| 1. |
|
|
| 2. |
- Adman, Per, et al.
(författare)
-
171 forskare: ”Vi vuxna bör också klimatprotestera”
- 2019
-
Ingår i: Dagens nyheter (DN debatt). - Stockholm. - 1101-2447.
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- DN DEBATT 26/9. Vuxna bör följa uppmaningen från ungdomarna i Fridays for future-rörelsen och protestera eftersom det politiska ledarskapet är otillräckligt. Omfattande och långvariga påtryckningar från hela samhället behövs för att få de politiskt ansvariga att utöva det ledarskap som klimatkrisen kräver, skriver 171 forskare i samhällsvetenskap och humaniora.
|
|
| 3. |
- Andersson, Anders, et al.
(författare)
-
A transcriptional timetable of autumn senescence
- 2004
-
Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 5:4, s. R24-
-
Tidskriftsartikel (refereegranskat)abstract
- Background We have developed genomic tools to allow the genus Populus (aspens and cottonwoods) to be exploited as a full-featured model for investigating fundamental aspects of tree biology. We have undertaken large-scale expressed sequence tag (EST) sequencing programs and created Populus microarrays with significant gene coverage. One of the important aspects of plant biology that cannot be studied in annual plants is the gene activity involved in the induction of autumn leaf senescence. Results On the basis of 36,354 Populus ESTs, obtained from seven cDNA libraries, we have created a DNA microarray consisting of 13,490 clones, spotted in duplicate. Of these clones, 12,376 (92%) were confirmed by resequencing and all sequences were annotated and functionally classified. Here we have used the microarray to study transcript abundance in leaves of a free-growing aspen tree (Populus tremula) in northern Sweden during natural autumn senescence. Of the 13,490 spotted clones, 3,792 represented genes with significant expression in all leaf samples from the seven studied dates. Conclusions We observed a major shift in gene expression, coinciding with massive chlorophyll degradation, that reflected a shift from photosynthetic competence to energy generation by mitochondrial respiration, oxidation of fatty acids and nutrient mobilization. Autumn senescence had much in common with senescence in annual plants; for example many proteases were induced. We also found evidence for increased transcriptional activity before the appearance of visible signs of senescence, presumably preparing the leaf for degradation of its components.
|
|
| 4. |
- Höglund, Andreas, 1980-, et al.
(författare)
-
Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine
- 2009
-
Ingår i: Blood. - : The American Society of Hematology. - 0006-4971 .- 1528-0020. ; 113:18, s. 4281-4288
-
Tidskriftsartikel (refereegranskat)abstract
- Decitabine (also referred to as 5-aza-2'-deoxycytidine) is a drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed to be the blocking of DNA methylation and thereby reactivating silenced genes involved in harnessing MDS. When analyzing reactivation of genes involved in Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells by inducing DNA damage. This sensitization is grossly augmented by the MYC oncogene, which is overexpressed in BL, and occurs in cells lacking a functional p53 tumor suppressor pathway. In p53-deficient BL cells and p53(-/-) mouse embryo fibroblasts, Myc overrides a transient G2-block exerted by decitabine via activation of Chk1. This triggers aneuploidy and cell death that correlates with, but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase activation, and/or expression of the BH3-only protein Puma. In vivo modeling of Myc-induced lymphoma suggests that decitabine constitutes a potential new drug against lymphoma that would selectively sensitize tumor cells but spare normal tissue.
|
|
| 5. |
- Höglund, Andreas, 1980-, et al.
(författare)
-
Therapeutic implications for the induced levels of Chk1 in Myc- expressing cancer cells
- 2011
-
Ingår i: Clinical Cancer Research. - Philadelphia : Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 17:22, s. 7067-7079
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: The transcription factor c-Myc (or "Myc") is a master regulator of pathways driving cell growth and proliferation. MYC is deregulated in many human cancers, making its downstream target genes attractive candidates for drug development. We report the unexpected finding that B-cell lymphomas from mice and patients exhibit a striking correlation between high levels of Myc and checkpoint kinase 1 (Chk1). Experimental Design: By in vitro cell biology studies as well as preclinical studies using a genetically engineered mouse model, we evaluated the role of Chk1 in Myc-overexpressing cells. Results: We show that Myc indirectly induces Chek1 transcript and protein expression, independently of DNA damage response proteins such as ATM and p53. Importantly, we show that inhibition of Chk1, by either RNA interference or a novel highly selective small molecule inhibitor, results in caspase-dependent apoptosis that affects Myc-overexpressing cells in both in vitro and in vivo mouse models of B-cell lymphoma. Conclusion: Our data suggest that Chk1 inhibitors should be further evaluated as potential drugs against Myc-driven malignancies such as certain B-cell lymphoma/leukemia, neuroblastoma, and some breast and lung cancers. Clin Cancer Res; 17(22); 7067-79. (C) 2011 AACR.
|
|
| 6. |
- Kruse, Thomas, et al.
(författare)
-
Large scale discovery of coronavirus-host factor protein interaction motifs reveals SARS-CoV-2 specific mechanisms and vulnerabilities
- 2021
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Viral proteins make extensive use of short peptide interaction motifs to hijack cellular host factors. However, most current large-scale methods do not identify this important class of protein-protein interactions. Uncovering peptide mediated interactions provides both a molecular understanding of viral interactions with their host and the foundation for developing novel antiviral reagents. Here we describe a viral peptide discovery approach covering 23 coronavirus strains that provides high resolution information on direct virus-host interactions. We identify 269 peptide-based interactions for 18 coronaviruses including a specific interaction between the human G3BP1/2 proteins and an ΦxFG peptide motif in the SARS-CoV-2 nucleocapsid (N) protein. This interaction supports viral replication and through its ΦxFG motif N rewires the G3BP1/2 interactome to disrupt stress granules. A peptide-based inhibitor disrupting the G3BP1/2-N interaction dampened SARS-CoV-2 infection showing that our results can be directly translated into novel specific antiviral reagents.
|
|
| 7. |
- Lindelöf, Linnea, et al.
(författare)
-
A survey of ficolin-3 activity in Systemic Lupus Erythematosus reveals a link to hematological disease manifestations and autoantibody profile
- 2024
-
Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 143
-
Tidskriftsartikel (refereegranskat)abstract
- The complement system plays a central role in the pathogenesis of Systemic Lupus Erythematosus (SLE), but most studies have focused on the classical pathway. Ficolin-3 is the main initiator of the lectin pathway of complement in humans, but its role in systemic autoimmune disease has not been conclusively determined. Here, we combined biochemical and genetic approaches to assess the contribution of ficolin-3 to SLE risk and disease manifestations. Ficolin-3 activity was measured by a functional assay in serum or plasma samples from Swedish SLE patients (n = 786) and controls matched for age and sex (n = 566). Genetic variants in an extended 300 kb genomic region spanning the FCN3 locus were analyzed for their association with ficolin-3 activity and SLE manifestations in a Swedish multicenter cohort (n = 985). Patients with ficolin-3 activity in the highest tertile showed a strong enrichment in an SLE cluster defined by anti-Sm/DNA/nucleosome antibodies (OR 3.0, p < 0.001) and had increased rates of hematological disease (OR 1.4, p = 0.078) and lymphopenia (OR = 1.6, p = 0.039). Genetic variants associated with low ficolin-3 activity mapped to an extended haplotype in high linkage disequilibrium upstream of the FCN3 gene. Patients carrying the lead genetic variant associated with low ficolin3 activity had a lower frequency of hematological disease (OR 0.67, p = 0.018) and lymphopenia (OR 0.63, p = 0.031) and fewer autoantibodies (p = 0.0019). Loss-of-function variants in the FCN3 gene were not associated with SLE, but four (0.5 %) SLE patients developed acquired ficolin-3 deficiency where ficolin-3 activity in serum was depleted following diagnosis of SLE. Taken together, our results provide genetic and biochemical evidence that implicate the lectin pathway in hematological SLE manifestations. We also identify lectin pathway activation through ficolin-3 as a factor that contributes to the autoantibody response in SLE.
|
|
| 8. |
- Nilsson, Konrad, et al.
(författare)
-
Causes, pattern, predictors, and prognostic implications of new hospitalizations after transcatheter aortic valve implantation : a long-term nationwide observational study
- 2022
-
Ingår i: European Heart Journal - Quality of Care and Clinical Outcomes. - : Oxford University Press (OUP). - 2058-5225 .- 2058-1742. ; 8:2, s. 150-160
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: The aim of this study was to investigate the pattern, causes, and predictors of all new hospitalizations in patients who underwent transcatheter aortic valve implantation (TAVI).METHODS AND RESULTS: The nationwide Swedish TAVI registry was merged with other mandatory healthcare registries, which enabled the analysis of all TAVI procedures, new hospital admissions, and death between the years 2008 and 2017. A total of 2821 patients underwent TAVI with a mean of 2.5 hospitalizations during a mean follow-up of 2.2 years. Hospitalizations were associated with worse prognosis. Heart failure (HF) was the most common cause of hospitalization with 19% having at least one hospitalization due to HF causing, 16% of all-cause admissions, and 50% of cardiovascular admissions. Male gender, age >90 years, high Charlson Comorbidity Index, atrial fibrillation, present neurologic disease, severe renal impairment, peripheral vascular disease, New York Heart Association class IV, mild or moderate mean aortic valve gradients, and pulmonary hypertension were associated with an increased risk for all-cause hospitalizations or death. For cardiovascular hospitalization or death, the pattern was similar, with the addition of impaired systolic left ventricular function as a predictor.CONCLUSION: Multiple hospitalizations after TAVI are common and are often caused by HF. Reducing the rate of HF hospitalizations is important to mitigate the burden on the healthcare system due to new hospitalizations after TAVI.
|
|
| 9. |
- Papaioannou, Konstantinos-Georgios, 1983-, et al.
(författare)
-
Healthy eating is associated with sarcopenia risk in physically active older adults
- 2021
-
Ingår i: Nutrients. - : MDPI. - 2072-6643. ; 13:8
-
Tidskriftsartikel (refereegranskat)abstract
- Healthy Diet and physical activity may play important roles in the maintenance of muscle health during aging. The aim of the present study was to explore the impact of adherence to healthy dietary patterns on sarcopenia risk in a sample of physically active older men and women, while considering adherence to guidelines on muscle strengthening activities (MSA) and protein intake. Based on a sample of 191 physically active men and women (65–70 years), dietary intake was assessed using a 90-items food-frequency-questionnaire (FFQ) and Healthy Diet Score (HDS) was calculated. Physical activity was assessed by accelerometry and self-report. A sarcopenia risk score (SRS) was derived based on three indicators of muscle health: muscle mass was assessed using bio-electrical impedance and handgrip strength and 5 times sit-to-stand (5-STS) were determined by standardized procedures. Analysis of covariance (ANCOVA) was used to examine differences in SRS and its components across sex-specific tertiles of HDS, with adjustments for covariates including total energy intake, protein intake and MSA. A significant main effect (p < 0.05) of HDS on SRS was observed, where those belonging to the highest HDS tertile had lower SRS compared to those in the lowest tertile. A corresponding significant effect was observed for 5-STS performance, with better performance in those with the highest HDS adherence compared to those with the lowest. The present study supports guidelines emphasizing diet quality beyond amounts of macro-and micronutrients in the prevention of age-related deterioration of muscle health. Importantly, the benefits from healthy dietary patterns are evident in older adults who already adhere to guidelines for health-enhancing physical activity.
|
|
| 10. |
- Ryve, Andreas, et al.
(författare)
-
Kartläggning av forskning om formativ bedömning, klassrumsundervisning och läromedel i matematik : Delrapport från skolforsk-projektet
- 2015
-
Rapport (övrigt vetenskapligt/konstnärligt)abstract
- The current project focuses on mathematics education, and is partitioned into three subprojects mapping research on formative assessment, classroom teaching, and curriculum programs in mathematics. The rationale for focusing on these three areas is that they are all highly relevant for understanding and improving Swedish mathematics education and students’ knowing of mathematics. Therefore, the aim of the project is to map research on formative assessment, classroom teaching, and curriculum programs in mathematics education.The methodology of the literature review has been inspired by Gough, Oliver, and Thomas (2013), and we have focused on the mapping on journal articles published on Web of Science (WoS).The results from the sample of articles on formative assessment show that strategies of formative assessment in mathematics are positively correlated to students’ performance in mathematics with medium and large effect sizes. However, based on the current mapping it is difficult to specify aspects of how the formative strategies are to be implemented in order to promote students’ knowing of mathematics.Despite the change in perspective of what constitutes knowledge in mathematics to also include reasoning, problem-solving and communication, the map shows that research is mainly focused on examining teaching methods and their effects on students’ skills in mathematics. A closer examination of the studies that do focus on teaching for supporting students in developing competencies like reasoning and problem-solving shows that connections between and comparison of students’ solutions, as well as teachers’ ways of asking questions to support students in explaining their solutions clearly and in detail, are important for students’ learning of these competencies.A central finding stemming from this review of curriculum programs is the complexity involved in how the programs can support teachers in establishing classroom practices. Curriculum resources and teacher resources, as well as other influencing factors, impact the quality of instruction, and studies have begun to point out how curriculum resources and teacher resources uniquely and jointly impact classroom practices. Multiple research articles have expressed the need for teacher support in implementing curriculum programs, by means of professional development, teacher education and support provided by the curriculum programs themselves. Interesting in this regard is the state of the research field concerning the design of educative curriculum programs, and how teachers make use of such support. Studies have proposed design approaches, regarding both the actual development of educative curriculum programs as well as how to use them in teacher education to support prospective teachers’ development of knowledge. Further, although research has revealed that it is important to prepare for teaching in certain ways, we found very little research that explicitly analyzed how teachers actually prepare for teaching a mathematics lesson.Limitations of the project include: (1) the lack of searching in potentially relevant databases, (2) the fact that a relatively small proportion of articles found in the search have been coded, (3) that we have not engaged in deep considerations as to whether and in what ways results from international research are relevant in the Swedish context, and (4) that we therefore have not been able to synthesize the results of the study. In relation to the Swedish context (Hemmi & Ryve, 2014; Boesen et al., 2014), international research (Hattie, 2009; Smith & Stein, 2011), and the current project’s findings, we recommend that Skolforskningsinstitutet focus on two aspects of great importance for developing students’ knowing of mathematics. First, Skolforskningsinstitutet should synthesize research that supports actors, such as teachers and principals, in acting within school practices. In the case of teachers, support is needed to engage them in actively anticipating students’ thinking, using curriculum programs effectively, introducing mathematical content, acting in group work, formatively assessing students’ learning, and orchestrating whole-class mathematical discussions. Secondly, actors within school practices need support not only in initiating and implementing developments but also in institutionalizing such developments. Skolforskningsinstitutet should specify the kind of support needed in order to ensure that material, routines, competences, and organizations become integral and permanent features of Swedish school practice.
|
|
