| 1. |
- Bergemalm, Daniel, 1977-, et al.
(author)
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Systemic Inflammation in Preclinical Ulcerative Colitis
- 2021
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In: Gastroenterology. - : AGA Institute. - 0016-5085 .- 1528-0012. ; 161:5, s. 1526-1539.e9
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Journal article (peer-reviewed)abstract
- Background & Aims: Preclinical ulcerative colitis is poorly defined. We aimed to characterize the preclinical systemic inflammation in ulcerative colitis, using a comprehensive set of proteins.Methods: We obtained plasma samples biobanked from individuals who developed ulcerative colitis later in life (n = 72) and matched healthy controls (n = 140) within a population-based screening cohort. We measured 92 proteins related to inflammation using a proximity extension assay. The biologic relevance of these findings was validated in an inception cohort of patients with ulcerative colitis (n = 101) and healthy controls (n = 50). To examine the influence of genetic and environmental factors on these markers, a cohort of healthy twin siblings of patients with ulcerative colitis (n = 41) and matched healthy controls (n = 37) were explored.Results: Six proteins (MMP10, CXCL9, CCL11, SLAMF1, CXCL11 and MCP-1) were up-regulated (P < .05) in preclinical ulcerative colitis compared with controls based on both univariate and multivariable models. Ingenuity Pathway Analyses identified several potential key regulators, including interleukin-1β, tumor necrosis factor, interferon-gamma, oncostatin M, nuclear factor-κB, interleukin-6, and interleukin-4. For validation, we built a multivariable model to predict disease in the inception cohort. The model discriminated treatment-naïve patients with ulcerative colitis from controls with leave-one-out cross-validation (area under the curve = 0.92). Consistently, MMP10, CXCL9, CXCL11, and MCP-1, but not CCL11 and SLAMF1, were significantly up-regulated among the healthy twin siblings, even though their relative abundances seemed higher in incident ulcerative colitis.Conclusions: A set of inflammatory proteins are up-regulated several years before a diagnosis of ulcerative colitis. These proteins were highly predictive of an ulcerative colitis diagnosis, and some seemed to be up-regulated already at exposure to genetic and environmental risk factors.
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| 2. |
- Mihalič, Filip, et al.
(author)
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Conservation of Affinity Rather Than Sequence Underlies a Dynamic Evolution of the Motif-Mediated p53/MDM2 Interaction in Ray-Finned Fishes
- 2024
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In: Molecular biology and evolution. - : Oxford University Press. - 0737-4038 .- 1537-1719. ; 41:2
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Journal article (peer-reviewed)abstract
- The transcription factor and cell cycle regulator p53 is marked for degradation by the ubiquitin ligase MDM2. The interaction between these 2 proteins is mediated by a conserved binding motif in the disordered p53 transactivation domain (p53TAD) and the folded SWIB domain in MDM2. The conserved motif in p53TAD from zebrafish displays a 20-fold weaker interaction with MDM2, compared to the interaction in human and chicken. To investigate this apparent difference, we tracked the molecular evolution of the p53TAD/MDM2 interaction among ray-finned fishes (Actinopterygii), the largest vertebrate clade. Intriguingly, phylogenetic analyses, ancestral sequence reconstructions, and binding experiments showed that different loss-of-affinity changes in the canonical binding motif within p53TAD have occurred repeatedly and convergently in different fish lineages, resulting in relatively low extant affinities (KD = 0.5 to 5 mu M). However, for 11 different fish p53TAD/MDM2 interactions, nonconserved regions flanking the canonical motif increased the affinity 4- to 73-fold to be on par with the human interaction. Our findings suggest that compensating changes at conserved and nonconserved positions within the motif, as well as in flanking regions of low conservation, underlie a stabilizing selection of "functional affinity" in the p53TAD/MDM2 interaction. Such interplay complicates bioinformatic prediction of binding and calls for experimental validation. Motif-mediated protein-protein interactions involving short binding motifs and folded interaction domains are very common across multicellular life. It is likely that the evolution of affinity in motif-mediated interactions often involves an interplay between specific interactions made by conserved motif residues and nonspecific interactions by nonconserved disordered regions.
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| 3. |
- Persson, Ingemar, 1985-, et al.
(author)
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Sub-4 nm mapping of donor-acceptor organic semiconductor nanoparticle composition
- 2023
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In: Nanoscale. - : ROYAL SOC CHEMISTRY. - 2040-3364 .- 2040-3372. ; 15:13, s. 6126-6142
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Journal article (peer-reviewed)abstract
- We report, for the first time, sub-4 nm mapping of donor : acceptor nanoparticle composition in eco-friendly colloidal dispersions for organic electronics. Low energy scanning transmission electron microscopy (STEM) energy dispersive X-ray spectroscopy (EDX) mapping has revealed the internal morphology of organic semiconductor donor : acceptor blend nanoparticles at the sub-4 nm level. A unique element was available for utilisation as a fingerprint element to differentiate donor from acceptor material in each blend system. Si was used to map the location of donor polymer PTzBI-Si in PTzBI-Si:N2200 nanoparticles, and S (in addition to N) was used to map donor polymer TQ1 in TQ1:PC71BM nanoparticles. For select material blends, synchrotron-based scanning transmission X-ray microscopy (STXM), was demonstrated to remain as the superior chemical contrast technique for mapping organic donor : acceptor morphology, including for material combinations lacking a unique fingerprint element (e.g. PTQ10:Y6), or systems where the unique element is in a terminal functional group (unsaturated, dangling bonds) and can hence be easily damaged under the electron beam, e.g. F on PTQ10 donor polymer in the PTQ10:IDIC donor : acceptor blend. We provide both qualitative and quantitative compositional mapping of organic semiconductor nanoparticles with STEM EDX, with sub-domains resolved in nanoparticles as small as 30 nm in diameter. The sub-4 nm mapping technology reported here shows great promise for the optimisation of organic semiconductor blends for applications in organic electronics (solar cells and bioelectronics) and photocatalysis, and has further applications in organic core-shell nanomedicines.
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| 4. |
- Hill, Jason, et al.
(author)
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Spatiotemporal variations in retrovirus-host interactions among Darwin’s finches
- 2022
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 13:1
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Journal article (peer-reviewed)abstract
- Endogenous retroviruses (ERVs) are inherited remnants of retroviruses that colonized host germline over millions of years, providing a sampling of retroviral diversity across time. Here, we utilize the strength of Darwin’s finches, a system synonymous with evolutionary studies, for investigating ERV history, revealing recent retrovirus-host interactions in natural populations. By mapping ERV variation across all species of Darwin’s finches and comparing with outgroup species, we highlight geographical and historical patterns of retrovirus-host occurrence, utilizing the system for evaluating the extent and timing of retroviral activity in hosts undergoing adaptive radiation and colonization of new environments. We find shared ERVs among all samples indicating retrovirus-host associations pre-dating host speciation, as well as considerable ERV variation across populations of the entire Darwin’s finches’ radiation. Unexpected ERV variation in finch species on different islands suggests historical changes in gene flow and selection. Non-random distribution of ERVs along and between chromosomes, and across finch species, suggests association between ERV accumulation and the rapid speciation of Darwin’s finches.
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| 5. |
- Larimer, Mary E, et al.
(author)
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An International Comparison of a Web-Based Personalized Feedback Intervention for Alcohol use During the Transition out of High School in the United States and Sweden.
- 2021
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In: Prevention Science. - : Springer. - 1389-4986 .- 1573-6695. ; 22, s. 670-682
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Journal article (peer-reviewed)abstract
- Young adult drinkers engage in a range of drinking patterns from abstaining to heavy drinking in both the United States and Sweden. Heavy drinking during young adulthood in both countries is associated with a variety of negative consequences. Personalized feedback interventions have been identified as effective prevention strategies to prevent or reduce heavy drinking in the United States. This study examined transitions in drinking profiles and compared the efficacy of a personalized feedback intervention for 3965 young adults in the United States (1,735) and Sweden (2230) during their transition out of high school. Using goodness-of-fit criteria, results indicated that three drinking profiles exist among young adults transitioning out of high school: very low drinkers/abstainers, moderate to heavy drinkers, and very heavy drinkers. Latent Markov models revealed a moderating effect of country on personalized feedback intervention such that intervention condition participants in the United States were more likely to belong to the light drinker/abstainer or moderate to heavy profile relative to the very heavy drinking profile at 6-month follow-up. There was no significant effect of personalized feedback intervention in Sweden. Future research could investigate the impact of when personalized feedback interventions are administered and could examine if personalized feedback interventions should be more intentionally culturally adapted in order to be more effective.
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| 6. |
- Lindsay, Willow R, et al.
(author)
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Endless forms of sexual selection
- 2024
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Other publication (other academic/artistic)abstract
- The field of sexual selection has burgeoned with research into trait evolution in the context of ecology, sociality, phylogeny, natural selection, and sexual conflict. This paper is the product of a “stock-taking” workshop; our aim is to stimulate discussion, not to provide an exhaustive review. We identify outstanding questions organized into four thematic sections.1) Evolution of mate choice and mating systems. Variation in mate quality can generate mating competition and choice in either sex with implications for the evolution of mating systems. Limitations on mate choice may dictate the importance of direct vs. indirect benefits in mating decisions and consequently, mating systems. Specifically, polyandry evolves in response to the strength of pre- vs. post-copulatory selection. The evolution of polyandry may be related to diversity of pathogens and Major Histocompatibility Complex (MHC) genes. MHC genes are also potential cues of kinship in avoidance of inbreeding. The balance between inbreeding avoidance and inclusive fitness in mating decisions deserves greater attention.2) Sender and receiver mechanisms shaping signal design. Mediation of honest signal content likely depends on integration of temporally variable social and physiological costs that are a challenge to measure. The neuroethology of sensory and cognitive receiver biases is the main key to signal form and the ‘aesthetic sense’ proposed by Darwin. Since a receiver bias is sufficient to both start and drive ornament or armament exaggeration, without a genetically correlated or even coevolving receiver, this may be the appropriate ‘null model’ of sexual selection.3) Genetic architecture of sexual selection. Despite advances in modern molecular techniques, the number and identity of genes underlying performance remain largely unknown. A combination of genomic techniques and long-term field studies that reveal ecological correlates of reproductive success is warranted. In-depth investigations into the genetic basis of sexual dimorphism will reveal constraints and trajectories of sexually selected trait evolution.4) Sexual selection and conflict as drivers of speciation. Population divergence and speciation is often driven by an interplay between sexual and natural selection. To what extent sexual selection promotes or counteracts population divergence may differ depending on the genetic architecture of traits as well as covariance between mating competition and local adaptation, if traits have multiple functions and if sensory systems used in mate choice are locally adapted. Also, post-copulatory processes, e.g. selection against heterospecific sperm, may influence the importance of sexual selection. Sexual conflict can shape speciation processes, since mate choice selection on females can restrict gene flow whereas selection on males is permissive.We propose that efforts to resolve these four themes can catalyze conceptual progress in the field of sexual selection.
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| 7. |
- Litt, Dana M., et al.
(author)
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A cross-cultural comparison of factors associated with marijuana use among college students in the United States and Sweden
- 2021
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In: The international journal of alcohol and drug research. - : Ohio State University Press. - 1925-7066. ; 9:2, s. 52-58
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Journal article (peer-reviewed)abstract
- Aims: Marijuana is a popular drug among U.S. college students. In Sweden, the prevalence of marijuana use has been relatively low but is increasing. Brief, personalized interventions have been efficacious in reducing substance use, including marijuana, among college students in the U.S. However, prior to implementation of U.S. interventions in Sweden, it is important to compare factors associated with marijuana use among college students in the two countries. Design, Setting, and Participants: Data are from baseline assessments of two large college student intervention studies in the U.S. (N = 3,753, 39% male) and Sweden (N = 2,280, 35% male). Measures: Past 30-day prevalence and frequency of marijuana use was analyzed in regard to relevant demographic factors. The moderating role of nationality was also examined. Findings: Results support previous findings indicating marijuana use is more common in the U.S. than in Sweden. Most demographic factors were similar across the countries, except for relationship status and work status, in which associations with number of marijuana use days (but not odds of any marijuana use) were stronger for Swedish college students compared to U.S. college students. Conclusions: Based on overall similarities between the U.S. and Sweden, comparable interventions might be recommended in both countries.
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| 8. |
- Niklasson, Erik, et al.
(author)
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Assessment of anterior thigh muscle size and fat infiltration using single-slice CT imaging versus automated MRI analysis in adults
- 2022
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In: British Journal of Radiology. - London, United Kingdom : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 95:1133
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Journal article (peer-reviewed)abstract
- Objectives: We examined the longitudinal and cross- sectional relationship between automated MRI-analysis and single-slice axial CT imaging for determining muscle size and muscle fat infiltration (MFI) of the anterior thigh.Methods: Twenty-two patients completing sex-hormone treatment expected to result in muscle hypertrophy (n = 12) and atrophy (n = 10) underwent MRI scans using 2-point Dixon fat/water-separated sequences and CT scans using a system operating at 120 kV and a fixed flux of 100 mA. At baseline and 12 months after, auto- mated volumetric MRI analysis of the anterior thigh was performed bilaterally, and fat-free muscle volume and MFI were computed. In addition, cross-sectional area (CSA) and radiological attenuation (RA) (as a marker of fat infiltration) were calculated from single slice axial CT-images using threshold-assisted planimetry. Linear regression models were used to convert units.Results: There was a strong correlation between MRI- derived fat-free muscle volume and CT-derived CSA (R = 0.91), and between MRI-derived MFI and CT-derived RA (R = −0.81). The 95% limits of agreement were ±0.32 L for muscle volume and ±1.3% units for %MFI. The longi- tudinal change in muscle size and MFI was comparable across imaging modalities.Conclusions: Both automated MRI and single-slice CT-imaging can be used to reliably quantify anterior thigh muscle size and MFI.Advances in knowledge: This is the first study examining the intermodal agreement between automated MRI anal- ysis and CT-image assessment of muscle size and MFI in the anterior thigh muscles. Our results support that both CT- and MRI-derived measures of muscle size and MFI can be used in clinical settings.
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| 9. |
- Rubin, Carl-Johan, et al.
(author)
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Rapid adaptive radiation of Darwin's finches depends on ancestral genetic modules
- 2022
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In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:27
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Journal article (peer-reviewed)abstract
- Recent adaptive radiations are models for investigating mechanisms contributing to the evolution of biodiversity. An unresolved question is the relative importance of new mutations, ancestral variants, and introgressive hybridization for phenotypic evolution and speciation. Here, we address this issue using Darwin's finches and investigate the genomic architecture underlying their phenotypic diversity. Admixture mapping for beak and body size in the small, medium, and large ground finches revealed 28 loci showing strong genetic differentiation. These loci represent ancestral haplotype blocks with origins predating speciation events during the Darwin's finch radiation. Genes expressed in the developing beak are overrepresented in these genomic regions. Ancestral haplotypes constitute genetic modules for selection and act as key determinants of the unusual phenotypic diversity of Darwin's finches. Such ancestral haplotype blocks can be critical for how species adapt to environmental variability and change.
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| 10. |
- Wiik, Anna, et al.
(author)
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Muscle Strength, Size, and Composition Following 12 Months of Gender-affirming Treatment in Transgender Individuals
- 2020
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In: Journal of Clinical Endocrinology and Metabolism. - : ENDOCRINE SOC. - 0021-972X .- 1945-7197. ; 105:3, s. E805-E813
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Journal article (peer-reviewed)abstract
- Context. As many sports are divided in male/female categories, governing bodies have formed regulations on the eligibility for transgender individuals to compete in these categories. Yet, the magnitude of change in muscle mass and strength with gender-affirming treatment remains insufficiently explored. Objective. This study explored the effects of gender-affirming treatment on muscle function, size, and composition during 12 months of therapy. Design, settings, participants. In this single-center observational cohort study, untrained transgender women (TW, n = 11) and transgender men (TM, n = 12), approved to start gender-affirming medical interventions, underwent assessments at baseline, 4 weeks after gonadal suppression of endogenous hormones but before hormone replacement, and 4 and 12 months after treatment initiation. Main outcome measures. Knee extensor and flexor strength were assessed at all examination time points, and muscle size and radiological density (using magnetic resonance imaging and computed tomography) at baseline and 12 months after treatment initiation. Results. Thigh muscle volume increased (15%) in TM, which was paralleled by increased quadriceps cross-sectional area (CSA) (15%) and radiological density (6%). In TW, the corresponding parameters decreased by -5% (muscle volume) and -4% (CSA), while density remained unaltered. The TM increased strength over the assessment period, while the TW generally maintained their strength levels. Conclusions. One year of gender-affirming treatment resulted in robust increases in muscle mass and strength in TM, but modest changes in TW. These findings add new knowledge on the magnitude of changes in muscle function, size, and composition with cross-hormone therapy, which could be relevant when evaluating the transgender eligibility rules for athletic competitions.
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