| 1. |
- Abdul-Hussein, Saba, et al.
(författare)
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Phenotypes of Myopathy-Related Beta-Tropomyosin Mutants in Human and Mouse Tissue Cultures
- 2013
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 8:9
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in TPM2 result in a variety of myopathies characterised by variable clinical and morphological features. We used human and mouse cultured cells to study the effects of beta-TM mutants. The mutants induced a range of phenotypes in human myoblasts, which generally changed upon differentiation to myotubes. Human myotubes transfected with the E41K-beta-TMEGFP mutant showed perinuclear aggregates. The G53ins-beta-TMEGFP mutant tended to accumulate in myoblasts but was incorporated into filamentous structures of myotubes. The K49del-beta-TMEGFP and E122K-beta-TMEGFP mutants induced the formation of rod-like structures in human cells. The N202K-beta-TMEGFP mutant failed to integrate into thin filaments and formed accumulations in myotubes. The accumulation of mutant beta-TMEGFP in the perinuclear and peripheral areas of the cells was the striking feature in C2C12. We demonstrated that human tissue culture is a suitable system for studying the early stages of altered myofibrilogenesis and morphological changes linked to myopathy-related beta-TM mutants. In addition, the histopathological phenotype associated with expression of the various mutant proteins depends on the cell type and varies with the maturation of the muscle cell. Further, the phenotype is a combinatorial effect of the specific amino acid change and the temporal expression of the mutant protein.
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| 2. |
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| 3. |
- Billing, Erik, PhD, 1981-, et al.
(författare)
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The DREAM Dataset : Supporting a data-driven study of autism spectrum disorder and robot enhanced therapy
- 2020
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 15:8
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Tidskriftsartikel (refereegranskat)abstract
- We present a dataset of behavioral data recorded from 61 children diagnosed with Autism Spectrum Disorder (ASD). The data was collected during a large-scale evaluation of Robot Enhanced Therapy (RET). The dataset covers over 3000 therapy sessions and more than 300 hours of therapy. Half of the children interacted with the social robot NAO supervised by a therapist. The other half, constituting a control group, interacted directly with a therapist. Both groups followed the Applied Behavior Analysis (ABA) protocol. Each session was recorded with three RGB cameras and two RGBD (Kinect) cameras, providing detailed information of children’s behavior during therapy. This public release of the dataset comprises body motion, head position and orientation, and eye gaze variables, all specified as 3D data in a joint frame of reference. In addition, metadata including participant age, gender, and autism diagnosis (ADOS) variables are included. We release this data with the hope of supporting further data-driven studies towards improved therapy methods as well as a better understanding of ASD in general.
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| 4. |
- Bjerkeli, Pernilla J., et al.
(författare)
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Refill Adherence in Relation to Substitution and the Use of Multiple Medications: A Nationwide Population Based Study on New ACE-Inhibitor Users
- 2016
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Objective Generic substitution has contributed to economic savings but switching products may affect patient adherence, particularly among those using multiple medications. The aim was to analyse if use of multiple medications influenced the association between switching products and refill adherence to angiotensin-converting-enzyme (ACE) inhibitors in Sweden. New users of ACE-inhibitors, starting between 1 July 2006 and 30 June 2007, were identified in the Swedish Prescribed Drug Register. Refill adherence was assessed using the continuous measure of medication acquisition (CMA) and analysed with linear regression and analysis of covariance. The study population included 42735 individuals whereof 51.2% were exposed to switching ACE-inhibitor and 39.6% used multiple medications. Refill adherence was higher among those exposed to switching products than those not, but did not vary depending on the use of multiple medications or among those not. Refill adherence varied with age, educational level, household income, country of birth, previous hospitalisation and previous cardiovascular diagnosis. The results indicate a positive association between refill adherence and switching products, mainly due to generic substitution, among new users of ACE-inhibitors in Sweden. This association was independent of use of multiple medications.
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| 5. |
- Chawade, Aakash, et al.
(författare)
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Global expression profiling of low temperature induced genes in the chilling tolerant japonica rice jumli marshi
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:12, s. e81729-
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Tidskriftsartikel (refereegranskat)abstract
- Low temperature is a key factor that limits growth and productivity of many important agronomical crops worldwide. Rice (Oryza sativa L.) is negatively affected already at temperatures below +10°C and is therefore denoted as chilling sensitive. However, chilling tolerant rice cultivars exist and can be commercially cultivated at altitudes up to 3,050 meters with temperatures reaching as low as +4°C. In this work, the global transcriptional response to cold stress (+4°C) was studied in the Nepalese highland variety Jumli Marshi (spp. japonica) and 4,636 genes were identified as significantly differentially expressed within 24 hours of cold stress. Comparison with previously published microarray data from one chilling tolerant and two sensitive rice cultivars identified 182 genes differentially expressed (DE) upon cold stress in all four rice cultivars and 511 genes DE only in the chilling tolerant rice. Promoter analysis of the 182 genes suggests a complex cross-talk between ABRE and CBF regulons. Promoter analysis of the 511 genes identified over-represented ABRE motifs but not DRE motifs, suggesting a role for ABA signaling in cold tolerance. Moreover, 2,101 genes were DE in Jumli Marshi alone. By chromosomal localization analysis, 473 of these cold responsive genes were located within 13 different QTLs previously identified as cold associated.
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| 6. |
- Dahl-Halvarsson, Martin, et al.
(författare)
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Myosin Storage Myopathy in C. elegans and Human Cultured Muscle Cells
- 2017
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Myosin storage myopathy is a protein aggregate myopathy associated with the characteristic subsarcolemmal accumulation of myosin heavy chain in muscle fibers. Despite similar histological findings, the clinical severity and age of onset are highly variable, ranging from no weakness to severe impairment of ambulation, and usually childhood-onset to onset later in life. Mutations located in the distal end of the tail of slow/beta-cardiac myosin heavy chain are associated with myosin storage myopathy. Four missense mutations (L1793P, R1845W, E1883K and H1901L), two of which have been reported in several unrelated families, are located within or closed to the assembly competence domain. This location is critical for the proper assembly of sarcomeric myosin rod filaments. To assess the mechanisms leading to protein aggregation in myosin storage myopathy and to evaluate the impact of these mutations on myosin assembly and muscle function, we expressed mutated myosin proteins in cultured human muscle cells and in the nematode Caenorhabditis elegans. While L1793P mutant myosin protein efficiently incorporated into the sarcomeric thick filaments, R1845W and H1901L mutants were prone to formation of myosin aggregates without assembly into striated sarcomeric thick filaments in cultured muscle cells. In C. elegans, mutant alleles of the myosin heavy chain gene unc-54 corresponding to R1845W, E1883K and H1901L, were as effective as the wild-type myosin gene in rescuing the null mutant worms, indicating that they retain functionality. Taken together, our results suggest that the basis for the pathogenic effect of the R1845W and H1901L mutations are primarily structural rather than functional. Further analyses are needed to identify the primary trigger for the histological changes seen in muscle biopsies of patients with L1793P and E1883K mutations.
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| 7. |
- Dahlström, Örjan, et al.
(författare)
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Is "Football for All" Safe for All? : Cross-Sectional Study of Disparities as Determinants of 1-Year Injury Prevalence in Youth Football Programs
- 2012
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Ingår i: PLOS ONE. - : PLOS. - 1932-6203. ; 7:8, s. e43795-
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Tidskriftsartikel (refereegranskat)abstract
- Background: Football (soccer) is endorsed as a health-promoting physical activity worldwide. When football programs are introduced as part of general health promotion programs, equal access and limitation of pre-participation disparities with regard to injury risk are important. The aim of this study was to explore if disparity with regard to parents’ educational level, player body mass index (BMI), and self-reported health are determinants of football injury in community-based football programs, separately or in interaction with age or gender.Methodology/Principal Findings: Four community football clubs with 1230 youth players agreed to participate in the cross-sectional study during the 2006 season. The study constructs (parents’ educational level, player BMI, and self-reported health) were operationalized into questionnaire items. The 1-year prevalence of football injury was defined as the primary outcome measure. Data were collected via a postal survey and analyzed using a series of hierarchical statistical computations investigating associations with the primary outcome measure and interactions between the study variables. The survey was returned by 827 (67.2%) youth players. The 1-year injury prevalence increased with age. For youths with parents with higher formal education, boys reported more injuries and girls reported fewer injuries than expected; for youths with lower educated parents there was a tendency towards the opposite pattern. Youths reporting injuries had higher standardized BMI compared with youths not reporting injuries. Children not reporting full health were slightly overrepresented among those reporting injuries and underrepresented for those reporting no injury.Conclusion: Pre-participation disparities in terms of parents’ educational level, through interaction with gender, BMI, and self-reported general health are associated with increased injury risk in community-based youth football. When introduced as a general health promotion, football associations should adjust community-based youth programs to accommodate children and adolescents with increased pre-participation injury risk.
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| 8. |
- Dallora Moraes, Ana Luiza, et al.
(författare)
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Bone age assessment with various machine learning techniques : A systematic literature review and meta-analysis
- 2019
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 14:7
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Forskningsöversikt (refereegranskat)abstract
- Background The assessment of bone age and skeletal maturity and its comparison to chronological age is an important task in the medical environment for the diagnosis of pediatric endocrinology, orthodontics and orthopedic disorders, and legal environment in what concerns if an individual is a minor or not when there is a lack of documents. Being a time-consuming activity that can be prone to inter- and intra-rater variability, the use of methods which can automate it, like Machine Learning techniques, is of value. Objective The goal of this paper is to present the state of the art evidence, trends and gaps in the research related to bone age assessment studies that make use of Machine Learning techniques. Method A systematic literature review was carried out, starting with the writing of the protocol, followed by searches on three databases: Pubmed, Scopus and Web of Science to identify the relevant evidence related to bone age assessment using Machine Learning techniques. One round of backward snowballing was performed to find additional studies. A quality assessment was performed on the selected studies to check for bias and low quality studies, which were removed. Data was extracted from the included studies to build summary tables. Lastly, a meta-analysis was performed on the performances of the selected studies. Results 26 studies constituted the final set of included studies. Most of them proposed automatic systems for bone age assessment and investigated methods for bone age assessment based on hand and wrist radiographs. The samples used in the studies were mostly comprehensive or bordered the age of 18, and the data origin was in most of cases from United States and West Europe. Few studies explored ethnic differences. Conclusions There is a clear focus of the research on bone age assessment methods based on radiographs whilst other types of medical imaging without radiation exposure (e.g. magnetic resonance imaging) are not much explored in the literature. Also, socioeconomic and other aspects that could influence in bone age were not addressed in the literature. Finally, studies that make use of more than one region of interest for bone age assessment are scarce. Copyright: © 2019 Dallora et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 9. |
- Ejeskär, Katarina, 1969, et al.
(författare)
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The Unique Non-Catalytic C-Terminus of P37delta-PI3K Adds Proliferative Properties In Vitro and In Vivo
- 2015
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Ingår i: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- The PI3K/Akt pathway is central for numerous cellular functions and is frequently deregulated in human cancers. The catalytic subunits of PI3K, p110, are thought to have a potential oncogenic function, and the regulatory subunit p85 exerts tumor suppressor properties. The fruit fly, Drosophila melanogaster, is a highly suitable system to investigate PI3K signaling, expressing one catalytic, Dp110, and one regulatory subunit, Dp60, and both show strong homology with the human PI3K proteins p110 and p85. We recently showed that p37 delta, an alternatively spliced product of human PI3K p110 delta, displayed strong proliferation-promoting properties despite lacking the catalytic domain completely. Here we functionally evaluate the different domains of human p37 delta in Drosophila. The N-terminal region of Dp110 alone promotes cell proliferation, and we show that the unique C-terminal region of human p37 delta further enhances these proliferative properties, both when expressed in Drosophila, and in human HEK-293 cells. Surprisingly, although the N-terminal region of Dp110 and the C-terminal region of p37 delta both display proliferative effects, over-expression of full length Dp110 or the N-terminal part of Dp110 decreases survival in Drosophila, whereas the unique C-terminal region of p37 delta prevents this effect. Furthermore, we found that the N-terminal region of the catalytic subunit of PI3K p110, including only the Dp60 (p85)-binding domain and a minor part of the Ras binding domain, rescues phenotypes with severely impaired development caused by Dp60 over-expression in Drosophila, possibly by regulating the levels of Dp60, and also by increasing the levels of phosphorylated Akt. Our results indicate a novel kinase-independent function of the PI3K catalytic subunit.
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| 10. |
- Elgbratt, Kristina, 1969-, et al.
(författare)
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A quantitative study of the mechanisms behind thymic atrophy in G alpha i2-deficient mice during colitis development
- 2012
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library of Science. - 1932-6203. ; 7:5
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Tidskriftsartikel (refereegranskat)abstract
- Mice deficient for the G protein subunit G alpha i2 spontaneously develop colitis, a chronic inflammatory disease associated with dysregulated T cell responses. We and others have previously demonstrated a thymic involution in these mice and an aberrant thymocyte dynamics. The G alpha i2(-/-) mice have a dramatically reduced fraction of double positive thymocytes and an increased fraction of single positive (SP) thymocytes. In this study, we quantify a number of critical parameters in order to narrow down the underlying mechanisms that cause the dynamical changes of the thymocyte development in the G alpha i2(-/-) mice. Our data suggest that the increased fraction of SP thymocytes results only from a decreased number of DP thymocytes, since the number of SP thymocytes in the Gai2(-/-) mice is comparable to the control littermates. By measuring the frequency of T cell receptor excision circles (TRECs) in the thymocytes, we demonstrate that the number of cell divisions the G alpha i2(-/-) SP thymocytes undergo is comparable to SP thymocytes from control littermates. In addition, our data show that the mature SP CD4(+) and CD8(+) thymocytes divide to the same extent before they egress from the thymus. By estimating the number of peripheral TREC+ T lymphocytes and their death rate, we could calculate the daily egression of thymocytes. G alpha i2(-/-) mice with no/mild and moderate colitis were found to have a slower export rate in comparison to the control littermates. The quantitative measurements in this study suggest a number of dynamical changes in the thymocyte development during the progression of colitis.
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