| 1. |
- Sliz, E., et al.
(author)
-
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Kurki, MI, et al.
(author)
-
FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
-
In: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
-
Journal article (peer-reviewed)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
|
|
| 5. |
- Sul, Young-Taeg, 1960, et al.
(author)
-
Bone tissue responses to Mg-incorporated oxidized implants and machine-turned implants in the rabbit femur
- 2005
-
In: Journal of Applied Biomaterials & Biomechanics 2005. - 1724-6024. ; 3:1, s. 18-28
-
Journal article (peer-reviewed)abstract
- Previous studies have demonstrated a significant improvement in the bone response to oxidized titanium implants. Little is known about the effects of specific oxide properties on the bone tissue responses to titanium implants. This study in-vestigated the bone tissue responses to magnesium (Mg)-incorporated oxidized titanium implants and machine-turned titani-um implants in the rabbit femur. The oxidized implants were prepared using micro arc oxidation (MAO) methods. Surface oxide properties were characterized by using various surface analytic techniques, involving scanning electron microscopy (SEM) equipped with energy dispersive spectrometer (EDS), X-ray diffractometry (XRD), X-ray photoelectron spectroscopy (XPS) and optical interferometry. Screw shaped titanium implants, 10 machine-turned implants (controls) and 10 Mg-incorporated im-plants (tests) were inserted in the femoral condyles of 10 New Zealand white rabbits. After a 6-week healing period, resonance frequency analyses and removal torque measurements of the Mg-incorporated oxidized implants demonstrated significant im-provements in implant integration with bone in comparison to machine-turned implants, p=0.007 and p=0.017, respectively. Bone growth in the pores of the oxidized implants was probably incomplete at a follow-up of 6 weeks, as indicated by SEM and EDS measurements. Mg-incorporated titanium implants significantly improved bone responses as compared with machine-turned control implants. Considering the differences and similarities of the surface oxide properties of controls and test im-plants, the enhanced bone responses to Mg-incorporated implants could be explained by the Mg surface chemistry of the test im-plants. (Journal of Applied Biomaterials & Biomechanics 2005; 3: 18-28)
|
|
| 6. |
- Abelev, Betty, et al.
(author)
-
Measurement of prompt J/psi and beauty hadron production cross sections at mid-rapidity in pp collisions at root s=7 TeV
- 2012
-
In: Journal of High Energy Physics. - 1029-8479. ; :11
-
Journal article (peer-reviewed)abstract
- The ALICE experiment at the LHC has studied J/psi production at mid-rapidity in pp collisions at root s = 7 TeV through its electron pair decay on a data sample corresponding to an integrated luminosity L-int = 5.6 nb(-1). The fraction of J/psi from the decay of long-lived beauty hadrons was determined for J/psi candidates with transverse momentum p(t) > 1,3 GeV/c and rapidity vertical bar y vertical bar < 0.9. The cross section for prompt J/psi mesons, i.e. directly produced J/psi and prompt decays of heavier charmonium states such as the psi(2S) and chi(c) resonances, is sigma(prompt J/psi) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 8.3 +/- 0.8(stat.) +/- 1.1 (syst.)(-1.4)(+1.5) (syst. pol.) mu b. The cross section for the production of b-hadrons decaying to J/psi with p(t) > 1.3 GeV/c and vertical bar y vertical bar < 0.9 is a sigma(J/psi <- hB) (p(t) > 1.3 GeV/c, vertical bar y vertical bar < 0.9) = 1.46 +/- 0.38 (stat.)(-0.32)(+0.26) (syst.) mu b. The results are compared to QCD model predictions. The shape of the p(t) and y distributions of b-quarks predicted by perturbative QCD model calculations are used to extrapolate the measured cross section to derive the b (b) over bar pair total cross section and d sigma/dy at mid-rapidity.
|
|
| 7. |
- Kwon, David H., et al.
(author)
-
Bone tissue response following local drug delivery of bisphosphonate through titanium oxide nanotube implants in a rabbit model
- 2017
-
In: Journal of Clinical Periodontology. - : Wiley. - 0303-6979. ; 44:9, s. 941-949
-
Journal article (peer-reviewed)abstract
- Objectives: The objective of this study was to evaluate whether surface chemistry-controlled TiO2 nanotube structures may serve as a local drug delivery system for zoledronic acid improving implant-bone support. Methods: Twenty-four screw-shaped Ti implants with surface chemistry-controlled TiO2 nanotube structures were prepared and divided into a zoledronic acid-formatted test and a native control group. The implants were inserted into contra-lateral femoral condyles in 12 New Zealand White rabbits. Bone support was evaluated using resonance frequency analysis (RFA) and removal torque (RTQ), as well as histometric analysis following a 3-weeks healing interval. Results: Zoledronic acid-formatted TiO2 nanotube test implants showed significantly improved implant stability and osseointegration measured using RFA and RTQ compared with control (p<0.05), and showed significantly enhanced new bone formation within the root of the threads compared with control (p<0.05). Conclusions: TiO2 nanotube implants may prove to be a significant delivery system for drugs or biologic agents aimed at supporting local bone formation. Additional study of candidate drugs/agents, optimized dosage and release kinetics is needed prior to evaluation in clinical settings. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Sul, Young-Taeg, 1960, et al.
(author)
-
Optimum surface properties of oxidized implants for reinforcement of osseointegration: surface chemistry, oxide thickness, porosity, roughness, and crystal structure
- 2005
-
In: International Journal of Oral & Maxillofacial Implants. - Chicago, Ill. : Quintessence Pub. Co.. - 0882-2786 .- 1942-4434. ; 20:3, s. 349-59
-
Journal article (peer-reviewed)abstract
- PURPOSE: To investigate detailed surface characterization of oxidized implants in a newly invented electrolyte system and to determine optimal surface oxide properties to enhance the bone response in rabbits. MATERIALS AND METHODS: A total of 100 screw-type titanium implants were prepared and divided into 1 control group (machine-turned implants) and 4 test groups (magnesium ion-incorporated oxidized implants). Forty implants were used for surface analyses. A total of 60 implants, 12 implants from each group, were placed in the tibiae of 10 New Zealand white rabbits and measured with a removal torque test after a healing period of 6 weeks. RESULTS: For the test groups, the oxide thicknesses ranged from about 1,000 to 5,800 nm; for the control group, mean oxide thickness was about 17 nm. The surface morphology showed porous structures for test groups and nonporous barrier film for the control group. Pore diameter ranged from < or = 0.5 microm to < or = 3.0 microm. In regard to surface roughness, arithmetic average height deviation (Sa) values varied from 0.68 to 0.98 microm for test implants and 0.55 microm for control implants; developed surface ratio (Sdr) values ranged from 10.6% to 46% for the test groups and were about 10.6% for the control group. A mixture of anatase and rutile-type crystals were observed in the test groups; amorphous-type crystals were observed in the control group. After a healing period of 6 weeks, removal torque measurements in all 4 test groups demonstrated significantly greater implant integration as compared to machine-turned control implants (P < or = .033). DISCUSSION: Determinant oxide properties of oxidized implants are discussed in association with bone responses. Of all surface properties, RTVs were linearly increased as relative atomic concentrations of magnesium ion increase. CONCLUSIONS: Surface properties of the oxidized implants in the present study, especially surface chemistry, influenced bone responses. The surface chemistry of the optimal oxidized implant should be composed of approximately 9% magnesium at relative atomic concentration in titanium oxide matrix and have an oxide thickness of approximately 1,000 to 5,000 nm, a porosity of about 24%, and a surface roughness of about 0.8 microm in Sa and 27% to 46% in Sdr; its oxide crystal structure should be a mixture of anatase- and rutile-phase crystals.
|
|
