| 1. |
- Andersson, M, et al.
(författare)
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A Novel Selection System for Potato Transformation Using a Mutated AHAS Gene.
- 2003
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Ingår i: Plant Cell Reports. - : Springer Science and Business Media LLC. - 1432-203X .- 0721-7714. ; 22:4, s. 261-267
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Tidskriftsartikel (refereegranskat)abstract
- Acetohydroxyacid synthase (AHAS) is the target enzyme for a number of herbicides. A S653N mutation in the AHAS gene results in an increased tolerance to imidazolinone herbicides. We have investigated the use of the mutated gene as selection gene for potato transformation. This resulted in a transformation system with a very high transformation frequency and low rate of escapes. The mutated AHAS gene was introduced into transformed potato together with a -glucuronidase (GUS) gene. Selection on 0.5 M Imazamox yielded GUS expression in 93–100% of regenerated shoots. Furthermore the mutated AHAS gene was used as selection gene for production of high-amylopectin potato lines. The high transformation frequency was verified and potato lines with the desirable starch quality were obtained.
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| 2. |
- Andersson, Mariette, et al.
(författare)
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Targeted gene suppression by RNA interference: An efficient method for production of high-amylose potato lines
- 2006
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Ingår i: Journal of Biotechnology. - : Elsevier BV. - 1873-4863 .- 0168-1656. ; 123:2, s. 137-148
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Tidskriftsartikel (refereegranskat)abstract
- Production of high-amylose potato lines can be achieved by inhibition of two genes coding for starch branching enzymes. The use of antisense technology for gene inhibition have yielded a low frequency of high-amylose lines that mostly was correlated with high numbers of integrated T-DNA copies. To investigate whether the production of high-amylose lines could be improved, RNA interference was used for gene inhibition of the genes Sbe1 and Sbe2. Two constructs with 100 bp segments (pHAS2) or 200 bp segments (pHAS3) of both branching enzyme genes were cloned as inverted repeats controlled by a potato granule-bound starch synthase promoter. The construct pHAS3 was shown to be very efficient, yielding high-amylose quality in more than 50% of the transgenic lines. An antisense construct, included in the study as a comparator, resulted in only 3% of the transgenic lines being of high-amylose type. Noticeable was also that pHAS3 yielded low T-DNA copy inserts with an average of 83% of backbone-free transgenic lines being single copy events.
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| 3. |
- Arbajian, Elsa, et al.
(författare)
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In-depth genetic analysis of sclerosing epithelioid fibrosarcoma reveals recurrent genomic alterations and potential treatment targets
- 2017
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Ingår i: Clinical Cancer Research. - 1078-0432. ; 23:23, s. 7426-7434
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Sclerosing epithelioid fibrosarcoma (SEF) is a highly aggressive soft tissue sarcoma closely related to low-grade fibromyxoid sarcoma (LGFMS). Some tumors display morphological characteristics of both SEF and LGFMS, so called hybrid SEF/LGFMS. Despite the overlap of gene fusion variants between these two tumor types, SEF is much more aggressive. The present study aimed to further characterize SEF and hybrid SEF/LGFMS genetically in order to better understand the role of the characteristic fusion genes and possible additional genetic alterations in tumorigenesis.EXPERIMENTAL DESIGN: We performed whole exome sequencing, single nucleotide polymorphism (SNP) array analysis, RNA-sequencing (RNA-seq), global gene expression analyses and/or IHC on a series of 13 SEFs and 6 hybrid SEF/LGFMS. We also expressed the FUS-CREB3L2 and EWSR1-CREB3L1 fusion genes conditionally in a fibroblast cell line; these cells were subsequently analyzed by RNA-seq and expression of the CD24 protein was assessed by FACS analysis.RESULTS: The SNP array analysis detected a large number of structural aberrations in SEF and SEF/LGFMS, many of which were recurrent, notably DMD microdeletions. RNA-seq identified FUS-CREM and PAX5-CREB3L1 as alternative fusion genes in one SEF each. CD24 was strongly upregulated, presumably a direct target of the fusion proteins. This was further confirmed by the gene expression analysis and FACS analysis on Tet-On 3G cells expressing EWSR1-CREB3L1.CONCLUSIONS: While gene fusions are the primary tumorigenic events in both SEF and LGFMS, additional genomic changes explain the differences in aggressiveness and clinical outcome between the two types. CD24 and DMD constitute potential therapeutic targets.
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| 4. |
- Djamnezhad, Dariush, et al.
(författare)
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Social and Emotional Learning in Preschool Settings: A Systematic Map of Systematic Reviews
- 2021
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Ingår i: Frontiers in Education. - : Frontiers Media SA. - 2504-284X. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- The preschool years presents an important opportunity to support children's social and emotional development. Social and emotional learning (SEL) programs in early childhood education and care (ECEC) have gained an increased interest due to its potential to improve child health and educational outcomes. We aimed to identify existing systematic reviews on universal, curriculum-based SEL interventions in ECEC settings (children aged 0 to 7 years), assess their risk of bias, synthesize the findings and identify knowledge gaps. We undertook a systematic literature search in seven different databases. Reviews of studies without control groups were excluded. Each abstract and full text article was assessed independently, and disagreements were solved in consensus. Relevant reviews were assessed for bias using the ROBIS tool. Of 4912 records identified through database searches, two systematic reviews met the inclusion criteria. Both reviews were assessed as having a high risk of bias. The results were used to summarize existing knowledge and knowledge gaps. In conclusion, SEL interventions in preschool settings must be considered knowledge gaps. There is a need for more high-quality primary studies and further systematic reviews that adhere to strict scientific methods and address the overwhelming heterogeneity in field, in terms of interventions, settings and outcomes.
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| 5. |
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| 6. |
- Hofvander, Jakob, et al.
(författare)
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PHF1 fusions cause distinct gene expression and chromatin accessibility profiles in ossifying fibromyxoid tumors and mesenchymal cells
- 2020
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Ingår i: Modern Pathology. - : Elsevier BV. - 0893-3952. ; 33:7, s. 1331-1340
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Tidskriftsartikel (refereegranskat)abstract
- Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor frequently displaying gene fusions, most of which affect the PHF1 gene. PHF1 encodes plant homeodomain finger protein 1, which is involved in various processes regulating gene transcription, including those orchestrated by the polycomb repressor complex 2. Here, a series of 37 OFMTs, including 18 typical, 9 atypical, and 10 malignant variants, was analyzed with regard to transcriptomic features, gene fusion and copy number status, and/or single-nucleotide variants. The effects on gene expression and chromatin accessibility of three detected fusions (EP400–PHF1, MEAF6–PHF1, and PHF1–TFE3) were further evaluated in fibroblasts. Genomic imbalances showed a progression-related pattern, with more extensive copy number changes among atypical/malignant lesions than among typical OFMTs; loss of the RB1 gene was restricted to atypical/malignant OFMTs, occurring in one-third of the cases. RNA sequencing identified fusion transcripts in >80% of the cases analyzed, including a novel CSMD1–MEAF6. The gene-expression profile of OFMT was distinct from that of other soft tissue tumors, with extensive transcriptional upregulation of genes in OFMT. These findings were largely recapitulated in gene fusion-expressing fibroblast lines, suggesting that genes involved in, e.g., Wnt signaling and/or being regulated through trimethylation of lysine 27 in histone 3 (H3K27me3) are pivotal for OFMT development. The genes showing differentially higher expression in fusion-expressing cells paralleled increased chromatin accessibility, as revealed by ATAC sequencing. Thus, the present study suggests that OFMT develops through gene fusions that have extensive epigenetic consequences.
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| 7. |
- Hofvander, Jakob, et al.
(författare)
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Undifferentiated pleomorphic sarcomas with PRDM10 fusions have a distinct gene expression profile
- 2019
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Ingår i: Journal of Pathology. - : Wiley. - 0022-3417 .- 1096-9896. ; 249:4, s. 425-434
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Tidskriftsartikel (refereegranskat)abstract
- Undifferentiated pleomorphic sarcoma (UPS) is a highly aggressive soft tissue tumor. A subset of UPS is characterized by a CITED2–PRDM10 or a MED12–PRDM10 gene fusion. Preliminary data suggest that these so-called PRDM10-rearranged tumors (PRT) are clinically more indolent than classical high-grade UPS, and hence important to recognize. Here, we assessed the spectrum of accompanying mutations and the gene expression profile in PRT using genomic arrays and sequencing of the genome (WGS) and transcriptome (RNA-seq). The fusion protein's function was further investigated by conditional expression of the CITED2–PRDM10 fusion in a fibroblast cell line, followed by RNA-seq and an assay for transposase-accessible chromatin (ATAC-seq). The CADM3 gene was found to be differentially up-regulated in PRT and cell lines and was also evaluated for expression at the protein level using immunohistochemistry (IHC). The genomic analyses identified few and nonrecurrent mutations in addition to the structural variants giving rise to the gene fusions, strongly indicating that the PRDM10-fusions represent the critical driver mutations. RNA-seq of tumors showed a distinct gene expression profile, separating PRT from high-grade UPS and other soft tissue tumors. CADM3 was among the genes that was consistently and highly expressed in both PRT and fibroblasts expressing CITED2-PRDM10, suggesting that it is a direct target of the PRDM10 transcription factor. This conclusion is in line with sequencing data from ATAC-seq, showing enrichment of PRDM10 binding sites, suggesting that the amino-terminal fusion partner contributes by making the DNA more accessible to PRDM10 binding.
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| 8. |
- Hofvander, Per, et al.
(författare)
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A prokaryotic acyl-CoA reductase performing reduction of fatty acyl-CoA to fatty alcohol
- 2011
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Ingår i: FEBS Letters. - : Wiley. - 0014-5793 .- 1873-3468. ; 585, s. 3538-3543
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Annan publikation (refereegranskat)abstract
- The reduction of acyl-CoA or acyl-ACP to fatty alcohol occurs via a fatty aldehyde intermediate. In prokaryotes this reaction is thought to be performed by separate enzymes for each reduction step while in eukaryotes these reactions are performed by a single enzyme without the release of the intermediate fatty aldehyde. However, here we report that a purified fatty acyl reductase from Marinobacter aquaeolei VT8, evolutionarily related to the fatty acyl reductases in eukaryotes, catalysed both reduction steps. Thus, there are at least two pathways existing among prokaryotes for the reduction of activated acyl substrates to fatty alcohol. The Marinobacter fatty acyl reductase studied has a wide substrate range in comparison to what can be found among enzymes so far studied in eukaryotes. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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| 9. |
- Hofvander, Y, et al.
(författare)
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Amning idag.
- 1998
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Bok (övrigt vetenskapligt/konstnärligt)
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| 10. |
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| 11. |
- Howner, K., et al.
(författare)
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Mapping Systematic Reviews on Forensic Psychiatric Care: A Systematic Review Identifying Knowledge Gaps
- 2018
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Ingår i: Frontiers in Psychiatry. - : Frontiers Media SA. - 1664-0640. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Forensic psychiatric care treats mentally disordered offenders who suffer mainly from psychotic disorders, although comorbidities such as personality disorders, neurodevelopmental disorders, and substance abuse are common. A large proportion of these patients have committed violent crimes. Their care is involuntary, and their caregivers' mission is complex: not only to rehabilitate the patient, but also to consider their risk for reoffending and their risk to society. The objective of this overview of systematic reviews is to identify, appraise, and summarize the existing knowledge in forensic psychiatric care and identify knowledge gaps that require further research. Methods: We undertook a systematic literature search for systematic reviews in five defined domains considered important in daily clinical practice within the forensic psychiatric care: (1) diagnostic assessment and risk assessments; (2) pharmacological treatment; (3) psychological interventions; (4) psychosocial interventions, rehabilitation, and habilitation; and (5) restraint interventions. The target population was mentally disordered offenders (forensic psychiatric patients aged >15 years). Each abstract and full text review was assessed by two of the authors. Relevant reviews then were assessed for bias, and those with moderate or low risk of bias were included. Results: Of 38 systematic reviews meeting the inclusion criteria, only four had a moderate risk of bias. Two aimed to incorporate as many aspects of forensic psychiatric care as possible, one investigated non-pharmacological interventions to reduce aggression in forensic psychiatric care, and one focused on women with intellectual disabilities in forensic care. However, most of the primary studies included in these reviews had high risks of bias, and therefore, no conclusions could be drawn. All of our identified domains must be considered knowledge gaps. Conclusion: We could not answer any of our research questions within the five domains because of the high risk of bias in the primary studies in the included systematic reviews. There is an urgent need for more research on forensic psychiatric care since all of our studied domains were considered knowledge gaps.
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| 12. |
- Jönsson, Anette, et al.
(författare)
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In old men Scheuermann's disease is not associated with neck or back pain: a Swedish cohort study
- 2023
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Ingår i: Acta Orthopaedica. - 1745-3674. ; 94, s. 236-242
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Tidskriftsartikel (refereegranskat)abstract
- Background and purpose - Scheuermann's disease is characterized by kyphosis and frequently mild back pain. As the level of kyphosis may progress over time, also the level of pain may increase. We evaluated the prevalence of Scheuer-mann's disease, and their pain, in Swedish elderly men. Patients and methods - The Osteoporotic Fractures in Men (MrOS) Study Sweden (n = 3,014) is a population -based prospective observational study of community-living men aged 69-81 years. At baseline, participants answered a questionnaire including history of neck/back pain during the preceding year and characteristics of any pain (severity, sciatica, and neurological deficits). Lateral thoracic/lumbar spine radiographs were taken of 1,453 men. We included the 1,417 men with readable radiographs. Scheuermann's dis-ease was defined as 3 or more consecutive vertebrae with > 5 & DEG; wedging with no other explanation for the deformity. Results - 92 of the 1,417 men (6.5%, 95% confidence interval 5.3-7.9) had Scheuermann's disease. 31% of men with and 31% without Scheuermann's disease reported neck pain (P = 0.90) and 51% with and 55% without the disease reported back pain (P = 0.4). Among men with Scheuer-mann's disease and back pain, none reported severe pain, 57% moderate, and 43% mild, compared with 7%, 50%, and 44% in those without Scheuermann's disease (P = 0.2). In those with Scheuermann's disease 63% reported no sciatica, 15% sciatica without neurological deficits, and 22% sciatica with neurological deficits, compared with 56%, 16%, and 28% in those without the disease (P = 0.6). Conclusion - The prevalence of Scheuermann's disease in elderly Swedish men is between 5.3% and 7.9%. The con-dition seems at this age not to be associated with neck or back pain.
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| 13. |
- Puls, Florian, et al.
(författare)
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PRDM10 -rearranged Soft Tissue Tumor : A Clinicopathologic Study of 9 Cases
- 2019
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Ingår i: American Journal of Surgical Pathology. - 0147-5185. ; 43:4, s. 504-513
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Tidskriftsartikel (refereegranskat)abstract
- Gene fusion transcripts containing PRDM10 were recently identified in low-grade undifferentiated pleomorphic sarcomas (UPS). Here, we describe the morphologic and clinical features of 9 such tumors from 5 men and 4 women (age: 20 to 61 y). Three cases had previously been diagnosed as UPS, 3 as superficial CD34-positive fibroblastic tumor (SCD34FT), 2 as pleomorphic liposarcoma, and 1 as pleomorphic hyalinizing angiectatic tumor. The tumors were located in the superficial and deep soft tissues of the thigh/knee region (4 cases), shoulder (2 cases), foot, trunk, and perineum (1 case each) ranging in size from 1 to 6 cm. All showed poorly defined cellular fascicles of pleomorphic cells within a fibrous stroma with frequent myxoid change and a prominent inflammatory infiltrate. All displayed highly pleomorphic nuclear features, but a low mitotic count. Most tumors were well circumscribed. One of 9 tumors recurred locally, but none metastasized. Immunohistochemically, all were CD34+ and showed nuclear positivity for PRDM10; focal positivity for cytokeratins was seen in 5/6 cases. PRDM10 immunoreactivity was evaluated in 50 soft tissue tumors that could mimic PRDM10- rearranged tumors, including 4 cases exhibiting histologic features within the spectrum of SCD34FT. Except for 2/6 pleomorphic liposarcomas and 1/4 myxofibrosarcomas, other tumors did not show nuclear positivity but displayed weak to moderate cytoplasmic immunoreactivity. In conclusion, PRDM10-rearranged soft tissue tumor is characterized by pleomorphic morphology and a low mitotic count. Its morphologic spectrum overlaps with SCD34FT. Clinical features of this small series suggest an indolent behavior, justifying its distinction from UPS and other sarcomas.
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| 14. |
- Saba, Karim H., et al.
(författare)
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Loss of NF2 defines a genetic subgroup of non-FOS-rearranged osteoblastoma
- 2020
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Ingår i: Journal of Pathology: Clinical Research. - : Wiley. - 2056-4538. ; 6:4, s. 231-237
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Tidskriftsartikel (refereegranskat)abstract
- Osteoblastoma is a locally aggressive tumour of bone. Until recently, its underlying genetic features were largely unknown. During the past two years, reports have demonstrated that acquired structural variations affect the transcription factor FOS in a high proportion of cases. These rearrangements modify the terminal exon of the gene and are believed to stabilise both the FOS transcript and the encoded protein, resulting in high expression levels. Here, we applied in-depth genetic analyses to a series of 29 osteoblastomas, including five classified as epithelioid osteoblastoma. We found recurrent homozygous deletions of the NF2 gene in three of the five epithelioid cases and in one conventional osteoblastoma. These events were mutually exclusive from FOS mutations. Structural variations were determined by deep whole genome sequencing and the number of FOS-rearranged cases was less than previously reported (10/23, 43%). One conventional osteoblastoma displayed a novel mechanism of FOS upregulation; bringing the entire FOS gene under the control of the WNT5A enhancer that is itself activated by FOS. Taken together, we show that NF2 loss characterises a subgroup of osteoblastomas, distinct from FOS-rearranged cases. Both NF2 and FOS are involved in regulating bone homeostasis, thereby providing a mechanistic link to the excessive bone growth of osteoblastoma.
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| 15. |
- Schepke, Elizabeth, et al.
(författare)
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DNA methylation profiling improves routine diagnosis of paediatric central nervous system tumours: A prospective population-based study
- 2022
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Ingår i: Neuropathology and Applied Neurobiology. - : Wiley. - 0305-1846 .- 1365-2990. ; 48:6
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Paediatric brain tumours are rare, and establishing a precise diagnosis can be challenging. Analysis of DNA methylation profiles has been shown to be a reliable method to classify central nervous system (CNS) tumours with high accuracy. We aimed to prospectively analyse CNS tumours diagnosed in Sweden, to assess the clinical impact of adding DNA methylation-based classification to standard paediatric brain tumour diagnostics in an unselected cohort. Methods: All CNS tumours diagnosed in children (0-18 years) during 2017-2020 were eligible for inclusion provided sufficient tumour material was available. Tumours were analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier. The initial histopathological diagnosis was compared with the DNA methylation-based classification. For incongruent results, a blinded re-evaluation was performed by an experienced neuropathologist. Results: Two hundred forty tumours with a histopathology-based diagnosis were profiled. A high-confidence methylation score of 0.84 or more was reached in 78% of the cases. In 69%, the histopathological diagnosis was confirmed, and for some of these also refined, 6% were incongruent, and the re-evaluation favoured the methylation-based classification. In the remaining 3% of cases, the methylation class was non-contributory. The change in diagnosis would have had a direct impact on the clinical management in 5% of all patients. Conclusions: Integrating DNA methylation-based tumour classification into routine clinical analysis improves diagnostics and provides molecular information that is important for treatment decisions. The results from methylation profiling should be interpreted in the context of clinical and histopathological information.
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| 16. |
- Schepke, Elizabeth, et al.
(författare)
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Supratentorial CNS-PNETs in children; a Swedish population-based study with molecular re-evaluation and long-term follow-up
- 2023
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Ingår i: Clinical Epigenetics. - : Springer Science and Business Media LLC. - 1868-7075 .- 1868-7083. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundMolecular analyses have shown that tumours diagnosed as supratentorial primitive neuro-ectodermal tumours of the central nervous system (CNS-PNETs) in the past represent a heterogenous group of rare childhood tumours including high-grade gliomas (HGG), ependymomas, atypical teratoid/rhabdoid tumours (AT/RT), CNS neuroblastoma with forkhead box R2 (FOXR2) activation and embryonal tumour with multi-layered rosettes (ETMR). All these tumour types are rare and long-term clinical follow-up data are sparse. We retrospectively re-evaluated all children (0-18 years old) diagnosed with a CNS-PNET in Sweden during 1984-2015 and collected clinical data.MethodsIn total, 88 supratentorial CNS-PNETs were identified in the Swedish Childhood Cancer Registry and from these formalin-fixed paraffin-embedded tumour material was available for 71 patients. These tumours were histopathologically re-evaluated and, in addition, analysed using genome-wide DNA methylation profiling and classified by the MNP brain tumour classifier.ResultsThe most frequent tumour types, after histopathological re-evaluation, were HGG (35%) followed by AT/RT (11%), CNS NB-FOXR2 (10%) and ETMR (8%). DNA methylation profiling could further divide the tumours into specific subtypes and with a high accuracy classify these rare embryonal tumours. The 5 and 10-year overall survival (OS) for the whole CNS-PNET cohort was 45% +/- 12% and 42% +/- 12%, respectively. However, the different groups of tumour types identified after re-evaluation displayed very variable survival patterns, with a poor outcome for HGG and ETMR patients with 5-year OS 20% +/- 16% and 33% +/- 35%, respectively. On the contrary, high PFS and OS was observed for patients with CNS NB-FOXR2 (5-year 100% for both). Survival rates remained stable even after 15-years of follow-up.ConclusionsOur findings demonstrate, in a national based setting, the molecular heterogeneity of these tumours and show that DNA methylation profiling of these tumours provides an indispensable tool in distinguishing these rare tumours. Long-term follow-up data confirms previous findings with a favourable outcome for CNS NB-FOXR2 tumours and poor chances of survival for ETMR and HGG.
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| 17. |
- Sinclair, Julia M A, et al.
(författare)
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Identifying the most important research, policy and practice questions for substance use, problematic alcohol use and behavioural addictions in autism (SABA-A) : A priority setting partnership
- 2023
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Ingår i: Comprehensive Psychiatry. - 0010-440X. ; 124, s. 1-7
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autistic people are more likely to report problematic alcohol and other substance use when compared to the general population. Evidence suggests that up to one in three autistic adults may have an alcohol or other substance use disorder (AUD/SUD), although the evidence base for behavioural addictions is less clear. Autistic people may use substances or engage in potentially addictive behaviours as a means of coping with social anxiety, challenging life problems, or camouflaging in social contexts. Despite the prevalence and detrimental effects of AUD, SUD and behavioural addictions in community samples, literature focusing on the intersection between autism and these conditions is scarce, hindering health policy, research, and clinical practice.METHODS: We aimed to identify the top 10 priorities to build the evidence for research, policy, and clinical practice at this intersection. A priority-setting partnership was used to address this aim, comprising an international steering committee and stakeholders from various backgrounds, including people with declared lived experience of autism and/or addiction. First, an online survey was used to identify what people considered key questions about Substance use, alcohol use, or behavioural addictions in autistic people (SABA-A). These initial questions were reviewed and amended by stakeholders, and then classified and refined to form the final list of top priorities via an online consensus process.OUTCOMES: The top ten priorities were identified: three research, three policy, and four practice questions. Future research suggestions are discussed.
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