| 1. |
- Hu, H., et al.
(author)
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X-exome sequencing of 405 unresolved families identifies seven novel intellectual disability genes
- 2016
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In: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:1, s. 133-148
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Journal article (peer-reviewed)abstract
- X-linked intellectual disability (XLID) is a clinically and genetically heterogeneous disorder. During the past two decades in excess of 100 X-chromosome ID genes have been identified. Yet, a large number of families mapping to the X-chromosome remained unresolved suggesting that more XLID genes or loci are yet to be identified. Here, we have investigated 405 unresolved families with XLID. We employed massively parallel sequencing of all X-chromosome exons in the index males. The majority of these males were previously tested negative for copy number variations and for mutations in a subset of known XLID genes by Sanger sequencing. In total, 745 X-chromosomal genes were screened. After stringent filtering, a total of 1297 non-recurrent exonic variants remained for prioritization. Co-segregation analysis of potential clinically relevant changes revealed that 80 families (20%) carried pathogenic variants in established XLID genes. In 19 families, we detected likely causative protein truncating and missense variants in 7 novel and validated XLID genes (CLCN4, CNKSR2, FRMPD4, KLHL15, LAS1L, RLIM and USP27X) and potentially deleterious variants in 2 novel candidate XLID genes (CDK16 and TAF1). We show that the CLCN4 and CNKSR2 variants impair protein functions as indicated by electrophysiological studies and altered differentiation of cultured primary neurons from Clcn4(-/-) mice or after mRNA knock-down. The newly identified and candidate XLID proteins belong to pathways and networks with established roles in cognitive function and intellectual disability in particular. We suggest that systematic sequencing of all X-chromosomal genes in a cohort of patients with genetic evidence for X-chromosome locus involvement may resolve up to 58% of Fragile X-negative cases.
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| 2. |
- Hudson, Lawrence N, et al.
(author)
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The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project
- 2017
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In: Ecology and Evolution. - : John Wiley & Sons. - 2045-7758. ; 7:1, s. 145-188
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Journal article (peer-reviewed)abstract
- The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.
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| 3. |
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| 4. |
- Levis, Brooke, et al.
(author)
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Comparison of major depression diagnostic classification probability using the SCID, CIDI, and MINI diagnostic interviews among women in pregnancy or postpartum : An individual participant data meta-analysis
- 2019
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In: International Journal of Methods in Psychiatric Research. - : WILEY. - 1049-8931 .- 1557-0657. ; 28:4
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Journal article (peer-reviewed)abstract
- Objectives: A previous individual participant data meta-analysis (IPDMA) identified differences in major depression classification rates between different diagnostic interviews, controlling for depressive symptoms on the basis of the Patient Health Questionnaire-9. We aimed to determine whether similar results would be seen in a different population, using studies that administered the Edinburgh Postnatal Depression Scale (EPDS) in pregnancy or postpartum.Methods: Data accrued for an EPDS diagnostic accuracy IPDMA were analysed. Binomial generalised linear mixed models were fit to compare depression classification odds for the Mini International Neuropsychiatric Interview (MINI), Composite International Diagnostic Interview (CIDI), and Structured Clinical Interview for DSM (SCID), controlling for EPDS scores and participant characteristics.Results Among fully structured interviews, the MINI (15 studies, 2,532 participants, 342 major depression cases) classified depression more often than the CIDI (3 studies, 2,948 participants, 194 major depression cases; adjusted odds ratio [aOR] = 3.72, 95% confidence interval [CI] [1.21, 11.43]). Compared with the semistructured SCID (28 studies, 7,403 participants, 1,027 major depression cases), odds with the CIDI (interaction aOR = 0.88, 95% CI [0.85, 0.92]) and MINI (interaction aOR = 0.95, 95% CI [0.92, 0.99]) increased less as EPDS scores increased.Conclusion Different interviews may not classify major depression equivalently.
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| 5. |
- Livheim, Fredrik, et al.
(author)
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The Effectiveness of Acceptance and Commitment Therapy for Adolescent Mental Health : Swedish and Australian Pilot Outcomes
- 2015
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In: Journal of Child and Family Studies. - : Springer Science and Business Media LLC. - 1062-1024 .- 1573-2843. ; 24:4, s. 1016-1030
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Journal article (peer-reviewed)abstract
- Depression, anxiety and stress are common problems among adolescents. Teaching young people coping strategies in school-based intervention programs is one promising approach hoped to remedy the negative consequences of distress in adolescence. The aim of the two pilot studies was to examine the effect of a brief intervention based on the principles of Acceptance and Commitment Therapy (ACT) on depressive symptomatology (Australian study, N = 66) and stress (Swedish study, N = 32) among adolescents screened for psychosocial problems in school settings. In both studies, subjects were assigned to receive the ACT-group-intervention, or a control intervention featuring individual support from the school health care. The Australian study was a planned comparison, with random allocation for girls, plus one replication of a boys group. The Swedish study used a randomized controlled design. The ACT-intervention was an 8-session manualized group program. The Australian study showed significant reductions in depressive symptoms with a large effect, and significant reductions in psychological inflexibility with a medium effect when compared to the control group who received standard care. In the Swedish study, the ACT-intervention group, when compared to the control group, reported significantly lower levels of stress with a large effect size, and marginally significant decrease of anxiety, and marginally significant increased mindfulness skills. Taken together, the ACT-intervention seems to be a promising intervention for reducing stress and depressive symptoms among young adolescents in school and should be tested in full-sized studies. Limitations of these two pilots include small samples.
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| 6. |
- Olin, Pontus, et al.
(author)
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Development of a Semicontinuous Spray Process for the Production of Superhydrophobic Coatings from Supercritical Carbon Dioxide Solutions
- 2015
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In: Industrial & Engineering Chemistry Research. - : American Chemical Society (ACS). - 0888-5885 .- 1520-5045. ; 54:3, s. 1059-1067
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Journal article (peer-reviewed)abstract
- Superhydrophobic surfaces have been fabricated in a continuous spray process, where an alkyl ketene dimer (AKD) wax is dissolved in supercritical carbon dioxide (scCO(2)) and sprayed onto the substrate. The mass of extracted AKD from scCO2 has been investigated as well as the pressure, temperature, and flow of CO2 at the steady-state spray conditions. Several different substrates such as glass, aluminum, paper, poly(ethylene terephthalate) (PET), and polytetrafluoroethylene (PTFE) have been successfully coated, and the superhydrophobic properties have been evaluated by measurement of water contact angle, water drop friction, scanning electron microscopy (SEM), and surface topography. The most efficient spray process, considering surface properties and mass of extracted AKD, is obtained at the lowest temperature investigated, 67 degrees C, and the highest pressure evaluated in this study, 25 MPa. We also show that the influence of preexpansion conditions (p, T) on the surface temperature at the selected spray distance (3 cm) is negligible by measurement with an infrared camera during spraying.
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| 7. |
- Sakthikumar, Sharadha, et al.
(author)
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SETD2 Is Recurrently Mutated in Whole-Exome Sequenced Canine Osteosarcoma
- 2018
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In: Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 0008-5472 .- 1538-7445. ; 78:13, s. 3421-3431
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Journal article (peer-reviewed)abstract
- Osteosarcoma is a debilitating bone cancer that affects humans, especially children and adolescents. A homologous form of osteosarcoma spontaneously occurs in dogs, and its differential incidence observed across breeds allows for the investigation of tumor mutations in the context of multiple genetic backgrounds. Using whole-exome sequencing and dogs from three susceptible breeds (22 golden retrievers, 21 Rottweilers, and 23 greyhounds), we found that osteosarcoma tumors show a high frequency of somatic copy-number alterations (SCNA), affecting key oncogenes and tumor-suppressor genes. The across-breed results are similar to what has been observed for human osteosarcoma, but the disease frequency and somatic mutation counts vary in the three breeds. For all breeds, three mutational signatures (one of which has not been previously reported) and 11 significantly mutated genes were identified. TP53 was the most frequently altered gene (83% of dogs have either mutations or SCNA in TP53), recapitulating observations in human osteosarcoma. The second most frequently mutated gene, histone methyltransferase SETD2, has known roles in multiple cancers, but has not previously been strongly implicated in osteosarcoma. This study points to the likely importance of histone modifications in osteosarcoma and highlights the strong genetic similarities between human and dog osteosarcoma, suggesting that canine osteosarcoma may serve as an excellent model for developing treatment strategies in both species. Significance: Canine osteosarcoma genomics identify SETD2 as a possible oncogenic driver of osteosarcoma, and findings establish the canine model as a useful comparative model for the corresponding human disease.
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| 8. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 9. |
- Turner, Lucy M., et al.
(author)
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Transporting ideas between marine and social sciences: experiences from interdisciplinary research programs
- 2017
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In: Elementa. - : University of California Press. - 2325-1026. ; 5:14
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Journal article (peer-reviewed)abstract
- The oceans comprise 70% of the surface area of our planet, contain some of the world’s richest natural resources and are one of the most significant drivers of global climate patterns. As the marine environment continues to increase in importance as both an essential resource reservoir and facilitator of global change, it is apparent that to find long-term sustainable solutions for our use of the sea and its resources and thus to engage in a sustainable blue economy, an integrated interdisciplinary approach is needed. As a result, interdisciplinary working is proliferating. We report here our experiences of forming interdisciplinary teams (marine ecologists, ecophysiologists, social scientists, environmental economists and environmental law specialists) to answer questions pertaining to the effects of anthropogenic-driven global change on the sustainability of resource use from the marine environment, and thus to transport ideas outwards from disciplinary confines. We use a framework derived from the literature on interdisciplinarity to enable us to explore processes of knowledge integration in two ongoing research projects, based on analyses of the purpose, form and degree of knowledge integration within each project. These teams were initially focused around a graduate program, explicitly designed for interdisciplinary training across the natural and social sciences, at the Gothenburg Centre for Marine Research at the University of Gothenburg, thus allowing us to reflect on our own experiences within the context of other multi-national, interdisciplinary graduate training and associated research programs.
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