| 1. |
- Haiman, Christopher A., et al.
(författare)
-
A common variant at the TERT-CLPTM1L locus is associated with estrogen receptor-negative breast cancer
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:12, s. 61-1210
-
Tidskriftsartikel (refereegranskat)abstract
- Estrogen receptor (ER)-negative breast cancer shows a higher incidence in women of African ancestry compared to women of European ancestry. In search of common risk alleles for ER-negative breast cancer, we combined genome-wide association study (GWAS) data from women of African ancestry (1,004 ER-negative cases and 2,745 controls) and European ancestry (1,718 ER-negative cases and 3,670 controls), with replication testing conducted in an additional 2,292 ER-negative cases and 16,901 controls of European ancestry. We identified a common risk variant for ER-negative breast cancer at the TERT-CLPTM1L locus on chromosome 5p15 (rs10069690: per-allele odds ratio (OR) = 1.18 per allele, P = 1.0 x 10(-10)). The variant was also significantly associated with triple-negative (ER-negative, progesterone receptor (PR)-negative and human epidermal growth factor-2 (HER2)-negative) breast cancer (OR = 1.25, P = 1.1 x 10(-9)), particularly in younger women (<50 years of age) (OR = 1.48, P = 1.9 x 10(-9)). Our results identify a genetic locus associated with estrogen receptor negative breast cancer subtypes in multiple populations.
|
|
| 2. |
- Oystese, Kristin Astrid B., et al.
(författare)
-
Distribution of E- and N-cadherin in subgroups of non-functioning pituitary neuroendocrine tumours
- 2022
-
Ingår i: Endocrine. - : Springer Nature. - 1355-008X .- 1559-0100. ; 77:1, s. 151-159
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Clinically non-functioning pituitary neuroendocrine tumours (NF-PitNETs) present a varying degree of aggressiveness, and reliable prognostic markers are lacking. We aimed to characterise the distribution of E- and N-cadherin in corticotroph, PIT1 and null-cell NF-PitNETs, and link it to the course of the tumours. Methods The distribution of E- and N-cadherin was investigated by immunohistochemistry in a retrospective cohort of 30 tumours of the less common NF-PitNETs (corticotroph (N = 18), PIT1 (N = 8) and null-cell PitNETs (N = 4)). Immunoreactive scores (IRS) were compared to previously presented cohorts of gonadotroph NF-PitNETs (N = 105) and corticotroph functioning PitNETs (N = 17). Results We found a low IRS for the extra-cellular domain of E-cadherin (median 0 (IQR 0-0, N = 135)), a medium to high IRS for the intra-cellular domain of E-cadherin (median 6 (IQR 4-9)) and a high IRS for N-cadherin (median 12 (IQR 10.5-12)) throughout the cohort of NF-PitNETs. The corticotroph NF-PitNETs presented a higher IRS for both the extra- and intra-cellular domain of E-cadherin (median 0 (IQR 0-1) and median 9 (IQR 6-12), respectively) than the gonadotroph NF-PitNETs (p < 0.001 for both comparisons). Presence of nuclear E-cadherin was associated with a weaker staining for the intra-cellular domain of E-cadherin (median 4 (IQR 0.5-6) and median 9 (IQR 9-12), for tumours with and without nuclear E-cadherin, respectively), and with a lower rate of re-intervention (p = 0.03). Conclusions Considering our results and the benign course of NF-PitNETs, we suggest that a high N-cadherin and downregulation of membranous E-cadherin are not associated with a more aggressive tumour behaviour in these subgroups of NF-PitNETs.
|
|
| 3. |
- Axell, Cecilia, 1965-, et al.
(författare)
-
Artificial Intelligence in Contemporary Children’s Culture : A Case Study
- 2022
-
Ingår i: PATT 39. - : Memorial University of Newfoundland. - 9780889015050 ; , s. 376-386
-
Konferensbidrag (refereegranskat)abstract
- The overall aim of the school subject technology is to develop pupils’ understanding of technological solutions in everyday life. A starting point for this study is that it is important for teachers in technology to have knowledge of pupils’ prior conceptions of the subject content since these can both support and hinder their learning. In a previous study we found that when pupils (age 7) talk about digital technology and programming, they often refer to out-of-school experiences such as films, television programmes and books. Typically, their descriptions include robots with some form of intelligence. Hence, it seems like children’s culture may have an impact on the conceptions they bring to the technology classroom. In light of this, it is vital that technology teachers have knowledge about how robots and artificial intelligence (AI) are portrayed in children’s culture, and how pupils perceive these portrayals. However, knowledge about these aspects of technology in children’s culture is limited.The purpose of this study is to investigate how artifacts with artificial intelligence are portrayed in television programmes and literature aimed at children. This study is the first step in a larger study aiming to examine younger pupils’ conceptions and ideas about artificial intelligence. A novice conception of artificial intelligence can be described as an understanding of what a programmed device may, or may not, “understand” in relation to a human, which includes discerning th edifferences between the artificial and the human mind. Consequently, as a theoretical framework for investigating how artificial intelligence is portrayed in children’s culture, the concepts of Theoryof Mind (ToM) and Theory of Artificial Mind (ToAM), are used. The empirical material presented in this paper, i.e. four children’s books and a popular children’s television programme, was analysed using a qualitative thematic analysis. The results show that the portrayal of AI is ambiguous. The structure and function of the robot has elements of both human and machine, and the view of the human fictional characters of the robot is sometimes that of a machine, sometimes of a human. In addition, the whole empirical material includes portrayals of AI as a threat as well as a saviour. As regards implications, there is a risk that without real-life experiences of robots, the representations children’s books and other media convey can lead to ambivalent feelings towards real robots.
|
|
| 4. |
- Axell, Cecilia, 1965-, et al.
(författare)
-
You give a little bit more love to animals than to robots
- 2023
-
Ingår i: International journal of technology and design education. - : SPRINGER. - 0957-7572 .- 1573-1804.
-
Tidskriftsartikel (refereegranskat)abstract
- Although digital technology is an important part of young peoples lives, previous research implies that they have a limited understanding of what programming is and its connection to the digital devices they encounter every day. In order to create conditions for meaningful teaching in and about programming in technology education, more knowledge about younger students pre-understanding and experiences is needed. In the light of this, the aim of this case study was to explore young pupils descriptions of the concept programming, in connection with being introduced to programming as a teaching content in technology education. The study is based on semi-structured interviews with 16 children in year 1 (7-year-olds) in a primary school in Sweden. In their descriptions of programming as an activity, the pupils mainly used technological descriptions-a theory of artificial mind perspective. However, when they talked about the objects with which they associated programming, psychological descriptions-a theory of mind perspective-were more clearly present. Then, a less pronounced distinction between humans and machines was made. Anthropomorphic references were used, such as when the pupils referenced childrens culture such as movies and television programs. However, the term programming was difficult for many of the pupils to grasp. They also had difficulty in finding a function for programming, as well as explanations and arguments for why they learn programming in school. The results of this study indicate that these 7-year-old pupils perceive programming as something complex. This at the same time as they describe how programmed and programmed artefacts (including AI devices) are highly present in their everyday lives, in their leisure environments, and in school. This mirrors how technology has become an intelligent and active agent, rather than a mere tool in their lives-an aspect that teachers may forget to take advantage of.
|
|
| 5. |
- Banwart, Steven A., et al.
(författare)
-
Process-based modeling of silicate mineral weathering responses to increasing atmospheric CO2 and climate change
- 2009
-
Ingår i: Global Biogeochemical Cycles. - 0886-6236 .- 1944-9224. ; 23, s. GB4013-
-
Tidskriftsartikel (refereegranskat)abstract
- A mathematical model describes silicate mineral weathering processes in modern soils located in the boreal coniferous region of northern Europe. The process model results demonstrate a stabilizing biological feedback mechanism between atmospheric CO2 levels and silicate weathering rates as is generally postulated for atmospheric evolution. The process model feedback response agrees within a factor of 2 of that calculated by a weathering feedback function of the type generally employed in global geochemical carbon cycle models of the Earth's Phanerozoic CO2 history. Sensitivity analysis of parameter values in the process model provides insight into the key mechanisms that influence the strength of the biological feedback to weathering. First, the process model accounts for the alkalinity released by weathering, whereby its acceleration stabilizes pH at values that are higher than expected. Although the process model yields faster weathering with increasing temperature, because of activation energy effects on mineral dissolution kinetics at warmer temperature, the mineral dissolution rate laws utilized in the process model also result in lower dissolution rates at higher pH values. Hence, as dissolution rates increase under warmer conditions, more alkalinity is released by the weathering reaction, helping maintain higher pH values thus stabilizing the weathering rate. Second, the process model yields a relatively low sensitivity of soil pH to increasing plant productivity. This is due to more rapid decomposition of dissolved organic carbon (DOC) under warmer conditions. Because DOC fluxes strongly influence the soil water proton balance and pH, this increased decomposition rate dampens the feedback between productivity and weathering. The process model is most sensitive to parameters reflecting soil structure; depth, porosity, and water content. This suggests that the role of biota to influence these characteristics of the weathering profile is as important, if not more important, than the role of biota to influence mineral dissolution rates through changes in soil water chemistry. This process-modeling approach to quantify the biological weathering feedback to atmospheric CO2 demonstrates the potential for a far more mechanistic description of weathering feedback in simulations of the global geochemical carbon cycle.
|
|
| 6. |
|
|
| 7. |
- Berg, Astrid, et al.
(författare)
-
Children's emergent mechanistic reasoning in chemistry: a case study about early primary students' reasoning about the phenomenon of thermal expansion of air
- 2024
-
Ingår i: CHEMISTRY EDUCATION RESEARCH AND PRACTICE. - : ROYAL SOC CHEMISTRY. - 1109-4028. ; 25:1, s. 92-114
-
Tidskriftsartikel (refereegranskat)abstract
- The importance of introducing students to mechanistic reasoning (MR) early in their schooling is emphasised in research. The goal of this case study was to contribute with knowledge on how early primary students' (9-10 year-olds) MR in chemistry is expressed and developed in a classroom practice framed by model-based inquiry. The study focuses on the first lesson in a sequence of six that was developed as part of a design study. The teaching was designed to ensure student agency and create conditions for the students to develop, test, and evaluate simple particle models in interaction with observations cooperatively and under teacher guidance. During the lesson, students were encouraged to express their tentative explanatory models in drawing and writing, and to act as molecules to dramatize the expansion of air. A mechanistic reasoning framework based on the characterisation of system components (entities, properties, activities, organisation) was developed and used to analyse children's mechanistic reasoning. The framework included multimodal analysis of communication (speech, gestures, writing, drawing, bodily motion) and evaluation of student reasoning based on e.g., the presence of gaps in terms of explanatory black boxes or missing pieces. The results show that: (1) In model-based inquiry, young children can navigate across different representational levels in their reasoning and engage in MR; (2) children's black-boxing can be seen as an indication of epistemic work in the process of model-based inquiry; and (3) asking students to engage in multiple modes of representations support the development of student MR in model-based inquiry.
|
|
| 8. |
|
|
| 9. |
- Berg, Astrid, 1964-, et al.
(författare)
-
Introducing programming in an early primary technology classroom : the distinction between human and robot
- 2024
-
Ingår i: Programming and computational thinking in technology education. - Leiden : Brill Academic Publishers. - 9789004687912 ; , s. 271-290
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Since 2018, programming is a content in the technology subject in Sweden. Thus, teachers must develop new subject-specific competence to be able to realize their teaching in and about programming. This is especially challenging for primary teachers since primary technology education is a young subject and lacks a common professional base of proven experience. Research focusing on the classroom practices that are now taking form, and which are based on teachers’ use of tutorials provided from different resources, is scarce. Hence, our understanding of which programming-related knowledge is possible to develop through participation in these practices is very limited. As a novice, understanding the meaning of programming assumes an understanding of what a computational device may—or may not— ‘understand’ in relation to a human. When it comes to introducing early primary pupils to the concept of programming, there are examples of tutorials describing activities that focus on this very issue. In the study reported in this chapter, we explore an activity during an introductory lesson in programming in an early primary classroom, where the teacher used such a tutorial aimed to prompt reflections about the differences between a human and a robot. The aim of the study was to explore what content is constituted and hence what knowledge pupils are enabled to develop during this introductory activity. The results showed that the constituted content focused on a central difference between human and robot; humans, as opposed to robots, have own will and ability to think. However, the analysis also showed that the pupils had ideas beyond this rather narrow content, and that classroom conversations with the youngest pupils about the differences between a human and a robot are, in several ways, challenging to orchestrate.
|
|
| 10. |
- Berg, Astrid, et al.
(författare)
-
Kemiinnehåll i undervisningen för nybörjare. : En studie av hur ämnesinnehållet får konkurrera med målet att få eleverna intresserade av naturvetenskap.
- 2007
-
Ingår i: Nordina. ; 3:2/07, s. 146-162
-
Tidskriftsartikel (refereegranskat)abstract
- This study describes the dilemma of making science interesting on the one hand, and to introduce students into a scientific teaching practise on the other in a laboratory based teaching practise. The study was conducted in a grade four class in Swedish compulsory school by video- and tape-recorded classroom observations. The recordings and copies of students’ writing and drawing were analysed by using a two-fold strategy. Firstly, the constituted content was analysed by focusing the classroom communication, the tools used and the teacher’s guiding. Secondly, the various laboratory experiments where analysed in order to identify the potential chemistry content. The result indicates that the constituted chemistry content is reduced and sometimes wrong in relation to the potential content. This can be explained by a teaching tradition that focuses on the importance of making science interesting and fun. However, striving for this may create a learning-situation where students do not learn how to use tools to make relevant hypotheses and observations. What can be regarded as irrelevant hypotheses and observations is not questioned. Further, right or wrong results in the scientific practise are not dealt with neither in the self-produced texts nor in the classroom discussions. One main conclusion is that students enjoy the lessons but the introduction into the scientific practise is not facilitated.
|
|
| 11. |
|
|
| 12. |
- Berg, Agneta, 1950-, et al.
(författare)
-
Nurses' reflections about dementia care, the patients, the care and themselves in their daily caregiving
- 1998
-
Ingår i: International Journal of Nursing Studies. - : Elsevier. - 0020-7489 .- 1873-491X. ; 35:5, s. 271-282
-
Tidskriftsartikel (refereegranskat)abstract
- In this study the aim was, through interviews, to disclose 13 nurses personal knowledge about the patients, themselves, and care provision, using a phenomenological-hermeneutic analysing method. Caring for people with severe dementia meant an intertwined life world emanating from making and doing together and the delicate interpretative work that the care provision required. The intertwined life world consisted of the interaction between the nurses and the patients separate lives, their common life and the environment, culminating in mutual dependency. Making together signifies the relationship being based on the nurses knowledge and skills as nurses i.e. the task they had to perform. Doing together signifies the relationship being based on the oneness of the nurses and the patients with severe dementia as ordinary human beings. The delicate interpretation process required, to adapt care to the individual patient, was based on knowledge about the patients personality, life history and disease progression in combination with the nurses interpretation of the current situation. The nurses searched for meaning and that, in turn, meant that the patients inner world was determined by the nurses and thus the patient was seen as being in their hands. It seems important to further understand the human aspects of both the nurse and the patient and to examine this dynamic, ongoing, vulnerable interpretation process, critically, in order to achieve high quality nursing care for the patients with severe dementia, and an experience of well-being in nurses everyday working lives.
|
|
| 13. |
- Berg, Astrid, et al.
(författare)
-
Observationer i kemiklassrummet - att lära sig se kemiska reaktioner
- 2010
-
Ingår i: Innehållet i fokus - kemiundervisning i finlandssvenska klassrum. - Stockholm : Stockholms universitets förlag. - 9789176566657 ; , s. 37-69
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- I flera jämförande internationella studier hamnar de finska eleverna i toppen. Hur bedrivs kemiundervisningen i finlandssvenska klassrum? Rapporten består av sex kapitel där författarna bl.a. tar upp följande frågor: Vad kännetecknar undervisningspraktiken i en finlandssvensk klass? Vilka texter används i klassrummet? Vad betraktas som viktig respektive mindre viktig kunskap? I ett av kapitlen analyseras vilka frågor läraren ställer till eleverna och vilken feedback som ges. I studien ingick fyra lärare, och i det avslutande kapitlet analyseras deras provkonstruktion och bedömningsarbete.Texterna vänder sig till alla som är intresserade av bedömningsfrågor, kunskapsfrågor, lärande och undervisning. Forskningsprojektet är finansierat av Vetenskapsrådet.
|
|
| 14. |
- Berg, Astrid, et al.
(författare)
-
Representational challenges in animated chemistry: self-generated animations as a means to encourage students reflections on sub-micro processes in laboratory exercises
- 2019
-
Ingår i: Chemistry Education Research and Practice. - : ROYAL SOC CHEMISTRY. - 1756-1108 .- 1109-4028. ; 20:4, s. 710-737
-
Tidskriftsartikel (refereegranskat)abstract
- A central aspect of learning chemistry is learning to relate observations of phenomena to models of the sub-microscopic level of matter, and hence being able to explain the observable phenomena. However, research shows that students have difficulties discerning and comprehending the meaning of the sub-micro level and its models, and that practical work in its traditional form fails to help students to discern the relation between observations and models. Consequently, there is a strong call for new teaching activities to address these issues. This paper emerges from a growing number of studies showing that learning is supported when students are set to cooperatively create their own multimodal representations of science phenomena. In this paper, we explore the approach of letting students create their own stop-motion animation as a means to explain observations during practical work. The students work of producing a phenomenon in the laboratory and creating an animation was recorded (audio-video) to capture students verbal and non-verbal interactions and use of resources. Data was analysed using a thematic content analysis with a deductive approach aimed at identifying the aspects of chemistry content that are being reasoned. The analysis showed that the task enabled students to engage in reasoning concerning both the observations and the sub-micro-level models, and how they relate to each other. The task also enabled students to reason about features of the representation that are needed to make sense of both the observational and sub-microscopic aspects of a phenomenon, as well as reflecting upon the meaning of a model.
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
- Ekvall, Ulla, 1946-, et al.
(författare)
-
Lärobok och kemipraktik
- 2010. - 1
-
Ingår i: Innehållet i fokus. - Stockholm : Stockholms universitets förlag. - 9789176566657 ; , s. 119-144
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
- Eriksson, Inger, 1952-, et al.
(författare)
-
Vilket kemiinnehåll görs tillgängligt i finlandssvenska och svenska klassrum? Kemitexter som redskap för naturvetenskapligt lärande
- 2010
-
Ingår i: Resultatdialog 2010. - Stockholm : Vetenskapsrådet. - 9789173071840 ; , s. 51-56
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Svenska och finska (och finlandssvenska) elevers naturvetenskapliga prestationer uppvisar markanta skillnader i internationella mätningar som PISA. Mot bakgrund av att Finland och Sverige har ett till synes likartat skolsystem är det inte helt enkelt att förstå varför de finska och finlandssvenska eleverna presterar så mycket bättre än de svenska. Vad är det som skapar sådana skillnader? Många olika förklaringar har förts fram, tex i relation till lärarutbildning. Men vilket kemilärande möjliggörs i svenska och finlandssvenska undervisningspraktiker? Kemiinnehållet i läromedel från Sverige och Finland är i stort det samma och i finlandssvenska skolor fram till 2007 användes ofta svenska läromedel. I projektet genomfördes 20-40h videobandade klassrumsobservationer relaterade till kemiundervisningen i tre skolor vardera i Svenskfinland (2007-08) och Sverige (2009). Observationerna, kombinerade med intervjuer och dokumentationer, fokuserade periodiska systemet och kemiska bindningar. De första analyserna ger en bild av att det finns skillnader i innehållets behandling och vad som karaktäriserar de konstituerade undervisningspraktikerna i de båda länderna. I finlandssvenska skolor fokuseras t.ex. faktareproduktion (memorering), formelskrivning och detaljerade provfrågor, samma läromedel används i alla skolor. I svenska skolor betonas förståelse av vardagsfenomen, diskussioner och prov som skiljer på G, VG och MVG-frågor där G-frågor utgörs av enkla faktakunskaper. Undervisningen i de finlandssvenska skolorna framstår således som mera lika varandra medan undervisningen i de svenska skolorna uppvisar större variation gällande innehållets behandling och klassrumskommunikation.
|
|
| 23. |
|
|
| 24. |
- Hultén, Magnus, 1970-, et al.
(författare)
-
Animerad kemi : Elever i grundskolans tidiga år förklarar kemiska samband
- 2020
-
Bok (övrigt vetenskapligt/konstnärligt)abstract
- Kemi har under stora delar av 1900-talet varit ett ämne som elever tidigast mötte i årskurs 5. Då behandlades ofta fenomen som smältning, stelning, kokning och avdunstning. Dessutom studerades egenskaper hos luft och vatten. Att elever innan de börjar högstadiet skulle resonera kring dessa fenomen i termer av vad som sker på submikronivå, med hjälp av antaganden om enkla partikelmodeller, har aldrig varit ett uttalat mål för undervisningen i kemi förrän introduktionen av Lgr 11. I den här studien har en grupp bestående av två lärare, en rektor och fyra forskare utformat och genomfört undervisning om egenskaper hos luft samt fenomenen smältning och stelning med elever i årskurs 3 och 4. Eleverna har inte bara beskrivit det som skett med egna ord, utan också lärt sig att beskriva det som sker på submikronivå i ord och bild. För att kunna göra detta har de, tillsammans med läraren, utvecklat enkla partikelmodeller. Projektet har kallats "Animerad kemi” och är ett forskningsprojekt finansierat av Skolforskningsinstitutet.
|
|
| 25. |
- Kolnes, Anders Jensen, et al.
(författare)
-
TGFBR3L is associated with gonadotropin production in non-functioning gonadotroph pituitary neuroendocrine tumours
- 2023
-
Ingår i: Pituitary. - : Springer. - 1386-341X .- 1573-7403. ; 26:2, s. 227-236
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose Transforming growth factor-beta receptor 3-like (TGFBR3L) is a pituitary enriched membrane protein selectively detected in gonadotroph cells. TGFBR3L is named after transforming growth factor-beta receptor 3 (TGFBR3), an inhibin A co-receptor in mice, due to sequence identity to the C-terminal region. We aimed to characterize TGFBR3L detection in a well-characterized, prospectively collected cohort of non-functioning pituitary neuroendocrine tumours (NF-PitNETs) and correlate it to clinical data.Methods 144 patients operated for clinically NF-PitNETs were included. Clinical, radiological and biochemical data were recorded. Immunohistochemical (IHC) staining for FSH beta and LH beta was scored using the immunoreactive score (IRS), TGFBR3L and TGFBR3 were scored by the percentage of positive stained cells.Results TGFBR3L staining was selectively present in 52% of gonadotroph tumours. TGFBR3L was associated to IRS of LH beta (median 2 [IQR 0-3] in TGFBR3L negative and median 6 [IQR 3-9] in TGFBR3L positive tumours, p < 0.001), but not to the IRS of FSH beta (p = 0.32). The presence of TGFBR3L was negatively associated with plasma gonadotropin concentrations in males (P-FSH median 5.5 IU/L [IQR 2.9-9.6] and median 3.0 [IQR 1.8-5.6] in TGFBR3L negative and positive tumours respectively, p = 0.008) and P-LH (median 2.8 IU/L [IQR 1.9-3.7] and median 1.8 [IQR 1.1-3.0] in TGFBR3L negative and positive tumours respectively, p = 0.03). TGFBR3 stained positive in 22% (n = 25) of gonadotroph tumours with no correlation to TGFBR3L.Conclusion TGFBR3L was selectively detected in half (52%) of gonadotroph NF-PitNETs. The association to LH beta staining and plasma gonadotropins suggests that TGFBR3L may be involved in hormone production in gonadotroph NF-PitNETs.
|
|
| 26. |
- Mohr, Sebastian, et al.
(författare)
-
Hoxa9 and Meis1 Cooperatively Induce Addiction to Syk Signaling by Suppressing miR-146a in Acute Myeloid Leukemia.
- 2017
-
Ingår i: Cancer cell. - : Elsevier BV. - 1878-3686 .- 1535-6108. ; 31:4
-
Tidskriftsartikel (refereegranskat)abstract
- The transcription factor Meis1 drives myeloid leukemogenesis in the context of Hox gene overexpression butis currently considered undruggable. We therefore investigated whether myeloid progenitor cells transformed by Hoxa9 and Meis1 become addicted to targetable signaling pathways. A comprehensive (phospho)proteomic analysis revealed that Meis1 increased Syk protein expression and activity. Syk upregulation occurs through a Meis1-dependent feedback loop. By dissecting this loop, we show that Syk is a direct target of miR-146a, whose expression is indirectly regulated by Meis1 through the transcription factor PU.1. In the context of Hoxa9 overexpression, Syk signaling induces Meis1, recapitulating several leukemogenic features of Hoxa9/Meis1-driven leukemia. Finally, Syk inhibition disrupts the identified regulatory loop, prolonging survival of mice with Hoxa9/Meis1-driven leukemia.
|
|
| 27. |
- Oystese, Kristin Astrid Berland, et al.
(författare)
-
The role of E and N-cadherin in the postoperative course of gonadotroph pituitary tumours
- 2018
-
Ingår i: Endocrine. - : Springer Science and Business Media LLC. - 1355-008X .- 1559-0100. ; 62:2, s. 351-360
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: Gonadotroph tumours are the most abundant of the clinically silent pituitary tumours. There is a lack of reliable prognostic markers predicting their clinical course. Our aim was to determine the level of E-cadherin and N-cadherin in a cohort of clinically silent gonadotroph pituitary tumours, and compare them to the rate of reintervention.Methods: Tumour tissue from primary surgery was retrospectively investigated and compared with clinical data. Immunohistochemical (N=105) and real time-qPCR (N=85) analyses for the levels of N-cadherin and the extra- and intracellular domains of E-cadherin were performed. The immunoreactive scores (IRS) and mRNA relative quantity were compared to the rate of reintervention.Results: The tumours presented a high IRS for N-cadherin (Median 12 (IQR 12-12)) and almost no immunoreactivity for the extracellular domain of E-cadherin (Median 0 (IQR 0-0)). The membranous staining for the intracellular domain of E-cadherin varied (Median 6 (IQR 4-6). Reduced membranous expression of the intracellular domain of E-cadherin was associated with nuclear presence of the same domain. Nuclear staining for the intracellular domain of E-cadherin was associated with a lower rate of reintervention (p=0.01).Conclusion: We found that silent gonadotroph tumours presented high IRS for N-cadherin and low IRS for the extracellular domain of E-cadherin. A substantial proportion of the tumours presented nuclear staining for the intracellular domain of E-cadherin, accompanied by a reduced membranous expression of the intracellular domain of E-cadherin. Absence of nuclear staining for the intracellular domain of E-cadherin served as an independent predictor of reintervention.
|
|
| 28. |
- Oystese, Kristin Astrid, et al.
(författare)
-
Estrogen Receptor alpha, a Sex-Dependent Predictor of Aggressiveness in Nonfunctioning Pituitary Adenomas : SSTR and Sex Hormone Receptor Distribution in NFPA
- 2017
-
Ingår i: Journal of Clinical Endocrinology and Metabolism. - : Oxford University Press. - 0021-972X .- 1945-7197. ; 102:9, s. 3581-3590
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Nonfunctioning pituitary adenomas (NFPAs) are fairly common and require a multidisciplinary approach. Reliable markers of a clinically aggressive course are lacking. Medical treatment is not available, and transsphenoidal surgery is the preferred primary treatment. Objective: We aimed to characterize the somatostatin, estrogen, and progesterone receptor distribution for NFPAs and compare it with factors of tumor aggressiveness. Design: Tumor samples for immunohistochemistry (n = 145) and quantitative reverse transcription polymerase chain reaction (n = 106) analyses of somatostatin receptor (SSTR) 1, SSTR2, SSTR3, SSTR5, estrogen receptor alpha (ER alpha), and progesterone receptor (PR) were measured by immunoreactive score (IRS) andmessenger RNA relative quantity and retrospectively compared with variables of aggressiveness. Setting: All patients were operated at the same tertiary referral center. Participants: A total of 164 patients with NFPA and tumor tissue from the primary operation were included. Results: SSTR3 was expressed abundantly by immunohistochemistry in all NFPAs. The IRS of ER alpha correlated with that of SSTR2 in male patients only (males, P<0.001; females, P = 0.8). Low ER alpha level was linked to a higher reintervention rate (P = 0.001) and earlier reintervention (P = 0.004) in male patients only (females, P = 0.95 and P = 0.65, respectively). Absence of ER alpha together with age provided a good prediction model for reintervention in male patients with gonadotroph adenomas. Conclusions: SSTR3 is expressed abundantly in NFPAs and is therefore a possible target for medical treatment. Absence of ER alpha together with young age may predict tumor recurrence in groups of NFPAs. Further validation in systematic prospective studies is needed.
|
|
| 29. |
- Quadri, Marialuisa, et al.
(författare)
-
LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies : a genome-wide linkage and sequencing study
- 2018
-
Ingår i: The Lancet Neurology. - 1474-4422. ; 17:7, s. 597-608
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Methods: Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Findings: Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent—albeit limited—evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Interpretation: Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Funding: Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Läkarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Européene Contre la Maladie d'Alzheimer (LECMA).
|
|
| 30. |
- Römhild, Josephine, et al.
(författare)
-
Inter-rater agreement of the Quality of Life-Alzheimer's Disease (QoL-AD) self-rating and proxy rating scale : Secondary analysis of RightTimePlaceCare data
- 2018
-
Ingår i: Health and Quality of Life Outcomes. - 1477-7525. ; 16:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background: To assess the quality of life of people with dementia, measures are required for self-rating by the person with dementia, and for proxy rating by others. The Quality of Life in Alzheimer's Disease scale (QoL-AD) is available in two versions, QoL-AD-SR (self-rating) and QoL-AD-PR (proxy rating). The aim of our study was to analyse the inter-rater agreement between self- and proxy ratings, in terms of both the total score and the items, including an analysis specific to care setting, and to identify factors associated with this agreement. Methods: Cross-sectional QoL-AD data from the 7th Framework European RightTimePlaceCare study were analysed. A total of 1330 cases were included: n = 854 receiving home care and n = 476 receiving institutional long-term nursing care. The proxy raters were informal carers (home care) and best-informed professional carers (institutional long-term nursing care). Inter-rater agreement was investigated using Bland-Altman plots for the QoL-AD total score and by weighted kappa statistics for single items. Associations were investigated by regression analysis. Results: The overall QoL-AD assessment of those with dementia revealed a mean value of 33.2 points, and the proxy ratings revealed a mean value of 29.8 points. The Bland-Altman plots revealed a poor agreement between self- and proxy ratings for the overall sample and for both care settings. With one exception (item 'Marriage' weighted kappa 0.26), the weighted kappa values for the single QoL-AD items were below 0.20, indicating poor agreement. Home care setting, dementia-related behavioural and psychological symptoms, and the functional status of the person with dementia, along with the caregiver burden, were associated with the level of agreement. Only the home care setting was associated with an increase larger than the predefined acceptable difference between self- and proxy ratings. Conclusions: Proxy quality of life ratings from professional and informal carers appear to be lower than the self-ratings of those with dementia. QoL-AD-SR and QoL-AD-PR are therefore not interchangeable, as the inter-rater agreement differs distinctly. Thus, a proxy rating should be judged as a complementary perspective for a self-assessment of quality of life by those with dementia, rather than as a valid substitute.
|
|
| 31. |
- Österlund, Lise-Lotte, 1962-
(författare)
-
Redox models in chemistry : A depiction of the conceptions held by secondary school students of redox reactions
- 2010
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- According to previous research, students show difficulties in learning redox reactions. By the historical development different redox models exist to explain redox reactions, the oxygen model, the hydrogen model, the electron model and the oxidation number model. This thesis reports about three studies concerning conceptions held by secondary school students of redox reactions. A textbook analysis is also included in the thesis. The first study was an investigation of the students’ use of redox models in inorganic contexts, their use of the activity series of metals, and the students’ ability to transfer redox knowledge. Then the students’ work with an open-ended biochemical task, where the students had access of the textbook was studied. The students talk about redox reactions, the questions raised by the students, what resources used to answer the questions and what kind of talk developed were investigated. A textbook analysis based on chemistry books from Sweden and one book from England was performed. The redox models used as well as the dealing with redox related learning difficulties was studied. Finally, the students’ conceptions about redox in inorganic, organic and biochemistry after completed chemistry courses were studied. The results show that the students were able to use the electron model as a tool to explain inorganic redox reactions and the mutuality of oxidation and reduction was fundamental. The activity series of metals became a tool for the prediction of reducing agent in some reactions. Most of the students rejected that oxygen is a prerequisite for a redox reaction. In the biochemical task the resource most used to answer the raised questions were the students’ consultation of the textbook – together or individually. Most questions resulted in short answers and the majority of these questions were answered. Questions concerning redox were analysed by the students and integrated into a chemical context but they could neither identify the substances oxidised or reduced nor couple the concepts to transfer of hydrogen atoms. The majority of these redox questions became unanswered. The textbook helped the students to structure a poster as well as to answer basic chemistry questions. For questions about organic and biochemical redox, the book was of no help. The textbook analysis showed that all historical redox models are used. Different models are used in inorganic, organic and biochemistry. The mutuality of oxidation and reduction is treated differently in subject areas. The textbooks did not help the reader linking the different redox models that were used. Few redox-related learning difficulties are addressed in the books. After completed chemistry courses the students had major problems to justify a redox reaction explained by transfer of hydrogen atoms both in the organic and biochemistry examples.
|
|
