| 1. |
|
|
| 2. |
- Baird, Denis A., et al.
(författare)
-
Identification of Novel Loci Associated With Hip Shape : A Meta-Analysis of Genomewide Association Studies.
- 2019
-
Ingår i: Journal of Bone and Mineral Research. - : Wiley-Blackwell. - 0884-0431 .- 1523-4681. ; 34:2, s. 241-251
-
Tidskriftsartikel (refereegranskat)abstract
- We aimed to report the first genomewide association study (GWAS) meta-analysis of dual-energy X-ray absorptiometry (DXA)-derived hip shape, which is thought to be related to the risk of both hip osteoarthritis and hip fracture. Ten hip shape modes (HSMs) were derived by statistical shape modeling using SHAPE software, from hip DXA scans in the Avon Longitudinal Study of Parents and Children (ALSPAC; adult females), TwinsUK (mixed sex), Framingham Osteoporosis Study (FOS; mixed), Osteoporotic Fractures in Men study (MrOS), and Study of Osteoporotic Fractures (SOF; females) (total N = 15,934). Associations were adjusted for age, sex, and ancestry. Five genomewide significant (p < 5 × 10-9 , adjusted for 10 independent outcomes) single-nucleotide polymorphisms (SNPs) were associated with HSM1, and three SNPs with HSM2. One SNP, in high linkage disequilibrium with rs2158915 associated with HSM1, was associated with HSM5 at genomewide significance. In a look-up of previous GWASs, three of the identified SNPs were associated with hip osteoarthritis, one with hip fracture, and five with height. Seven SNPs were within 200 kb of genes involved in endochondral bone formation, namely SOX9, PTHrP, RUNX1, NKX3-2, FGFR4, DICER1, and HHIP. The SNP adjacent to DICER1 also showed osteoblast cis-regulatory activity of GSC, in which mutations have previously been reported to cause hip dysplasia. For three of the lead SNPs, SNPs in high LD (r2 > 0.5) were identified, which intersected with open chromatin sites as detected by ATAC-seq performed on embryonic mouse proximal femora. In conclusion, we identified eight SNPs independently associated with hip shape, most of which were associated with height and/or mapped close to endochondral bone formation genes, consistent with a contribution of processes involved in limb growth to hip shape and pathological sequelae. These findings raise the possibility that genetic studies of hip shape might help in understanding potential pathways involved in hip osteoarthritis and hip fracture. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
|
|
| 3. |
- Benedict, Christian, et al.
(författare)
-
Acute sleep deprivation increases serum levels of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in healthy young men.
- 2014
-
Ingår i: Sleep. - : Oxford University Press (OUP). - 1550-9109 .- 0161-8105. ; 37:1, s. 195-8
-
Tidskriftsartikel (refereegranskat)abstract
- To investigate whether total sleep deprivation (TSD) affects circulating concentrations of neuron-specific enolase (NSE) and S100 calcium binding protein B (S-100B) in humans. These factors are usually found in the cytoplasm of neurons and glia cells. Increasing concentrations of these factors in blood may be therefore indicative for either neuronal damage, impaired blood brain barrier function, or both. In addition, amyloid β (Aβ) peptides 1-42 and 1-40 were measured in plasma to calculate their ratio. A reduced plasma ratio of Aβ peptides 1-42 to 1-40 is considered an indirect measure of increased deposition of Aβ 1-42 peptide in the brain.
|
|
| 4. |
- Blomberg, Anders, 1956, et al.
(författare)
-
Establishing the barnacle Balanus improvisus as a potent invertebrate monitoring system in marine ecotoxicogenomics
- 2009
-
Ingår i: SETAC Europe 19th Annual Meeting Abstract Book, Göteborg 31 May - 4 June, 2009.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- There is a need for potent invertebrate systems for assessing the impacts of environmental contaminants on marine ecosystems. Balanus improvisus, a marine athropod, has a number of promising characteristics that make it a good candidate in such efforts. We have conducted sequencing of a cDNA library from the cyprid larval stage and identified several detoxification systems as well as novel B. improvisus specific genes. To investigate the toxicological gene expression response in this organism, we performed a short-term exposure experiment of the cyprid larvae to two different biofouling substances. From a natural population of B. improvisus, 300 - 1000 cyprids were treated for 23 hours with 390nM CuO or with two different concentrations (10nM or 10μM) of meditomidine. Protein expression changes were studied by 2D-PAGE analysis after DIGE labelling. For gene expression analysis by DNA miroarrays total RNA was extracted and used for cDNA and cRNA/aRNA templates. Roughly 2000 B. improvisus genes were studied represented by 3000 different probes on the arrays (each in duplicates). Candidate genes were confirmed by qPCR. A number of protein expression changes were detected on the 2D gels as a result of the different treatments. Interestingly, the response to the different treatments clearly formed distinct groups in principle component analysis. The DNA microarray analysis revealed several genes as toxicity indicators, e.g. various heat shock proteins, some proteases and factors involved in regulatory processes (transcription factors). Our data indicate that B. improvisus may serve as a tool to evaluate the impacts of marine pollution, and thus to fill the niche as an important invertebrate marine model organism for ecotoxicology and environmental genomics.
|
|
| 5. |
- Braide, Karin, et al.
(författare)
-
Salvage radiation therapy in prostate cancer: relationship between rectal dose and long-term, self-reported rectal bleeding
- 2021
-
Ingår i: Clinical & Translational Oncology. - : Springer Science and Business Media LLC. - 1699-048X .- 1699-3055. ; 23:2, s. 397-404
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose To quantify the relationship between the rectal dose distribution and the prevalence of self-reported rectal bleeding among men treated with salvage radiotherapy (ST) delivered by three-dimensional conformal radiotherapy (3DCRT) for prostate cancer. To use this relationship to estimate the risk of rectal bleeding for a contemporary cohort of patients treated with volumetric modulated arc therapy (VMAT) ST. Methods and patients Rectal bleeding of any grade was reported by 56 (22%) of 255 men in a PROM-survey at a median follow-up of 6.7 years after 3DCRT ST. Treatment plan data were extracted and dose-response relationships for the rectal volumes receiving at least 35 Gy (V-35Gy) or 63 Gy (V-63Gy) were calculated with logistic regression. These relationships were used to estimate the risk of rectal bleeding for a cohort of 253 patients treated with VMAT ST. Results In the dose-response analysis of patients in the 3DCRT ST cohort, both rectal V(35Gy)and V(63Gy)were statistically significant parameters in univariable analysis (p = 0.005 and 0.003, respectively). For the dose-response models using either rectal V(35Gy)or V-63Gy, the average calculated risk of rectal bleeding was 14% among men treated with VMAT ST compared to a reported prevalence of 22% for men treated with 3DCRT ST. Conclusions We identified dose-response relationships between the rectal dose distribution and the risk of self-reported rectal bleeding of any grade in a long-term perspective for men treated with 3DCRT ST. Furthermore, VMAT ST may have the potential to decrease the prevalence of late rectal bleeding.
|
|
| 6. |
|
|
| 7. |
- Chen, Y. H., et al.
(författare)
-
Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
- 2023
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 55, s. 44-53
-
Tidskriftsartikel (refereegranskat)abstract
- Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
|
|
| 8. |
|
|
| 9. |
- Conaway, H Herschel, et al.
(författare)
-
Retinoids inhibit differentiation of hematopoietic osteoclast progenitors.
- 2009
-
Ingår i: The FASEB journal. - Bethesda, Md. : Wiley. - 1530-6860 .- 0892-6638. ; 23:10, s. 3526-38
-
Tidskriftsartikel (refereegranskat)abstract
- Whether vitamin A promotes skeletal fragility, has no effect on fracture rate, or protects against bone loss is unclear. In the present study, effects of retinoids on osteoclast differentiation in cultured mouse bone marrow cells (BMCs), bone marrow macrophages (BMMs), spleen cells, and RAW264.7 cells were evaluated by analyzing osteoclast formation and expression of genes important in signal transduction and osteoclast function. All-trans-retinoic acid (ATRA) did not stimulate osteoclastogenesis in BMCs, but inhibited hormone and RANKL-induced gene expression and formation of osteoclasts. In BMMs, spleen cells, and RAW264.7 cells, osteoclast differentiation and formation stimulated by M-CSF/RANKL were inhibited (IC(50) = 0.3 nM) by ATRA. The effect was exerted at an early step of RANKL-induced differentiation. ATRA also abolished increases of the transcription factors c-Fos and NFAT2 stimulated by RANKL and suppressed down-regulation of the antiosteoclastogenic transcription factor MafB. By comparing effects of several compounds structurally related to ATRA, as well as by using receptor antagonists, evaluation pointed to inhibition being mediated by RARalpha, with no involvement of PPARbeta/delta. The results suggest that activation of RARalpha by retinoids in myeloid hematopoietic precursor cells decreases osteoclast formation by altering expression of the transcription factors c-Fos, NFAT2, and MafB.
|
|
| 10. |
- Conaway, H Herschel, et al.
(författare)
-
Retinoids stimulate periosteal bone resorption by enhancing the protein RANKL, a response inhibited by monomeric glucocorticoid receptor.
- 2011
-
Ingår i: The Journal of biological chemistry. - 1083-351X .- 0021-9258. ; 286:36, s. 31425-36
-
Tidskriftsartikel (refereegranskat)abstract
- Increased vitamin A (retinol) intake has been suggested to increase bone fragility. In the present study, we investigated effects of retinoids on bone resorption in cultured neonatal mouse calvarial bones and their interaction with glucocorticoids (GC). All-trans-retinoic acid (ATRA), retinol, retinalaldehyde, and 9-cis-retinoic acid stimulated release of (45)Ca from calvarial bones. The resorptive effect of ATRA was characterized by mRNA expression of genes associated with osteoclast differentiation, enhanced osteoclast number, and bone matrix degradation. In addition, the RANKL/OPG ratio was increased by ATRA, release of (45)Ca stimulated by ATRA was blocked by exogenous OPG, and mRNA expression of genes associated with bone formation was decreased by ATRA. All retinoid acid receptors (RARα/β/γ) were expressed in calvarial bones. Agonists with affinity to all receptor subtypes or specifically to RARα enhanced the release of (45)Ca and mRNA expression of Rankl, whereas agonists with affinity to RARβ/γ or RARγ had no effects. Stimulation of Rankl mRNA by ATRA was competitively inhibited by the RARα antagonist GR110. Exposure of calvarial bones to GC inhibited the stimulatory effects of ATRA on (45)Ca release and Rankl mRNA and protein expression. This inhibitory effect was reversed by the glucocorticoid receptor (GR) antagonist RU 486. Increased Rankl mRNA stimulated by ATRA was also blocked by GC in calvarial bones from mice with a GR mutation that blocks dimerization (GR(dim) mice). The data suggest that ATRA enhances periosteal bone resorption by increasing the RANKL/OPG ratio via RARα receptors, a response that can be inhibited by monomeric GR.
|
|
