| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Shungin, Dmitry, et al.
(författare)
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New genetic loci link adipose and insulin biology to body fat distribution.
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 518:7538, s. 187-378
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Tidskriftsartikel (refereegranskat)abstract
- Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
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| 3. |
- Wang, Yifan, et al.
(författare)
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The BRCA1-Δ11q alternative splice isoform bypasses germline mutations and promotes therapeutic resistance to PARP inhibition and cisplatin
- 2016
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Ingår i: Cancer Research. - 0008-5472. ; 76:9, s. 2778-2790
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Tidskriftsartikel (refereegranskat)abstract
- Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this study, we investigated the impact of mutations on BRCA1 isoform expression and therapeutic response. Cancer cell lines and tumors harboring mutations in exon 11 of BRCA1 express a BRCA1-Δ11q splice variant lacking the majority of exon 11. The introduction of frameshift mutations to exon 11 resulted in nonsense-mediated mRNA decay of full-length, but not the BRCA1-Δ11q isoform. CRISPR/Cas9 gene editing as well as overexpression experiments revealed that the BRCA1-Δ11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length BRCA1, both in vitro and in vivo. Furthermore, spliceosome inhibitors reduced BRCA1- Δ11q levels and sensitized cells carrying exon 11 mutations to PARPi treatment. Taken together, our results provided evidence that cancer cells employ a strategy to remove deleterious germline BRCA1 mutations through alternative mRNA splicing, giving rise to isoforms that retain residual activity and contribute to therapeutic resistance.
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| 4. |
- Danielsson, Susanna, 1964, et al.
(författare)
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Epilepsy in young adults with autism: a prospective population-based follow-up study of 120 individuals diagnosed in childhood.
- 2005
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Ingår i: Epilepsia. - : Wiley. - 0013-9580 .- 1528-1167. ; 46:6, s. 918-923
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Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Little is known about the long-term outcome of epilepsy in autism and the epilepsy characteristics of adults with autism. This prospective population-based study was conducted in an attempt to point out differences on a group basis between adults with autism with or without epilepsy, and to describe the occurrence, the seizure characteristics, and the outcome of epilepsy in autism. METHODS: One hundred eight of 120 individuals with autism diagnosed in childhood and followed up prospectively for a period of 13-22 years were reevaluated at ages 17-40 years. As adults, the majority had mental retardation and autistic disorder or autistic-like condition. Interviews were performed with the caretakers of 42 of 43 individuals with a history of epilepsy, and their medical records were reviewed. RESULTS: Adults with autism and mental retardation constituted a severely disabled group. On a group basis, both the cognitive level and the adaptive behavior level were lower in the epilepsy group than in the nonepilepsy group (p<0.05). In all, 38% had epilepsy. One third had epilepsy onset before age 2 years. Remission of epilepsy was seen in 16%. Partial seizures with or without secondarily generalized seizures were the dominating seizure type. CONCLUSIONS: In a community sample of individuals with autism followed up from childhood through to adult age, one of three had epilepsy since childhood/adolescence. Severe mental retardation and autism are significantly associated with epilepsy, especially in female patients. Seizure frequency has a great impact on the individuals' lives. Specialist medical care is needed in this severely communication-disabled population.
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| 5. |
- Frick, Matilda, 1979-, et al.
(författare)
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Elever med adhd och autism : psykologiska och pedagogiska perspektiv
- 2023
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Bok (populärvet., debatt m.m.)abstract
- Boken presenterar konkreta strategier som kan användas i klassrummet för att främja lärande och delaktighet hos elever med adhd och autism.I den första delen, Psykologiska perspektiv, beskrivs diagnoskriterier, utredningsprocessen, hur adhd och autism uttrycks i vardagen samt en rad sociala och kognitiva förklaringsmodeller som är relaterade till tillstånden.Den andra delen, Pedagogiska perspektiv, knyter de psykologiska teorierna till olika vardagssituationer i skolan och redogör för olika strategier för stöd, såsom ledarskap i klassrummet, struktur i tid och rum, stöd för motivation, lärande och kamratrelationer. Boken riktar sig till specialpedagoger, speciallärare, lärare och skolpsykologer verksamma i skolan.
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| 6. |
- Gillberg, Christopher, 1950, et al.
(författare)
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Bengt Hagberg.
- 2015
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Ingår i: Acta paediatrica (Oslo, Norway : 1992). - : Wiley. - 1651-2227 .- 0803-5253. ; 104:10
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 7. |
- Gustafsson, Mika, et al.
(författare)
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A validated gene regulatory network and GWAS identifies early regulators of T cell-associated diseases
- 2015
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Ingår i: Science Translational Medicine. - : AMER ASSOC ADVANCEMENT SCIENCE. - 1946-6234 .- 1946-6242. ; 7:313
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Tidskriftsartikel (refereegranskat)abstract
- Early regulators of disease may increase understanding of disease mechanisms and serve as markers for presymptomatic diagnosis and treatment. However, early regulators are difficult to identify because patients generally present after they are symptomatic. We hypothesized that early regulators of T cell-associated diseases could be found by identifying upstream transcription factors (TFs) in T cell differentiation and by prioritizing hub TFs that were enriched for disease-associated polymorphisms. A gene regulatory network (GRN) was constructed by time series profiling of the transcriptomes and methylomes of human CD4(+) T cells during in vitro differentiation into four helper T cell lineages, in combination with sequence-based TF binding predictions. The TFs GATA3, MAF, and MYB were identified as early regulators and validated by ChIP-seq (chromatin immunoprecipitation sequencing) and small interfering RNA knockdowns. Differential mRNA expression of the TFs and their targets in T cell-associated diseases supports their clinical relevance. To directly test if the TFs were altered early in disease, T cells from patients with two T cell-mediated diseases, multiple sclerosis and seasonal allergic rhinitis, were analyzed. Strikingly, the TFs were differentially expressed during asymptomatic stages of both diseases, whereas their targets showed altered expression during symptomatic stages. This analytical strategy to identify early regulators of disease by combining GRNs with genome-wide association studies may be generally applicable for functional and clinical studies of early disease development.
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| 8. |
- Nilholm, Claes, 1957-, et al.
(författare)
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Systematik och reflektion : Om att sammanställa forskning
- 2022
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Ingår i: Utbildning och Demokrati. - : Örebro Universitet. - 1102-6472 .- 2001-7316. ; 31:2, s. 7-28
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Tidskriftsartikel (refereegranskat)abstract
- On being systematic and reflective when compiling researchThe purpose of this article is to demonstrate the importance of compila- tions of research being both systematic and reflective. The general point about the importance of reflection is illustrated by describing how a specific approach to compiling research, SMART (Systematic Mapping and Analysis of Research Topographies), has been used. SMART is based on a pragmatic perspective. This entails an openness to different scientific research traditions. The pragmatic starting point also means that compilations of research are linked to questions about how society and democracy can be developed. In this article, we describe how the ap- proach has been used to compile research on 1) inclusion and 2) teaching, respectively. Finally, the article discusses 1) the importance of compila- tions of research being both systematic and reflective 2) the question of how we should understand the increasing number of research reviews in the field of education science and 3) implications of the reasoning in the article for policy and practice.
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| 9. |
- Olsson, Ingrid I., et al.
(författare)
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A didactic perspective on negotiations and collaborations between different actors within the Swedish support system : children with autism spectrum disorders included in community-based preschool settings
- 2020
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Ingår i: Nordic Journal of Studies in Educational Policy. - : Informa UK Limited. - 2002-0317. ; 6:1, s. 58-68
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Tidskriftsartikel (refereegranskat)abstract
- In the present study, a didactic perspective was used to examine collaborations and negotiations between preschools and habilitation centres concerning intensive behavioural interventions for children with autism spectrum disorders in inclusive settings in Swedish preschools. The didactic triangle was used as the theoretical tool to analyse information derived from a qualitative case-study in two preschools exemplifying ‘high quality practice’. Direct content analysis was used to analyse data with a focus on the child, the pedagogue, and the subject. Data were collected through multiple sources during a 12-month period, including observations and interviews. A model of aspects of the collaboration between preschools, habilitation centres, and families was conceptualized based on the didactic triangle: the ‘pedagogue cornerstone’ encompassed competence, attitudes, and collaborations; the ‘child cornerstone’ encompassed learning in relation to specific goals; the ‘subject cornerstone’ encompassed both subjects shared with typically developing peers and subjects related to the specific challenges. In addition, the preschool principals were described as important. Different factors in relation to tensions and collaborations between organizations concerning inclusive education were elaborated. Implications for preschools, inter-organizational collaboration, and future research are discussed.
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| 10. |
- Olsson, Ingrid I., et al.
(författare)
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Adolescents and social support situations
- 2016
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Ingår i: Scandinavian Journal of Psychology. - : Wiley. - 0036-5564 .- 1467-9450. ; 57:3, s. 223-232
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Tidskriftsartikel (refereegranskat)abstract
- The present study concerned adolescents' needs for social support with a focus on specific situations. The Adolescent Need for Social Support Questionnaire (ANSSQ) was developed based on qualitative interviews with typically developing adolescents about situations in which they need parent support. The questionnaire was tested on a sample of 380 Swedish 15-year-olds. A 3-component structure reflecting the dimensions "Home and school", "Low mood", and "Sex and alcohol" was tested in SEM analyses. Scales based on these dimensions, measuring support from parents and peers, yielded satisfactory psychometric results. Parent support was preferred over peer support for "Home and school" situations; in the other two areas peers were more likely to be the support providers. Females turned more often to parents and friends for support than males. Seeking parental support was positively related to adolescent disclosure and negatively related to adolescent secrecy, indicating convergent and discriminant validity. Further validation of the ANSSQ is discussed. The current study points to possibilities for adapting measures of social support to contexts.
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