effects have remained obscure. We currently demonstrate interactions between Shb and c-Abl and that Shb regulates c-Abl kinase activity. The data suggest that c-Abl binds to tyrosine phosphorylated Shb via a concerted effort involving both the c-Abl SH3 and SH2 domains. The biological significance of the Shb/c-Abl interaction was presently tested in overexpression experiments and was found to promote hydrogen peroxide-induced cell death. We also show by Shb knockdown experiments that Shb regulates c-Abl activity and modulates cell death in response to the genotoxic agent cisplatin and the endoplasmic reticulum stress-inducer tunicamycin. The findings are in agreement with the notion of Shb playing a pivotal role in modulating c-Abl pro-apoptotic signaling in response to various stress stimuli.
|
|
| 36. |
|
|
| 37. |
|
|
| 38. |
- Oberg, C, et al.
(författare)
-
Expression of protein tyrosine kinases in islet cells : possible role of the Flk-1 receptor for beta-cell maturation from duct cells.
- 1994
-
Ingår i: Growth Factors. - 0897-7194 .- 1029-2292. ; 10:2, s. 115-26
-
Tidskriftsartikel (refereegranskat)abstract
- To elucidate the expression of genes of importance for beta-cell replication and the production of insulin, single-stranded cDNAs from different preparations of insulin producing cells were used as template for the polymerase chain reaction (PCR) using primers specific for protein tyrosine kinases (PTKs). In RINm5F cells, as well as in fetal rat islets, the receptor PTK fetal liver kinase-1 (Flk-1) was expressed among other receptor and cytoplasmic tyrosine kinases. To elucidate the putative effects of stimulation of the Flk-1 receptor, fetal rat islet-like structures were cultured in the presence of the ligand for this receptor, vascular endothelial growth factor (VEGF). VEGF was found to stimulate both the insulin content/islet DNA ratio and the accumulation of insulin in the culture medium without affecting the rates of beta-cell replication. To investigate the localization of expression of the Flk-1 receptor in the pancreas, serial sections of fetal pancreata were immunostained for Flk-1 and insulin. Expression of Flk-1 was detected in endothelial-like cells and cells lining pancreatic ducts. The latter are considered to contain precursor cells for the endocrine pancreas. In conclusion, specific protein tyrosine kinases are expressed in islet cells, and are presumably participating in the regulation of islet function. Specifically, the receptor PTK Flk-1 may play a role of beta-cell maturation from pancreatic duct cells.
|
|
| 39. |
- Oberg-Welsh, C, et al.
(författare)
-
Cloning of BSK, a murine FRK homologue with a specific pattern of tissue distribution.
- 1995
-
Ingår i: Gene. - 0378-1119 .- 1879-0038. ; 152:2, s. 239-42
-
Tidskriftsartikel (refereegranskat)abstract
- A novel protein tyrosine kinase (PTK) was previously identified by us from the rat insulin-producing cell line, RINm5F, by polymerase chain reaction (PCR). By using this PCR fragment to screen a cDNA library from the mouse insulin-producing cell line beta TC-1, a cDNA clone of about 2.0 kb was obtained which encodes the entire amino acid (aa) sequence of the corresponding PTK. The deduced aa sequence reveals strong homology with the members of the SRC family of intracellular PTKs. We have designated the gene as BSK (beta-cell Src-homology tyrosine kinase). Southern blot analysis after PCR with primers specific for BSK confirmed its expression in fetal and adult islets of Langerhans, in RINm5F cells and in mouse kidney. Northern blots using poly(A)+RNA from non-beta-cell tissues showed that the BSK cDNA hybridized to three mRNA transcripts (2.9, 3.1 and 5.0 kb) present in kidney, liver and lung. Extensive homology of BSK with the recently identified human gene FRK was observed. It is concluded that Bsk is a murine Frk homologue with a specific pattern of tissue expression.
|
|
| 40. |
|
|
| 41. |
|
|
| 42. |
- Oberg-Welsh, C, et al.
(författare)
-
Effects of certain growth factors on in vitro maturation of rat fetal islet-like structures.
- 1996
-
Ingår i: Pancreas. - 0885-3177 .- 1536-4828. ; 12:4, s. 334-9
-
Tidskriftsartikel (refereegranskat)abstract
- We have previously studied the expression of protein tyrosine kinases in different preparations of insulin producing cells by polymerase chain reaction (PCR). Among the tyrosine kinases thus identified were the fibroblast growth factor receptor-4 (FGFR-4), c-Kit, the insulin-like growth factor (IGF-I) receptor, and the cytoplasmic tyrosine kinase Jak2, which associates with the activated receptor for growth hormone (GH). To elucidate the putative biological effects of the receptors identified, fetal islet-like structures were cultured in the absence or presence of the ligands to the receptors identified, namely, acidic FGF (aFGF), stem-cell factor (SCF), IGF-I, and GH, whereafter insulin and DNA contents as well as insulin secretion to the culture medium were determined. Nerve growth factor (NGF), the ligand to the tyrosine kinase receptor Trk-A, was also included. aFGF and GH were found to stimulate insulin release to the culture medium, whereas SCF augmented insulin contents/DNA as well as islet DNA contents. No effects of NGF or IGF-I were detected. Immunohistochemical studies of fetal rat pancreas showed localization of the c-Kit protein to the pancreatic ducts, whereas immuno-reactivity against FGFR-4 could be detected in both endocrine and exocrine parts of the pancreas as well as in the pancreatic ducts. It is concluded that tyrosine kinase receptors may be involved in the maturation of pancreatic beta cells.
|
|
| 43. |
- Ramirez, M. I., et al.
(författare)
-
Technical challenges of working with extracellular vesicles
- 2018
-
Ingår i: Nanoscale. - : Royal Society of Chemistry (RSC). - 2040-3364 .- 2040-3372. ; 10:3, s. 881-906
-
Tidskriftsartikel (refereegranskat)abstract
- Extracellular Vesicles (EVs) are gaining interest as central players in liquid biopsies, with potential applications in diagnosis, prognosis and therapeutic guidance in most pathological conditions. These nanosized particles transmit signals determined by their protein, lipid, nucleic acid and sugar content, and the unique molecular pattern of EVs dictates the type of signal to be transmitted to recipient cells. However, their small sizes and the limited quantities that can usually be obtained from patient-derived samples pose a number of challenges to their isolation, study and characterization. These challenges and some possible options to overcome them are discussed in this review. © 2018 The Royal Society of Chemistry.
|
|
| 44. |
- Rojas, Cristian R., et al.
(författare)
-
On the Equivalence of Least Costly and Traditional Experiment Design for Control
- 2008
-
Ingår i: Automatica. - : Elsevier BV. - 0005-1098 .- 1873-2836. ; 44:11, s. 2706-2715
-
Tidskriftsartikel (refereegranskat)abstract
- In this paper we establish the equivalence between least costly and traditional experiment design for control. We consider experiment design problems for both open and closed loop systems. In open loop, equivalence is established for three specific cases, relating to different parametrisations of the covariance expression (i.e. finite and high order approximations) and model structure (i.e. dependent and independently parameterised plant and noise models). In the closed loop setting, we consider only finite order covariance expressions. H(infinity) performance specifications for control are used to determine the bounds on the covariance expression for both the open and closed loop cases.
|
|
| 45. |
- Rojas, Cristian R., 1980-, et al.
(författare)
-
Robustness in Experiment Design
- 2012
-
Ingår i: IEEE Transactions on Automatic Control. - 0018-9286 .- 1558-2523. ; 57:4, s. 860-874
-
Tidskriftsartikel (refereegranskat)abstract
- This paper focuses on the problem of robust experiment design, i.e., how to design an input signal which gives relatively good estimation performance over a large number of systems and model structures. Specifically, we formulate the robust experiment design problem utilizing fundamental limitations on the variance of estimated parametric models as constraints. Using this formulation we design an input signal for situations where only diffuse a priori information is known about the system. Furthermore, we present a robust version of the unprejudiced optimal input design problem. To achieve this, we first develop a closed form solution for the input spectrum which minimizes the maximum weighted integral of the variance of the frequency response estimate over all model structures.
|
|
| 46. |
|
|
| 47. |
|
|
| 48. |
|
|
| 49. |
- Singh, A., et al.
(författare)
-
Reactive Oxygen Species Modulate the Barrier Function of the Human Glomerular Endothelial Glycocalyx
- 2013
-
Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2
-
Tidskriftsartikel (refereegranskat)abstract
- Reactive oxygen species (ROS) play a key role in the pathogenesis of proteinuria in glomerular diseases like diabetic nephropathy. Glomerular endothelial cell (GEnC) glycocalyx covers the luminal aspect of the glomerular capillary wall and makes an important contribution to the glomerular barrier. ROS are known to depolymerise glycosaminoglycan (GAG) chains of proteoglycans, which are crucial for the barrier function of GEnC glycocalyx. The aim of this study is to investigate the direct effects of ROS on the structure and function of GEnC glycocalyx using conditionally immortalised human GEnC. ROS were generated by exogenous hydrogen peroxide. Biosynthesis and cleavage of GAG chains was analyzed by radiolabelling (S35 and 3H-glucosamine). GAG chains were quantified on GEnC surface and in the cell supernatant using liquid chromatography and immunofluorescence techniques. Barrier properties were estimated by measuring trans-endothelial passage of albumin. ROS caused a significant loss of WGA lectin and heparan sulphate staining from the surface of GEnC. This lead to an increase in trans-endothelial albumin passage. The latter could be inhibited by catalase and superoxide dismutase. The effect of ROS on GEnC was not mediated via the GAG biosynthetic pathway. Quantification of radiolabelled GAG fractions in the supernatant confirmed that ROS directly caused shedding of HS GAG. This finding is clinically relevant and suggests a mechanism by which ROS may cause proteinuria in clinical conditions associated with high oxidative stress.
|
|
| 50. |
- Vieillard, Jennifer, et al.
(författare)
-
Adult spinal Dmrt3 neurons receive direct somatosensory inputs from ipsi- and contralateral primary afferents and from brainstem motor nuclei
- 2023
-
Ingår i: Journal of Comparative Neurology. - : John Wiley & Sons. - 0021-9967 .- 1096-9861. ; 531:1, s. 5-24
-
Tidskriftsartikel (refereegranskat)abstract
- In the spinal cord, sensory-motor circuits controlling motor activity are situated in the dorso-ventral interface. The neurons identified by the expression of the transcription factor Doublesex and mab-3 related transcription factor 3 (Dmrt3) have previously been associated with the coordination of locomotion in horses (Equus caballus, Linnaeus, 1758), mice (Mus musculus, Linnaeus, 1758), and zebrafish (Danio rerio, F. Hamilton, 1822). Based on earlier studies, we hypothesized that, in mice, these neurons may be positioned to receive sensory and central inputs to relay processed commands to motor neurons. Thus, we investigated the presynaptic inputs to spinal Dmrt3 neurons using monosynaptic retrograde replication-deficient rabies tracing. The analysis showed that lumbar Dmrt3 neurons receive inputs from intrasegmental neurons, and intersegmental neurons from the cervical, thoracic, and sacral segments. Some of these neurons belong to the excitatory V2a interneurons and to plausible Renshaw cells, defined by the expression of Chx10 and calbindin, respectively. We also found that proprioceptive primary sensory neurons of type Ia2, Ia3, and Ib, defined by the expression of calbindin, calretinin, and Brn3c, respectively, provide presynaptic inputs to spinal Dmrt3 neurons. In addition, we demonstrated that Dmrt3 neurons receive inputs from brain areas involved in motor regulation, including the red nucleus, primary sensory-motor cortex, and pontine nuclei. In conclusion, adult spinal Dmrt3 neurons receive inputs from motor-related brain areas as well as proprioceptive primary sensory neurons and have been shown to connect directly to motor neurons. Dmrt3 neurons are thus positioned to provide sensory-motor control and their connectivity is suggestive of the classical reflex pathways present in the spinal cord.
|
|
