| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Tierney, W., et al.
(författare)
-
A creative destruction approach to replication : Implicit work and sex morality across cultures
- 2021
-
Ingår i: Journal of Experimental Social Psychology. - : Elsevier BV. - 0022-1031 .- 1096-0465. ; 93
-
Tidskriftsartikel (refereegranskat)abstract
- How can we maximize what is learned from a replication study? In the creative destruction approach to replication, the original hypothesis is compared not only to the null hypothesis, but also to predictions derived from multiple alternative theoretical accounts of the phenomenon. To this end, new populations and measures are included in the design in addition to the original ones, to help determine which theory best accounts for the results across multiple key outcomes and contexts. The present pre-registered empirical project compared the Implicit Puritanism account of intuitive work and sex morality to theories positing regional, religious, and social class differences; explicit rather than implicit cultural differences in values; self-expression vs. survival values as a key cultural fault line; the general moralization of work; and false positive effects. Contradicting Implicit Puritanism's core theoretical claim of a distinct American work morality, a number of targeted findings replicated across multiple comparison cultures, whereas several failed to replicate in all samples and were identified as likely false positives. No support emerged for theories predicting regional variability and specific individual-differences moderators (religious affiliation, religiosity, and education level). Overall, the results provide evidence that work is intuitively moralized across cultures.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Satizabal, Claudia L., et al.
(författare)
-
Genetic architecture of subcortical brain structures in 38,851 individuals
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:11, s. 1624-
-
Tidskriftsartikel (refereegranskat)abstract
- Subcortical brain structures are integral to motion, consciousness, emotions and learning. We identified common genetic variation related to the volumes of the nucleus accumbens, amygdala, brainstem, caudate nucleus, globus pallidus, putamen and thalamus, using genome-wide association analyses in almost 40,000 individuals from CHARGE, ENIGMA and UK Biobank. We show that variability in subcortical volumes is heritable, and identify 48 significantly associated loci (40 novel at the time of analysis). Annotation of these loci by utilizing gene expression, methylation and neuropathological data identified 199 genes putatively implicated in neurodevelopment, synaptic signaling, axonal transport, apoptosis, inflammation/infection and susceptibility to neurological disorders. This set of genes is significantly enriched for Drosophila orthologs associated with neurodevelopmental phenotypes, suggesting evolutionarily conserved mechanisms. Our findings uncover novel biology and potential drug targets underlying brain development and disease.
|
|
| 8. |
- Abbasi, R., et al.
(författare)
-
IceTop : The surface component of IceCube
- 2013
-
Ingår i: Nuclear Instruments and Methods in Physics Research Section A. - : Elsevier BV. - 0168-9002 .- 1872-9576. ; 700, s. 188-220
-
Tidskriftsartikel (refereegranskat)abstract
- IceTop, the surface component of the IceCube Neutrino Observatory at the South Pole, is an air shower array with an area of 1 km(2). The detector allows a detailed exploration of the mass composition of primary cosmic rays in the energy range from about 100 TeV to 1 EeV by exploiting the correlation between the shower energy measured in IceTop and the energy deposited by muons in the deep ice. In this paper we report on the technical design, construction and installation, the trigger and data acquisition systems as well as the software framework for calibration, reconstruction and simulation. Finally the first experience from commissioning and operating the detector and the performance as an air shower detector will be discussed.
|
|
| 9. |
- Eijsbouts, C., et al.
(författare)
-
Genome-wide analysis of 53,400 people with irritable bowel syndrome highlights shared genetic pathways with mood and anxiety disorders
- 2021
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 53:11, s. 1543-1552
-
Tidskriftsartikel (refereegranskat)abstract
- Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain–gut interactions underlying IBS. © 2021, The Author(s).
|
|
| 10. |
- Chen, Zhishan, et al.
(författare)
-
Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
-
Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
|
|
| 11. |
- Huyghe, Jeroen R., et al.
(författare)
-
Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
-
Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
-
Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Biram, Adi, et al.
(författare)
-
B Cell Diversification Is Uncoupled from SAP-Mediated Selection Forces in Chronic Germinal Centers within Peyer's Patches.
- 2020
-
Ingår i: Cell reports. - : Elsevier BV. - 2211-1247. ; 30:6
-
Tidskriftsartikel (refereegranskat)abstract
- Antibodies secreted within the intestinal tract provide protection from the invasion of microbes into the host tissues. Germinal center (GC) formation in lymph nodes and spleen strictly requires SLAM-associated protein (SAP)-mediated Tcell functions; however, it is not known whether this mechanism plays a similar role in mucosal-associated lymphoid tissues. Here, we find that in Peyer's patches (PPs), SAP-mediated Tcell help is required for promoting B cell selection in GCs, but not for clonal diversification. PPs of SAP-deficient mice host chronic GCs that are absent in Tcell-deficient mice. GC B cells in SAP-deficient mice express AID and Bcl6 and generate plasma cellsin proportion to the GC size. Single-cell IgA sequencing analysis reveals that these mice host few diversified clones that were subjected to mild selection forces. These findings demonstrate that Tcell-derived help to B cells in PPs includes SAP-dependent and SAP-independent functions.
|
|
| 15. |
- Bölte, Sven, et al.
(författare)
-
The Gestalt of functioning in autism spectrum disorder : Results of the international conference to develop final consensus International Classification of Functioning, Disability and Health core sets
- 2019
-
Ingår i: Autism. - : Sage Publications. - 1362-3613 .- 1461-7005. ; 23:2, s. 449-467
-
Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder is associated with diverse social, educational, and occupational challenges. To date, no standardized, internationally accepted tools exist to assess autism spectrum disorder–related functioning. World Health Organization’s International Classification of Functioning, Disability and Health can serve as foundation for developing such tools. This study aimed to identify a comprehensive, a common brief, and three age-appropriate brief autism spectrum disorder Core Sets. Four international preparatory studies yielded in total 164 second-level International Classification of Functioning, Disability and Health candidate categories. Based on this evidence, 20 international autism spectrum disorder experts applied an established iterative decision-making consensus process to select from the candidate categories the most relevant ones to constitute the autism spectrum disorder Core Sets. The consensus process generated 111 second-level International Classification of Functioning, Disability and Health categories in the Comprehensive Core Set for autism spectrum disorder—one body structure, 20 body functions, 59 activities and participation categories, and 31 environmental factors. The Common Brief Core Set comprised 60 categories, while the age-appropriate core sets included 73 categories in the preschool version (0- to 5-year-old children), 81 in the school-age version (6- to 16-year-old children and adolescents), and 79 in the older adolescent and adult version (⩾17-year-old individuals). The autism spectrum disorder Core Sets mark a milestone toward the standardized assessment of autism spectrum disorder–related functioning in educational, administrative, clinical, and research settings.
|
|
| 16. |
- de Schipper, Elles, et al.
(författare)
-
Ability and Disability in Autism Spectrum Disorder : A Systematic Literature Review Employing the International Classification of Functioning, Disability and Health-Children and Youth Version.
- 2015
-
Ingår i: Autism Research. - : Wiley. - 1939-3792 .- 1939-3806. ; 8:6, s. 782-94
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: This study is the first in a series of four empirical investigations to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Autism Spectrum Disorder (ASD). The objective was to use a systematic review approach to identify, number, and link functional ability and disability concepts used in the scientific ASD literature to the nomenclature of the ICF-CY (Children and Youth version of the ICF, covering the life span).METHODS: Systematic searches on outcome studies of ASD were carried out in Medline/PubMed, PsycINFO, ERIC and Cinahl, and relevant functional ability and disability concepts extracted from the included studies. These concepts were then linked to the ICF-CY by two independent researchers using a standardized linking procedure. New concepts were extracted from the studies until saturation of identified ICF-CY categories was reached.RESULTS: Seventy-one studies were included in the final analysis and 2475 meaningful concepts contained in these studies were linked to 146 ICF-CY categories. Of these, 99 categories were considered most relevant to ASD (i.e., identified in at least 5% of the studies), of which 63 were related to Activities and Participation, 28 were related to Body functions, and 8 were related to Environmental factors. The five most frequently identified categories were basic interpersonal interactions (51%), emotional functions (49%), complex interpersonal interactions (48%), attention functions (44%), and mental functions of language (44%).CONCLUSION: The broad variety of ICF-CY categories identified in this study reflects the heterogeneity of functional differences found in ASD--both with respect to disability and exceptionality--and underlines the potential value of the ICF-CY as a framework to capture an individual's functioning in all dimensions of life. The current results in combination with three additional preparatory studies (expert survey, focus groups, and clinical study) will provide the scientific basis for defining the ICF Core Sets for ASD for multipurpose use in basic and applied research and every day clinical practice of ASD.
|
|
| 17. |
- Icenogle, Grace, et al.
(författare)
-
Puberty Predicts Approach But Not Avoidance on the Iowa Gambling Task in a Multinational Sample
- 2017
-
Ingår i: Child Development. - : Wiley. - 0009-3920 .- 1467-8624. ; 88:5, s. 598-1614
-
Tidskriftsartikel (refereegranskat)abstract
- According to the dual systems model of adolescent risk taking, sensation seeking and impulse control follow different developmental trajectories across adolescence and are governed by two different brain systems. The authors tested whether different underlying processes also drive age differences in reward approach and cost avoidance. Using a modified Iowa Gambling Task in a multinational, cross-sectional sample of 3,234 adolescents (ages 9-17; M = 12.87, SD = 2.36), pubertal maturation, but not age, predicted reward approach, mediated through higher sensation seeking. In contrast, age, but not pubertal maturation, predicted increased cost avoidance, mediated through greater impulse control. These findings add to evidence that adolescent behavior is best understood as the product of two interacting, but independently developing, brain systems. © 2016 The Society for Research in Child Development, Inc.
|
|
| 18. |
- Jakobsdottir, Johanna, et al.
(författare)
-
Rare Functional Variant in TM2D3 is Associated with Late-Onset Alzheimer's Disease
- 2016
-
Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 12:10
-
Tidskriftsartikel (refereegranskat)abstract
- We performed an exome-wide association analysis in 1393 late-onset Alzheimer's disease (LOAD) cases and 8141 controls from the CHARGE consortium. We found that a rare variant (P155L) in TM2D3 was enriched in Icelanders (similar to 0.5% versus < 0.05% in other European populations). In 433 LOAD cases and 3903 controls from the Icelandic AGES substudy, P155L was associated with increased risk and earlier onset of LOAD [odds ratio (95% CI) = 7.5 (3.5-15.9), p = 6.6x10(-9)]. Mutation in the Drosophila TM2D3 homolog, almondex, causes a phenotype similar to loss of Notch/Presenilin signaling. Human TM2D3 is capable of rescuing these phenotypes, but this activity is abolished by P155L, establishing it as a functionally damaging allele. Our results establish a rare TM2D3 variant in association with LOAD susceptibility, and together with prior work suggests possible links to the beta-amyloid cascade.
|
|
| 19. |
- Luukkonen, Panu K., et al.
(författare)
-
The PNPLA3 I148M variant increases ketogenesis and decreases hepatic de novo lipogenesis and mitochondrial function in humans
- 2023
-
Ingår i: Cell Metabolism. - : Elsevier. - 1550-4131 .- 1932-7420. ; 35:11, s. 1887-1896.e5
-
Tidskriftsartikel (refereegranskat)abstract
- The PNPLA3 I148M variant is the major genetic risk factor for all stages of fatty liver disease, but the underlying pathophysiology remains unclear. We studied the effect of this variant on hepatic metabolism in homozygous carriers and non-carriers under multiple physiological conditions with state-of-the-art stable isotope techniques. After an overnight fast, carriers had higher plasma b-hydroxybutyrate concentrations and lower hepatic de novo lipogenesis (DNL) compared to non-carriers. After a mixed meal, fatty acids were channeled toward ketogenesis in carriers, which was associated with an increase in hepatic mitochondrial redox state. During a ketogenic diet, carriers manifested increased rates of intrahepatic lipolysis, increased plasma b-hydroxybutyrate concentrations, and decreased rates of hepatic mitochondrial citrate synthase flux. These studies demonstrate that homozygous PNPLA3 I148M carriers have hepatic mitochondrial dysfunction leading to reduced DNL and channeling of carbons to ketogenesis. These findings have implications for understanding why the PNPLA3 variant predisposes to progressive liver disease.
|
|
| 20. |
- Steinberg, Laurence, et al.
(författare)
-
Around the world, adolescence is a time of heightened sensation seeking and immature self-regulation
- 2018
-
Ingår i: Developmental Science. - : Wiley. - 1363-755X .- 1467-7687. ; 21:2
-
Tidskriftsartikel (refereegranskat)abstract
- The dual systems model of adolescent risk-taking portrays the period as one characterized by a combination of heightened sensation seeking and still-maturing self-regulation, but most tests of this model have been conducted in the United States or Western Europe. In the present study, these propositions are tested in an international sample of more than 5000 individuals between ages 10 and 30 years from 11 countries in Africa, Asia, Europe and the Americas, using a multi-method test battery that includes both self-report and performance-based measures of both constructs. Consistent with the dual systems model, sensation seeking increased between preadolescence and late adolescence, peaked at age 19, and declined thereafter, whereas self-regulation increased steadily from preadolescence into young adulthood, reaching a plateau between ages 23 and 26. Although there were some variations in the magnitude of the observed age trends, the developmental patterns were largely similar across countries.
|
|
| 21. |
- Treusch, Sebastian, et al.
(författare)
-
Functional links between Aβ toxicity, endocytic trafficking, and Alzheimer's disease risk factors in yeast
- 2011
-
Ingår i: Science. - Washington : American association of advancement in science. - 0036-8075 .- 1095-9203. ; 334:6060, s. 1241-1245
-
Tidskriftsartikel (refereegranskat)abstract
- Aβ (beta amyloid peptide) is an important contributor to Alzheimer's disease (AD). We modeled Aβ toxicity in yeast by directing the peptide to the secretory pathway. A genome-wide screen for toxicity modifiers identified the yeast homolog of phosphatidylinositol binding clathrin assembly protein (PICALM) and other endocytic factors connected to AD whose relationship to Aβ was previously unknown. The factors identified in yeast modified Aβ toxicity in glutamatergic neurons of Caenorhabditis elegans and in primary rat cortical neurons. In yeast, Aβ impaired the endocytic trafficking of a plasma membrane receptor, which was ameliorated by endocytic pathway factors identified in the yeast screen. Thus, links between Aβ, endocytosis, and human AD risk factors can be ascertained using yeast as a model system.
|
|
