| 1. |
- Governa, Valeria, et al.
(författare)
-
Landscape of surfaceome and endocytome in human glioma is divergent and depends on cellular spatial organization
- 2022
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 119:9
-
Tidskriftsartikel (refereegranskat)abstract
- Therapeutic strategies directed at the tumor surfaceome (TS), including checkpoint inhibitor blocking antibodies, antibody drug conjugates (ADCs), and chimeric antigen receptor T (CAR-T) cells, provide a new armament to fight cancer. However, a remaining bottleneck is the lack of strategies to comprehensively interrogate patient tumors for potential TS targets. Here, we have developed a platform (tumor surfaceome mapping [TS-MAP]) integrated with a newly curated TS classifier (SURFME) that allows profiling of primary 3D cultures and intact patient glioma tumors with preserved tissue architecture. Moreover, TS-MAP specifically identifies proteins capable of endocytosis as tractable targets for ADCs and other modalities requiring toxic payload internalization. In high-grade gliomas that remain among the most aggressive forms of cancer, we show that cellular spatial organization (2D vs. 3D) fundamentally transforms the surfaceome and endocytome (e.g., integrins, proteoglycans, semaphorins, and cancer stem cell markers) with general implications for target screening approaches, as exemplified by an ADC targeting EGFR. The TS-MAP platform was further applied to profile the surfaceome and endocytome landscape in a cohort of freshly resected gliomas. We found a highly diverse TS repertoire between patient tumors, not directly associated with grade and histology, which highlights the need for individualized approaches. Our data provide additional layers of understanding fundamental to the future development of immunotherapy strategies, as well as procedures for proteomics-based target identification and selection. The TS-MAP platform should be widely applicable in efforts aiming at a better understanding of how to harness the TS for personalized immunotherapy.
|
|
| 2. |
|
|
| 3. |
- Surendran, Praveen, et al.
(författare)
-
Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals
- 2020
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 52:12, s. 1314-1332
-
Tidskriftsartikel (refereegranskat)abstract
- Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to similar to 1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency <= 0.01) variant BP associations (P < 5 x 10(-8)), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were similar to 8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.
|
|
| 4. |
- Andersson Varga, Pernilla, 1961, et al.
(författare)
-
Att försöka få grepp om genrepedagogik(en) – exemplet Läslyftet
- 2022
-
Ingår i: SMDI 15 Språk och litteratur – en omöjlig eller skön förening? Lunds universitet, 23–24 november 2022..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I den svenska skolkontexten framställs genrepedagogik som inflytelserik och ofta använd (Bergh Nestlog, Danielsson & Krog 2018, Borsgård 2021, Hansson 2013, Kinderberg 2021, Liberg, Wiksten Folkeryd & af Geijerstam 2012, Nygård Larsson 2015, Walldén 2019). Dock är den inhemska forskningen om vad som förstås som genrepedagogisk undervisning eller hur den iscensätts relativt begränsad. Ännu mindre vet vi om i vilken utsträckning pedagogiken förekommer i svensk skola. I detta paper undersöks hur Sydneyskolans genrepedagogik uppfattas och rekontextualiseras (Bernstein 2000) i den statliga fortbildningssatsningen Läslyftet vars syfte är att stärka lärares kompetens att undervisa språk- och kunskapsutvecklande i alla ämnen och på alla stadier i svensk skola. I analysen av materialet används verktyg som hämtas från de teorier som Sydneyskolans genrepedagogik vilar på – systemisk funktionell lingvistik (Halliday 2004), genreteori (Martin 1992) och Vygotskijs sociokulturella teorier (Vygotskij 1986). Flertalet av de Läslyftsartiklar som presenterar genrepedagogiken reducerar den till arbete enligt cirkelmodellen, där pedagogiken beskrivs som ett arbetssätt uppdelat i tre eller fyra faser, närmast jämförbara de faser som skrivprocessen (Flower & Hayes 1980) inrymmer. I den mån genrepedagogiken förankras teoretisk, gäller det främst stöttning, men vad som ska stöttas förblir ofta oklart. Språkvetenskapliga teorier tas enbart upp i ett fåtal artiklar, och genrepedagogikens potential att stärka elevernas kritiska förhållningssätt till text förbigås. Den preliminära slutsatsen av studien är att rekontextualiseringen av genrepedagogiken inom Läslyftet är förenklad och ibland också förvanskad, vilket gör att den potential som inryms i Sydneyskolans ursprungliga version av genrepedagogik inte kommer i bruk.
|
|
| 5. |
- Andersson Varga, Pernilla, 1961, et al.
(författare)
-
Att försöka få grepp om genrepedagogik(en) i den svenska skolkontexen.
- 2022
-
Ingår i: Skriv! Les! Nordisk forskerkonferanse om lesing, skriving, og literacy. NTNU Trondheim, 10-11 maj, 2022..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I den svenska skolkontexten framställs genrepedagogik(en) som inflytelserik och ofta använd (Bergh Nestlog, Danielsson & Krog 2018, Borsgård 2021, Hansson 2013, Kinderberg 2021, Liberg, Wiksten Folkeryd & af Geijerstam 2012, Nygård Larsson 2015, Walldén 2019). Dock är den inhemska forskningen om vad som förstås som genrepedagogisk undervisning eller hur den iscensätts relativt begränsad. Ännu mindre vet vi om i vilken utsträckning pedagogiken förekommer i svensk skola. I detta paper undersöks hur Sydneyskolans genrepedagogik uppfattas och rekontextualiseras (Bernstein 2000) på olika nivåer i det svenska utbildningssystemet.
|
|
| 6. |
|
|
| 7. |
- Andersson Varga, Pernilla, 1961, et al.
(författare)
-
Getting to grips with genre pedagogy - Mapping and analysing the recontextualisation of Sydney school genre pedagogy in the Swedish educational context
- 2023
-
Ingår i: Linguistics and Education. - 0898-5898. ; 78
-
Tidskriftsartikel (refereegranskat)abstract
- In Sweden, genre pedagogy is repeatedly put forward as influential. However, there is little research on how it is understood and applied in practice. This article is an attempt to get to grips with how genre pedagogy has been recontextualised in the Swedish school context. This is done by discourse analyses of curriculum and syllabuses, a professional development programme on literacy and teacher guides claiming to draw on genre pedagogy. We conclude that the recontextualisation of genre pedagogy is a simplification, primarily focusing on the pedagogical know-how through a student-centred application of the Teaching and Learning Cycle, while knowledge about language and the underlying ideology aiming at redistributing educational capital is downplayed or absent.
|
|
| 8. |
|
|
| 9. |
- Bott, Lukas Thomas, et al.
(författare)
-
Coulomb dissociation of O-16 into He-4 and C-12
- 2023
-
Ingår i: NUCLEAR PHYSICS IN ASTROPHYSICS - X, NPA-X 2022. - : EDP Sciences. - 2100-014X. ; 279
-
Konferensbidrag (refereegranskat)abstract
- We measured the Coulomb dissociation of O-16 into He-4 and C-12 within the FAIR Phase-0 program at GSI Helmholtzzentrum fur Schwerionenforschung Darmstadt, Germany. From this we will extract the photon dissociation cross section O-16(alpha,gamma)C-12, which is the time reversed reaction to C-12(alpha,gamma)O-16. With this indirect method, we aim to improve on the accuracy of the experimental data at lower energies than measured so far. The expected low cross section for the Coulomb dissociation reaction and close magnetic rigidity of beam and fragments demand a high precision measurement. Hence, new detector systems were built and radical changes to the (RB)-B-3 setup were necessary to cope with the high-intensity O-16 beam. All tracking detectors were designed to let the unreacted O-16 ions pass, while detecting the C-12 and He-4.
|
|
| 10. |
- Campbell, Richard A., et al.
(författare)
-
Direct Impact of Nonequilibrium Aggregates on the Structure and Morphology of Pdadmac/SDS Layers at the Air/Water Interface
- 2014
-
Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 30:29, s. 8664-8674
-
Tidskriftsartikel (refereegranskat)abstract
- We discuss different nonequilibrium mechanisms by which bulk aggregates directly modify, and can even control, the interfacial structure and morphology of an oppositely charged polyelectrolyte/surfactant (P/S) mixture. Samples are categorized at the air/water interface with respect to the dynamic changes in the bulk phase behavior, the bulk composition, and the sample history using complementary surface-sensitive techniques. First, we show that bulk aggregates can spontaneously interact with the adsorption layer and are retained in it and that this process occurs most readily for positively charged aggregates with an expanded structure. In this case, key nonequilibrium issues of aggregate dissociation and spreading of surface-active material at the interface have a marked influence on the macroscopic interfacial properties. In a second distinct mechanism, aggregates inherently become trapped at the interface during its creation and lateral flocculation occurs. This irreversible process is most pronounced for aggregates with the lowest charge. A third mechanism involves the deposition of aggregates at interfaces due to their transport under gravity. The specificity of this process at an interface depends on its location and is mediated by density effects in the bulk. The prevalence of each mechanism critically depends on a number of different factors, which are outlined systematically here for the first time. This study highlights the sheer complexity by which aggregates can directly impact the interfacial properties of a P/S mixture. Our findings offer scope for understanding seemingly mysterious irreproducible effects which can compromise the performance of formulations in wide-ranging applications from foams to emulsions and lubricants.
|
|
| 11. |
- Campbell, Richard A., et al.
(författare)
-
Effects of Bulk Colloidal Stability on Adsorption Layers of Poly(diallyldimethylammonium Chloride)/Sodium Dodecyl Sulfate at the Air-Water Interface Studied by Neutron Reflectometry
- 2011
-
Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 115:51, s. 15202-15213
-
Tidskriftsartikel (refereegranskat)abstract
- We show for the oppositely charged system poly(diallyldimethylammonium chloride)/sodium dodecyl sulfate that the cliff edge peak in its surface tension isotherm results from the comprehensive precipitation of bulk complexes into sediment, leaving a supernatant that is virtually transparent and a depleted adsorption layer at the air/water interface. The aggregation and settling processes take about 3 days to reach completion and occur at bulk compositions around charge neutrality of the complexes which lack long-term colloidal stability. We demonstrate excellent quantitative agreement between the measured surface tension values and a peak calculated from the surface excess of surfactant in the precipitation region measured by neutron reflectometry, using the approximation that there is no polymer left in the liquid phase. The nonequilibrium nature of the system is emphasized by the production of very different interfacial properties from equivalent aged samples that are handled differently. We go on to outline our perspective on the "true equilibrium" state of this intriguing system and conclude with a comment on its practical relevance given that the interfacial properties can be so readily influenced by the handling of kinetically trapped bulk aggregates.
|
|
| 12. |
- Campbell, Richard A., et al.
(författare)
-
Multilayers at Interfaces of an Oppositely Charged Polyelectrolyte/Surfactant System Resulting from the Transport of Bulk Aggregates under Gravity
- 2012
-
Ingår i: The Journal of Physical Chemistry Part B. - : American Chemical Society (ACS). - 1520-5207 .- 1520-6106. ; 116:27, s. 7981-7990
-
Tidskriftsartikel (refereegranskat)abstract
- We show conclusively that multilayers at interfaces of an oppositely charged polyelectrolyte/surfactant system can result from the transport under gravity of bulk aggregates with internal molecular structure. This process was demonstrated by measurements of poly-(diallyldimethylammonium chloride)/sodium dodecyl sulfate solutions at the air/liquid and solid/liquid interfaces using neutron reflectometry. In the latter case a novel approach involving the comparison of reflection up versus down measurements provided key evidence. Interfacial multilayers indicated by a strong Bragg peak and clear off-specular scattering are exhibited under three conditions: (1) only for samples in the phase separation region, (2) only for fresh samples where a suspension of bulk aggregates remains in solution, and (3) only when the creaming or sedimentation process occurs in the direction of the interface under examination. This bulk transport mechanism is an alternative route of formation of interfacial multilayers to surface induced self assembly The two processes evidently give rise to interfaces with very different structural and rheological properties. Such directionality effects in the formation of nanostructured liquid interfaces may have implications for a broad range of soft matter and biophysical systems containing macromolecules such as synthetic polymers, proteins, or DNA.
|
|
| 13. |
- Campbell, Richard A., et al.
(författare)
-
New Perspective on the Cliff Edge Peak in the Surface Tension of Oppositely Charged Polyelectrolyte/Surfactant Mixtures
- 2010
-
Ingår i: The Journal of Physical Chemistry Letters. - : American Chemical Society (ACS). - 1948-7185. ; 1:20, s. 3021-3026
-
Tidskriftsartikel (refereegranskat)abstract
- We present how dramatically the nonequilibrium nature of an oppsitely charged polyelectrolyte/surfactant mixture can affect the interfacial properties. We show for the first time that the cliff edge peak in the surface tension of the poly(diallydimethylammonium chloride)/sodium dodecyl surfate system is produced as a direct result of depletion of surface-active material from the bulk solution due to a show precipitation process in the phase separation region. Simple illustrations are given of how to control the production of the peak, to eliminate the feature for equivalent aged solutions through the use of different sample handling methods, and even to change its characteristics at short surface ages. The potential to tune nonequilibrium, steady-state interfacial properties for such strongly associating system is clearly demonstrated. We propose that our findings in general may be applicable to a broad range of mixture containing surfactants and oppositely charged macromolecules such as polymers proteins and DNA.
|
|
| 14. |
- Cserni, Gabor, et al.
(författare)
-
Distinction of isolated tumour cells and micrometastasis in lymph nodes of breast cancer patients according to the new Tumour Node Metastasis (TNM) definitions
- 2011
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 47:6, s. 887-894
-
Tidskriftsartikel (refereegranskat)abstract
- Isolated tumour cells and micrometastases represent two different staging categories and are often dealt with differently when identified in sentinel lymph nodes of breast cancer patients. The reproducibility of these categories was found to be suboptimal in several studies. The new edition of the TNM (Tumour Node Metastasis) is expected to improve the reproducibility of these categories. Fifty cases of possible low-volume nodal involvement were represented by one to four digital images and were analysed by members of the European Working Group for Breast Screening Pathology (EWGBSP). The kappa value for interobserver agreement of the pN (TNM) staging categories and of the isolated tumour cells category were 0.55 and 0.56 reflecting moderate reproducibility, and the kappa of the micrometastatic category (0.62) reflected substantial reproducibility. This is an improvement over the results gained on the basis of the previous edition of the TNM. Maximal adherence to the category definitions supplemented by explanatory texts in the staging manual should result in more homogeneous nodal staging of breast cancer. (C) 2010 Elsevier Ltd. All rights reserved.
|
|
| 15. |
- Cserni, Gábor, et al.
(författare)
-
Distribution pattern of the Ki67 labelling index in breast cancer and its implications for choosing cut-off values.
- 2014
-
Ingår i: Breast. - : Elsevier BV. - 1532-3080. ; 23:3, s. 259-263
-
Tidskriftsartikel (refereegranskat)abstract
- The Ki67 labelling index (LI - proportion of staining cells) is widely used to reflect proliferation in breast carcinomas. Several cut-off values have been suggested to distinguish between tumours with low and high proliferative activity. The aim of the current study was to evaluate the distribution of Ki67 LIs in breast carcinomas diagnosed at different institutions by different pathologists using the method reflecting their daily practice. Pathologists using Ki67 were asked to provide data (including the LI, type of the specimen, receptor status, grade) on 100 consecutively stained cases, as well as details of their evaluation. A full dataset of 1709 carcinomas was collected from 19 departments. The median Ki67 LI was 17% for all tumours and 14% for oestrogen receptor-positive and HER2-negative carcinomas. Tumours with higher mitotic counts were associated with higher Ki67 LIs. Ki67 LIs tended to cluster around values ending with 5 or 0 both in cases where the values were obtained by counting the proportion of stained tumour cell nuclei and those where the values were obtained by estimation. On the basis of the distribution pattern described, some currently used Ki67 LI cut off values are not realistic, and it is proposed to select more realistic values ending with 0 or 5.
|
|
| 16. |
- de Vries, Paul S., et al.
(författare)
-
Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
-
Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
-
Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
|
|
| 17. |
|
|
| 18. |
- Donini, Lorenzo M, et al.
(författare)
-
A consensus document on definition and diagnostic criteria for orthorexia nervosa
- 2022
-
Ingår i: Eating and Weight Disorders. - Milan : Springer. - 1124-4909 .- 1590-1262. ; 27, s. 3695-3711
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with “correct” eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included.Methods: 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A–Definition, Clinical Aspects, Duration; B–Consequences; C–Onset; D–Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants.Results: 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON.Conclusions: This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel.Level of evidence: Level V: opinions of expert committees.© 2022, The Author(s).
|
|
| 19. |
- Donini, Lorenzo M., et al.
(författare)
-
Correction : A consensus document on definition and diagnostic criteria for orthorexia nervosa
- 2023
-
Ingår i: Eating and Weight Disorders. - Milan : Springer. - 1124-4909 .- 1590-1262. ; 28
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- In this article Rebecca C. Reynolds was missing from the author list. The complete correct author group is given below. Lorenzo M. Donini, Juan Ramón Barrada, Friederike Barthels, Thomas M. Dunn, Camille Babeau, Anna Brytek-Matera, Hellas Cena, Silvia Cerolini, Hye-hyun Cho, Maria Coimbra, Massimo Cuzzolaro, Claudia Ferreira, Valeria Galfano, Maria G. Grammatikopoulou, Souheil Hallit, Linn Håman, Phillipa Hay, Masahito Jimbo, Clotilde Lasson, Eva-Carin Lindgren, Renee McGregor, Marianna Minnetti, Edoardo Mocini, Sahar Obeid, Crystal D. Oberle, Maria-Dolores Onieva-Zafra, Marie-Christine Opitz, María-Laura Parra-Fernández, Reinhard Pietrowsky, Natalija Plasonja, Eleonora Poggiogalle, Adrien Rigó, Rachel F. Rodgers, Maria Roncero, Carmina Saldaña, Cristina Segura-Garcia, Jessica Setnick, Ji-Yeon Shin, Grazia Spitoni, Jana Strahler, Nanette Stroebele-Benschop, Patrizia Todisco, Mariacarolina Vacca, Martina Valente, Màrta Varga, Andrea Zagaria, Hana Flynn Zickgraf, Rebecca C. Reynolds & Caterina Lombardo. The original article [1] has been corrected. © 2023, Springer Nature Switzerland AG.
|
|
| 20. |
- Erzurumluoglu, A. Mesut, et al.
(författare)
-
Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci
- 2020
-
Ingår i: Molecular Psychiatry. - : Nature Publishing Group. - 1359-4184 .- 1476-5578. ; 25:10, s. 2392-2409
-
Tidskriftsartikel (refereegranskat)abstract
- Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.
|
|
| 21. |
- Flannick, Jason, et al.
(författare)
-
Data Descriptor : Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
- 2017
-
Ingår i: Scientific Data. - : Springer Science and Business Media LLC. - 2052-4463. ; 4
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (> 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
|
|
| 22. |
- Fretts, Amanda M., et al.
(författare)
-
Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores : a meta-analysis of 50,345 Caucasians
- 2015
-
Ingår i: American Journal of Clinical Nutrition. - : Elsevier BV. - 0002-9165 .- 1938-3207. ; 102:5, s. 1266-1278
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Recent studies suggest that meat intake is associated with diabetes-related phenotypes. However, whether the associations of meat intake and glucose and insulin homeostasis are modified by genes related to glucose and insulin is unknown. Objective: We investigated the associations of meat intake and the interaction of meat with genotype on fasting glucose and insulin concentrations in Caucasians free of diabetes mellitus. Design: Fourteen studies that are part of the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium participated in the analysis. Data were provided for up to 50,345 participants. Using linear regression within studies and a fixed-effects meta-analysis across studies, we examined l) the associations of processed meat and unprocessed red meat intake with fasting glucose and insulin concentrations; and 2) the interactions of processed meat and unprocessed red meat with genetic risk score related to fasting glucose or insulin resistance on fasting glucose and insulin concentrations. Results: Processed meat was associated with higher fasting glucose, and unprocessed red meat was associated with both higher fasting glucose and fasting insulin concentrations after adjustment for potential confounders [not including body mass index (BMI)]. For every additional 50-g serving of processed meat per day, fasting glucose was 0.021 mmol/L (95% CI: 0.011, 0.030 mmol/L) higher. Every additional 100-g serving of unprocessed red meat per day was associated with a 0.037-mmol/L (95% CI: 0.023, 0.051-mmol/L) higher fasting glucose concentration and a 0.049-1n-pmon (95% CI: 0.035, 0.063-1n-pmol/L) higher fasting insulin concentration. After additional adjustment for BMI, observed associations were attenuated and no longer statistically significant. The association of processed meat and fasting insulin did not reach statistical significance after correction for multiple comparisons. Observed associations were not modified by genetic loci known to influence fasting glucose or insulin resistance. Conclusion: The association of higher fasting glucose and insulin concentrations with meat consumption was not modified by an index of glucose- and insulin-related single-nucleotide polymorphisms.
|
|
| 23. |
- Fuchsberger, Christian, et al.
(författare)
-
The genetic architecture of type 2 diabetes
- 2016
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
-
Tidskriftsartikel (refereegranskat)abstract
- The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.
|
|
| 24. |
- Gascón, Jordi, et al.
(författare)
-
Performance of two immunoassays for the determination of atrazine in sea water samples as compared with on-line solid phase extraction-liquid chromatography-diode array detection
- 1996
-
Ingår i: Analytica Chimica Acta. - : Elsevier BV. - 0003-2670. ; 330:1, s. 41-51
-
Tidskriftsartikel (refereegranskat)abstract
- Two immunoassay formats, magnetic particles-based assay (Atrazine RaPID assay and Atrazine High-Sensitivity RaPID assay) and microtiter plate based assay (Department of Entomology and Environmental Toxicology, University of California in Davis) were evaluated for the determination of atrazine in sea water samples. The results obtained were compared and validated with those obtained by using on-line solid phase extraction followed by liquid chromatography-diode array detection (on-line SPE-LC-DAD). The correlation between both techniques was good when analyzing levels of atrazine ranging from 0.01 to 5 μg/l in samples showing salt concentration values varying from 0 to 35 g/l and pH values from 2 to 10. One of these immunoassays (Atrazine High-Sensitivity RaPID assay) was employed to directly analyze atrazine in real estuarine and coastal water samples. The same samples were analyzed after filtration and C18 Empore disks extraction.
|
|
| 25. |
- Gorlova, Olga, et al.
(författare)
-
Identification of Novel Genetic Markers Associated with Clinical Phenotypes of Systemic Sclerosis through a Genome-Wide Association Strategy
- 2011
-
Ingår i: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 7:7
-
Tidskriftsartikel (refereegranskat)abstract
- The aim of this study was to determine, through a genome-wide association study (GWAS), the genetic components contributing to different clinical sub-phenotypes of systemic sclerosis (SSc). We considered limited (IcSSc) and diffuse (dcSSc) cutaneous involvement, and the relationships with presence of the SSc-specific auto-antibodies, anti-centromere (ACA), and anti-topoisomerase I (ATA). Four GWAS cohorts, comprising 2,296 SSc patients and 5,171 healthy controls, were meta-analyzed looking for associations in the selected subgroups. Eighteen polymorphisms were further tested in nine independent cohorts comprising an additional 3,175 SSc patients and 4,971 controls. Conditional analysis for associated SNPs in the HLA region was performed to explore their independent association in antibody subgroups. Overall analysis showed that non-HLA polymorphism rs11642873 in IRF8 gene to be associated at GWAS level with lcSSc (P = 2.32x10(-12), OR = 0.75). Also, rs12540874 in GRB10 gene (P = 1.27 x 10(-6), OR = 1.15) and rs11047102 in SOX5 gene (P = 1.39x10(-7), OR = 1.36) showed a suggestive association with lcSSc and ACA subgroups respectively. In the HLA region, we observed highly associated allelic combinations in the HLA-DQB1 locus with ACA (P = 1.79x10(-61), OR = 2.48), in the HLA-DPA1/B1 loci with ATA (P = 4.57x10(-76), OR = 8.84), and in NOTCH4 with ACA P = 8.84x10(-21), OR = 0.55) and ATA (P = 1.14x10(-8), OR = 0.54). We have identified three new non-HLA genes (IRF8, GRB10, and SOX5) associated with SSc clinical and autoantibody subgroups. Within the HLA region, HLA-DQB1, HLA-DPA1/B1, and NOTCH4 associations with SSc are likely confined to specific auto-antibodies. These data emphasize the differential genetic components of subphenotypes of SSc.
|
|
| 26. |
- Hegedüs, Luca, et al.
(författare)
-
The Prognostic Relevance of PMCA4 Expression in Melanoma : Gender Specificity and Implications for Immune Checkpoint Inhibition
- 2022
-
Ingår i: International Journal of Molecular Sciences. - : MDPI AG. - 1661-6596 .- 1422-0067. ; 23:6
-
Tidskriftsartikel (refereegranskat)abstract
- PMCA4 is a critical regulator of Ca2+ homeostasis in mammalian cells. While its biological and prognostic relevance in several cancer types has already been demonstrated, only preclinical investigations suggested a metastasis suppressor function in melanoma. Therefore, we studied the expression pattern of PMCA4 in human skin, nevus, as well as in primary and metastatic melanoma using immunohistochemistry. Furthermore, we analyzed the prognostic power of PMCA4 mRNA levels in cutaneous melanoma both at the non-metastatic stage as well as after PD-1 blockade in advanced disease. PMCA4 localizes to the plasma membrane in a differentiation dependent manner in human skin and mucosa, while nevus cells showed no plasma membrane staining. In contrast, primary cutaneous, choroidal and conjunctival melanoma cells showed specific plasma membrane localization of PMCA4 with a wide range of intensities. Analyzing the TCGA cohort, PMCA4 mRNA levels showed a gender specific prognostic impact in stage I–III melanoma. Female patients with high transcript levels had a significantly longer progression-free survival. Melanoma cell specific PMCA4 protein expression is associated with anaplasticity in melanoma lung metastasis but had no impact on survival after lung metastasectomy. Importantly, high PMCA4 transcript levels derived from RNA-seq of cutaneous melanoma are associated with significantly longer overall survival after PD-1 blockade. In summary, we demonstrated that human melanoma cells express PMCA4 and PMCA4 transcript levels carry prognostic information in a gender specific manner.
|
|
| 27. |
- Hipkiss, Anna Maria, et al.
(författare)
-
Genrepedagogik(en) på mellanstadiet – försvenskad, förenklad, förvanskad(?).
- 2022
-
Ingår i: SMDI 15 Språk och litteratur – en omöjlig eller skön förening? Lunds universitet, 23–24 november 2022..
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- I svensk skolkontext framställs genrepedagogik(en) som inflytelserik och ofta använd (Bergh Nestlog, Danielsson & Krog 2018, Hansson 2013, Kindenberg 2021, Liberg, Wiksten Folkeryd & af Geijerstam 2012, Walldén 2019). Dock är den inhemska forskningen om vad som förstås som genrepedagogisk undervisning eller hur den iscensätts relativt begränsad. I detta paper undersöks hur Sydneyskolans genrepedagogik rekontextualiseras (Bernstein 2000) i två lärarhandledningar för mellanstadiet (ZickZack Skrivrummet och Klara svenskan) och en vanligt förekommande kursbok för grundlärarprogrammet mot 4-6 (Stärk språket, stärk lärandet av Pauline Gibbons 2018). I analysen används verktyg från de teorier som Sydneyskolans genrepedagogik vilar på – systemisk funktionell lingvistik (Halliday 2004), genreteori (Martin 1992) och Vygotskijs sociokulturella teorier (Vygotskij 1986). De två lärarhandledningarna fokuserar på genomförandet av cirkelmodellen. Här blir det tydligt att pedagogiken i olika utsträckning har rekontextualiserats till den svenska skolkontexten. Ett exempel är att delar av cirkelmodellen genomförs utan den explicita lärarstöttning som är en av grundtankarna. Istället erbjuds elever att arbeta med övningar på egen hand eller tillsammans med en klasskamrat. Stärk språket, stärk lärandet utger sig inte för att vara genrepedagogisk. Samtidigt bygger delar av innehållet på en tidig generation av genrepedagogiken, där tyngdpunkten ligger på genreskrivande. Pedagogiken för fieldbuilding genom läsning har en annan inriktning än i senare generationers genrepedagogik (se Rose & Martin 2012). Huvudtanken i Stärk språket, stärk lärandet är vikten av att lärare tillämpar en pedagogik som stöttar andraspråkslevers kunskapsutveckling genom samtal och skrivande av genretypiska texter. De lingvistiska kunskaper som krävs för att genomföra genrepedagogisk undervisning är däremot inget som tillhandahålls vare sig i Gibbons bok eller i lärarhandledningarna. Studiens preliminära slutsats är att den genrepedagogik som rekontextualiseras i såväl lärarhandledningarna som i kursboken är starkt förenklad och ofullständig. Därmed riskerar också den kompensatoriska potential som är kärnan i Sydneyskolans genrepedagogik att gå förlorad.
|
|
| 28. |
- Hipkiss, Anna Maria, et al.
(författare)
-
(Practicing and) testing pupils’ subject specific literacy in history and chemistry
- 2023
-
Ingår i: WRAB 2023: Writing Research Across Borders VI, From early literacy learning to writing in professional life, 18–22 February 2023, NTNU, Trondheim, Norway.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- This study is part of a collaborative project between a comprehensive school and a university in Sweden – a project funded through a government initiative to support such collaboration for the benefit of both parties. In the project, the potential of genre pedagogy for strengthening subject literacy in school subjects is explored, with special attention paid to social and natural sciences and Swedish. The school, located in an underprivileged, suburban area, has a pupil population with diverse language backgrounds. For most of the pupils, Swedish is a second language. Since pupils from this background are overrepresented among those who do not succeed in school, further efforts are needed to improve the situation, not least for reasons of equity and fairness. This proposal investigates writing assignments and tests in year 6 chemistry and history, two subjects that require different types of subject specific writing, in this instance exemplified by historical recount in history and procedural recount in chemistry. Data has been collected in a year 6 (pupils 12-13 years of age) in a Swedish primary school. Data consists of texts collected from a history unit focusing Sweden in the 1600’s and a chemistry unit focusing household chemicals. Test questions and pupil answers in history and laboratory instructions and pupil laboratory reports in chemistry along with test questions and pupil answers have been analysed. The analyses are based in genre theory (Martin & Rose, 2008) and tasks and responses have been analysed for genre, including stages and phases and prevalence of subject specific lexicogrammar. The results of text analyses are also understood in light of previous studies of lesson activities in the work units in order to be able to make connections between what has been taught as regards writing and what pupils later produce individually in writing. In history the pupils were expected to answer test questions asking them to retell and/or present reasons for or consequences of significant events from Sweden’s Great Power Era. In chemistry they were expected to produce laboratory reports, often as co-constructions with individual focus on hypothesizing. In the test they were for example expected to be able to describe and distinguish between mixtures and solutions. The analysis of the history texts (both tasks and responses) reveals that although some pupils manage to produce texts where they use and unpack subject typical concepts, in line with the pattern introduced during the lessons, many would require more practise to be able to retell and/or explain historical events in writing. The analysis of chemistry texts has shown that the pupils are well-versed in the structure of the laboratory report as it is continually modelled by the teacher up until the aspect of hypotheses, which pupils often formulate on their own. These hypotheses vary in focus and breadth as in pupils guessing wildly what might happen or making hypotheses based on teacher introductions. As the hypotheses are individually constructed, there is also less subject specific knowledge on display. Being able to express contents through the expected genre, has been in focus for this study. In both subjects, joint reading and writing are used as tools for developing the pupil’s disciplinary literacy. The many second language pupils in this study seem to need stronger scaffolding in order to understand and be able to express historical knowledge in writing. In contrast, pupils in chemistry received strong scaffolding when preparing laboratory reports and were to the main part successful in this task. However, as the history unit does not include writing of longer subject specific texts, the next step could be to read and collect notes for joint constructing a longer, coherent text in which the teacher models and the pupils practise historical reasoning in writing. In chemistry, the next step is likely to model the construction of hypotheses and the discussions of the results of laboratory work
|
|
| 29. |
|
|
| 30. |
- Hipkiss, Anna Maria, et al.
(författare)
-
Spotlighting pedagogic metalanguage in Reading to Learn - How teachers build legitimate knowledge during tutorial sessions
- 2018
-
Ingår i: Linguistics and Education. - : Elsevier BV. - 0898-5898. ; 47, s. 93-104
-
Tidskriftsartikel (refereegranskat)abstract
- This paper presents an analysis of professional metalanguage and is a contribution to the discussion of professional development in literacy teaching. By analysing tutorial sessions within a professional development programme, we investigate how teachers and experts leading the professional development programme, negotiate the new literacy metalanguage that is to be built and appropriated during the PD programme. LCT (Legitimation Code Theory), in particular the dimension of Semantics, has been used for analysing and visualising the negotiations and signs of development of the new metalanguage. (C) 2018 Elsevier Inc. All rights reserved.
|
|
| 31. |
- Hipkiss, Anna Maria, et al.
(författare)
-
Teaching in Flexible Spatial and Digital Conditions
- 2021
-
Ingår i: EARLI 2021. ; , s. 314-314
-
Konferensbidrag (refereegranskat)abstract
- This study explores the opportunities and challenges of teaching under flexible spatial and digital conditions of the learning environment of a newly build school, analyzing how teaching is organized and what curricular genres can be discerned, what resources and practices are offered to stimulate students meaningmaking and what framing, relations and accessibility can be distinguished by the flexibility of furniture and classroom space. The analyses of a teacher team’s planning and teaching of the thematic work project on Space in years 2-3 (ages 8 to 9) and another teacher team’s thematic work project onCommunication in years 4-7 (ages10 to12) reveal varied teaching strategies between teacher-led and student-centered forms offering students linguistic, visual and audiovisual resources to make meaning of shared content in different school subjects. The young students practice reading comprehension, both of written texts and films, that also serves their knowledge-building about space. The older students display skills relating to different subjects through different technological and digital resources.
|
|
| 32. |
- Jankovskaja, Skaidre, et al.
(författare)
-
Non-Invasive, Topical Sampling of Potential, Low-Molecular Weight, Skin Cancer Biomarkers : A Study on Healthy Volunteers
- 2022
-
Ingår i: Analytical Chemistry. - : American Chemical Society (ACS). - 0003-2700 .- 1520-6882. ; 94:15, s. 5856-5865
-
Tidskriftsartikel (refereegranskat)abstract
- Monitoring of low-molecular weight cancer biomarkers, suchas tryptophan (Trp) and its derivative kynurenine (Kyn), might beadvantageous to non-invasive skin cancer detection. Thus, we assessedseveral approaches of topical sampling of Trp and Kyn, in relation tophenylalanine (Phe) and tyrosine (Tyr), on the volar forearm of six healthyvolunteers. The sampling was performed with three hydrogels (made ofagarose or/and chitosan), hydrated starchfilms, cotton swabs, and tapestripping. The biomarkers were successfully sampled by all approaches, butthe amount of collected Kyn was low, 20 +/- 10 pmol/cm2.Kynquantification was below LOQ, and thus, it was detected only in 20% oftopical samples. To mitigate variability problems of absolute amounts ofsampled amino acids, Tyr/Trp, Phe/Trp, and Phe/Tyr ratios were assessed,proving reduced inter-individual variation from 79 to 45% and intra-individual variation from 42 to 21%. Strong positive correlation was foundbetween Phe and Trp, pointing to the Phe/Trp ratio (being in the 1.0-2.0 range, at 95% confidence) being least dependent onsampling materials, approaches, and sweating. This study leads to conclusion that due to the difficulty in quantifying less abundantKyn, and thus the Trp/Kyn ratio, the Phe/Trp ratio might be a possible, alternative biomarker for detecting skin cancers.
|
|
| 33. |
- Kanoni, Stavroula, et al.
(författare)
-
Analysis with the exome array identifies multiple new independent variants in lipid loci
- 2016
-
Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 25:18, s. 4094-4106
-
Tidskriftsartikel (refereegranskat)abstract
- It has been hypothesized that low frequency (1-5% minor allele frequency (MAF)) and rare (<1% MAF) variants with large effect sizes may contribute to the missing heritability in complex traits. Here, we report an association analysis of lipid traits (total cholesterol, LDL-cholesterol, HDL-cholesterol triglycerides) in up to 27 312 individuals with a comprehensive set of low frequency coding variants (ExomeChip), combined with conditional analysis in the known lipid loci. No new locus reached genome-wide significance. However, we found a new lead variant in 26 known lipid association regions of which 16 were >1000-fold more significant than the previous sentinel variant and not in close LD (six had MAF <5%). Furthermore, conditional analysis revealed multiple independent signals (ranging from 1 to 5) in a third of the 98 lipid loci tested, including rare variants. Addition of our novel associations resulted in between 1.5- and 2.5-fold increase in the proportion of heritability explained for the different lipid traits. Our findings suggest that rare coding variants contribute to the genetic architecture of lipid traits.
|
|
| 34. |
- Kasos, Krisztian, et al.
(författare)
-
Bilateral electrodermal activity in the active-alert hypnotic induction
- 2018
-
Ingår i: International Journal of Clinical and Experimental Hypnosis. - : Informa UK Limited. - 0020-7144 .- 1744-5183. ; 66:3, s. 282-297
-
Tidskriftsartikel (refereegranskat)abstract
- Shifts in hemispheric dominance were previously proposed to play a role in hypnosis. Participants (N = 32) were exposed to an active–alert hypnosis induction and a music-control condition while electrodermal activity was registered bilaterally, providing information on alterations in hemispheric dominance. The results suggest that highly hypnotizable participants show a shift to right-sided and low hypnotizable participants demonstrated a shift to left-sided electrodermal dominance in response to the induction, whereas no change in laterality is present in the control condition. Additionally, the authors found that self-reported hypnosis experiences were also associated with a shift in laterality. These results underline the importance of the shift to right hemispheric activity in hypnosis and underscore the importance of hemispheric changes in shaping subjective experience.
|
|
| 35. |
- Kraja, Aldi T., et al.
(författare)
-
New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
-
Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
-
Tidskriftsartikel (refereegranskat)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
|
|
| 36. |
- Kristo, Michael J., et al.
(författare)
-
The application of radiochronometry during the 4th collaborative materials exercise of the nuclear forensics international technical working group (ITWG)
- 2018
-
Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 315:2, s. 425-434
-
Tidskriftsartikel (refereegranskat)abstract
- In a recent international exercise, 10 international nuclear forensics laboratories successfully performed radiochronometry on three low enriched uranium oxide samples, providing 12 analytical results using three different parent-daughter pairs serving as independent chronometers. The vast majority of the results were consistent with one another and consistent with the known processing history of the materials. In general, for these particular samples, mass spectrometry gave more accurate and more precise analytical results than decay counting measurements. In addition, the concordance of the U-235-Pa-231 and U-234-Th-230 chronometers confirmed the validity of the age dating assumptions, increasing confidence in the resulting conclusions.
|
|
| 37. |
- Larsen, Kristoffer, et al.
(författare)
-
Presence of activated mobile fibroblasts in bronchoalveolar lavage from patients with mild asthma
- 2004
-
Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 170:10, s. 1049-1056
-
Tidskriftsartikel (refereegranskat)abstract
- Activated fibroblasts are suggested to be involved in the deposition of extracellular matrix in the formation of peribronchial fibrosis in asthma. We report the novel finding of activated elongated fibroblasts accompanied by elevated numbers of eosinophils in bronchoalveolar lavage fluid from 5 out of 12 patients with mild asthma (= 42%), whereas no fibroblasts were observed in the control subjects without asthma (n = 17). The elongated fibroblasts migrated twice as far when compared with fibroblasts from corresponding bronchial biopsies from the same patients, accompanied by an induced expression of RhoA and Rac1, indicating that the increased expression of these proteins are linked to increased migratory capabilities. Moreover, the elongated fibroblasts had an elevated production of the proteoglycans biglycan, versican, perlecan, and decorin, which correlated to an active cytoplasm in these cells. Differential expression patterns between the two fibroblast groups in motility-regulating proteins, such as cofilin, nuclear chloride ion channel protein, and heat-shock protein 20, were identified by two-dimensional electrophoresis and mass spectrometry. These findings indicate the presence of activated and mobile fibroblasts accompanied by an induced inflammatory response outside the airway epithelium in patients with mild asthma, results that may play a role in formation of airway fibrosis.
|
|
| 38. |
- Lundgren, Edvin, et al.
(författare)
-
Geometry of the valence transition induced surface reconstruction of Sm(0001).
- 2002
-
Ingår i: Physical Review Letters. - 1079-7114 .- 0031-9007. ; 88:13, s. 136102-136102
-
Tidskriftsartikel (refereegranskat)abstract
- We present a structural determination of the surface reconstruction of the Sm(0001) surface using surface x-ray diffraction, scanning tunneling microscopy, and ab initio calculations. The reconstruction is associated with a large (22%) expansion of the atomic radius for the top monolayer surface Sm atoms. The mechanism driving the surface reconstruction in Sm is unique among all elements and is connected to the strong correlations of the 4f electrons in Sm and the intermediate valence observed in certain Sm compounds. The atoms constituting the top monolayer of Sm(0001) have vastly different chemical properties compared to the layer underneath and behave as if they were an adsorbate of a different chemical species.
|
|
| 39. |
- Mahajan, Anubha, et al.
(författare)
-
Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
-
Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
|
|
| 40. |
- Manning, Alisa, et al.
(författare)
-
A Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk
- 2017
-
Ingår i: Diabetes. - : AMER DIABETES ASSOC. - 0012-1797 .- 1939-327X. ; 66:7, s. 2019-2032
-
Tidskriftsartikel (refereegranskat)abstract
- To identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.
|
|
| 41. |
- Marouli, Eirini, et al.
(författare)
-
Rare and low-frequency coding variants alter human adult height
- 2017
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 542:7640, s. 186-190
-
Tidskriftsartikel (refereegranskat)abstract
- Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height increasing alleles of STC2 (giving an increase of 1-2 centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways.
|
|
| 42. |
- Megyesfalvi, Zsolt, et al.
(författare)
-
Expression patterns and prognostic relevance of subtype-specific transcription factors in surgically resected small-cell lung cancer : an international multicenter study
- 2022
-
Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 257:5, s. 674-686
-
Tidskriftsartikel (refereegranskat)abstract
- The tissue distribution and prognostic relevance of subtype-specific proteins (ASCL1, NEUROD1, POU2F3, YAP1) present an evolving area of research in small-cell lung cancer (SCLC). The expression of subtype-specific transcription factors and P53 and RB1 proteins were measured by immunohistochemistry (IHC) in 386 surgically resected SCLC samples. Correlations between subtype-specific proteins and in vitro efficacy of various therapeutic agents were investigated by proteomics and cell viability assays in 26 human SCLC cell lines. Besides SCLC-A (ASCL1-dominant), SCLC-AN (combined ASCL1/NEUROD1), SCLC-N (NEUROD1-dominant), and SCLC-P (POU2F3-dominant), IHC and cluster analyses identified a quadruple-negative SCLC subtype (SCLC-QN). No unique YAP1-subtype was found. The highest overall survival rates were associated with non-neuroendocrine subtypes (SCLC-P and SCLC-QN) and the lowest with neuroendocrine subtypes (SCLC-A, SCLC-N, SCLC-AN). In univariate analyses, high ASCL1 expression was associated with poor prognosis and high POU2F3 expression with good prognosis. Notably, high ASCL1 expression influenced survival outcomes independently of other variables in a multivariate model. High POU2F3 and YAP1 protein abundances correlated with sensitivity and resistance to standard-of-care chemotherapeutics, respectively. Specific correlation patterns were also found between the efficacy of targeted agents and subtype-specific protein abundances. In conclusion, we investigated the clinicopathological relevance of SCLC molecular subtypes in a large cohort of surgically resected specimens. Differential IHC expression of ASCL1, NEUROD1, and POU2F3 defines SCLC subtypes. No YAP1-subtype can be distinguished by IHC. High POU2F3 expression is associated with improved survival in a univariate analysis, whereas elevated ASCL1 expression is an independent negative prognosticator. Proteomic and cell viability assays of human SCLC cell lines revealed distinct vulnerability profiles defined by transcription regulators.
|
|
| 43. |
- Megyesfalvi, Zsolt, et al.
(författare)
-
Unfolding the secrets of small cell lung cancer progression : Novel approaches and insights through rapid autopsies
- 2023
-
Ingår i: Cancer Cell. - 1535-6108. ; 41:9, s. 1535-1540
-
Tidskriftsartikel (refereegranskat)abstract
- The understanding of small cell lung cancer (SCLC) biology has increased dramatically in recent years, but the processes that allow SCLC to progress rapidly remain poorly understood. Here, we advocate the integration of rapid autopsies and preclinical models into SCLC research as a comprehensive strategy with the potential to revolutionize current treatment paradigms.
|
|
| 44. |
- Mogren, Anna, et al.
(författare)
-
Conceptual work on ESD from a school improvement perspective
- 2018
-
Konferensbidrag (refereegranskat)abstract
- Chair: Anna Mogren, PhD, Karlstad University SwedenDiscussant: Professor Arjen Wals, Wageningen University, The Netherlands & Gothenburg University,SwedenThis symposium places Education for Sustainable Development ( ESD) within the field of school improvementtheory and research. In a number of studies, the Whole school approach in ESD is suggested and referred toas the work of embedding ESD into existing school visions and action plans (Breiting, Mayer & Mogensen2005 “Quality Criteria for ESD-schools”; Hargreaves 2008; Scott 2013.) The symposium therefore focuses onhow the research field of school improvement – which investigates, how efforts to help schools becomeincreasingly effective learning environments for the full range of their students have been more or lesssuccessful – might inform and challenge ESD and the ESD the Whole school approach.If ESD is to be framed and studied from a “within perspective” as an ongoing school improvement processrather than as an add-on activity to existing organisational arrangements and educational practices, it isnecessary to discuss models of school improvement in terms of their contribution to ESD. It is also importantto identify models of school improvement that can identify drivers and barriers for ESD implementation atorganisational level as well as on teaching and learning level (see Scherp 2013; Reezigt & Creemers 2005“Comprehensive framework for effective school improvement” ; Rolff 2010 “Trias of school development”;Rolff 2002 “P.dagogische Qualit.tsmanagement (PQM)”.In school improvement theory, a school’s organisation is commonly understood as reflexive in relation tocontext and supportive to the action of all members of the school community and their cooperation.Further, research suggests there are basic mechanisms contributing to effective school improvement such asgoal setting for improvement, pressures to improve, cyclical improvement processes and autonomy (seeScheerens & Demeuse 2005). Further, the school culture ought to be build up on dialogue supported byschool leadership. By this definition of school organisation, school improvement refers to collectivelysupporting factors in the organisation, to the end that students’ possibilities for learning in relation to acomplex surrounding world are enhanced.The recognition of multiple perspectives within the school organisation, e.g. cultural, structural, political andtransformational is central in investing possible models of school improvement. The search for schoolimprovement models that can discern those perspectives that are closely linked to ESD is crucial. Suchmodels of school improvement have the potential to constitute the link between the research fields of ESDand school improvement. They could serve as a tool for further research on how the Whole school approachis constructed in formal education, which is searched for in the practical work on ESD implementation.In this symposium examples from ongoing research projects on ESD where models of school improvementare used, considered or asked for in a German, Swedish and Hungarian context are presented. Thesymposium will explore the potential of integrating, adapting and rejecting theoretical perspectives andempirical evidence from school improvement into the ESD research field through intention papers with thegoal of developing knowledge about- how selected conceptual work on the Whole school approach in ESD draw on models andperspectives from school improvement theory,- how in an empirical case study a school improvement model was used to measure the ESD Wholeschool approach,- how school improvement has informed efforts and plan for upscaling ESD implementation in Eco-Schools to a larger number of public schools.Following questions from the audience, Arjen Wals (Wageningen University, The Netherlands & GothenburgUniversity, Sweden) will draw together the discussion and to explore implications for research in ESD.
|
|
| 45. |
- Nelwamondo, Aubrey N., et al.
(författare)
-
Uranium assay and trace element analysis of the fourth collaborative material exercise samples by the modified Davies-Gray method and the ICP-MS/OES techniques
- 2018
-
Ingår i: Journal of Radioanalytical and Nuclear Chemistry. - : Springer Science and Business Media LLC. - 0236-5731 .- 1588-2780. ; 315:2, s. 379-394
-
Tidskriftsartikel (refereegranskat)abstract
- An international group of laboratories participating in CMX-4 subjected three samples to comparative nuclear forensic analysis using uranium assay and trace element analysis techniques to determine if the samples had similar or different origins. Uranium assay indicated that two pellet samples (ES-2 and ES-3) were nearly pure UO 2 while the black powder sample ES-1 was primarily UO 2 with UO 3 and/or U 3 O 8 forms present as impurities. Trace element analysis by five of the six participating laboratories reported molybdenum concentrations below 10 µg/g U in all of the exercise samples, suggesting the same likely facility of origin for all three samples.
|
|
| 46. |
- Nepomuceno, Thales C., et al.
(författare)
-
BRCA1 frameshift variants leading to extended incorrect protein C termini
- 2023
-
Ingår i: Human Genetics and Genomics Advances. - : Elsevier. - 2666-2477. ; 4:4
-
Tidskriftsartikel (refereegranskat)abstract
- Carriers of BRCA1 germline pathogenic variants are at substantially higher risk of developing breast and ovarian cancer than the general population. Accurate identification of at-risk individuals is crucial for risk stratification and the implementation of targeted preventive and therapeutic interventions. Despite significant progress in variant classification efforts, a sizable portion of reported BRCA1 variants remain as variants of uncertain clinical significance (VUSs). Variants leading to premature protein termination and loss of essential functional domains are typically classified as pathogenic. However, the impact of frameshift variants that result in an extended incorrect terminus is not clear. Using validated functional assays, we conducted a systematic functional assessment of 17 previously reported BRCA1 extended incorrect terminus variants (EITs) and concluded that 16 constitute loss-of-function variants. This suggests that most EITs are likely to be pathogenic. However, one variant, c.5578dup, displayed a protein expression level, affinity to known binding partners, and activity in transcription and homologous recombination assays comparable to the wild-type BRCA1 protein. Twenty-three additional carriers of c.5578dup were identified at a US clinical diagnostic lab and assessed using a family history likelihood model providing, in combination with the functional data, a likely benign interpretation. These results, consistent with family history data in the current study and available data from ClinVar, indicate that most, but not all, BRCA1 variants leading to an extended incorrect terminus constitute loss-of-function variants and underscore the need for comprehensive assessment of individual variants.
|
|
| 47. |
- Nilsson, Anna, et al.
(författare)
-
Fine Mapping the Spatial Distribution and Concentration of Unlabeled Drugs within Tissue Micro-Compartments Using Imaging Mass Spectrometry
- 2010
-
Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7, s. e11411-
-
Tidskriftsartikel (refereegranskat)abstract
- Readouts that define the physiological distributions of drugs in tissues are an unmet challenge and at best imprecise, but are needed in order to understand both the pharmacokinetic and pharmacodynamic properties associated with efficacy. Here we demonstrate that it is feasible to follow the in vivo transport of unlabeled drugs within specific organ and tissue compartments on a platform that applies MALDI imaging mass spectrometry to tissue sections characterized with high definition histology. We have tracked and quantified the distribution of an inhaled reference compound, tiotropium, within the lungs of dosed rats, using systematic point by point MS and MS/MS sampling at 200 mu m intervals. By comparing drug ion distribution patterns in adjacent tissue sections, we observed that within 15 min following exposure, tiotropium parent MS ions (mass-to-charge; m/z 392.1) and fragmented daughter MS/MS ions (m/z 170.1 and 152.1) were dispersed in a concentration gradient (80 fmol-5 pmol) away from the central airways into the lung parenchyma and pleura. These drug levels agreed well with amounts detected in lung compartments by chemical extraction. Moreover, the simultaneous global definition of molecular ion signatures localized within 2-D tissue space provides accurate assignment of ion identities within histological landmarks, providing context to dynamic biological processes occurring at sites of drug presence. Our results highlight an important emerging technology allowing specific high resolution identification of unlabeled drugs at sites of in vivo uptake and retention.
|
|
| 48. |
|
|
| 49. |
- Nilsson, C. L., et al.
(författare)
-
Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
- 2013
-
Ingår i: Journal of Proteome Research. - : American Chemical Society (ACS). - 1535-3893 .- 1535-3907. ; 12:1, s. 134-149
-
Tidskriftsartikel (refereegranskat)abstract
- A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC–MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
|
|
| 50. |
- Priskorn, Lærke, et al.
(författare)
-
RUBIC (ReproUnion Biobank and Infertility Cohort) : A binational clinical foundation to study risk factors, life course, and treatment of infertility and infertility-related morbidity
- 2021
-
Ingår i: Andrology. - : Wiley. - 2047-2919 .- 2047-2927. ; 9:6, s. 1828-1842
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Infertility affects 15%–25% of all couples during their reproductive life span. It is a significant societal and public health problem with potential psychological, social, and economic consequences. Furthermore, infertility has been linked to adverse long-term health outcomes. Despite the advanced diagnostic and therapeutic techniques available, approximately 30% of infertile couples do not obtain a live birth after fertility treatment. For these couples, there are no further options to increase their chances of a successful pregnancy and live birth. Objectives: Three overall questions will be studied: (1) What are the risk factors and natural life courses of infertility, early embryonic loss, and adverse pregnancy outcomes? (2) Can we develop new diagnostic and prognostic biomarkers for fecundity and treatment success? And (3) what are the health characteristics of women and men in infertile couples at the time of fertility treatment and during long-term follow-up?. Material and Methods: ReproUnion Biobank and Infertility Cohort (RUBIC) is established as an add-on to the routine fertility management at Copenhagen University Hospital Departments in the Capital Region of Denmark and Reproductive Medicine Centre at Skåne University Hospital in Sweden. The aim is to include a total of 5000 couples equally distributed between Denmark and Sweden. The first patients were enrolled in June 2020. All eligible infertile couples are prospectively asked to participate in the project. Participants complete an extensive questionnaire and undergo a physical examination and collection of biospecimens (blood, urine, hair, saliva, rectal swabs, feces, semen, endometrial biopsies, and vaginal swabs). After the cohort is established, the couples will be linked to the Danish and Swedish national registers to obtain information on parental, perinatal, childhood, and adult life histories, including disease and medication history. This will enable us to understand the causes of infertility and identify novel therapeutic options for this important societal problem.
|
|
