| 21. |
- Egerod, Kristoffer L, et al.
(författare)
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A Major Lineage of Enteroendocrine Cells Coexpress CCK, Secretin, GIP, GLP-1, PYY, and Neurotensin but Not Somatostatin.
- 2012
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Ingår i: Endocrinology. - : The Endocrine Society. - 0013-7227 .- 1945-7170.
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Tidskriftsartikel (refereegranskat)abstract
- Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the CCK promoter demonstrated a distribution pattern of CCK-eGFP positive cells that extended throughout the intestine. Quantitative PCR and liquid chromatography-mass spectrometry proteomic analyses of isolated, FACS-purified CCK-eGFP-positive cells demonstrated expression of not only CCK but also glucagon-like peptide 1 (GLP-1), gastric inhibitory peptide (GIP), peptide YY (PYY), neurotensin, and secretin, but not somatostatin. Immunohistochemistry confirmed this expression pattern. The broad coexpression phenomenon was observed both in crypts and villi as demonstrated by immunohistochemistry and FACS analysis of separated cell populations. Single-cell quantitative PCR indicated that approximately half of the duodenal CCK-eGFP cells express one peptide precursor in addition to CCK, whereas an additional smaller fraction expresses two peptide precursors in addition to CCK. The coexpression pattern was further confirmed through a cell ablation study based on expression of the human diphtheria toxin receptor under the control of the proglucagon promoter, in which activation of the receptor resulted in a marked reduction not only in GLP-1 cells, but also PYY, neurotensin, GIP, CCK, and secretin cells, whereas somatostatin cells were spared. Key elements of the coexpression pattern were confirmed by immunohistochemical double staining in human small intestine. It is concluded that a lineage of mature enteroendocrine cells have the ability to coexpress members of a group of functionally related peptides: CCK, secretin, GIP, GLP-1, PYY, and neurotensin, suggesting a potential therapeutic target for the treatment and prevention of diabetes and obesity.
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| 22. |
- Finkel, Deborah, et al.
(författare)
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Longitudinal twin study of subjective health : Differences in genetic and environmental components of variance across age and sex
- 2020
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Ingår i: The journals of gerontology. Series B, Psychological sciences and social sciences. - : Oxford University Press. - 1079-5014 .- 1758-5368. ; 75:1, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The current analysis examines sex differences in longitudinal changes in genetic and environmental influences on three measures of subjective health.Method: Sample includes 7372 twins (mean intake age = 73.22) with up to 8 waves of measurement (mean = 3.1). Three subjective health (SH) items were included: general self-rated health (SRH), health compared to age peers (COMP), and impact of health on activities (ACT) which previous research shows capture different frames of reference.Results: Latent growth curve modeling indicated significant differences across gender and frame of reference in trajectories of change with age and in genetic and environmental contributions to change. Men have higher mean scores on all three SH measures, indicating better SH, but there were no sex differences in pattern of change with age. Accelerating declines with age were found for SRH and ACT, whereas COMP improved with age. Results indicated more genetic variance for women than men, but declining genetic variance for both after age 70. Increasing shared environmental variance with increasing age was also found for both sexes.Discussion: As aging triggers a re-evaluation of the meaning of "good health," physical aspects of health may become less important and shared cultural conceptions of health may become more relevant. This change in conceptions of good health may reflect both aging and the change in composition of the elderly population as a result of selective survival.
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| 23. |
- Gardner, Michael, et al.
(författare)
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Gender and telomere length : Systematic review and meta-analysis
- 2014
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Ingår i: Experimental Gerontology. - : Elsevier. - 0531-5565 .- 1873-6815. ; 51, s. 15-27
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Forskningsöversikt (refereegranskat)abstract
- Background: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods: We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results: Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions: Telomere length is longer in females thanmales, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. (C) 2013 Published by Elsevier Inc.
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| 24. |
- Kemp, John P, et al.
(författare)
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Phenotypic dissection of bone mineral density reveals skeletal site specificity and facilitates the identification of novel loci in the genetic regulation of bone mass attainment.
- 2014
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 10:6
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Tidskriftsartikel (refereegranskat)abstract
- Heritability of bone mineral density (BMD) varies across skeletal sites, reflecting different relative contributions of genetic and environmental influences. To quantify the degree to which common genetic variants tag and environmental factors influence BMD, at different sites, we estimated the genetic (rg) and residual (re) correlations between BMD measured at the upper limbs (UL-BMD), lower limbs (LL-BMD) and skull (SK-BMD), using total-body DXA scans of ∼ 4,890 participants recruited by the Avon Longitudinal Study of Parents and their Children (ALSPAC). Point estimates of rg indicated that appendicular sites have a greater proportion of shared genetic architecture (LL-/UL-BMD rg = 0.78) between them, than with the skull (UL-/SK-BMD rg = 0.58 and LL-/SK-BMD rg = 0.43). Likewise, the residual correlation between BMD at appendicular sites (r(e) = 0.55) was higher than the residual correlation between SK-BMD and BMD at appendicular sites (r(e) = 0.20-0.24). To explore the basis for the observed differences in rg and re, genome-wide association meta-analyses were performed (n ∼ 9,395), combining data from ALSPAC and the Generation R Study identifying 15 independent signals from 13 loci associated at genome-wide significant level across different skeletal regions. Results suggested that previously identified BMD-associated variants may exert site-specific effects (i.e. differ in the strength of their association and magnitude of effect across different skeletal sites). In particular, variants at CPED1 exerted a larger influence on SK-BMD and UL-BMD when compared to LL-BMD (P = 2.01 × 10(-37)), whilst variants at WNT16 influenced UL-BMD to a greater degree when compared to SK- and LL-BMD (P = 2.31 × 10(-14)). In addition, we report a novel association between RIN3 (previously associated with Paget's disease) and LL-BMD (rs754388: β = 0.13, SE = 0.02, P = 1.4 × 10(-10)). Our results suggest that BMD at different skeletal sites is under a mixture of shared and specific genetic and environmental influences. Allowing for these differences by performing genome-wide association at different skeletal sites may help uncover new genetic influences on BMD.
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| 25. |
- Maxwell, Karen L., et al.
(författare)
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Protein folding : Defining a "standard" set of experimental conditions and a preliminary kinetic data set of two-state proteins
- 2005
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Ingår i: Protein Science. - : Wiley. - 0961-8368 .- 1469-896X. ; 14, s. 602-16
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Tidskriftsartikel (refereegranskat)abstract
- Recent years have seen the publication of both empirical and theoretical relationships predicting the rates with which proteins fold. Our ability to test and refine these relationships has been limited, however, by a variety of difficulties associated with the comparison of folding and unfolding rates, thermodynamics, and structure across diverse sets of proteins. These difficulties include the wide, potentially confounding range of experimental conditions and methods employed to date and the difficulty of obtaining correct and complete sequence and structural details for the characterized constructs. The lack of a single approach to data analysis and error estimation, or even of a common set of units and reporting standards, further hinders comparative studies of folding. In an effort to overcome these problems, we define here a "consensus" set of experimental conditions (25°C at pH 7.0, 50 mM buffer), data analysis methods, and data reporting standards that we hope will provide a benchmark for experimental studies. We take the first step in this initiative by describing the folding kinetics of 30 apparently two-state proteins or protein domains under the consensus conditions. The goal of our efforts is to set uniform standards for the experimental community and to initiate an accumulating, self-consistent data set that will aid ongoing efforts to understand the folding process.
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| 26. |
- Midtgaard, Kaare S., et al.
(författare)
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Biomechanical significance of the collateral ligaments in transolecranon fracture-dislocations
- 2021
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Ingår i: Journal of shoulder and elbow surgery. - : MOSBY-ELSEVIER. - 1058-2746 .- 1532-6500. ; 30:6, s. 1245-1250
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is widely accepted that transolecranon fracture-dislocations are not associated with collateral ligament disruption. The aim of the present study was to investigate the significance of the collateral ligaments in transolecranon fractures. Methods: Twenty cadaveric elbows with a mean age of 46.3 years were used. All soft tissue was dissected to the level of the capsule, leaving the anterior band of the medial collateral ligament (MCL) and lateral collateral ligament (LCL) intact. A standardized, oblique osteotomy starting from the distal margin of the cartilage bare area of the ulna was made. The elbows were loaded with an inferiorly directed force of 5 and 10 N in the intact, MCL cut, LCL cut, and both ligaments cut states. All measurements were recorded on lateral calibrated radiographs. Results: The mean inferior translation with intact ligaments (n 20) when the humerus was loaded with 5 and 10 N was 1.52 mm (95% confidence interval [CI], 1.02-2.02) and 2.23 mm (95% CI, 1.61-2.85), respectively. When the LCL was cut first (n = 10), the inferior translation with 5 and 10 N load was 4.11 mm (95% CI, 0.95-7.26) and 4.82 mm (95% CI, 1.91-7.72), respectively. When the MCL was cut first (n - 10), the inferior translation when loaded with 5 and 10 N was 3.94 mm (95% CI, 0.796-7.08) and 5.68 mm (95% CI, 3.03-8.33), respectively. The inferior translation when loaded with 5 and 10 N and both ligaments cut was 15.65 mm (95% CI, 12.59-18.79) and 17.50 mm (95% CI, 14.86-20.13), respectively. There was a statistical difference between the intact and MCL cut first at 10 N and when both ligaments were cut at 5 and 10 N. Conclusions: The findings suggest that collateral ligament disruption is a prerequisite for a transolecranon fracture-dislocation. An inferior translation of more than 3 mm suggests that at least one of the collateral ligaments is disrupted, and more than 7.5 mm indicates that both collateral ligaments are disrupted. (C) 2020 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.
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| 27. |
- Pahlen, Shandell, et al.
(författare)
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Age-moderation of genetic and environmental contributions to cognitive functioning in mid- and late-life for specific cognitive abilities
- 2018
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Ingår i: Intelligence. - : Elsevier. - 0160-2896 .- 1873-7935. ; 68, s. 70-81
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Tidskriftsartikel (refereegranskat)abstract
- Age moderation of genetic and environmental contributions to Digits Forward, Digits Backward, Block Design, Symbol Digit, Vocabulary, and Synonyms was investigated in a sample of 14,534 twins aged 26 to 98 years. The Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium contributed the sample, which represents nine studies from three countries (USA, Denmark, and Sweden). Average test performance was lower in successively older age groups for all tests. Significant age moderation of additive genetic, shared environmental, and non-shared environmental variance components was observed, but the pattern varied by test. The genetic contribution to phenotypic variance across age was smaller for both Digit Span tests, greater for Synonyms, and stable for Block Design and Symbol Digit. The non-shared environmental contribution was greater with age for the Digit Span tests and Block Design, while the shared environmental component was small for all tests, often more so with age. Vocabulary showed similar age-moderation patterns as Synonyms, but these effects were nonsignificant. Findings are discussed in the context of theories of cognitive aging.
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| 28. |
- Reynolds, Chandra A., et al.
(författare)
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Gene-Environment Interplay in Physical, Psychological, and Cognitive Domains in Mid to Late Adulthood : Is APOE a Variability Gene?
- 2016
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Ingår i: Behavior Genetics. - : Springer Nature Switzerland AG. - 0001-8244 .- 1573-3297. ; 46:1, s. 4-19
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Tidskriftsartikel (refereegranskat)abstract
- Despite emerging interest in gene-environment interaction (GxE) effects, there is a dearth of studies evaluating its potential relevance apart from specific hypothesized environments and biometrical variance trends. Using a monozygotic within-pair approach, we evaluated evidence of G×E for body mass index (BMI), depressive symptoms, and cognition (verbal, spatial, attention, working memory, perceptual speed) in twin studies from four countries. We also evaluated whether APOE is a 'variability gene' across these measures and whether it partly represents the 'G' in G×E effects. In all three domains, G×E effects were pervasive across country and gender, with small-to-moderate effects. Age-cohort trends were generally stable for BMI and depressive symptoms; however, they were variable-with both increasing and decreasing age-cohort trends-for different cognitive measures. Results also suggested that APOE may represent a 'variability gene' for depressive symptoms and spatial reasoning, but not for BMI or other cognitive measures. Hence, additional genes are salient beyond APOE.
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| 29. |
- Surakka, Ida, et al.
(författare)
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A Genome-Wide Association Study of Monozygotic Twin-Pairs Suggests a Locus Related to Variability of Serum High-Density Lipoprotein Cholesterol
- 2012
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Ingår i: Twin Research and Human Genetics. - : Cambridge University Press (CUP). - 1832-4274 .- 1839-2628. ; 15:6, s. 691-699
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association analysis on monozygotic twin-pairs offers a route to discovery of gene-environment interactions through testing for variability loci associated with sensitivity to individual environment/lifestyle. We present a genome-wide scan of loci associated with intra-pair differences in serum lipid and apolipoprotein levels. We report data for 1,720 monozygotic female twin-pairs from GenomEUtwin project with 2.5 million SNPs, imputed or genotyped, and measured serum lipid fractions for both twins. We found one locus associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors (P = 3.98 × 10-8). We followed up the association in further genotyped monozygotic twins (N = 1,261), which showed a moderate association for the variant (P = 0.200, same direction of an effect). In addition, we report a new association on the level of apolipoprotein A-II (P = 4.03 × 10-8).
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| 30. |
- Vo, Tina T., et al.
(författare)
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Does sleep duration moderate genetic and environmental contributions to cognitive performance?
- 2022
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Ingår i: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 45:10
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Tidskriftsartikel (refereegranskat)abstract
- While prior research has demonstrated a relationship between sleep and cognitive performance, how sleep relates to underlying genetic and environmental etiologies contributing to cognitive functioning, regardless of the level of cognitive function, is unclear. The present study assessed whether the importance of genetic and environmental contributions to cognition vary depending on an individual’s aging-related sleep characteristics. The large sample consisted of twins from six studies within the Interplay of Genes and Environment across Multiple Studies (IGEMS) consortium spanning mid- to late-life (Average age [Mage] = 57.6, range = 27–91 years, N = 7052, Female = 43.70%, 1525 complete monozygotic [MZ] pairs, 2001 complete dizygotic [DZ] pairs). Quantitative genetic twin models considered sleep duration as a primary moderator of genetic and environmental contributions to cognitive performance in four cognitive abilities (Semantic Fluency, Spatial-Visual Reasoning, Processing Speed, and Episodic Memory), while accounting for age moderation. Results suggested genetic and both shared and nonshared environmental contributions for Semantic Fluency and genetic and shared environmental contributions for Episodic Memory vary by sleep duration, while no significant moderation was observed for Spatial-Visual Reasoning or Processing Speed. Results for Semantic Fluency and Episodic Memory illustrated patterns of higher genetic influences on cognitive function at shorter sleep durations (i.e. 4 hours) and higher shared environmental contributions to cognitive function at longer sleep durations (i.e. 10 hours). Overall, these findings may align with associations of upregulation of neuroinflammatory processes and ineffective beta-amyloid clearance in short sleep contexts and common reporting of mental fatigue in long sleep contexts, both associated with poorer cognitive functioning.
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