| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Krizek, Filip, et al.
(författare)
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Atomically sharp domain walls in an antiferromagnet
- 2022
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:13
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Tidskriftsartikel (refereegranskat)abstract
- The interest in understanding scaling limits of magnetic textures such as domain walls spans the entire field of magnetism from its physical fundamentals to applications in information technologies. Here, we explore antiferromagnetic CuMnAs in which imaging by x-ray photoemission reveals the presence of magnetic textures down to nanoscale, reaching the detection limit of this established microscopy in antiferromagnets. We achieve atomic resolution by using differential phase-contrast imaging within aberration-corrected scanning transmission electron microscopy. We identify abrupt domain walls in the antiferromagnetic film corresponding to the Néel order reversal between two neighboring atomic planes. Our work stimulates research of magnetic textures at the ultimate atomic scale and sheds light on electrical and ultrafast optical antiferromagnetic devices with magnetic field–insensitive neuromorphic functionalities.
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| 3. |
- Angenendt, Linus, et al.
(författare)
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Chromosomal Abnormalities and Prognosis in NPM1-Mutated Acute Myeloid Leukemia : A Pooled Analysis of Individual Patient Data From Nine International Cohorts
- 2019
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Ingår i: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 37:29, s. 2632-2642
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Nucleophosmin 1 (NPM1) mutations are associated with a favorable prognosis in acute myeloid leukemia (AML) when an internal tandem duplication (ITD) in the fms-related tyrosine kinase 3 gene (FLT3) is absent (FLT3-ITDneg) or present with a low allelic ratio (FLT3-ITDlow). The 2017 European LeukemiaNet guidelines assume this is true regardless of accompanying cytogenetic abnormalities. We investigated the validity of this assumption.METHODS: We analyzed associations between karyotype and outcome in intensively treated patients with NPM1(mut)/FLT3-ITDneg/low AML who were prospectively enrolled in registry databases from nine international study groups or treatment centers.RESULTS: Among 2,426 patients with NPM1(mut)/FLT3-ITDneg/low AML, 2,000 (82.4%) had a normal and 426 (17.6%) had an abnormal karyotype, including 329 patients (13.6%) with intermediate and 83 patients (3.4%) with adverse-risk chromosomal abnormalities. In patients with NPM1(mut)/FLT3-ITDneg/low AML, adverse cytogenetics were associated with lower complete remission rates (87.7%, 86.0%, and 66.3% for normal, aberrant intermediate, and adverse karyotype, respectively; P < .001), inferior 5-year overall (52.4%, 44.8%, 19.5%, respectively; P < .001) and event-free survival (40.6%, 36.0%, 18.1%, respectively; P < .001), and a higher 5-year cumulative incidence of relapse (43.6%, 44.2%, 51.9%, respectively; P = .0012). These associations remained in multivariable mixed-effects regression analyses adjusted for known clinicopathologic risk factors (P < .001 for all end points). In patients with adverse-risk chromosomal aberrations, we found no significant influence of the NPM1 mutational status on outcome.CONCLUSION: Karyotype abnormalities are significantly associated with outcome in NPM1(mut)/FLT3-ITDneg/low AML. When adverse-risk cytogenetics are present, patients with NPM1(mut) share the same unfavorable prognosis as patients with NPM1 wild type and should be classified and treated accordingly. Thus, cytogenetic risk predominates over molecular risk in NPM1(mut)/FLT3-ITDneg/low AML.
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| 4. |
- Ademuyiwa, Adesoji O., et al.
(författare)
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Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
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Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
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Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
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| 5. |
- Adolfsson, Lisa, 1984, et al.
(författare)
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Enhanced Secondary- and Hormone Metabolism in Leaves of Arbuscular Mycorrhizal Medicago truncatula.
- 2017
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Ingår i: Plant physiology. - : Oxford University Press (OUP). - 1532-2548 .- 0032-0889. ; 175:1, s. 392-411
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Tidskriftsartikel (refereegranskat)abstract
- Arbuscular mycorrhizas (AM) are the most common symbiotic associations between a plant's root compartment and fungi. They provide nutritional benefit (mostly inorganic phosphate [Pi]), leading to improved growth, and nonnutritional benefits, including defense responses to environmental cues throughout the host plant, which, in return, delivers carbohydrates to the symbiont. However, how transcriptional and metabolic changes occurring in leaves of AM plants differ from those induced by Pi fertilization is poorly understood. We investigated systemic changes in the leaves of mycorrhized Medicago truncatula in conditions with no improved Pi status and compared them with those induced by high-Pi treatment in nonmycorrhized plants. Microarray-based genome-wide profiling indicated up-regulation by mycorrhization of genes involved in flavonoid, terpenoid, jasmonic acid (JA), and abscisic acid (ABA) biosynthesis as well as enhanced expression of MYC2, the master regulator of JA-dependent responses. Accordingly, total anthocyanins and flavonoids increased, and most flavonoid species were enriched in AM leaves. Both the AM and Pi treatments corepressed iron homeostasis genes, resulting in lower levels of available iron in leaves. In addition, higher levels of cytokinins were found in leaves of AM- and Pi-treated plants, whereas the level of ABA was increased specifically in AM leaves. Foliar treatment of nonmycorrhized plants with either ABA or JA induced the up-regulation of MYC2, but only JA also induced the up-regulation of flavonoid and terpenoid biosynthetic genes. Based on these results, we propose that mycorrhization and Pi fertilization share cytokinin-mediated improved shoot growth, whereas enhanced ABA biosynthesis and JA-regulated flavonoid and terpenoid biosynthesis in leaves are specific to mycorrhization.
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| 6. |
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| 7. |
- Berg, Gunnar, et al.
(författare)
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Skolans kommunalisering och de professionellas frirum : Rapport utarbetad på uppdrag av utredningen om skolans kommunalisering
- 2014
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- FörordAllt fler är överens om att lärarna är skolans viktigaste resurs. Diskussionen om skolan handlar därför i hög grad om hur vi ska ge bästa tänkbara förutsättningar för lärarna att bedriva en bra undervisning. Man brukar säga att lärare och rektorer är exempel på professioner eller, lite beroende på definitionen, semiprofessioner. För alla grupper av professionella är det av yttersta vikt med autonomi i yrket –så även för lärare och rektorer. När effekterna av skolans kommunalisering ska bedömas är det därför relevant att analysera på vilket sätt lärarnas och rektorernas handlingsutrymme för självständiga professionella handlingar i den svenska skolan förändrats från tiden närmast före skolans kommunalisering och framåt. I denna rapport visas bland annat att staten vid olika tidsperioder tillerkänt skolans professionella varierande grad av handlingsutrymme för professionella handlingar i skolans vardagsarbete. I rapporten talas om att skolan före kommunaliseringen kännetecknades av central regelstyrning, som i samband med kommunaliseringen ersattes av en decentraliserad målstyrning. Numera utmärksstyrningen av centraliserad resultatstyrning. Vidare framhålls i rapporten att lärarna och rektorerna av olika skäl inte alltid använt det frirum för professionella handlingar som staten medgett.Undersökningen har genomförts efter ett uppdrag från denna utredning till professor Gunnar Berg, som utarbetat rapporten i samverkan med en grupp forskare bestående av Fia Andersson, Göran Bostedt, Judit Novak, Jan Perselli, Frank Sundh och Christer Wede. Forskarna ansvarar själva för innehållet i rapporten.Utredningen om skolans kommunalisering (U 2012:09)Leif Lewin Särskild utredare
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| 8. |
- Bergström, Anders, et al.
(författare)
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Origins and genetic legacy of prehistoric dogs
- 2020
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 370:6516, s. 557-563
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Tidskriftsartikel (refereegranskat)abstract
- Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.
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| 9. |
- Casanova, Ruben, et al.
(författare)
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Inactivation of the entire Arabidopsis group II GH3s confers tolerance to salinity and water deficit
- 2022
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Ingår i: New Phytologist. - : Wiley. - 0028-646X .- 1469-8137. ; 235, s. 263-275
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Tidskriftsartikel (refereegranskat)abstract
- Indole-3-acetic acid (IAA) controls a plethora of developmental processes. Thus, regulation of its concentration is of great relevance for plant performance. Cellular IAA concentration depends on its transport, biosynthesis and the various pathways for IAA inactivation, including oxidation and conjugation. Group II members of the GRETCHEN HAGEN 3 (GH3) gene family code for acyl acid amido synthetases catalysing the conjugation of IAA to amino acids. However, the high degree of functional redundancy among them has hampered thorough analysis of their roles in plant development. In this work, we generated an Arabidopsis gh3.1,2,3,4,5,6,9,17 (gh3oct) mutant to knock out the group II GH3 pathway. The gh3oct plants had an elaborated root architecture, showed an increased tolerance to different osmotic stresses, including an IAA-dependent tolerance to salinity, and were more tolerant to water deficit. Indole-3-acetic acid metabolite quantification in gh3oct plants suggested the existence of additional GH3-like enzymes in IAA metabolism. Moreover, our data suggested that 2-oxindole-3-acetic acid production depends, at least in part, on the GH3 pathway. Targeted stress-hormone analysis further suggested involvement of abscisic acid in the differential response to salinity of gh3oct plants. Taken together, our data provide new insights into the roles of group II GH3s in IAA metabolism and hormone-regulated plant development.
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| 10. |
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| 11. |
- Choi, Thomas Y., et al.
(författare)
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Managing extended supply chains
- 2021
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Ingår i: Journal of Business Logistics. - : Wiley. - 0735-3766 .- 2158-1592. ; 42:2, s. 200-206
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Tidskriftsartikel (refereegranskat)abstract
- We address how to manage extended supply chains that lie beyond the first-tier suppliers. The first-tier suppliers have their suppliers who provide them with goods or services. While lower-tier suppliers are often not an explicit concern of the focal firm, the firm's performance not only depends on the performance of its first-tier suppliers, but also on the performance of their suppliers and beyond. These lower-tier suppliers are much less visible and may not even be known to the focal firm. Our intention is to bring awareness to the importance of these lower-tier suppliers and capture possible strategies that buying companies may pursue to manage them. Extended supply chains are complex and involve evolving relationships between various buyers and suppliers that are located along different tiers of the chain and across different parts of the globe. We address several topic areas and suggest emerging research focuses that should be considered in coming years.
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| 12. |
- Dreyling, Martin, et al.
(författare)
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Ibrutinib combined with immunochemotherapy with or without autologous stem-cell transplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients with mantle cell lymphoma (TRIANGLE) : a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network
- 2024
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Ingår i: The Lancet. - 0140-6736. ; 403:10441, s. 2293-2306
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Tidskriftsartikel (refereegranskat)abstract
- Background: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. Methods: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II–IV mantle cell lymphoma, aged 18–65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1–5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1–4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1–19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. Findings: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84–92) versus 72% (67–79; hazard ratio 0·52 [one-sided 98·3% CI 0–0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67–79) versus 86% (82–91; hazard ratio 1·77 [one-sided 98·3% CI 0–3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3–5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3–5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). Interpretation: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. Funding: Janssen and Leukemia & Lymphoma Society.
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| 13. |
- Gröjer, Jan-Erik, et al.
(författare)
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Do Capital Markets Learn?
- 2004
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Ingår i: Presented at the EAA annual congress in Prague, 2004.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 14. |
- Hattinger, Monika, 1969-, et al.
(författare)
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Collaboration for lifelong-learning and contract education : towards a competence development model
- 2020
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Ingår i: VILÄR. - Trollhättan : Högskolan Väst. - 9789188847867 ; , s. 26-28
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Competence development and continuous lifelong learning are increasing due to skill transformations in the surrounding world which have an impact on workplaces. Upskilling, down-skilling, re-skilling, and the need of totally new skills are intensified that changes the conditions for a sustainable work practice. Old academic degrees need to be updated and for those lacking one, employees are required to build up academic credits. A constant knowledge and skills development of employees are therefore vital for the changed work conditions, meaning for both the organization and for the individual lifelong learning. In such situation, the university can play asignificant role for educating and supporting the working life with higher education in forms that are adjusted to organizational competence needs. With contract education - CE, the Swedish universities can educate staff for competence development on all educational levels, even those without an earlier academic degree. However, only organizations (including private companies and public authorities) can commission a service from a higher education institution. Individuals are not allowed to buy a course place, which is regulated through the jurisdiction of Uppdragsförordningen 2002:760. Despite the many possibilities with CE to collaborate with the surrounding society, it put pressures on the university toorganize, support and create new routines for the teaching and administrativepersonnel for the contract educational process of customer dialogue, needs inventory, course design, implementation, and follow-up on initiatives.Given such background, a collaborative development project between six universities in Sweden was conducted between November 2017 until January 2021. Overall aim was to increase the knowledge of CE by developing a collaborative model forcompetence development. The project was designed to enhance the knowledge informs of models, methods, and documentation in three development areas for CE; 1) organization and work processes, 2) customer dialogue, needs inventory and course design, and 3) incentives and collaboration skills. Both the conditions of the university’s internal abilities, restrictions, and structures (i.e., area 1) as well as the incentives and capabilities for external organizations (customers) involved in the activities (i.e., area 2), have been in focus. Area 3 concerned the teacher’s abilities to grant collaborative qualifications by teaching and engaging with external partners.In an initial case study of area 1 and 2, and we asked: What are the university conditions for organizing contract education, and how is the educational process directing and supporting the working life knowledge requirement?The second study focused on area 3 and we asked: How does the university grant collaboration skills and qualifications for teachers and leaders involved in contract education?Study one summarized eight universities responses showing that four universities have a centralized organization for running CE of which two universities have a university enterprise for CE. The other four universities are decentralized organized. It is not clear which organization is most beneficial. However, it seems that central functions are essential for a long-term external collaboration with key customers. The variation of administrative support is large, and there are also many universities lacking a full-fledge support organization for developing sustainable internal routines as well as external collaborations. When it comes to the educational process of routines for CE, most universities in the study show a very similar process, concerning the steps of curricula development, contract development, calculation, and student admission etc. However, there are various efficiency between the universities built on volume and experience of CE, which effect the time from initialization to evaluation of a CE course. The second and small document and interview study (six interviews) was targeting the teacher’s incitement, skills, and their ability to grant contract education work as accreditation in their professional academic career. This study shows that universities generally lack support for skills acquisition regarding “collaboration” skills both for professional development and further qualification. It also shows that the six included universities in the project, have diverse documentation and work practices for collaboration skills accreditation. However, this study and the project itself have pushed, the included universities to start up evaluation of their documents and routines around accreditation.A summary report for the whole project including a competence development model and methods and as well as findings from the two studies, raises the overarching need to develop the external collaboration university – working life, as well as knowledge about the university conditions for planning, developing, and running contract education as one successful competence model for lifelong learning. Contract education is therefore argued to support work-integrated and lifelong learning through collaborative forms between university and the working life.
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| 15. |
- Hebert, C., et al.
(författare)
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Magnetic circular dichroism in electron energy loss spectrometry
- 2008
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Ingår i: Ultramicroscopy. - : Elsevier BV. - 0304-3991 .- 1879-2723. ; 108:3, s. 277-284
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Tidskriftsartikel (refereegranskat)abstract
- The measurement of circular dichroism in the electron microscope is a new, emerging method and, as such, it is subject to constant refinement and improvement. Different ways can be envisaged to record the signal. We present an overview of the key steps in the energy-loss magnetic chiral dichroism (EMCD) experiment as well as a detailed review of the methods used in the intrinsic way where the specimen is used as a beam splitter. Lateral resolution up to 20-30 nm can be achieved, and the use of convergent beam techniques leads to an improved SIN ratio. Dichroic effects are shown for Ni and Co single crystal; as a counterexample, measurements were carried also for a non-magnetic (Ti) sample, where no dichroic effect was found.
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| 16. |
- Jansen, Willemijn J, et al.
(författare)
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Association of Cerebral Amyloid-β Aggregation With Cognitive Functioning in Persons Without Dementia.
- 2018
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 75:1, s. 84-95
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early event in Alzheimer disease (AD). Understanding the association between amyloid aggregation and cognitive manifestation in persons without dementia is important for a better understanding of the course of AD and for the design of prevention trials.To investigate whether amyloid-β aggregation is associated with cognitive functioning in persons without dementia.This cross-sectional study included 2908 participants with normal cognition and 4133 with mild cognitive impairment (MCI) from 53 studies in the multicenter Amyloid Biomarker Study. Normal cognition was defined as having no cognitive concerns for which medical help was sought and scores within the normal range on cognitive tests. Mild cognitive impairment was diagnosed according to published criteria. Study inclusion began in 2013 and is ongoing. Data analysis was performed in January 2017.Global cognitive performance as assessed by the Mini-Mental State Examination (MMSE) and episodic memory performance as assessed by a verbal word learning test. Amyloid aggregation was measured with positron emission tomography or cerebrospinal fluid biomarkers and dichotomized as negative (normal) or positive (abnormal) according to study-specific cutoffs. Generalized estimating equations were used to examine the association between amyloid aggregation and low cognitive scores (MMSE score ≤27 or memory z score≤-1.28) and to assess whether this association was moderated by age, sex, educational level, or apolipoprotein E genotype.Among 2908 persons with normal cognition (mean [SD] age, 67.4 [12.8] years), amyloid positivity was associated with low memory scores after age 70 years (mean difference in amyloid positive vs negative, 4% [95% CI, 0%-7%] at 72 years and 21% [95% CI, 10%-33%] at 90 years) but was not associated with low MMSE scores (mean difference, 3% [95% CI, -1% to 6%], P=.16). Among 4133 patients with MCI (mean [SD] age, 70.2 [8.5] years), amyloid positivity was associated with low memory (mean difference, 16% [95% CI, 12%-20%], P<.001) and low MMSE (mean difference, 14% [95% CI, 12%-17%], P<.001) scores, and this association decreased with age. Low cognitive scores had limited utility for screening of amyloid positivity in persons with normal cognition and those with MCI. In persons with normal cognition, the age-related increase in low memory score paralleled the age-related increase in amyloid positivity with an intervening period of 10 to 15 years.Although low memory scores are an early marker of amyloid positivity, their value as a screening measure for early AD among persons without dementia is limited.
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| 17. |
- Jansen, Willemijn J, et al.
(författare)
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Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis.
- 2015
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Ingår i: JAMA. - : American Medical Association (AMA). - 1538-3598 .- 0098-7484. ; 313:19, s. 1924-38
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Tidskriftsartikel (refereegranskat)abstract
- Cerebral amyloid-β aggregation is an early pathological event in Alzheimer disease (AD), starting decades before dementia onset. Estimates of the prevalence of amyloid pathology in persons without dementia are needed to understand the development of AD and to design prevention studies.
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| 18. |
- Lihavainen, Jenna, et al.
(författare)
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Salicylic acid metabolism and signalling coordinate senescence initiation in aspen in nature
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Deciduous trees exhibit a spectacular phenomenon of autumn senescence driven by the seasonality of their growth environment, yet there is no consensus which external or internal cues trigger it. Senescence starts at different times in European aspen (Populus tremula L.) genotypes grown in same location. By integrating omics studies, we demonstrate that aspen genotypes utilize similar transcriptional cascades and metabolic cues to initiate senescence, but at different times during autumn. The timing of autumn senescence initiation appeared to be controlled by two consecutive “switches”; 1) first the environmental variation induced the rewiring of the transcriptional network, stress signalling pathways and metabolic perturbations and 2) the start of senescence process was defined by the ability of the genotype to activate and sustain stress tolerance mechanisms mediated by salicylic acid. We propose that salicylic acid represses the onset of leaf senescence in stressful natural conditions, rather than promoting it as often observed in annual plants.
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| 19. |
- Majerle, Mitja, et al.
(författare)
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Peak neutron production from the 7Li(p,n) reaction in the 20-35 MeV range
- 2020
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Ingår i: ND 2019. - : E D P SCIENCES. - 9782759891061
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Konferensbidrag (refereegranskat)abstract
- New experimental data on the peak neutron production in the Li-7(p,n) reaction were collected during several irradiation campaigns at the NPI CAS. Time-of-flight method was used to measure the number of the peak neutrons in the forward direction, and the number of produced Be-7 nuclei was determined using gamma-spectrometry. The new measurement results are compared with experimental data from the literature and used for the validation of several different systematics and nuclear data libraries developed over the years.
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| 20. |
- Marschall, Tobias, et al.
(författare)
-
Computational pan-genomics : status, promises and challenges
- 2018
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Ingår i: Briefings in Bioinformatics. - : Oxford University Press (OUP). - 1467-5463 .- 1477-4054. ; 19:1, s. 118-135
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Tidskriftsartikel (refereegranskat)abstract
- Many disciplines, from human genetics and oncology to plant breeding, microbiology and virology, commonly face the challenge of analyzing rapidly increasing numbers of genomes. In case of Homo sapiens, the number of sequenced genomes will approach hundreds of thousands in the next few years. Simply scaling up established bioinformatics pipelines will not be sufficient for leveraging the full potential of such rich genomic data sets. Instead, novel, qualitatively different computational methods and paradigms are needed. We will witness the rapid extension of computational pan-genomics, a new sub-area of research in computational biology. In this article, we generalize existing definitions and understand a pan-genome as any collection of genomic sequences to be analyzed jointly or to be used as a reference. We examine already available approaches to construct and use pan-genomes, discuss the potential benefits of future technologies and methodologies and review open challenges from the vantage point of the above-mentioned biological disciplines. As a prominent example for a computational paradigm shift, we particularly highlight the transition from the representation of reference genomes as strings to representations as graphs. We outline how this and other challenges from different application domains translate into common computational problems, point out relevant bioinformatics techniques and identify open problems in computer science. With this review, we aim to increase awareness that a joint approach to computational pan-genomics can help address many of the problems currently faced in various domains.
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| 21. |
- Mischak, Harald, et al.
(författare)
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Comprehensive human urine standards for comparability and standardization in clinical proteome analysis
- 2010
-
Ingår i: Proteomics - Clinical Applications. - : Wiley. - 1862-8346 .- 1862-8354. ; 4:4, s. 464-478
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Urine proteomics is emerging as a powerful tool for biomarker discovery. The purpose of this study is the development of a well-characterized "real life" sample that can be used as reference standard in urine clinical proteomics studies. Experimental design: We report on the generation of male and female urine samples that are extensively characterized by different platforms and methods (CE-MS, LC-MS, LC-MS/MS, 1-D gel analysis in combination with nano-LC MS/MS (using LTQ-FT ultra), and 2-DE-MS) for their proteome and peptidome. In several cases analysis involved a definition of the actual biochemical entities, i.e. proteins/peptides associated with molecular mass and detected PTMs and the relative abundance of these compounds. Results: The combination of different technologies allowed coverage of a wide mass range revealing the advantages and complementarities of the different technologies. Application of these samples in "inter-laboratory" and "inter-platform" data comparison is also demonstrated. Conclusions and clinical relevance: These well-characterized urine samples are freely available upon request to enable data comparison especially in the context of biomarker discovery and validation studies. It is also expected that they will provide the basis for the comprehensive characterization of the urinary proteome.
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| 22. |
- Mischak, Harald, et al.
(författare)
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Implementation of proteomic biomarkers : making it work
- 2012
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Ingår i: European Journal of Clinical Investigation. - : Wiley. - 0014-2972 .- 1365-2362. ; 42:9, s. 1027-1036
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Tidskriftsartikel (refereegranskat)abstract
- While large numbers of proteomic biomarkers have been described, they are generally not implemented in medical practice. We have investigated the reasons for this shortcoming, focusing on hurdles downstream of biomarker verification, and describe major obstacles and possible solutions to ease valid biomarker implementation. Some of the problems lie in suboptimal biomarker discovery and validation, especially lack of validated platforms with well-described performance characteristics to support biomarker qualification. These issues have been acknowledged and are being addressed, raising the hope that valid biomarkers may start accumulating in the foreseeable future. However, successful biomarker discovery and qualification alone does not suffice for successful implementation. Additional challenges include, among others, limited access to appropriate specimens and insufficient funding, the need to validate new biomarker utility in interventional trials, and large communication gaps between the parties involved in implementation. To address this problem, we propose an implementation roadmap. The implementation effort needs to involve a wide variety of stakeholders (clinicians, statisticians, health economists, and representatives of patient groups, health insurance, pharmaceutical companies, biobanks, and regulatory agencies). Knowledgeable panels with adequate representation of all these stakeholders may facilitate biomarker evaluation and guide implementation for the specific context of use. This approach may avoid unwarranted delays or failure to implement potentially useful biomarkers, and may expedite meaningful contributions of the biomarker community to healthcare.
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| 23. |
- Novak, Jiri, 1977-
(författare)
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On the Importance of Accounting Information for Stock Market Efficiency
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- This thesis contributes to the discussion on the importance of accounting information for stock market efficiency. As any analysis of market efficiency depends on the use of adequate risk proxies, the thesis first investigates the ability of commonly used risk factors to explain the cross-sectional variation of Swedish stock returns. The findings suggest that capturing risk is indeed very complicated, as neither CAPM beta nor size and book-to-market equity ratio are significantly associated with realized monthly returns. The relative bid-ask spread is found to be the strongest of all the analyzed factors; nevertheless it does not seem to be related to momentum in the manner predicted in the conceptual argument presented earlier in the paper. Second, the thesis documents that simple accounting summary measures, such as earnings and book value of equity, can be used as benchmarks for the identification of mispriced stocks. Contrarian investment strategies (CISs) based on these simple measures earn a substantial value premium of 11-14%. In addition, we find that their effectiveness is compromised by noise that is caused by transitory earnings and accounting conservatism. Controlling for these factors increases the magnitude of the value premium and improves the consistency of the CIS. This suggests that the information reflected in key accounting measures is not fully reflected in stock prices. Finally, this thesis shows that the structure of accounting information matters too. It documents that the transition from the Swedish GAAP to IFRS in 2005 not only changed the average goodwill charges reported by companies, but also affected valuation of goodwill-intensive companies. This suggests that investors were not able to see through the conservative treatment of goodwill prior to the adoption of IFRS and that they recognized its higher persistence only after being provided with accounting information directly highlighting it. It is sometimes suggested that the structure of financial reporting “per se” should not be relevant to the valuation of companies, because the presentation itself does not the affect expected operating performance and because investors and analysts can “see through” and properly discount for various reporting formats. This thesis concludes that, contrary to this proposition, the structure of accounting does matter for equity valuation and that changes in representation do impact on stock prices.
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| 24. |
- Novak, Martin, et al.
(författare)
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Incentive Learning Underlying Cocaine-Seeking Requires mGluR5 Receptors Located on Dopamine D1 Receptor-Expressing Neurons
- 2010
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Ingår i: JOURNAL OF NEUROSCIENCE. - : Society for Neuroscience. - 0270-6474. ; 30:36, s. 11973-11982
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Tidskriftsartikel (refereegranskat)abstract
- Understanding the psychobiological basis of relapse remains a challenge in developing therapies for drug addiction. Relapse in cocaine addiction often occurs following exposure to environmental stimuli previously associated with drug taking. The metabotropic glutamate receptor, mGluR5, is potentially important in this respect; it plays a central role in several forms of striatal synaptic plasticity proposed to underpin associative learning and memory processes that enable drug-paired stimuli to acquire incentive motivational properties and trigger relapse. Using cell type-specific RNA interference, we have generated a novel mouse line with a selective knock-down of mGluR5 in dopamine D1 receptor-expressing neurons. Although mutant mice self-administer cocaine, we show that reinstatement of cocaine-seeking induced by a cocaine-paired stimulus is impaired. By examining different aspects of associative learning in the mutant mice, we identify deficits in specific incentive learning processes that enable a reward-paired stimulus to directly reinforce behavior and to become attractive, thus eliciting approach toward it. Our findings show that glutamate signaling through mGluR5 located on dopamine D1 receptor-expressing neurons is necessary for incentive learning processes that contribute to cue-induced reinstatement of cocaine-seeking and which may underpin relapse in drug addiction.
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| 25. |
- Novak, P., et al.
(författare)
-
Magnetism in the magnetoelectric hexaferrite system (Ba1-xSrx)(2)Zn2Fe12O22
- 2007
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Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 76:2, s. 024432-
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Tidskriftsartikel (refereegranskat)abstract
- The hexaferrite system (Ba1-xSrx)(2)Zn2Fe12O22 possesses a rich magnetic phase diagram and for strontium content x=0.75 exhibits a magnetoelectricity, the existence of which is intimately connected to the noncollinear arrangement of the iron spins. The system comprises seven cation sublattices, two of which have tetrahedral coordination. The tetrahedral sublattices are partly occupied by Fe and partly by Zn. Using ab initio-calculated exchange interactions we show that the magnetism in the (Ba1-xSrx)(2)Zn2Fe12O22 system is sensitive to the Fe and Zn distributions. The region of existence of the noncollinear spin structure and hence of ferroelectricity is determined and found to be rather narrow. The critical temperature of magnetic ordering is calculated using molecular field and random phase approximations. The results are in good agreement with the experiment.
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| 26. |
- Patterson, Nick, et al.
(författare)
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Large-scale migration into Britain during the Middle to Late Bronze Age
- 2022
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; , s. 588-594
-
Tidskriftsartikel (refereegranskat)abstract
- Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age1. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2-6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain's independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.
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| 27. |
- Raska, Milan, et al.
(författare)
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Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells
- 2007
-
Ingår i: Journal of Molecular Biology. - : Elsevier BV. - 1089-8638 .- 0022-2836. ; 369:1, s. 69-78
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Tidskriftsartikel (refereegranskat)abstract
- Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr.
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| 28. |
- Regber, Susann, 1956-
(författare)
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Barriers and Facilitators of Health Promotion and Obesity Prevention in Early Childhood : A Focus on Parents, Results from the IDEFICS Study
- 2014
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Childhood obesity has increased dramatically during the past thirty years. Parents are key persons in their children’s lives and their efforts to create healthy lifestyles are very important. However, social and economic determinants of health also affect parents’ opportunities to promote a healthy lifestyle.Aims: To explore barriers and facilitators in promoting healthy lifestyles and preventing childhood obesity, focusing on parental roles.Methods and main findings: Three studies originated from the Identification and Prevention of Dietary- and Lifestyle-induced health Effects in Children and InfantS (IDEFICS) study of determinants for two to nine-year-old children’s health in eight European countries. The fourth study was a qualitative interview study conducted in southwest Sweden.Paper I: In focus group discussions (20 focus groups with children and 36 with parents), parents described lack of time, financial constraints, availability and food marketing techniques as barriers for promoting healthy eating. School policies about food varied; only Sweden and Estonia provided free school lunches. Children described great variation in the availability of unhealthy foods and beverages in their homes.Paper II: Objectively measured Body Mass Index (BMI) of children (n=16 220) were compared to parents’ perception of and concern for their children’s health and weight status. In all weight categories and all countries, a substantial proportion of parents failed to accurately judge their child’s weight status. In general, parents considered their children to be healthy, irrespective of their weight status. Parents of children with overweight or obesity systematically underestimated their children’s weight status across eight European countries. Accurate parental weight perception in Europe differed according to geographic region.Paper III: Swedish IDEFICS participants (n=1825) were compared with an age- and sex-matched referent population (n=1825), using registers from Statistics Sweden and the Swedish Medical Birth Register. Longitudinal child growth data (n=3650) were collected from child health centers and school health services. Families with low income, less education, foreign background or single parenthood were underrepresented in the IDEFICS study. BMI at inclusion had no selection effect but, at eight years of age, the obesity prevalence was significantly greater among referents.Paper IV: A qualitative content analysis was used to interpret the findings from interviews with nurses (n=15) working at child health centers in the southwest of Sweden. The BMI Chart to identify overweight and obesity in children facilitated greater recognition but nurses used it inconsistently, a barrier to prevention. Other barriers were obesity considered a sensitive issue and that some parents wanted overweight children.Conclusion: Parents may not perceive their child’s growth trajectory from overweight to obesity, and the preschool years may pass without effort to change lifestyle. Therefore, objective measurement and information of children’s BMI weight status by healthcare professionals is of great importance. To reach all parents and avoid selection bias, health surveys or health promoting activities must be tailored. Health promoting activities at the family level as well as the societal level should start early in children’s lives to prevent childhood obesity.
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| 29. |
- Reimers, Sonka, et al.
(författare)
-
Defect-driven antiferromagnetic domain walls in CuMnAs films
- 2022
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- Efficient manipulation of antiferromagnetic (AF) domains and domain walls has opened up new avenues of research towards ultrafast, high-density spintronic devices. AF domain structures are known to be sensitive to magnetoelastic effects, but the microscopic interplay of crystalline defects, strain and magnetic ordering remains largely unknown. Here, we reveal, using photoemission electron microscopy combined with scanning X-ray diffraction imaging and micromagnetic simulations, that the AF domain structure in CuMnAs thin films is dominated by nanoscale structural twin defects. We demonstrate that microtwin defects, which develop across the entire thickness of the film and terminate on the surface as characteristic lines, determine the location and orientation of 180∘ and 90∘ domain walls. The results emphasize the crucial role of nanoscale crystalline defects in determining the AF domains and domain walls, and provide a route to optimizing device performance.
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| 30. |
- Reimers, Sonka, et al.
(författare)
-
Defect-driven antiferromagnetic domain walls in CuMnAs films
- 2023
-
Ingår i: 2023 IEEE International Magnetic Conference - Short Papers, INTERMAG Short Papers 2023 - Proceedings. - 9798350338362
-
Konferensbidrag (refereegranskat)abstract
- Antiferromagnetic (AF) materials offer a route to realising high-speed, high-density data storage devices that are robust against magnetic fields due to their intrinsic dynamics in the THz-regime and the lack magnetic stray fields. The key to functionality and efficiency is the control of AF domains and domain walls. Although AF domain structures are known to be sensitive to magnetoelastic effects, the microscopic interplay of crystalline defects, strain and magnetic ordering remains largely unknown. Here, we reveal, using photoemission electron microscopy combined with scanning x-ray diffraction microscopy and micromagnetic simulations, that the AF domain structure in CuMnAs thin films is dominated by nanoscale structural twin defects, which determine the location and orientation of 180° and 90° domain walls. The results emphasise the high sensitivity of the AF domain structure to the crystallographic nanostructure and provide a route to optimisng device performance.
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| 31. |
- Rubino, Stefano, 1978-, et al.
(författare)
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Energy-loss magnetic chiral dichroism (EMCD) : Magnetic chiral dichroism in the electron microscope
- 2008
-
Ingår i: Journal of Materials Research. - 0884-2914 .- 2044-5326. ; 23:10, s. 2582-2590
-
Forskningsöversikt (refereegranskat)abstract
- A new technique called energy-loss magnetic chiral dichroism (EMCD) has recently been developed [P. Schattschneider, et al. Nature 441, 486 (2006)] to measure magnetic circular dichroism in the transmission electron microscope (TEM) with a spatial resolution of 10 nm. This novel technique is the TEM counterpart of x-ray magnetic circular dichroism, which is widely used for the characterization of magnetic materials with synchrotron radiation. In this paper we describe several experimental methods that can be used to measure the EMCD signal [P. Schattschneider, et al. Nature 441, 486 (2006); C. Hébert, et al. Ultramicroscopy 108(3), 277 (2008); B. Warot-Fonrose, et al. Ultramicroscopy 108(5), 393 (2008); L. Calmels, et al. Phys. Rev. B 76, 060409 (2007); P. van Aken, et al. Microsc. Microanal. 13(3), 426 (2007)] and give a review of the recent improvements of this new investigation tool. The dependence of the EMCD on several experimental conditions (such as thickness, relative orientation of beam and sample, collection and convergence angle) is investigated in the transition metals iron, cobalt, and nickel. Different scattering geometries are illustrated; their advantages and disadvantages are detailed, together with current limitations. The next realistic perspectives of this technique consist of measuring atomic specific magnetic moments, using suitable spin and orbital sum rules, [L. Calmels, et al. Phys. Rev. B 76, 060409 (2007); J. Rusz, et al. Phys. Rev. B 76, 060408 (2007)] with a resolution down to 2 to 3 nm.
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| 32. |
- Rusz, Jan, et al.
(författare)
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Magnetic circular dichroism in electron microscopy
- 2008
-
Ingår i: Acta Physica Polonica. A. - 0587-4246 .- 1898-794X. ; 113:1, s. 599-604
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Tidskriftsartikel (refereegranskat)abstract
- Although the analogies between the electron energy loss spectra and X-ray absorption spectra were recognized long ago, the possibility to observe the magnetic circular dichroism in the electron microscope was demonstrated only recently. This technique combines the atom specificity with the high spatial resolution of the transmission electron microscope. Being a very young technique, there are still many open questions concerning the optimization of the signal to noise ratio. In this paper we study the dichroic signal dependence on the sample thickness, acceleration voltage and incoming beam tilt angle of bcc-Fe and fcc-Ni.
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| 33. |
- Rusz, Jan, et al.
(författare)
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Spin and orbital moment sum-rules for the electron energy loss chiral magnetic dichroism
- 2008
-
Ingår i: Physica. B, Condensed matter. - : Elsevier BV. - 0921-4526 .- 1873-2135. ; 403:5-9, s. 1614-1615
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Tidskriftsartikel (refereegranskat)abstract
- We present analytical sum-rules for the electron energy loss chiral magnetic dichroism experiment. Predictions of the sum-rules are simulated for Fe, Co and Ni crystals with artificialy varied spin and orbital moments by means of the LDA + U method. These are then compared to directly calculated magnetic moments and found to be in close agreement. (C) 2007 Elsevier B.V. All rights reserved.
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| 34. |
- Rusz, Jan, et al.
(författare)
-
Sum rules for electron energy loss near edge spectra
- 2007
-
Ingår i: Physical Review B. Condensed Matter and Materials Physics. - 1098-0121 .- 1550-235X. ; 76:6, s. 060408-
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Tidskriftsartikel (refereegranskat)abstract
- We derive four sum-rule expressions for spectra measured in electron energy loss near edge structure experiments. These sum rules permit the determination of spin and orbital magnetic moments, spin-orbit interaction, and number of states, analogously to the sum rules of x-ray magnetic circular dichroism. The derivation of the sum rules is based on dynamical electron diffraction theory and the properties of the mixed dynamic form factor. The accuracy of the sum rules is tested by a complete evaluation of the thickness-dependent electron energy loss spectra for iron, cobalt, and nickel crystals. We find that the sum rules reproduce both spin and orbital moments with very good accuracy. Our results provide a foundation for the use of the energy loss magnetic chiral dichroism technique as a quantitative probe of element-specific magnetic properties.
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| 35. |
- Schmitt, Roland, et al.
(författare)
-
The Combined Role of Galactose-Deficient IgA1 and Streptococcal IgA-Binding M Protein in Inducing IL-6 and C3 Secretion from Human Mesangial Cells: Implications for IgA Nephropathy.
- 2014
-
Ingår i: Journal of Immunology. - : The American Association of Immunologists. - 1550-6606 .- 0022-1767. ; 193:1, s. 317-326
-
Tidskriftsartikel (refereegranskat)abstract
- IgA nephropathy (IgAN) is characterized by mesangial cell proliferation and extracellular matrix expansion associated with immune deposits consisting of galactose-deficient polymeric IgA1 and C3. We have previously shown that IgA-binding regions of streptococcal M proteins colocalize with IgA in mesangial immune deposits in patients with IgAN. In the present study, the IgA-binding M4 protein from group A Streptococcus was found to bind to galactose-deficient polymeric IgA1 with higher affinity than to other forms of IgA1, as shown by surface plasmon resonance and solid-phase immunoassay. The M4 protein was demonstrated to bind to mesangial cells not via the IgA-binding region but rather via the C-terminal region, as demonstrated by flow cytometry. IgA1 enhanced binding of M4 to mesangial cells, but not vice versa. Costimulation of human mesangial cells with M4 and galactose-deficient polymeric IgA1 resulted in a significant increase in IL-6 secretion compared with each stimulant alone. Galactose-deficient polymeric IgA1 alone, but not M4, induced C3 secretion from the cells, and costimulation enhanced this effect. Additionally, costimulation enhanced mesangial cell proliferation compared with each stimulant alone. These results indicate that IgA-binding M4 protein binds preferentially to galactose-deficient polymeric IgA1 and that these proteins together induce excessive proinflammatory responses and proliferation of human mesangial cells. Thus, tissue deposition of streptococcal IgA-binding M proteins may contribute to the pathogenesis of IgAN.
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| 36. |
- Simura, Jan, et al.
(författare)
-
Plant Hormonomics: Multiple Phytohormone Profiling by Targeted Metabolomics
- 2018
-
Ingår i: Plant Physiology. - : Oxford University Press (OUP). - 0032-0889 .- 1532-2548. ; 177, s. 476-489
-
Tidskriftsartikel (refereegranskat)abstract
- Phytohormones are physiologically important small molecules that play essential roles in intricate signaling networks that regulate diverse processes in plants. We present a method for the simultaneous targeted profiling of 101 phytohormone-related analytes from minute amounts of fresh plant material (less than 20 mg). Rapid and nonselective extraction, fast one-step sample purification, and extremely sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry enable concurrent quantification of the main phytohormone classes: cytokinins, auxins, brassinosteroids, gibberellins, jasmonates, salicylates, and abscisates. We validated this hormonomic approach in salt-stressed and control Arabidopsis (Arabidopsis thaliana) seedlings, quantifying a total of 43 endogenous compounds in both root and shoot samples. Subsequent multivariate statistical data processing and cross-validation with transcriptomic data highlighted the main hormone metabolites involved in plant adaptation to salt stress.
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| 37. |
- Verbeeck, J., et al.
(författare)
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Optimal aperture sizes and positions for EMCD experiments
- 2008
-
Ingår i: Ultramicroscopy. - : Elsevier BV. - 0304-3991 .- 1879-2723. ; 108:9, s. 865-872
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Tidskriftsartikel (refereegranskat)abstract
- The signal-to-noise ratio (SNR) in energy-loss magnetic chiral dichroism (EMCD)-the equivalent of Xray magnetic circular dichroism (XMCD) in the electron microscope-is optimized with respect to the detector shape, size and position. We show that an important increase in SNR over previous experiments can be obtained when taking much larger detector sizes. We determine the ideal shape of the detector but also show that round apertures are a good compromise if placed in their optimal position. We develop the theory for a simple analytical description of the EMCD experiment and then apply it to dynamical multibeam Bloch wave calculations and to an experimental data set. In all cases it is shown that a significant and welcome improvement of the SNR is possible.
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| 38. |
- Wada, Yoshinao, et al.
(författare)
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Comparison of methods for profiling O-glycosylation: Human Proteome Organisation Human Disease Glycomics/Proteome Initiative multi-institutional study of IgA1.
- 2010
-
Ingår i: Molecular & cellular proteomics. - 1535-9484. ; 9:4, s. 719-727
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Tidskriftsartikel (refereegranskat)abstract
- The Human Proteome Organisation Human Disease Glycomics/Proteome Initiative recently coordinated a multi-institutional study that evaluated methodologies that are widely used for defining the N-glycan content in glycoproteins. The study convincingly endorsed mass spectrometry as the technique of choice for glycomic profiling in the discovery phase of diagnostic research. The present study reports the extension of the Human Disease Glycomics/Proteome Initiative's activities to an assessment of the methodologies currently used for O-glycan analysis. Three samples of IgA1 isolated from the serum of patients with multiple myeloma were distributed to 15 laboratories worldwide for O-glycomics analysis. A variety of mass spectrometric and chromatographic procedures representative of current methodologies were used. Similar to the previous N-glycan study, the results convincingly confirmed the pre-eminent performance of MS for O-glycan profiling. Two general strategies were found to give the most reliable data, namely direct MS analysis of mixtures of permethylated reduced glycans in the positive ion mode and analysis of native reduced glycans in the negative ion mode using LC-MS approaches. In addition, mass spectrometric methodologies to analyze O-glycopeptides were also successful.
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