| 1. |
- Niimi, Yoshiki, et al.
(författare)
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Combining plasma Aβ and p-tau217 improves detection of brain amyloid in non-demented elderly
- 2024
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Ingår i: Alzheimer's Research and Therapy. - 1758-9193. ; 16:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Maximizing the efficiency to screen amyloid-positive individuals in asymptomatic and non-demented aged population using blood-based biomarkers is essential for future success of clinical trials in the early stage of Alzheimer’s disease (AD). In this study, we elucidate the utility of combination of plasma amyloid-β (Aβ)-related biomarkers and tau phosphorylated at threonine 217 (p-tau217) to predict abnormal Aβ-positron emission tomography (PET) in the preclinical and prodromal AD. Methods: We designed the cross-sectional study including two ethnically distinct cohorts, the Japanese trial-ready cohort for preclinica and prodromal AD (J-TRC) and the Swedish BioFINDER study. J-TRC included 474 non-demented individuals (CDR 0: 331, CDR 0.5: 143). Participants underwent plasma Aβ and p-tau217 assessments, and Aβ-PET imaging. Findings in J-TRC were replicated in the BioFINDER cohort including 177 participants (cognitively unimpaired: 114, mild cognitive impairment: 63). In both cohorts, plasma Aβ(1-42) (Aβ42) and Aβ(1-40) (Aβ40) were measured using immunoprecipitation-MALDI TOF mass spectrometry (Shimadzu), and p-tau217 was measured with an immunoassay on the Meso Scale Discovery platform (Eli Lilly). Results: Aβ-PET was abnormal in 81 participants from J-TRC and 71 participants from BioFINDER. Plasma Aβ42/Aβ40 ratio and p-tau217 individually showed moderate to high accuracies when detecting abnormal Aβ-PET scans, which were improved by combining plasma biomarkers and by including age, sex and APOE genotype in the models. In J-TRC, the highest AUCs were observed for the models combining p-tau217/Aβ42 ratio, APOE, age, sex in the whole cohort (AUC = 0.936), combining p-tau217, Aβ42/Aβ40 ratio, APOE, age, sex in the CDR 0 group (AUC = 0.948), and combining p-tau217/Aβ42 ratio, APOE, age, sex in the CDR 0.5 group (AUC = 0.955), respectively. Each subgroup results were replicated in BioFINDER, where the highest AUCs were seen for models combining p-tau217, Aβ42/40 ratio, APOE, age, sex in cognitively unimpaired (AUC = 0.938), and p-tau217/Aβ42 ratio, APOE, age, sex in mild cognitive impairment (AUC = 0.914). Conclusions: Combination of plasma Aβ-related biomarkers and p-tau217 exhibits high performance when predicting Aβ-PET positivity. Adding basic clinical information (i.e., age, sex, APOE ε genotype) improved the prediction in preclinical AD, but not in prodromal AD. Combination of Aβ-related biomarkers and p-tau217 could be highly useful for pre-screening of participants in clinical trials of preclinical and prodromal AD.
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| 2. |
- Yoshimura, Takeshi, et al.
(författare)
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GlcNAc6ST-1 regulates sulfation of N-glycans and myelination in the peripheral nervous system
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Highly specialized glial cells wrap axons with a multilayered myelin membrane in vertebrates. Myelin serves essential roles in the functioning of the nervous system. Axonal degeneration is the major cause of permanent neurological disability in primary myelin diseases. Many glycoproteins have been identified in myelin, and a lack of one myelin glycoprotein results in abnormal myelin structures in many cases. However, the roles of glycans on myelin glycoproteins remain poorly understood. Here, we report that sulfated N-glycans are involved in peripheral nervous system (PNS) myelination. PNS myelin glycoproteins contain highly abundant sulfated N-glycans. Major sulfated N-glycans were identified in both porcine and mouse PNS myelin, demonstrating that the 6-O-sulfation of N-acetylglucosamine (GlcNAc-6-O-sulfation) is highly conserved in PNS myelin between these species. P-0 protein, the most abundant glycoprotein in PNS myelin and mutations in which at the glycosylation site cause Charcot-Marie-Tooth neuropathy, has abundant GlcNAc-6-O-sulfated N-glycans. Mice deficient in N-acetylglucosamine-6-O-sulfotransferase-1 (GlcNAc6ST-1) failed to synthesize sulfated N-glycans and exhibited abnormal myelination and axonal degeneration in the PNS. Taken together, this study demonstrates that GlcNAc6ST-1 modulates PNS myelination and myelinated axonal survival through the GlcNAc-6-O-sulfation of N-glycans on glycoproteins. These findings may provide novel insights into the pathogenesis of peripheral neuropathy.
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| 3. |
- Aharonian, Felix, et al.
(författare)
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Temperature structure in the Perseus cluster core observed with Hitomi
- 2018
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Ingår i: Publications of the Astronomical Society of Japan. - : Oxford University Press (OUP). - 0004-6264 .- 2053-051X. ; 70:2
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Tidskriftsartikel (refereegranskat)abstract
- The present paper explains the temperature structure of X-ray emitting plasma in the core of the Perseus cluster based on 1.8-20.0 keV data obtained with the Soft X-ray Spectrometer (SXS) on board the Hitomi Observatory. A series of four observations was carried out, with a total effective exposure time of 338 ks that covered a central region of similar to 7' in diameter. SXS was operated with an energy resolution of similar to 5 eV (full width at half maximum) at 5.9 keV. Not only fine structures of K-shell lines in He-like ions, but also transitions from higher principal quantum numbers were clearly resolved from Si through Fe. That enabled us to perform temperature diagnostics using the line ratios of Si, S, Ar, Ca, and Fe, and to provide the first direct measurement of the excitation temperature and ionization temperature in the Perseus cluster. The observed spectrum is roughly reproduced by a single-temperature thermal plasma model in collisional ionization equilibrium, but detailed line-ratio diagnostics reveal slight deviations from this approximation. In particular, the data exhibit an apparent trend of increasing ionization temperature with the atomic mass, as well as small differences between the ionization and excitation temperatures for Fe, the only element for which both temperatures could be measured. The best-fit two-temperature models suggest a combination of 3 and 5 keV gas, which is consistent with the idea that the observed small deviations from a single-temperature approximation are due to the effects of projecting the known radial temperature gradient in the cluster core along the line of sight. A comparison with the Chandra/ACIS and the XMM-Newton/RGS results, on the other hand, suggests that additional lower-temperature components are present in the intracluster medium (ICM), but not detectable with Hitomi/SXS giving its 1.8-20 keV energy band.
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| 4. |
- Kato, Kenji, et al.
(författare)
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Chronic widespread pain and its comorbidities : a population-based study
- 2006
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Ingår i: Archives of Internal Medicine. - : American Medical Association (AMA). - 0003-9926 .- 1538-3679. ; 166:15, s. 1649-1654
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Tidskriftsartikel (refereegranskat)abstract
- Associations between CWP and most comorbidities are mediated by unmeasured genetic and family environmental factors in the general population. The extent of mediation via familial factors is likely to be disorder specific.
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| 5. |
- Kato, Kenji
(författare)
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Genetic epidemiological studies of the functional somatic syndromes : chronic widespread pain and chronic fatigue
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fibromyalgia and chronic fatigue syndrome are two symptom-defined conditions with many physical symptoms in common, such as muscle pain, fatigue, unrefreshing sleep, and impairment in memory or concentration. These two conditions often co-occur and frequently co-exist with other symptom-defined conditions (e.g., irritable bowel syndrome and recurrent headache), have a female predominance, and share psychosocial or psychiatric characteristics. It has been suggested that fibromyalgia, chronic fatigue syndrome, and other symptom-defined conditions can be considered as syndromes that share underlying pathogenesis, and hence named ¡°functional somatic syndromes¡±. To date, little is known about the causes of functional somatic syndromes and their co-occurrence (comorbidity). The present study aimed at investigating the etiology of this comorbidity with a focus on chronic widespread pain (the cardinal symptom of fibromyalgia) and chronic fatigue. Data were obtained from the participants in the Screening Across the Lifespan Twins (SALT) study of the population-based Swedish Twin Registry. All living, contactable, and consenting twins born in Sweden before December 1958 were contacted between March 1998 and December 2002 to participate in a computer-assisted telephone interview. Of 61,355 eligible twins, 44,897 individuals (73.2%) participated in the interview which screened, amongst others, for chronic widespread pain, chronic fatigue, irritable bowel syndrome, recurrent headache, major depression, and generalized anxiety disorder. Zygosity was determined using questions regarding childhood similarity. Psychological risk factors (personality and stress) were assessed using questionnaires administered to monozygotic and same-sex dizygotic twins in 1972-73. Univariate and multivariate twin analyses were implemented in order to estimate the relative importance of genetic and environmental influences on chronic widespread pain, to assess sex differences in the estimates, and to determine the etiological model that best explains the comorbidity of the functional somatic syndromes. Matched case-control and co-twin case-control analyses were performed in order to evaluate the associations between chronic widespread pain and its comorbid conditions, to examine premorbid risks of psychological factors for chronic fatigue, and to assess familial (genetic and family environmental) influences on these associations. Modest genetic influences and no family environmental influences were found in chronic widespread pain. The estimates did not differ significantly by sex. Strong associations were found between chronic widespread pain and chronic fatigue, followed in magnitude by irritable bowel syndrome. Associations of chronic widespread pain with psychiatric disorders were no longer significant when discordant monozygotic twins were used, whereas associations with most of the other conditions decreased but remained significant, suggesting familial influences on the associations. Emotional instability and perceived stress were significantly associated with chronic fatigue screened ¡Ý 25 years later in subjects aged < 65. When monozygotic twins were used, the association with emotional instability was no longer significant but that with perceived stress increased in the severer definition of chronic fatigue, suggesting different effects of genetic influences on the associations. Finally, for women a model with two latent traits shared by four functional somatic syndromes and two psychiatric disorders best explains the etiology of their comorbidities. The psychiatric disorders loaded on only one of the two latent traits, suggesting that the two latent traits reflect the affective and non-affective (or physiological) aspects of functional symptoms. Each illness is also influenced by genetic and environmental factors specific to each. In conclusion, the comorbidity of functional somatic syndromes is attributed to latent etiological traits (one of which is affective and the other not) shared by these syndromes, whereas the differences among them are attributable to genetic and environmental factors specific to each illness.
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| 6. |
- Kato, Kenji, et al.
(författare)
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Importance of genetic influences on chronic widespread pain
- 2006
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Ingår i: Arthritis and Rheumatism. - : Wiley. - 0004-3591 .- 1529-0131. ; 54:5, s. 1682-1686
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Tidskriftsartikel (refereegranskat)abstract
- Individual differences in the likelihood of developing chronic widespread pain reflect modest genetic influences. There are no significant sex differences in the type or expression of the genes responsible for chronic widespread pain or in the magnitude of the relative importance of these influences on chronic widespread pain.
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| 7. |
- Kato, Kenji, et al.
(författare)
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Premorbid predictors of chronic fatigue
- 2006
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Ingår i: Archives of General Psychiatry. - : American Medical Association (AMA). - 0003-990X .- 1538-3636. ; 63:11, s. 1267-1272
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Tidskriftsartikel (refereegranskat)abstract
- Elevated premorbid stress is a significant risk factor for chronic fatigue-like illness, the effect of which may be buffered by genetic influences. Emotional instability assessed 25 years earlier is associated with chronic fatigue through genetic mechanisms contributing to both personality style and expression of the disorder. These findings suggest plausible mechanisms for chronic fatiguing illness.
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| 8. |
- Naghavi, Mohsen, et al.
(författare)
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Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013
- 2015
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Ingår i: The Lancet. - 1474-547X .- 0140-6736. ; 385:9963, s. 117-171
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Tidskriftsartikel (refereegranskat)abstract
- Background Up-to-date evidence on levels and trends for age-sex-specifi c all-cause and cause-specifi c mortality is essential for the formation of global, regional, and national health policies. In the Global Burden of Disease Study 2013 (GBD 2013) we estimated yearly deaths for 188 countries between 1990, and 2013. We used the results to assess whether there is epidemiological convergence across countries. Methods We estimated age-sex-specifi c all-cause mortality using the GBD 2010 methods with some refinements to improve accuracy applied to an updated database of vital registration, survey, and census data. We generally estimated cause of death as in the GBD 2010. Key improvements included the addition of more recent vital registration data for 72 countries, an updated verbal autopsy literature review, two new and detailed data systems for China, and more detail for Mexico, UK, Turkey, and Russia. We improved statistical models for garbage code redistribution. We used six different modelling strategies across the 240 causes; cause of death ensemble modelling (CODEm) was the dominant strategy for causes with sufficient information. Trends for Alzheimer's disease and other dementias were informed by meta-regression of prevalence studies. For pathogen-specifi c causes of diarrhoea and lower respiratory infections we used a counterfactual approach. We computed two measures of convergence (inequality) across countries: the average relative difference across all pairs of countries (Gini coefficient) and the average absolute difference across countries. To summarise broad findings, we used multiple decrement life-tables to decompose probabilities of death from birth to exact age 15 years, from exact age 15 years to exact age 50 years, and from exact age 50 years to exact age 75 years, and life expectancy at birth into major causes. For all quantities reported, we computed 95% uncertainty intervals (UIs). We constrained cause-specific fractions within each age-sex-country-year group to sum to all-cause mortality based on draws from the uncertainty distributions. Findings Global life expectancy for both sexes increased from 65.3 years (UI 65.0-65.6) in 1990, to 71.5 years (UI 71.0-71.9) in 2013, while the number of deaths increased from 47.5 million (UI 46.8-48.2) to 54.9 million (UI 53.6-56.3) over the same interval. Global progress masked variation by age and sex: for children, average absolute diff erences between countries decreased but relative diff erences increased. For women aged 25-39 years and older than 75 years and for men aged 20-49 years and 65 years and older, both absolute and relative diff erences increased. Decomposition of global and regional life expectancy showed the prominent role of reductions in age-standardised death rates for cardiovascular diseases and cancers in high-income regions, and reductions in child deaths from diarrhoea, lower respiratory infections, and neonatal causes in low-income regions. HIV/AIDS reduced life expectancy in southern sub-Saharan Africa. For most communicable causes of death both numbers of deaths and age-standardised death rates fell whereas for most non-communicable causes, demographic shifts have increased numbers of deaths but decreased age-standardised death rates. Global deaths from injury increased by 10.7%, from 4.3 million deaths in 1990 to 4.8 million in 2013; but age-standardised rates declined over the same period by 21%. For some causes of more than 100 000 deaths per year in 2013, age-standardised death rates increased between 1990 and 2013, including HIV/AIDS, pancreatic cancer, atrial fibrillation and flutter, drug use disorders, diabetes, chronic kidney disease, and sickle-cell anaemias. Diarrhoeal diseases, lower respiratory infections, neonatal causes, and malaria are still in the top five causes of death in children younger than 5 years. The most important pathogens are rotavirus for diarrhoea and pneumococcus for lower respiratory infections. Country-specific probabilities of death over three phases of life were substantially varied between and within regions. Interpretation For most countries, the general pattern of reductions in age-sex specifi c mortality has been associated with a progressive shift towards a larger share of the remaining deaths caused by non-communicable disease and injuries. Assessing epidemiological convergence across countries depends on whether an absolute or relative measure of inequality is used. Nevertheless, age-standardised death rates for seven substantial causes are increasing, suggesting the potential for reversals in some countries. Important gaps exist in the empirical data for cause of death estimates for some countries; for example, no national data for India are available for the past decade.
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| 9. |
- Ohishi, Kazuki, et al.
(författare)
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The internal magnetic field in a ferromagnetic compound Y 2 Co 12 P 7
- 2023
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Ingår i: Journal of Physics: Conference Series. - : IOP Publishing. - 1742-6588 .- 1742-6596. ; 2462:1
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Konferensbidrag (refereegranskat)abstract
- The internal magnetic field in a ferromagnetic compound, Y2Co12P7 with T C = 150 K, was studied with μ +SR using a powder sample down to 2 K. The wTF-μ +SR measurements revealed the presence of a sharp magnetic transition at T C = 151 K, and the ZF-μ +SR measurements clarified the formation of static magnetic order below T C. The presence of two muon spin precession signals in the ZF-μ +SR spectrum below T C indicates the existence of the two different muon sites in the lattice. By considering the muon sites and local spin densities at the muon sites predicted with DFT calculations, the ordered magnetic moments of Co were successfully determined.
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| 10. |
- Ohishi, Kazuki, et al.
(författare)
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The internal magnetic field in a ferromagnetic compound Y2Co12P7
- 2023
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Ingår i: Proceedings 15th International Conference on Muon Spin Rotation, Relaxation and Resonance (SR). - : IOP Publishing. ; 2462
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Konferensbidrag (refereegranskat)abstract
- The internal magnetic field in a ferromagnetic compound, Y2Co12P7 with T-C = 150 K, was studied with mu(+) SR using a powder sample down to 2 K. The wTF-mu(+) SR measurements revealed the presence of a sharp magnetic transition at T-C = 151 K, and the ZF-mu(+) SR measurements clarified the formation of static magnetic order below T-C. The presence of two muon spin precession signals in the ZF-mu(+) SR spectrum below TC indicates the existence of the two different muon sites in the lattice. By considering the muon sites and local spin densities at the muon sites predicted with DFT calculations, the ordered magnetic moments of Co were successfully determined.
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