| 1. |
- Sliz, E., et al.
(författare)
-
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)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. |
- Tabassum, R, et al.
(författare)
-
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
|
|
| 3. |
- Juutinen, S, et al.
(författare)
-
Band structures in Ba-132
- 1995
-
Ingår i: PHYSICAL REVIEW C-NUCLEAR PHYSICS. - : AMER INST PHYSICS. ; 52:6, s. 2946-2954
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Excited states of Ba-132 were studied in an experiment utilizing the Sn-124(C-13,5n) reaction at a beam energy of 65.5 MeV. The level scheme of Ba-132 was considerably extended from what was previously known. Evidence is presented for neutron h(11/2) alig
|
|
| 4. |
|
|
| 5. |
- Kantele, A., et al.
(författare)
-
Safety and immunogenicity of ETVAX (R), an oral inactivated vaccine against enterotoxigenic Escherichia coli diarrhoea: a double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa
- 2023
-
Ingår i: Journal of Travel Medicine. - 1195-1982.
-
Tidskriftsartikel (refereegranskat)abstract
- Background: No licensed human vaccines are available against enterotoxigenic Escherichia coli (ETEC), a major diarrhoeal pathogen affecting children in low- and middle-income countries and foreign travellers alike. ETVAX (R), a multivalent oral whole-cell vaccine containing four inactivated ETEC strains and the heat-labile enterotoxin B subunit (LTB), has proved promising in Phase 1 and Phase 1/ 2 studies.Methods: We conducted a Phase 2b double-blinded, randomized, placebo-controlled trial amongst Finnish travellers to Benin, West Africa. This report presents study design and safety and immunogenicity data. Volunteers aged 18-65 years were randomized 1:1 to receive ETVAX (R) or placebo. They visited Benin for 12 days, provided stool and blood samples and completed adverse event (AE) forms. IgA and IgG antibodies to LTB and O78 lipopolysaccharide (LPS) were measured by electrochemiluminescence.Results: The AEs did not differ significantly between vaccine (n = 374) and placebo (n = 375) recipients. Of the solicited AEs, loose stools/diarrhoea (26.7/25.9%) and stomach ache (23.0/20.0%) were reported most commonly. Of all possibly/probably vaccine-related AEs, the most frequent were gastrointestinal symptoms (54.0/48.8%) and nervous system disorders (20.3/25.1%). Serious AEs were recorded for 4.3/5.6%, all unlikely to be vaccine related. Amongst the ETVAX (R) recipients, LTB-specific IgA antibodies increased 22-fold. For the 370/372 vaccine/placebo recipients, the frequency of =2-fold increases against LTB was 81/2.4%, and against O78 LPS 69/2.7%. The majority of ETVAX (R) recipients (93%) responded to either LTB or O78.Conclusions: This Phase 2b trial is the largest on ETVAX (R) undertaken amongst travellers to date. ETVAX (R) showed an excellent safety profile and proved strongly immunogenic, which encourages the further development of this vaccine.
|
|
| 6. |
- Grachova, E V, et al.
(författare)
-
The structure and dynamic behaviour of disubstituted derivatives of Rh6(CO)16 containing heterobidentate bridging phosphine ligands
- 2003
-
Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9234 .- 1477-9226. ; :12, s. 2468-2473
-
Tidskriftsartikel (refereegranskat)abstract
- The solution structures and dynamic behaviour of [Rh6(CO)14(µ-PX)][PX = diphenyl(2-pyridyl)phosphine, (PN); diphenyl(2-thienyl)phosphine, (PS); diphenyl(vinyl)phosphine, (PV)] have been studied by multinuclear NMR and the X-ray structure of [Rh6(CO)14(µ,3-PV)] is reported. In solution, the above clusters undergo a variety of localised CO-exchanges and the mechanisms of these are discussed. The PV ligand in [Rh6(CO)14(µ,3-PV)] is hemilabile and exhibits facile exchange/reorientation of the vinyl group.
|
|
| 7. |
|
|
| 8. |
- Tunik, S P, et al.
(författare)
-
Chiral hexarhodium clusters containing heterobidentate phosphine ligands, a structural and reactivity study
- 2003
-
Ingår i: Dalton Transactions. - : Royal Society of Chemistry (RSC). - 1477-9234. ; :12, s. 2457-2467
-
Tidskriftsartikel (refereegranskat)abstract
- Some intrinsically chiral [Rh6(CO)14(µ,2-PX)] clusters have been synthesized, beginning with reactions of [Rh6(CO)16–x(NCMe)x](x= 1, 2) with PX, where PX represents the bidentate bridging ligands diphenyl(benzothienyl)phosphine (1), diphenyl(2-thienyl)phosphine (2), di(2-thienyl)phenylphosphine (3), tris(2-thienyl)phosphine (4), diphenyl(2-pyridyl)phosphine (5) and diphenylvinylphosphine (6). The ligand tris(2-furyl)phosphine (7) shows no bridging capability. When x= 1 the initial products are the clusters [Rh6(CO)15(1-PX)] which undergo spontaneous CO loss to form [Rh6(CO)14(µ,2-PX)]. The structures of the [Rh6(CO)15(1-PX)] clusters have been elucidated by IR, NMR spectroscopy and FAB-MS spectrometry, and have been found to involve phosphorus atom coordination to a rhodium atom. In addition, the solid state structures of the [Rh6(CO)14(µ,2-Ph2P(2-benzothienyl))](8), [Rh6(CO)14(µ,2-Ph2P(2-thienyl))](9), [Rh6(CO)14(µ,2-PhP(2-thienyl)2)](10) and [Rh6(CO)14(µ,2-Ph2P(pyridyl))](12) clusters have been determined by X-ray crystallography. The various types of chirality exhibited by these clusters are discussed. A simple model is proposed to account for the ratios of stereochemical isomers found in the Rh6(CO)14(µ,2-PhP(2-thienyl)2 cluster. The kinetics of formation of the bridged clusters from the monosubstituted [Rh6(CO)15(1-PX)] clusters have been studied.
|
|
| 9. |
- Tunik, S P, et al.
(författare)
-
Reactions of [H2OS3(CO)(10)] with conjugated diynes (RC2C2R ') containing nucleophilic oxygen in beta position of a substituent (R = Ph, R ' = CH2OH, C(O)Ph; R = R ' = CMe2(OH))
- 2003
-
Ingår i: Organometallics. - : American Chemical Society (ACS). - 1520-6041 .- 0276-7333. ; 22:17, s. 3455-3465
-
Tidskriftsartikel (refereegranskat)abstract
- Reactions of [H2Os3(CO)10] with a series of diynes, RC2C2R' (1: R = Ph, R' = CH2OH; 2: R = Ph, R' = C(O)Ph; 3: R = R' = C(OH)Me2), have been studied. It was found that upon coordination to the triosmium cluster, the nucleophilic oxygens of the R' substituents of 1 and 2 take part in intramolecular cyclization reactions to give [HOs3(CO)10{-1:2-PhCH2(C=CH-C=CH-O)}] (5) and [HOs3(CO)10{-1:1-Ph(C=CH-C=C-O)CPh}] (6), respectively, both of which contain furan rings coordinated to the cluster core. On heating of the latter compound, the furan moiety remains intact, but a carbonyl group dissociates from the cluster, leading to the formation of [HOs3(CO)9(3-1:3:1-Ph(C=CH-C=C-O)CPh)] (7) with a closed "C3Os3" pentagonal pyramidal structure. Reaction of [H2Os3(CO)10] with 3 does not lead to cyclization of the diyne; instead, the clusters [Os3(CO)10{3-2-(RCH=CH-C2R)}] (8) and [Os3(CO)10{3-2-(RC2C2R)}] (9) are formed. Deuterium labeling of the starting compounds has been used in the reaction of [H2Os3(CO)10] with HOCH2C2C2CH2OH in order to investigate possible mechanisms of the cyclization reaction. The crystal and molecular structures of clusters 5, 7, and 9 are presented.
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
- Molnár, F., et al.
(författare)
-
Boron, sulphur and copper isotope systematics in the orogenic gold deposits of the Archaean Hattu schist belt, eastern Finland
- 2016
-
Ingår i: Ore Geology Reviews. - : Elsevier BV. - 0169-1368 .- 1872-7360. ; 77, s. 133-162
-
Tidskriftsartikel (refereegranskat)abstract
- The Hattu schist belt is located in the western part of the Archaean Karelian domain of the Fennoscandian Shield. The orogenic gold deposits with Au–Bi–Te geochemical signatures are hosted by NE–SW, N–S and NW–SE oriented shear zones that deform 2.76–2.73 Ga volcanic and sedimentary sequences, as well as 2.75–2.72 Ga tonalite–granodiorite intrusions and diverse felsic porphyry dykes. Mo–W mineralization is also present in some tonalite intrusions, both separate from, and associated with Au mineralization. Somewhat younger, unmineralized leucogranite intrusions (2.70 Ga) also intrude the belt. Lower amphibolite facies peak metamorphism at 3–5 kbar pressures and at 500–600 °C temperatures affected the belt at around 2.70 Ga and post-date hydrothermal alteration and ore formation. In this study, we investigated the potential influence of magmatic-hydrothermal processes on the formation of orogenic gold deposits on the basis of multiple stable isotope (B, S, Cu) studies of tourmaline and sulphide minerals by application of in situ SIMS and LA ICP MS analytical techniques.Crystal chemistry of tourmaline from a Mo–W mineralization hosted by a tonalite intrusion in the Hattu schist belt is characterized by Fe3 +–Al3 +-substitution indicating relatively oxidizing conditions of hydrothermal processes. The range of δ11B data for this kind of tourmaline is from − 17.2‰ to − 12.2‰. The hydrothermal tourmaline from felsic porphyry dyke swith gold mineralization has similar crystal chemistry (e.g. dravite–povondraite compositional trend with Fe3 +–Al3 + substitution) and δ11B values between − 19.0‰ and − 9.6‰. The uvite–foitite compositional trend and δ11B ‰ values between − 24.1% and − 13.6% characterize metasomatic–hydrothermal tourmaline from the metasediment-hosted gold deposits. Composition of hydrothermal vein-filling and disseminated tourmaline from the gold-bearing shear zones in metavolcanic rocks is transitional between the felsic intrusion and metasedimentary rock hosted hydrothermal tourmaline but the range of average boron isotope data is essentially identical with that of the metasediment-hosted tourmaline. Rock-forming (magmatic) tourmaline from leucogranite has δ11B values between − 14.5‰ and − 10.8‰ and the major element composition is similar to that of the metasediment-hosted tourmaline.The range of δ34SVCDT values measured in pyrite, chalcopyrite and pyrrhotite is from − 9.1 to + 8.5‰, which falls within the typical range of sulphur isotope data for Archaean orogenic gold deposits. In the Hattu schist belt, positive δ34SVCDT values characterize metasediment-hosted gold ores with sulphide parageneses dominated by pyrrhotite and arsenopyrite. The δ34SVCDT values are both positive and negative in ore mineral parageneses within felsic intrusive rocks in which variable amounts of pyrrhotite are associated with pyrite. Purely negative values were only recorded from the pyrite-dominated gold mineralization within metavolcanic units. Therefore the shift of δ34SVCDT values to the negative values reflects precipitation of sulphide minerals from relatively oxidizing fluids. The range of measured δ65CuNBS978 values from chalcopyrite is from − 1.11 to 1.19‰. Positive values are common for mineralization in felsic intrusive rocks and negative values are more typical for deposits confined to metasedimentary rocks. Positive and negative δ65CuNBS978 values occur in the ores hosted by metavolcanic rocks. There is no correlation between sulphur and copper isotope data obtained in the same chalcopyrite grains.Evaluation of sulphur and boron isotope data together and comparisons with other Archaean orogenic gold provinces supports the hypothesis that the metasedimentary rocks were the major sources of sulphur and boron in the orogenic gold deposits in the Hattu schist belt. Variations in major element and boron isotope compositions in tourmaline, as well as in the δ34SVCDT values in sulphide minerals are attributed to localized involvement of magmatic fluids in the hydrothermal processes. The results of copper isotope studies indicate that local sources of copper in orogenic gold deposits may potentially be recognized if the original, distinct signatures of the sources have not been homogenized by widespread interaction of fluids with a large variety of rocks and provided that local chemical variations have been too small to trigger changes in the oxidation state of copper during hydrothermal processes.
|
|
| 15. |
|
|
| 16. |
- Pakkanen, S. H., et al.
(författare)
-
Specific and Cross-reactive Plasmablast Response in Humans after Primary and Secondary Immunization with Vi Capsular Polysaccharide Typhoid Vaccine
- 2017
-
Ingår i: Scandinavian Journal of Immunology. - : WILEY. - 0300-9475 .- 1365-3083. ; 86:4, s. 207-215
-
Tidskriftsartikel (refereegranskat)abstract
- Secondary immunization with polysaccharide vaccines may imply a risk of hyporesponsiveness. Despite the wide use of typhoid Vi capsular polysaccharide vaccine, its potential tendency to hyporesponsiveness has been inadequately addressed. While previous studies have explored serum antibody responses, we applied a more sensitive approach, a single-cell assay for circulating plasmablasts, to compare primary and secondary responses. Twelve subjects received primary and booster doses of the Vi vaccine (Typherix (R)) at 30-to 37-month intervals. Plasmablasts specific to the Vi or typhoidal O antigens or cross-reactive with paratyphoid and non-typhoidal Salmonella strains were identified as antibodysecreting cells (ASC) with ELISPOT. Before vaccinations, none had plasmablasts specific to the antigens tested. Twelve of 12 subjects showed a Vi-specific response after primary, but only eight of 12 after booster vaccination. All responded to typhoidal O-9,12 antigen after both immunizations. The geometric mean of plasmablasts specific to the Vi antigen was 59 (95% CI 24-119) and 1 (0-54) IgA + IgG + IgM-ASC/10(6) peripheral blood mononuclear cell (PBMC) after primary and booster immunizations, respectively, and 20 (9-49) and 56 (29-103) to the O-9,12 antigen. We detected 1 (0-28) and 17 (6-36) ASC/10(6) PBMC cross-reactive with Salmonella Paratyphi A; 3 (0-30) and 22 (8-48) with S. Paratyphi B; 3 (0-29) and 18 (7-47) with S. Paratyphi C; 19 (10-34) and 51 (26-94) with Salmonella Enteritidis; and 1 (0-35) and 23 (9-52) with Salmonella Typhimurium, respectively. One-third of the vaccinees, although responding to the O-9,12 antigen, failed to respond to the Vi antigen after booster immunization, suggesting hyporesponsiveness in part of the vaccinees. The findings warrant further investigation.
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
